Животные модели в медицинских исследованиях: возможности и ограничения

An animal that is used recurrently in research
An animal model (short for animal disease model) is a living, non human, often genetic engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of harming a human. Although biological activity in an animal model does not ensure an effect in humans, many drugs, treatments and cures for human diseases are developed in part with the guidance of animal models. Animal models representing specific taxonomic groups in the research and study of developmental processes are also referred to as model organisms.

Animal models observed in the sciences of psychology and sociology are often termed animal models of behavior. It is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Animals lack self consciousness, self reflection and consideration; moreover, hallmarks of the disorder such as depressed mood, low self esteem or suicidality are hardly accessible in non humans. However, depression, as other mental disorders, consists of endophenotypes that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular, genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and the causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into pathology of depression. In addition, animal models of depression are indispensable for identifying novel therapies for depression.

Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary, obese and glucose intolerant. This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise. Animal models of psychiatric illness give rise to other concerns. Qualitative assessments of behavior are too often subjective. This would lead the investigator to observe what they want to observe in subjects, and to render conclusions in line with their expectations. Also, the imprecise diagnostic criteria for psychiatric illnesses inevitably lead to problems modeling the condition; e. g., since a person with major depressive disorder may experience weight loss or weight gain, insomnia or hypersomnia, we cannot with any certainty say that a rat with insomnia and weight loss is depressed. Furthermore, the complex nature of psychiatric conditions makes it difficult/impossible to translate human behaviors and deficits; e. g., language deficit plays a major role in autistic spectrum disorders, but – since rodents do not have language – it is not possible to develop a language impaired "autistic" mouse.

Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament enacted the first law for animal protection preventing cruelty to cattle see text. This was followed by the Cruelty to Animals Act of 1835 and 1849, which criminalized ill treating, over driving, and torturing animals. In 1876, under pressure from the National Anti Vivisection Society, the Cruelty to Animals Act was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over (see text). Today, these three principles are central to the laws and guidelines governing the use of animals and research. In the U. S., the Animal Welfare Act of 1970 (see also Laboratory Animal Welfare Act) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program see AWA policies. In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by a local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement. Replacement refers to efforts to engage alternatives to animal use. This includes the use of computer models, non living tissues and cells, and replacement of "higher order" animals (primates and mammals) with "lower" order animals (e. g. cold blooded animals, invertebrates, bacteria) wherever possible (list of common model organisms approved for use by the NIH). Reduction refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine the minimum number of animals that can be used to get a statistically significant experimental result. Reduction involves methods to maximize information provided while minimizing the number of animals applied. Refinement refers to efforts to make experimental design as painless and efficient as possible in order to minimize the suffering of each animal subject. While significant advances have been made in the care and treatment of animals, this is an ever evolving debate. Animal rights and protection groups such as the ASPCA, PETA and BUAV continue to advocate for the best laboratory conditions, and experimental protocols possible for animals in research. Pressure from these groups has also led to novel modes of experimentation, which does not involve the sacrifice of live animals. One aspect of this debate; however, continues to be difficult to resolve: the classification of animals according to a hierarchy, which protects some species more than others. Next to humans, primates are the most protected species in experimentation. The rationale for this has both evolutionary and philosophical underpinnings. Because chimpanzees and other non human primates can demonstrate intelligence, and social structure that they have a life experiences that is more cognitively complex than lower species. Conversely, this kind of moralizing of complexity of interaction and thought could be considered "specieisism." Ultimately, this is an argument not likely to be resolved, however most people are more comfortable with the idea of experimentation that involves worms or flies than mice, dogs, or monkeys.

Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture and in vitro studies provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human induced pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non invasive study of human subjects. Recent advances in genetics and genomics can identify disease associated genes, which can be targeted for therapies.