The bacteriophage, its role in immunology: how Macfarlane Burnet's phage research shaped his scientific style

The Australian scientist Frank Macfarlane Burnet-winner of the Nobel Prize in 1960 for his contributions to the understanding of immunological tolerance-is perhaps best recognized as one of the formulators of the clonal selection theory of antibody production, widely regarded as the 'central dogma' of modern immunology. His work in studies in animal virology, particularly the influenza virus, and rickettsial diseases is also well known. Somewhat less known and publicized is Burnet's research on bacteriophages, which he conducted in the first decade of his research career, immediately after completing medical school. For his part, Burnet made valuable contributions to the understanding of the nature of bacteriophages, a matter of considerable debate at the time he began his work. Reciprocally, it was while working on the phages that Burnet developed the scientific styles, the habits of mind and laboratory techniques and practices that characterized him for the rest of his career. Using evidence from Burnet's published work, as well as personal papers from the period he worked on the phages, this paper demonstrates the direct impact that his experiments with phages had on the development of his characteristic scientific style and approaches, which manifested themselves in his later career and theories, and especially in his thinking regarding various immunological problems.     

The Philosophical Origins of Mitchell's Chemiosmotic Concepts

Mitchell's formulation of the chemiosmotic theory of oxidative phosphorylation in 1961 lacked any experimental support for its three central postulates. The path by which Mitchell reached this theory is explored. A major factor was the role of Mitchell's philosophical system conceived in his student days at Cambridge. This system appears to have become a tacit influence on his work in the sense that Polanyi understood all knowledge to be generated by an interaction between tacit and explicit knowing. Early in his life Mitchell had evolved a simple philosophy based on fluctoids, fluctids and statids which was developed in a thesis submitted for the z at the University of Cambridge, England. This aspect of his work was rejected by the examiners and became a tacit element in his intellectual development. It is argued from his various publications that this philosophy can be traced as an underlying theme behind much of Mitchell's theoretical writing in the 50's leading, through his notion of vectorial metabolism, to the formulation and amplification of the chemiosmotic theory in the sixties. This philosophy formed the basis for Mitchell of his understanding of biological systems and gave him his unique approach to cell biology. This revised version was published online in July 2006 with corrections to the Cover Date.     

Abraham Flexner and the development of the Yale School of Medicine. 1999

Abraham Flexner first toured the Yale University School of Medicine in preparation for his report of 1910, but it was just the beginning of his relationship with the school. While his review of Yale in his report was generally favorable, he mentioned several shortfalls that needed to be improved to make the school acceptable. Throughout the next twenty-five years, Flexner worked with Deans George Blumer and Milton C. Winternitz to improve the school's finances, infrastructure, and quality of education through his work with the Carnegie Foundation and General Education Board. Flexner has been given great accolades for his work on medical education for the country, but little mention is made of him at Yale, even though he was one of the most influential figures in the development of Yale in the last century.     

Team Work Load in an English General Practice—I

A survey of the total care provided by a general practitioner and his paramedical team for 3,137 patients in Teesside in 1972 showed that even in this area of high morbidity and mortality the work load was very small. The doctor held an average of 2·3 consultations per patient per year, and the overall average for the team of doctor, nurse, and health visitor was only 3·1. By delegating work to a team of trained paramedical workers, by increasing the proportion of personal medicine, and by engaging the co-operation of his patients, the general practitioner reduced his work load considerably, without any apparent reduction in standard of care.     

The excluded philosophy of evo-devo? Revisiting C.H. Waddington's failed attempt to embed Alfred North Whitehead's "organicism" in evolutionary biology

Though a prominent British developmental biologist in his day, a close friend of Theodosius Dobzhansky, and a frequent correspondent with Ernst Mayr, C.H. Waddington did not enter the ranks of "architect" of the Modern Synthesis. By the end of his career, in fact, he recognized that other biologists reacted to his work "as though they feel obscurely uneasy"; and that the best that some philosophers of biology could say of his work was that he was not "wholly orthodox" (Waddington 1975c, 11). In this essay, I take Waddington's self-assessments at face value and explore three potential reasons why his work did not have more of a direct impact: Waddington's explicit support for the philosophy of Alfred North Whitehead; a lack of institutional support; and Waddington's occasional marginalization from the core network of American neo-Darwinians. Though excluded from the Modern Synthesis in the mid-20th century, it now appears that Waddington's work does undergird the emerging evo-devo synthesis. Whether this indicates concomitant, if implicit, support for Whiteheadian philosophy is an interesting question not explored here.     

Abraham Flexner and the development of the Yale School of Medicine

Abraham Flexner first toured the Yale University School of Medicine in preparation for his report of 1910, but it was just the beginning of his relationship with the school. While his review of Yale in his report was generally favorable, he mentioned several shortfalls that needed to be improved to make the school acceptable. Throughout the next twenty-five years, Flexner worked with Deans George Blumer and Milton C. Winternitz to improve the school's finances, infrastructure, and quality of education through his work with the Carnegie Foundation and General Education Board Flexner has been given great accolades for his work on medical education for the country, but little mention is made of him at Yale, even though he was one of the most influential figures in the development of Yale in the last century.     

In defense of Louis Pasteur: Critique of Gerald Geison's deconstruction of Pasteur's discovery of molecular chirality

Louis Pasteur discovered the phenomenon of molecular chirality, based on his studies of tartrate crystals. His finding remains one of the most important discoveries in the history of chemistry and a fundamentally important chemical phenomenon, with essential implications in biology. In his 1995 book The Private Science of Louis Pasteur, the eminent historian of science Gerald L. Geison (1943‐2001) was highly critical of much of Pasteur's work including his discovery of molecular chirality. The in‐depth analysis provided in this article indicates, however, that the negative assessment of Pasteur's chirality work by Geison is entirely without scientific basis. Criticisms of Pasteur in the book for other “transgressions” in his chirality work, such as supposed influences of his personal biases and stubbornly held a priori notions, misrepresentation of his scientific work in his publications and lectures, and unethical and career‐minded conduct, are also not supported by the evidence. Other troubling features of the book include a broad failure to assure accuracy in a variety of fundamental and important information, including errors in names, dates, events, referencing, indexing, and French‐language text.     

Hunters and Horticulturalists: A Preliminary Report of the 1972–4 Excavations in the Manim Valley,Papua New Guinea

Ole Christensen, a PhD scholar in the Department of Prehistory in the Research School of Pacific Studies at the Australian National University, was killed in a car accident on his way to work on 16 December last year. Ole was a Canadian citizen of Danish birth, whose parents settled in rural Alberta. He took his BA(Hons) in 1970 and his MA in 1972, both in the Department of Archaeology at the University of Calgary. His MA thesis, ‘Banff Prehistory: prehistoric subsistence and settlement in Banff National Park, Alberta’, is evidence of an early interest in economically and ecologically oriented archaeology, which he furthered by taking courses and laboratory work in pollen analysis. A visit to South America in 1970 with an archaeological team investigating early farming settlements in the Cauca Valley, Colombia, combined with a long standing interest in Polynesian anthropology to encourage him to seek to do graduate work on tropical agricultural systems somewhere in the Pacific. When he subsequently applied for the ANU scholarship which he took up in early 1972, he seemed a highly suitable person to work in association with the Department of Prehistory's project into New Guinea Highlands' agricultural history then about to start at Kuk in the upper Wahgi valley (see Mankind, 3:177–83). The proposition put to Ole was that he should undertake a study of the hydraulic technology and agrarian organization of one of the large scale agricultural systems operating in drained swamp that still flourish in Irian Jaya at the Paniai (Wissel) Lakes and in the Baliem valley, to supplement the archaeological work in the Wahgi where such systems had once but no longer existed. He felt, however, that his ethnographic background was too slim and he chose instead to do work for which he was better trained, the study of resource utilization over time in a side valley off the Wahgi close to the site of the Department's swamp excavations. The beautifully designed project that he carried out is described in the following article by him. It is based on a seminar he gave at ANU shortly before his death. I should like to make two points about this project that the article does not stress. One is the wealth of plant materials recovered from the excavations by wet sieving every ounce of excavated soil, when the nearest water source was sometimes some hundreds of precipitous yards away. The abundant pandanus seeds found in all levels of the excavated sites and their change over time from thick-walled, allegedly wild, to thin-walled, allegedly cultivated, varieties may hold important evidence for the chronology of horticulture in New Guinea and the question of whether an independent development of plant domestication took place there. The second point I want to make is that against his expectations he found himself to be a born and insatiable ethnographic fieldworker. With his Wurup friends he surveyed and recorded all the resource zones in terms of which his selection of sites for excavation was made and took part in all the activities of food procurement and processing that were responsible for the archaeological evidence that he set out to recover and interpret. A practical man of quiet and simple tastes, he was as settled in his bush house at Wurup as in his rural retreat near Canberra. He was unassertive, tolerant and deeply sympathetic and made undemanding and unobtrusive friendships with people in both homes. He is a loss to them and to his profession. His colleagues at the University of Calgary are establishing an academic prize in his memory. To his colleagues at ANU falls the responsibility of ensuring that the important work of this promising young scholar is brought to completion.     

Oswald T. Avery: Nbel Lureate or noble luminary?

In 1944, Oswald T. Avery and his associates reported that DNA was the chemical substance acting to genetically transform species of pneumococcal bacteria. Many believe that Avery warranted the Nobel Prize for this discovery. Avery's work is evaluated here in light of the Nobel archives, which have made public the names of those who nominated Avery for this award and the basis for each of the nominations. Based on the archival record, it seems that key biological chemists "were not convinced by Avery's claim that DNA was the basis of heredity, that no geneticists nominated Avery, and that most nominators overlooked Avery's work on DNA in favor of his work on the immunogenicity of the bacterial capsule. Three critical scientific factors that adversely affected acceptance of Avery's work were the possibility of protein contamination of DNA, the role of DNA transformation limited to a few species of bacteria, and the possibility that DNA was acting as a chemical mutagen on the true genetic substance. In addition, Avery's own idiosyncratic behavior may have unintentionally confounded acceptance of his groundbreaking discovery.     

Some of the best online Darwin resources

Ask most men or women in the street who Charles Darwin was and the chances are that they will know something of the work he did: the work that has revolutionised our understanding of the living world and our place in it. The 200th centenary of his birth was in February 2009. Over the 150 years since the publication of his seminal work On the Origin of Species by means of Natural Selection, the quality of his scientific thinking, experimenting and writing — leading to the formulation of his ideas about evolution — has had the single most profound impact on the development of modern biology. During this year a number of dedicated Darwin websites have been created and this edition of Webwatch describes a small number of the best of them.     

INDUSTRIAL INJURIES OF FARM WORKERS

Most industrial employees receive physical examinations to evaluate their physical fitness in relation to their work. The farm worker is neglected in this matter, in that he is hired for almost any type of work without physical evaluation. As a result, his accident rate is high. His efficiency at his work is low. His time loss from work because of sickness and accident is high, and the employer pays a very high rate of insurance for the patient''s care and his own legal protection.Physical fitness cards should be carried by all farm laborers so that they would be put in properly graded jobs.     

Riccardo (Rico) Wittek (1944-2008)

Riccardo (Rico) Wittek died 26 September 2008 in Switzerland. Rico was well known for his work on the molecular biology of poxviruses and for his work with the World Health Organization on biosafety that led to international guidelines for work with dangerous infectious agents. His colleagues Erwin G. Van Meir, Daniel Lavanchy, and Bernard Moss have written Rico''s memorial.Lynn W. EnquistEditor in Chief, Journal of Virology     

Last judgment: the visionary biology of J.B.S. Haldane

This paper seeks to reinterpret the life and work of J. B. S. Haldane by focusing on an illuminating but largely ignored essay he published in1927, “The Last Judgment” – the sequel to his better known work, Daedalus (1924). This astonishing essay expresses a vision of the human future over the next 40,000,000 years, one that revises and updates Wellsian futurism with the long range implications of the “new biology” for human destiny. That vision served as a kind of lifelong credo, one that infused and informed his diverse scientific work, political activities, and popular writing, and that gave unity and coherence to his remarkable career. This revised version was published online in July 2006 with corrections to the Cover Date.     

<Emphasis Type="BoldItalic">Regeneration</Emphasis>: Thomas Hunt Morgan’s Window into Development

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration (1901). In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of regeneration studies by looking in depth at Regeneration and evaluating Morgan’s contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan’s earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research.     

Explaining the freemartin: Tandler and Keller vs. Lillie and the question of priority

The correct explanation for the freemartin phenotype in the female twin of a female-male pair in cattle was first reported by Tandler and Keller (1911. Deutsche Tier?rzt Wochenschr 19:148-149). This same explanation for the freemartin was independently discovered by Lillie (1916. Science 43:611-613). Today both set of scientists are given credit for this discovery; it is the basis for much of the subsequent work on the developmental basis for sex differentiation in vertebrates. Even though Lillie published after Keller and Tandler, he gets credit for this discovery because: (1) Keller and Tandler published in a veterinary journal and as a consequence their work was not disseminated as broadly throughout the larger scientific community; this problem was compounded by the fact that their definitive 1916 paper was published under wartime conditions during World War I, and (2) Lillie was an influential scientist with a group of graduate students who could elaborate on and extend his work; they published a number of papers on the freemartin. At some point while Lillie was doing his initial work on the freemartin he may have become aware that Keller and Tandler were also working on the freemartin problem; this information may have shaped his decision on when to publish.     

Revisiting Metchnikoff's work in light of the COVID-19 pandemic

Revisiting Metchnikoff''s work in light of the COVID-19 pandemic illustrates how much this amazing scientist was a polymath, and one could speculate how much he would have been fascinated and most interested in following the course of the pandemic. Since he coined the word “gerontology”, he would have been intrigued by the high mortality among the elderly, and by the concepts of immunosenescence and inflammaging that characterize the SARS-CoV-2 infection. While Metchnikoff''s work is mainly associated with the discovery of the phagocytes and the birth of cellular innate immunity, he regularly invited his closest collaborators to investigate humoral immunity, and it was in his laboratory that Jules Bordet made his major discovery of the complement system. While Metchnikoff and his team investigated many infectious diseases, he also contributed to studies linked to vaccination, such as those on typhoid fever performed in chimpanzees, illustrating that non-human primates can provide animal models which are potentially helpful for understanding the pathophysiology of the COVID-19 virus. In the present review, we illustrate how much his own work and the investigations of his trainees were pertinent to this new disease.     

Biological adaptabilities and quantum entropies.

The entropy-based theory of adaptability set forth by Michael Conrad in the early 1970s continued to appear in his work for over two decades, and was the subject of the only book he published in his lifetime. He applied this theory to a host of subjects ranging from enzyme dynamics to sociology. This paper reviews the formalism of adaptability theory, clarifying some of its mathematical and interpretive difficulties. The theory frames the computational tradeoff principle, a thesis that was the most frequently recurring claim in his work. The formulation of adaptability theory presented here allows the introduction of quantum entropy functions into the theory, revealing an interesting relationship between adaptability and another one of Conrad's deep preoccupations, the role of quantum processes in life.     

Husserl's Crisis as a crisis of psychology

This paper places Husserl's mature work, The Crisis of the European Sciences, in the context of his engagement with--and critique of--experimental psychology at the time. I begin by showing (a) that Husserl accorded psychology a crucial role in his philosophy, i.e., that of providing a scientific analysis of subjectivity, and (b) that he viewed contemporary psychology--due to its naturalism--as having failed to pursue this goal in the appropriate manner. I then provide an analysis of Husserl's views about naturalism and scientific philosophy. Some central themes of the Crisis are traced back to Husserl's earlier work and to his relationship with his teacher, Franz Brentano, with whom he disagreed about the status of "inner perception" as the proper scientific method for a phenomenological analysis. The paper then shows that Husserl was well aware of at least one publication about the crisis of psychology (Bühler's 1927 book), and it teases out some aspects of the complicated relationship between Husserl and members of the Würzburg School of thought psychology: The latter had drawn on Husserl's writings, but Husserl felt that they had misunderstood his central thesis. I conclude by placing Husserl's work in the wider context of scientific, cultural, and political crisis-discourses at the time.     

Christiaan Eijkman

One century ago, Christiaan Eijkman was appointed Professor of Bacteriology at the Utrecht University, The Netherlands. Despite his appointment to teach bacteriology, Christiaan Eijkman made his main contribution to medical science not in bacteriology but in nutrition. He discovered that Beri-Beri was not an infection but a nutritient deficiency (later called vitamin-deficiency) and was awarded the Nobel Prize for Medicine in 1929 for these observations. These landmark studies were made in the former Dutch East Indies. Interestingly, the results of his studies were presented in the Dutch language, in the medical journal of the Dutch East Indies. As a professor of Bacteriology, his work was the beginning of an important school in biochemistry in The Netherlands.