- Five years ago, Gary White had a 14-pound tumour in
his gut, and he was given eight months to live. Now, he's 49, sailing
and spending time with his kids -- thanks, doctors say, to regular
injections of a mild virus. Could the common cold really cure
cancer?
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- Gary White considered himself a buff 44-year-old and
chalked up his bloating belly to beer with the boys. He even bought
himself an ab exerciser. Then, in 1997, he stopped short on the
basketball court one day -- and the bulge didn't stop with
him.
He felt fluid lurch and roll, wash over his innards and
slosh like a tsunami against his gut. White quit the game and hauled
himself to the hospital. The ultrasound nurse gasped at the screen:
"What is that?" A blob bigger than any baby had spread through his
abdominal cavity. It was cancer -- mesothelioma, a rare, multisyllabic
monster so far gone that the doctors gave him eight months at
best.
Go home, they said. Get your affairs in order. Kiss your
wife goodbye.
Yet five years later, White is still here, broad
and strong, with his wife, his two kids and his buddies. He has even
fulfilled a lifelong dream, sailing a 43-foot Spindrift to second
place in the Caribbean 1500. And his 14-pound tumour? It's posted like
a trophy on the Internet.
Chemotherapy -- and a surgeon who
dared to extract the massive growth -- bought him a few extra months.
But the Connecticut man credits something else for keeping his cancer
at bay: a flu virus, pumped into his bloodstream six times a month for
the past three years.
Dozens of dying men and women are now
being deliberately infected with viruses as doctors determine if these
microscopic bugs can kill the cancers without killing the patients.
People desperate to beat their disease have volunteered to catch the
flu, a cold, even a modified version of herpes.
Results from
animal studies have been astounding. Injected with viruses, human
tumours in mice have shrunk and vanished completely without harming
the animal. And viruses have worked against not just one cancer, but
nearly every malignancy medicine knows, whether breast, lung, liver,
colon, ovarian or even brain.
White's is the first human face
to emerge from the early experiments, but it won't be the last. Nine
cancer patients in Ottawa received infusions at Christmas with the
same virus. Canadians are among the leaders in the field. University
of Calgary researchers have completed the first trial designed to test
the safety of a reovirus, a bug common to the human gut and nasal
passages, in people.
Eighteen patients with sarcomas (cancers
of the bone and soft tissue), breast, skin, head and neck cancers
suffered no serious side effects over a recent 14-week trial. Some of
their tumours even showed signs of shrinking and one tumour
disappeared completely. The Alberta group is now conducting a Phase 2
trial, testing 45 prostate-cancer patients and in another experiment,
will treat people with brain cancer.
"The results are
encouraging, but this is a whole new area that we're exploring," said
Dr. John Bell, a senior scientist with Cancer Care Ontario involved in
the Ottawa trials. Still, he says, in the lab "there hasn't been a
cancer that isn't vulnerable to a virus."
Bell's group at the
Ottawa Regional Cancer Centre has started human safety tests with the
Newcastle virus, a flu bug that strikes chickens. They are
collaborating with Provirus Inc. in Maryland, which has already tested
Newcastle in more than 70 American patients, including Gary White,
whose case will be included next month in the Journal of Clinical
Oncology.
California's Onyx Pharmaceuticals Inc. and Stanford
University are testing a genetically altered adenovirus -- better
known as a common cold bug -- in patients with head, neck or liver
cancers.
Harvard is running trials with a modified herpes
virus, and lab research is underway on a weakened polio virus at Duke
University and on measels at the Mayo Clinic.
Scientists are
struggling to contain their excitement: Imagine beating the big C with
a little-c weapon as wild and mild as the common cold.
Of
course, curing cancer in mice has made front-page headlines before.
And scientists, too familiar with the failures, are cautious as they
await answers: Is Gary White a statistical blip?
Using one
disease to fight another sounds like a handy, if risky, strategy. But
it works with antibiotics. And making friends of our viral foes to
battle cancer offers a special irony: The defects that make cancerous
cells vulnerable to viruses are the very same ones that make them
malignant.
"Tumour cells have already undergone genetic changes
to become cancerous," said Bell, also a professor of medicine at the
University of Ottawa. "They have thrown out genes that inhibit their
growth, but at the same time, they've thrown out their anti-viral
programming."
Unfortunately, some scientists suggest patients
may have to decide whether they are willing to live the rest of their
lives with the symptoms of a flu or worse.
But, as Bell said,
"Cancer is such an awful disease that patients are willing to be
infected."
And according to Provirus consultant Dr. Andrew
Pecora, the director of the Cancer Center at Havensack Medical School
in New Jersey, who supervised White's experimental treatment, "It may
be that you add this treatment to standard therapy and all of a sudden
you're curing people."
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- The concept of fighting cancer with viruses actually
stretches back through a 100-year history, rife with bizarre anecdotes
of tumours regressing when a cancer patient battles a cold, a flu or
some other infection. Advances in genetics and molecular biology have
only recently explained these weird observations, pushing them from
the fringes of medicine into mainstream research.
One of the
first reports, Bell said, dates back to an Italian physician who
roamed the countryside in the early 1900s vaccinating people against
rabies. The doctor noted curiously that prostitutes, whose sex work
plagued them with high rates of cervical cancer, had their tumours
regress after they received the rabies vaccine.
Later, reports
from the 1940s and 1950s suggested that measles could quell
lymphoma.
"A lot of these exposures to viruses were unintended,
and only a few trials were on record," said Duke University virologist
Matthias Gromeier. In part, said Gromeier, who is studying a modified
polio virus to treat brain cancer, the records are slim because some
experiments conducted were highly unethical: "People just fed the
polio virus to cancer patients in the Soviet Union in the
1950s."
Doctors were also limited to the viruses they could
harvest. That meant distilling mumps and measles viruses from people's
saliva or pus, and injecting this unpurified form directly into a
patient. If results were promising, the point was moot: The patients
were probably too sick with infections to care.
The next
report, from the 1960s, is so often cited that doctors confess to
wondering how much of it is urban legend.
But the details, Bell
said, go something like this: A Hungarian chicken farmer with a deadly
case of stomach cancer was sent home to die. But while tending his
chickens, which happened to be suffering an outbreak of the Newcastle
disease virus, the farmer contracted the chicken flu and his cancer
completely regressed.
Skeptics dismiss the accounts as
preposterous, while more than one desperate cancer patient has since
trekked to Hungary for shots of this avian flu. But even in
established scientific circles, anecdotes have always circulated to
suggest an intriguing link between infections and halting
cancer.
"It's been floating around for years," said medical
oncologist Don Morris, who runs reovirus trials at Calgary's Tom Baker
Cancer Centre. "It's common to hear that cancer patients who pick up a
virus get a regression of their disease."
Despite all the
tempting tidbits, research idled until the past decade. It went
nowhere, Bell said, because scientists could not explain the
phenomenon. Did viruses simply supercharge a patient's immune system
to fight cancer? How could you find out?
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- Dr. Patrick Lee is a virus man. Raised in Hong Kong
and educated in Edmonton, he decided early to devote himself to the
arcane world of these microscopic pathogens. He trained in the
seventies at the University of Alberta and under the fathers of modern
virology at Duke, where he learned the enemy's tricks and grew to
admire them.
Unlike bacteria that can multiply on a doorknob, a
subway seat or a bowl of soup, viruses are parasites that depend on a
host cell for their survival. But once a single virus particle busts
through a cell wall, it can replicate from 1,000 to 10,000 times
within two days.
"It's amazing," said Lee, his enthusiasm
unmasked. "It makes identical copies of itself over and over again
until the cell finally ruptures and the virus progeny drift out to
infect other cells."
In 1981 at the University of Calgary,
where the virologist and biochemist is now a professor of medicine,
Lee turned his attention to the mechanics of the reovirus (short for
respiratory enteric orphan). The common bug has triggered colds and
stomach upsets in nearly 90 per cent of us before we reach the age of
3. If a scientist wanted to learn how viruses manage to latch on and
break into a cell in the first place, the reovirus was a good
candidate to study.
Lee soon discovered that the bug attaches
itself to a single sugar molecule on the surface of a host cell. Then
a graduate student proposed an experiment to see if the reovirus would
hitch itself to a second receptor if he blocked out the
first.
"It was a weird idea and I told him that it was a stupid
experiment," Lee said. "But he went ahead and did it anyway, and it
didn't work." Yet what flowed from the faulty investigation wasn't
stupid at all.
Analyzing the student's information, Lee noticed
something strange that accidentally led him to discover how the
reovirus could penetrate cells in a lab dish at an uncanny rate. At
first, he thought the reovirus was fooling the cell into thinking it
was some other normal molecule. "My heart was pounding so fast I
couldn't believe it. I thought I figured out how a virus tricks the
cell."
But by the early 1990s, Lee became troubled by the
notion that a single virus particle could coax a healthy cell to throw
its door wide open. And that is when it dawned on him that the door
was already wide open -- because this was no healthy cell. The virus
experiments had been conducted in cancer cells, which are used
routinely in research because they're easy to grow.
Lee's
experiments later proved that a biochemical signalling system called
the RAS pathway, important for growth and survival, is flicked into
overdrive in a cancer cell. "In the normal cell," he explained, "this
is like a light that's only turned on sometimes," leaving a virus
groping in the dark on the stoop of a healthy cell.
But in the
cancer cell, the RAS pathway is more like a porch light on the
prairie, never shutting off, allowing the virus to find its way to the
front door and march right in.
Lee's remarkable finding, along
with staggering studies that demonstrated the reovirus wiping out a
wide range of tumours in mice, was published in Science in 1998. It
turned up in headlines around the world, and researchers were
immediately attracted to the notion that something as ubiquitous as a
virus might selectively kill cancer cells without killing healthy
ones.
"It's the stuff of which we all dream, to have that flash
of insight," said Michael Wosnick, director of research at the
National Cancer Institute of Canada. "And all logic says it should
work."
"I think we're going to find out that some viruses are
going to be good at targeting some cancers, and that other viruses
will get other cancers," Bell said.
While the Calgary group
prepared to move the lab findings into clinical trials, Lee's work
helped to explain why other research teams were already collecting
evidence of the stunning anti-cancer properties of
viruses.
Among them was the Harvard team led by Robert Martuza,
who had described in 1991 how a genetically weakened herpes virus
could kill tumours in animals, and Andrew Pecora's Hackensack group in
New Jersey, which was then preparing to launch the first trial of the
Newcastle virus in human patients.
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- Pecora's group ran ads on the radio in the spring of
1998, looking for people with solid tumours who had exhausted every
other treatment available. White heard about the plea for "guinea
pigs," and he called in.
Pecora told White that he was running
a Phase 1 trial for an experimental therapy. Such trials, he
explained, are not conducted to gauge whether a new treatment is
effective, but to determine the maximum dose a human can safely
tolerate.
In other words, the trial wasn't designed to save
White's life. Was he still interested?
White explained that he
had spent 12 years as an administrator at the Connecticut Department
of Mental Retardation, a facility that closed in the late 1980s with
high levels of asbestos. He figured the exposure probably caused his
cancer (a legal settlement would later confirm his suspicions). White
described his surgery, the drugs that were literally hosed into his
abdomen, how his "disease ate the chemo for lunch," and the miserable
prognosis he had heard at hospitals from New Haven to New
York.
Then Pecora told White about the Newcastle virus. "He was
pretty revved up and excited," White remembered. "I decided to try
it."
The regimen, he learned, would involve three infusions of
the Newcastle virus a week for two consecutive weeks, and then two
weeks off. After the first round, he and other patients in the trial
developed soaring temperatures of 104 degrees. White ended up in the
hospital for a few days, but he decided to stick with it.
Bell,
who is now involved in Ottawa's Newcastle flu trials, said that in
those first days down in Hackensack, even the researchers held their
breath. "This was the first time it had been infused into patients,
there were some sleepless nights."
"Some of the older patients,
who had fragile immune systems, couldn't take it," White said. Already
battered by powerful drugs and radiation, some dropped out. "You are
really very ill in the beginning. But then you start to build up
antibodies and then you get tolerance."
The initial dose in the
Ottawa trial has been lowered to counter this dramatic reaction to a
foreign substance. "We're allowing for a desensitization period, and
thus [causing] less side effects," Bell explained. But otherwise, they
are following the highest safe dosage established by the first
Hackensack trial.
There are all sorts of things researchers are
just coming to understand about using viruses as medicines, Bell said.
Some patients in the first trial were pulled out early because doctors
were under the mistaken impression that their tumours were getting
larger. But California's Onyx group recently reported that tumours
initially swell as part of the natural inflammatory reaction to
infection.
"When the swelling went down, they found the tumours
actually shrank," Bell said.
A year into White's treatment, he
finally heard an encouraging medical report: "There was no sign of
progressing disease." The only worrisome feature remained a tumour
near his pelvis, which his surgeon removed and pathologists anxiously
studied. When they tried to grow White's biopsied tumour cells in the
lab, they stumbled on a happy fact -- infected with the replicating
virus, the cells would not grow.
"The cancer cells were all
necrotic and dying," Pecora said. Healthy immune-system cells were
also penetrating the tumour.
The Hackensack trial ended within
the year, but with White's remarkable progress, the U.S. Food and Drug
Administration allowed him to continue the experimental treatment on
compassionate grounds.
He has since packed a lot of life into
the three years he never knew he would have. He has seen his daughter
graduate from college and his son graduate from high school. He bulked
up his 6-foot-3 frame, started shooting hoops again, and "cashed in
some chips" with his legal-settlement money to go down to New Orleans
and buy his prized sailboat, called the Anam Cara, after the Celtic
for "trusted friend."
He raced the Anam Cara from Virginia to
the British Virgin Islands, and he and his wife, Katherine, a
schoolteacher, started talking about taking a year off, maybe sailing
around the world.
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- Any notion that cold viruses are harmless as therapy
evaporated with the death of Jesse Gelsinger in 1999, during a
gene-therapy experiment. The 18-year-old patient, who suffered from a
rare metabolic disorder, was injected with a weakened adenovirus that
was to deliver a corrective gene for his ailing liver.
Daniel
Sze, an assistant radiology professor at Stanford and Onyx consultant,
said Gelsinger received a dose 20 to 30 times higher than the one Sze
has been injecting into patients' arteries to target liver cancer. But
Gelsinger's death still has made some patients reluctant to join
anti-cancer virus trials, according to Harvard neurosurgery professor
Antonio Chiocca.
"The history of science has not been geared to
think of viruses as a positive thing," said Chiocca, who has been
running trials using the modified herpes virus to treat brain cancer
at Massachusetts General Hospital. "Patients have to understand this
is still highly experimental, we're not cowboys just injecting this
into tumours."
Newcastle is the first replicating virus to be
called into battle against cancer by being pumped into human patients
intravenously. Most other trials are relying on injecting viruses
directly into tumours. But safely channelling the pathogen into the
bloodstream is the ultimate goal.
As Don Morris in Calgary put
it, "People don't die from a tumour. They die from spread disease."
The obstacle, as the Gelsinger case showed, is figuring out how to
safely fill a patient's system with an infectious agent -- one you
can't control. After all, a dose of a single virus can Xerox itself
into as many as 10,000 viruses within 48 hours. What other drug gets
stronger with time?
"It's a balance scale," Morris said. "Too
much virus and too little immune system can kill the patient. Too much
immune system and too little virus, and the treatment doesn't
work."
Calgary's reovirus likely performed so well in safety
trials, Morris said, because most people already have antibodies to
it.
Similarly, Onyx is using a cold virus altered to target a
gene commonly missing from cancer cells, not because it's the most
powerful tool in the medical shed, but because it may be one of the
safest. "If it mutates back into its original form," Sze said, "it's
going to give you a cold -- it's not going to give you AIDS or
something."
But for now, Chiocca said, scientists are still
trying to understand what is safe: "We haven't seen anything dramatic
to make us say, 'Stop the trial and let's just start treating
patients.' But anything that is safe and effective in cancer treatment
is a bonus."
Whatever dosage doctors determine, cancers seem to
grow back without the steady presence of a viral attack. It's quite
possible, Chiocca agreed, that patients might have to consider whether
they would live with a permanent cold.
The question might be
whether patients are "willing to turn a fatal disease into a chronic
one," Pecora said. "People live with arthritis all the time. They take
drugs that have side effects, but they live with it."
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- After all, he added: "There will always be some
reaction to the virus. But if it works in other people as it did Gary,
what does it matter?"
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- Gary White is on the water this week, sailing the
Anam Cara for what will likely be the last time. Doctors found another
tumour on his rib cage earlier this year. Surgeons removed it, but he
missed more than a month of his viral treatments
recovering.
"I've never gone that long without them," said
White, now 49.
Thoughts of sailing away with his wife on the
high seas have been reined in. He asked his doctors if should he take
the chance and leave. "I asked them, 'Should I stay, dock the boat in
Florida and sell it?' They told me to dock the boat."
Reactions
to the treatments have slipped into a predictable routine for White.
And only one of the six 30-minute infusions a month triggers side
effects. After the first, desensitizing dose on Mondays comes the
dreaded Wednesday, when within 10 minutes of the virus seeping into
his bloodstream, it starts: "I get beet red, flushed, I feel chest
pressure, pounding and cramping my lower back. The nurse says it
sounds like labour pains.
"There's a lull, and then I get nasty
tremors for 15 or 20 minutes and they wrap me with heated towels -- it
sucks."
But after 20 minutes, White said, it's over. "Then I'm
ready to go. I can play golf half an hour after getting most of my
treatments."
As he prepared to sell his beloved boat, White was
already thinking of his next adventure, "maybe an RV."
As he
summed it up, "It's been a long, strange trip. I've been living on the
edge of a knife all this time, and I'm not afraid of death. But it's
hard to make plans."
He's also not thrilled with being anchored
to the 2-hour drives through New Jersey's industrial corridor from his
home in Storrs, Conn., to Hackensack six times a month. "That's a lot
of time in New Jersey.
"But what the heck?" White said. "I'm
alive."
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All Rights Reserved.
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