Andrew Knight

Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare.

Widespread reliance on animal models during preclinical research and toxicity testing assumes their reasonable predictivity for human outcomes. However, of 20 published systematic reviews examining human clinical utility, located during a comprehensive literature search, animal models demonstrated significant potential to contribute toward the development of clinical interventions in only two cases, one of which was contentious. Included were experiments expected by ethics committees to lead to medical advances, highly-cited experiments published in major journals, and chimpanzee experiments-the species most generally predictive of human outcomes. Seven additional reviews failed to demonstrate utility in reliably predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Results in animal models were frequently equivocal, or inconsistent with human outcomes. Consequently, animal data may not generally be considered useful for these purposes. Regulatory acceptance of non-animal models is normally conditional on formal scientific validation. In contrast, animal models are simply assumed to be predictive of human outcomes. These results demonstrate the invalidity of such assumptions. The poor human clinical and toxicological utility of animal models, combined with their generally substantial animal welfare and economic costs, necessitate considerably greater rigor within animal studies, and justify a ban on the use of animal models lacking scientific data clearly establishing their human predictivity or utility.

The Future of Teratology Research is In Vitro

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite of, rather than because of, animal-based methods. Despite strict validation criteria that animal-based teratology studies would fail to meet, three in vitro alternatives have done so. The embryonic stem-cell test (EST) is the best of these. We argue that the poor performance of animal-based teratology alone warrants its cessation; it ought to be replaced by the easier, cheaper and more repeatable EST, and resources made available to improve this and other tests even further.

The costs and benefits of animal experiments

List of Tables List of Figures List of Abbreviations Acknowledgements Series Preface Introduction PART I ANIMAL COSTS Global Laboratory Animal Use Types of Laboratory Animal Use mpacts on Laboratory Animals PART II HUMAN BENEFITS Human Clinical Utility of Animal Models Human Toxicological Utility of Animal Models Factors Limiting the Human Utility of Animal Models PART III ALTERNATIVE STRATEGIS Non-Animal Research and Testing Methodologies Reduction and Refinement of Laboratory Animal Use PART IV EDUCATIONAL ANIMAL USE AND STUDENT IMPACTS Educational Animal Use Effects of Harmful Animal Use on Students PART V CONCLUSIONS AND POLICY RECOMMENDATIONS The Costs and Benefits of Animal Experimentation 13 Regulatory Developments and Policy Recommendations Contents Glossary References Index

The beginning of the end for chimpanzee experiments

The advanced sensory, psychological and social abilities of chimpanzees confer upon them a profound ability to suffer when born into unnatural captive environments, or captured from the wild – as many older research chimpanzees once were – and when subsequently subjected to confinement, social disruption, and involuntary participation in potentially harmful biomedical research. Justifications for such research depend primarily on the important contributions advocates claim it has made toward medical advancements. However, a recent large-scale systematic review indicates that invasive chimpanzee experiments rarely provide benefits in excess of their profound animal welfare, bioethical and financial costs. The approval of large numbers of these experiments – particularly within the US – therefore indicates a failure of the ethics committee system. By 2008, legislative or policy bans or restrictions on invasive great ape experimentation existed in seven European countries, Japan, Australia and New Zealand. In continuing to conduct such experiments on chimpanzees and other great apes, the US was almost completely isolated internationally. In 2007, however, the US National Institutes of Health National Center for Research Resources implemented a permanent funding moratorium on chimpanzee breeding, which is expected to result in a major decline in laboratory chimpanzee numbers over the next 30 years, as most are retired or die. Additionally, in 2008, The Great Ape Protection Act was introduced to Congress. The bill proposed to end invasive research and testing on an estimated 1,200 chimpanzees confined within US laboratories, and, for approximately 600 federally-owned, to ensure their permanent retirement to sanctuaries. These events have created an unprecedented opportunity for US legislators, researchers, and others, to consider a global ban on invasive chimpanzee research. Such a ban would not only uphold the best interests of chimpanzees, and other research fields presently deprived of funding, but would also increase the compliance of US animal researchers with internationally-accepted animal welfare and bioethical standards. It could even result in the first global moratorium on invasive research, for any non-human species, unless conducted in the best interests of the individual or species.

The Poor Contribution of Chimpanzee Experiments to Biomedical Progress

Biomedical research on captive chimpanzees incurs substantial nonhuman animal welfare, ethical, and financial costs that advocates claim resultin substantial advancements in biomedical knowledge. However, demonstrating minimal contribution toward the advancement of biomedical knowledge generally, subsequent papers did not cite 49.5% (47/95), of 95 experiments randomly selected from a population of 749 published worldwide between 1995 and 2004. Only 14.7% (14/95) were cited by 27 papers that abstracts indicated described well-developed methods for combating human diseases. However, detailed examination of these medical papers revealed that in vitrostudies, human clinical and epidemiological studies, molecular assays and methods, and genomic studies contributed most to their development. No chimpanzee study made an essential contribution, or, in most cases, a significant contribution of any kind, to the development of the medical method described. The approval of these experiments indicates a failure of the ethics committee system. The demonstrable lack of benefit of most chimpanzee experimentation and its profound animal welfare and bioethical costs indicate that a ban is warranted in those remaining countries—notably the United States—that continue to conduct it.

Use of Schwartz Centre Rounds in a UK hospice: Findings from a longitudinal evaluation

Abstract Schwartz Centre Rounds® aim to explore the human and emotional impact of everyday work by giving healthcare staff the opportunity to come together in a safe but open environment. We evaluated the experience of introducing Schwartz Centre Rounds in a UK hospice over 1-year using a mixed method approach. These rounds were reported as providing staff with a greater appreciation of the interprofessional approach. Individuals were more actively acknowledged by other colleagues as a result of contributions at rounds with an appreciation of a wider team, spanning the whole organisation. This appeared to relieve feelings of isolation and enhance a sense of shared purpose. Some staff chose not to attend but valued their contribution to the organisation without witnessing the emotional impact of hospice work. Our findings indicate that Schwartz Rounds offer staff the environment to explore the human element of their work and appear to improve interprofessional working.

Conscientious Objection to Harmful Animal Use within Veterinary and Other Biomedical Education.

Simple Summary Classes in which animals are harmed are controversial within veterinary and other life and health sciences courses. Increasingly, students object to the harmful use of animals, and request humane teaching alternatives. Such cases can raise important animal welfare, legal and administrative concerns for universities. Several have implemented formal policies to guide their responses, maximising the likelihood of optimal and consistent outcomes. This paper reviews the development of these conscientious objection policies within Australian veterinary schools, and examines their underlying legal foundations. It concludes with recommendations for other universities considering how to respond to such cases. Abstract Laboratory classes in which animals are seriously harmed or killed, or which use cadavers or body parts from ethically debatable sources, are controversial within veterinary and other biomedical curricula. Along with the development of more humane teaching methods, this has increasingly led to objections to participation in harmful animal use. Such cases raise a host of issues of importance to universities, including those pertaining to curricular design and course accreditation, and compliance with applicable animal welfare and antidiscrimination legislation. Accordingly, after detailed investigation, some universities have implemented formal policies to guide faculty responses to such cases, and to ensure that decisions are consistent and defensible from legal and other policy perspectives. However, many other institutions have not yet done so, instead dealing with such cases on an ad hoc basis as they arise. Among other undesirable outcomes this can lead to insufficient student and faculty preparation, suboptimal and inconsistent responses, and greater likelihood of legal challenge. Accordingly, this paper provides pertinent information about the evolution of conscientious objection policies within Australian veterinary schools, and about the jurisprudential bases for conscientious objection within Australia and the USA. It concludes with recommendations for the development and implementation of policy within this arena.

Which drugs cause cancer? For.

# Which drugs cause cancer? {#article-title-2} Animal tests yield misleading results FOR Despite President Nixons War on Cancer, launched in 1971, and billions of dollars spent since then, cancer remains the second-leading killer of Americans. Around 40% of us will get cancer, and half of us will die from it.1 This cease-less tide of human suffering starkly questions the effectiveness of our strategies, including the accuracy of our methods for identifying human carcinogens. Millions of laboratory animals have been sacrificed for this purpose. Thousands of chemicals, including ever-increasing numbers of therapeutic drugs, are consequently described as potentially carcinogenic. Yet, are animal experiments really predictive of human carcinogenicity? The agency most responsible for protecting Americans from environmental contaminants is the Environmental Protection Agency (EPA), and the chemicals of greatest public health concern are described within its Integrated Risk Information System (IRIS) toxic chemicals database. We recently surveyed this database to assess the human utility of animal carcinogenicity data. Most chemicals lack human exposure data and possess only animal carcinogenicity data. In the majority of cases, however—58.1% (93/160)—we found that the EPA considered the animal data inadequate to support the useful human carcinogenicity classifications of probable carcinogen or non-carcinogen.2 But at least the animal data were predictive for 42% of chemicals. Or were they? A comparison of EPA carcinogenicity classifications with those assigned by the World Health Organizations International Agency for Research on Cancer (IARC) yielded disturbing results. For the 128 chemicals with human or animal data assessed by both agencies, human carcinogenicity classifications were similar only for those 17 possessing significant human data. For the 111 primarily reliant on animal data, the EPA was far likelier than the IARC to assign carcinogenicity classifications indicative of greater human risk.2 The IARC is widely recognized as the worlds leading authority on carcinogenicity assessments. Such profound differences … Correspondence to:

Orca Behavior and Subsequent Aggression Associated with Oceanarium Confinement

Simple Summary Orca behaviors interacting with humans within apparent friendship bonds are reviewed, and some impediments to the human evaluation of delphinid intelligence are discussed. The subsequent involvement of these orcas and their offspring in aggressive incidents with humans is also documented and examined. This is particularly relevant given that the highest recorded rates of aggressive incidents have occurred among orcas who had previously established unstructured human friendship bonds prior to their inclusion within oceanaria performances. It is concluded that the confinement of orcas within aquaria, and their use in entertainment programs, is morally indefensible, given their high intelligence, complex behaviors, and the apparent adverse effects on orcas of such confinement and use. Abstract Based on neuroanatomical indices such as brain size and encephalization quotient, orcas are among the most intelligent animals on Earth. They display a range of complex behaviors indicative of social intelligence, but these are difficult to study in the open ocean where protective laws may apply, or in captivity, where access is constrained for commercial and safety reasons. From 1979 to 1980, however, we were able to interact with juvenile orcas in an unstructured way at San Diego’s SeaWorld facility. We observed in the animals what appeared to be pranks, tests of trust, limited use of tactical deception, emotional self-control, and empathetic behaviors. Our observations were consistent with those of a former Seaworld trainer, and provide important insights into orca cognition, communication, and social intelligence. However, after being trained as performers within Seaworld’s commercial entertainment program, a number of orcas began to exhibit aggressive behaviors. The orcas who previously established apparent friendships with humans were most affected, although significant aggression also occurred in some of their descendants, and among the orcas they lived with. Such oceanaria confinement and commercial use can no longer be considered ethically defensible, given the current understanding of orcas’ advanced cognitive, social, and communicative capacities, and of their behavioral needs.

Vegetarian versus Meat-Based Diets for Companion Animals.

Simple Summary Many owners of companion animals are interested in vegetarian diets for their animals, as concerns increase about the consequences of animal farming, for health, animal welfare, and the environment. However, are vegetarian diets for cats and dogs nutritionally balanced and healthy? This article comprehensively reviews the evidence published to date from four studies that have examined the nutritional adequacy of vegetarian diets for cats and dogs. To obtain additional information, we surveyed 12 pet food companies detailed in the most recent study. We also examined the nutritional soundness of meat-based companion-animal diets, and reviewed the evidence concerning the health status of vegetarian, carnivorous and omnivorous companion animals. Both cats and dogs may thrive on vegetarian diets, but these must be nutritionally complete and reasonably balanced. Owners should also regularly monitor urinary acidity, and should correct urinary alkalinisation through appropriate dietary additives, if necessary. Abstract Companion animal owners are increasingly concerned about the links between degenerative health conditions, farm animal welfare problems, environmental degradation, fertilizers and herbicides, climate change, and causative factors; such as animal farming and the consumption of animal products. Accordingly, many owners are increasingly interested in vegetarian diets for themselves and their companion animals. However, are vegetarian canine and feline diets nutritious and safe? Four studies assessing the nutritional soundness of these diets were reviewed, and manufacturer responses to the most recent studies are provided. Additional reviewed studies examined the nutritional soundness of commercial meat-based diets and the health status of cats and dogs maintained on vegetarian and meat-based diets. Problems with all of these dietary choices have been documented, including nutritional inadequacies and health problems. However, a significant and growing body of population studies and case reports have indicated that cats and dogs maintained on vegetarian diets may be healthy—including those exercising at the highest levels—and, indeed, may experience a range of health benefits. Such diets must be nutritionally complete and reasonably balanced, however, and owners should regularly monitor urinary acidity and should correct urinary alkalinisation through appropriate dietary additives, if necessary.