Andy Dillin is a young man. He is thirty-six years old, and he is just getting started.
He works as a molecular biologist and geneticist at the Salk Institute in La Jolla, California. Over the past year, he has published three papers that have received a lot of attention and that seem to bring closer to reality the possibility that humans will one day be able to, in his words, "change the aging program."
Changing the aging program means three different things. The thing that's gotten the most attention is the possibility of increasing life span. The thing by which Dillin justifies his work in the here and now is the possibility that his work may lead to treatments for such age-related diseases as Alzheimer's, cancer, and diabetes. And the thing that gets Dillin most excited -- and most philosophical -- is the possibility that by addressing age-related diseases, he is addressing something else entirely: youthfulness.
For many decades, science had difficulty talking about aging for the same reason that even now it has trouble talking about youthfulness. Science has trouble talking about things it can't measure in a lab. And because the aging process in humans (or even mice) takes so long, science's understanding of aging was based on observation rather than experiment. As a result, what Dillin calls the "prevailing dogma" grew up around aging: Creatures grow old because they wear out over time. Cells grow old because they wear out over time. Aging was simply an accumulation of abuse. It was not something the body did; rather, it was something the body had done to it.
There were even chicken-and-egg questions about the relationship between aging and the diseases associated with it. Given that anyone who gets old enough will develop cancer or diabetes or heart disease or Alzheimer's, maybe aging did not exist in and of itself but was instead the by-product of disease.
What changed the understanding of aging was a worm. Granted, it was a very special worm -- a worm bred as a model for studies of cell development by Sydney Brenner, who won the Nobel Prize in 2002. Still, it was a worm, a roundworm, or nematode, called C. elegans. It was small, it was fecund, it stood up well to laboratory manipulation, and, best of all, it got its living and dying over with in about three weeks.
Then, in the early '90s, a scientist at the University of California at San Francisco, Cynthia Kenyon, demonstrated the influence of genes on aging by mutating one C. elegans gene and doubling the worm's life span. One gene, twice the life. A few years later, Andy Dillin worked in Kenyon's lab and was struck then -- as he is now -- by the fact that what seemed the most profound manipulation of an animal's life span was really just a matter of simple genetics.
When Dillin came to Salk five years ago, he was determined to find out how the longevity pathway that Kenyon discovered actually worked. "It was an insulin-signaling pathway," he says, "and so it affected a lot of things other than longevity, like growth and diabetes. I wanted to find out how it specifically affected longevity, and if it could affect longevity without affecting the other things. I figured it would take my entire career as a scientist." Instead, he found it -- a specific protein in the insulin-receptor pathway, henceforth called the "longevity protein" -- three years later, at the age of thirty-four.
At around the same time, he identified a gene that accounts for the increase in longevity of animals on diet restriction. This sounds esoteric, but it's not. In fact, scientists have known for a long time that animals whose caloric intake is 30 or 40 percent less than normal live much longer than animals that eat as much as they want. The problem is that very few animals would volunteer to push themselves toward starvation in order to extend their lives, notwithstanding the sect of two thousand or so humans currently doing just that. What Dillin's lab did, however, was identify the gene responsible for the increases in longevity associated with diet restriction. It was called PHA-4,but in the press it became the "longevity gene," because when knocked out, it made diet restriction useless, and when amped up, it made diet restriction unnecessary. In particular, it allowed the American media to voice the hope that one day a treatment would be developed that would enable us to enjoy the benefits of diet restriction while in fact eating as much as we damn well please.
It doesn't end there. At around the same time, Dillin also discovered that when he extended the lives of his worms, he made them immune to Alzheimer's.
Dillin revealed these results in three papers published in the space of one year, beginning in 2006. It was a startling achievement -- a collaborator at Salk calls him the most successful young scientist in the world -- but even as news of his accomplishments moved from the scientific press to the mainstream media, his philosophically inclined mother sent him a quote from her favorite author, Friedrich Nietzsche: "You have made your way from the worm to man. And much within you is still worm." In fact, everything her son had discovered he had discovered in a creature that is nearly invisible to the eye and that, by his own accounting, lives "to eat, shit, and reproduce, and that's about it." There would be an incalculable jump in complexity from worm to man. At the same time, most of the genes found in C. elegans are also found in humans; the longevity protein and the longevity gene are structurally no different in worms and in people. And over the past year, Dillin's lab has undertaken and succeeded in the difficult business of replicating its experimental results in mice.
So here is where the question of youthfulness comes up. Youthfulness is what Dillin suspects is making the animals resistant to Alzheimer's. It is not that the effects of the disease are being blocked by a specific agent; it's that cellular functioning has been kicked into a higher gear for the entire organism.
One of the papers Dillin has yet to publish has to do with a compound -- a drug -- found by his lab that also makes the worms resistant to Alzheimer's. His lab did not set out to find a drug; it intended to find a research tool that would allow him to investigate the insulin-signaling and PHA-4 pathways without having to mutate any genes, which can't return to normal. He had one of the research associates working in his lab test a series of compounds found in nature, and was surprised to find one that prevents the Alzheimer's symptoms more effectively than the mutated genes did. The compound also seemed to extend the life spans of the worms, although Dillin doesn't yet know exactly how it works. Once he informed the Salk Institute what his lab had found, Salk improved upon the compound and changed its chemical structure so that it is, in effect, a novel compound. It is not found in nature anymore. It is a proprietary property.
"I always thought that it was going to take a combination of drugs to increase life span," Dillin says. "But the new drug is just a single compound, and it works sooooo good." And yeah, he says it just like that -- sooooo good. Generally, he's very open, generous, and forthcoming when he's talking about his work. When he talks about the drug, however, he gets a little cagey, a little coy, almost a little smug. It's as though he were holding a trump card and has forgotten to be poker-faced. Or maybe he simply can't bring himself to believe the reality of his good fortune. Because there is an element of fortune -- luck -- in all of science, and fortune has favored Dillin's lab to the extent that people ask him what he must ask himself: Can it be this easy?