Leroy Hood says when he left the University of Washington in late 1999 to start an institute of multi-disciplinary team of scientists to study what he called “systems biology,” people snickered, saying “it was just a crazy way to raise money.”

Almost a decade later, the work of the Seattle-based Institute for Systems Biology still baffles a lot of people, even some very smart biologists I know. But Hood says it has carved out enough support to continue growing in the midst of an economic downturn. He made those comments in downtown Seattle this morning during a wide-ranging talk that was part of the Technology Alliance’s Science & Technology Discovery Series.

The Institute for Systems Biology now has 14 faculty members, 230 employees, and an annual budget of $35 million, Hood says. The Institute’s budget is leaping ahead to $55 million this year, thanks to the first installment of a five-year, $100 million grant from the government of Luxembourg. This tiny European nation has thrown its financial resources behind Hood’s method of using high-powered computers to study networks of genes, and how they interact, rather than the traditional ways of biology that Hood says are too narrow, looking at one gene, or one protein in isolation. He says the holistic approach of studying entire biological systems will lead science down the path to a historic attitude shift from reactively treating disease to what he calls P4 medicine, or predictive, preventive, personalized, and participatory medicine.

“Your physician will not think of you in terms of your diseases, but in terms of mediating your wellness,” Hood says.

As always, the indefatigable 70-year-old pioneer of high-speed gene sequencing packed a lot of information in this talk. Here are some of the highlights:

—On the P4 medicine vision: People will carry around a handheld device that extracts a pinprick of blood that will run analyses of tiny amounts of signature proteins in the blood. It would serve as early warning signs of a biological network that’s been thrown out of whack, and threatens to morph into a disease. It could tell you the status of your current immune defenses, whether you have any ongoing infections, and offer clues to all your previous exposures to pathogens, and your susceptibility to future bug exposures. The data would be sent to your doctor, who reviews it with you. “Physicians will be grand integrators of information,” he says.

—On politics: “The problem with most politicians is they are one or two-trick ponies,” Hood says. “We need a systems politics that recognizes mankind’s 10 or 15 biggest challenges.” He adds that President Obama “comes closer to a systems politician” than any he’s seen in a long time, and he even added. “If I was 10 or 15 years younger, I’d love to run for office just to see if this could work.”

—On the growing acceptance of systems biology: About 150 scientific centers around the world are now devoted to systems biology, although none are in medical schools. The nation’s top 5 medical schools …Next Page »

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I leave students (and even some of my colleagues) with several pieces of advice. First, I stress the importance of a good cross-disciplinary education. Ideally, I suggest a double major with the two fields being orthogonal-say, biology with computer science or applied physics. Some argue that there is insufficient time to learn two fields deeply at the undergraduate level.

I argue that this is not true. If we realize that many undergraduate courses now taught are filled with details that are immediately forgotten after the course is finished, we must then learn to teach in an efficiently conceptual manner. As I noted above, as an undergraduate at Caltech I had Feynman for physics and Pauling for chemistry, and both provided striking examples of the power of conceptual teaching.

Second, I argue that students should grow accustomed to working together in teams: In the future, there will be many hard problems (like P4 medicine) that will require the focused integration of many different types of expertise.

Third, I suggest that students acquire an excellent background in mathematics and statistics and develop the ability to use various computational tools. Fourth, I argue that a scholar, academic, scientist, or engineer should have four major professional objectives: (a) scholarship, (b) education (teaching), (c) transferring knowledge to society, and (d ) playing a leadership role in the local community to help it become the place in which one would like one’s children and grandchildren to live.

Fifth, with regard to the scientific careers of many scientists-they can be described as bellshaped curves of success-they rise gradually to a career maximum and then slowly fall back toward the base line. To circumvent this fate, I propose a simple solution: a major change in career focus every 10 or so years. By learning a new field and overcoming the attendant insecurities that come from learning new areas, one can reset the career clock. Moreover, with a different point of view and prior experience, one can make fundamental new contributions to the new field by thinking outside the box. Then the new career curve can be a joined series of the upsides of the bellshaped curve, each reinvigorated by the ten-year changes.

Finally, science is all about being surrounded by wonderful colleagues and having fun with them, so I recommend choosing one’s science, environment, and colleagues carefully. I end this discussion with what I stressed at the beginning-I am so fortunate to have been surrounded by outstanding colleagues who loved science and engineering. Science for each of us is a journey with no fixed end goal. Rather, our goals are continually being redefined.

(Editor’s note: This is an excerpt from an essay that appeared earlier this year in the Annual Review of Analytical Chemistry.)

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Nothing robs pharma officials of more sleep than unexpected toxicity linked to one of their companies’ medicines. Recently they’ve lost more shuteye than ever as reports on cardiac risks of widely-used diabetes drugs have fanned public anxiety about drug hazards. Now Congress is moving to intensify FDA surveillance of ill effects possibly caused by medicines. “We’re going to find adverse events associated with every drug,” says Keith Elliston, CEO of Genstruct, a Cambridge-based pharmaceutical consultant. That means the industry will urgently need better ways to tell whether such events really are caused by drugs, and, if so, to identify at-risk patients early. “To do that,” he adds, “we have to understand more about drugs’ mechanisms of action.”

As you’ve probably guessed, Genstruct’s specialty is figuring out how medicines do their things. The closely held company uses systems biology, an emerging discipline in which scientists try to capture enough of the complexity of living systems in computer models to predict what they will do when perturbed by drugs or illness. If Elliston is right, systems biology can prevent toxicity issues from erasing billions of dollars of pharmaceutical sales and turning patients away from needed therapies.

A Genstruct collaboration with Pfizer supports his thesis. Like many drug companies, Pfizer has been developing PDE4 inhibitors, anti-inflammatory compounds that may alleviate everything from asthma to rheumatoid arthritis. Unfortunately, one of its promising PDE4 inhibitors was found to cause severe blood-vessel damage in rats. That ordinarily would have killed the drug. But when Pfizer enlisted Genstruct to analyze the toxicity, says Elliston, systems biology revived the project.

Genstruct assembled all the available data on PDE4 inhibition in a computerized model comprising a network of interacting genes, proteins, and other molecules. The model highlighted key cause-and-effect relationships, revealing that the vascular injury was probably a rodent-specific effect—among other things, the model riveted attention on a central mediator of the damage that turned out to be an enzyme found at much higher levels in rats than in humans. The analysis also identified early-warning indicators of the toxic effect that might be used in human trials of PDE4 inhibitors to prevent drug-induced harm.

Genestruct is not the only biotech company betting on the market created by vanishing public tolerance for drug risks. In Mountain View, CA, Perlegen Sciences is focused on finding gene variants that make certain people react badly to specific drugs. One of its flagship projects seems prescient in the wake of reports that diabetes drugs made by GlaxoSmithKline (Avandia), and by Takeda Pharmaceuticals/Eli Lilly (Actos), elevate risk of heart attacks. Hoping to develop a competing drug in the same family as Avandia and Actos, Perlegen earlier collected 3,000 DNA samples from patients treated with the drugs in an effort to identify gene variants associated with the medicines’ tendency to cause fluid retention—a side effect that may aggravate heart failure. Perlegen hoped its competing drug could be offered with a proprietary genetic test that would enable the medicine to be targeted at patients unlikely to suffer harm from the side effect.

The privately held company’s first pass at the problem proved disappointing. “We’d hoped to find [gene variants] accounting for 50 percent” of fluid-retention cases on the drugs, says David R. Cox, Perlegen’s chief scientific officer. “But what we found accounted for only 16 percent.” Perlegen hasn’t given up—it’s now re-analyzing the patients’ DNA with “high-throughput” gene sequencers from 454 Life Sciences, recently acquired by Roche Group. The new technology “enables you to cost-effectively explore for rare gene variations,” says Cox, which often underlie the most troublesome adverse events—those afflicting a small fraction of patients, making them extremely difficult to detect before drugs reach the market and are prescribed to many thousands of people.

Cox says Perlegen doesn’t plan to try resurrecting canceled drugs. But it does hope to develop genetic tests for targeted prescribing of existing drugs that many people already depend on but that have come under a cloud due to unexpected adverse reactions. “In another setting,” he says, such reactions “are called icebergs. We now have the ability [to address their risks] in an expeditious way.”

Pharmaceutical executives no doubt hope he’s right—they can’t afford very many more Titanics.

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