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Michael Smith (April 26, 1932 – October 4, 2000) was a British-born Canadian biochemist and businessman. He shared the 1993
Nobel Prize in Chemistry The Nobel Prize in Chemistry () is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outst ...
with Kary Mullis for his work in developing site-directed mutagenesis. Following a PhD in 1956 from the
University of Manchester The University of Manchester is a public university, public research university in Manchester, England. The main campus is south of Manchester city centre, Manchester City Centre on Wilmslow Road, Oxford Road. The University of Manchester is c ...
, he undertook
postdoctoral research A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary acade ...
with Har Gobind Khorana (himself a Nobel Prize winner) at the British Columbia Research Council in
Vancouver, British Columbia Vancouver is a major city in Western Canada, located in the Lower Mainland region of British Columbia. As the List of cities in British Columbia, most populous city in the province, the 2021 Canadian census recorded 662,248 people in the cit ...
, 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 Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...
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 Blackpool is a seaside town in Lancashire, England. It is located on the Irish Sea coast of the Fylde peninsula, approximately north of Liverpool and west of Preston, Lancashire, Preston. It is the main settlement in the Borough of Blackpool ...
,
Lancashire Lancashire ( , ; abbreviated ''Lancs'') is a ceremonial county in North West England. It is bordered by Cumbria to the north, North Yorkshire and West Yorkshire to the east, Greater Manchester and Merseyside to the south, and the Irish Sea to ...
, 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 Vancouver Island is an island in the northeastern Pacific Ocean and part of the Canadian province of British Columbia. The island is in length, in width at its widest point, and in total area, while are of land. The island is the largest ...
, 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."No Ordinary Mike: Michael Smith, Nobel Laureate" C Astell and E. Damer, Ronsdale Press 2004 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 The eleven-plus (11+) is a standardised examination administered to some students in England and Northern Ireland in their last year of primary education, which governs admission to grammar schools and other secondary schools which use academ ...
, 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 A Doctor of Philosophy (PhD, DPhil; or ) is a terminal degree that usually denotes the highest level of academic achievement in a given discipline and is awarded following a course of graduate study and original research. The name of the deg ...
in 1956 for research into the
stereochemistry Stereochemistry, a subdiscipline of chemistry, studies the spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereoisomers, which are defined ...
of
diol A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol may also be called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. They are used as protecting gro ...
s.


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 Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
. The application of principles of physics and chemistry to living organisms was new at that time;
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
had been identified as the
genetic material Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic aci ...
of a cell, and Khorana and others were investigating how DNA encoded the
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...
that constituted an
organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...
. 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 The University of Wisconsin–Madison (University of Wisconsin, Wisconsin, UW, UW–Madison, or simply Madison) is a public land-grant research university in Madison, Wisconsin, United States. It was founded in 1848 when Wisconsin achieved st ...
, 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 The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services which manages public health, containing nine out of the department's twelve operating divisions. The assistant s ...
Research Grant. Concurrently with conducting research for FRB, Smith held the positions of associate professor at the
University of British Columbia The University of British Columbia (UBC) is a Public university, public research university with campuses near University of British Columbia Vancouver, Vancouver and University of British Columbia Okanagan, Kelowna, in British Columbia, Canada ...
'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 The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical r ...
in England with
Fred Sanger Frederick Sanger (; 13 August 1918 – 19 November 2013) was a British biochemist who received the Nobel Prize in Chemistry twice. He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other prot ...
placed Smith at the forefront of research into the organization of
genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
and
genomes A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
and methods of
sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...
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
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s 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 Frederick Sanger (; 13 August 1918 – 19 November 2013) was a British biochemist who received the Nobel Prize in Chemistry twice. He won the 1958 Chemistry Prize for determining the amino acid sequence of insulin and numerous other prot ...
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 The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR),
Site-Directed Mutagenesis Site-directed mutagenesis is a molecular biology method that is used to make specific and intentional mutating changes to the DNA sequence of a gene and any gene products. Also called site-specific mutagenesis or oligonucleotide-directed mutagenes ...
and
Synthetic Biology Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms. It applies engineering principles to develop new biological parts, devices, and systems or to redesign existing systems found in nat ...
. 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 The ''Journal of Biological Chemistry'' (''JBC'') is a weekly peer-reviewed scientific journal that was established in 1905., jbc.org Since 1925, it is published by the American Society for Biochemistry and Molecular Biology. It covers research i ...
'' in 1978. For the team's work in developing oligonucleotide-directed site-directed mutagenesis, Smith shared the 1993
Nobel Prize in Chemistry The Nobel Prize in Chemistry () is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outst ...
with Kary Mullis, the inventor of
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
.


Administrator

Smith was an administrator in 1981 at the Faculty of Medicine elected representative to the UBC Senate. He served on the advisory committee of the Canadian Institute for Advanced Research Evolutionary Biology Program and on the Biotechnology Sector Committee of British Columbia. 1982 Smith launched the Centre for Molecular Genetics in the Faculty of Medicine and became its director in 1986. He was the interim scientific director of the UBC Biomedical Research Centre in 1991.


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 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 The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both a ...
. 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 The University of Washington (UW and informally U-Dub or U Dub) is a public research university in Seattle, Washington, United States. Founded in 1861, the University of Washington is one of the oldest universities on the West Coast of the Uni ...
founded
ZymoGenetics ZymoGenetics, Inc was one of the oldest biotechnology/pharmaceutical companies in the USA, based in Seattle, Washington. The company was involved in the development of therapeutic proteins. Located on Lake Union, the address of the ZymoGenetics ...
in
Seattle Seattle ( ) is the most populous city in the U.S. state of Washington and in the Pacific Northwest region of North America. With a population of 780,995 in 2024, it is the 18th-most populous city in the United States. The city is the cou ...
, Washington, US. The company began working on recombinant proteins in an international initiative with
Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, with production facilities in nine countries and affiliates or offices in five. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S ...
of Denmark.
Recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
is used mostly in basic research. ZymoGenetics was acquired by
Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...
. 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 Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
. 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. *1977 UBC Jacob Biely Faculty Research Prize *1981 Canadian Biochemical Society Boehringer Mannheim Prize *1981 Fellow of the
Royal Society of Canada The Royal Society of Canada (RSC; , SRC), also known as the Academies of Arts, Humanities, and Sciences of Canada (French: ''Académies des arts, des lettres et des sciences du Canada''), is the senior national, bilingual council of distinguishe ...
*1984 Science Council of British Columbia Gold Medal * 1986 Elected a Fellow of the Royal Society (FRS) of London *1986 Gairdner Foundation International Award for Chemistry *1986 UBC Killam Research Prize *1988 Genetics Society of Canada Award of Excellence *1989 Canadian Federation of Biological Societies G. Malcolm Brown Award *1992 Flavelle Medal, Royal Society of Canada *1993 Nobel Prize for Chemistry (shared with Kary B. Mullis) *1994 Principal Award, the Manning Innovation Awards Foundation Prize *1994 Order of British Columbia *1994 UBC Peter Wall Distinguished Professor of Biotechnology *1994 Golden Plate Award of the
American Academy of Achievement The American Academy of Achievement, colloquially known as the Academy of Achievement, is a nonprofit educational organization that recognizes some of the highest-achieving people in diverse fields and gives them the opportunity to meet one ano ...
*1995
Companion of the Order of Canada The Order of Canada () is a Canadian national order and the second-highest honour for merit in the system of orders, decorations, and medals of Canada, after the Order of Merit. To coincide with the centennial of Canadian Confederation, the ...
*1999 BC Biotechnology Award for Innovation and Achievement *2004 Biography ''No Ordinary Mike'' published. Recognition of his achievements also included several
honorary degree An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or '' ad hon ...
s. The following are named in Smith's honour: *2001 Michael Smith Foundation for Health Research founded *2004 UBC Biotechnology Laboratories was renamed the Michael Smith Laboratories *2004 Canada's Michael Smith Genome Sciences Centre named in his honour *2004 University of Manchester named its new biological sciences research centre the Michael Smith Building *2005 Opening of the Smith-Yuen Apartments in Vancouver His certificate of election to the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
reads:


References


External links


"Michael Smith (Biochemist)"
''The Canadian Encyclopedia''. * {{DEFAULTSORT:Smith, Michael 1932 births 2000 deaths Alumni of the University of Manchester Businesspeople in the pharmaceutical industry Businesspeople from Vancouver Canadian biochemists Canadian company founders Canadian geneticists Canadian medical researchers Canadian Nobel laureates Companions of the Order of Canada English emigrants to Canada Fellows of the Royal Society Foreign associates of the National Academy of Sciences Members of the European Molecular Biology Organization Members of the Order of British Columbia Naturalized citizens of Canada Nobel laureates in Chemistry People educated at Arnold School People from Blackpool Academic staff of the University of British Columbia Scientists from Vancouver 20th-century Canadian chemists University of Wisconsin–Madison faculty Canadian fellows of the Royal Society