Down the Rabbit Hole

John Ioannidis is what I would call a science critic. I don't mean that he's anti-science. On the contrary. He's a science critic in the same sense that a movie critic or a literary critic likes movies or books, but has something to say about which ones are better than others, and how they are composed and achieve or fail to achieve their artistic objectives.

He joins colleagues in critiquing the Big Science initiatives of NIH, which has been directing more than half of its funding to genomic and stem cell research. Contrary to early expectations, it turns out that the relationship between the genome and specific diseases is far too complex to provide targets for prevention or treatment. Even when a specific genetic cause of a disease is known, as in sickle cell anemia, the knowledge doesn't necessarily translate into a therapeutic target.

Similarly (and relevant to the cancer "moon shot,") the extremely diverse mutations associated with cancer, and the adaptive nature of tumors (they evolve in response to selection pressure from treatments), mean that understanding the specific mutations associated with cancers is of limited value for treatment. Stem cells have also so far failed to yield any approved treatments.

The writers call for a redirection of NIH funding away from these "big ideas," and to more strictly evaluate proposals in these areas. The challenge is that right now, these fields are academically prestigious, and yield high impact publications, promotions and tenure, and awards. Furthermore, scientists get pigeonholed in their narrow programs of research, and proposal review committees generally don't like it when they try to step out in a new direction. So there are vested interests which are difficult to overcome.

I actually think that there is more to be gained by what they call translational science -- getting doctors to do what we already know is best for patients -- and investment in social determinants of health, than by the "blue sky" biomedical research Ioannidis and friends call for. Sure, we should do some of that, but we can save lives and improve the health of billions of people just by putting what we already know to work. But that isn't very glamorous.