“There isn’t a single advance in vaccine, immunotherapy or autoimmunity research that doesn’t incorporate (his) thinking.”
So said Australian Nobel Laureate Professor Peter Doherty of Professor Jacques Miller’s contributions to understanding the immune system.
When Miller joined the institute in 1966, it was hot on the heels of his game-changing discovery of the thymus, for which Sir Gustav Nossal counts him as “the living person who most deserves the Nobel Prize and never got it”.
Building on his earlier discovery, Professor Miller, with Dr Graham Mitchell, set out to prove that the thymus produces immune cells (T cells) that are essential for the immune response.
Just two years later, Miller makes another landmark discovery about the immune system.
Together with “brilliant” young PhD student Graham Mitchell, Miller proves that cells from the thymus (T cells) help cells from the bone marrow (B cells) to generate antibodies, revealing that immune cell collaboration and communication is central to immunity.
“What we discovered was that there are in fact two types of white blood cells: T cells, which are produced in the thymus, and B cells which are produced in the bone marrow,” Miller says. “Furthermore, we discovered that B cells are the cells that produce antibodies, and that T cells actually interact with the B cells to help them produce antibodies!”
This is the first indication that cellular communication underlies the immune response to infection. It is a central tenet of what is called adaptive immunity – in which the body ‘learns’ and ‘remembers’ antigens so it can respond more rapidly in the future.
It is a groundbreaking discovery, so much so that many had difficulty accepting it.
“At first, many thought we were up the creek with these T and B cells,” Miller later recalled.
Eminent Australian scientist Bede Morris, unable to accept the discovery as true, dismissively likened B and T cells to the first and last letters of the word ‘b******t’.
How did Miller react?
“I just laughed,” he says. “It was so obvious that B cells and T cells were different types of lymphocytes, came from different sources, had different functions, but had to react when antibody had to be made.”
Nossal later wrote: “Despite [Morris’] protestations, Miller and Mitchell turned out to be correct, and were showered with prizes and honours.”1
Professor Miller and his colleagues, through their work, ushered in a new field of biomedical research: T cell biology. There are now at least six different types of T cells known to perform a variety of functions in the immune system and response.
“We now understand a lot of things that we didn’t before,” Miller says.
“For example, we know how to boost the response to a vaccine because we understand the function of T cells. Understanding the immune response helps us understand the timeline of an infection and how the immune response develops to respond to this attack. Then you have autoimmune diseases such as rheumatoid arthritis, diabetes or multiple sclerosis, where the T cells, rather than fighting off foreign infections, turn against your own body and cause disease. And of course there is cancer. Can some cancers be cured if we can activate T cells against the cancer cells themselves? This is currently happening in clinical trials around the world. So the whole of my work has tremendous implications in every field of medicine.”
1 Nossal G, Diversity and Discovery: the Walter and Eliza Hall Institute 1965-1996, Miegunyah Press, 2007, p101