A group of researchers are attempting to gain approval to run a human trial of metformin with the aim of evaluating its ability to very slightly slow down the aging process. This is not ambitious at all from a technological perspective. It will make no real difference to aging, in comparison to what is plausible and possible via other methods, and the use of established drugs in this fashion is not a road to human rejuvenation. Instead this is an attempt to force change on the FDA from within the bounds of the system of regulation, which at present does not recognize aging as a medical condition amenable to treatment. By denying commercialization, funding for research and development is stifled all the back back down the chain, and this must change if we are to see faster progress in the future.
On a blazingly hot morning this past June, a half-dozen scientists convened in a hotel conference room in suburban Maryland for the dress rehearsal of what they saw as a landmark event in the history of aging research. In a few hours, the group would meet with officials at the U.S. Food and Drug Administration (FDA), a few kilometers away, to pitch an unprecedented clinical trial - nothing less than the first test of a drug to specifically target the process of human aging.
A scientist named Nir Barzilai tuned up his PowerPoint and launched into a practice run of the main presentation. His practice run kept hitting a historical speed bump. He had barely begun to explain the rationale for the trial when he mentioned, in passing, "lots of unproven, untested treatments under the category of anti-aging." His colleagues pounced. "Nir," interrupted S. Jay Olshansky, a biodemographer of aging from the University of Illinois, Chicago. The phrase "anti-aging ... has an association that is negative." "I wouldn't dignify them by calling them 'treatments,'" added Michael Pollak, director of cancer prevention at McGill University in Montreal, Canada. "They're products." Barzilai, a 59-year-old with a boyish mop of gray hair, wore a contrite grin. "We know the FDA is concerned about this," he conceded, and deleted the offensive phrase.
Then he proceeded to lay out the details of an ambitious clinical trial. The group wanted to conduct a double-blind study of roughly 3000 elderly people; half would get a placebo and half would get an old (indeed, ancient) drug for type 2 diabetes called metformin, which has been shown to modify aging in some animal studies. Because there is still no accepted biomarker for aging, the drug's success would be judged by an unusual standard - whether it could delay the development of several diseases whose incidence increases dramatically with age: cardiovascular disease, cancer, and cognitive decline, along with mortality. When it comes to these diseases, Barzilai is fond of saying, "aging is a bigger risk factor than all of the other factors combined." But the phrase "anti-aging" kept creeping into the rehearsal, and critics kept jumping in. "Okay," Barzilai said with a laugh when it came up again. "Third time, the death penalty."
The group's paranoia about the term "anti-aging" captured both the audacity of the proposed trial and the cultural challenge of venturing into medical territory historically associated with charlatans and quacks. The metformin initiative, which Barzilai is generally credited with spearheading, is unusual by almost any standard of drug development. The people pushing for the trial are all academics, none from industry (although Barzilai is co-founder of a biotech company, CohBar Inc., that is working to develop drugs targeting age-related diseases). The trial would be sponsored by the nonprofit AFAR, not a pharmaceutical company. No one stood to make money if the drug worked, the scientists all claimed; indeed, metformin is generic, costing just a few cents a dose. Patient safety was unlikely to be an issue; millions of diabetics have taken metformin since the 1960s, and its generally mild side effects are well-known.
Finally, the metformin group insisted they didn't need a cent of federal money to proceed (although they do intend to ask for some). Nor did they need formal approval from FDA to proceed. But they very much wanted the agency's blessing. By recognizing the merit of such a trial, Barzilai believes, FDA would make aging itself a legitimate target for drug development.