Robert L. Noble Prize (1998); Fellow of the Royal Society of Canada; Honorary DSc McMaster University (2009)
Scientific career
Fields
Molecular biology, Virology, Gene therapy
Institutions
McMaster University, University of Leiden
Frank Lawson Graham (born 1942) is a Canadian molecular biologist and virologist whose discoveries transformed modern molecular biology and biotechnology. He is best known for developing the Calcium phosphate transfection technique and creating the HEK 293 cell line, both of which became essential tools in modern molecular biology and biotechnology and for gene transfer, recombinant vaccine production, and gene therapy research.[1][2]
Graham was born in Canada in 1942. He obtained an Honours Bachelor of Science in Mathematics and Physics from the University of Manitoba in 1964 and a Master's degree in Theoretical Physics from the University of Toronto in 1965. He then pursued graduate studies in biology, earning a Ph.D. in Medical Biophysics from the University of Toronto (Ontario Cancer Institute) in 1970. His doctoral thesis was titled The Mechanism of Action of Cytosine Arabinoside.[3]
Postdoctoral research and discovery of calcium phosphate transfection
In 1970, Graham joined the Laboratory for Physiological Chemistry at the University of Leiden in the Netherlands as a post-doctoral fellow under Dutch virologist Alex van der Eb, supported by a fellowship from the National Cancer Institute of Canada.[4]
During this period he developed the calcium phosphate transfection technique, a simple and efficient method for introducing DNA into mammalian cells.[1] The discovery enabled the first reproducible transformation of rodent cells by adenovirus DNA and allowed Graham and van der Eb to map the transforming genes of human adenovirus type 5 to the left region of its genome.[5][6]
Creation of the HEK 293 cell line
In 1973, Graham used adenovirus 5 DNA to transform human embryonic kidney cells, establishing the HEK 293 cell line.[7][2] The cell line became one of the most widely used human cell lines for production of recombinant proteins and viral vectors, including those employed in gene therapy and vaccine manufacture.[1]
Academic career at McMaster University
Graham returned to Canada in 1975 to join the faculty of McMaster University in Hamilton, Ontario. He served as Assistant Professor (1975–1980), Associate Professor (1980–1983), and Professor (1983–2003) in the Departments of Biology and Pathology, later becoming Distinguished University Professor (2004) and Professor Emeritus (2003).[8]
At McMaster, Graham expanded his research on adenoviruses to develop adenoviral expression vectors and recombinant vaccines. Working with Ludvik Prevec, he engineered a recombinant adenovirus expressing the rabies virus glycoprotein, leading to an oral vaccine bait used across Canada and the United States to control rabies in wildlife.[1] His group and collaborators also advanced adenovirus-based systems for cancer immunotherapy and experimental treatments of genetic and infectious diseases.[8]
Scientific impact
Graham’s work laid the molecular foundation for the use of adenoviruses as vectors for gene transfer and for the rise of gene therapy as a biomedical discipline. His techniques enabled the creation of replication-defective viral vectors now central to gene-based therapeutics and vaccine production, including several adenovirus-based COVID-19 vaccines.[2]
He has authored or co-authored hundreds of peer-reviewed publications and supervised numerous graduate students whose research further extended adenovirus vector technology.[8]
Honours and awards
Graham’s contributions have been recognized through numerous distinctions, including:[3][8][1]
Robert L. Noble Prize for Cancer Research (1998)
Fellow of the Royal Society of Canada (1999)
Honorary Doctor of Science, McMaster University (2009)
Distinguished University Professor, McMaster University (2004)
Community of Distinction Inductee, McMaster University (2011)
He has also served as a Research Scholar and Terry Fox Cancer Research Scientist for the National Cancer Institute of Canada and as an advisor to major research agencies in Canada, the United States, and Europe.[8]
Later career
Following retirement from McMaster in 2003, Graham became Co-founder, President and CEO of AdVec Inc., a biotechnology company developing adenovirus-based gene-transfer vectors. He resides in Italy and continues to contribute to the scientific community as a consultant and mentor.[1][8]
Legacy
Graham’s discoveries—the calcium phosphate transfection method and the HEK 293 cell line—remain cornerstones of modern cell and molecular biology. These innovations have enabled advances in biomedical research from recombinant vaccine production to the clinical realization of gene therapy. The National Research Council of Canada described his work as having "lit the spark that turned gene therapies from theoretical possibility to therapeutic reality."[1]
1 2 A Brief Professional Biography (Report). McMaster University. 2024.
↑ Interview with Frank Graham (Report). Leiden University. 2024.
↑ Graham, F.L.; van der Eb, A.J. (1973). "A new technique for the assay of infectivity of human adenovirus 5 DNA". Virology. 52: 456–467. doi:10.1016/0042-6822(73)90341-3.
↑ Graham, F.L.; van der Eb, A.J.; Heijneker, H.L. (1974). "Size and location of the transforming region in human adenovirus type 5 DNA". Nature. 251: 687–691. doi:10.1038/251687a0.
↑ Graham, F.L.; Smiley, J.; Russell, W.C.; Nairn, R. (1977). "Characteristics of a human cell line transformed by DNA from human adenovirus type 5". Journal of General Virology. 36 (1): 59–72. doi:10.1099/0022-1317-36-1-59.
1 2 3 4 5 6 Curriculum Vitae – Frank L. Graham (Report). McMaster University. 2022.
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