Dare to Be 100: 30 Billion Gene Folly

03/05/2015 03:52 pm ET | Updated May 04, 2015

The Feb. 20 issue of Science features a major article entitled "The NIH plots a million person mega-study." Its projected goal is to generate a monster "precise medicine" system. Reading the fine print behind this proposal it is clear that what is intended is creation of a huge gene registry, 1 million persons, 30,000 genes per each. "Precise medicine" is code for the pretense of knowing everyone's gene portrait as an urgent clinical goal, as an intimate assay of risks and outcomes of a large slice of the population.

The projected budget is in excess of $1 billion. The godparent of this project is Francis Collins, director of the NIH. He points out that because of tech advances the cost of this project have fallen precipitously, cheaper no question but any more valuable?

I have been actively involved in this domain since the launching of the Human Genome Project in 2003. From the start I was concerned that its hype was far greater than its reality. Its full flowering generated an avalanche of genome-wide association studies, or GWAS for short. Hundreds of thousands of research papers, decades of intellectual firepower were devoted to the GWAS enterprise. There was the lure of implicit receipt of Nobel prizes and bonanzas of profit. Pursuit of the "gene for cancer" or "gene for Alzheimer's" or the "gene for compulsive gambling" infected the academic establishment. Great industries resulted in their pursuit of a perceived jackpot. Acres of university medical laboratories were consecrated to the holy grail of everything genomic offered up by the gene jockeys. Academic advancement was strictly tied to a genic orientation.

The ballyhoo has been steady and loud, but now the reality appears that GWAS has been a historic failure of physical and intellectual effort. The medical gains that have resulted from the gene fixation have been extraordinarily meager and a terrible waste of societal capacity. Lewontin's book "Not in our Genes" (1) and dozens of other proclamations have revealed the paucity of the gene manifesto.

To clear the air and to set the record straight 10 years ago an international group of us met at the NIH for three days. After our deliberations we sent our recommendations to the director of the NIH Elias Zerhouni. We suggested that the Gene Institute be closed and in its stead a new Institute of Systems Biology opened. The silence of the response was deafening.

One detail that has been discussed intrigues me. It goes by the name of M. health. It concerns the incorporation of personal self-monitoring devices which taken at their flood would yield behavioral data of great expanse. In my judgment this is where the real action should be. This area has been captured by the new term environment wide association studies, EWAS, created by my colleague CJ Patel, late of Stanford but now consecrated in a new high lab at Harvard. (2) I have written of my admiration and expectations of him before. He needs to be front and center in this new M. health enterprise.

We need more science, but we need more correct science. Perpetuation of the gene fixation is the wrong direction. EWAS, the inclusion of the interaction of the gene with its environment is critical. It is the next paradigm.

All of us, except Collins maybe, knows that it ain't the cards we're dealt that matters, but how we play the hand.


(1) Lewontin, R. Rose, S., Kamin, L. Not in our Genes, 1984; Pantheon Books, New York
Patel, CJ et al. Systematic Evaluation of Environmental and Behavioral Factors Associated with all cause mortality in the United States, NHAS.2013 Int. J. Epidem.;42:1795-1810.