Canon Fodder—A Case for Contrarian Science
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Cannon fodder are expendable soldiers deployed as “food” for enemy cannon fire when there is no hope of ultimately prevailing: generals dispose of “worthless” soldiers by sacrificing them to the cannon. Here, I adopt the term Canon fodder to describe contrarian scientific concepts dismissed because they do not conform to conventional wisdom: reviewers dispose of “unworthy” science by sacrificing it to the canon.
It is a rare opportunity to be invited to opine to one’s peers on a topic of choice. Actually, my peers are my chosen topic. Specifically, peer review. Twenty-five years ago, I eschewed job security as an interventional cardiologist in favor of academic research. Consequently, I needed NIH R01 funding. After my initial attempts failed spectacularly, one of my mentors (it was Jeff Robbins or Rick Walsh, or perhaps both) provided surprising guidance: I should compose my grant application with 4 specific aims, then discard the most exciting aim and submit what remained. This would avoid provocation in favor of the conventional and acceptable. It was sage advice from highly successful senior investigators (I learned this the hard way, by initially disregarding it and suffering the consequences).
I envisioned testing the neurohormonal hypothesis of heart failure1 by expressing in cardiac myocytes a signaling molecule common to neurohormonal pathways postulated to mediate pathological hypertrophy. I would use the then-new mouse α-myosin heavy chain (α-MHC) promoter2 to drive cardiac-specific expression of the α subunit of heterotrimeric G-protein, Gq, the common proximal transducer for angtiotensin II (type 1), endothelin, and norepinephrine (α-adrenergic) signaling.3 I reasoned that cardiomyocyte-specific activation of Gq signaling would circumvent hemodynamic effects (eg, hypertension) of Gq-coupled neurohormones. If the planned Gαq transgenic mice developed hypertrophy and heart failure, then cardiomyocytes were autonomously responding to neurohormonal signaling, thus proving the neurohormonal hypothesis. My first postdoctoral …