Jean Dausset - Research

Research

Dausset began his research shortly after obtaining his medical degree in 1945, while working as an intern in the hematology lab at the Children’s Hospital in Boston. His first paper was published in 1950, and dealt with the detection of incomplete antibodies using trypsinized erythrocytes in a plasmatic medium, a technique that displayed improved sensitivity over other techniques used at the time. He went on to publish more works in the field of hematology, including developing a technique in 1952 for the removal of plasma from red blood cells to be used in transfusions to patients somehow intolerant of whole blood transfusions. In 1952 he returned to France and continued his research, particularly focusing on hemolytic anemia, and publishing several works dealing with various forms of blood cell agglutination. It was during this period of research, in 1954, when Dausset first observed an anti-leucocyte agglutinating substance, though it was not until 1958 that he identified an isoantibody specific to leucocytes, and published his findings. It was this finding and the extensive cascade of work that followed that would ultimately earn Dausset his Nobel Prize.

General research in antibodies, agglutination, and anemia continued in the years following this 1958 paper. In 1962, Dausset published an examination of the correlation between leuco-agglutination and skin graft tolerance, his first observation of the antigens’ impact on histocompatibility. His next paper on the subject was published in 1964, when he observed a clear relationship between leucocyte antigen compatibility and antibody response to skin grafts. This finding sparked a flurry of research in the topic of histocompatibility, and by the end of 1965 Dausset had published over a dozen papers exploring leucocyte antigens and their relevance to histocompatibility. After identifying that a two-allele leucocyte antigen group had an influence on histocompatibility and observing the induction of hyper-sensitivity to skin grafts following injection of leucocyte fractions, Dausset developed a system for grouping leucocyte antigens on the basis of histocompatibility. Following this, he put forth the hypothesis that all known leucocyte antigens were part of a single complex, a complex which he named Hu-1. This complex would later become known as one of the Major Histocompatibility Complexes (MHC), specifically those termed Human Leucocyte Antigens (HLA). Dausset’s further work in 1965 examining the effects of Hu-1 antigen injection on skin graft rejection further confirmed the conclusion that this Hu-1 complex was indeed a transplantation antigen, a conclusion which would in time have profound effects on the transplantation process.

In the years to come, Dausset continued his research on the Hu-1 complex. Through 1966 and 1967 he published several more papers on the subject, including a paper summarizing the relevance of Hu-1 antigens to oncogenesis and transplantation, development of the use of a platelet complementation fixation test to identify which antigens are present, and the discovery that Hu-1 is homologous to the mouse H-2 complex, which also functions in histocompatibility. Toward the end of 1967 he confirmed through familial studies that all discovered antigens were in fact part of a single system. Following 1967, Dausset participated in numerous other studies pertaining to the complex (which was renamed HLA in 1968), particularly those examining the genetic basis for the antigens’ transmission, along with publishing a number of other papers for which he claimed primary authorship. For his contribution to these studies as well as his ultimate role in the discovery of this crucial antigen, Jean Dausset received the Nobel Prize in Physiology and Medicine in 1980.

Following his reception of the Nobel Prize, Dausset’s personal research slowed considerably. He contributed to multiple studies, particularly a number relating to genetics, but did not publish anything for which he claimed primary authorship for over a decade. He retired in 2003, at the age of 87.