Wag the dogma

In a recent News & Views article in Nature Genetics¹, David Goldstein offered that “The natural world is not famous for making life easy for human geneticists.” A fair statement, although most would probably agree that at least the hard-won intellectual foundations of the field are secure. What a surprise, then, to pick up February's issue of Harper's Magazine, and to read that the entire enterprise has been revealed to be a sham.

In a long essay entitled “Unraveling The DNA Myth”, Barry Commoner declares that the fruits of the Human Genome Project, along with other findings of modern genetics, have undermined everything geneticists thought to be true about their subject. Francis Crick's central dogma is dead, and the creaky, DNA-based edifice of genetics and biotechnology is baseless. The central dogma, according to Commoner, assumes that “an organism's genome...should fully account for its characteristic assemblage of inherited traits.” He continues, arguing that “The premise, unhappily, is false. Tested between 1990 and 2001 in one of the largest and most highly publicized scientific undertakings of our time, the Human Genome Project, the theory collapsed under the weight of fact. There are far too few human genes to account for the complexity of our inherited traits.” What's more, “the downfall of the central dogma...also destroyed the scientific foundation of genetic engineering.”

That would certainly be newsworthy, and yet, as Commoner points out, “Scientists and journalists somehow failed to notice.” One explanation, which he favors, is a wag-the-dog–like scenario, in which, in order to deflect attention from the fact that billions of dollars are being poured into a field that is on shaky ground, scientists stifle dissent and pretend that evidence of biological complexity has not put the lie to the central dogma.

An alternative explanation for the indifference that has greeted the downfall of the central dogma is that, in the strictest sense, it isn't true. Crick's original proposal² had nothing to do with the relationship between an organism's genome and its inherited traits; it simply stated that information flow in the cell goes from nucleic acids to proteins. The obvious exception to this statement is the prion hypothesis, whose father, Stanley Prusiner, was awarded a Nobel Prize, a rather odd way for the scientific community to express its disapproval of heretical ideas.

In another sense, there is broad agreement on the points that Commoner raises. It has been widely held, for at least 25 years³, that biological complexity probably has more to do with complex gene regulation than with gene number. And even if one takes Commoner's broader view of the central dogma, it is hard to see what the fuss is about. The often obscure path from genotype to phenotype is, of course, dependent on the protein–protein interactions that underlie alternative splicing, post-translational modification, gene silencing and epigenetic regulation, in addition to a whole host of environmental factors. Commoner seems to be arguing that geneticists have documented this complexity, but have not taken it to heart: “Divergent evidence is duly reported and, often enough, generates intense research, but its clash with the governing theory is almost never noted.”

But what can this mean? That geneticists really think their subject can be reduced to the simplified shorthand they sometimes employ in public pronouncements? Surely not. That because the Human Genome Project has been subject to hype, there is no there there? Can it really have escaped Commoner's notice that the availability of a complete genome sequence, or even a partial one, is a great boon to the study of the complexity he insists is being swept under the rug?

Lest this be taken as a dismissal of all criticism, it is important to add that the relationship between genetics and biotechnology deserves more rigorous review (see page 355). Finally, the Harper's article should prompt us to heed the words of Horace Freeland Judson⁴: “Less is not more....Oversimplification creates confusion that no reader can comprehend: fuller explanation will bring enlightenment. More can simplify.” Bearing this in mind, geneticists need to do a better job of conveying the fact that biology is complicated, and that the human genome sequence has not made understanding it easy—just a little less hard.