September 2001

Under Biology's Hood

Continued from page 1

By Technology Review

TR: You thought the Human Genome Project was worth long-term investment, but initially not everybody felt that way?

Hood: I went to the first meeting held on the Human Genome Project in the spring of '85 at the University of California, Santa Cruz. Robert Sinsheimer, the chancellor, had $35 million and was considering spending it on an institute to sequence the human genome. He invited 10 or 12 scientists to consider this for two or three days. My lab had started working on the DNA sequencer in the early '80s, and the publication describing the first prototype was in 1986. So the Human Genome Project and DNA sequencing came together.

There were three things that stood out in my mind about that first meeting. One was the enormous technological challenges the Human Genome Project presented, both in sequencing and mapping, but also in computation and analysis. The second thing that was exciting was to see how it would transform biology and medicine. I was an advocate for this project, and was there ever bitter opposition. Hostile, aggressive and negative interactions resulted. And the reason for that, which is the third thing that really impressed me, is the genome introduced to biology a completely new approach, which I've since come to call "discovery science." It's the idea that you take an object and you define all its elements and you create a database of information quite independent of the more conventional hypothesis-driven view.

What people really resisted in the Human Genome Project were two major things. One, "It's going to cost too much money-it's going to take money away from me." And this was never correct. The project started with a large bolus of new money and has since brought lots of new money to science. The second argument against the Human Genome Project was that it was trivial, it wasn't really science. It was referred to as a fishing expedition, or a mindless collecting of facts. What they did not realize is how these databases were going to transform how we think about biology and medicine.

TR: Can you describe those changes?
Hood: First, discovery science is now an accepted concept. Second, the human genome has provided us with a genetics parts list for humans and the other model organisms whose genomes have been sequenced. We must do biology to figure out how these parts function, and now we have them-genes, control sequences, etc.-in databases. Third, the Human Genome Project has given us access to human variability, the genetic variations which make humans different from one another-different in physiology and different in disease predisposition. And it's in this arena that medicine will be utterly transformed over the next 20 years or so.

TR: Do these changes raise ethical issues?
Hood: I think a big issue is how we're going to educate the public about the revolution that is coming in medicine. What will happen over that 20- to 25-year time period is that we will move from what I call reactive medicine-you get sick, they try to fix you-to what I would call predictive medicine-they look, for example, at your genes and determine whether you have a bad gene for breast cancer, so you will have a 70 percent likelihood that at the age of 60 you'll have breast cancer. In this stage, you can make predictions, but you can't do much about it. The final stage will be the preventive stage where we will be able to take defective genes, understand the pathways in which they operate and how to manipulate those pathways so you can circumvent the limitations of the defective gene. Ideally, you would be able to take pills that could reverse those limitations in a preventive fashion.

This preventive medicine is going to wreak enormous challenges for how we educate physicians. The fact is, the physicians we're educating today are going to be practicing in that era, and most of them do not have the faintest idea about the coming revolution in medicine. Medical schools are, in general, resistant to responding to this certain future. In my experiences, their attitude is, "Well, that is an interesting proposition, but we do not have time to think about it today." The same will be true of society at large. There are also the ethical issues of genetic privacy, germ-line genetic engineering, and genes that influence human behavior.