Recorded: 28 May 2003
The 1986 symposium was intended to be about human genetics. It was a particular interest of Jim Watson’s who was then I would say at the peak of his career as the director of Cold Spring Harbor Laboratory. And he put together a program, which involved many, if not all, of the leading figures in human genetics. Part of the impetus for the meeting was the emergence of the idea that you could map human disease genes. An operation which began in earnest just a few years before and which I had a hand in starting. And I came to the meeting with Eric Lander, who at that time was working with me and we had together, put together a paper, which you can see, which essentially proposed a number of things that could be done if you had a suitably dense map of polymorphic markers of the human genome. And it basically said that you could do all the kinds of genetics that you had hoped to do with a human, but could only be done in Drosophila or worms or something or mice before then. That you could ethically and appropriately and sensibly do the science of real genetics with humans. And that was pretty much our intention was to deliver that paper which Eric did deliver. And I think that that was one of the main themes of the meeting was what you could do in human genetics.
The meeting is, however, not famous for that although that would have been a good thing for _____________ ??. The reason that the meeting is famous is because there was at the same put forward very forcibly by Wally Gilbert mainly, the proposal that we should forthwith drop everything and sequence the genome. And there were a variety of comments about this proposal including some strongly cautionary ones including myself. There’s a famous picture that’s up there somewhere of me talking to Wally in the front of the room there about this. It was a very interesting discussion. On the one side there were people stimulated by a bunch of meetings that are very famous and most of which I went to in which few of the leading interested scientists discussed the technical feasibility of doing any such thing. And the conclusion of all those meetings was very similar. It was going to be hard but anyone could see it could be done. No one knew how much it would cost or how long it would take but it could be done. And then there were the consequences for at a time of difficulty in funding, the consequences for everybody else. And it was this latter issue that was on a lot of people’s minds including mine. And I made as I recall very forcibly the argument that we should not run into this without understanding that it is possible if you give the government a very attractive simple minded target that they could suck all the resources out of everything else that was valuable. And the example that I used and I continue to use to this day is the space shuttle. So the space shuttle basically completely decimated planetary astronomy of every other kind.
So in the end—Jim and I think this is probably other than the double helix itself his greatest contribution—Jim, of course, was passionately devoted to the idea that we should have a human genome sequence. But he also understood the objection and he did and I think the exactly the right thing. He made it possible for the National Academy to convene a committee of people who were selected from among the fore leaders, truly covering the entire spectrum of pros and anti’s—from the strongest pro’s to the rabid anti’s. __________________ ??.
And that was the Alberts committee and that, of course, came out with a compromise proposal which was what happened in the end. The compromise was that a) we would not sequence immediately, that we would learn how to sequence first. b) We would not sequence the human alone, but we would sequence—spend actually a quarter of the money on the so-called model organisms; both to learn the sequence and also to have some reference against which to compare the human sequence because it was already clear at that time and emerged very strongly from the committee that the only way we had of really understanding what most of human genes do is to compare them to the mouse genes or the worm genes or the fly genes or the yeast genes. And in fact that’s how it’s turned out to be. Most of the human genes, even to this day, are annotated by analogy or orthologies – a new word that has arisen- with their counterparts in other organisms.
David Botstein is a prominent geneticist whose advocacy for gene mapping was crucial in laying the groundwork for the Human Genome Project. Botstein received his Ph.D. from the University of Michigan for his research on bacteriophage synthesis. As a member of the MIT faculty he continued working with phage P22 DNA and discovered many bacterial and yeast genes. He served as Vice President of Science at Genentech before becoming professor at the Stanford School of Medicine where he led in sequencing the first large eucaryotic genome.
On July 1, 2003 he was appointed as Director of the Lewis-Sigler Institute for Integrative Genomics at Princeton University. At Princeton he will continue to expound upon genome projects, explore the relationship between genes within the genome, and uncover how diseases like cancer alter the expression of genes.
Botstein researched at the CSHL while on sabbatical from 1974-1975. At the 1986 CSHL symposium on Human Genetics he played a crucial role in advocating for the Human Genome Project. While serving on the National Research Council Committee he emphasized that money be laid aside to fund the sequencing of other simpler organisms with which the human genome can be compared. Like Jim Watson, he has passionately supported the Human Genome Project since its inception.