Professor Michael Smith (1932-2000)
Nobel Laureate in Chemistry, 1993
"for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies"
Michael Smith was awarded the Nobel Prize in Chemistry in 1993 for his discovery of the molecular biology technique known as site-directed mutagenesis. This technique allows researchers to precisely mutate a DNA sequence to better understand the significance of proteins and genes. Site-directed mutagenesis along with polymerase chain reaction, discovered by Kary B. Mullis who also won the Nobel Prize in 1993, were the main driving forces of the biotechnology field.
Michael Smith was born in Blackpool, England on April 26, 1932 into a working class family. He was seven when World War II started. Blackpool was spared from most of the German bombing raids, but Smith was unlucky enough to be at home one night when bombs barely missed his house. Both his mother and father worked outside the home in order to support the family. Money was extremely tight and his parents told him he could only continue his education if he received scholarships. At age eleven, all English children took a test called the “Elevenplus” exam. If the child did well they could go to a private school and then to a university, otherwise they went to public school and then learned a trade. Fortunately, Smith did very well on the exam and was offered a scholarship to the local private school, Arnold School. He resisted going because he thought the kids there were stuffy and he would lose all his old friends. His mother, however, saw this as a great opportunity and insisted that he went.
Smith didn’t enjoy being at Arnold School. He missed his old friends, had lots of homework and thought the school food was disgusting. He was also bad at sports, which kept him from bonding with the other students. On top of that, he was teased mercilessly because of his overbite. Fortunately, this led him to see a dentist who introduced him to the Boy Scouts while correcting his teeth. There he made many friends and developed an appreciation for the outdoors that he kept for the rest of his life. Smith also found that he excelled at science, and his chemistry teacher Sidney Law pushed him to succeed.
It’s important to be flexible and to change direction when an opportunity presents itself
- Michael Smith
Throughout his scientific career Smith persisted despite several rejections. He continually changed tracks and learned areas of research that were completely foreign to him. When applying for universities in 1950, Smith found that he was unable to attend Oxford or Cambridge since his Latin proficiency was poor. However, he was fortunate enough to get into the honors program at the prestigious University of Manchester. He studied hard and managed to get a scholarship, but was extremely disappointed to be only a B student. He graduated with a PhD in 1956, doing most of his doctorate work in cyclohexane diol organic chemistry.
After graduating most of his friends were lining up post-doctorate rotations in the United States. Smith also looked at these universities but he was rejected everywhere he applied. One of his friends knew a position was available with Dr. Gobind Khorana in Vancouver and encouraged Smith to apply there. Khorana studied DNA and triphosphate synthesis, something Smith was not trained in, but he interviewed anyway and was hired. There he was trained in the field of molecular biology. Smith had certainly chosen a prestigious lab; Khorana himself won the Nobel Prize in Chemistry in 1968 for his work toward understanding the genetic code.
In 1961 Smith once again changed tracks and worked at the Fisheries Research Board of Canada Laboratory in Vancouver for several years, publishing papers about marine biology. This was once again not his original area of research, but he was still able to maintain his own research in DNA chemistry in a lab at the University of British Columbia. He collaborated so much with other professors there that he was awarded a UBC professor of biochemistry in the Faculty of Medicine in 1966, where he worked until he retired in the spring of 1996.
The Discovery that Led to the Nobel Prize
“In research you really have to love and be committed to your work because things have more of a chance of going wrong than right. But when things go right, there is nothing more exciting”
- Michael Smith
Smith created a molecular biology technique known as site-directed mutagenesis. This technique lets a scientist create specific mutations in an organism such as bacteria, plants, and animals, by precisely altering the base pairs that make up its DNA. Base pairs could be added, deleted, or switched to ultimately change the genes and/or proteins encoded within the DNA. Before this technique was invented scientists had to expose many organisms to a mutagen such as radiation in order to create mutations. They then had to screen all the organisms in order to determine which one had the mutation they were looking for. This process could take several years, since it was based largely on chance. Site-directed mutagenesis allowed scientists to quickly and reliably create the exact mutation they want, leading to a better understanding of the function of proteins and genes. This paved the way for the biotechnology field which has led to discoveries such as new anti-cancer drugs and genetically modified plants.
Smith’s idea for site-directed mutagenesis came in 1976 when he was on sabbatical in Fred Sanger’s lab in Cambridge. According to him, he was in the university cafeteria having tea with other professors and discussing how a strand of DNA can anneal with its complementary strand. He realized that this quality could be used to create specific mutations in the DNA. The technique didn’t work originally and it took several years for his lab to perfect it. He submitted his first article describing site-directed mutagenesis to Cell, a first rate science journal. The editors noted that the technique was not of general interest and rejected the article. Smith however was convinced that the technique would be of great use to researchers. He resubmitted the paper to another journal where it was accepted and scientists everywhere learned about the technique. Today, site directed mutagenesis is a standard technique used in molecular biology laboratories throughout the world.
A scientific explanation of how site-directed mutagenesis works:
Scientists start with a single-stranded plasmid containing the DNA of interest. A short stretch of single-stranded DNA called a primer is created that contains the desired mutation. This primer is complementary to the area of the plasmid where the mutation will be inserted. The primer is annealed to the single stranded plasmid and elogated using a polymerase to create a whole double-stranded plasmid. The end result is a plasmid where one DNA strand has original DNA sequence and the complementary strand has the mutation. The plasmid is then placed into an organism such as bacteria. The bacteria and its plasmid divide, creating daughter bacteria with either fully normal or fully mutated plasmids. The plasmids can then be harvested from the bacteria and sequenced to determine if the mutation is present.
Smith was very committed to his research and worked hard in his laboratory. He worked six days a week doing experiments, writing papers, and supervising students. He often got in to lab early in the morning and stayed late into the evening. His casual, enthusiastic approach to teaching appealed to many students. Smith also made time for pursuits outside of the lab. Thanks to his early years as a Boy Scout, he remained an avid lover of the outdoors. He enjoyed skiing, sailing, fishing, and hiking in the forests of Canada when not in the lab. He also apparently had a love for fine wine and restaurants. He married in 1960 and separated in 1983 after having three children.
His Further Contributions to Science
"It is important to have a scientifically literate public because there are so many things in our lives driven by science and technology."
- Michael Smith
Throughout his life Smith worked hard to promote the advancement of sciences, especially through his generous donations. The Nobel Prize awarded him half a million dollars and Smith donated all of it to several groups. Half of his prize went toward the research of schizophrenia genetics. The other half was split between Science World BC, which trains elementary school science teachers, and the Society for Canadian Women in Science and Technology, which encourages women to get involved in science. Not only did he contribute his own money, but he also challenged the Canadian government to match his contributions, which they eventually met or even exceeded. Smith also donated other awards he received. He donated the companion grant from the Royal Bank Award he received in 1999 to the British Columbia Cancer Foundation. He also shut down his lab shortly after winning the Nobel Prize in order to keep his funds available to future scientists.
Besides his donations, Smith also made other major contributions to science. He cofounded a Seattle-based biotechnology company called Zymogenetics Inc. in 1981. The company was responsible for creating a yeast strain that was implanted with the human insulin gene. Zymogenetics teamed up with the drug company Novo-Nordisk to commercialize a process that used yeast to produce human insulin. Smith apparently made a small fortune in 1988 when he sold his share of the company’s stocks.
In 1986 the dean of UBC asked Smith to create a new institute at the university focusing on the proliferating biotechnology field. He founded the Biotechnology Laboratory in 1987 and enjoyed recruiting researchers and students there. It was announced in 2000 that a building in the institute was to be named after him. Smith also helped to set up a genome sequencing institute in British Columbia. Throughout the rest of his life he pushed the Canadian government for more funding for the sciences and also traveled the world educating people about science.
Smith died from cancer on October 4, 2000. However, his legacy of giving back to the scientific community lives on. The Michael Smith Awards, created from his contributions, annually award people and organizations that make an outstanding contribution to the promotion of science in Canada. The University of British Columbia gives out ten graduate student fellowships a year in his name. The Michael Smith Foundation for Health Research in British Columbia, created in 2001 in his name with a government grant, works to enhance health research in the area. Michael Smith's contributions to science obviously reached far beyond his Nobel Prize winning discovery.
Awards and Acclamations
- 25 honorary doctorates
- Career Investigator of the Medical Research Council of Canada in 1966
- Fellow of the Royal Society of Canada, 1981
- Gold Medal from the Science Council of British Columbia, 1984
- Fellow of the Royal Society of London, 1986
- Gairdner Foundation International Award, 1986
- G. Malcolm Brown Award, 1989
- Scientific Leader of the Protein Engineering Network of Centres of Excellence from 1990-1994
- Nobel Prize in Chemistry, 1993
- Order of British Columbia, 1994
- Canadian Medical Association Medal of Honour, 1994
- Henry Friesen Award, 1994
- Principal Award from the Earnest C. Manning Awards, 1994
- Companion of the Order of Canada, 1995
- Canadian Medical Hall of Fame, 1995
- Foreign Associate of the National Academy of Sciences, USA, 1996
- UBC University Killam Professor and Peter Wall Distinguished Professor of Biotechnology
- Director of the Genome Sequence Centre at the British Columbia Cancer Research Centre in Vancouver
- Director of the Canada Foundation for Innovation in 1997
- Royal Bank Award in 1999
- Nobel Prize autobiography: http://www.nobel.se/chemistry/laureates/1993/smith-autobio.html
- Biography: http://www.science.ca/scientists/scientistprofile.php?pID=18
- Michael Smith Awards: http://www.nserc.ca/msmith/about_e.htm
- UBC Biography: http://www.publicaffairs.ubc.ca/media/releases/2000/mr-00-68.html
- Another Biography: http://bhrc.ca/biotecareers/people/132.html
- The Nobel Prize Annual for 1993, Nobel Prize Series