Morten Simonsen 1921–2002

Abstract

Morten Simonsen completed his MD programme at the University of Copenhagen in 1947 and finished his PhD exam in 1953. His PhD thesis dealt with kidney transplantation in dogs at a time when immunological tolerance had not been discovered and when there were no immunosuppressive agents. His scientific talent was not highly appreciated in Copenhagen at the time, and he moved to the UK to become the Director of the MRC Transplantation Unit in East Grinstead, Sussex, a laboratory soon to become a leading research centre in the field of transplantation immunology. Morten Simonsen made several discoveries that had profound effects on the immunological community. His first major finding was the graft-versus-host reaction. Billingham, Brent and Medawar (Philos Trans R Soc Lond 1956;239B:357) had observed that most mice rendered tolerant to homografts (now allografts) by injecting them as a newborn with lymphocytes from adult donors became ill with time and eventually died of a disease they coined ‘runt disease’. They did not particularly emphasize this finding and considered it as a consequence of infections with ‘passenger viruses’ transferred with the donor lymphocytes. However, Simonsen showed, by a clever use of F1 hybrids, that the runt disease was caused by an immunological reaction of the injected lymphocytes against antigens of the recipients and not by virus infections, and named the phenomenon the graft-versus-host reaction. He also showed that the injection of lymphocytes into allogeneic mice and chicken caused splenomegaly in the recipients. The degree of spleen enlargement was proportional to the number of lymphocytes injected. This was the first quantitative test of T lymphocytes, although T and B cells had yet to be discovered. One of Simonsen's findings caused trouble for the clonal selection theory postulated by Burnet and Jerne, namely his demonstration of the ‘factor of immunization’. He compared the level of splenomegaly induced by normal lymphocytes and by lymphocytes from mice that had been immunized against the recipient. If donor and recipient differed at the major histocompatibility locus (H-2), there was no effect of immunization, whereas if they were H-2 compatible, but differed at minor histocompatibility loci, there was a marked factor of immunization, e.g. much fewer lymphocytes from immunized animals were required to cause a certain level of splenomegaly, as compared with lymphocytes from normal animals. In addition, he showed that a very large proportion (2–5%) of lymphocytes were reactive against H-2 antigens, whereas very few (<1/1000 or even fewer) reacted against a cluster of minor histocompatibility antigens. Simonsen's title ‘The clonal selection hypothesis evaluated by grafted cells reacting against their host’ (Cold Spring Harb Symp Quant Biol 1967;32:517) reflects his scepticism about the concept at the time. Although the factor of immunization did not overturn the clonal selection hypothesis, we still do not understand the mechanism behind the high frequency of reactive T cells against major histocompatibility complex antigens. ‘The elusive T cell receptor’ is the title (Transplant Rev 1972;10:36) of a paper by Simonsen at a time when it was generally agreed (and by many scientists experimentally verified) that the T-cell receptor was of immunoglobulin nature. He remained intellectually sceptical even to the most fashionable movements in immunology. It took some 14 years before Mark Davies and Tak Mak revealed the truth. From their discoveries we now know that the genes coding for immunoglobulin and T-cell receptors are totally different. In spite of the wide international recognition, Simonsen was not much appreciated by his Danish colleagues. He publicly argued for the development of basic and experimental immunology in Denmark – a subject that to a large extent had been ignored in Denmark in spite of the impressive development of the subject internationally. He was eventually appointed the Professor of Experimental Immunology and Director of the Institute of Experimental Immunology at the University of Copenhagen, and he led Denmark into the modern experimental immunology and the present day high-quality basic immunology. Simonsen was highly respected by the immunological community, and he received a number of prizes including the Anders Jahre's prize for medicine and the Paul Ehrlich prize. He became an honorary member of the Scandinavian Society for Immunology in 1989 and the American Association of Immunologists in 1997. Morten Simonsen was a rare representative of a critical and truly intellectual scientist. Göran Möller Editor Professor of Immunology, Karolinska Institutet, Stockholm, Sweden e-mail: [email protected]