Professor Jacques Miller

50th anniversary (1961-2011): Professor Jacques Miller discovers the function of the thymus

Fifty years ago, in a little shack adjoining converted horse stables at Pollard’s Wood, Buckinghamshire (UK), Professor Jacques Miller made a discovery that would revolutionise our understanding of the immune system, infection and disease.

Professor Miller discovered that the thymus, an organ that sits between the heart and rib cage, was critical for development and function of the immune system.

At the time, the thymus was considered to be a vestigial organ with no function, a ‘graveyard’ for dying T cells at best, and Professor Miller’s finding was initially met with scepticism and disbelief.

Professor Miller is now credited as the last person to have identified the function of a major organ.

A Eureka moment: the thymus is essential to immunity
A second major discovery
Implications for humanity
Awards
External links

A Eureka moment: the thymus is essential to immunity

It was whilst working as a PhD student at the Chester Beatty Research Institute at The Institute of Cancer Research in the UK that Professor Miller made his celebrated discovery.

Professor Jacques Miller Professor Miller was on a scholarship to study the development of leukaemia in mice infected in early life with murine leukemia virus. He had an interest in virology (the study of viruses) and was particularly interested in the role the thymus played in infection, as this was the organ where he thought the virus grew before it spread to the rest of the body.

As part of his research, Professor Miller decided to test whether newborn mice that had their thymus removed – a routine procedure known to have no detrimental effect in adult mice – were less likely to develop the virus-related leukaemia in later life.

“Mouse leukaemia begins in the thymus, which is an organ above the heart and under the sternum,” Professor Miller said. “I decided to study why this was the case. It was known that removal of the thymus, called thymectomy, prevented leukaemia development in adult mice. So I decided to see whether removing the thymus of newborn mice, followed by infection with the virus, also prevented the development of leukaemia.”

Professor Miller said the results were surprising.

“I found out that mice that had been thymectomised in very early life could not resist infections, and failed to thrive,” Professor Miller said.

“This was very surprising, as removal of the thymus in older mice has no such detrimental effect. Further studies showed that the mice could not generate normal immune responses; for example, they could not produce an immune response to reject skin grafts from non-matching donors, and they had very few immune cells in their body.”

Professor Miller knew there was only one conclusion.

“It was a Eureka moment: I realised that the thymus, rather than being an organ that had become redundant during the course of evolution, was in fact absolutely crucial to the development of the immune system,” he said.

A second major discovery

In 1966, following his PhD (1960) and DSc (1965), Professor Miller was recruited back to Australia to work at the Walter and Eliza Hall Institute by Sir Gustav Nossal.

Professor Miller said he was very grateful to Gus Nossal for having invited him to head a new unit at the institute in 1966. “Let me just say that I have been very lucky to have such wonderful companions and fellow workers throughout my time at the institute,” he said.

The discovery of the function of the thymus revolutionised the field of immunology and led Professor Miller to another major research finding whilst at the Walter and Eliza Hall Institute.

“My first PhD student Graham Mitchell and I decided to prove once and for all that the thymus produces the immune cells that we now call T cells, which are essential for the immune response,” Professor Miller said.

“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. 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.”

These were quite radical ideas at the time, and a lot of people were dubious about our results. Dr Miller cites one example in which a prominent scientist likened the idea to the first and last letters of the word ‘bull***t’.

But Professor Miller was unperturbed. “It was obvious to us that B cells and T cells were different types of lymphocytes, came from different sources, had different functions, but had to interact for antibodies to be produced,” he said.

Implications for humanity

The best explanation of the implications of Professor Miller’s discovery may come from Australian Nobel Laureate Professor Peter Doherty.

“There isn't a single advance in vaccine, immunotherapy or autoimmunity research that doesn't incorporate (his) thinking," he said at a recent event celebrating Professor Miller on the 50th anniversary of discovery of the function of the thymus.

Professor Miller and his colleagues, through their work, ushered in a new field of biomedical research: T cell biology. Understanding the function and role of T cells became a major field of research, and there are now at least six different types of T cells known to perform a variety of functions in the immune system and response.

Professor Jacques Miller The thymus is now known to be the ‘training ground’ for T cells, one of the key cells of the immune system particularly important for immune responses to viruses, bacteria and cancers. It is in the thymus that T cells mature and are ‘educated’ to recognise foreign invaders such as viruses and bacteria, and also learn to differentiate between self and non-self proteins.

Professor Miller said that the discoveries made by him and his colleagues changed the landscape of modern medicine.

“We now understand a lot of things that we didn’t before,” Professor Miller said.

“For example, we know how to boost the response to a vaccine because we understand the function of T cells. Understanding of 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.”

Awards

Former Prime Minister John Howard and Professor Miller

Professor Miller has been accorded many major international prizes and is a Fellow of the Australian Academy of Science (1970), a Fellow of The Royal Society (1970), a Foreign Associate of the US Academy of Sciences (1982) and a Companion of the Order of Australia (2003). He was awarded the Prime Minister’s Science Prize in 2003 and received the Royal Society of London Copley Medal in 2001. In 2011, Thomson Reuters predicted that Professor Miller would likely receive the Nobel Prize for Physiology or Medicine.

Professor Miller worked at the Walter and Eliza Hall Institute until his retirement in 1996 and continues to be involved in immunological research at the institute.

The Walter and Eliza Hall Institute of Medical Research