ASBESTOS. Benzene. Saccharin. Hair Dyes. Nitrite in bacon. Kepone in Virginia waters. Chemical waste in the Love Canal. Lead in the air. Now that we have poisoned ourselves with these and other chemicals -- what Ralph Nader calls "modern mass suicide" -- what can we do?
Despite some black prophesies, a hold new idea, pursued by a small but growing number of scientists, is emergoing. Their research lends credence to the thrilling contemplation that human intelligence -- the same intelligence that got us into the predicament -- may yet help rescur us.
The central question these researchers are asking is: Can we make ourselves more immune to such ravages? Can we outwit our own dangerous creations? The scientists believe that, to some degree at least, we can.
At the simplest level they are seeking ways to flush dangerous chemicals out of the dody. At the most sophisticated they are experimenting with ways to neutralize the effect of a cancer-causing substance by creating a kind of immunizing shield around vulnerable cells.
The work is still scattered and in its infancy, and scientists warn there is no miracle antidote or pill around the corner to transform us into a superspecies, able to withstand the chemical assaults of modern civilization. They are especially concerned that their work not be used as an excuse for continued pollution of the environment, streesing that removing pollutants is still the most foolproof course.
Nevertheless, they exude a controlled sense of excitement, calling their experiments "hopeful" and "promising," They have, indeed, had some significant successes. Flushing Out Kepone
ONE INVOLVED the workers at a chemical plant in Hopewell, Va., who were poisoned by the pesticide Kepone made in the plant. Some workers developed tremors, stuttering, memory loss, even hallucinations. Kepone, proclaimed a carcinogen in animal tests, also got into the workers' livers and testes.
Seeking a way to flush out the Kepone, Dr. Philip S. Guzelian of the Medical College of Virginia hit on the idea of administering cholestyramine, a drug used by physicians to lower blood cholesterol. The drug, he says, attached itself to the Kepone as it circulated from the blood into the intestine, and sharply accelerated the poison's excretion. Consequently, he says, the Kepone in all 22 workers who took the drug was reduced to "undetectable" levels, and the damage was often not only halted but reversed. He says the symptoms disappeared in all but three workers, who were left permanently impaired.
Dr. Guzelian notes that the drug was not only able to pick up Kepone circulating in the blood but also to draw it out of fatty tissues. Also important, he says, was the discovery that most of the elimination of kepone, and probably of other pesticides, is done not in the liver, as previously believed, but in the intestine.
Armed with this information, Dr. Guzelian now is trying to determine if the same drug or others to determine if the same drug or others will remove other pesticides from the body. Recently, he says, he used cholestyramine to remove chlordane, a connon pesticide, from two people who were acutely poisoned.
Does this mean such a drug could be used to reduce the general burden of pesticides in our systems -- and that people already on the drug may be coincidentally rdding their systems of dangerous chemicals? It's possible. But Dr. Guzelian and other scientists say there is not nearly enough research to recommend any such substance as a safe detoxifying agent for the entire population. At present, they insist, it should be used only on persons known to be acutely poisoned. Doing the Impossible
ALONG THE same lines, Dr. Jack Schubert, of Michigan's Hope College, a veteran researcher from the Manhattan Project days announced last fall a breakthrough in removing toxic metals from the body, mainly radioctive plutonium, which, if left in he cells, gives off ionizing radiation that causes cancer.
For years scientists have injected compounds called "chelating" agents to try to detoxify workers poisoned by heavy metals and youngsters poisoned by lead. Dr. Schubert describes a chelating agent as an organic compound that seeks out the metal molecules in the body, captures them, and washes them away in the ruine. But, he says, success has been limited. "Even with intensive treatment -- once or twice a week -- removal of only 15 to 20 percent was considered good." It was though that metals such as plutonium, cadmium and lead were irretrievably locked in the lymph system, the liver and the bones.
However, by mixing the chelating substances with common aspirin, he was able to "do something everyone thought was impossible" -- remove 100 percent of the plutonium from the bodies of laboratory mice. "It's a whole new ball game," he says. The new mixture, he claims, is literally a trillion times more effective, and he predicts it will work on other types of metals.
For example, he says, after giving mice a lethal dose of cadmium, he gave half of them the new chelating agent; they all survived while the untrated mice died. Moreover, Dr. Schubert believes that with slight modification the new chelating combination will unlock and wash away many other toxic chemicals stored in the tissues, including pesticides. He is doing research to try to confirm that.
A government official points out that Dr. Schubert's findings have not yet been confirmed by other labs ("although that's not unusual") and that the Food and Drug Administration has not approved the new combination of chelating agents for use in humans. Dr. Schubert says some doctors get around that by first injecting ordinary chelating compounds and then giving large doses of aspirin. "It works, although not as well," he says. He cautions that aspirin alone is not effective. NCI's "Chemoprevention"
RESEARCHERS AT the National Cancer Institute are working on another goal: to make the chemical assaults on the cells less harmful.
While the exact mechanism of cancer is still mysterious, researchers know it is a long disease process, usully taking 20 to 30 years before the malignancy appears. As NCI's Dr. Michael B. Sporn explains, cancer must be initiated; the genetic material (DNA) in the cells is changed in some WAY -- MUTATED -- BY CHEMICALS, RADIATION OR UNKNOWN GENETIC FACTORS. Since nobody is free of cellular chemical assaults, everybody has been "initiated" to cancer. "Whether or not it progresses is another question," says Dr. Sporn.
In certain people, he says, the mutated cells cluster into forerunners of cancer called precancerous lesions. At that sage, one of three things can happen: The lesion can regress or disappear; it can grow slowly and pose no threat to life, or it can erupt into a malignant growth that may metastasize and cause death.
Traditionally, physicians don't treat cancer until it becomes a malignant growth. The NCI strategy, called "chemoprevention," is to try to intercept the disease process much earlier -- during initation or progression -- before the out-of-control lump called cancer appears.
One idea is to dispatch chemicals to rearm damaged cells and shore up their defenses. Some of the most remarkable successes in studies conducted by Dr. Sporn have come from vitamin A-like substances concocted in the laboratory. Since vitamin A controls the differentiation of cells -- keeping them healthy and "behaving in a normal, proper way" -- and since cancer involves a loss of this differentiation, the theory was that vitamin A might keep cancer-prone cells in line.
Scientists tried natural vitamin A and found it did have some protective effect and that people with vitamin A deficiencies were higher cancer risks. Still, the high doses of vitamin A that were most effective were also toxic. So researchers modified vitamin A, increasing its potency and lowering its toxicity, and came up with what they call synthetic retinoids.
According to Dr. Sporn, numerous animal studies show the retinoids can dramatically halt the progress of cencer in animals exposed to carcinogens. "In some cases," he says, "the risk was cut in half, three-quarters or by 90 percent." The retinoids worked against cancer of the lung, breast, skin, bladder -- almost all common cancers.
Moreover, Dr. Sporn rmarks that the vitamin A-lkie derivatives not only can arrest the cancer process but can actually repair cells damaged by carcinogens, thus reversing what was though to be a relentless march toward cancer. The animal studies were so successful that an experiment is now under way in five cities (Boston, Chicago, Iowa City, Richmond and Seattle) with 100 persons who have had bladder cancer surgery. The purpose is to determine if retinoids will prevent th recurrence of cancerous lesions. Working With Vitamin C
DESPITE persistent campaigns by the federal government, notably the Fda/, to denigrate the role of massive doses of vitamins to combat any disease, vitamin C also has potential for preventing cancer. VITAMIN C is added to cured meats such as bacon and ham because it inhibits the formation of carcinogenic nitrosamines. Vitamin C can also prevent some harmless chemicals from metabolizing into carcinogens within to body.
Most important, vitamin C, in both animal and human studies, has blocked the progress of colon cancer, the largest type of cancer in this country next to skin cancer. It will strike 112,000 Americans this year and kill more than 50,000, according to the American Cancer Society.
if so harmless a substance as vitamin C could be used to curb this toll, it would indeed by a remarkable achievment, as Dr. Jerome DeCosse, head of surgery at Memorial Sloan Kettering in New York City, remarks. Dr. DeCosse, however, warns that although the evidence is promising, it is far from conclusive and won't be for as least a decade.
A preliminary study of his showed that the precancerous lesions (called polyps) of some patients have disappeared after they took 3,000 milligrams of lvitamin C a day, which is considered a high does but no unsafe. (Linus Pauling has said he often takes 10,000 milligrams a day without ill Effect.) The vitamin C is taken in timereleased capsules because researchers believe it must continously flow over the damaged cells in the colon to counteract cancerous progression.
Dr. DeCosse, in collaboration with a British physician, is now conducting a larger study, at St. Mark's Hospital in London, which he says should show within six months whether vitamin C is truly effective. If it is, Dr. DeCosse thinks doses of vitamin C would be in order for certain patients with colon polyps. The theory is that if you eliminate the ployps, you prevent the development of colon cancer. But absolute proof of that would require many years of follow-up research. Protective Shilds
DIGGING EVEN deeper into biological mysteries are scientists, often supported by Nci/ funds, who are trying to thwart cancer at the earliest possible stage, even before the cellular changes that set the cancer process in motion. There's no question it can be done in animals, according to Dr. Lee Wattenberg of the University of Minnesota Medical School, a leading authority in the area. He and others have given mice and rats doses of known carcinogens -- along with chemical inhibitors -- and found that a significant number of them never develop pre-cancer signs. Dr. Wattenberg admits he doesn't know exactly how the protective chemicals work, but he theorizes that they may stimulate the cells' defense mechanisism, in effect wrapping them in a protective shield. This shield may prevent the interaction betwen the cell and the carcinogen that is necessary to bind the two together and cause DNA damage.
Dr. Wattenberg says a large number of chemicals, both natural and synthetic, will to a degree immunize animal cells against cancer attack. Among them: butylated hydroxyanisole (BHT), the drugs Antabuse and phenobarbital, certain pesticides, selenium salts, and lnatural substances found in such vegetables as cabbage and broccoli. The chemicals have worked against a variety of cancer sites: lung, stomach, skin, breast, liver, intestine and bladder.
However, according to Dr. Wattenberg, a massive dose of carcinogen may override the protection, and the chemicals must be taken in either simultaneously with or immediately prior to carcinogenic exposure. Strangely, he says, in some cases if you give the inhibiting chemicals after the carcinogens, you get an opposite effect: The chance of cancer is increased.
Dr. Wattenberg cautions against deliberately taking any of these chemicals to forestall cancer. He warns that not nearly enough information is available to make their luse safe. He does believe, though, that some of the differences in cancer rates in the country can be explained not only by exposure to carcinogens, but by accidental exposure to chemical cancer-preventers in the environment. For example, one study showed that the higher the blood levels of selenium, the lower the cancer death rates in several U.S. cities.
There may be any number of existing chemicals that would work if tested. But why depend on chance? Why not, by shifting around a few molecules, create new, safer and more potent chemicals to protect cells from cancer attack? Dr. Wattenberg thinks that can be done.
He notes that although carcinogens have varying chemical structures, once in the body they have similar patterns for attacking cells. Thus, he thinks chemicals can be laboratory-designed to neutralize certain classes of carcinogens, such as chlorinated hydrocarbons, aflatoxin, tars or nitrosamines. Currently, he is attempting to synthesize chemicals that he hopes will protect cells against five different classes of carcinogens. What's Ahead?
The big/ question, of course, is: Where will this research lead? To anti-cancer pills? Widespread cancer immunity? Scientists, well aware of the sinister connotations of biological manipulation, will predict no such thing. Many, however, do not rule out the eventuall use of anti-cancer chemicals for people at high risk, such as those who already have pre-cancerous lesions or a previous occurrence of cancer. Of course, that could follow only after long-term trials in which the new chemicals, to be used as drugs, were determined safe and efective.
As for widespread prophylacti use on the pupulation, "Not likely," says Dr. Wattenberg, because of the danger. One reason scientists are testing natural substances, such as vitamin C and vitamin-A derivatives, is because of a greater chance of safety. But even drugs once though safe have a way of showing up hazardous after prolonged use.
Giving substances to people at high risk is one thing, but dispensing them to an entire, relatively healthy population is another. "Almost anything in all probability given over a long time might adversely affect some people," says Dr. Wattenberg. "It would be difficult, if not impossible, to be sure it was absolutely safe."
Furthermore, there may be no need to immunize an entire population; although everyone is exposed to carcinogens, not everyone succumbs to cancer. There's also the practical drawback: A prophyiactic would have to be consumed continually, taken in the way carcinogens are, slowly and steadily. "There could not be one big super-pill you take once or occasionally," says Dr. Wattenberg.
Most of all, scientists fear even limited use of preventives might give polluters a license to continue. "It is exceedingly important," Dr. Wattenberg recently warned other scientists, "that the inhibitors not be used as a mechanism for allowing increased exposures to carcinogens or increasing tolerance levels to cancer-producing substances." Dr. Schubert agrees that the prophylactic use of antidotes in liew of cleaning up the environment and industrial plans would be "immoral."
When Dr. Walter Weizen, program manager for human health studies at the Department of Energy, was asked whether nulear plants could use prophylactic chemicals on workers, he exploded: "No way. It would be bad medical practice." A couple of years ago companies routinely using chelating agents on workers exposed to lead -- cleansing their blood and sending them back for more exposure -- were severely criticized. In Novermber the Occupational Safety and Health Administration brought a complaint against an Indiana company, charging it allowed excessive levels of lead in the air and routinely subjected its workers to prophylactic treatments.
Even so, it could be argued that the new chemicals, if they could be proved relatively safe, are little more than a sophisticated counterpart to vaccines used against infectious diseases. Also, conferring biological immunity against chemical carcinogens could be regarded as an artificial compression of evolution. If we could wait long enough, evolution might give us increased resistance, just as, through generations of exposure, insects have become resistant to pesticides. It might all be part of the hopeful rush for survival seen by anthropologists like Lionel Tiger, who believes that optimism if built into human genes.
The pioneering scientists tolerate no such philosophical diversions. The most they hope for is a recognition that by trying to combat cancer before it erupts, they are setting off in a new direction -- one that, especially in light of our dismal cure rates for cancer, is a more compassionate and sensible solution to our self-poisoning. It is certainly preferable to building more cancer wards.