Jacques Francis Albert Pierre Miller is mainly known by his seminal contributions to the understanding of the physiologic role of the thymus gland in the development and maturation of the immune system. He was born in Nice, France, and educated in Australia, where he attended Saint Aloysius' College in Sydney, before studying medicine at the University of Sydney School of Medicine. During his medical studies, Miller also achieved a B.S. in bacteriology, in 1953. After his medical residency at Royal Prince Alfred Hospital in Sydney, he was granted a Gaggin Fellowship to do research at the University College, London, United Kingdom, where he investigated mouse leukemia at the Chester Beatty Research Institute. Miller observed that many types of lymphocytic leukemia in mice, either induced by virus, radiation, chemical carcinogens, or spontaneous leukemia occurring in high-leukemic strain mice, always began in the thymus, and then spread. Other studies had previously reported that the surgical removal of the thymus in young mice would prevent both spontaneous and induced leukemia, although this procedure had not yet being used for virus-induced leukemia. Therefore, Miller infected mice with Gross virus at birth and removed their thymus when they were one month old. Leukemia was prevented. These studies gave Miller a strong indication that the thymus played an important role in the physiology of the immune system.
After completing a Ph.D. degree in 1960, Miller continued his research on mouse leukemia at the Institute until 1963. Miller was the first investigator to discover the relevant role of the thymus gland in body growth and in the immune system response. Until 1961, medical science had no clear idea of such a role, in spite of the standard experiments of surgically removing the gland from adult animals to observe the impact of the lack of the organ upon the organism or its behavior. No apparent change was reported apart from the fact that in adult mammals, the thymus seemed to have undergone atrophy (shrinkage). Miller decided to remove the thymus (thymectomy) of one-day-old mice in order to observe whether this early removal would have some consequence on the animal development. The mice could not develop properly, and died within two-three months later. Autopsies disclosed that the mice had lesions in the liver, similar to those found in viral hepatitis, and showed a deficiency of lymphocytes in the lymph nodes and spleen, which was never found in adult mice after thymus removal. At the time, another group had already shown that lymphocytes were the cells responsible for the initiation of the immune response, which led Miller to the suspicion that the deficiency he found in his animals was due to the early removal of the thymus. Contrary to the current belief of the time, Miller suspected that the thymus could be the site of production of lymphocytes, which would eventually mature into competence in other places other than the thymus. He published an article advancing this hypothesis in 1961 in the scientific journal The Lancet. Miller's suppositions were later proved correct by several independent research groups.
Miller spent most of 1963 at the National Institutes of Health in Maryland, working with germ-free mice, testing the ability of both immuno-incompetent (with an intact immune system) and thymectomised (thymus removed) animals to reject grafts, therefore assessing their immune system response. Because the mice showed tolerance to grafts from unrelated mice and even rats, it became clear that the thymus gland played some important role in the immune system. However, what this specific role could possibly be took another decade of research to be understood.
After returning to London where he stayed until 1966, Jacques Miller moved again to Australia to work as the head of experimental pathology at the Walter and Eliza Hall Institute of Medical Research. Together with Graham Mitchell, he worked on the identification of the types of lymphocytes that could restore the immune response in immuno-incompetent mice. They showed for the first time the existence of two subsets of lymphocytes in mammalians, one originated from bone marrow and the other from the thymus, which have complementary functions in the immune response. Another accomplishment by Miller was the demonstration of the mechanisms of recognition and tolerance of tissues and proteins from the body by its own immune cells, as well as the causes of the delayed-type hypersensitivity reaction (i.e., allergies), using transgenic mice.
Jacques Millers' discoveries about the function of thymus was vital to current understanding of the immune system and had wide implications to the advancement of knowledge in areas such as cancer, autoimmune diseases, AIDS, allergy, viral immunity, and transplant rejection. He served on the World Health Organization in the field of eradicable diseases, as well as on the International Research Agency for Cancer. He became a Fellow of the Australian Academy of Science and of the Royal Society in 1970. He shared with Max Cooper the Sandoz Prize of Immunology in 1990, and received in the same year the Peter Medawar Prize of the Transplantation Society. He was awarded with the Florey Faulding Medal in 2000 for his pioneering contributions to immunology and the thymus physiology.
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