The curious case of the 1960 Nobel Prize to Burnet and Medawar.

The 1960 Nobel Prize was awarded to Macfarlane Burnet and Peter Medawar for immunological tolerance. The Nobel Archives reveal that the two were never nominated together by anyone; Burnet had repeatedly been nominated for his virology studies, and the Medawar group (including Rupert Billingham and Leslie Brent) had been nominated independently for their transplantation work. A review of the 1950s literature suggests that tolerance had not yet, by 1960, reached the level of acceptance and acclaim in the immunological community to appear to justify the award. Burnet probably should have received the Prize for his virus work, and perhaps also for his Clonal Selection Theory, whereas Billingham and Brent should have shared in a Prize with Medawar for transplantation. If a Prize were to be given for tolerance, most agree that Ray Owen should have shared in it, for his work on cattle chimerism. It is suggested that the 1960 Nobel Prize to Burnet and Medawar for immunological tolerance may have been given for the wrong reasons and to the wrong associates.

Promethean Evolution: A Comparison of the Immune and Neural Systems.

In contrast to normal Darwinian evolution involving adaptation to past challenges, it has been suggested that evolution has devised two unique biological mechanisms to permit the host to anticipate future challenges: the adaptive immune response and neural memory functions. Certain phenomenological similarities, some sharing of names, and the participation in both systems of a group of physiologically active molecules suggested to many that the two might be intimately related. This article compares the two systems in terms of the familiar parlance of immunology-specificity, repertoire, degeneracy, memory, mediators, pathways, and genetics-to show that they differ in most respects, except insofar as they may utilize some of the same agents, many of which participate in the normal functions of other tissues and systems of the body. Indeed, this very difference provides a further demonstration of the wonders of the evolutionary process.

Evolution of biomarker research in autoimmunity conditions for health professionals and clinical practice.

Medical abzymology has made a great contribution to the development of general autoimmunity theory: it has put the autoantibodies (Ab) as the key brick of the theory to the level of physiological functionality by providing such Ab with the ability to catalyze and mediate direct and independent cytotoxic effect on cellular and molecular targets. Natural catalytic autoantibodies (abzymes) while being a pool of canonical Abs and possessing catalytic activity belong to the new group of physiologically active substances whose features and properties are evolutionary consolidated in one functionally active biomolecule. Therefore, further studies on Ab-mediated autoAg degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations and thus a supplementary tool for assessing the disease progression and predicting disability of the patients and persons at risks. This chapter is a summary of current knowledge and prognostic perspectives toward catalytic Abs in autoimmunity and thus some autoimmune clinical cases, their role in pathogenesis, and the exploitation of both whole molecules and their constituent parts in developing highly effective targeted drugs of the future to come, and thus the therapeutic protocols being individualized.

Reflections on the clonal-selection theory.

How do we account for the immune system's ability to produce antibodies in response to new antigens? It has been 50 years since F. Macfarlane Burnet published his answer to this question: the clonal-selection theory of antibody diversity. The idea that specificity for diverse antigens exists before these antigens are encountered was a radical notion at the time, but one that became widely accepted. In this article, Nature Reviews Immunology asks six key scientists for their thoughts and opinions on the clonal-selection theory, from its first proposal to their views of it today.

Dr. Arthur Conan Doyle and the case of congenital syphilis.

In 1894, Dr. Arthur Conan Doyle wrote "The Third Generation," a short story involving the transmission of congenital syphilis from generation to generation. Analysts of his writings have interpreted the pathogenetic mechanism involved in modern terms: infection of mother by father and then transplacental infection of the fetus. However, a review of the contemporary literature and the history of the concepts of congenital and "hereditary" syphilis demonstrates that the late 19th-century understanding of the process involved a Lamarckian transmission of paternal infection, via the sperm at the moment of conception. It was undoubtedly this concept that Doyle learned in medical school in the late 1870s and that provided the background to his story.

Labeled antigens and antibodies: the evolution of magic markers and magic bullets.

The ability to label antigens and antibodies with simple chemicals and even with whole proteins fostered new approaches to basic studies of the immune system as well as new methods of immunodiagnosis and immunotherapy. This was especially true following the introduction of monoclonal antibodies, which enhanced the specificity of many of these applications. The uses to which these labeled immunoreagents were put were legion, and those who employed them might come from any field of biology or medicine. Many of these technical elaborations were critical to progress in immunology and in many other biomedical sciences. They illustrate also the often complex interplay between technology and theory.

The collected papers of Paul Ehrlich : why was volume 4 never published?

In the 1950s, Sir Henry Hallett Dale undertook to compile and publish all the scientific papers of Nobel laureate Paul Ehrlich. He was assisted in this venture by Dr. Fred Himmelweit and by Ehrlich's former secretary, Martha Marquardt. A four-volume series was announced, but only three volumes saw the light of day, between 1957 and 1960. This report presents the result of a five-year effort to determine the reason for the failure to complete the undertaking, in which all potential sources were pursued and queried. In the end, the mystery remains unsolved.

Philip George Houthem Gell.

Philip Gell was one of a small but outstanding group of immunologists who led Britain during the postwar years to a leading role in this increasingly important biomedical discipline. He pioneered in those studies that helped to change the field from an earlier, narrowly chemical approach to one with much broader biological and medical implications. He helped to train and guide an entire generation of scientists, both domestic and foreign, and did all of this with a most becoming modesty. But he was more than just a narrowly oriented scientist; his interest in horticulture, in poetry, in philosophy and in the interrelationship of art and science was mediated by the interplay of a keen mind with a broad fund of general knowledge.

Splitting the difference: the germline-somatic mutation debate on generating antibody diversity.

In the debate about the mechanism for the generation of immunological diversity, the initial positions of both 'somaticists' and 'germliners' were diametrically opposed. Then, as data developed favoring first one and then the other side, concessions were made, until the final solution showed that each had been at least partially correct.