Frank L. Graham

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.

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.

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.

During this period he developed the calcium phosphate transfection technique, a simple and efficient method for introducing DNA into mammalian cells. 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.

In 1973, Graham used adenovirus 5 DNA to transform human embryonic kidney cells, establishing the HEK 293 cell line. 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.

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).

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. His group and collaborators also advanced adenovirus-based systems for cancer immunotherapy and experimental treatments of genetic and infectious diseases.

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.