NIH to Review its Portfolio
The IOM report sets a high bar for chimpanzee studies while at the same time recognizing areas of research where chimpanzees are still needed.
On December 15, 2011, the Institute of Medicine (IOM) released its long-awaited report, “Assessing the Necessity of Chimpanzees in Biomedical and Behavioral Research.” Following a briefing where the key findings were presented, NIH Director Francis Collins announced that NIH accepted the report and would begin implementing its recommendations.
Noting the two-edged sword represented by chimpanzees’ closeness to humans, the IOM panel recommended additional guidelines for when to permit research involving chimpanzees. The panel’s criteria are intended to determine whether the research is absolutely necessary to answer an important research question, as opposed to when it is useful. The criteria address issues such as the public health importance of the research question, availability of non-chimpanzee research models, whether the animals are housed in a species-appropriate habitat, whether the research can be performed ethically in human subjects, and whether forgoing chimpanzee research would significantly slow or prevent important research advancements.
Based on a review of current NIH-funded grants, the panel estimated that half of currently funded research might not meet these criteria and ought to be phased out. The panel also believes the need for chimpanzee research will decrease further in the future. However, it did not endorse a ban on chimpanzee research. Rather, it said that current and future research that meets the criteria should continue, and that the U.S. should retain the capacity for chimpanzee research to address future health threats in cases where there is no other research model.
NIH to Implement Recommendations
Immediately after the report was issued, NIH Director Francis Collins released a statement endorsing its recommendations. Collins also announced an interim moratorium on new grants for chimpanzee research while NIH reviews current and proposed research using the new criteria. He said that the criteria will be applied to research with chimpanzees owned by NIH, supported on NIH grants, or housed in NIH funded facilities. According to the IOM panel, there are 937 chimpanzees at five NIH-supported facilities, including four National Primate Centers and the Alamogordo Primate Facility. Of this total, 612 animals are owned by the NIH, and many of the others have been part of various NIH-funded research projects. At present there are 27 extramural and 10 intramural research grants involving chimpanzees.
In accepting the report, NIH Director Collins said the agency will develop “a complete plan for implementation of the IOM’s guiding principles and criteria.” A working group within NIH’s Council of Councils will be asked to develop implementation plans and to “consider the size and placement of the active and inactive populations of NIH-owned or supported chimpanzees.” In response to a question about whether NIH would retire chimpanzees not on active research protocols meeting the IOM criteria, Collins pointed out that “retired” chimpanzees cannot be returned to research. For that reason, he will ask the NIH working group to assess what chimpanzee population should be maintained to meet current and future research needs. Collins also said that the working group would consider research projects individually and would not recommend rapid termination of projects where additional data can readily be collected to complete the study. A subsequent NIH policy announcement stated that any research projects not deemed acceptable under the new criteria would be phased out “in a fashion that preserves the value of research already conducted.”
Further Criteria Proposed
Although all proposals for research with chimpanzees already undergoes an ethical review, there are no uniform criteria to evaluate the absolute necessity of such research. Therefore, the panel proposed a broad set of principles to apply to all research with chimpanzees, as well as specific criteria for biomedical research as well as behavioral and comparative genomics research.
General Principles:
- The knowledge gained must be necessary to advance the public’s health,
- There must be no other research model by which the knowledge could be obtained, and the research cannot be ethically performed on human subjects,
- The animals used in the proposed research must be maintained in either ethologically appropriate physical and social environments or in natural habitats.
Criteria for Biomedical Research:
- There is no other suitable model available, such as in vitro, non-human in vivo, or other models, for the research in question, and
- 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
Criteria for Behavioral and Comparative Genomics Research:
- 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, in a manner that minimizes pain and distress, and is minimally invasive.
These recommendations seem to differ from current practice in two particular areas. They would not allow basic research even if it poses minimal risk, and they would preclude research to benefit of chimpanzees and other apes, such as recent effort to develop an Ebola vaccine. The omission of research to benefit animal health is understandable since the panel was charged with evaluating NIH-supported research. However, NIH Director Collins decided to apply the guidelines not only to the research NIH funds, but also to animals it owns and research conducted in facilities it supports. The omission of minimally invasive basic research is more significant. Although comparative genomics research was mentioned in the criteria, comparative biology, comparative psychology, and comparative medicine were not. Inquiries in these areas may be beneficial to both human and chimpanzee health and ought to be permitted when the impact on the animal would be minor.
Summary of Findings
The panel concluded that although the chimpanzee “has been a valuable animal model in past research, most current use of chimpanzees for biomedical research is unnecessary, based on the criteria established by the committee.” These criteria distinguished between instances where chimpanzees were necessary to the research, as opposed to whether they were useful. Areas of research that the panel thought could be phased out include the study of malaria, HIV/AIDS, basic immunology, and a therapeutic vaccine and anti-viral drugs for chronic hepatitis C infection. Other current research areas likely to meet the new criteria include the development of certain monoclonal antibodies and a vaccine to prevent hepatitis C infection. However, even in these areas there are caveats. With respect to the development of monoclonal antibodies, the panel believes that new technologies will obviate the need for chimpanzees in the future, but those technologies still have to be refined and disseminated. With respect to a prophylactic vaccine for hepatitis C, the panel was evenly split on the question of whether continued chimpanzee research was necessary, leaving it up to an NIH working group to make the final assessment.
Nevertheless, the panel cautioned that in the future an emerging or re-emerging disease “may present challenges to treatment, prevention, and/or control that defy non-chimpanzee models.” In addition, the committee endorsed comparative genomics research with chimpanzees since their genetic proximity to humans may shed light on human development, disease mechanisms, and susceptibility. The panel also noted that such research is more likely to be acceptable when it requires only blood or other biological samples that have already been collected or that will cause minimal pain and distress to collect. In addition, the panel acknowledged a need for some research on social and behavioral factors related to disease development, prevention and treatment.
NIH commissioned the IOM study at the request of Senators Tom Harkin (D-IA), Tom Udall (D-NM) and Jeff Bingaman (D-NM) in the wake of controversy over NIH’s decision to move 176 chimpanzees from the Alamogordo facility to the Texas Biomedical Research Institute in San Antonio. In developing the report, the 12-member panel received expert testimony existing and anticipated alternatives to chimpanzees in biomedical and behavioral research and reviewed scientific evidence including the literature. The panel also commissioned a paper the topic “Comparison of Immunity to Pathogens in Humans, Chimpanzees, and Macaques” that was published as a 70-page appendix to the 90-page report. In addition, the panel considered nearly 6,000 comments from sources ranging from scientific experts to members of the public concerned about the treatment of chimpanzees. Finally, it applied its new criteria to current chimpanzee research identified in NIH’s RePORT database.