The future of genomics is now the subject of serious debate. In fact, the New York Times has reported that the gene itself is having an identity crisis. This has enormous implications for genetic medicine and the entire biotechnology enterprise.
The New England Journal of Medicine recently published a set of articles that discuss the state of the art in genome-wide association studies (summarized here). The trouble, all agree, is that common genetic 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 article 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."
All this means that although genomic sequencing has improved dramatically, how to proceed is controversial. Some researchers suggest that the focus should shift away from association studies. They are 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.
Good science is, as it often does, 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, and that genetic explanations are far more complex than many once thought.
