Bursting the genomics bubble

Here’s the pre-edited version of a Muse that’s just gone up on Nature News. There’s a bunch of interesting Human Genome Project-related stuff on the Nature site to mark the 10^th anniversary of the first draft of the genome (see here and here and here, as well as comments from Francis Collins and Craig Venter). Some is celebratory, some more thoughtful. Collins considers his predictions to have been vindicated – with the exception that ‘The consequences for clinical medicine have thus far been modest’. Now, did you get the sense at the time that it was precisely the potential for advancing clinical medicine that was the HGP’s main selling point? Venter is more realistic, saying ‘Phenotypes — the next hurdle — present a much greater challenge than genotypes because of the complexity of human biological and clinical information. The experiments that will change medicine, revealing the relationship between human genetic variation and biological outcomes such as physiology and disease, will require the complete genomes of tens of thousands of humans together with comprehensive digitized phenotype data.’ Hmm… not quite what the message was at the time, although in fairness Craig was not really one of those responsible for it.

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The Human Genome Project attracted investment beyond what a rational analysis would have predicted. There are pros and cons to that.

If you were a venture capitalist who had invested in the sequencing of the human genome, what would you now have to show for it? For scientists, the database of the Human Genome Project (HGP) may eventually serve as the foundation of tomorrow’s medicine, in which drugs will be tailored personally to your own genomic constitution. But for a return to the bucks you invested in this grand scheme, you want medical innovations here and now, not decades down the line. Ten years after the project’s formal completion, there’s not much sign of them.

A team of researchers in Switzerland now argue in a new preprint [1] that the HGP was an example of 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, Didier Sornette and Ryan Woodard of ETH in Zürich say 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 benefits of the HGP were over-hyped [2]. Even advocates now admit that the benefits for medicine may be a long time coming, and will require further advances in understanding, not just the patience to sort through all the data.

This stands in contrast to some of the claims made while the HGP was underway between 1990 and 2003. In 1999 the International Human Genome Sequencing Consortium (IHGSC) leader 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’re still missing fundamental understanding of how even diseases with a known heritable risk are related to the makeup of our genomes [4]. Collins’ portrait of a patient who, in 2010, is prescribed ‘a prophylactic drug regimen based on the knowledge of [his] personal genetic data’ is not yet 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 [5]. Collins’ claim,shortly after the unveiling of the first draft of the human genome in June 2000, that ‘new gene-based ‘designer drugs’ will be introduced to the market for diabetes mellitus, hypertension, mental illness and many other conditions’ [6] no longer seems a foregone conclusion, let alone a straightforward extension of the knowledge of all 25,000 or so genes in the human genome.

This does not, in the analysis of Gisler and colleagues, mean that the HGP was money poorly spent. Some of the benefits are already tangible, such as much faster and cheaper sequencing techniques; others may follow eventually. The researchers are more interested in the issue of how, if the HGP was such a long-term investment, it came to be funded at all. Their answer invokes the notion of bubbles borrowed from the economic literature, which Sornette has previously suggested [7] as a driver of 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 to be 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’ [8]. In economics such bubbles can end in disastrous speculation and financial ruin, but in technology they can be useful, creating long-lasting innovations and infrastructures that would have been deemed too risky a venture under the cold glare of reason’s spotlight.

For this reason, Gisler and colleagues say, it is well worth understanding how such bubbles occur, for this might show governments how to catalyse long-term thinking that is typically (and increasingly) absent from their own investment strategies and those of the private sector. In the case of the HGP, the researchers argue, the controversial competition between the public IHGSC project and the private enterprise conducted by the biotech firm Celera Genomics worked to the advantage of both, creating an sense of anticipation and hope that expanded the ‘social bubble’ as well as in the end reducing the cost of the research 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 really deliver economically or medically on such massive investment. Worse, the hype might have incubated a harmful rash of genetic determinism. As Gisler and colleagues point out, other ‘omics’ programmes are underway, including an expensively funded NIH initiative to develop high-throughput techniques for solving 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

1. Gisler, M., Sornette, D. & Woodard, R. Preprint http://www.arxiv.org/abs/1003.2882.

2. Roberts, L. et al., Science 291, 1195-1200 (2001).

3. Collins, F. S. New England J. Med. 28, 28-37 (1999).

4. Dermitzakis, E. T. & Clark, A. G. Science 326, 239-240 (2009).

5. Pearson, H. Nature 460, 164-169 (2009).

6. Collins, F. S. & McKusick, V. A. J. Am. Med. Soc. 285, 540-544 (2001).

7. Sornette, D. Socio-econ. Rev. 6, 27-38 (2008).

8. Keynes, J. M., The General Theory of Employment, Interest and Money (Macmillan, London, 1936).