Animal Research at CDC: Achieving a Delicate Balance
For many, scientific research involving the use of animals is a nagging moral question of the potential health benefits to all humans versus the treatment of the animal test subjects. For others, it is an issue in which the end never justifies the means, calling for acts of sometimes extreme civil disobedience. Ask Ron Otten, PhD, CCID, NCHHSTP, for his position on the issue, and the answer is unequivocal but hardly unexamined. "There has always been some inner conflict for me, but a lot of that was put to rest during my travel in east Africa," he says. "I have seen the valuable role that animal research can fulfill—not only in the field of HIV/AIDS research but across the spectrum. The bottom line is, we need this… It has its place."
A research microbiologist in the Division of HIV/AIDS Prevention, Laboratory Branch, Dr. Otten has more than a passing interest in and knowledge of the realities of animal care and research at CDC. In addition to working as a lead scientist within the Laboratory Branch, he also serves as the chairperson of the Institutional Animal Care and Use Committee (IACUC) for CDC's Atlanta facility. The committee is appointed by the agency's Institutional Official (IO) to oversee its animal program, facilities, and procedures. (CDC maintains an IACUC at each of the three sites where animal research is performed—Atlanta, Fort Collins, and Morgantown.) IACUC's 11 voting members and two alternates meet twice monthly to review, approve, monitor, and oversee the use of animals for research, teaching, training, or exhibition.
IACUC oversight is not unlike that provided by an Institutional Review Board (IRB) in cases of research involving human subjects. Under FDA regulations, an IRB is designated to review and monitor biomedical research involving human subjects and has the authority to approve, require modifications in, or disapprove research. This group review serves an important role in the protection of the rights and welfare of human research subjects—just as the IACUC system protects the welfare of animals.
Following Branch and Division-level approval, IACUC receives research proposals from the agency's attending veterinarians for review of their appropriateness and compliance with accepted, mandated standards for the use of animals. Aspects of proposals to be examined might include anything from the specific number of animals to be used to the anticipated level of pain or distress likely to be experienced by subjects. Upon completion of its review, the Committee may either approve the proposal or make recommendations for revisions if it finds something lacking. The revised proposal will then come back to IACUC for either another full Committee review or possibly a "designated review" by a portion of its members. Although the proposed use of any animal receives careful consideration, CDC policy requires extra scrutiny when non-human primates or companion animals are being used. IACUC even has the authority to suspend a protocol if it determines that an investigator is involved in anything not specifically approved in the original research proposal.
In the Division of HIV/AIDS Prevention, Laboratory Branch, there are three essential categories of "products" which require animal research: vaccines, anti-retroviral drugs, and topical microbicides. Vaccines (which Dr. Otten describes as "the Holy Grail"), new drugs as a way to treat those already infected or possibly prevent infection in the first place, and topical gels known as microbicides used by sexually active individuals to decrease HIV transmission/acquisition are each a high priority both in the US and resource-poor countries. While, according to the Foundation for Biomedical Research (FBR), practically all research animals are rodents, research and preclinical evaluations in each of these HIV/AIDS prevention areas requires the use of non-human primates almost exclusively. (Contrary to popular perception, dogs, cats, and non-human primates together account for less than one-half of one percent of all animals used in research, according to FBR.) Dr. Otten estimates that several dozen non-human primates are currently involved in HIV/AIDS research at CDC.
But Is It Really Necessary?
Some may ask, why not simply use computer modeling or other methods that do not require these animals? "Some things just have to be done in the context of a living immune system," explains Dr. Otten. "Even the most sophisticated technology can't mimic the complex cellular interactions that occur in a living system." Most scientists agree that animal systems provide invaluable insights into human ones because there are striking similarities between the genetic and physiological systems of animals and humans. While advances achieved through research with animals are often enhanced by knowledge obtained through non-animal methods—such as mathematical and computer models, cell and tissue cultures, clinical observation, and epidemiology—these alternatives serve only as adjuncts to basic animal research.
So what are the benefits and specific medical advances attributable to animal research? The list is long and dates back to the development of a smallpox vaccine in 1796 as a result of research using cows. Dr. Otten cites a current clinical trial underway in the US and Africa of an antiretroviral drug in which—thanks to CDC's use of an animal model that mimics the conditions of high-risk human sexual exposures—it was determined that a combination of two drugs yielded far more positive results than the single one initially under evaluation. This combination of published and unpublished CDC data was the first proof-of-concept information using a living system to indicate that a more potent drug regimen (with an acceptable safety profile) will work for pre-exposure treatment to repeatedly prevent sexual transmission of a closely related, HIV-like virus. The clinical trial was able to be promptly modified to make use of the findings. "Human clinical research is served because the products we can develop using animal research allow us to examine them before—or sometimes during—clinical trials," he says.
Ensuring the Best Care Possible
So if there is simply no getting around the need for animal research, what can be done to guarantee the ethical, humane treatment of these creatures? And who will oversee the terms of their care? For both humane and scientific reasons, researchers are necessarily concerned about the condition of the animals they study—there is no constituency for inhumane or irresponsible treatment. Poor care results in unreliable research data, while pain and distress are thought to have a negative impact on the immune system. In addition to ensuring the appropriateness of the research, IACUC is also tasked with full oversight of all animal programs at CDC (including conditions of facilities, etc.). In that role, the full committee conducts two reviews of the agency's facilities annually and makes reports/recommendations to the IO based on its findings.
And how do CDC's animal care facilities rate today? "While there is always room for improvement in anything—and here I might cite funding, staffing, or in-depth understanding of the issues—our animal programs and our current oversight mechanisms are quite adequate," remarks Dr. Otten. "Moving forward, we're in great shape."
Though it may never be easy to reconcile our love and appreciation for animals and the essential need for animal research, knowing that the animals are treated respectfully, responsibly, and as humanely as possible, strengthens our understanding of and respect for animal research. At CDC, IACUC works to make that happen.