Credit: CEPH

Jean Dausset, who died in Majorca, Spain, on 6 June 2009, aged 92, will always be remembered for the discovery of the human leukocyte antigen (HLA) tissue system, one of the most significant scientific breakthroughs of the twentieth century. The HLA system — a collection of genes that encode polymorphic molecules expressed on the surface of cells — determines the biological identity of an individual's cells and tissues. Because recognition of HLA molecules by the immune system allows it to distinguish self cells from foreign cells, this discovery laid the foundations for successful organ transplantation. Dausset not only pioneered the scientific and medical research into HLA, but also embraced and promoted the sociological and philosophical impacts of this finding.

Dausset was born in Toulouse, France, into a provincial bourgeois family, and spent his youth in Biarritz before the family moved to Paris. He completed his medical education at the Faculty of Medicine at the University of Paris. During the Second World War, he joined the French army transfusion service and participated in the Tunisian and Normandy campaigns. It was in the Army Medical Corps, where he oversaw large numbers of blood transfusions, that his drive to understand the causes of frequent adverse reactions against blood cells was born. As part of the Marshall Plan, he attended Harvard University for a year, in 1948, where he worked as a clinical haematologist at the Peter Bent Brigham Hospital. On his return to Paris, he specialized in immunohaematology.

In 1952, Dausset made the seminal observation that serum from patients who had received multiple blood transfusions caused marked agglutination of white blood cells (leukocytes). Dausset attributed this leukoagglutination to an antibody in the serum directed against the white blood cells. In 1958, he described the first human leukocyte antigen, which he named MAC (now known as HLA-A2), in a single-author publication. He went on to define the genetic region that encodes the complex system of cell-surface antigens, which he termed HU-1, later renamed human leukocyte antigen.

In the 1960s, Dausset teamed up with the surgeon Felix Rapaport in Paris. Together they performed hundreds of skin-graft experiments on volunteers, correlating graft survival with the extent of HLA incompatibility and thereby demonstrating the role of HLAs in human transplantation. He considered these volunteers the 'real heroes' of the discovery of the HLA system and always acknowledged their contribution on receipt of honours.

Today, many years after his discovery, tissue typing (determining the combination of HLAs on cells) is an essential tool for selecting donors for organ and bone-marrow transplantation. Dausset's pioneering work on the HLA system was recognized in 1980 when he was awarded the Nobel Prize in Physiology or Medicine, together with Baruj Benacerraf and George Snell, for “their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions”.

Although Dausset's own contributions were not in the field of immunology, he always insisted that HLAs were important in the control of immune responses as established by Hugh McDevitt, a colleague he particularly admired. They both anticipated that the HLA system contributed to susceptibility or resistance to disease, including autoimmune disease. With extraordinary prescience, Dausset extended this principle to espouse the concept of a new form of medicine that used an individual's genetic profile to predict disease — he named this 'predictive medicine' and foresaw its potential in personalized disease prevention.

Dausset recognized that the HLA system was a tool that could be used to analyse the genetics and migration patterns of populations. His interest in the anthropological implications of his discovery took him on a voyage to Easter Island, where he collected blood samples from this isolated population for genetic analysis.

He also realized that the HLA model could be extended to the entire human genetic system and, in 1984, together with Daniel Cohen, created the Human Polymorphism Study Centre (CEPH) — a resource that facilitates genetic studies of human populations. The genotyping of large numbers of reference families by the CEPH, and the sharing of this information with scientific peers, contributed to the determination of the first genetic linkage map of the human genome, and led the way to the discovery of genes that predispose to numerous diseases.

In addition to his medical research, Dausset worked as a French government adviser from 1955 to 1958, and was instrumental in shaping French law integrating science education and medicine, leading to the creation of the CHU (University Hospitals). In 1969, he founded France Transplant, an organization that coordinated organ transplantation across France. With Jean Bernard, his colleague at the Hopital St Louis, Paris, he established the French Bone Marrow Donors Registry of unrelated donors for bone-marrow transplantation. When these organizations were taken over by national administration, he voiced concern that the humanistic nature of these endeavours would be diluted by bureaucracy. Dausset was eventually elected president of the Universal Movement for Scientific Responsibility (MURS), and actively campaigned against patenting the human genome sequence.

Dausset never had a mentor. The discovery of the HLA system stemmed from his own vision and was initially driven solely by his ferocious determination. By contrast, for more than 50 years as a scientist, he embodied a spirit of international collaboration, gathering around him numerous students, colleagues and friends, whom he encouraged and supported. This extended worldwide community, which had a strong South American and Hispanic flavour, firmly established him as the 'father of HLA'. He enjoyed this parental status and designated the immunologist Rose Payne the 'mother' of HLA.

A passionate collector of modern plastic arts, for a time he owned an art gallery in Saint Germain des Prés, Paris. He poetically summarized his philosophy of life in the title of his autobiography Clin d'Oeil à la Vie (A Wink at Life). His wife Rosita, daughter Irène and son Henri were a constant support. Dausset died peacefully in Majorca, surrounded by his family and immersed in the Hispanic culture he was so fond of. His uniqueness will endure.