Michael Smith (chemist)

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 (Hannah, Lindsay and Angus), 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, which separated the top 20 percent of pupils, who might then receive an academic education, from the rest, who would not. A scholarship enabled Smith 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.

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. This was an era of great change in the ways in which questions in biology were approached. Principles of physics and chemistry were being applied to living organisms. 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 was ready for a new challenge; he 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. His greatest interest remained the synthesis of olgonucleotides and the characterization of their properties. A sabbatical at the University of Cambridge 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 then investigated the creation of mutations of any site within a viral genome. If possible, then the result could be an efficient method to engineer heritable changes in genes. His team experimented, finally, in 1977, confirming Smith's theory.

Site-specific Mutagenesis

In the late 1970s, Smith was concentrating exclusively 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.

Mentor

Smith knew that a productive laboratory depended on good graduate students, post-doctoral fellows and technicians to carry out the practical aspects of his work. He encouraged talented scientists from diverse backgrounds and challenged them to work independently.

Administrator

Smith was first and foremost a research chemist, but he understood the importance of sound administration in running an efficient, productive laboratory, and of participating in the process of decision making relating to funding and allocation of resources. He served his university and the wider academic community in many ways, including (but not limited to):

Centre for Molecular Genetics

1982 Smith launched the Centre for Molecular Genetics in the Faculty of Medicine and became its director in 1986.

Biotechnology Laboratory and PENCE

In 1987, the Biotechnology Laboratory, one of three provincial "Centres of Excellence" was established at UBC. The new facility subsumed the Centre for Molecular Genetics, and Smith became its director. He played an important role in drawing together scientists, and in writing the proposal for what would become the "Protein Engineering Network of Centres of Excellence" or PENCE.

Genome Sequence Centre

Throughout the 1980s, Smith and his colleagues at the Canadian Institute for Advanced Research (CIAR) were interested in establishing a facility that would enable Canada to play a part in what had become known as the Human Genome Project, an international initiative whose goals were to:

Eventually, funding was secured from the BC Cancer Agency and in 1999 the Genome Sequence Centre was established with a mandate to develop and deploy genomics technologies in support of the life sciences, and in particular cancer research. The Genome Sciences Centre also provided technology to Genome Canada and Genome BC projects in the areas of human health, the environment, forestry, agriculture, and aquaculture.

Commercial ventures

In 1981 Smith ventured into the business world as a pharmaceutical entrepreneur. In collaboration with Professors Earl W. Davie and Benjamin D. Hall of the University of Washington founded ZymoGenetics in Seattle, Washington, US. The company began working on recombinant proteins in an international initiative with Novo Nordisk of Denmark. Recombinant DNA is used mostly in basic research. ZymoGenetics was acquired by Bristol-Myers Squibb. Further applications of recombinant DNA are found in human and veterinary medicine, in agriculture, and in bioengineering.

Awards and honours

Smith received many awards in addition to the Nobel Prize, and was known for his generosity. He donated half of the Nobel Prize money to researchers working on the genetics of schizophrenia. The other half he gave to BC Science World and to the Society for Canadian Women in Science and Technology. He received the Royal Bank Award in 1999, and donated the companion grant to the BC Cancer Foundation.

Recognition of his achievements also included several honorary degrees. The following are named in Smith's honour:

His certificate of election to the Royal Society reads: