New York Times, April 17, 2001

Approaching Biology From a Different Angle

by Andrew Pollack


SEATTLE--It was a major coup in 1991 when the University of Washington, with a $12 million grant from Microsoft's chairman, William H. Gates, lured Dr. Leroy Hood to create and head a molecular biotechnology department.

Dr. Hood, after all, was, and still is, a biotechnology superstar. In the 1980's, while at the California Institute of Technology, he led the team that invented the DNA sequencer, the machine that made the Human Genome Project possible.

At the news conference in February announcing the publication of the genome papers, Dr. Francis S. Collins, director of the National Human Genome Research Institute, singled out Dr. Hood, saying, "We would not be here today if not for the innovation in technology."

Dr. Hood has also helped show how the immune system creates its arsenal of antibodies. And he has helped start more than half a dozen companies, including Amgen, the largest biotech company, and Applied Biosystems, the leading maker of genetic analysis equipment.

A little more than a year ago, Dr. Hood quit the university and delivered a stinging message. The university, he said, and universities in general, are unfit for the new age of biology.

So now, at 62, Dr. Hood is starting over. He has formed a nonprofit research center, the Institute for Systems Biology, which he hopes will transform the study of biology.

Systems biology is a loosely defined term, but the main idea is that biology is an information science, with genes a sort of digital code. Moreover, while much of molecular biology has involved studying a single gene or protein in depth, systems biology looks at the bigger picture, how all the genes and proteins interact. Ultimately the goal is to develop computer models that can predict the behavior of cells or organisms, much as Boeing can simulate how a plane will fly before it is built.

But such a task requires biologists to team up with computer scientists, engineers, physicists and mathematicians. The structure of universities makes that difficult, Dr. Hood said.

"To do this kind of thing you have to have them shoulder to shoulder and next door," he said at his new institute, near the University of Washington campus.

Shoulder to shoulder would not be an overstatement here, where 150 researchers are so cramped that some share tiny offices. And there is an eclectic mix of collaborators, among them Dr. George Lake, an astronomer who has developed computer simulations for NASA; Dr. Ger van den Engh, a biophysicist developing a machine to sort cells at high speed; and Dr. Andrew F. Siegel, a University of Washington statistician.

But whether Dr. Hood, the man once viewed as Seattle's savior, can succeed is unclear. He has not been able to raise the $200 million endowment he is seeking. And, some biotech leaders in Seattle say, his messy divorce from the university has soured potential donors, including Mr. Gates, who would not comment.

Dr. Hood has certainly been busy since coming here. He started a drive to find genes involved in prostate cancer, set up programs to improve the teaching of science in public schools, decoded much of the genome of rice and helped start five companies.

But for all his admirers, Dr. Hood has critics, who say he is better at starting things than at managing or finishing them. He moves from one project to another like a whirlwind, sometimes leaving those in the previous effort disenchanted.

Rosetta Inpharmatics, a company Dr. Hood helped to found a few years ago, for instance, now has virtually no relationship with him. The gene sequencing center Dr. Hood set up to decode the rice genome under contract to Monsanto closed when the project ended, forcing the university to lay off 130 people.

"He starts things, that's what he does," said Dr. Maynard V. Olson, a prominent geneticist, who was recruited by Dr. Hood but then had many disputes with him. "There is a trail of acrimony in most of these cases."

But others say that scientists who can marshal resources--and few are better at it than Dr. Hood--are badly needed. "He's an opportunist, a scientific opportunist, in that he knows what to pick up, and I think that's important," said Dr. Sydney Brenner, a molecular biologist on the scientific advisory board of Dr. Hood's new institute.

Systems biology is certainly hot now. Dr. Brenner set up the Molecular Sciences Institute in Berkeley a few years ago to do similar work. And despite Dr. Hood's complaints, universities are flocking to cross-disciplinary biology. James Clark, the Silicon Valley entrepreneur who founded Netscape, gave Stanford $150 million to set up such a program. Three University of California campuses received a total of $300 million from the state to do likewise.

Dr. Hood grew up in Montana, where his scientific prowess was apparent early. In high school, he was one of 40 finalists in the Westinghouse Science Talent Search, for a geology project. As a senior he taught sophomore biology. He also was the quarterback on a successful football team, the yearbook editor and a state debate finalist.

He graduated from Caltech, earned a medical degree from Johns Hopkins and returned to Caltech for a doctorate in biochemistry and, in 1970, a job as an assistant professor of biology.

He credits Prof. William J. Dreyer there with the key advice: "If you really want to change a discipline, invent some new technology that will let you go beyond what people have seen before."

So Dr. Hood's lab went to work on inventions, starting with a protein sequencer, a machine that could read the order of amino acids in a protein with far greater sensitivity than existing machines. The machine helped Dr. Stanley B. Prusiner of the University of California at San Francisco determine the structure of the prion — the protein now implicated in mad cow disease.

"Just because we developed a machine that could look at things 100 times more sensitively, it opened up new fields," Dr. Hood said. Indeed, such machines, he added, have led to a new type of science he calls "discovery science." Instead of testing hypotheses with experiments, discovery science involves generating big databases of information, without always knowing in advance what the data will be used for.

The most prominent example, of course, is the Human Genome Project, made possible by the DNA sequencer his lab also developed.

Dr. Hood has not only developed machines, however. In 1987 he shared an Albert Lasker Medical Research Award with Dr. Philip Leder of Harvard and Dr. Susumu Tonegawa of the Massachusetts Institute of Technology for unraveling how the body can make the millions of different antibodies it needs. Dr. Tonegawa went on to win the Nobel Prize.

At Caltech, Dr. Hood ran a sprawling laboratory and traveled so often to give speeches or raise money that one of the "Hoodlums," as lab members called themselves, posted a missing child alert on the bulletin board with Dr. Hood's picture.

But friction arose between Dr. Hood and Caltech over what he said were his efforts to cross department lines. So he moved, with about 25 people from his lab, to Washington. Other scientists were recruited and his department seemed to thrive.

But the department ran out of space and Dr. Hood said he was told he would have to wait for a new building. So he began thinking of raising money on his own to set up an institute, initially within the university. The university, however, said it would be a conflict for him to run the department and the institute. There were also clashes over the extent Dr. Hood could work with companies.

Some members of his department, meanwhile, grumbled that Dr. Hood was neglecting his duties as chairman and leaving them in the dark about the institute.

"I think Lee was chronically overextended," said Dr. John Yates, a former associate professor in the department, who is now at the Scripps Research Institute and at Syngenta in San Diego. "That never leads to a good management style."

One morning in December 1999, Dr. Hood called a faculty meeting and announced he was resigning that afternoon.

Dr. Paul Ramsey, the University of Washington medical school dean, declined to be interviewed. But Dr. Olson, the geneticist, said the university "showed tremendous flexibility" in trying to accommodate Dr. Hood.

After Dr. Hood left, the university set up its own institute anyway, called the Cell Systems Initiative. It is headed by Dr. Robert Franza, once a close colleague of Dr. Hood.

Meanwhile, the department of molecular biotechnology still lacks a chairman and is down to three full- time professors, about a third its level a few years ago.

It is far too early to judge the success of Dr. Hood's new institute, which he founded with two University of Washington colleagues, Dr. Ruedi Aebersold, a protein expert, and Dr. Alan Aderem, an immunologist. As a test of its approach, scientists here have developed a computer model of how yeast metabolizes sugar. But the model so far does not match reality.

The institute now supports itself with research contracts from governments and companies, some of which Dr. Hood brought with him from the university. It has also raised $5 million from an anonymous donor and $5 million from Merck & Company. But the institute needs an endowment to make it independent of the year-to-year grant hunting.

For his efforts, Dr. Hood himself has become modestly wealthy. He rises at his home on Lake Washington at 4 or 5 and runs six miles or so several times a week. He also climbs mountains and kayaks.

For his honeymoon 37 years ago, he took his bride, Valerie Logan, on what was to have been a 150-mile backpacking trip. After a day, she cut the trip in half. They have two grown children.

Ms. Logan has been working on one of Dr. Hood's pet programs, which provides science training to teachers in public schools. Dr. Hood and a colleague are writing a college text, emphasizing, of course, the systems approach.

Copyright 2001 New York Times. All rights reserved. International copyright secured.
Filel Date: 4.23.01