Ethical Considerations for Common Mouse Models of Cancer (Preprint)

BACKGROUND Animal Ethics Committees (AECs) are concerning possibilities for public participation in the regulation of animal research. AECs are accountable for approving and monitoring research within Accredited Animal Research Establishments (AARE) (https://www.animalethics.org.au/animal-ethics-committees). In the way of making mouse models of cancer, several new considerations should be mentioned before the study design. OBJECTIVE To consider both personnel and animal welfare decisions at each stage of making mouse models of cancer, it is essential to have comprehensive information on the animal models. METHODS Three main cancer models are including; chemically induced mouse models, genetically engineered mouse models (GEMMs), xenograft nude mice, and Avatar. Some genetic changes in GEMMs are passing through next generations and not only do they have pain and suffering but also, they impose some environmental changes on mice. RESULTS Several phenotypes are required regarding the target of tumor model that expressed research are typically wisely investigated, but those that have an influence on the animal's welfare but have little or no effect on the disease procedure are often less carefully considered. CONCLUSIONS Complete analysis and regulations of animal welfare can offer beneficial information for researchers. This information is similarly essential to allow members of the institutional animal care and use committee to make necessary cost: benefit ethical review of animal studies. CLINICALTRIAL Not Applicable

Animal researchers shoulder a psychological burden that animal ethics committees ought to address

Animal ethics committees (AECs) typically focus on the welfare of animals used in experiments, neglecting the potential welfare impact of that animal use on the animal laboratory personnel. Some of this work, particularly the killing of animals, can impose significant psychological burdens that can diminish the well-being of laboratory animal personnel, as well as their capacity to care for animals. We propose that AECs, which regulate animal research in part on the basis of reducing harm, can and ought to require that these harms to researchers are reduced as well. The paper starts by presenting evidence of these burdens and their harm, giving some examples showing how they may be mitigated. We then argue that AECs are well placed to account for these harms to personnel and ought to use their power to reduce their occurrence. We conclude by responding to four potential objections: (1) that this problem should be addressed through health and safety administration, not research ethics administration; (2) that the proposal is unjustifiably paternalistic; (3) that these harms to laboratory animal personnel ought to occur, given their treatment of animals; and (4) that mitigating them may lead to worse treatment of research animals.

Reviewing the Review: A Pilot Study of the Ethical Review Process of Animal Research in Sweden

The use of animals in research entails a range of societal and ethical issues, and there is widespread consensus that animals are to be kept safe from unnecessary suffering. Therefore, harm done to animals in the name of research has to be carefully regulated and undergo ethical review for approval. Since 2013, this has been enforced within the European Union through Directive 2010/63/EU on the protection of animals used for scientific purposes. However, critics argue that the directive and its implementation by member states do not properly consider all aspects of animal welfare, which risks causing unnecessary animal suffering and decreased public trust in the system. In this pilot study, the ethical review process in Sweden was investigated to determine whether or not the system is in fact flawed, and if so, what may be the underlying cause of this. Through in-depth analysis of 18 applications and decisions of ethical reviews, we found that there are recurring problems within the ethical review process in Sweden. Discrepancies between demands set by legislation and the structure of the application form lead to submitted information being incomplete by design. In turn, this prevents the Animal Ethics Committees from being able to fulfill their task of performing a harm–benefit analysis and ensuring Replacement, Reduction, and Refinement (the 3Rs). Results further showed that a significant number of applications failed to meet legal requirements regarding content. Similarly, no Animal Ethics Committee decision contained any account of evaluation of the 3Rs and a majority failed to include harm–benefit analysis as required by law. Hence, the welfare may be at risk, as well as the fulfilling of the legal requirement of only approving “necessary suffering”. We argue that the results show an unacceptably low level of compliance in the investigated applications with the legal requirement of performing both a harm–benefit analysis and applying the 3Rs within the decision-making process, and that by implication, public insight through transparency is not achieved in these cases. In order to improve the ethical review, the process needs to be restructured, and the legal demands put on both the applicants and the Animal Ethics Committees as such need to be made clear. We further propose a number of improvements, including a revision of the application form. We also encourage future research to further investigate and address issues unearthed by this pilot study.

A less invasive system for the direct measurement of ventilation in fish

Most previous systems for quantifying ventilatory flow in fish involve prior anesthesia and difficult surgery to sew or glue membranes to the animal, which are undoubtedly stressful. By modification of the original “van Dam box” design and incorporation of an electromagnetic blood flow probe, we have developed a less invasive system that avoids these problems and provides breath-to-breath measurements of ventilatory flow in real time. The fish can be quickly moved in and out of the apparatus, facilitating repeated measurements on the same animal after different treatments. We have used the system to document the hyperventilatory and hypoventilatory responses to environmental hypoxia and hyperoxia, respectively, in both ∼400-g trout (Oncorhynchus mykiss) and 10-g goldfish (Carassius auratus); the method is easily adaptable to fish of other sizes. Separate experiments on trout have demonstrated that responses to these treatments in buccal pressure amplitude, breathing frequency, and ventilation index are not altered by the attachments used in the apparatus. This less invasive methodology may prove more acceptable to animal ethics committees.

Moving Beyond the Absence of Pain and Distress: Focusing on Positive Animal Welfare

For many years, researchers, veterinarians, animal ethics committees, and regulators have focused on minimizing pain and distress as a primary goal of refinement when working with animals in science. More recent publications as well as a shift in animal ethics and public opinion have emphasized promotion of positive affective states, culminating in the concept of positive animal welfare. Robust measures are required to know when positive animal welfare states are occurring, and a number of measures are proposed and discussed. Regardless of whether there are newer methods available that focus exclusively on measuring positive affective states, consistent consideration of research animal behavioral programs, refinement, and adopting periodic stand-alone animal welfare assessments for all species involved will help to push the care and practices of research animals towards an increased focus on positive animal welfare.

Mapping French Laypeople’s Views on Nonhuman Animal Experimentation

French positions regarding nonhuman animal experimentation were examined. A total of 163 participants were presented with 72 vignettes depicting an experimental protocol. They were composed according to a five-factor design: (a) the fate of the animal (e.g., was sacrificed for the purpose of further analyses), (b) environment in which the animal was raised, (c) main objective of the experiment (purely theoretical vs. therapeutic), (d) degree of pain inflicted, and (e) species involved (rabbit, coyote, or chimpanzee). Through cluster analysis of participants’ acceptability judgments, six qualitatively different positions were found. Four had already been described by observation of the functioning of animal ethics committees: Animals have Rights, Ethics in the name of Animals, Ethics in the name of Patients, and Ethics in the name of Science. Female participants held the Animals-have-Rights position three times more often than males. Male participants held an Ethics-in-the-name-of-Science position four times more often than females.

Emotions and Ethical Decision-Making in Animal Ethics Committees

Ethical evaluation of projects involving animal testing is mandatory within the EU and other countries. However, the evaluation process has been subject to criticism, e.g., that the committees are not balanced or democratic enough and that the utilitarian weighting of harm and benefit that is normally prescribed is difficult to carry out in practice. In this study, members of Swedish Animal Ethics Committees (AECs) completed a survey aiming to further investigate the decision-making process. We found that researchers and animal laypersons make significantly different ethical judgments, and hold disparate views on which ethical aspects are the most relevant. Researchers were significantly more content than laypersons with the functioning of the committees, indicating that the ethical model used suited their preferences better. We argue that in order to secure a democratic and proper ethical evaluation, the expectations of a scientific discourse must be acknowledged, while giving room for different viewpoints. Further, to fulfil the purpose of the project evaluations and meet public concern, the functions of the different AEC member categories need to be clarified. We suggest that one way of achieving a more thorough, balanced and inclusive ethical evaluation is to allow for more than one model of ethical reasoning.

There is more to the 3Rs than Replacement: Reduction and Refinement in animal experimentation

According to Wikipedia, the earliest references to animal experimentation appear in Greek writings of the 2nd and 4th Century BC1. Needless to say, we have come a long way in the intervening years. Animal experimentation is now regulated by law in many countries. ‘Animal ethics committees’, typically made up of lay people, scientists and vets, are required to undertake a cost–benefit analysis for proposed projects, weighing up the likely benefit to society against any harm and suffering animals may experience. Furthermore, the ethical framework first described by William Russell and Rex Burch in their seminal 1959 publication2 – the so-called 3Rs: the use of non-animal methods to achieve the same scientific goals (replacement), or where this is not possible, that researchers use methods which cause the minimum pain and suffering (refinement) while also obtaining the best information possible from the fewest number of animals (reduction) – is now also a legal requirement in many countries. Thanks in part to initiatives such as the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), recent years have seen a massive increase in the number of techniques developed which aim to replace the use of animals in research, teaching and testing, an achievement which should be celebrated.