Future Perfect -- Thanks To Bill Gates' $12-Million Endowment, Scientist Leroy Hood Continues His Search For A New Genetic Destiny

SOMETIMES PUBLIC DEFEATS OBSCURE more significant private victories.

So it was at the University of Washington on Nov. 10, 1990, when a chance conversation high above the Husky playing field proved to be pleasant salve to the pain of an unexpected 25-22 loss to UCLA that cost the Huskies any chance of a No. 1 football ranking that year.

Lee Huntsman, director of the UW's Center for Bioengineering, was sharing a luxury box with Bill Gates, the billionaire chairman of Microsoft. Huntsman seized the opportunity to tell Gates about a California scientist named Leroy Hood.

Hood's resulting recruitment with $12 million of Gates' money may one day far overshadow that unhappy football game. It could prove more important to the UW, to Seattle's economy, to the future of medicine, and, most of all, to you: It could help determine what you someday learn about your own genetic inheritance, and could save your life, or that of your children or grandchildren.

Knowing our genetic blueprints could also plague us with agonizing new choices. Will we want to know we are predisposed to certain diseases? Will we want fertilized fetuses screened for genetic perfection? Will genetic makeup determine who can get health insurance, pursue a certain career, land a job, run for office?

The Brave New World of the 21st century is just around the corner, folks, and one of its pioneers is coming to Seattle.

If Hood was unknown to nearly everyone in the football stands that day, in the field of genetic engineering he was one of the most famous scientists in the world: someone the UW had been trying to lure north for nearly 10 years.

As director of a large molecular biotechnology lab at the California Institute of Technology in Pasadena, Hood had overseen development of machines to identify and manufacture genes and in the process had revolutionized his field.

While most university biology labs average perhaps 10 scientists producing five or 10 research papers a year, Hood oversees a staff of more than 40 scientists in a lab that runs round the clock and generates important papers at a rate of nearly one a week.

Hood himself has co-written five textbooks in the field, is an editor of five professional journals, has written or co-written nearly 400 scientific papers, has received five honorary degrees, and has won virtually every significant scientific prize in his field except the Nobel.

Many thought he should have gotten that award, too, in 1987, when he shared the prestigious Albert Lasker Medical Research Award for discoveries in antibody diversity with Philip Leder and Susumu Tonegawa. Only Tonegawa got the Nobel for the same work.

And Hood is a key adviser and visionary in the federal government's $3-billion, 15-year program to decode human heredity, called the Human Genome Project. This is a gigantic undertaking expected to utterly transform health care in the 21st century by allowing scientists to combat more than 3,000 diseases that have been traced to genetics.

It was no secret that Hood was not entirely happy at Caltech and was open to the idea of moving to Seattle. Still, the university had neither the space nor the money to accommodate Hood's large laboratory.

So the chance of the UW landing a superstar like Leroy Hood - the kind of scientist who serves as a recruiting magnet for other top scientists, brilliant students, and generous grants, who in the words of vice provost Alvin Kwiram creates "critical mass" - seemed remote.

Unless someone like Gates stepped in.

Gates had never attended the UW, but his mother Mary is on the Board of Regents. Moreover, Gates was interested in Hood's field. He saw bioengineering as the other hot field of the future besides computers, and had invested $5 million in a start-up Bothell bioengineering firm called Icos, headed by George Rathman, who had previously run industry pioneer Amgen in California.

"He loves to talk to the scientists, loves to challenge us with his viewpoint," said Rathman of Gates. "I think he just figures the work is hellishly important."

Deciphering human genetics was in some ways a computational problem, Rathman notes, the kind of thing computers excel at. "Bill Gates just thinks this is the nicest mystery in the world, how the human body works."

Gates was intrigued by Huntsman's pitch at the football game, and subsequently met Hood for dinner. The two immediately hit it off: the software genius intrigued by genetics, and the biologist most famous for developing machines and pushing computers to automate his field.

Reading the genetic code is going to produce billions of bits of information that must be sorted and analyzed to be of any use. Humans can't do it, but computers can. "In 10 years, computers will be every bit as important to biology as chemistry," Hood would say later. The scientist gave three public lectures in Seattle, and Gates showed up for all three.

Almost a year after the UCLA game, in October of 1991, the bombshell was dropped. Lee Hood was coming to Seattle in the summer of 1992 to head a new department of molecular biotechnology, financed by the largest individual donation the UW had ever received, Gates' $12-million gift.

Some $3 million will be used for an endowment that will pay Hood $140,000 to $150,000 annually from its interest earnings. Another $3.5 million will be used for laboratories, $2 million for equipment, $1 million for office support, and $2 million in seed money for specific biotechnology research projects.

University officials were ecstatic. In football terms, it was as if the school didn't have Coach Don James and had just recruited him. Or better yet, as if it found a James and he brought a huddle of starters with him. At least 15 Caltech scientists are expected to follow Hood to the UW.

In economic terms, Hood's lab could become the seed to grow Seattle's next Boeing, or its next Microsoft. There are already about 50 biotechnology laboratories in the Seattle area employing several hundred people and ranking the city about sixth in the nation as a center of activity.

Hood is taking a pay cut to come to Seattle, gambling that here - at a hungry university with a rising reputation - he will find support for his vision of a marriage of biological research and computer technology. Collaboration between his basic researchers and the medical school staff "will produce something great," he forecasts.

"Some people in my field think my emphasis on computers and tools is overblown," Hood said. "I think they're wrong. History will prove them wrong."

His vision is to link basic science and modern technology for nothing less than explaining why you are you: how the genetic code in the union of egg and sperm produces a unique individual and spells out many of your future abilities and future diseases.

He is not shy about the significance of that. "There is going to be a change in the 21st century in how people do things and how they think," Hood said. "Biotechnology is going to change the world."

WHEN LEE HOOD SAYS HE WANTS TO change the world, he means changing your life, fundamentally and irrevocably. If the work that Hood and hundreds of other microbiologists are doing succeeds in letting us read our entire genetic blueprint in the 21st century, it could present issues and choices never known before.

The promise is the prevention or cure of cruel diseases, the curbing of disabilities, the realization of innate talents.

The perils come from misuse. Consider these dilemmas:

-- You are genetically predisposed to a ghastly, crippling disease. With prior warning, you can reduce your risk with diet or exercise, but not eliminate it. Do you want to know your possible fate?

-- The old joke about not being able to get life or health insurance unless you can prove you don't need it comes true. Sorry, an insurer or employer says, your genetic printout shows you are susceptible to a fatal disease that could hit as early as your 30s - even though it may never show up at all.

-- Instead of risking a pregnancy or abortion with a genetically flawed fetus, you are given the choice of test-tube fertilization, with the embryo screened for its genetic makeup before being re-planted in the mother's uterus. You artificially fertilize a dozen times before getting the mix of genes you want for your child.

-- In a similar vein, wealthy, well-educated parents screen their embryos for high intelligence, while the poor and ill-educated do not. In a few generations, an achievement gap opens between classes and races. Prejudices become cemented in genetics.

-- Hospitals that allow a genetically flawed pregnancy are sued for "wrongful birth." Or parents insistent on natural birth campaign for the right not to have an abortion of a genetically flawed fetus.

-- Suppose genes are discovered that indicate talents for skills such as music or art or athletics, or perhaps a predisposition for anti-social behavior? A 1988 Harvard study suggested a biological basis even for shyness. Do you really want to know your talents, or follow your heart?

-- A presidential candidate with a huge lead in the polls sees his campaign wrecked by the leaking of a genetic report of a predisposition in his family toward schizophrenia, or alcoholism.

These scenarios are not guaranteed. The point is that the implications of genetic knowledge are immense and only barely imagined.

The temptation to have "perfect" children may be overwhelming, even though many extraordinary people have achieved despite, or because of, handicaps. Julius Caesar had epilepsy. Abraham Lincoln may have had a growth disorder. Vincent van Gogh was insane, and several artists such as Monet may have had vision problems that allowed them to see the world in new ways. Goya may have been influenced by lead poisoning from his paints. Physicist Stephen Hawking has been a brilliant theoretician despite Lou Gehrig's disease, or perhaps in part because of his wheelchair confinement.

Would such people be weeded out in the genetic paradise of the future?

Hood is well aware of such concerns. "It doesn't do much good to tell someone they are going to have Huntington's disease if we can't do anything about it," he noted.

But that's the point, he added: Society can't let fears about genetic abuse overshadow its marvelous promise.

The promise involves shifting the entire emphasis of medicine from treating disease to preventing it. A genetic printout with a health plan could be delivered with a baby's birth certificate.

Such advances are still years, probably decades, away. Meanwhile, to turn our back on understanding would be the worst kind of miserable folly.

HOOD'S GOAL IS TO READ AND understand the genetic blueprint of that astonishing creation, the human body. After conception, that first fertilized cell has within it the information to grow an adult human. Its estimated 50,000 to 100,000 genes tell trillions of subsequent cells when, where and how to grow.

No one else has quite the set of genes you do. They color your skin and eyes, determine your height, help set your intelligence and likely control many of your talents.

And if some of your genes are flawed - if, in effect, there are typographical errors in your genetic script - you may eventually become seriously sick, or even die. Multiple sclerosis, cystic fibrosis, muscular dystrophy, diabetes, at least one form of alcoholism, Huntington's disease, Alzheimer's disease, schizophrenia, heart disease and breast cancer are just a few of the more than 3,000 diseases already tied to specific genes. Their presence doesn't always dictate you'll get sick, but they can make you more susceptible.

This blueprint is called the Human Genome. The Genome is composed of the 23 pairs of chromosomes in each of your cells, and the chromosomes in turn are composed of double-stranded DNA molecules. These molecules are "words" built out of a kind of four-letter "alphabet": four nucleotides called adenine, guanine, cytosine and thymidine.

There are an estimated 3 billion of these nucleotide letters. That is roughly equivalent to 13 sets of the Encyclopedia Britannica - 13 sets squeezed into each of your cells.

The significance of this is enormous. There, waiting to be read, is the recipe that controls our lives. But no one has read it yet.

By the early 1960s, less than a decade after the discovery of DNA, scientists were already talking excitedly about identifying specific disease-causing genes and then devising strategies to correct or get around them.

The tools available were frustratingly primitive, however. As a Caltech graduate student, Hood was forced to spend weeks trying to determine a small part of the amino-acid sequence of a single protein sample.

Cells are made of proteins, large molecules consisting of chains of amino acids arranged in a sequence dictated by the nucleotides of a gene. Analysis of proteins and amino acids is fundamental to finding and identifying genes.

Unfortunately, while biologists knew the experiments they wanted to do, they were hamstrung by the inability to get enough purified bits of cell material - proteins, amino acids, and genes - to do them.

"Basically, you had to be a good plumber," Hood said of the laborious process. A single mental lapse during weeks of work, or contamination by a particle of oxygen, could wreck an entire experiment.

Hood's mentor at Caltech at that time was an irreverent visionary named William Dreyer, who argued that progress in science was the result not just of great ideas, but of basic technology that allowed ideas to develop: such things as the microscope, accurate clocks, electricity and computers. Some scientists were offended by Dreyer's emphasis on technology leading to discovery, but Hood became an apostle.

In 1975, Hood assembled a Caltech team to build a protein sequencer, a machine that uses automated chemical analysis to determine a protein's structure. Hood compares it to a machine that snips one of a string of alphabet-marked pearls and examines each pearl to see what letter it is. The machine was like a booster rocket to microbiological research. A colleague named Jim Strauss had had to give up study of a virus because he couldn't collect enough purified protein under existing methods to do so; Hood's machine cut the amount needed from 25 milligrams to one.

By 1980, it was possible to do such work with 1/10,000th the amount of protein needed before.

Hood followed this with machines to synthesize DNA and protein, and with a DNA sequencer. As a result, biologists who once had to kill 1,000 mice to get enough protein to experiment with now need only one or two; a gene synthesis that once took 20 chemists five years to build can now be done by a technician using part of one day.

Ironically, Hood was turned down by 19 companies before he helped start Applied Biosystems to manufacture the machines. Costing from $40,000 to $150,000, they are now a standard part of bioengineering laboratories around the world, having sold from 600 to 1,200 copies each. Hood has poured all his royalties from these back into his lab.

Hood's machines helped make possible the biotechnology industry that, after hundreds of millions of dollars of speculative investment, is beginning to churn out drugs and new plant hybrids.

His lab has done far more than develop machines, however. It has worked on a safe vaccine for hepatitis. It helped discover a new kind of renegade protein called prions. It came up with a simple blood test to diagnose T-cell leukemia. It helped discover how the AIDS virus attaches to cells. It discovered that multiple sclerosis is caused by certain immugens.

HOOD HIMSELF NEVER SITS STILL. His planetary wanderings to spell out his vision of the marriage of biology and technology became so notorious in his own lab that his scientists kidded he was as footloose as a rock star. They printed up and donned "Lee Hood World Tour" T-shirts.

The scientist speaks so frequently because he is good at it, able to tailor a speech for audiences ranging from Nobel laureates to the lay public. He is an educator, an avid recruiter of bright students and an originator of a program to bring high-school teachers into his lab to give them a taste of the scale and pace of modern science.

Hood sleeps only four to six hours a night. When he had to commute to work in the Washington, D.C., area, he used the time when he was stalled in traffic jams to teach himself how to play the harmonica.

Most important, Hood shares a grand vision. While scientists have succeeded in reading and manipulating individual bits of the vast genetic encyclopedia, they want to read it all, cover to cover, 3 billion nucleotides long: the Human Genome Project.

Yet skeptics warn that biologists' reach still exceeds their grasp. The combined work of labs around the world is deciphering 100,000 nucleotide letters a week. At that rate it will take hundreds of years to get the job done. Hood's strategy is twofold: turn the grunt work of reading the code over to a new generation of machines, and the mind-numbing task of analyzing it over to computers.

He wants to mold hybrid scientists, Ph.Ds with degrees in both biology and some other discipline, such as computers. "These are the people in the 21st century who are really going to make a difference," he said.

And making a difference is what Lee Hood is all about.

"The most driven person I have ever known," describes one of his closest friends, UW physics professor Eric Adelberger. "He has an unquenchable drive to do things."

WHEN HOOD BECAME MONTANA'S second student ever to win the Westinghouse Science Talent Award, the highest science honor a high-schooler can receive, the school band in Shelby and many of his classmates turned out to greet the train as he returned with the prize from Washington, D.C.

One could joke that that was the low point of Hood's career.

Straight-A scholar. Student-body president. Editor of the yearbook. Actor. Debate team. Quarterback of a football team that went undefeated for three seasons and won its final championship game in a blizzard, 29-0.

"He was one of our best quarterbacks ever," recalled John Kavanaugh, a classmate who publishes the Shelby Promoter weekly. "Not so much for speed; he was just smart." In his senior year, Hood taught biology to his classmates.

Hood believes his small-town origins were an advantage. "When I left Shelby, I had the view there was nothing I couldn't do," he said.

Born in Missoula in 1938, the son of a Mountain Bell engineer and the grandson of a cowboy, Hood has retained the down-to-earth manner of a Montana native. "He even looks the same, the stinker," Kavanaugh said of the famous microbiologist who came to his 30-year class reunion.

Hood's face looks 10 years younger than his 53 years. His body looks 20 years younger. He habitually rises at 4 or 5 a.m., runs six miles several times a week, and for relaxation climbs mountains, scales cliffs and rafts rivers.

Ted Young, a UW biochemistry professor who is a longtime friend, recalled one particularly grueling hike in British Columbia in which everyone else in the party staggered into camp exhausted. Hood said, "Gee, guys, what are we going to do tomorrow?"

Hood credits his early success to his teachers, including one who insisted he attend college at a place he'd never heard of, Caltech. "Terrific teachers make the difference," Hood said. "If you want smart kids, get good teachers."

For his own children, Eran, 23, and Marqui, 21, Hood invented an imaginary science-fiction character named Harry Golden he told them stories about. Hood would put Golden in peril and his kids had to think of ways to extract him. "It taught them thinking skills," he said. Golden was the one who could talk about difficult subjects such as drugs and sex.

Hood married his high-school sweetheart. He met Valerie, who lived in Cut Bank 25 miles away, at a statewide drama and debate conference where he asked her to dance. Like everything else, she recalled, Hood was a good dancer.

They went to different colleges, but kept up what Valerie called a "postage-stamp relationship" over seven years. It was only when she was going to take a job abroad that he proposed.

During the engagement, Hood took her to buy a backpack. The couple had little money, and she hesitantly suggested that maybe she should try backpacking before buying one. The suggestion died. "I could tell by the look on his face that if hiking didn't work out, the wedding was off," she recalled.

For their honeymoon, Hood planned a 150-mile hike with five major ascents. Weather cut that in half with two ascents, but the sport got in Valerie's blood; the couple later climbed Mount Rainier together.

Hood still makes an annual outing with scientist friends to scale peaks and raft rivers from the Sierras to Alaska. What do they talk about? "The meaning of life," said Adelberger. "He's also witty and pretty good at repartee, though I'm a better joke-teller than he is."

As a student at Caltech, Hood was shocked to find his grades putting him in the middle of class rankings his freshman year, but soon worked his way to the top. "He worked much harder than I did," recalled Adelberger, who was his roommate. "He helped me work harder, and I helped him lighten up."

He earned a medical degree at Johns Hopkins a year ahead of schedule, then returned to Caltech as a researcher for the National Institute of Health. Except for a four-year stint at NIH in Bethesda, M.D., in the late 1960s, Hood has been at Caltech ever since, earning a Ph.D. in immunology.

Hood proved to be a good researcher but an even better visionary and leader. "He has two exceptional attributes," assessed Valerie. "One is to define really important problems, and the other is to describe these problems in ways people can understand. He finds the really important things to work on."

Over the years, Hood built a small empire of superb scientists, but became increasingly frustrated at Caltech's lack of a medical school or sympathy with biotechnology.

Then in 1990, a few months before that Husky game, a scandal erupted during what he calls "the worst period of my life." Two researchers in his lab, James Urban and Vipin Kumar, seemed to be making exciting progress toward curing multiple sclerosis in mice, and had produced three papers with Hood. Then it was learned Kumar had taken a research shortcut and fudged some data, while Urban had fabricated experimental results for work he had not yet done.

Hood ordered a Caltech investigation, immediately withdrew the three papers, ordered the research redone, and followed a letter of recommendation he had written for the two scientists with one warning potential employers of the investigation. "I've never had my integrity questioned," Hood said. "I'd run that lab for 20 years, and this didn't happen until year 19."

Most scientists, stung by recent media allegations of increasing fraud and misconduct in their profession, applauded Hood's swift crackdown.

But Eli Sercarz, a microbiologist at UCLA, complained in a letter to Science magazine in December that Kumar's career was wrecked for a naive mistake. Kumar declined to comment for this story. Sercarz, a longtime Hood associate, calls Hood "a world-class scientist of Nobel stature trying to do the best he can," but who he nevertheless thinks may have judged his underlings too harshly.

Some suggested the incident was evidence Hood was spreading himself too thin - that the kind of mammoth operation he had created is impossible for even a Lee Hood to police. Hood says he has tightened peer review of research in his lab, requires his scientists to keep scrupulous notebooks of their work, and doesn't intend to let a similar incident occur in Seattle.

Indeed, this mini-scandal seems unlikely to dog Hood. If the scientist ever becomes controversial to the lay public, it will likely be not over laboratory conduct but because of the ethical issues his research poses.

Hood receives a dozen offers a year to leave his lab and go into private industry. The last such offer would have increased his salary sevenfold. He turned it down, to come to the University of Washington. Why?

"The attraction was doing things you think will change the world," he said.