Wednesday, January 20, 2010

Lessons from Nature

Pharmaceutical altruism?
There are a couple of interesting stories up on the Nature website today, one rather surprising, and the other not at all a surprise.  The first, "GlaxoSmithKline goes public with malaria data", (described here, if you can't link to the Nature story) tells of the pharmaceutical company's decision to release much of its data related to anti-malaria drug development into the public domain.
GlaxoSmithKline is to deposit more than 13,500 structures of possible drugs against malaria into the public domain, along with associated pharmacological data. The move marks the first large-scale public release of such structures by a pharmaceutical company, and it could lead to others following suit.
What's also important, says Bernard Pécoul, head of the Geneva-based Drugs For Neglected Diseases initiative, is that GSK intend not only to release the structures but also relevant data they hold on the 'druggable properties' of the compounds such as its solubility, absorption, metabolism or toxicological profile, which will help with weeding out compounds which would be dead-ends in terms of drug development. "This is extremely precious information," says Pécoul.
Two things strike us here -- one, GSK is a profit-making company, so why is it releasing this heretofore proprietary information?  Because it won't cost them much, and they are hoping it's good for their public image, as The Guardian points out here. Malaria infects hundreds of millions of people every year, a million of whom die, children in particular, but most of these people are poor, living in countries that can't afford to invest in health, which means that malaria isn't a potential profit-making disease.  Thus, in spite of its endemicity in many parts of the world, its designation as a 'neglected tropical disease.'  A vaccine, elusive as its proven to be against this disease, might be profitable, but anti-malarial drugs, no.

That said, data sharing and the beginning of the coordination of research into malaria control is potentially a big step.  In the long run, money spent on controlling infectious diseases has much more potential to prevent debilitation and death for more people than the vast amounts of money being spent on genetic research.

Reductionism and complexity -- again
The second story of interest at Nature today, "Health benefits of red-wine chemical unclear", is a cautionary tale about reductionist science.  For years, contrary to the usual puritan approach to enjoyable substances, we've been hearing that drinking red-wine can extend our lives.  That's red-wine, not white, and it has to be wine, not grape juice.  Some years ago, researchers believed they had isolated the substance that had these beneficial effects. It's a compound, found in grape skins, called resveratrol, which is produced by some plants when they are under attack (so why unfermented grape juice is not equivalent is confusing).   
Resveratrol's health benefits are thought to result from its activation of enzymes called sirtuins, which were linked to longevity 10 years ago when Leonard Guarente from the Massachusetts Institute of Technology in Cambridge found that yeast with additional copies of the gene that encodes sirtuin, called sir2, lived significantly longer than did those that had the usual two copies. Four years later, Guarente's former post-doc David Sinclair published work showing that resveratrol activated sirtuins in yeast and extended the organism's lifespan. Sinclair later went on to show that resveratrol fed to worms and flies lengthened lifespan by acting through the sirtuins.
Naturally enough, companies were quickly established to manufacture and sell this stuff, but recent findings suggest that other components are much more effective than resveratrol at activating the longevity molecules it has been found to activate in yeast, and that perhaps resveratrol doesn't activate these molecules in vivo at all, and anyway, it only works in association with another compound.  Maybe.

The lesson here, other than the possible dangers of premature commitment to an idea, is that what happens at the cellular level isn't necessarily replicable at the organismal level.  The fact that a compound isolated from red-wine (where it's found at rather low levels, in fact) might extend the life of a yeast cell doesn't necessarily mean that it will have anything like that effect on a whole animal. This is a well-known problem, as are the problems of complexity and reductionism which rear their ugly heads here once again. None of this is a surprise.  Unless you've already built a company to make and sell resveratrol.

1 comment:

Ken Weiss said...

Hell's bells, and I just bought 6 cases of a pretty good claret! Well, it must be good for _something_ that some researcher will discover, so an ounce of prevention being better than a pound of cure, I think I'll go have a bit of prevention....