Dean Hamer

Dean Hamer

A weeklong electronic journal.
July 5 2000 9:00 PM

Dean Hamer

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Yesterday was my first day back at work after a week of teaching and writing at Dartmouth College. The laboratory was unusually quiet because everybody was out of town for the extended July 4 weekend. There was only the hum of the freezers and incubators and computers to keep me company.

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I spent most of the morning answering voice- and e-mail messages from reporters. They were still asking about the draft sequence of the human genome announced last Monday.

When I first walked into a genetics laboratory, as a freshman at Trinity College in Hartford, Conn., in the fall of 1969, nobody had ever actually seen a gene or held one in their hands. Scientists knew what genes were in the abstract but not in the flesh. They knew that genes were strings of digital information written in a four letter code, but they couldn't separate one gene from another or tell you how the encoded information eventually led to a living, breathing organism.

That's all changed. We now know at least the rough order of the more than 3 billion Gs, As, Ts, and Cs that make up the human genetic blueprint. They spell out some 50,000 genes, each one directing the synthesis of a different ingredient of life. More than half the sequence has been determined in just the past six months, at the rate of 1,000 bases a second of raw sequence. There are still a few gaps in the "working draft" of the sequence, but they will be filled in soon.

As you probably know, the announcement was made by two competing teams of scientists, one from Celera, a private company, and the other from the National Human Genome Research Institute, which is part of the National Institutes of Health where I work. I can see the Genome Institute's main building from the hall outside my lab. In its basement are row after row of freezers, holding rack upon rack of miniature plastic test tubes, each containing some of the thousands upon thousands of DNA fragments that were used to decode the sequence. Genes have gone from something utterly abstract to something totally concrete in less than three decades, a remarkably short period of time.

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The new sequence data is going to make life a whole lot easier for my research group. In the past, when we found a locus for some interesting behavioral trait like cigarette smoking or nicotine addiction, it was still a long, hard haul to find the actual gene. Genetic experiments can narrow down the search to a few million base pairs, but that's still a huge amount of DNA to slog through. Now all the grunt work has been done for us. All we have to do is sit down at the computer terminal--assuming we know what to look for, that is.

The genome sequence doesn't solve all our problems. We still don't know what most of the human genes do. That's where we come in--looking for the connections between a person's DNA and his expressed characteristics.

It's tough work. The behavioral traits we are interested in are influenced by dozens or more genes, not to mention the effects of upbringing, environment, and culture. Typically we have to look at hundreds or even thousands of individuals to see anything significant. That's why we have our own thousands of test tubes, each from a different research participant, sitting in our freezers. Each frozen droplet of DNA has its own story to tell.

Checking the records from the past week, I see that eight new subjects have been added to our protocol. That's progress, but it's not as quick as I'd like. I make a note to step up the search for a new research assistant.

The genome project is not only changing the content of science; it's also changing the way we do it. When I was a freshman at Trinity College, biology was still a small enterprise. A scientist would come up with an idea, set up an experiment to test it, and see what happened. I read the papers of the early heroes of molecular biology with awe. Such elegant, lean experiments. Experiments that took imagination and intellectual derring-do. Experiments that made me wonder, "Why didn't I think of that?"

Now biology is big business. The science behind the genome project consists mostly of a bunch of very expensive machines run by an army of technicians. It couldn't be less elegant if it tried. And yet Celera stock has soared to more than $100 a share, despite negative earnings of hundreds of millions a year.

With all that money floating around, it's no surprise that there are no heroes of the genome project. All the leaders have been tarnished, rightly or wrongly, by allegations of greed or pride. Is that the price we must pay for progress?

Reminder: Double session at the gym tomorrow.