Michael Smith CC OBC FRS[1] (April 26, 1932 – October 4, 2000) was a British-born Canadian biochemist and businessman.

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.

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.

In 1975–1976, a sabbatical at the MRC Laboratory of Molecular Biology in England with Fred Sanger[2][9][10] placed Smith at the forefront of research into the organization of genes and genomes and methods of sequencing large DNA molecules.

In 1978, Smith, in collaboration with former Fred Sanger lab sabbatical colleague Clyde A. Hutchison III,[11] 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.

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.

[11] 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.

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.

Throughout the 1980s, Smith and his colleagues at the Canadian Institute for Advanced Research advocated for the establishment of a facility that would enable Canada to play a part in what had become known as the Human Genome Project.

His certificate of election to the Royal Society reads: He has made many contributions to the chemistry and molecular biology of nucleotides and polynucleotides.

With nucleotides these include developing general procedures for synthesis of nucleoside 5'-mono- and polyphosphates, and 3'-5' cyclic phosphates.