Lee Hood, the visionary but often difficult biotech star lured by Bill Gates to the University of Washington, was about to jump ship — and to ask his backer for $200M to boot. It would not go well.

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Editor’s note: Excerpted from  Luke Timmerman’s book, “Hood: Trailblazer of the Genomics Era.”

Two weeks before Christmas 1999, Lee Hood appeared to have it all: A loving family. Money. Fame. Power. He counted Bill Gates, one of the world’s richest men, as a friend and supporter. Eight years earlier, Gates had given the University of Washington $12 million to lure the star biologist from Caltech in what The Wall Street Journal called a “major coup.” Hood’s assignment: build a first-of-its-kind research department at the intersection of biology, computer science, and medicine.

Even at 61, the former quarterback of an undefeated high school football team could still do 100 pushups in a row. He ran at least three miles a day. He climbed mountains. He traveled the world to give scientific talks to rapt audiences. Hood did indulge in a luxurious art-filled mansion along Lake Washington, but otherwise cared little for the finer things in life. Those who worked closely with him said he still had the same wonder and enthusiasm for science he had as a student.

Lee Hood

1986: Led the team at Caltech that developed first automated DNA sequencer prototype.

1980-2013: Co-founder of more than a dozen biotech companies, including Amgen (1980), Applied Biosystems (1981), and Seattle’s Rosetta Inpharmatics (1996) and Arivale (2013).

1991: Recruited by Bill Gates to the University of Washington to lead first Department of Molecular Biotechnology.

2000: Co-founded the Institute for Systems Biology in Seattle

2013:Won the National Medal of Science, with President Obama citing his “pioneering spirit, passion, vision, inventions and leadership” that led to “transformative commercial products and several new scientific disciplines.”

Source: Luke Timmerman

Yet here, at the turn of the millennium, Hood was miserable. Just as his once-controversial vision for “big science” was becoming a reality through the Human Genome Project, he didn’t feel like a winner. He felt suffocated.

He had a new vision, and felt the university bureaucrats who were in charge kept getting in his way. It was time for Hood to have a difficult conversation with his biggest supporter.

On a typically dark and gray December day in Seattle, Hood climbed into in his dinged-up Camry and drove across the Highway 520 floating bridge over Lake Washington to meet Gates, the billionaire CEO of Microsoft. Hood came to say he had resigned his endowed Gates-funded professorship at UW.

A new institute free from university red tape was the only way to fulfill his dream for biology in the 21st century.

Gates was well aware of Hood’s record of achievements and its catalytic potential for medicine. Hood led the team at Caltech that invented four research instrument prototypes in the 1980s, including the first automated DNA sequencer. The improved machines that followed made the Human Genome Project possible and transformed biology into more of a data-driven, quantitative science. Researchers no longer had to spend several years — an entire graduate student’s career — just to determine the sequence of a single gene. With fast, automated sequencing tools, a new generation of biologists could think broadly about the billions of units of DNA that held the instructions to make proteins that do the work within cells. Thousands of labs around the world — at research institutions, diagnostic companies, and drugmakers — used the progeny of Hood’s prototype instruments as everyday workhorses.

New technologies

Building on his success at Caltech, Hood recruited teams at the University of Washington that continued to create new technologies that enabled biologists to work through the next logical steps.

Hood certainly wasn’t the only biologist looking far ahead, imagining what these automated tools could enable. Once biologists had the full parts list of the human genome on their computers, many believed it would lead to greater understanding of disease, paving the way for precise diagnostics and, ultimately, “personalized medicine.”

But Hood had an unusually clear and far-reaching view for how biologists could fully exploit the new instruments. His enthusiasm inspired many bright scientists to devote themselves to his vision and to do their best work.

Not everyone bought what Hood was selling. Many people throughout his career saw a man who took excessive credit for discoveries made by others, including young scientists who toiled for him around the clock. Critics saw a self-promoting narcissist, someone who could be blind to the ways his actions sometimes hurt people.

He had contradictions: Influenced by his teachers, Hood was dedicated to youth science education his entire career, yet he did little to mentor his own graduate students. He had a big ego — an “unshakable confidence,” in his own words — but he was seldom arrogant or cruel, like many star scientists could be.

Passionate as he was about his vision, Hood could be strangely detached from the people he asked to carry it out. He thought he was entitled to special treatment, which frustrated university leaders. One subordinate described Hood’s management style as “creative anarchy.” He was quick to point the finger at others when things went wrong, while hardly ever admitting a mistake of his own.

Like many biotech entrepreneurs, Hood made promises he couldn’t keep. He predicted his work would lead to a personalized medicine revolution within a few years. It didn’t. Competitive to the core, he drove himself to stay at the cutting edge. That meant starting multiple projects at once, getting them operational, then leaping ahead to the next thing. He left the slow, painstaking, meticulous work of science to others.

Ever since James Watson and Francis Crick discovered the double helix structure of DNA in 1953, the world had been turned on to the promise of molecular biology. Scientists spent the last half of the 20th century drilling ever deeper into understanding one gene, and usually the one protein created by that gene’s instructions, at a time.

Yet at the start of the 21st century, Hood believed biology was ready for more ambitious goals. The time was right, he argued, for scientists to look at hundreds or thousands of genes and proteins together in the complex symphony that makes up a whole human organism with trillions of cells. Biology, like physics, had an opportunity to turn into “big science” — fueled by big money, big teams, and big goals.

The way to tackle such complexity, Hood said, was through what he called “systems biology.” It was a new twist on an old idea that involved bringing scientists together from various disciplines of biology, chemistry, physics, mathematics, and computer science. He wanted the power to recruit the right people to the University of Washington for this mission.

He wanted to choose whom to hire and whom to fire. He needed the flexibility to raise his own money from wealthy donors. If he wanted to out-license a technology for further development to a company, or start a new company, he didn’t want to ask permission. Hood demanded a multimillion dollar facility with enough room for all of his scientists.

As negotiations at the University of Washington dragged on, Hood realized he wasn’t going to get what he wanted. And university officials were growing weary with his entrepreneurial break-all-the-rules attitude. When officials suggested he had run afoul of a new state ethics law, Hood felt threatened and embittered. Abruptly, he quit.

For his final act, Hood wanted to be the boss. In his early 60s, he decided to give up his department chairmanship and tenured faculty position. He had to start his own research institute. It was time to put his money and his reputation on the line.

On that gloomy day in December 1999, Hood wanted to break the news to Gates in person.

Straight talk

The men sat down in a couple of comfortable chairs in Gates’s office in Building 8 at the Microsoft campus in Redmond. Hood got quickly to the point.

He’d resigned his endowed Gates professorship at UW because the bureaucracy of a public institution would never be flexible enough to let him achieve his goals for multidisciplinary systems biology. Hardly stopping for breath, Hood barreled through his long list of grievances with administrators who didn’t share his vision. In the same breath, he rhapsodized about the opportunity for systems biology.

The billionaire listened for a solid 15 to 20 minutes. When Hood had said his piece, Gates cut to the heart of the matter.

“How are you going to fund this institute?” he asked.

“Well, that’s part of the reason I’m here…” Hood replied.

Gates interjected.

“I never fund anything I think is going to fail,” Gates said.

Hood was stunned. He hadn’t expected Gates to commit on the spot to bankrolling a new institute. But he didn’t expect to be flatly dismissed. Gates was a kindred spirit, an entrepreneur, a fellow impatient optimist.

Years earlier, they had bonded on a safari in East Africa; Hood listened to Gates talk about the “digital divide” as hippopotamuses grunted in the night. The recruitment of Hood helped raise the University of Washington to international prominence in genomics and biotechnology during the 1990s. Given that success, Hood thought he could talk his friend into providing as much as $200 million for a new institute.

The harsh truth, for Hood at least, took years to sink in. Gates didn’t give his institute a penny in its first five years. Their friendship didn’t end, but the two men would never be quite so close again.

“I definitely disappointed Lee,” Gates said years later.

Reflecting on Hood’s split with the university nearly 15 years later, Gates took a nuanced view. He was intrigued by Hood’s new vision, but he also saw why he didn’t work well with others in the university.

“He’s a wonderful guy, but a very demanding guy. He’s kind of a classic great scientist,” Gates said. “These things are never black and white.”

Others who were close to the situation understood why the meeting had gone badly.

“This gift to the University of Washington to create Molecular Biotechnology was surely the biggest thing he (Gates) had done in philanthropy,” said Roger Perlmutter, a former student of Hood’s who went on to run R&D at Amgen and Merck. “It was all done to bring Lee here. And then in short order, it unravels? It was a kick in the teeth.”

If Hood’s first thought was that he had possibly damaged his relationship with his most important benefactor, his second thought was that his vision was right and he needed to find other support. He had some money already. Much of it was through his shares in Amgen, the biotech company he advised from its early days, and which went on to become one of the best performing stocks of the 1990s.

He also made millions from royalties on DNA sequencers sold by another company he helped start — Applied Biosystems. Hood had other wealthy friends and companies he could call.

There was a lot to think about beyond science. Even though he was hailed as one of biotech’s great first-generation entrepreneurs, Hood had never played an executive role in running those enterprises.

Now, he would have to act as a startup CEO responsible for not just vision and fundraising, but day-to-day operations. He knew he wasn’t a skilled administrator. He was impatient in meetings, lacked empathy, and made clear to all around him that he didn’t want to hear any bad news. He had a bad habit of avoiding sensitive personnel matters, like whether to fire people.

None of that deterred him. Hood had always overachieved, going back to his childhood in Montana. He craved the adulation of others. He always found it on the football field, in the classroom, the lab, the lecture hall, and the boardroom.

When people told him he couldn’t do things, he would grit his teeth, and prove them wrong.