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Using Teamwork to Tackle Disease

By David Shook Among the scientists who championed the Human Genome Project in the 1980s and 1990s, Leroy Hood is perhaps the most inventive. The 64-year-old Missoula (Mont.) native pioneered the field of so-called predictive medicine -- identifying genes that predispose people to certain diseases.

Hood, who holds a PhD in biochemistry and an MD, created a sequencing machine that reads the order of amino acid subunits in a protein, thus giving scientists clues about immune-system antibodies and key hormones in the development of blood cells. Among his other inventions is a so-called DNA synthesizing machine that strings together fragments of genes for use in DNA mapping and gene cloning.

These inventions allowed for significant breakthroughs in molecular biology, such as the isolation of prion, the protein responsible for mad cow disease. And in the last few weeks, Hood's DNA-sequencing technology helped to decode the genetic structure of the SARS virus. On Apr. 24, Hood was awarded the $500,000 Lemelson-MIT Prize, largely in recognition for these three inventions.

He's the co-founder of several biotechnology companies, including Amgen (AMGN), Applied BioSystems, and MacroGenics. But his efforts now are focused on "systems biology," a branch of predictive medicine that brings biologists, chemists, engineers, and computer scientists together to analyze all elements in a biological system (such a system could be a certain type of cancer, a bacteria, or a small living organism, like a fruit fly).

Before Hood's DNA-sequencing approach won widespread acceptance, the quest to understand disease involved the slow and meticulous discovery of one gene or protein at a time. The hope now is that by gaining a clear picture of an entire biological system -- for example, prostate cancer -- doctors will be able to more easily develop treatments for it.

I recently spoke with Hood about his work and the near-term outlook for predictive medicine. Edited excerpts of our conversation follow:

Q: What's your vision of predictive medicine?

A: In another 10 years we'll have identified hundreds or even thousands of genes that collectively predispose people for many common diseases. We'll be able to do complete human genome sequences on individuals. And with that knowledge we can better monitor people for incipient signs of a disease.

We'll be using a person's blood to determine the state of their health today and their DNA to forecast their future health.

Q: What are some of the ways that you could test my blood today for signs that I may be susceptible, or likely, to develop a disease?

A: We've identified genes that predispose people to certain subsets of diseases such as Huntington's, cystic fibrosis, and certain types of breast cancer. Today, we can take blood samples and interrogate those genes, and if you have the mutant forms of them we can make predictions about how the disease may emerge and progress.

Q: What about the privacy issues raised by predictive medicine?

A: I think in parallel with predictive medicine we must have a preventive component of medicine. We think we can find ways to replace defective genes or find very rational means for circumventing those defects or genetic limitations. But that effort must be coupled with prevention. If we can do that, who will worry about others knowing that you have a gene for breast cancer if you can take a pill at age 30 and probably never develop the disease.

Q: Your institute is using the systems-biology approach to better understand the human immune system. Can you explain this form of studying the body and what you think it can accomplish?

A: The fact is, we develop vaccines today pretty much the same way we developed them 100 years ago. We don't understand how all the components of immunity give rise to vaccines.

So we've gathered scientists, technicians, and engineers across many different disciplines working together with the idea that we can design and implement a strategy to make new vaccines that are highly effective, more targeted, and more rapid in their action.

Q: So this is mainly about the development of new vaccines?

A: There are other major areas of concentration in systems biology. There is, for example, a broad spectrum of diseases engendered by the immune system acting against its own cells. These are auto-immune diseases. Some of the more well-known ones are multiple sclerosis, diabetes, and arthritis. We're hoping to gain fundamental insights into these diseases and how to deal more effectively with them.

A third focus for us is putting together a detailed understanding of cancer biology. We're looking at prostate cancer, in particular, using systems biology. We've come to several interesting conclusions thus far: Prostate cancer isn't one disease, it's five or six. We can use molecular signatures to identify each kind in a patient, and the various types are stratified from the very benign disease to the very malignant.

Also, we're now studying blood assays from patients that will allow us to identify the onset of various types of cancer and to follow its progression more closely than is possible today.

Q: Are drug companies adopting aspects of predictive medicine and systems biology in their drug development?

A: One of the key aspects of systems biology is having cross-disciplinary groups working together -- the biologists, chemists, and computer scientists all working together on one system. The pharmaceutical industry, for the most part, doesn't have that yet. It still has the silos that keep the cardiovascular researchers separate from the neurological scientists, who are separate from the cancer researchers.

In the pharmaceutical industry's defense, these companies have to be skeptical of new fads, and systems biology is still somewhat of a new fad. But I think over time more scientists will come to realize the importance of this approach.

Q: So there's skepticism about systems biology among your peers in molecular biology?

A: I recall that from the very beginning of the Human Genome Project -- from about 1985 to 1990 -- I witnessed a great deal of aggression and even hostile opposition on the part of 80% to 90% of the biologists involved in the project. That experience taught me how fearful scientists can be about fundamental change and how they tend to hesitate in embracing new opportunities in scientific discovery.

I see that skepticism brewing to a lesser degree as it pertains to systems biology. The key for us will be to show how a complex organism such as the human immune system can be better understood through systems biology. I think in the next several years we'll be able to show that clearly. Shook covers biotechnology issues for BusinessWeek Online. Follow The Biotech Beat every week, only on BusinessWeek Online

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