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Is modern genetics a blind alley? Yes

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1156 (Published 30 March 2010) Cite this as: BMJ 2010;340:c1156
  1. James Le Fanu, general practitioner
  1. 1Mawbey Brough Health Centre, London SW8 2UD
  1. james.lefanu{at}btinternet.com

    Genetic research has yet to make the promised impact on medical practice. James Le Fanu thinks that it never will, but D J Weatherall (doi:10.1136/bmj.c1088) believes it already has and will continue to do so

    In the 17th century William Harvey’s medical contemporaries dismissed his discovery of the circulation of the blood as being of no diagnostic or therapeutic importance. Indeed, it was not till the advent of cardiac surgery nearly 300 years later that the knowledge that “blood is driven into a round by a circular motion” would find practical application.

    Given this, and other similar historical precedents, it seems unwise to argue that modern genetics is a blind alley—not least because it might more readily be described as a four lane highway.

    Since the discovery of the revolutionary techniques of gene sequencing in the late 1970s, modern genetics—together with neuroscience—has come to dominate the biomedical research agenda. Funding has doubled and doubled again in the recent past, reaching around $100bn (£65bn; €74bn) worldwide.1 This endeavour is immensely productive, generating billions of bytes of biological data each week and a tidal wave of original studies and scientific journals that occupy an ever greater acreage of library space every year.2 Modern genetics has become the largest single research field in the history of biology, driven forward by the expectation that “like a mechanical army [it will] destroy ignorance . . . promising unprecedented opportunities for science and medicine.”3

    Practical benefits

    And yet for all this cornucopia of new facts and knowledge, its influence on everyday medical practice remains scarcely detectable. This is not to deny that there have been substantial achievements and fascinating insights, but even they fall far short of original expectations. Nearly 10 years have elapsed since the completion of the first draft of the human genome project with its ability to pinpoint the mutations responsible for more than 1000 monogenic disorders. But the realistic prospect of their prevention through antenatal screening remains limited to the thalassaemias and Tay Sachs disease.

    Meanwhile the possibilities of their treatment, whether with gene replacement or targeted therapies, remain as elusive as ever.4 Again, the ingenious techniques of biotechnology may have given us human insulin, antiretroviral drugs, herceptin, infliximab, and similar valuable compounds but they remain overwhelmingly the exception in what the chief executive of Genentech has described as “the largest money losing industry in the history of mankind.”5

    The standard response to such observations is to concede that it has all turned out to be much more complicated than previously supposed, which is certainly true. None the less, the presumption holds that the remarkable capacity of modern genetics to generate yet more biological data must eventually, like a bulldozer, drive a causeway to the realisation of those “unprecedented opportunities.”

    Small component of disease

    Perhaps, but the suspicion grows, within the genetic establishment itself, there might be something deeply flawed about the whole enterprise. “The mountain has laboured and brought forth a mouse,” observed Steve Jones, professor of genetics at University College London last year.6 Could it be those powerful knowledge generating methodologies might explain in part the current paucity of original ideas in medicine by diverting attention (and resources) from the more fruitful forms of clinical research that flourished 30 or 40 years ago when the rate of important medical innovations was so much greater than it is now?7 8

    It is thus conceivable that modern genetics might be a blind alley. There are two further reasons for supposing so. The first, obvious in retrospect, is that natural selection has ensured that genetics is not a particularly important or modifiable factor in human disease. There are only a handful of common genetic diseases, and even they are not very common. And although there is undoubtedly a genetic component to many adult illnesses, this can only be one of several factors, most of which remain as yet unknown. Meanwhile the practicalities of doing something about it—other than for a small minority—remain insuperable.

    The further and more substantial constraint on the possibilities of modern genetics is that the power of its techniques in delineating the architecture of the genome has forcibly drawn to our attention our ignorance about the most elementary aspects of gene function. The astonishing revelation, for example, that we share the same modest number of 20 000 genes as the millimetre long worm Caenorhabditis elegans suggests we know next to nothing about the mechanisms of genetic inheritance.9 It must thus be highly improbable that the future of medicine might lie in understanding disease at the most fundamental reductionist level of the gene and the proteins for which they code. Those who might doubt this verdict need look no further than the recent findings of the massive sophisticated Genome Wide Association Studies (GWAS), whose investigations show that genetics accounts for less than 5% of the heritability of obesity, diabetes, Crohn’s disease, and other common conditions.10 11

    This takes us to the end of the alley (or highway). There is no way out, and the sooner we recognise it the better because the current dominance of medical genetics threatens to bury the true spirit of intellectual inquiry under an avalanche of undigested (and indigestible) facts.

    Notes

    Cite this as: BMJ 2010;340:c1156

    Footnotes

    • Competing interest: None declared.

    References

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