Uncovering Thymus Function

UNCOVERING THYMUS FUNCTION JA CC¿UES F. A. P. MILLER* In our infinite ignorance we are all equal.—Sir Karl Popper. The applause was thunderous. No, it was not a recital at the Festival Hall, nor was it one of Beethoven's symphonies, rather it was a symphony in words. Peter Medawar had just delivered the Tercentenary Lecture of the Royal Society in London. I had never heard such an inspiring and stimulating talk given with such fluency, clarity, and wit. Cellular immunology had really come of age: we now understood why foreign tissue grafts were rejected and how tolerance to these might be induced by the inoculation of foreign hemopoietic cells into embryos or newborn animals. We also knew, from work brilliantly performed by another famous immunologist, Jim Gowans, that small lymphocytes were not short-lived cells as had been thought before. On the contrary, they were cells with a long lifespan, recirculating from blood through lymphoid tissues into lymph and able to initiate immunological reactions when appropriately stimulated by antigen. I always enjoyed the brilliant lectures given in London by Peter Medawar and Jim Gowans. They were towering figures, both physically and in their impact on the science of immunology. Their infectious enthusiasm made me wish that I had been working on lymphocytes and on immunological tolerance rather than on mouse leukemia. When I came to London as a Gaggin Research Fellow in 1958, after receiving my medical degree in Sydney, Australia, I was keen on doing cancer research but did not know exactly what aspects to investigate. Many of the The author would like to thank the University of Queensland for the Gaggin Fellowship which allowed him to pursue his early studies on thymus function in London. He would also like to acknowledge colleagues who encouraged him during the early years, in particular the late Sir Alexander Haddow and the late Sir Peter Medawar. He is also grateful to Sir Gustav Nossal for his enthusiastic encouragement and support, and to his colleagues and students at the Institute throughout the last three decades. *Thymus Biology Unit, The Walter and Eliza Hall Institute ofMedical Research, P. O. Royal Melbourne Hospital, Victoria 3050, Australia.© 1996 by The University of Chicago. All rights reserved. 0031-5982/96/3903-0950$01.00 338 Jacques F. A. P. Miller ¦ Uncovering Thymus Function scientists at the Chester Beatty Research Institute, where I had elected to study for the PhD degree, were busily engaged in looking for new chemical carcinogenic compounds. I was reluctant to be involved in adding more compounds to an ever-growing list and would have preferred to work on a model in which pathogenetic mechanism could be deciphered. Hence I did not feel inclined to join any of those laboratories. Fortunately, I was told that totally different work was going on at Pollards Wood, a satellite of the Institute situated some distance away from London, at Chalfont St. Giles in Buckinghamshire. There, sitting in the middle ofbeautiful gardens and woods, was a magnificent Tudor-style mansion. All its rooms had been converted to well-equipped laboratories and offices. There was also a kitchen and a dining room. As the estate had previously belonged to Bertram Mills, the circus owner, it had housed animals such as horses, dogs, and elephants in various structures. These had also been converted to laboratories or animal houses. The Thymus in Mouse Leukemia At Pollards Wood, I was interested by the work of R. J. C. Harris on the development of sarcomas in turkeys caused by the Rous sarcoma virus. Rather than joining him in this study, he suggested that I might like to investigate the pathogenesis of lymphocytic leukemia induced in mice by what was presumed to be a virus recently discovered by Ludwik Gross in the United States. I felt enthusiastic about this, as I had already had some experience with working on a virus-induced disease of mice with Professor Patrick de Burgh during my B.Med.Sci. year at the University of Sydney [I]. Pollards Wood was a beautiful place in which to work, even though I was given only a small amount of space in one of the converted horse stables. I...