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Table Talk : Opinion Breaker : Bruce Ames: Standing By His Scientific Guns

TIMES STAFF WRITER

“Would you like a coffee?” asks Bruce Ames sociably. It might seem an odd offer. Ames is famous for having pointed out that a cup of coffee contains 10 milligrams of natural carcinogens.

As a matter of fact, Ames, who is 65, likes coffee. He and his Italian wife collect old espresso machines, and he brews a respectable cup. Besides, Ames never meant to scare people away from coffee. He was making a point about pesticides: Ten milligrams is how much artificial pesticide residue the average person ends up ingesting in a year. In other words, eating non-organic produce for a year is no more dangerous than drinking one cup of coffee. And what’s the harm in that?

Ames’ scientific credentials are imposing: chief of the microbial genetics section at the National Institutes of Health, chairman of the biochemistry department at University of California, Berkeley, member of the National Academy of Sciences. He has published 300 science papers, won numerous scientific awards and served on the board of directors of the National Cancer Institute.

At one time, he was a well-known critic of pesticides and synthetic food additives such as saccharin. “There is no question that society is going to pay for all the pesticides that have been used in the past,” he told the New York Times ominously in 1977, “through increases in birth defects and cancer, but no one knows exactly what the price will be and when it will be paid.”

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But about 15 years ago he started casting doubt on the idea that pesticides pose a major health risk. Today he’d go further and suggest that panic about the dangers of technology leads to policies that are not just inappropriate but downright dangerous to our health.

He sits in his office in Berkeley, surrounded by ceiling-high cases full of books and periodicals, and tells how his ideas developed, beginning the tale in the mid-1960s, when he was still at the National Institutes of Health, years before he became either an opponent or an advocate of pesticides.

“I was always sort of half in genetics and half in biochemistry,” he says. “We were mutating bacteria to see how (genetic) regulatory pathways worked. I was interested in how genes got turned on and turned off.

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“And then at one point, as a sort of side project, I started wondering about all the new chemicals coming into the environment. I was reading too many labels on potato chip packages,” he says, chuckling. “I thought if some of these chemicals were mutagens (agents that change genes), that wouldn’t be good.

“In those days, people didn’t know what was causing cancer. There was an old theory that chemicals that caused cancer were mutagens--they were working by mutating the DNA. But a lot of carcinogens turned out not to be mutagens, and people said no, carcinogens are working in some mysterious way, but not as mutagens.

“Now, being a geneticist, all my intuition said mutagens had to be carcinogens. Cancer is when you have a cell that is different in some way, and the way you get that is by mutating it. Then in the cancer field a few people started showing that, say, benzopyrene, which is a very un reactive compound, isn’t the real carcinogen. It’s metabolized in the body into other chemicals, and some of those are reactive.”

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Ames had developed a simple test (see box) that for many purposes replaced the older way of finding out whether a chemical might be carcinogenic. Before Ames, the only way to test for carcinogenicity was to try a chemical on animals, mostly rats or mice, for several years to see whether any of them developed cancer. Typically, the amount of the chemical given would be the Maximum Tolerated Dose (MTD), which is just less than the amount that would kill them outright by poisoning. Since virtually all chemicals are poisonous at very high doses, Ames and many other scientists believe that MTD tests do not show that a chemical is carcinogenic at low doses, only that cells may become cancerous under extreme stress.

Ames also stresses that MTD levels bear no relationship to the amount of a chemical a person encounters in the real world. However, MTD tests were mandated by the so-called Delaney Clause, an addition to the 1958 Federal Food, Drug and Cosmetic Act, which makes it illegal for processed foods to contain any detectable amount of a chemical that has ever been found to cause cancer, no matter how high a dose it took. Many authorities believe the Delaney Clause imposes an unrealistic standard of safety; last year Carol Browner, administrator of the Environmental Protection Agency, spoke of replacing it with a “negligible risk” standard.

“An animal cancer test costs a million dollars and takes two or three years,” says Ames, “and (the Ames test) was something you could do in an afternoon. Companies are desperate to weed out bad chemicals--it’s bad for business to poison people--and they’re right on top of things, because it’s their own money that’s involved. So the minute our test came out and we showed that most of the classical carcinogens could be picked up as mutagens, every company in the world dealing with chemicals wrote for the strains, and thousands of labs all over the world use our test.”

Ames says he never thought about patenting the test, so he’s never made a penny from it. At any rate, the test made him famous and a hero of the anti-pesticide movement.

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But in the late 1970s, his thinking changed.

“I got into the field because I was thinking about synthetic chemicals,” he says. “But synthetic chemicals are just a drop in the bucket compared to the chemicals in the natural world. People started using our test and finding there were mutagens in celery and in a cup of coffee. The natural world is full of mutagens.

“Then the whole environmental movement came up--'If it’s man-made, it’s bad; if it’s natural, it’s fine.’ Well, that didn’t fit with anything I knew about toxicology, so I became increasingly suspicious of this kind of thing.

“Every plant has 50 or 100 chemicals that it uses to kill off insects or predators. Plants don’t have claws or teeth or immune systems and they can’t run away. How do they defend themselves? Chemical warfare. Practically all of plant evolution is chemical warfare. We’ve pointed out that 99.9% of the pesticides we encounter are natural.”

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As a toxicologist, Ames saw no reason to expect these natural pesticides to be safer than synthetic pesticides, to which they’re often chemically related. “People say, ‘Oh, (these natural pesticides) have been around, we can deal with them.’ But the way we deal with them is by general defenses that are good against synthetics too. Animals don’t deal with chemicals one at a time, because they need to deal with tens of thousands of natural poisons.”

Having concluded that synthetic pesticides were not the danger he had once suspected, Ames turned his inquiry to the causes of cancer. “I started talking with the best epidemiologists,” he says. “Cancer is very complicated, so it’s taken a long time to sort all this out. Now I think we understand most of the causes of cancer, and we know how to prevent a lot of cancer.

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“The incidence of cancer goes up very sharply with age. Mice live two years; by the end of their life span about a third of them have cancer. Monkeys live 20 or 30 years; by the end of their life span about a third of them have cancer. People live 80 or 90 years; by the end of our life span, about a third of us have cancer.”

The sharp upturn toward the end of life, says Ames, suggests that cancer isn’t just caused by getting exposed to mutagens; the cells themselves must be getting less resistant. “If you ask evolutionary biologists why there is aging,” he says, “they’ll say aging is trade-offs. They don’t think that animals die out of altruism, to make room for others. That doesn’t fit anything they know about evolutionary biology.

“It’s trade-offs, and the main trade-off is between reproduction and maintenance. Animals put a lot of their energy into reproduction--they reproduce fast and get out their children--and maintaining the body takes second place. Plus, in the old days, humans were dying early of disease and infections, they only lived to be 30 or 40. Now that we’ve conquered all those diseases, we’re living long enough to get cancer.”

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It turns out that our own metabolism exposes us to danger, because it’s based on one of the most reactive chemicals, oxygen. When a cell burns fat or carbohydrates to get energy, the byproducts include not only water but unstable compounds related to water that have extra electrons in the molecule: hydrogen superoxide, hydrogen peroxide, hydroxyl radical. These “free radicals” quickly unload their spare electrons on other molecules in the cell; when the other molecule is DNA, it can mean trouble.

“A trillion molecules of oxygen go through each cell per day,” says Ames. “A current estimate is that only 100,000 of them actually wound some part of the DNA strand, and the cell has DNA repair mechanisms that fix all but about 1,000 oxidative hits a day.

“So that’s pretty good, when you think about it. But that means every day you’re accumulating 1,000 more lesions (wounds) in every cell, so by the time you’re old, we find a few million oxygen lesions per cell. And when the cell divides, those turn into mutations, or some percentage of them does. Most mutations don’t matter, but some are in key genes and then you have cancer.”

These days Ames is particularly interested in the importance of diet. “I think that’s where the gold is,” he says. “Gladys Block, a professor at Berkeley, has analyzed 172 epidemiological studies from around the world, and what comes out overwhelmingly is that fruits and vegetables protect you against cancer. If you compare the group eating the most fruits and vegetables with the group eating the least--most being four or five portions per day and least being zero or one--the difference is two- to three-fold for practically every type of cancer. Fruits and vegetables are our source of antioxidants, such as Vitamin C and carotenoids and a good part of our Vitamin E.

“The studies suggest that antioxidants protect not only against cancer but against heart disease, against cataracts, against certain kinds of brain dysfunction. And it makes sense to me, because there’s all this oxidant damage going on to your DNA, to your proteins, to your lipids, that we can measure.

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“If you ask top epidemiologists what the causes of cancer are, they’ll say about a third is due to smoking, about a third is due to bad diet. About a third is due to chronic infections such as hepatitis-B virus, hepatitis-C virus--they cause liver cancer, the main cancer in China and Africa. About 20% is due to hormones--this is going to add up to more than 100% because cancer is multi-causal. And then a little bit is due to occupation, a few percent, and pollution, I think, less than 1%.”

All this has made Ames more critical than ever of the anti-pesticide movement. “Pesticides lower cancer rates,” he insists, “because they make fruits and vegetables cheaper and people buy more of them.

“It’s all a matter of where you want to put the money. EPA regulations are costing 2% of the GDP, according to EPA’s own figures. We’re talking about hundreds of billions of dollars. They’re trying to save a hypothetical life for $50 million per life saved, but you could give that money to the Highway Department and save a life for, say, $300,000, improving a freeway. If you put the money into basic research, you’re probably saving a life for $100,000. And I think (the life saved by EPA) is a hypothetical life anyway.

“Life is very complicated. And to simplify all these things and just sell scare stories, all it does is kill people, because it diverts resources from more important things.

“With all the scare stories, people don’t know what’s important anymore. And it turns out what’s important is what your mother told you: Don’t smoke, eat a good diet, settle down and live a moderate life. Your mother was right.”


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