Jim’s Genome, and Yours

Welcome to the Age of Personal Genomics

I had a celebrity sighting in mid-town Manhattan a few weeks ago. It was unmistakable: the unkempt sparse white hair, the glasses slipping a bit on the nose, the eyes intense in conversation, the head leaning into the world—this was James Watson, who 55 years ago, with the late Francis Crick, played around with some cardboard cutouts representing nucleic acids and (with some help from Rosie Franklin’s X-rays) built the strange spiral that changed the world.

I nearly yelled out, “Dr. Watson, thank you!”—I do that sort of thing sometimes—but something held me back, probably the incredibly stupid remark he made last year about people of African descent. He said in an interview promoting his latest book that he thought they might have lower intelligence for genetic reasons. Aside from the fact that there is no reason to believe this, and the added fact that such statements have done untold harm to millions, you don’t say things like that if you’re in a position of responsibility you’d like to keep.

Larry Summers, the president of Harvard, lost his job a couple of years ago for disparaging women’s inherent scientific ability, and Watson duly lost his—he was for decades head of the great Cold Spring Harbor Laboratory—for blundering bias. He was never known for diplomacy, and let’s just say that in his eighties he’s not the diplomat he used to be.

Anyway, I didn’t want him to think I might be thanking him for that. I wanted to thank him for much else—co-discovering the structure of DNA, shepherding countless scientists through the rise of molecular genetics, making the big leap to large-scale genomics, educating Presidents, kick-starting the sequencing of the human genome, and penning entertaining if self-serving popular books about how science is done.

What I didn’t know until a couple of weeks later, when the April 17 issue of Nature was published, was that Jim Watson’s genes (or at least their sequence) were about to become public property. Not yet done with pioneering, he volunteered as the guinea pig for a new kind of genome sequencing that is faster and cheaper than ever before.

Not exactly cheap yet, however: $1.5 million was the price tag for this bit of medical testing. But when you consider that the sequencing a few years ago of J. Craig Venter’s DNA cost $100 million, Watson was done at practically WalMart prices.

Venter’s a bit of a cowboy. He spent his youth not in the lab but at the front as a medic in Vietnam, and while watching young men die he formed a no-nonsense approach to medical research, including speed. He assembled hundreds of millions in capital and beat the government’s project (which Watson started) to the first detailed sequence of the human genome.

So now we have the genomes of two gene pioneers, and while it’s not yet cheap enough for the rest of us, it will be pretty soon. There’s a big prize offered for the $1000 genome, and someone will get there. Then what?

Well, we can all know a little more about what we came into the world with. Unfortunately, of the tens of thousands of genes and other regulatory elements in each of our cells, we have no idea what most of them do, and it will take two centuries or so to find out. In genomics they call this annotation, defined as “the process of attaching biological information to sequences.”

Organismal biologists call it development, and its complexity makes sequencing at any speed look like child’s play.

Take Dr. Watson, for instance. Over three million of his nucleotides (out of three billion) depart in some way from the human genome project’s reference base. Of these, 11,000 or so could change the amino acid sequence, and thus the function, of a protein.

Among these were twelve known single-gene defects that if paired with another defective gene would result in a disease. But they are so rare in the population that there would be little point in even including them in genetic counseling.

This would be true for most of us. Furthermore, the most common diseases are each influenced by many genes, and we now know only a small fraction of what we would need to know to tell you that you are at higher or lower risk. When the cost of sequencing your genome comes down to a cool grand, it will still in almost all cases not be worth the price.

But what about the specter of abuse? Who can get our genetic information and what can they do with it? Coincidentally, as Watson’s genome was published, protective legislation was making its way through Washington. A bill called GINA, the Genetic Information Nondiscrimination Act, would prohibit the use of genetic information in any way by employers, potential employers, and health insurers and plans to decide whom to hire, fire, or cover. By April 30 it had passed the House and Senate, and a Presidential signature is expected. So perhaps we can worry a little less.

As for James Watson’s genome, there is no doubt at all that future historians of science, armed with much better annotation, will be probing it for clues to his brilliant career, and perhaps also to his awful stumbles.

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