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Biological Chemistry

Bruce Ames

Developer of test for carcinogens now champions micronutrients for preventing disease

by Elizabeth K. Wilson
February 14, 2011 | A version of this story appeared in Volume 89, Issue 7

Credit: Jim Block
Credit: Jim Block

Bruce N. Ames is 82, but doesn’t miss a beat. He fairly skips through the halls of Children’s Hospital Oakland Research Institute (CHORI) in Oakland, Calif., where he is a senior scientist, and into his office stacked with colorful folders, cartoons, and awards. Once seated, he launches straight into what’s been on his mind for the past several decades: Despite U.S. Food & Drug Administration recommendations, Americans still don’t get enough micronutrients in their diets to stave off disease.

“I’m passionate about disease prevention,” he says. “And all the low-hanging fruit in disease prevention is in nutrition.”

Ames, a biochemistry professor who spent much of his career at the University of California, Berkeley, is perhaps most well-known for developing the Ames test in the 1970s. His eponymous assay can help determine a molecule’s potential carcinogenicity and is still in wide use today. He is a biochemistry and molecular biology professor emeritus at UC Berkeley, he’s a member of the National Academy of Sciences, and his list of awards includes the Japan Prize and the U.S. National Medal of Science.

Some of his current ideas about food and disease prevention are likely to raise eyebrows with the Whole Foods set: “There’s no evidence that organic food is better for you,” he says. Excluding the high, toxic exposures to pesticides experienced by farm workers, he says, the amounts of these substances that most people encounter on their fruits and vegetables are so small as to be insignificant contributors to diseases like cancer—especially when one considers the natural, toxic compounds present in many fruits and vegetables.

The real culprit of most causes of cancer and diseases of aging, he maintains, is inadequate intake of several dozen key micronutrients. Ames sums the problem up: Smoking and bad diets. “Obese people are actually starving—starving for nutrients,” he says.

But Ames doesn’t stop at “eat your vegetables” platitudes, although he does joke that before modern medicine, “the kids whose moms didn’t tell them to eat broccoli were selected out.” His goal is to expose the disease-protecting biochemical mechanisms that involve vitamins, trace minerals, and amino acids. The effects of chronic deficiencies in these micronutrients may go unnoticed for years, but the substances play key roles in processes such as DNA replication.

His epiphany came from a case study of a patient who had had his spleen removed. The man’s blood contained high levels of broken chromosomal DNA, which would have been filtered out, undetected, in someone with a normal spleen. The man was also moderately deficient in folic acid, which was known to cause chromosome breaks in mice.

But as the man was given supplements of folic acid, the levels of these damaged bits of genomic DNA in his blood dropped to normal. Unlike an epidemiological study, which is fraught with complications, this kind of study “establishes causality,” Ames says. It suggests that folic acid helps ameliorating DNA damage during cell replication, he explains. The principle holds for many micronutrients involved in enzymatic processes, he says, such as vitamin K, vitamin D, or trace minerals like selenium.

These types of analyses led Ames to develop what he calls “triage theory,” in which the body judiciously rations nutrients to the biochemical processes needed most urgently for survival. For example, vitamin C goes straight to collagen formation, thus preventing scurvy, and vitamin D is shunted to bone metabolism, thereby preventing rickets. But the body still needs more of these nutrients for a number of largely undetected processes that involve DNA replication. The effects of shortages won’t show up for years, Ames says.

Though his theories haven’t yet caught fire with the general scientific community, and even as the causes and effects of many micronutrient insufficiencies remain to be sorted out, Ames champions supplementation. “Vitamins and minerals are dirt cheap,” he says.

Ames likes to joke that he was never a good student, “but I am pretty creative,” he says. Nevertheless, his career began auspiciously. In 1953, at the tender age of 24, Ames got his Ph.D. in biochemistry at California Institute of Technology, where he rubbed shoulders with the likes of Linus Pauling. He even recalls developing a brief crush on Pauling’s daughter Linda while attending a party at their house.

Ames has been married for more than 50 years to Giovanna Ferro-Luzzi, a biochemist who was also at UC Berkeley. They have two children, Sofia and Matteo. Ferro-Luzzi, now also a scientist at CHORI, is a native Italian, whose Mediterranean diet influenced the family’s eating style. “We eat spinach, garlic, lots of fish, nuts,” Ames says.

Recently, Ames and his longtime collaborator and former postdoc, Joyce C. McCann, have been publishing a series of meta-analyses of individual nutrients that support triage theory, including one on vitamin K (Am. J. Clin. Nutr., DOI: 10.3945/ajcn.2009.27930) and another on vitamin D (Fed. Am. Soc. Exp. Biol. J., DOI: 10.1096/fj.07-9326rev). They’re now submitting a paper on selenium.

Ames is also pushing his ideas to market. In 2002, when his research showed that the supplement acetyl l-carnitine and the antioxidant α-lipoic acid improved memory and energy in old rats, he started the company Juvenon to market the supplements. He diverts all his profits to fund clinical trials.

You may not get scurvy or rickets from modest micronutrient deficiencies, he says, “but the price you pay from moderate deficiency is increasing age-related diseases.”



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