- 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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- Copyright © 2002 Bell Globemedia Interactive Inc.
All Rights Reserved.
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