Resveratrol: gushing about fountains of youth
60 Minutes had a segment last Sunday about the wonders of Resveratrol, a molecule found in red wine that may be responsible for its beneficial effects. Resveratrol is a putative activator of SIRT1, one of the Class III histone deacetylases, or Sirtuins. It is a fascinating and exciting story, and there’s no doubt that the sirtuins (and HDACs in general) are an important new area of biology and target class.
Here’s the clip:
However, it is pretty frustrating that 60 Minutes makes almost no effort to look at this story from a critical, scientific perspective. There was no atempt to critically evaluate or question any of the scientific claims being made, or to try to get the other sides of the story. Moreover, the promises being sold – by both Safer and the Sirtris scientists – are unrealistic, and their generic caveats about the difficulty of drug development are inadequate to pop the overinflated expectations being set up.
On the science: there are lively discussions in the literature about every piece of the puzzle. Is Resveratrol really a selective activator of SIRT1, or was its discovery an artifact of the particular fluorescent assay used for the screen which discovered it, as Kaeberlein argued in JBC in 2005?
Not at all clear. Could it be hitting something else entirely, in addition to effects (if any) on SIRT1? Chances are it does. Are there other components responsible for the effects of red wine that are being missed? What mediates the effects of SIRT1 activation on metabolism and survival?
There is a tacit assumption that since GSK was willing to drop $750M for Sirtris, what they’re working on must be good. But in case you haven’t noticed, companies make bad investments all the time (Lundbeck paying $100M for Flurizan a month before it failed comes to mind). Moreover, even if there is a significant probability of failure, a risky investment still makes sense as part of a portfolio within a company the size of GSK. And regardless of the utility of Resveratrol, Sirtris has assembled a lot of IP around the sirtuins, which are bound to be useful for something.
Finally, there is the problem of making unrealistic promises. Drs. Sinclair and Westphal start off cautiously, but by the end of the interview they’re promising long healthy lives for everyone and drugs in 5 years, “to be conservative”. Elixirs of youth and tales about 90-year-olds sell, and as the WSJ recently reported, Dr. Sinclair helped a company called Shaklee to sell “Vivix™ Cellular Anti-Aging Tonic”, a Resveratrol supplement. (Sinclair resigned from Shaklee’s scientific advisory board after the WSJ raised the question).
Sirtris is a great success so far, and Resveratrol is a seductive story. That’s all the more reason to be skeptical, and at least try to ask some probing questions. Though I’m sure it’s a great week to be in the Resveratrol supplement business.
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