CAAT Newsletter: Vol. 13, No. 3, Summer 1996

Conference Highlights

Public Responsibility in Medicine and Research (PRIM&R) - Animal Care and Use: Hot Zones, Grey Zones and Go Slow Zones

Boston Mass., March 14-15, 1996

By Deborah Rudacille

Public Responsibility in Medicine and Research (PRIM&R) is an educational forum founded by a consortium of Massachussetts teaching hospitals in 1973, to help institutions understand and implement the growing body of state and national legislation related to biomedical research. Although based in Boston, the group has from its inception drawn a national audience to its excellent workshops and conferences, holding four-to-five meetings annually on a wide variety of topics. These range from conflict of interest and scientific misconduct to AIDS research and special needs of research populations such as children, women and minorities. "Research ethics for human and animal subjects remains our main focus," according to Joan Rachlin, J.D., M.P.H., executive director of PRIM&R. Despite significant growth and popularity, PRIM&R has chosen to remain independent, foregoing the economic temptation to become a membership organization. "We value highly our interdisciplinary character and multiple constituencies," Rachlin noted. "We want to stay open to all of these groups, without any one becoming dominant, as we believe would happen if we became a membership group."

The interdisciplinary character of PRIM&R was amply illustrated at this year's conference on animal related issues, held in Boston March 14-15, 1996. "Animal Care and Use: Hot Zones, Grey Zones, and Go Slow Zones," drew over 400 attendees from across the United States, who convened to discuss a wide array of ethical and scientific issues related to laboratory animal care and use. The meeting clearly demonstrated the degree to which regulatory agencies such as the United States Department of Agriculture (USDA), charged with implementing the Animal Welfare Act, appropriate offices of the National Institutes of Health such as OPRR (Office for Protection from Research Risks), accreditation groups like AAALAC (American Association for the Accreditation of Laboratory Animal Care), and scientific animal protection groups such as SCAW (Scientists Center for Animal Welfare) have begun working cooperatively to enhance the quality of laboratory animal programs and to facilitate learning and education.

Many of the meeting's panels and workshops focused on recent or impending changes in U.S. guidelines and/or regulations related to animal use. For example, both U.S. Public Health Service Policy on the Humane Care and Use of Laboratory Animals and the Guide for the Care and Use of Laboratory Animals, published by ILAR (Institute for Laboratory Animal Resources), have been revised for the first time in ten years. The latter highly influential document, whose standards are used by AAALAC to determine accreditation, was discussed in both a workshop and a full session panel chaired by ILAR director Thomas Wolfle, D.V.M. As noted by the members of the panel (including the first public member to sit on the revision committee), the first sentence of the report provides an indication of the guide's new tone, "strongly affirming the conviction that all who care for or use animals in research, teaching or testing must assume responsibility for their well-being."

The new guide utilizes an outcome-based approach, with performance standards which emphasize that "animal environment, housing and management should maximize species-specific behavior and minimize stress-related behavior" according to Katherine Bayne, M.S., Ph.D., D.V.M., Associate Director for Accreditation, AAALAC, who served on the committee. AAALAC has not yet defined a specific date on when the new guide will be implemented on site visits, Bayne said, adding that "there will be a gradual phase-in of the new standards."

W. Ron de Haven, D.V.M., Regional Director for Animal Care and Use, USDA, provided insight into proposed regulatory changes including a possible two-year phase-out of Class B animal dealers. The elimination of Class B dealers has been a goal of the animal protection community for some time. Class B dealers, who do not breed or otherwise produce animals on-site, current supply approximately 40% of the dogs and cats currently purchased by research institutions. Of that number, Class B dealers acquire 35% from individuals, 30% from other dealers, and 35% from pounds and shelters.

Recent USDA prosecution of individual Class B dealers, together with ample evidence of slipshod record keeping by many unprosecuted dealers amid continuing public concern about lost or stolen pets winding up in research laboratories, has apparently persuaded USDA to take action. deHaven expects that the proposal will appear in the Federal Register later this year. Similarly, a working group headed by Andrew N. Rowan, Ph.D., former scientific director of FRAME and current director of the Center for Animals and Public Policy, Tufts University School of Veterinary Medicine, is re-examining the USDA categories for pain and distress in laboratory animals in order to produce a more cogent and useful system of categorization later this year. Working with USDA, the committee will recommend revisions to existing classifications, which are widely perceived as inadequate. This work is made more difficult, as Rowan noted, by the lack of objective criteria for assessing pain and even more subjective and anecdotal standards for defining "distress."

Despite such positive indications of cooperation and progress, the meeting was not without its share of controversy. Invitations extended to Suzanne Roy, program director for In Defense of Animals, an animal rights organization based in California, and Henry Spira, head of New York based Animal Rights Coalitions, prompted calls by some researchers to boycott the conference earlier this year. This outcry was noted by Ms. Roy in her presentation on the final day of the conference, which focused on the need for stringent oversight of animal use in biomedical research. Roy discussed cases currently being investigated by her group, including one in which 378 violations of the Animal Welfare Act were filed by USDA against New York University Medical Center and NYU neuroscientist Ronald Wood.

Noting that her organization and other animal protection groups are regularly contacted by individuals within the research community who state that they are unable to have their concerns addressed within the system, Roy commented that "those of you who are doing things the right way have nothing to fear from us." Spira, whose Campaign to Abolish the Draize Test led to widespread changes in cosmetic product development and safety testing, was unable to attend the conference.

Conference co-chair Andrew Rowan confirmed in his introduction to a panel titled, "The Future of Animal Use in Biomedical Research," that PRIM&R has always supported and facilitated dialogue among individuals representing multiple perspectives, with the caveat that the dialogue, "although impassioned," be courteous and respectful of other viewpoints. Both disagreement and courtesy were exemplified in the sessions dealing with the meeting's most controversial topic, xenotransplantation. A panel presentation called "Xenotransplantation: the Ethics, the Science, the Risk of Animal to Human Transmission, and Implications for the IACUC" examined the many difficult issues confronted by the scientific community and society as a whole in attempting to grapple with the problem of a shortage of human donors for organ transplantation and the proposed solution to that shortage--animal to human animal organ transfer.

Alan Berger, executive director of the Animal Protection Institute, first thanked the program committee for the invitation to speak and for promoting "healthy discussion" and then noted that only about 20% of adults in the United States are currently identified as organ donors. Berger commented that "clearly, the current system of procurement is not working," and recommended a more aggressive effort to recruit human donors, including a default organ donation system in which all are considered potential organ donors unless otherwise requested, prior to proceeding with further efforts to implant animal organs in humans. He identified three issues as major problems in xenotransplantation--poor use of resources, possible transmission of infectious disease, particularly non-human primate viruses, and ethical constraints.

Berger's second point, the risk of lethal species-crossing viruses being spread via organ transfer, was more formally discussed by Louisa Chapman, M.D., medical epidemiologist in the Division of AIDS, STD and TB Research, Centers for Disease Control, who provided a "Public Health Perspective on Xenotransplantation." Pointing out that there is strong evidence that HIV 1 and HIV 2 are the result of simian immunodeficiency viruses crossing over into human populations and that the disease "spread silently through the human population for at least ten years," she concluded that "the public health consequences of such viral diseases are greatest when the outward manifestation of the zoonotic disease is least apparent." The cross-species transfer of Herpes B virus, which Chapman termed "iatrogenic" {created by medical intervention} provide a further indication of the need for caution.

Finally, the many difficult issues faced by institutional animal care and use committees (IACUCs) in their routine operations provided a sub-text for discussions in nearly every session. As noted by Katherine Bayne of AAALAC, "since 1985, IACUC performance and functions have evolved." Seasoned IACUCs are far more sophisticated and aggressive in examining protocols and this sometimes creates conflict. In a workshop titled "Alternatives in Research," William Stokes, D.V.M., associate director, animals and alternatives resources, National Institute for Environmental Health Sciences, who had earlier that afternoon delivered a plenary lecture on the Three Rs, suggested that recalcitrant investigators who object to IACUC oversight functions actually be appointed to the committee, in order to become better acquainted and perhaps supportive of the process. This suggestion was greeted with laughter by one member of the group who said that her IACUC had tried that solution and found that "in one case it worked beautifully...but the other investigator was a nightmare."

A somewhat general philosophical discussion of pain and distress in laboratory animals at another workshop was interrupted by a man who noted that as a new member of an IACUC he needed more basic data on exactly what procedures one could assume would result in pain or distress and how he as an IACUC member could address the issue. The workshop chairs, Rowan and deHaven, noted that "tumor induction, use of adjuvants, restraint, and death as an endpoint," are all problematic issues for IACUCs and must be treated seriously. They also acknowledged that pain and distress are "consistently under-reported" and that "certain types of studies should automatically be classified as Category E [unrelieved pain and distress] unless the institution can prove otherwise."

Perhaps the wisest and wittiest comment at the conference was delivered by Franklin Loew, D.V.M., Ph.D., dean of the College of Veterinary Medicine, Cornell University, who quoted Oscar Wilde -- "The most difficult thing to predict is the future,"-- when asked to prophesy about the continued need for animals in biomedical research. "Over the past 15 years, there has been a decline, a leveling off in animal use, however with the accelerating research in xenografts, the possibility of HIV vaccination, and recent rapid advances in the neurosciences, it is possible that animals will be used in greater numbers in coming years," Loew said. "I don't think that society would benefit from a cessation of animal use in research. To the contrary, I think that society would be harmed. However, our fellow citizens will continue to perform a moral calculus when they hear about research animal use. They need to know that the work is being undertaken for high-enough stakes."

The PRIM&R conference testifies to the willingness of many in the research community to discuss openly and even to argue passionately about both the moral and scientific calculations which must be performed prior to undertaking work with animals. Such discussions will surely prove crucial in influencing the desire of the public to impede or facilitate the continued use of animals in biomedical research.