Leroy Hood and the tool-driven revolution in biology

The Galisonian view of science - named after historian of science Peter Galison - says that science is driven as much or even more by new techniques and instruments as by new ideas. Sadly most people have always placed theoretical ideas at the forefront of scientific revolutions, a view enforced by Thomas Kuhn's famous book "The Structure of Scientific Revolutions". But a study of the history of science shows that new tools have been as instrumental in opening up whole new areas of science as new ideas. In fact one may argue that ideas allow you to largely explain while novel tools allow you to largely discover new things.

From the viewpoint of tool-based science, scientists like Faraday, Rutherford, Woodward, and Lamb are as important as Newton, Dirac, Heisenberg and Pauling. To this list of tool-builders and users must be added the name of Leroy Hood. Hood is one of the most important pioneers of the genomics revolution. Seeing far ahead of most biologists in the 1980s when he was at Caltech, he invented four tools that were to revolutionize the theory and practice of genomics: the protein sequencer, the protein synthesizer, the DNA synthesizer and the DNA sequencer. At a time when most biologists positively looked down upon technology development and engineers, Hood blazed new paths in combining chemistry, instrumentation and biology. His tools not only allowed biologists to do things better, but allowed them to discover new things which they hadn't imagined before.

Luke Timmerman has written a valuable biography of Hood which would be of interest to anyone interested in the recent history of the gene. I picked it up encouraged by Keith's favorable review (http://omicsomics.blogspot.com/…/veteran-biotech-reporter-l…) and am glad I did. My only reservation is that Timmerman could have done a much better job embedding Hood's inventions in the bigger story of genetics and molecular biology. There were parts of the book where I thought the science could have been fleshed out much more, so if you are looking for a concomitant work of popular science along with a biography, this is not really it.

Hood's essential qualities were ingrained during a vigorous upbringing in rural Montana. His father was a peripatetic telephone engineer who did not give praise easily. He and Hood's mother taught their children to be self-reliant, resilient and hard-working. Throughout his career Hood has been a force of nature, displaying these qualities to an unprecedented extent and leaving behind some of his more talented competitors by sheer tenacity and dedication. As he recounts, the most valuable class for him in high school was not math or science but debating. He was also his high school's star quarterback. Even now, at the age of 75, he runs 3 miles every day and does a hundred push ups. He has also combined great scientific talent with a passion for public speaking and entrepreneurship; through these skills he has raised hundreds of millions of dollars from universities, funding agencies and wealthy philanthropists and made millions of his own. He has given generously to the cause of middle and high school education. No obstacle has been daunting for him, and by any of the usual metrics his career has been stunningly successful; as his website points out, "in addition to his ground-breaking research, Hood has published 750 papers, received 36 patents, 17 honorary degrees and more than 100 awards and honors, and has founded or co-founded 15 biotechnology companies including Amgen and Applied Biosystems."

Hood got his undergraduate and graduate degrees from Caltech along with an MD from Johns Hopkins. Caltech sought him out as an assistant professor right after graduation. Hood's early contributions were to immunology where he figured out the basis of antibody diversity. But soon he began to broaden his horizons and became one of the first biologists to truly appreciate the impact of new technology on biology. He had an amazing talent to spot big picture problems, drive himself mercilessly to crack them and recruit world class people to solve them. Using his unique skill set he built the first protein sequencer and DNA sequencer and licensed them out to the company Applied Biosystems. The DNA sequencer is at the very heart of the genomics revolution. Gene sequencing is no longer just a tool for faster and more efficient molecular biology, but it has transformed itself into a formidable instrument to explore stunning new domains of biology, from the creation of new organisms to the cracking of the genetic code for all kinds of diseases to the exploration of the world's biodiversity. Hood's work showed that not only can technology enable science but it can actually give rise to new science.

Unfortunately Hood's grand visions and the size of his lab and research projects (at one point his lab numbered more than a hundred people) soon ran afoul of Caltech's desire to stay a small, tightly knit school. Very soon he had a falling out with the faculty. One of his students who is now the head of research at Merck was then a professor at the University of Washington. He persuaded the medical school at UW to invite Hood for a few lectures. The chairman of the department in turn persuaded Bill Gates to attend those lectures. Gates who had started taking an interest in biology in the late 90s was entranced by Hood and immediately agreed to endow a $12 million dollar faculty position at UW for Hood. Hood's moved to UW was accompanied by breathless press releases proclaiming that his appointment was one of the most momentous events in the history of the university.

At UW Hood became the father of a new science: systems biology. He was no longer content to just explore genes and whole organisms, instead he wanted to bring about a completely unified view of biology by connecting atoms to molecules to cells, all the way to whole organisms and ecosystems. It was a grand vision, and one which only someone like Hood could pull off. Systems biology is now a mainstay of cutting edge biological science, bringing together biologists, mathematicians, computer scientists and other. But Hood got there first, being one of the first scientists to bring together interdisciplinary subject experts.

Sadly it was here that Hood's failings become clear, and Timmerman pulls no punches in narrating them. Hood was a big picture thinker, not a detail-oriented person. He left the day to day running of his labs to postdocs and research associates. More importantly, he was terrible at interpersonal relationships. He almost never took interest in his students' lives, never picked up the check when he "took them out" for lunch and regularly played favorites. He was not an unkind person, but he was simply too busy, driven to succeed and tone deaf to the everyday human relationships that make any endeavor successful. He was not above claiming credit for others' discoveries, not intentionally but because of his relentless drive to finish that simply left him clueless about such things. He rubbed people the wrong way at Caltech and UW and found even the generous support at UW insufficient for his systems biology vision. Predictably enough, when some of his key allies passed away, he had a falling out at UW too after he tried to sell them a plan for an independent new institute. Confident that his friend Bill Gates would fund it, he went to see Gates at Microsoft, only to be turned away with an icy dismissal (Gates: "I never fund things that I think are going to fail."). Undaunted, Hood poured $5 million of his own money into the institute. Personally too he faced a tragedy: his wife Valerie who he had married out of college succumbed to Alzheimer's disease.

Since then, the Institute for Systems Biology in Seattle has become a thriving research institute that is at the forefront of investigating both basic and applied genetics. Hood continues to be a powerhouse, crisscrossing the world giving talks about how biology is going to revolutionize human life. The system's research may or may not help discover new cures for important diseases, but what's more important is the vision and accomplishment of one man in achieving all that: Lee Hood. Hood is a fantastic example of what happens when passionate tenacity for a cause, a deep appreciation of the impact of technology on science, a passion for entrepreneurship and a relentless pursuit of the big picture come together to create an explosive mix. In the DNA sequencers that are humming softly in hundreds of thousands of industrial and academic laboratories and hospitals around the world, reading and rewriting the code of life, Lee Hood's legacy keeps humming on too.