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Ames, Bruce N. (1928- )

Ames, Bruce N. (1928- )

American biochemist and molecular biologist

Bruce N. Ames is a professor of biochemistry and molecular biology at the University of California at Berkeley. He is best known for the development of a test used as an indicator of the carcinogenicity (cancer-causing potential) of chemicals. Known as the Ames test, it measures the rate of mutation in bacteria after the introduction of a test substance. Ames's research led to a greater appreciation of the role of genetic mutation in cancer and facilitated the testing of suspected cancer-causing chemicals. He also developed a database of chemicals that cause cancer in animals, listing their degree of virulence. Ames has been involved in numerous controversies involving scientific and environmental policies relevant to cancer prevention. In the 1970s he vociferously advocated strict government control of synthetic chemicals. In the 1980s, however, the discovery that many natural substances were also mutagenic (causing gene mutation), and thus possibly cancer causing, led him to reverse his original position.

Ames was born in New York City, the son of Dr. Maurice U. and Dorothy Andres Ames. His father taught high school science and then became assistant superintendent of schools. Ames himself graduated from the Bronx High School of Science in 1946. He received a B.A. in biochemistry from Cornell University in 1950 and a Ph.D. in the same field from the California Institute of Technology in 1953. Ames worked at the National Institutes of Health, primarily in the National Institute of Arthritis and Metabolic Diseases, from 1953 to 1967. In 1968 he moved to the Department of Biochemistry and Molecular Biology at the University of California at Berkeley as a full professor. He was Chairman of the Department from 1984 to 1989. In addition he became Director of the National Institute of Environmental Health Science at the University in 1979.

In the 1960s and early 1970s Ames developed a test that measured the degree to which synthetic chemicals cause gene mutation (a change in the deoxyribonucleic acid , or DNA , the molecule that carries genetic information). He began by deliberately mutating a Salmonella bacterium. The changed bacterium could not produce an amino acid called histidine that normal bacteria produce and that they need to survive. The next step was to add just enough histidine to allow the bacteria to live, and to add, as well, the synthetic chemical being tested. If the added chemical caused genetic mutation, the abnormal gene of the Salmonella bacteria would mutate and again be able to produce histidine. When this happened the added chemical was marked as a suspected carcinogen, because cancer is associated with somatic cell mutation (that is, mutation of any cells with the exception of germ cells).

Over eighty percent of organic chemicals known to cause cancer in humans tested positive as mutagens in the test developed by Ames and his colleagues. This result gave support to the theory that somatic mutation causes cancer and helped to validate the use of the test for initial identification of mutagens when considering synthetic chemicals for industrial and commercial use. In addition to these practical results, the research of Ames and a colleague, H. J. Whitfield, Jr., led to important advances in understanding the biochemistry of mutagenesis. Beyond his work in genetic toxicology, Ames made important discoveries in molecular biology, including ground-breaking studies on the regulation of the histidine operon (the gene or locus of the gene that controls histidine) and the role of transfer ribonucleic acid (RNA ) in that regulation.

In the 1980s Ames set up a database of animal cancer test results with colleague Lois Swirsky Gold of Lawrence Berkeley Laboratory. The database is used to determine whether a chemical has tested positive as a carcinogen and gives the degree of its virulence. From these data Ames developed a value measuring the carcinogenic danger of a chemical to humans. HERP (daily Human Exposure dose/Rodent Potency dose) is the value determined by comparing the daily dose of a chemical that will cause cancer in half a group of test animals with the estimated daily dose to which humans are normally exposed. The result is a percentage that suggests the degree of carcinogenicity of a chemical for humans.

In the 1970s Ames was a conspicuous advocate of particular regulatory and environmental public policies that relate to the cancer-causing potential of synthetic substances. In the 1970s Ames asserted that even trace amounts of mutagenic chemicals could cause a mutation (and thus possibly cancer). He found that tris (2,3-dibromopropyl) phosphate, the chemical that was used as a flame retardant on children's pajamas, was a mutagen in the Ames test; he was instrumental in getting it banned. Similarly he found that some hair dyes contained mutagens. His advocacy led to governmental regulations that forced manufacturers to reformulate their products. In his position on the regulation of synthetic chemicals, he was a natural ally of environmentalists.

However, in the early 1980s Ames reversed his position, arguing that there is no scientific evidence that small doses of most synthetic chemicals cause human cancers; he also argued that, in the absence of such evidence, they should not be controlled. This about-face was partly a result of a growing body of knowledge concerning the mutagenic properties of numerous chemicals found in nature. Ames began arguing against the existing large public expenditures for pollution control and the regulation of synthetic chemicals, noting that cancer might just as plausibly be caused by the chemicals in plants. His arguments were based primarily on three factors: his argument that more scientific evidence should be required before controls are implemented; his attitude toward the setting of priorities, which he argued should be centered on basic research rather than regulation; and finally his belief that the large public expenditures incurred by the regulatory process hurt American economic competitiveness.

Ames and his colleague Gold have also argued that the use of bioassays (animal tests) of chemicals to predict their carcinogenic potential in humans should be abandoned. In a typical bioassay, rats are given a maximum tolerated dosage (MTD) of a particular chemical daily for a period of time (such as a year). The maximum tolerated dosage is as much as the animal can be given without immediately becoming ill or dying. At the end of the time period, the number of animals that have developed cancers is tabulated as an indicator of the cancer causing potential of the chemical being tested. Ames suggested that it is often the large dosage itself, rather than the nature of the particular chemical that induces the rat cancers. He argued that, since humans are not normally exposed to such large doses, the assays were not valid for predicting human cancers.

Ames's arguments have some support both within and outside scientific communities. However, he also has numerous critics. Those taking issue with his positions have noted that pollution control, for example, involves far more than just carcinogenicity. These critics suggest that Ames has not offered a substitute for animal assays (the Ames test has not proved to be such a substitute), and that neither he nor they have a good idea of what goes on at low dosages. Some argue that Ames has an over-simplified view of the regulatory process, which is based on a consideration of animal assays but also on other factors. It has also been argued that the discovery that many naturally occurring chemicals have a high mutagenic rate (just as synthetic chemicals) should not lead to the conclusion that synthetic chemicals pose less risk than was previously supposed. Such an assumption places too much emphasis on mutagenic rate as a sole indicator of carcinogenicity, ignoring the complex, multi-stage developmental process of the disease.

Yet the disagreements between Ames and his critics are based on several points of commonalitythat cancer is a complex multi-stage process that is not fully understood; that there is no perfect test or group of tests that can fully predict the potential carcinogenicity of many substances in humans; and that public regulatory and environmental policies must be made and carried out in spite of this deficiency of knowledge. As for Ames, he has described his public-policy activism as a hobby, and he has noted that his recent scientific work includes studies in the biochemistry of aging.

Elected to the National Academy of Sciences in 1972, Ames has received many awards, including the Eli Lilly Award of the American Chemical Society (1964), the Mott Prize of the General Motors Cancer Research Foundation (1983), and the Gold Medal of the American Institute of Chemists (1991). He is the author or coauthor of more than 250 scientific articles.

See also Chemical mutagenesis; Molecular biology and molecular genetics

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