Cancer is our century's way of dying --- our internal nuclear explosion, a suicide mission by a terrorist cell whose demands cannot be met. Each of us has a memory of a friend turning into a skeleton, with powerful drugs puffing up cheeks and slurring speech, sinking the eyes and sharpening the contours of the nose. Death comes as an anticlimax; the person we remember left us long before.
Treatment reflects the preoccupations of society. In this novel Cancer Ward , Aleksandr Solzhenitsyn equates radiotherapy -- a massive bombardment of the body with X-rays -- with Stalin's remaking of Russia. The America of the 1960s embraced chemotherapy -- we had to destroy to cells to save them. In the 1970s, we rebelled against irreversible steps such as surgery, and protested the side effects of chemicals and radiation. Exotic treatments such as Laetrile, an extract of apricot pits, became fashionable, and the search was on for the natural and the organic. The theme of the early 1980s promises to be "multi-modality therapy": strengthening our self-defense while refining the traditional methods of radiotherapy, chemotherapy and surgery.
Doctors say that they are saving more patients than ever before. According to the National Cancer Insitutute, cancer survival rates in the 1970s improved by as much as 10 percent for about six of the hundred or so diseases collectively called cancer. Even so, about 420,000 Americans will die of cancer this year -- the second most common cause of death after heart disease -- and 800,000 new cancer cases will be diagnosed.
Cancer specialists share a sense of defeat, pained by their failure to win the war on cancer declared by the Nixon administration in the early 1970s. They are still baffled by elementary questions such as those probing the differences between the cancerous cell and its parent, the normal cell. They are frustrated by their failure to control whatever it is that causes a tumor. They are sensitive to public pressure, for example no longer insisting on radical mastectomy -- amputation -- but removing only the cancerous portion of the breast. They are angered by criticism, such as that by Sen. Paula Hawkins (R-Fla.), who has assailed the $1 billion a year the National Cancer Institute has been spending as an example of government profligacy.
The program the National Cancer Institute singled out this year as its "most exciting" calls for identifying the natural substances in the body that could be mobilized against cancerous growths. The work is being done in the laboratories of the Frederick (Md.) Cancer Research Center, 45 miles northwest from Washington. The Frederick Center is unique because it combines theoretical research, laboratory testing and production of medicines, treatment of patients and an analysis of the results. Its promise is to; reduce the time that usually elapses between discovery and application, a year or two in the case of most medicines.
The substances the Frederick Center is testing on patients are called "biological response modifiers" -- or "biologicals" -- in contrast with "chemicals" used in chemotherapy. The bestknown biological thus far is interferon, and the great hopes interferon raised in the mid-1970s are responsible for the Frederick Center's emphasis on biologicals.
Biologicals are secreted by the normal cell to regulate growth and to defend itself against alien cells such as tumor cells. Injected into the body to fight cancer cells, biologicals appear to have fewer toxic effects than other anti-tumor drugs. Determining the effectiveness and toxicity of biologicals is the first phase of the experiment that began in April at the Frederick Memorial Hospital, a 250-bed community hospital.
Ira Eaton, 55, is one of the first 11 patients in the program. A resident of Thurmont, a 30-minute drive from Frederick, Eaton has cancer of the colon. He has made no secret of it since the doctor told him on the phone one Sunday evening four years ago. "It was like being hit by a two-by-four," Eaton recalled in a conversation in his home a few days before he entered the hospital. "Up to that time, I had real good health, didn't I, honey?" Jeanette Eaton nodded, her eyes fixed on the Cotactin Mountains framed by the picture window. Her husband had had surgery three times in three years, as well as radiation and chemotherapy.
"I was taking treatments on Fridays so I could have the whole weekend to rest up before going to work at the Moore plant -- a real nice place and one of the largest printers of business forms in the country," recalled Eaton. For 25 years, he has worked there as a printer -- a three-minute walk from his tidy two-bedroom brick house surrounded by an acre of lawn.
Green is Jeanette and Ira Eaton's color. The carpeting in their living room is pistachio, the sofa is jade. The ceramic leprechaun on the windowsill, the porcelain birds and the globe lamps on the end tables all have dabs of emerald and chartreuse.
"Green is the color of hope," Ira Eaton explained.
"And we need lots and lots of hope," Jeanette Eaton added.
"I am right thankful for the new medicine," he said. "It's not like that doggone chemotherapy that puts poison in your body. It used to make me feel nauseated. Not real sick, you understand, just nauseated.
"I am fighting cancer. But I get disgusted too. Every time I had surgery I thought I ought to be all right. But, by golly, there came another tumor, and a dull ache that comes with it."
"The doctors really give us hope this time," Jeanette Eaton said. "Right, hon?"
"Right," he answered his wife of 25 years. "I'll do anything that gives hope."
The scientists who devised the experiment of which Ira Easton is a part are very, very careful with predictions.
"There have been too many false starts, too many disappointments," says Dr. Stephen Sherwin, the clinical oncologist in charge of the program at the hospital. "We have to be skeptical. All I can say is this: We believe that interferon and other medicines of a similar type we are now testing hold promise for some types of cancer."
His colleague, molecular geneticist Dr. Michael Yarmolinsky, compares the current understanding of cancer to a child's understanding of the electronics of a radio -- all that the child knows is how to turn dials.
"We make progress in some small way every day," he says, "but we are far, far away, perhaps as far as 50 years, from understanding in detail the mechanisms of normal, much less abnormal, cellular developments. What may happen is that we at the center will find some preventive measure or information useful to treatment. But I don't believe in the silver bullet -- a magic cure to all cancer.We require a lot of silver bullets. But before we get to one bullet, we must understand some underlying processes of life itself. That means basic research."
The center's director, Dr. Michael Hanna Jrs., balances the caution of a scientist with the ebullience of a fundriaser. "In five years, something dramatic will come out of our center," he says. "It may be nothing more than an important little insight that will open up new possibilities. Or it may be a major new thrust in cancer treatment. I believe firmly that the time is right, the technologies are here and new concepts are on the verge of being tested and proven. One scientist cannot do it, but we have some of the best minds in different fields of biomedical science, and together we can do it. At the center we have what we call a critical mass."
"I'd be surprised if we at the center found a cure to cancer," says Dr. Robert Yuan, a molecular biologist. "But I'd be equally surprised if we don't."
What makes the Frederick Center different from other research agencies, he says, is that "a lot of the key researchers here are in their early 40s, and they may be peaking professionally at about the same time."
Sherwin is 32, wiry, with a curly black beard, a natty New Yorker educated at Yale and Harvard Medical School and trained at the National Cancer Institute. At 52, Yarmolinsky, a slender man who favors corduroy jackets, is regarded as an elder statesman by his colleagues. He is a product of Harvard, Johns Hopkins and seven years in France's medical research institutes. Hanna is 43, from Cleveland, Notre Dame and the Oak Ride national nuclear laboratories, a smooth-talking, powerfully built immunologist who became the Frederick Center's chief administrator in 1979. A graduate of Antioch College and Albert Einstein College of Medicine, Yuan, 42, is tweedy, placid and whimsical enough to call himself an amateur.
In the 1970s scientists began exploring the unknown realm of hundreds of biologicals, some of them rare and present in the body in minute amounts. In the past few years, the revolution in genetic engineering provided the technology to manufacture the biologicals in quantities sufficiently large and pure. "What we don't know at the moment is what happens when when we give large doses, or, indeed what constitutes a large dose," Sherwin says. "Though these substances are natural, we have to monitor carefully what happens when we increase their levels in the body."
The Frederick Center is currently working with up to 20 biologicals. One of trhe most promising among them is called monoclonal antibody, a protein that has the important quality of being able to attack a specific type of tumor. Another biological is pyrans, which makes the body step up its production of interferon. Lymphokines, still another type of biological, play a key role in activating the body's immunological system.
The interferon given to Ira Eaton and three other inpatients at the Frederick Memorial Hospital was supplied by New Jersey manufacturer Hoffman-LaRoche, which produced it jointly with the San Francisco firm Genentech. After 28 days, the inpatients become outpatients, but they will continue to receive interferon in combination with some ther biological or even a chemical. Four new inpatients are then selected, again from the Frederick region and again in response to referrals by local physicians and on a first-come-first-served basis. Like Ira Eaton, all the cancer victims have to be in otherwise good physical condition; the program's directors decline patients suffering from heart, liver, kidney or bone marrow ailments because the treatment may aggravate existing problems. The experiment will eventually involve 80 patients in different hospitals of the National Cancer Institute network, which includes the Veterans Administration Medical Center in Washington. Scientists expect to have conclusions about side effects and dosage by the end of the year.
The consensus at the Frederick Center is that interferon may not rank as the most potent biological. But, scientists say, it is important to test it in order to settle the argument about its effectiveness. "Interferon may not be the wonder drug it was expected to be," says Sherwin, "but it may reduce tumors in specific cases. We have to give it a try."
The Frederick Center's current priority is to develop a capability to manufacture and test other categories of biologicals. The hunch is that the cancer treatment of the 1980s will rely on a combination of biologicals -- rather than any single one -- which will work in conjunction with the three conventional cancer therapies of radiation, chemotherapy and surgery.
One of the persistent questions about cancer has to do with why the body turns off its natural defenses. "What starts a tumor is a mystery," I remember a close friend, himself a physician, saying to me as he broke the news of his own cancer.
In a key experiment peformed at the Frederick Center, skin cancer was transplanted to a mouse not exposed to ultraviolet rays. The tumor would not grow. But in a mouse that was irradiated with ultraviolet rays and received a tumor induced by ultraviolet rays, the tumor did grow.
Scientists concluded that ultraviolet rays, which are present in sunlight, lower the body's resistance to skin cancer. Ultraviolet rays induce the formation of some kind of unknown substance in the skin. That substance circulates in the body and turns off the immunity system so the tumor can evade the body's defense system and become established.
The Frederick Center is now looking for those substances that enable the body to resist.
"We need to understand better what regulates the abnormal growth of the cancer cell," says Sherwin. "Then we may gain insights into new forms of cancer therapy."
"People who study, say, colon cancer are no less likely to come up with important contributions to cures as those who study, say, bacteria," says Yarmolinsky. "Historically, the advances made in cancer therapy came from studies of bacteria, not of cancer patients."
He favors more basic research, and is alarmed by the Reagan administration's budget slashes. "The overall effect will be a setback to science because fewer students will go into science and scientists will go into safer rather than truly innovative programs," he argues. "Our technological edge in gene-splicing, for instance, will disappear, and the damage to the American leadership in science may be irreversible. The kind of initial studies that led to genetic engineering in the 1970s are unlikely to get funded today."
"We aren't that affected," Hanna says, explaining that Litton Bionetics, Inc. operates the Frederick Center and receives each year an amount of money determined by the National Cancer Institute. "With our operating expenses of $25 million in fiscal 1981 we are highly visible in the scientific community. Our setup is ideal because we take the best features from government and industry. Industry expects a return of a proper size on its investments, but in our case our center provides Litton Industries, a multi-billion-dollar corporation, an opportunity to offer some of its managerial and scientific talent as a public service. The government is restricted by being a bureaucracy, but in our case we are free to phase out and start programs. Everything at the center is owned by the government, which also has the right to patent whatever we develop." The Frederick Center has five major labs. Three of them manufacturing medicines have what is called shower-in-shower-out facilities: A hot shower is compulsory upon entering and leaving to reduce the possibility of workers contracting infection -- or the spread of a contagious disease. Fluids of various colors, hissing and gurgling, pass through nearly 100 miles of pipes, and in and out of vats standing in rows.
Researchers at the Frederick Center dismiss the dangers of new life forms that might be created by genetic engineering.
"That's last year's fear," Yarmolinsky says. "Except for [Nobel Laureate] George Wald, no reputable scientist worries about blobs. But we've grown up with Frankenstein. We love to be able to be afraid -- particularly when we are safe."
Ethan Signer, a biology professor at Massachusetts Institute of Technology, is alarmed by the scientists' insistence that the public trust them. "Before we know it, it's going to be possible to breed legless astronauts who take up less space in a space capsule," Signer says. "Or perhaps even clones of the rich and powerful. Familiarity breeds negligence, and every new life form increases the chance of accidental escape."
The history of the Frederick Center offers a mixed metaphor of our times.
Its 70 acres and 67 buildings are scattered throughout the 1,200 acres of Fort Detrick, a U.S. Army base. Founded under President Franklin D. Roosevelt as a supersecret germ warfare center, during the Cold War its labs produced a variety of lethal toxins. In the 1970s, when anti-war groups called for the closing of Fort Detrick, the army acknowledged three accidental deaths at the base, a suicide due to LSD experiments and gas-warfare "vulnerability studies" conducted in the New York subway system and the U.S. Congress.
In 1971, President Nixon decided that germ warfare was immoral as well as impractical. He flew by helicopter to Fort Detrick's immaculate lawn to proclaim his determination to turn swords into plowshares. He called "the conquest of cancer" his administration's top priority. But the booklets that the Frederick Cancer Research Center hands out these days make no mention of Richard Nixon and credit the center's creation simply to "a Presidential mandate."
In one of the cancer labs once used for bacterial research, the loudest noise came from a radio blaring a song by the Beach Boys. The equipment -- vacuum pumps, centrifuges and banks of refrigerators -- produced no more of a whir than a kitchen blender. Stacked on every counter were lucite trays and discs with bacterial cultures dyed in colors ranging from fuchsia to beige. Each strain represented another mutation of the famous Escherichia coli, the bacterial equivalent of the laboratory mouse. The work bench had filters to remove unwanted viruses and ultraviolet lights to keep the air sterile. The air was circulated in such a way that a lab technician's cole, if he had one, wouldn't be transferred to the bacteria on the bench, nor would the bacteria get to the technician.
The lab has just hired three genesplicers, the newest speciality in biological sciences. Their job is to insert genes into harmless bacterial -- usually the E. coli -- and to construct them so they produce biological response modifiers.
Manufacturing biologicals in the traditional way -- by isolating them from cell cultures -- is slow, laborious and expensive. Gene-splicing permits cleaner, faster and more reliable production. The market value of an injection administerd to the patients at Frederick Memorial Hospital is still between $500 and $1,000, down from several thousands of dollars only a year ago, but the bill is paid by the National Cancer Institute. At the moment, the center's six large fermentation vats -- 300 liters each, about 70 gallons, -- cannot supply more than a dozen patients a month.
The technology is awe-inspiring. Chemical surgery is performed within one millionth of a speck of dust. Genesplicing enables scientists to create new species. "We play God," more than one molecular biologist has said.
Here and there, one has a chance to smile. "Sterility level off" read a handscrawled note taped to a panel of gauges in one of the labs. The familiarity of the sign "Out of Order" came as a relief in this Star Wards universe of stainless steel married to color-coded polymer.
A floor above the spacious labs are tiny cubicles where molecular biologists spin out their chemical formulae to sum up the birth and death of cells. Each cubicle has a desk, a chair, a bookcase, a filing cabinet, a blackboard and barely enough space for a visitor's chair. Their assignment is to rewrite Genesis 1, the first sentences of the Bible.
For them, in the beginning is DNA (deoxyribonucleic acid). Without it, all is unformed and void. Coded in DNA's double helix are the shape of an acorn, the soaring of eagles and a right hand's cunning. Then there is a separation between the waters above and the waters below: DNA and RNA (ribonucleic acid). RNA brings forth thousands and thousands of proteins: insulin, growth hormone, enzymes, antibodies.
But how does DNA tell RNA which protein to product? How does DNA turn on and off cell division? How does DNA start, regulate and stop the growth of, say, an arm and make sure that the other arm grows symmetrically? And, even more fundamental, how does the body tell DNA what to do?
A normal cell is disciplined, responds to command and cooperates. A cancer cell, an intruder, produces uncontrolled, unwanted, maniacal growth. Some normal cells fight cancer cells, but not always. "The key is to keep resisting." my cancer-stricken friend said. "One has to accept the inevitable, but one shouldn't give up."
'I am intrigued by the cell fighting a foreign DNA while accepting a DNA it considers native," Yuan says. "It is as if the cell said, 'You don't have the right passport, so I won't let you in.' I am working on a theory how the cell identifies native and foreign DNA. On the cellular level, I am raising the issue of self versus nonself."
Yuan is the son of Taiwan's last consul general in Havana and the grandson of a foreign minister of the Republic of China. He was born in Paris, grew up in Cuba and studied in Switzerland and the United States. He became an American citizen last year.
"For me, the essential question in life is how we pass characteristics from one generation to another," he says. "I am interested in how we transmit messages -- proteins and proverbs.
"Research ideas may come from anywhere.It is a way of looking at a problem that matters.
"I am fond of throwaway experiments. If you have nothing to do, you are between two experiments and you have time on your hands, you let all kinds of ideas come to your head. And those ideas and those experiments often turn out to be the ones that matter." A smile flickers across his face. "Businessmen and administrators want everything tidy. But ideas are not tidy -- they are often ridiculous. And when you write your paper on the experiment, you hide your original motive -- because it was, after all, a stupid idea, a long shot, a nonstarter. You can't say you did it for the hell of it."
It is a long way -- several worlds away -- from Ira Eatons's dull ache to the deliberations of scientists who talk about cancer as if they were trying to solve a mathematical equation. Using bits of Greek and Latin spliced together, words like antigens and monoclonal and leukemogenesis, they appear to be part chemists, part theologians.
Cancer researchers speak in a code, the meta-language of our country and our century. The translations are offered in metaphors appropriate to the listener's brand and level of technology. "RNA is like a proofreader scanning a text," and "DNA is an on-and-off switch."
The most emotional statement I heard at the Frederick Center was this: "It would be gratifying to be able to ease a patient's suffering," said Sherwin. I had asked him how he would feel if research at the center led to a cure. Later I found out that his father had died of cancer.
The usual journalistic questions seem crude. "What are your chances of finding a cure?" or "How many years will it take for the drug you are researching to become available in our neighborhood pharmacy?" produce a waffle as perfect as an assistant secretary of state appraising the chances for Middle East peace.
Perhaps medical scientists must be detached; their minds should be on chemical formulae and grand designs rather than on a patient's aches. They are high priests in charge of saving the body.
But we want a crash program, we want to be able to look at a timetable. We demand answers from our highly paid doctors, from our well-trained scientists engaged in experiments incomprehensible to us layment. We want to put the heat on medical science. After all, if we can send a man to the moon . . .
As my friend was wasting away, suffering from more and more side effects, he insisted that he had to try every treatment. "I am a patient now," he said, "but I am still a physician."
He conceded that his lung cancer was hopeless. Toward the end, he said in a voice that was barely audible: "We don't know what makes a cancer cell run amok. We don't know how to stop cancer. We don't know."
"We don't know" are a physician's saddest words.