Of Mice and Men

Bruce Ames Interview

Virginia Postrel from the November 1994 issue

(Page 2 of 7)

Ames: Yes, at these enormous doses. Saccharin is a carcinogen at high doses, and everything we know about the theory says there's no risk at all at low doses. I think that some sizable percentage of all the chemicals we're calling carcinogens are going to be like that.

Now if something's a mutagen. it can both damage the DNA and kill cells. If you get to high enough doses where it's killing cells as well as damaging the DNA, then you're getting an extra multiplier. For a mutagen there might be a small risk at any level. But in most cases you also get this big multiplier that's only a high-dose effect. So all this says is that the risk numbers people are throwing around are going to just be wrong. And the further you get from the dose you gave the rat, the less you want to worry about it.

Reason: People do want to know what causes cancer.

Ames: That's what I'm very much interested in. Cancer is primarily a degenerative disease of old age. It goes up very sharply with age. Rats live about two to three years and by the end of their lifetime, 30 percent of them have cancer. At 1 year old, very few have cancer. Mice have a slightly shorter lifespan, and the curve is shifted to the left. And people show a similar relation, except we live to 80 years. This suggests that cancer is a degenerative disease of old age, in the same way as heart disease and cataracts and all the other things you'll find out about soon enough as you get older. It doesn't mean that external factors can't influence it--we know cholesterol influences heart disease, and smoking is 10 years off your life, so if everybody stopped smoking the curve would move out. But underlying it all, the reason there is more cancer is more people are going up that curve. More people are living longer and longer every year, and as we're living longer we see an increase in cancer.

Reason: The incidence of childhood leukemia would seem to go against the idea that cancer is an aging disease. Ames: There is some risk of cancer at any age. But what people have recently turned up is that male smokers are more likely to have kids with childhood leukemia. So smoking has genetic effects. With cancer you need a number of hits--a number of different mutations-- and if you have one genetically, from a father who smokes, then the other one can occur soon afterwards and show up as childhood cancer.

Reason: Male smokers but not female smokers?

Ames: Studies show that smoking by either parent increases the child's risk of cancer.

Reason: Lately breast cancer has started to get a lot of attention in the media.

Ames: OK, now with breast cancer, the two best people right now are down in Los Angeles, and they think they are solving it--Brian Henderson and Malcolm Pike at USC, two of the world's leading epidemiologists. They've been studying breast cancer for a long time. It seems to be mainly hormones. It was known for a long time that women who have lots of children have very low rates of breast cancer, and nuns have very high rates of breast cancer. It has to do again with cell division. Every time a woman has her cycle, she has cell division in the breast, so that seems to be a critical risk factor. Childbirth interrupts that.

We know how to prevent breast cancer: You live like a Chinese peasant who lived 100 years ago. You work in the fields, on a meager diet, so you have your first period at age 17 and then you start having a child every year. It's a good recipe for not getting breast cancer but not very practical. The question is, Can one intervene with hormones? What Henderson and Pike say is that it's known that if you take out a woman's ovaries, it stops ovulation, but that is another solution that is not very practical. But certain birth control pills do something similar. So Henderson and Pike are coming up with a complex of hormones that they think would make a good oral contraceptive and also cut the risk of breast cancer dramatically. They're trying to test it out and get it through the FDA. If they're right, it's going to be terrific. If they're not right, somebody else will figure it out in five years.

I think people are going to figure out the causes of cancer and heart disease and aging. It's coming very fast, and it's due to science and technology and a healthy economy. Basic science is the child of a healthy economy. The reason you have all these scientists in the United States is because we can afford to spend money on basic research.

Reason: How accepted are your views among cancer researchers?

Ames: Well, we've had a controversy going back and forth in Science recently, and I got fan letters from all sorts of people that I really respect in the world, saying, Keep on, you're on the right track, we agree with you. And there are people who disagree. But I do think I'm winning the scientific wars.

Let's go back to what's really causing cancer. If you ask the epidemiologists, after years and years of studies, they say eating more fruits and vegetables lowers the cancer rate.

Reason: Regardless of what kind of cancer?