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By John Tierney F YOU ARH SOMEONE who believes that nature's way is the True Path, that corpo- rate chemicals lead only to New Jersey's Cancer Alley, that if the Creator had meant for us to consume dioxin He or She would have given us Agent Orange groves - then you are probably someone who would not enjoy visiting the Berkeley Natural Grocery with Bruce Ames. He starts off at 'the produce bins, la- beled 0, U, and C (organic, unsprayed, and commercial). Most of the produce is 0, naturally, and the store's other aisles are laden with things like Supernatural Granola, preservative-free dog food, Natural Tumbleweed Chickens, and brochures about dangerous chem- ical additives in ice cream. Otherwise, though, there's nothing funky about the place; it has the roomy, bright, antiseptic feel of any supermarket. It is health food gone mainstream. You can think of it as a gleaming testimonial to Bruce Ames (although he would certainly prefer you didn't). For it was his laboratory procedure, the Ames Test, that alerted scientists and consumers to the dangers of hun- dreds of synthetic chemicals. He provided the evi- dence - and, occasionally, the rhetoric - that got things banned. He was a scientific hero of the envi- ronmental movement. But now he has a bemused look as he picks up an organic mushroom. "Filled with carcinogens," he says and moves on to the cabbage and broccoli, which contain a compound similar to dioxin, the dread chemical contaminant in the herbicide Agent Orange. "I'm sure it has all the same properties as dioxin, it's just that nobody's ever done the same tests as with dioxin, because toxicologists weren't looking at plants until just recently. Now we're finding all these weird chemical structures, these natural pesticides that the plants evolved for de- fenses against predators, and they make up five to ten percent of the plant's weight. Everyone worries about exposure to dioxin, but there's a lot more of this other stuff in cabbage and broccoli." On to the organic potatoes, which have a chem- ical that attacks the nervous system. "The original potatoes in the Andes had so much of this toxin that the Indians had to wash and grind them with clay to remove it." Today's potatoes have lower levels, but a meal of nothing but bitter green po- tatoes - those that have sat too long in the sun - can still cause nausea and stomachaches. He points accusingly to that most wholesome of foods, that staple of communes, that emblem of a movement: alfalfa sprouts. Just when you thought it was safe to go back to the land. Killer Sprouts. "Alfalfa sprouts are full of some really nasry Bruce Ames chemicals that cause lupus if the dose is high enough," Ames says breezily, sounding almost cheerful, which in fact is his outlook these days. He helped launch the now thinks that most cancer scares of the past two decades have been hysterical false alarms. In his recent work - probably the greatest blow ever to cancer scare of the environmental movement - he estimates that the natural cancer agents in our diet are 10,000 times more plentiful than the synthetic ones. To the 1960s Ames, this is actually good news. He's not worried by the amount of poison in alfalfa sprouts, which is nowhere near the level that caused a disorder like and 1970s. lupus in lab animals (sprouts made up 40 percent of the animals' diet). So if we're willing to risk sprouts, there's no reason to fear the still smaller doses in Now he says pesticides. "I don't want to worry people about vegetables - vegetables are good to eat. They also contain things mushrooms are that seem to prevent cancer. It's just that all of life is a combination of things, some potentially toxic. But generally you don't get enough so it's toxic, so more threatening it's not worth worrying about." What Ames worries about these days is the at- dtude embodied in this store. It reminds him of the than PCBs, but... time he saw a bag of charcoal marked No Artificial Additives. "How silly can you get? The charcoal Not to Worry ILLUSTRATIONS BY JAMES YANG ALAN E. COBER DON WELLER' January/February 1988 HIPPOCRATES 29

itaelf is just pure carcinogens." Browsing in the herbal aisle, he finds comfrey tablets, made from a plant that has served for centuries as a folk remedy for skin problems and is used in a popular tea. "This comfrey is just chock-full of carcinogens," Ames says, squinting through his thick glasses at the bottle. "If somebody took a lot of the tablets, it might well poison them or eventually cause cancer. It wrecks your liver and your lungs." Why do people equate nature with benevolence? Why is this store here? "Basically, what they're selling is a fear of modern technology. It's not un- reasonable for people to think that way, because they just read story after story about toxic this and toxic that. But everything's toxic if you get into the right dose." He shrugs. "It will take a while for people to get over all that," he says, and in this philosophical mood he decides to buy some organic plums. "I usually don't buy organic food," he says, noting that it costs more and sometimes has mold, which, of course, contains carcinogens. "But as long as I'm here..." On his way out the door, plums in hand, Ames allows himself a smile. He seems relieved to get away from the organic earnestness of it all. But he tries to be tolerant. "Oh well," he says, "let a thousand flowers bloom, or something." There was once a town in the heart of America where all life seemed to live in harmony with its surroundings.... Along the roads, laurel, vibur- num, and alder, great ferns and wildflowers de- lighted the traveler's eye.... Then a strange blight crept over the area and everything began to change. Some evil spell had settled on the community.... No witchcraft, no enemy action had silenced the rebirth of new life in this stricken world. The people had done it themselves. -R.chd Canos, "A Fabk for Tomorrow," in Silnn Spring If you mention the manifesto that started the environmental movement to Bruce Ames, he can- not help pointing out a little problem with the opening fable. There was a blight on this town that even its author, Rachel Carson, didn't know about. "Here's this nice sylvan view of ferns," Ames says, "and one of the most common ones, the bracken fern, is absolutely full of carcinogens." In fact these chemicals, which can be passed on through cow's milk or enter the soil when the plants die, might even be deadlier than the DDT that so concerned Carson, Ames says. "One would have to look at it from a weight level, but there's much more bracken fem being spread over the world than DDT." Still, Ames thinks of Silent Spring as a useful book. "It awoke people to things," he says. In 1964, two years after its publication, he looked at the list of ingredients on a bag of potato chips. It occurred to him that no one knew whether those chemicals were safe. That seemed worth worrying about. At the time Ames wasn't even in the field of cancer research. Thirty-six years old, the son of a 30 HIPPOCRATFS Janwry/Febraary 1988 In 1964 Ames high-school science teacher in Manhattan, a gradu- ate of the Bronx High School of Science, Cornell University, and the California Institute of Tech- nology, he was a biochemist doing basic research on the genetics of bacteria. His specialty was Sal- monella, a bug notorious for causing food poison- ing, not cancer. Ames, however, saw a connection, and he brought to the problem certain skills that are probably best explained by his wife, Giovanna Ferro-Luzzi Ames, who, like her husband, is a bio- chemist at the University of California at Berkeley. (They met at a meeting of the Enzyme Club in Bethesda, Maryland, in 1958, when he was at the National Institutes of Health.) "Bruce has this capacity for not remembering whether he's had breakfast or not, but twenty years later he'll remember something about an enzyme," she says. "He has a wonderful ability to synthesize. He's also a terrific experimenter, and one of his looked at the great virtues in the lab is his laziness. He won't just sit down to do an experiment -he'll spend three days trying to figure out how to do it quicker." artlflclal Ames's instinctive laziness made him - look for an easy way to test those chemicals in the potato chips -something simpler and cheaper than feed- ingredients in ing them to rats and mice in experiments requiring months or years of painstaking work. With his bacteria, he could study hundreds of millions of potato chips. It subjects in a few days. Over the next decade-"It was just a hobby on the side, because I was still doing my basic science" - he cleverly developed a oeeurred to him way to determine whether a chemical was causing genetic mutations in the bacteria. While perfecting the test he remembered an old theory that increased that no one its importance, the theory that cancer was triggered by mutations in a cell's genes. The results were spectacular. Ames and cowork- knew whether ers reported in 1975 that when they tested known carcinogens-chemicals that had been found to cause cancer in animals-almost 90 percent of those chemieals them caused mutations in the bacteria. This not only bolstered the theory that cancer begins with mutations, it gave scientists a quick way to screen were safe. any new chemical for potential dangers. The world beat a path to Ames's lab, and to date more than 5,000 different chemicals have been subjected to the test in 3,0001aboratories around the world. Ames says he never thought of trying to profit from the test. When pressed, he guesses that it might have made millions. "I don't have any way to spend money. I can already travel as much as I want to, because I get piles of invitations to speafC all around the world. And if I'm away from my lab for more than two weeks, I get itchy." On paper this setl iment may look too saintly to be believed, but in person Ames makes it seem convincing. He has a quiet, kindly tone of authority as he patiently explains why things are the way they are. Even when he lapses into overstatement- broad generalizations about nature or society, sweeping indictments of his critics - you find your- self wanting to believe him. He sounds so sensible, 51579 5465

PEANUT BITTTER, BA51L, AND BfER: RlWKtNO THE R1SKS ?o wu•tc the cancer risks of common substances, Bruce Ames and colleagues considered two questions: How much of the material causes considerable rates of cancer in lab animals, and how much of it might an average person be exposed to over a lifetime? Their rankings (gold rows) don't predict an individual's actual chances of developing cancer, but they do show comparisons: The risk from industrial formaldehyde is 5,800 times that from tap water, for instance. Ames says he doubts most of these materials pose much risk at all in small, everyday amounts; a worker's exposure .to industrial chemicals is one of the few major hazards on the list (see "The Risks Worth Worrying About," page 35). Interspersed with Ames's listing are actual risks of common RANKING S4URC9 PQTEMI4 RISK 3 3 C..kM baoa (about 15 slices a day): contains dimethylnitrosamine, a preservative by-product 4 i 30 p ia in 300 Mf M:& (residues in diet): PCBs were once used in oil for transformers OOE/DpT (residues in diet): DDE is a by-product of pesticide DDT Taaw.br (1 quart a day): contains chloroform, a by-product of chlorination SwMM.Mg poN (1 hour a day): child's exposure to chloroform by swallowing chlorinated water r..wt Mutl.r (2 tablespoons a day): contains aflatoxin, a mold Co.dr+wba (1 cup a day): contains symphytine, a natural pesticide Dt.toel. (12 ounces a day): contains saccharin Rwasrr.ao (1 a day): contains hydrazines, natural pesticides OrW Mi (3/4 of a teaspoon a day): contains estragole, a natural pesticide llM..odim ingredient in pain reliever (2 pills a day) IMasrdr (14 hours a day): formaldehyde vapors emitted from furniture, carpeta, and wall coverings 200 ewr (12 ounces a day): contains ethyl alcohol 4,700 Wi.. (8 ounces a day): contains ethyl alcohol 5P0 Fmsddalryr. (6 mg a day): worker's daily exposure activities (brown rows), calculated by physicists Richard W lson• and Edmund Crouch. To make comparisons between the two lists, the relative risk from tap water, which appears in both, was defined as 1. So, for example, Ames's ranking suggests the lifetime cancer risk from drinking a daily diet cola is comparable to the cancer risk due to everyday background radiation. (Such com- parisons are clouded by various uncertainties. Ames's ranking is imprecise because it assumes that people react to carcinogens the same way rats and mice do and that the effects of low doses can be estimated for substances that cause cancer at high doses. Wilson and Crouch's estimates may be off by as little as S percent for home accidents and as much as 1,000 percent for tap water.) ~dbewlA~.MM~I ~p/Ma~./~A17.tOp.0~0~27t:RWUOMnOEAGQa~3oNnw.ApY17.t9~7•ps~7{7. cancer cancer 3 in 10 million chance of developing cancer over a year cancer Coataafs.tM wd water (1 quart a day): Silicon Valley well, contains trichloroethylene cancer cancer cancer cancer cancer cancer caneer i x '.661 -- y;X,07 ® e 0 ~71 ~4~+cAlrNidN~ 1[l'rtbe L- : ` ' ... •1 . N 1~'l;x1''''y~foYe M '•' ~~~ '. r7411 aY . ~ ® ~ M 5,00 ~nce dyiitguY ` : <'•. ,frtii~3puaioip iuee s~~' 4. m4;S00chaao"dymgwluleon~' duiy in orie ear=~,'~•.~G'~, _ aP~g~Y'i ~ in oneyeu~ i~ ~...rar3Md (1 pill a day): a sleeping pill cancer • - - ~ 1N.OOi •. E08 (1S0 mg a day): worker's maximum legal exposure 'canoer Jauuuy/February 1488 H[PPOCRA'IF. SS 31

I which is one reason he made such a good witness for environmentalists during the 1970s. He got involved in one public battle as a result of a routine class exercise, a sort of Show and Test in which his students would bring in the chemical of their choice for an Ames Test. One student brought in hair dye that turned out to be highly mutagenic, and Ames went on to find mutagens in other hair dyes as well. When Ames wrote up the results he was urged by his department chairman at Berkeley to leave out the brand names, but Ames insisted. After the publicity and a federal proposal to require warning labels, manufacturers removed the chem- icals from their hair dyes. And Ames was on to another battle, this one triggered by his inability to buy pure cotton pajamas for his children. "In 1972 the Consumer Product Safety Commis- sion started worrying because a few kids got burned in fires. Now usually that's because their cigarette-smoking parents leave matches around, or the parents are smoking in bed and fall asleep. So some kids got burnt - a few hundred or thousand per year - and the commission decided, well, we'll put everybody in asbestos r.ightshirts. Well, it wasn't quite that bad, but they started making all these strict rules forcing everyone to add things to fabrics to make them flame-resistant. "So I got really furious. I didn't like the idea of this chemical rubbing against the kids' skin without knowing what effect it had. Our kids liked cotton pajamas, we don't smoke, and I thought that was an unwarranted intrusion of the government into people's choice." Ames subjected one common flame-retardant in pajamas, a chemical called Tris, to the Ames Test. It flunked, and Ames's testimony helped ban it. Today Ames isn't sure how dangerous those pa- jamas or hair dyes really were. Yes, they contained carcinogens, but no one knew then (or knows now) what doses were absorbed by the body. In the 1970s, though, such uncertainties didn't faze many environmentalists or journalists. To whip up public frenzy, all one had to do was put "cancer-causing" in front of a chemical's name. And for this state of affairs Ames deserves part of the blame. For he wrote a paper in 1971 that gave scientific legitimacy to the "one-molecule theory." He warned that "one molecule of a mutagen is enough to cause a mutation" and is therefore worth worry- ing about. He recommended that humans not be exposed to any chemical that causes mutations in bacteria - unless the chemical has definitely been shown not to cause mutations or cancer in animals, or unless the benefit outweighs the possible risk. Had this suggestion been strictly followed, the United States could have shut down virtually every business and starved every citizen. Sixteen years later, Ames calls the suggestion simplistic. In his defense, he says that he was at least willing to reconsider when the embarrassing counter- evidence started turning up in the late 1970s. Ames could see in his own lab that nature was 32 HtPPOCRATES January/February 1988 not benign: Red wine, for instance, caused his sal- monellae to mutate. He and others expanded the list of cancer-causing suspects to include lettuce, celery, parsley, spinach, figs, cocoa powder, fava beans, beets, radishes, rhubarb, mustard, black pepper, cola, some natural root beers (now banned), and the molds on corn, grain, nuts, peanut butter, bread, cheese, fruit, and in apple juice. Lis- turbing results also came from Japan, where re- searchers discovered that charring food produced carcinogens. Grilled hamburgers, browned muf- The hst of fins, roasted coffee beans - suddenly the world was looking very carcinogenic. Once Ames and his colleagues got over their cancer-causing surprise, they realized how blind they'd been. Why shouldn't nature be carcinogenic? Why had so many people assumed that evil sprang only from suspects their own hands? "It's a very funny way of looking at things," Ames says. "Only in the modern West- ern world, where everyone is so wealthy and now included healthy, can you even think of the idea that nature is, benign. Whereas in all of previous history, nature was something to be fought." lettuce, parsley, It's been argued that because these natural poi- sons have been around for so long, perhaps humans have evolved defenses against them. Or perhaps we radishes, corn, can tolerate these foods because they contain other chemicals that counteract the poisons. But Ames considers this wishful thinking. He doubts that a and bread. resistance to slow-acting cancers played a major role in natural selection-most early humans re- produced and died long before cancer from these Suddenly some chemicals would have set in. And while it's true that foods such as broccoli seem to contain and- . carcinogens, there's no reason to assume that they environmental counteract only natural carcinogens. Presumably they protect us against synthetic ones as well. Ames first reported the bad news about nature in controversies 1983. Much of the information had been around for years, but coming from Ames it was shocking. "The ideological wall of silence that surrounded looked a bit silly. nature had been breached," wrote Edith Efron in The Apocahptics, a scathing and generally con- vincing indictment of the scientists and regulators responsible for the cancer scares of the past 25 years. "The first great apocalyptic defector had made his public appearance." This past April, Ames delivered another blow. He and two colleagues at Berkeley, Renae Magaw and Lois Swirsky Gold, published a systematic ranking of the relative dangers of carcinogens that people are commonly exposed to (page 31). Sud- denly some environmental controversies looked a little silly. A few years ago, for instance, the Environmental Protection Agency had banned EDB, a fumigant widely used on grain and fruit. Ames calculated that before the ban, a person's average daily dose of EDB residue was far less carcinogenic than a single raw mushroom. When traces of trichloroethylene turned up in well water in Woburn, Massachusetts, and California's Silicon Valley, the outcry caused

wells to be shut and lawsuits to be filed blaming the pollution for causing cancer. Ames found that drinking a liter of water from the most "contami- nated" well in Silicon Valley was 1,000 times safer than drinking two glasses of wine, and 15 times safer than breathing indoor air for a day. Woburn's well water, he reported, was actually less car- cinogenic than ordinary tap water, which has tiny traces of carcinogens because of chlorination. "It is important," Ames wrote, "not to divert society's attention from the few really serious haz- ards, such as tobacco or saturated fat (for heart disease), by the pursuit of hundreds of minor or nonexistent hazards." For Ames, it no longer made sense to fret about one molecule of a carcinogen. Although he acknowledges that some synthetic substances are dangerous, he now believes that man-made pollutants are generally an insignificant risk to the public. He bases this not merely on his own results but on statistics showing that the pro- liferation of synthetic chemicals in the past 30 to 40 years has not markedly increased the overall U.S. cancer rate (see page 35). Ames is no longer popular among environmen- talists. The journal Science, where his reports ap- peared, published a sharply critical letter in 1984 signed by 18 academics, union officials, and envi- ronmentalists. At the top of the list was Samuel Epstein, a pathologist-toxicologist at the University of Illinois and author of The Politics of Cancer. The letter accused Ames of "trivializing" cancer risks and pointedly noted that "such strategies are ap- plauded by corporations resisting regulation of their carcinogenic products and processes." Ames gets irritated by this kind of criticism and says he supports some regulation. "Obviously you don't want every chemical company to dump their garbage out the back door. But I don't like this attitude that any businessman is going to poison his grandmother for a buck. There are incentives to have integrity and to not make carcinogens." Beyond such philosophical squabbling, Ames's critics raise several substantive objections, the first being that cancer isn't the only problem. "The chemicals on Ames's list cause other dis- eases," says Devra Lee Davis, director of the Na- tional Academy of Science's Board on Environmen- tal Studies and Toxicology. "They cause neuro- logical problems, heart disease, respiratory prob- lems, reproductive difficulties. Often the effects are hard to measure because people aren't dying- they're getting a little sicker or stupider-but the problems are still real." Ames concedes that there are other problems and he would like to see them studied. He suggests ranking the risks of teratogens, substances that cause birth defects. Ames suspects, though, that nature is again going to turn out to be worse than humanity. The recent concern about soil contami- nated by dioxin from incinerators caused him to do some comparisons. To equal the teratogens con- tained in one beer, he concludes, you'd have to eat two pounds of dioxin-contaminated dirt. Ames's critics alao question the accuracy of his cancer risk ratings, given the vast uncertainties in the data he uaed. For one thing, the ranking is based on animal experiments, which are horribly unreli- able. Chemicals that cause cancer in rats sometimes don't cause them in mice, and sometimes not even in other groups of rats. So what they do to humans is mostly a matter of conjecture, especially since it's unclear exactly what doses humans are receiving and how long the poisons stay in the body. Alcohol, for instance, ranks high on Ames's list, but its dan- ger may be mitigated because it's water soluble and is excreted quickly from the body. Then there is the 552-colas-a-day problem. That was the effective dose of cydamates consumed by "It is important rats in the famous study of the artificial sweetener. Because lab animals are typically fed unrealistically huge doses, scientists have to extrapolate what not to divert would happen at small doses, generally by assum- ing there's a simple linear relationship, even though ~ no one knows whether this assumption is correct. soclety s "Our animals will tell us that a compound is a carcinogen, but not much more," says Marvin Legator, a genetic toxicologist at the University of attention from Texas Medical Branch in Galveston. "None of the science that we do, in extrapolating from animals to man, allows us to come up with any hard the few really number that has any meaning at all. With all the uncertainties, Ames's ranking system could be off a thousandfold." serious hazards Ames readily acknowledges that no one knows the actual risk to people from these poisons, either natural or synthetic. Personally, he suspects that all such as tobacco the risks have been overstated because of the huge doses used in the animal experiments. A chemical that's toxic in high doses may well have no effect at by the pursuit of low doses, he says. But no matter what the danger really is, if 99.99 percent of the carcinogens in our diet come from natural sources rather than man- minor or ufactured ones, as Ames estimates, then how much difference could that other .01 percent make? Of course, Ames could be wrong in estimating nonexistent that we get 10,000 times more of the natural car- clnogens than the synthetic ones. But he argues that this is the best estimate available from the data - hazards." the same kind of estimate, he points out, that envi- ronmentalists have been using to make "worst-case scenarios" to justify regulation of chemicals. This year, for instance, environmentalists have been cit- ing an estimate from a National Academy of Sci- ences report that synthetic pesticides may be causing 20,000 cases of cancer a year. This figKre is not only derived from those unreliable animal ex- periments, it's based on further assumptions that the report's authors acknowledge are unre- alistically pessimistic. They admit, for example, that they deliberately err on the high side in estimat- ing ing chemicals' inherent toxicity. They also assume that every food gets the maximum dose of pesticide allowed by law - and even at these doses, Ames calculates, the carcinogenic risk from the pesticides 34 HIPPOCRATES January/February 1988 515 7 9 5469

THE RISKS QYORTH WORRYING ABOUT These are the major causes of anur that many-though not a0-experts agree on. If Americans gave up to- baao, for example, the number of cancer deaths would drop by at least 2S percent. Eating habits may have the greatest influence. Researchers are still investigating diet, but preliminary advice is emaging: To lower the chanca of colon cancer, eat fiber-rich foods such as whole- grain breads and cereals as well as fresh fruits and vegetables. Many kinds of anar may be inhibited by eating spiaach, carrots, apricots, and otha foods high in beta-arotene, a chemical related to vitamin A, and by eating cabbage, broccoli, auliflowa, and other vegetables containing substances called indoles. Dried peas and beaas may help pre- vent cervical cancer, among others. Because high-fat diets may promote breast, colon, and prostate anca, • cut back the fat you eat to between 20 and 30 percent of the total number of calories in your diet. m ToMem Smoking causes lung and mouth cancer. Chewing tobacco leads to esophageal and throat cancer. Tobacco is also related to cancer of the pancreas, kidney, and bladder. PfRCENT OF ALL U.S. GANGER DEAIHS qiafCriNS TNE "EPIOEiWIC" Despite the booming use of ryntbetie chemicals, the slight rise in the ova- all cancer death rate over the last 30 years suggests there is no corres- ponding canca epidemic (inset). Smoking accounts for the sharp increase in lung cancer. Stomach cancer's decline is attributed to .changes in diet. Tbe graphs fail to show some cancer hot spots: Black men die from cancer at an average rate three times that of white men, black women twice that of white womea. [ate diagnosis and poor ac- cess to medical care account for the differences in most asee. Environ- tnental pollutants are suspected of ausiag several local outbreaks or "- du:tan of anoer, though most cases : remain unresolved. 25 b 40 Dl* Nutritional deficiencies and excesses contribute to cancer of the 10 to 70135 R W.t mouth, digestive tract, pancreas, lung, prostate, breast, and utenuL oowwab aea.vtdl Oeatptliw Working with asbestos has been linked to lung and gastroin- 2b i testinal cancer. Nickel workers have above-average rates of nose and throatranc+er. In the smelting industry, workers exposed to arsenic have higher rates of lung and skin cancer. Exposure to vinyl chloride, benzene, and chromium compounds has been linked to liver, bone marrow, and lung cancer, respectively. Workers manufacturing plastics, dyes, and leath- er goods also face greater cancer risks. MoeYok Heavy drinking contributes to cancer of the mouth, throat, 2 to 4 esophagus, and liver. Wtiaat a.d oaraaitm Infectious agents have been linked to cancer of the ito 10 liver, bladder, cervix, and blood system and to Kaposi's sarcoma. PolYtle.: Airborne industrial pollutants and residues from burning fuels Iassthan i to S may contribute to respiratory cancer. Polluted drinking water is suspected in cancer of the large intestine, bladder, and blood system. Su.pft Prolonged exposure to ultra-violet rays causes skin cancer. leas thaa 1 to 3 Radlaklo.: Occupational exposures and medical use contribute to cancer of 1 the blood system, breast, thyroid, lung, stomach, colon, and bladder. Radott: Radon gas, which gets trapped in buildings, causes lung cancer. laathaa 1 to 2 Saotal babavlot: Multiple sex partners and first intercourse at an early age 1 have been linked to cervical cancer. Drtgm Some estrogens, steroids, and tumor-killing drugs can cause cancer 1 of the Gve; uterus, vagina, bladder, and blood system. AuWAdrd. m.c..nranac FWwoa aWlknre wa oama Er-1 r~todaauiew.Myhw, 1w1. ta.e~lw.r.nete~.r~n»M.rbqwne~arwdw.aorrwr~.+w. o.o.~a..~nr..aw.q~.wa.o.eweani.au.avea++~~ JanuaryiFebnwry 1988 HIPPOCRATES 3S

6 is still only equal to a glass of wine a week. Whatever the dangers of natural cardnogens, Ames's opponents say, we should still play it safe with cancer agents that we manufacture ourselves. Carcinogens can interact unpredictably with each other. The combined risk of asbestos and cigarettes, for instance, is greater than the sum of the two individual risks. So even if there are many car- cinogens in nature, why increase the risk by throw- ing unpredictable new ones into the system? "If Ames is "I think Bruce is an extraordinary scientist, and for the most part I accept his notions," says New York University's Arthur Upton, formerly the direc- s1ying that tor of the National Cancer Institute. "But if he's saying that because the levels of man-made pollu- tants are small and the potency is low, we should because the ignore them-that goes too far. I don't see any evidence today that we are poisoning ourselves as a society-there are isolated instances, surely - but levels of man- I am concerned that we are doing things to the environment that may be very deleterious to us in the long run, and very hard to reverse." made pollutants Legator agrees. "There is never a reason for not bringing down the risk of cancer if it's doable," he says. "You don't split hairs on whether one cotrl- are small and pound is more potent than another, because we don't have the tools to make that discrimination. We have to decide based not on biology but on the potency is economic, engineering, and social factors. We have to get the lowest levels possible without crippling an industry or a vital technology." low, we should Ames concedes that it makes sense to study and regulate synthetic chemicals, especially ones pres- ent in large doses in the workplace. "But you have ignore them- to remember that it costs money to get down to the lowest possible dose. You don't want to end up spending huge amounts of money for a minimal that goes gain. Maybe the money is better spent on AIDS or basic cancer research. And there are other eosts- you end up putting your best scientists and reg- too far. n ulators on problems that may not be significant. "All I'm saying is that man-made pollutants don't seem to be a relatively significant hazard. I'm just trying to present a way of prioritizing what to look at. We should pay more attention, for in- stance, to alcohol and tobacco than this little pesticide residue. And we should pay more atten- tion to natural carcinogens. Just because a sub- stance is natural doesn't mean we can't do something atiout it." Radon, for instance, is a natural substance that worries Ames. In 1985 he warned Congress that radioactive radon gas seeping into homes appeared to be causing 10,000 cancer deaths per year, more than all forms of manufactured pollution. Yet it was getting little attention from the Environmental Protection Agency. "Millions of houses with radon have much more radioactivity than the area around Three Mile I!f- land ever got," Ames says. "I suspect the problem is much worse than all the air pollution or toxic waste dumps, but it was hard to get EPA interested be- cause they're so involved with these other things. Ln The trivia displaces the important things." ~ In principle, of course, thate's no reason that the %D EPA can't be concerned with radon and pesticides L„ (and, in fact, the agency has recently started paying ~ more attention to radon). But the government esti- tj mates that 60,000 chemicals are now in use, with hundreds of new ones added each year, and there's no practical way to test them all. It costs the Na- tional Toxicology Program $1.8 million to test a single one, and so far about half of all those tested - roughly 175 -have turned out to be carcinogenic. Some scientists, such as Epstein and Legator, be- lieve that many of the dangerous ones have already been identified, and that there will turn out to be a manageably small number of carcinogens to regu- late. Ames, however, thinks there will be so many that scientists and government agencies couldn't possibly monitor each one. "The other problem," Ames says, "is that when you restrict a technology, you often end up with an alternative that's even more dangerous." If we stopped chlorinating water, in an effort to eliminate traces of carcinogens, we'd run a greater risk of dysentery. Modern dry-cleaning solvents may be slightly carcinogenic -which is why there's been a movement to ban them -but at least they don't start fires the way the old solvents did. Concerns about pesticides have already prompted plant breeders to develop new insect-resistant crops that require less spraying, but Ames thinks that may make food more carcinogenic by increasing levels of natural pesticides within the plants. "I guess people can say, 'If there's any risk, I'll chuck it.' But there's no life at all without some risk. Every organism pollutes. You breathe carcinogens out your mouth after you drink a beer. Sunshine is a carcinogen, but do you want to put up an umbrella every time you cross the street? Then you run the risk of poking someone's eye out." Ames's favorite example of faulty risk assess- ment is a story from the tabloid Weekly World News headlined, "Health Nut So Scared of Food Additives He Starves to Death." It's taped on Ames's office door next to a quotation from the 18th century philosopher David Hume: "Nothing can be more unphilosophical than those systems which assert that virtue is the same with what is natural and vice with what is unnatural." For the first time in the history of the world, every human beiirg is now subjected to contact with dan- gerous chemicals, from the moment of conception until death. -Rachel Carson, Silent Spring, 1962. For the first time in the three-and-a-half-billion-year history of life on this planet, living things are bur- dened with a host of man-made poisonous sub- stanus...-Barry Commoaer, The New Yorker,1987. If you believe Bruce Ames's arguments, the above two statements are intellectual forms of man-made January/February 1988 HIPPOCRAI'ES 37

"Don't worry," . pollution. The first is false; the second is technically correct but in some ways more troubling. Whereas Carson was mainly interested in controlling a few pesticides, Commoner uses this "man-made sub- stances" bogeyman to justify his modest proposal for shutting down most of the petrochemical indus- try, not to mention restructuring the rest of the economy. (He would replace the industry's prod- ucts with what he calls perfectly serviceable natural substitutes, and he would use "social governance" rather than the profit motive to choose technologies for other industries. Instead of the profit motive, he argues, why don't we choose a technology based on its sodal consequences?) During the past 25 years, almost all of humanity has become healthier and longer-lived, yet the doomsday rhetoric persists. It is unfair, of course, to damn an entire move- ment for the opinions of a crusader like Com- moner Most environmentalists presumably do not . says Ames, and want to shut down the petrochemical industry or restructure the economy. They would simply like the government to keep the more dangerous pollu- he offers some tants out of their air, water, food, and workplaces. But you cannot make choices about pollutants and risks without getting entangled in ideology. And blessedly simple you cannot grasp Bruce Ames's message without understanding the ideological gulf between him and Commoner. advice for The difference is that Ames doesn't really trust in avoiding the few the wisdom of governments when it comes to pro- tecting your welfare. His youthful socialist leanings were disabused by visits to the Soviet Union and China and by his own encounters .%;ith the federal bureaucracy. He recalls what happened when he real hazards. announced the Ames Test. "I was a little naive. I thought, Ah, when I intro- duce this test all the government agencies will re- quire industry to use it. It was just other way around. Every industry in the world wrote to get the test, because it's in their economic interest to weed out carcinogens, and every government agen- cy hemmed and hawed and was reluctant to do anything for fear of upsetting the applecart. "I don't think everything industry does is right. You need rules about polluting. But you also have to recognize that government agencies have their own agendas and don't work terribly well. If you ask regulators to be concerned about things with very low hypothetical risk, you're just going to scare the public and get the whole country tied up in bureaucracy. "My hunch," Ames says, "is that environmental organizations include some people who just hate capitalism and some people who think they're sav- ing the world. It's become kind of a religion." Lately Ames has been reading the libertarian theo- ries of philosopher Robert Nozick, author of Anar- chy, State, and Utopia, who maintains that all utopian states are doomed because individuals hold. mutually incompatible visions of utopia. Thus the ideal state is the minimal one that imposes no uto- pian visions on its members. Environmentalism has its utopian side, as another philosopher on Ames's reading list, Robert Nisbet, has pointed out. "Environmentalism is now well on its way to becoming the third great wave of redemptive strug- gle in Western history, the first being Christianity, the second modern socialism," Nisbet writes. All three movements began with a desire to restore "a sacred age of the remote past." For Christians it was Adam and Eve before the Fall; for Marxists it was primitive communism, the original state before private property. For environmentalists it was "the immaculate continent" before humanity. For those in need of prelapsarian myths, Ames's work must be a blow. He seems to have ruined the last refuge of millenialists who have lost faith in God and socialism. If you can't trust in the creator of the Garden of Eden, if you can't trust in the benevolent communal impulses of the Garden's in- habitants, all that remains is the Garden itself. And now it turns out to be carcinogenic. Well, at least the Garden's defamer is optimistic. At age 58, Ames says that he doesn't spend any time worrying about getting cancer himself. He also offers some blessedly simple advice. "In terms of environmental pollution, it might pay to have your house checked for radon. If you're in an occupation with risky chemicals, you.should be careful - you don't want to breathe too much of them. You definitely shouldn't smoke. Alcohol is a carcinogen, but it remains to be seen whether a beer a day is really much risk. I'm not afraid to have a glass of wine with dinner. But certainly overdoing alcohol is a risk. You probably want to eat less fat - saturated fat is bad for heart disease and maybe for cancer - and more green vegetables, which seem to protect against cancer. Eat a balanced diet and don't eat too much of any one thing. Don't get too much sunshine if you're fair-skinned. Beyond that don't worry; technology is making the world safer and life expectancy gets longer every year." You may prefer to worry, and you may be right. It could turn out that humanity really is producing some version of Rachel Carson's "stricken world." But if anything is dear from Ames's work, it is that science is not going to provide any absolute protec- tion or guidance. The choices are mainly ideologi- cal: which unknown dangers to fear, whether to let the state or the individual decide which risks are worth taking. There's a lot of room for reasonable positions in between Commoner and Ames. In deciding which end of the spectrum you pre- fer, it may be worth keeping in mind one distinc- tion. Barry Commoner, having concluded that there are natural alternatives for most petrochemi- cal products - from detergents to fertilizers to plas- tics - would like to dismantle the industry respon-. sible for a good portion of the things in your home. Bruce Ames would never dream of trying to close the Berkeley Natural Grocery. 0 John Tierney is a contributing editor. His last feature for HIPPOCRATEs was "Stress, Success, and Samoa." 38 HIPPOCRATES January/February 1988 515 7 9 5 4 7 3

4 HEALTH MAGAZINE as rated by U.S. News and World Report H1PRJCRAIES WHICH IS MOST HAZARDOUS TO YOUR HEALTH? According to cancer expert Bruce Ames, it's not what you think (see page 28) By John Tierney EXERCISE: NOW MUCH DO YOU REALLY NEED? WHY TALL PEOPLE COME OUT ON TOP THE FIRST WRINKLE CREAM NIGHTMARFS AK' Whatthe well~read ~ are readWg Compliments of Eastern Airlines Jan/Feb 1988 U U.S. $3.00 CANADA 33M DI8FU1r tJrR1L FEBRUARY 23

THF i+:.'..".~ : C "i :fE.1LTH !. MECICINE H1PFCCRETES Editor ERIC W. SCHRIER ManayngF.ditor MICHAELGOLD Art Director JANE PALECEK Senior Fditon SHERIDAN WARRICK SUSAN WEST Writen BENEDICT CAREY LISA DAVIS DEBORAH FRANKLIN ('opy F+liror ANN BARTZ FAinw.+t r..,nAin•tor JOHN KIEFER FAirr..:nl R..rvrlt V.SI FRIE FAHEY MARY JA4!cS Fdirnri~l ~1titNwry DIAafF FtSFNHARDT M ARY HUSSFFt D CHRISTINA SPONSF.LLI . o...d,r-;~..• N.natee I INhA K. S\IITH A.-:.unt Art Ilirectnr KFI I Y DOE F..cs;ve PnMisber JOHN D. KLINrEL Ceweral Mannja JOHN P. SHEEHY r'srrolatinn ntinetoc JAMFS E. TUCKF.R rirc.latioa Manager SUSAN HANSHAW Circulseio. Asmtant RANDY ROBERTSON Adnimlstr.tive Mua•nt SUZANNE HILL Bnnk4eeper WANDA COOPER PP,".h.. JAMES S. MARTAY a.a..;,te P,1hw.hrr A,ti..nwt Mao-seert MARJORIE WEISS SANnRA MAURIELLO nANETTE MF.HL M:awNt Mnwieer SHFRRIF. MYERS 4A..r.isinR ('mw4:..~ PATRICIA POWERS Adreaisins Assi.-t CYNTHIA GENDRICH t'~••~trrinn Fditnry William F. Allman Wini,m Bnly Patrick Cooke Stephen S. Hall Patricia Long Russ Rymer John Tiemey Editor:d Advi+nry B++ard: Director, Denis Kollar, M.D.; Donald J. DAnsio, M.D.; Michael DeBakey, M.D.; Norbert Freinkel, M.D.; Olga Jonasson, M.D.; Don M. Long, M.D., Ph.D.; Floyd D. Loop, M.D.; John Naiarian, M D.; Annette Oestreicher; Carolyn Piel, M.D.; Don Trunkey, M.D. Diercwn atsd Officen of Hippocrates, Inc.: Co-('hairmea J. Russell Denan A. Douglas Peabody President Eric W. Schrier Vice President James S. Martay Seemary/Treasurer John D. Klingel Charles A. Burton Mark M. F4mhron Annem Oestrei~her AdvMnrs Sherri Cvroll Howard N* ^•-^vaki Richard D. Parsons Paul Rense Sn•+:+1 r'nnadrints Rnti•rt G. Rryant Thomas B. Jacob F,~--a-n t>-nis Kolhr, !r1.D. Leslie A. McCurdy I T H I S I S S U E A Tale of Two Endings ARLY LAST YEAR, senior editor Dan Warrick caught wind of a murder story. Two teenage girls from neighboring English villages had been raped and strangled; in each case, the body was left in the bushy fringes of a pleasant country lane. Investigators felt sure the killings were the work of one man, but beyond that they had few leads. What made Warrick think this was a story for HIPPOCRATES? After three years of dead ends, the British police had turned to a new technique of medical detection known as DNA fingerprinting. The chances of two individuals having the same DNA patterns are 30 billion to one. That makes the technique a convincing means of matching a suspect to such evidence as bloodstains and semen samples-which is why the Leicestershire Constabulary took the unprecedented step of asking for blood samples from 5,500 of the area's young men. To Warrick, the story seemed the perfect way to introduce readers to this powerful new tool and to dramatize its human impact. The only problem, from a journalistic perspec- tive, was that events were still unfolding. ' "You'll be entering in the middle of this case," Warrick remembers telling writer Anthony Schmitz. "We're content to do this story without wrapping it up like a standard paperback novel. We've got to present DNA fingerprinting through the people and the color and flavor of life in the villages-but there's no real ending." Schmitz flew to England, retraced the steps of the victims, interviewed the townspeople and the detectives, and turned in a classic murder mystery. In a quiet, moody conclusion, he left the case unresolved and the villagers still cautious and worried. Then, several weeks before press time, editorial researcher Valerie Fahey was on the telephone to England, checking a few last points in Schmitz's manuscript with a local rector, the Reverend John Young. When Fahey asked if the rector feared for the safety of his own tecnage daughters, Young dropped the bomb: "Oh, the suspect's been found. He was in court earlier today." For Fahey, Schmitz, and Warrick, the pace of the next few days was more like that of a daily newspaper than a bimonthly magazine. In a frenzy of phone calls, they pieced together the facts. Sc'hmitz, tapping some key contacts he had grown friendly with over a few pints of ale in a village pub, delivered a new conclusion. After nearly four years of frustration, the police seemed confident that they had their man. Was it a DNA fingerprint that did the suspect in? Yes-and no. Or at least not in the way you might expect. Our storn'-"Murder on Black Pad," which begins on page 48- got just what every mystery story needs, a surprise ending. ~ 6W HtPr'oCRATES (ISSN 0R92-2977) is published bimonthly by Hippocrates, Inc., 47S Gate Five Rd., Suite 100, Sausaliro, CA 94965. Copyright C1988 by Hippocrates, Inc. All rights reserved. U.S. subscriptions $24 per year. • Canadian suhcrriptinns S.1tl per vcar. Foreign subscriptions $36 per year. The opinions espreceed hy authora do not necessarily reflect the policy of Hippixrates, Inc. All material in this maRazine ie provided for inGorn:ation only, and may not be construed as medical advice or instruction. No action should he taken based uptm thc contents of this magazine; instead, appropriate health professionals should be consulted. Editorial Correspondence:'4'S Gate Five Rd.. Suite 100, Sausalito, CA 94965. (41S) 332-5866. Unsolicited manuscripts will be returned only if accompanied by a stamped envelope. Advertising Offices: Hippocrates, 201 E. 42nd St., Suite 3108, New York, NY 10017. (212) 490-7806. Hippocrata,121 West Wacker t)rice. Suite 2016, Chicago,lL 60601. (312) 641-5667. Subscription Correspondence and Change of Address: Hippocrates, P.O. Box 56892, Boulder, CO 80322-6892. Or call toll-free,1-800-525-0643. 6 HIPPM'R ATFS January/February 1988