UPDATE NOTE #1: The cause and cure of cancer was published by John Beard in 1902. Beard’s studies have continually been ignored or attacked by orthodox medicine in spite of the fact that his theory has been clinically demonstrated to be correct over and over again throughout history. Beard actually discovered stem cells at the turn of the century. He called them trophoblasts. All trophoblast cells originate in the yolk sac and have to migrate into, and throughout, the growing embryo – when a stem cell loses its power to differentiate into the cell type of its parent tissue it becomes cancerous and grows out of control.
UPDATE NOTE #2: If you heard that the Kelley enzymes were “burning people up” and were too strong, here is the situation. Sometime in the near past, Dr Kelley decided to double the amount of glandulars in the pancreatic enzymes. This caused problems, probably due to the amount of protomorphogens [PMGs] they contained. Protomorphogens are the blueprints for the new cells. Since they are mineral containing proteins, they initiate antibody responses if they spill over into the intercellular spaces or blood stream [e.g, in trauma or degenerative disease processes]. If tissue breakdown exceeds tissue repair, these PMGs interfere with recovery since histamine is released when they hook up with antibodies [Royal Lee originally called these, Natural Tissue Antibodies]. Antibodies surrounding sick and diseased tissue stifle growth and repair [demonstrated in the chicken heart and many other experiments during the early 19th and 20th century]. When body organs are diseased, such as in rheumatic heart disease, PMGs often effect recovery by clearing out the antibodies collecting around damaged cells that are releasing the protein contents. The PMGs prepared from animal tissue link up with the troublemaking antibodies and carry them off, allowing the cell breathing space in which to repair or reproduce. When the protomorphogen hooks up with the antibody to clear it away to make room for healthy tissue growth, histamine is released. This can cause sharp pains, dull aches, feeling of impending cold onset, flu type symptoms or just plain sick syndrome, depending upon the amounts of PMGs taken in. PMGs are prepared from glandulars. If the heart is being attacked, beef heart PMG is fed. If the Liver is in need of repair, Liver PMG is fed. Stories abound about heart patients who were kept alive by eating pounds of fresh beef heart over a hundred years ago. This type of medical information was swept under the rug by medical criminals and medical students were denied access to such information because these items could not be patented by the drug companies. High levels of PMGs in the Kelley pancreatic enzymes were probably the result of his use of increased amounts of glandulars. According to my reporting source, the pancreatic enzyme effect of the Kelley enzymes are claimed to be higher than all the others on the market for which assays are available for comparison. It is my personal opinion that all of the enzymes being marketed by reputable companies are OK for use. The most comprehensive explanation of protomorphogen is found in Dr Royal Lee’s work, Protomorphology, The Principles of Cell Regulation.
UPDATE NOTE #3: Dr William Donald Kelley passed away on
1. CANCER DEFINITION AND DISCUSSION –
2. LEARN ABOUT THE AMAZING EFFECT OF BLOOD ROOT SALVE IN DRAWING TUMORS OUT OF THE BODY THROUGH THE SKIN. THE EFFECT OF BLOOD ROOT DEFIES ALL SCIENTIFIC THOUGHT AND PHYSIOLOGICAL FUNCTION. BRAIN TUMORS HAVE BEEN DRAWN DOWN THROUGH THE LYMPHATICS AND THEN OUT THROUGH THE SKIN ON THE BACK OF THE NECK. I HAVE PERSONALLY WITNESSED THE POWERFUL EFFECTS OF BLOOD ROOT SALVE DRAWING TUMORS OUT OF THE BREAST.
3. WARNING AGAINST THE USE OF ABORTION PILL RSU-486.
4. PSA TEST, THE GREAT MEDICAL SCAM OF THE 80s
5. THE ENZYME TREATMENT OF CANCER AND ITS SCIENTIFIC BASIS BY JOHN BEARD , 1911 [this is Beard’s original book].
WHAT IS CANCER?
Diabetes is the inability of the body to metabolize properly, sugars and carbohydrates. Cancer is nothing more than the very simple inability of the body to metabolize proteins properly. And that's all cancer is. William Donald Kelley, DDS
[note: William Donald Kelley
passed away on
Until the reader understands what cancer is, they will be unsuccessful in applying the proper treatment.
The commonly held view of cancer is incorrect. Cancer is not a tumor, metastasis or blood or lymph invasion.
A malignant tumor is a SIGN of cancer, a SYMPTOM of cancer, a malignant tumor is NOT cancer.
Cancer is the inability of the body to metabolize proteins due to a lack of pancreatic enzymes. It is the pancreatic enzyme that digests the cancer cell. Pancreatic enzymes will attack and digest any cell foreign to the body but will not harm normal body cells. Pancreatic enzymes taken by mouth escape digestion and are absorbed intact into the system. The enzymes have survived boiling in hydrochloric acid at a temperature of several hundred degrees. Pig enzymes are most similar to humans and are the preferred source by some doctors. Beef enzymes are a close second.
Cancer is a failure of the pancreas to produce enough pancreatic enzymes to keep the daily growth of trophoblast cells in the body under control. All trophobasts originate in the yolk sac. They are now called STEM CELLS.
It appears as though the pancreatic enzyme is the ONLY bodily defense against the growth of malignant tumors arising out of the trophoblasts/stem cells scattered throughout the body. Other apparent cures are probably the result of the facilitation [by the supposed curative substance or procedure] of the pancreatic enzymes to do their job in digesting cancer cells.
Everyone grows malignant tumors in their bodies every day. Trophoblast Cells designed to form the placenta in every pregnancy are found scattered all throughout the body and when triggered into reproducing, begin to form malignant tumors.
Pancreatic enzymes “sniff out” these incipient tumors and digest them. Pancreatic enzymes do not attack and digest normal body cells.
This is why the fetal pancreas turns on so early in gestation. It helps digest the trophoblast cells of pregnancy which eat into the uterine lining to “prepare the bed” for the embryo. Those trophoblast cells are the same cells that form malignant tumors.
The true cause of cancer was announced in 1902 and published in 1911. It was later described as The Unitarian Trophoblastic Theory of Cancer.
The cause of cancer has been steadfastly ignored by mainstream medicine for an entire century because the cure has nothing to do with medicine nor drugs, nor heroic or mystifying procedures. Millions and millions of people have suffered and died unnecessarily because of criminal interference by organized medicine and the pharmaceutical industry, aided and abetted by government bureaucrats and the alphabet soup of bureaucracies, in particular, the NIH, CDC and FDA. xxx
If you are growing tumors
and have been told you have cancer – unless you have the cancer of pregnancy
[80-90% of which respond to orthodox drug treatments with Methotrexate etc.]
your best chance for recovery is to begin pancreatic enzyme therapy and follow
the protocol developed by Dr William Donald Kelley, the
The more affluent patient should contact Dr Nicholas Gonzalez of NYC. Initial fee $2800 with appointments scheduled at six month intervals costing $650 initially.
In reviewing the different approaches to cancer in alternative medicine one must keep in mind that anything that facilitates the effectiveness of pancreatic enzymes in the body will appear to be a cancer cure. For example, a sympathetic dominant, overly acid cancer patient with solid tumors who engages in a vegetarian based diet cure for cancer might achieve enough pH balance to increase the effectiveness of their pancreas and recover. On the other hand, a parasympathetic dominant cancer victim with lymphomas and blood related cancers might be able to effect the same result by resorting to an entirely different, meat based diet. The latter patient who tries to go vegetarian and eats lots of green salads etc. thinking that is the healthy thing to do will make matters worse.
Orthodox medicine attacks malignant tumors with poisonous drugs which add to the poisons that result from the tumor breakdown. This often overwhelms the system and the patient dies from the toxins released by the tumor breakdown plus the drug effects, plus their basic malnourished state and junk food diet. In my opinion, most cancer patients die from the medical treatment long before they would die of their cancers.
When using the proper therapy [pancreatic enzymes plus vitamins, minerals and essential food factors], the patient only has to contend with the poisons from the tumor breakdown. Coffee enemas that stimulate the liver help this process along and help the body to rid itself of toxins. The coffee enema was a standard in medical care for over seventy years and was used to rescue patients from toxic shock syndrome. It was originally used for pain relief during the Crimean war when supplies of painkilling drugs were exhausted. I have just been informed by Dr Kelley’s son that Pam MacDougall, a long time Kelley colleague uses infrared sauna for eliminating detoxification effects. As soon as I gather the material on this I will add it to this discussion.
Patients have to stop pancreatic enzymes [and their other nutritional supplements] for periods of time to enable their liver to clean out the toxins. Presently, patients stay on the protocol for up to 15 to 20 days and then rest for five days to enable to the system to cleanse itself of the toxic tumor breakdown products.
During the five day abstention from the vitamins and enzymes of the protocol - purges, liver flushes and “clean sweep” techniques are used to help clean out the body.
The bigger the dose of pancreatic enzyme the greater the destruction of the tumor masses.
The greater the destruction of the tumor mass the worse the patient feels.
If you are treating yourself for cancer with pancreatic enzymes and don’t feel bad, one of three possibilities exist:
1. you are not taking enough enzymes
2. your tumors are very small
3. something is blocking the effect of the pancreatic enzymes.
This latter point is one of the most important guidelines for the recovering cancer patient.
SUGGESTED READING ON CANCER added Jan 24, 2004
1. John Beard’s reprint advertised on this website.
2. The Immortal Cell by Gerald B Dermer who spent half his adult life as a cancer researcher. He describes cancer research as, “…a scientific and medical scandal of the highest order...a tale of poor science and the pressures that induce cancer scientists to do unsound work.”
3. A New Approach to the Conquest of Cancer, Rheumatic and Heart Diseases by Howard H Beard, PhD [no relation to John Beard] Note: I listened to Dr Beard lecture in 1973. He claimed that he had some tumors growing in his bowels and when they got too big he just stopped the donuts and took some pancreatic enzymes. He told this story in a humorous, joking manner when asked about his personal diet but it was my opinion that he was serious about the tumors in his bowel. Howard Beard recommended the urine pregnancy test as a cancer diagnosis since anyone with HcG in their urine had to be pregnant or have cancer. Back in those days we were doing pregnancy tests on males to help diagnose cancer – everyone thought we were crazy.
4. One Answer to Cancer By Dr William Donald Kelley. Dr Kelley explains why no one can cure your cancer and that you have to do it yourself. He gives you the guidelines to accomplish the task. It helps to have someone knowledge to help you along the way. The nutritional treatment of cancer is a full time job and the patients need lots of help. For example, using the Gonzalez enzymes require up to 96 capsules of pancreatic enzymes a day in six divided doses with one dose between two and four AM at a time when the body is most alkaline. Pancreatic enzymes work in an alkaline environment.
Dr Duffy’s advice to CANCER patients and ANYONE INTERESTED IN THEIR HEALTH WHO WOULD LIKE TO KNOW EXACTLY HOW TO EAT ACCORDING TO THEIR OWN PERSONAL METABOLIC TYPE OR WHO WOULD LIKE TO KNOW HOW TO CURE THEIR CANCER AT HOME:
College Health Store
Tel 1-888-477-3618 toll free from within
Ask for the nutritional catalog that contains the pancreatic enzymes and other nutritional items necessary to comply with the Kelley cancer treatment protocol. ALSO ASK FOR A COPY OF THE NUTRITIONAL PROTOCOL FOR YOU TO FOLLOW.
The remarks herein are also supported by the study published in the peer reviewed journal, Nutrition and Cancer vol. 33, no.2, 1999 (June). The question of the effectiveness of ORAL pancreatic enzymes was finally settled and reported in 1965 in the J of Exp Med. Initially, investigators thought that pancreatic enzymes could not survive digestion and exert their effects on cancer cells after being absorbed through the digestive system. This was found to be untrue. Pancreatic enzymes survive the digestive process and then go about their business of digesting cancer cells – regardless of their location. This was demonstrated on a strain of lab mice that routinely develop and die of cancer within six months. When these mice were placed on pancreatic enzymes, 100% of them survived and lived out normal lifespans! – 100& of the controls, fed the usual rations, died of cancer as usual.
This article should also serve to expose the chicanery of Chris Wallace with his latest ABC “Primetime” show (Jan 2002); the criminal activity of the major news networks; the curious activity of Stephen Barrett, known as the chief “quackbuster” for organized medicine; the destructive and misleading activities of Tony Fauci and gang at the CDC/NIH; and all the medical quacks practicing orthodox medicine and those churning out useless, junk-science based “scientific” papers at the public’s expense. This latter group was properly exposed by Gerald B. Dermer, a cancer researcher who spent a good part of his life doing cancer research and then dropped out to expose it as a colossal fraud. Read his book, The Immortal Cell: Why Cancer Reseach Fails.
Any MD with common sense and the power to think for him/her self who has practiced orthodox medicine five or more years eventually realizes that they’re doing more harm than good. Some of them then begin to look around for a less harmful approach – often ending up in non therapeutic activities such as radiology, psychiatry etc. I have been told this over and over by MDs I have met over the years.
In 1973, this writer taught a seminar on the Kelley nutritional treatment of cancer to a group of Chiropractors in Tallmadge, Ohio, at which time I was called a quack by some of my colleagues and threatened with de-licensing etc. The techniques that I taught at that seminar, while based upon the fundamental idea of John Beard as interpreted by Dr Kelley, have been perfected over the years by Dr Kelley and Dr Gonzalez and now represent statistically, by peer reviewed study, the best approach available for the cancer patient. This is regardless of the type or location of the cancer with the possible exception of the cancer of pregnancy.
A case by case approach based upon biochemical individuality is now being used by Nicholas Gonzalez MD, in NYC and others. Effective biochemical and other forms of screening, individualized diets, physical examinations, nutrient supplementation and special detoxification techniques have now been formulated into the best approach to cancer in history. The treatment of cancer is now highly successful.
The established protocols have been demonstrably successful with pancreatic cancer. Gonzalez in NYC has published the results of the effectiveness of the nutritional approach to cancer which far exceeds anything available in the orthodox approach in most cancers [see choriocarcinoma below].
Julius Cohnheim (1839-1884) described the embryonal rest theory, surmising that when the embryo is formed, an excess of germ cells are formed which later, subjected to certain environmental stimuli, can multiply out of control. The result would be cancer if it were not for [as later discovered by John Beard] a properly functioning pancreas producing the enzymes necessary to keep such growths under control.
These germ cells, called trophoblasts by John Beard are none other than the STEM CELL of modern research. They originate in the yolk sac and migrate to all sections of the body where they become the “seeds” for future tissue growth depending upon their location.
Cohnheim’s idea had to wait for the Scot, John Beard to figure out the connection between the pancreas and cancer. Beard observed that the developing embryo is immediately surrounded by a layer of trophoblasts which eat into the lining to prepare a nest for the developing egg where they continue to multiply until the day the fetal pancreas turns on. Trophoblasts are wild and wooly cells, primitive and undifferentiated parts of the placenta and if unchecked by pancreatic enzymes, become the most rapidly destructive cancer, choriocarcinoma. Orthodox drug therapy is effective in 80-90% of choriocarcinoma via the use of Methotrexate and other drugs [Dr Gonzalez, pers comm.].
At a certain time in the development of the embryo, the seemingly unchecked growth of these cells would abruptly stop at a specific day in every species observed by Beard. This led to his theory that perhaps the use pancreatic enzymes would be effective in the treatment of cancer since it was these very pancreatic enzymes that digested and eliminated the potentially cancer forming trophoblasts of pregnancy.
Beard gave us the answer to the DIRECT cause of cancer – it has been kept out of sight, ridiculed and ostracized by organized medicine ever since he reported his findings in 1902 (Lancet 1:1758) in an article entitled The Trophoblastic Theory of Cancer.
In 1911 Beard published a book, “The Enzyme Treatment of Cancer” and
shortly thereafter, forty clinics in
hCG is the molecule used in pregnancy tests to establish pregnancy. hCG also indicates the presence of malignant cells. hCG in the urine indicates one of three possibilities: a pregnant female, a male with cancer, or an un-pregnant female with cancer.
HCG is a negatively charged glycoprotein hormone (a “sialoglyocprotein”). Howard Beard developed the “Anthrone” urine test to detect hCG in the urine as a specific pathognomonic sign of cancer except in the pregnant female. The pharmaceutically supported establishment criminals in government bureacracies have managed to keep this information under the rug until 1992 when Acevedo’s research was finally published in the establishment mouthpiece for cancer, the journal Cancer 1992;69:1818-28 and 1829-42 finally published the truth along with Cancer Det Prev 1995;19:37. The chief investigator said, “hCG, the hormone of pregnancy…is a common phenotypic characteristic of cancer.”
In another study The Michigan State Department of Biomechanics reported 96% effectiveness in the Furda Biochemical analysis ability to predict cancer based on protein electrophoresis analysis. (pers comm. H.Eidenier Jr). In 1994 Krichevsky reported that ALL cancer cells express hCG in all its forms including the related human luteinizing hormone (Endocrin 1994;135:1034-39).
So the truth is finally out officially. In 1942 Ernst T. Krebs Jr rediscovered Beard’s thesis and history and in July 1950 they published an article in the Medical Record entitled, “The Unitarian Trophoblastic Thesis of Cancer.” Krebs stated, “cancer is trophoblast in special and temporal anomaly, hybridized with, and vasularized by, hostal or somatic cells and in irreversible and fiercely malignant antithesis to such.” (Townsend Letter Feb/Mar 1993 p175).
Krebs co-discovered Laetrile (Vitamin B17), found especially in apricot kernels. Vigorous nutritional therapy has been responsible for deaths attributed to too rapid breakdown of tumors that release overwhelming toxins into the body. Underactivity of the Liver would contribute to such deaths and this is the reason for the insistence on the use of coffee enemas on a daily basis by patients on the nutritional cure of cancer to insure Liver breakdown of the highly toxic products of tumor breakdown.
Dr Kelley cured himself of pancreatic cancer by simple, natural means. Although his approach was only about thirty per cent effective in the very beginning because he used a strictly vegetarian approach, he quickly found out that other methods had to be brought into the equation.
Kelley had the will to perform the thousands of painstaking studies on the effects of the various vitamins, minerals and essential food factors necessary to figure out an effective protocol for all the metabolic types. The Kelley approach is being successfully used by Gonzalez in NYC [greatly improved as new products are discovered and developed]. The protocol is practically a guaranteed success for those who use it properly. [Any patient who has been given six months to live stands a good chance of full recovery]
The nutritional treatment of cancer is based upon John Beard’s trophoblastic theory of cancer which includes the use of pancreatic enzymes and detoxifying methods including the liver flush and coffee enema. The use of detoxifying methods are absolutely essential in all cancer patients and is lifesaving in some due to the enormous amount of toxins released from tumor break-down. Many cancer patients thought to be dying of cancer drug effects are in fact dying from the poisonous products of tumor breakdown. If that is not detoxified by coffee enemas and liver flushes, the patient will often die even though the signs of cancer [tumors] are disappearing in their body.
Basically the nutritional approach to cancer involves the use of large amounts of pancreatic enzymes, diet tailored to the individual biochemical needs of the patient and the rigorous use of the coffee enema, liver flushes, special detoxification techniques and purges.
The quackbusters who have been ridiculing the coffee enema are referred to the Merck Manual from 1898 to 1977. Coffee enema is recommended in that prestigious medical manual.
Medical literature reveals that coffee
enemas have been used in hospital emergency situations for conditions as serious
as septic shock and was first used by nurses in the days of
The treatment of cancer is a do-it-at-home approach and is a full time job. Minimum enemas per day is usually two and some patients require as many as six to eight. Coffee enemas using strictly fresh ground ORGANIC coffee are necessary along with the consumption of as many as 180 vitamin tablets per day depending upon the severity of the situation. Cost is estimated at one twentieth of the cost of orthodox medical treatment, most of the latter of which ends up killing the patient. Hardly anyone dies of cancer these days, most people die from the medical treatment.
One thing is certain, the NUTRITIONAL, NATURAL cure for cancer is available. Those in government positions who continue to support the drug oriented orthodox medical approach to cancer while suppressing information vital to the public health and welfare should be identified and brought before a jury and tried for crimes against humanity in accordance with the principles laid down at Nuremberg. There is no question in my mind that if this were accomplished properly, many of the leading figures in our government bureacracies today would be found guilty of villainous acts against the public good.
The number of people victimized by the Nazi medical crimes
pale in comparison to the numbers of innocent victims in the USA today who are
dying from medical quackery being rendered by doctors practicing orthodox
medicine. This is particularly true in regards to those being treated by the
deadly drugs used for AIDS, a myth similar to fictional epidemic [SMON] in
The situation is totally out of control and has now reached mind boggling proportions.
The makers of Bayer Aspirin just admitted to killing over 80 Americans with a useless cholesterol drug being commercialized to improperly influence the elderly who do better with higher cholesterol levels!
Every member of the orthodox medical fraternity and every
person who benefits from tax supported medical research resulting in the
propagation of destructive propaganda from orthodox medicine are equally guilty.
These co-conspirators should be brought to trial and tried under principles laid
The NIH and the CDC especially, are a plague on humankind and causing more deaths, ill health, maiming, and unnecessary business losses [Mad cow, Hoof and Mouth insanity etc], than all of the wars of history and will continue to do so until a public consciousness is awakened and proper actions as suggested herein are put into effect.
Dr Duffy’s advice to cancer patients and ANYONE INTERESTED IN THEIR HEALTH WHO WOULD LIKE TO KNOW EXACTLY HOW TO EAT ACCORDING TO THEIR OWN PERSONAL METABOLIC TYPE:
1. Cancer patients
call Kelley’s health food store in
College Health Store
toll free from within the
2. Call 1-888-477-3618 toll free and order Dr Kelley’s SELF TEST and take it from there, he will recommend the specific nutrition for each metabolic type after you complete the comprehensive (2 to 3 hours) questionnaire - cost is only $19.95 for the SELF TEST. [call 1-817-594-0705 if you are out of the country]
3. Dr Kelley recommends the Navarro urine
test to diagnose the presence of cancer. The telephone number for the Navarro
clinic, [long distance to the Philipines] is 011-632-714-7442 or 847-359-3634.
4. If you are not a do-it-yourselfer call Dr Gonzalez in NYC 1-212-213-3337. My advice for those calling Gonzalez – if you do not appear to be fully committed to his therapy you probably won’t be accepted as a patient.
MORE TO COME
The following was added on
Every age is afflicted by armies directed by criminals who promote the use of force and violence to achieve their selfish ends. Armies of the past were easily recognized – they wore identifiable uniforms and carried recognizable weapons. They were easily differentiated by the man-on-the-street.
Not so with the new criminally directed army.
The violent, destructive army of today, which has been slowly forming over the centuries, gaining power little by little through the years is the army of the white coats – the doctors – operating under the direction of criminals with the force of bureaucracy-endowed power.
The white coats are the most destructive element on the planet today. They have adulterated our foods, our drinking water, and our bodies, with their quack remedies.
Most importantly, they have robbed us of our right to choose for ourselves, the type of treatment we desire for ourselves and our children.
They have brought into the American culture MANDATORY MEDICINE, COMPULSORY VACCINATION.
COMPULSORY MEDICINE IN ANY FORM OTHER THAN MOMENTARY QUARANTINE FOR A SPECIFIC REASON AND SPECIFICALLY LIMITED TIME PERIOD IS TOTALLY UNACCEPTABLE IN A FREE SOCIETY OR IN ANY SOCIET Y. –
COMPULSORY MEDICINE OF ANY TYPE IS REPUGNANT.
WARNING AGAINST USE OF ABORTION PILL RSU-486
The abortion pill is made up of two different pills administered in series. The first is Mifepristone. The second is Cytotec. Searle manufactures Cytotec and issued the following warning on its use: Doctors are warned not to use it "off label" for induction of labor and abortion because it can lead to severe bleeding and uterine ruptures requiring surgery. It might cause death. Cytotec is the only drug available presently to accompany the Mifepristone. CYTOTEC WAS ORIGINALLY DESIGNED AND APPROVED TO BE USED IN THE PREVENTION OF ULCERS. THIS IS AN EXAMPLE OF THE POLITICALLY MOTIVATED, DRUG PROFIT SUPPORTED JUNK SCIENCE THAT IS NOT ONLY CONDONED, BUT ENCOURAGED BY, YOUR GOVERNMENT.
The Mifepristone is being made in
A CLASSICAL EXAMPLE OF MEDICAL QUACKERY
21st CENTURY STYLE:
THE NON SPECIFICITY
OF "PROSTATE SPECIFIC" ANTIGEN
By Daniel H Duffy Sr, DC
On a recent visit to His MD, he was examined in orthodox fashion and found to have an elevated PSA for which an incredibly expensive drug was prescribed. It cost over $1000 for 90 pills. Three of the pills immediately made him sick so he stopped taking the drug after his first three doses.
Of course, he only paid five of the $1000 plus dollars it cost - we the taxpayers paid the rest - thanks to the criminal efforts of LBJ - the great provider of MEDICARE.
All of LBJ's
programs demonstrably failed - especially the negative income tax fiasco which
really backfired but not before it tore apart the negro and hispanic families in
which it resulted in divorce rates as high as >80percentile. [if you would
like to read about that see
1. PSA means Prostate Specific Antigen.
2. PSA is NOT specific and has LITTLE to do with the prostate specifically.
3. PSA is found in females with breast, lung and uterine cancers. [whoops!] In fact, the highest levels of PSA have been found in females RECOVERING from breast cancers. [J Nat'l Cancer Inst Oct 6, 1999, Fortier, AH et al] Surprise, surprise, the ladies that made the best recoveries were the ones with the highest PSA levels!!
4. PSA appears to be an anti-angiogenic molecule. For those of you unfamiliar with the term, one of the features of cancer is that it has an enormous appetite and therefore needs a huge blood supply to feed it, so wherever you see cancer growing, you will see angio-genesis taking place – the creation of new vascular tissue. [That's why shark cartilage became popular.]
5. PSA appears to inhibit the usual increases in circulation necessary to feed the cancer and to support its rapid growth and proliferation.
6. Nicholas Gonzalez MD of NYC reports patients who have shown PSA levels of a hundred or more for long periods of time who are doing just fine as they recover from their cancers - he opines that increased PSA levels indicates a GOOD response by the body, NOT a BAD response. [audio tapes 12 and 17 spring 1999 lecture, ACAM – see ordering info below]. Dr Gonzalez uses the nutritional protocol that he learned from his teacher, the orthodontist and scientist, Dr William Donald Kelley of Grapevine, Texas, who is one of my three nominees for the Nobel prize in medicine [along with George J Goodheart DC and James Pershing Isaacs MD]. Gonzalez also reports a properly recovering cancer patient with a CEA of 350,000, the highest in medical history. See the article on the site on the AMAS test to learn about the CEA which is another cancer marker. When a tumor breaks down it dumps all the CEA into the blood stream. BE CAREFUL ABOUT WHAT YOU THINK ABOUT BLOOD TEST LEVELS AND TUMOR SIZES, MORE IS OFTEN NOT WORSE, AND BIGGER, ESPECIALLY, IS OFTEN NOT WORSE than smaller!!! Some tumors tend to encapsulate and get bigger not smaller!!
7. So giving a toxic drug for a "specific" antigen which is not at all "specific" is just one more in a long line of examples of medical quackery being propagated by present establishment sources. It’s sort of like giving a deadly drug for a non infectious, non transmissible disease [AIDS] allegedly caused by an unproved virus [HIV]. It can also be compared to injecting newborn babies with foreign proteins and heavy metal poisons to “protect” them from adult diseases in dope addicts. Note that I use the old familiar term for these human wastrels – “dope addicts” rather than “substance abusers” – dope addict is more apropos. Sort of like calling a bum a bum, rather than a homeless person. Using the euphemism “homeless person” might make you feel better but hey, life is not fair, some people are bums. Face it. Others are criminals. Face it. Not facing it results in what we’re discussing here. Highly educated people committing crimes against humanity and getting away with it largely because our language is politically correct. If we were in the habit of calling bums what they are, and dope addicts what they are, we might not find it so difficult to call an MD a quack and a criminal and begin to take steps to put them where they belong, behind bars, not out on the street preying on the innocent and the ignorant.
highly educated, brilliant doctor, Thomas Stamey published the original study on
PSA in the
The activities of Dr Stamey raise several questions:
1. Do you think that Dr Stamey should be held accountable for those unnecessary surgeries?
2. What do you think would happen to the tobacco industry executives or the auto industry executives or the toy industry executives if they were caught killing, maiming or harming so many people – especially innocent children like those suffering from quack vaccine induced disabilities and death?
3. Do you
think the deaths of prostate cancer patients resulting from misdiagnosis and
maltreatment became part of the statistics used to place the practice of
orthodox medicine in third place on the list of causes of unnecessary deaths in
4. Are you beginning to get the right idea about the dreadful effects orthodox medicine in the 21st century?
I'll say it
once again, CONSENSUS-DRIVEN, ORTHODOX MEDICINE IS CRIMINAL BEHAVIOR, IT IS BAD
FOR YOUR HEALTH AND IT IS THE ROOT SOURCE OF ALL OF THE MEDICAL QUACKERY
OF THE 21st CENTURY. It is also the greatest threat to life and limb and health
in all recorded history. Do you REALLY think that orthodox medicine is only
number three in the cause of deaths in the
And we want to trust these people and accept what they have to say about VACCINES??? We want to trust these consensus driven quacks to inject our neonates with poisons? We want to accept the dribble and gobbledook nonsense they continue to propagate about vaccines, phantom diseases, phantom viruses, and now…prions???
CRISIS MEDICINE, ON THE OTHER HAND, IS A BLESSING TO HUMANITY - IT WILL SAVE YOUR LIFE IN AN EMERGENCY, RESCUE YOU FROM CONGENITALLY INFLICTED PROBLEMS, AND SPARE YOU MOST OF THE UNNECESSARY PAIN AND SUFFERING FROM TRAUMA AND ACCIDENTS – don’t confuse one with the other, don’t throw the baby out with the bath water.
PASS THIS ON TO AS MANY PEOPLE AS POSSIBLE, ESPECIALLY YOUR LEGISLATORS.
ORDER THE GONZALEZ AUDIO TAPES FROM:
Professional Audio Recording
Gonzalez's talks are available from the ACAM
THE ENZYME TREATMENT OF CANCER
AND ITS SCIENTIFIC BASIS
BEING COLLECTED PAPERS DEALING WITH THE ORIGIN, NATURE, AND SCIENTIFIC TREATMENT OF THE NATURAL PHENOMENON KNOWN AS MALIGNANT DISEASE.
JOHN BEARD, D.Sc.
“When, from a correct General Principle, one develops the conclusions in special cases of its application, new surprises, for which one was not previously prepared, always make their appearance. And, since the conclusions unfold, not according to the author’s caprice, but after their own laws, it has often made the impression upon me that really it was not my own work which I wrote down, but merely the work of another.
Hermann Von Helmholtz
CHATTO & WINDUS
“Man,” writes the learned and genial Carl Ernst von Baer, “considers himself just as necessarily in the centre of his mental horizon as of his mathematical one.” When, in the closing hours of the last day of the nineteenth century, I wrote this citation in the original German, as the opening words of the preface of the first of a series of memoirs upon the history of the germ-cells, I little reckoned that the controversy regarding their story, which was the final link in the general principle of an antithetic alternation of generations, would be carried on around the side-issue—the special case in von Helmholtz’s sense—of the origin, nature, and scientific treatment of cancer. All. Of these are concerns of embryology, for they are problems of reproduction, growth, and there stereo-chemical processes of life. In the discussion of a similar problem of embryology—that of parthenogenesis (pFdogenesis) or virgin reproduction in fly-maggots (Ceidomya) –von Baer used the above words. His account of this discovery of Wagner’s has its special interest in connection with the present work.
Carl Ernst von Baer writes: * “that at first the dis-
*Baer, Carl Ernst von: “Über Prof. Nic. Wagner’s Entdeckung von Larven, die sich fortpflanzen, Herrn Ganin’s verwandte und engänzende Beobachtungen und über die Paedogenesis überhaupt,” in Mélanges Biologiques, v., 1865, pp. 203-308; loc. cit., pp 241-243.
covery appears to be received with doubt” –that even the well-known worker on the parthenogenesis of bees, von Siebold, expressly said that it appeared to him to be incredible—“only shows how unexpected it was and how little one was prepared for it. It is thus a testimony of its importance, and, so to speak, a compliment for it. I should like to recall an expression of Wilhelm von Humboldt’s who, when someone criticized one of his earlier philological works adversely, in a reply expressed himself somewhat as follows: ‘A book which immediately on its first appearance finds general approval really does not deserve to be printed at all, for it contains only that which in the convictions of all is completely accepted, or at lease for which they were entirely prepared.’ That is very true, for the really new, when it is far-reaching and thorough, can only gradually find an entrance, because numerous convictions must be altered in order to make its proper place for the new-comer. That the corals were inhabited by animals was first discovered by the naval surgeon Peyssonel, in the years 1723-1725, and it was no less a man than the great Réaumur who rejected the discovery as an absurdity in 1727, when Peyssonel had communicated his finds to him. These researches had been carried on for several years, and they were indeed numerous and careful, for Peyssonel says: ‘In the tubes of Tubipora there sit animals, what one believes to be flowers in the noble corals’” (Corallium rubrum, the red coral of commerce) “ ‘are also animals; for they occur at all seasons of the year, they retract themselves when they are touched, and when one lifts the corals out of water, in the Madreporarian corals the animals resemble the sea-anemones; the skeleton of the coral on decomposing gives off an animals odour, and even the chemical investigation proves the presence of animal substances.’
All these grounds Réaumur mentions, but concludes that the corals are plants which excrete a stony substance, and that if one sees animals in them these must be parasites which have wandered into them. He finds it quite out of question , as one sees, to imagine the existence of branched animals. Out of consid-eration for the individual, he does not mention the name of him who had asserted such remarkable things, In this way Peyssonel remained quite unknown and unrecognized. But when, later on, Trembley made known his observations on the fresh-water polypes, and in the buds of these one had before his eyes a branched, animal, Réaumur asked the botanist, Bernard de Jussieu, who was going to the seaside, to examine what connection this had with the corals. When, then, De Jussieu expressed himself in favour of their animal nature, Réaumur at last believed it himself, and withdrew his former judgment. Peyssonel, who learnt in the West Indies that Réaumur had not published the memoir sent to him, but that later on the correctness of his discovery had been recognized, in 1751 sent a new memoir, not to Paris, but to London, where in appeared in 1753 in the Philosophical Transactions. Thus, thirty years passed before he succeeded in publishing his discovery, and five years more before, by the publication of the tenth edition of Linnæus’s “Systema Naturæ’ (1758), it gained general acceptance. How many and angry writings did there not appear against Harvey’s account of the circulation of the blood, because it was not known what to do with the air or the spirits (Archæi) which were supposed to reside in the arteries, and when Harvey died, twenty years after the publication of his discovery, it had not yet become generally accepted. Much longer still was it before the discovery of Copernicus found general acceptance, and
the earth had to describe its path round the sun many times before the Holy Chair allowed it to be spoken of publicly.”
At that time, in view of the history of science, it was quite anticipated, that the new facts concerning the history and continuity of the germ-cells from generation to generation would obtain a hostile welcome and reception, and that their discoverer would undoubtedly win a reward for all his patient labours similar to the recompenses meted out in past times to all those pioneers, termed by Robert Browning, “God’s elect,” from Khalif Al-Mamun, who dared to measure the earth and to describe it as a globe, down to Pasteur, who in our own day, among other brilliant deeds, caused “chemistry to take possession of medicine” (Duclaux). But the anathema did not come then; it was reserved for another occasion, and one of far greater import for human welfare and hopes. On the one hand, some of the germ-cell finds could be annexed—apparently—by others; on the other, they seemed to fit in so well with Weismann’s conceptions of a hypothetical germ-plasm – a thing non-existent—that to many it appeared possible to incorporate them with the doctrines of this distinguished zoologist. To another, again, they looked like furnishing in fact a confirmation of the vague speculations of Richard Owen, and this has led to the assignment of the actual work and discoveries to him, who actually never did any investigations at all into the history of the germ-cells. In fine, in one way or another, the germ-cell finds wee disposed of and dispersed. Some of them—some of the more fundamental points—were cast aside and ignored; others, the more obvious, were annexed or parcelled out, and ascribed to this, that, or the other embryologist or zoologist, and practically nothing at all was left over to
the credit of the original
observer, who, indeed, ought to have congratulated himself on the –for his
welfare—fortunate turn of events. All this has reference to
Then came the time, the “divisions” and “brigades” being complete and ready, and eager to take the field, when the general principle of an antithetic alternation of generations, with an actual tangible continuity of germ-cells from generation to generation, had to be applied to the special case of cancer or malignant disease. Since it has long been one of my maxims in research to reap and garner the harvest completely, leaving as little gleanings as possible for others, this application of the general principle could not be left undone. Cancer stood defiantly in the way, and an immediate decisive campaign against it was inevitable.
New conclusions were
reached, one after the other, and in due course these were published. Mankind in
general , and medical mankind in particular, wee supposed to be waiting the
advent of some new scientific discovery concerning the nature of cancer, in the
hope that this would lead ultimately to success in its non-operative medical
treatment. The reception give to the new conclusions in
Two of the discoveries referred to by von Baer—those of Copernicus and Harvey—had this feature in common:
that, at the time they were published, it was not, and could not be, foreseen that they possessed intrinsic vital importance for mankind. None the less, they were denounced, and their authors along with them. Did the histories of the discoveries of Morton, Simpson, Semmelweis, Lister, and—last and greatest—Pasteur not prove the contrary, one might have concluded that the main reasons for the opposition to, and the denouncement of, Copernicus and Harvey, for example, were that these discoveries had no apparent bearing on the physical welfare of humanity. If so, mankind would welcome eagerly any discoveries relating to the scientific nature and treatment of cancer, even though, as an old and very wise friend re-marks, they were made by a chimney-sweep.
Actual experiences have not tallied with these anticipations. Whether it would have been otherwise had the discoveries been made and published twenty-five or thirty years earlier –for instance, in my student days, or at the time when the late Sir James Paget concluded (1887), that operative interference with can-cer was not advisable, --is a moot question. In the light of actual events, since the scientific man especially learns from experience, I have surmised, perhaps rightly, that all these denunciations of scientific discoveries and of their authors –the latter including among many other Khalif Al-Mamun, Servetus, Coperniucus, Giordana Bruno, Galileo, Vesalius,*
* “In the same year (1543, when appeared the treatise of Copernicus on the ‘Revolutions of the Heavenly Bodies’), Vesalius, a young Belgian anatomist, published his “Structure of the Human Body,’ a volume rich in facts ascertained by dis-section. Some of these facts were held to contradict the teaching of Galen. Next year Vesalius was driven by the hostility of the medical profession to burn his manuscripts and relinquish original work; he was not yet thirty years of age” (L. C. Miall, ‘History of Biology,’ 1911, p. 20).
De Dominis, Harvey, Buffon, Morton, Simpson, Semmelweis, Lister, and Pasteur, etc.—have been due, not so much to religious motives and the odium theologicum, as to the innate constitution of human nature and its intolerance of the new and the strange, even though this be calculated to be of surpassing benefit to humanity.
As to the particular instance dealt with in this book I have nothing at all to retract—even at the stake—concerning my scientific conclusions as to the origin, nature, and rational treatment of the natural phenomenon known as cancer or malignant disease. The words of Galileo, Eppur si muove, were a definite enough statement on his position. Pasteur told his opponents that he lived in a realm of which they knew nothing and into which they had no entry. These words of his also I adopt. Cancer is a natural phenomenon, germinal in origin and asexual (trophoblastic) in nature, and it is one which, by the laws of Nature, must yield to the magic influences of the all-powerful ferments, trypsin and amylopsin. Of these, trypsin has been described—rightly—by a scientific man, Dr. Emil Westergaard, as far “more powerful than dynamite.”
Those who think differently, or think they think differently, or who don’t think at all, and who without adducing any but negative finds without value in science, persist in denying the scientific research nugatory, all scientific evidences in utter disregard of truth itself, are endeavouring, possibly without even knowing it, to render all scientific research nugatory, all scientific progress an impossibility. The logical sequel to all such futile and vain opposition to scientific truth and progress would be, not the creation and lavish endowment of institutes for cancer research, but the foundation of societies for the prevention of cruelty to cancer.
No apology is offered for the very frequent use of the
term “science” and its variations in the present writing. The writer is actuated solely by his deep reverence for the truths of Nature: her facts and truths are to him everything, and human “authority” nothing. Neither praise nor blame, nor even abuse nor ridicule, is asked for, sought after, or desired. The actual discoveries entailed in the finding out of Nature’s remedies for malignant disease possibly are, be it admitted, trifling; perhaps, too, they deserve no human praise, much less do they call for ridicule. The long years spent in daily and nightly labours in the search after the general principle of an antithetic alternation of generations as the basis of the life-cycle of all the higher animals, including man, were something different, and the results were their own and only reward. Why the publication of true facts of Nature—such as are recorded in this book—should earn for their author the recompense of ridicule I know not. Baseless assertions—such as that “trypsin” is without action upon living cancer-cells—are not evidences, and in no civilized court of justice would they be admitted as such. One thing is now clear, and the whole world may be challenged to contradict it: this is, that if it be asserted—as it has been more than once publicly by British official researchers—that trypsin is devoid of action upon living cancer-cells, then this same “trypsin” would also be found by an physiological chemist to be destitute of action upon all other albuminous substances in this universe. A “trypsin” devoid of action upon cancer-cells can also have no action at all upon milk, and yet it is mainly by its action upon milk that trypsin is usually estimated by chemists and by manufacturers of ferment preparations. Since a strong solution of trypsin, when injected daily hypodermically, has been known to liquefy a large living recurrent epithelioma or skin-cancer in less
than fourteen days, it follows, that those who assert, that “trypsin” is devoid of action upon living cancer-cells, might state with equal truth, that the “trypsin” they used had also no action at all upon anything else-
that is, was quite inert.
Looking back over the history of the ferment, trypsin, in science, though really discovered, but not named, by Baron Corvisart in 1857, it was for some ten years in danger of being forgotten. Then, in 1867, Professor W. Kühne took it up for research purposes, and in 1876 he gave it the name it bears of “trypsin,” from TpúXw, “I wear away.” That is, it took Kühne nine years to establish this ferment securely as a possession of science. Why should I expect to be more fortunate than he? If nine years were required to set at rest the question of the mere actual existence of such a ferment as trypsin, it is perhaps quite out of question to say how many times the earth will have to describe its path round the sun -–n conformity with the doctrine of Coperniucus—before mankind will admit the truth of my discoveries concerning Nature’s uses of trypsin and its complement, amylopsin. It may be that they, including many surgeons, would rather themselves die of cancer than admit the truth. Like the other happenings in the history of the reception of my cancer studies, this would not be at all a new attitude, for, according to Brewster, “a protégé of Kepler’s, of the name of Horky, wrote a volume against Galileo’s discovery” of the satellites of Jupiter, “after having declared ‘that he would never concede his four new planets to that Italian from Padua, even if he should die for it.’” But sooner or later, if not now –possibly in the far-off future, when the inertia of the past two thousand years shall have ceased to be, and a new advance of the human intellect shall commence –it will be recognized
that, while the ferments of cancer came into existence in the dim and distant past in an ascending series of complexity, for the purpose of building-up asexual generation, trypsin and its modification, amylopsin, were evolved millions of years ago as things even more powerful than the ferments of cancer, and for the primary purpose of pulling down asexual generation, in order that something new –a sexual generation—might arise, blossom, and people the earth. That these latter ferments have also a very great digestive import, and are, therefore –to man, as the centre of the universe—of personal and even great commercial value, happens to be a corallary to what was their original use, and to the uses which they are still first of all given by Nature in every normal development.
Each one of us human beings, in the course of the gestation in which he or she arose, as a prime condition of his or her existence and persistence, was compelled by the iron necessity of Nature to destroy a natural phenomenon of the same nature as cancer –to wit, the trophoblast or asexual generation of normal development—and by no other means than the secretion of pancreatic ferments. This is the reason which confers a lasting truth on the words which I wrote down on December 8, 1904, and which, almost immediately, gave the solution of the problem of cancer—“The mammalian embryo solved the problem of cancer ages ago.” “Still it moves,” commented Galileo. If the enzyme treatment of cancer be abandoned for the next century—if trypsin and amylopsin be maligned as “useless” or “futile” in cancer—all the same every human being who comes into this world in that time will never omit to employ his own pancreatic ferments in his development—never fail, since failure means death, to the pancreatic or enzyme
treatment of cancer in his own gestation—for the suppression of normal trophoblast or asexual generation. For otherwise this, as the most deadly form of cancer known—chiro-epithelioma—would inevitably destroy him—and his parent. In normal development, trypsin and amylopsin, unheeding human medical and surgical perversity, intolerance, and ignorance, will continue to destroy cancer, or trophoblast, or asexual generation, as in the past has happened for untold millions of years, for long ages before man was evolved.
For this is one of Nature’s fundamental postulates, one of her inexorable laws for the continued existence of a race of human beings to people the earth, and without its strict and unbending observance there would be no living human beings upon the earth, no surgeons, no “cancer experts,” loudly parading and proclaiming publicly their ignorance of the origin and nature of cancer, and –no problems of cancer.
* * * * *
It is a pleasant duty to put on record here how much in recent years the
writer owes to the help of Messrs. Fairchild Brothers and Foster, of
no man on earth could have a greater satisfaction than he in seeing this enzyme treatment succeed.
Of the portions of the
book which have been published previously,
8, Barnton Terrace,
THE PROBLEMS OF CANCER
I. EMBRYOLOGICAL ASPECTS AND ETIOLOGY OF CARCINOMA 48
II. THE EMBRYOLOGY AND ETIOLOGY OF TUMOURS 67
III. THE PROBLEMS OF CANCER 95
IV. THE CANCER PROBLEM 108
V. THE INTERLUDE OF CANCER 122
VI. THE ASYMMETRY OF THE CYCLE OF LIFE, BEING “THE END OF THE THREAD” 143
THE PANCREATIC OR ENZYME TREAT OF CANCER
VII. GENERAL DIRECTIONS FOR THE PANCREATIC OR ENZYME TREATMENT OF CANCER
IN ITS VARIOUS FORMS 188
VIII. TWO RECENT CASES 209
IX. ON THE RELATIONS OF TRYPSIN AND AMYLOPSIN 223
X. A PUBLISHED TEST OF “THE TRYPSIN TREATMENT OF CANCER” 230
XI. THE CRUCIAL TEST OF THE NATURE OF CANCER 235
XII. “SCIENCE IS PREVISION” 243
APPENDIX A :
APPENDIX B: PICK: IN THE “DISCUSSION ZU DEN VORTRÄGEN ÜBER DIE ÆTIOGIE DES CARCINOMS,”
IN “BERLINER KLIN. WORCHENSCHRIFT,” 1905, NO. 13. ABSTRACT OF THE REMARKS
CONTRIBUTED BY THE PATHOLOGIST DR. L. PICK TO THE DISCUSSION ON THE
ETIOLOGY OF CANCER, IN
APPENDIX C: THE LIFE-CYCLE OF THE HIGHER ANIMALS AND ALTERNATION OF GENERATIONS 255
APPENDIX D: THE NAPELS CASE OF EPITHELIOMA OF THE TONGUE 265
APPENDIX E: THE FUNCTION OF THE CORPUS LETEUM 267
APPENDIX F: THE TREATMENT OF TUBERCULOSIS IN SANATORIA 271
APPENDIX G: SOME OF THE SUCESSFUL CASES REPORTED IN PAST YEARS, ALL OF WHICH WERE TREATED
WITH GENUINE PREPARATIONS OF TRYPSIN AND AMYLOPSIN 273
APPENDIX H: NEGATIVE RESULTS IN SCIENCE 277
APPENDIX K: SCIENTIFIC PRIORITY 279
APPENDIX L: “ENCEPHALOID” CANCER OF THE BREAST 280
APPENDIX M: THE GERMAN PREPARATIONS 281
FIGS. FACING PAGE
I-4. ILLUSTRATING THE GERM-CELLS OF FISHES AND THEIR MIGRATIONS INTO THE EMBRYONIC
5. DIAGRAM OF THE LIFE-CYCLE OF A BACK-BONED ANIMAL 124
AFTER FOUR MONTHS’ TREATMENT,
SHOWING NECROTIC TUMOR IN SITU.
7. AFTER REMOVAL OF DEAD TUMOUR EN MASSE. TUMOUR LIFTED OUT WITH DISSECTING
FORCEPS WITHOUT BLEEDING OR OOZING.
NO TUMOUR LEFT: PARTS HEALED
IN FIG. 6) HAD BEEN LIFTED OUT OF THE CHEEK WITH FORCEPS 210
10. PHOTOGRAPH OF THE SLIDE OF THE TUMOUR WHICH WAS PREPARED BY A PATHOLOGIST
CAPTAIN LAMBELLE, HAS BEEN ERASED 212
11. MICRO-PHOTOGRAPH OF A PORTION OF THE SLIDE OF FIG. 10. PREPARED BY MR. A.
ENZYME TREATMENT OF CANCER
AND ITS SCIENTIFIC BASIS
Some years ago a former fellow-student—M.D. (Lond.), Fellow of the Royal College of Physicians, London, physician to a large hospital in London – remarked that a single case of cure of undoubted cancer would establish the truth of the writer’s published statements, and bring the whole world to his feet. Not long after then, here and there cures were published; but to these I will not refer; for, unlike those of the York case, the scientific proofs of them are not in my possession, and in one way or another it may be said of many of them, that the evidences in their favour were incomplete or inconclusive, which latter was, indeed, the verdict pronounced, without adducing scientific evidences, upon “trypsin” by Sir Henry Morris, Bart., late President of the Royal College of Surgeons, London, as recently as 1908. To a profession such as the medical one, which does not yet grasp the nature of the scientific evidences, the results of the pancreatic or enzyme treatment, even in the most favourable cases, might easily have been taken to be “inconclusive.” The scientific facts that certain tumours had yielded to the stereo-chemical test—the highest court of appeal—and thereby had shown their malignant
nature, were not evidences to those, who knew nothing at all of modern embryology or of stereo-chemistry, and who relied implicitly upon the microscopical examination and appearances of a portion of the growth taken before or after operation. Then there were the countless failures,* many of them due, as I am now convinced, to faulty preparations, or to injections which were very much too weak for their work. In this way great difficulties had to be surmounted, quite apart from what has been termed the “conservatism” of the medical profession. Apart from the latter, these difficulties seem now to have been removed. Definite statements can be made concerning the requirements of really efficacious preparations for the treatment, and a successful case of cure, not standing isolated, can be, and is, produced in the present writing.
*For the sake of the scientific truth, the published opinion of Professor
F. Blumenthal, of the
the eighth section of “The Belfast Address” the physicist, Professor John
Tyndall, wrote: “But there is in
the true man of science a desire stronger than the wish to have his beliefs
upheld—namely, the desire to have them true. And this stronger wish causes him to
reject the most plausible support if he has reason to suspect that it is
vitiated by error.” That is the
writer’s position to-day. Six years
ago he stated publicly that, in the secretion of that important digestive gland,
the pancreas, Nature had furnished a potent means of coping with cancer. Even though there had been no other
successes at the hands of Captain Lambelle, R.A.M.C. or of other, the successful
issue of the case of the
A surgeon, who published as
a “scientific report” an account of the failure of the enzyme treatment at his
hands in a large series of (mostly very advanced) cases, remarked to the writer
not long ago that a single case of success would not prove his thesis. The exact opposite of this assertion has
been maintained quite recently by the Moseley Professor Surgery in
*”Encephaloid cancer,” a term used by pathologists to define soft cancer from hard cancer, or scirrhus. Encephaloid cancer is so termed because of its brain-like softness. It is described as quick-growing and rapidly fatal (see Appendix L).
1910, he writes concerning this case: “By the way, that case of encephaloid breast cancer is alive and free from recurrence—diagnosed October, 1908. I saw her on November 29, as near as mortal man can say ‘cured.’” Further comment on the above is not needed.
I was well aware, as any scientific man is, that negative results in
scientific experiments never proved anything at all in science, but was also
under the impression that very many scientific discoveries of great moment had
been the outcome of single successful experiments. The fall of an apple from a tree
revealed the law of universal gravitation to
*Looking at the matter from the point of view of practical embryology, the so-called “cures” of cancer by surgical operation are probably in all cases without exception examples of the “cure” of a benign tumour, a more or less reduced “embryoma.” Naturally benign tumours are of common occurrence, and whether diagnosed by microscopical examination or only clinically , the diagnosis of cancer is not one which can be regarded as conforming to a scientific criterion. When one thinks of the extraordinary frequency of recurrence after surgical operation, one can only conclude that, in the absence of the crucial stereo-chemical tests, either of adequate injections of sufficiently potent preparations of trypsin and amylopsin, or of examination of the tumour albumins by means of the polarimeter, at present there is no valid evidence extant that operation has ever cured a single case of malignant disease, though it may quite well have induced it, as the X rays have often done. Sir James Paget. A scientific
surgical operation are not in blocks of certain dimension; but assuming that surgery ever does cure even a single case of cancer—a very big assumption which, as a scientific man, I make only for the sake of argument—each case of cure would be of the nature of a single successful experiment. I do not for a moment deny that surgery does, and has done, many very wonderful thing, but to assert that it ever knowingly cures a single case of cancer is a scientific absurdity.
(continued from page 5 footnotes)
man of high standing because of the extent and nature of his investigations, doubted whether operation was ever advisable in case of cancer, and on the evening of my Liverpool lecture of 1905, I heard a prominent surgeon declare that he would not be willing, even in the most favourable case of cancer in which he had operated, to stake a sovereign against its recurrence.
It behooves me to add a few words of explanation of Captain Lambelle’s
connection with the work. In his
address, “Science and Immortality” (London, 1904), Sir William Osler, in the
finest written compliment any of my researches had ever received, described
(p.58) “the patiently worked-out story of the morphological continuity of the
germ-plasm” (i.e., the germ-cells) as
“one of the fairy-tales of science.”
Shortly after then their author was to have an unexpected and much
greater compliment, because of a practical kind, paid to these
investigations. As a scientific man
the writer places his trust, in true military fashion, in “divisions” and
“brigades,” represented by the published records of observation and experiment,
and not in “fairy-tales of science.”
The investigation, one of the most powerful of my “divisions,” which
immediately preceded the cancer work was into the history of the germ-cells, the
forerunners of eggs and sperms, from generation to generation. Some of the published results of these
researches found their way as far as
In the first instance these failed, as any experienced practical
embryologist would have foretold.
This officer, Captain F. W. Lambelle, M.D., was shortly afterwards
ordered home again, and, on reporting himself to the Director-General at the War
Office, he related the foregoing facts and his deep interest in my scientific
researches. This led the
Director-General to station Captain Lambelle with the 2nd Light
Dragoons (The Royal Scots Greys), at that time in garrison in
announced, Captain Lambelle entered my little room in full uniform, and saluting, introduced himself, we have been close friends. He worked for himself over much my material—a collection also, like the Scots Greys, “Second to None!”—and he read all my published papers, which, unlike some scientific people, he thoroughly understood and appreciated; in fact, he evinced the deepest interest in all the problems and their solutions which had occupied my leisure hours during many years. At that time I happened to be, noiens velens, in the thick on the cancer-business, and he often expressed his regrets that the nature of his work, with young healthy soldiers, gave him no chances of looking into cancer-matters practically for himself. Subsequently, his appointment as operating surgeon of the Military Hospital, York—the hospital of the Northern Command—placed, one after the other, four cases of cancer in his way, and of these he cured three, the fourth dying from hæmorrhage as the treated dead sloughing tumour came away. One of these cases fully recorded in this book. The other two successful cases are not laid stress upon by him, simply because, although the clinical diagnoses of cancer were ample, the microscopical evidences, upon which scientifically I personally lay no stres at all, were lacking.* In order to say the surgeons who have set up this arbitrary stand of the microscopical appearances of cancer as a criterior—often a very deceptive one—the requisite slides of sections of the tumour have to be produced as completing the surgical diagnosis.
In his last letter to me before sailing to
*Compare Professor Richardson’s opinion as cited on p. 4.
amount to more than 60,000
tryptic units and 120,000 amylolytic ones.
That is to say, for his last published case the strengths and doses of
injections employed during the vital period of the treatment can be stated. This can be said also only of the report
of Messrs. Ball and Thomas. Dr.
Bainbridge, according to his own statement, used injections of five strengths of
trypsin, but in his report he does not discriminate among these, or give
figures, from which even approximate calculations, or any at all; can be
made. All of those in this country,
or elsewhere, who, publicly or privately, have condemned the treatment, with the
single exception mentioned above, whatever its scientific value, have furnished
no particulars of strengths or doses and of the total number of injections
exhibited; in fact, not one of them has given a scientific verdict, for not one
of them has produced any evidences that he ever employed any ferments
whatever. In 1906 and 1907 the
statement was often made by several very prominent
*The first injections of “trypsin” employed in 1906 were all, or nearly all, made up from Fairchild Brothers and Foster’s “trypsin in powder.” This, which is no longer on sale anywhere, was a very potent preparation, and it had been on the market for many years. At the beginning of April, 1906, the manufacturers of this “trypsin in powder,” as they announced by advertisements in the chief British medical and chemical newspapers, withdrew it from sale. Tis step placed others makers of “trypsin injections” upon their own resources, or very largely so. There was already a “famine in the land” as regards “trypsin,” so much of one that I heard through friends of several cancer patients who were being treated with raw sweetbreads,
compared with Captain Lambelle’s usual dose of one thousand (1,000) tryptic units plus two thousand (2,000) amylolytic units, 1 ampoule or 1 c.c. of each.
(continued from page 9 footnotes)
glands. I have always considered
the withdrawal of this “trypsin in powder” as a very wise step, but one of its
direct consequences would appear to have been the extensive employment,
especially in and about
assertion shall be made without at the same time the production of the evidences for it.
Of course, “trypsin” is not a cure for cancer, a fact stated by the writer in Nature four years ago. The evidences for this, it may be added, are forthcoming in abundance whenever asked for. What has destroyed cancer without injury to the patient in cases not too far advanced, and what will do the like again and again, is the use of properly prepared injections of trypsin of a strength of at least a thousand Roberts tryptic units of activity plus equal amounts of amylopsin of two thousand to two thousand four hundred (2,000 to 2,400) Roberts amylolytic units of strength per cubic centimetre, and the doses of injections and their frequency must be adapted to the needs of the particular case under treatment.
As “failure is easier of attainment than success in anything,” it would be possible to the end of time for some surgeon, or official cancer researcher, to declare that trypsin and amylopsin were “useless,” or “futile,” in the particular cases treated by him, and used as he employed them. Scientifically, all such verdicts are worthless, unless the evidences for them be produced in full; and these must include the previous history of the case, the duration of the treatment, the preparations used, definite statements as to their purity, all necessary details as to their quantitative values, their doses, and the number of these. Science, as a mistress, makes exacting demands upon the observer, and the mere designation of a document as a “scientific report” does not alone confer any scientific value upon its contents.
The view generally accepted by mankind, even by all medical men, has long been that cancer is “an incurable disease.” How often have I not heard this expression, even from very prominent surgeons! Not only was
cancer incurable, but it was
a disease of the nature and origin of which the whole of the medical profession,
by its own confession, often proclaimed by leading surgeons in public orations,
knew nothing at all about. Under
such circumstances it could hardly be strange that it should not be in
conformity with the generally accepted, when a scientific man, who knew very
well what he was speaking about, and who, like Pasteur, had earned the right to
an opinion by his investigations of many long year, announced that cancer was
not a disease, but a natural phenomenon, that it was germinal in origin and
asexual (trophoblastic) in nature.
This was all something new, which had never been said before by anyone,
living or dead. As at the present
time we were supposed, but possibly erroneously, to have outlived the Dark Ages,
and as, at all events, those who made me, the scientific Germans, who have
advanced far beyond the Dark Ages, had long advocated and practised “the freedom
of science in the modern state,” it was something to be examined
scientifically. It is interesting
to see how this was realized in
A recent part of the German Journal of Cancer Investigation (vol. x., part 1) contains the report of a special Cancer Congress, held in May, 1910. Here Professor C. Neuber, well known for his researches into the chemistry of cancer, writes on p. 70 regarding the position of chemistry in cancer research in words which recall Duclaux’s declaration concerning chemistry and medicine. Neuberg affirms that where the problems of the nature of tumours are in question, chemistry will never retreat from the field of conflict. Duclaux said: “With Pasteur chemistry took possession of medicine. It is easy to foresee that she will never loosen her hold upon it."” As a study of
the following pages will show, my fundamental discoveries of the nature of cancer, and of the places of the two all-powerful ferments, trypsin and amylopsin, in the treatment of this natural phenomenon, not disease, were founded in the first instance in the science of embryology. This is as true for the separate reasons advanced for the employment of trypsin and of amylopsin as it is for those urged in 1902 as demonstrating the asexual (trophoblastic) nature of cancer.* Afterwards, from 1906, the chemical evidences—the stereo-chemical ones—began to reveal themselves to the observer, who was not like that genius Pasteur, “a mere chemist,” but a practical embryologist, who had chanced to have some sort of elementary chemical education at the hands of Sir Henry Roscoe and of that pioneer of comparative physiological chemistry, the late Professor C. F. W.
*Sexual and Asexual, Sexual Generation and Asexual Generation.—In animals and in plants two modes of reproduction are recognized, the sexual one, by means of germ-cells, eggs, and sperms, and the asexual by budding, which is really a process of continuous indefinite cell-division, with no eggs or sperms. In an animal or plant a sexual generation is one which bears reproductive organs, in which eggs or sperms, or both, arise. On the other hand, an asexual generation of an animal or plant is one which never bears reproductive organs, eggs or sperms, or both, but which reproduces in the way indicated above, really by cell-division. In plants the asexual generation is the flowering plant, which is capable of indefinite unrestricted increase, as, for example, a Gloire de Dijon rose or the fine white chrysanthemum, Niveus. Origianlly there was but one plant of each of these. The sexual generation of a flowering plant is a small microscopic entity contained with the flower. In animals all the individuals which bear sexual organs belong to the sexual generation, which the asexual generation are represented in various ways. Thus, in the sea-ploypes, by the colony of polypes, while here the medusæ or “jelly-fish” are sexual; in worms, starfish, etc., but what are known as larvæ, while here the wor, starfish, etc., are sexual; and lastly, in the highest animals or mammals the asexual generation is present only during uterine life, as what Hubrecht termed the trophoblast. This latter used to be regarded as one of the “fœtal membranes” under the name of chorion.
Krukenberg. Thus it came about that, while the line of first advance was purely embryological, later a junction could be effected with the science of stereo-chemistry, and a further base for operations obtained in the fundamental discoveries of Pasteur on the asymmetry of naturally occurring organic compounds.
The following remarks* (literally translated), by Professor F.
* Blumenthal, F., “Innere Behandlung und Fürsorge bei Krebskranken,” in Zeitschr. F. Krebsforschung, 1910, vol. X., pp. 137-138.
† It would appear not to have occurred to Professor Blumenthal that this statement might have reference to inert ferments. Since the experiments, which must be supposed to have led to this erroneous conclusion, have never yet been published, and since they are, indeed, not mentioned in a single word in the Third Scientific Report of the Imperial Cancer Research Fund, published in 1908, and, lastly, since there are no scientific or other evidences extant to show that ferments of any kind or sort had ever been employed in these unpublished experiments, I feel bound to ask Professor Blumenthal to explain, as a scientific man, why he cites these unpublished experiments, and non-existent evidences? It is common enough to note in scientific publications that published experiments or evidences have been ignored by the author, but it is something quite new to find unpublished experiments and mythical evidences cited in a
trypsin I have also noticed a disagreeable complication, which consists in this, that often the digestive power of the trypsin passed over also to sound tissue, and a disagreeable destruction of this came to pass. Recently Sticker and Falk have improved the trypsin-therapy in that they have united the action to trypsin to charcoal, by which means, after a single injection, this action persists much longer, since this carbenzyme is not so quickly used up as ordinary trypsin.”
(continued from page 14 footnotes)
paper. Moreover, as Professor
Blumenthal is quite aware, the results of his own experiments with “tryspin” are
in direct contradiction with the verdict pronounced, without the production of
any evidences, by officials of this cancer research. It reminds one of the reception
accorded to von Siebold’s discovery
of two sorts of spermatozoa in a fresh-water diœcious snail, Paludina vivipara, in 1836. Within an easy walk of Würzburg, this
snail is readily found in great numbers, and the first time that these two sorts
of sperms were seen by me was in 1882, in living material obtained not far from
Würzburg. None the less, when von
Siebold published his find, the professor of Anatomy in the
ultimately, if used in
solutions of sufficient strength, liquefies them, as maintained by myself,
Blumenthal, and—“in some cases”—by Bainbridge, or it has no action upon them, as
stated in 1906, and again in 1907 by official researchers. One or other of these statements must be
false. The official assertion was
unsupported by the production of any evidences whatever, the former rests upon
the independent testimony of four* different observers, situated as widely apart
In the later pages of this book I have explained why it comes about that in some cases trypsin may act upon
* As I recognize, while finally reading through this manuscript before sending it to press, a fifth observer of the formation of “liquid cancer” can be cited. From the charts of Captain Lambelle’s case of sarcoma, and from his description on a subsequent page of the course of his case of lympho-sarcoma, it is clear that in what he speaks of as “sero-purulent fluid” in the one case, and “purulent fluid” in the other, he was really dealing with liquefied cancer.
† The General Superintendent of this cancer research himself writes as follows: “It is surprising how many people are unconvinced that the scientific examination of such claims presupposes exact knowledge of the ingredients of the remedy. In the absence of this knowledge, negative conclusions could always be ascribed to error” (British Medical Journal, May, 27, 1911, p. 1221). One wonders whether he knew this when the unpublished experiments with “trypsin” were carried out, if so, why he failed to act upon it.
“normal” somatic tissues. It is in very advanced cancer cases, where the tissues have been much acted upon by the ferments and toxic products of cancer, and have thereby been injured. In this connection the finds of Yoshimoto and Neuberg concerning the auto-digestion of cancerous liver, and of portions bordering upon the cancer, are of much import.
As to the improvements in the treatment brought about by Sticker and Falk, I content myself with the record of them, and make no comment beyond saying that, in my opinion, no “trypsin-therapy” which is unaccompanied by abundant animal amylopsin will be, or can be, satisfactory in the long run.
In the long, interesting article, summing up what he considers to be our
present knowledge of the chemistry of cancer, published in the “Ergebnisse der
Physiologie” (1910), Professor F. Blumenthal, of
*The prospectus states that “this new edition represents the results of a fresh survey, undertaken in every department of knowledge by the most eminent authorities, up to the year 1910.”
the reason of my advocacy of
trypsin in cancer that the pancreas-gland was believed to be a t fault in cancer
patients. Versions of the reasons
similar to these two have been given in other places—thus, in the Münchener Medizinische
Wochenschrift. They are both
quite incorrect. My only connection
with the first was in publishing in the Lancet of
My theories of cancer, its origin and nature, differ toto cœlo from those advanced by any other observer, living or dead. The theory of the germinal origin of cancer, which says that a cancer arises primarily from a latent germ-cell, does not mean that cancer is embryonic in origin or character. Germ-cells, such as fertilized eggs, give rise to something else than embryo or soma: they produce on occasion trophoblast (asexual generation). I know that some embryologist, for whom chemistry and physiology have no existence in their researches, describe the trophoblast of Hubrecht as merely another name for what they term “extra-embryonic epiblast.” To use the latter term does not signify anything more than where in normal development the supposed portion of epiblast lies—i.e., beyond the embryo. I do not agree with them that trophoblast is epiblastic (embryonic skin) in character, or that their description of it as “extra-embryonic epiblast” in any way defines it embryologically. Their account is merely descriptive, and it gives no information whatever concerning the chemical, physical, or physiological characters of this “extra-embryonic epiblast” or trophoblast, which, quite unlike ordinary epiblast or embryonic skin, eats and erodes the maternal tissues.
In very simple words I will now endeavour to summarize what is meant by
the germinal origin and the asexual or trophoblastic nature of cancer. To these shall be added brief accounts
of the reasons advanced six years ago for employing “the secretion of that
important digestive gland, the pancreas,” including the two ferments, trypsin
and amylopsin, in the scientific treatment of cancer. It is appropriate that this should be
written down on
One of the most remarkable of the many brilliant things done by the illustrious French chemist, Louis Pasteur, was the giving of two public scientific lectures, in 1860, “On the Asymmetry of Naturally Occurring Organic Compounds,” which include the albumins, sugars, starches, etc., found or formed in animals or plants. In a scientific instrument, known as a polarimeter, these compounds always rotate the plane of polarized light to the right or to the left. Therefore, by chemists they are described briefly as dextro- or lævo- (d- or l-) compounds—for example, dextrose, or d-sugar, and lævulose or 1-sugar. That is, as they occur in living nature, animals or plants, they are never “compensated mixtures” of both stereo-isomers—never, for instance, of dextrose, and lævulose—and in such “compensated mixtures” all rotation is absent, because the one compound twists the plane of polarized light as much to the right as the other does to the left. When the chemist is able to manufacture any of these compounds in the laboratory, he has never been able to make the one compound, the 1- one, without an equal amount of the other, the d- one. To get them separated he has had to employ expedients, such as fermentation by yeast, etc., when one of the two might be attacked and pulled down, but not the other. The fact that all living organisms, whether animal or plant, manufacture or contain invariably only the one stereo-isomer, and not the other, has often been commented upon. Thus, by Professor W. J. Pope, who writes that while d-glucose (d- sugar) is a valuable foodstuff, we should be unable to digest its opposite or anithesis, 1-glucose, although they have the same chemical composition—that is, are isomers or stereo-isomers. Humanity is, therefore, according to him, composed of dextro-men and dextro-women; and, putting his words, which will
be found in Chapter VI., in simpler language, just as we ourselves should probably starve if provided with food of organic compounds the opposites in light-rotation of those to which we are accustomed, so our opposites, the lævo-men, if they were to come among us now, when we have not yet succeeded in manufacturing the more important foodstuffs artificially, would find our food, even our bodies, not suitable for their nourishment. That is, these foodstuffs would require to be changed, or “inverted.” If we our-selves had to digest compensated mixtures, we should need a double digestive apparatus. He supposes that in course of time the one set of compounds as articles of food has vanished. If it were scientifically true, as well as “generally accepted,” that the fertilized egg gave rise directly to an embryo or individual, then one of the sets would have vanished from the nutrition of all higher animals. Now, one of my discoveries has been that Pope’s hypothetical lævo-men do exist, and that they are represented by, among other things, the cancers. In this way the second set of nutritive compounds has not vanished, but at its basis the antithesis of two sets of things—compounds of carbon, defined by Pasteur—is the same antithesis as that of two sets of living things, asexual and sexual respectively, discovered and in the researches of more than twenty years described by me as occurring in the cycle of life of a fish, a frog, or a man, etc.
The fertilized egg, and any of the (primary) germ-cells which arise later on, possess the intrinsic property (potentiality) of developing in the one direction or the other; in the asexual, with the cleavage of the fertilized egg, when trophoblast first raises, as in every normal development; in the sexual, when a primary germ-cell, which itself is
derived ultimately from the fertilized egg, unfolds as an embryo or individual. What I found was that Nature employed this peculiarity of the antithetic or opposite character of certain naturally occurring compounds, all containing carbon, and many of them also nitrogen, as the chemical basis of the cycle of animal life. She did not attempt to unite both sets of the compounds, the 1- ones and the d- ones, in any one form, animal or plant; neither did she dispense with one of the sets. Had she done either of these things, had she been able to do it, she would have carried out the “generally accepted” view of direct development, egg leading directly to embryo. Then the egg would produce the hen, and the hen the egg, and so on ad infinitum. On the contrary, in order to get back to the fertilized egg again, Nature had found it necessary to separate the “compensated mixtures” into their components, to use at one time the one set, made up of certain 1- and other d- compounds, and then to use the other set, made up of the opposite ones; that is, she swings the pendulum of life first in the one direction, and then in the other, and in this way brings it back again to the starting-point—the fertilized egg.
As pointed out in Chapter VI., in connection with the account of Professor Pope’s lecture, by means of two generations, asexual and sexual, which alternate in the life-cycle from egg to egg. Nature not only utilizes two of the apparent possibilities afforded by the existence of stereo-isomeric compounds, but also she is thereby enabled to bring round again and again the cycle of life to its starting-point. Under the orthodox and “generally accepted” view of direct development these things have not been explained, but they have simply been ignored. The like orthodox views have also, notoriously, been
impotent to elucidate cancer, and the reasons for this failure lie on the surface.
Normally, in development, the fertilized egg, by forming trophoblast (asexual generation), swings the pendulum in the direction of dextro-albumins, lævo-starches, and 1- sugars, etc., and later the primary germ-cell, by unfolding as a sexual individual or embryo (sexual generation), in which new eggs or sperms arise, reverses the swing of the pendulum in the direction of the formation of lævo-albumins, dextro-sugars, d-starches, etc. Abnormally, some primary germ-cell, originally destined to give rise to a twin identical with the individual harbouring it, either, ab origine, does this by producing a monstrosity, or a benign tumour—an “embryoma”—or, remaining latent, anon it swings the pendulum in the opposite direction, and produces a cancer, which is trophoblastic (asexual) in nature—that is, is the same product as would arise normally from a fertilized egg. A cancer thus is not somatic, not embryonic, not “gametoid tissue” (Farmer, Moore, and Walker), not derived from an “embryonic rest” (Remak-Cohnheim), but it is trophoblast (asexual generation), the very antithesis or opposite of embryo or soma (sexual generation), embryologically and chemically.
When Professor Pope spoke of dextro men and women, he would, in my opinion, have done better to have used the terms “lævo-men” and “lævo-women.” For while the sugars and starches of our foodstuffs are d-compounds, the nitrogenous or albuminous constituents are 1-compounds. This leads one also to point out to the non-chemical reader that the one generation—say the sexual one, man—does not use exclusively compounds of one rotation, 1- or d-ones, but these stereo-isomeric compounds form series, some of them being 1-compounds,
others d-compounds. The like is true of the ferments, which certain of the albumins give rise to as modifications of themselves. Trypsin is like the albumin from which it is derived lævo-rotatory; it converts d-starches into d-sugars, among other things, but not 1-ones, and thus not the 1-glycogen or animal starch of cancer. It acts upon and pulls down certain d-compounds of cancer. On the other hand, the proteolytic or albumin-attacking ferment of cancer is a dextro-rotatory body, like the (dextro-rotatory) of cancer, from which it is derived. It attacks and pulls down, not the living dextro-totatory albumins of cancer, but the living lævo-rotatory albumins of the human body.
The conception I have formed of one action of amylopsin in the enzyme treatment of cancer is briefly as follows: Acting upon the living d-albumins of cancer, trypsin pulls them down in the chemical scale a certain distance, but not into simple harmless products. On the contrary, some of the products of its action are very poisonous, and to all appearance these are dextro-rotatory, like cancer albumin. As compounds of this rotation they can be acted upon and reduced to simple harmless compounds by the ferment amylopsin, owing to its configuration, its lævo-rotatory character. †
* For an opportunity of determining these facts concerning the rotations
of trypsin and amylopsin I am indebted to Mr. P. W. Squire,
It was not my purpose to calculate their “specific rotations.”
† The following natural question was recently put to the writer by a surgeon keenly interested in these matters: “If
The first and only reasons advanced by me publicly at Liverpool, now six years ago to the day, for the use of pancreatic ferments in cancer, were that at a certain period of development every normal embryo, or soma, or sexual individual, commenced to suppress the trophoblast or asexual generation of normal development. This came to pass by the initiation of the functioning of the sweetbread or pancreas-gland, with its powerful ferments, the two chief of which are trypsin and amylopsin.
(continued from page 24 footnotes)
trypsin acts upon dextro-albumins, of what use is it in the ordinary adult body, seeing that the albumins of human food are lævo-albumins?” No more than Nature does would I separate amylopsin in its action from trypsin, for, like Nature, we must associate the two ferments. Trypsin and amylopsin, acting upon the dead lævo-albumins of our food-stuffs: Trypsin only pulls these down to a limited extent, converting them into substances capable of absorption, and on these amylopsin has no action. These are built up again into living lævo-albumins by cell ferments in the body-cells. Trypsin and amylopsin acting upon the living dextro-rotatory albumins of asexual generation or cancer: Trypsin at once attacks these, and pulls them down into quite other bodies than those which its forms from dead lævo-albumins. These bodies, or some of them, are rank poisons to the human body, but, as they are further acted upon amylopsin, and by it pulled down into simple, harmless products, the two ferments, trypsin and amylopsin, acting here together, pull down the cancer-albumins, these products of the action of trypsin are chemically relatively highly organized and can be used as food by the cells of the body. This not the case with the products, to which the action of trypsin and amylopsin on cancer-albumins, living or dead, gives rise. He who doubts the truth of the above had better, before publishing his doubts, study the recent work of Professor Abderhalden and his pupils.
cancer cells (in the test-tube). Nor have I ever held, as some have done, that because they supposed, erroneously, that trypsin had some action in “splitting up” glycogen or animal starch, that it “dissolved” glycogen, therefore it should be used in cancer cases. From the start I wished all the ferments—trypsin, amylopsin, and steapsin—of the pancreas gland to be used in the injections employed.* The import of trypsin was, of course, clear, for it was known, since the work of Corvisart and Kühne, to attack and pull down dead 1-albumins, and I anticipated—rightly, in spite of all the contradictions extant, which are false—that it would, and scientifically regarded must, pull down the living d-albumins of cancer or trophoblast. † The special reasons for the employment of very potent injections of amylopsin, which normally converts starch into a d-sugar, termed “glucose,” came later on. It was found that the injections first used, which were very deficient in amylopsin, being sometimes, indeed, almost chemically pure trypsin, produced after some six to eight weeks, according to the strengths employed, very bad symptoms. These were first reported to me by French and Italian physicians, and I told them that, as this treatment followed the lines of what happened in a normal human gestation from the seventh week onwards, they
* For evidence of this, reference need only be made to the
following fact: Early in
1906, when the
† The evidences of the truth
of this will be found in the text under the description of the course of the
should treat these symptoms
as they would the vomiting of pregnancy.
I then found that for this and for the covulsive illness sometimes
happening in pregnancy, and known as “eclampsia,” there was no rational
treatment extant in medicine. So
once again a new problem had to be solved embryologically. It was, What induced these bad symptoms
in pregnancy, leading up to eclampsia, and in cancer ending with the continued
injected of trypsin, in something identical with eclampsia? With continued improvements in the
treatment, especially in the preparation of the injections, when put up
scientifically, these bad symptoms do not now arise to anything like the extent
that they die in 1906, for example.
They were, in an ascending sereies, nausea, vomiting, pain in the back,
“sleeping in any position,” drowsiness, mental and physical torpor, high
arterial tension, and albuminuria, culminating on occasion in convulsions,
lasting several hours, with complete unconsciousness (coma). Only one case of the latter (mentioned
farther on) was ever reported to me.
It happened that there was an extensive experimental study of eclampsia
in one of the German medical journals for 1905 by Professor Zweifel, as well as
the report of a lecture by him in the
milk nutrition, etc., from the standpoint of the embryologist. Certain of my researches, published some ten years earlier, when applied to the problem, furnished the solution with ease. One German medical man has described the following advocacy of amylopsin in cancer as “fantastic,” which is merely a pious “opinion,” not a scientific argument; but I am willing to admit that sometimes Nature may do things which to some people, like a certain King of Spain, may appear to be “fantastic.” Whether it be a “fantastic” fact or not, genuine amylopsin always does its work in the scientific treatment of cancer.
In the days of long ago, in our ancestry, as in that of all mammals, and as now happens in most marsupials, like the kangaroo, opossum, etc., birth took place at what I have termed the “critical period.” This is the moment in development when the embryo is first complete in all its parts. In a rabbit it is after some fifteen days out of a total gestation of thirty; in a human being in the seventh week of pregnancy, out of the total of nine months. With birth at this period the milk-nutrition was initiated. In this amylopsin is not of any use, and can be dispensed with. When, as she did, Nature prolonged the gestation, in order to bring the young into the world in a more perfect form, she deferred in so doing more and more the start of the milk-nutrition. In prolonging the gestation, she forgot, or omitted to introduce, amylopsin at an earlier period and not the “unconscious memory” remained that it was not needed until the milk-period had passed. Consequently there is an absence of amylopsin during all fœtal life. Usually the difficulties caused by this can be surmounted if the mother produce sufficient amylopsin, but from the seventh week of gestation pregnancy is a sorry business, owing to
This absence of amylopsin in
the fœtus. To this day, to my
knowledge, such is the “conservatism” of the medical profession, amylopsin has
not been employed as an injection in any case of threatened eclampsia.* But in cancer it has for some years past
been used along with trypsin, and it has never failed to perform its task of
removing the bad symptoms. The
first case in which it was injected, in 1906, was that of a very distinguished
artist and art-critic, who was suffering from an advanced cancer, recurrent
after three operations. I had
previously told his physician—a
How the term “tryspin treatment” came to find its
*This is a very remarkable fact. To many physicians of both sexes the writer has explained the scientific reasons for concluding that the source of eclampsia was to be sought and found in an absence or deficiency of amylopsin in the maternal blood, to be remedied, of course, by hypodermic or intramuscular injections of genuine amylopsin of 2,000 units of activity per cubic centimetre. So far as he is aware, though more than one of these has expressed intentions of “trying” this scientific remedy, there is no single case of actual or threatened eclampsia, in which such injections were made. Instead thereof, the barbarous remedy of stripping the capsules of the kidneys is still often resorted to, and only recently a new device has been sug-gested seriously—to wit, amputation of the breasts.
way into general use is still a mystery to me. It was, I believe, first employed by an anonymous writer—still quite unknown to me—in the Daily Mail, somewhere about the end of January, 1906. It caught on, and nothing I could do ever altered the name of the treatment. But with certain other happenings this use of the term “trypsin treatment” was a disastrous occurrence. Since early in 1906 I have always used the designation of “the pancreatic or enzyme treatment.” An “enzyme” is another name for a ferment. Again and again I have insisted upon the fact that a “trypsin treatment” of cancer was about the most deadly remedy which could be devised. It is impossible to estimate how many treated cases all over the world have failed from toxæmia owing directly to this use of trypsin without abundant amylopsin.
Particular attention may be directed to the following: The scientific
treatment of cancer or malignant disease advocated by me is not, and it never
was, a “trypsin treatment.” From
the days of its first annunciation—
things are in conformity with the enzyme treatment of cancer.
Moreover, it is not suggested in this book that the injection of 60,000
genuine tryptic units and 120,000 amylolytic units in the space of four months
will cause any and every malignant tumour to shell out or encapsulate. At times a cancer may shell out on less,
as happened, for exaple, in the
1904 one of my main theses has been that, just as in normal development there was an antithesis or opposite character, of two generations—sexual and asexual respectively—so the like antithesis obtained, of necessity, in the ferments employed by these for their nutrition. The ferments of the asexual generation or trophoblast were therefore the antitheses or opposites of the pancreatic ferments, trypsin and amylopsin; and as cancer was in nature asexual generation (trophoblast), so its ferments mush be identical with those employed by the trophoblast of normal development. All life-processes take place through the action of ferments, and without these there would be no life, such as we know it. It follows from this that the action of cancer ferments upon substances on which trypsin and amylopsin, or normal cell-ferments, will also act, cannot be the same as that of the latter; that is, the products of the fermentation must be different when used upon the same sub-stratum. The proof of this, and the answer in the affirmative to the above question, has really been furnished quite recently by German scientific chemists. In the paper by Professor Neuberg, already cited (p. 12), he writes that “Comprehensive investigations into unusual ferment phenomena of tumours have been made by E. Abderhalden, with P. Rona, A.H. Koelker, F. Medigreceanu, and L. Pincussohn. They showed that often, but not constantly in human and animal tumours enzymes can be detected which split up polypeptids and peptones quicker than normal cell-ferments do. In addition, it was established that extracts of caner (die Krebssäfte) split up polypeptids in entirely atypical fashion. While, for example, normally cell-ferments hydrolize d-alanyl-glycyl-glycin to d-alanin and glycyl-glycyl, tumour fluid splits it into glycocoll and d-alanyl-glycin. The pulling
down (Abbau) of cancer (carcinoma) takes place thus at quite other points (Stellen) of the animo-acid compounds that those at which all other peptolytic ferments attack.” All this is in complete accord with the scientific foundations of the enzyme treatment of cancer, and it is exactly what one might expect under the view of the trophoblastic or asexual nature of cancer, advocated by me. As Blumenthal urges, it alone, apart from all other considerations, is sufficient to refute and render untenable the “embryonic views,” such as the Remak-Cohnheim one. Professor Abderhalden, in speaking of the foregoing finds, remarks that it is improbable that the atypical pulling-down of the silk peptone is accidental, and he describes the enzymes concerned in this al “atypical ferments of tumours.” Again, Yosimoto found that the proteolytic autolysis (albuminous self-digestion) of cancerous liver was much increased over the normal, not only in the tumour portion, but in those free from tumour. Neuberg, studying the like self-digestion of liver-cancer, discovered a characteristic produce—fiz., reducing pentose, which in the self-digestion of normal liver is not produced.
In the Third (and latest) Report of the Imperial Cancer Research Fund (1908) the word “ferment” occurs but twice in its 440 pages. Dr. W. Cramer writes (p. 433): “The effect which a growing tumour produces on a normal organism* is a problem of nutrition similar to the growth of a fœtus in a pregnant animal. It cannot be explained by attributing to a cancer-cell the formation of pathogenic substances of a hypothetical nature, such as a ‘cancer ferment,’ or a ‘cancer toxin.’” The reader will not how this is rendered in the Introduction to the Report by the Editor: “Dr. Cramer’s paper shows how
*A “normal position” is here understood to mean a rat inoculated with a malignant tumour.
precise bio-chemical methods can now be applied to the study of the growth of cancer, and brings new and exact information as to the nature of the relations existing between the tumour and the animal bearing it. The effect which a growing tumour produces upon a normal organism is the problem of nutrition similar to the growth of a fœtus in a pregnant animal; it cannot be explained by assuming the formation of pathogenic ‘cancer ferments’ or ‘cancer toxins.’” In the foregoing the italics are mine, and they are introduced to draw attention to the method of citing the “new and exact information.”
As demonstrating the exact opposite of this information, one may cite the following recent words of Blumenthal and Neuberg: “Moreover, we consider the question of the abnormal enzymatic (ferment) processes in tumours as completely cleared up, since it has also been answered in a positive sense by Abderhalden and his colleagues, working with quite other methods.” The original German of this passage will be found in a short article by Blumenthal and Neuberg on “Proteolytische Fermente der Krebszelle,” in 1909; also to the same author, in Zeitschr. F. Kresborchung, vol. X., 1910; and to Blumenthal, “Ergebnisse der Physiologie,” “Die chemische Vorgäange bei der Krebskrankeit,” pp. 363-428, 1910; separate edition of the memoir (Asher-Spiro, Berlin), 1910.
In a review of Bainbridge’s report, the Lancet (October 9, 1909, p. 1079) states: “A negative result of this kind has the great value we have indicated, in that the medical profession have before them chapter and verse
for their placing no faith in trypsin, and none in persons who persist in advocating its use by repeating stories of alleged ‘cures’ when, as a matter of fact, the patients referred to have been proved to have died from the disease.” Scientifically, it is not necessary to do more than insist on the fallacy of lying any stress at all upon “a negative result,” and in the present instance this happens to be specially true, for “the medical profession,” if it were “placing faith” in the evidences furnished by Bainbridge’s report, would find it now difficult, but impossible, to cite from it any real scientific grounds for this. The “chapter” may be found easily, for the “scientific report” has been scattered broadcast, but the “verse” is a present blank. In the chemical experiment the observer must satisfy, not only himself concerning his reagents, but also the requirements of science.
As Bainbridge employed five different strengths of trypsin injections, of which the strongest is stated to have been six time the strength of the weakest, and as he furnished no particulars to show in which cases each of these injections had been employed, or the total number and sizes of the doses in a given time, the “chapter and verse” of his evidence can carry no sort of conviction to any logical mind. The reference to patients “proved to have died from the disease” in the citation above is, of course, to the single case of Miss K. H., which has never once been cited by me as a “cure,” or even believed for a moment to have been “cured.” This case (No. 7 of Bainbridge’s report) furnishes a far more useful and instructive object-lesson of the value of surgery in cancer than of trypsin and amylopsin.
The following is the history of this case as give on pp. 20 and 21 of Bainbridge’s report: “Duration of disease previous to enzyme treatment: about three
years. Previous treatment: removal of growth
from left breast,
Dr. Morton’s treatment with 5 to 10 minims of “trypsin” thrice weekly during some six months in 1906 may be dismissed as no treatment at all. I doubt whether with the strengths then on sale, which no endeavours of mine could persuade manufacturers to increase, the patient received in all more than one of the doses mentioned in this book—viz., 1,000 tryptic units. According to Bainbridge’s report, and its author, as the surgeon concerned, perhaps knows the facts better than any anonymous critic, the order of events was the very opposite of that usually assumed. The knife failed twice before Bainbridge evoked the ferments. There might, indeed, be some point, if little truth, in the statement here referred to, had the patient derived any benefit at all from “submission to the knife.”
Looking back over the field of my researches since the
summer of 1888, twenty-three years ago, at various phases of the journey, it was all a lonely pilgrimage
“Towards the unknown region,
Where neither ground is for the feet,
Nor any path to follow.”
New problems, entailing
fresh, patient labours, constantly arose, and the solutions of these brought,
invariable, new surprise in their train.
The start of the work was the discovery of a transient nervous apparatus
in the development of a fish; this was the one end of the slender thread. Its unravelling was always intensely
interesting and absorbing to the observer, and the thread went on, and on, and
on, always continuously, unlike any other thread of research known to me in the
whole history of embryology. Then,
at last, the other end came in sight, twenty-five years after the observer first
began, in Semper’s old research institute in the ancient
The first piece of work upon the thread occupied some five or six years; for that time was required to work out, night after night, and put together the results, which are recorded, with eight plates, in the memoir upon “The History of a Transient Nervous Apparatus” (1896). This was clearly an asexual structure, the work upon it a prelude to the cancer investigations. There are, indeed, published researches extant, such as Professor A. Goette’s immense monograph upon the development of a toad, Bombinator, which took a longer time; but, so far as I know the literature of embryology, there is no other embryological monograph which covers so long a period of development, or span of time, some seventeen
months, as this. It is nearly twice the length of time of a human pregnancy from conception to birth.
But this is not the place to write a history of a quarter of a century’s researches in embryology. Suffice it to say that the chain of researches is now a complete one, every link has been tested, and no flaw discovered. As one outcome of this systematic investigation, a single case of successful cure of malignant disease, quite apart from others recorded in the published literature, is brought before the whole work, and the invitation is give that any test of its truth be applied to it. All the methods employed are published in full. The remedies suggested and the modes of using them may be rejected or ignored; but the truth, if scientific truth have any place at all in this world, must be admitted. The facts are: that in a case of malignant disease, termed by the pathologists a “round-celled sarcoma”—named by me, scientifically, irresponsible trophoblast or asexual generation—which was recurrent and inoperable after two extensive surgical operations upon it; the remains of the tumour, under the influence of the all-powerful ferments, trypsin and amylopsin, finally shelled out, leaving the patient free from all trace of malignant disease, and, in fact, “cured.” I ask that these scientific fact, which cannot be denied, be admitted, and that with this the tardy acknowledgment be made, that when, on January 20,1905, a scientific man, whose sole object was the revelation of the truths of Nature, stated publicly that “in the secretion of that important digestive gland, the pancreas,” Nature had provided a potent remedy for cancer: what he then said was nothing more than scientific truth, which is the greatest of all truth.
This, Nature’s remedy, may be taken or left; but the truth may be denied no longer. It is beyond my power
to prevent mankind, in happy ignorance of what the cycle of life really is, from awaiting some other solution of the problems. In doing this futile thing mankind may watch, and hope, and pray, until the crack of doom; but all in vain. Even if the scientific solution were to dawn upon official research, it could—in this universe, at all events, and as it is constituted—be none other than that offered by Nature! No denial can any longer have the smallest value against the supreme truth, that when properly—that is scientifically-applied, the pancreatic ferments, trypsin and amylopsin, being the most powder things in the whole range of organic nature, are efficacious agents against cancer.
At the present time science and scientific research are not things to be made light of, to be scoffed at and jeered at in the market-place, or to be ignored. With the publication of the facts contained in this book, the responsibility is shifted to other shoulders than those of the scientific observer. All I ask is, that these truths of Nature, which she has given as a revelation of boundless and priceless import to a world which was not ready for them—that these shall not be denied, but be received reverently as what they are—true facts of Nature. Cancer is a natural phenomenon, not a disease; although it may bring disease in its train. Its treatment—that of a natural phenomenon—has been committed legally, logically, rationally, and scientifically not to the hands of the scientific observer, who has discovered its origin and nature. It is the business of the scientific observer, not that of the medical man or surgeon, to study and elucidate natural phenomena. Let the truth be acknowledged
for its own sake. As the writer is “not even a medical practitioner,” the adoption of the treatment in all or any cases of cancer is not compulsory; but it may not for a moment be imagined that scientifically it is intended to make good the failures of surgery.*
The statement made in this book that cancer is a natural phenomenon, not a disease is unassailable. It rests upon scientific evidences, which are impregnable against all attacks; but it may be questioned whether civilized mankind as a whole has any real conceptions of the nature of natural phenomena in general. Some are beneficent. The sun rises, and its heat and light render this earth habitable to man. Owing to natural phenomena, the seasons return in orderly fashion, bringing, among other things, spring, with its fresh, new green; summer, with its wealth of flower; and autumn, with its harvest of fruit and grain. Other natural phenomenon are maleficent—malignant. The volcano, also a natural phenomenon, has in the past buried or destroyed countless cities; and even in our own day this has happened. Some naturalists have been of opinion that the fossil remains of innumerable animals, now extinct—often found in great multitudes heaped together-owed their present existence, as imperfect records of past events, to catastrophes which were also
*While for the sake of humanity the enzyme treatment may be
refused to no case of cancer, recurrent after one or more operation, if such
cases fail, from the point of view of pure science, they may not be regarded and
cited as “test cases”; for in them there always lies the possible source of
error of experiment of previous operative interference. With a positive result, as in the
natural phenomena. Last, cancer, with all its malignancy—a thing which laughs to scorn the impotence of the surgeon’s knife, which yearly claims its thousands upon thousands of human victims *--is at its scientific basis only a maleficent natural phenomenon, such as these. We come into being and exist as human beings because of beneficent natural phenomena, and as human beings we continue, for a span of time, to subsist, in spite of maleficent natural phenomena. The course of some natural phenomena is unalterable by human agency; others, again, by a knowledge of the working of Nature, of science, can have their maleficent action stemmed and averted; and, as a scientific man, I affirm that cancer belongs to the category of these.
To those, surgeons and others, who have not, like the writer, foolishly devoted their lives to scientific research and experiment, but wisely to more mundane pursuits—such as the acquirement of wealth—let the following warnings be uttered: “If you wish to set up what you term ‘test cases,’ pray let them be such as shall fulfil in every way the requirements of science. Do not vitiate your experiments from the very start, as has happened, by choosing some 66 per cent. Of the cases, in which there lay the pernicious ‘error of experiment’ of previous surgical operation, once or several times over. Remember also that if your cases be chosen rightly—that is, scientifically—even then there remain the reagents employed, and how used. Do not forget that in this, as in every scientific chemical experiment, the observer must not only satisfy himself regarding his reagents, but be prepared,
*On the basis of the present population of the United Kingdom of
Great Britain and
if called upon to do so, to produce scientific evidences concerning their nature and composition.* Above all, do not for a moment imagine that you ‘have tried trypsin in cancer, and have found it useless,’ when to all intents and purposes you might just as well have been testing the effects of a solution of glycerine and water. Do not think it is ‘science’ to perform mere elementary qualitative experiments upon your injections, showing that they have some action upon starch and upon white of egg. Lastly, under the erroneous idea that it thereby makes the thing a scientific document, do not publish any account of your negative experiments with trypsin and amylopsin with the sub-title, “A Scientific Report,’ unless the document in question fulfil, like my scientific memoirs and like this book, in all respects the requirements of science.”
The greatest exaction of science is truth. This is why the expression, “scientific truth,” is so far-reaching and invincible. In the opening passages of this Introduction two points were referred to, and to them at its close I return. “There is,” said Tyndall, in somewhat different words, “in the true scientific man a desire far greater than to have his conclusions ‘generally accepted’: it is the ardent wish to see them verified in fact.” Again, it was pointed out that the problems of the origin, nature, etc., of cancer formed but a special case, a side-issue, of the application of a general principle. This general principle, revealed by my researches of more than twenty years, was of an antithetic alternation of generations with a continuity of germ-cells from generation to generation as the basis of the cycle of life. This, the law of animal development, waw what during many years of research Carl Ernst von Baer groped for, but in vain. In this
*Apparently this rule of science has no applications in official cancer research.
connection a confession on
p. 451 of von Baer’s “Autobiography” (second edition, 1886) is of great
interest. Here, in a review of his
own published embryological researches, he writes: “Und der Generations-Weschsel
For the past century, to go no farther back innumerable attempts have been made—all in vain—to solve the problems of cancer, or malignant disease. In Dr. Jacob Wolff’s monumental work, “Die Lehre
von der Krebskrankheir,” vol. i., the list of investigators given includes more than a thousand names—to be exact 1,004. Why, of these, did 1,003 fail, and but a single on succeed? The answer to this is not far to seek, and, indeed, it is contained in the true solution which is detailed in the following pages. All scientific research, to be successful in the end and enduring, must start in correct principles, or, at any rate, not in false ones. Until in recent years a practical embryologist of long-working experience applied the general principle of an antithetic alternation of generations to the problem of cancer, it had always been attacked from the standpoints of three embryological dogmas, which have this in common—that they are false, though “generally accepted.” These are epigenesis, or direct building-up of the embryo from the products of the fertilized egg (Harvey and Wolff); somatic origin of germ-cells, as “chips” of the “old block” (Huxley); and recapitulation in development, as maintained by Haeckel and his followers. If these doctrines, which are pretty “generally accepted,” were true, if they contained a particle of truth, the solutions of the problems of cancer would follow inevitably out of them. If they were false, as they are, their applications to cancer could but lead to failure, and this has been the case. Years ago, as opposed to these dogmas and as scientifically true, I set up, on grounds of observation, the three doctrines of evolution with predestination (Weismann anticipating me in this), a morphological continuity of germ-cells, and an antithetic alternation of generations.
This trilogy of doctrines is in reality one and indivisible. If this trilogy were scientifically correct, its application to the problems of cancer must end in their resolution, and this has, in fact, happened. It would not have
taken place under any constitution of the visible universe other than the one which includes this general principle of an antithetic alternation of generations as the basis of the cycle of life of animals and plants. It would have been lacking, were this general principle untrue, had my researches since 1888 been false as well as “heterodox.” Were direct development or epigenesis, somatic origin of germ-cells, etc. Nature’s method, cancer would not, could not, have been liquefied by injections of pancreatic ferments in London, New York, Berlin, and York; no malignant tumours at all would have disappeared under the influence of injections of pancreatic ferments; and Lambelle’s ex-pensioned drummer would long ago have perished miserably from the ravages of malignant disease, as countless other cases still do every day, week, and year all over this earth. It follows that the current dogmas of direct development or epigenesis, set up in the eighteenth century by the researches of Harvey and Caspar Friedrich Wolff, somatic origin of germ-cells, and recapitulation in development which are taught in all, or almost all, the Universities of the civilized world, and which are supposed to underlie the sciences of embryology, zoology, and anatomy, not to mention physiology and pathology, etc.—that these are false, even though they be “orthodox.” Therefore, the general principle of an antithetic alternation of generations has not only resulted in the overthrow and rout of cancer, but its decisive success in this has demonstrated how necessary it is, in the interest of truth itself, that without further delay—unless scientific truth have ceased to be a requirement of science—the scientific house be put in order, the false dogmas be cast out and rejected as worthless, and the Golden Rule of an antithetic alternation of generations be set up as a fundamental scientific general principle of the sciences of
life—embryology, biology, etc. Orthodoxy will not in science render false doctrines true, and Tyndall’s words become a mere mockery and delusion unless they apply to the embryologist and biologist, as well as to the physicist and chemist.
Twenty years ago my general principle—an antithetic alternation of generations with a continuity of germ-cells from generation to generation as the basis of the cycle of life—was almost within my grasp; that is, had almost been established by facts of observation. After a few more years of patient research this was so—at last. Those, and those only, who know and appreciate the history of the growth of human scientific knowledge—“The Growth of Truth” (Osler) can realize the true import of this. Two of the greatest scientific investigators of the nineteenth century were Hermann von Helmholtz and Louis Pasteur. As investigator they were incomparable, beyond comparison with others or with each other. What the latter thought about general principles in scientific research is cited, else in this book, and it may be found in full in his live, “La Vie de Pasteur,” written by Vallery-Radot. The illustrious physicist and physiologist, Hermann von Helmholtz, wrote his view in the following beautiful lines: “When, from a correct general principle, one develops the conclusions in special case of its application, new surprises, for which one was not previously prepared, always make their appearance. And since the conclusions unfold, not according to the author’s caprice, but after their own laws, it has been made the impression upon me that really it was not my own work which I wrote down, but merely the work of another.”*
* “Wenn man aus einem richtigen Allgemeinen Principe die Folgerungen in den einzelnen Fällen seiner Anwendung für sich entwickelt, so kommen immer neue Überraschungen zum Vor-
(footnotes from page 46)
schein, auf die man vorher nicht gefasst war. Und da sich die Folgerungen nicht nach der Willkür des Autor, sondern nach ihren eigenen Gesetze entwickeln, so hat es mir oft den Eindruck gemacht, als wäre es gar nicht meine eigene Arbeit, die ich niederschreibe, sondern als ob ich nur die Arbeit eines Anderen neiderschriebe” (From a letter written to Sir William Thomson [Lord Kelvin] in 1860).
THE PROBLEMS OF CANCER
EMBRYOLOGICAL ASPECTS AND ETIOLOGY OF CARCINOMA*
At a time when so much is being attempted in the investigation of the problem of the nature of cancer, it may appear presumptuous on the part of an embryologist to express opinions and conclusions regarding this grave question. It has long been a subject of earnest research by physicians and pathologists, who naturally are familiar with actual facts and finds concerning carcinoma, foreign to the embryologist. But hitherto the physician and the surgeon, the pathologist and the gynæcologist, have failed utterly to establish anything concerning the etiology of cancer, and without the intervention of the embryologist success may be as distant in the future as in the past.
As indicated by the above title, the present chapter is intended to deal with aspects of carcinoma as they strike an embryologist, and not every embryologist, but one particular investigator. At the outset it may be asked, “Is the etiology of carcinoma an embryological problem?” As the thing itself and its manifestations demonstrably fall within the province of the surgeon and the pathologist, for it confronts them almost daily, it is possibly not
very clear why the problem of the nature of cancer should be an embryological one at all. It is a disease carrying with it death and destruction. On the other hand, the problems of the embryologist, as generally understood, treat not of disease, but of the blossoming-forth of life itself—of the phenomena which culminate in the appearance of new living beings. Death and decay would seem to be things of which, from his researches, the embryologist might be expected to obtain no practical knowledge. He is supposed to be concerned with “das Werden,” while das Vergehen” is beyond the scope of his researches. Would that it were so! Unless he shut his eyes to plain facts, “das Vergehen” in the midst of das Werden”—death in budding life itself—is continually before him.
The conviction impressed upon the writer’s mind from many years devoted to the study of the mode of the development of the higher animals, the vertebrata, is that everywhere and at any point atrophy and death and degeneration of cell, of organs, of organism, of embryos themselves, are among the commonest phenomena under the eyes of the embryologist. His textbooks, even his published researches, may be silent of these; for, as a rule, he believes himself to be concerned solely with the coming-into-being; and the opposite aspect, the decline of life, he leaves severely alone. It is not, in his tacit opinion, a theme of the science of embryology. This view of the problems of the science has for many years failed to commend itself to the writer, and in his own researches he has endeavoured to take account of everything happening and capable of being observed during the developmental cycle, whether progressive or retrogressive.
The manifestations of life present themselves under the headings of either form and structure, or function. Embryological research deals largely with form and structure, or, more exactly, with the coming about of these. And as, according to the testimony of pathologist, cancer, when it appears, is something new to the organism,--a neoplasm, a foreign thing, not growing and functioning after the manner of the individual containing it, increasing by cell-division after unknown laws, which appear to defy all law, carrying with it widespread eroding destruction, only comparable to that dealt out by some parasites—the phenomena of cancer would have analogies at least to many such lying within the domain of the embryologist. Cancer is something with a beginning; it increases like a developing embryonic germ by cell-division; it invades territory at first foreign to it, and it differs only from a parasitic organism in the fact that its mode of reproduction is what may be defined as asexual. And thus, while as a rule its cycle is limited to the individual harbouring it, carcinoma is something with for itself an indefinite life-cycle, which is only bounded by the life of its host, but which cannot be carried directly over, by germs or fertilized gametes, to another organism.* That the resemblance between the life-cycle of a cancer and that of a higher animal should be incomplete is natural; for the former is an abnormal product, and it is in the nature of such to differ in some or other important details from the typical or normal.
The problem of the nature of cancer has long been before the writer in his investigations; in fact, ever since
*It has, however, been shown by
he learnt, from the researches of Welms* and other, that it had been encountered occasionally along with those curious tumours, the “dermoid cysts” of ovary or testis—the “embryomata,” or rudimentary embryos of Wilms. The latter speaks of this occasional connection † of the two—it had in 1902, according to Wilms, been observed some nine times—as a remarkable fact (p. 86), in that, in an organism of one or two years of age, the development of carcinoma can happen. As this relates to the presumed age of the embryoma, and not to that of the individual harbouring the latter, the validity of the conclusion is not apparent. On his part the writer must reject it. For the past two year, from time to time, in researches upon the germ-cells, observations have been made which appeared to have bearings upon the nature of carcinoma. ‡ This period may not seem a long one; but beyond it life the investigations of other twelve years, without which the standpoint of to-day would be an impossibility. If, therefore, no study of cancers underlie the present chapter, the approach of the problem is not a sudden one; but it as been preceded by prolonged observation, and, moreover, animal life is the same whether it be that of a hyroid polype upon a shell of the seashore, or that of a cancer within an individual of the human race.
The immediate cause of the present writing was as follows: In a recent paper, dealing with the understudy theory of heredity, in an altogether different connection,
* Wilms, Max, “Über die Dermoidcysten und Teratome,” etc. in Deutsches Archiv f. klin. Med., v. 55,1895, pp. 1-108, Pl. 3; also Martin, “die Krankheiten des Eierstockes,” etc., Leppzic, 1899, pp. 576-614.
† Chorio-epithelioma, even in the male, and usually in the testis, has, of recent years, turned out to be not uncommon.
‡ Some years ago, at Liverpool, Mr. H. J. Styles, F.R.C.S., published figures of all the supposed “cancer-parasites,” and showed what they really wee. All of these have been seen by the writer in degenerating germ-cells of development.
a few comments had been written down upon the mode of growth exhibited by certain organisms, and a comparison drawn between this and the pernicious growth of the human chorion in certain cases.* And it was not until long after the proof had been returned that it was seen how in this comparison the key to the problem of the nature of cancer had been given away. If the pernicious growth of the chorion be really carcinomatous-and it is recognized† as such by pathologists under the names of malignant placentoma, deciduoma, chorio-epithelioma or destructive placental polyp‡-the nature of cancer is clear as the light of day. And it has seemed desirable to offer the present essay, in order that at least a warning note might thereby be uttered, and an earnest attempt made to point to the futility of investigation in the direction of a cul-de-sac, such as the probable one of cancer, as due t o unicellular organisms.
In the following, the facts concerning carcinoma, as
*The passage in question is as follows : “It should be mentioned that De Vries and Weisman have already notedthe resemblance in mode of growth between the flowering plant and the colonial hydrozoa. Many of the latter also possess the indefinite unrestricted power of growth so characteristic of the aporophyte of the higher plants. As a rule the asexual generations of the higher animals do not exhibit this faculty. They rarely obtain a chance of showing it, for it is their usual fate to undergo early suppression by the sexual generation. When, as happens sometimes in cases of abortion in the human subject, the embryo is got rid of prior to the critical period, or at any rate, before the asexual generation has here been suppressed, the latter may go on growing indefinitely if left in the uterus. I refer, of course, to the unrestricted and pernicious growth of the chorion, when left in the womb after an abortion.” (Transactions of the Botanical Society, Edinburgh, 1902, pp. 140-141).
† The carcinomatous character of the pernicious growth of the chorion was first clearly recognized by Professor F. Marchand in 1895.
‡ Ziegler, Ernst, Allgemeine Pathologie, v.11, p. 488 10 Aufl, 1901.
established by pathological research, such as those given in the latest edition of Ziegler’s “Pathologie,” will be taken for granted. It will be assumed that at the basis there is morphologically but one form of cancer, no matter how different it may appear to be in diverse localities.
A cancer of the skin is naturally different from one of the uterus or liver, for it grows and increases under other conditions. Ziegler, for one, adduces reasons against the supposed origin of cancer from some effects of unicellular organisms, and to his objections something more can be added. It is not in the nature of parasitic maladies to lead to cellular increase, such as is characteristic of cancer ; and, while the phenomena of destruction possibly present themselves prominently to the surgeon and the pathologist, those of indefinite unrestricted cellular increase and multiplication most impress the embryologist. And if the nature of cancer to be brought out in the course of the following be the true one, any further one is a superfluity.
The conclusions are based chiefly, but not entirely, upon researches in Elasmobranch fishes,* and to any but vertebrate embryologists there might appear to be no warrant for applying results obtained in animals so low down in the scale to man himself. But the broad outlines, the laws, and even most of the details of the development, are the same in man as I the fishes, and the life-cycle of the former can be interpreted in terms of that of the latter. The starting-point goes back more than two years to the beginning of researches upon germ-cells, and with these to the earlier work of Wilms upon the embryolomata. The results of the work, and of previous necessary
* Also upon researches in mammalian development, especially upon the trophoblast (larva or phorozoon, asexual generation), allantoic placenta, critical period, and span of gestation.
inquiries , dating as long ago as 1888 cannot be given at all in detail here. A general survey of the chief conclusions will be found in “Heredity and the Epicycle of he Germ-Cells.”* The nature of cancer is really known, but not recognized. Failure to perceive the true nature of carcinoma has hitherto been due to one simple fact : the views generally-universally- held regarding the course of the cycle of development from egg to egg are erroneous.
Were an embryologist of to-day asked what in outline was the cycle of development in one of the higher forms-say a fish, chick or mammal- he would probably be amazed at the question. “The hen lays the egg, the latter gives birth to a new hen,” and so, as Kleinenberg once remarked of something else, under the eyes of the delighted and astonished spectator, the cycle is completed. This supposed cycle has never really been witnessed, for the very good reason that it does not exist. The hen neither produces the egg, nor is it the chief, nor even the immediate task of the latter to give rise to a new hen. As the establishment of this and of the true life-cycle have filled in the working hours of the writer during many years, it may be obvious that the production of the evidences must be beyond the limits of this book. Indeed, no attempt will be made to prove here what the true life-cycle is, and wherein its details lie ; the results of previous work will be assumed, and for fuller information the reader may be referred to the original memoirs.
In the higher animals-the Metazoa-what is termed “direct development” does not, and cannot exist. It has been found that the cycle of animal development, even of the highest forms, resembles very closely that of
* Biologisches Centralblatt, 1902, vol. xxii., pp. 321-328, 353-360, and 398-408.
a fern or a flowering plant. In the line from the egg to the egg there are two generations-an asexual form, and one, which, as it is the bearer of sexual organs, is spoken of as the sexual generation. Under prevailing views of development the line of ancestry from generation to generation is exceedingly simple-too simple, indeed, to explain the facts ; so simple that Nature could not adopt it in practice, were she to make the trial. It may be represented thus : egg→embryo or sexual generation→egg→embryo, etc., the egg producing the embryo ; the latter, when mature, forming from its own tissues new eggs. This is undoubtedly, one of the most impossible conceptions which ever formed part of a science. [emphasis added by DHD Sr] The amended cycle of development and the course of heredity are as follow : egg→trophoblast (phorozoon or bearing animal, asexual generation) → primitive germ-cell→primary germ-cells→secondary germ-cells→gametes, eggs or sperms→fertilized egg.* In the line of ancestry, as given here, a line which, apart from the asexual generation, is one of unicellular organisms, the embryo finds no place. It arises from one of the primary germ-cells, whose number is always a definite one-2, 4, 8, 16, 32, etc.-and the rest enter the embryonic body to form its sexual products. A more detailed account of this cycle will be found in “Heredity and the Epicycle of the Germ-Cells.” The four important items in the cycle are : (1) The gametes, egg and sperm, by whose union, to form a zygote, a new cyle is initiated ; (2) the first product of the zygote, the phorozoon, trophoblast, or asexual generation ; (3) the primary germ-cells, destined for future generations ; and (4), only important to enable the completion of the cycle, the embryo or sexual generation.
Any and every primary germ-cell, if it develop or unfold
* See Fig. 5, Chapter V.
as such, normally gives birth to an embryo, and as elsewhere indicated, the embryomata of Wilms arise, and must do so, from such primary germ-cells. This unfolding of a primary germ-cell is equivalent to its landing in a cul-de-sac ; its powers of growth and increase and its life are thereby limited. The contrast between this and the larva or asexual generation in these respects is very striking. The latter, like the corresponding generation in plants, often possesses indefinite unrestricted powers of growth in an apical fashion.* In many animals there is only one apical region of growth in the asexual generation ; in the hydroid polypes there may be many such, and Weismann and De Vries have already noted their powers of indefinite unrestricted growth. That which brings to a sharp and sudden close the growth of the asexual generation, if there be but one growing point, is the cutting off
* Of great, but hitherto unrecognized, importance in this direction, are certain results of experimental embryology-such as those of Driesch, Morgan, and others, upon echinoderma, and of E.B. Wilson and others upon Amphiosus, ETC. (For a full account see E.B. Wilson’s “The Cell,” second edition, 1900 ; or Korshelt und Heider, “Lehrbuch der vergleichende Entwicklungsgeschichte, Allemeiner Teil,” Jena, Gustav Fischer, 1902 ; or J.W. Jenkinson, “Experimental Embryology,” Oxford, at the Clarendon Press, 1909). Space does not permit of a description and discussion of these experiments. The general result is, that in certain animals, if the cells of the early cleavage of the egg be separated, each of them will give rise to a diminutive larva, the size of this varying directly with the size of the original blastomere. These minute larva are often, but erroneously, spoken of as “embryos.” Though they may go on living for a considerable time, no case is known in which an embryo with sexual organs arises upon such a larva, as would of course, happen in a normal development. Allied to this latter circumstance is the fact that the in vertebrate larva obtained by embryologists by artificial fecundation, never give rise to the sexual form, no matter how long they may be kept living in the laboratory. The writer has reared Echinus (sea-urchin) larva for fifteen days without the formation of a sea-urchin upon any of them. Many other similar facts could be mentioned.
of this from the organism, its conversion into a primitive germ-cell, and the consequent formation of primary germ-cells from this. Normally, as already stated, the further development of a primary germ-cell results in an embryo, not in a larva (asexual generation).
Coming now to the primary germ-cells, upon which many observations have been made, it has elsewhere been established that their number is always a member of the geometrical series : 2, 4, 8, 16, 32, etc., or 2 to the nth power where n is one of the numerals 1, 2, 3, 4, 5, 6, etc., and that the greatest number of primary germ-cells in any embryo will be 2n-1. Thus the total number in the common dog-fish (Scyllium Cannicula) is 128 ; in the male smooth skate (Raja Batis), 256 : in the female, 512 ; and the greatest number in the embryo of one of these 127 (in Scyllium), 255 (in the male skate), and 511 (in the female skate). But for convenience and brevity, dealing with one form only- say, the dog-fish (Pristiurus)-of the 127 primary germ-cells, it never happens that all, or anything like that, reach the normal position-the germinal ridge or nidus. Usually, at the most from 90 to 100 of them arrive here, the remainder being found in all sorts of unusual places, where many of them degenerate.
Here may be inserted a very brief account of some unpublished finds, which for this reason have escaped the attentions of some observers intent upon “annexation.” Some ten years ago my observations proved to me that in certain dog-fishes (Scyllium and Pristiuris)
The single ovary of the adult female arose by the degeneration during development of the left embryonic ovary and the persistence of the right one. There were at the time many indications-even strong evidences-that the find in the female skate of twice as many primary germ-cells as in the male was a general rule for the back-boned
or vertebrates. But the numbers appeared to work out to the same (about 128) in
both (potentially) male and female embryos of the above two dog-fishes. I was
sure in my own mind that the real number in potentially female embryos of each
was not 128, but 256. This was the position when, in 1903, the writer was
compelled to lay aside his germ-cell researches, in
order to undertake a campaign against cancer. Owing to this, the publication of
the series of germ-cell memoirs was interrupted, for no time could be found to
extend the tedious countings of germ-cells in embryos of these two dog-fishes.
This task was afterwards undertaken on my material by an able amateur microscopist-my friend W. T. Haydon, an
The number of Elasmobranch embryos hitherto examined is several hundred, belonging to different species, and in all these under a certain age no single embryo has been seen, in which all the germ-cells present might be described as normally placed. The percentage of vagrant germ-cells varies ; it is usually from 10 to 12 per cent. In Pristiuris, and from 25 to 30 per cent. In Raja Batis. The places where these occur are numerous : in the body cavity, upon the splanchnic (gut) mesoblast, on the subintestinal veins, in kidney tubules, in the pericardium, in the liver, in the skin, in any part of the gut epithelium, especially in the rectum, rarely in the head or gill region, and practically always there are some in the immediate
neighborhood of the stomach in connection with the yolk-stalk. Undoubtedly, many of these germ-cells degenerate, and few, if any, of the vagrant ones, after a certain early period, ever find their way to the germinal nidus. The embryomata of Wilms are to be regarded as products of such vagrant or of persistent (in ovary or testis) primary germ-cells. But-and this is remarkable-very many such vagrant germ-cell occur in places where embryomata are not usually encountered : thus, in the immediate neighborhood of the stomach, in the liver, in or under the skin and in the rectum. In nearly every embryo one of more germ-cells may be found in the yolk-stalk, in the immediate neighborhood of the pylorus, and also in the rectal epithelium.
It may be therefore suspected that if the germ-cells of many of these places-e.g., liver, pylorus, rectum, etc.-ever do develop, they must give rise to some product not of the nature of an embryo, not an “embryoma.” It is not without interest that the common situations for the origin of cancer are the very ones in which vagrant germ cells are usually met with : thus, in the rectum, near the pylorus (yolk stalk), other parts of the gut, in the kidneys, in the skin, etc. Apparently, cancer of the tongue, of the oesophagus, of the larynx, and of the mammary gland, at first glance form exceptions, but this is not really so. Tongue, esophagus, and larynx are products in the higher forms of a rebuilding of the gill region ; oesophagus and mammary glands are closely associated with the pericardium, where vagrant germ-cells (and at times embryomatat as products of these) are often found. That cancer should arise in what embryologically are holes and corners-places where layers and folds come together, as in tongue and larynx-is readily explicable. Such vagrant germ-cells are intruders in the situations
originally taken up by them, and it has often been noted how they would appear to be hustled about from pillar to post, when in the way, until they land in some corner or other. Normally, if the paradox be allowable, the development of such a vagrant germ-cell should result in a more or less complete twin-embryo ; but any gradation of this down to a very rudimentary embryo may be found in practice. Figured in Ziegler’s “Pathologie” may be seen all sorts of steps, from complete identical twins, only abnormal in being united at some point, through those more completely united, to others forming more or less complete embryos, embedded within or projecting from a normal one, down to mere cysts or absolutely rudimentary embryos.* No one has ever witnessed the development of such a rudimentary embryo or embryoma, and probably it will never be seen ; but the connection between them and vagrant or persistent (in ovary or testis) primary vagrant germ-cells is not less certain than that between an onion and the seed originally planted. In the same way, the hypothesis that the vagrant primary germ-cells of certain regions-thus those of the neighborhood of the stomach and of the rectum-if they develop, give rise, not to an embryo, but to an asexual generation of indefinite unrestricted powers of growth, can never be converted into a fact by direct observation. It can only be inferred from the facts. But it is a very simple explanation of all the facts, and its probability is increased by other considerations.
But why should a vagrant vagrant germ-cell, when developing into a cancer cell, omit or skip the formation of an embryo, and proceed with a different portion of the life cycle?
* A much fuller series of such embryonic monstrosities, forming a very
interesting and instructive collection, will be found in Ernst Schwalbe, “Die
Morphologie der Missbildungen,” etc. Part II.,
One reason* is perhaps clear. It is that the further growth of a vagrant germ-cell, or its progeny, to form a cancer takes place at a much later period than that at which its embryological development into a more or less complete embryo should have happened. (The instances of cancer with embryomata, noted by Wilms, do not form exceptions.) Moreover, it must not be forgotten that we are dealing here with pathological conditions, with phenomena which in some glaring way do not conform to the normal. Cancer is, more or less, an attribute of later sexual life or of old age. For this reason one is inclined to suppose that it is not immediately due to the further development of a vagrant vagrant germ-cell itself : that this latter first of all divides many times, as it would do if in the germinal nidus, and that it ultimately forms more or less normal forerunners of gametes, oocytes or spermatocytes. These would be in abnormal situations and under abnormal conditions, and under some stimulus, they would develop as though parthenogenetically, but abnormally, to form a trophoblast.
At the basis, cancer is nothing more than the production abnormally of an asexual generation within a sexual generation. Elsewhere analogies may be seen. In hermaphroditism we witness the conversion of the forerunners of male eggs (in what are really females) into sperms. In certain ferns, abnormally upon the asexual generation or fern-plant, what the botanists term “apogamy” is met with-i.e., the appearance of a new sporophyte upon the original one ; the formation of a sexual generation or gametophyte, and of sexual organs being skipped. It has been urged from a botanical side that comparison between apogamy in certain ferns and carcinoma in a mammal would not be justified, because the former was an abnormal condition. But we are dealing with abnormalities,
* Compare p. 20, et seq. of the Introduction.
page 62 is missing and presumed to be a picture page
a few comments had been written down upon the mode of growth exhibited by certain organisms, and a comparison drawn between this and the pernicious growth of the human chorion in certain cases.* And it was not until long after the proof had been returned that is was seen how in this comparison the key to the problem of the nature of cancer had been given away. If the pernicious growth of the chorion be really carcinomatous—and it is recognized † as such by pathologists under the names of malignant placentoma, deciduoma, chorio-epithelioma or destructive placental ploype ‡--the nature of cancer is clear as the light of day. And it has seemed desirable to offer the present essay, in order that at least a warning note might thereby be uttered, and an earnest attempt made to point to the futility of investigation in the direction of a cul-de-sac, such as the probable one of cancer, as due to unicellular organisms.
In the following, the facts concerning carcinoma, as*The passage in question is as follows: “It should be mentioned that De Vries and Weism
w the mammals;* the animal lowest in the scale in which it has been recorded being the short-headed phalanger (Belideus breviceps).† The disease is a corollary to uterine gestation.
If the cycle of development of the higher animals really be that concluded by the writer, if his interpretation of the phenomena of mammalian development—which are not in the least based upon facts or factors noted in cancer, but upon normal development here—if these be correct, the nature of carcinoma is not hypothetical at all, but is actually known. More than one font cannot be assumed, and it one fountain-head be shown, all other
* See. However, the closing lines of this chapter.
† Bland-Sutton. J.: “Evolution and Disease,”
explanations become superfluous. In certain cases in human development, where either no embryo arises within the chorion, or when the embryo becomes aborted or dies prior to the suppression of the asexual generation, the latter—the chorion—may go on gowing indefinitely, and may give rise to what pathologists and gynæcologists recognize to be a form of cancer, placentoma, or chorio-epithelioma (Marchand). For years now I have recognized, and, in homologizing this structure with the larval skin of an amphibian, Hubrecht has gone a long way in the like direction, that the human chorion represents the main portion or whole of the asexual generation here. In certain cases, therefore, we here witness the conversion of the chorion—i.e., of the asexual generation—into a malignant tumour, a carcinoma.
What other proof could be asked for? That this proof of the nature of cancer is not in agreement with accepted views of normal development cannot be set down to the fault of the writer. He holds, and has long maintained, such views to be false and unfounded in fact, and moreover, it has been attempted to indicate the right way. The arguments and conclusions have been neither refuted nor confirmed, but they have been ignored. But embryologists, are living, and have long been existing therein, in a mental universe, where but a tithe of the facts observed are explicable under their views. Under the conception of development as an antithetic alternation of generations—especially as laid down in “Hereditary and the Epicycle of the Germ-Cells” *--all the known facts of development fit in, all are capable of easy and natural explanation. And the elucidation of the etiology of carcinoma follows as a natural corollary to the law of the
*Bilogisches Centralblatt, 1902, vol. xxii., pp. 321-328, 353-360, and 398-408.
development cycle. The embryologist and pathologist may ignore and neglect the plain and palpable fact, but on no theory of direct development—a thing only existing for the higher animals in the human imagination—can any explanation whatever of the nature of carcinoma be advanced. This would have been recognized clearly long ago had some embryologist taken the trouble, as the writer has done since 1888, to trace out in full the details of the life-cycle of one of the higher animals from egg to egg. The idea of direct development, accepted without examination of the evidences, and the erroneous belief in the somatic (body) origin of germ-cells, have retarded the advance of knowledge to an extent difficult to estimate.
The nature of the argument employed in the present writing may be summarized as follows: Granted the facts of the origin, migrations, and history of the germ-cells of vertebrates, and assuming the course of the life-cycle to be that previously indicated, by hypothesis cancer is derived from vagrant primary germ-cells, which, instead of forming a more or less complete embryo or embryoma, skip this, and give rise to an asexual generation of indefinite unrestricted powers of growth. This is, of course, purely hypothetical, but it becomes the true explanation by the following facts: On the one hand, as my researches have shown, the hypothetical verirrte Keime, or “lost germs,” of pathologists not only exist, but they are numerously represented, and by things capable of abnormal development—the vagrant primary germ-cells. On the other hand, the carcinomatous nature of such an abnormal growth of an asexual generation has been demonstrated abundantly by Marchand for the instances of the pernicious growth of the chorion, chorio-epithelioma. If such a chorion, or trophoblast, the representative more
or less complete of the asexual generation, when robbed of its embryo, or when it fail to form such, can—and this is established—give origin to a malignant carcinomatous tumour, the nature of cancer is clear. The vagrant primary germ-cell is the seed, while its fruit, sometimes represented by an embryoma, may, on occasion, take the form of a carcinoma.
In the foregoing pages, written in 1902, cancer is spoken of as “a disease,” for not until the researches had advanced much farther did it become clear that cancer was a natural phenomenon. The origin of a cancer from “a vagrant germ-cell” is urged; but on grounds, given later, it soon became necessary to restrict this power of independent development to some few only of the vagrant germ-cells. Its asexual nature is clearly defined in the foregoing, and while at that time its restriction to mammals seemed clear (although in 1895 its occurrence in some other vertebrates had been recorded, as I found later on), below the mammals it is still anything but common. Even now (1911) no case is known in reptiles, and but a few instances have been found in birds, while in many thousands of frogs examined the writer has only encountered on undoubted case of epithelioma. Considering its frequency in mammals, especially in man, the statement made above of its connection with uterine gestation would still appear to have a basis of fact under-lying it. The adaptation of the asexual generation (trophoblast) to uterine life, shown by the occurrence of uterine gestation, favours its abnormal development in mammals as a parasitic cancer, as in no other class of back-boned animals. In the following chapter an attempt will be made to show how the tumours are related among themselves, and to the individual harbouring such a new formation.
THE EMBRYOLOGY AND ETIOLOGY OF TUMOURS
A. THE EMBRYOLOGY OF TUMOURS.
The etiology of tumours is one of the darkest regions of pathology. This is by no means due to lack of hypotheses, rather to the absence of material basis for any of those current. It cannot fall within the scope of the work to treat of anything like all the different ideas at some time or other maintained.*
The writer’s purpose will be served best by referring only to views as to the nature of pathological growths, based in some form or other upon embryology. † One cannot read the writings of the pathologists of the twenty-five years without being struck by the un-
* For these, and their name
is legion, see Wolff, Jacob: “Die
Lehre von der Krebskrankheit,”
† To account for tumours the two views most advocated at present appear to be that of “embryonic rests” or displacements, and that of metaplasy. Under “metaplasy” pathologists understand change in the character of tissue-cells, even in later life. Both are purely hypothetical, and each of them, has been described as savouring of the miraculous. From the modern embryological standpoint both of them may be said to be impossibilities. Regarding “metaplasy,” as little as a man can return to his childhood, so little an any of the cells of his body take on embryonic characters, or change their nature. If any one small part of the body can do this, why not grant the same superhuman power to the whole?
doubted tendency on the part of, at any rate, many of them to assign some sort or other of embryo-logical basis to very many, if not all, tumours. I should be the last person in the world to deprecate this, convinced as I am that far more tumours than almost any pathologist now living possibly imagines to be explicable embryologically have such a basis. I only differ from many pathologist in regarding these neoplasms from an embryological standpoint which is as strange to them as it is to the majority of embryologists. The pathologist who is an exponent of a developmental etiology of tumours naturally endeavors to bring them under the laws of embryology, as given in current textbooks. Since my work of many years past has clearly brought home to me the erroneous, baseless, and impossible nature of many of the tenets and doctrines of modern embryology—e.g., direct development, somatic origin of germ-cells, and epigenesis—it must, of course, be equally clear than an “embryology of tumours” founded on these can only be fallacious.
A tumour, whether simple or complex, is a living thing, and, like everything living, it comes gradually into being, it unfolds and manifests itself, and in this way it has its own developmental history. This statement may appear somewhat metaphorical, but its meaning is clear enough if it be said that very many tumours, from the most complicated teratomata down to cancer (carcinoma and sarcoma), are but bizarre manifestations of some portion of an animal life-cycle. The truth of this could not become apparent hitherto for two reasons: on the one hand, the views maintained as to the normal cycle of development were erroneous; and, on the other, the true science of embryology is as yet almost a terra incognita to pathologists. But, just as there is a science of normal
development waiting for recognition in our Universities, *--one whose continued neglect and exclusion will continue to revenge itself upon mankind, as it has already done in the past, by a corresponding retardation of priceless knowledge—so there is also (a branch of the foregoing, and only to be understood in the light of it) an important field of abnormal embryology, largely represented by the tumours and their problems—a knowledge of which can only be advance by aiding and fostering the former.
In his magnificent monograph upon tumours Borst writes eloquently of this pathological embryology as a large and interesting region of knowledge, through whose mystical portals we penetrate at the moment with feebly burning torches of comprehension (Erkenntniss), but with the highest expectations. The torches here spoken of may be identified as those of the science of normal embryology, than which there is possibly no department of knowledge of more moment to mankind, and by whose light alone these dark, but to mankind gravely important, regions can be illumined adequately.
In studying the views presently advocated as to the etiology of tumours, the following points are apparent to the embryologist. In their basis, so far as this is embryological, they are but modification of the Remak-
*The writer seeks no such
post, although aware that in the last two years of his life the creation of such
a University Chair in London for him was the cherished wish of the late George
Bond Howes, Professor of Zoology in the Royal College of Science, South
Kensington. But it may be pointed
out that, unlike
Cohnheim theory of embryonic rests,* and the descriptions and classifications of the tumours usually adopted have no embryological groundwork whatever, proceeding, as they do, from the simple to the complex, instead of from the most complicated teratomata—the embryomata of Wilms—to the simple tumours represented by but one tissue—a “connective tissue” or an epithelium. †
The “rest-theory” of Remak-Cohnheim, and their followers is a natural corollary of epigenesis as the mode of the development; and so little as the possibility of this mode of development can be admitted, as little can the existence of such rest of embryonic tissues, organs, or structures, be allowed. ‡ With the rejection of the Remak-Cohnheim theory, the modification suggested by Ribbert also falls to the ground. If the embryo be not gradually built up from a pile of material, as a house is erected, there can be no superfluous bricks or other structures to ball back upon as the seed of later tumours. Even were the development epigenetic—and this is certainly not the case—the actual existence of such rests has never yet been demonstrated; nor is it shown by the occasional appearance of a supernumerary or accessory organ or structure, such as an extra kidney, thymus,
* The theory of “embryonic rests” as the source of tumours is almost invariably attributed to the pathologist Cohnheim. As shown in another chapter, it was first enunciated by the embryologist Remak, and for this reason and for clearness it will be referred to in these pages as the “Remak-Cohnheim” theory.
† To his knowledge Wilms and C. P. White are the only authors who, like the writer, regard the neoplasms in this “inverted” fashion. It may help to support their attitude in this important matter to add that the writer arrived at the conclusion that, as a rule, the tumours were approached in the wrong order, before seeing their writings.
‡ The recognition of the impossibility of epigenesis as the mode of the development was first made by Weismann in his “Germplasm” (1893).
adrenal, ovary, or spleen. In no embryological sense can such be considered to represent the missing hypothetical rests. Such structures have not been known to give rise to tumours.
Perhaps the theory of embryonic rests has undergone its most important and most scientific alterations at the hands of Wilms,* of whose views—to some extent, at the least—Borst† is also an exponent. Of Wilms’s researches on tumours, and especially of the facts laid bare by them, it is not too much to say that they are epoch-making. But of his embryological conclusions it must be added that they are necessarily false, because based on the premisses of an impossible embryology.
The lost germs or rest of Remak-Cohnheim are replaced by Wilms by what he terms “germinal shuntings” (Keimausschaltungen). Essentially, Wilm’s theory is almost as simple as that to be here advocated, and, like the later, the hypothesis of germ-shuntings will readily explain many tumours. The germ-shuntings of Wilms are conceived as follows: At various periods of the development, from the earliest to undefined later ones, prior to the completion of the parts of the embryo, there are single cells or little groups of such, set apart to furnish some structure of the embryo. These are often serially repeated (metameric segmentation) in great numbers. Some on or more of these may be shunted out of the normal connection ( ? by what ) at almost any period of the devlopment. According to Wilms, this shunting is not to be regarded as a displacement, for the thing shunted actually remains in the organ to which it really
*Wilms, Max: “Die Mischgeschwülste,” Leipzic, 1899-1903, 3 Hefte.
`† Borst, Max: “Die Lehre
von den Geschwülsten,”
belongs.* If this hypothetical shunting—which, to may mind, in a normal development is physically impossible without disaster to the developing embryo—happen in the earliest periods, it will be in connection with cells of the cleavage, and one or more of these may become the abnormally placed seeds of a tumour or tumours. As an example, to be commented upon later in its true bearings, Wilms himself found in one case not less than five embryomata or rudimentary embryos in one ovary! These represent under Wilms’s views five blastomeres of the cleavage. I do not know whether or not there be any upholder of epigenetic development who is prepared to grant the subtraction of this number of cleavage-products without utter disaster to the further development. As will be seen anon, the experimental researches of Driesch, Herbst, and other—Bonnet notwithstanding—do not in the least support Wilms and Bonnet in their extravagant suppositions. Again, according to Wilms, if the happening be at a later period, it may concern, for instance, a part of one or more mesoblastic somites, and, as we know the fate of these, the structure of a tumour arising subsequently can be foretold. Thus a tumour in the region of the vertebral may be made up of “embryonic mesenchyme,” or formative tissue, cartilage, and bone; or of the first, or of the first and second of these. Such a tumour Wilms derives from a “shunted” mesoblastic somite, because such a somite gives rise normally to these tissues. Now that, for example,
*On closer examination, contradictions in Wilm’s statements may be found. Thus, to account for some tumours, or parts of such, Wilms requires “germs” from mesoblastic somites, and these may, according to him, be displaced physically into—for example—the kidney or uterus. In this way Wilms’s theory is seen to have very much in common with the earlier one of Remak-Cohnheim.
somites may be shunted, actually or but physiologically, from the normal connection is purely hypothetical, and nothing of the kind has ever been witnessed. Rudimentary somites occur even in the trunk region in some animals, but these are rudimentary, and probably always disappear.
Wilms regards his germs as things destined in reality to form parts of “the embryo,” and therefore as belonging to this.* Under his views cases of five embryomata in one ovary require the shunting into this of five blastomeres during the early development; that is to say, in this instance the original fertilized egg must have been divided up in some way or other into at least six portions, one of which formed a normal embryo, while the remaining five retained at lease the potentialities of each becoming an abnormal embryo or embryoma. It is open to doubt whether any upholder of epigenesis will admit the possibility of the course of events happening in this way. As it would seem a new hypothesis is needed to account for each of the five embryomata, with an additional one to explain the continued normal character of the development after such a shaking and shunting.
Equally formidable difficulties are furnished by the well-known instances of multiple tumours, of various kinds, in one individual. Indeed, the doctrine of epigenesis as the mode of the development labours under quite sufficient insuperable intrinsic difficulties without having to bear the burdens imposed upon it by such
* As decisive against the origin of tumours from cells, or tissues, of the individual in which they develop, may be cited the facts that very many of them are encapsulated from the surroundings—thus, tumours of the kidneys, breast, and parotid; and that various observers—thus, Wilms and Borst—deny any passage or transition of normal tissues into them. The encapsulation of many tumours is of embryological interest, because many of the aberrant germ-cells exhibit this feature.
serious tamperings with the development , as Wilms’s theories demand. Nor should it be forgotten that, while on the one hand Wilms speaks of an embryonic “over-production” (!), he states that the germs of his tumours develop in exactly those organs to whose edifice under normal circumstances they ought to have contributed.
Underlying the doctrine of the shunted germs are the dogmas of epigenesis and somatic origin of germ-cells. The latter is an absolute necessity to the former. Since the founder of this (Professor Waldeyer) has seen reason to reject his former conclusions in favour of a morphological continuity of germ-cells, the greatest stronghold of epigenesis has fallen.* Brilliant as are Wilms’s actual investigations of the tumours, when regarded from the objective embryological standpoint, the “shunted germs,” evoked to account for the facts, are just as hypothetical and chimerical as any other “lost germs” ever conceived of by pathologists.
Wilms’s theory, ingenious, and enticing though it be, is but a clearer defined modification of that of embryonic rests. As with the latter, epigenesis and hypothesis are its main bases; and as to the Remak-Cohnheim theory, the objection can be urged that it is an unnecessary multiplication of causes. This is well illustrated by Wilms’s and Borst’s distinctions of monogerminal and bigerminal tumours. Double monsters and certain teratomata are regarded as bigerminal, and, placed in contrast
*See Waldeyer, W.” “Die Geschlechtszellen,” Abdruck aus dem “Handbuch der vergleichenden und experimentellen Entwickelungsgeschichte der Wirbeltiere,” von Dr. Oscar Hertwig, vol. i., 1903, pp. 404-405. With the “prevision,” of which Pasteur so often spoke, on p. 405 Waldeyer writes: Die” Folgerungen aus dieser Lehre von der Kontinuität der Geschlechtszellen sind fast unbsehbar für die gesamte Biologie” (The consequences of this doctrine of the continuity of germ-cells are almost incalculable for every branch of Biology).
with the remaining complicated “three-layered” tumours, which, as due to developmental abnormalities of a single embryo, are stated to be monogerminal. As, according to Wilms, all possible transition between the most complicated embryomata and the simpler tumours exist, there would appear to be no grounds for this and similar increases in the hypotheses.
Apart from its entirely hypothetical character, its lack of support in facts of embryology, and its continual and unnecessary multiplication of causes, the theory of germ-shuntings labours under other difficulties. It is not easy to conceive any adequate cause for such shuntings during development, and the difficulty is greatly increased when cases of multiple tumours in very different parts of the body, each of which requiring one or more shuntings at some period or other, are taken account of; for with them a normal development would appear to be quite out of question. But, granted the possibility of such shuntings, the real difficulties begin. What causes such a shunted germ, ignoring all laws of differentiation, to embark upon a career of damage, riot, and destruction of its own? To take an instance from Wilms, typical of many such: the germ of an osteo-sarcoma will be a cell or germs of the periosteum of some bone. Normally, like its fellows, it ought to have contributed to the formation of that bone. Instead, thereof, at some period or other, after lying dormant, it breaks all bounds, and proceeds on a line of development of its own. This is such that, unless brought to a stop by some extrinsic cause or other (operation or death of the host), it may be the parent-cell of more progeny than all the other bone-producing cells in the body! In find, Wilms ascribes to his shunted germs far greater embryological potentialities than Nature ever endowed them with. On the other
hand, some of the aberrant and vagrant germ-cells described by the writer undoubtedly possess, as was once remarked to the writer by a human anatomist, far greater potentialities for mischief than any germs ever conceived of by pathologists.
Not only the embryonic rests and the germinal shuntings, but a host of subsidiary hypotheses—among others, those of Borst, relating to the tumours of the sacral and cerebral regions—become superfluous in the light of the much simpler theory of tumour-formation as due to—(1) the abnormal development of a persistent primary germ-cell, and (2) the bizarre pathological manifestation by this of some greater or less portion of a life-cycle. Under this view most, if not all, tumours receive a simple explanation, and under it, also, it must be manifest that previous attempts—that of Wilms excepted—to explain the tumours, in taking the simpler ones as the starting points, have really begun at the wrong end of the scale. Neither in theory nor in practice can the degree in greatest possible reduction of an embryoma or rudimentary embryo be defined, and, in fact, in actual practice and theory a simple tumour will represent a low degree of such reduction.
Certainly, regarded as pathological manifestations of some greater or less portion of a life-cycle, all the peculiarities of very many tumours are fully explained. A germ-cell, developing abnormally, may after its developmental unfolding has begun, undergo degenerative changes of various kinds and degrees as to greater and smaller portions of its parts, or some foundations may remain latent, wholly or in part; and in this way a single cell, or a larger or smaller group of such, endowed with certain well-defined potentialities, may be left as the actual seed, as the origin, of the tumour thereby arising
Matters would appear to be complicated in some cases by the existence of two well-marked portions in a normal life-cycle: the asexual one, represented by the chorion (trophoblast); and the sexual one, taken up by an embryo, or Metazoon. Some tumours—some ovarial teratomata, described by Wilms—exhibit attempts to include the whole life-cycle, in that, along with a pathological bizarre embryo, cancer, representing the asexual generation, is encountered. In other tumours, again, there would appear to be nothing of the asexual generation; and still others, the malignant cancers, confine themselves entirely to being abnormal manifestations of the asexual portion—the first part of the life-cycle.
The comparative embryology of tumours may now be considered more in detail. The see or seeds of tumours are unquestionably some or other of the vagrant (or if in ovary or testis, persistent) primary germ-cells, treated of at greater length in the writer’s works upon the germ-cells. So far (1911) they have only been found from fishes to reptiles; but from various considerations it is not open to doubt that they occur even in the highest vertebrates, and in man himself. Apparently they have been noted by Roux and Barfurth in the frog, and by me in the salamander (S. maculosa). In all the embryos yet studied by me under a certain age—i.e., with the limits during which germ-cells are easily found in embryos—no single embryo examined has been devoid of them.
The mode of the development and the life-cycle, in practically all its details, are the same in mammals as in fishes, and unquestionably the whole organization and development of man follow closely along, but along higher lines than, those of a fish. It is therefore concluded that, could one but hit upon some easy method of distinguishing germ-cells during the early development of man and
mammals, the occurrence of vagrant ones in various parts of the body, skin, pericardium, pylorus, rectum, liver, kidney, etc., would be as common a phenomenon here as in the fishes.
The germ-cells of vertebrates generally are, since 1900, beginning to be regarded as undoubted products of the egg-cleavage.* Since Wilms, Bonnet, Marchand, and Borst consider certain teratomata, at any rate, to be the offspring of cleavage-products, there would appear to be an identity between their conclusions and my own in this respect. Nothing could well be farther from the true facts. Taking Wilms as the leading exponent of the one side, the divergences between the two views work out as follows;
By Wilms and other certain tumours, not by any means all, are referred to cleavage-cells, not identified as germ-cells, but really destined to form some part of the embryonic body. These cleave-cells are “shunted” from the normal connection at some very early, but not defined, period of the development. As so derived, they are parts of the organism in which they occur. Against the above, the writer’s conceptions may be stated in the following:
Most, if not all, true tumours are pathological manifestations of some portion of a life-cycle, and they are due to abnormal attempts at development on the part of aberrant germ-cells, derivatives of the cleavage, and destined, not for the embryonic body, but for future generations. Such vagrant or persistent germ-cells are the sister-cells of the one by whose unfolding the “embryo” or individual arose, and, developing pathologically alongside and within another (sister) form,
*Compare the recent monographic works on Embryology by Korschelt und Heider, and by Waldeyer.
with degeneration of some of their products, they leave as the basis of a tumour a greater or less number of cells, endowed with more or fewer potentialities. As so derived, they are not parts of the organism, but are its sisters or brothers, identical with it in ultimate characters.
As indicating the amount of agreement between my conclusions and those of Wilms, and the extent to which I have adopted his views, except in so far as these are embryological, the following passage from his latest work (1903) may be cited: “The groups of tumours are of equal value in their etiology; they differ among themselves only in that the one groups arises from cells of the earliest period of development—the time of the cleavage; the other, from cells of somewhat later time—the period of the formation of the germinal layers” (p. 270). This I would amend as follows: “In their etiology the tumours are of equal value, and they are the results of pathological bizarre attempts at development on the part of aberrant primary germ-cells, originally identical, in characters, and, in fine, in all respects, with that primary germ-cell, by whose unfolding the individual harbouring such a tumour arose. As the offspring of primary germ-cells, they may be referred to cells of the cleavage, but not to such appertaining to the embryo. They never arise from cells of the period of embryo-formation (Zeit der Keimblattbildung).
The comparison sufficiently emphasizes the divergences, and, be it added, the existence of ovarial and testicular embryomata is decisive against their derivation from cleavage-cells in the sense of Wilms and Bonnet; for none such appertaining to the embryo can find their way into these organs, but instead thereof there are germ-cells, which originally go back to the cleavage. In passing, Wilms’s denial of the possible origin of an embry-
oma from a germ-cell of the testis may be cited as an instance of a refusal to recognize the plain and simple facts of the writer’s researches upon the germ-cells.
As further evidence for the origin of embryomata from cleavage-cells (of the embryo), Wilms refers to the unilateral nature of many of them. This is supposed to indicate something corresponding to the results of Roux’s well-known experiments upon the egg-cleavage of he frog, which many years ago were believed to demonstrate the “prospective destinies” of, say, the first four products of the cleavage. It must always be difficult to determine what the researches into so-called “experimental embryology” really demonstrate, more especially in view of the discrepancies in the results of the different observers; but to most of them it would probably be more correct to apply the term “experimental pathology,” for the finds border on pathology rtather than upon embryology. Normal larvæ of reduced size may have been obtained by such experiments; normal embryos—Roux’s “hemi-embryods” are not such—have never been a result. Roux’s particular finds probably ensued not because he had experimentally halved the cleaving germ, but because in trying to do this he had induced pathological changes. If the hem-embryomata referred to by Wilms be hem-embryos in Roux’s sense, this ought also to apply to the individual harbouring them. As a matter of fact, it is a pathological change in the embryomata which induces the halving, as evidenced by several pathological skate embryos, described by me, in nearly all of which there were marked reductions, either in the head-end or on one side of the body.
Marchand and (formerly) Wilms have been disposed to derive the embryomata from fertilized polar bodies. The writer must emphatically reject this view. Wilms
relinquished it, because in one instance he found not less than five embryomata in a single ovary, and, of course, this number of polar bodies has been met with nowhere in the animal kingdon. Even two embryomata, a tera-toid in the cranial cavity and an ovarian embryoma—a condition recorded—suffice to negative the possibility; for it has been pointed out to me that nowadays it would appear to be the rule in mammals that only one polar body should be formed.*
Wilms (loc. Cit., p. 250) sums up his ideas pretty clearly in the following: “In other words, double monstrosities, fœtal inclusions, and embryomata are all, indeed, to be referred back to an over-production (!) in the early development, but only in the double formations (Bildungen) do the cleavage-cells (Furchungskuglen) and the formation proceeding from them develop at the same time; in the other cases the one of the two only attains development at a later period.”
Before treating of the comparative embryology of the tumours at length, one or two other things call for notice. Marchand, and finally Wilms, consider all the teratomata as of equal value morphologically. With this I would express cordial agreement. A vagrant germ-cell, developing pathologically in pericardium, abdomen, sacral region, or elsewhere, to form a more or less rudimentary embryo, in doing this is giving rise to something exactly comparable to an embryoma of ovary or testis. On p. 251 of “Die Mischgeschwülste,” Wilms writers: “A series of sacral teratomata is remarkably completely developed. An embryo en miniature in the most exquisitve fashion may be developed.” He goes on to say that he himself possesses
*This was written in 1903, but now (1911) more recent researches of Sobotta, Burckhard, van der Stricht, Lams, Doorme, and J.P. Hill, have shown that in certain mammals the first polar body is formed in the ovary, and afterwards disappears.
of a sacral teratoma from the
The mixed tumours here referred to by Wilms—the tumours into whose nature and characters he has carried out such brilliant observations—furnish the key to the general problem of the etiology of the tumours in general. Wilms’s writings upon the mixed tumours of the kidney, vagina, uterus, mammary gland, and parotid, are of intense interest, even to the embryologist. To my mind they justify completely his conclusion that they and the embryomata are of like etiology (loc. Cit., p. 279). In his further attempts to trace their embryological history one cannot agree with him; for, just as he derives the embryomata from blastomeres (of the embryo), and not from vagrant germ-cells, so he assigns as the origin of the mixed tumours “shunted germs” of later and later periods. Certain of the vagrant germ-cells, defined later on, amply suffice to account for the mixed tumours also; indeed, the basis for these and other tumours may be found in (1) the actual existence of vagrant and aberrant germ-cells, and (2) the embryological fact that
each and every primary germ-cell (those of the ovary and testis, of course, included) possesses the faculty of that primary germ-cell, which unfolded as an embryo, of doing likewise.
Of great significance with reference to the question of the germ-cell origin of tumours are the comparatively frequent instances of tumours arising in multiple centres. Some of the recorded cases may be cited from Borst (Iloc. Cit., p. 57, A, et seq.). In the same individual, tumours have been found in liver, uterus, ovary, kidney, skin, etc.; or, again, in the paired organs of the two sides. Babesiu found in the uterus, in the middle of a myoma, a columnar eqpithelial cancer, and Niebergall recorded a complicated uterine tumour of myoma, polypes, sarcoma, and cancer. Equally important and significant to the embryologist are the facts relating to the occasional presence of different tumours at the same time in different parts of the body. Borst (loc. Cit., p. 58) gives the following instances:
1. Cancer of the stomach with ovarial cystoma and fibroma of uterus.
2. Cancer of skin and of rectum.
3. A teratoid of the cranial cavity and an ovarian embryoma.
4. Uterine myoma, lipoma of kidney, enchondroma of lung.
5. Cancer of the thyroid, and multiple fibromata of kidney and uterus, with large papillomata of skin.
Borst looks upon all these and other recorded cases as accidental! They are interesting, however, in the light of—(1) the hypothetical germ-shunts; (2) the various places in which vagrant germ-cells, may be found, and (3) the probably necessity of a certain physiological condition or nidus for the development and growth of a tumour of a certain character.
In the comparative account of the tumours I shall follow the lines laid down by Wilms, and, therefore, it is his summary of them, not mine. His account of their comparative anatomy appears to me to be logical and convincing; and in giving his results in tabular form I should like to say with what intense interest and instruction I have studied his writing. As elsewhere stated, the highest and most complicated tumours—the cystic embryomata of ovary and testis (Wilms)—are at the basis instances of identical twins with one abnormal embryo, the enbryoma. If nothing else would account for their pathological development, the circumstance that neither they nor any of the less complicated tumours can, from their mode of origin, contain sexual organs might suffice. They are, therefore, sterile embryos; and in other directions my researches have convinced me that embryonic sterility may be the source of pathological changes.
From the facts established concerning the tumours by pathologists, it is clear to the comparative anatomist and embryologist that in certain respect they present certain analogies to instances of parasitism among animals. They differ, however, markedly in being, from the mode of their development, sterile organism, even in the best-developed cases. The resemblances between tumours and parasitic Metazoa or higher animals may be exemplified by a short account of certain snails parasitic upon Echioderms (starfish and the like). The series is derivable from free-living Eulima species. It may be taken as beginning with Mucronalia eburnea, which is an external parasite, and possesses the full organization of a snail. Stylifer linckiœ is also an ecto-parasite, but it is partially encapsulated upon the host. In this case the foot is rudimentary, and the radula is absent.
Through other species of Styifer, Entocolax ludwigii is reached. This is parasitic in the body-cavity of a seacucumber (a Holothurian), and with the endoparasitism the shell, mantle, gills, and sense organs disappear. The series culminates in Entoconcha mirabilis, parasitic in the sexual organs of a sea-cucumber (Synapta digitata). This is nothing but a worm-like sac, containing (hermaphrodite) sexual organs. In its organization there is nothing whatever of molluscan characters, and its true nature can only be made out in one or other of two ways: by the comparative anatomy of the series of such parasitic mollusca, which reveals all the stages from highly organized forms down to absolute reduction of most or all of the organs, or by the study of the development; for, as Johannes Müller showed in one of his classic works, Entoconcha is a true gasteropod, with shell and other organs.
As it is impossible to follow the whole development of a tumour from its first start, and as many of them attain only a very low degree of embryonic differentiation, the series of forms in them, leading from the highest to the lowest, from the most organized to the simple onles, can only be followed after the method of comparative anatomy, and this is the plan adopted by Wilms in his researches. From the results of a study of tumours made in this way, and with the facts established by the writer’s researches upon the germ-cells, and the course of the cycle of development of the higher animals, the following conception* of the true nature of a neoplasm or tumour is obtained.
A tumour is a more or less reduced, more or less incom-
*It should be specially noted that in this definition malignant tumours (carcinoma and sarcoma) are excluded—only tumours representing the sexual generation are included.
pletely differentiated sterile Metzaoan or higher animal organism, which, starting by the abnormal development of a vagrant primary germ-cell, and growing under conditions unfavourable to the complete and normal differentiation of all its parts, unfolds and develops those things, for whose growth the nidus is suitable, the rest degenerating. And, exactly as identical twins are the offspring of two sister or brother germ-cells, identical in ancestry from the same primitive germ-cell, and identical in all ultimate characters, so also any higher animal, and a tumour within it, stand in the same relations of ancestry from one primitive germ-cell, have the like ultimate characters (identity) at the starting-point of their development; but, unlike fully-developed identical twins, the individual and its tumour develop in different directions: the one upwards along the track of higher and higher organization, the other downwards, along the roadway of abnormality, of degeneration, of arrest, even at times—when the asexual generation is represented—of riot, destruction, and disaster.
The highest tumours, then, are (1) the cystic embryomata. On these follow (2) the solid embryoid or teratoid tumours of the ovary, containing skin, gut, and “mesoderm” and derivatives of these. (3) The less highly developed ones of the testis. Like the foregoing, these are “three-layered,” the skin is scanty, they contain gut and trachea, the head-region is rudimentary, and their growth is unlimited. Borst has recorded in them ganglion cells and sympathetic ganglia. (4)Teratoid tumours, where the “embryonic” tissue is mainly sarcomatous (cancer or asexual generation). (5)Teratoid tumours of the testis with the epidermal layer lacking. (two-layered tumours of Wilms). There teratoids lead to (6) the more complicated sacral and parotid tumours, and
as in them, there are, according to Wilms, all transitions down to the simplest, these latter being sarcoma (cancer, or asexual generation). (7) Mixed tumours of the breast, kidney, cervix, uterus, vagina, and parotid. These are sometimes, not often, two-layered (epidermis), and they are usually made up of tissues, which can best be described as sarcamatous (cancer, or asexual generation).
B. THE ETIOLOGY OF TUMOURS.
The foregoing really forms a continuation of extension of the section on “Dermoid Cysts and Teratomata,” in a memoir* published by me some years ago. On p. 671 it was written, “How, it may be asked, shall one limit the possible reduction of an embryoma? Where shall the line be drawn?” The present chapter offers an answer to that question. As the writer suspected in 1900, no line can be drawn between an embryoma and a simple tumours. In this connection, apart from the references to the writings of Wilms, it may be of interest to quote from another writer and able pathologist, L. Pick. † On p. 1193, in discussing the bearings of his finds, Pick writes: “As I have already shown elsewhere, it would be false to identify in an embryoma that which, of sorts of tissue or organs, is finally preserved with that which was originally laid down in it in the germ. We know that here occasionally only a certain kind of tissue attains development, that alongside this all other tissues wither in their development—indeed, completely vanish—or by the one-sided tumour-like growth
*Beard, J.: “The Germs Cells,” part. I., Raja batis,, in Zool. Jahrb., Anat. Abteil., 1902, vol. xvi., pp. 615-702; loc. Cit., p. 669.
† Pick, L.: “Zur Kenntniss
der Teratome: Blasenmolenartige
Wucherung in einer “Dermoidcyste” des Eierstocks,” in Berliner klin. Wochenshr.,m
of the one sort of tissue may be actually destroyed, or ‘suffocated.” In this way at one time a true embryoma may be found in the curious form of an isolated tooth, at another time, perhaps, as a sort of glioma, or as an ovarian true thyroid-struma, or, again, as a chorio-epithelioma with metastases.”
In other respects Pick’s communication is of great interest. His researches have established for, at
any rate some, ovarial teratomata, as Schlagenhaufer’s* had already done for the
like tumours of the testis, the occurrence of a choiron or trophoblase—in the
instance recorded in a more or less degenerate condition. Their finds throw a considerable amount
of welcome light upon the (according to Wilms†) frequently malignant character
of the testicular embryomata, and the cases—some nine in 1902, to which Pick’s
instance furnished a tenth—other the occurrence of cancer in connection with an
ovarian embryoma. As in the
ordinary chorio-epithelioma of gestation, in embryomata of ovary and testis,
carcinomatous growth, when present, is now (1903) recognizable as having arisen
from the asexual generation (chorion or trophoblast). These words were actually read to a
large audience, as occurring in a paper on “The Embryology of Tumours,” by me,
*Schlangenhaufer, Fr.: “Über das Vorkommen chorio-epithelioma and traubenartiger Wucherunger in Teratomen,” in Wiener klin. Wochenshr., 1902, Nos. 22-23.
†Wilms, M.: “Die mischgeschwülste,” 1902, iii., p. 242.
and this included the above
words, and sent it to the editor of Ziegler’s Beiträge, and of the Centralblatt für allgemeine Pathologie,
the celebrated pathologist and man of science, the late Geheimrat Dr. Ernst von
Ziegler, Professor in Ordinary of Pathology in the University of Freidburg in
Breisgau, with the request that he would publish it in the latter scientific
journal. He replied that not only
would he do so, but that he would have it translated into German, so that more
people might read it. It appeared
in full in vol. xiv., pp. 513-520, 1903.
In March, 1905, some two years later, a discussion took place in
Embryologists and pathologists might have been expected to have taken the following words † by the late
*For a summary and translation of this, see Appendix B.
†Giacomini, C.: “Probleme aus Entwickelungsanomalien d. menschlichen Embryo,” in Ergebn. Anat. U. Entwickelungsgesch, in 1894, vol. iv., pp. 615-649; loc. Cit., p. 640. The actuall words are: “Das Chorion ist von allen Bildungen des Eies diejenige, welche vor jeder anderen entsteht, sich bald von den anderen Teilen unabhängig macht, und indem es frühzeitig seine Zellen entwickelt, in den Stand gesetzt wird, zu leben und zu entwickeln, auch wenn alle anderen Teile des Eies durch irgend welchen Umstand aufgehört haven, zu existieren.”
Professor C. Giacomini seriously to heart, instead of ignoring them: “Of all the structures of the egg, the chorion is that which arises before every other, quickly makes itself independent of the others, and, by the quick development of its cells, is placed in a position to live and to develop even when all other parts of the egg, through some cause or other, have ceased to exist.”
In recent years the writer has urged again and again that in researches upon animal development two things must be kept sharply separate: the embryo or sexual form and the asexual foundation—in human development the chorion or trophoblast—upon which it arises. According to orthodox embryology this chorion or trophoblast is a part of the embryo, although it is invariably present before any part of an embryo; although it may persist after the complete disappearance of the embryo; although it is never formed from or by an embryo; and although ultimately it never makes any part of the embryonic body! Logically, how can it be maintained that a structure which arises before an embryo, and out of no part of it, and which never goes to form any part of any organ of the body, is embryonic or fœtal in nature? What is there to prevent, as Pick suggest, the total disappearance of all parts of an ovarian or testicular embryoma except the (pathological) chorion or trophoblast? The persistence and further growth of this would but, and does, result in cancer (carcinoma). He who doubts this had better read the facts as they were described in 1905 by Dr. L. Pick and as they are given in abstract in the Appendix. As the chorion is always present before an embryo, nothing in the abnormal development of a vagrant or aberrant germ-cell would appear to forbid the arrest of this prior to the appearance of any trace of an “embryoma,” with the natural sequel—a carcinoma.
But, surely, now, the etiology of cancer is as clear as that of the tumours in general!
Very shortly after the date of writing the above, a little further light was obtained in another direction. It is a natural question to ask, “Can any and every primary germ-cell undergo abnormal development, or is this power limited to certain of them?” A full reply to this would entail prolonged investigation into the developmental problems of identical twins, triplets, etc. For a long time now (1911) this matter has engaged the writer’s attention more or less, but though some landmarks can be recognized, the end is not yet in sight. So far as I can see, the whole doctrine of the tumours and cancer centres in the problems of identical twins, triplets, etc.—in fine, in the question of the number of embryos which may arise from one egg, and therefore be contained in one chorion or trophoblast.
A full discussion of identical twins, etc., must be reserved for another
occasion, in a projected book upon
heredity. Here it need only be
stated that their occurrence is probably more frequent than has been supposed
hitherto. By competent authorities
it has been estimated that in man identical twins form 25 per cent. of all
twins. Their comparative frequency
alone is against the idea of their occurrence being due to, say, a chance
division of the developing egg. The
absurd supposition of their etiology by “the splitting of a germ” was exposed by
me in a letter in the Lancet,
the writer has several times
come across them in utero. There exists, however, a case in
literature of embryology, published in three different scientific journals of
high standing—that of an armadillo, the “tatu” (Prapus hybirdus) where, according to von
Jhering,* from seven to twelve young are formed within one chorion—that is, as
products of one egg. The
observation tallies with, and is allied to, that already recorded by A. von
Kölliker † in 1879, of four fœtuses
within one chorion in a related species, Dasypus (Prapous) novemcinctus (the nine-banded
armadillo). Not long after the
above was written, aided by a small grant from the Carnegie Trust, I was able,
with the kind assistance of Professor von Jhering, to obtain from
A further step may now be taken, and it may be insisted that the tumours, including cancer, date back to this condition as their source. In the course of ages, one or more of the former identical twins, triplets, etc., has become rudimentary; but it, or they, may reappear
*von Jhering, H.: “Über ‘Generationswecjsel’ bei Säugetieren,” in Biol. Centralblatt, in 1886, vol. vi., pp. 532-539; also in Berliner Sitzungsberichte and Arch. F. Physiologie, 1886.
† von Kölliker, A.: “Entwicklungsgeschichte des Menschen,” II. Augl., 1879, p. 362.
in the form of embryomata, finally of tumours, even of cancer. In this way it comes to be recognized that there must be a vast difference among the various vagrant and aberrant germ-cells in potentialities for mischief. Some few, and not all—how many in each case it is at the moment impossible to say, and it may never be determined—possess the potentiality of developing like the embryo containing them. If they do this normally, identical twins, triplets, etc., may result. If they do not degenerate, and degeneration is probably often their fate, they may come to lie somewhere or other in the embryo, even in its sexual organs. Here they may be encapsulated for a longer or shorter time, and, finally, one or more of them may commence (abnormal) development, and form an embryoma, or other tumour even, by attempting to begin the whole cycle anew, with arrest in the embryonic portion—a cancer.* Vagrant germ-cells in development are, I imagine, far too numerous for anything like all to be required to account for the tumours and for cancer. Probably it may be regarded as sufficient if there be in every development at least one, three, or seven such, which, if they do not degenerate, may become the seed of later tumours. To the embryologist it is of great interest to establish that, as in the upward direction the embryomata pass step by step into identical twins, triplets, etc., so as gradually in the downward one
*It should be mentioned that pure embryomata, as true, benign tumours, are probably in all cases congenital—that is, commencing their development at the same time as the individual harbouring them. Apparently, this does not invariably exclude the appearance of malignancy in some of them at a later time. On the other hand, malignant disease (carcinoma and sarcoma) is not congenital, but the seed of such a tumour is to be found in certain of the latent germ-cells, as described in the text. Of course, cancer is hereditary, no matter what all the official cancer-researchers in the world may say. The true nature of heredity is as far from their thoughts as the principles of modern embryology.
they merge into the simple tumours, and that any portion of the life-cycle of normal development may manifest itself as a tumour.
From the above it may have become manifest that for the elucidation of the nature of the tumours two things are needed: pathology, a much fêted and daily more and more endowed branch of learning; and embryology, the science of the coming-into-being of life, at present the handmaid of many sciences, and almost without a habitation to call its own.* This despised and rejected branch of human knowledge, whose task it is to treat of the “Werden und Vergehen” of living things, is in importance second to none. Without its light, much possible knowledge in other sciences is enshrouded in thick pitchy darkness; without it one branch of pathology at least could have no real scientific existence. In certain direction we may turn to pathology for the collection of the facts, but to embryology for their explanation. The pathologist may know the facts, but that knowledge gives him no key to their solution; for this lies in the study of the normal development of living things—embryology.
*Eighteen years ago there died an English embryologist, a wealthy man,
who had for years devoted some of his means towards the advancement of
science. In the medical faculty, in
which he taught, embryology was lectured upon by five different medical
professors to large classes of students, while he, a specialist, had practically
no students. His course was not
prescribed in the regulations.
Embryology is to-day (1911) in
THE PROBLEMS OF CANCER*
Under this title the
following remarks were published in the Lancet in 1904 as a summary of a
University lecture. The objects in
view were to throw some embryological light on the possible lack of import of a
practical kind attaching to certain recently published observations on so-called
“heterotypic” mitoses or cell-divisions in cancer-cells; to point to the
futility of regarding carcinoma as due in origin to some sort of “conjugation”
of leucocytes of the body; and, lastly, while insisting upon the fundamental
identity of carcinoma and sarcoma, to indicate how the problems of cancer
finally ended embryologically in those identical twins and their origin. The import, or absence of import, of the
first two—the “heterotype” mitoses and the supposed “conjugation”—has now been
generally recognized, and the original position taken up regarding these has
been abandoned by official cancer research in
The fundamental problem, the very basis of embryology, is the course of the life-cycle in the higher animals, including man. This question of the mode of the development far exceeds in import all other problems of pure embryology. It touches upon, without at present offering any explanation of, the nature of life itself. But while the latter is now beyond human grasp, and may elude it for ever, the solution of the great problem of the life-cycle, seemingly so complex, albeit so simple, furnishes results of overwhelming import for all the sciences of life. The history of embryology tells us how for centuries the fight, whether epigenesis or preformation, went on; how, on the one side, the development was regarded as analogous to the building of a house, “part being added to part,” and how, on the other, men like Haller denied any coming into being, the embryo being preformed in all its parts. So slow is real progress in a science like embryology, and so greedily receptive of error is the human mind, that in our day we hardly dare hope to see the last of the two rival erroneous doctrines of epigenesis and preformation. Like the chameleon of the story, “the creature’s neither one no t’other.” Underlying the phenomena of development in the higher animals there are an antithetic alternation of asexual and sexual generations, a morphological continuity of germ-cells, which, paraphrasing Robinson’s eloquent words, go back to a beginning so remote as to be utterly beyond our knowledge, and pass to a future of which we can form no conception whatever. Under the phenomena presented by the germ-cells in their cycle direct development and epigenesis can find no places. Looked at in the light of the facts, they are impossibilities
and, like the recapitulation theory, merely illusions of the human imagination. An antithetic alternation is seen to be an iron necessity of the development as soon as it is perceived that an organism, an asexual one, must develop upon which germ-cells can arise; while the sexual generation, “the embryo” of embryologists, is called forth from one of these germ-cells to contain and to nourish the rest for a certain brief span of time. Moreover, the facts of development, which to some extent have been unearthed during the past fifteen years within this city, throw a flood of new light upon the crude materialism of modern embryological textbooks. The biophores of Weismann and the pangens of De Vries become shadowy entities of the real existences of which there are no evidences. And while with humility admitting that to say it is to furnish no explanation of the riddle of life, it must be recognized that the characters or qualities of animals or plants are certainly not present in the germ in the shape of ultra-microscopic particles of chromatin, the pangens or biophores, but that all the wonderful and infinite variety of animate nature has its fount in unconscious memories of germ-cells.*
Modern embryology, not to be confused with that extant in textbooks, claims as its own two vastly important regions of human knowledge. These are the facts and nature of heredity and genetic variation and
*For a fuller account of the theory of heredity based in the unconscious memories of germ-cells, set up by Professor Ewald Hering, now Director of the Physiological Institute in the University of Leipzic, in 1870, see Beard, J.: “Philosophical Biology,” in Ainsworth Davis’s “Science of To-Day,” vol. ii., 1909, pp. 37-64, with list of literature, which should also include Samuel Butler’s “Unconscious Memory,” first edition, 1880, revised edition, 1910 (Fifield, London), and the presidential address to the British Association for the Advancement of Science, 1908, by Professor Francis Darwin.
that portion of pathology treating of the tumours or neoplasms, benign and malignant. The phenomena termed “heredity” are germinal in nature, and in this way they fall within the province of the embryologist, not in that of the mathematician. But at first sight it is, perhaps, not so clear that neoplasms—living things possessing simple or complicated structures, but devoid of any useful functions—should be entities about whose nature the embryologist need concern himself at all. As recently as four years ago—that is, in 1900—but few of the higher teratomata were recognized as embryonic in nature. Now almost the other extreme has been reached, and possibly there are few tumours, benign or malignant, the embryonic nature of which has not been advocated by some observer or other, usually a pathologist. By embryonic is meant that their tissues would be identical with—even, according to some observers, derived from—some of those making up an embryonic body, that they would be, in the word employed by Wilms, “embryomata.” As to their origin, apart from the so-called “parasitic theories,” which are more remarkable for the things they leave untouched than for the “facts” they explain, for benign or malignant tumours, or for both, certain erroneous views, not really based in embryology, have within the last year been advocated at home and abroad. Malignant neo-plasms, such as cancer, have been supposed to arise from somatic cells of the individual, either with or without a conjugation of such. To my mind there is a little evidence—and that is none at all—to show that somatic cells could, or do, conjugate with their fellows or with other cells, such as leucocytes. Indeed, the appearances described and figured as conjugation in a cancer are capable of other and simple explanations. Certainly, if
they represent a real
conjugation, the preparation ought to carry conviction to the minds of
embryologists and cytologists, such as, to name three Würzburg ones, Stöhr,
Schultze, and Sobotta. This is
improbable, for the true nature of the preparations shown last July* at
Very common among pathologists is a modification of the Remak-Cohnheim
theory of embryonic rests as the basis of neoplasms. This doctrine of “shunted germs,” only
possible under the erroneous dogma of epigenesis, has many followers, especially
to produce the whole life-cycle, with the exception of the embryonic part. In an unmixed cancer or sarcoma there is absolutely nothing whatever of an embryo; there is not a vestige of a somatic cell.
To reinforce their attitude several supporters of the doctrine of shunted germs have invoked the aid of fertilized polar bodies. Every elementary student knows these, and is aware that nowhere in the animal kingdom have they ever been known to exhibit any potentialities worth of the least notice. To the embryologist versed in recent advances the theory of fertilized polar bodies, with its allied assumptions of all sorts of embryonic rests or germinal shunts, must seem to be one of the most absurd ideas ever enunciated in science. Like the somatic origin and the supposed “conjugation,” this must be rejected. Fortunately or unfortunately, the number of polar bodies formed by the mammalian egg is far too limited to permit of their introduction into the question. No mammal is known in which more than one polar body* arises; while, for example, Wilms found as many as five embryomata in one ovary, and Baart de la Faille † recorded a case of quadruplets where three of the fœtuses hung as more or less incomplete parasites from the palate of the fourth. On the present occasion a few words more must suffice regarding the manifold embryological aspects
* 1911. No mammal is known in which more than one persistent polar body is formed.
† Vide Schatz: “Klinische
Beiträge zur Physiologie des Fœtus,” Archiv für Gynäkologie, 1900. The original paper, by Baart de la
Faille, is said to be very rare.
The specimen is described (p. 252) with some others by E. Schwalbe in
Ziegler’s “Beiträge zur Pathologischen Anatomie,” 1904, vol. xxxvi., pp.
242-272, “Der Epignathus und seine Genese.” This case is illustrated by an excellent
figure in Schwalbe’s “Die Morphologie der Missbildungen des Menschen und der
Tiere,” part ii.,
of neoplasms. They form, and this requires emphasis, only one set of many degenerative and retrogressive phenomena encountered at all sorts of stages of the cycle in comparative embryology. Truly, in dealing practically with embryology, “in the midst of life we are in death.” “Das Werden” is ever accompanied by “das Vergehen.”
The whole doctrine of the tumours centres in the problems of identical twins. Than these latter there is nothing more replete with interest in embryology. Of vast import is the recognition of the existence of two kinds of these. There are identical twins, which come as it were out of the same mould, and there is a second and rarer kind—the “looking-glass-image” twins.* The occurrence of the latter throws welcome light upon various zoological and anatomical questions—on the right-handed and left-handed snails, fishes, etc.—as well as upon the phenomena of reversed viscera. Ion other direction identical twins pass gradually into double monsters, and these in their turn into the higher tumours or teratomata. At the basis of the tumours is the fact that from one fertilized egg a multiplicity of embryos may arise, just as from one such in a sea-polype a legion of jelly-fish may take their birth. As in the polar bodies of oögenesis (egg-formation) we have rudimentary or abortive gametes (conjugating-cells), so in the development of the higher animals we meet with rudimentary or
*These looking-glass image twins are the greatest wonder in animate
nature. Along with Captain Lambelle
and a former pupil, Dr. M. M. Morrison, a few years ago the writer had a unique
opportunity of examining and photographing two of these (twin boys) in the south
abortive germ-cells, originally really destined to form embryos. In other words, in the history of the race there has been a reduction in the number of actual normal embryos arising, but with the persistence of such “embryonic” germ-cells (embryonic in destiny) and the retention by these of more or less of the “memories” needed to unfold an individual of the species. As shown two years ago in the Lancet,* a malignant tumour—and this is true of both cancer and sarcoma—is nothing more than an irresponsible trophoblast or chorion, the asexual generation, which in every normal development is the forerunner of an embryo. Though not recognized, or, at all events, not stated by them, the researches of Farmer, Moore, and Walker, † as well as those of Bashford and Murray,‡ have confirmed the truth of this view, and to the hilt. For it is an inalienable property of the trophoblast of normal development that upon it germ-cells arise. Once these have come into existence, it is but a
† Farmer, Moore, and Walker: “Resemblances Exhibited by the Cells of
Malignant Growths in Man and those of
‡ “The Zoological Distribution, the Limitations in the Transmissibility,
and the Comparative Histological and Cytological Characters of Malignant New
Growths” (Scientific Reports of the Imperial Cancer Research Fund, No. l,
London, 1904). First of all, cancer
was “embryonic,” and then it was not; it arose, for the second or third time in
history, from a “conjugation” of body-cells, and then it did not; the “infective
venereal tumour of bull-dogs” was an infective granuloma, and then, on the very
same evidences, it was a true sarcoma, because like the writer, Mr. Shattock
said it was. It is given to
official research to change its opinions as often as it sees fit. The above paper was put out with a great
flourish as a confirmation of the work of Farmer, Moore, and Walker, and I was
assured that the original discovery could have been made by official
research. Then at a later period
this confirmation was withdrawn, for which see the Proceedings of the Royal
question of a certain limited number of cell divisions before they present the phenomena associated by many embryologists with the reduction of chromosomes. In short, the proof furnished by the researches of Farmer, Moore, and Walker, of the occurrence of divisions in cancer and sarcoma cells usually associated with the maturation of germ-cells, was the one thing lacking to establish beyond question the true nature of a malignant tumour as the pre-embryonic portion of the life-cycle, the asexual generation. While at present it would be wrong to assume that such cell divisions must of necessity occur at some time or other in all malignant tumours—for even a malignant tumour may conceivably be so reduced or retrograded as to be unable to repeat the whole cycle of the germ-cells, just as no tumour is known to form actual sperms—it is now beyond doubt that the occurrence of such division in certain cases proves a malignant neoplasm to be the pre-embryonic portion of the life-cycle. It is a life-cycle with the embryo omitted. Germ-cells never do arise, and never could have arisen, from somatic or embryonic cells or tissues.
The true science of the tumours, then, has its embryological basis in the facts and phenomena of identical twins, triplets, etc. The facts of normal development, as seen in identical twins, as well as in certain armadillos, many sheep, etc., demand that we should recognize that just prior to the unfolding of an embryo there are “n” divisions of germ-cells, resulting usually in one embryonic cell and a certain as yet undefined number of retrograde or rudimentary gametes, these have now lost to a greater or less degree—this varying in different cases—their powers of undergoing a completely normal development. They are not to be confused with those
germ-cells destined for the sexual organs of the individual. A malignant neoplasm, due to the spontaneous development of such a retrograde germ-cell, which in the days of long ago would have given rise to an identical twin, has lost to a greater or less degree those potentialities, those unconscious memories, which would have permitted it to complete the full life-cycle of normal development, ending in the formation of a normal embryo. The memories which it retains condition the character of the tumour to which it will give rise, and it is these rudimentary memories, stimulated by its environment in some particular organ, which result now in a sarcoma, now in a carcinoma, mimicking the structure in which it lies. This explains why in one development a certain germ-cell will produce an identical twin, while the corresponding germ-cell in another instance develops into a monster, or into an embryoma, or into such with a malignant tumour, or into a mixed and malignant neoplasm, or, lastly, into a simple sarcoma or carcinoma. All depends upon the amount of unconscious memory retained by those retrogressive germ-cells, which formerly gave birth to normal embryos, identical twins, triplets, etc. Nay, one may safely take a further step in the like direction. Chorio-epithelioma, a deadly form of cancer in pregnancy, usually rises in instances where either no embryo has been formed (hydatid mole), or it has been aborted at the critical period* as a monstrosity. Is it at all unlikely that here, for some reason or other, either the wrong germ-cell had developed, or, at any rate, that such a one had early usurped the place of the developing
*For a full account of the “critical period” and its peculiarities see J. Beard, “Certain Problems of Vertebrate Embryology,” 1896, and “The Span of Gestation and the Cause of Birth,” 1897, both published by Gustav Fischer, Jena.
one? This would be one the memories of which could but result in a malignant tumour—that is to say, one mimicking the structure of correct chorion. If this be true, we have in chorio-epithelioma merely a form of cancer arising very early in the life of the individual, and invading a new host, the unfortunate mother.
The things that we have been dealing with are startling enough, and it
may be asked. What steps are being
taken to apply them in practice and to carry our embryological knowledge of the
malignant neoplasms still further?
Practically none. Beyond the
*Judging by the recent investigations of Abderhalden and his pupils, and those of Blumenthal and Neuberg, as described in the Introduction, this is now (1911) not the case. As it has turned out in the sequel, cancer was vulnerable along at least two lines of attack, the embryological one, and the stereo-chemical one. It is really along the latter that the above observers are, slowly but surely, advancing.
† This did not take place.
independent establishment of a science of the utmost moment to mankind—the true science of life, embryology. In these condition, and given abundant material of the right sort, we may hope to witness soon advances in our knowledge of the malignant neoplasms of which we can now form no conception, and the vast importance of which it is impossible to gauge.
The three most important points in the above chapter appear to be the recognition that the problems of cancer finally merge into those of identical twins, triplets, etc., of the fundamental identity of sarcoma and carcinoma, and the mimicry of the tumours. The latter, of course, was not new, but it was a revival of a doctrine enunciated early in the nineteenth century by Fleischmann, and later on advocated by the late Sir James Paget. At the time this chapter was written down (October, 1904) the writer was deeply engrossed in the microscopical study of malignant tumours. This work was interrupted by a controversy with Mr. Roger Williams, F.R.C.S., which was started by the latter in the Lancet, and the letters of both sides will be found in that journal of the closing months of 1904 and early in 1905.
In the course of this, in a reply to my opponent, I wrote down the words: “The mammalian embryo solved the problem of cancer ages ago.” After writing this, I looked at it, and said to myself, “Yes, it is quite true, but—how?” Then the thought came, Why are you bothering about the microsocical details of these tumours? You ought to be working at the things which occupied you ten years ago. Without further loss of time I got out all my material relating to the critical period, and the two papers, “On Certain Problems,” etc., and “The Span of Gestation,” which
I had published on these problems, and sat down again to study all. Then—at once—it was seen that the problem of the “how” had been solved ten years earlier, but that no great stress had been laid upon the solution—the commencing activities of the pancreas gland at the critical period. This was the starting-point of Chapter IV., dealing with the chief problem of cancer.
THE CANCER PROBLEM*
In the following simple
story the correctness will be assumed of all the conclusions as to the etiology
and nature of cancer which were advanced in, for example, the abstract of my
lecture on the “Problems of Cancer,” published in the Lancet of
1. Enbryomata (benign neoplasms). –Pathological manifestations of some greater or less portion of an embryo. They are composed of real tissues—that is, normal or somatic (“embryonic”) cells or tissues. At its basis each is a greater or less portion of a twin, triplet, quadruplet, etc., identical with the individual containing it. They are not endowed with indefinite powers of growth, and they nourish themselves like other normal tissues.
2. Amphimyxomata (malignant neoplasms). –Combinations of embryomata and trophoblastomata. Pathological manifestations or attempts to reproduce the whole life-cycle, including trophoblast and embryo. They are transitional forms. (The mixed tumours of Wilms are not all malignant, some being merely embryomata.)
3. Trophoblastomata (malignant neoplasms). Pathological manifestations of the asexual
portion (trophoblast) of the life-cycle and sometimes—whether or not always is not at
present known—attempting to repeat the germ-cell portion of the life-cycle, as shown
by the researches of Farmer, Moore, and Walker. They are not known to differentiate actual functional gametes, eggs or sperms. They never include or repeat any part of an
embryo. They are never composed of somatic (“embryonic”) cells, though they may
mimic such or even resemble no other cells in the body. As Sir James Paget pointed
out long ago,* they are “imitation tissues.” They exhibit powers of unlimited growth
and increase, and they nourish themselves by eroding and destroying normal cells and
tissues in a manner exactly like that of the trophoblast of normal development.
To illustrate the points to be considered, I have put out
*The designation of a malignant neoplasms as an “imitation tissue” was
first used by the writer about a year ago (1903) in an address to the
certain microscopical preparations of transient ganglion cells, parts of the asexual generation of a dogfish. These may be taken to typify the trophoblast of a mammal or the cells of a malignant tumour. The preparations show: (a) cells in full functional activity prior to the critical period, and (b) cells which, with the passing of the critical phase, have entered upon their long, slow course of degeneration by simple atrophy. It would have been preferable to exhibit preparations of trophoblast, but those made after this method some years ago are now faded. The facts in the two cases, the mammal (sheep, pig, and others) and the fish (Scyllium, Raja, and others), are, however, quite similar. There is, indeed, only one mode of development in vertebrate animals. Freshly made preparations of human trophoblast of, say, the fifth and ninth weeks of gestation would display the like bloom on the one side of the critical period and the same decay on the other. Such figures of mammalian trophoblast have, indeed, been published already in the writings of my friend Dr. J. P. Hill.
The question which I wish to discuss is one which interested me exceedingly some years ago, long before its significant bearings upon the cancer problem were obvious. In a nutshell it is this: Why do these and certain other cells of a fish development, like those of the mammalian trophoblast, go on flourishing for a certain definite portion of the early development, whilst the parts of the sexual generation, “the embryo,” are unfolding, and then with an almost tragic suddenness commence to degenerate and die? What brings this remarkable change to pass, one which in human development is lacking, if “the embryo” be absent or very abnormal?
Cancer is an irresponsible trophoblast. The unfolding
of an embryo would stay its growth just as the formation of the sexual generation ends the growth of a shoot of a flowering plant. How does “the embryo” bring about this result? It does not devour the trophoblast, but it must produce something which, as was pointed out two years ago,* brings the degeneration to pass. Only in ordinary chorio-epithelioma is the malignant neoplasm a persisting portion and derivative of the trophoblast of the immediately previous gestation. Any ordinary cancer or sarcoma is anew development of trophoblast, due to the attempt of a germ-cell to start the cycle anew. Except in mode of nutrition, this irresponsible trophoblast does not resemble normal trophoblast, but it often mimics the structure in which it lies or it is like no other organ or tissue in the body. In any and every higher mammalian (Eutherian) development there is the potentiality of a malignant tumour, † chorio-epithelioma, and this danger exists until the degeneration of the trophoblast is an assured but not completed fact. As researches made some years ago, but never published, demonstrated,
* The Lancet,
† So far as is at present known, chorio-epithelioma does not occur in any mammal except man. The multiplicity of embryos in most other cases is against its happening. In almost every gestation in the pig, and often in the rabbit, there are abortive embryos, from the trophoblast of which a malignant tumour might arise but for the presence and influence of the other embryos. In the course of the discussion the case of a full-time anencephalic (headless) human fœtus was cited as against the validity of the conclusions advanced. In this the entire alimentary canal and pancreas were absent. A little cross-examination elicited the information that nothing was known as to its fœtal membranes, and that it was one of twins. The latter point is decisive in explaining how this monster had escaped the weeding-out of the critical period. Had it been a single embryo, not a twin, it would undoubtedly have been aborted at the critical period, and, moreover, hydatid mole or chorio-epithelioma would very possible have followed.
in the pre-critical period the staining of the trophoblast cells resembled that of the function transient ganglion cells-with methyl-blue eosin they took on an exquisite blue stain. With the passing of the critical period the cells of the trophoblast, as Hill has shown for the bandicoot (Perameles), no longer took on the blue stain, but absorbed ever more and more the red eosin. The like change will be noticed in the transient ganglion cells of the fish; it is also seen in the merocytes* of the yolk.
Rather less than two years ago I really commenced to work at the problems of malignant neoplasms from their embryological aspects. The starting-point for research here was obtained from certain results of prolonged investigations into the mode of vertebrate development. From these it had been established beyond question that in the normal life-cycle of development in any of the higher animals there were two generations—an asexual one, the “larva,” or phorozoon, and a sexual one, “the embryo”—that the former was mainly, if not entirely, represented in mammalian development by the trophoblast, and that in every normal development the trophoblast was suppressed by the sexual generation, its de-generation commencing at the critical period with the completion of all the parts of the embryo. For the past eight years it had been recognized that at the critical period a change in nutrition always occurred. In 1902† the conclusion was advanced that cancer was an irresponsible trophoblast, the continued and unbounded
*”Merocytes” are certain curious nuclei, or, perhaps cells, with no particular cell-substance around them as a rule, which occur in the yolk-sac of many fishes. Often they are much elongated and branched, due to incomplete cell-division (pluiripolar mitoses). Apparently they are asexual structures. The writer has, as yet, not published all his observations upon these merocytes.
† The Lancet,
growth of which was favoured by the absence of an “embryo” or sexual generation.
At that time there appeared to be one hopeful outlook for cancer research along the lines of embryology. It was that in every normal development the trophoblast, which in the absence of a completed embryo might become a malignant tumour, chorio-epithelioma, was invariably suppressed and degenerated. The task was to find out how this came about; for there appeared to be good reason for the hope, if not for the sure belief, that the factor or factors which brought about this result in normal development might also be potent when directed against an irresponsible trophoblast or cancer. To find these factors would be the solution of a general scientific problem of which apparently cancer was but a special case. These factors have now been found, and in consequence cancer ceases to be a problem for the embryologist. A scientific solution of a certain problem has been obtained; whether or not this be at the same time a solution of the cancer problem in its medical aspects would not be for the embryologist to predict. He can only guarantee the truth of the embryological findings and conclusions, and maintain that these would remain, even though they should fail utterly when applied in the treatment of malignant tumours.
The change in nutrition initiated at the critical period in vertebrate animals, from fishes to man, is based in the commencing functional activities of the pancreas-gland or sweetbread. This introduces an alkaline digestion by means of the pancreatic juice with its various ferments. But what of the pre-critical nutrition? There are many ways in which this might be investigated. One might examine normal trophoblast, cancer or sarcoma, blastoderm of a fish—such as the skate—cleaved eggs of an amphibian, or
blastoderm of a bird, all these being in the main homologous structures or asexual generations. What is found to obtains in the one must hold good in the others, for there is but one mode of vertebrate development. In this direction, when dealing with the yolk and merocytes or fish-development and with the mammalian trophoblast in past years, some results had already been obtained; and in taking up the thread anew one’s thoughts reverted naturally to the chick and frog. In a recent publication Professor M. M. Hartog* writes (p. 587): “One thing is clear as the result of this: all probability henceforward is in favour of the view that in the animal, as in the plant, a cell can only utilize its reserves secondarily and mediately—by the internal secretion of an enzyme.” The author commences his paper by commenting upon the known facts that it has been shown in every case examined that in the utilization of reserves in plants a ferment or enzyme is always present, which in suitable circumstances can effect in vitro the same process—usually of hydrolysis—which the living organism performs. He next proceeds to demonstrate that in the early development of animals, in the cells of the frog’s egg, in which cleavage is ended, but no embryo yet present, and in the blastoderm of the three or four day’s chick, there is a proteolytic ferment present. Under proper precautions, this in acidulated solution (from 003 to 007 per cent hydrochloric acid) gives the biuret reaction showing the presence of peptone. The reaction is absent in neutral or slightly alkaline solution.
*Hartog, M. M.: “Some Problems of Reproduction—II.,” Quarterly Journal of Microscopical Science, 1904, vol. xlvii., pp. 583-608.
On p. 587 he arrives at the
important conclusion that the digestion in the frog’s egg (prior to the
appearance of an embryo) and in the blastoderm of the chick (with the embryo
removed) must be a purely intracellular acid one.* For comparative and other reasons I now
apply this conclusion to the trophoblast of a mammal and to the cells of a
malignant neoplasm. No more than
those of the trophoblast do the cells of a cancer contain yolk. None the less, in both the digestion
must be the “ancestral” acid “peptic” (intracellular) one, characteristic of the
asexual generation of a vertebrate, for this has been handed down as an
unconscious memory from the time when the mammalian yolk-sac contained food
material. Recent researches,
especially those of
† petry, Eugen: “Ein Beitrag zur Chemie maligner Geschwüste,” Zeitschrift für Physiologische Chemie, 1899, vol. xxvii., p. 398.
researches, this is evidently of an (? Intracellular) acid nature, like that recorded by Hartog for the chick blastoder, etc. Petry’s work is cited in the latest edition (1903) of Hoppe-Seyler’s “Handbuch der Chemicschen Analyse” 9p. 387) as proving the presence of enzymes in malignant tumours.
In this connection it would be of interest to cite some of the discussions upon “Extrazelluläre und Intrazelluläre Verdauung” and upon the enzymes or ferments in Verworn’s “Allegemeine Physiologie” (pp. 161 et seq.) In studying the history of the yolk-sack of fishes I made many observations upon this question some years ago. At times one meets with cases in the yolk sac which are more “extracellular” than “intracellular.” Ultimately, indeed, the latter passes into the former. In the sequel therefore, the term “intracellular” will be used within brackets to indicate not so much its actual nature nowadays as its origin in past times from a real intracellular digestion occurring in the presence of yolk. In the chick or skate the yolk is contained in a yolk-sac; in a frog, within the cells of the cleavage. None the less, the ferment is the like one.* The trophoblast of normal
*It should not be forgotten that, as Verworn remarks (op. Cit., p. 171,) there exists a “quite overwhelming abundance of ferments.” Hartog would seem to assume that the one discovered by him in the cleaved frog’s egg and in the blastoderm of the chick, which must be common to the asexual generations of vertebrates, is the same as, for example, the enzyme of the mammalian stomach.. For present purposes it is not needful to insist upon this. Here it will be maintained that this enzyme of the blastoderm trophoblast, or malignant tumour can only act in a slightly acid medium, and that in all probability it is a much weaker one than that characteristic of then the pancreas. The existence of the asexual enzyme and of the sexual one may account for the necessary existence of a gastric and an intestinal digestion. The sexual generation is of later origin in time than the asexual one, and its evolution has been bound up with that of a new digestive gland and enzyme, the pancreas, etc.
development, like the trophoblastoma of chorio-epithelioma, nourishes itself by an (intracellular) acid digestion. A malignant tumour, a cancer or sarcoma, nourishes itself in exactly the like manner. Like the trophoblast, it eats and erodes its way, destroying tissues by an (intracellular) acid digestion. Only by such could a cancer erode bone.* To describe in detail what should follow would be to recite much of two papers † published long ago as well as some other points noted since that time. The solution of the question is possibly the resolution of the problem of cancer. The mammalian embryo solved this ages ago; indeed, it “inherited” the solution from “ancestors” much lower down in the scale. The very existence of “the embryo” throughout the higher animals is dependent upon the suppression, the degeneration and death, of the asexual foundation upon which it came into being. In many invertebrata the sexual generation eats up “often by phagocytes or wandering cells” the asexual foundation or “larva”; and it must be recognized that in the higher forms it practically digests it. On the present occasion no account of the work required to establish it need be given; much, not all, of it is contained in my published memoirs. The fact may be stated briefly that in fish and mammal alike it is the
*This remark about the power of cancer to erode living bone was a trap for the unwary, deliberately set by the writer. As had before happened, it caught its victim with certainty; for at once it was asserted, as I had often before heard it, that the wall of an aneurysm could erode bone also—thus, the vertebral column—and did I therefore mean to suggest that this was an acid-erosion, etc.? The reply to this is, that the pressure of the aneurysm here kills the bone, and that the dead, not living, bone is then removed by the agency of some enzyme of the leucocytes or white blood cells.
† Beard, J.: “Certain Problems of Vertebrate Development,” 1896, and the
“Span of Gestation and the Cause of Birth,” 1897, both published by Dr. Gustav
commencing functional activity of the pancreas which initiates the degenerative changes in the asexual generation. At this epoch, the critical period, the fish commences to feed itself on yolk, not by an (intracellular) acid “peptic” digestion, but by an alkaline pancreatic one. In some of the textbooks of physiology stands the statement that the human pancreas at birth “contains tryspin and the fat-decomposing ferment, but not the diastatic one”* (Zweifel); but, as I know from my comparative observations of years past, its activities really commence at the time the anus is formed, early in the seventh week of gestation, at a period when in the days of long the organism would have begun to digest the yolk of its now empty yolk-sac. The pancreas functions throughout fœtal life in a mammal, though it has nothing to digest except the trophoblast.
During fœtal life the pancreas gland is pouring out its secretion into an intestine which at the present day contains no food to be digested, for the food of the fœtus has been prepared by the pancreatic digestion of the mother. To the fœtus in utero this alkaline digestion is of no direct use, but it has an indirect import in acting upon trophoblast. The commencing activities of the pancreas during fœtal life initiate an alkaline digestion by means of the most powerful and important of all the digestive juices. To which of its ferments the observed results be due does not concern us. † If the secretion be
* The diastatic ferment is, of course, amylopsin. Here, therefore, on the first appearance in a medical journal of an advocacy of pancreatic, ferments in cancer, amylopsin is noted, and its absence at birth mentioned along with the name of Zweifel as the discoverer of this fact.
† The writer had intended,
in correcting the proof for the Lancet, to insert the following note,
which was actually spoken at
absent, neither the asexual structures of a fish development nor the cells of chorio-epithelioma do, or can, degenerate.
continued from page 118
its parts, begins to nourish itself by an alkaline pancreatic digestion, and with a ferment known as trypsin. If this latter be wanting, the asexual generation, the trophoblast, may become a malignant tumour of the deadliest description; in its presence it becomes harmless and slowly degenerates. Clearly, then, since cancer is an irresponsible trophoblast, the ferment, which brings about the degeneration of this in normal development ought to possess potency when directed against the cells of a malignant tumour.” For reasons of scientific priority, which also led me to read to the audience the abstract of Liverpool lecture, published next day in full in the Liverpool Daily Post and Mercury, it seems desirable to draw attention to this matter here also.
* Two recently recorded cases of tumours of the pancreas may be
cited. In the Berliner klinische Wochenschrift, 1904,
p. 479, Herr Ury, “Berichtet über einen Fall von Pancreas-carcinom mit Fett -
Stühlen, wlche, durch Darrichung von Pancreon wesentlich gebessert wurden,” and
in the Journal of Medical Research,
to note, that just as cancer is found everywhere in the vertebrata, just as there is one mode and one only of vertebrate development, so the pancreas gland and its secretion are a common heritage of vertebrate animals.
Briefly, as I conceive it, in normal development and in a malignant tumour the matter is simply a question of the victory of a stronger enzyme over a weaker one. In view of all this, the events in a malignant tumour—such as, for example, the “heterotype” mitoses—lose much of their importance. They may still possess an interest for the cytologist and embryologist, and even a passing one for the pathologist. But to the physician and surgeon these abortive attempts to form gametes cease in treatment to have any import whatsoever.
Practically all that was sought after from my own researches regarding cancer has now come to light. Embryologically, the problem of cancer has been to discover the antithesis of two enzymes and in particular to find out the enzyme capacity of destroying a weaker one, and thus of leading to the degeneration of the tumour by simple atrophy. The whole story is but another example of that antithetic alternation which underlies all the phenomena of living things. The solution of the problem of the functional relation of embryo and trophoblast—how the latter nourishes itself by an (intracellular) acid “peptic” digestion and degenerates slowly by a pancreatic digestion—becomes at the same time the embryological, if not the medical, resolution of the problems of malignant neoplasms, as well as of chorio-epithelioma. As an embryologist, who is not a physician or surgeon, my task is ended. The further applications of the scientific and theoretical solution of the problem may safely be left in the hands of those who know far better how to employ it. But they may not forget that in nature the degenera-
tion and disappearance of these asexual structures, sometimes quick are often exceedingly slow, though sure. Not that it is likely that the surgeon has removed his last malignant tumour, but that, as one of the results of the work* begun more than sixteen years ago, they physician has possibly had forged for him a light and not dangerous weapon, only second, if not equal, in potency to the surgeon’s knife. †
*Most of the work has been carried out in
† As later events have proved, this estimate—with deference to certain transparently anonymous critics—was much too modest. The pancreatic ferments, trypsin and amylopsin, when direct scientifically against the living cells of cancer or sarcoma, are infinitely more potent than the knife of any surgeon!
THE INTERLUDE OF CANCER*
“In preda al duol non mi lasciar!”
MAZZONI: Cavalleria Rusticana.
With the results of the preceding chapter, the writer regarded the problem as no longer one for the embryologist. It seemed to him that any further problems of cancer were rather for comparative physiological chemistry than for such a branch of science as embryology. This has, indeed, turned out to be correct. As appeared in the sequel, cancer was vulnerable by two lines of attack—embryology and stereo-chemistry. At the present time (1911) the scientific Germans—wuch as Abderhalden, Blumenthal, Neuber, and others—are advancing slowly, but surely, along the line of stereo-chemistry. That they have been anticipated in this advance is shown in the following chapters of this book, as well as in the introduction. In the present chapter, therefore, there is presented a connected account not merely of what is given in preceding pages, but also of many things worked out in years now long past. The following lines contain an attempt to show how various purely embryological problems and their solutions bear upon the problems of cancer.
*From the Medical Record
The embryologist never tells the story of his work in the order of his researches. He cannot; for in these he pushes his way little by little, step by step, from the known to the unknown, and at any given time he may be working in two directions—upwards from the starting-point of the fertilized egg, and downwards from the finished embryo. Thus it happened, that what, logically regarded, should have been the first investigation in 1888—the history of the germ-cells—was actually the last, as it was also the coping-stone which crowned the work, and made it lasting.
The actual cancer researches have been a mere interlude in the whole—an intermezzo. “The prey of pain let me not be!” The solution of the problems of cancer was but a corollary of what had gone before, and it followed naturally and irresistibly out of the germ-cell results, the course of the life-cycle, and the conclusions as to the germinal continuity and heredity. Since the embryological theories of the textbooks are, to apply the words of Pasteur, a mass of baseless hypotheses, it follows that the solution of the problems of cancer can be grasped properly only by a comprehension of the course of the cycle of life from generation to generation, as my researches of past years have revealed it.
The starting-point of a new cycle is the fertilization of an egg, and the outline history of the cycle is not complete until we have shown how new eggs, new reproductive elements, arise; and until we have reached the point at which these are ready for fertilization, to start the cycle anew. An egg is fertilized and development begins by its cleavage; an ever-increasing number of cells is formed in this way, and anon we reach a point, at which the orthodox embryologist says that the egg-cleavage is finished. What has then come into being? The usual
reply is, “ A new organism, an embryo.” No such thing! At the close of cleavage, in none of the higher animals is any trace of an embryo present. Something is there, but not an embryo. I will ask the reader to regard this developing egg from the start of cleavage as a living organism, but not an embryo.
The criterion of anything in embryology is the fate or destination of the cells. In a worm’s egg, which has cleaved five times, giving 32 cells, or in a skate’s egg, which has undergone ten division, resulting in 1,024 cells, there is not a single cell present which is embryonic in destiny. Nearly all the cells are predestined to form portions of an asexual foundation or larva, termed by me the “phorozoon,” or bearing animal. This is a transient organism; for, as a rule, its life is very brief. It has a part to play in the cycle, and, like the Moor, when it has done its appointed task, it can go. The results upon which, generally speaking, my conclusions are founded have been obtained by what my late friend and teacher—Professor George Bond Howes, Huxley’s assistant and successor—was wont to term the comparative morphological (and physiological) method. Under it there is but one mode of development for all the higher animals: in essentials the life-cycle is always similar, not only from fishes to man, but from worms and even lower forms to fishes. These “phorozoa,” or asexual generations of various marine organisms, have long been known. Often, and until a connection therewith was established, they received names distinct from those of the sexual generations. Thus, the larva, “phorozoon,” or asexual generation of a brittle star, is still known as a Pluteus, and so on.
The late Professor N. Kleinenberg first set up (1886) the doctrine of development by substitution of organs. Under this, every organ of the larva (asexual generation)
FIGURE 5 (two pages) GO HERE!!
was ultimately replaced by a corresponding, but differently developed, organ of the adult form (sexual generation). For a variety of reason, into which space forbids entry here, it soon became clear to the writer that Kleinenberg’s doctrine was inadequate, and that, instead of a substitution of organs, there was in development in reality a substitution of organisms. The sexual organism replaced the asexual one. This was seen to be an alternation of generation, and as there was no homology or close likeness between the asexual form or its organs, it was an antithetic alternation of generations.*
Now that we have the mention of the word “antithetic,” it may be permitted in passing to point out how Pasteur’s researches started in the antithesis of the two sorts of tartrate crystals: mine in that of two nervous systems in the life-history of a fish. Here we are dealing with anatomical antithesis; later we shall come to recognize physiological antithesis—that of two ferments.
The tracing of the asexual generation in the backboned animals or vertebrata, from fishes to man, was not without its own special difficulties. These were due rather to expecting too much, and to failing at first to realize that the higher one ascended in the scale of life, the greater became the organization of the sexual form or generation, and the more insignificant the asexual one, until in the highest animals, the mammals and man, the asexual generation became reduced to the almost structureless chorion or trophoblast, as Professor A. W. Hubrecht named it in 1889. Many people, quite ignorant of all the embryological advances of recent years, appear to imagine that I not only introduced the
*See Appendix C, “The netazoan Life-Cycle and Alternation of Generation.”
name “trophoblast,” but also invented the thing, to which it is applied in embryology. These things are not true. The name was invented for a thing defined by Hubrecht in 1889, and the thing itself has existed for untold millions of years!
In 1895 the standpoint had been attained that in every life-cycle of a higher animal, such as man, there were two generations: an asexual one—the trophoblast, and a sexual one—the metazoan individual or person. The puzzle was not how the first of these arose, for clearly it could be demonstrated any day in the week that it was the direct product of the cleaved or segmented egg (vide Fig. 5, phorozoon or larva). Somehow or other there arose gradually upon it the sexual generation by a process of evolution or unfolding.
How! Something resembling the spore mother cells of plants was required. That was very apparent. (See the table of Revised Comparison.) It was not until towards the close of 1900, when the firstharvest of the germ-cell researches had been reaped, that the problem was cleared up. The germ-cell researches had been reaped, that the problem was cleared up. The germ-cells arose before the embryo, as products of a single cell, the primitive germ-cell (U.K.Z. of the diagram, Fig. 5), in a direct line from the fertilized egg. They came into being upon the asexual generation or trophoblast. To contain and to nourish these germ-cells for a brief span of time another organism was need, a sexual one, endowed with sexual organs.
How was the sexual organism obtained? In embryology things do not come into existence out of nothing! True, there are embryologists who look upon holes or cavities as the sources of important organs, but the writer at all events is not a “hole-morphologist”!*
*Any more than the author of this expression, the late Professor N. Kleinenberg, was.
TABLE OF REVISED COMPARION OF ANIMAL AND PLANT LIFE-CYCLES.
ASEXUAL GENERATION ASEXUAL GENERATION
Zygote or fertilized egg Zygote or fertilized egg
(2 n). (2 n).
Phrozoon or trophoblast. Sporophyte or flowering
| plant (2 n).
Formation of primitive Formation of primitive
germ-cell (2 n). spore mother cell (2 n).
Formation of primary Formation of spore mother-
germ-cells (2 n). cells. (2 n). (Reduction
| and sex determination).
“Apospory” (reduction Spore formation
SEXUAL GENERATION SEXUAL GENERATION
A primary germ-cell (2 n). A spore (1 n).
Origin of embryo by un- Origin of sexual generation
folding of a primary or gametophyte from one
germ-cell, inclusion of spore ( 1 n ).
rest in the individual |
of the sexual generation |
(2 n). |
Ripening of germ-cells. Ripening of germ-cells.
Reduction and sex deter- Reduction previously
Sperm. Egg. Sperm. Egg.
In the above table n equals the reduced number of chromosomes, and 1 n signifies the emancipated cell, 2 n the duplicated or conjugated cell, the “conjugation” or joining together being carried out at fertilization. The “reduction” is the undoing of the previous duplication effected at conjugation. 127
The unit from which anything arises is the single cell. There was only one source from which such a sexual generation could arise: this was by the evolution or unfolding—the sacrifice—of one germ-cell for the well-being of the rest, and to contain. At the epoch of the formation of the primary germ-cells all were alike in origin and potentialities. All were so many potential individuals of the species. If two developed independently, the result would be identical twins; if three, triplets, and so on.
Reviewing matters, starting with the fertilized egg, this gives rise to an asexual generation—the trophoblast, upon which there arises an “apical cell”—the primitive germ-cell. This latter divides a certain limited number of times, this number being a fixed one for the species; but while it is n in the male, it is n plus 1 in the female. The products are 2, 4, 8, 16, 32, 64, 128, 256, 512, etc. In the diagram it is depicted as 128. These 128 germ-cells are the primary germ-cells. It is they which enter the embryonic body (Fig. 4) when this arises, and it is some of them which come to occupy all sorts of abnormal position. But all the line of primary germ-cells are not destined for future generations. Some few of them, 1, 2, 4, or 8, are embryonic in destiny. At least one of these must unfold to form an embryo. If any of the others do so, the result is identical twins, triplets, etc. If any of these “embryonic” germ-cells lie dormant within the developed embryo, they may become the seed of future tumours, as will appear later on. The line of heredity, so far revealed, leads from fertilized egg to the primary germ-cells, and thence through all the history of the germ-cells within the “reproductive glands” to new eggs and sperms; that is, all things considered, the cycle is one of unicellular organism, the germ-cells, in
the history of which the sexual generation or individual is but an incident.
Another important question to be solved some fifteen years ago was the how and the when of the suppression of the asexual generation. This latter, whether represented by the transient nervous apparatus and other structures of a fish, or by the trophoblast of a mammal, went on flourishing for a certain—not very long—space of time, and then, quite suddenly, all growth was stopped, and its degeneration was initiated. In years long gone by how often have I not watched these asexual structures under the microscope, seen them flourish and blossom, and then—subito, as the Italians say—begin to fade away, as though blighted! The correlation of phenomena is often of the greatest importance to the embryologist in his work; and when this sudden fading away was first established, it was also noted that the commencing formation of the posterior fissure of the spinal cord was a concomitant phenomenon. This led to one of the many little research excursions I have made right up the back-boned series to the mammals, and to the study of human embryos themselves. A whole array of interesting and connected events was soon unearthed, and the putting together of these culminated in the discovery of the critical period—one of the most momentous finds ever made!
“There is a period in the development of every vertebrate embryo, during which, and only then, it resembles the embryo of any other vertebrate in a corresponding phase in certain general features. But while it thus agrees exactly with any other embryo of this period in characters, which are common to all vertebrate animals it differs from the embryo of any other class in certain special class features, and also from any other embryo 9
of the same class, but of a different order in other and ordinal characters. Immediately before this period is reached it begins to put on generic and specific characters, and thus it then begins to differ from all other embryos in these.” In other words, the embryo then first asserts its presence, announces its own individuality. It is then first present as a complete thing. It then first begins to use its own digestive apparatus, especially its pancreas gland, and in a higher mammal to feed itself by means of the allantoic placenta. This critical period is common to all back-boned animals in their development. At this period the average marsupial is born into the world, and then it first begins its long mammary nutrition.. In so great a hurry is it to get into the world that it forms its anus in the act of being born. The human embryo does the same at the like period, in the seventh week of gestation, as though it were a marsupial, although it has no use for this aperture for many months to come. Then the allantoic placenta—an organ of the embryo or sexual generation, like the pancreas gland—first begins to function, and then normally the trophoblast begins to function, and then normally the trophoblast begins to fade, to be suppressed, and to degenerate.
Though ferments first made their appearance in my published writings in 1892—for I pride myself on having been one of the very few pupils the late Professor C. F. W. Krukenberg ever had—it was not until 1904 that their all-important bearings upon the critical period were evident. In human gestation, if at the critical period the embryo be wanting or very abnormal (a very abnormal human embryo can only persist as one of identical twins), the phenomena of the critical period are lacking, and the normal trophoblast, which always begins its life by eroding the uterine epithelium and wall, may go on with this process, exhibit indefinite powers of growth, and eat
its way through uterus and other organs, finally blocking the lungs and brain of the mother. This is chorio-epithelioma, recognized to be a form of cancer by Professor F. Marchand in 1895. This is without doubt the most deadly form of cancer. Here the sexual generation being unable to suppress the asexual one or trophoblast, the latter exhibits the characteristics of asexual generations, the powers of indefinite growth and increase. Pathologists at present distinguish wrongly between two forms of chorio-epithelioma, a malignant one and a benign one. The latter has no real existence, for in it the trophoblast cells are all dead and undergoing the characteristic degeneration due to the action of pancreatic ferments. A “benign” chorio-epithelioma, as Professor Schmorl found, may happen in any gestation, for the trophoblast cells of the pre-critical periods, which have invaded the maternal organs—even the lungs—are normally also brought to commencing degeneration at the critical period.
In 1902 the conclusion was reached that cancer was asexual generation or irresponsible trophoblast, and in these words for the first time in human history the nature of cancer was laid bare.
Its origin was not at first so clear, but by the year 1904 it was recognized that the problems of like or identical twins, upon which the writer was then and since engaged, threw light upon its origin. Owing to their extra-embryonic origin aberrant germ-cells are quite common, and they may be met with anywhere in the embryonic body. The ordinary aberrant germ-cells, which usually degenerate, were much too abundant a source to furnish the origin of a cancer. Entia non sunt multiplicanda. The etiology of double monsters and of malignant tumours was traceable to the phenomena of
like twins. The facts concerning these, as well as those relating to Hermann von Jhering’s finds in the armadillo (Praopus hybridus), which my work has fully confirmed, furnished the key. This armadillo, the “tatu,” produces all its young in one chorion or trophoblast, and therefore they are all indentical, of the like sex, and all products of one egg. The whol doctrine of the tumours, benign and malignant, centres in the phenomena of like twins—that is, in a former multiplicity of embryos, all products of one egg. To-day the “tatu” (P. hybridus) produces seven to twelve such, all derived from a single egg, all of the like sex, and some of them more or less rudimentary!
These latter tell a very significant story* to the embryo-
*Because hypothetical, the following may find a place as a foot-note. From the consideration comparatively of a variety of embryological phenomena, well known to the investigator, it is obvious that the procedure, where only a single embryo is going to arise from one of the primary germ-cells, will not be quite the same when two or more embryos are destined to unfold. The setting apart of one cell will be preceded by one or two divisions, giving one functional cell and possibly three abortive ones. But if the development shall result in, say, triplets, there will be, not merely two division, but at least three, if not four. Of the products, which are all primary germ-cells, three will unfold as embryos, three may be abortive or rudimentary, and, if there be eight all told, two will remain as “embryonic cells,” which later on, in some or other of the individuals arising, may become the seed of tumours, benign or malignant. But these cell division have a curious tendency to be in twos or pairs, or even in threes; so that in the formation of triplets, instead of eight cells, there may be sixteen concerned. How many of these will be abortive, and how many “embryonic” in potentialities, is at present impossible to say. The armadillo, Praopus hybridus, with its seven to twelve young in one chorion or trophoblast, affords an instance where at least sixteen cells must originally in every case have arisen at the line of primary germ-cells and in addition to those cells destined to become the sexual products. Of these sixteen cells, seven normally give rise to fully-developed embryos, five to more or less rudimentary ones, and there still remain four, which—as cancer, is not known here—may be abortive.
ologist. They recall to him other similar phenomena in embryology. Reductions in numbers of units (cells), formerly of importance, but which now persist, not because they are really required, but because their existence and persistence are parts of an old scheme of the cycle of animal life.
footnotes continued from page 132
But if the number of young here arising at every gestation were much reduced, while all the preliminaries were retained, what a rich harvest of tumours might be the result! In a case of identical triplets, cited by Professor H. H. Wilder, at least two of the sisters died of cancer.
The line of primary germ-cells of the diagram (Fig. 5) is not made up of one only, destined to form an embryo, and of n-1, destined for a future generation, but it is composed of a limited number, 2 or 4 or 8, often not so many, embryonic in destiny, of which as a rule one only becomes a normal embryo, and n-2, or n-4, etc., are set apart to provide for the cycle of unicellular organisms or germ-cells. Such a persistent embryonic germ-cells, encapsulated within the individual, may at any time, by illness, injury, irritation, or other cause—such as declining years—weakening the system, be awakened into activity. The “age incidence” of cancer is scientific nonsense, for it is only relative. Whenever this happens—the time is long past when it should have unfolded as an embryo, it attempts to resume the cycle, and its “unconscious memories” only enable it to try to repeat the asexual portion of the cycle. Such an encapsulated germ-cells can only do one or other of two things in the end—and live. It may develop, and it only does this congenitally with the developing individual, or it may attempt to go on with the life-cycle—trophoblast.* In this way it becomes an irresponsible trophoblast, and it may imitate or mimic anything in its environment. Whatever it mimic—something existent or non-existent—it is always an “imitation tissue,” and behind the domino or mask an irresponsible trophoblast.
In nearly all the foregoing, morphological aspects have been under consideration. It now behooves us to take account of the physiological and functional ones. The
* This is more fully shown in the Introduction (p.23) and in the later chapters.
critical period in a fish or mammal or man is that at which the embryonic organs as a whole first begin to function. The fish begins to feed itself, digesting the yolk by intestinal digestion. The mammal or human embryo begins to do the like (in the absence of food-yolk) by means of the commencing functional activities of the allantoic placenta. At this epoch in the fish the pancreas gland manifests its activities by the presence of abundant zymogen granules in the cytoplasm of its cells, That these result in the secretion of pancreatic ferments is shown by the digestion of yolk within the gut. Owing to this digestion, the fish, like the mammal, gets ever bigger and bigger. None of the yolk enters its stomach, for this has then as little functional activity as the stomach of a mammal has during fœtal life. An internal yolk-sac is formed for the reception of the yolk from the external one, and the yolk-duct opens into the duodenum. This fact alone indicates to the embryologist that the pancreas gland is functioning. In an average marsupial at the critical period this gland certainly begins its functional activities, for the animal is then born, begins its mammary nutrition, and digests the milk. If a certain thing happen at the critical period of a fish, or a marsupial, I know from experience that something corresponding to it will take place at the like period in a higher mammal or a man. A fish forms its anus at this period, so does a marsupial, while in the act of being born, and so does a man, although he does not need it for some seven months more. As the pancreas gland begins its functions in a fish or an average marsupial, so it must do in the development of a man. Otherwise there would be no essential unity in the mode of the development. Undoubtedly, under the action of the pancreatic ferments, the asexual structures of a fish development begin
to degenerate, and, as represented by the trophoblast, they do the like in a mammal or a man.
This leads to an inquiry as to modes of nutrition, regarding which the
reader may find much interesting information in Verworn’s “General Physiology,”
and still more in Otto von Fürth’s “vergleichende chemische Physiologie der
* Now (1911) the writer would desire to call special attention to these words, written and published more than fours years ago, but hitherto unheeded.
even a medical man,” the
tubercle bacillus, like the trypanosome, or the organism of yellow fever, or
that of malaria, etc., can no more live in the presence of these higher ferments
than the cancer-cell can. This has
been shown apparently, in one case at lease, clinically and pathologically for
the tubercle bacillus, by my friend Dr. Margaret A. Cleaves,* of
* Cleaves, M. A.” “The Physiological Action of the Pancreatic Enzymes,
with Special Reference to Hematology, Urinology, and Clinical Pathology,” Medical Record,
† Now (1911) for tuberculosis, malaria, sleeping-sickness, yellow fever, etc., I would advise the use of injections of 500 tryptic units per ampoule, plus 1,000 to 2,000 amylolytic units per amploule (vide Appendix F). Compare also Bätzner, Wilhelm: “Trypsinbehandlung d. Chir. Tuberculose,” in Arch. Klin, Chir., vol. xcv., Heft 1, 1911.
Of the ferments of the sexual generations, by far the most important is that first discovered by the Court physician, Baron Corvisart, and to which afterwards Professor W. Kühne gave the name of “trypsin.” It is this enormously powerful ferment, trypsin, upon which Nature relies for the suppression of trophoblast in normal mammalian gestation. Lower down in the scale than the mammals she associates with it its complement, amylopsin. Fœtal blood of a mammal does not contain this latter, and the fœtal pancreas gland does not produce it. In the human pancreas gland amylopsin is not formed until some few months after birth. The reason of this is not far to seek. When in the ancestral mammals uterine development was initiated, along with it and following its close there was evolved the mammary nutrition. In this amylopsin is not needed, and its production by the pancreas gland was postponed until the milk nutrition was done with. The mammary nutrition is (on the testimony of more than one embryologist: thus, on that of my friend J. P. Hill, as well as on my own) older in time than the allantoic placenta. The latter was introduced to defer the birth period, and by prolonging the gestation, as detailed in my “Span of Gestation,” to bring the young into the world in a more perfect state. In prolonging the gestation, the mammary nutrition was postponed, and in this way the appearance of amylopsin upon the scene put off to an even later period. This has led to grave difficulties and dangers in human gestation, for there is no such thing in nature as a ferment possessing both proteolytic and amylolytic powers.*
The proper scientific treatment of cancer is the enzyme or pancreatic one. If trypsin alone be used, bad symp-
*Although a ferment, possessing such powers, has been advertised in medical newspapers.
toms very soon arise, all of which recall the vomiting of pregnancy and eclampsia. Trypsin alone is a very deadly remedy for cancer, the reason being that in killing the cancer albumins this enzyme does not split them up to harmless simple products. What the products of the action of trypsin alone are it is impossible to say, for they may quite conceivably vary with the amount of the injection, its strength, and with the size of the tumour. Anyway, some of them are rank poisons to the organism, and they lead to nausea, vomiting, pain in the back, drowsiness, high arterial tension, albuminuria, œdema, etc., and even to convulsions, lasting several hours. The cause of such symptoms and of the eclampsia of pregnancy did not long puzzle the embryologist, who perceived that it was the absence of the complementary ferment, amylopsin, which induced them. Nature had committed a grave error in omitting amylopsin from fœtal blood, and in relying solely on trypsin. In normal gestation, if anything went wrong with the maternal pancreas gland, and if the maternal supply of amylopsin became diminished or ceased, then serious symptoms were bound to follow. To my knowledge, at the moment of writing, injection of amylopsin have not yet been given in any case of eclampsia, but they have, whenever used in cases of cancer, removed all the bad symptoms named.
The preparations employed in the enzyme treatment of cancer should be
like those first used in
has been destroyed It must be an extract of the pancreas gland as free as possible from trypsin. (Compare Chapter VII.)
This treatment is not intended for use against benign tumours, which are composed of real or somatic tissues, and which are not killed or broken up by trypsin. Owing to this, the injections furnish a chemical test of the true nature of a tumour, whether it be benign or malignant. Thus, some pathologists look upon adenomata as benign, or at all events as only potentially malignant. To my mind, there are “imitation tissues,” and I should anticipate that any and every adenoma would yield to the chemical test.
Owing to the circumstance that the cycle of life is really a continuous procession and succession of unicellular organisms, germ-cells, from which there arise asexual generation or trophoblast, and embryo or sexual generation, the tumours can be classified into three groups, as follows:
1. Embryomata (benign neoplasms).—Pathological manifestations of some greater or less portion of the sexual generation—“the embryo.” They are composed of real tissues—that is, normal or somatic (“embryonic”) cells or tissues. At its basis each is greater or less portion of a twin, triplet, etc., identical with the individual containing it. They are not endowed with indefinite powers of growth, and they nourish themselves like other normal tissues.
2. Amphimyxomata (malignant neoplasms).—Combinations of embryomata and trophoblatomata. Pathological manifestations or attempts to reproduce the whole life-cycle-including trophoblast and embryo. They are transitional forms. (The mixed tumours of Wilms are not all malignant, some being merely embryomata.)
3. Trophoblastomata: Cancer and Sarcoma (malignant neoplasms).—Pathological man-ifestations of the asexual portion (trophoblast) of the life-cycle. They are not known to differentiate functional gametes, eggs or sperms. They never include or repeat any part of an embryo. They are never composed of somatic (“embryonic”) cells, though they may mimic such, or even resemble no other cells in the body. As Fleischmann, Paget, and Bland-Sutton pointed out, they are “imitation tissues.” They exhibit powers of unlimited growth and increase, and they nourish themselves by eroding and destroying normal cells and tissues in a manner exactly like that of the trophoblast of normal gestation, and by means of a ferment acting intracellularly—viz., malignin.
As the two latter divisions are made up of malignant tumours, it is for them, and not for the members of the first group, that the enzyme treatment is intended.
In the foregoing simple story I have endeavoured to the best of my
ability to give in outline some idea of the course and nature of my scientific
work and conclusions since the days of May-June, 188, when I worked on the
a new sun is rising. Epigenesis, somatic origin of germ-cells, and recapitulation in development, are fading away into thin air before the mighty powers of Evolution with predestination (Weismann), an actual tangible continuity of germ-cells from generation to generation, and an antithetic alternation of generations as the mode—the only possible one—of animal development.
The suspicion entertained at Liverpoole in 1905, then expressed to two Professors of the University of Liverpool, and which is somewhat reinforced by the references to the work of Pasteur in the present chapter, that the problems of cancer had been lifted into the field of chemistry, soon showed itself to be a reality. Not only were the questions still pending chemical ones, but they belonged to a branch of chemistry with which the name of Pasteur will ever be associated as its founder—stereo-chemistry. This is more clearly revealed in the following chapter.
THE ASYMMETRY OF THE CYCLE OF LIFE, BEING
“THE END OF THE THREAD.” *
In past years every new unravelling of the thread led to new problems. But no matter how many side branches or collateral issues came up, the main course of the thread was continuous, and the observer’s senses were concentrated upon it, to the exclusion of all else. Among other things the thread passed through the problems of heredity and genetic variation, the determination of sex, the continuity of germ-cells, the problems of identical twins, and by reason of these, as well as from the nature of the cycle of life, through the embryology of neoplasms, and of cancer itself. For a long time I had imagined the cancer studies to have been an interlude in the work, but no, the thread of research passed directly through the problems of cancer. And now, quite unexpectedly, the end of the thread has been reached, because portions of it had been unravelled by some of the greatest workers in science, because Louis Pasteur, one of the greatest investigators who ever lived, van’t Hoff, Le Bel, and Wislicenus had lived and laboured, because their researches had founded stereo-chemistry, or chemistry, in space.
The present chapter is simply “The End of the Thread.”
*From the Medical Record.
Like my fellow-workers, I had been taught to regard the development of any of the higher animals as “direct”; that is to say, from the fertilized egg a new sexual organism, a worm or a fish, a bird or a man, arose directly. From the tissues or soma of this sexual organism new reproductive products, eggs or sperms, sprang. In this way the simple cycle of “egg-sexual organism, egg-sexual organism” repeated itself ad infinitum. Under this, still generally accepted, conception of development the germ-cells were somatic in origin, and the gradual building up (epigenesis) of a new sexual organism happened directly, when such an egg had been fertilized. Such, briefly, was the simple embryological creed which my teachers, Milnes Marshall, Huxley, and Carl Semper, taught. During some eight or ten of the early years of my original work this was my embryological faith, if an investigator may have any scientific creed.
Epigenesis, direct development, and a somatic origin of germ-cells, have now long been associated with another embryological dogma, the capitulation theory, according to which any higher animal “climbs its own genealogical tree in the course of its development.” To what lengths and depths of scientific error this latter doctrine can lead, see the fifth revised of Haeckel’s “Evolution of Man.”
My embryological faith was perfectly orthodox when, on
made in some other fishes and amphibians, and especially in the smooth skate, Raja batis.* The transient nervous apparatus of ganglion cells and nerve fibres in the skate development functioned for a time, for about three months from the start out the total of circa seventeen, and then quite suddenly began to fade away, and to undergo a slow but sure degeneration.
The two nervous systems crop up again and again in my published writings since 1888, and, as indicating the import long attached to this antithesis, I find myself writing in 1905 a paper, “The Cancer Problem,” † opening with a recital of some of the facts in the history of the transient ganglion cells. All my original work, from 1888 down to to-day, is impregnated with facts concerning the two nervous systems, and the antithesis underlying them. The discovery of that antithesis has impelled and influenced all my work since that time.
With the termination of the period of research marked by the publication of “The Interlude of Cancer,” I recognized that my original work was approaching and tending to converge to the work of Pasteur. The researches had led finally into problems of the chemistry of the ferments, and especially of the extracellular enzymes, trypsin and amylopsin. It is not too much to say that Pasteur had founded a science of the ferments. True, he laboured for many years at the problems of intracellular enzymes, such as the yeast organism, the mould, Penicillium, etc., and the enzymes trypsin and
*Beard, J. : “The Early Development of Lepidosteus osseus,.” Proc. Roy. Soc.
Lond., 1889, vol. xlvi., p. 108-118.
Ibid: Ichtyopsida : An Account
of the Development and Degeneration of Ganglion Cells and Nerve Fibres,
† Ibid: “The Cancer Problem,”
amylopsin, for a knowledge of which the world is so greatly indebted to Corvisart* and Kühne † never entered into the sphere of Pasteur’s researches.
The interesting thing is, according to his own testimony, ‡ that Pasteur’s work, like mine since 1888, centred in the fundamental discovery of an antithesis. Some medical men of Pasteur’s day denied the truth of his conclusions, either on flimsy evidences or on none at all—just as happens to-day. Equally they sought to deny the scientific investigator the right to any opinion on a question regarded by them as medical, but which was really scientific. “What!” cried Pasteur, “I have been engaged for twenty years in research on a subject, and have no right to an opinion? And the right of verifying, controlling, discussing, and questioning belongs more especially to him who has done nothing to clear up the matter, to one who has just read more or less attentively my works with his feet on the fender! You say, my dear colleague, that in the actual state of science it is better to have no opinion. Ah, well! I, even I, have one, and no of sentiment, but of reason, for I have acquired the right by twenty years of assiduous work. My opinion, or better, my conviction is, that in the actual state of science of which you speak spontaneous generation, is a chimæra, for my experiences are complete, and they all prove that spontaneous generation is a chimæra. As to my opponents, proof in hand I have contradicted every one of their assertions, and they have never dared
*Corvisart, Lucien: “Sur une Fonction peu connue du Pancreas,”
† Kühne, Wilhelm: “Ueber das Verhalten verschiedener organisirter und
sog. Ungeformter Fermente,” and “Über das Trypsin (Enzym des Pandreas),” Verhandl. Des. Heidelb. Naturhist. Med.
Vereins. N. s.,
‡ Vallery-Radot, René: “La Vie de Pasteur,”
seriously contradict one of mine.” In passing, be it remarked that every work=d of this passage might be applied to happenings at the present time regarding the problems of cancer. Then Pasteur explained how the whole series of his marvellous discoveries, chemical, bacteriological, or medical, hung together and formed a complete chain—e.g., anthrax, the pure fermentation of beer, the acetification of vinegar, the diseases of vines, the means of preventing them, and, lastly, going back seventeen years, the first link in the chain of discoveries, that of the double tartrate crystals, and the facts concerning their dimorphism.* “The best proof that an observer is right is the uninterrupted fruitfulness of his work.” †
Pasteur worked for seventeen years at his chain of discoveries; it was in 1907 nineteen years since the first link of my chain was forged. The thread each of us obtained at the start was the discovery of the antithesis of two things: he, the two kinds of tartrate crystals; I, the two distinct and separate nervous systems in the life-cycle of a fish.
Why should all this be? What connection was there between the two facts, which, apparently, were as wide apart as the poles? The evident fact has already been referred to, that in 1904 the two independent lines of work were converging, but it was more than this. It was a union. The thing which impelled Pasteur’s work incited mine also. The antithesis he discovered was in
*Pasteur, Louis: “De la Dissymmétrie Moléculaire des Produits Organiques Naturels.” Lecom professée devant la Société Chimique, 1860.
† This chain-like character of Pasteur’s researches has been commented upon by others—thus by Miall (“History of Biology,” 1911)—but I doubt whether any of the commentators have grasped the true significance of Pasteur’s meaning.
reality that also found by me. The asymmetry of the naturally occurring organic compounds, like that of the tartrate crystals, was the same asymmetry as that of the two nervous systems, and the facts of both observers were based in the fundamental verity of the asymmetrical carbon atom, first stated by van’g Hoff and Le Bel.* Therefore, the researches and discoveries of Pasteur and the writer, as fundamentally classified, are chapters, long or short, in the science of stereo-chemistry. Behind the work, which culminated in and formed the real scientific basis for my publication on “The Interlude of Cancer,” there are the researches in stereo-chemistry of Pasteur, van’t Hoff, Le Bel, and Wislicenus, and the eternal truth of the asymmetrical carbon atom.
It is not fitting on this occasion to write a treatise on the science of stereo-chemistry or chemistry in space. It has long been recognized by chemists—though this fundamental scientific truth would appear to have had as little influence on physiology as upon medicine—that because the carbon atom is asymmetrical, like the pentavalent nitrogen one, † isomeric compounds may be built up in more than one direction. To take a comparatively simple instance of these isomeric compounds, the tartrate crystals of Pasteur’s researches, the one is the looking-glass image in crystalline form of the other. The one in solution turns the plane of polarized light to the right, is dextro-rotatory; the other to the left, is lævo-rotatory. The ferment of the yeast organism acts upon the lævo-tartrate; that of the mould, Penicillium, upon the dextro-tartrate. On the other hand, the yeast
*Richardson, G. M.: “The Foundations of Stereo-Chemistry” Memoirs by
Pasteur, van’t Hoff, Le Bel, and Wislicenus. Translated and edited.
† Wedekind, Edgar: “Zur Stereochemie des füunfwertigen Stickstoffes,”
organism is without action on the dextro-tartrate; the Penicillium leaves the lævo-tartrate untouched. This, as Pasteur demonstrated, is one method of separating the two in a mixture. Now, it is a remarkable fact that when any of these isomeric compounds are manufactured in the laboratory, equal amount of the dextro- and of the lævo- compounds make their appearance in the mixture. Pasteur first noted the fact that all the artificial products of the laboratories and all the sorts of minerals encountered in nature are without action on polarized light, unlike all the naturally occurring organic compounds. This has only altered since 1860, according to Duclaux, in that, while chemists can manufacture certain of these compounds in mixtures of equal amounts of the isomers, they can also be separated by the action of ferments, which are specific in this direction. For other alterations see the works of Pope and van’t Hoff.* In the two lectures Pasteur demonstrated that the naturally occurring organic compounds rotate the plane of polarized light to the right or to the left, and in this way are dextro- or lævo- rotatory. As Duclaux writes, “Nature alone knows how to manufacture the one isomer without producing the other.” “A living cell is a laboratory of dissymmetrical forces, or a dissymmetrical protoplasm, acting under the influence of the sun.”
In his “Chemical Statics and Dynamics,” Dr. J. W. Mellor † writes as follows: “It is interesting to observe that only the dextro-sugars occur in Nature(?), and that these are the only sugars which can be assimilated as foodstuffs by the yeast-plant. No organism capable of
*van’t Hoff, J. H.: “Stereo-Chemie nach van’t Hoff’s Dix Années dans l’Histoire d’une Theorie, neu bearbeitet von W. Meyerhoffer,” 1892.
† Mellor, J. W. : “Chemical Statics and Dynamics,”
digesting artificially synthesized lævo-sugars is known.” He then quotes from Professor W. J. Pope.* “It would seem to follow, as a legitimate conclusion, that while d-glucose is a valuable foodstuff, we should be incapable of digesting its enantiomorphously related isomeride l-glucose. Humanity is, therefore, composed of dextro-men and dextro-women. And just as we ourselves would probably starve if provided with food enantiomorphously related to that to which we are accustomed, so, if our enantiomorphously related isomerides, the lævo-men, were to come among us now, at a time when we have not yet succeeded in preparing synthetically the more important foodstuffs, we should be unable to provide them with the food necessary to keep them alive.” The term “enantiomorphism,” to describe the properties of the isomeric compounds, was coined by Pasteur.
*Pope, William J.: “Recent Advances in Stereo-Chemistry,” Nature, 1903, vol. lxviii., pp. 280-283.
among us, and they do pull down and build up again in the opposite direction, for the “lævo-men” are the cancers.
In the light of the antithetic alternation of generations and of the natural antithesis of the compounds arising in the two generations, the following passage from Professor Pope’s address (p. 283) is of interest. It is also instructive, because of the generally accepted but false views of the question: “Again, suppose that at its origin life were carried on non-enantiomorphously, and that it involved the consumption and the production only of non-enantiomorphous substances and of compensated mixtures, it may well be foreseen that a stage in development might arise when each individual, in view of the increasing complexity of his vital processes, would have to decide to use only the one enantiomorphous component of his compensated food, and so evade an otherwise necessary duplication of his digestive apparatus. Acting intelligently or fortuitously, one half of the individuals would become dextro-beings, while the other halve would become lævo-individuals; the succeeding generations would thus be of two enantiomorphously related configuarations.” He then goes on to express his own opinion that in course of time one configuration, the weaker one, would disappear permanently. But in this opinion the facts of botanical and embryological science are not taken into account. It is, however, only necessary to make the “succeeding generations,” spoken of, alternate in order to meet the scientific requirements of Nature, and so to make the passage absolutely true as a statement of scientific fact. This is done by inserting in the closing passage the word “alternating,” when it would read: “the succeeding generations alternating would thus be of two enantiomorphously related configurations.”
Pasteur did, indeed, foresee that in his finds there was given the basis of a science of comparative physiology. It is sad to reflect that in 1860 he wrote as follows, and that in all the intervening years his weighty words have been ignored by physiologists and physicians alike: “I have, in fact, set up a theory of molecular asymmetry, one of the most important and wholly surprising chapters of science, which opens up a new, distant, but definite horizon, for physiology.” Before the present writing was penned, this horizon for physiology seemed as distant as in 1860, for as a general rule the facts concerning the asymmetrical carbon atom and the naturally occurring organic compounds find no mention in current textbooks of modern physiology.
“Who can foresee the organization that living matter would assume, if cellulose were lævo-rotatory, instead of being dextro-rotatory?” Pasteur was a” a mere chemist,” and “not evena a medical man.” He was not a biologist, though most of his researches were biological, and he was not an embryologist. Had he been well versed in the biology of his own day, the suggestion of a hypothetical lævo-cellulose might have opened up an immense field to his further researches. At the time he wrote, Hofmeister’s researches* on the life-histories of various plants, with the main facts concerning the alternation of generations therein observed, were already the possession of science. † If there be a dextro-
*Hofmeister, Wilhelm: “Vergleichende Untersuchungen,” 1850.
† In his “History of Botany” the late Professor Julius von Sachs writes in terms of eloquence and amiration of Hofmeister’s researches: “The result of these ‘Comparative Investigations, 1851,’ was of such grandeur as in the realm of descriptive botany has not since happened a second time.” He speaks of “the brilliance of the grand sum total, ‘alternation of generations’ had proved itself to be the highest law of development in plants,
footnotes continued from page 152
governing the whole long
series.” He dilates on “the grand
picture which Hofmeister had drawn up of the genetic connections of the members
*Duclaux, E.: “Pasteur, Histoire d’un Espirit,”
The cycle of life, animal or vegetable, is asymmetrical, because the antithetic alternation of generations underlying it is founded on the asymmetry of these atoms. The generations, sexual or asexual, alternate according as the compounds are built up in the one direction or the other, for at its basis development is the building-up of naturally occurring compounds. In both animals and plants enzymes or ferments are the chief actors in this. The new organism, whether animal or plant, destroys that upon which it arose, and builds up in the opposite direction. The birth of the new fern-plant implies the destruction of the prothallus. The embryo or sexual generation of a mammal, or a man, destroys the asexual generation, the trophoblast, or chorion, upon which it arose, and builds up its compounds in the opposite direction to that employed by the latter. So also the cancer. This irresponsible trophoblast or asexual generation destroys the naturally occurring organic compounds and the sexual organism upon which it arose, and builds up in the opposite direction.
The action of a ferment is always a specific one. It fits the substance upon which it
acts, “as a key fits a lock” (Emil Fischer). Other substances it leaves untouched,
even isomeric compounds having an opposite rotation. As Dr. Margaret A. Cleaves* wrote in the
Medical Record of
*Cleaves, M. A.: “The Physiological Action of the Pancreatic Enzymes,
with Special Reference to Hematology, Urinology, and Clinical Pathology,” Medical Record,
with only those substances that attract and have an opposite isomeric form.” Confining one’s attention to cancer, the cancer-ferment malignin acts upon and pulls down the lævo-albumins of the living human body. As I have stated with von Leyden,* Blumenthal, † and Bergell, ‡ and more recently this was confirmed by Neuberg and Ascher, the action of trypsin on the living albumin of cancer is specific. Quoting further from Dr. Cleaves, “The only possible explanation of the effect of trypsin on pathological conditions capable of giving a tryptic reaction must be that certain proteid molecules—e.g.., in cancerous conditions—are capable of being attacked by trypsin, because of their special configuration.” In other words, the conclusion (foreseen by Dr. Cleaves also) may be drawn, that the albumin or albumins of cancer are dextro-rotatory. All this has been denied, without evidences beyond bald assertion, by various “authorities,” official researchers and medical journalists. As the lævo-albumins of the healthy living human body are not acted upon by trypsin, whereas the albumins of a living cancer are, it follows, as day succeeds night, that the latter must be dextro-albumins. No amount of contradiction in official reports, or in medical newspapers, can ever alter the truth of this fact, for “all enzymes are capable of entering into chemical action with only those substances which attract and have the opposite isomeric form.”
Much has been written about glycogen in tumours.
*Leycen, E. von, and Bergell, P.: “Ueber die Therapeutische Anwendung von Pancreatin in Carcinoma,” Zeitschr. F. klin. Med.., 1907, vol. lxi., pp. 360-365.
† Blumenthal, V.: “Die Chemische Abartung der Zellen beim Kreb,” Zeitschr. F. Krebsforschung, 1907, vol. v., pp. 182-189; “Die Chemische Vorgänge bei der Krebskrankheit,” Ergbn. D. Exper. Path. U. Therap., 1907, vol. i., pp. 65-104.
‡ Bergell, P.: “Zur Chemie der Krebsgeschwülste,” Zeitschr. F. Krebsforschung, 1907, vol. v., pp. 204-208.
Brault thought that the malignancy of a tumour varied directly as its richness in glycogen. Another medical man, impressed with this view, sought some substance which would “break up” this glycogen of a tumour, and hit upon trypsin. But the curious thing is that not only, of course, has trypsin no action upon the glycogen of a cancer, but the like is true of amylopsin. The latter at once converts the dextro-glycogen of the liver, but as Dr. Cleaves has shown in her paper already cited, amylopsin has no action upon the glycogen occurring naturally in a cancer. The reason is because the latter glycogen is a lævo-one. The interpretation to be placed upon the leucocytic phenomena of the Cleaves “trypto-glycogenic reaction” (the enormous increase of the eosinophile leucocytes under the enzyme treatment of cancer and their attraction by the glycogen of the tumour) is that amylopsin leaves the glycogen of a cancer untouched, but that it stimulates the leucocytes to seize it and to invert it. Just as isomeric compounds in the form of starches occur in both generations of plants, so also isomeric compounds of glycogen or animal starch are found in sexual and asexual generations of animals, including cancer. But, if the dextro-compound occur naturally in the one generation, the lævo-sugar in “the allantois.” According to him, (p. 398) it disappears towards the fifth or sixth month of
*Bernard, Claude: “Lecon de Physiologie Expérimental,’
intra-uterine life of the calf, a fact which goes to show the lævo-sugar to be formed in the trophoblast, and not in the allantois. Doubtless, its disappearance coincides with the development of large numbers of leucocytes in the fœtus. To my knowledge this lævo-sugar has more recently been rediscovered “ in the placenta,” but I am not aware that the fact has been republished. Of course, the “allantois” and the “placenta” are synonymous, but the real source of the lævulose in both instances was asexual generation or trophoblast.
The asymmetrical carbon atom, like its colleague, the pentavalent nitrogen one, has hitherto found as little place or mention in medicine or in physiology as has an antithetic alternation of generations. Man has thus found it possible to dispense with things and phenomena indispensable to Nature, and but for which he would have no existence! Whatever matter may be, whatever the nature of what we term “living matter,” at the basis of life lie the fundamental facts of the asymmetrical carbon atom and the isomeric compounds. At the base of all animal or plant life, too, because of these facts, there rests the antithetic alternation of generations. With the start of the asexual or the sexual phase of the cycle, the naturally occurring compounds are built up in the one direction or in the other. With the beginning of the next phase of the cycle, the alternate one, sexual or asexual, the swing of the pendulum about the asymmetrical carbon atom is on the other side, and the naturally occurring organic compounds are built up in the opposite direction. In animal life, that of the higher animals, the compounds are built up after the fertilization of the egg, and in the life-period of the asexual generation in the direction of lævo-sugar, lævo-glycogen, and dextro albumins. This evolution of compounds is the antithesis
of that which obtains with the unfolding of the sexual generation, “the embryo” or individual. Here the naturally occurring organic compounds are evolved in the direction of dextro-sugars, dextro-glycogen, and lævo-albumins. It is of great interest to compare together animals and plants in this connection. As I wrote some years ago; “the plan carried out in animals has been such as to favour the ever greater and greater amplification of the sexual generation. In plants, as elsewhere already insisted, the reverse is the case. Here the asexual generation has undergone increased amplification without ever being able to attain to any very high degree of histological differentiation. The sexual generation of plants is at the best a miserable failure from the morphological point of view, and this must be set down to the factors indicated, and still more to others yet to be described. The higher one ascends, the smaller it becomes, until, in the highest flowering plants, it has almost reached the vanishing point, without, however, being able to disappear entirely. In animals it is the phorozoon or asexual generation which makes the bravest show in the lower metazoa; but even here it is usually overshadowed in degree of morphological differentiation by the embryo or sexual generation. In the higher forms it becomes reduced; but, like the rudimentary sexual generation of the higher plants, it cannot vanish, for it also has its assigned task in the reproductive round.” The scientific investigator does not, of course, deal in a priori agruments. Were he to do so, he would expect to find the condition exactly the same in plants as in animals. For is it not “generally held,” and for this reason scientifically correct, that animals and plants have a common ancestry? Do not zoologists and botanists agree that at the bottom of the scale animals
and plants merge together, and that some of the lower organisms may be described equally well as animals or as plants? The scientific truth of the matter is that there is no merging together of the two kingdoms. Such a blending is impossible, because of the asymmetrical carbon atom. None the less, the asymmetrical carbon atom vouches the unity of organic nature.
It is clear that, if in any group of organisms, animals, plants, bacteria, fungi, etc., there be two phases of the life-cycle, asexual and sexual, there are for any given case two directions in which the naturally occurring organic compounds can be built up. But it should not be forgotten that the number of possible isomeric compounds increases with their complexity. The sexual generation of animals is characterized by dextro-sugars, dextro-glycogen, and lævo-albumins. In the corresponding sexual generation of plants, such as the fern prothallus, these are absent, being replaced by enantiomorphous compounds with the opposite rotations. It is the asexual generation of plants, the flowering plant, and not the sexual generation, which possess dextro-sugar, destro-starch, and lævo-albumins. The harmony of this is twofold. It realizes the apparent possibilities, and from the point of view of animal life it is of overwhelming important that it should be so. Ultimately, of course, all animals are dependent on plants for their foodstuffs. Were the sexual generations of plants the producers of the foodstuffs of animals, the latter, owing to the insignificance of the former, would find existence a very serious problem. The sexual generations of plants form substances resembling those fabricated by the asexual generations of animals, trophoblast, or cancer. Even if obtainable in sufficiently large quantities, the substances found naturally in a cancer would not be suitable as the
foodstuffs of an animal—a man, for example. But, as the asexual mode of reproduction, whether of a plant or of a cancer, is the more prolific one, there has been, hitherto at all events, no failure of the part of the asexual generation of plants to furnish ultimately the foodstuffs of animals. The conditions met with in animals are reversed in plants. Here a lævo-cellulose, a lævo-sugar, a lævo-starch, and one or more dextro-albumins must be sought for, not in the asexual generation as in animals, but in the sexual one, as represented by, for example, the fern prothallus. “Science is prevision,” said Pasteur. Because of the truth of this one is able to set up the following table of comparisons:
Sexual generation or individual. Asexual generation, trophoblast or cancer
Lævo-albumins, not acted upon when Dextro-albumins, not acted upon when
living by trypsin and amylopsin, but living by their own intracellular ferment,
attacked in life and pulled down by the malignin, but attacked in life by trypsin
cancer-ferment, malignin. and amylopsin.
Dextro-sugars. Lævo- sugar.
Pigment melanin. Pigment not melanin (in melanosarcoma),
Asexual generation (flowering plant Sexual generation (fern prothallus).
or fern). Dextro-albumin.
It would be interesting, were sufficient information available, to inquire into the conditions met with in bacteria and fungi. These are fundamentally neither animals nor plants. So far as the facts are known regarding their compounds and their ferments, some of them
seem to resemble the asexual generation of animals, rather than that of plants. In given circumstances many of them can attack the living compounds of the sexual generations of animals, or of the asexual generations of plants, pulling them down and building up in an opposite direction. As the plants and the animals are not genetically connected, so also, in all probability, the bacteria and the fungi have no genetic relationships with each other, or with the animals or the plants. Like the two latter, they are separate evolutions.
In 1889, in his study of the placentation of the hedgehog, Erinaceus europœus, Professor A. A. W. Hubrecht* set up the term “trophoblast” (p. 298), at the same time assigning to it, as the name implies, a nutritive significance. The nutritive import of the trophoblast of normal mammalian gestation has since that time been confirmed by many other embryologists, notably by Professor E. van Beneden and M. Duval, and it has been “generally accepted.” In the light of our present knowledge, a significance different from that seen in it by Professor Hubrecht must be recognized in “trophoblast.” Trophoblast has, and can have, no nutritive import for the developing embryo. This is quite obvious, once it is noted that the natural compounds formed in it are built up in the wrong direction to be useful as food for the developing sexual organism. The term, therefore, cannot be employed in future in a physiological sense. As Duclaux said: “Nature alone knows how to manufacture the one isomer without producing the other.” The chemist in the laboratory manufactures equal amounts of both isomers. May one deny Nature the power to do the like
*Hubrecht, A. A. W.: “The Placentation of Erinaceus europœus,” Quart. Journ. Micros. Sci., 1889, vol. xxx., pp. 283-404, 13 plates.
on occasion? Certainly not. It must be concluded, that in the fertilized egg she can build up in both directions. By the first few cleavages of the egg—usually the first —she can separate off portions as cells, endowed solely with the powers of producing the isomeric compounds of trophoblast, while retaining for the cell in the line of heredity the property of forming both. With the start of the evolution of an embryonic body, again by cell-division, she can separate off one or more original embryonic cells with powers the opposites of those possessed by trophoblast, all this taking place before any extra-cellular enzymes, such as trypsin and amylopsin, are formed. Full agreement, therefore (in a sense), may be expressed with the conclusion of Duclaux, that “to introduce in a cell principles immediately different, and the inverse of those which existed there, it is necessary to act upon it at the moment when it is most plastic, to take the cell of the germ and try to modify it” (p. 66). But, as Duclaux also observes, this cell has an heredity, and this determines not only its being, but what it shall become.
As may be gathered from the foregoing, the enzyme treatment of cancer professes to be, as is, a scientific one. Mankind in general, and surgeons in particular, have long looked for a cure for cancer. Presumably, this was to replace the knife. Now, at last, science and scientific research have offered not a cure, but the scientific treatment of and the cure of cancer. At once the surgical demand was altered into the request for a cure after the fact of operation on the living cancer. Scientifically, this demand cannot be met. Cancer is a natural phenomenon, not a disease. To “operate” upon living asexual generation is unnatural. As a scientific remedy, the enzyme treatment of cancer makes no claim to be the cure for cancer after it has been interfered with opera-
tively once or oftener. As a natural treatment, it is not
intended for post-operative “inoperable” recurrent cases. Did surgeons know that cancer was in its
nature asexual generation, they would never touch a living cancer with the
knife. For it is the property of
asexual generation, animal or vegetable, that it can be subdivided
indefinitely. In evidence of this
fact one need only refer to all the inoculations of cancer which, starting from
one original mouse-tumour, have been made into other mice. But on may also cite the very numerous
observations made in recent years in what has been termed “experimental
embryology,” but which would be designated more correctly “experimental
pathology.” Very numerous
observations in this unnatural subject will be found in the many volumes of the
Archiv für Entwicklungsmechanik, in
the Journal of Experimental Zoology,
and elsewhere. Many of the
observations were made upon fertilized eggs in cleavage, and the experiments
were almost as successful in subdividing the asexual generation represented by
an egg in cleavage as are the gardener’s proceedings in making and rooting
cuttings from a chrysanthemum plant.
The student of all these published experiments will notice, that the
organisms experimented upon never reverted to the normal. These experiments proclaim the truth of
the statement, that by operation a living cancer may be, and usually is,
subdivided indefinitely. Moreover,
let the words of the late Professor of Medicine in the
be successful. Nature does not “operate” upon living
asexual generation, and perhaps for this reason she has not evolved an
infallible mode of treating scientifically the failures of surgical
operation. Dr. Rice’s case* of
laryngeal cancer may be cited as an instance of the successful treatment of an
unoperated tumour, as also the Naples case of inoperable cancer of the tongue.
† Within the past few days (1907)
another case of the like kind has been reported privately as cured. Here, in October, 1906, on operation a
When official researchers are heard proclaiming to mankind that the enzymes, trypsin and amylopsin, have no action upon living cancer-cells, this is not merely a denial of the truth and validity of all my embryological work of the past nineteen years. (That is nothing new.
*Rice, Clarence C.: “Treatment of Cancer of the Larynx by Subcutaneous
Injection of pancreatic Extract (Trypsin),” Medical Record,
† Beard, J.: “The Scientific Criterion of a Malignant Tumour,” Medical Record,
‡ See Appendix G, No. 3.
§ Wiggin, F. H.: “Case of Multiple Fibro-Sarcoma of the Tongue,” Journ. Amer. Med. Assoc.,
Were it to-day a new scientific discovery that “two and two make four,” its truth would be challenged!) But by such negations the fundamental truths of the science of stereo-chemistry are also impugned, as well as the asymmetrical carbon atom. In short, when the efficacy of the enzyme treatment of cancer is question or denied, the constitution of the visible universe is condemned.
“Sooner or later a conviction may dawn upon investigators that the laws governing animal development lie deep, and that to discover them we must also take wider and more comprehensive views of our problems. Moreover, it should not be forgotten that little things, like a few stray ganglion cells, may hide an all-important story, and that here, as elsewhere, in the apparent exception itself the key to the mystery often lies concealed.”
THE PANCREATIC OR ENZYME TREATMENT
About three years ago a
medical correspondent in New York suggested to the writer that in a year or two
he would perhaps review the history of the enzyme or pancreatic treatment of
cancer during the years from 1906, pointing out the mistakes he and others had
made, and withdrawing those things in his scientific conclusion which had not
stood the test of time and experiment.
The reply then made was: “When that time comes, I shall have nothing to
retract.” This is true to-day, and
nothing in the first “Scientific Report”* issued by the New York Skin and
*Bainbridge, William Seaman, A.M., Sc.D., M.D.: “The Enzyme Treatment for Cancer” (Scientific Report on Investigations with Reference to the Treatment of Cancer, No. 1, 1909, New York, pp. 1-34.
on January 20, 1905, in a public lecture in Liverpool, “the secretion of that important digestive gland, the pancreas,” was clearly indicated as the scientific means of routing cancer, nothing at all was known as to doses and strengths of pancreatic injections, or even as to the proper modes of making up potent and keeping solutions of trypsin and amylopsin. Failures galore must have resulted, even if medical men had given the treatment to their best, instead of to their very worst, cases—as a rule, to advanced inoperable, or to post-operative recurrent inoperable, cases. There have, indeed, been many failures, even without the list published by Dr. Bainbridge, but—there have also been some successes. In the face of any successes, of Dr. Bainbridge’s own words (p. 32), “That injecto trypsini, in some cases, seems to cause more rapid disintegration of” (to ‘liquefy’ according to Beard) “cancerous tissue,” and “that injectio amylopsini seems to diminish cachexia in some cases, in accordance with the claims of Beard and other,” of what value are the failure—what do they prove in science? There are few—indeed, there are no—scientific discoveries of import to man which escape the like fate, if others attempt to confirm them, or if, and more usually (such is human nature), others seek to refute them. To take an instance suggested by a medical friend with reference to this report, how many of those, who in one way or another, with weak or with inert injections, or with minimal doses, or single injections, or with none at all, have sought to test my conclusions, could confirm the scientific researches of Starling on secretin? Not one! From some knowledge of the history of science, and of the receptions accorded by mankind to many scientific discoveries of import to the human race, and from a close knowledge and experience of the medical profession
--for have not several thousand medical men now in practice passed through my hands as pupils?--what else could be expected, than that witha very little knowledge, or with none at all, adverse verdicts should be pronounced upon the thing without any delay to examine the scientific evidences?
So little scientific care is, as a rule, bestowed upon the publication of the results of the enzyme treatment that, notwithstanding the publication of semi-polar accounts of my work in the Lancet and the Medical Record, I never yet read an accurate description* of the scientific basis of the matter from a medical pen in the pages of any medical newspaper. Most of the medical writers appeared not even to know what trophoblast was. It would be an easy, not to add an instructive, task to show that my work on the germinal origin and trophoblastic nature of cancer, with all its consequences (trypsin and amylopsin), differed in no way in the reception it encountered at the hands of the medical profession from previous discoveries recorded in the history of medicine. Have the names and labours of Pasteur, Lister, Morton, and Corvisart—to name but a few—been forgotten?
Scientific objections, which might have been raised, but which were never produced until it was too late, have been noted by others. Here I will add anew one. According to my finds, in any normal human gestation, Nature only allows the equivalent of cancer—trophoblast—to grow for a little less than seven weeks before she introduces the suppressing and destroying ferment or ferments. This is a point which should be borne in mine,
*There is one surgical exception to this. In the Appendix of his book, “The Control of a Scourge” (pp. 293 et seq.), Mr. C. P. Childe, B.A., F.R.C.S., gives a correct scientific account of the “pre-embryonic or trophoblastic theory” of cancer.
but which hitherto has usually been ignored, in attempting to remove by ferments an “inoperable,” usually recurrent cancer of two years’ or more standing, or in a laboratory vainly trying, aided by weak, or even inert, ferments, to cure a moust of a tumour “about as big as itself.” The processes employed by Nature in destroying asexual generation (trophoblast) are probably, like so many of her methods, self-regulating, and in view of this one might not be so sanguine of imitating her successfully, had not undoubted success been obtained.
More than once official cancer researchers have publicly described the pancreatic ferments, usually through other spokesmen, as devoid of action upon living cancer-cells, but in not one of the three “Scientific Reports” of the Imperial Cancer Research Fund are any evidences at all for this untrue assertion to be found. The photographs contained in this book, as well as the evidences concerning the liquefaction of cancer, amply refute this false and erroneous conclusion. Of course, the probability—nay, certainty—is that inert ferment-jpreparations had been employed in the unpublished experiments relied upon. Such official researchers may be asked to note that I have never urged the use of inert ferments in cancer, and have never supposed that such would have any action upon cancer-cells—or upon any proteid or other substance whatever, for that matter.
Four years ago a medical correspondent, Captain in the Indian Medical Service, wrote from Bushire, making the pertinent remark: “It is a pity that your opponents do not try to meet your ‘facts,’ instead of taking their stand upon their ‘opinions,’” The reply to this was not difficult to find. As Dr. Bainbridge sagely remarks on p. 4 of his “Scientific Report”: “The irresponsible trophoblast does not concern us here.” The reasons
and evidences for my conclusions as to the nature of cancer and its treatment on natural or scientific lines were beyond them. “Was der Bauer nit kennt, das frisst er nit.” What the leader-writer or ex-cancer researcher never learnt, that he is not likely to try and refute. Even “mecial science” would tilt in vain against the organization of the visible universe, though it has often made the essay, as witness Pasteur’s experiences.
In his essay “on Liberty,” which as a weighty, scientific document may be recommended to the attion of those who write on and of “medical science,” John Stuart Mill says: “The dictum that truth always triumphs over persecution is one of those pleasant falsehoods which men repeat after one another till they pass into commonplaces, but which all experience refutes.”
The passage cited was laid down by Mill in 1878, and possibly human nature has changed since then. The reader will note that all experience refutes the dictum. Medicine, which includes, or should include, the applications of certain sciences to human needs, has its own history in this respect. It is much simpler, and requires infinitely less knowledge, a modicum of crass ignorance often sufficing, to stifle a truth in its birth than to refute it on scientific grounds. To attempt to do the latter, moreover, entails the observance of certain canons of science, one of these being that no assertion shall be made without the production of the evidences. This is, perhaps, the real reason why the evidences for the asexual (trophoblastic) nature of cancer, etc., have never been attacked on scientific grounds.
The numerous “negative results” obtained by Dr. Bainbridge and by many other medical men are not scientific evidences against the truth of my conclusions.
They only prove that in certain cases, where as a rule the pancreatic ferments were administered as an alternative to the Last Sacrament, these ferments, as there exhibited, did not cure cancer, in the New York Skin and Cancer Hospital; though on the testimony of others they did cure it in Naples, in York and in other places.
On reading the thirty theses, advanced as conclusions, mostly without the
evidences, by Dr. Bainbridge, I am reminded of another phase of this cancer
problem. Some years ago two
*Vide Appendix H.
† Marshall, Francis H. A., and Jolly, William A.: “Results of Removal and Transplantation of Ovaries,” in Trans. Roy. Soc. Edinburgh, 1907, vol. xv., with two plates; also “The Nature of the Ovarian Influence upon the Uterus as illustrated
to-day the sole impediment in the way of the successful transplantation of living trophoblast is the Act of Parliament relating to vivisection.
When Mr. Walter Ball and Mr. E. F. Thomas saw fit to publish an account of how they tried “the trypsin treatment,” to their credit be it said, they did give particulars, as will appear anon, such that a good insight could be obtained into, and an estimate made of what they had really done. The like cannot be said of Dr. Bainbridge’s report. It winds up with thirty theses or conclusions, but the evidences establishing the truth of these are not to be found in the text. This is as true of the favourable points as of the unfavourable ones. The references to the liquefying action of trypsin on cancer-cells, and to the beneficial effects of amylopsin, might seem to refute this, but no evidences of these are adduced anywhere in this “scientific report,” and certainly the writer would feel inclined to doubt them, had he not witnessed them elsewhere again and again.
footnotes continued from page 171
by the Effects of Excision
and Grafting of Ovaries,” in Coll. Rep. Univ. Edin., Physiol. Dept., 1907-08,
No. ii; and “Results of Ovarian Transplantation,” in Seventeenth Internate.
of science and of scientific
truth I feel it my duty to record them.
The first intimation was in these words under the above date: “A
pensioned fireman had a cancer of the tongue and jaw removed at King’s
*The mention of this softness is very interesting in connection with the
happenings of the
evidences, and they were not at all numerous. The opinion then formed was, that, in the course of two or three days more, even these evidences of epithelioma would have vanished. Very shortly afterwards the same hospital physician had a similar result in an American patient suffering from cancer of the tongue.
This liquefaction of cancer, which, it may be added, can only be carried out safely in the presence of large quantities of amylopsin, is, of course, a stereo-chemical reaction. Now, Dr. Bainbridge admits (p. 32) that it occurs “in some case” and not in others; why there was an apparent exception to this chemical reaction. The reason, of course, was, that in many of the very advanced cases experimented upon the strengths and doses of the injections were inadequate to perform this chemical reaction. But this obvious explanation seems never to have occurred to the author.
Regarded from the point of view of science, this liquefaction of a living malignant tumour by means of adequate injections of trypsin and amylopsin is seen to be of momentous importance. It stamps the treatment, when scientifically given, as one continuous and sustained stereo-chemical reaction. Obviously, the liquefaction of the tumour and of any metastases is the aim of the treatment. To the writer it does not seem that great difficulties will usually be encountered with glandular metastases or again and again he has known these to disappear, even when the main tumour continued its career of growth and destruction. But in two ways at least the matter has great practical import. Since the liquefaction is the goal to be aimed at, and since all toxic
effects produced by the action of trypsin upon the tumour-cells can be averted by sufficiently powerful injections of genuine amylopsin of great strength, made along with those of trypsin, in all probability in the long run a considerable shortening of the vital and crucial period of the treatment can be, and will be, obtained. Again, the resulting liquefaction may be looked upon as being in essence a separation of the tumour into two main portions,--a liquid one, which either must be got rid of as a “sero-purulent” discharge, or, getting into the blood, must be excreted by the skin and kidneys; and a more solid portion, the skeleton or framework of the tumour-cells, which, it near the surface, may be sloughed out; if deeper, then encapsulated. In many cases it may be desirable once the phenomena of liquefaction have been induced, to remove the dead tumour by operation, and, so it appears to me, it is at such a time, when every tumour-cell has ben killed and its albumins liquefied, that surgical intervention is called for, if at all.
The eighth thesis (p. 32) must be specially noted and challenged. It reads: “That because of the tendency of injectio trypsini to disintegrate the tissues, it may to a direct menace to life—(a) by eroding large blood-vessels(when the disease is contiguous to these structures, as when deep in the neck or in the ;elvis), thus causing death by hæmorrhage; (b) when given in large doses, over considerable periods of time, by overwhelming the system with toxic products (tumour toxins), thus, in some cases, hastening death.” Regarding (a), I deny flatly that trypsin has any such action on normal somatic tissues as that attributed to it by Bainbridge. His conclusion is not in accord with the tenets of stereo-chemistry. The statement is a new answer to the old riddle: “Why do the stomach and intestines not digest
themselves in life?” The reply here given is tantamount to
saying, “Because they do.” The
scientific answer to the conundrum is, that those ferments, such as trypsin and
amylopsin, which build up the somatic albumins in life, do not pull them down in
the living state, but that the antitheses of these ferments, their
stereo-isomers, the ferments of cancer, do attack and pull down such albumins in
life. In the cases mentioned by
Bainbridge it is the fault of the tumour—that is, of its ferments, not that of
the “trypsin” injection, and in such cases as much danger at least attaches to
any possible treatment, even to surgery.
The erosion of a “large vessel” is caused by the tumour, and not be the
“trypsin.” The flimsy inaccuracy of
the statement (a) is shown by the following considerations: Wherever the cancer
may be, the injections are never made into it, but hypodermically, or deep into
the muscles, at some distance from it.
made against time, in order
to save the life of a very distinguished man, a brilliant artist and
In certain cases, and in these only, there are two dangers inherent in the enzyme treatment. These are (a) perforation, due to shrinkage of the tumour under the action of the ferments, as in œsophageal and gastric cancer; and (b) hæmorrhage, really due to the like cause, as in uterine and some pelvic cases. The physician should, however, note that these dangers are present in such cases, whatever treatment be adopted, or even if the cancer be allowed to pursue its course merrily; and that
they do not arise always, though threatening to do so, as in the Uppingham case of cancer of the stomach and liver.
In his report Dr. Bainbridge does not conceal a tendency to belittle the experiences of other physicians. Some of “the earlier claims of cures” were not so “absurd” as he imagines, and the “strange symptoms” and “terrific” results from small doses were, in my opinion, correct. The author overlooks the circumstance that he was not using the same injections as these observers, that he had profited by the increased experiences of the makers. Looked at scientifically, the writer would anticipate “terrific” results, even serious ones, from the use of small doses of trypsin in certain cases of cancer, where the tumour was large and the antitryptic power of the blood small. His remarks upon this and other matters only reveal to the scientific observer a lack of scientific imagination and of the capacity to adapt means to ends, which is so important in scientific experiment. If an injection be deficient in amylopsin, as also if it be not properly freed from poisonous peptones, even the use of no more than 1 c.c. daily may, as I have known to happen, be attended by serious consequences. Like the literature in general, the experimental results of Dr. S. Pinkus* receive no notice in this “scientific report.” This investigator found the following things after injecting certain unnamed sterile solutions of “pancreatin preparations” in dogs and guinea-pigs: “Here one or two injections sufficed to raise the temperature from 1° to 18° permanently; in all cases there was a strong local reaction, invariably leading to further necroses. Five cavies and the dog No. 4 died in eight to ten days.” It is also added that
Pinkuss, A., and Pinkus, S.: “Die Krebskrankheit und ihre therapeutische Beeinflussung durch Fermente,” Sonderabdruck aus der Medizinische Klinik, 1907, Nos. 28 and 29; 15 pages.
all the disturbances subsided when an injection of genuine amylopsin was substituted.
The thirtieth and final thesis of Bainbridge’s report reads that the enzyme treatment “does not cure cancer.” At the time this verdict was published, Captain Lambelle had reported his latest case of success to the War Office of Great Britain, and this report is given verbatim on a succeeding page. Even though there had been no others, even though Rice, Golley, Wiggin, Campbell, Goeth, Cutfield, Guarracino, and others, had had no successful cases, even if the remains of the cancer of the tongue in the Naples case had not been seen by two of the leading physicians of Naples (vide Appendix D) to shell out, “like the kernel of a nut,” I am prepared to take my stand, and now do so, upon the result of the published case of the recurrent sarcoma in York alone, to maintain that it has established the truth of my theses, and to declare that with this result all the essential portions of the problem, regarded scientifically, are solved once and for all. Bainbridge’s thirtieth thesis is false. He, who would set up the frivolous objection that the York case was one of malignant sarcoma, not of cancer, and that sarcoma does “not come within the definition of cancer,” may be invited to study the eleventh chapter of the present writing, and before urging this multiplication of causes scientifically to make for himself the crucial tests with the polarimeter to prove that cancer and sarcoma are not identical. In the cycle of animal life, as also in the visible universe, there is not room for two fundamentally different malignant tumours, cancer and sarcoma. The embryological evidences upon which this distinction has been founded, like those of this science underlying all current pathological classifications of malignant tumours, are absurd and unscientific.
When Captain Lambelle first sent me the three original photographs of his
case, he remarked that the outcome was “just as in the
As to the “thorough scientific test” of which the author writes on p. 3, I demur to this, just as I question the accuracy of the statement on p. 5, that “at all times during the trial of the enzyme treatment I (Dr. Bainbridge) have been in close touch with Dr. Beard.” † Since I first met Dr. Bainbridge, in September, 1906, with the single exception of Case 7, I have been entirely
*Beard, J. : “The Action of Trypsin unpon the Living Cells of Jensen’s
Mouse-Tumour,” in British Medical
† Compare also the Lancet (October 9, 1909, p. 1079): “We would point out, as a proof of the straightforward character of the inquiry, that throughout touch seems to have been kept with Dr. Beard.” In the sense understood by the Lancet this is incorrect.
ignorant of his doing. No information was at any time vouchsafed to me. Of the 100 cases, one (No. 49) was not cancer, sixty-six were post-operative failures, and eighteen were “inoperable,” making eighty-nine out of the 100. Of the remaining eleven, four are described as “lost sight of” and three as “alive.” Of the class of case which a scientific test demands—viz., an absolutely unoperated one-the100 cases include seven, as against sixty-six recurrent cases after one or several operations. Of these seven cases, three were “lost sight of,” three were “alive,” and one was dead. Five of the cases at least were syphilitic, and my experience hitherto has been that no good results can be hoped for in cases suffering from such a complication as syphilis. Ten of them had been treated with the X rays, which, looked at scientifically, must be regarded as one of the best stimulants of cancer ever discovered. How far the eighteen inoperable cases wee suitable ones for the treatment it is impossible to say. Here, as in all other respects, Dr. Bainbridge was his own judge, jury, prosecuting advocate, etc., and all the scientific man need say to sum up shortly what the report is, apart from all other considerations, there are in it no evidences at all to show that Dr. Bainbfidge ever considered, much less sought to eliminate, all or any possible sources of error in his experiments.
On the fifth line of his “scientific report” the author refers to the determination he had expressed in 1907 to give the enzyme treatment “a thorough, scientific test.” A study of his report reveals that (1) five strengths of trypsin injections were used, of which the strongest is stated to have had six times the potency of the weakest; but no attempt is made in the report to discriminated between these five injections, or the cases in which each
was employed, and there are no records of the doses or their number in a given time. (2) One case (No. 49) was “goitre,” not cancer; of the remaining ninety-nine, sixty-six were post-operative failures; that is, in a test assumed by the author to have been “a thorough, scientific test,” two out of every three cases contained the pernicious source of error of previous operation. (3) Lambelle’s results show—and this I have always maintained—that a treatment of less than three months cannot be considered adequate; I would even add an additional month, and regard 120 days as a general minimum, not maximum. Therefore (4) the hundred cases treated by Bainbridge may be summed up as follows:
(a) Exclude from the result, because no injections were given, Nos. 35,49,52,&92 = 4
(b) Exclude, because no real treatment was given, or because “lost sight of,” or ceased
treatment. Nos. 11,31,37,38,39,40,41,43,44,45,47,48,57,58,63,70,75,86,88,89,94
97, and 99 =23
( c) Exclude No. 7 (Miss K.H.), for obvious reasons = 1
(d) According to the report, there was “improvement,” or prolongation of life, in Nos.
5,6,8,14,16,17,18,19,20,22,26,28,34,42,46,50,60,72,78,80,and 100 =21
(e) Treated for more than ninety days, Nos. 3,12,23,32,51,66,76,79,81,82,84,98 =12
(f) Exclude, because treated for less than ninety days, with an average treatment of
forty-six days, or six weeks four days, Nos. 1,2,4,9,10,13,15,21,24,25,27,29,30,
But of those under (e) we are bound to exclude from a “scientific test”—
(1) The post-operative failures, Nos. 23, 76,79,82,and 84 = 5
(2) Owing to previous X-ray treatment, Nos. 3, 51 and 66 = 3
leaving under the heading (e) 4 per cent.
The sum of these numbers, 4, 23, 1, 21, 12, and 39 makes up the total of 100. Of the four cases remaining under (e), No. 12 was a surgical failure after the enzyme treatment, and the remaining three were evidently very advanced and malignant cases. The lack of anything more than “improvement” and “prolongation of life” in the twenty-one cases under (d), and the failure of the four cases under (e) might conceivably be due to injections too weak or doses too small, or to both, for those particular cases. I am, however, reminded of Blumenthal’s opinion (2), and the possibility or probability must not be overlooked that they may have been so advanced and hopeless that no possible treatment could have saved them. The like probably held the nine “test” cases treated by Messrs. Ball and Thomas.
The impression made upon the mind of another, who more than once has had success* withthe enzyme treatment, and who understands and fully appreciates its scientific foundations—I mean Captain F. W. Lambelle, M.D., R.A.M.C., lately operating surgeon of the Military Hospital, York—may be cited.
*In all four cases, treated as described in the present writing. They were (1) chondro-sarcoma of ribs; (2) encephaloid carcinoma of breast; (3) lympho-sarcoma, induced by X-ray treatment for carotid aneurysm by another medical man; and (4) round-celled sarcoma of jaw. The fate of the third is described in the present writing. The other three are, I believe, alive and well. Concerning (2) see Appendix L.
Regarding the case of lympho-sarcoma, it may be mentioned, as showing the true inwardness orf th pathological distinction of sarcoma and carcinoma, that in the microscopical examination of sections of the treated tumour after death the keratinous remains of tumour-cells were “mistaken” for epithelial cells by an official pathologist, and the diagnosis of “epithelioma” was given. I do not term this a mistake, for it was clear evidence of as little, “epithelial cells” as those of epithelioma or of trophoblast.
He writes: “In reading Dr. W. Seaman Bainbridge’s report one is struck by two repeated phrases, which seem to dominate his whole theme—(1) the patient ‘died’ within a few months of treatment by ferments have been undertaken; (2) the treatment was ‘negative in all respects.’ Though Dr. Bainbridge’s report is lacking in many details, which would have greatly helped in establishing its value as a scientific report, it is evident from (1) that the great majority of the cases which came under treatment were in an advanced stage of the disease. What does failure in such cases mean? Does Dr. Bainbridge as a surgeon condemn the operation for strangulated hernia simply because in a strangulated hernia case of five days’ duration the patient’s chances of recovery are one in ten or less? With regard to (2), the treatment was “negative”; it is also stated that ‘the control cases did as well with injections of glycerin and sterile water, or sterile water alone plus the régime, as did the others with the full enzyme treatment.’ These statements may be capable of some other interpretation than that which Dr. Bainbridge gives. Dr. Bainbridge has only shown that in his hands the treatment of cancer by ferments has been a failure, and it has yet to be shown wherein lay the cause of the want of success, remembering that failure is always easier of attainment than success in anything, and that on the frontiers of science still more so is this the case. Nor is that failure surprising to me, when I read how little Dr. Bainbridge has understood of the enzyme treatment, for in his summary he says, ‘that aiding digestion, increasing elimination, and decreasing local absorption are the most important features of the treatment’ Dr. Bainbridge’s report may be ‘negative in all respects,’ for paragraph 7 of his summary is proof that Dr. Bainbridge has never seen the effects of trypsin upon a malignant growth. He says ‘that, while it may accelerate the breaking down in the centre of the tumour mass, the periphery is found to be actively growing.’
Herein he describes the normal life-history of an unchecked cancerous growth—the growth goes on its own course merrily, without restraint from the enzyme treatment exhibited.*
“In the four years a fair amount of pathological evidence has been acquired, which is not in accordance with Dr. Bainbridge’s experience; and, without going minutely into details, let me cite two cases which seem to me to indicate (1) that trypsin does attack cancerous growths; (2) that trypsin can destroy cancerous growths:
“Case 1.—Male, 51. Lympho-sarcoma. Superficial cervical glands. Died from hæmmorhage from separating sloughing tumour. Naked-eye inspection of the tumour showed no gland-tissue whatever-it was a dense fibrous stroma pent up with purulent fluid. Microscopically, all that remained of the malignant cells were keratinous masses, in which the individual cells were unrecognizable. The treatment had exerted a selective action on the malignant cells, had destroyed them almost entirely, and their necrotic remains were in process of removal by leucocytes.
“Case 2.—Male, 25.
Round-celled sarcoma of upper jaw.
Primary growth removed by operation…recurrence in all the glands of the
left side of the face. Treatment
“What happened in both these cases was that under the action of trypsin the tumour became gangreous.
*If the account be taken of the “heterolytic” cancer-ferment termed by me “malignin,” and of the antitryptic properties of the blood in most, if not all, cancer cases, it must be clear that Dr. Bainbridge produces no evidence at all that he has ever had free pancreatic ferments in the blood of any of his unsuccessful cases. Nay, in view of Captain Lambelle’s apt criticism concerning the natural course of cancer, described by Dr. Bainbridge in his report, it is quite palpable that Dr. Bainbridge, in any of these unsuccessful cases, had never exhibited sufficient trypsin and amylopsin to neutralize the cancer ferment or ferments present.
The periphery of the growth in each case was marked out be a red line—an ‘area of demarcation’ as plain as in a gangrenous limb. In Case 1—a failure just short of success—we can see the process set forth, the influence of the trypsin upon the peripheral portions of the growth being to stem the invasion of the malignant cells, and to rouse the adjacent somatic tissues to that process of repair pathology calls inflammation. In Case 2 the gangrene of the tumour became complete, and the sloughing tumour was lifted from its bed without leaving one bleeding-point, nor so much as an oozing granulation.”
It will be demonstrated presently that from a knowledge of ferment powers (in the tryptic and amylotytic units set up by the late Sir William Roberts, M.D. F.R.S., Professor of Medicine in the Owens College, Manchester), and from the details furnished by the authors themselves, a fairly accurate estimate may be made for each individual case of the actual amount of trypsin and of amylopsin exhibited in the cases reported by Messrs. Ball and Thomas. In leaving the report under notice it may be remarked, with some emphasis upon its scientific value, that a similar estimate can be made in not a single on the cases described by Dr. Bainbridge. In view of more recent clinical work of others, it may be stated that the amylopsin injections employed by Dr. Bainbridge were very much too weak; that his four weaker trypsin injections. All of which I have more than once tested, were in strength quite inadequate for their work; and that regarding the fifth and strongest trypsin injection, the “special quadruple X,” which to my knowledge has never been sent to Great Britain, and possibly never furnished to anyone except Dr. Bainbridge, I can say nothing, beyond that I doubt whether it possesses more than 750 Roberts
tryptic units, whereas it should have 1,000 such at least.
One criticism, if it can be called such, has been made to the effect that
the theoretical basis on which “the trypsin treatment of cancer” is built
contains too many unknown factors to be accepted as sound. There is a learned ring about this empty
statement, but it lacks all evidences.
I suppose that, as the factors are unknown, they cannot be named. One might as well say, “The theoretical
basis upon which
As to the researches of Achalme, von Bergmann, Guleke, and
GENERAL DIRECTIONS FOR THE PANCREATIC OR ENZYME
TREATMENT OF CANCER IN ITS VARIOUS FORMS
When, in January, 1906, trypsin began to be employed in the treatment of cancer in many places, Fairchild’s “trypsin in powder,” and Merck’s trypsin, were the best-known preparations of this enzyme upon the market. Fairchild’s “trypsin in powder” was a very potent substance, prepared by this firm for “dissolving diphtheritic membrane,” and, so I understand, long used successfully for this purpose. In recent years it had been superseded by Behring’s “antidiptheritic serum,” a substance the nature of which is still unknown. Regarded scientifically, the innovation cannot be described as an advance. The sole mistake made by Messrs. Fairchild Brothers was in advocating its use as a powder, and not in the form of a hypodermic injection of trypsin (and amylopsin). There is no doubt in my mind to-day that certain of the injections of trypsin and of amylopsin, in combination, would with certainty and without any of the dangerous complications (serum-anaphylaxis) attaching to the usage of a “serum” dissolve this membrane, and cure diphtheria. But, of course, at present the medical profession is wedded to “sera,” which may be described briefly as unknown substances of uncertain action. So much for the preparations of “trypsin”
obtainable some years ago. When injections for use in cancer were first on sale, none of the makers did, or could, furnish any general direction as to how they should be employed. Many were the letters received by the writer, especially from French and Italian physicians and surgeons, asking for some directions as to the procedure to be adopted. These requests led to the first “general directions” from my pen. These latter were constantly being altered in accordance with the reports received and the knowledge gained. Even in their final formed, as printed for my convenience in 1907, they professed to lay down no strict course applicable to all cases. It was written: “The question of proper dosage is not yet decided finally, and it will probably be found to vary with different cancer.” Many of his friends and correspondents will, if need be, confirm the statement that all along the writer’s chief concern has been to impress upon physicians and chemists the urgent necessity of seeing that every dose of trypsin was accompanied by an adequate amount of amylopsin. The one injection was termed, unfortunately, injectio trypsini by the makers, but those with which I was in any way concerned always contained some amylopsin, a quantity which I could never get made large enough for the requirements. As will be seen, this has now been brought about in another way.
Even now it is not for me to lay down any fixed limit of size of tumour, or of time for the previous growth of the tumour, beyond which success cannot be hoped for; but it must be insisted, and emphasis laid upon the point, that no treatment can be considered adequate, unless it be such as will more than overcome, more than negative, the antitryptic (toxic) properties of the cancer ferment, malignin. To find in very bad cases, as some
have done, trypsin in the urine* is not enough; it must be shown that this is not antitrypsin (vide Bainbridge’s Report, p. 14: “The above experiments showed the presence in the urine in cases on the trypsin treatment, in non-cancerous patients, and in patients with cancer who had not been treated by trypsin, of an enzyme possessing properties of digestion similar to trypsin”).
This is cited as one instance where the actual ferment present was not determine. In the same way, if sugar be noted in the urine, it must be determined that it is not lævulose.
Dr. Bainbridge and others have, of their own initiative, set up what they term “test cases.” In a scientific sense no case can be regarded as a test one, where any other treatment had been employed previously, or where the conditions of the “test,” like the Ball and Thomas ones, and those of Dr. Bainbridge, had been laid own by the authors themselves without the agreement of the investigator, and without the scientific observance of the rules relating to “errors of experiment.” As will later on be done with one series of these “test,” so any other “scientific tests” shall be placed in their proper scientific aspects, including all the cases published by Dr. Bainbridge, when the authors see fit to reveal in scientific fashion what they have really done in the process of carrying out their “scientific experiments.”
Then there are the preparations and the dosage. Scores,
*Similarly, in the first of the cases recorded by Dr. A. Pinkuss, in the paper already cited (p.12), it is stated that trypsin was first detect in the urine after forty-eight injections, and from thence onwards it remained mostly positive. Considering the strengths of injections used, it appears more likely that antitrypsin from the cancer was mistaken for trypsin, and this surmise is rather confirmed by the statement that a rigor was only observable on the forty-third day or treatment.
if not hundreds, of those in this country who, if asked, would give an adverse opinion of the pancreatic enzymes in cancer have never even employed them.. This may be illustrated.
A former pupil, a physician in this city, has urged that the medical man
is bound to trust to chemists for his drugs, etc., and as an instance he cited
digitalis. To which the reply was
obvious. If a physician, using
digitalis, did not get the reaction he anticipated, he would naturally suspect
the preparation, and would inquire as to its true chemical character, but he
would not, in the absence of the expected reaction, condemn the use of
digitalis. This, however, has been done again and again with preparations of
trypsin (and amylopsin), in the absence of any proof or knowledge that the
preparations used contained any enzymes whatever. It is illogical and absurd to
condemn a scientific treatment, as some eminent surgeons in
Early in July, 1909, I spent several hours in the society of a well-known
In certain independent laboratory estimations of these preparations, made by a fully competent chemist and physician in February, 1907, the tryptic power per ampoule of these preparations was found to be 9·6 Roberts tryptic units. That is to say, if preparations of such a strength of trypsin (9·6 units), and of the very slight amylolytic power of 0·37 amylolytic units, were now used for what Captain Lambelle and I regard as full normal doses, given daily or every other day, the following would be the procedure: The full daily dose of 1,000 tryptic units would require the use of quite 100 ampoules of 9·6 units, and the full dose of amylopsin could be obtained from more than 5,000 ampoules of the strength of 0·37 unit, ore more than five litres. I commend these figures to certain transparently anonymous scribes, cancer researchers and ex-researchers, in the English medical press.
It has been pointed out that little or no evidences of the value of
pancreatic ferments in malignant disease have been published in
The writer has not a single record of a request for injections as strong as 250 or 500 tryptic units from any French physician. Some French and Italian cases were
treated with the first Fairchild injections, which have long been recognized as far too weak, and which are not now on sale anywhere. In France and Italy, whence came the first rush of request in 1906, a very large number of cases in 1906 received injections, which at that time were found to possess a tryptic power of 9·6 tryptic units.
Before me lies a “list of doctors and hospitals” in
For we have never seen that
a tumour which was circumscriptly brought to a dissolution of its cells by a
tryptic ferment, reacted by increased growth to this procedure, either locally
or generally.” According to my calculations, based upon Table V. of Dr. Hald’s
paper, to be cited presently, the “trypsin” employed in the
Hitherto in his publications the writer has not committed himself to definite statements as to the actual and relative strengths of the injections of enzymes, or their amount. The actual treatment of every single case, the writer being “not even a medical practitioner,” exactly as Pasteur was “not even a medical man,” was absolutely in the hands of the physician concerned. But I doubt whether any physician or surgeon can say truthfully that I ever told him that he was giving too large or too strong injections of trypsin and amylopsin. Again, the manufacturers placed on sale just such preparations as