Foundations of discovery: honouring the work of Canadian researcher Dr. Frank Graham

 

- Ottawa, Ontario

""

Dr. Frank Graham

The foundations of science are built from one generation to the next, with the work of past generations often leading to important discoveries in the present. Dr. Frank Graham is an internationally-renowned scientist who has been referred to as a pioneer in the fields of molecular virology and gene therapy, particularly with the use of adenovirus as a vector for transfer and expression of foreign genes in mammalian cells.

In 1975, Dr. Graham began working at McMaster University in Hamilton. During his time there, he became an oft-cited biologist for his work in defining the mechanisms of cancer transformation caused by adenoviruses.

In the 1970s, prior to beginning his career at McMaster, Dr. Graham worked in the Netherlands first as a post-doc and later as a research associate in the lab of Dutch scientist Dr. Alex van der Eb. During this time, he developed a new method called calcium phosphate transfection for introducing DNA into eukaryotic cellsFootnote 1. Using this technique he was able to determine the size and location of the transforming genes of human adenovirus (that is the viral genes responsible for oncogenicity)Footnote 2 and also generated the cell line called HEK293 that contains and expresses the human Adenovirus 5 (Ad5) transforming genesFootnote 3. This unique cell line is now widely used for academic research and in the pharmaceutical and biotechnology industries around the world.

On his return to Canada, Dr. Graham continued to characterize the HEK293 cell line and, in collaboration with colleagues at McMaster, used it in the development of numerous Ad5-based viral vectors for gene transfer and potential recombinant viral vaccinesFootnote 4.

In particular, in collaboration with Dr. Ludvik Prevec, Dr. Graham engineered an Ad5 vector expressing rabies antigens that has led to the development of a vaccine bait against rabies that is broadly used in Canada and the US for control of rabies in wildlifeFootnote 5. These vectors, and those made by other laboratories, are designed to have deletions of the viral genes responsible for transformation and are defective for growth in cells other than HEK293 cells. This makes such vectors relatively safe for use as human vaccines.

Since the 1970s, the HEK293 cell line has undergone significant modifications in laboratories across the globe. For example, the NRC has developed a proprietary version of the HEK293 cell line, referred to as HEK293-SF-3F6, which has known and specific properties that make it a very strong starting point for the subsequent development of vaccines and therapeutics for human health.

Dr. Graham is a recipient of the Robert L. Noble Prize from the Canadian Cancer Society and is Professor Emeritus in the Departments of Biology and Pathology and Molecular Medicine at McMaster University. He is also recognized as a Distinguished University Professor by McMaster. A Fellow of the Royal Society of Canada, Dr. Graham retired from McMaster University in 2003 and now resides in Italy.