Twenty-five years ago I opened the newest issue of Science magazine and almost fell off my chair. A little-known scientist named Craig Venter had published a paper identifying hundreds of important human genes in one fell swoop using random DNA sequencing. Venter had seized the opportunity to road-test a prototype automated DNA sequencer — and he never looked back. It was a stunning validation of the potential power of automated sequencing, paving the way for the Human Genome Project.
The man credited for that disruptive technology — Lee Hood — doesn’t enjoy the same public profile as Venter or a few other pioneers in the genome arena. But over an extraordinary career (Hood turns 79 next year), Hood has left his mark on technology, science, and personalized medicine. Hood’s DNA sequencer was the lead guitar in a quartet of homegrown instruments he designed to sequence and synthesize the building blocks of both proteins and DNA.
Bill Gates, who lured Hood from Caltech to the University of Washington in Seattle in the early ’90s, likened Hood to the Pied Piper. Hood helped launch biotech companies including Applied Biosystems and Amgen; championed the field of systems biology; and was preaching personalized medicine long before it became fashionable. And now his remarkable journey finally gets the narrative it deserves. In Hood, biotech writer and Forbes contributor Luke Timmerman has authored (and self-published) a masterful guide to one of the most important scientists of the 20th century.
Timmerman’s story plays out in a straightforward sequence, beginning with Hood’s upbringing in Montana. Hood’s younger brother was born with Down syndrome, which might have played some role in steering Hood toward genetics research. Hood excelled in the classroom but found time for many outdoor pursuits, while his sturdy physique helped him shine on the football field. It is in this account of Hood’s early years that Timmerman’s otherwise meticulous reporting has its only lapse: He reveals that Hood starred in glee club … without further comment.
At Caltech, Hood attended lectures by the legendary Richard Feynman and Linus Pauling and played on the Caltech football team at the Rose Bowl. His research career flourished; key discoveries on the immune system he made at NIH earned him the prestigious Lasker Award.
Over a span of a few years at Caltech in the early 1980s, Hood’s research team transformed the life sciences and biotechnology by developing the aforementioned quartet of automated technologies to both sequence and synthesize proteins and DNA. Of these four, the “ultimate prize” — as Timmerman puts it — was to fashion an automated method for DNA sequencing. “I kind of knew it was important,” Hood recalled later. “I didn’t know it was going to be historic!”
Back in the mid-1980s, the world was using the dideoxy sequencing method invented by Nobel laureate Fred Sanger. It was a tedious process, relying on messy gels and radioactive chemicals. Hood tasked a “hotshot” chemist, Lloyd Smith, with leading the effort to automate the process. By attaching different fluorescent dyes to the four building blocks of DNA, Smith and his colleagues were able to read out the DNA sequence by using a laser to track the dyes as they progressed through the gel. This technology was commercially fine-tuned by Applied Biosystems, which rose to dominate the sequencing market for almost two decades. Michael Crichton paid tribute by using the term “Hood sequencers” in Jurassic Park.
But as with any successful, ambitious scientist, there were tensions. Smith and his colleagues were upset that their boss didn’t share credit at the triumphant 1986 press conference for the publication of the sequencing instrument in Nature. Smith reflected that Hood “wasn’t being vindictive, he was just wrapped up in the moment.” Hood’s constant travel distanced him from his lab — a point group members sarcastically made by printing “Lee Hood World Tour” T-shirts.
In the closing chapters, Timmerman discusses Hood’s prescient views on the future of health care. In a 1996 interview in the Los Angeles Times, Hood predicted that in 20 years’ time, “your entire genome and medical history will be on a credit card. You just put it in there [a computer] and a physician will instantly know what he’s dealing with.” While we’re not quite there yet, that vision is nowhere near as fanciful as it must have seemed at the time.
Almost a decade before the term “precision medicine” became cool, most notably with former President Barack Obama’s launch of the Precision Medicine Initiative in 2015, Hood was championing what he called “P4 medicine” — the four Ps being “predictive, preventive, personalized, and participatory.” By this time, Hood had made the agonizing decision to build his own research center, the Institute for Systems Biology (ISB), believing we needed a more data-driven, holistic approach to genetics, biology, and medicine.
Hood’s latest biotech start-up, Arivale, bears some similarities to Venter’s Human Longevity spinoff, Health Nucleus. Based on the 100K Wellness Project that originated at the ISB, Arivale offers a personalized “scientific path to wellness” in the form of a suite of genetic, proteomic, and microbiome assays designed to be conducted on an ongoing basis. (A 12-month program costs $3,499.) Hood’s own personal wellness program is going well: Motivated by finally analyzing his own personal genome sequence, Hood’s improved lifestyle and diet helped him to shed pounds, returning him close to his college football-playing weight.
In a fascinating epilogue, Timmerman reflects on Hood’s contributions to science in general and genomic medicine in particular. He points out that Hood, who attended the first workshop to discuss the feasibility of sequencing the human genome in 1985 (chaired by the University of California’s Robert Sinsheimer), could have been the perfect leader for the Human Genome Project. But circumstances and his perpetual restlessness conspired against him.
Hood is a splendid account of the life of a great American scientist, whose family looked on with pride as President Obama bestowed the National Medal of Science on him in 2013. The plentiful testimonials are instructive. The keys to Hood’s success? Sage Bionetworks co-founder Stephen Friend said Hood was like Tiger Woods in the zone: “It comes down to total faith, not an atom, not a molecule of hesitation.”