I had the privilege of chairing the Institute of Medicine Committee on the Necessity of Chimpanzees in Biomedical and Behavioral Research in 2011, an effort that has lessons not only about the questions presented to it, but also about the policy and practice of the use of chimpanzees in research and about animal research policy in general. In this essay I will assess the impact and implications of the committee’s work and at the same time clarify what I see as its limits.
The rapid implementation of the committee’s recommendations by Dr. Collins ushered in a sea change in the criteria used to assess the necessity of the use of chimpanzees in research.
The committee was multidisciplinary, with the expertise among the members representing a broad range of topics: virology, immunology, infectious disease, vaccinology, cancer, primatology, veterinary medicine, patient advocacy, and bioethics. It held its first meeting on May 26, 2011, and met two other times—once for a one-and-a-half day public workshop in August 2011, and the last time in a private session in October 2011. After the peer review process, the committee’s report and recommendations were issued on December 15, 2011. The committee’s most important and lasting contribution was the articulation of the criteria for justifying the use of chimpanzees in research, with separate criteria for biomedical and behavioral studies.
The committee recommended that the NIH limit the use of chimpanzees in biomedical research to those studies that meet the following three criteria:
- There is no other suitable model available, such as in vitro, non human in vivo, or other models, for the research in question;
- The research in question cannot be performed ethically on human subjects; and
- Forgoing the use of chimpanzees for the research in question will significantly slow or prevent important advancements to prevent, control, and/or treat life-threatening or debilitating conditions.
The committee also recommended that the NIH limit the use of chimpanzees in comparative genomics and behavioral research to those studies that meet the following two criteria:
- Studies provide otherwise unattainable insight into comparative genomics, normal and abnormal behavior, mental health, emotion, or cognition; and
- All experiments are performed on acquiescent animals, using techniques that are minimally invasive, and in a manner that minimizes pain and distress.
For both sets of criteria, the animals used in the proposed research must be maintained either in ethologically appropriate physical and social environments or in natural habitats. Comparative genomics and behavioral research using stored samples are exempt from these criteria.
When the committee examined the existing areas of biomedical research involving chimpanzees funded by the NIH, it concluded that nearly every one of them failed to meet the criteria for necessity. There were only two exceptions. One of them was research in the pipeline for developing monoclonal antibodies that rely on the chimpanzee model, though such ongoing research will be completed within a few years. The other exception was the development of a prophylactic vaccine for hepatitis C, on which the committee was evenly divided between those who felt such research satisfies the criteria and those who felt that it does not. The sticking point in the hepatitis C vaccine debate centered on whether a challenge trial is necessary before undertaking the first efficacy trials in humans. Challenge trials, in which vaccinated individuals are intentionally exposed to the infectious agent, cannot be performed ethically in human subjects. First trials of efficacy in humans can be, and are, performed without prior challenge trials in animals—HIV vaccine trials in populations known to be at risk of HIV are a prime example. Some members of the committee felt that while early-phase efficacy research without challenge can indeed be carried out ethically in human trials, challenge studies are required to identify appropriate candidate vaccines. The other members felt that challenge trials could be important but were not necessary. Even for that single area of disagreement there was consensus that rapid advances in the development of nonprimate animal models (so-called humanized mouse models, in particular) would mean that chimpanzees would be unnecessary within a few years. On the other hand, a substantial proportion of behavioral research did meet the committee’s criteria. This included noninvasive research performed on acquiescent chimpanzees, as long as the animals are maintained in ethologically appropriate environments.
At the conclusion of the report’s release briefing, Francis Collins, the NIH director, held a teleconference to announce his endorsement of its findings and the immediate implementation of its recommendations. NIH halted future funding of research involving chimpanzees pending the creation of a process for reviewing new applications for such research. It also instituted a process for review of all current NIH-funded projects involving chimpanzees to assess whether they met the new criteria.
Lessons from the Committee
The most common and, in my view, most important question I have been asked since the release of the committee’s report is one or another version of the following: Since it came so close, why didn’t the committee recommend a total prohibition on research involving chimpanzees? Some versions were not so much questions but criticisms that the committee had not gone far enough in its recommendations. This question, or criticism, is about more than the will of the committee, raising important and challenging issues about the moral status of chimpanzees, the charge to the committee, and the policy landscape related to animal research in general and for great apes in particular.
Any substantive discussion or debate about a potential prohibition on the use of chimpanzees was limited by the charge to the committee, which stated that it should “explore contemporary and anticipated biomedical research questions to determine if chimpanzees are or will be necessary for research discoveries and to determine the safety and efficacy of new prevention or treatment strategies” (my italics). The key phrases are related to whether there are anticipated future uses that would satisfy the committee’s criteria. The committee quickly acknowledged that since it is impossible to predict the future, it could not recommend a prohibition on all future research given the remote but possible emergence or reemergence of an infectious disease for which research would satisfy the committee’s criteria. That said, the committee’s strongly held view is that establishing strict criteria that include high standards for justified use will go a long way toward limiting any foreseeable future use.
The analyses and critiques of the committee’s report started almost immediately upon its release and continued in a steady stream. That was hardly surprising given the high level of interest in the issue and the careful attention the committee’s deliberations received from across the full spectrum of stakeholder perspectives. What is more surprising is the near consensus on core aspects of the committee’s work, the report, and its implications: (1) that the report was fair, balanced, and accurate, (2) that the report paid insufficient attention to and did not adequately explain the ethics of research involving chimpanzees, (3) that the report and its recommendations will have a significant policy impact, and (4) that the adoption and implementation of the recommendations represent a watershed in animal research policy. While heartening to receive generally positive assessments, there are a number of aspects that deserve explanation and explication, and then there is the criticism regarding the paucity of ethics in the report. I briefly address each of the four areas below.
The report was fair, balanced, and accurate.
The IOM process works to assure that committee members have the expertise relevant to the committee’s task, and IOM staff are expert at accessing and collecting information as required. The chimpanzee committee was especially well served by the IOM process, which identified a group with the relevant mix of expertise that functioned remarkably well together and was committed to reaching consensus in its efforts. These were key characteristics for a committee presented with a highly contentious charge whose members clearly understood the policy implications of their recommendations. Along with its aim to reach a consensus, the committee was committed to undertaking its task with an open mind—it held no preconceptions about the need for using chimpanzees and was willing to review the information it found and make whatever recommendations the findings supported. The staff compiled the large amounts of information relevant to the committee’s task, and the evidence supporting the committee’s conclusions was clear and ample. Finally, the committee felt that it was very important to operate in public to the extent possible and to make its process transparent, both of which contributed to stakeholder trust in the process and the outcome.
All these features together created a process and an outcome that I believe are rightly perceived as fair and accurate. The fact that so much of the committee’s work was performed in public or with public access allowed the full range of interested stakeholders to assess the perspectives sought and considered. These factors led to a process and a report perceived—I believe rightly—as balanced.
The report paid insufficient attention to ethics.
While the majority of the responses to the report’s recommendations were positive, one consistent and significant criticism focused on the limited discussion of ethics. This criticism argues that it is odd for a report assessing the use of chimpanzees to have paid so little attention to what seems to be among the core questions motivating the appointment of the committee in the first place: Is it ethically acceptable to conduct invasive research on chimpanzees, given their close genetic relationship to humans? The criticism holds that answering this fundamental question is primary to any discussion of when chimpanzees are scientifically necessary for research, if ever.
Two factors help explain the committee’s limited discussion of ethics in its report. First of all, the charge to the committee omitted any mention of the ethics of research on chimpanzees. As a result, the committee did not include the relevant expertise to assess that issue; in fact, I was the only scholar of bioethics on the committee. Second, the charge to the committee did not allow it to recommend a prohibition. In spite of these limitations, the committee made clear, both in public sessions and in its report, that ethics is at the core of any consideration of the necessity of the use of chimpanzees. Specifically, it recognized “that any assessment of the necessity for using chimpanzees as an animal model in research raises ethical issues” and that “the chimpanzee’s genetic proximity to humans and the resulting biological and behavioral characteristics not only make it a uniquely valuable species for certain types of research, but also demand greater justification for their use in research than is the case with other animals.” So while it did not assess whether it was ethically acceptable to use chimpanzees for research, the committee made its recommendations with a clear sense that they raised the bar for justification of the use of chimpanzees, and did its best to articulate a rationale for that position.
The report will have a significant policy impact.
Those of us in bioethics working on national-level committees hope that our efforts will make an impact—on practice, policy, or at least on the thinking of those who read the results of our work. The fact that Francis Collins endorsed the committee’s recommendations and implemented them on the day the report was released represented the sort of policy impact that we all aim for but rarely realize. The reasons for the rapid implementation will be debated, but I expect they include a combination of strong findings in support of clear recommendations that confirmed a trajectory that has been underway for some time, and an endorsement of a change in policy that will institute a clear process for reviewing any proposed future use of chimpanzees. In addition, there is vocal public and government sentiment to support restrictions.
The policy changes represent a watershed in animal research policy.
The rapid implementation of the committee’s recommendations by Dr. Collins ushered in a sea change in the criteria used to assess the necessity of the use of chimpanzees in research. Among the most surprising of the committee’s findings was that there were no documented criteria for assessing the necessity of proposed chimpanzee use in NIH-funded research. The process internal to the NIH was apparently ad hoc and performed by a committee without membership from outside NIH. Similarly, the review process at the four primate centers lacked written criteria or guidelines. Thus, the decision to halt future NIH funding of research involving chimpanzees until the criteria recommended by the committee could be implemented represented a significant departure from past policy. The criteria, once implemented, will impose the strongest restrictions to date on the use of any animal species for research in the United States, a major change in animal research policy in general. And the committee’s inclusion of a criterion that human subjects must be ruled out on ethical grounds as part of the justification for the use of chimpanzees turns the traditional presumption regarding the use of research animals on its head—again, a major change in animal research policy.
All in all, I believe it is fair to say that the committee’s recommendations and the process of its work represent a success for bioethics-related consensus committees. The combination of topic, timing, and public stakeholder sentiment may have aligned in unique ways that contributed to that success. But even if it turns out to be a special case of sorts, there are lessons to be learned for the future.
Jeffrey Kahn is the Robert Henry Levi and Ryda Hecht Levi Professor of Bioethics and Public Policy in the Johns Hopkins Berman Institute of Bioethics. He is also professor in the Department of Health Policy and Management in the JHU Bloomberg School of Public Health. His most recent book is the forthcoming eighth edition of Contemporary Issues in Bioethics (Cengage Publishing), edited with Tom Beauchamp, LeRoy Walters, and Anna Mastroianni. His research interests include the ethics of research, ethics and public health, and ethics and emerging biomedical technologies.