Tak Wah Mak

Microbiology and Immunology

Discovered the T-Cell receptor, a key to the human immune system

"Don’t be afraid to tackle science if you enjoy it."

Tak Mak is a very imaginative fellow. When asked to describe his work as an immunologist, instead of telling a story about himself he came up with the following tale concerning the life of an imaginary T-cell.

Tommy T-Cell is a biodetective. His job is to patrol the human body, investigating suspicious characters. Think of the cells in the human body as shops on a city street. Billions and trillions of police detectives like Tommy T-Cell are driving by all the time, looking in all the shop windows for something unusual going on. Each T-cell is trained to find one — and only one — type of criminal. There are several different kinds of T-cells. Tommy is known as a helper T-cell, part of the body’s immune system, but you can think of him as a cop.

As Tommy cruises through blood and tissue he meets a macrophage, a specialized cell that’s a combination reconnaissance and disposal unit in the body. Macrophages go around collecting bits of your own living and dead cells. They find parts of invading viruses and bacteria, dust, pollen and any junk that’s floating around. They stick pieces of this garbage on their outside surfaces in special places where detectives like Tommy can see them. Tommy has unique Y-shaped spikes called receptor sites all over his surface, and they recognize one kind of garbage. (In 1983 Tak Mak discovered these T-cell receptors.) Tommy’s got about 5,000 receptor sites and each one is exactly the same. No other T-cell has spikes like Tommy’s. His are specially designed to collect a tiny bit of protein from a virus that causes colds. Tommy tries his receptors on the macrophage, but nothing happens, so he moves on. The whole thing takes less than a second.

As Tommy floats along, he remembers his days years ago at the body’s police academy, the thymus, where he learned how to tell foreign invaders from good cells that belong to the body. The T in T-cell is for “thymus,” because that’s where T-cells come from. The thymus is a fist-sized gland located just above the heart. It’s bigger and more active in babies than in adults. In the first years of life, the thymus gives all the T-cell detectives in the body their lifelong assignments. T-cells start out in the thymus as police cadets. They are trained by special macrophages that show new T-cells every possible little bit of garbage that a normal healthy body produces. These bits are called “self.” T-cells whose receptors recognize “self” are killed in the thymus before they can leave; if they ever got out, they would become bad cops that attack good cells instead of invaders.

Tommy finally cruises up to a macrophage that shows him a piece of a cold virus. He checks it with his receptors. It’s a match. The virus has been in the body for only five minutes, but Tommy leaps into action. First he sends out chemicals that signal regular police officers in the body — B-cells — to make antibodies. Antibodies are like heat-seeking missiles that zero in on a particular virus and kill it. Tommy, the helper T-cell, also calls in a SWAT team of killer T-cells and together they go out in search of the invader. They start dividing rapidly, doubling in number about every six hours. It takes four days before millions of T-cells, B-cells and killer T-cells are mobilized to kill all the virus in the body. Immune-system cells are some of the fastest-dividing cells we have inside us.

One day, Tommy is cruising the body on his usual rounds when he meets a thug in a black leather jacket, an AIDS virus. He decides to check him out with his receptors, but before he can do anything the little creep gets right inside Tommy through a tiny hole near the handle that Tommy uses when he visits macrophages. Viruses don’t usually attack T-cells, but AIDS does. That’s what makes AIDS so bad. Now that Tommy has the AIDS virus, little bits of AIDS proteins will appear on his surface. This makes him look very bad to other cells in the immune system. Tommy sees a killer T-cell coming and says his prayers: he knows that a killer T-cell is trained to kill anything that looks foreign. The killer T-cell sees that bit of AIDS on Tommy and, without a second thought, kills his boss. That’s the end of Tommy.

The tragedy of AIDS is that T-cells are the mastermind detectives of the body’s defence system, the ones that organize the other cops. Once AIDS is inside a T-cell, those T-cells look like spies to the rest of the immune system. So the body kills off its best cops, which then makes it harder to fight AIDS and any other infection. Most people with AIDS actually die of a common disease, such as a chest infection that would never kill some-one with a healthy immune system.

As a young scientist ...

Tak Mak was the son of a successful businessman in southern China. After the Communists took power in 1949, Mak’s father moved the family to Hong Kong to escape the turmoil of political revolution. They were very well off and lived in a predominantly white, upper-middle-class district made up mainly of Dutch, Danish, Swedish, Norwegian and British families. They lived next door to the consulates of Norway and Denmark. “It was a rich neighbourhood,” says Mak. He was the only Asian kid on his street, but like all the other boys he liked to play marbles in the dirt and kick soccer balls around.

Mak wasn’t particularly interested in school, but his mother insisted that he do well and study hard. It helped that at school he was in a very bright group of about 20 kids. Most of them went to universities all over the world. Mak went to the University of Wisconsin in Madison.

In the early 1970s, after he had received his doctorate (PhD) from the University of Alberta, Mak began his research at the Ontario Cancer Institute in Toronto. He is still a senior scientist there today. After his discovery of the T-cell receptor he became a professor at the University of Toronto, and in 1993 he also became director of the Amgen Research Institute in Toronto, which develops, patents and markets transgenic mice — animals that carry immune-system genes transferred from human beings. During his years at Amgen, Mak led a team that produced 20 patented molecular discoveries for use in drug development. In 2004 Mak left Amgen to become director of a new Institute for Breast Cancer Research.

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