Lee Hood's New Quest in
Biotechnology Innovations
by
University of Washington biotechnologist Lee Hood has always aimed to close the gap between biology and technology. His ideas on laboratory automation, first ignored, have helped launch several star biotech firms. Now Hood plans a new biotechnology institute to surpass the university department that he himself established.
An avid mountain climber, biotechnologist Lee Hood took to it naturally as a child growing up in rural Montana. The technical climbing he still practices generally consists of "going up vertical cliff faces." The Montana mountains may have been an excellent training ground for a career marked by innovative solutions to daunting problems.
In the 1960s, Hood became the first biologist
to bridge seriously the gap between biology and technology, and he
has since pioneered the automation of crucial tasks such as protein
and DNA sequencing. As he puts it, his career "has grown up" with the
biotechnology industry.
Others consider Hood's career not a child of biotechnology, but one of the industry's prime movers. "When Lee began [automated] protein and DNA sequencing on microscale, those were not very popular things for biologists to be doing. He had the vision to realize the impact that [these techniques] would have on the science," says David Galas, president and chief scientific officer at Seattle-based Darwin Molecular Corporation, a gene-based drug discovery company for which Hood has consulted since its inception. Hood's quests rarely focus on fundamental biological questions, turning instead to improving the techniques so that they can be used to answer deeper, more complex questions. In the 1980s, "a lot of biologists looked down their nose at that sort of thing, saying, 'That's not science,'" Galas recalls.
But there are few detractors now. Without
Hood's storied accomplishments in automated analysis - his
automated fluorescence sequencer is the most successful large
analytical instrument ever sold - the ambitious
Human Genome Project
would never have risen above the status of pipe dream.
"He has been very much a visionary," Galas says.
Hood won't argue, though his easygoing nature - striking in one who has successfully battled, and risen above, the disdain of his peers - prevents him from wording it quite so bluntly. Hood says that when he was getting his Ph.D. at the California Institute of Technology, his mentor, William Dreyer, "taught me to always think ahead of the pack, and stay geared to the most important problems. If you want to change science, you invent new technology - that has the biggest impact."
He was introduced very early to the
complexities of biology. Dreyer felt that his graduate project - to
determine how the immune system generates its huge number of different antibodies
- would be a "Saturday afternoon thing," Hood claims, with a touch
of exaggeration. They'd badly underestimated the endeavor, as it
turned out. "I started out as a protein chemist, but had to switch
midstream to molecular biology and use those techniques to finally solve the
problem." By his second year of graduate school, Hood was drawing big
crowds at presentations on the subject.
During his tenure at Caltech, he contributed technology consultation and intellectual capital to the formation of nine biotech companies, including such stars as Amgen and Applied Biosystems. But it took time to break through. He recalls struggling to convince mid-level managers at instrumentation companies that his automated machines would be the wave of the future. A tour of nineteen companies got him nowhere, and it wasn't until a venture capital firm became intrigued by the idea that Hood found the backing he had been searching for. Thus was born Applied Biosystems, now a divison of Perkin-Elmer. He learned his lesson well, today vowing never to lose touch with the top brass at companies: "[The middle managers] were not visionaries. . . . They just couldn't see how the biology was going to change."
Not satisfied with moonlighting with the biotech industry, Hood hoped to erode further the boundaries between instrumentation, computation, and experimental biology. Perhaps he simply got tired of his peers looking down their noses at his approach. "In academia you got no credit" for consulting with companies, he says. "In fact it was a negative." So he began a drive to start a molecular biotechnology department at Caltech. But the school's small campus, and the absence of a medical school, soon had him searching for other places to pursue his vision.
In the late eighties he began talking to Lee Huntsman, provost at the
University of Washington, about moving to the Seattle school. Huntsman
had an ace up his sleeve, as it turned out.
Mary Gates - mother of software mogul Bill - is an active member of
university's board of regents, and she talked her son into attending a
brunch held by the university president the morning before one of the
school's home football games. Huntsman bent Gates' ear and convinced him
to attend one of Hood's visiting lectures. With an already
longstanding interest in biotechnology, Gates showed up for several of
Hood's lectures, and was soon sold. His $12 million grant helped found
the University of Washington's Department
of Molecular Biotechnology, formed in 1992, which Hood has directed since.
The windfall wasn't the result of persuasion
or politicking, Huntsman says. "Gates is not susceptible to
anyone's enthusiasm. . . . He is very knowledgeable about these sorts of
things, and he recognized Lee Hood as a man of demonstrated excellence and
innovation."
Hood shows no sign of slowing down. The molecular biotechnology department has been predictably fertile, producing, among other innovations, a new technique for synthesizing DNA chips, and several software programs to handle DNA sequencing. Another program can take protein sequences generated from a mass spectrometer analysis and determine, if the gene is present in the database, the gene that encodes the protein.
Still looking ahead, Hood is now gathering a
$100 million endowment for an independent biotechnology institute.
He envisions computer scientists, engineers, and molecular
biologists working side by side to consider complex sequencing and molecular
pathway problems, and to develop the software and instruments to solve
them. Hood hopes to attract partner companies with "orthogonal
interests" - a choice of phrase that reflects Hood's mathematical bent.
Companies from the computer, instrument, and
pharmaceutical industries, he believes, could be poised to develop and
market the innovations that result from work carried out at the
institute. For instance, he is seeking a software company to help develop a
database capable of managing everything from patient records to
sophisticated molecular analysis of patient samples.
Monsanto is
already on board in an effort to sequence the corn genome.
Though the vision seems grandiose, many who have worked with Hood won't bet against him. "He can handle complexity like nobody else I've ever seen," says Lee Rowen, a University of Washington researcher whose work with Hood extends back to their Caltech days. "His strengths lie in the direction of reading trends, understanding where the action's going to be, and attracting people to his lab" to carry out the work, she says.
"[He chooses projects] on the basis of how
they fit into a much broader vision of where the science is
going," Galas says. But Hood manages to keep one eye on the technical
details. "He inspires people to solve small problems while he keeps
his eye on the larger vision."
Hood's current vision of biology's future - one that he sees the institute working to fulfill - is the study of networks. In the search for the genetic causes of diseases, for instance, most research has focused on a search for single altered genes. But the majority of genetic diseases are known to be more complex, with alterations to multiple genes raising a person's susceptibility, but not necessarily predetermining a disease condition. Transcriptional control, embryonic development, and environmental factors all almost certainly play a role in the onset of different conditions. In collaboration with the Fred Hutchinson Cancer Research Center, also based in Seattle, members of the institute will conduct large population-based studies of polymorphisms in genes important for immunity, cardiovascular function, cancer, and mental health. Armed with very high-throughput automation, the institute's researchers hope to untangle the roles of multiple "risky" alleles, and puzzle out the genetic mechanisms that drive inherited diseases. He even plans to set up a Web site where potential collaborators can read about the ongoing projects and evolving capabilities at the institute, and apply for assistance in tackling their own problems.
Grand plans, no doubt. But Hood has already seen his share of detractors through the course of his career, so he is unfazed. He sees it as just another mountain to climb: "I've always liked getting to the top of things."
Jim Kling writes in Washington State about science and the environment. His work has appeared in Science, Nature Biotechnology, The Scientist, and Popular Science magazine's Web site.
Endlinks
Web Sites mentioned in this column:
Department of Molecular Biotechnology, University of Washington - chaired by Lee Hood. The site details the department's history, goals, and educational outreach.
Leroy Hood Laboratory - research interests, staff, and publications.
Gene Chip Breakthrough - Fortune (March 31, 1997) magazine article detailing the commercial evolution of the DNA chip and describing how someday it may be used to guide breast cancer therapy.