PCRM Position Paper on Animal Research
Approved by the PCRM Board of Directors, July 21, 2010
The primary purpose of medical research is to promote human health, and the most direct research methods focus on the study of human populations, individuals, and tissues. Animal research has been used as an alternative method when the study of humans is deemed impractical or unethical, or when animal biology is of primary interest. Animals are frequently used in biological and medical research, in the testing of drugs and commercial products, and in educational exercises in the sciences. While the number of animals used in the United States is not known, estimates range into several tens of millions annually.
Ethical concerns are raised by the use of animals in experimental studies, particularly when they are subjected to painful procedures or toxic exposures. These concerns are accentuated by studies showing marked stress responses in animals undergoing common laboratory procedures. For example, routine handling, venipuncture, and gavage (the administration of test compounds through an oral tube) elicit striking elevations in pulse, blood pressure, and steroid hormone release that can persist for an hour or more after the event. Similarly, routine features of the laboratory environment—isolation, confinement, social disruption, noise, and restrictions on physical movement—have been shown to be noxious for animals. Together, these bodies of evidence indicate that even experiments that appear to be minimally invasive can be highly stressful for the animal subjects, and this finding applies to commonly used rodent species as well as larger and less frequently used animals. Stress effects are relevant to humane concerns as well as to the interpretation of scientific findings. Research on immune function, endocrine and cardiovascular disorders, neoplasms, developmental defects, and psychological phenomena are particularly vulnerable to stress effects.
Promoting Nonanimal Methods
Ethical concerns have propelled the exploration of methods that replace animal use. However, such methods may also have scientific advantages related to cost or applicability to human disease. For example, toxicologists seeking more efficient methods have turned to cellular screening tests for many applications and have sometimes realized substantial savings in the process. Trauma training, once conducted almost universally using animals, is now commonly taught with simulators that are cheaper and are designed to more closely mimic critical aspects of patient care.
In August 2007, the US National Research Council published Toxicity Testing in the 21st Century: A Vision and a Strategy,which described limitations of animal-based toxicology tests and proposed a new focus on non-animal methods that may present potential advantages over animal tests. In January 2008, the Environmental Protection Agency and the National Institutes of Health’s National Toxicology Program and Chemical Genomics Center signed a Memorandum of Understanding pledging joint funding and research for the replacement of animals in toxicology testing with nonanimal methods. Both documents support the concept that replacement of animal-based methods in toxicology promises practical benefits, aside from humane advances.
It is incumbent on scientists and institutions using animals for research, testing, or educational purposes to actively investigate and implement alternatives. The federal Animal Welfare Act regulations require that research personnel be trained in methods of searching for alternatives to animal use, and the NIH Guide for the Care and Use of Laboratory Animals encourages efforts to develop and use scientifically valid alternatives to animal research. There are three broad scenarios for doing so:
1. In some cases, alternatives are readily available. For example, nonanimal methods in medical education have already been implemented for a wide variety of applications at many medical schools, but are not yet in use at all institutions.
2. In other cases, nonanimal methods may not be apparent. In such cases, development of suitable alternative means should be a high priority. For example, many laboratories produce monoclonal antibodies for research or diagnostic purposes by placing antibody-producing cells in the abdomen of animals, often causing significant pain and distress as the cells produce large amounts of fluid (ascites). While antibodies can also be produced by cellular techniques, there are major technical challenges in so doing for some cell lines.
Pharmaceutical testing presents challenges for the replacement of animal tests. While animal tests leave much to be desired as means of identifying drug-related risks, no alternative test methods are yet acceptable to the Food and Drug Administration for many toxicology endpoints.
In these cases, the most appropriate course of action is neither to assume that nonanimal methods will be easily produced nor to be resigned to the continued use of animals. Rather, it is incumbent on investigators and research-supporting institutions to make the replacement of animals a priority.
3. For many applications, the replacement of animal use occurs most appropriately, not through a specific alternative method, but by a substantially different approach to the clinical problem at hand. For example, some research centers are assessing the toxic effects of recreational psychoactive drugs by testing them on animals. Another strategy relies on assessing their effects through noninvasive neurological and psychometric testing on humans who have been using such compounds voluntarily.
The Need for Discussion and Collaboration
To address the ethical and practical issues raised by animal research, scientists and research-sponsoring institutions benefit from information sharing, discussion, and debate representing a wide variety of opinions. Toward that end, governmental bodies in the U.S. (e.g., the Environmental Protection Agency) and abroad dealing with animal testing issues have implemented policies that ensure that animal welfare advocates and scientists advocating for alternatives to animal tests are represented on scientific and regulatory panels.
In recent years, it has become clear that viewpoints vary greatly on this issue and are highly mutable as new information comes forward. It is helpful to recognize that, generally speaking, implementing nonanimal methods is neither a simple matter nor a theoretical impossibility. While animal welfare considerations mandate a commitment to the replacement of animals, there are areas for which alternatives have not yet been developed or have not yet gained acceptance by regulatory bodies. The impediments to their development and acceptance relate to both technical difficulties and attitudinal issues. In the course of scientific inquiry, many investigators have credited the use of animals with the elucidation of key points, and it remains a matter of conjecture as to whether the same discoveries could have been accomplished by other means. In contrast, the use of animals in education has undergone dramatic changes in the past decade. Most medical schools have eliminated the use of animals from their curricula, and instructional methods at other educational levels have also evolved in the face of changing technologies. A reasonable viewpoint, we believe, is for investigators and institutions using animals to explore and implement nonanimal methods with all due haste and without limit, recognizing that in some cases the practical challenges inherent in doing so are considerable.
PCRM should continue and expand collaborative efforts to address the need for alternatives to animal use. In cooperation with physicians at Harvard University and the Massachusetts General Hospital, PCRM developed educational materials demonstrating clinical alternatives to animal use in medical instruction, and progress in implementing alternatives has been documented in surveys published by PCRM physicians in the Journal of Medical Education and Academic Medicine. PCRM toxicologists have served on scientific panels for the Environmental Protection Agency and on the Board of Directors of the Toxicology Excellence for Risk Assessment. PCRM physicians have published invited papers on animal research issues in Scientific American and Lancet Oncology. Working with outside scientists, PCRM developed a new laboratory technique for assaying insulin that provides alternatives to the ascites method for producing monoclonal antibodies and to the use of fetal calf serum for in-vitro cellular growth. These efforts complement PCRM’s primary research work, which focuses on clinical trials in human participants, and are enriched by communication and collaboration with other research organizations.
The process of replacing animals in research, testing, and education is supported by studies showing that routine laboratory procedures and typical laboratory environments are more stressful for animals than is commonly appreciated. Nonetheless, the challenges of replacing animals are often considerable, raising major scientific, economic, and regulatory issues.
The exploration and implementation of nonanimal methods should be a priority for investigators and research institutions and should take advantage of a wide variety of viewpoints to ensure progress toward scientific, human health, and animal protection goals.