Dr. Bruce Ames

Biochemist, Children's Hospital Oakland Research Institute

Dr. Bruce Ames Bruce Ames is a biochemist based at the Children's Hospital Oakland Research Institute, where he relocated in 1999 after a 30-year tenure in the Department of Molecular & Cell Biology at Berkeley. Ames is a generalist who describes himself as "incorribly distractable," but this has been no handicap for him. Over the course of his 50-year career, Ames has invented an industry-standard test for identifying mutagenic chemicals; compiled a database of over 1400 carcinogenic chemicals; examined the carcinogenic and other adverse effects of vitamin and mineral deficiency; and devised a treatment to slow age-related damage and restore metabolic function in elderly rats and, perhaps, humans. All these endeavors fit under the broad category of "cellular metabolism", and all can be directly or indirectly related to the universal physiological changes observed with age. Study of these topics and others has led Ames to publish over 450 papers and consistently rank in the top few hundred most-cited scientists.

The Ames lab currently investigates two related areas of metabolism: the effects of inadequate vitamin and mineral intake on cellular function, and the oxidative damage done to mitochondria with increasing age. The pathologies associated with inadequate nutrition and oxidative damage read like a hit list of the top killers in the developed world: cancer, heart disease, obesity, Alzheimer's and other neurodegenerative diseases. Although Ames' efforts are very much prescriptive, his overall intent is to find new ways to prevent these conditions by optimizing current health, rather than searching for post-onset cures for specific ailments. In other words, Ames' current research goal is to draw up the blueprints for a generalized "metabolic tune-up."

Vitamins for disease prevention

The number-one prescription given by Ames' current blueprint is absurdly simple: Take your vitamins! Standard one-a-day multivitamin capsules contain the FDA's recommended daily allowance (RDA) of several vitamins and minerals whose deficiency in rats, Ames and co-workers have shown, induces breaks in DNA by oxygen free-radicals and other mechanisms; causes mitochondrial damage, slowing oxygen metabolism; and inactivates genes that protect against cancer, including p53 and zinc-superoxide dismutase. Particuarly important in these regards are the nutrients B-12, folic acid, B-6, niacin, C, E, iron, and zinc. Ames has proposed that up to half of Americans fail to consume the RDA for at least one of these nutrients.

One objection raised by some nutritionists to the one-a-day multivitamin plan is that it's too simplistic, giving people a false sense of security at the expense of an overall healthy balanced diet. Ames does not dispute that a balanced diet is vital to overall health; in fact, he thinks that even standard multivitamins lack some vital nutrients. "The one-a-day doesn't have enough calcium or magnesium," he says, "and you need fiber too." Another missing set of nutrients are the omega-3 fatty acids, found in fish oil, which apparently are not included in one-a-days because consumers tend to balk at fishy-smelling capsules. Still, the low cost and convenience of one-a-days, Ames thinks, make them the best way to ensure daily delivery of most of the nutrients needed for a smooth-functioning metabolism.

Oxygen exposure and its cures

The other current focus of the Ames lab's studies in metabolism is to correct the aging-related metabolism decay seen in mitochondria. Mitochondria, the organelles familiar to high school biology students as the "powerhouses of the cell", are responsible for turning the food we eat into energy usable by the cell through a complex cycle ending in acceptance of free electrons by the element oxygen. When this process goes awry, highly reactive oxidants are generated. These oxidants often end up damaging the mitochondrial proteins responsible for metabolism, making the entire process less efficient. However, Ames' lab has shown that dosing mitochondria with two standard biological metabolites, acetyl carnitine (ALCAR) and lipoic acid (AL), can reverse this oxidative damage and restore metabolic efficiency. In particular, aged rats fed an ALCAR-LA combination showed improvements in motor and cognitive skills. The success of these supplements led Ames to set up a non-profit business, Juvenon, to market them, with the goal of raising funding for FDA clinical trials in humans. Ames put his stock in a foundation.

Of passion and potato chips

What are the key factors in Ames' scientific success? Dedication, collaboration, creativity, rabid intellectual curiousity — and, the interviewer suspects, a bit of a gift at self-promotion. One hobby of Ames' is armchair economics; he views the enterprise of scientific research, both academic and commercial, as part of one big ideological marketplace. "Science is a lot like business," he says, referring to the high degree of intellectual competition. "Creativity is our stock in trade." Ames' main competitive strategy in this marketplace has been to read the biological literature broadly, then be the first to connect the dots between various far-flung sub-disciplines, relying on the judgement of specialist colleagues to help him fill the gaps in his own knowledge. "I like to go into new fields where there's not a lot of work," Ames says. "And I was always around lots of very smart people."

Despite becoming interested in chemical mutagenesis in the 1960s as a result of reading the ingredients on a potato chip box, Ames doesn't have any easy advice regarding which currently under-studied scientific topics will pay off in the future. "It's a hard question. You have to read a lot," he says. "You have to have the discipline to do the things you want to do." The most valuable general piece of advice Bruce Ames would like to instill in undergraduates is this: "Do something you're passionate about." This advice is certainly not uncommon, but talking with Ames for even a few minutes gives the impression that he has followed it every day of his life.

Several other interviews and press releases about Ames' work may be found at his Web site. Particularly informative is his autobiographical essay, "An Enthusiasm for Metabolism".