By David Shaywitz, MD
The central dogma of drug discovery is that academic basic research -> industry applied research -> new medical product. The disappointing number of impactful new medical products have been a source of endless soul searching, and could in theory be attributable to any (and all) of the steps in this model – and might also, as some have suggested, reflect the need for an entirely new conceptual framework.
The latest issue of Nature features a spot-on commentary (subscription only) by Glenn Begley and Lee Ellis (nicely summarized in this terrific Reuters article) that focuses in on the first arrow, the translation of academic oncology basic research into application by industry, and highlights the uncomfortable and inconvenient truth that by now isn’t a very well-kept secret: basic science is unbelievably fragile, and a lot of it doesn’t stand up to serious scrutiny.
This observation is absolutely consistent with my own experience and observations (see here, here, here, and here), as well as with those of Bruce Booth (this is a terrific discussion), and of course the pioneering research of Stanford Professor John Ioannidis, whose work I discussed six years ago (here), and who has been profiled extensively since (e.g. this piece from The Atlantic).
We could spend a lot of time discussing why science is fragile; Begley and Ellis, for example, emphasize the need for a cultural change in the way preclinical research is conducted, particularly in the field of cancer.
At the end of the day, I suspect that the problem involves some combination of the law of small numbers, the appeal of narrative, the structural advantages of reinforcing dogma, and the difficulties of publishing negative results that might challenge it, especially if the dogma was advanced by senior leaders in the field who tend to play critical roles in reviewing papers for high-profile journals and in selecting which new research gets funded. While the process may ultimately be self-correcting (and I certainly believe that science “works”), the cycle time for this can be a lifetime (literally – in some cases I’ve heard it said you need to wait for someone to pass away before contrary ideas can truly gain traction).
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