Nature News: Bursting the Genomic Bubble

Published online 31 March 2010 | Nature | doi:10.1038/news.2010.145

Bursting the genomics bubble
The Human Genome Project attracted investment beyond what a rational analysis would have predicted. There are pros and cons to that, says Philip Ball.

Philip Ball

If a venture capitalist had invested in sequencing the human genome, what would she have to show for it?

For scientists, the Human Genome Project (HGP) might lay the foundation of tomorrow’s medicine, with drugs tailored to your genetics. But a venture capitalist would want medical innovations here and now, not decades hence. Nearly ten years after the project’s formal completion, there’s not much sign of them.

A team of researchers in Switzerland now argue that the HGP was a ‘social bubble’, analogous to the notorious economic bubbles in which investment far outstrips any rational cost-benefit analysis of the likely returns. Monika Gisler and her colleagues at ETH in Zürich say in a preprint1 on arXiv that “enthusiastic supporters of the HGP weaved a network of reinforcing feedbacks that led to a widespread endorsement and extraordinary commitment by those involved in the project”.

Some scientists have already suggested that the HGP’s benefits were hyped2. Even advocates admit that medical benefits may be a long time coming, and will require advances in understanding, not just the patience to sort through all the data.

Hope and hype

This contrasts with some of the claims made while the HGP was underway between 1990 and 2003. In 1999 the leader of the International Human Genome Sequencing Consortium (IHGSC) Francis Collins claimed that the understanding gained by the sequencing effort would “eventually allow clinicians to subclassify diseases and adapt therapies to the individual patient”3.

That might happen one day, but we still don’t understand how many diseases with a known heritable risk are related to our genomes4.

Collins’ portrait of a patient who, in 2010, is prescribed “a prophylactic drug regimen based on the knowledge of [his or her] personal genetic data” is not on the horizon. And going from knowledge of the gene to a viable therapy has proved immensely challenging even for a single-gene disease as thoroughly characterized as cystic fibrosis (see ‘One gene, twenty years’).

Collins’ claim, on the eve of the first draft of the human genome in 2000, that “gene-based designer drugs will be introduced to the market for diabetes mellitus, hypertension, mental illness and many other conditions”5 no longer seems a foregone conclusion, let alone a straightforward extension of a knowledge of all 25,000 or so genes in the human genome.

Speculate to accumulate?

But this does not, say Gisler and her colleagues, mean that the HGP was a waste of money. Some of the project’s benefits are already tangible, such as faster and cheaper sequencing; others may follow eventually. The researchers are more interested in how, if the HGP was such a long-term investment, it came to be funded at all.

Their answer invokes the economics of bubbles. Gisler’s colleague Didier Sornette has previously suggested6 that these bubbles can drive other technical innovations, such as the mid-nineteenth-century railway boom and the explosive growth of information technology at the end of the twentieth century.

In economics, bubbles seem an expression of what John Maynard Keynes called animal spirits, whereby the instability stems from “the characteristic of human nature that a large proportion of our positive activities depend on spontaneous optimism rather than mathematical expectations”7. Such bubbles can end in disastrous speculation and financial ruin, but in technology they can be useful, creating long-lasting innovations and infrastructures that the cold glare of reason would have been deemed too risky.

For this reason, Gisler and colleagues say, it is worth understanding what causes such bubbles, for this might show governments how to catalyse long-term thinking that is increasingly absent from their own investment strategies and those of the private sector.

Permanent revolution

In the case of the HGP, the researchers argue, the competition between the public IHGSC project and the private effort by the biotech firm Celera Genomics worked to the advantage of both, creating anticipation and hope that expanded the social bubble and making the research cheaper by engaging market mechanisms.

To that extent, the ‘exuberant innovation’ that social bubbles can engender seems a good thing. But it’s possible that the HGP will never deliver economically or medically on such massive investment. Worse, the hype might have incubated a rash of genetic determinism.

As Gisler and colleagues point out, other ‘omics’ programmes are underway, including an expensive NIH initiative to develop and use high-throughput techniques to solve protein structures. Before animal spirits transform this into the next ‘revolution in medicine’, it might be wise to ask whether the HGP has something to tell us about the wisdom of collecting huge quantities of stamps before we know anything about them.

References
Gisler, M., Sornette, D. & Woodard, R. Preprint http://www.arxiv.org/abs/1003.2882.
Roberts, L. et al. Science 291, 1195-1200 (2001).
Collins, F. S. New Engl. J. Med. 28, 28-37 (1999).
Dermitzakis, E. T. & Clark, A. G. Science 326, 239-240 (2009).
Collins, F. S. & McKusick, V. A. J. Am. Med. Soc. 285, 540-544 (2001).
Sornette, D. Socio-econ. Rev. 6, 27-38 (2008).
Keynes, J. M. The General Theory of Employment, Interest and Money (Macmillan, London, 1936).

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