In the quest for a better understanding of the human body, the automated DNA sequencer was a breakthrough innovation, giving scientists new insights into the hidden code of life.
The Caltech team that created that instrument was led by a charismatic and controversial figure named Leroy “Lee” Hood, who was later brought by Bill Gates to work at the University of Washington in Seattle. Eight years later, he left the university to launch the Institute for Systems Biology, which was recently acquired by Providence Health & Services, a Seattle-based healthcare group.
Lee Hood is the subject of a new biography, “Hood: Trailblazer of the Genomics Age,” by Luke Timmerman, a longtime biotechnology journalist and the founder and editor of Timmerman Report. Timmerman speaks with GeekWire’s Todd Bishop on this week’s GeekWire radio show and podcast about his experience working on the book, offering thoughts on Hood’s importance to the Seattle area and the world of biotechnology.
Listen to the discussion starting at 9:45 in the audio player below, and continue reading for an edited transcript.
Todd Bishop: What is the significance of Leroy Hood in science, technology and our understanding of humanity overall?
Luke Timmerman: Hood is a fascinating character and hugely important to our understanding of the last 50 years of biology. The reason he’s not a household name is partly because biotech is high science. It’s complicated, it is a bit hard to get across to a mainstream audience. I saw a character here who is just supremely driven and brilliant and complicated and flawed in all of the usual human ways, and I thought here is a person with an amazing story, it hasn’t been told in book form, and by gosh, if I do a decent job at this I could engage people in a human drama and convey quite a bit of interesting science along the way.
TB: One of the most interesting dramas you explore in the book is at Caltech, where Hood led a team that created a number of important instruments in biotechnology and genetics, but the most significant of those was the automated DNA sequencer. What is that and why does it matter so much?
Timmerman: This is the instrument that’s probably the most important thing in modern biology today. It enabled the human genome project, which gave us the first template of the digital code, so to speak, that makes up human beings. The subsequent improvements in those instruments have made it possible now to sequence an entire human genome, you and me, for about a thousand dollars in a day’s time. … Scientists can compare healthy people to diseased people in ways they could never even have dreamed of back when Hood started on this journey more than 35 years ago.
TB: What then can scientists do with that information? Are we talking about curing disease, preventing disease? What is the outcome of that kind of data?
Timmerman: It’s premature to say that. It’s more about gathering information and learning at this point, but there are some drugs that are based on this more fine-grained understanding of genetic differences that are approved by the FDA on the market and helping people with certain forms of cancer and other diseases.
TB: I understand that the International Space Station just took delivery of its first DNA sequencer?
Timmerman: Yes. People are even talking about putting DNA sequencers on a thumb drive.
TB: Was this an authorized biography of Lee Hood, or unauthorized? It is unvarnished, for sure — there are positives and negatives. You get the sense of the real character including, as you said, his flaws.
Timmerman: I approached it like Walter Isaacson did with Steve Jobs. He did many interviews over several years’ time with Jobs and got access to a lot of his papers. I made a similar proposal to Hood, which was exactly that — that I would need extensive access over a period of years, I would like access to his private and confidential papers, as well as all kinds of public records. I told him that I would speak to all of his friends and enemies and family and just try the best I could to understand the whole person, but at the end of the day it would be my editorial control. He would not have the right to approve or disapprove the book. He said that sounded good, that in fact doing it this way, it would be more likely to be widely read than if he were to do it some other way.
TB: What are his biggest strengths and his biggest weaknesses — his biggest drawbacks — as you reported on them?
Timmerman: He’s brilliant. He’s extremely driven, a very forceful personality. You know this, having interviewed him.
TB: Very charismatic.
TB: He’s got the eyes.
Timmerman: Yes. There’s an intensity there to that gaze. It’s unmistakable once you’ve seen it. He also has an extreme ego. He calls it an unshakable confidence, and that’s what it takes to compete at the highest level in science. When you’re out there doing things that people say can’t be done, haven’t been done, you have to find a way through that. That ego, that self-centeredness, that belief in oneself is both his great strength and his weakness at times. It alienates people sometimes.
TB: You tell anecdote after anecdote about that in the book, including one scene where he is essentially on stage talking about the automated DNA sequencer and he forgets to credit the collaborators who actually did the work in his lab, under his leadership. Was that just an oversight or was that something that he did on purpose, do you think?
Timmerman: I do think that was an oversight. I think he was caught up in the moment and not really thinking about those people. I think he was excited about the achievement and explaining it to a lay audience, but the people who did the work for years in his lab were understandably upset.
TB: You mentioned Walter Isaacson and Steve Jobs, and I know that inspired you to pursue this kind of biography of Lee Hood. Are there similarities between Hood and Jobs?
Timmerman: Yes, although I looked at Hood’s flaws as you alluded to, and I did not see anything along the lines of abandoning one’s own daughter. … I think Hood had that charismatic ability that Jobs had, that ability at times to exercise the reality distortion field to force people to suspend their skepticism and their disbelief to pursue that really audacious and big idea. They were similar in that respect.
TB: We were talking about what Lee Hood did at Caltech and the team there. He was then brought to Seattle through a grant from Bill Gates to the University of Washington. Tell us that story.
Timmerman: It’s really interesting. Gates, in those days — this is the early ’90s. He was in his mid-thirties. Remember he had the big glasses and the mop of hair? He was just starting to get interested in biology. He didn’t have any formal schooling in this subject, but he read about the DNA sequencer and the beginnings of the human genome project in the late ’80s and around 1990 he got interested. He saw computational possibilities here, that biology could become more like an information science. Then along came this guy Lee Hood, who could explain that whole side of biology in a way that he could understand and he could figure out how IT could work in this area.
TB: How did Gates end up funding Hood’s arrival in Seattle?
Timmerman: It’s a long and interesting backstory that I cover in the book. One of Hood’s former protégés was on the faculty here in immunology, a guy named Roger Perlmutter, who’s now the president of Merck Research Labs by the way. Roger had this idea that maybe he could help recruit Lee Hood from Caltech. He had heard that Hood was having some difficulties at Caltech. There had been a mutiny of sorts in the Biology Department against some of Hood’s empire building. There had been a fraud in Hood’s lab, so things were very difficult for Hood and he was starting to look around and thinking about where he might be able to spread his wings again and pursue a genomics dream. Roger Perlmutter seized that moment and planted the bug in many people’s ears in the UW administration, and they got around to enlisting the help of Bill Gates.
TB: We should say that fraud you mentioned, Lee Hood was ultimately responsible because he was overseeing the lab, but it involved a paper that he was not directly involved in, if I’m remembering that correctly?
Timmerman: Hood’s name was on the paper as the senior author, as the director of the lab, but he did not actually perform the experiments. … It was a lower level person, but he did bear the responsibility for everything that happened in his lab and it was a stressful time. He was not accused of any specific wrongdoing himself, but, again, it was a serious situation that he had to take care of.
TB: He came to the University of Washington and started essentially a new department here that’s at the intersection of biology and technology and computer science. That really was one of Lee Hood’s characteristics, was this systems biology approach that brings together different disciplines. Was the idea to put that into action at the University of Washington?
Timmerman: Yes. They didn’t call it systems biology back then in the beginning. They called it molecular biotechnology, but he did recruit a lot of people who were thinking about the next steps. If you’ve got all this information about the DNA, the genes, what’s next? Proteins. Those are the functional workhorses that come from the genes, do the work in the cells, so can we figure out in a more systematic way what the proteins are doing in the cell? Can we in a more automated way count particular cells, let’s say cancer cells or certain immune cells you might want to monitor? This is all about developing a more quantifiable form of biology, and that’s where you can lean on the strength of computing.
TB: Eight years later, Lee Hood goes to Bill Gates and says he’s done, he’s not going to be at the University of Washington anymore. He’s going to start his own institute. What happened? Why did he not work out at the UW?
Timmerman: Hood was used to a lot of flexibility at Caltech in terms of how he operated. If he wanted to order some supplies, he could just direct an assistant to go buy it, or if he needed to raise the money he would go give a talk to the little ladies who raise money in Pasadena, raise the money, and go out and buy that thing, and that’s just not how a bureaucratic state run institution operates. There are rules and procedures and he chafed under those rules and procedures.
TB: Bill Gates had brought him here with a $12 million grant and then Lee Hood went to him and said, “I’m done.” What did that do their relationship?
Timmerman: It created a rift, some tension. It didn’t cause them a falling out. They even to this day remain in touch and you could say are friends, but Hood expected or certainly hoped that Gates would continue to fund his ambitions at the new Institute for Systems Biology, and that never really happened.
TB: If I remember correctly, it took a number of years in the Gates Foundation until they made like a small grant, but it was pretty nominal in the scheme of things, especially when you compare it to what he did at the UW.
Timmerman: Gates could have created a much bigger type of institute here in Seattle around Lee Hood and he did not do that.
TB: Hood’s Institute for Systems Biology was just recently acquired essentially, although they use a different word. It became an affiliate of Providence. They’re the big health system here. What’s the story behind that?
Timmerman: You have to understand the finances. Hood started the Institute for Systems Biology with his own money back in 2000. At the time it was said to be from an anonymous donor. Well, that was him. Every since, for fifteen years, he’s been trying to raise money from various sources. He’s had some success, certainly in recruiting scientists who can win Federally funded National Institutes of Health (NIH) grants, and a couple of partnerships of note, but he’s always had to make payroll at the end of the day with his own funds, and that’s put a lot of financial burden on him. Now being part of a larger hospital chain, they can consolidate finances and relieve that personal financial burden on Hood.
TB: There’s also the issue of succession planning, which was always, I think, based on your reporting, a source of tension inside the Institute for Systems Biology. Now as part of Providence, that does not become as much of an issue I would imagine?
Timmerman: That’s right. Nobody wants to talk about it, but if he were to get hit by a bus, who would replace him? Now essentially that is somebody else’s responsibility at Providence to hire his replacement and keep the science going.
TB: What happens to the Institute for Systems Biology in all of this? Is it as impactful as it might have been on it’s own? Is it more impactful because they’re combining with another institution?
Timmerman: I think that’s very much an open question. Providence has a long history of clinical care, but not a lot of history as a scientific organization, so how are they going to deal with these people off in the corner who experiment on yeast? It’s a bit of a culture challenge for a place like Providence and the jury is out.
TB: In the meantime, the Institute for Systems Biology has spun off a number of startups, and the most prominent one of late is called Arivale. That is an effort essentially to offer personalized health and genomics testing to individuals. The idea is you go in and you have a personal coach and they review the results of your genetic testing and help you figure out how to adjust your approach and improve your health. What do you think of that startup and where is it headed?
Timmerman: It’s very ambitious. I think it may be a little bit ahead of its time, because the last I heard they were charging about four thousand dollars per person for this consult. That’s a lot of money. Most people just don’t throw that around for something that’s not going to be covered by their insurance. They may get some wealthy people who are curious and want to try it out to see if they can optimize their health and achieve what Hood likes to call “scientific wellness”. You can look at a person’s genome as well as things that change dynamically over time. The call it the metabolome. The metabolites that reside in your blood after you eat a turkey sandwich for lunch are different than if you ate a caesar salad. You can look at the genome, the metabolome, the proteins. They even take stool samples and you can look at your microbiome, the state of the microbes that live with you in your guts. Is there something really out whack there that maybe could be corrected pretty easily?
TB: There’s one story of a participant in the program who switched from, I believe it was tuna sushi to salmon once a week and that made a radical change in his health.
Timmerman: Yes. Scientists will look at this and say that’s not really science. It’s not really being done in the context of a controlled clinical trial. You can say maybe that switch of the turkey sandwich or the tuna sandwich did something for you, but there could be other factors that improved your health. That’s part of the challenge, the skepticism that Hood will encounter. He has to be very careful about not overstating what this can do for your health. Otherwise, he could be running afoul of regulators.
TB: As you look at Lee Hood and his legacy, how should people assess his impact?
Timmerman: He’s one of the most influential biologists of his generation and really of the last 50 years. The development of automated DNA sequencing, it’s one of the most important inventions in biology of that time period. It gave rise to the modern world of genomics and a more information intense and quantified version of biology. It’s really a remarkable transformation and he did as much or more than anybody else to set the wheels in motion. Getting this information on every biologist’s desktop, I mean it’s impossible to know where that will lead.
We are seeing some of the payoff that Hood and others talked about 30 years ago. There are examples of genetically tailored drugs for cancer that have been developed in just a couple of years and for small amounts of money, like twenty million dollars, and successful drugs. There is a long-term opportunity here to make drug development a little more predictable, a little less risky, a little more reliable in its ability to address some of these major illnesses, health challenges, but this is not going to happen overnight. This is a century-long quest. This is the guy who helped set the wheels in motion to make that happen.
TB: When people look at his contribution in the Seattle region in particular, is it a disappointment that he did not stay at the University of Washington or was he able to accomplish things that he wouldn’t have at that institution?
Timmerman: I think both were probably better off for having had their messy divorce, as I say. Hood went his own way and started his Institute, continued to start companies and did some good biology for a number of years, and the University of Washington has continued on in a very successful way in genomics.
“Hood: Trailblazer of the Genomics Age” is available for $19.95 as a PDF download via Timmerman Report. Readers can also place a pre-order for a signed hard copy, or buy the Kindle eBook edition. An excerpt is available at Undark.com.