Jean Dausset French immunologist, Nobel Prize laureate in Physiology or Medicine 1980 Date of Birth: 19.10.1916 Country: France

Biography of Jean Dausset

Jean Baptiste Gabriel Joachim Dausset, a French immunologist, was born in Toulouse as the fourth child of Henri Pierre Julius Dausset, a successful doctor specializing in radiology and rheumatism, and Elizabeth (Bruyard) Dausset. He spent his early years in Biarritz and when he was 11 years old, his family moved to Paris. He attended the Lycée Michelet and graduated with a diploma in mathematics. Following in his father's footsteps, Dausset enrolled in the medical school at the University of Paris in the late 1930s.

During the early years of World War II, in 1939, Dausset was called into medical service in the French army, and the following year, after the occupation of France by Germany, he joined the Free French Forces in North Africa. In Tunisia and France, Dausset observed numerous blood transfusions that caused severe reactions in patients, even when the blood types of the patient and the donor were the same. He later described these adverse reactions, explaining that they were due to the presence of active anti-A antibodies in the plasma of the donors. He discovered that these antibodies appeared after vaccination with diphtheria and tetanus toxoids, which contained a soluble component called the A substance. Karl Landsteiner's discovery of the major blood groups in humans made blood transfusion mostly a safe procedure when the blood types of the donor and recipient matched. Blood groups in humans differ based on the presence or absence of certain proteins (antigens) on the erythrocytes. The reaction between antibodies and foreign antigens causes incompatibility between the blood groups of the donor and recipient. Landsteiner's ABO antigen system explained the reasons for most reactions of this type, although other blood antigens and antibodies also participate in such reactions.

After being discharged from military service in 1945, Dausset earned his medical degree from the University of Paris. The following year, he was appointed director of the laboratory at the French National Blood Transfusion Center. In the mid-1940s and early 1950s, he studied various biological aspects of blood transfusion, focusing on the problem of pathological reactions.

Some patients who underwent multiple blood transfusions or received treatment with certain medications developed reactions associated with leukocytes, in addition to the reactions involving erythrocytes described by Landsteiner. In 1952, Dausset reported a patient whose blood contained antibodies against an antigen found in the leukocytes of some other individuals but not in the patient's own leukocytes. In 1958, when Dausset joined the research at the Faculty of Medicine of the University of Paris, he discovered several variants of the MAC antigen on the surface of leukocytes in the French population. He used the designation MAC (initials of three donors in whose blood he found these antigens) to describe these antigens. Anti-MAC antibodies were formed when MAC-negative recipients received blood from MAC-positive donors. Dausset noted that blood transfusion is a form of organ transplantation.

In the early 20th century, it was discovered that tissues transplanted from one person to another are almost always rejected, except in cases of close donor-recipient relationship (especially identical twins). Dausset hypothesized that the MAC antigen is one of the factors that allows the body to distinguish its own tissues from those of another organism.

In 1962, Dausset was appointed adjunct professor of medicine at the University of Paris. The following year, he became the chief biologist in the hospital system of Paris and co-chairman of the Institute for Hematology. After Dausset's discovery of MAC antigen variants, other researchers obtained data on newly discovered antigens that required explanation. In 1965, at a working session organized by Bernard Amos to coordinate histocompatibility research (compatibility of different tissues for successful transplantation), Dausset proposed that most of these antigens are part of a unified system according to the theory proposed by George D. Snell and his colleagues in the 1940s. At that time, Snell demonstrated that tissue rejection in mice is controlled by several physically linked genes called the major histocompatibility complex (MHC). Dausset believed that MHC exists in humans. He argued that transplant antigens exist in great diversity not because many variant forms (alleles) are derived from a single set of genes. It became evident that, like in mice, MHC in humans consists of several genes called the human lymphocyte antigens (HLA) group. As each gene occurs in multiple allelic forms, there are millions of different combinations of HLA system antigens.

In 1967, Dausset and his colleague Felix T. Rapaport began studying skin grafts between members of the same family. Their results indicated that transplants between family members with the same HLA antigen type were more successful than in cases where there were differences in HLA antigen type. These findings strongly encouraged Dausset to recommend to surgeons the matching of donor organs based on HLA antigen type during transplantation. HLA typing techniques led to a significant improvement in the viability of transplanted organs, but only in cases where the donor and recipient are related, especially twins. Among unrelated individuals, genetic differences other than those identified by Dausset caused transplant rejection, despite matching based on HLA antigens. In 1967, Amos and his colleague Fritz Bach discovered another gene called HLA-D (named so because it was the fourth described gene in the HLA system), which was the human equivalent of the immune response (IR) genes in the MHC of mice. Baruj Benacerraf and other researchers found that IR genes not only affect the survival of transplanted organs but also play a vital role in the body's ability to mount an immune response against certain diseases. In the early 1970s, it became evident that HLA-D genes were a significant factor in the link between HLA types and specific diseases. In 1967, Dausset investigated the interaction between the HLA system and the development of various diseases, becoming the first to do so in this field. Although these results were preliminary, his efforts stimulated the work of other scientists. Based on these studies, it was shown that certain HLA types are associated with an increased risk of developing certain diseases such as joint disorders, diabetes, and autoimmune diseases. Dausset hypothesized that "each HLA haplotype (a group of alleles contributed by each parent)... has a unique gene configuration that determines a specific immune response, favorable in some environmental conditions and unfavorable in others."

In 1968, Dausset was appointed director of the French National Institute of Scientific Research. In the same year, he began teaching immunohematology, the study of antigens and antibodies of various blood components, at the University of Paris. Additionally, since 1978, he became a professor of experimental medicine at the Collège de France. Throughout the 1970s, he also served as a visiting professor at universities in New York, Brussels, and Geneva. The function of MHC gene products (antigens) was not fully understood, but in the mid-1970s, a number of scientists, including Benacerraf, demonstrated that the interaction between different cells, especially of the immune system, is limited by MHC, meaning that both interacting cells must carry the same MHC antigens on their surfaces. Dausset hypothesized that the "restriction phenomenon is probably the most direct evidence of the role of HLA complex products in the immune response of humans." Although much remained to be learned about the structure of MHC genes, their activities in the body, and the regulatory pathways for medical purposes, it became clear that MHC is a central element in understanding the immune system as a whole.

Dausset shared the Nobel Prize in Physiology or Medicine in 1980 with Benacerraf and Snell "for their discoveries concerning genetically determined structures on the cell surface that regulate immune reactions." In his presentation speech, George Klein emphasized the importance of the research conducted by the three laureates, who "succeeded in transforming what initially appeared to be the area of basic experiments on inbred mice, understood only by a few, into a coherent biological system of great significance for the understanding of the mechanisms of cellular recognition, immune responses, and transplantation rejection."

Dausset continued his work at the university in Paris, where he continued his HLA research at the Saint-Louis Hospital.

In 1962, Dausset married Rosa Mayoral Lopez, and they had a son and a daughter. His lifelong motto, which he never deviated from, was "Vouloir pour valoir," which loosely translates to "What you wish, you can achieve."

In addition to the Nobel Prize, Dausset received the International Gardener Foundation Award (1977) and the Wolf Prize in Medicine from the Wolf Foundation in Israel (1978). He was a member of the French Academy of Sciences and Medicine, the Royal Academy of Medicine of Belgium, an honorary member of the Yugoslav Academy of Sciences and Arts, an honorary member of the American Academy of Arts and Sciences, and a knight of the Legion of Honor.