An Interview with Dr. Leroy Hood
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Hood (continued): I think those relationships are absolutely critical, as I indicated before, and they're critical in a number of ways. First, it means people that come to biology from computation, or theoretical physics, or electrical engineering, must understand biology in a deep sense, because I think their ability to contribute is going to be directly proportional to the sophistication of their understanding of biology. Second, they have to be in an environment where they can directly feed their their computational insights back into the kind of biology that's being done in this iterative kind of cycle. That is, the computational people, as well as the experimental people, must communicate and talk with one another in formulating the next round of iterative experiments so they can juxtapose theory with experiment, and move from more descriptive aspects of biological systems to their graphical formulation and ultimately, their mathematical modeling, and so forth.

I would emphasize as strongly as I could the intimate interrelationships that are really going to determine the success of those groups that are practicing systems biology. That is, those who do it only with the biologists or those who attempt to do it only with the people in either computational biology or bioinformatics, will fail.

Stewart: What are the biggest challenges you've faced in applying a systems-based approach to biological research?

Hood: The biggest challenge was that it didn't fit into the classic academic infrastructure for doing science. We found that bringing together the true, cross-disciplinary scientists was rendered difficult by the fact that our academic center, and most academic centers, live in a world of departments. And the departments tend to create barriers both in how their students are educated and what the expectations are for faculty.

We found that there were real limitations in the resources we needed to raise to create both our technical high-throughput facilities and our computational facilities. We also found there are real difficulties in salary scales. That is, you need software engineers and indeed other kinds of engineers, and you need to be to be able to compete with the best, at least on a par with industry, and in academia this is obviously extremely difficult to do.

And then there are simple things, like systems biology is a teamwork-type of process, and that runs into tenure where the expectation is that when you're young and most creative you do really safe things all by yourself. That doesn't fit nicely into the teamwork that's necessary for systems biology.

So I think the biggest challenge we met, which took me three and a half years to realize, was that it wasn't going to work in the classic academic infrastructure and that we had to strike out and do this thing independently. We did so about a year and a half ago and it's been strikingly successful. We've been just absolutely delighted. I wish I'd realized this years earlier and not wasted a considerable amount of effort trying to basically fit a square peg into a round hole.

Stewart: You've spoken quite a bit to the motivation for starting up the independent Institute for Systems Biology, and I understand it has a unique organizational philosophy, and it is really prospering at a time when many of the venerable research institutes are suffering. How is the ISB model different from the academic and biotech pharmaceutical models of research?

Hood: It's different in many dimensions. One, we have a true cross-disciplinary faculty. We've got eight faculty members and among them they represent physics, computer science, chemistry, and engineering, as well as biology. Two, we make an enormous effort to have this faculty be interactive and to educate ourselves with regard to the deep problems in biology. Three, we have put in place and are integrating together beautifully all of these high-throughput facilities that capture information at the DNA level, and at the RNA level, at the protein level, and at the interaction level, and cellular levels, and so forth. Very few academic institutions have any means whatsoever for this kind of sophisticated, broad integration of technology.

Fourth, we've made a lot of key industrial partnerships, for three purposes. One, in some cases we take on very long-term problems and companies that have substantial resources are willing to go along with us and help us take on these long-term problems. Two, we have collaborations in at least one case where we, together with a company, are creating a very high throughput platform for proteomics. This is going to cost a substantial amount, so sharing between ISB and the company to do this very challenging thing is working out extremely well. Then finally, and maybe most importantly, we've got a lot of collaborations with companies that have leading-edge technologies that we aren't working on ourselves. ISB is developing a lot of new technology, but we can't develop everything. So we see ourselves as an integrator of technologies by making partnerships with small companies, and bringing their leading-edge technologies into these integrative platforms we have. In doing so, we are giving them biological reality and a type of benchmarking they just can't get any other place. I think this ability to integrate all of these technologies together, and to bring them in both from industry and academia, is one of the unique aspects of the Institute.

The real constraint in academia with these kind of industrial partnerships is the challenges they face in dealing with intellectual property, and the fact that in general, there are not very good people that are dealing with this at universities. So, it takes a long time, and never, ever gets done very well. We certainly ran into that in spades as well.

I think society doesn't realize that science education is the real basis for inquiry-based thinking, and inquiry-based thinking, I would argue, is equivalent to the three R's.

If you look at it overall, the Institute also is really interested in how this new systems biology is going to fundamentally change education in biology. We think it's going to push it toward a view of biology as an informational science. In fact, I'm, with others, writing a textbook on this area, and this is something the Institute is going to push. We're also cognizant of a strong need to bring science to society, so we're interested in Third World medicine. We're interested in ethical questions of modern genetics. We're interested in how intellectual property needs to be changed in biology--in the context of these very new views of biology. We have major programs on kindergarten through twelfth-grade science education and I think we've been a real pioneer and leader in changing the educational system in Seattle.

Stewart: I'd love to talk just a little bit more about that. You've been active in education your whole career, including writing many textbooks, and you've been very involved in kindergarten through twelfth-grade programs. How do you feel we're doing as a society at teaching science, both at the university level and in the lower grades, and what changes would you like to see specifically?

Hood: I think in general we aren't teaching science well at all, particularly in the kindergarten through twelfth-grade arena, and the reason for that is that society doesn't understand how difficult it is to teach science. The teachers themselves, particularly at the lower levels, aren't very well educated in science. For example, it's estimated that 2 percent to 3 percent of the elementary teachers have not had much, if any, science background at all. So how can somebody who's never had any background in science teach science to kids?

I think society doesn't realize that science education is the real basis for inquiry-based thinking, and inquiry-based thinking, I would argue, is equivalent to the three R's. As these kids move out into a world of communication and information it's going to be critical that they can think analytically and position themselves for reasonable opportunities and options in the future. The simple fact is, and it's been documented 50 different times, that we're failing in that endeavor. I think we're basically failing because we don't understand how to teach science, which I think you need to teach by hands-on, inquiry-based approaches.

At the college level, in general, the teaching is better. At least you can argue people understand the topics much better. But I still think much of the science teaching at the college level fails for similar reasons. The real essence of teaching is really teaching inquiry-based thinking. It isn't didactic lectures. It isn't sitting up and giving them a thousand facts. It's not having them recite back in rote memory form the formulas for all the amino acids. Rather, it's getting students engaged in an educational process, where they actively think and query and analyze what it is you're teaching them. There are some colleges that can do that pretty well, but most places don't.

In terms of biology, I hope that when we bring out this new textbook about biology as an informational science it will be a real lead in moving the teaching of biology, frankly at all of these levels, away from biology as a classification discipline--where you've got 5,000 words that have been defined and used once or twice throughout the entire text--to very much more of a conceptual, analytic, inquiry-based kind of teaching. That's really what we propose to do. The text we're going to write is going to be for the upper undergraduate level, and for cross-disciplinary scientists initially, but we envision doing something for kindergarten through twelfth-grade science later on, too.

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