Project A wants to investigate in as much depth as possible (given their budget) the effects of nail-biting on arthritis.
Project B wants to investigate in as much depth as possible (given their budget) the effects of learning a programming language on Alzheimer's disease.
I know which of these seems like a better choice for funding, even though I don't really know for certain what the long-term impact of either will be.
In support of project A: fibromyalgia, which has arthritic-type symptoms, is partly linked to anxiety, of which one of the common manifestation is nail-biting. Could evidence of nail-biting be a useful tool as part of differential diagnosis, or a predictor?
In support of project B: the idea of a 'cognitive reserve' in preventing the onset of Alzheimer's disease is fairly well established, even though it has no disease-modifying therapy once the symptoms of decline are already apparent. To what extent can learning a programming language aid that cognitive reserve?
I see your point though, but I'm not sure how well it applies to funding large-scale data collection work like the HGP. Or the LHC, to use an example in another field.
(But I should note that I deliberately chose projects where it seemed obvious which one was better, so that I didn't need to do any calculations or even think very hard about which one to prefer. In reality, sometimes it's not obvious, and you should think hard and do calculations and it still might not be obvious, and the specific project being discussed is probably one of those cases.)
If we want the big advances, we have to push the boundaries of what's known, but it's unclear where, exactly, the big breaks will happen. But doing these kind of mega-projects is, I think, basically a good thing, as it gets us out of the day-to-day of publishing easy papers, and into attacking the 'big' problems in new ways.
To say it another way, I think that playing the lotto with the goal of earning money is a mistake. The fact that some people win it and in fact make money doesn't change the fact that they were wrong to play it in the first place if their goal was net gain of money.
That said I have no idea what the expected value of the HGP was so I have no idea whether it was a good decision. I just want to chime in in support of thinking about the probabilities involved in the right way.