Autobiography of Jules A Hoffmann
I was born in Luxembourg where I grew up during the difficult post-war years. My father was a high-school teacher in Biology and a fervent entomologist. He spent his spare-time collecting and identifying insects and he conveyed his passion for this exceptionally diverse group of animals to me during our numerous field studies. My scientific work has always focused on insect models since that period. Outside this field, my main interests are languages and history.
After High School, I left Luxembourg for the University of Strasbourg (France), where I majored in Biology. There, I felt attracted by the laboratory of Pr Pierre Joly, who worked on endocrine regulations of development and reproduction in grasshoppers, a major pest in African countries. Pr Joly offered me a position with the French National Research Agency (CNRS) and I started studying the antimicrobial defenses in grasshoppers. The choice of this problem was motivated by the fact that my host-laboratory had worked for several decades on transplantations of endocrine organs between grasshoppers: although these experiments had been routinely performed under septic conditions, no microbial developments were ever observed in the recipient insects, suggesting that grasshoppers had efficient mechanisms to counter opportunistic microbial infections. Virtually nothing was known on antimicrobial defenses in insects at that time, beyond the classical observations of Metchnikoff at the end of the 19th century, on the engulfment of microbes by blood cells (phagocytosis).
During the studies which led to my Ph.D. defense in 1969, I focused on the origin of blood cells in grasshoppers and discovered a well-developed blood-forming tissue (hematopoietic tissue) in the vicinity of the heart vessel. Selective X-ray treatment of this tissue resulted in a massive septicemia and, more surprisingly, in an arrest of the endocrine control of molting. The latter is governed by the steroid hormone ecdysone, which had just been characterized in Germany by the renowned biochemist Peter Karlson. I went for a postdoctoral stay in his laboratory in Marburg in 1973, while our group in Strasbourg started analysing the biological and biochemical contexts of infections in grasshoppers.
In 1978, upon the retirement of Pr Joly, I became Director of the laboratory which, under the name of ‘Endocrinology and Immunology of Insects’ continued to work in the two directions: (1) endocrine studies focusing on the biosynthesis and metabolism of the molting hormone ecdysone and its biological roles in reproduction and development; (2) the antimicrobial defenses, the latter studies shifted gradually to biochemical identifications of the induced antimicrobial molecules which largely contribute to the survival of infected insects. This direction was boosted by the discovery of the antimicrobial peptide cecropin in infected pupae of the moth Hyalophora cecropia, by Pr Hans Boman in Stockholm where my co-worker (and wife) Danièle Hoffmann spent a postdoctoral period in 1979.
By 1990, the laboratory had considerably grown. To the initial research competences of experimental and cell biology, biochemistry and chemistry, we had added molecular genetics. We decided to concentrate our future efforts on the antimicrobial defenses and abandon our previous insect model organisms for the gentically tractable model Drosophila. In the 15 or so years which followed that decision, we were able to characterize in this species several families af inducible antimicrobial peptides, and to decipher the control of expression of their genes. We were also able to identify the receptor molecules which recognize diverse microorganisms and activate the signaling cascades leading to the expression of the immune-response genes (namely to that of the antimicrobial peptide genes). By then, our studies, in conjunction with those of several other groups in Europe, the US and Japan, had led to a comprehensive view of the fly immune system and had established it as a paradigm of innate immunity. These studies had also contributed to a more global understanding of innate defenses in other animal groups, namely in mammals, in particular as regards the roles of Toll receptors.
During the 80s and 90s, I had been involved in several advisory committees of our research agency CNRS, many of which I chaired, and in 1994, the agency appointed me as Director of the prestigious CNRS Institute of Cellular and Molecular Biology (IBMC) in Strasbourg. Our laboratory moved from the Institute of Zoology which had hosted us so far, to the IBMC, a move which I would surely not have anticipated during the ‘grasshopper years’.
In 1992, I had been elected a Member of the French National Academy of Sciences and served as Vice-President and President of this Academy from 2005 to 2008. This was for me an exceptionally interesting period during which I came to personally know remarkable scientists in various fields from Mathematics to Astronomy, from Climate Science to Theoretical Physics, to name but a few. It was also an opportunity to encounter the Presidents and Councils of the major foreign Academies with whom I still maintain warm relations.
It goes without saying that the scientific achievements of our laboratory over the many years, as recounted above, are to be credited to a long list of collaborators of high intellectual and human calibers. Many in this list are now Distinguished Class Professors and heads of well-recognized groups in the field, here in France and in other countries. I express my admiration and warm gratitude to all of them.
28 September 2011, Hong Kong