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Forty Years with the Gamma Globulins

Svante Arrhenius, the famous Swedish physicochemist, the father of the hypothesis on ionic dissociation of substances in solution, was also the first person to grasp that the interaction between 'toxins and antitoxins' was based on classical biochemical principles. He published a book on the subject, which has now been forgotten but which must be regarded as a real classic. These studies were published in 1902. Arrhenius died in 1927 and consequently I had no scientific contact with him. Still, I remember that at my school we regarded him with great admiration because he was the first Swede to receive a Nobel prize. He was warden of our school. During the last part of the nineteenth century, Paul Ehrlich in Germany made his fundamental studies on what he called Antikorper, antibodies. Ehrlich and Arrhenius were personal friends and certainly influenced each other. It is characteristic of Ehrlich's sense of molecular biology that he always thought about well-defined substances, bodies, when thinking about activity, antibodies that neutralized noxious factors. His Antikorper contained side chains that carried 'haptophoric' groups. These groups corresponded to haptens on, for example, bacteria or red blood corpuscles. They are what we now call receptors, antigenie sites, or epitopes. At the same time Bordet in France worked on complement with functions much less well defined as regards active molecules. The well-known American immunologist Elvin Kabat has written about 'the Ehrlich-Bordet war'. Ehrlich, of course, was an early pioneer in real molecular immunology and his ideas are surprisingly modern. In many discussions of immunological problems, not to mention factors in blood coagulation, one was inclined to ask, as did my old teacher Hans Fischer: 'Please show me the crystals'. Our knowledge of biochemistry in these fields has recently become literally more substantial. Ehrlich was a great discoverer in very many fields, chiefly working on a chemical basis. One of Ehrlich's pupils, von Dungern, published a paper in 1900 about the production in rabbits of antibodies against foreign red cells. He found that if he injected this antibody into another rabbit, the latter was unable to mount an immune response against these red cells. In other words, this phenomenon was known 70 years before it was rediscovered and led to the present efficient prophylaxis against haemolytic disease of the newborn due to Rhesus incompatibility. This period was rich in immunological discoveries. Wassermann invented his famous test for the diagnosis of syphilis. The test was rather complicated and it was later found that several steps were unnecessary; yet it worked 100% correctly. Kabat pointed out that if the spirochete had not been discovered first, the Wassermann test may well have been regarded as a sign of autoimmunity and thus syphilis would have been classified as an autoimmune widespread' collagen disease! The connection between the immunological reactions in syphilis and the spirochete is still not easy to define immunologically. For many years this test was the most important in diagnostic immunology. A French clinician, Widal, invented a very simple agglutination test dependent on what were called precipitating antibodies against certain bacteria. French tradition says that Widal was on a pleasure-trip to the Near East when he read in a newspaper about the agglutinating powers of some antibodies against bacteria. He immediately conceived the idea that this could be used for the diagnosis of typhoid fever and similar infections and returned to Paris, where this new method was worked out and published very rapidly. Antibodies had thus become important throughout the field of infection, even for diagnostic purposes. Another interesting chapter in the science of antibodies was written by Landsteiner, when he conceived the idea of blood groups.