Lloyd Smith Receives the ABRF Award

The ABRF Award for Outstanding Contributions to Biomolecular Technologies was presented during ABRF '97: Techniques at the Genome-Proteome Interface on February 11, 1997 in Baltimore, MD. Dr. Lloyd M. Smith received the award for his outstanding contributions to the automation of DNA sequence analysis. The ABRF Award is made possible by the generous support of the Hewlett-Packard Corporation.

 

Each year the ABRF Award recognizes outstanding contributions to the development of instrumentation or methodology in the biological sciences. This award is part of our commitment to recognize the central role that methodology plays in the discovery process.

 

This year, the fourth ABRF Award honored Dr. Lloyd M. Smith, who pioneered the development of automated, fluorescence-based DNA sequence analysis. Dr. Smith studied biochemistry at the University of California at Berkeley before obtaining his Ph.D. in Biophysics from Stanford University in the laboratory of Harden McConnell. After moving to the California Institute of Technology to work with Leroy Hood, he conceived the idea of using fluorescence detection to enable automation of the sequencing process.

 

Because there was no suitable chemistry available at that time, Dr. Smith had to invent a new chemistry for this purpose. He synthesized a derivative of thymidine that possessed a suitably protected aliphatic amino group at the 5' carbon position, as well as a phosphoramidite moiety at the 3' hydroxyl. Use of this derivative in the terminal addition of solid-phase oligonucleotide synthesis left a reactive amino group, which could be coupled to a set of four fluorescent dyes to generate primers for enzymatic sequencing reactions. He developed a prototype instrument that automated the electrophoretic separation and detection of the fluorescent reaction products, and he designed and built a novel fluorescence detection system, suitable for excitation at two wavelengths and emission measurements at four wavelengths. Using this apparatus, he proved the principle of this four-dye fluorescence-based automated DNA sequencing approach by obtaining sequence data for the M13 bacteriophage, published in a seminal paper in Nature in 1986.

 

Although Dr. Smith worked to effect commercialization of this technology, he decided to remain in an academic environment. In 1987 he joined the Chemistry Department
ABRF Award, presented at the ABRF '97 Meeting, February 11, 1997, Baltimore, MD. Shown left to right are: Dr. Jerome Bailey, Senior Research Scientist, Hewlett-Packard Co.; Dr. Lloyd M. Smith, Awardee; and Dr. Ruth Hogue Angeletti, President, ABRF. Photograph courtesy of Ron Niece.
of the University of Wisconsin, where he continues his work as a world leader in the development of advanced DNA sequencing technologies.

 

The impact of Dr. Smith's work has been at many levels. The availability of a fast and reliable method of DNA sequencing fostered an explosion in cDNA cloning efforts that hastened the pace of understanding biological processes. With this technology in place, genomic exploration became a reasonable goal, not just a visionary's dream. As the present set of genome projects is completed, new quests can be envisioned. Even more important, we are at the edge of a fundamental change in the way experimental biology is conducted. The resulting changes are providing a treasure of experimental opportunities for the ABRF community, not just for nucleic acids scientists, but also for protein and peptide chemists.

 

The first ABRF Award was presented to Frederick Sanger for his contributions to sequencing both proteins and nucleic acids. In 1995, the second award recognized Klaus Biemann's career-long work in the application of mass spectrometry to the biological sciences. Last year's award honored David Lipman for development of computational methods for analysis of protein and DNA sequences.



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Created: 1st April 1997
Last modified: 23rd April 1997