"They Sweat for Science": The Harvard Fatigue Laboratory and Self-Experimentation in American Exercise Physiology.

In many scientific fields, the practice of self-experimentation waned over the course of the twentieth century. For exercise physiologists working today, however, the practice of self-experimentation is alive and well. This paper considers the role of the Harvard Fatigue Laboratory and its scientific director, D. Bruce Dill, in legitimizing the practice of self-experimentation in exercise physiology. Descriptions of self-experimentation are drawn from papers published by members of the Harvard Fatigue Lab. Attention is paid to the ethical and practical justifications for self-experimentation in both the lab and the field. Born out of the practical, immediate demands of fatigue protocols, self-experimentation performed the long-term, epistemological function of uniting physiological data across time and space, enabling researchers to contribute to a general human biology program.

Teleomechanism redux? Functional physiology and hybrid models of life in early modern natural philosophy.

The distinction between 'mechanical' and 'teleological' has been familiar since Kant; between a fully mechanistic, quantitative science of Nature and a teleological, qualitative approach to living beings, namely 'organisms' understood as purposive or at least functional entities. The beauty of this distinction is that it apparently makes intuitive sense and maps onto historico-conceptual constellations in the life sciences, regarding the status of the body versus that of the machine. I argue that the mechanism-teleology distinction is imprecise and flawed using examples including the 'functional' features present even in Cartesian physiology, the Oxford Physiologists' work on circulation and respiration, the fact that the model of the 'body-machine' is not a mechanistic reduction of organismic properties to basic physical properties but is focused on the uniqueness of organic life; and the concept of 'animal economy' in vitalist medicine, which I present as a 'teleomechanistic' concept of organism (borrowing a term of Lenoir's which he applied to nineteenth-century embryology)--neither mechanical nor teleological.

A life dedicated to research and ideal: Johannes Müller between empirical universality and idealistic vitalism mirrored in lecture notes from 1851.

Until the mid-nineteenth century, "physiology" was a comprehensive theory of life, expounded and shaped by Johannes P. Müller (1801-1858). Biologists and medical doctors still refer to him today. In the summer term of 1851, Müller gave a lecture on the Comparative Anatomy of animals. This lecture was attended and recorded by Ernst Zeller (1830-1902), a future physician and zoologist, and has recently been published together with a German transcript. In this paper, we situate Johannes Müller within the intellectual history of his time. Through his "empirical idealism," we show how he opposed the speculative tendencies of the romantic understanding of nature, the emerging evolutionism, and the growing splits in the natural sciences. Müller focused on recognizing living nature as a whole and realizing ideal "phenomena" through his empirical research. He considered the notion of the soul of the world. Müller's lecture transcript serves as a poignant testament to German scientific culture in the mid-nineteenth century, a few years before the publication of Darwin's Origin of Species. It also provides valuable insights into the self-contained epistemological foundations of morphology.

["Purified empiricism": Johann Christian Reil's (1759-1813) attempts at a foundation of medicine in relation to its tradition, kantianism, and speculative philosophy]. / "Geläuterte Empirie": Johann Christian Reils (1759-1813) Versuche zur Grundlegung der Medizin im Spannungsfeld von Tradition, Kantianismus und spe- kulativer Philosophie.

Johann Christian Reil's (1759-1813) importance lies in his theoretical approach to medicine. Following Kant in his early work, he attempts to combine medical experience with an underlying conceptual structure. This attempt is directed against both the chaotic empiricism of traditional medicine and speculative theories such as vitalism. The paper starts from his early reflections on the concept of a life force, which he interprets in the way of a non-reductive materialism. In the following, the basic outlines of his Theory of Fever will be shown. The Theory is a systematic attempt at finding a new foundation for diagnosis and therapy on the basis of the concept of fever, which is understood as modification of vital processes. The paper ends with a discussion of his later work, which has remained controversial so far. It shows that the combination of practical empiricism and scientific theory remained rather unstable in this early phase of the development of modern medicine.

Laws of organization and chemical analysis: Blainville and Müller.

When "general physiology" emerged as a basic field of research within biology in the early nineteenth century, Henri Ducrotay de Blainville (1777-1850) on the one hand and Johannes Peter Müller (1801-1858) on the other appealed to chemical analysis to account for the properties and operations of organisms that were observed to differ from what was found in inorganic compounds. Their aim was to establish laws of vital organization that would be based on organic chemical processes, but would also be of use to explain morphological and functional differences among life forms. The intent of this paper is to specify for each of these leading physiologists the different presuppositions that provided theoretical frameworks for their interpretation of what they conceived of as laws of organization underpinning the dynamics of vital phenomena. Blainville presumed that the properties of organic compounds depended on the chemical properties of their constitutive molecules, but combined according to patterns of functional development, and that the latter could only be inferred from an empirical survey of modes of organization across the spectrum of life forms. For Müller, while all vital processes involved chemical reactions, in the formative and functional operations of organisms, these reactions would result from the action of life forces that were responsible for the production of organic combinations and thus for vital and animal functions. As both physiologists set significant methodological patterns for their many disciples and followers, their respective quasi-reductionist and anti-reductionist positions need to be accounted for.

The emergence of Applied Physiology within the discipline of Physiology.

Despite the availability and utilization of the physiology textbooks authored by Albrecht von Haller during the 18th century that heralded the modern age of physiology, not all physicians or physiologists were satisfied with its presentation, contents, or application to medicine. Initial reasons were fundamental disagreements between the "mechanists," represented by Boerhaave, Robinson, and von Haller, and the "vitalists," represented by the faculty and graduates of the Montpellier School of Medicine in France, notably, Bordeu and Barthez. Subsequently, objections originated from Europe, United Kingdom, and the United States in publications that focused not only on the teaching of physiology to medical and secondary students, but on the specific applications of the content of physiology to medicine, health, hygiene, pathology, and chronic diseases. At the turn of the 20th century, texts began to appear with applied physiology in their titles and in 1926, physician Samson Wright published a textbook entitled Applied Physiology that was intended for both medical students and the medical profession. Eleven years later, physicians Best and Taylor published The Physiological Basis of Medical Practice: A University of Toronto Texbook in Applied Physiology Although both sets of authors defined the connection between applied physiology and physiology, they failed to define the areas of physiology that were included within applied physiology. This was accomplished by the American Physiological Society (APS) Publications Committee in 1948 with the publication of the Journal of Appplied Physiology, that stated the word "applied" would broadly denote human physiology whereas the terms stress and environment would broadly include work, exercise, plus industrial, climatic and social factors. NIH established a study section (SS) devoted to applied physiology in 1964 which remained active until 2001 when it became amalgamated into other SSs. Before the end of the 20th century when departments were changing their titles to reflect a stronger science orientation, many established laboratories and offered degree programs devoted to Applied Physiology. We concluded that Applied Physiology has been an important contributor to the discipline of physiology while becoming an integral component of APS.

["A change in medical thinking?" or "over-eager literary activity?" August Bier, homeopathy and the Nobel Prize 1906-1936]. / Ein "Umschwung des medizinischen Denkens" oder "eine übereifrige literarische Tätigkeit"? August Bier, die Homöopathie und der Nobelpreis 1906-1936.

This essay explains the nomination and evaluation procedure for the Nobel Prize for Physiology or Medicine. Its research is based on original files and on the example of August Karl Gustav Bier (1861-1949). It discusses the minutes of the Nobel Committee for physiology or medicine, which are kept in the Nobel Archives, as well as the unusually high number of nominations of August Bier and the nominations submitted by him; it also describes the reasons why August Bier, in the end, never received the Nobel Prize. The essay focuses mainly on the reception of Bier's homeopathic theses by the Nobel Prize Committee and his nominators.

The investigator as volunteer subject.

It is particularly within the past three decades that increased attention has been focused on human experimentation, both in regard to the scientific design that ensures the greatest chance of success and to conformity to ethical principles that are most likely to receive public approbation. The story of man's experimentation on man dates back to prehistoric times. In the past two centuries, these investigations have been carried out at an increasing level of sophistication. In this saga, the narratives of the auto-experimenters define a special group of investigators, to many of whom the term "heroic" can be applied. When investigators involve themselves as subjects of their research, a situation of informed consent is often assumed to exist. Discussions concerning voluntarism and ethical propriety have been much less voluminous when the investigators have themselves been subjects that when this is not so. It is within the past half century that physiologists particularly have often been auto-experimenters, and Dr. Earl Wood belongs to the best of this illustrious group.

Oddi: the paradox of the man and the sphincter.

Ruggero Oddi was born of a modest family in the small town of Perugia, Italy, in 1866. While still a young medical student, he identified the sphincter and in addition characterized its physiological properties. At the early age of 29 years, he was appointed as the director of the Physiological Institute at Genoa, but a dalliance with drugs and fiscal improprieties resulted in his being relieved of this eminent position in Italian Physiology. He subsequently sought employment as a physician in the Belgian colonial medical service and briefly spent time in the Congo. The deterioration of his physical status and his use of Vitaline, a homeopathic preparation, led to the demise of his medical career. For reasons that are unclear, he then traveled to Africa where he died in Tunisia. In the last 50 years, the use of sophisticated methodology has allowed delineation of aspects of the neural and hormonal regulatory mechanisms of the sphincter. Its exact role in disease has not been determined, although its relationship to the putative entity of biliary dyskinesia has been suggested. The paradox of both the sphincter and its original discoverer remain to be resolved.

The neuroscience of Helmholtz and the theories of Johannes Müller. Part 1: Nerve cell structure, vitalism, and the nerve impulse.

Hermann Helmholtz made monumental contributions to the neural sciences in the second half of the nineteenth century. Among his earliest achievements were experiments that challenged vitalism, microscopic studies on the structure of the nerve cell and its processes, and the first reasonable estimates of the speed of nerve transmission based on physiological experiments. In this, the first of a two-part article, we review Helmholtz's early contributions in biographical context and with reference to Johannes Müller's own thoughts. We reveal how Johannes Müller, considered by many to be the greatest physiologist of the first half of the nineteenth century, helped to launch and shape Helmholtz's career. We also show that Helmholtz was only willing to accept some of his mentor's theories, even though he had great admiration for Müller. The point will be made that Helmholtz owed a great debt to Müller, but even from his student days in Berlin he was an independent thinker with his own agenda, and never his strict disciple.

[Division and specialization of the Western European physiology].

The 19th century has been thought to be the turning point that the experimental method began to take strong root as the core to solve many physiological subjects, and the discipline of physiology got firmly fixed as the specialized one in the western Europe. Authors found the following characteristics in the process of the division and specialization of the 19th century western physiology. 1) It was the process of its separation from the discipline of anatomy that was necessary in the development of physiology as the independent, specialized division. Newly grown ideas, that there were working functions specialized study, were the important background and basis of the development of physiology as the specialized discipline. 2) It was not until the force and influence of the metaphysical concept on the living things (vitalism) grew weak that physiology could become the specialized discipline. The new materialistic concept about living things made it possible for the researchers of that time to apply the physico-chemical method in the study of physiological problems. 3) Institutionalization of the physiological research and education accelerated its development and specialization. The followings appeared in the mid-19th century: specialized professorship, division as the separated subject in the undergraduated medical school curriculum, laboratory settings for the purpose of physiological study, establishment of independent academic societies and publication of their own journals. Two main factors, namely, both the settlement of the new physiological thought and method of the very scientific nature and the institutionalization within the academic and medical societies, exerted influences on each other in the ground of the 19th century western Europe. Through that process, the discipline of physiology took root deep as the independent specialized division in the societies of science and medicine.

Charles Edouard Brown-Séquard's departure from the Medical College of Virginia: incompatible science or incompatible social views in pre-Civil War southern United States.

Charles Edouard Brown-Séquard was one of the most colorful characters in modern physiology. His scientific methods of self-experimentation and animal vivisection led to many great observations, including the eponymous syndrome of hemisection of the spinal cord. Despite his renown, he stayed but one year in his first major academic post. Details of his sojourn at the Medical College of Virginia (now part of Virginia Commonwealth University) in Richmond were divined from perusal of archival material, letters, and from the available literature. His notoriety in the field of physiology landed him a post at the Medical College of Virginia in 1854 as the chair of physiology. During a brief time here, he was able to publish his landmark monograph of 1855 on the pathways of the spinal cord "Experimental and Clinical Researches on the Physiology and Pathology of the Spinal Cord." He had a near-death experience while experimenting on himself to determine the function of the skin. It was rumored that his English was poor, his lectures unintelligible, and his scientific methods disturbing to the neighbors and that for those reasons he was asked to vacate his post. Personal communications and other accounts indicate a different view: his mixed-blood heritage and his views on slavery were unpopular in the pre-Civil War southern United States. These disparate viewpoints lend an insight into the life and career of this pioneer in modern medicine and experimental design and to the clash of science and social views.

Regulating agents, functional interactions, and stimulus-reaction-schemes: the concept of "organism" in the organic system theories of Stahl, Bordeu, and Barthez.

In this essay, I sketch a problem-based framework within which I locate the concept of "organism" in the system theories of Georg Ernst Stahl, Théophile Bordeu, and Paul-Joseph Barthez. Around 1700, Stahl coins the word "organism" for a certain concept of order. For him, the concept explains the form of order of living bodies that is categorically different from the order of other (dead) bodies or composites. At the end of the century, the "organism" as a specific form of order becomes a major topos in many discourses. I will not so much focus on experiments and objects as on basic problems that contribute to the general framework of the concept of organism as a key concept of the vitalist movement between 1700 and 1800. For this purpose, I will investigate the combination of three explanatory tools. These tools refer to regulating agents, functional interactions, and stimulus-reactions-schemes within individual organic systems of forces. They are related to various themes--especially to energy, sensibility, and sympathy. I will retrace some aspects of these relations.

Irritability and sensibility: key concepts in assessing the medical doctrines of Haller and Bordeu.

This article addresses the doctrinal controversy over the various characterizations of irritability and sensibility. In the middle of the eighteenth century, this scientific debate involved some encyclopaedist physicians, Albrecht von Haller (1709-1777), Jean-Jacques Ménuret de Chambaud (1733-1815), and Théophile de Bordeu (1722-1776). The doctor from Bern described irritability as an experimental property of the muscle fibers and made it the basis of a neo-mechanism in which organic reactions are related to the degree of irritation of the fibers. The practitioners from Montpellier considered sensibility, a property of living matter, to be a spontaneous activity of the organ and developed around this notion an original conception of the organism as the sum of the specific lives of each part. Beyond conceptual divergences, two ways of thinking whose philosophical presuppositions (conception of living matter, mechanism, and organicism), were in opposition, while their epistemological principles (experience versus observation) and their medical practices (active medicine and expectant medicine) went on to evolve in different directions. The privileged place granted to experimentation and assessment enabled physiology to be articulated as an autonomous scientific discipline; the pre-eminence of observation and attention to the radical specificity of the living being constituted the bases of clinical medicine.

Can matter mark the hours? Eighteenth-century vitalist materialism and functional properties.

Eighteenth-century Montpellerian vitalism and contemporaneous French "vitalist" materialism, exemplified by the medical and biological materialism of La Mettrie and Diderot, differ in some essential aspects from some later forms of vitalism that tended to postulate immaterial vital principles or forces. This article examines the arguments defending the existence of vital properties in living organisms presented in the context of eighteenth-century French materialism. These arguments had recourse to technological metaphors and analogies, mainly clockworks, in order to claim that just as machines can have functional properties which its parts do not possess (e.g., showing time), so living organisms can, as material entities, also have organic or vital properties which its material parts do not possess. Such arguments, with the help of a healthy dose of epistemological scepticism, tend to strike a balance between two positions concerning the ontology of life which we now tend to label "vitalism" and "emergentism." Although there is nothing inconsistent in viewing vital properties as emergent, some ambiguity results if one does not draw a clear distinction between properties and functions. The philosophical problems related to these ambiguities are revealed in Diderot's apparent hesitation concerning sentience as "a general property of matter or the product of organization."

Form--a matter of generation: the relation of generation, form, and function in the epigenetic theory of Caspar F. Wolff.

The question, how organisms obtain their specific complex and functional forms, was widely discussed during the eighteenth century. The theory of preformation, which was the dominant theory of generation, was challenged by different alternative epigenetic theories. By the end of the century it was the vitalist approach most famously advocated by Johann Friedrich Blumenbach that prevailed. Yet the alternative theory of generation brought forward by Caspar Friedrich Wolff was an important contribution to the treatment of this question. He turned his attention from the properties of matter and the forces acting on it towards the level of the processes of generation in order to explain the constitution of organismic forms. By regarding organic structures and forms to be the result of the lawfulness of ongoing processes, he opened up the possibility of a functional but non-teleological explanation of generation, and thereby provided an important complement to materialist and vitalist approaches.

What ever happened to Francis Glisson? Albrecht Haller and the fate of eighteenth-century irritability.

This article investigates the reasons behind the disappearance of Francis Glisson's theory of irritability during the eighteenth century. At a time when natural investigations were becoming increasingly polarized between mind and matter in the attempt to save both man's consciousness and the inert nature of the res extensa, Glisson's notion of a natural perception embedded in matter did not satisfy the new science's basic injunction not to superimpose perceptions and appetites on nature. Knowledge of nature could not be based on knowledge within nature, i.e., on the very knowledge that nature has of itself; or--to look at the same question from the point of view of the human mind--man's consciousness could not be seen as participating in forms of natural selfhood. Albrecht Haller played a key role in this story. Through his experiments, Haller thought he had conclusively demonstrated that the response given by nature when irritated did not betray any natural perceptivity, any inner life, any sentiment interiéur. In doing so, he provided a less bewildering theory of irritability for the rising communities of experimental physiology.