Claude Bernard and life in the laboratory

History and Philosophy of the Life Sciences - Ayurveda is a traditional system of healthcare that is native to India and has a rich documented literature of its own. Most of the historians agree...     

Claude Bernard: primer of the second biomedical revolution

Claude Bernard, the son of a Beaujolais winegrower, moved to Paris to pursue his literary ambitions and went on to become one of the fathers of modern life sciences. What did Bernard do to earn universal renown? And are his teachings relevant to modern science?     

The Claude Bernard lecture, 1987. Embryonic chimeras: a tool for studying the development of the nervous and immune systems

Chimeras have been constructed in the avian embryo following the observation of the particular structure of the interphase nucleus in the Japanese quail (Coturnix coturnix japonica). In all embryonic and adult cell types of this species a large amount of heterochromatin is associated with the nucleolus, making quail cells readily distinguishable from those of the chick where the constitutive heterochromatin is evenly dispersed in the nucleus. These structural differences have been used to devise a cell-marking technique through which cell migrations and cell interactions during embryogenesis can be followed in the embryo in ovo by grafting quail cells into chick embryos or vice versa. This method was applied to the ontogeny of the neural crest and of the immune system. Recently quail-chick chimeras have been allowed to hatch and the immunological status of the embryonic grafts after birth scrutinized. Xenogeneic tissue grafts made in the embryo are rejected after birth with a more or less prolonged delay according to the nature of the graft. However, rejection can be prevented and a permanent state of tolerance induced for the embryonic tissue grafts by isotopically implanting the thymic epithelium from the same quail donor.     

Animals as sentinels: using comparative medicine to move beyond the laboratory

The comparative medicine approach, as applied to the study of laboratory animals for the betterment of human health, has resulted in important medical and scientific progress. Much of what is known about the human health risks of many toxic and infectious hazards present in the environment derives from experimental studies in animals and observational (epidemiological) studies of exposed human populations. Yet there is a third source of "in vivo" knowledge about host-environment interactions that may be underused and -explored: the study of diseases in naturally occurring animal populations that may signal potential human health threats. Just as canaries warned coal miners of the risk of toxic gases, other nonhuman animals, due to their greater susceptibility, environmental exposure, or shorter life span, may serve as "sentinels" for human environmental health hazards. Traditionally, communication between human and animal health professionals about cross-species sentinel events has been limited, but progress in comparative genomics, animal epidemiology, and bioinformatics can now provide an enhanced forum for such communication. The "One Health" concept involves moving toward a comparative clinical approach that considers "shared risks" between humans and animals and promotes greater cooperation and collaboration between human and animal health professionals to identify and reduce such risks. In doing so, it also creates new opportunities for the field of comparative medicine that can supplement traditional laboratory animal research.     

From physiology to fitness: the costs of a defensive adaptation in rattlesnakes

The costs of using and maintaining presumed adaptations are unknown for most animals. Energetically expensive traits, such as some agonistic and antipredator behaviors in animals, may incur trade-offs with other aspects of an animal's life history, such as feeding and reproduction. However, infrequent and brief use may reduce the costs of vigorous behaviors. The shaker muscles in the tails of rattlesnakes are an excellent system for studying the potential costs of a specialized defensive system. The high energetic cost of rattling may increase feeding requirements or use energy that could otherwise be available for reproduction. I used energetic modeling to test whether the cost of rattling in western diamond-backed rattlesnakes (Crotalus atrox) can be high enough to increase feeding demands or reduce fecundity and fitness. Only very frequent and prolonged rattling would increase feeding needs and perhaps reduce fecundity to some degree. Typically, rattling probably incurs very low costs to feeding, reproduction, and hence fitness. These and other results suggest that many seemingly expensive adaptations may have minimal costs to energy budgets, reproduction, and fitness.     

Inositide signaling in the nucleus: From physiology to pathology

A inositide-dependent signaling exists in the nucleus. In this review we focused to the nuclear PI-PLC signaling activity, its downstream effects and its role in haematological malignancies. PI-PLC β1 is involved in the physiological control of the cell cycle and by acting on the Cylin D3 promoter plays a crucial role in the process of C2C12 myoblast differentiation. In hematological malignancies recent studies showed that PI-PLC β1 mono-allelic deletion correlates with a higher risk of AML evolution. Moreover it has been shown that PI-PLC β1 promoter is hypermethylated in high-risk MDS patients and that the amount of PI-PLC β1 mRNA could predict the clinical response to azacitidine, a well known demethylating drug.All in all the data reviewed here pave the way to a new prognostic and therapeutic strategy in some haematological malignancies.     

Charting a global future for education in physiology

The 2005 Claude Bernard Distinguished Lecture was presented at the XXXV International Congress of Physiological Sciences (IUPS) in San Diego, CA, by Ann J. Sefton. Dr. Sefton is an Emeritus Professor of Physiology of the University of Sydney and co-Chair of the IUPS Education Committee. A full profile of Dr. Sefton is included in this issue's The Physiology Teacher.     

From tibialis anterior to Tai Chi: biofeedback and beyond

This keynote presentation highlights events that have contributed to scientific explorations of one research clinician. Steve Wolf traces his scientific roots to early studies in single motor unit control under the guidance of his primary mentor, John Basmajian, MD. This work led to subsequent studies on the role of EMG feedback in predicting successful outcomes in upper extremity use and in ambulatory capabilities among patients with chronic stroke. These findings are contrasted to further efforts to condition entire reflexes rather than individual muscles through use of operant-conditioning paradigms. The findings from applications of EMG biofeedback to stroke patients became the basis for minimal motor criteria in the treatment of the impaired upper extremities of patients with chronic stroke, using forced use or constraint-induced movement therapy. Last, investigations into center of pressure feedback using computerized balance machines resulted in a series of experiments that ultimately led to the finding that Tai Chi as an exercise form for older adults can have a substantially favorable effect in delaying the onset of fall events.     

Expanding course goals beyond disciplinary boundaries: physiology education in an undergraduate course on psychoactive drugs

The topic of psychoactive drugs is one of inherent interest to college students. We used this insight to design and implement a multidisciplinary undergraduate course with psychoactive drugs as the central theme. The Medical Science of Psychoactive Drugs examines the biological mechanisms underlying all major effects of psychoactive drugs, including the effects on the brain and other organs and tissues. Physiological principles, molecular mechanisms, and genetic factors involved in drug-induced therapeutic and adverse effects are emphasized. The course is open to undergraduate students at all levels and carries no prerequisites, and enrollment is limited to approximately 50 students. Major teaching modes include lecture, short homework papers on topics related to the previous class meeting, small-group discussions at several points during each class, and whole class discussions. Because of the diversity of students' knowledge of basic science, we employ a variety of methods designed to help students grasp the necessary scientific concepts. Our methods are intended to be inquiry based and highly interactive. Our goals are 1) to foster the development of an organized knowledge base about psychoactive drugs that will have practical applicability in the daily lives of the students; 2) to promote the rational application of this knowledge in thinking about current medical, social, legal, and ethical issues involving psychoactive drugs; and 3) to cultivate science literacy, critical thinking, and communication skills among students.     

From Metchnikoff to Monsanto and beyond: the path of microbial control

In 125 years since Metchnikoff proposed the use of Metarhizium anisopliae to control the wheat cockchafer and brought about the first field trials, microbial control has progressed from the application of naturalists' observations to biotechnology and precision delivery. This review highlights major milestones in its evolution and presents a perspective on its current direction. Fungal pathogens, the most eye-catching agents, dominated the early period, but major mycological control efforts for chinch bugs and citrus pests in the US had questionable success, and interest waned. The discoveries of Bacillus popilliae and Bacillus thuringiensis began the era of practical and commercially viable microbial control. A program to control the Japanese beetle in the US led to the discovery of both B. popilliae and Steinernema glaseri, the first nematode used as a microbial control agent. Viral insect control became practical in the latter half of the 20th century, and the first registration was obtained with the Heliothis nuclear polyhedrosis virus in 1975. Now strategies are shifting for microbial control. While Bt transgenic crops are now planted on millions of hectares, the successes of more narrowly defined microbial control are mainly in small niches. Commercial enthusiasm for traditional microbial control agents has been unsteady in recent years. The prospects of microbial insecticide use on vast areas of major crops are now viewed more realistically. Regulatory constraints, activist resistance, benign and efficacious chemicals, and limited research funding all drive changes in focus. Emphasis is shifting to monitoring, conservation, integration with chemical pesticides, and selection of favorable venues such as organic agriculture and countries that have low costs, mild regulatory climates, modest chemical inputs, and small scale farming.