It was once considered the “holy grail of immunology.” But in 1984, scientist Tak Mak quelled the quest, discovering the T-cell receptor (TCR), a key determinant of immune response.
This discovery led to an explosion of advances in the understanding of human immunology and how to manipulate it under circumstances as diverse as autoimmunity, transplantation and cancer.
Western will recognize Mak’s extraordinary scientific career, spanning the fields of biochemistry, virology, genetics, cancer metabolism and clinical therapy, with an honorary degree at fall convocation, Friday, Oct. 22. (See more complete convocation details below.)
Also receiving honorary doctorates are writer and visual artist Shani Mootoo, historian Natalie Zemon Davis and lawyer and community philanthropist Janet Stewart.
Snaring the snark
Mak once compared the hunt for the TCR to that of the travails described in the Lewis Carroll poem, The Hunting of the Snark, in which adventurers search for an elusive creature on a remote island.
“At a personal level,” Mak wrote in 2007, “the capture of the snark thrust me on a lifelong journey through what is perhaps the most fascinating of biological sciences.”
Tak Mak (supplied photo)
Mak was born in southern China and raised in Hong Kong. He earned his BSc and MSc degrees from the University of Wisconsin (Madison) and his PhD from the University of Alberta. He conducted his postdoctoral work at the Ontario Institute of Cancer Research, under the mentorship of Ernest McCulloch and James Till, who discovered hematopoietic stem cells.
Currently, Mak is the director of the Campbell Family Institute for Breast Cancer Research and senior scientist at Princess Margaret Hospital, and a professor at the University of Toronto in the departments of medical biophysics and immunology.
From dishwasher to discoveries
Mak’s first work in a lab was as a young biochemistry student, washing dishes. Earning $1.25 per hour, he washed test tubes and beakers for one of his early mentors, virologist Roland Rueckert. When there were no more dishes to wash, Rueckert invited Mak to help with research experiments for the same rate of pay.
“That marked the beginning of my scientific career,” said Mak, who co-authored his first paper with Rueckert in 1974, a mere decade before his seminal work with the T-cell receptor fundamentally changed understanding of the immune system and accelerated the development of cancer therapy.
In 1995, Mak and his team used genetically modified “knockout mice” to define the function of a protein receptor that down-regulates T-cell responses and establishes an immune checkpoint. This discovery led to the development of checkpoint inhibitors, agents that apply a unique molecular approach to the immunotherapy of cancer now entering clinical practice.
Mak’s team has gone on to identify and develop new classes of anti-cancer drugs designed to exploit the genomic instability (caused by defects in certain processes that control the way cells divide) and metabolic adaptations of aggressive cancers. Some have received investigational new drug approval and are in clinical trials. The movement of this innovative approach from the basic research laboratory to the clinic is an uncommon and celebrated achievement in translational medicine.
In 2017, Mak co-founded Agios Pharmaceuticals, whose leukemia drug IDHIFA became the first clinically approved therapy to target cancer metabolism.
Linking the immune system to the brain
Recently, Mak’s lab made a breakthrough discovery, showing that the brain communicates with the immune system via a population of t cells that produces the neurotransmitter acetylcholine, and that this process has key functions in maintaining effective anti-viral immunity. They believe acetylcholine is used by immune cells to trigger a chemical chain reaction that loosens blood vessels, opening a doorway into infected tissues. This finding solves a century-old mystery and has profound implications on the understanding of cancer and autoimmune and neurodegenerative diseases.
In 2000, Mak became an officer of the Order of Canada, and in 2004, was inducted into the Canadian Medical Hall of Fame. In 2018, he was awarded the Canadian Institutes of Health Research (CIHR) Gold Leaf Prize for Discovery.
Throughout his career, Mak notes his biggest honour has been working alongside his mentors, peers and trainees, tackling some of the most challenging health-care puzzles of our time.
In a 2020 interview with the academic journal Cell Death and Differentiation, Mak said, “We are witnessing one of the most exciting periods in the history of science. I feel lucky to have participated in the breakneck progress of the last four decades, and I am grateful to the thousands of my fellow scientists who have worked tirelessly to reveal the inner workings of normal and abnormal cells.”
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Western is celebrating graduating students through a virtual fall convocation beginning at 7 p.m. EST on Friday, Oct. 22. Three degree-specific, pre-recorded ceremonies will be posted online on Western’s fall convocation 2021 page, allowing graduates, their families and loved ones to watch the ceremony that applies to them, whenever they like. Each ceremony will include celebratory music by Convocation Brass, with administration and faculty on stage, and remarks from this year’s honorary degree recipients.
An orator will read out each graduating student’s name, which will also be featured on individually displayed slides throughout the ceremony. Approximately 3,000 graduating students will then join 328,000 Western alumni from more than 160 countries. Graduates will receive their parchments by mail.
