How M A Many Animals Surrvive Animal Testing

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Ethical and Scientific Considerations Regarding Fauna Testing and Research

• Nancy Brook

Ethical and Scientific Considerations Regarding Brute Testing and Enquiry

• Hope R. Ferdowsian,
• Nancy Brook

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• Published: September vii, 2011
• https://doi.org/10.1371/journal.pone.0024059

Citation: Ferdowsian 60 minutes, Beck N (2011) Ethical and Scientific Considerations Regarding Beast Testing and Research. PLoS ONE 6(9): e24059. https://doi.org/10.1371/journal.pone.0024059

Editor: Catriona J. MacCallum, Public Library of Scientific discipline, United kingdom

Published: September 7, 2011

Copyright: © 2011 Ferdowsian, Brook. This is an open-access article distributed under the terms of the Artistic Commons Attribution License, which permits unrestricted utilise, distribution, and reproduction in any medium, provided the original writer and source are credited.

Funding: The authors are grateful to the National Science Foundation (grant SES-0957163) and the Arcus Foundation (grant 0902-34) for the financial support for the corresponding conference, Animals, Research, and Alternatives: Measuring Progress 50 Years Afterwards. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: HRF and NB are employed past Physicians Committee for Responsible Medicine, which is a non-governmental organization which promotes higher ethical standards in enquiry and alternatives to the use of animals in research, education, and grooming. Physicians Committee for Responsible Medicine is a nonprofit system, and the authors adhered to PLoS Ane policies on sharing data and materials.

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of beast utilize, principles which have since been referred to every bit the "3 Rs". These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the hurting and distress to which animals are exposed, and replace the employ of animals with non-animal alternatives when possible. Despite the attention brought to this outcome by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the "3 Rs" capture crucially important concepts, they practice not adequately reflect the substantial developments in our new knowledge near the cerebral and emotional capabilities of animals, the private interests of animals, or an updated understanding of potential harms associated with animal inquiry. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress l Years Later on, which aims to spur upstanding and scientific advancement.

Introduction

One of the most influential attempts to examine and affect the use of animals in research can be traced back to1959, with the publication of The Principles of Humane Experimental Technique [1]. William Russell and King Burch published this seminal book in response to marked growth in medical and veterinary enquiry and the concomitant increase in the numbers of animals used. Russell and Burch'southward text emphasized reduction, refinement, and replacement of brute use, principles which have since been referred to equally the "3 Rs". These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and supervene upon the use of animals with non-animal alternatives when possible.

Despite the attending brought to this issue by Russell and Burch, the number of animals used in research and testing has continued to increase. Contempo estimates suggest that at least 100 million animals are used each year worldwide [2]. However, this is likely an underestimate, and it is impossible to accurately quantify the number of animals used in or for experimentation. Full reporting of all animal use is non required or made public in most countries. Nevertheless, based on available information, information technology is clear that the number of animals used in research has not significantly declined over the by several decades.

The "3 Rs" serve as the cornerstone for current creature research guidelines, but questions remain well-nigh the adequacy of existing guidelines and whether researchers, review boards, and funders accept fully and fairly implemented the "3 Rs". Further, while the "3 Rs" capture crucially important concepts, they practice not adequately reverberate the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals; an updated understanding of the harms inherent in animate being research; and the changing cultural perspectives about the place of animals in lodge [3], [4]. In addition, serious questions have been raised about the effectiveness of animate being testing and inquiry in predicting anticipated outcomes [five]–[thirteen].

In August 2010, the Georgetown University Kennedy Institute of Ideals, the Johns Hopkins University Center for Alternatives to Animal Testing, the Found for In Vitro Sciences, The George Washington Academy, and the Physicians Committee for Responsible Medicine jointly held a two solar day multi-disciplinary, international briefing in Washington, DC, to address the scientific, legal, and political opportunities and challenges to implementing alternatives to brute research. This two-twenty-four hour period symposium aimed to advance the study of the upstanding and scientific issues surrounding the use of animals in testing and research, with particular emphasis on the adequacy of electric current protections and the promise and challenges of developing alternatives to the use of animals in basic research, pharmaceutical enquiry and development, and regulatory toxicology. Speakers who contributed to the conference reviewed and contributed new knowledge regarding the cerebral and affective capabilities of animals, revealed through ethology, cerebral psychology, neuroscience, and related disciplines. Speakers also explored the dimensions of impairment associated with animal inquiry, touching on the upstanding implications regarding the use of animals in research. Finally, several contributors presented the latest scientific advances in developing alternatives to the employ of animals in pharmaceutical research and evolution and regulatory toxicity testing.

This Collection combines some papers that were written post-obit this conference with an aim to highlight relevant progress and research. This Overview provides a cursory summary of the ethical and scientific considerations regarding the apply of animals in research and testing, some of which are highlighted in the accompanying Collection.

Analysis and Discussion

Ethical Considerations and Advances in the Understanding of Animal Cognition

Anticipation around burgeoning medical inquiry in the late 1800s and the starting time half of the 20^th century sparked concerns over the employ of humans and animals in enquiry [fourteen], [15]. Suspicions around the use of humans were deepened with the revelation of several exploitive enquiry projects, including a series of medical experiments on large numbers of prisoners by the Nazi German authorities during Globe State of war Ii and the Tuskegee syphilis report. These abuses served as the impetus for the establishment of the Nuremberg Code, Declaration of Helsinki, and the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974) and the resulting Belmont Report [16]–[18]. Today, these guidelines provide a platform for the protection of human research subjects, including the principles of respect, beneficence, and justice, as well as special protections for vulnerable populations.

Laws to protect animals in inquiry have also been established. The British Parliament passed the first set of protections for animals in 1876, with the Cruelty to Animals Act [xix]. Approximately ninety years after, the U.South. adopted regulations for animals used in research, with the passage of the Laboratory Beast Welfare Act of 1966 [20]. Subsequent national and international laws and guidelines take provided basic protections, but at that place are some significant inconsistencies amongst electric current regulations [21]. For instance, the U.S. Animal Welfare Human action excludes purpose-bred birds, rats, or mice, which incorporate more than than 90% of animals used in inquiry [twenty]. In contrast, certain dogs and cats accept received special attention and protections. Whereas the U.Southward. Animate being Welfare Act excludes birds, rats and mice, the U.Southward. guidelines overseeing research conducted with federal funding includes protections for all vertebrates [22], [23]. The lack of consistency is farther illustrated by the "U.Due south. Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research and Training" which stress compliance with the U.Southward. Animal Welfare Deed and "other applicative Federal laws, guidelines, and policies" [24].

While strides take been made in the protection of both human and animal inquiry subjects, the nature of these protections is markedly different. Human research protections emphasize specific principles aimed at protecting the interests of individuals and populations, sometimes to the detriment of the scientific question. This differs significantly from animal inquiry guidelines, where the importance of the scientific question being researched unremarkably takes precedence over the interests of private animals. Although scientists and ethicists have published numerous manufactures relevant to the ethics of animal research, current animal research guidelines practice not articulate the rationale for the key differences between human and fauna inquiry guidelines. Currently, the majority of guidelines operate on the presumption that creature research should proceed based on wide, perceived benefits to humans. These guidelines are generally permissive of creature research independent of the costs to the individual animal as long as benefits seem achievable.

The concept of costs to individual animals can be further examined through the growing body of research on creature emotion and noesis. Studies published in the terminal few decades take dramatically increased our understanding of creature sentience, suggesting that animals' potential for experiencing impairment is greater than has been appreciated and that current protections demand to exist reconsidered. Information technology is now widely acknowledged by scientists and ethicists that animals can feel pain and distress [25]–[29]. Potential causes of harm include invasive procedures, disease, and deprivation of basic physiological needs. Other sources of harm for many animals include social deprivation and loss of the ability to fulfill natural behaviors, among other factors. Numerous studies have demonstrated that, fifty-fifty in response to gentle treatment, animals tin show marked changes in physiological and hormonal markers of stress [30].

Although pain and suffering are subjective experiences, studies from multiple disciplines provide objective evidence of animals' abilities to feel pain. Animals demonstrate coordinated responses to hurting and many emotional states that are similar to those exhibited past humans [25], [26]. Animals share genetic, neuroanatomical, and physiological similarities with humans, and many animals express pain in ways similar to humans. Animals also share similarities with humans in genetic, developmental, and environmental risk factors for psychopathology [25], [26]. For example, fear operates in a less organized subcortical neural circuit than pain, and it has been described in a wide multifariousness of species [31]. More complex markers of psychological distress take also been described in animals. Varying forms of low have been repeatedly reported in animals, including nonhuman primates, dogs, pigs, cats, birds and rodents, amid others [32]–[34]. Anxiety disorders, such as mail service-traumatic stress disorder, have been described in animals including chimpanzees and elephants [35], [36], [37].

In improver to the capacity to experience physical and psychological hurting or distress, animals also display many linguistic communication-similar abilities, complex problem-solving skills, tool related cognition and pleasure-seeking, with empathy and self-awareness as well suggested by some enquiry. [38]–[44]. Play behavior, an indicator of pleasure, is widespread in mammals, and has as well been described in birds [45], [46]. Behavior suggestive of play has been observed in other taxa, including reptiles, fishes and cephalopods [43]. Self-awareness, assessed through mirror self-recognition, has been reported for chimpanzees and other groovy apes, magpies, and some cetaceans. More recent studies have shown that crows are capable of creating and using tools that require access to episodic-like retention germination and retrieval [47]. These findings suggest that crows and related species brandish testify of causal reasoning, flexible learning strategies, imagination and prospection, similar to findings in great apes. These findings also challenge our assumptions well-nigh species similarities and differences and their relevance in solving ethical dilemmas regarding the use of animals in research.

Predictive Value of Beast Data and the Bear on of Technical Innovations on Beast Use

In the concluding decade, concerns have mounted well-nigh how relevant animal experiments are to human health outcomes. Several papers have examined the concordance between animal and human data, demonstrating that findings in animals were not reliably replicated in human clinical enquiry [5]–[13]. Recent systematic reviews of treatments for various clinical atmospheric condition demonstrated that brute studies have been poorly predictive of human outcomes in the fields of neurology and vascular affliction, amongst others [7], [48]. These reviews have raised questions about whether human diseases inflicted upon animals sufficiently mimic the disease processes and treatment responses seen in humans.

The value of beast use for predicting man outcomes has also been questioned in the regulatory toxicology field, which relies on a codified set of highly standardized animal experiments for assessing diverse types of toxicity. Despite serious shortcomings for many of these assays, most of which are l to 60 years old, the field has been wearisome to prefer newer methods. The yr 2007 marked a turning indicate in the toxicology field, with publication of a landmark report by the U.S. National Research Quango (NRC), highlighting the demand to comprehend in vitro and computational methods in order to obtain data that more accurately predicts toxic effects in humans. The report, "Toxicity Testing in the 21^st Century: A Vision and a Strategy," was deputed past the U.S. Environmental Protection Bureau, partially due to the recognition of weaknesses in existing approaches to toxicity testing [49]. The NRC vision calls for a shift away from creature utilise in chemical testing toward computational models and high-throughput and high-content in vitro methods. The study emphasized that these methods tin provide more predictive data, more than quickly and affordably than traditional in vivo methods. Subsequently published manufactures accost the implementation of this vision for improving the current system of chemical testing and assessment [50], [51].

While a sea change is underway in regulatory toxicology, in that location has been much less dialogue surrounding the replacement of animals in enquiry, despite the fact that far more animals are used in basic and applied research than in regulatory toxicology. The use of animals in research is inherently more than difficult to approach systematically considering research questions are much more diverse and less proscribed than in regulatory toxicology [52]. Because researchers often use very specialized assays and systems to address their hypotheses, replacement of animals in this area is a more than individualized endeavour. Researchers and oversight boards have to evaluate the relevance of the research question and whether the tools of modern molecular and cell biological science, genetics, biochemistry, and computational biological science can be used in lieu of animals. While none of these tools on their own are capable of replicating a whole organism, they do provide a mechanistic agreement of molecular events. It is important for researchers and reviewers to assess differences in the clinical presentation and manifestation of diseases among species, as well as anatomical, physiological, and genetic differences that could touch on the transferability of findings. Another relevant consideration is how well animal information can mirror relevant epigenetic effects and human genetic variability.

Examples of existing and promising non-animate being methods have been reviewed recently by Langley and colleagues, who highlighted advances in fields including orthodontics, neurology, immunology, infectious diseases, pulmonology, endocrine and metabolism, cardiology, and obstetrics [52].

Many researchers have too begun to rely solely on man data and cell and tissue assays to accost large areas of therapeutic research and development. In the area of vaccine testing and evolution, a surrogate in-vitro human being immune system has been developed to help predict an individual'due south immune response to a particular drug or vaccine [53], [54]. This system includes a blood-donor base of operations of hundreds of individuals from diverse populations and offers many benefits, including predictive high-throughput in vitro immunology to assess novel drug and vaccine candidates, measurement of allowed responses in various homo populations, faster cycle time for discovery, better pick of drug candidates for clinical evaluation, and reductions in the fourth dimension and costs to bring drugs and vaccines to the market. In the case of vaccines, this system tin be used at every stage, including in vitro disease models, antigen selection and adjuvant effects, safety testing, clinical trials, manufacturing, and authorization assays. When compared with information from animal experiments, this arrangement has produced more accurate pre-clinical data.

The examples above illustrate how innovative applications of technology tin generate data more meaningful to humans, and reduce or supplant animal use, but advances in medicine may as well require novel approaches to setting research priorities. The Dr. Susan Beloved Research Foundation, which focuses on eradicating breast cancer, has challenged research scientists to move from beast enquiry to breast cancer prevention research involving women. If researchers could better understand the factors that increment the risk for breast cancer, besides equally methods for effective prevention, fewer women would crave treatment for breast cancer. Whereas animal research is largely investigator-initiated, this model tries to address the questions that are central to the care of women at hazard for or afflicted by breast cancer. This arroyo has facilitated the recruitment of women for studies including a national projection funded by the National Institutes of Wellness and the National Institute of Ecology Health to examine how environment and genes affect breast cancer risk. This study, which began in 2002, could not have been achieved with animal research [55].

Similarly, any arroyo that emphasizes testify-based prevention would provide benefits to both animals and humans. Resources limitations might require a strategic arroyo that emphasizes diseases with the greatest public health threats, which increasingly fall within the scope of preventable diseases.

Determination

It is articulate that at that place have been many scientific and ethical advances since the first publication of Russell and Burch's book. Even so, some in the scientific community are beginning to question how well data from animals translates into germane knowledge and treatment of homo conditions. Efforts to objectively evaluate the value of animal research for understanding and treating human affliction are particularly relevant in the mod era, considering the availability of increasingly sophisticated technologies to address research questions [9]. Ethical objections to the employ of animals accept been publically voiced for more than than a century, well earlier there was a business firm scientific understanding of animate being emotion and cognition [15]. Now, a amend understanding of animals' capacity for pain and suffering is prompting many to take a closer await at the homo utilize of animals [56].

Manufactures in the accompanying Collection simply briefly affect the many scientific and ethical issues surrounding the use of animals in testing and research. While it is important to admit limitations to not-animate being methods remain, recent developments demonstrate that these limitations should be viewed as rousing challenges rather than insurmountable obstacles. Although give-and-take of these problems can be difficult, progress is most probable to occur through an ethically consequent, prove-based approach. This drove aims to spur further steps frontwards toward a more coherent ethical framework for scientific advancement.

Acknowledgments

The authors thank the conference speakers and participants for their participation.

Writer Contributions

Conceived and designed the experiments: HRF NB. Contributed reagents/materials/analysis tools: HRF NB. Wrote the paper: HRF NB.

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