2023-04-30 03:03:17
If the objective is to predict the result of the interaction of a drug, vaccine or food with a live experimental unit without interference, clear criteria must be ensured in favor of the individuals involved.
Diego Diaz David and Natalia Cardillo*
[email protected]
[email protected]
Much water has flowed under the bridge of animal studies.
We might go back to milestones in world history, such as the infamous dog Laika (she did not survive her journey orbiting the earth in Sputnik II) or the no less famous “Pavlov dog” (the one with sound-stimulated salivation). . What is not usually collected in the history of science books is that Pavlov did not only work with “the dog” but with several.
However, in addition to being a pioneer in the study of the nervous system and experimental psychology, he was also a pioneer in the ethical treatment of experimental animals.
At a time when there was no animal welfare law and any mistreatment was allowed, he was a pioneer in anesthetizing animals before subjecting them to any painful process and in avoiding vivisections or unnecessary pain.
In fact, he always considered his dogs an indispensable part of his team, and thanks to that we know the names of many: Mancha, Comadreja, Falcon, Gitano. Towards the end of his days, his students gave Pavlov an album with 40 photos of his dogs and in 1935 a monument to the dog was erected at his research center. As Pavlov himself said: “Let the dog, man’s helper and friend since prehistoric times, offer himself as a sacrifice to science. But our human dignity obliges us to ensure that this always happens without unnecessary pain.”
the discussion
Currently, the discussion regarding the need for animal testing is a hot topic that arouses various interpretations, including extreme positions (never! always!). Since the beginning of the 1960s we have heard regarding the 3R criteria, formulated by two English biologists, Russel and Burch, in their book “The Principle of Humane Experimental Technique”. These principles speak of replacing, reducing, and refining.
Replacement alternatives refer to methods that replace the use of animals with a non-animal model (eg computer models) or use animals with less perception of pain (eg invertebrates).
The reduction alternatives refer to the use of a rational number of animals, in order to obtain sufficient data to respond to the investigation, or else, the maximization of the information obtained per animal without compromising their welfare.
Refinement alternatives refer to procedures adopted to minimize pain and distress, as well as to improve animal welfare.
The replacement of animals by in vitro techniques or species other than the target is applicable to pre-clinical studies, especially for drugs for human use. However, in clinical studies it is essential to use animals of the same destination species (according to specialists, this will be the case for at least 50 more years), without leaving aside the reduction and refinement criteria, which implicitly include the concept to ensure animal welfare.
Animal welfare experts rely on five criteria or “freedoms” that must be ensured during trials: freedom from thirst, hunger and malnutrition; free of discomfort; free from pain, trauma and other illnesses; free to express themselves with the company of other animals of their species and enough space; free from fear and stress.
Who should ensure animal welfare in clinical trials?
It is the primary responsibility of the principal researchers and their directees (secondary researchers, monitors, field staff, etc.), who must be trained to assess conditions and behaviors associated with animal welfare. In some countries, it is even possible to access tertiary and postgraduate degrees in animal welfare and ethics.
No less important should be the concern on the part of sponsors and state control agencies.
Additionally, in the academic field and more recently in the private sphere, the role of the Institutional Committees for the Care and Use of Laboratory, Research or Experimentation Animals (CICUAL or CICUAE) was incorporated.
They are made up of a multidisciplinary team of scientists, doctors, veterinarians and civil representatives who evaluate the clinical trial proposal and must ensure the dignified and justified treatment of animals, as well as ensure that it complies with the regulations of good clinical practices and the procedure manuals or previously established protocols.
Prior approval by these Committees is considered a fundamental requirement for any type of animal testing in many countries.
Why look for animal welfare in clinical trials?
The growing knowledge regarding the behavior and physiology of animals allows us to understand what factors can alter normal parameters. However, researchers do not always consider such effects in their experimental designs, negatively impacting the reproducibility of the study, the use of the animal model, and the quality of the results.
If the objective of a clinical study is to predict the result of the interaction of a drug, vaccine or food with a living experimental unit without interference, it must be ensured that the individuals enjoy the previously described freedoms. It is easy to predict that a malnourished animal should not be enrolled in a clinical study, but less obvious conditions such as an impoverished environment (housings where animals cannot develop their full behavioral repertoire and meet their behavioral needs) are also important altering factors. animal physiology. Neuroscientist Marian Diamond, in the late 1960s, demonstrated how environments can affect an individual’s biology in experiments that were fundamental to understanding brain plasticity: rats kept in the most enriched housing conditions exhibited changes significant at the level of the cerebral cortex.
Another situation occurs in studies in which it is a sine qua non condition to restrict any of these freedoms, as occurs, for example, with studies on the efficacy of antiparasitics with artificial infestation or those that reproduce confined rearing systems. It is essential in these situations to conduct the study with the greatest responsibility, avoiding neglecting other variables and being very careful in determining and putting into practice the ethical and humanitarian exclusion criteria (withdrawal of an animal from the study).
Regulatory framework
The international guiding principles for biomedical research were developed by CIOMS and ICLAS in 1985, and as of 2012, considerations were enunciated on the scientifically and ethically justified use of vertebrate animals in scientific activities and the incorporation of the 3R principles in the design and execution of activities involving animals.
In Argentina, National Animal Protection Law 14,346 is the only regulatory framework in force since 1954 and although (included in the Penal Code), it condemns acts of animal cruelty, it does not establish their conception as living, sentient beings and subjects of law, nor regulations on scientific practices with animals.
That is why the conformation of the CICUAL/E ensures a multidisciplinary perspective, by incorporating the scientific, veterinary and common citizen vision in the evaluation of these practices, which promote not only animal welfare, but also the justified use in the statistical rigor and validity of the study results.
* Diego Diaz David is a PhD in Veterinary Sciences – Natalia Cardillo is a PhD in Parasitology and Public Health.
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