I’ve been meaning to write about this Stat profile of Jing-ke Weng at the Whitehead Institute, who’s searching for medicinally active compounds in exotic plants. That’s a field with a long and honorable history – some ferociously active compounds come from plant sources, and some terrific drugs have, too. But it’s been a while since one of those has showed up. Any guesses as to the most recent one? My own, off the top of my head, is Taxol/taxotere, which goes back nearly 50 years, and I think that arteminisin is almost exactly as old. Has there been anything since then? There have been whole companies founded on the idea of finding new natural products drugs (Shaman Pharmaceuticals, anyone?), but it’s been a very hard way to earn a living.
That’s partly because a lot of medicinally active substances have already been discovered, and you can spend a fair amount of your time discovering them again if you aren’t careful. And another big problem is that you can find some sort of plant extract that shows activity in an assay, but when you fractionate it, instead of one of the fractions turning out to have the Wonder Drug in it, none of the fractions actually have much activity at all. That one happens over and over, too, and is presumably due to polypharmacology of some sort.
One answer to this situation is to say “Forget your reductionist ways and embrace the whole plant extract”, but there are some problems with that. For one, the whole plant extract may well not be so active when dosed orally, as opposed to your cell or enzyme assay. For another, if you can’t narrow down to single active compounds, then does that mean that you have to go harvest the whole plant every time you want to treat people? The balance of active compounds in the extract can vary widely according to the season and growing conditions; polypharmacology can be a delicate balancing act. This can well mean that trying to farm the plant itself may not give you what you want, so you can face the problem of stripping it from the wild if that has to be the source. That situation is what looked like happening with taxol, and others, until a better synthetic source was found for the single active compound. But if there isn’t one, what then?
Weng’s group is looking for active compounds, because of just these problems, and I wish this effort good luck. No one can say that this idea is exhausted, and if something interesting comes out of it, odds are that it could be very interesting indeed. Modern analytical chemistry is a big help, of course, as is modern molecular biology (if you can get some more tractable organism to make the active stuff for you). It ain’t going to be easy, still. The Whitehead Institute, at any rate, is sufficiently hopeful, and I’m glad that someone is willing to put up the funds.