Valerie Logan had been the one who wanted to move to downtown. Whenever the family had moved in the past, Valerie took on the logistics with gusto. Hood could keep his eye on the science, as always. “Val had been the master organizer, the master doer,” Hood said. “She really enjoyed it.”
But this time she was flustered. She shied away from the work. Not only was she forgetful about where things were around the house, she didn’t know where to look. Hood made an appointment at a memory-loss clinic. Valerie got the grim diagnosis: Alzheimer’s disease.
Hood knew that meant a long, progressive decline. Slowly but surely, his wife would lose her memory, her personality, her ability to handle the basic tasks of daily living, even control over bodily functions. He also knew how little hope there was for treatment. It was heartbreaking.
Hood confided in his old college friend, Eric Adelberger, on a camping trip to the Arctic National Wildlife Refuge in the early 2000s. For the first time in many years, Hood wasn’t bending his friend’s ear with monomaniacal intensity for systems biology. He started talking to a friend as a friend—the way he had as a young man.
“Lee knew it was Alzheimer’s,” Adelberger said. “We had both felt that if we ourselves were to get Alzheimer’s, we didn’t want to go on living as if we were vegetables. We talked a lot. It was an open conversation, like the old days.”
Losing Valerie bit by bit was devastating. They’d met in high school. They both came from small-town Montana. They had shared values on the big things in a marriage—how to raise kids to be independent and to appreciate education. They loved the outdoors, traveling, and books. Valerie was vigorous and fit like her husband, sharing his zest for adventure. In their midfifties, they climbed Washington State’s Mount Rainier, going all the way to the summit at 14,409 feet.
In Seattle, Valerie threw her energy into science education work, overseeing a small staff at the Institute for Systems Biology that revamped K–12 science teaching strategies around the state. She mingled with the business community and helped Hood raise money for science education reform.
Most importantly, she was his confidant and emotional rock. She provided perspective. At times, she kept his ego in check. “She challenged me on almost anything she felt I was wrong about, or arrogant about,” Hood said. “She had no hesitation about doing that—sticking a pin in my puffed-up balloon. She was not a subservient wife.”
When Hood needed help navigating tricky interpersonal conflicts at Caltech and the University of Washington, Valerie was there for him. Sometimes she sat in on important meetings to help her intellectually brilliant, but emotionally dim, husband better read people.
Now, at dinner with friends, she couldn’t say much or follow the conversation. She became stressed in noisy situations. She struggled in unfamiliar places, unsure how to navigate the stairs when visiting her grandchildren in Alaska.
In 2005, Valerie’s decline was noticeable but not debilitating. By 2010, it was unmistakable. Hood needed to become something he’d never been in his life: a caregiver for someone else. He didn’t know what to do.
After Valerie was found wandering around dodgy parts of their Seattle neighborhood, Hood hired a part-time caregiver. But that was part-time. Hood needed to help his wife brush her teeth and take showers. Once, in the airport together, she lost control of her bowels. Hood shuddered at the memory. “I can’t deal with that sort of thing,” he said. For a man who fiercely valued independence, it was a hard concession to make. “He is so independent and so capable, he handles so many things himself,” his daughter, Marqui, said. “But [he] does realize it takes a family.” With much urging from friends and family, Hood hired full-time help.
More than anything else, Hood missed his wife’s companionship. She was the only person he could truly open up to about the hard moments in life, such as when Caltech’s biologists revolted, or when Bill Gates brushed off his systems biology dream. Hood was a resilient personality who could always pick himself up and charge ahead toward the next big goal. It was Logan who helped give him that strength. It shook him to the core when she wasn’t there. He reflected:
I’m psychologically pretty impervious to stress, in that I don’t let it get me down. I’ll tell you, the thing I feel most is an overwhelming sadness. I’m really lonesome. Because I spent a lot of time with Valerie. Those are the things I feel the most. . . .
There was a lot of stress in leaving Caltech. She knew all the details about that. There has been stress at various times of my life, and Valerie was always the one I could sit down and talk to. She didn’t always have answers, but at least she was sympathetic and responsive. She’s a very good listener. She cared, she was always sympathetic, and always an active problem solver. . . .
For a variety of reasons, the last few years at ISB have been really stressful. It’s been very, very hard not to have Valerie to talk to about all these kinds of things. It lets you decompress. Talking verbally is a good way to problem solve for me.
It also was hard, as a biologist, to be unable to help his wife. Scientifically, so many questions remained unanswered at the time of Valerie’s diagnosis that it was hard even to know the most promising angle of attack. Hood noticed that some Alzheimer’s patients appeared to have even more perturbed molecular networks in the liver than they do in the brain. It was a curious finding, which researchers don’t fully understand. “It’s a really hard problem,” Hood said. “What the networks are, how they get perturbed, which ones initially get perturbed, and how you think about ways to avoid that.” Some scientists thought the disease might, at an early stage, be more treatable with physical exercise and cognitive exercise. Hood was interested in prevention. In the early 2010s, he sought to find a group of signature proteins floating in the blood that might be telltale early warning signs of Alzheimer’s disease. But the work never bore much fruit. Alzheimer’s never became a primary focus of Hood’s research.
Few at the Institute for Systems Biology knew the pressure Hood was under at home. “At some point he circled the wagons, and inside the circle was Lee and Valerie,” Adelberger said. “He didn’t open up to anyone outside.” Instead, Hood turned to books for advice and solace. One was Still Alice, a novel by neuroscientist Lisa Genova, later made into a movie.
Hood said he didn’t want to make people feel uncomfortable. “I have really good friends here, but I don’t think they want to hear about my problems,” Hood said. “I think they enjoy me because I’m interesting and I can talk about science. People don’t want to talk about things like Alzheimer’s. It hits too close to us.”
Hood did see friends. He spent time at his retreat in the San Juan Islands with Tom Cable, a retired Seattle venture capitalist. Hood didn’t have a TV in his own vacation home. When he wanted to watch a football game, he’d go over to his friend’s house. The two men would unwind on weekends in front of the TV, cheering for the University of Washington Huskies and the Seattle Seahawks.
Hood made a new level of commitment to family. His travel schedule had been the biggest source of tension in his fifty years of marriage to Valerie. “She felt she was being cheated, and she felt the kids were being cheated,” Hood said. “In retrospect, I can’t argue with that at all. If I had it to do over again in life, I would have traveled a lot less.” He vowed to visit his granddaughters every month. That meant he would fly from Seattle to Juneau, Alaska, to see Eran and his daughters one month, and the following month head in the other direction, to Los Angeles, to visit Marqui and her girls. Hood was proud of his children. Eran was an avid outdoorsman and a hydrologist who studied glaciers in Alaska. Marqui became an anti-discrimination lawyer. Hood also thoroughly enjoyed the time with his grandchildren. He directed his assistant in the fall of 2012 to book the dates on his calendar two years in advance, to make sure he scheduled work trips around these visits.
As Valerie slipped away, Hood clung to his work. He didn’t realize that the Institute for Systems Biology was in danger of slipping through his fingers as well.
First, Ruedi Aebersold resigned. The cofounder and proteomics whiz left in 2004 to run a government lab in his native Switzerland. Officially, Aebersold and his wife said they wanted to be close to family. He had a generous offer. The Institute for Systems Biology had made it through the treacherous early years and wouldn’t collapse if a cofounder left. Aebersold further claimed that if he and his wife were going to retire in their home country, then they needed to move before they got too old to qualify for Swiss retirement benefits. “There was nothing that drove me away,” Aebersold insisted.
Unofficially, he had other reasons to leave. Aebersold saw an uncertain financial future for the institute, given its lack of an endowment. The Swiss government lab wouldn’t continually be scrambling for grant funding.
Like every other accomplished scientist, Aebersold also had an ego. He’d taken a big career risk to cofound the institute. Although he made significant contributions, he was forever destined to operate in Hood’s shadow. “When I tell people I worked at the Institute for Systems Biology, people say ‘Oh, you worked at Lee Hood’s institute,’” Aebersold said.
Louis Coffman was among many who urged Hood to take on the role of elder statesman. “I told him, ‘Lee, the sun has shone brightly on you for good reason, for good cause. It will set. Let it shine on someone else, like Alan [Aderem] or Ruedi [Aebersold]. Somebody,’” Coffman said. Hood couldn’t run the institute forever, and Aebersold was fifteen years younger. But as a reserved, introverted personality, Aebersold said he had no desire to succeed Hood and take on all the networking, fund-raising, public speaking, and media outreach that take time away from science. Hood wasn’t interested in taking a back seat, either.
Losing a respected scientist and proven grant winner was a blow. Hood only briefly tried to persuade Aebersold to stay. He never brooded over losses. “Lee is a very pragmatic person,” Aebersold said. Within minutes of hearing the bad news, Hood switched into problem-solving mode. “He said, ‘How can we make this a win-win?’ That’s what we tried to do,” Aebersold said. He was offered an honorific faculty title, and he remained cordial when informally discussing science with Hood and former colleagues at the institute. Hood was pleased.
Aderem was floored by Hood’s nonchalant reaction to the resignation of their cofounder.
“This is an opportunity,” Hood said.
“How the fuck is this an opportunity?” Aderem shot back.
Aebersold’s departure put more pressure on the institute’s junior scientists. They were not as well positioned to win competitive federal grants, the institute’s lifeblood. John Aitchison, one of the institute’s first scientists, remembers whipping together an application for a systems biology center in two weeks. Normally, that process would take six months. “We were writing grant after grant,” Aitchison said. “We were getting burned out.”
Donors still weren’t coming through with an endowment. The science was part of it. Systems biology was an abstract concept. You couldn’t put it on a bumper sticker, like “A Cure for Cancer.” It didn’t pull on anyone’s heartstrings. Even the most intellectually curious observers found it esoteric. “There were examples of [our] systems work in microbes or yeast,” Aebersold said. Hearing that, “a person like Bill Gates or someone else with a lot of money will start to go to sleep. Why should they put $1 million into figuring out how yeast processes glucose? It’s scientifically fantastically interesting, but is it something that’s going to make a big impact on someone’s life?” Donors couldn’t see it.
The funding situation, along with Hood’s age of sixty-six, stirred speculation about the future of the institute. Succession planning had been a casual topic of discussion almost from the institute’s beginning in 2000. Naturally, by Aebersold’s departure in 2004, the conversations had intensified. Some on the board argued that Hood was one-of-a-kind and it would be impossible to replace him. When Hood goes, the institute should shut down, they said. Others wanted the institute to endure. That meant grooming a successor, or multiple people who could shoulder various aspects of Hood’s role.
Getting the timing right, as board member Perlmutter put it, was a “high-wire act.” Organizations don’t want to wait so long that they’re caught flat-footed when the charismatic founder dies—as famously happened at Walt Disney Co. Organizations don’t want to reach for the hook too early either. Merck forced out its legendary CEO, Roy Vagelos, in 1994 when he reached the mandatory retirement age of sixty-five. The company then struggled, while Vagelos remained productive for two more decades, making important contributions at a pair of successful biotech companies, Theravance and Regeneron Pharmaceuticals. But let the leader linger too long, and organizations tend to lose younger, ambitious talents who don’t want to wait around for their turn.
Like Alan Aderem, the institute’s remaining scientific cofounder. “You can’t sit here and be the crown prince forever,” Perlmutter once told Aderem. The board, determined not to have another high-profile loss, urged Hood to create a succession path for Aderem. Aderem was given a seat on the board and elevated to the No. 2 position. The plan was clear. Aderem would continue running his own immunology lab, but he also would gain boardroom experience and handle internal management—which Hood was happy to unload. Hood would still lead the institute, craft the vision, and handle fund-raising and external partnership talks. Essentially, Hood would be CEO. Aderem would be the chief operating officer and heir apparent.
Aderem waited. And waited. When would Hood step aside? When I first asked him about retirement in 2002, when he was sixty-four, Hood said he planned to run the institute four to six more years. It was a reasonable thing to say to a local newspaper reporter. But by age seventy, Hood had no intention of riding off quietly into the sunset. He felt great physically. He wanted to keep going. He worked hard to dispel any notions people might have that his best days were behind him. “I’m doing the most ambitious things, by far, that I’ve ever done in my career,” Hood told me days before his seventieth birthday. “Right now.” His whole identity was wrapped up in his work, thinking about the future, being on the leading edge. The institute was an expression of everything he held dear. It was an expression of his values in science, education, business, and the transfer of knowledge to society. He had fought his entire career for the power to operate on his own terms. Finally, he had it. He couldn’t let go.
The man’s schedule remained relentless.
For his seventieth birthday celebration, at the swanky W Hotel downtown, more than two hundred people attended—including Irv Weissman of Stanford, George Church of Harvard, and Lee Silver of Princeton. Hood’s staff showed a series of tributes they’d videotaped. Most of them focused on Hood’s stamina. Software mogul Bill Gates, in his video tribute, said:
Congratulations on your seventieth birthday. I can hardly believe you’re that old. Your energy is amazing. I know in the next decade you’re going to achieve even more fantastic things. I feel sure some of your breakthroughs will make a difference to people all over the world, and I’ll do my best to make sure they get deployed. Keep up the good work. . . . I’m a big believer in the great work Lee is driving at the Institute for Systems Biology.
“He’s absolutely unstoppable,” Aderem said. “The guy’s a maniac.”
Hood worked an average of eighty-four hours a week—twelve hours a day, seven days a week—all the way through 2012, the year he turned seventy-four. He took home about $382,000 in salary that year, about $100,000 more than the next highest-paid officer. He was on the road almost every week, routinely logging more than fifty trips a year.
“I remember saying, ‘Lee, people come here to the institute to rub shoulders with you,’” Coffman said. “I remember once he was going off to a trip to Galveston [Texas]. I remember saying, ‘What on earth could possibly be going on in Galveston that’s more important than you being here?’. . . He was just going to give talks. He loved being in the spotlight.”
With Hood constantly on the road, the all-for-one, one-for-all start-up culture faded. The institute developed a revolving door, especially on the administrative side. Directors and vice presidents of fund-raising, operations, finance, and business development all came and went. Many arrived with sterling credentials, eager to work with a legend. They quickly found they couldn’t work with him.
For example, when Larry Herron, then vice president of fund-raising, sensed a donor was about to bite, he would lay out a follow-up plan designed to reel in the check within six weeks. He knew how much hand-holding philanthropists required. Hood usually thought that was unnecessary. He didn’t want to make multiple follow-up phone calls, especially for a small amount of money.
Herron also wanted Hood to create a long-range strategic plan. Many prospective donors liked Hood’s message, Herron said, but they were uncertain about the longevity of the institute, without a succession plan or even a well-written ten-year to twenty-year organizational plan. Hood felt a written plan would create constraints, making it harder to pivot to the next hot thing, whatever it might be. Nimbleness served Hood well scientifically. But potential donors interpreted it as being wishy-washy, lacking in commitment to the causes they held dear. “I remember telling him, these people are in demand all the time because they’re rich,” Herron said. “I’d say, ‘You’re one of the more intriguing people they’ll meet, but you’re hardly the only one. Why should they invest in a smart guy in Seattle who’s running an institute and can’t tell them what he’s going to be doing in five years?’ We had those conversations many times.”
Despite Hood’s general kindness, generosity, and loyalty to his employees, his tone deafness for people’s feelings was often the final straw. Herron recalled once being savagely criticized in a consultant’s report. The report said that fund-raising at the institute was a disaster and Herron should be fired. Hood, apparently without reading the report, distributed it among Herron’s administrative peers for review. Alarmed, Herron called the boss while he was traveling in China. Herron was proud of some fund-raising wins that occurred on his watch, particularly a $6 million donation from Bill Bowes, the California venture capitalist. He wanted to know if Hood agreed with the consultant’s damning summary. No, Hood didn’t. The boss told Herron he was doing well and should stay. Still, embarrassed by the episode and frustrated by internal conflicts, Herron quit a few months later.
The institute continued to lose money—sometimes millions of dollars a year—despite respectable grant support. With no big-name donor, Hood continued trying to forge “strategic partnerships” with foreign governments. His pitch went something like this: give the Institute for Systems Biology a lot of money and we’ll help create a biotech industry in your country—one that puts your country on the leading edge. Painfully, Hood had spent a lot of time and money in the early years of the institute chasing deals with various governments. Nothing had materialized. Finally, after seven years of talks, the government of Luxembourg bit.
It was a godsend. Then it almost brought down his entire institute.
Luxembourg, a tiny European nation few Americans could find on a map, was an odd place for Hood to emerge victorious. It was one of the few countries on earth he’d never visited. He didn’t know any scientists there. Luxembourg is a landlocked country smaller than the state of Rhode Island, bordered by Belgium, France, and Germany. The head of state is a grand duke. It’s the wealthiest country in the world based on per capita gross domestic product, as tallied by the International Monetary Fund, but the population is less than that of Seattle. The economy was dominated in the first half of the twentieth century by steel production, before Luxembourg diversified into financial services. By the time Hood was selling his concept of strategic partnerships and economic development, Luxembourg was looking to diversify again. An acquaintance from the consulting firm PricewaterhouseCoopers helped broker a meeting.
Money was no object. “You can ask for whatever you like,” the consultant said.
Hood asked for $100 million over five years. It was time to be bold.
The University of Luxembourg was then only four years old. In biology, “they had no idea what they were doing,” Hood said. Advisers to Hood were skeptical, given the string of failed partnerships elsewhere. “If you succeed in this, I’ll believe in the tooth fairy,” one institute board member said.
Unlike other places where decisions can die in committee, Hood said, he needed to persuade only one man—Jeannot Krecké, the country’s economic minister. Partly on the advice of PwC, Luxembourg found a couple of other top scientists, Lee Hartwell at the Seattle-based Fred Hutchinson Cancer Research Center and Jeff Trent at Arizona’s Translational Genomics Research Institute—to join the proposed collaboration.
There was no formal scientific review. The idea was for Hood and the Institute for Systems Biology to help establish a bioscience research center in Luxembourg that could spin off companies. Personalized medicine was the big idea.
Luxembourg was particularly intrigued by one development from the Institute for Systems Biology. It was a test that promised to detect lung cancer at its earliest and most treatable stage. The test needed only a small sample of blood to hunt for traces of signature proteins thrown off by tumor cells in the bloodstream. An initial attempt at commercialization in the United States had failed; the measuring devices weren’t sensitive enough. By 2008, the underlying technology had improved. Hood was eager to try again, and Luxembourg was ready to get behind it.
Luxembourg would invest in a company, Integrated Diagnostics, to commercialize the test. Hood rhapsodized that this application of personalized medicine would be the crowning achievement of his career. The data supporting the venture were thin, but it hardly mattered. Luxembourg had faith in Hood and his Midas touch. “Their whole motivation was about 90 percent economics and 10 percent science,” Hood said.
Talks moved fast. Hood negotiated without keeping his administrative staff in the loop, and the deal was basically complete by the time Hood presented the contracts internally. Confusion swirled. Hood didn’t see why this might bother his team. Any details that needed working out seemed minor.
In June 2008, Hood made the dream announcement. Luxembourg pledged $100 million over five years to the Institute for Systems Biology. Maybe Hood wouldn’t raise a philanthropic endowment, but this was the next best thing: a big pot of money with no strings attached. Within months, the financial crisis whipsawed the global economy, but Hood was riding high. When the Luxembourg deal was struck, the institute had fourteen faculty members, 230 employees, and an annual budget of $35 million. The budget leaped ahead to $55 million in 2009, enabling Hood to hire dozens more employees and begin outfitting a building twice the size, with room for 330 employees. People at the institute scrambled to figure out what to do with the loot. “It was like a moderately sized python engorging an extraordinarily large pig,” Herron said.
Almost immediately, infighting over the money turned nasty.
David Galas was put in charge of managing the Luxembourg collaboration. Hood had known Galas since the early days of the Human Genome Project. Back then, Hood was pushing the project, the Department of Energy was in the driver’s seat, and Galas was a well-placed official in the department. Galas went on to become the CEO of Darwin Molecular, the start-up cofounded by Hood that did well for investors Bill Gates and Paul Allen. When the company was sold, Hood hired Galas as a faculty member at the Institute for Systems Biology. The two had a close relationship—a friendship—for more than twenty years.
Luxembourg officials, ever mindful of economic development, wanted not just to support basic research at the Institute for Systems Biology—they wanted an ownership stake in some of the business applications that grew out of the research. That’s where things got murky for Hood and Galas. Both would serve as cofounders and officers of the for-profit spin-off company, Integrated Diagnostics. Simultaneously, both had responsibilities to the institute, which was a nonprofit. Both the nonprofit and the for-profit depended on Luxembourg cash. Hood and Galas were the ones in contact with the Luxembourg benefactors. People within the institute wondered: How could they strike a fair deal for the company and the institute when they were negotiating with themselves?
Hood shrugged off the objections, as he did many times throughout his career, saying the conflict was easily manageable, and he meant to do well for both sides. But a promise wasn’t enough. Even if the conflict of interest were effectively managed, there were legal governance controls and accounting issues that couldn’t be taken lightly. The nonprofit institute had loaned the for-profit company $288,000 during 2008, according to federal tax records. The company had physically set up shop within the nonprofit institute. It wasn’t entirely clear to many inside the institute how the money, say, for office rent, was being controlled, accounted for, and paid back to the institute.
Handled with great care and attention to detail, the situation could be managed. Handled cavalierly, it could potentially jeopardize the institute’s tax-exempt nonprofit status. That would be the death knell for an organization that lives on federal research grants.
The blurring of lines between nonprofit and for-profit, the confusion over who knew what, and who had the power to do what, raised concerns at the board level. Three respected trustees on the institute’s board—Steve Clifford, Jon Runstad, and Hank Riggs—resigned in rapid succession. Around this time, Perlmutter scaled back his involvement after becoming chairman of the board of his alma mater, Reed College. Perlmutter said he believed the conflicts of interest were manageable, if treated with care.
But Hood wasn’t careful. He had always seen big pots of money as “fungible” for any purpose he saw fit. He had always run into conflict with careful financial managers, had always made them nervous about audits. Hood could never bring himself to think in “columns and rows” on spreadsheets, as Perlmutter put it. Hood wasn’t paying attention to how Galas managed the money, either, or the simmering internal conflicts over the money.
“He’s a true visionary. He sees the future very clearly. Sometimes he’s not so good in the present,” Perlmutter said.
The board resignations were kept quiet; few on staff knew. What couldn’t be hidden was that a culture of team spirit had been eroded by fear, suspicion, and the emergence of rival factions. Aderem clashed bitterly with Galas over the money. Aderem, who had raised $97 million through federal research grants during his decade at the institute, was so nervous about how the Luxembourg money was being handled that he vowed not to take any of it (although his lab moved into the nice new building along with everyone else).
Galas worked closely on the partnership along with his wife, Diane Isonaka, and another institute scientist, Joseph Nadeau. There were no peer reviews and no clear system for prioritizing which projects got funded and which didn’t. Some good research did receive funding, including important work by Hood’s team to sequence the genomes of a family with a rare disease called Miller syndrome. But many scientists in-house were concerned at what they saw as an overly subjective funding process. The thing looked like a private slush fund, at least to those in the Aderem camp.
Months went by before Hood began to sense that something was amiss. A longtime scientific ally, Eric Davidson at Caltech, thought Hood suffered from a certain gullibility and naïveté about human nature. Hood had a tendency to remain loyal, he said, to people who ultimately stabbed him in the back. Each time, he didn’t see it coming. “Some of this is from the cultural and social history of the Midwest,” Davidson said, referring loosely to Hood’s small-town upbringing in the northern plains of Montana. “Valerie is the same way. Out of that grows a lot of do-gooder attitudes. If you want to take a broader point of view, how often do people who are trying to do good end up being betrayed by the people they are trying to do good for? It happens all the time. He has that streak. It’s caused him untold troubles.”
At the suggestion of his finance chief, Jim Ladd, Hood asked for an independent review by an experienced organizational psychologist. The review went on for more than a year. The psychologist found an institute split into factions, built-up animosity, impatience, and thwarted ambitions of those who saw themselves as the rightful successors to Hood. The leader had serious blind spots about what was happening around him.
With the help of the organizational psychologist, Hood began to look in the mirror. He surprised many close colleagues by showing some humility. He took the unusual step of accepting responsibility for his mistakes, acknowledging that his actions, or lack of actions, helped create a combustible situation. He admitted he should have been “more cynical,” seen the personnel problems coming and nipped them in the bud. “That was a major failing on my part. No question,” Hood said. But it was too late.
Alan Aderem had had enough. Not only was he disturbed by the Luxembourg partnership, but he could clearly see that Hood—even at age seventy-two—wasn’t going anywhere. In 2011, Aderem accepted an offer to become the president of the nonprofit across the street: Seattle Biomedical Research Institute, later renamed the Center for Infectious Disease Research.
Aderem’s exit was a body blow. Aderem took forty people with him, along with a $7 million grant from the Bill & Melinda Gates Foundation. Aderem said he was still a friend and admirer of Hood. But now he could advance his own ideas on how to apply systems biology. Aderem, a native of South Africa, wanted to use the computational tools of systems biology for global health purposes, like vaccines for the developing world. Hood was wedded to his broader concept of personalized medicine.
“Alan has wanted to assume a leadership role for some time,” Hood said, “and I’m not ready to step down.”
But Aderem and his team’s departure was only the beginning.
Within a year, half of Hood’s administrative staff was in open revolt, threatening to resign unless he fired Galas, Isonaka, and Nadeau over their handling of the Luxembourg money and some angry outbursts over petty issues, like the paint scheme at the new office. A board member urged an internal investigation, which revealed a series of e-mails that Hood interpreted as insubordinate. Hood dreaded firing anyone—especially friends whose wedding he had attended—but he couldn’t ignore the open revolt. The situation was so heated that lawyers stood at Hood’s side as witnesses during the trio of terminations, as personal belongings were picked up and hauled out. The institute was thunderstruck by the chain of events.
The Luxembourg collaboration wasn’t renewed. The partnership’s scientific director, Rudi Balling, said Luxembourg officials had gotten what they wanted in the five-year term. With the Institute for Systems Biology’s help, the country had set up its own systems biology center with thirteen researchers and 180 employees. Nearly two hundred published papers described the scientific work in Luxembourg. The new center no longer needed mentoring; it could stand on its own. Despite the tensions, the partnership had been successful.
It wasn’t until this point, in the fall of 2012, that Hood voluntarily brought up succession planning. He was seventy-four.
In seeking to replace high-caliber scientists like Aebersold and Aderem, however, Hood was in a tough spot. By this time, Hood’s reputation as a self-absorbed demigod tended to repel the best scientists. Weissman, the Stanford biologist and Hood’s lifelong friend, was among those who said Hood began to attract second-rate people. Working with Hood meant sublimating one’s own ego, taking a back seat. Many top people weren’t interested. Hood could recruit scientists with certain kinds of skills, but no one with the whole package. The institute was struggling not only with the lack of a $100 million endowment, but with an annual deficit of about $5 million—also not attractive. During a period of financial strain, and some uncertainty about the institute’s long-term prospects, Hood had merger talks with a couple universities. He wanted to see if they would essentially take over the institute, financially support it, and keep it in Seattle. That never got beyond the talking stage. Getting a world-class successor at the freestanding institute, he said, hinged on his ability to make the job attractive. That was going to be difficult.
Hood, of course, was as excited as ever about his vision for personalized medicine. That always got him going in the morning. Systems biology laid the building blocks for “predictive, preventive, personalized” medicine. By studying whole networks of genes and cells, physicians could see when someone was at risk of disease and starting to fall out of molecular equilibrium. They could act much earlier, before symptoms became too severe. Treatments could be tailored for the precise molecular defect in the individual. Hood later added a fourth p, for “participatory”—“P4” medicine, for short. Public participation was essential. Large numbers of patients would need to volunteer to contribute blood, saliva, or tissue samples so that scientists could map out human biological networks and then compare them from one person to the next.
Hood delivered his gospel-like message via presentations that contained little hard data. Many biology peers dismissed it as salesmanship and sloganeering. Hood struck a few modest partnerships, including one with Ohio State University. He didn’t disrupt the American health-care system. Mark Davis, the Stanford biologist and former student whom Hood tried to chase down in the T cell receptor race, in early 2013 said:
The P4 thing, it’s such bullshit. It’s not helpful. It pains me to say that, because I admired his intellect and worked with him in a great period of his professional life when he made his reputation. But in recent times, I think he maybe got too impressed with himself or found he could get by being this sort of vague visionary.
Most serious scientists don’t pay much attention to him anymore. He doesn’t say anything we don’t already know.
Health economists, health insurers, and policy makers also were unimpressed, for different reasons. Personalized medicine promised to be expensive, just as policy makers were seeking to corral health-care costs. Hospitals were usually unwilling to share samples with scientists, partly out of concerns about legal liability and patient privacy. They were in the habit of tossing out samples in the medical waste. It was hard to imagine they’d suddenly start encouraging people to participate based on some futuristic notion of the greater good.
Hood, ever the optimist, switched gears.
It was the summer of 2013, when the lucrative Luxembourg contract was due to expire. President Barack Obama had recently presented him the National Medal of Science, with his family there to share in the moment. The institute’s culture had stabilized. The time was right to reimagine the future of the Institute for Systems Biology.
He would embark on a breathtakingly ambitious wellness study.
The idea was vintage Hood: inspiring in scope, far beyond the capabilities of existing technologies, and way too expensive for any one person or agency to bankroll by itself. The idea was to enroll one hundred thousand people, sequence their genomes and follow them for twenty years. The ultimate price tag of such a project, to the extent it could be estimated at all, would surely run into the tens of billions of dollars. As usual, he started with an intoxicating vision. He could fill in the details on the fly.
He dubbed it “the Framingham study of wellness.” The project, drawing inspiration from the monumental six-decade heart study of health-care workers in a small Massachusetts town, had an even more audacious aim. The hundred thousand people would be asked to give blood, saliva, and stool samples every three months to track a litany of other molecular markers that fluctuate over time and might signal the onset of disease. Patients would be informed of any warning signs so they could change their behavior and see what difference it made.
Yet again, this was to be the big achievement of Hood’s life, his true legacy. The first year alone, with just 108 healthy volunteers, was quite doable. It was estimated to cost $2.5 million. Hood had no firm commitments to finance the rest of the study. Yet.
Hood hadn’t lost his entrepreneurial streak. While raising money for the rigorous scientific wellness study, Hood simultaneously worked to start a for-profit company that would do a cheaper, more modest form of wellness monitoring for consumers. That sort of thing was beyond the pale for many peers in biology, who consider wellness to be in the realm of the hucksterism seen on late-night TV infomercials. Hood risked a late-career embarrassment akin to Linus Pauling’s obsession with vitamin C. Hood knew it. “Wellness is kind of a schlocky, semicommercial, questionable-reputation kind of thing, and it’s been around for some time,” he said. “We plan to insert quantitative scientific analysis into it and provide it with real measurements.”
Hood himself joined the 108 original volunteers. Within months, he declared it was both a scientific and personal revelation.
Through the early years of genomics, Hood never bothered to get his own genome sequenced. Scientists such as James Watson and Craig Venter did. By waiting for the technology to improve, Hood knew his genome sequence would be cheaper and more accurate. The information would be interesting personally. But how could it advance science? The way, he realized, was not to look at his genetic code in isolation, but to compare it with that of three generations of Hood family members. Because family members share so much DNA, researchers are able to compare the genomes and focus on differences that count. Hood’s lab had already successfully sequenced the genomes of a family of four with the rare Miller syndrome. Researchers were able to identify the genetic cause of the disease: exciting. Equally important, the work, published in 2010, was the first to demonstrate the usefulness of sequencing a whole family. This was a stirring finding. It showed how by gathering interesting data, you could turn it into practical medical knowledge.
In August 2013, Hood gathered about thirty of his family members at the Montana ranch near the Bitterroot River. All gave blood samples that could be sequenced in a large study. By looking comparatively at families with similar genomes, Hood was hoping to narrow the search for medically interesting variations, including some that get passed down through inheritance. Complete Genomics, a sequencing company in the San Francisco Bay Area on whose board Hood sat, agreed to sequence the genomes for $1,500 apiece. To protect family members’ privacy, Hood kept the only master list of names identifying the samples. They sit on a piece of paper in a secure location, to avoid any possibility of computer hacking, Hood says. “I’d like to write a series of papers on this as a classic study of a family,” he said.
So Hood had his genome. He added the battery of the tests from the wellness study. Hood found he had deficiencies in vitamins C, B1, and B12. These were at least partly caused by genetic mutations that made it more difficult for him to get the recommended daily allowance. He was able to correct the deficiencies by taking high-dose supplements. He learned a bit about the genetic basis for his risk of cardiovascular disease (his great-grandfather, grandfather, and father all died of heart attacks before the age of seventy). Based on the flood of wellness data he gathered over time, Hood made some significant lifestyle changes. He continued to do his set of more than one hundred push-ups every morning, along with sit-ups and stretching exercises. Now he increased his exercise routine from twenty minutes to about seventy-five minutes a day. That included time on weight machines and treadmills. He greatly reduced carbohydrates from his diet, and he all but quit eating dessert when going out for dinner. He started sleeping seven hours a night, instead of his usual five to six hours.
The results, Hood said in the fall of 2014, were spectacular. On the verge of turning seventy-six, he said he felt the best he had in years. As if he’d found his own fountain of youth. He shed thirteen pounds, getting down to 180, and wanted to drop about five more to get back to his college football–playing weight.
Hood was so fired up about the potential for this sort of quantitative, data-driven approach to wellness that he entertained notions of making a pitch to Congress to fund a ten-year wellness project that would dwarf the Human Genome Project. “The preliminary analyses are just revolutionary,” Hood said. “I’ve gone around the world and country. Everywhere I’ve gone there is enormous enthusiasm for this. I’m thinking very seriously of taking this project to Congress and making it a second genome project. I could go to Congress and say, ‘Look, I can promise you more with this project than I ever could with the genome project.’” Such grand notions ignored the partisan gridlock in Congress. Not to mention the long-term trend toward cutting biomedical research budgets rather than increasing them.
Hood also butted up against wide and deep skepticism among biologists, physicians, statisticians, and regulators. They widely believed that much of the wellness data being gathered was trivial or meaningless. They wanted to see clinical trial results.
The established players had reason to be skeptical. Sure, an individual could have beneficial experiences based on wellness data, but they could get that benefit from any number of changes: eating more fruits and vegetables, or sleeping eight hours a night. Without rigorous controls in a study, scientists couldn’t say for sure what effect any of those changes might be having. In testing new drugs, scientists have learned that blinded clinical trials can wipe away most of the bias from physicians and patients in a study. Nobody knows who is getting the new health intervention being tested, whether it’s a drug or something else. Patients are randomly assigned to a new drug or a placebo to further reduce the effect of other factors and help researchers zero in specifically on what the new intervention is doing. Conclusions are reached based only on the results of many, many people who got either a new drug or a placebo. That’s the gold standard of medical evidence that physicians use to make decisions.
Doctors had spent years moving away from anecdotes and gut feel and toward this more statistically rigorous form of evidence-based medicine. The problem with those randomized clinical trials, for Hood, was that they dealt in medians and averages. They couldn’t say precisely how a given treatment would affect an individual. Some people might get tremendous benefit from a new treatment, while others wouldn’t be helped at all. And yet the focus would be on the median or the average. Evidence-based medicine was certainly better than gut feel and hunches, Hood agreed. But still in many respects, it amounted to generalized recommendations and prescriptions that weren’t well tailored to individuals.
To Hood, that wasn’t good enough. Every individual patient was genetically unique. If a study with three thousand people was N of 3,000, this would be N of 1. Traditionalists scoffed. Medicine had a long history of getting carried away with excitement over anecdotal successes that couldn’t be repeated. But Hood argued, and some scientists agreed with him, that the new data-heavy form of biology made it possible for individual patients to serve as their own study control, to filter out biases. For example, the physician would take a wide range of measurements at the beginning of a study, perturb the patient’s organ system with a new drug or supplement, and see how it changed the body’s molecular profile—before symptoms emerged. The new biology produced huge amounts of data, making it possible to measure changes at the molecular level and to connect those changes with observable, and clinically meaningful results, like a reduction in disease symptoms.
Hood chided skeptics in the medical profession, the pharmaceutical industry, and the Food and Drug Administration for being slow to embrace the new tools of science and the emerging forms of data analysis. “They’ve lived the old-fashioned way,” Hood said. “They need to start thinking in new ways. N-of-1 experiments are going to become important. This is enormously controversial. But I guarantee you, I’ve been right in the past, and I’m going to be right on this one.” Still, the big federal grants didn’t materialize.
The for-profit wellness monitoring company found a friendlier reception. What if you could package a complete genome along with other changing quantitative measurements of health—from blood, saliva, and stool—and throw in some wellness “coaches” to help consumers interpret the data and make appropriate lifestyle changes? So the US government didn’t want another top-down, Human Genome Project–type revolution. Maybe this could be a bottom-up, consumer-driven revolution.
Maveron, the venture capital firm cofounded by Starbucks mogul Howard Schultz, had shown special aptitude for investing in start-ups that tapped into consumer attitudes and desires. They were interested. Other venture capitalists were, too. By July 2015, the company, called Arivale, raised $36 million to bring “scientific wellness” to the masses. For $2,000 apiece, early adopters could get the same program that Hood said had changed his state of wellness. At that price, the company lost money on each test. Within a few months, Arivale raised the price to $4,000 a person. Consumers who wanted the test would have to pay out of pocket—insurers wouldn’t cover it.
Hood wasn’t the only major scientist gravitating toward wellness in the 2012–13 period. He couldn’t help but wince when he saw other high-profile biologists beat him to the punch with big ideas. Google offered former Genentech CEO Arthur Levinson, a distinguished scientist, a blank check to pursue life-extension research at a company called Calico. Craig Venter raised $70 million in March 2014 for a start-up called Human Longevity—double what Hood’s company raised.
Retirement? Hood continued to keep up a schedule that would wear out men thirty years younger. By February 2013, Hood was serving as a board member for thirteen for-profit and nonprofit organizations. He simultaneously sat on scientific advisory boards for sixteen other companies and organizations. (“I learned almost as much from my interactions with companies as I did from interactions I had at scientific meetings,” Hood later told a reporter at the Scientist.) At age seventy-five, his curriculum vitae—which included all of his peer-reviewed papers, awards, guest lectures, and company affiliations—stretched to an astonishing seventy-five pages. His contemporary Irv Weissman’s was thirty-three pages at that time.
Privately, though, Hood started to feel the effects of aging.
He talked with friends about what it’s like to slow down, to feel more aches and pains. His posture stooped. His chin would often tilt down, giving him the appearance of a battering ram. A hand tremor, which had been a minor nuisance for years, became more noticeable. Although he had a reputation for taking catnaps during seminars, Hood appeared to sleep longer and more deeply during science talks later in his career. One scientific collaborator said Hood once fell asleep in an important meeting with high-powered pharmaceutical executives.
Mortality began to loom.
There was his wife’s slow fade. By early 2014, after many talks within the family, Hood finally agreed: it was time for Valerie to go to a home where she could get round-the-clock care. The family picked a comfortable assisted-living facility in Seattle’s Madison Valley neighborhood, about a fifteen-minute drive from Hood’s condo. “I have all sorts of feelings,” Hood said shortly afterward. “One, I feel guilty that I’m not going to take care of her and provide a home. Two, we’ve been married fifty years. I haven’t lived by myself for a long time. I’m going to spend a lot of time visiting her.” To recognize his wife’s long-standing commitment to science education, Hood made sure that his institute’s Center for Inquiry Science was renamed the Logan Center in her honor. An annual community fund-raiser for the cause would be done in her name, not his.
Hood’s father had died at sixty-nine of cardiovascular disease. He was deeply shaken when, one day in the fall of 2015, his longtime Caltech peer and friend, Eric Davidson, died suddenly at age seventy-eight.
For all that, Hood had some of his happiest moments in these years with his grandchildren. Although he didn’t climb mountains anymore, he was in good enough shape to get down on the floor and play. Marqui, who had some difficult times with her dad as a teenager, became closer to him. She spoke with joy about how the world-class scientist in his seventies could show up at her house and forget about everything for a few hours to be a grandfather.
When I was small, one of my strongest memories was playing tickle monster with him. He’d get on his hands and knees and chase us until we’d become hysterical. A lot of memories are so salient to me, because I have the experience of watching him do this with my kids [ages three and five] now.
He has an element of being able to be in the moment and have immense enthusiasm for what’s going on in that moment. . . . It makes him a great grandfather.
The Arivale-inspired changes also got Hood feeling more optimistic about his longevity. Nearing his seventy-seventh birthday, Hood said he felt so good that he imagined staying active well into his nineties. A year earlier, he had pegged it at eighty. He looked to Francis Crick as a model of how a scientist could remain productive to the end. Crick—the codiscoverer of the DNA double helix and one of history’s most influential biologists—spent his final years studying neuroscience at the Salk Institute in San Diego. There he remained a creative and influential thinker into his eighties. Hood had visited Crick in San Diego just a couple months before he died in 2004, and the two had a stimulating conversation about how systems biology might help crack some of the tough problems in neuroscience. “The only thing you could notice is that after a few hours, he got tired,” Hood said.
Most longtime friends and colleagues couldn’t imagine Hood ever riding into the sunset gracefully. “He’ll die on some trip looking for accolades,” said Eric Adelberger. “From my point of view, it would be sad. It would be nice if he could somehow become more open to more things. Appreciate his life. Be reflective.”
After seeing many succession plans fizzle, Aderem said Hood would simply work on science and business until he physically couldn’t. The Institute for Systems Biology didn’t grow into a powerhouse with twenty-five faculty-led research groups, as Hood once envisioned. By early 2016, it had nine faculty-led research teams. Fund-raising was a constant battle in an era of demoralizing federal research spending cuts. The institute subleased some excess space at its South Lake Union headquarters to a branch of Northeastern University.
Then, Seattle real-estate mogul Dave Sabey, a director of the institute, had an idea. He was friendly with Rod Hochman, the CEO of Providence Health & Services in Seattle. Providence was also a health-care network, like Kaiser Permanente. It operated by collecting insurance premiums from members and providing care through thirty-four hospitals and six hundred physician clinics spread across five states: Alaska, California, Montana, Oregon, and Washington. The Providence network had eighty-two thousand employees—doctors, nurses, physician assistants. It was the third-largest US nonprofit health-care system.
Sabey knew that Providence had an interest in making a splash in the genomics and personalized medicine world. He brokered a meeting with Hood.
Providence was an unusual match for Hood at first glance. It was a fully integrated, nonprofit Catholic health-care system. It had a far-flung group of donors deeply committed to its mission of providing top-quality health care, including to indigent people and those in rural areas. The organization had no scientists, and few connections to Hood’s realm.
What Providence did have was money. The Patient Protection and Affordable Care Act—commonly known as Obamacare—shouldered many expenses for the care of uninsured people. Before, Providence had paid the bills for uninsured health care out of charity care accounts. Now revenue surged 16 percent in a year, and it had $5.8 billion in cash reserves.
Flush with cash, Providence needed to figure out how to put its money to productive use. As Obamacare tightened the screws on reimbursement rates, hospital chains merged to achieve greater economies of scale. In this new world order, the hospital chains sometimes marketed themselves to the public and to donors based on factors other than their quality of care. Some pitched their access to cutting-edge technologies and research prowess.
In Seattle, the University of Washington Medical Center did everything from research in the petri dish all the way through patient care. Virginia Mason Medical Center, another major Seattle hospital, had a long affiliation with the Benaroya Research Institute. There, across the street, scientists could do cutting-edge research and collaborate with physicians who treated patients. Here was a chance for Providence to brag about the same.
Providence could tap its powerhouse network of donors in five states and offer them something tantalizing and new: the possibility of helping to realize, through research, a grand vision for personalized medicine.
Eventually, for Hood, Providence was a match made in heaven. The financial strength of Providence was almost irresistible. It could provide the sort of financial stability he could never achieve on his own. “For fifteen years, I have struggled every single year to make payroll,” Hood told me in early 2016. No longer would the institute live in fear that it would dissolve.
Equally important, Hood hit it off with Hochman, a physician by training, not a finance guy or lawyer like some hospital CEOs.
They struck a deal. Providence essentially acquired the Institute for Systems Biology. Financial terms weren’t disclosed. The arrangement, technically an “affiliation agreement,” allowed the institute to remain a freestanding 501(c)(3) nonprofit organization, with its own board, but with financial results consolidated under the umbrella of Providence. Hood would become a Providence employee, with the title of chief science officer for the network. The institute, as always, would have to continue to recruit strong scientists who could find grant support for their research. Providence would provide the cushion where grants fell short. It also would consider funding projects that were too speculative for peer reviewers at the NIH.
And Hood would have not one boss, but two.
Hood said he could live with that at this stage in his career. They assured him that he would retain his operating autonomy and that bureaucracy would be kept to a minimum. “They have their red tape. Every large organization does,” Hood said, reflecting on the deal a few weeks after it was announced. “I think I’ve wired my reporting so I can deal with it.” He spoke of spending more time on science and less time traveling the world in a fruitless search for partnerships.
Overnight, Providence delivered the financial ballast that made the institute more attractive to potential scientific recruits. Hood’s first wish: double the institute faculty, which he had wanted to do for years but couldn’t afford.
The Arivale program also got a boost. Providence agreed to study its own health-care workers to see what secrets the genome, blood, saliva, and stool held about improving their health.
And Hood turned again to Alzheimer’s. He wanted to look at several hundred genetic variations, to determine what puts people at risk of developing Alzheimer’s. Then he would track people over time, evaluate a variety of changes to their behavior and lifestyle, and see whether symptoms could be delayed. Such ideas had been sitting on the shelf at the institute, waiting for funding.
Aderem, the cofounder of the Institute for Systems Biology, marveled at how the man remained a fountain of ideas—some good, some not so much—into his late seventies. Succession planning was not among them.
With his intense gaze, Hood looked ahead. He brimmed with enthusiasm: exciting scientific ideas awaited. The Hood legacy would not be charted or planned. Hood would continue to follow his scientific instincts wherever they might lead. Younger scientists were welcome to join him on the journey. There just wouldn’t be a carefully plotted passing of any torch.
“Lee’s succession plan,” Aderem said, “is death.”