Of Mice and Men

Bruce Ames Interview

In the 1970s, Bruce Ames was a hero to environmentalists--the inventor of the Ames Test, which allows scientists to test chemicals to see whether they cause mutations in bacteria and perhaps cancer in humans. His research and testimony led to bans on such synthetic chemicals as Tris, the flame-retardant used in children's pajamas. A world renowned cancer researcher with a calm, reasoned manner, Ames was an ideal witness in the case against man-made chemicals. As science writer John Tierney aptly described him in Hippocrates, "He has a quiet, kindly tone of authority as he patiently explains why things are the way they are....He sounds so sensible. which is one reason he made such a good witness for the environmentalists in the 1970s."

But it's a scientist's imperative to change his mind when the data change-- and recent data have made Ames deeply suspicious of high dosage chemical testing and especially of the notion that man-made chemicals are uniquely dangerous. We are, he has discovered, surrounded by mutagens--not only synthetic chemicals but also natural ones--and blindly banning suspicious modern substances can do more harm than good.

Today, Ames, a professor of biochemistry and molecular biology at the University of California at Berkeley, stands on the other side of the chemical-ban debate. In 1990, he spoke out against California's Proposition 128, which would have banned many pesticides, and he has been highly critical of the ban on Alar. The best way to prevent cancer, Ames now believes, is to "eat your veggies." Any government action that makes fruits and vegetables more expensive ultimately causes cancer. In recent years, Ames has added a dollop of the economist's sense of trade-offs to the cancer researcher's zeal for prevention.

Ames discussed cancer research and environmental politics with Editor Virginia Postrel at his Office in Berkeley.

Reason: You've become well known for saying that we shouldn't worry so much about man-made chemicals causing cancer, that natural carcinogens are far more common and we shouldn't worry about them either. Why is that?

Ames: It isn't that we shouldn't worry about man-made chemicals. In certain occupations, people can be exposed to very high levels. But pollution is pretty much irrelevant to cancer--the kind of pollution that we're getting with water pollution, or with pesticide residue, is in such tiny amounts.

People got off on the wrong track about man-made chemicals. They said, Look, we know workers can get cancer from high doses of beta naphthalene or vinyl chloride. We shouldn't have the workers be guinea pigs--we should test these things in rats. And that was reasonable. So they started testing the industrial chemicals in rats.

Reason: And they picked these chemicals because they were known to be associated in high doses with cancer?

Ames: Originally the driving force was high-dose occupational exposure. but soon it came out to be testing every synthetic chemical and half of them came out positive in rat tests. I think we're drawing the wrong conclusions from high-dose rat tests. They are testing enormously high doses--the maximum tolerated dose in the rats or the mice, which means you find the level that causes overt toxic effects and back off just a little bit and feed the animal that amount every day for a lifetime. That sends toxicologists up the wall because that's a very high dose, and they are afraid that will do something that isn't relevant to low doses.

But the control. which people should have thought of but they didn't, is what about all the chemicals in the natural world? People got in their head, well, if it's man-made somehow it's potentially dangerous, but if it's natural, it isn't. That doesn't really fit with anything we know about toxicology. When we understand how animals are resistant to chemicals, the mechanisms are all independent of whether it's natural or synthetic. And in fact, when you look at natural chemicals, half of those tested came out positive.

Of course. almost all the world is natural chemicals, so it really makes you rethink everything. A cup of coffee is filled with chemicals. They've identified a thousand chemicals in a cup of coffee. But we only found 22 that have been tested in animal cancer tests out of this thousand. And of those, 17 are carcinogens. There are 10 milligrams of known carcinogens in a cup of coffee and that's more carcinogens than you're likely to get from pesticide residues for a year!

Reason: Why not conclude that you shouldn't drink coffee'

Ames: But half of all the things tested are coming out positive. The point isn't to worry so much about cups of coffee, but to rethink what we're doing with animal cancer testing We're eating natural pesticides, which are natural chemicals that plants use to try to kill off insects that try to eat them. And we eat roughly 1,500 milligrams of them per day. We eat 0.09 milligrams of synthetic pesticide residues. So we're talking about incredibly tiny amounts of synthetic pesticides, and yet the same percentage of natural chemicals come out positive.

So then the question is, What's wrong with high-dose animal cancer tests? I've been arguing in the literature that cell division is a risk factor for cancer, as is mutation. A mutagen damages your DNA, and everybody agrees that that's a risk factor for cancer, and cancer can occur with accumulated mutations. But when the cell divides, DNA damage is converted to mutations. So what we 'v been arguing is that raising either increases your risk of cancer--either the rate of cell division or the rate of mutagenesis. So when you test these enormous doses of a chemical, cell division can be caused in various ways. It's like a chronic wounding experiment. When you wound tissue. you get a lot of cell proliferation, because you get signals for the cells to come in and heal the wound and start dividing. So I think that a sizable percentage of the chemicals are only going to be a risk factor in high doses--like saccharin.

Reason: Because they have this wounding effect?

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