Fashioning the Immunological Self: The Biological Individuality of F. Macfarlane Burnet

During the 1940s and 1950s, the Australian microbiologist F. Macfarlane Burnet sought a biologically plausible explanation of antibody production. In this essay, we seek to recover the conceptual pathways that Burnet followed in his immunological theorizing. In so doing, we emphasize the influence of speculations on individuality, especially those of philosopher Alfred North Whitehead; the impact of cybernetics and information theory; and the contributions of clinical research into autoimmune disease that took place in Melbourne. We point to the influence of local experimental and intellectual currents on Burnet’s work. Accordingly, this essay describes an arc distinct from most other tracings of Burnet’s conceptual development, which focus on his early bacteriophage research, his fascination with the work of Julian Huxley and other biologists in the 1920s, and his interest in North Atlantic experimental investigations in the life sciences. No doubt these too were potent influences, but they seem insufficient to explain, for example, Burnet’s sudden enthusiasm in the 1940s for immunological definitions of self and not-self. We want to demonstrate here how Burnet’s deep involvement in philosophical biology – along with attention to local clinical research – provided him with additional theoretic tools and conceptual equipment, with which to explain immune function.     

Postcolonial Ecologies of Parasite and Host: Making Parasitism Cosmopolitan

The interest of F. Macfarlane Burnet in host–parasite interactions grew through the 1920s and 1930s, culminating in his book, Biological Aspects of Infectious Disease (1940), often regarded as the founding text of disease ecology. Our knowledge of the influences on Burnet’s ecological thinking is still incomplete. Burnet later attributed much of his conceptual development to his reading of British theoretical biology, especially the work of Julian Huxley and Charles Elton, and regretted he did not study Theobald Smith’s Parasitism and Disease (1934) until after he had formulated his ideas. Scholars also have adduced Burnet’s fascination with natural history and the clinical and public health demands on his research effort, among other influences. I want to consider here additional contributions to Burnet’s ecological thinking, focusing on his intellectual milieu, placing his research in a settler society with exceptional expertise in environmental studies and pest management. In part, an ‘‘ecological turn’’ in Australian science in the 1930s, derived to a degree from British colonial scientific investments, shaped Burnet’s conceptual development. This raises the question of whether we might characterize, in postcolonial fashion, disease ecology, and other studies of parasitism, as successful settler colonial or dominion science.     

René Stet’s impact on the study of teleost major histocompatibility genes: evolution from loci to populations

René Josephus Maria Stet pursued a 35-year-long scientific career contributing to human immunology, shrimp immunity and teleost immunity. His most significant contributions, however, were to the field of teleost major histocompatibility (MH) gene research from 1988 to 2007, a field in which he was a leader and an innovator. This review will discuss his work on these genes, highlighting the impact he had in three temporally overlapping phases of his career that can be characterized as MH gene discovery, MH gene function and evolution and population dynamics of teleost MH genes.     

Sercarzian immunology--In memoriam. Eli E. Sercarz, 1934-2009

During his long career as a principal investigator and educator, Eli Sercarz trained over 100 scientists. He is best known for developing hen egg white lysozyme (HEL) as a model antigen for immunologic studies. Working in his model system Eli furthered our understanding of antigen processing and immunologic tolerance. His work established important concepts of how the immune system recognizes antigenic determinants processed from whole protein antigens; specifically he developed the concepts of immunodominance and crypticity. Later in his career he focused more on autoimmunity using a variety of established animal models to develop theories on how T cells can circumvent tolerance induction and how an autoreactive immune response can evolve over time. His theory of "determinant spreading" is one of the cornerstones of our modern understanding of autoimmunity. This review covers Eli's entire scientific career outlining his many seminal discoveries.     

Selfhood, Immunity, and the Biological Imagination: The Thought of Frank Macfarlane Burnet

The language of self and nonself has had a prominent place inimmunology. This paper examines Frank Macfarlane Burnet's introductionof the language of selfhood into the science. The distinction betweenself and nonself was an integral part of Burnet's biological outlook– of his interest in the living organism in its totality, itsactivities, and interactions. We show the empirical and conceptualwork of the language of selfhood in the science. The relation betweenself and nonself tied into Burnet's ecological vision of host-parasiteinteraction. The idiom of selfhood also enabled Burnet to organizeand unify a diversity of immune phenomena. Rather than approach thelanguage of self and nonself as a bluntly imposed metaphor, we focuson its endogenous origins and immanent uses in immunology.     

Antibody diversification by somatic mutation: from Burnet onwards

The clonal selection theory proposed by Burnet required a genetic process, for which there was then no precedent, which randomizes the region of the gene(s) responsible for the specification of gamma-globulin molecules. Work over the subsequent half-century substantiated Burnet's speculation, revealing two distinct novel genetic processes. During early development (when Burnet first thought the randomization took place) programmed gene segment rearrangement catalysed by the RAG1/RAG2 recombinase generates a substantial diversity of immunoglobulin molecules (the primary repertoire). Somatic hypermutation (triggered by the activation-induced deaminase (AID) DNA deaminase) then occurs following antigen encounter in man and mouse, yielding a secondary repertoire. This hypermutation allows both limitless diversification as well as maturation of the antibody response by a process of somatic evolution akin to that envisioned by Burnet in later formulations of the clonal selection theory. AID-triggered antigen receptor diversification probably arose earlier in evolution than RAG-mediated repertoire generation. Here I trace our insights into the molecular mechanism antibody somatic mutation from when it was first proposed through to our current understanding of how it is triggered by targeted deamination of deoxycytidine residues in immunoglobulin gene DNA.     

Ernst Mayr,naturalist: His contributions to systematics and evolution

Ernst Mayr's scientific career continues strongly 70 years after he published his first scientific paper in 1923. He is primarily a naturalist and ornithologist which has influenced his basic approach in science and later in philosophy and history of science. Mayr studied at the Natural History Museum in Berlin with Professor E. Stresemann, a leader in the most progressive school of avian systematics of the time. The contracts gained through Stresemann were central to Mayr's participation in a three year expedition to New Guinea and The Solomons, and the offer of a position in the Department of Ornithology, American Museum of Natural History, beginning in 1931. At the AMNH, Mayr was able to blend the best of the academic traditions of Europe with those of North America in developing a unified research program in biodiversity embracing systematics, biogeography and nomenclature. His tasks at the AMNH were to curate and study the huge collections amassed by the Whitney South Sea Expedition plus the just purchased Rothschild collection of birds. These studies provided Mayr with the empirical foundation essential for his 1942Systematics and the Origin of Species and his subsequent theoretical work in evolutionary biology as well as all his later work in the philosophy and history of science. Without a detailed understanding of Mayr's empirical systematic and biogeographic work, one cannot possibly comprehend fully his immense contributions to evolutionary biology and his later analyses in the philosophy and history of science.     

Nobuhiko Katunuma: an outstanding scientist in the field of proteolysis and warm-hearted 'Kendo Fighter' biochemist

Professor Nobuhiko Katunuma is well known for his outstanding contribution to the understanding of proteolysis in general and cysteine proteinases and their inhibitors in mammals. In fact, he is a world pioneer in the field. In 1963, he started his highly successful scientific career as a Professor at the Institute for Enzyme Research, the University of Tokushima. During the initial 30 years of his career, he was interested in vitamin B6 metabolism and discovered the acceleration of turnover rates of pyridoxal enzyme in apoprotein formation. After this period, his interest expanded to lysosomal cystein proteinases and their endogenous inhibitors. After determining the crystal structure of human cathepsin B, he generated a series of chemically synthesized specific inhibitors of cathepsins. These inhibitors are currently used throughout the world and some of them have been applied therapeutically in various diseases. During his career and even at present, Professor Katunuma has been studying Biochemistry in Medicine and also practicing to become a 'Kendo sword fencing Fighter'.     

Hans Zinsser: a tale of two cultures

Hans Zinsser, president of the Society of American Bacteriologists in 1926, was known as much for his literary and textbook writing as for his scientific contributions. He was a widely known scientist and person of letters. His early interests in poetry and other forms of literature were maintained and developed during his career as a microbiologist, and his most enduring legacy is based on his writing about microbiology for a general readership as well as his reflective and philosophical autobiography.     

The genius of Wilhelm Hofmeister: the origin of causal-analytical research in plant development

Friederich Wilhelm Benedikt Hofmeister (1824-1877) stands as one of the true giants in the history of biology and belongs in the same pantheon as Darwin and Mendel. Yet by comparison, he is virtually unknown. If he is known at all, it is for his early work on flowering plant embryology and his ground-breaking discovery of the alternation of generations in plants, which he published at age 27 in 1851. Remarkable as the latter study was, it was but a prelude to the more fundamental contributions he was to make in the study of plant growth and development expressed in his books on plant cell biology (Die Lehre von der Pfanzenzelle, 1867) and plant morphology (Allgemeine Morphologie der Gewächse, 1868). In this article we review his remarkable life and career, highlighting the fact that his scientific accomplishments were based largely on self-education in all areas of biology, physics, and chemistry. We describe his research accomplishments, including his early embryological studies and their influence on Mendel's genetic studies as well as his elucidation of the alternation of generations, and we review in detail his cell biology and morphology books. It is in the latter two works that Hofmeister the experimentalist and biophysicist is most manifest. Not only did Hofmeister explore the mechanisms of cytoplasmic streaming, plant morphogenesis, and the effects of gravity and light on their development, but in each instance he developed a biophysical model to integrate and interpret his wealth of observational and experimental data. Because of the lack of attention to the cell and morphology books, Hofmeister's true genius has not been recognized. After studying several evaluations of Hofmeister by contemporary and later workers, we conclude that his reputation became eclipsed because he was so far ahead of his contemporaries that no one could understand or appreciate his work. In addition, his basically organismic framework was out of step with the more reductionistic cytogenetic work that later came in vogue. We suggest that the translation of the cell and morphology books in English would help re-establish him as one of the most notable scientists in the history of plant biology.     

Lysenko's contributions to biology and his tragedies.

Trofim Denisovich Lysenko's life and work have been much analyzed and discussed in the world's literature. It is well known that Lysenko is notorious and has been regarded as a charlatan. Less well known is that he once made greater contributions to Biology and has been misunderstood in some aspects. In this paper, Lysenko s contributions to plant physiology, genetics, agro-biology and evolutionary biology are briefly reviewed. His tragedies and mistakes, such as mixing science and politics, denying the existence of genes, failing to build up suitable scientific collectives for the metabolism-biochemical studies of heredity, as well as his theoretical one-sidedness, are also discussed, thus reconsidering the case of Lysenko from a comprehensive and objective viewpoint.     

Analytical ultracentrifugation and the characterization of chromatin structure

This mini review consists of two parts. The first part will provide a brief overview of the theoretical aspects involved in the two kinds of experiments that can be conducted with the analytical ultracentrifuge (sedimentation velocity and sedimentation equilibrium) as they pertain to the study of chromatin. In the following sections, I describe the analytical ultracentrifuge experiments which, in my opinion, have contributed the most to our understanding of chromatin. Few other biophysical techniques, with the exception of X-ray scattering and diffraction, have contributed as extensively as the analytical ultracentrifuge to the characterization of so many different aspects of chromatin structure. In the course of his scientific career, Professor Henryk Eisenberg has made many important contributions to the theoretical aspects underlying ultracentrifuge analysis, especially in the analysis of solutions of polyelectrolytes and biological macromolecules [H. Eisenberg, Biological macromolecules and polyelectrolytes in solution, Clarendon Press, Oxford, 1976]. As an example he has devoted some of his research effort to the characterization of chromatin in solution. This review includes these important contributions.     

Light-driven quinone reduction in heliobacterial membranes

Vyacheslav Vasilevich (V.V.) Klimov (or Slava, as most of us called him) was born on January 12, 1945 and passed away on May 9, 2017. He began his scientific career at the Bach Institute of Biochemistry of the USSR Academy of Sciences (Akademy Nauk (AN) SSSR), Moscow, Russia, and then, he was associated with the Institute of Photosynthesis, Pushchino, Moscow Region, for about 50 years. He worked in the field of biochemistry and biophysics of photosynthesis. He is known for his studies on the molecular organization of photosystem II (PSII). He was an eminent scientist in the field of photobiology, a well-respected professor, and, above all, an outstanding researcher. Further, he was one of the founding members of the Institute of Photosynthesis in Pushchino, Russia. To most, Slava Klimov was a great human being. He was one of the pioneers of research on the understanding of the mechanism of light energy conversion and of water oxidation in photosynthesis. Slava had many collaborations all over the world, and he is (and will be) very much missed by the scientific community and friends in Russia as well as around the World. We present here a brief biography and some comments on his research in photosynthesis. We remember him as a friendly and enthusiastic person who had an unflagging curiosity and energy to conduct outstanding research in many aspects of photosynthesis, especially that related to PSII.     

Paul Ehrlich's passion: the origins of his receptor immunology.

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 point out how Ehrlich's concept matured over 20 years, while it governed his studies in histological staining, in cell physiology, in hematology, and finally in his major contributions in experimental immunology.     

Quantitative and qualitative approaches to GOD: the first 10 years of the clonal selection theory

Of the contentious issues surrounding the clonal selection theory, one of the most influential was that of the mechanism for the generation of diversity of antibody specificity. While Burnet's qualitative theory assumed a very large antibody repertoire, Talmage provided a detailed quantitative argument supporting only 5000 individual globulin patterns that provided an antiserum its specificity through combinatorial action. This methodological difference between the two men, and the mechanistic difference between their models, is key to the understanding of the clonal selection theory, its later acceptance and the proportion of credit paid to Burnet.     

W. Montague Cobb (1904–1990): Physical Anthropologist, Anatomist, and Activist

William Montague Cobb's life and work reflect a profound integration of art, literature, social activism, and science. This article presents some of the highlights of his academic development and professional contributions. We have considered his early academic development within the contexts of the formative years of American physical anthropology, Howard University Medical School, and the social issues in American society that influenced Cobb. His approaches to teaching, anatomical and anthropological research, and medicine are unique, and yet are closely reasoned and creative reflections of the major currents of academe and the broader society with which he dealt. Imbued with a sense of social responsibility, Cobb's applied anthropology involved the accumulation of extensive data on the one hand, and the formation of organizations for social activism on the other. It was directed toward solving problems of health care and racism. His work thereby served to balance the widespread distortion and neglect of medical and racial problems facing A fro-America between 1930 and the present day. He was also a principal builder of black medical and scientific institutions, and he preserved the record of his coworkers' contributions through his many biographies. This work represents no more than a sketch of his rich and prolific career (during which he produced more than 1,100 publications); the emphasis of this biographical study has been to ascertain the circumstances and attitudes that helped mold the first Afro-American Ph.D. in physical anthropology.     

A biographical sketch of Charles F. Yocum: “It's the biochemistry, stupid”

Charles F. Yocum has been a leader in the applications of biochemical techniques to the resolution and reconstitution of Photosystem II. His formal science education began as an undergraduate in biochemistry at Iowa State University and continued with graduate work in photosynthesis, first at the Illinois Institute of Technology and later at Indiana University. Following postdoctoral work at Cornell University, he joined the faculty of the University of Michigan where he has remained throughout his academic career. Charlie's contributions to a biochemical understanding of photosynthesis, particularly Photosystem II have been considerable, but most notably include his initial isolation of the first highly active oxygen-evolving particle from higher plant chloroplasts, the well-known and widely utilized `BBY particles'. In the aftermath of that isolation, Charlie's research further resolved these particles into ever finer and simpler, but active, Photosystem II complexes. In addition, Charlie's research has provided significant insight into the roles of both Cl⁻ and Ca²⁺ as required cofactors in photosynthetic oxygen evolution. This revised version was published online in June 2006 with corrections to the Cover Date.     

Lorenz Hiltner, a pioneer in rhizosphere microbial ecology and soil bacteriology research

Lorenz Hiltner is recognized as the first scientist to coin the term “rhizosphere” in 1904. His scientific career and achievements are summarized in this essay. Most of his research he performed in the Bavarian Agriculture–Botanical Institute (later named the “Bavarian Institute of Plant Growth and Plant Protection”) in Munich, where he was the director from 1902 to 1923. Beginning with intensive and thorough investigations on the germination and growth of different crop plants (legumes and non-legumes) Hiltner became convinced, that root exudates of different plants support the development of different bacterial communities. His definition of the “rhizosphere” in the year 1904 centered on the idea, that plant nutrition is considerably influenced by the microbial composition of the rhizosphere. Hiltner observed bacterial cells even inside the rhizodermis of healthy roots. In analogy with fungal root symbionts, Hiltner named the bacterial community that is closely associated with roots “bacteriorhiza.” In his rhizosphere concept, Hiltner also envisioned, that beneficial bacteria are not only attracted by the root exudates but that there are also “uninvited guests,” that adjust to the specific root exudates. Based on his observations he hypothesized that “the resistance of plants towards pathogenesis is dependent on the composition of the rhizosphere microflora.” He even had the idea, that the quality of plant products may be dependent on the composition of the root microflora. In addition to his scientific achievements, Hiltner was very dedicated to applied work. Together with F. Nobbe he had the first patent on Rhizobium inoculants (Nitragin). He continuously improved formulations and the effectivity of the Rhizobium preparations and he also initiated seed dressing with sublimate for plant protection of seedlings. Thus, Hiltner tightly linked breakthroughs in basic research to improved rhizosphere management practices. In addition, he wrote a pioneering monograph on plant protection for everybody’s practical use. His emphasis on understanding microbes in the context of their micro-habitat, the rhizosphere, made him a pioneer in microbial ecology. Even now, in the era of genome and postgenome analysis with our better understanding of plant nutrition and soil bacteriology, his ideas and contributions are as fresh as they were more than 100 years ago.     

Shigeru Tsuiki: a pioneer in the research fields of complex carbohydrates and protein phosphatases

Dr Tsuiki made three major contributions during his illustrious career as a biochemist. First, he developed the procedure for mucin isolation from bovine submaxillary glands. His work became the basis for mucin biochemistry. Second, he identified four distinct molecular species of mammalian sialidase. Subsequent studies based on his work led to the discovery that sialidase plays a unique role as an intracellular signalling factor involved in the regulation of a variety of cellular functions. Finally, he established the molecular basis for the diversity of mammalian protein phosphatases through protein purification and molecular cloning. His work prompted the functional studies of protein phosphatases.     

Personal reminiscences about Morton Grossman and the founding of the Center for Ulcer Research and Education (CURE)

The Center for Ulcer Research and Education (CURE) from its onset was primarily the work of one man: Professor Morton Grossman, or "Mort" as he was known and called by all. Mort's legacy includes a large body of scientific publications, the first National Institutes of Health Digestive Diseases Center (CURE), and, most importantly, a group of scientists who have become academic leaders and who have made important contributions in the fields of upper gastrointestinal (GI) tract secretion, hormones and receptors, mucosal defense mechanisms, the design and conduct of randomized clinical trials, and ulcer epidemiology. Indeed, Mort is considered to be a founding father of modern academic GI research. I was fortunate to have known and worked with Mort and would like to memorialize his contributions so that his memory can inspire the next generation of academicians.