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Forever Young

S.Jay Olshansky

Ageless Quest: One Scientist's Search for Genes that Prolong Youth. Lenny Guarente. x + 154 pp. Cold Spring Harbor Laboratory Press, 2003. $19.95.

One of the greatest pleasures a scientist can experience is the "Aha!" moment—an inspired idea or discovery that can define a research career. Most scientists are, as they themselves will admit, just big kids working on somewhat more complex questions than those they faced when younger, and all are driven by a childlike enthusiasm and excitement that is unparalleled in the working world. Ageless Quest, by Lenny Guarente, is the tale of a series of "Aha!" moments that led the author, a molecular biologist, down a path in search of the fountain of youth and then onto a path that eventually diverges in the potentially lucrative, but in my view dangerous, direction of scientific entrepreneurship.

Guarente's book begins with an account of his fortuitous journey into the field of research on aging. It's a familiar story: I expect that many scientists fell into their current discipline (as I did) somewhat by accident. The majority of the book is devoted to chronicling Guarente's transformation from a precocious child into an internationally recognized scientist.

Author Lenny Guarente <em>(left)</em> with Mark Ptashne . . .Click to Enlarge Image

There are many ways to study aging—ranging from the work of theoretical scientists considering the larger picture of why human beings age to bench scientists working to understand time-dependent changes in cells and genes. Guarente's piece of the puzzle is in a very narrow corner of the field—the genetic study of yeast organisms. He chose to study yeast, he says, for a variety of reasons: The cells are easy to grow, many biological processes that occur in yeast also occur in animal cells, and genetically different strains of yeast have vastly different (but conveniently short) life spans.

The downside of studying simpler organisms is their biological distance from humans—although this does not stop some of the scientists studying yeast from inappropriately extrapolating their findings to more complex organisms. Ironically, Guarente tells particularly well the story of his initial giddiness at the prospect that his pet "aging gene" in yeast might be a universal regulator of aging in all organisms, and of his later discovery that life is rarely that simple. The history of the field is littered with similar episodes.

An interesting, confusing and little-understood difficulty faced by scientists working on aging today is that of distinguishing between forces (both biological and environmental) that influence duration of life and those that influence the biological rate of aging (the rate at which damage to the building blocks of life—proteins, carbohydrates, lipids, DNA—accumulates). Medications that normalize blood pressure may reduce the risk of death from stroke, for example, without affecting the rate of aging. Some scientists assume that any intervention that extends duration of life will by definition slow one or more of the biological processes of aging. Guarente falls into this trap often throughout the book.

When I was interviewed recently on BBC radio along with another scientist who studies aging, we were asked how long it would be before methods of stopping or reversing the aging process are devised. The young scientist next to me boasted without hesitation that it would be 5 to 10 years at most. Scientists of every era have been asked the same question, and the young, who have no sense of history, always give the same answer: The secret to the fountain of youth is just a few short years away—all we need to do is concentrate more of our resources on solving the problem. Alchemy provides a classic example of this hopefulness—gold was originally sought after as the most potent antiaging substance on Earth.

Not surprisingly, then, Guarente suggests at the end of his book that the first commercial products that will slow aging will appear in the next 10 to 20 years, and that it is only a matter of time before aging itself is declared a disease. Such a declaration is particularly important for entrepreneurs interested in selling antiaging remedies to the public, because getting U.S. Food and Drug Administration approval of a drug requires showing that it effectively treats a disease.

In the first 12 chapters of the book, Guarente exudes the excitement, enthusiasm for research and conceptual insights that I most admire among scientists. Although I certainly did not understand fully all of the detailed concepts from genetics and molecular biology that are scattered liberally throughout the book, I did follow and appreciate the process of discovery and his line of reasoning along the way. Such relentless, dispassionate pursuit of answers and willingness to develop, discard and revise hypotheses is, in fact, what drew me to the world of science in the first place.

It is because I have always regarded science as a noble profession that I cringe when I see scientists step over the line into entrepreneurship. Scientist-entrepreneurs are not a new phenomenon, of course; some scientific discoveries have been driven by the pursuit of wealth. The field of aging, unfortunately, has a particularly long and sordid history of hucksterism that dates back thousands of years; in the past decade alone we have witnessed an explosion of antiaging quackery. The problem is one of good science being exaggerated and misused to justify the sale of an elixir that, it is promised, will slow the aging process or make one grow younger. One prominent scientist in the field of aging has created a company that is already selling such a potion to the public.

So after reading Guarente's outstanding account of the steps toward scientific discovery, I was disappointed to read in chapter 13 that he has recently become an entrepreneur, creating with a colleague a company with the unfortunate name Elixir. A well-established scientist creates a company and becomes an entrepreneur not to obtain integrity or authority (commodities worth their weight in gold in the world of science, which Guarente has already obtained through hard work—and now risks), but to seek wealth. To move from Guarente's descriptions of keen insights, well-crafted experiments and hypothesis-driven research to his discussions of meetings with business executives, who have no other interest than to make money, was disheartening to me. Admittedly, he is concerned about the inevitable conflict of interest between the science conducted in his laboratory and the translation of that science into drug development. But it will take all of his will to resist the temptation to exaggerate and extend his research for the purpose of creating and selling a product for profit.

My reservations about the book apply just to this chapter. Guarente's account of his search for genes that influence the aging process is impressive. I was fascinated by his line of reasoning and admired the dedication of all of the investigators; I appreciated his candor about his universal aging gene not panning out. Do not let the book's technical jargon dissuade you from reading this enjoyable story of a talented research scientist's journey. More of us should take the time to chronicle such events, thereby inspiring and nurturing young scientists. Pick up Ageless Quest and read it carefully—just keep your skeptical eye open when Elixir comes out with its first antiaging product.

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