David Botstein on Infrastructure of the HGP
  David Botstein     Biography    
Recorded: 28 May 2003

There’s also two other things that are very important to understand. Everyone got it right at the beginning in the committee that as infrastructure the human genome project was going to be extremely valuable. You may recall that Francis Collins has variously been quoted that in order to get to the cystic fibrosis gene by the positional cloning paradigm at a cost anywhere; I’ve heard numbers from fifty to three hundred million dollars. That’s certainly the right order of magnitude of how much was expended. Obviously at that rate to find all of the diseases genes was impossibly expensive. By spending a couple of billion dollars upfront you can reduce that problem to something that a single graduate student can do in a year or two. That in fact was foreseeable at the time and came to pass. So that alone was as worthwhile as infrastructure even if none of it could be interpreted. So that was a very powerful argument. So to map first—get the genetic map and get the physical map—were justifiable completely apart from the sequence. The reason it was being done at that moment was in the hope of getting the sequence before Jim [Watson] retired or something or some such time-driven thing.

But the truth of the matter is that it was absolutely justifiable as sensible research planning. To give you an idea I made the calculation at the time which no one disputed, that at that time, in the yeast community, which is a tiny genome—yeast has a tiny genome. Roughly one third of all the money going into yeast research was going into amateur sequencing. So people would find a gene of interest, they’d learn some biology about it, then they’d have to sequence it. It would take a year for some graduate student by hand to get it through the thousand or two thousand bases and get it right or close to right. It was tremendously inefficient and annoying to those of us who had many graduate students who wanted to do this. And it was very expensive and the idea that you could have the sequence once and then you’d just do a little snippet of sequence and know exactly where you are that that was really a great foreseeable improvement in infrastructure struck everybody right at the beginning. ________________?? although there was doubt and remains doubt about how much of the sequence can be interpreted that in the end didn’t carry very much because so much of it was clearly useful apart from that.

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.