Lloyd M. Smith

Born: October 3, 1954 | Berkeley, CA, UM

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. Smith attended the 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. 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. Working with Michael Hunkapiller on commercialization of his technology, he became a consultant for Applied Biosystems (ABI). 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. 

The information listed below is current as of the date the transcript was finalized.

			

Interview Details

Interview no.: Oral History 0407
No. of pages: 40
Minutes: 99

Interview Sessions

David C. Brock and Richard Ulrych
2 March 2008
New Orleans, Louisiana

Abstract of Interview

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. 

Education

Year Institution Degree Discipline
1976 University of California, Berkeley BA Biochemistry
1981 Stanford University hD Biophysics

Professional Experience

Stanford University

1981
Postdoctoral Fellow
1981 to 1982
Lecturer, Chemistry

California Institute of Technology

1982 to 1985
Postdoctoral Research Fellow
1985 to 1987
Senior Research Fellow, Division of Biology

University of Wisconsin, Madison

1987 to 1992
Assistant Professor, Analytical Sciences Division, Department of Chemistry
1992 to 1995
Associate Professor, Analytical Sciences Division, Department of Chemistry
1995 to 2010
Professor, Analytical Sciences Division, Department of Chemistry
1999 to 2001
Chair, Analytical Sciences Division, Department of Chemistry
2001 to 2010
Director, Genome Center
2003 to 2004
Chair, Analytical Sciences Division, Department of Chemistry
2006 to 2010
Chair, Analytical Sciences Division, Department of Chemistry

Honors

Year(s) Award
1977 to 1981

NIH Pre-Doctoral Trainee

1982 to 1985

NIH Post-Doctoral Trainee

1985

Chosen as one of Science Digest's Top 100 Innovators

1989 to 1991

Eli Lilly Analytical Chemistry Award

1989 to 1994

NSF Presidential Young Investigator Award

1994

Kazusa DNA Research Institute, Japan, Inaugural Speaker

1994 to 1999

H. I. Romnes Faculty Fellowship, University of Wisconsin-Madison

1997

Association of Biomolecular Resource Facilities Award for Development of Automated DNA Sequencing

1999 to 2004

WARF Kellett Mid-Career Faculty Researcher Award, University of Wisconsin-Madison

2003 to 2008

John D. MacArthur Professorship, University of Wisconsin-Madison

2005

American Chemical Society Award in Chemical Instrumentation

2008 to 2010

Vilas Associate Award

2008

Jay Goodwin Lecturer, Auburn University

2009 to 2010

Member, Faculty of 1000

2009

W. L. Hubbell Professor of Chemistry

2010

American Association for the Advancement of Science Fellow

2010

Pittsburgh Analytical Chemistry Award

Table of Contents

Early Years
1

Grew up in Berkeley, California. One of four children. Father a physicist at Lawrence Berkeley National Laboratory. Mother professor of mathematics. Attended public schools.

College Years
7

Attends University of California, Berkeley. Uncertain what to study. Takes sister's advice to study biology. Does well in chemistry. Declares major in biochemistry. Disappointed in biochemistry, tries physics. Loves physics. Undergraduate lab work in biophysical chemistry with Wayne Hubbell. Membranes. Synthetic chemistry. Nine months as technician in Hubbell's lab. Becomes very careful as technician.

Graduate School Years
13

Takes Hubbell's advice to study with Harden McConnell at Stanford University. Synthetic systems. Study of diffusion in membranes led to instrumentation thesis. Large number of papers as graduate student. Interest in immunology. PhD in biophysics.

Postdoctorate Years
18

Enters Leroy Hood's lab. Immunology and instrumentation. Huge lab. Months of sequencing. Fluorescence to label DNA. Works with Michael Hunkapiller at California Institute of Technology. Applied Biosystems (ABI). Chemistry of dyes. Becomes consultant to ABI. New understanding of relationship between academia and industry. Founds own company, Third Wave Technologies (now Hologic). Paper leads to article in Nature. Patents on invention. European vacation.

Faculty at University of Wisconsin
31

More and better sequencing. Competition from E. I. du Pont de Nemours and Company. Electrophoresis. Another laser system. Use of matrix-assisted laser desorption/ionization (MALDI) on nucleic acids. Array technology. Pyrosequencing. Affymetrix. Gene expression chips. Many genome projects led to diagnosis of problems with instrumentation, not chemistry. Electrospray; optical detection; proteomics. Surface invader arrays. Future of confluence of instrumentation, chemistry, and computation. All driven by computers and lasers. Parallelism. Informatics required to make sense of masses of data. Continuing importance of thinking.

Index
38

About the Interviewer

David C. Brock

David C. Brock is a senior research fellow with the Center for Contemporary History and Policy at the Chemical Heritage Foundation. As a historian of science and technology, he specializes in the history of semiconductor science, technology, and industry; the history of instrumentation; and oral history. Brock has studied the philosophy, sociology, and history of science at Brown University, the University of Edinburgh, and Princeton University.

In the policy arena Brock recently published Patterning the World: The Rise of Chemically Amplified Photoresists, a white-paper case study for the Center’s Studies in Materials Innovation. With Hyungsub Choi he is preparing an analysis of semiconductor technology roadmapping, having presented preliminary results at the 2009 meeting of the Industry Studies Association.

Richard Ulrych

Richard Ulrych was the director of institutional grants and strategic projects at the Chemical Heritage Foundation.