The Human Genome Project: What Happens When You Do Budget-Limited Science (or You Get What You Pay For)

Yes, you read the title correctly--I'll get to that in a bit. Nicholas Wade's article about the Human Genome Project (HGP), "A Decade Later, Genetic Map Yields Few New Cures" has been getting a lot of play. Thankfully, ScienceBlogling Orac summed up perfectly my thoughts about both the science and hype surrounding the HGP, so I don't have to. But this post by Mike Mandel has been getting some play:

My nomination for the most significant economic event of the past decade: The failure of the Human Genome Project to thus far deliver medically significant results.

I dunno: the collapse of Big Shitpile, leading to the highest unemployment in decades seems kinda important too. Open Helix has a good, pithy response:

I'm sorry: if you based your expectations on what you were told by biotech executives and academics with a foot in those companies, you need better filters. But it does explain how everyone fell for credit default swaps too, I suppose.

What a lot of people seemed to have missed in Wade's article is this part (italics mine):

The Human Genome Project was started in 1989 with the goal of sequencing, or identifying, all three billion chemical units in the human genetic instruction set, finding the genetic roots of disease and then developing treatments. With the sequence in hand, the next step was to identify the genetic variants that increase the risk for common diseases like cancer and diabetes.

It was far too expensive at that time to think of sequencing patients' whole genomes. So the National Institutes of Health embraced the idea for a clever shortcut, that of looking just at sites on the genome where many people have a variant DNA unit. But that shortcut appears to have been less than successful.

Far too expensive. When budgets are limited, you're forced to generate the data that is easier to get--and cheaper. So when Mandel describes the HGP as an economic flop so far--and he would be inclined to do so since he is interested "the innovation shortfall"--he fails to understand that we didn't invest in the HGP adequately. Seriously, compare the $3 billion for the HGP to the billions in tax breaks companies get every year for R&D. Or inflation-adjust the Manhattan Project. Let's not even talk about the Marine Corps' Osprey program. By comparison, the HGP was done on the cheap.

Even so, it did a great deal of good that Mandel doesn't acknowledge. Mandel:

What about jobs? Successful new innovations create new jobs-that's what history tells us. If the Human Genome Project had led to a wave of new diagnostic test and treatments, the jobs would have followed.

What the HGP did that is essential--and largely unmentioned--is that it drove sequencing technology; there is a whole new sector that didn't exist ten years ago. Anytime your ability to generate data blows Moore's Law out of the water, you're doing something right. The most important thing the HGP did is teach us how to sequence better, faster, and cheaper (and I mean sequence in a broad sense--informatics matter too). We wouldn't be in the position to look for rare genetic variants were it not for the HGP in the first place.

We have finally entered the era of population genomic, for critters big and small (which is why I find the claims of a "post-genomic era" to be silly). By analogy, the HGP put a guy on the moon, and brought him home without killing anybody. Now we're ready to do some good geology (which took NASA five more space flight to get a geologist up there, Jack Schmitt). In this sense, the HGP has been tremendously successful.

The claims of underaccomplishment seem endemic to large scale (however one wants to define that term) science projects. I've heard similar complaints about the Human Microbiome Project (HMP): Why aren't you sequencing deeper? Why not more people? At more time points? Answer: budgets. And I'm certain if we had larger budgets--more money--the HMP would turn out even better. But it too, like the HGP, needs to be viewed to a considerable extent as an exercise in how to do this work, how to solve many of the technological and computational problems, so that the next round of science will be able to capitalize on this and address biomedical problems (and, in my opinion, it has already started to be successful in that).

If you want it all in one go, then you need to spend it all in one go. Until then, you get what you paid for.