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Answering Questions With Questions

Posted by Pete Shanks on April 23rd, 2009


DNA

The future of genomics is now the subject of serious debate. This has enormous implications for genomic medicine and, not incidentally, for the careers of those in the field.

The New England Journal of Medicine has published a set of articles that discuss the state of the art in genomewide association studies. (Nicholas Wade had a good summary in Thursday's New York Times.) The trouble, all agree, is that common variations are only linked to a small proportion of common diseases.

Moreover, most of the variations found "do not map to amino acid changes in proteins" but instead seem to affect gene expression, and to do so in various ways, according to the Review by John Hardy and Andrew Singleton. The genetic link to a disease such as diabetes may be real, but associated with so many different parts of the genome, each having a very small effect, that, writes David Goldstein, "in pointing at everything, genetics would point at nothing."

(As an aside, this raises doubts about the future of private genomics companies, which Goldstein derides as doing "recreational genetics" whose data have "little or in many cases no clinical relevance.")

There's also the very basic issue that the whole concept of "the gene" has been in doubt for some time now. And in any case, as Hardy and Singleton point out, "Genomewide association studies identify loci and not genes per se."

By coincidence, also in last week's New York Times, Nicholas Kristof wrote about research suggesting that IQ is not strictly inherited, and can be raised by good schooling and similar interventions. Whatever IQ is, it apparently is not absolutely determined by genes -- whatever they are.

Meanwhile, according to Science Daily last week, research into epigenetics has demonstrated that adjusting the temperature of fruit-fly embryos affected their eye color, in heritable ways. Is this Lamarckian? Maybe. Stuart Newman has previously speculated that "very ancient organisms were probably more Lamarckian" (modern ones by and large are not, he stressed) and that "the resurgence of Lamarck is something to be looking for in the next couple of years."

Genomic sequencing has improved dramatically, but how to proceed is controversial. Some researchers suggest that the focus should shift away from association studies. They were strongly endorsed by Steve Jones, one of  Britain's leading geneticists, writing in the Daily Telegraph, who worries about "throwing good money after bad":

[M]any geneticists now think that the constant pressure to sample thousands and thousands more people for a myriad of unknown genes that have a tiny effect may be misplaced. Instead, we would be better off abandoning the scattergun approach, and reading off the entire three thousand million DNA letters of a much smaller number of individuals, healthy and unhealthy, to see in detail what might have gone wrong.

Jones opens his piece by admitting that he is biting the hand that feeds him, in "criticis[ing] the research programme of the Wellcome Trust," the largest private source of medical funding in the UK, and the second largest in the world. (He says he is expressing the views of "a pack of renegade biologists" but, perhaps for the obvious reason, does not name any others.)

The director of the Trust hit back strongly, defending their funding decisions, but admitted that:

Maybe it was not as simple as some people hoped ... Of course it has turned out there are hundreds of genes involved in common diseases and they have individually small effects.

Once again, it seems, good science is raising more questions than answers. Airing them can only be healthy -- but reminds us all that genomic medicine may be further away than once thought.

Previously in Biopolitical Times:





Posted in Animal Technologies, Biotech & Pharma, Genetic Selection, Pete Shanks's Blog Posts, Sequencing & Genomics


Comments

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  1. Comment by Leah Gordon, Apr 28th, 2009 9:44am

    I have to write a paper on this subject and it's going to take forebverrrrrrrrrrr please please please co'please help me!


 


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