Oral history interview with Lloyd M. Smith

  • 2008-Mar-02

Lloyd M. Smith grew up in Berkeley, California, one of four children. His father was a physicist at Lawrence Berkeley National Laboratory and his mother a professor of mathematics. Lloyd attended the Berkeley public schools, which he says were excellent. He developed no overwhelming interest in any of the sciences until he was a student at University of California, Berkeley. There he liked biology, chemistry and physics and chose to major in biochemistry. He worked in Wayne Hubbell's lab, studying membranes and synthetic chemistry. On Hubbell's advice he enrolled in graduate school at Stanford University, entering Harden McConnell's lab to work on diffusion in membranes, obtaining his PhD in biophysics and publishing nine papers. Now interested in instrumentation and in immunology, he accepted a postdoc with Leroy Hood at the California Institute of Technology. During months of sequencing he thought up the first fluorescence-based automated DNA sequencing instrument, thus combining his love of physics with his love of biology and chemistry.

Working with Michael Hunkapiller on commercialization of his technology, he became a consultant for Applied Biosystems (ABI), learning first-hand of the complications of relationships between academia and industry. With what became the seminal paper describing his work accepted for publication in the journal Nature, he spent several weeks in Europe.

Smith accepted an assistant professorship at the University of Wisconsin, eventually becoming Director of the Genome Center and Chair of the Analytical Sciences Division in the Department of Chemistry. There Smith developed another laser system for sequence analysis and began the use of matrix-assisted laser desorption/ionization (MALDI) on nucleic acids. He also founded his own company, Third Wave Technologies. He discusses such new methods as array technology; gene expression chips and Affymetrix; pyrosequencing; electrospray; and proteomics. He explains how parallelism has enhanced Moore's Law, and the roles of computers and lasers as drivers of all these innovations. He revels in the confluence of instrumentation, chemistry, and computation. Though he acknowledges that informatics is now required to make sense of the huge volumes of data enabled by technology, he emphasizes the continuing need for thinking.

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