Smith, Michael (1932-2000), a British-born Canadian biochemist, invented a method of producing altered versions of genes precisely and rapidly, helping to make genetic engineering feasible. He shared the 1993 Nobel Prize for chemistry with the American biochemist Kary B. Mullis, who did separate work in the chemistry of genes.
Smith was born in Blackpool, Lancashire, England. He studied chemistry at the University of Manchester, graduating in 1953 and gaining a doctorate in 1956. He then began postgraduate work at the University of Vancouver in Canada, working on the synthesis of large, biologically important molecules involved in the genetic machinery of cells. After a brief time in the United States, he returned to Vancouver, working with the Fisheries Research Board of Canada and carrying out biochemical research. In 1966, he joined the faculty of the University of British Columbia. He eventually became a Canadian citizen.
In 1971 and 1972, Smith visited the Laboratory of Molecular Biology at the University of Cambridge in England. There he had the idea that would win him the Nobel Prize. Until then, biochemists had no way of producing a deliberate mutation (alteration) in a gene. All they could do was expose the genetic material called deoxyribonucleic acid (DNA) to mutation-inducing influences, such as chemicals or radiation, and see what mutations occurred. Smith’s technique of site-directed mutagenesis used the single-stranded DNA of a virus that invades bacteria. The virus uses the genetic machinery of the bacteria to reproduce. Smith spliced a normal copy of a gene being studied into one strand of the virus DNA. Then he attached another copy of the gene to a second strand, a copy that differed from the first gene in just one detail—it contained a known mutation. He used both strands of DNA to infect bacteria, which copy the strands thousands of times. The two versions of the gene, normal and mutated, produce proteins, and these can be compared to discover the effect of the mutation. The process can be repeated over and over again as new mutations are introduced systematically into the gene. Smith’s technique, which today can be automated, enormously speeded up research into the biochemistry of genes.
In 1981, Smith cofounded Zymogenetics, Inc., a biotechnology company in Seattle, and developed a commercial process for producing human insulin in yeast. In 1988, he sold his interest in the company. In later years, Smith founded the Biotechnology Laboratory at the University of British Columbia.
