Only seven years after publishing his first paper, Lee Hood was a big deal in biology. He had already become synonymous with studying antibodies, using the protein chemistry that was common then. The unusual thing about Lee was that he wasn’t afraid to embrace the engineering side of science. Bioengineering was barely a field, generally concerned with nutrition and plastic prosthetic limbs. “Genetic engineering” was a term hardly used, just before the dawn of recombinant DNA. In fact, “engineer” was not a term bestowed with glory or genius: it was around this time that rocket engineers renamed themselves “rocket scientists.” Young biologists who wanted to develop better techniques in the lab were destined to become lowly technicians. Lee was already beginning to change that. He was making it socially acceptable (and, to some of us, irresistible) to engineer instruments for biology.
I first met Lee around 1978, when he visited the Harvard BioLabs and gave a talk in one of our small conference rooms. He was obsessed with DNA cloning and sequencing, even though all of his work was in proteins. Lee had just published a paper in Nature that did little to dispel the fact that he was an outsider in the field of DNA, while those of us he was talking to in the room were quite familiar—including the ultimate insider, Wally Gilbert. But somehow you could already see that Lee had a very attractive vision for where DNA could go: automation. Not everyone shared his vision, of course. As a grad student in Wally’s lab, I had just written some software to read DNA sequences automatically using a drum scanner, and when I proudly showed it around, one person said, “Why do you want to automate reading? It’s the only part of DNA sequencing that’s fun.”
But Lee already knew very well why, and he steadily began working to bring his vision to fruition. Lee had a simply stated set of four goals: to enable the automated reading and writing of proteins and of DNA. His greatest contribution to biology was aggregating teams to accomplish these goals. By July 1984, he published a paper in Nature titled “A Microchemical Facility for the Analysis and Synthesis of Genes and Proteins.” It nailed three of the four quadrants. Two years later, the title of Lee’s June 1986 Nature paper beckoned with the term “automated DNA sequence analysis.” But, in his enthusiasm, he had oversold. I could not find any automation. The reactions and gels were done manually, the data came like chart recordings, and these were interpreted by pencil on the charts. Soon, however, collaborating with Applied Biosystems to commercialize a DNA sequencer, Lee nailed it. The quadrants were full. Yet the innovation continued: ink-jet printing of DNA arrays, next-generation sequencing, mass spectrometry for proteomics.
The enthusiasm Lee brings to biology spreads well beyond the engineering of instruments. He has helped establish more than a dozen biotech companies. He is happy to sit on companies’ scientific advisory boards, some of which we work on together: Genomatica, Complete Genomics, Cellular Dynamics, MyMercuryRisk, Nabsys, and AbVitro. He is passionate about P4 medicine: predictive, preventive, personalized, and participatory. He has established a standard for sharing data worldwide. And yet he still hasn’t forgotten about those coming up behind him.
Lee has for many decades helped create programs for teaching biology and biotech to high school students. He has written textbooks for undergraduates (which I used even if my courses did not assign them). When Lee first arrived in Seattle in 1992, he wanted high school students across the state of Washington to learn DNA sequencing hands-on. High school! Hands-on! How? Clearly not using the radioactive technique that was common then, nor using his own expensive invention, the ABI sequencer. Instead, he chose a nonradioactive version of my eight-year-old “genomic sequencing” method. I was stunned and thrilled. The most important thing to Lee was sharing his enthusiasm and encouraging people to participate. I would say that this still encapsulates Lee to this day.
George Church
Professor of Genetics
Harvard Medical School