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Michael SmithCanadian biochemist
Date of Birth: 26.04.1932
Country:  Canada |
Content:
- Biography of Michael Smith
- Research and Career
- Directed Mutagenesis
- Later Career and Recognition
- Smith enjoyed working at his workbench, sailing, and skiing.
Biography of Michael Smith
Early Life and EducationMichael Smith was born in Canada to parents Rowland and Mary Agnes Smith. His parents, who worked in a cafeteria and his father's garden in the village of Marton-Moss near Blackpool, were poor. Smith attended a local school at the church from the age of five for six years. Thanks to a scholarship, he then studied at the local private school, Arnold School, where his chemistry teacher, Sidney Lowe, sparked his interest in chemistry. In 1950, with the financial support of the Blackpool Education Committee, Smith enrolled at the University of Manchester and graduated in 1953. He obtained his doctorate degree in 1956, under the supervision of organic chemist H.B. Henbest, with his research focusing on cyclohexanediols.
Research and Career
In the summer of 1956, Smith learned that Nobel laureate in Physiology or Medicine (1968), Har Gobind Khorana, had a vacancy for work on synthesizing biologically important organophosphates. Smith wrote to Khorana and was invited to work as an intern in Vancouver, Canada. He arrived in Vancouver in September 1956 and was tasked with developing an efficient method for synthesizing nucleoside-5-phosphates. This research led to the expansion of carbodiimide reactions with acids, including phosphoric acid esters, and the development of a general method for obtaining nucleoside-3,5-cyclophosphates, the biological significance of which was discovered later. The protective group class studied during this work is now used in modern automated synthesis of DNA and RNA fragments. In 1960, Smith joined the Enzyme Research Institute at the University of Wisconsin, where he worked on the synthesis of oligoribonucleotides, a major chemical problem in the field of nucleic acids at the time.
In early 1961, Smith moved to the Fisheries Research Laboratory in Vancouver. Here, he published numerous articles on crabs, mollusks, salmon, and other marine life. However, thanks to a grant from the National Institutes of Health in the United States, he was able to continue his work in nucleic acid chemistry. He developed a new method for synthesizing nucleoside-3,5-cyclophosphates. Smith became a Canadian citizen in 1964. The laboratory conditions did not favor academic research, as it was located on the campus of the University of British Columbia. In 1966, Smith became a professor of biochemistry at the university's medical faculty, where he remained. The only exceptions were his internships at the Rockefeller University, the Laboratory of Molecular Biology in Cambridge, and Yale University.
Directed Mutagenesis
Smith was the first to develop the technique of directed mutagenesis in the early 1970s and spent several years refining it. In 1978, Smith and his colleagues achieved early successes in directed mutagenesis of a bacteriophage DNA molecule, and by 1982, they were able to produce large quantities of an enzyme in which any selected amino acid in its sequence could be replaced using their method. This technique became a new way to study protein function. By inducing a mutation in the nucleotide sequence of a gene, the amino acid sequence and therefore the function of the modified protein could be modified. Prior to Smith's method, the technique of creating genetic mutations was imprecise and often a random process, and the experiment itself was laborious and time-consuming. Smith improved this situation by creating the technique of directed mutagenesis, which involved specific mutagenesis at the desired site of a gene. This allowed researchers to determine the role and location of each amino acid in the structure and function of the protein.
Directed mutagenesis became a powerful tool in genetic engineering. In addition to its value for fundamental research, directed mutagenesis found numerous applications in medicine, agriculture, and industry. For example, it could be used to create a variant of a protein that is more stable, more active, or more useful than its natural precursor. In 1981, Smith was invited to be a scientific co-founder of the new biotechnology company "Zymos." One of the company's first contracts was with the Danish pharmaceutical company "Novo," which requested the development of a technology for the production of human insulin in yeast culture. As a result of their joint efforts, the method was developed. Later, Smith became the founder of the biotechnology company "ZymoGenetics Inc."
Later Career and Recognition
In 1986, Smith established a biotechnology laboratory at the University of British Columbia and simultaneously served as a research director in one of the gene engineering companies he had founded in 1990. In 1991, he became the director of the Biomedical Research Institute located on the campus of the University of British Columbia. However, administrative difficulties related to the institute's status change and funding led Smith to step down from this position after a year.
In 1993, Smith, along with Kary Mullis, received the Nobel Prize in Chemistry "for contributions to the establishment of directed mutagenesis, based on oligonucleotides, and its development for studying proteins." In 1995, in an interview, he predicted changes in biological science. With the completion of the Human Genome Project, the complete nucleotide sequence of DNA for all genes became known. These genes code for the approximately 100,000 different varieties of proteins needed by the organism, but we understand only about 5,000 of them. Deciphering the information about the connection between nucleotide sequences of the genome and the remaining amino acid sequences will be a challenging task.
