When 150 attorneys and staffers from a Seattle law firm arrived at a local club to hear a luncheon speech in October, they were clearly out of their depth. Most hadn't gone beyond high school biology, and here they were, about to be addressed by a leading expert on molecular biotechnology. Yet when Leroy Hood finished, the crowd was bubbling over with enthusiasm for the potential of human genetics research. "He communicates his own excitement," says William H. Gates Jr., a partner at Preston, Thorgrimson, Shidler, Gates & Ellis.
Gates should know. Last year his son, William H. Gates III, co-founder and CEO of software star Microsoft Corp., gave the University of Washington $12 million to recruit Hood and endow a new department of molecular biotechnology. Its goal: create faster, more sophisticated technology to decipher the volumes of information held in human genes and to apply that knowledge to solve problems in biology and medicine. "Computation," says Hood, "is the future of biology."
TWO-FISTED EXPERTS. Hood, 54, has a golden chance to prove it. Gates, an avid biotech investor, knew Hood's work even before a uw official approached him in late 1990 about providing an endowment to recruit the scientist. Then at the California Institute of Technology, Hood was itching for a chance to create his own department and direct interdisciplinary research. Gates's donation clinched the deal, and last October, uw announced the lab. It opened this September, with an annual budget of $5.5 million in federal research grants and a staff of 43, some 24 from Caltech alone.
"Camp DNA," as Hood's staff calls it, will train PhDs in molecular biology to be proficient in computer science, engineering, math, or applied physics. "We want to train biologists who will develop new tools and ways to apply them," says Hood, who believes that only dual experts can design the ever-faster machines needed to decipher DNA. Beyond that, some $2 million of Gates's grant will fund young scientists' projects that are too early-stage or risky to win government backing.
Hood sees more than money in a tie-in with Gates. Until recently, biologists versed in computers have developed most of the software for gene sequencing, the process for deciphering genes. But the escalating complexity of genetic research requires higher-skilled programmers. "People like me should no longer be doing this," says Tim Hunkapiller, a biologist who is Hood's chief computing expert. Hood wants to explore ways his scientists and Microsoft's researchers can collaborate on the software needed to run the equipment his team plans to invent--and analyze the mountains of data created by gene sequencing.
GENE READER. Such big visions are routine for Hood. While at Caltech in the 1980s, he invented a machine that automatically sequences DNA--or reads the codes of human genes responsible for everything from hair color to cancer and heart disease. That $100,000 instrument now is standard equipment in genetic research. In all, Hood's lab developed 15 instruments using computers, robots, sensors, and chemical analyzers to automate tasks in biotechnology. Over 22 years, his Caltech group spawned four companies, including Applied Biosystems Inc., which sells the DNA-sequencing machines his lab invented.
Sequencing machines, the cornerstone of modern genetic research, essentially unravel the order of the four constituent-base molecules, known as G, C, A, and T, that make up genes. The machines use fluorescent colors to mark the bases: red, green, blue, and yellow. A computer then "reads" the colors, identifying the order of the bases within the genes. This helps scientists understand the function of the 4,000 or so genes on any one of the 46 human chromosomes. It also makes it possible to create tests for genetically based diseases, some 3,000 of which already have been identified. And it's crucial for developing therapies to correct genetic defects and for designing genetically engineered drugs. In short, "DNA sequencing is the future of medicine," says J. Craig Venter, a former researcher at the National Institutes of Health and founder of the Institute for Genomic Research in Maryland, which has a $70 million sequencing contract with the federal government.
Problem is, current technology is so slow that it would take $6 billion and 10 years to decipher the 3 billion bases contained in just one set of human chromosomes. Given the cost and time, the ability to "sequence larger segments of DNA in less time" is critical, says George B. Rathmann, chairman of Icos Corp., a Seattle-based biotech company.
That is just what Hood intends to do. In two years, he plans to unveil a machine that will be 20 to 50 times as fast as today's devices. In the longer term, Hood's group is exploring "nanofabrication" to speed up gene sequencing. This would involve putting 100 to 500 gene fragments on a tiny chip, using biosensor techniques to read the DNA structure, then feeding this information into a miniature computer for processing. Such a system could decode in a third of a day the amount of genetic material it now takes a year to unravel, says Hood.
GENOME PITCHMAN. Hood's grand plans don't surprise those who know him. With a PhD from Caltech in biochemistry and a medical degree from Johns Hopkins University, he has won renown for his research in understanding human auto-immune diseases. That work earned him a prestigious Albert Lasker Medical Research Award in 1987. And in 1990, he located the site of one of the genes that predispose people to multiple sclerosis.
Hood is hardly an ivory-tower academic, however. He is one of the most effective pitchmen for the controversial Human Genome Project, a $3 billion effort in the U.S. to identify all human genes. He constantly promotes the potential of genetic manipulation to improve the human condition by giving at least one speech a week, testifying before Congress, and appearing on national TV. "Hood is seductive and engaging," says Arthur L. Caplan, director of the University of Minnesota's Center for Biomedical Ethics, who thinks Hood glosses over negative impacts of genetic screening and other ethical issues. "He is someone I have to be wary of."
Although he works tirelessly for his cause, the Montana-born Hood still finds time for his original love, the outdoors. The grandson of a cowboy, he spent his honeymoon on a 120-mile wilderness climb in the Sierras. And he periodically braves the perils of mountaineering to climb peaks in Washington, British Columbia, and Alaska.
CATCHING FLAK. Hood exercises his penchant for risk-taking at work, as well. He sees huge potential for a company that can sequence genes quickly and inexpensively for the federal government and drugmakers. Frederick Avery Bourke Jr., a Connecticut businessman and philanthropist, has pledged to deliver most of the $50 million investment for a Seattle-based company that he and Hood plan to found within six months. Theoretically, a sequencing assembly line might even let doctors routinely analyze genes of patients. The startup also would decode genes with commercial potential for the diagnosis and treatment of disease.
Hood will face plenty of competition in these endeavors. Three other laboratories, including Los Alamos, the European Molecular Biology Laboratory in Heidelberg, Germany, and one at the University of Wisconsin are trying to develop faster sequencers. And if the sequencing company gets off the ground, it, too, could find rivals in other startups and existing biotech companies. In fact, the would-be company has already run into flak. Bourke touched off controversy earlier this year when he tried--and failed--to poach two top researchers from the Human Genome Project to head the new company. Now, he's looking for a chief executive plus several top scientists for the company, along with commitments from instrumentation, automation, and software companies to develop technology.
Neither the competition from other labs nor the risks of a startup daunt Hood's backers, who think his track record, expertise, and financial support almost assure uw's lab--or any company he founds--of a head start. "He'll be one of the people who'll lead the way to dramatic advances over the next 10 years," says Microsoft's Gates. Seattle's biotech community seems certain of that. "Lee Hood," says icos' Rathmann, "is an incredible catalyst for good things."
HOOD'S AMBITIOUS AGENDA Hood developed the pioneering automated equipment that sequences, or identifies, fragments of DNA, thus helping scientists uncover the functions of the 50,000 to 100,000 genes in the human body. He has just lured 13 top scientists to a new department at the University of Washington to develop the next generation of machines BASIC SCIENCE Hood's team will try to solve mysteries in human biology, such as the genetic basis of human development and the immune system Hood will provide seed money to young researchers and graduate students for projects too embryonic, or far-fetched, to qualify for government funding TECHNOLOGY Hood's team will develop a machine to "read" DNA that is 20 to 50 times faster than today's devices SPIN-OFFS Hood expects to start a company that will sequence DNA for the federal government and for biotech, drug, and other companies DATA: BW