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the multibillion-dollar human genome project’s effort  to detail the entire set of human genes was biology’s moonshot. But it might have never made it off the launch pad without one key piece of technology-the automated DNA sequencer. Labs crammed full of these machines, each rapidly determining the sequence of bits of DNA, were the fuel that made the project feasible. Leading the team that developed the sequencer shortly before the genome project was initiated in the mid-1980s is just one of the achievements that has helped turn Montana native Leroy Hood into a biotech superstar. Now 62, the Caltech-trained biologist has laid the foundations for a string of biotech companies, helped unravel the mysteries of the immune system and mad-cow-disease-causing prions, built-with $12 million from Bill Gates-a molecular biotechnology department at the University of Washington, and left the university behind to found his own institute, Seattle’s Institute for Systems Biology.

Founded in January 2000 with an anonymous $5 million donation, the Institute is a vehicle for what Hood sees as a whole new kind of biology-one that focuses, not on individual genes, proteins and other factors, but on how they come together in complicated systems to make us healthy or ill. Fulfilling this vision of “systems biology” will require that researchers mix lab work with computer modeling and eschew highly focused and hypothesis-driven experiments in favor of the factory style approach typified by the genome project itself. The payoff, Hood says, will be a fundamental transformation of medicine. And he’s eager to develop the  technologies to make it happen.

Doing that, while at the same time trying to build his institute’s endowment, keeps the biologist busy. TR senior editor Rebecca Zacks caught up with Hood this spring in a series of phone calls-5:30 in the morning was convenient for him-to his home, office, and an airport lounge.

TR: You’re perhaps best known for leading the team that invented the DNA sequencer as a young Caltech professor in the early 1980s. But that was just one of four technologies you worked on at Caltech, right?
Hood: We had a deep interest in developing tools that would push biology ahead over the next 15 years. We had a clear vision of four instruments that would change the world: the DNA synthesizer, the DNA sequencer, the protein synthesizer, and the protein sequencer. They allowed one to decipher and synthesize biological information more effectively than was previously possible.

TR: Why are these tools so important?
Hood: The relationship between biology and technology is interesting. Most biologists are indifferent to technology-they use it, but they don’t really see it as a fundamental part of biology. Indeed, it is new or more sensitive technology that can open up new horizons in biology. A great example is the protein sequencer [a device that determines the identity and order of the amino-acid building blocks that make up a particular protein]. The sequencer we developed was about 100 times more sensitive than previous versions. It let us analyze many proteins that were heretofore utterly inaccessible to analysis. We carried out six projects and each of them opened up a new and interesting field. For example, we sequenced a hormone called erythropoietin with Amgen, and that sequence was key to their cloning the gene which led directly to the development of the first billion-dollar drug of the biotech industry.

TR: Still, you didn’t always get an enthusiastic response when you proposed these tools-even with the DNA sequencer?
Hood: I sent in a couple of grants to the National Institutes of Health in the early ’80s when we were just starting to develop the DNA sequencer, and neither was funded. Comments were, “Grad students can do it cheaper,” or “It’s impossible.”

I went to the president of Caltech in ‘78 or ‘79 and said, “Look, we are developing four instruments that will change biology. My colleagues are suggesting that they should be made available to the general scientific community. Hence, we should commercialize them.” And he said, “Caltech isn’t really interested in commercialization. If you want to, you have permission to go out and commercialize them, but we’re not interested in that kind of thing.” Over the next two years I went to about 19 companies and got 19 nos. It was around 1980 when a venture capitalist from San Francisco called me and said, “I’ll put in a couple of million to develop these instruments you’ve been shopping around. Why don’t we start a company?” That company became Applied Biosystems [which merged with scientific instrument maker Perkin-Elmer in a $330 million stock deal in 1993].
 
TR: What other firms did you help found?
Hood: I was in on the beginning of Amgen, and I’ve been involved in founding seven or eight other companies since. I got involved in the biotech revolution in the early days. It was intellectually exciting to be involved as a scientific advisor. One learned an enormous new science and enjoyed the science without any of the responsibility of making money. Companies go through this maturational process where they need founding scientists as scientific advisors for the first few years, and then they mature and function independently. It is a healthy process.

TR: Were you ever tempted to get more involved in the business side?
Hood: Not at all. The key issue always for me was the freedom to approach new problems. With a company, no matter how flexible the opening opportunity seems, in the end you have to make money and subjugate your interests to making money. What is so wonderful about academic research is you can explore what you wish. The other issue is the ability to attack long-term problems. You are not constrained to making money within two or at most three years.

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