U of T’s Dr. Tak Mak became the first Canadian this November to receive the Paul Ehrlich and Ludwig Darmstaedter Prize, Germany’s most prestigious award for biomedical research. He is sharing it with Stanford University’s Mark Davis. The award comes with an endowment of 100,000 Euros (roughly 150,000 CAD). Dr. Mak will receive the award in Frankfurt on March 14, 2004.
Dr. Mak is a professor in U of T’s department of medical biophysics and immunology. He is also a senior scientist at Princess Margaret Hospital’s Ontario Cancer Institute, and the founding director of the University Health Network’s Advanced Medical Discovery Institute. In 1984 Dr. Mak cloned the T-cell receptor genes, a landmark scientific achievement. Once scientists could make copies of the T-cell receptor gene, they could more easily study it in the lab environment. Knowing how the T-cell receptor functions and how to improve its action will help scientists find cures for cancer, AIDS, and many other diseases. Dr. Mak commented that he thought 90 per cent of the award was for his cloning of T-cell receptor genes.
The immune system specializes in recognizing and destroying antigens, substances that cause diseases. Cells called thymocytes play a crucial role in this recognition and destruction. T-cell receptors are proteins located on the surface of these thymocytes. According to Dr. Mak, “T-cell receptors can detect shapes that do not belong to the body, and then mobilize the immune system to eliminate these structures, which are often bacteria, viruses and in some cases cancer cells.” With T-cell receptors, T-cells can recognize cells in the body that have, say, been infected by a virus and need to be destroyed to prevent the disease from spreading.
The immune system does not kill the body’s own tissues because T-cell receptors can tell the difference between foreign agents and the body’s own cells. However, an inability to distinguish between foreign and native structures results in the immune system mistakenly identifying the body’s own cells as foreign, and attempts to destroy them. Diseases like lupus and rheumatoid arthritis result from such an inability.
HIV viruses, however, are especially tricky in that they infect the immune system cells, thymocytes, themselves. The body ends up destroying the very cells it needs to fight off disease. As a result, the immune system weakens over time, and the body becomes less able to fight off other diseases. People with AIDS can die from the common cold if their immune system has deteriorated enough.
There is evidence that cancer development can be prevented with T-cell receptors. The immune system could recognize cancer cells during the early growth of a tumor and kill the cells before they multiply. “Once developed however, cancer is relatively resistant to immune destruction through T-cell receptor recognition,” says Dr. Mak. Currently, “Scientists are trying to manipulate the immune system and instruct thymocytes to use their T-cell receptors to recognize and attack HIV infected cells and cancer cells better.”
When asked what he is presently working on, Dr. Mak said, “My lab does some work in studying molecules that assist T-cell receptors in their activation process, but otherwise we mainly focus how cancer cells are wired, and want to know how to find drug targets.”
Dr. Mak holds many honorary degrees from universities all over North America and Europe. He is an officer of the Order of Canada, a fellow of the Royal Society of London, and a foreign associate of the National Academy of Sciences in the U.S.
