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Karl Landsteiner applied the sciences of biochemistry, pathology, microbiology, and immunology in medical research to great success during the first half of the 20th century. Although he is principally known for elucidating the major blood group antigens A and B and their isoantibodies for which he was awarded the Nobel Prize in Physiology or Medicine, Landsteiner made many other important medical discoveries. In that respect, he ascertained that paralytic poliomyelitis was due to a virus, the pancreas was damaged in cystic fibrosis, simple chemicals called haptens were able to combine with antibodies, and the Rh antigen that was later found to be the principal cause of hemolytic anemia of the newborn was found in most humans. Moreover, Landsteiner's book "The Specificity of Serological Reactions" was a precursor to the molecular revolution in immunology that occurred after Second World War. Finally, he was one of the leaders of the American Association of Immunology and of the Journal of Immunology.

This article interweaves a history of Ray Owen's early work with a broader account of the conceptual landscape of immunology in the mid 1950's. In particular, Owen's openness to the very possibility of chimeric phenomena is recognized.

Arthur Mourant's The Distribution of the Human Blood Groups (1954) was an "indispensable" reference book on the "anthropology of blood groups" containing a vast collection of human genetic data. It was based on the results of blood-grouping tests carried out on half-a-million people and drew together studies on diverse populations around the world: from rural communities, to religious exiles, to volunteer transfusion donors. This paper pieces together sequential stages in the production of a small fraction of the blood-group data in Mourant's book, to examine how he and his colleagues made genetic data from people. Using sources from several collecting projects, I follow how blood was encountered, how it was inscribed, and how it was turned into a laboratory resource. I trace Mourant's analytical and representational strategies to make blood groups both credibly 'genetic' and understood as relevant to human ancestry, race and history. In this story, 'populations' were not simply given, but were produced through public health, colonial and post-colonial institutions, and by the labour and expertise of subjects, assistants and mediators. Genetic data were not self-evidently 'biological', but were shaped by existing historical and geographical identities, by political relationships, and by notions of kinship and belonging., (Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.)

The research program of my laboratory included three major topics: the structures and immunology of human carbohydrate blood group and glycosphingolipid antigens; the tissue distribution, subcellular localization and biosynthesis of glycosphingolipids; and the structural basis of the binding of carbohydrates by antibodies and lectins.

Karl Landsteiner, a Viennese M.D. and pathologist, discovered in the years 1900–1901 the first human blood groups, ABO groups. Furthermore, he made numerous significant contributions to various fields of the biomedical science. In this paper I report on his life and work in Vienna, The Hague and New York.

Cyril Clarke was an outstanding general physician and lepidopterist. Late in his career, and stimulated by his work on the genetics of mimicry in butterflies, he became interested in the evolving field of medical genetics. His work on the relationship of blood groups to particular diseases led him and his team in Liverpool to evolve a remarkably successful approach to the prevention of Rhesus haemolytic disease of the newborn., (© 2012 Blackwell Publishing Ltd.)

Ludwik Hirszfeld, together with his wife Hanka, was the first to study the blood groups in large numbers of subjects (soldiers) during World War I at the Macedonian front. They found significant differences in the distribution of the ABO blood groups, that is, type A was more common in soldiers from North Central Europe, whereas type B was more common in those from Eastern Europe. Their data were later (in the 1920s and 1930s) misused by German nationalists to support the concept of Aryan supremacy. The Hirszfelds also discovered Salmonella paratyphi C, now known as Salmonella hirzfeldi. Their landmark studies drew others to this new field of seroanthropology, most notably Arthur Mourant, as well as Robin Race and Ruth Sanger, who wrote "Blood Groups in Man" detailing the antigenic differences among various peoples., (Copyright 2010. Published by Elsevier Inc.)

Since the first issue of TRANSFUSION in 1961, there has been a tremendous expansion in not only the number of blood group antigens identified but also in our knowledge of their biochemical basis, function, and more recently, associated DNA changes. As certain techniques became available, our ability to discover and elucidate blood group antigens and appreciate their contribution to biology became possible. In particular, Western blotting, monoclonal antibodies, cloning, and polymerase chain reaction-based assays have led to an explosion of our knowledge base. The study of blood groups has had a significant effect on human genetics where they serve as useful markers in genetic linkage analyses. Indeed blood groups have provided several "firsts" in certain aspects of genetics. Blood group-null phenotypes, as natural human knockouts, have provided valuable insights into the importance of red blood cell membrane components. This review summarizes key aspects of the discovery of blood groups; the inconsistent terminology that has arisen; and the contribution of blood groups to genetics, safe transfusion, transplantation, evolution, and biology.

The discovery of ABO blood group was a major step in mastering transfusion therapy. Karl Landsteiner (1868-1843) was the author of this discovery. This paper retraces the hard career of this American scientist of Austrian origin, and describes the circumstances that led his research to the discoveries, which were turning points in the history of the immunology.

Collecting, processing and dispensing blood for hemotherapy has evolved into transfusion medicine (TM), a newly recognized discipline. Joining my efforts to those of collaborators all over the world during this period of transformation, my scientific career spanned from the investigation of the immunogenetics of Bombay (OhOh) blood to the establishment of the academic TM program at the University of California, San Francisco (UCSF) (San Francisco, Calif). The twin discoveries of class-specific antibodies against immunoglobulin A (IgA) causing anaphylactic transfusion reactions and of anti-IgA of limited specificity defining A2m(1) as the first genetic marker of IgA led to the award of the Julliard Prize. My precocious appointment as the head of the Bombay Municipal Blood Center in India launched my academic career in 1969 as the Chief of the blood bank at UCSF Medical Center. Viral hepatitis, then the principal risk of transfusion, engaged me in the molecular analyses of purified hepatitis B virus (HBV) and its surface antigen. Consequently the first HBV vaccine, derived from infected plasma (superseded by cloned HBV envelope protein) and hepatitis B immune globulin were developed for clinical trials that led to Food and Drug Administration-licensed biologic products for prophylaxis and therapy. The advent of HIV/AIDS in the early 1980s raised renewed concern about transfusion safety and led me to push for hepatitis B core antibodies blood screening for improved transfusion safety. The triennial International Symposia on Viral Hepatitis and Liver Disease, which I started in 1972, continue to be the foremost forum for the contemporary assessment of hepatitis prevention and treatment. Besides viral hepatitis, I undertook multiplexed flow cytometric analyses for markers of infection by blood-borne viruses and their polymerase chain reaction-amplified gene products, kinetics of HIV replication in peripheral blood lymphocytes, leukocyte depletion for safer transfusion, and removal/inactivation of blood-borne viruses. The TM training and research programs I initiated at UCSF in the 1980s with National Institutes of Health support enabled me to recruit new faculty members who continue to foster the worldwide advancement of transfusion safety.

The first blood transfusions in humans were xenotransfusions, carried out by Jean-Baptiste Denis beginning in 1667. Richard Lower, Matthäus Purmann and Georges Mercklin also experimented with the use of animal blood for transfusion until this practice was forbidden in 1670, after the death of one of Denis's patients. In the middle of the 19th century, xenotransfusion was rescued from oblivion by the work of Pierre Cyprien Oré. Franz Gesellius and Oscar Hasse fervently defended xenotransfusion, but Emil Ponfick and Leonard Landois stressed the potentially harmful effects of inter-species transfusion from 1874 onward. Xenotransfusion was abandoned completely following the discovery of blood groups by Karl Landsteiner in 1900. From 2000, because of progress in xenotransplantation and the need of blood supply, xenotransfusion is again being considered. Pigs are the best potential donors. The development of alpha-1,3-galactosyltransferase gene-knockout pigs has overcome the first hurdle to xenotransfusion. The main obstacle to porcine red blood cell transfusion is now the cellular response involving macrophages or natural killer cells.

The National Blood Group Reference Laboratory (NBGRL) in Israel was established in Jerusalem in 1971 and transferred to Magen David Adom (MDA), National Blood Services in 1995. This laboratory was the inspiration of the first author of this article for over 30 years. The realization of this vision was made possible by the cooperation of colleagues and laboratory workers in blood transfusion services throughout the country. The aim of the service was to provide diagnostic help in resolving immunohematologic problems found in the blood banks and clinics in Israel. In the beginning, only a part-time technician performed the work and testing was done using very limited reagents. The service was expanded by personal visits to all of the 22 blood banks in Israel to explain the aim of this new service and to educate them about the importance of resolving each and every case. One major issue was the cost involved in referring problems but it was decided at the outset that these would be covered by the government to ensure that a workup would be performed for all referred cases. The expansion of the service could not have been achieved without the help of the SCARF program. This voluntary service enabled us to identify the first rare donors in Israel, resolve complex cases, and find compatible blood for our patients. To illustrate the importance of the NBGRL in Israel and the rapid resolution of cases referred, several individual stories are described. The purpose of this review is to show the importance of the NBGRL in identifying rare blood groups and in providing and coordinating services and the importance of keeping in close contact with the rare donors to encourage and promote their donations, which may save lives.

The Redelberger antigen (Rba) was first discovered in 1974 on the RBCs of a blood donor who was an employee of the Community Blood Center in Dayton, Ohio. The discovery was made as a result of the investigation of a reagent contamination problem. Two examples of the Rba antigen were subsequently identified in the United Kingdom,but no "new"examples have been identified in the United States or Europe. Anti-Rba is a commonly occurring antibody, often found in combination with other antibody specificities, especially in combination with other antibodies to low-incidence antigens.

Throughout the history of medicine, there have been difficulties in forensic proving of unsolved paternities, making this a major andrological-forensic challenge. In the Roman empire, children procreated by incest, called 'incestuosi', had no rights at all and other illegitimates, e.g. children born of prostitutes or as a result of adultery, could not assert rights towards the father. Only through the 'corpus iuris civilis' of the Roman Emperor Justinian I (6th century ad) could claims of alimony be made in some cases. In later times, evidence of presumable impotence of a potential father was determined by the congressus, where defined juristical 'sexual fights' had to be held before official matrons, surgeons and priests. Men had to demonstrate their erectile and ejaculatory function. A special significance must be attributed to the microscopical discovery of spermatozoa by the medical student Johann Ham in 1677 and the further investigation by Antoni van Leeuwenhoek. After centuries of personally biased and scientifically incorrect concepts of paternity determination, the discovery of the blood grouping system by Karl Landsteiner at the beginning of the 20th century paved the way for sophisticated techniques to prove or rather to disprove paternity. In 1921, Reuben Ottenberg from New York was the first to suggest the application of the system to medico-legal questions, but it was not before the 1950s that legal courts accepted this method. A famous example of disregarding clear blood grouping results was the case of the movie star Charles Chaplin in California in 1946. Modern DNA techniques, today the golden standard in forensic medicine, have also been applied recently for historical investigations. One of the very illustrious examples is the dispute about Thomas Jefferson, third President of the US, fathering a child of one of his slaves.

Ruth Ann Sanger's scientific career was concerned with the delineation and mapping of human blood group genes by simple manual methods using, as tools, blood group antibodies and the agglutination reaction followed by statistical analysis of the results. Her active period coincided with the flowering of the whole subject of blood groups, which was initiated by the recognition of the clinical significance of the Rh antigens and the rediscovery of the antiglobulin reaction by Coombs, Mourant and Race (Coombs et al. 1945). In these days of 'high-technology' research, it is salutary to recognize that the complex body of knowledge that has been accumulated about blood groups has been derived by using the very simple technique of the visible cross-linking of red cells by antibodies specific for the blood group antigens present on the red cell surface. Ladsteiner had by chance discovered the ABO blood group system in 1900 with the use of the agglutination reaction, but little progress was made in the next 45 years and we know that the main reason for this is that most blood group antibodies are not physically capable of bringing about the cross-linking and agglutination of red cells on their own. This problem was solved by the introduction of the antiglobulin reaction, which uses a secondary antibody to bring about the cross-linking of blood group antibodies already attached to red cells.

One hundred years after his discovery of the AB0 blood groups, the monumental work of Austrian physician Karl Landsteiner (1868-1943, Nobel Prize 1930) on the specificity of serological reactions is widely recognised. His work on isoantigen reactions included the discovery, together with Levine and Wiener, of the Rhesus factor. Landsteiner did much to develop our understanding of autoantibody reactions and also contributed insights into the aetiology of infectious diseases that were rampant in his time. His work in immunochemistry included the discovery of hapten antigenicity. However, most of all he wanted to be remembered for his theory on the specificity of serological reactions, which he had strongly substantiated with his own work. Landsteiner suffered from the shortages in Vienna at the end of World War I. He and his family moved to the Netherlands in 1919. There he worked as pathologist at the Red Cross Hospital in The Hague until his move to the Rockefeller Institute in New York in 1923. Nowadays, his work is celebrated for its numerous excellent contributions to the fields of transfusion and transplantation medicine, population genetics, immunology, and infectiology.

During the course of the twentieth century, at least 270 authenticated alloantigens have been recognised on the red cell surface. Most of these have been classified into 26 blood group systems, each of which represents a single gene or a cluster of two or three closely-linked homologous genes. Most blood group polymorphisms result from single nucleotide changes encoding amino acid substitutions in cell surface proteins. Many other mechanisms, including recombination between homologous genes, are also involved, especially in the complex Rh and MNS systems. There are at least three common molecular backgrounds to the RhD-negative phenotype. Some blood group antigens are carbohydrates, the polymorphisms resulting from mutations within genes encoding glycosyltransferases. Red cell surface proteins perform a variety of functions. For some the functions are well understood, but for most they can only be surmised from the structure of the protein. Putative functions include, membrane transport, cell adhesion, complement inactivation, binding chemokines, and anchoring the plasma membrane to the cytoskeleton. Some erythroid cell surface antigens may serve their primary purpose during erythropoiesis. Analysis of the development of these proteins on erythroid cells during erythropoiesis, ex vivo, has provided clues to their functions and a useful set of markers for the study of erythropoiesis.

In this review an attempt is made to list the most important events in the search for genetic markers in the blood of animals. In chronological order, blood groups, biochemical polymorphisms, lymphocyte antigens and DNA markers have been discovered and used in practice. Of all practical uses, parentage verification and exclusion are regarded as the most important, and it can be said with pride that the South African Stud Book is as infallible as any other stud book in the world.