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The Use of Animals in Biomedical Research

Our current understanding of the workings of the body is the result of more than two centuries of research on the function of normal cells, tissues, organs, and whole organisms, and on disease processes. The teaching of medicine and veterinary medicine is founded upon this knowledge, which has also been instrumental in the development of medical advances for both people and animals. Nearly all of this knowledge — and the medical treatments that have resulted from it — have been made possible either directly or indirectly by research that was performed on animals.

These advances in the prevention and treatment of disease have depended on knowledge about the causes of disease; information about how disease affects the body; and drugs, medical devices and surgical procedures that cure disease. The knowledge, materials and skills on which prevention and treatment of disease are based have come from both pre-clinical and clinical studies in human and animal biology and medicine and from experimentation with both human and animal subjects. Most research and testing involving human patients, however, is based on the results of animal experimentation. Although there have been incredible strides made in animal alternatives over recent years, there is often no way to model the extraordinary complexity of a living organism without using a living model. Continued progress in the prevention and treatment of disease will depend on the responsible use of animals in research for some time to come.

Model species are used to test hypotheses that would be difficult or impossible to test in humans or another target species. In general, one species is used as a model for another when, despite other differences between them, the two species strongly resemble each other in particular ways that are the objects of the study. The similarity between animals and humans is illustrated by the fact that many drugs — antibiotics, for example — are used to treat both human and animal patients. In fact, the spillover of human medicine into veterinary medicine is immense.

Fundamental molecular mechanisms and those involved in cell differentiation and propagation are frequently the same across a wide range of species. Therefore, for many fundamental principles of biology, using nonhuman animals as models can provide valuable insight into human cell processes. Control of experimental conditions is an important aspect of drawing scientific conclusions, and using animal models enables greater control of experimental variables than can be achieved in humans. In certain uses of animals as models, such as mouse “knock-out” models, in which individual genes are switched off to study the physiological or other effect, researchers can even control the genetic makeup of the animals to ensure homogeneity.

Researchers draw upon the full range of species to study life processes and the species of choice will depend on the type of life or disease process being modeled. Many basic biological processes are best studied in simple organisms because these organisms are easiest to grow or examine and/or because the process being studied is not obscured by biological complexity. Mammals are very useful to scientists, however, because they are closest to us in evolutionary terms and allow life and disease processes to be studied in greater depth.

The majority of research with animals (~95%) involves rats and mice as experimental subjects, with nonhuman primates accounting for less than one percent of the total.

Opponents of the use of animals in research often use the availability of alternative, non-animal research methods as evidence that research using animals is unnecessary. While it is true that non-animal methods — such as tissue culture, computer modeling, research using human test subjects and population studies — are used and have value in research, these methods are generally used in addition to animal studies; they do not replace them. This is because studies often require more than knowing how individual molecules, cells or tissues behave. Scientists must grasp the bigger picture, which depends on understanding not only the processes of the living body, but also how they interact.

A vast majority of the scientific community considers that the societal benefits that have been provided by the use of animals in research justify their use. If life science is to continue to advance human and animal health, it must have public support as well. Public support ultimately depends upon public confidence that research using animals is properly and humanely conducted and is productive and beneficial. Polls conducted over the past 25-30 years show that the public increasingly accepts the need for the use of animals in research, providing that certain conditions are met.

These are:

• that the animals experience no unnecessary suffering;
• that the research is for serious medical or lifesaving purposes; and
• that there is no reliable alternative to their use.

It is important to recognize that although a significant amount of work using animals is basic research whose benefits to improved health are not always apparent; this work is highly valuable in providing a foundation for future medical advances.

A CASE IN POINT…

 The Use of Animals in the Development of Polio Vaccine

My own experience of more than 60 years in biomedical research amply demonstrates that without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death, not only amongst humans, but also amongst animals.

– Polio vaccine developer Albert Sabin

One of countless examples of the use of animals as models of human disease is the development of polio vaccine. Polio was a crippling disease until the development of a vaccine in the mid-1950s, an event of such magnitude that some historians have called it one of the greatest achievements of the 20^th century.

Polio is an infectious disease that can strike at any age, but mainly affects young children. The virus enters through the nose or mouth and once it enters the bloodstream, it can invade the central nervous system. Polio virus invades only certain types of nerve cells, particularly the anterior horn cells of the spinal cord, and in the process of multiplying, the virus may damage or destroy these nerve cells in the limbs, trunk and brainstem, resulting in paralysis and sometimes death.

In 1916, a polio epidemic began in the U.S. that killed 6,000 people and paralyzed 27,000 others annually. In the early 1950s, more than 20,000 cases of polio were reported each year. After the introduction of effective vaccines in the late 1950s and early 1960s, polio was brought under control and effectively eliminated as a public health problem in the developed world. By 1979, after polio immunization had become routine, there were only 10 cases reported in the U.S., and in 1991, the Western Hemisphere was declared polio-free.

The research that produced the polio vaccine required the use of living nerve tissue to ensure that the virus used for vaccine production causes the paralysis typical of polio; no human or tissue culture alternative existed. The polio vaccine also uses a live attenuated virus, which is known to sometimes revert to virulence, so animals are still the only practical way of predicting the potential virulence of each batch of polio vaccine. This previously involved an intra-cerebral injection of the vaccine into monkeys, which is highly predictive of virulence.

More recently, in a refinement to the use of animals in polio vaccine research, mice have been genetically engineered to have the receptors for polio virus, providing an alternative animal model of the disease. The use of genetically modified (GM) mice to establish the virulence of the vaccine provides an accurate model of humans in this respect. This is a good illustration of how mice, and in particular GM mice, can be used as models for human pathogens. Besides being genetically similar to humans, mice are small and inexpensive to maintain. Their short life span and rapid reproductive rate make it possible to study disease processes in many individuals, thus gaining a greater understanding of the progression of the disease within a short space of time.

Source:  “Polio,” a monograph published by the Massachusetts Society for Medical Research. North Chelmsford, MA: MSMR (2004).

The use of animals in research is a privilege granted with the understanding and expectation that such research is conducted according to the highest ethical and legal standards. The widely-accepted stance for all use of animals in research is to minimize animal suffering while maximizing the benefits to medicine, health and fundamental understanding of life. It is this stance that guides the work of the Institutional Animal Care and Use Committee (IACUC).

The IACUC is the body that is charged with ensuring the proper care, use and welfare of animals involved in research at an institution. Under the 1985 amendment to the U.S. Animal Welfare Act, IACUCs were established to review all protocols for procedures involving live warm-blooded animals, whether or not pain or distress is likely to occur. If the proposed procedures are appropriate and comply with ethical and regulatory standards, the IACUC provides institutional approval to conduct the study. In addition, the IACUC has the responsibility to review periodically the condition of the animal facility(ies), as well as policies, procedures and operational functions of the facility and the institution’s animal care and use program.