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It may be a sign of incipient old age, but I find myself increasingly convinced that the key question in biology these days is philosophical, not scientific. It is the question of what balance should exist, given that the financial pie is not only finite but likely to be shrinking for some time, between large-scale, top-down, 'big science' projects that are primarily aimed at information gathering, and hypothesis-driven, individual-investigator initiated 'little science' projects. The seesaw has tilted pretty heavily in favor of the big stuff lately. I have nothing against such programs in principle, but it seems to me that in practice there are too many of dubious merit and low benefit-to-cost ratio. They are never pitted against small science projects when they are reviewed, and because they are attractive to administrators - they produce lots of data that can be shown proudly to superiors, politicians and citizens - they become very difficult to kill, even if the data are not very useful or the original mission has been fulfilled, because too many influential reputations and comfortable livelihoods are vested in their continuation. As I see it, there is a danger that these 'zombie programs' will take over biology, and investigator-initiated research, which is where most breakthroughs come from, is already getting short shrift as a consequence. It's time we stop letting that happen by default, and ask how priorities in biomedical research should be set, and by whom.

Open questions: Zombie projects, translational research, and the real secret of the inside of the cell