Michael Smith (April 26, 1932 – October 4, 2000) was a British-Canadian biochemist and businessman. He shared the 1993 Nobel Prize in Chemistry with Kary Mullis for his work in developing site-directed mutagenesis. Following a PhD in 1956 from the University of Manchester, he undertook postdoctoral research with Har Gobind Khorana (himself a Nobel Prize winner) at the British Columbia Research Council in Vancouver, British Columbia, Canada. Subsequently, Smith worked at the Fisheries Research Board of Canada Laboratory in Vancouver before being appointed a professor of biochemistry in the UBC Faculty of Medicine in 1966. Smith's career included roles as the founding director of the UBC Biotechnology Laboratory (1987 to 1995) and the founding scientific leader of the Protein Engineering Network of Centres of Excellence (PENCE). In 1996 he was named Peter Wall Distinguished Professor of Biotechnology. Subsequently, he became the founding director of the Genome Sequencing Centre (now called the Michael Smith Genome Sciences Centre) at the BC Cancer Research Centre.
Education and early life Smith was born April 26, 1932, in Blackpool, Lancashire, England. He immigrated to Canada in 1956 and became a Canadian citizen in 1963. Smith married Helen Wood Christie on August 6, 1960, on Vancouver Island, BC, Canada. The couple had three children (Tom, Ian and Wendy) and three grandchildren, but separated in 1983. In his later years, Smith lived with his partner Elizabeth Raines in Vancouver until his death on October 4, 2000. Smith first attended St. Nicholas Church of England School, a state-run elementary school. At the time, few children from state schools in England went on to further academic education, however Smith did well in the eleven plus exam, and was an exception. A scholarship enabled him to attend the Arnold School for Boys. A further scholarship allowed him to study Chemistry at the University of Manchester, where he pursued his interest in industrial chemistry and was awarded a BSc followed by a PhD in 1956 for research into the stereochemistry of diols.
Career
Researcher Smith's research career began with a post-doctoral fellowship at the British Columbia Research Council under the supervision of Khorana, who was developing new techniques of synthesizing nucleotides. The application of principles of physics and chemistry to living organisms was new at that time; DNA had been identified as the genetic material of a cell, and Khorana and others were investigating how DNA encoded the proteins that constituted an organism. In 1960, when Khorana was offered and accepted a university position with excellent laboratory facilities in the Institute for Enzyme Research at the University of Wisconsin–Madison, Smith moved with him. After a few months in Wisconsin, Smith returned to Vancouver as a senior scientist and head of the Chemistry Division with the Vancouver Technological Station of the Fisheries Research Board (FRB) of Canada. In this role he conducted studies on the feeding habits and survival of spawning salmon, as well as identification of olfactory stimuli guiding salmon to their birth stream. His main research interest, however, continued to be nucleic acid synthesis, for which he received a United States Public Health Service Research Grant. Concurrently with conducting research for FRB, Smith held the positions of associate professor at the University of British Columbia's (UBC) Department of Biochemistry and honorary professor in the Department of Zoology. In 1966, Smith was appointed a research associate of the Medical Research Council of Canada, working within UBC's Department of Biochemistry. Smith's particular area of interest remained the synthesis of oligonucleotides and the characterization of their properties. In 1975–1976, a sabbatical at the MRC Laboratory of Molecular Biology in England with Fred Sanger placed Smith at the forefront of research into the organization of genes and genomes and methods of sequencing large DNA molecules. He returned from England as one of the world's leading molecular biologists. Smith and his team began to investigate possibility of the creation of mutations of any site within a viral genome. If possible, this process could be an efficient method to engineer heritable changes in genes. Finally, in 1977 they confirmed Smith's theory.
Site-specific Mutagenesis In the late 1970s, Smith concentrated on projects in molecular biology and how the genes within the DNA molecule act as reservoirs and transmitters of biological information. In 1978, Smith, in collaboration with former Fred Sanger lab sabbatical colleague Clyde A. Hutchison III, introduced a new technique known as "oligonucleotide-directed site-directed mutagenesis" into molecular biology, resolving the problem of how to efficiently determine the effect of a single mutant gene. They developed a synthetic DNA technique for introducing site-specific mutations into genes. This permitted comparison of different protein molecules, revealing the role of the initial mutation. The new technology enabled rapid identification and deliberate alteration of genes for the purpose of changing the characteristics of an organism. It raised the level of possibility of new diagnostic strategies and new treatments for genetic diseases, and even creation of novel artificial forms of life, as the progenitor technique for polymerase chain reaction (PCR), Site-Directed Mutagenesis and Synthetic Biology.
The team's paper describing site-directed mutagenesis was published as "Mutagenesis at a Specific Position in a DNA Sequence" in the Journal of Biological Chemistry in 1978. For the team's work in developing oligonucleotide-directed site-directed mutagenesis, Smith shared the 1993 Nobel Prize in Chemistry with Kary Mullis, the inventor of polymerase chain reaction. Using site-directed mutagenesis, scientists have been able to dissect the structure and function relationships involved in protein plaque formation in the pathophysiology of Alzheimer disease; study the feasibility of gene therapy approaches for cystic fibrosis, sickle-cell disease, and hemophilia; determine the characteristics of protein receptors at neurotransmitter binding sites and design analogs with novel pharmaceutical properties; examine the viral proteins involved in immunodeficiency disease; and improve the properties of industrial enzymes used in food science and technology.
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