Enjoy.
July 5, 1994
SCIENTIST AT WORK: Bruce N. Ames; Strong Views on Origins of Cancer
By JANE E. BRODY
WHEN it comes to controversy, Dr. Bruce N. Ames, though not physically intimidating at 5 feet 9 inches tall, is no shrinking violet. The man who invented the leading laboratory test to screen chemicals for their ability to damage genes has years of solid science and the accolades of countless colleagues behind him when he makes such provocative and socially unpopular statements as these:
"I think pesticides lower the cancer rate."
"Pollution seems to me to be mostly a red herring as a cause of cancer."
"Environmentalists are forever issuing scare reports based on very shallow science."
"Standard animal cancer tests done with high doses are practically useless for predicting a chemical's risk to humans."
"Nearly all the polluted wells in the U.S. seem less of a hazard than chlorinated tap water."
"99.9 percent of the toxic chemicals we're exposed to are completely natural -- you consume about 50 toxic chemicals whenever you eat a plant."
"Elimination of cancer is not in the cards, even if we get rid of every external factor."
"Nearly half of all natural chemicals tested, like half of synthetic chemicals, are carcinogenic in rodents when given at high doses."
"We're shooting ourselves in the foot with environmental regulations that cost over 2 percent of the G.N.P., much of it to regulate trivia."
Coming as they do from a highly respected scientist who does not do consulting work for industry, such remarks are especially irritating to those who believe that modern industry has touched off an epidemic of cancer and birth defects by contaminating the air, water, soil and food with toxic chemicals.
Dr. Ames, a biochemist and molecular biologist at the University of California at Berkeley, where he directs the National Institute of Environmental Health Sciences Center, is a member of the National Academy of Sciences and is the recipient of an outstanding investigator grant from the National Cancer Institute and of many highly prestigious awards for excellence in research. His hundreds of technical publications, many in an arena rife with public, political and scientific controversy and punctuated with passionate emotions, have made him one of the two dozen most often cited scientists in the world.
Now 65 years old, Dr. Ames feels he is racing against the clock to "solve aging and/or cancer before my neurons decay." Not that his colleagues have noticed any dulling of his tack-sharp scientific mind, his rapid-fire ripostes and his widely admired ability to unify disparate areas of research into a common, logical construct of how cancer starts, flourishes and eventually consumes its host.
Even his detractors consider Dr. Ames to be a brilliant scientist who moves with remarkable ease from pure biochemistry into public health. Dr. Malcolm Pike, an epidemiologist at the University of Southern California in Los Angeles, applauds his "enormous ability to see the big picture" and his willingness to be "a protagonist who is prepared to get up and argue some very unpopular things." Dr. Walter C. Willet, an epidemiologist at the Harvard School of Public Health, calls him "one of the most innovative thinkers in the world of science, able to bridge the gap between laboratory science and human disease."
But others, like Dr. David Rall, former director of the National Institute of Environmental Health Sciences, believe his generalizations are based on incomplete data, since "most of the chemicals we're exposed to haven't been adequately tested for carcinogenicity."
As Dr. Ames sees it, "Much of cancer is built in; a good part of it is due to aging."
"If you plot cancer versus age," he said, "you'll see that in 60 million years, evolution took us from short-lived creatures like rats, where a third have cancer by the age of 3, to long-lived creatures like humans, where a third have cancer by the age of 80. There's very little human cancer until after the age of 30; then it increases sharply with age." Metabolic Rate and Cancer
Why, he wondered, should that be? He found several explanations. First, cancer risk is linked to metabolic rate: the faster the rate at which the body burns fuel, the greater the likelihood of developing cancer. Rats, for example, have a metabolic rate eight times as fast as humans.
"What in metabolism is doing us in?" Dr. Ames asked, not waiting for an answer. "Oxidation. We burn fat and carbohydrates in the presence of oxygen to produce energy and water. But en route, we make superoxide, hydrogen peroxide and hydroxyl radicals, the same mutagenic free radicals that are produced by radiation. In each human cell the DNA is hit about 10,000 times a day by mutagenic oxidants, and in each rat cell about 100,000 times a day."
"You'd think that exercise would be bad, since it raises the metabolic rate, uses oxygen and increases the production of free radicals," Dr. Ames continued. "But as you become adapted to exercise, the body's antioxidant defenses go up and the risk of heart disease goes down, so there's a net benefit."
While there is no way to stop the body's production of free radicals, he explained, human cells are replete with enzymes that block their damaging effects. These innate antioxidant defenses, he said, are bolstered by antioxidant nutrients like vitamin C, vitamin E and carotenoids in fruits and vegetables, which can suppress all stages of the cancer process.
"Diet is at least as important as smoking as a cause of cancer," he said in a tone reminiscent of parents coaxing children to eat their broccoli. "If you don't eat your vegetables, you're irradiating yourself in a sense. Gladys Block has shown that the rate for practically every type of cancer is doubled among people who don't eat fruits and vegetables. Probably every vitamin in foods is part of some defense system." Dr. Block is an expert on cancer and nutrition at Berkeley. Pesticides as Cancer Weapon
Dr. Ames considers pesticides an anticancer weapon because their use increases the yield of fruits and vegetables and lowers their cost, enabling more people to consume foods that appear to protect against cancer.
Dr. Block has found that even with help from pesticides, only 9 percent of Americans eat the recommended minimum of a total of five servings of fruits and vegetables daily. This dietary failing, along with a menu high in fat and low in fiber, accounts for at least a third of cancers in industrialized nations, Dr. Ames and others have concluded from analyses of cancer rates and dietary habits in many populations.
A slightly built, bookish man, Dr. Ames is a native of New York who graduated from the Bronx High School of Science and Cornell University. He says his findings about the origins of cancer and bodily defenses against it have strongly influenced his living habits.
"I never smoked, and when I married my Italian wife 34 years ago, I switched my diet from Jewish cooking to Italian cooking and never looked back," he said. "I eat lots of fruits and vegetables and fish, but meat in moderation and few processed foods. We use mainly olive oil, and each day I take 250 milligrams of vitamin C, 400 international units of vitamin E and a one-a-day. I eat a good diet, so the supplements are just for insurance. However, I believe in moderation. I don't think people should take massive doses of vitamins."
In poor countries, he said, a third of cancers result from chronic infections: hepatitis B and C and liver cancer, human papilloma virus and cervical cancer, Helicobacter pylori and stomach cancer, to name a few.
"The selection process in human evolutionary history favored reproduction and selected for mechanisms like white-cell defenses that protect humans during early life," he said. "But we paid a price for that protection in the form of increased cancer. Those white cells that guard against our demise from infection use nasty mutagens to incinerate their targets."
Microorganisms that cause chronic infections also kill cells and stimulate cell division, he said, and high rates of cell division are associated with increased mutagenesis and carcinogenesis.
Mutagens damage the DNA that makes up genes. Cancer results from multiple mutations, which means that most, if not all, mutagens are also potential carcinogens. Although cells have enzymes that continually cruise along the DNA and repair it by clipping genetic aberrations out of the lineup, as people age the mutation rate gradually exceeds the body's ability to remove these bad actors, giving cancer a chance to establish a foothold.
"What's amazing is how well defended we are against the damaging effects of chronic infections," Dr. Ames observed. "It takes 30 years or so to get those cancers."
Even if a cell's DNA is seriously damaged by a mutagen, however, cancer will not result unless that cell is actively dividing. Herein lies Dr. Ames's problem with animal tests using high doses of suspect chemicals. These "maximum tolerated doses" injure cells and tissues and set off reparative cell division. Dr. Ames maintains that in many cases it is the accelerated cell division, not the chemical per se, that is causing cancer. Stimulation of cell division may also account for the role of certain hormones in cancer, like the contribution of the body's estrogen to cancers of the breast and uterus.
But people are rarely exposed to anything like the large doses of chemicals used in animal tests, and at the more typical low doses that enter the body, there is no toxic damage to produce cell division and therefore they are not likely to increase cancer risk, he said.
"The dose makes the poison," Dr. Ames said, quoting a maxim of toxicology. "At some level, every chemical becomes toxic, but there are safe levels below that. You cannot extrapolate linearly from a high dose to a low dose and end up with a realistic risk estimate. A tenfold reduction in dose would produce much more than a tenfold reduction in cancer risk."
He pointed out that about 40 percent of chemicals that cause cancer in rodents at high doses are not mutagens, which suggests that the toxic dose, not the chemical per se, is often the problem.
In fact, Dr. Ames and others have shown that exposures to low levels of toxins induce natural defense mechanisms, including various enzymes, antioxidants and the melanin that forms in sun-exposed skin. Then, when a larger dose of the insult is encountered, the defense systems are primed to act protectively, Dr. Ames said.
"Environmental pollutants are not an important cause of cancer," he said. "They account for a tiny percent of cancers in Americans, but might be a problem in people like farm workers who apply pestIcides if they are heavily exposed. Hysteria about pollutants is costing us an enormous amount. We spent a huge amount of money getting traces of the metal degreaser trichloroethylene out of our water, which had a possible hazard 100 times below that of the average amount of chloroform in chlorinated tap water, although in fact neither may be a real hazard." Natural and Synthetic Pesticides
People fret about pesticide residues, but 99.99 percent of the pesticides Americans consume are natural constituents of plants, Dr. Ames said. He has calculated that the typical American eats about 1,500 milligrams a day of natural pesticides, which is 10,000 times the average daily consumption of 0.09 milligrams of synthetic pesticide residues.
Like the synthetic pesticides, about half the natural pesticides that have been tested are carcinogenic in rodents. In trying to reduce dependence on synthetic pesticides, some agricultural scientists are breeding plants with higher levels of natural pesticides, in effect trading one toxin for another, Dr. Ames said. For example, a new insect-resistant variety of celery was found to contain 6,200 parts per billion of carcinogenic chemicals called psoralens, whereas normal celery had only 800 parts per billion of these chemicals.
"On average, half of all chemicals tested, natural or synthetic, are carcinogenic in animals," Dr. Ames said, adding: "It is not true that our bodies are better able to defuse natural toxins than synthetic ones. Our defenses are general ones; they do not discriminate between natural and synthetic chemicals.
"I don't mean to suggest that there aren't real problems with some synthetic chemicals, but the environmentalists are wildly exaggerating the risks. If our resources are diverted from important things to unimportant things, this doesn't serve the public."
Photo: Dr. Bruce N. Ames in his biochemistry laboratory at the University of California at Berkeley. (Michael Jones for The New York Times) Chart: "What Causes Cancer? The World According to Ames" Dr. Bruce Ames maintains that Americans spend far too much time and money trying to clean up insignificant causes of cancer and that the most important causes of cancer can be controlled by individual efforts or public health measures like vaccines. The proportions listed below reflect his opinions and may equal more than 100 percent because two or more factors are sometimes involved in triggering cancer. Factor: Diet Estimate of share: One-third Comments: Too much fat, too few fruits and vegetables and too little fiber are consumed to provide adequate intake of protective nutrients. Factor: Smoking Estimate of share: One-third Comments: Cancer risk rised in direct proportion to the duration of smoking and number of cigarettes smoked each day. Factor: Chronic Infections Estimate of share: One-third in poor countries Comments: Inflammatory reactions release potent mutagens; vaccines and other public and personal health measures could prevent many infections. Factor: Hormones Estimate of share: One-fifth Comments: Hormones stimulate cell division and can be influenced by diet and drugs, e.g., antiestrogens. Factor: High Occupational Exposures Estimate of share: A few percent Comments: Regulatory standards and employers can protect workers Factor: Pollution Estimate of share: Less than 1 percent Comments: Heavy air pollution may slightly increase risk. (pg. C10)