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The early work on the discovery of the function of the thymus, an interview with Jacques Miller

This interview is part of a series of articles to mark the 25th anniversary of Cell Death and Differentiation.

The thymus was the last major organ to have its function discovered in 1961. Thymus-derived cells (now known as T cells) were shown to mediate immune responses. The presence of T cells in human cancers showed that they had the potential to destroy tumor cells. More recently, a large family of T-cell subsets with different functions have been identified. Here, Cell Death and Differentiation asks Jacques Miller about his early work on thymus and T cells.

Fig. 1
figure 1

Jacques (left), Gus Nossal (right) in 1967. In 1966, Gus Nossal succeeded Sir MacFarlane Burnet as director of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia. He invited Jacques Miller (then at the Institute of Cancer Research in London) to head a new Laboratory at WEHI in Melbourne, Australia.

In 1930, my mother returned to France by ship for health reasons. Finding that she was pregnant, she decided to have the baby in France and so, having been conceived in China, I was born in France, in Nice, in April 1931. In 1932, she went back to China with her three children, Jacqueline, the eldest, Jeanine her second and me. She was back in France in 1935, both for her health and to allow Jacqueline to receive what she thought would be a good education at a boarding school. Some months later, when we were just about to return to China, Jacqueline was diagnosed with pulmonary tuberculosis. Because of this, the family decided to go to Switzerland which, in those days, was the place where tuberculosis could best be managed. We spent 3 years in Vennes-sur-Lausanne, in a beautiful chalet with an unimpeded view of Mt Blanc, and I do remember my sister Jeanine and I playing together with Jacqueline, even when she was coughing blood stained sputum.

In March 1939, my father joined us on a long service leave, but when World War II broke out 6 months later, he was recalled to Shanghai. Believing that Switzerland would be invaded, he decided that the whole family should return to China. We left Lausanne by car very quickly, crossing Northern Italy on our way to Trieste, and there managed to get the last passenger boat out of Italy.

When France capitulated in 1940, the French Concession was automatically taken over by Vichy officials. My father, who did not accept France’s surrender, rallied to the Gaullists and became active politically. He secretly smuggled young Frenchmen, who wanted to join the British forces, out of the French concession onto British ships leaving for Britain. In 1940, he was actually invited by the British War Office to join the London Headquarters as a link between the French and British Treasury. But in December of that year, only a few years before the discovery of streptomycin, Jacqueline died, aged 17. Because of this, and as these were the months of the blitz in London, my father finally declined the offer from London for the family’s sake. However, it was evident that he had to leave Shanghai, for he was next on the list of Gaullists to be arrested by Vichy officials. He also knew from his knowledge of Japanese, that Japan would enter the war very soon, and that he would be at great risk, as he spoke and wrote their language fluently. Some deal was made with the British authorities in Shanghai: we were given British passports and our surname was translated into English - hence Miller. We left in August 1941, taking the last cargo boat out of Shanghai bound for Batavia (now known as Jakarta). There we boarded a passenger ship and arrived in Sydney on the 25th of September 1941, just less than 3 months before the bombing of Pearl Harbor.

Prior to arriving in Australia, Jeanine and I had never been to school. We had teachers at home, wherever we lived. The last one in Shanghai was a 36-year old Viennese with a PhD who had escaped a Nazi prison. Instead of learning much from him, we spent our time having great fun with him. So, we arrived Australia knowing only a very few words of English!

Because my father had been impressed by the knowledge, culture and broad mindedness of the Jesuits in Shanghai, with whom any subject could be discussed, he decided that I should go to a Jesuit college, St Aloysius’ College, and Jeanine went to a convent close by.

At Aloysius I met and frequented a brilliant young Austrian boy, a refugee from Vienna, who was a year ahead of me. His name is Gus Nossal and we became life-long friends. I have followed one year behind in his footsteps first at school, then at the Sydney Medical School, and finally at the Royal Prince Alfred Hospital in Sydney.

During my medical studies at Sydney University, I was pleased to interrupt them to do a year’s research as a B.Med.Science student in the laboratory of Professor de Burgh, again following in the footsteps of Gus Nossal. I too was given the task of deciphering how ectromelia virus multiplied in liver cells, but rather than continuing on the line of work that previous B.Med.Science students had performed with normal liver, I thought it more interesting to determine whether the virus might interfere with some crucial biochemical events during liver regeneration after partial hepatectomy. Two papers resulted from this work.

As a Ph.D. student, Dr Harris was meant to act as my supervisor, although my official supervisor had to be a full Professor of the University of London, which in my case was Professor Sir Alexander Haddow, the director of the Chester Beatty Research Institute. Barely a few months after my arrival, Dr Harris was offered a much better position at the National Institute for Medical Research in Mill Hill near London. I was therefore left without a close supervisor but lucky to inherit his animal space.

Pollards Wood was a large estate that had previously belonged to Bertram Mills, a circus owner. It had a magnificent Tudor-style mansion situated in the middle of beautiful gardens and woods. The rooms had been refurbished to well-equipped laboratories and offices. Scattered throughout the estate were buildings that had previously housed animals such as horses, dogs and elephants. They had also been converted to laboratories or animal quarters. A van from the main Institute in South Kensington came once or twice every week to bring mail and whatever supplies were required. Even though I was given only a small shack and a small amount of space in one of the converted horse stables, it was a delight to work in such pleasant surroundings, away from the crowd, the noise, and the pollution of greater London.

“You, young people, you are the future of your country. You are also in many ways the future of the world! That is because you have chosen a career in science. And it is only through science that humanity can improve its lot on many fronts. It is by scientific knowledge that we can increase the world’s food supply and eventually end poverty. It is through scientific knowledge that we can reverse the effects of climate change that threaten our planet and all the species that live there. It is by the use of scientific knowledge that we can change our energy production methods to those that use renewable and clean energy. It is through scientific knowledge that we can prevent epidemics and we can ameliorate or even cure many diseases, now including cancer.

Science is a worthwhile activity. It is something you can enjoy doing (while being paid for it). Of course, you need to work hard. You need to ask the right questions and to formulate a hypothesis that can be tested experimentally. And then you need patience, persistence, and perseverance. You need to repeat your experiments more than once and you need to thoroughly check your data. And if your data are solid, you need not be disturbed if your interpretation is not widely accepted. You may be wrong in your interpretation but that does not matter, as long as your data are firm and reproducible. And you need not to be discouraged if your work cannot be translated into something useful that can for example be used in a clinical context. It can take many years from bench to bedside. In my case, it took nearly 60 years from the discovery of thymus function and of T and B cells to the use of T and B cells as cells that produce monoclonal antibody, and as killer cells in cancer immunotherapy.

In conclusion I would just say that the future belongs to you. Hence good luck, work hard and have fun whilst doing so”.

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Miller, J. The early work on the discovery of the function of the thymus, an interview with Jacques Miller. Cell Death Differ 27, 396–401 (2020). https://doi.org/10.1038/s41418-019-0462-y

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