Although relatively few monographs have had a seminal effect on the development of an important field of the biological sciences, there is no doubt that Landsteiner’s book, first published in German in 1933 and later in English, had a major impact on the development of modern immunology. So, what was the background of the man who wrote this extraordinary work?

Karl Landsteiner (1868–1943) was born and educated in Vienna. From 1898 to 1908 he worked at the Institute of Pathological Anatomy at the University of Vienna and later became a professor. He left Austria for The Netherlands in 1919 and in 1922 he moved to the United States where he worked at the Rockefeller Institute for Medical Research in New York.

At the end of the 19th century several workers had observed that normal red cells clump when exposed to serum from patients with a variety of infectious diseases. At the time, it was believed that this was caused by the patients’ inflammatory disease. While still a young assistant in the Institute of Pathological Anatomy, Landsteiner studied the reactions between the red cells and sera of 22 healthy individuals and found that certain sera would agglutinate the cells of particular people. Originally, he was able to separate these samples into three types, which he called A, B, and C; the serum of A clumped the cells of B; the serum of B clumped the cells of A; and the serum of C clumped both the cells of A and B, but the cells were not clumped by A or B serum.

In his excellent account of the history of the discovery of blood groups, Louis K. Diamond quotes Philip Levine, Landsteiner’s assistant, as pointing out how this careful work was so characteristic of Landsteiner, who had previously observed red cell agglutinins and hemolysins in the sera of sick patients but, not satisfied by these observations, had turned to investigating a larger number of healthy people. In his brief but thorough paper in 1901 which described these findings, Landsteiner also pointed out that blood isoagglutinins retained their activity after drying and redissolving and that he could observe agglutination with serum extracted after two weeks from a dry blood clot. This observation of course predicted the importance of these findings for forensic medicine in the future. The conclusion of this paper read “finally, it might be mentioned that the reported observations may assist in the explanation of various consequences of therapeutical blood transfusions.” This throw-away summary must surely compete with Watson and Crick’s final sentence about the possible genetic function of DNA at the end of their famous Nature paper in 1953 that described its structure! Landsteiner continued to make valuable contributions to the further development of knowledge about the blood groups, notably in his work with Wiener which, together with that of Levine, characterized the Rhesus blood group system. He was awarded the Nobel Prize for his fundamental discovery of the blood groups in 1930.

In The Specificity of Serological Reactions, Landsteiner’s intention was to provide an account of the experiments on antigens and serological reactions with simple compounds that he had carried out himself and with his colleagues, and hence to explore the basis for the phenomenon of serological specificity. He emphasized that his main objectives were to discuss the chemical aspects of immunological reactions to offer a comprehensive bibliography for the use of workers in the field, and to provide an explanation of elementary concepts and phenomena of serology for readers not acquainted with the subject. The book is divided into five major sections, including serological specificity of proteins, antigens and antibodies, and a discussion of artificial conjugated antigens and serological reactions with simple chemical compounds. It finishes with a description of chemical investigations of specific cell substances including carbohydrates and lipids. Each section has an extensive bibliography and there is an equally extensive list of textbooks, reviews, and monographs relating to the field. Considering the vast range of the subject, the fact that the book is only 178 pages long is a remarkable testament to Landsteiner’s extremely tight prose. Indeed, Diamond points out that of the 345 publications listed in his bibliography, 240 consisted of articles of 6 pages or fewer and the majority were only 2 pages!

Despite this economical style of writing there are some remarkably interesting discussions of biological mechanisms throughout this book. For example, rounding up the section on the specificity of cell antigens he underlines the lack of knowledge about individual differences of proteins or data about their inheritance. In order to explain the protein changes in the genesis of new species he suggests that either one could imagine, in accordance with current theories, the occurrence of numerous small variations accompanying single mutations of genes, or assume that special mutations cause the transformation, or that a change in the protein constitution takes place only after numerous mutations. Indeed, the book is peppered with fascinating vignettes of this type, which make quite remarkable reading in the light of current knowledge about protein structure and human evolution. There is no doubt that this remarkable book, covering the life work of an even more remarkable scientist, had, and continues to have, a very strong influence on the development of immunology in particular and evolution and other broader aspects of biology in general. As well as its clinical application, the discovery of blood groups has played a major role in research into mechanisms of human evolution and also in a variety of disease processes. But Landsteiner’s broader investigation of specificity was undoubtedly one of the major factors in the extraordinary developments in the field of immunology, beginning in the first half of the 20th century. Despite the fact that it was written 75 years ago, its remarkable approach to the investigation of extremely complex biological phenomena, and the thoroughness of its citation to the work of others, still offers a valuable model for young research scientists of today.