Target based approaches to biology: terrible science?

gravenewworld

http://www.sciencedirect.com/science...59644612003674


I couldn't agree more with that article. The FDA doesn't actually require a mechanism to be explained for a therapy, as long as you say what X does and it does what you say, then you can gain approval for use.

Whatever happened to science like we did back in the old days, where discoveries were made using a phenotypic approach? Has mechanistic science and molecular biological targeting been an utter failure?

atyy

Every target based approach ultimately depends on guesswork, because of the tremendous complexity of the human body. However, a mechanistic understanding can help direct our guesses.

For example, it's said that "an understanding of osmosis and the intestinal absorption of glucose forms the basis for a simple therapy that has saved millions of lives, particularly in less-developed countries.". A mechanistic understanding helped us understand why drinking water alone did not help rehydration, but needed salt and glucose.

Another example are the angiogenesis inhibitors that eventually made it to the clinic from basic research. "Angiostatin and a companion agent also identified by Folkman's laboratory, endostatin, were licensed by a biotech company called EntreMed. And EntreMed never made a dime off either drug. The two drugs failed to show any clinical effects in both Phase 1 and Phase 2. Avastin was a completely different anti-angiogenesis agent, discovered and developed by another team entirely, and brought to market a decade after O'Reilly's experiment. What's more, Avastin's colorectal-cancer trial—the one that received a standing ovation at ASCO—was the drug's second go-around. A previous Phase 3 trial, for breast cancer, had been a crushing failure. Even Folkman's beautifully elaborated theory about angiogenesis may not fully explain the way Avastin works."

Another example where basic research and very good luck was required is deep brain stimulation for Parkinson's. The therapy was arrived at by a theory from basic research. The final version of the therapy is believed to work for reasons other than those originally envisaged from basic research, so basic research was not enough. However, I do not believe we would have known where to poke for good luck without the basic research.