Gonadal sex and animal experimentation: Perfection vs. 3R principle?

Replicability of experimental results and optimal use of experimental animals are everybody's concern. Current efforts towards increased replicability include guidelines and checklists as tools for experimenters, referees, editors and publishers. Guidelines are also provided for appropriate use of animals. To ensure the quality of experimental results, the number of animals must be adequate, that is, sufficiently large, for the purpose of the given experiment. To comply with current ethical recommendations, the use of animals should be reduced as much as possible. Therefore, determination of the number of animals for a given scientific objective includes contrasting considerations. Current guidelines for animal experimentation, notably from the National Institute of Health, mandate (with very few exceptions) inclusion of animals of both sexes in experimental designs statistically powered to address the difference between the two groups. Notably, absence of evidence for sex differences between the organ or system functions under study does not qualify as an exception. Mandatory, equal representation of both sexes raises several questions including ethical ones. Other guidelines, by public regulators and major publishers, do not seem to have a similar selective focus on sex differences. In summary, current concerns about replicability of scientific results are justified. Concomitantly, the knowledge of sex differences also between non-reproductive, non-endocrine organ functions is increasing. In principle, sex matters in any experimental context. However, an indiscriminate demand for inclusion of both sexes in all experimental protocols seems a waste of animals, money and time, violating traditional principles of animal experimentation, particularly that of reduction.

Refinement techniques in non-human primate neuroscientific research.

Non-human primates (NHP) are widely considered an essential model for biomedical research because of their close genetic, anatomo-functional and cognitive similarities to humans. These same reasons also raise particular ethical concerns for the unavoidable harm caused to these animals, in particular to those involved in neuroscientific studies. Besides reducing the number of animals needed to the absolute minimum, it is therefore essential to implement procedures allowing, at the same time, to minimize the harm to the animals and maximize the quality and ecological validity of the data. Technological progresses have made possible, for example, to self-train monkeys in their home cage with positive reinforcement techniques and to adopt various types of telemetric systems for wirelessly recording neuronal activity in freely behaving animals. Example of full application of these techniques are still very limited in the literature, but different recent international projects and pioneering studies are paving the way for turning to the use of new technologies to get a more "ethically acceptable" NHP neuroscientific research.

An IQ Consortium Perspective on The Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on the Need for Nonhuman Primates in Biomedical Research, Production and Testing of Products and Devices (Update 2017).

The recent Scientific Committee on Health, Environmental and Emerging Risks Final Opinion on "The need for nonhuman primates in biomedical research, production and testing of products and devices" (2017 SCHEER) highlights approaches that could significantly contribute to the replacement, reduction, and refinement of nonhuman primate (NHP) studies. Initiatives that have the potential to affect NHP welfare and/or their use are expected to be appropriate, fair, and objective and publicly disseminated information focused on NHPs in biomedical research, which includes toxicologic and pathologic research and testing, should be objectively evaluated by stakeholder scientists, researchers, and veterinarians. Thus, IQ Consortium member companies convened to develop an informed and objective response, focusing on identifying areas of agreement, potential gaps, or missing information in 2017 SCHEER. Overall, the authors agree that many positions in the 2017 SCHEER Opinion generally align with industry views on the use of NHPs in research and testing, including the ongoing need of NHPs in many areas of research. From the perspective of the IQ Consortium, there are several topics in the 2017 SCHEER that merit additional comment, attention, or research, as well as consideration in future opinions.

Una utopía ética desmadrada: la intervención animalista positiva en la naturaleza / A runaway ethical utopia: positive animalist intervention in Nature / Una utopia ètica extralimitada: la intervenció animalista positiva en la naturalesa

Podemos reconocer la importancia de las totalidades y los sistemas (ser holistas) en lo ontológico, y mantener no obstante el individualismo moral: son las vidas de los organismos individuales las que cuentan moralmente. Especies y ecosistemas tienen sólo un valor moral derivado. Nos importan, moralmente, los centros de sintiencia y consciencia que llamamos individuos. Pero en la naturaleza son sobre todo las totalidades las que cuentan... Aunque nuestra mejor teoría moral sea individualista, sucede que, ontológicamente, los individuos cuentan poco -¡la realidad es sistémica, evolutiva y relacional! Nuestra mejor ontología no será individualista. (Se basará, más bien, en sistemas complejos adaptativos). No entender esto explica, creo, buena parte de los desencuentros entre animalismo y ecologismo. Necesitamos desarrollar ideas no fosilistas de liberación (humana y animal). La propuesta de una intervención animalista positiva generalizada en la naturaleza me parece una utopía ética desmadrada (fuera de madre, de la Madre Tierra en este caso: Gaia/Gea)

We may recognize the importance of totalities and systems (being holistic) in the ontological, and still maintain moral individualism: it is the lives of individual organisms that count morally. Species and ecosystems have only a derived moral value. We care, morally, for the centers of sentience and consciousness we call individuals. But in nature it is above all the totalities that count... Although our best moral theory may be individualistic, it happens that, ontologically, individuals count little -the reality is systemic, evolutionary and relational! Our best ontology will not be individualistic. (It will be based, rather, on complex adaptive systems). Not understanding this explains, I believe, a good part of the disagreements between animalism and environmentalism. We need to develop non-fossilistic ideas of liberation (human and animal). The proposal of a positive animalist intervention generalized in nature seems to me to be a runaway ethical utopia ("desmadrada", that is "outside of mother", of Mother Earth in this case: Gaia/Gea)

Podem reconèixer la importància de les totalitats i els sistemes (holismes) en el seu aspecte ontològic i mantenir, no obstant, l'individualisme moral: són les vides dels organismes individuals les que moralment importen. Espècies i ecosistemes tenen només un valor moral secundari. Ens importen, moralment, els centres de sintiència i consciència que anomenem individus. Però en la naturalesa són sobretot les totalitats les que interessen. Encara que la nostra millor teoria moral sigui individualista, succeeix que, ontològicament, els individus importen poc-;la realitat és sistèmica, evolutiva i relacional! La nostra millor ontologia no serà, per tant, individualista. Es basarà, més aviat, en sistemes complexos adaptatius. No entendre això explica, crec, bona part dels desacords entre l’animalisme i l’ecologisme. Necessitem desenvolupar idees no fossilitzades d'alliberament (humà i animal). La proposta d'una intervenció animalista positiva generalitzada en la naturalesa em sembla una utopia ètica extralimitada (fora de mare, de la Mare Terra en aquest cas: Gaia/Gea)

Los métodos alternativos: un reto para las administraciones y para los científicos / Alternative methods: a challenge for governments and scientists

La normativa actual que regula en el ámbito europeo la utilización de los animales con fines científicos establece con absoluta rotundidad que su prioridad absoluta es el fomento y la implantación de los enfoques alternativos a los métodos tradicionales de utilización de los animales. Insistimos sobre dos aspectos que consideramos relevantes. En primer lugar es necesario aclarar que los métodos alternativos no son solo aquellos en los que se alcanza el Reemplazo total de los animales, sino que también comprenden aquellos otros métodos y estrategias en las que se reduce el número de animales utilizados (Reducción) o se refinan las condiciones en los que éstos se utilizan y mantienen (Refinamiento). En segundo lugar quisiéramos animar a la comunidad científica a dar los pasos que sean necesarios para poder implementar también en el ámbito de las 3 erres el cambio de paradigma que los avances y el desarrollo que en el campo de la biología molecular y de sistemas están haciendo posible en toxicología. En el futuro es posible que algunas pruebas puedan consistir ya no tanto en analizar los efectos que determinadas sustancias tóxicas tienen sobre los animales, sino más bien en evaluar los cambios metabólicos que a nivel molecular son los que realmente causan los mencionados efectos sobre los animales (y lógicamente el ser humano) (AU)

Current European regulations on the use of animals for scientific purposes categorically states that the first priority is the development and implementation of alternative approaches to traditional methods using animals. We insist on two aspects that we consider relevant. First able it is necessary to clarify that alternative methods are not only those in which the total replacement of animals is reached, but also include those other methods and strategies in which the number of animals used decreases (reduction) or refine the conditions under which they are used and maintained (Refinement). Secondly, we would like to encourage the scientific community to take the steps necessary to also implement in the field of the 3Rs principle that progress and development in the field of molecular biology and systems are possible in toxicology. In the future it is possible that some studies may consist not so much as to analyze the effects that certain toxic substances have on the animals, but rather to evaluate metabolic changes at the molecular level that actually cause the effects on animals (and logically on humans) (AU)

Alternativas a los animales de laboratorio en la docencia / Alternatives to laboraroty animals in education

En este artículo se hace una revisión sobre la utilización de animales y de métodos alternativos en docencia y se constata que todavía se siguen utilizando animales, a pesar de los avances tecnológicos que permiten cada vez métodos mejores y más efectivos para reemplazar a los animales en las prácticas docentes. Así mismo se analizan las ventajas y las limitaciones que pueden presentar estos métodos y se hace una revisión bibliográfica de los últimos artículos publicados en este sentido. A pesar, de existir muchos docentes que utilizan métodos alternativos, no existen demasiados artículos que nos informen de la situación de las alternativas ni tampoco de los beneficios que aportan a los estudiantes (AU)

This paper is a review on the use of laboratory animals and alternatives methods in education. Laboratory animals are still used despite technological advances that allow better alternative methods and more effectives to replace animals in laboratory practices. Moreover, we analyze the advantages and limitations of these alternative methods and we review the literature of the last years in this field. Although, there are many teachers who use alternative methods, there are not too many papers giving information about the real situation of alternatives neither the benefits for students (AU)

The ethics of wildlife research: a nine R theory.

The commonsense ethical constraints on laboratory animal research known as the three Rs are widely accepted, but no constraints tailored to research on animals in the wild are available. In this article, we begin to fill that gap. We sketch a set of commonsense ethical constraints on ecosystem research parallel to the constraints that govern laboratory animal research. Then we combine the animal and ecosystem constraints into a single theory to govern research on animals in the wild.

Animal welfare and use of silkworm as a model animal.

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

The use of nonhuman animals in biomedical research.

Opposition to the use of animals in biomedical research rests on diverse scientific and ethical arguments. Here I offer a response to key objections and argue that the responsible use of animals in biomedical research with the goal of advancing medical knowledge, science and human health, is scientifically and morally justified. My views are unlikely to be shared uniformly across the scientific community. Thus, I hope this personal perspective persuades other scientists, public health officials, scientific organizations and our academic leadership to join the debate and invites opponents of animal research to create an atmosphere where civil discourse can take place, free of threats and intimidation. The public deserves an open and honest debate on this important topic.

Food additives: an ethical evaluation.

BACKGROUND: Food additives are an integral part of the modern food system, but opinion polls showing most Europeans have worries about them imply an urgent need for ethical analysis of their use. SOURCES OF DATA: The existing literature on food ethics, safety assessment and animal testing. AREAS OF AGREEMENT: Food additives provide certain advantages in terms of many people's lifestyles. AREAS OF CONTROVERSY: There are disagreements about the appropriate application of the precautionary principle and of the value and ethical validity of animal tests in assessing human safety. GROWING POINTS: Most consumers have a poor understanding of the relative benefits and risks of additives, but concerns over food safety and animal testing remain high. AREAS TIMELY FOR DEVELOPING RESEARCH: Examining the impacts of food additives on consumer sovereignty, consumer health and on animals used in safety testing should allow a more informed debate about their appropriate uses.

[Bioethical aspects of experiments on the animals].

The principles of humane attitude toward laboratory animals, the main rules of defense and application of vertebral animals in scientific investigations, which are coordinated with European convention content, were presented. Recommendations for organization and activities of bioethics committees and commissions, which conduct the expert estimation of scientific investigations, using laboratory animals, were presented.

Ethical implications of using the minipig in regulatory toxicology studies.

Two key questions are addressed in this article. What are the potential harms to minipigs relative to the harms for dogs and non-human primates and can these harms be reduced more easily in minipigs than in other species? Are there potential benefits resulting from the use of minipigs relative to dogs and non-human primates? In considering the answers to these questions, we present an ethical framework which was developed taking into account the viewpoint of all concerned parties. This ethical matrix provides a framework upon which to identify and explore issues raised by the moral imperative to seek a fair compromise between the differing needs of different interest groups, which includes both the moral agents and the moral patients. The moral agents are the different groups of human stakeholders including society at large, regulatory bodies, industrialists and animal care staff. The moral patients are the laboratory animals, both breeding stock held by the animal supplier, and experimental animals in laboratories. In considering these animals it cannot be assumed that dogs, monkeys and minipigs differ with regard to the pain and suffering that they may experience and undergo when treated in studies designed for safety assessment. On this basis we rejected the argument that minipigs are more acceptable experimental animals than dogs or monkeys despite the fact that their use may prove less offensive to some groups within society at large. Species selection must be made on a case-by-case basis where the benefits are assessed by weighing the scientific evidence relating to the predictivity of the animal model, against the harm that may accrue to the animals both from the test procedures and their lifetime experience within the laboratory environment.