Mobile Monkeys and Modified Microbes: Medical Experimentation between Metropolitan and Colonial Laboratories, 1880-ca. 1925.

Following the medical breakthroughs of Pasteur and Koch after 1880, the use of simians became pivotal to laboratory research to develop vaccines and cultivate microbes through the technique of serial passage. These innovations fueled research on multiple diseases and unleashed a demand for simians, which died easily in captivity. European and American colonial expansion facilitated a burgeoning market for laboratory animals that intensified hunting for live animals. This demand created novel opportunities for disease transfers and viral recombinations as simians of different species were confined in precarious settings. As laboratories moved into the colonies for research into a variety of diseases, notably syphilis, sleeping sickness, and malaria, the simian market was intensified. While researchers expected that colonial laboratories offered more natural environments than their metropolitan affiliates, amassing apes, people, microbes, and insects at close quarters instead created unnatural conditions that may have facilitated the spread of undetectable diseases.

Public perception of laboratory animal testing: Historical, philosophical, and ethical view.

The use of laboratory animals in biomedical research is a matter of intense public debate. Recent statistics indicates that about half of the western population, sensitive to this discussion, would be in favor of animal testing while the other half would oppose it. Here, outlining scientific, historical, ethical, and philosophical aspects, we provide an integrated view explaining the reasons why biomedical research can hardly abandon laboratory animal testing. In this paper, we retrace the historical moments that mark the relationship between humans and other animal species. Then starting from Darwin's position on animal experimentation, we outline the steps that over time allowed the introduction of laws and rules that regulate animals' use in biomedical research. In our analysis, we present the perspectives of various authors, with the aim of delineating a theoretical framework within which to insert the ethical debate on laboratory animals research. Through the analysis of fundamental philosophical concepts and some practical examples, we propose a view according to which laboratory animals experimentation become ethically acceptable as far as it is guided by the goal of improving humans and other animal species (i.e., pets) life. Among the elements analyzed, there is the concept of responsibility that only active moral subjects (humans) have towards themselves and towards passive moral subjects (other animal species). We delineate the principle of cruelty that is useful to understand why research in laboratory animals should not be assimilated to a cruel act. Moreover, we touch upon the concepts of necessity and "good cause" to underline that, if biomedical research would have the possibility to avoid using animals, it would surely do that. To provide an example of the negative consequences occurring from not allowing laboratory animal research, we analyze the recent experience of Covid-19 epidemic. Finally, recalling the principle of "heuristics and biases" by Kahneman, we discuss why scientists should reconsider the way they are conveying information about their research to the general public.

A Belmont Report for Animals?

Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, and principled effort has addressed the use of (nonhuman) animals in research. Although published policies regarding animal research provide relevant regulatory guidance, the lack of a fundamental effort to explore the ethical issues and principles that should guide decisions about the potential use of animals in research has led to unclear and disparate policies. Here, we explore how the ethical principles outlined in the Belmont Report could be applied consistently to animals. We describe how concepts such as respect for autonomy and obligations to beneficence and justice could be applied to animals, as well as how animals are entitled to special protections as a result of their vulnerability.

A Note on Semmelweis's Animal Experiments and Their Historical Significance.

This article seeks to establish what animal experiments Semmelweis conducted, and when and why he conducted them, because the Semmelweis literature contains conflicting claims about these topics or has ignored them altogether. Semmelweis first conducted animal experiments between 22 March and 20 August 1849 with Rokitansky's assistant, Georg Maria Lautner, because his chief, Johann Klein, did not accept that by merely reducing the mortality rate from childbed fever with chlorine hand-disinfection, Semmelweis had proved his theory of the cause of childbed fever. However, Skoda concluded that the Lautner experiments did not resolve the doubts about Semmelweis's theory they were intended to resolve, and, therefore, asked the Academy of Sciences to award Semmelweis a grant to conduct further and more varied experiments with the physiologist, Ernst Ritter von Brücke. These additional experiments were conducted in the spring and summer of 1850, but yielded only ambiguous results, and led Brücke to conclude that questions about Semmelweis's theory could only be resolved by clinical observations, not animal experiments. This article discusses the reasoning behind these animal experiments, and Skoda's and Brücke's responses to them, and argues that their responses to the experiments caused Semmelweis to delay publishing his research until he had collected sufficient clinical evidence to prove his theory.

Assignment of culpability to animals as a form of abuse: Historical and cultural perspectives.

How the law regards animals reflects cultural trends that have varied widely from antiquity to the present. This article argues that cultural views of animals have shaped laws, attitudes, and practices worldwide. Whereas ancient (biblical and Mesopotamian) practices turned on economics, medieval concepts of animal culpability aligned with Christian beliefs of the primacy of humans. In medieval Europe, pets, farm animals, vermin, and insects could be held accountable for damage to persons and property. Considered entitled to due process, they were represented, tried, and punished - sometimes in public executions. Centuries of regarding animals as property subordinated to humans gave way to animal cruelty laws. It was not until the 19th century that respect for animal welfare, apart from economics, assumed legal significance. Presently, animals are not considered capable of criminal intent but can be "executed" for dangerousness. However, they may possess legal standing as civil complainants in animal rights cases. Contemporary trends include animal rights activism and courts conferring legal personhood to animals. The discussion concludes that there will be disparate approaches worldwide, based on prevailing views of animal sentience, spiritually based concepts and values, litigation arguing property and environmental law, and economics.

Livestock in biomedical research: history, current status and future prospective.

Livestock models have contributed significantly to biomedical and surgical advances. Their contribution is particularly prominent in the areas of physiology and assisted reproductive technologies, including understanding developmental processes and disorders, from ancient to modern times. Over the past 25 years, biomedical research that traditionally embraced a diverse species approach shifted to a small number of model species (e.g. mice and rats). The initial reasons for focusing the main efforts on the mouse were the availability of murine embryonic stem cells (ESCs) and genome sequence data. This powerful combination allowed for precise manipulation of the mouse genome (knockouts, knockins, transcriptional switches etc.) leading to ground-breaking discoveries on gene functions and regulation, and their role in health and disease. Despite the enormous contribution to biomedical research, mouse models have some major limitations. Their substantial differences compared with humans in body and organ size, lifespan and inbreeding result in pronounced metabolic, physiological and behavioural differences. Comparative studies of strategically chosen domestic species can complement mouse research and yield more rigorous findings. Because genome sequence and gene manipulation tools are now available for farm animals (cattle, pigs, sheep and goats), a larger number of livestock genetically engineered (GE) models will be accessible for biomedical research. This paper discusses the use of cattle, goats, sheep and pigs in biomedical research, provides an overview of transgenic technology in farm animals and highlights some of the beneficial characteristics of large animal models of human disease compared with the mouse. In addition, status and origin of current regulation of GE biomedical models is also reviewed.

History of Mechanical Ventilation. From Vesalius to Ventilator-induced Lung Injury.

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

The ethical challenges of animal research.

In 1966, Henry K. Beecher published an article entitled "Ethics and Clinical Research" in the New England Journal of Medicine, which cited examples of ethically problematic human research. His influential paper drew attention to common moral problems such as inadequate attention to informed consent, risks, and efforts to provide ethical justification. Beecher's paper provoked significant advancements in human research policies and practices. In this paper, we use an approach modeled after Beecher's 1966 paper to show that moral problems with animal research are similar to the problems Beecher described for human research. We describe cases that illustrate ethical deficiencies in the conduct of animal research, including inattention to the issue of consent or assent, incomplete surveys of the harms caused by specific protocols, inequitable burdens on research subjects in the absence of benefits to them, and insufficient efforts to provide ethical justification. We provide a set of recommendations to begin to address these deficits.

Recruiting "Friends of Medical Progress": Evolving Tactics in the Defense of Animal Experimentation, 1910s and 1920s.

In 1923, Thomas Barbour of Harvard announced the creation of a national lay organization, the Society of Friends of Medical Progress (FMP), to defend animal research in the United States against a resurgent antivivisection movement. After decades of successful behind-the-scenes lobbying and avoiding the public spotlight, medical scientists significantly altered their tactics and sought public engagement, at least by proxy. Although the authority of scientific medicine was rising, women's suffrage, the advent of the ballot initiative, and a growing alliance of antivivisectionists and other groups in opposition to allopathic medicine so altered the political landscape that medical scientists reconsidered formerly rejected ideas such partnering with laymen. Medical scientists, Walter B. Cannon and Simon Flexner chief among them, hoped that the FMP would relieve the scientists of a time-consuming burden and defend against government regulation of medical institutions without the charge of material self-interest. However, financial problems and the frequent conflicts that arose between the lay leadership and Flexner eventually undermined the FMP's value as a defender of animal experimentation and reveal the distrust of reformers like Flexner who did not believe that laymen could speak for scientific medicine.

Animals Used in Research and Education, 1966-2016: Evolving Attitudes, Policies, and Relationships.

Since the inception of the Association of American Veterinary Medical Colleges (AAVMC), the use of animals in research and education has been a central element of the programs of member institutions. As veterinary education and research programs have evolved over the past 50 years, so too have societal views and regulatory policies. AAVMC member institutions have continually responded to these events by exchanging best practices in training their students in the framework of comparative medicine and the needs of society. Animals provide students and faculty with the tools to learn the fundamental knowledge and skills of veterinary medicine and scientific discovery. The study of animal models has contributed extensively to medicine, veterinary medicine, and basic sciences as these disciplines seek to understand life processes. Changing societal views over the past 50 years have provided active examination and continued refinement of the use of animals in veterinary medical education and research. The future use of animals to educate and train veterinarians will likely continue to evolve as technological advances are applied to experimental design and educational systems. Natural animal models of both human and animal health will undoubtedly continue to serve a significant role in the education of veterinarians and in the development of new treatments of animal and human disease. As it looks to the future, the AAVMC as an organization will need to continue to support and promote best practices in the humane care and appropriate use of animals in both education and research.

Making animals alcoholic: shifting laboratory models of addiction.

The use of animals as experimental organisms has been critical to the development of addiction research from the nineteenth century. They have been used as a means of generating reliable data regarding the processes of addiction that was not available from the study of human subjects. Their use, however, has been far from straightforward. Through focusing on the study of alcoholism, where the nonhuman animal proved a most reluctant collaborator, this paper will analyze the ways in which scientists attempted to deal with its determined sobriety and account for their consistent failure to replicate the volitional consumption of ethanol to the point of physical dependency. In doing so, we will see how the animal model not only served as a means of interrogating a complex pathology, but also came to embody competing definitions of alcoholism as a disease process, and alternative visions for the very structure and purpose of a research field.

[Animal experiments and the major achievements in the history of biomedicine].

It is shown that major achievements in the history of biomedicine, obtained in experiments on animals: the discovery of blood circulation, the achievements of microbiology and development of the concept of immunity, the discovery of reflex and the doctrine of higher nervous activity, achievements of genetics, formation of modeling methods on animals and drug testing. It is stressed that the benefits for science and medicine, obtained through experimentation on animals, does not relieve scientists from responsibility.

[The ethical aspects of physiological experiment].

A modern classification of invasive procedures developed according to International Bioethical Principles has been presented. The experimental data convincingly demonstrate that using of noninvasive approaches and techniques give a good opportunity to reduce a number of animals recruited in experiment as well as to keep the normal (not distressful) physiological functions of animals. The data presented stress that development of noninvasive techniques is closely related both to scientific and social aspects of our life, allowing the scientists to provide high validity of experimental data obtained as well as to keep themselves as a human beings.

PERSONAL RECOLLECTIONS OF DR. HANS SELYE AND OF HIS INSTITUT DE MèDECINE ET DE CHIRURGIE EXPèRIMENTALES (IMCE).

This article is a short personal recollection of Dr. Hans Selye (HS) and of his institute in order to show, first, why and how he influenced us; second, who he was as a person, human being, physician, scientist, professor, mentor; third, what was the structure and functioning of the Institut de Mèdecine et Chirurgie Expèrimentales (IMCE) and fourth, what HS' contributions and accomplishments were.

From bench to bedside: Claude Bernard, Henry K. Beecher, MD, and science in anesthesia.

Success with the medical management of pain grew tremendously after William Thomas Green Morton's successful demonstration of surgical anesthesia in 1846: Henry K. Beecher's clinical and experimental contributions to anesthesia during and after World War II had a profound impact on how clinicians and experimentalists study human populations in medicine. Beecher found that pain research required human subjects because pain was different for each individual. Nearly 100 years before Beecher, Claude Bernard similarly considered the complexity and uniqueness of human research subjects. Bernard and Beecher both preferred animal subjects in research when appropriate, but suggested that studies involving some mental, bodily, and cognitive processes required human subjects. Although Beecher and Bernard's lives did not overlap, these two men similarly confronted the issues of complexity in human and animal research, particularly in those phenomena involving higher cognitive functions.

The behavioral pharmacology of anorexigenic drugs in nonhuman primates: 30 years of progress.

Comparatively few studies over the past 30 years have used pharmacological manipulations as a means of understanding processes underlying feeding behavior of nonhuman primates. In the 1970s and early 1980s, four laboratories provided data on the anorexigenic effects of a range of drugs on rhesus monkeys and baboons, and a fifth laboratory studied the effects of neuropeptides on feeding behavior of baboons. There were differences in the way anorexigenic drugs altered eating topography, and those that increased dopamine levels had greater abuse liability than those that increased serotonin levels. Studies in the 1980s and 1990s used foraging models and principles of behavioral economics to understand food-drug interactions. Experimenter-given anorexigenic drugs did not function as economic substitutes for food. Recent studies have examined the effects of a range of drugs on consumption of highly palatable food and model diet-induced obesity. Although some drugs, including stimulants, N-methyl-D-aspartate antagonists, and a cannabinoid antagonist increased the latency to standard food consumption, there was little evidence for a selective effect of any drug on highly palatable food consumption. Results obtained in nonhuman primates did not always confirm those observed in rodents. Future studies looking at sex differences and social factors may provide insight into factors related to human obesity.