Arthur M Silverstein

Johns Hopkins Medicine | JHUSOM · Institute of the History of Medicine

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...

This is a book about the development of Ilya Metchnikoff’s theories about the evolutionary origins of phagocytic cells and their immunological functions in protecting the body against infectious disease agents, and about the disputes that these concepts engendered. It is the seventeenth contribution to a series sponsored by the Saxony Academy of Sc...

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 parti...

During the early days of immunology, Paul Ehrlich's theories dominated the field. These included his concept of horror autotoxicus, which held that the individual could not form antibodies against its own tissues. In addition, the view that the "protective" immune mechanisms might cause disease seemed dysteleological, so that even the early demonst...

Metchnikoff fought hard to establish his phagocytic theory, and in the process many fields of science benefitted.

There have been many biographies written about the famous German scientist and Nobel Prize winner Paul Ehrlich, some by admirers and others by scientists analyzing one or another of the many fields of biomedical research to which Ehrlich made seminal contributions. But Hüntelmann's contribution is unique in several respects: it is probably the best...

Immunization with diazotized proteins induces the formation of antibodies specific for the attached chemical group—an approach that is applied to the study of antibody specificity by Karl Landsteiner and others. The use of labeled antigens for specificity studies proved to be only the tip of a technological iceberg; labeled antigens (and antibodies...

The secondary literature in the history of medicine contains numerous reports of immunological disputes, but little attention has been paid to the linguistic aspects of these disputes. Opposing theories are often associated with different terminologies, whose semantic implications may be unacceptable and even incomprehensible to the other side. Thi...

One of the characteristics of modern science is the willingness of the practitioner to cross disciplinary boundaries. This trend has surely accelerated in the biomedical sciences since the 1960s, and immunology has been one of the more important catalysts of this change. The molecular biologist studies the immunoglobulin gene superfamily; the oncol...

Ehrlich's side-chain theory is a concept of antibody formation; it speculated broadly about the structure and function of antibody. Implicit in the side-chain theory is a startling conceptual anticipation of the future—that the binding site of an antibody is a unique structure and might be immunogenic; that an anti-antibody might be formed against...

This chapter overviews the concept of immunologic specificity; it is an experimental science that can be viewed as the continuing quest for the meaning and basis of immunologic specificity. In surveying the history of the discipline, this search appears logically to be divisible into three somewhat overlapping phases. In addition, it is important t...

Resolution of the debate about the mechanism for the generation of diversity between paucigene and multigene proponents witnessed a splitting of the difference. Genetic basis of immunologic diversity, one of the arguments employed by the proponents of a paucigene model expanded by somatic variation, against those who espoused the idea that all spec...

This chapter describes the development of the concept of immunologic specificity, to trace the history of one of the most central ideas in immunology. The result is viewed as preliminary and incomplete, and as an invitation to others to add and to amend. By the 1930s, it was known that antibodies are protein in nature, that they belong to the class...

This chapter examines the history of Darwinian influences on immunological thought during the formative years of the discipline. Physiologist's interest in the cellular and molecular mechanisms of function paid overt attention to evolutionary theory. Their references to evolution were in the main implicit, and made in the context of organs and syst...

This chapter discusses the sociological contributions to the development of immunology to include an analysis of disciplinary leadership. It also cast light on some of the more modern trends in subdiscipline formation. The immunology in transition from 1951 to 1972 is significant because this was the era of most rapid change in immunology. Changes...

This chapter reflects the widespread contemporary view that the same mechanisms that provide for defense against infectious disease ought not to function also to embarrass the host. In the dawning years of the twentieth century, those investigators active in the young field of immunology had been brought up, with Metchnikoff and Ehrlich, to view th...

This chapter examines several examples of subdiscipline formation in order to illustrate further the various ways that they develop, how these specialties may manifest themselves, and the variety of their relationships with the parent discipline of immunology. The chapter also discusses ocular immunology; ophthalmology is one of the earliest of the...

An examination of the history of the cellular–humoral dispute illustrates several interesting points. It provides the historian of ideas with yet another example of how earlier and even outmoded concepts help to determine the structure and content of future thought, and how the intransigent commitment to a scientific dogma often prevents timely and...

The chapter aims to provide the history of theories of antibody formation that calls for attention the many contributions to its progress. The discovery of circulating antibody provides a new and almost impregnable rallying point for those who argued that humoral factors rather than cellular mechanisms are all important in explaining natural and ac...

This chapter highlights the cell bound antibodies on the influence of dogma. Sociologists of science point out that the great advances of one generation may often retard progress in the next. This is because each advance may induce a mindset in the scientist that slants the interpretation of data and may inhibit new speculations. Every science can...

The classical view of scientific progress that was advanced by analysts as philosopher Karl Popper and sociologist Robert Merton was one of a smooth and progressive evolution toward the ultimate goal—a complete understanding of the physical world. Scientists of all types shared this view, and the ideas represented by “smooth” and “progressive” were...

The central role that immunology has assumed among modern biomedical sciences, offers several good examples of interaction that combine both historical and ethnographic approaches. This chapter examines the interaction of technique and fact with theory, in terms of the consequences of the discovery of the phenomenon of immune hemolysis. This highli...

The field of immunology has not been exempt from a similar inability to explain certain findings, and provides two interesting examples. The first protective antibodies that were identified were those against diphtheria and tetanus toxins; these were shown not only to protect against the two diseases specifically. During the succeeding decade, a nu...

Burnet's concepts have taken different forms; some have proposed only subtle variations to the underpinnings of clonal selection theory proper, while others have boldly asserted a challenge to the central concept itself, suggesting that “the ruling paradigm” of modern immunology is no longer valid. A critical examination of Macfarlane Burnet's clon...

In his News Focus story “On the origin of the immune system” (1 May, p. [580][1]), J. Travis overlooked some important components of the Darwinian evolution of the acquired immune response. Travis, quoting molecular biologists, ascribes the “Big Bang” in immunological evolution to the

Publisher Summary Metchnikoff with his phagocytic theory and Ehrlich with his side-chain theory understood that the mechanisms proposed are part of a larger biological system whose evolution brought with it improvements in the organism's ability to nourish itself and, incidentally, to protect itself from infection. The teleologic appeal of Ehrlich'...

This much expanded second edition of A History of Immunology continues the tradition of the highly successful previous volume. It provides unparalleled insight into the concept of immunity and the field into which it has developed and examines how changing concepts and technologies have affected the course of the science. Each chapter examines an i...

Ontogenesis of the Immune ResponseImmunological Suppression of PathogenicityThe Immunological Activation of PathogenicityThe Immunological Modulation of PathogenesisImmunological Tolerance in Congenital InfectionSummaryAcknowledgementsReferencesDiscussion

Transplantation of the cornea presents the immunologist with a set of conditions which are unique in transplant biology, with respect to both donor tissue and recipient bed. These include: (1) the normal avascularity of the cornea; (2) the simplified anatomy of its layered structure; (3) the ability to exclude from the graft certain tissue elements...

The advances in bacteriology and immunology near the end of the nineteenth century validated Edward Jenner's discovery of a vaccine against smallpox and initiated the development of protective vaccines against other infectious diseases. Over time, this approach would save more lives than any other contribution of the new scientific medicine. This b...

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 notio...

The earliest discoveries in immunology were made in the context of the battle to ward off infectious diseases. These included Louis Pasteur's preventive vaccines, Ilya Metchnikoff's bacteria-eating phagocytes, and Behring and Kitasato's curative antidiphtheria and antitetanus sera. This chapter provides an adequate representation of the ways in whi...

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...

In lieu of an abstract, here is a brief excerpt of the content: In the medical world of the late 1890s, only Louis Pasteur commanded greater admiration and respect than did Emil Behring. Whereas Pasteur had pointed with his vaccination program to how infectious diseases might be prevented, Behring's discovery of serotherapy showed how a disease, o...

For many years Paul Ehrlich�s theory of horror autotoxicus - that autoimmune disease could not occur - dominated 20th Century thinking. It inhibited acceptance of both clinical and experimental observations testifying to the reality of such a possibility. Then, for almost one halfcentury, immunology lost its medical foundation, and became primarily...

Peter Medawar once pointed out that when a scientist describes his work for publication, historical revisionism inevitably intrudes1. No mention is made of false starts, wrong interpretations or rejected data; the results are presented in a logical order, as though the initial questions were obvious and led in a straight line to the results. How th...

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 appli...

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....

Hunziker et al.1, with their customary elegance of technique, have presented important new data about an old question: the relationship between chronic viral infection and an accompanying polyclonal activation of B cells and hyperglobulinemia. They confirm earlier evidence that: (i) persisting viral infection leads to polyclonal B cell activation2;...

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.

Imunology's founding fathers argued fiercely about whether Metchnikoff's phagocytes or Ehrlich's antibodies were the most important mediators of immunity. Antibodies won out, but even after lymphocytes re-established cellular immunology, the humoralist-cellularist divide persisted.

Historical Insight: During those periods when immunology was oriented toward medical or biological subjects, Darwinian concepts predominated. These included Metchnikoff's phagocytic theory and Ehrlich's receptor theory during the early years and Burnet's clonal selection theory after the 1950s. During the immunochemically oriented interim, instruct...

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....

The heuristic value of the phenomenon of immune hemolysis has extended far beyond the diagnostic complement fixation test. The discovery of immune hemolysis was immediately recognized not to be a unique phenomenon, but merely another manifestation of a more general type of reaction the destruction of a cell through the mediation of specific antibod...

This chapter opens with a discussion of relevance of mother's milk in pediatric immunology. Ehrlich was surely the first to inter-pret the basis for neonatal protection against many infectious diseases, demonstrating transplacental transfer of maternal antibodies and then the role of milk-borne antibodies in protecting the neonate. The fact that th...

The ability to develop resistance to further infection after an initial exposure to a disease is known as acquired immunity. The notion that immunity depends on the depletion of some element essential to the disease process took many forms. Citing the well-known cessation of bacterial growth in culture following an initial growth phase, Pasteur sug...

The concept of immunization with a toxin results in the formation of a blood-borne protective substance excited the medical world. The immunized host is not only protected from diphtheria or tetanus, but its blood can be transferred passively to protect naive recipients or even to cure the disease once started. Different donor animal species are em...

In this chapter, the technical aspects of tissue staining, and the variable staining qualities of a variety of tissues and cells are described. Moreover, this chapter is devoted to the study of the distribution of plasma cells in different tissues, and especially in the components of the lymphoid system: tonsil, peyers patches, regional lymph nodes...

Historical insight: The clonal selection theory of antibody formation has recently been subjected to challenge from many quarters. A review of its history and that of scientific theories in general points to the importance of distinguishing between the central hypotheses of a theory and its subsidiary implications.

For over 75 years, only humoral antibodies were known to mediate immunological specificity. The apparent absence of these in delayed-type hypersensitivity reactions was perplexing, and the dominant dogma of antibodies led to some curious hypotheses.

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 repor...

Bulletin of the History of Medicine 76.1 (2002) 158-160 Michael Dunnill. The Plato of Praed Street: The Life and Times of Almroth Wright. London: Royal Society of Medicine Press, 2000. xiii + 269 pp. Ill. £17.50 (1-85315-477-6). The first three decades following Louis Pasteur's establishment in 1880 of immunology as an experimental science of great...

This chapter discusses the question “end of immunology.” Immunology is not the only discipline that has seen pessimistic conclusions. History suggests that predictions about “definitive solutions” of scientific questions should be made with extreme caution. An analysis of the many instances of predictions of “the end” discloses a very significant e...

Dr. Miller makes two charges in connection with my suggestion that by 1926 Murphy had identified the lymphocyte as the active factor in graft rejection and in other immunological responses. First, he feels that I have inadmissibly interpreted Murphy's work in the context of modern knowledge of the lymphocyte, rather than in the context of the times...

Between 1912 and 1921, James Murphy established conclusively the role of the lymphocyte in tissue and tumor graft rejection and in protection against infection. Contemporary mainstream immunology paid little attention to these findings, until the lymphocyte was "rediscovered" with the advent of modern cellular immunology after the mid-1950s.

In 1892-93, Paul Ehrlich published a series of experiments on the passive transfer of maternal antibody to fetus and newborn that deserve to be better known. He pointed out the importance of mother's milk to neonatal well-being. He was the first to define the difference between active and passive immunity. He was the first to demonstrate immune eli...

What only one person accomplish in a lifetime? Pirquet, an exceedingly curious pediatrician with acute powers of observation and deduction, not only solved the riddle of serum sickness and developed the concept of allergy, but also made contributions to the study of nutrition and aging.

When we remember that immunology was barely a decade old and knowledge of circulating antibodies only two years old when Ehrlich performed the experiments described, we can appreciate the inventiveness of his experimental designs. With little wasted effort he planned simple and rapid experiments to answer crucial questions about the mechanism of pa...

The generators of B and T cell diversity produce specificities for both autochthonous and exogenous paratopes. A wide variety of positive and negative, central and peripheral mechanisms has evolved to regulate the immune response. All potential immunogens are recognized by the system using the same set of 'rules', without discrimination between 'se...

Throughout his career, the problems that attracted Louis Pasteur almost invariably involved considerations of specificity of structure and/or of action. Thus, his work on asymmetric crystals showed that chemical form not only specifies crystalline structure, but affects the affinity of ferments as well. In his studies of diseases of silkworms, of b...

The 1960 Nobel Prize was awarded to Macfarlane Burnet and Peter Meda-war 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...

In 1897, Paul Ehrlich published a selection theory of antibody formation that anticipated the theories of Jerne and Burnet by some 60 years. Ehrlich introduced into immunology the concept of the interaction of physiologically active substances with specific receptors, an idea that still dominates modern immunological thought. In this paper, we poin...

Bulletin of the History of Medicine 72.4 (1998) 731-733 Some months ago, the New York Times carried the report of an outbreak of a disease called ehrlichiosis, apparently due to infection by a tick-borne rickettsia. Few seemed to know why such an organism should have been named in honor of Paul Ehrlich, who had never worked on any microorganisms ex...

Since the time of Paul Ehrlich 100 years ago, we have known that the immunological apparatus somehow inhibits most damaging autoimmune responses while permitting a response to exogenous immunogens. With the discovery of tolerance, the concept of immunological surveillance, and especially with the discovery of HLA restriction of T-cell recognition,...

Just as different fads that seize the imagination of the general public are often carried to excess, so diagnostic or therapeutic fads may take over in the practice of medicine. Analysis of 33 surveys of the causes of uveitis reported by ophthalmologists over the course of 120 years shows how some diagnoses such as syphilis and tuberculosis fell fr...

In 1892-93, Paul Ehrlich published a series of experiments on the passive transfer of maternal antibody to fetus and newborn that deserve to be better known. He pointed out the importance of mother's milk to neonatal well-being. He was the first to define the difference between active and passive immunity. He was the first to demonstrate immune eli...

This chapter brings together those investigators who helped form and give substance to modern immunology. It examines the historical factors that set the stage for the development of immunology following World War II. It considers the two major eras in immunology that preceded the present biomedical one: the early age of bacteriology, with its emph...

Many of the most important developments that result in a fully functioning vertebrate immune system take place in the developing fetus. From a variety of gene segments there is assembled in B cells a congeries of antibody combining sites, one to a cell, which form the greater part of the large repertoire of immunological specificities that characte...

Immunology underwent a major change in direction during the 1950s and 1960s, from immunochemistry to immunobiology. A quantitative analysis of the participants at a large number of immunological meetings held during this critical period reveals much about the inner dynamics of the discipline. This new approach enables us to define the scientific le...

To handle the enormous amount of sources in modern and contemporary science, the historian can use different quantitative methods, particularly varieties of citation analysis. So far, all these methods have been based on publication data. Taking as its point of departure the fact that meetings constitute a pervasive, yet neglected, aspect of scienc...

Les etudiants en sciences biomedicales sont souvent preoccupes par la question de savoir comment la connaissance scientifique est construite, et comment relier la theorie a la pratique. L'immunologie offre de nombreux exemples qui permettent de repondre a ces questions a l'aide d'approches historiques et ethnographiques

A new method for the analysis of leadership and subdisciplinary structure of a scientific discipline is discussed. The database consists of lists of participants in international scientific meetings. Disciplinary leaders are identified by means of their frequency of participation. The subdisciplinary structure is mapped by means of cluster analysis...

I have attempted here to define three distinct eras in the 110-year history of the discipline of immunology. The first, extending from 1880 to about the First World War, centered around the new bacteriology and infectious diseases, and had a distinctly medical orientation. Several of the components of the original research program in immunology fai...

Experimental autoimmune dacryoadenitis was produced in Lewis rats by immunization with a single intradermal administration of a 3M KCl extract of exorbital lacrimal gland in CFA, when enhanced by simultaneous i.v. injection of killed Bordetella pertussis. No significant lacrimal lesions were observed in control animals immunized with the extracts o...

Experimental autoimmune dacryoadenitis was induced in 100% of Lewis rats by immunization with a KCl extract of Harderian gland in complete Freund's adjuvant (CFA), providing that the animals had received simultaneously i.v. injection of killed Bordetella pertussis. No significant pathological changes in the Harderian gland were observed in control...

An experimental model to investigate orbital granuloma formation in inbred rats was established. Animals sensitized to trinitrophenyl ovalbumin (TNP-OA) and challenged retro-orbitally with TNP-OA covalently linked o Sepharose 4B beads specifically developed a granulomatous response. This granulomatous reactivity was passively transferred into norma...