Here is a tremendous article from Boston's Daily Globe that ran in today's
(Part 1 of 5)
Progress, but no cure
Scientists, attacking on many fronts, make gains never made before
By Larry Tye and Richard Saltus, Globe Staff, 08/02/98
First of five parts
IT WASN'T SO LONG AGO that people were so terrified by the disease that
they wouldn't even utter its name.
So they called it the ''Big C.''
But today, cancer, which has resisted nearly every weapon medicine has
deployed against it since the ''war on cancer'' was launched 27 years ago,
is finally showing signs of vulnerability.
There's no miracle cure, and there may never be. But scientists and doctors
have come to know the enemy, intimately. They now know how cancer starts,
what it takes for tumors to grow, and even how cancer cells sometimes
And they are using that knowledge to battle back in what longtime
cancer-fighters say is the most promising push ever against the illness, a
campaign being waged on numerous fronts.
''I feel very optimistic,'' says Dr. Richard Klausner, who as director of
the National Cancer Institute is leading the charge. ''I am, as a
scientist, continuously amazed at how much we know now that we didn't know
a few years ago.
''What is clear to anyone looking at it is that the number of ideas and
strength of those ideas has gone up remarkably. That's real progress.
That's the type of progress we have to make if we're going to get,
ultimately, to our goal of curing cancer.''
That progress is most evident in the laboratories of molecular biologists
who devote their lives to unraveling the intricate machinery within
microscopic living cells. Some are learning how to turn off genetic growth
switches that get stuck in the ''on'' position, and to replace
tumor-suppressing genes that break and allow cells to spin out of control.
Others, relying on newfound understanding of the immune system, are
developing ways to marshal the body's own defenses.
And at Children's Hospital in Boston, Dr. Judah Folkman and his colleagues
have proven they can shrink tumors in mice by choking off the tumors' blood
supply. While recent media accounts raised unrealistic hopes about how fast
that strategy might be translated into treatment for humans, researchers
still say this is the most hopeful weapon on the horizon.
Five-year-old Emma Carey of Exeter, N.H., stands as living proof of how
such sophisticated knowledge of what goes on inside cancer cells already is
yielding important real-world applications - and of how much more it might
yield in the future.
When Emma was diagnosed with leukemia last year, doctors at Massachusetts
General Hospital used a new ''molecular diagnostics'' test to spot telltale
genetic alterations in her blood cells. With that genetic profile, ''we
could tell her parents that she has an excellent chance of survival, close
to 90 percent,'' says her physician, Dr. Howard Weinstein. Before long,
Weinstein adds, such genetic profiles may be used to tailor highly specific
treatment recipes to each individual.
Even while they are awaiting new payoffs from the laboratory, cancer
doctors are hard at work getting old tools to perform new functions. That
means concocting promising cocktails of old and new chemotherapy drugs,
targeting radiation to tumors in ways that make it more precise and potent,
and fine-tuning surgical techniques - all of which are extending and saving
the lives of patients today.
''The war on cancer has worked,'' says Dr. Vincent T. DeVita Jr., the
former NCI chief who helped launch that effort in 1971 and led it until
1988. ''My projection is that the reduction in mortality and incidence
rates will deepen every year. We'll hit a 30-percent reduction for breast
cancer alone by the year 2000, and overall rates will be down 25 percent.
''I don't think we'll do away with cancer,'' adds DeVita, who now runs the
Yale Cancer Center in New Haven. ''But it won't be the major killer it once
was. It will be controllable so people can live with it, like they do with
diabetes, and we'll be preventing a lot of cancer.''
Disease has long been one of humanity's scourges
To understand how far we've come, and how much remains to be done, it is
critical to understand the history of the long struggle against cancer.
The disease has always been one of humanity's scourges, but the stakes were
raised in the 1950s and '60s as more and more people began dying of cancer.
Part of that was attributable to the longer average lifespan of most
Americans, since cancer is primarily a disease of aging. More sedentary
lifestyles and increasingly fatty diets probably contributed as well. Most
of all, however, smoking caught on widely among men during World War I.
Women joined in not long after. A generation later the toll began to
surface in the form of soaring rates of lung cancer.
As cancer rates rose, doctors fought back, but with few weapons.
Researchers worked to add to the arsenal, but their approach was
hit-or-miss, relying more on happy accidents than on scientific acumen.
That's what happened near the end of World War II, when an Allied ship
loaded with sulfur mustard, a poisonous gas the Germans had used during
World War I, blew up in Italy's Bari Harbor. Doctors treating the injured
soldiers noticed that the gas had curious effects on key components of the
immune system - white blood cells were sharply depleted, lymphocytes were
impaired, and blood-forming bone marrow was damaged. That made them wonder:
If the gas impeded the normal workings of those cells, could it also curb
the much-feared lymphomas and leukemias in those tissues
Researchers at Yale University, Memorial Sloan-Kettering Hospital in New
York, and other cancer centers ran experiments, using a related gas called
nitrogen mustard. The results, which were kept secret until the end of the
war, confirmed that cancers did in fact regress when exposed to the gas,
and patients got better.
The good news was that medicine for the first time had an agent able to
shrink tumors, a discovery that seemed especially sweet since it had been
derived from an insidious poison. Soon, researchers were using what they
knew about mustard gas to concoct other anticancer drugs.
The bad news was that the tumors didn't stay down for long, generally
didn't respond to a second round of treatment, and the scientists didn't
know what to do when the ''cure'' fizzled.
''When I started in 1955 there were relatively few anticancer compounds
that were active, relatively few patients that would benefit from such
treatments, and relatively few scientific leads we could address and
develop and apply,'' recalls Dr. Emil Frei, now 74 and physician-in-chief
emeritus at Boston's Dana-Farber Cancer Institute.
But by the early '60s, when Dr. George Canellos joined the National
Institutes of Health, things had begun to turn around. ''There was a spirit
of discovery,'' says Canellos, now at Dana-Farber. ''It opened my mind to
the idea that drugs, medicine, could be used to successfully treat cancer,
where up to that time there was only surgery.... To resurrect people you
thought were destined to die, you have no idea the feeling that gives you.''
All America seemed to share the feeling that cancer was beatable when, on
Dec. 23, 1971, President Nixon signed the National Cancer Act and launched
a war on cancer he said should yield a cure within five years. To a country
that had managed to put a man on the moon two years earlier, anything
The early signs were encouraging, at least in terms of sheer activity. In
the five years after the act was signed, Congress appropriated more money
for cancer than over the previous 33 years. Cancer centers were funded
across the country, and many of the country's best scientists were drawn to
the field. And there were advances, big ones: researchers developed
powerful techniques for hunting down and isolating genes; physicians
pioneered ways to save the limbs of young patients with bone cancer; and
the US Food and Drug Administration approved early anticancer drugs like
doxorubicin and cisplatin.
But on the cancer wards, progress in beating back the deadly disease wasn't
happening as quickly as the public, and many doctors, had envisioned. Some
of the disappointment came from chasing false leads. In the late 1960s and
early '70s, many scientists were drawn to the idea that viruses caused most
cancers. In the early 1980s, they hailed the protein interferon as a cure
for everything from cancer to the common cold, which proved too optimistic.
Even more fundamental, and more disturbing, was the growing realization
that cancer cells had an uncanny ability to resist almost every drug thrown
at them; some even found ways to spit out toxic chemotherapies as fast as
they were applied, eventually resulting in the death of the patient.
Then came the insight that cancer was not a single disease, but ''at least
100 different entities,'' as Dr. Donnall Thomas, Nobel laureate and
Seattle-based bone marrow transplant pioneer, puts it. Making progress on
one form, such as leukemia, often didn't help with cancer of the lung,
bladder, and other organs.
At the discouraging bottom line were the numbers. Cancer deaths rose an
average of 0.4 percent per year between 1973 and 1990, and the number of
new cases climbed by 1.2 percent a year. Especially frustrating were
increases in lung, breast, and prostate cancer and the rising death toll
from non-Hodgkin's lymphoma and melanomas. This, doctors and patients
agreed, wasn't what was supposed to happen when America declared war on a
To some, it looked like a medical Vietnam. Critics suggested we were losing
the war and needed to radically rethink our strategy, focusing more on
prevention and boosting the budget for alternative therapies.
''The results of what is now 40 years of focus on treatment have been
seriously disappointing,'' says Dr. John Bailar. Bailar, a biostatistician
who chairs the Department of Health Studies at the University of Chicago,
is a longtime critic of the cancer establishment, and remains unimpressed
even with the recent downturn in cancer deaths and incidence. The NCI and
its sister agencies haven't achieved as much as they should have for the
money spent, he says, and a lot of what they have achieved has come through
prevention, not treatment.
But even in the '70s, most cancer doctors believed they were making
progress. While critics suggested that position was designed to perpetuate
the unprecedented flow of tax dollars for research, in retrospect their
arguments were compelling. Scientists were learning how the cancer cell
differs from normal cells, an understanding that often was advanced as much
through their failures as their successes. And despite the rising overall
cancer toll, progress was being made with cancer of the bladder, uterus,
and ovary; the seemingly relentless increases in rates of other important
cancers would finally reverse in the early 1990s.
''I think, personally, that the war on cancer was one of the greatest
experiments the US government ever did,'' says DeVita, the former NCI
chief. ''The information we have today on molecular biology, on
developmental biology, all those things came out of the cancer program.''
That's because the researchers were not narrowly focused on curing cancer.
The knowledge fueling today's new cancer therapies ''is a brilliant
vindication of curiosity-driven research,'' says Robert Weinberg, a leading
cancer scientist at the Massachusetts Institute of Technology and the
Whitehead Institute in Cambridge. The keys, he adds, were that basic
science took precedence over immediate bedside applications, and funding
came not just from the NCI but from a variety of public and private sources.
In 1976, `the pieces
finally came together'
Though cancer is an ancient disease, researchers didn't discover its root
causes until two decades ago.
Most Americans remember 1976 for its celebration of the nation's
bicentennial. But to cancer scientists, it was a watershed year because,
after decades of false starts and wrong turns in seeking to unmask the
origins of cancer, things suddenly went right.
As Weinberg put it in a recent book, ''In one stroke, everything fell into
place. The pieces finally came together.''
The breakthrough came in the San Francisco laboratory of two scientists,
Harold Varmus, now the director of the National Institutes of Health, and
Dr. J. Michael Bishop, now chancellor of the University of California in
San Francisco. They showed that cancer arises in human cells when certain
normal genes - later shown to be controllers of cell growth and division -
are damaged and metamorphose into cancer-causing ''oncogenes.''
Bishop, an articulate scientist with a love of English and metaphor, and
Varmus, an Amherst College grad and physician-turned-researcher, had teamed
up in the '70s to study a virus that causes cancer in chickens. That virus,
it turned out, does its dirty work by carrying a cancer-causing gene into
chicken cells: The gene triggers the cell's move to malignancy.
But the most stunning insight was yet to come. In 1974, a researcher in the
Bishop-Varmus lab found that normal chicken cells already contained a copy
of that cancer-causing gene, but in a slightly different, harmless form.
The virus had only borrowed - or stolen - it. And not only that: Further
experiments showed that most animals, including humans, have carried this
Jekyll-and-Hyde gene, which can become a cancer-causing oncogene, for eons.
These genes, scientists now know, can serve reliably for many years but,
when altered by chance, a carcinogenic chemical, or some other damaging
agent, can unleash a malignant monster.
Some people inherit a damaged gene, making them highly susceptible to
cancer, often at a dismayingly young age. But most cancers arise when genes
are disrupted by chemicals, radiation, dietary factors, or the aging
Since that singular discovery - for which Varmus and Bishop won the Nobel
Prize in 1989 - scores of oncogenes have been discovered. And in 1983,
another important type of gene came to light. These tumor suppressor genes
normally keep a lid on overly-zealous cell growth, but when they are
mutated or missing, they allow cells to divide rapidly and endlessly.
What all those discoveries mean is that today, scientists know that the
human cell is controlled by a highly-complex set of genetic signals that
normally let cells grow and divide in an orderly way as they replace other
cells or repair the body. Cancer is what happens when that control system
breaks down or has missing parts. Then, like a car with a stuck accelerator
or no brakes, the normal cell evolves into a rapidly dividing tumor cell
that escapes regulation and spawns millions or billions of similarly
With this detailed picture of cancer in hand, scientists have forged a new
set of weapons.
''We've finally gotten a handle on a variety of genetic events within the
tumor and events associated with the development of cancers, [and now we
can] intervene and block those signals or molecular events to interfere
with the progression of cancer,'' says Samuel Waksal, chief executive
officer of ImClone Systems in New York, a biotech company that is
developing sophisticated new cancer drugs.
In fact, scores of new drugs are pouring from pharmaceutical and biotech
companies, each aimed at a specific link in the Rube Goldberg -like chain
of events that turns cells cancerous.
Some of those medications, like the nearly two dozen ''angiogenesis
inhibitors'' based on research by Harvard's Folkman and others, aren't
aimed at the cancer cell at all. Instead, they seek to destroy the network
of tiny blood vessels that surround and support growing tumors. And because
the cancer cell doesn't ''see'' the attack, it can't plot an escape plan.
Folkman's most potent anti-angiogenesis drugs, endostatin and angiostatin,
got a huge media bounce this spring even though they aren't ready for human
tests. The enthusiastic stories misleadingly spoke of a ''cure'' and
''brought premature attention a little earlier than people in the field
wanted,'' Folkman said in a recent interview. They also raised expectations
to unrealistic levels, although Folkman remains optimistic the drugs will
prove effective in people.
Klausner, the NCI chief, is also optimistic about many of the new
therapies. ''I recognize that most of the ideas we test will not work out,
or we'll have to worm our way through a long discovery process,'' he says.
''But it's very reasonable to be excited and hopeful about the significant
increase, maybe even an exponential increase, in the number of ideas....
It's so hard to describe how important that is.''
Other researchers are more cautious. One enormous obstacle, they say, is
that tumors are made up of many types of cancer cells, possibly requiring
attacks by combinations of several agents. They also worry that the new
biologic drugs are hard to make and expensive to take.
''What we've learned over the years,'' says Dr. Howard Fine, who is trying
angiogenesis inhibitors in brain tumor patients at the Dana-Farber Cancer
Institute, ''is that cancer cells are smarter than we are.''
Lots of progress, but
cure is still elusive
Americans have been emotionally and financially backing the battle against
the wily cancer cell for 27 years. Now they're being told that, while there
is clear-cut progress, an out-and-out cure may never come. All of which
raises the question: Does the nation have the resolve to keep going?
Public opinion polls suggest it does, in a big way. Eighty-four percent of
Americans think there will be a cure for cancer in the next 50 years, and
64 percent are confident it will happen within a decade, according to a
nationwide Gallup survey conducted in May. In another Gallup poll last
fall, respondents ranked cancer as America's second most urgent health
problem, tied with rising medical costs and trailing only AIDS.
Washington seems equally committed, even congressional Republicans normally
wary of expensive federal programs. While President Clinton has called for
a 50- percent hike in funding for the NIH and NCI over the next five years,
Congress seems determined to spend even more.
''The Congress is, I think, poised to double funding for NIH over a
five-year period,'' says Representative John Porter, an Illinois Republican
who chairs the House Appropriations subcommittee that oversees funding for
medical research. On the Democratic side of the aisle, Senator Edward M.
Kennedy of Massachusetts, an architect of the 1971 National Cancer Act, is
equally determined: ''I'm strongly in favor of doubling the NIH budget now.''
Even with that resolve, and with evidence that death rates are declining,
more than 1,500 Americans will die of cancer every day this year. And the
millions more who are suffering from the disease are determined to know
what's available now, as well as what's happening in the laboratory.
''Until the day you're diagnosed with cancer, you have no reason to wonder
whether or not what the scientists are saying is true,'' says Laurel
Simmons of Cambridge, a graduate student in public health who was diagnosed
with chronic myelogenous leukemia in 1987, but is symptom-free today.
''When you are diagnosed,'' she adds, ''they tell you what your chances of
getting out of the hospital alive are. And one of the first things people
do, in a variety of ways, is confront the possibility of their death.''
One way cancer clinicians are trying to reduce such possibilities is by
using their new understanding of how the cancer cell works to alter the
diet, adjust workplace conditions, clean up environmental carcinogens,
change dangerous habits like smoking, and take other steps to prevent
cancer. ''The deep understanding of the genetics of cancer development in
cells that lead them to become cancer may well have its most profound
effect on prevention, ultimately, rather than on treatment,'' says Klausner.
Armed with that and other new weapons, America and its leaders seem
determined to recommit the country to the war on cancer that they launched
27 years ago.
''I have no problem thinking about it as a war,'' says Varmus, the NIH
chief. ''The problem is, there's not going to be a day of surrender. There
will be continual battles - and winning on one front, like testicular
cancer or childhood leukemia, or isolating genes that let you make risk
assessments - are steps forward. But they don't cause the other fronts to
''We're making a good deal of incremental advances on multiple fronts...
but this is unlike a war where all you need is to take that last bridge.''
This series is available
on the Globe Online at
This story ran on page A01 of the Boston Globe on 08/02/98.
Copyright 1998 Globe Newspaper Company.
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