Attachment 3 Working Group Report

Council of Councils Working Group on the
Use of Chimpanzees in NIH-Supported Research
Report

Contents
Executive Summary ........................................................................................................................ 2 
Overview and Organization of the Report ...................................................................................... 8 
Glossary of Terms Used in this Report ........................................................................................... 9 
Section 1. NIH-Supported Chimpanzee Research and Institute of Medicine Principles and
Criteria .......................................................................................................................................... 12 
NIH-Supported Research Involving Chimpanzees ................................................................... 12 
Committee on the Use of Chimpanzees in Biomedical and Behavioral Research.................... 13 
2011 IOM Report: Principles and Criteria ................................................................................ 14 
Section 2. Working Group on the Use of Chimpanzees in NIH-Supported Research ................. 16 
Working Group Charge ............................................................................................................. 16 
Working Group Leadership and Subgroups .............................................................................. 16 
Timeline of Major Activities ..................................................................................................... 18 
Section 3. Ethologically Appropriate Physical and Social Environments: A Key Concept in the
IOM Principles .............................................................................................................................. 19 
Background ............................................................................................................................... 19 
Ethologically Appropriate Physical and Social Environments for Captive Chimpanzees........ 19 
Social Environments ................................................................................................................. 20 
Physical Environments .............................................................................................................. 21 
Animal Program Management Considerations ......................................................................... 23 
Additional Considerations ......................................................................................................... 25 
Section 4. Review of Currently Active NIH-Supported Research Using Chimpanzees .............. 28 
Review Outcomes ..................................................................................................................... 28 
Working Group Recommendations on Currently Active Projects ............................................ 29 
Section 5. Size and Placement of Research-Active and Research-Inactive Populations of NIHowned and NIH-supported Chimpanzees ..................................................................................... 31 
Background ............................................................................................................................... 31 
Future Need for Chimpanzees in Research ............................................................................... 32 
Predictions of Future Need Based on the Assessments of the Emerging Diseases Subgroup .. 34 
Colony Size and Placement Recommendations ........................................................................ 35 
Section 6. Review Process for Future Proposals to Use Chimpanzees in NIH-Supported Research
....................................................................................................................................................... 38 
IOM Guidance ........................................................................................................................... 38 
Oversight Committee Composition........................................................................................... 38 
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Review Process ......................................................................................................................... 40 
Section 7: Conclusion ................................................................................................................... 47 
References ..................................................................................................................................... 48 
Acknowledgements ....................................................................................................................... 52 
Appendix A: Working Group on the Use of Chimpanzees in NIH-Supported Research
Membership Roster ....................................................................................................................... 53 
Appendix B: Biographies of Members of the Working Group on the Use of Chimpanzees in
NIH-Supported Research .............................................................................................................. 54 
Appendix C: Consultants to the Working Group on the Use of Chimpanzees in NIH-Supported
Research ........................................................................................................................................ 58 
Appendix D: Schedule of Meetings and Field Trips of the Working Group on the Use of
Chimpanzees in NIH-Supported Research ................................................................................... 59 
Appendix E: Summary of Expert Interviews ................................................................................ 61 
Appendix F: Summary of Public Input from NIH Requests for Information ............................... 64 
Appendix G: White Paper on the Use of Chimpanzees in New, Emerging, and Reemerging
Diseases Research ......................................................................................................................... 71 

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Executive Summary
This report summarizes the findings and recommendations of the Working Group on the Use of
Chimpanzees in National Institutes of Health (NIH)-Supported Research. The NIH formed this
committee within the Council of Councils, a federal advisory committee, to advise the NIH on
the implementation of the recommendations of the Institute of Medicine’s (IOM’s) Committee
on the Use of Chimpanzees in Biomedical and Behavioral Research regarding the use of
chimpanzees in NIH-sponsored research. In December 2010, the NIH asked the IOM to review
the current use of chimpanzees in NIH-funded biomedical and behavioral research that is needed
to advance the public’s health. The IOM committee focused its efforts on the nearly 700
chimpanzees owned or otherwise supported by the NIH.
In December 2011, the IOM committee completed its review, concluding that although the
chimpanzee has been a valuable animal model in the past, most current biomedical use of
chimpanzees is unnecessary. At the same time, the IOM committee concluded that chimpanzees
could still serve an important role in some areas of research but in these areas, the research must
be governed by a set of principles and criteria. These principles and criteria address the necessity
of the research for answering important public health questions, the need to use the chimpanzee
model to answer these questions, and whether the chimpanzee-housing and the research
conditions are appropriate for humans’ closest relative.
The NIH immediately accepted the IOM committee’s principles and criteria and assembled the
Working Group on the Use of Chimpanzees in NIH-Supported Research in February 2012. The
NIH charged the Working Group in February 2012 with:
 Developing a plan for implementation of the IOM’s guiding principles and criteria;
 Analyzing currently active NIH-supported research using chimpanzees to advise on
which studies currently meet the principles and criteria defined by the IOM report and
advising on the process for closing studies if any do not comply with the IOM
recommendations;
 Advising on the size and placement of active and inactive populations of NIH-owned or
-supported chimpanzees that may need to be considered as a result of implementing the
IOM recommendations; and
 Developing a review process for considering whether potential future use of the
chimpanzee in NIH-supported research is scientifically necessary and consistent with the
IOM principles.
On January 22, 2013, the Working Group delivered its report and recommendations to the NIH
Council of Councils. The Working Group’s recommendations are listed below. The body of this
report provides background information on all of these issues.
Ethologically Appropriate Physical and Social Environments: A Key Concept in the IOM
Principles
Throughout its report, the IOM committee used the term “ethologically appropriate physical and
social environments” as a central principle for how chimpanzees used in research should be
housed. Because the IOM report did not provide further details, the Working Group first defined
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the term “ethologically appropriate physical and social environments” as environments that not
only allow, but importantly, promote the full range of natural chimpanzee behaviors. The
Working Group then used this definition to make recommendations concerning the placement of
research chimpanzee populations.
The Working Group’s recommendations with respect to ethologically appropriate physical and
social environments are as follows:
Recommendation EA1: Chimpanzees must have the opportunity to live in sufficiently large,
complex, multi-male, multi-female social groupings, ideally consisting of at least 7
individuals. Unless dictated by clearly documented medical or social circumstances, no
chimpanzee should be required to live alone for extended periods of time. Pairs, trios, and
even small groups of 4 to 6 individuals do not provide the social complexity required to meet
the social needs of this cognitively advanced species. When chimpanzees need to be housed
in groupings that are smaller than ideal for longer than necessary, for example, during routine
veterinary examinations or when they are introduced to a new social group, this need should
be regularly reviewed and documented by a veterinarian* and a primate behaviorist.
*In this context, the Working Group defines a “veterinarian” as a licensed, graduate veterinarian with
demonstrated expertise in the clinical care and welfare of nonhuman primates (preferably chimpanzees) and
who is directly responsible for the routine clinical care of the animal(s) in question.

Recommendation EA2: The density of the primary living space of chimpanzees should be
at least 1,000 ft2 (93 m2) per individual. Therefore, the minimum outdoor enclosure size for a
group of 7 animals should be 7,000 ft2 (651 m2).
Recommendation EA3: Chimpanzees must be housed in environments that provide outdoor
access year round. They should have access to natural substrates, such as grass, dirt, and
mulch, to enhance environmental complexity.
Recommendation EA4: Chimpanzees should have the opportunity to climb at least 20 ft
(6.1 m) vertically. Moreover, their environment must provide enough climbing opportunities
and space to allow all members of larger groups to travel, feed, and rest in elevated spaces.
Recommendation EA5: Progressive and ethologically appropriate management of
chimpanzees must include provision of foraging opportunities and of diets that are varied,
nutritious, and challenging to obtain and process.
Recommendation EA6: Chimpanzees must be provided with materials to construct new
nests on a daily basis.
Recommendation EA7: The environmental enrichment program developed for chimpanzees
must provide relevant opportunities for choice and self-determination.
Recommendation EA8: Chimpanzee management staff must include experienced and
trained behaviorists, animal trainers, and enrichment specialists to foster positive human–
animal relationships and provide cognitive stimulation. Given the importance of
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trainer/animal ratios in maintaining trained behaviors, a chimpanzee population of 50 should
have at least 2 dedicated staff members with this type of expertise. Positive reinforcement
training is the only acceptable method of modifying behaviors to facilitate animal care and
fulfillment of management needs. Training plans should be developed for each animal, and
progress toward achieving established benchmarks should be documented.
Recommendation EA9: All personnel working with chimpanzees must receive training in
core institutional values promoting psychological and behavioral well-being of chimpanzees
in their care. These institutional core values should be publicly accessible.
Recommendation EA10: Chimpanzee records must document detailed individual animal
social, physical, behavioral, and psychological requirements and these requirements should
be used to design appropriate individualized chimpanzee management in the captive research
environment.
Chimpanzee Research Colony Size and Placement
The Working Group’s charge included advising the NIH on the size and placement of NIHowned and NIH-supported research-active and research-inactive chimpanzee populations. The
Working Group’s recommendations with respect to colony size and placement, including
whether additional chimpanzees are needed for research to prepare for new, emerging, and
reemerging diseases, are as follows:
Recommendation SP1: The majority of NIH-owned chimpanzees should be designated for
retirement and transferred to the federal sanctuary system. Planning should start
immediately to expand current facilities to accommodate these chimpanzees. The federal
sanctuary system is the most species-appropriate environment currently available and thus is
the preferred environment for long-term housing of chimpanzees no longer required for
research.
Recommendation SP2: A small population of chimpanzees should be maintained for future
potential research that meets the IOM principles and criteria. Based on an assessment of
current research protocols and interviews with content experts and current research facility
administrators, this colony is estimated to require approximately 50 chimpanzees. The size
and placement of this colony should be reassessed on a frequent basis (approximately every 5
years) to ensure that such a colony is still actually needed and that the animals are not
overused.
Recommendation SP3: This small chimpanzee colony should be maintained at a facility that
has the characteristics of ethologically appropriate physical and social environments
described in this report. Thus, plans should be made now to ensure that ethologically
appropriate physical and social housing conditions will be available within 3 to 5 years.
Maintaining the chimpanzee colony at a single facility could be advantageous to minimize
costs and maximize management flexibility.

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Recommendation SP4: The demographic constitution of this small chimpanzee colony is
important to maximize its utility for research. Ideally, the colony should be age and sex
stratified, have an approximately 50:50 sex ratio, and be composed primarily of animals that
are healthy and younger than 30 years. At least half of this population should be
physiologically naïve to infection (e.g., hepatitis or HIV). When this colony is formed, best
practices should be used for maintaining current social groupings, whenever possible, to
minimize adverse stress.
Recommendation SP5: The NIH should review its funding priorities for comparative
behavioral, cognitive, and genomics studies using chimpanzees. The NIH should consider
targeting funding for low-burden projects that can be conducted in nontraditional research
settings that can maintain ethologically appropriate environments or projects that use
materials collected during routine veterinary examinations.
Recommendation SP6: The NIH should not support any long-term maintenance of
chimpanzees intended for research on new, emerging, or reemerging diseases in animal
biosafety level 2 or greater biocontainment-level facilities.
Recommendation SP7: The NIH should not, on its own, revitalize breeding strategies to
derive a population of chimpanzees for any research, including for new, emerging, or
reemerging disease research.
Recommendation SP8: The NIH should collaborate with other federal agencies (i.e.,
Centers for Disease Control and Prevention and Food and Drug Administration) and
departments (i.e., Department of Defense and Department of Homeland Security) when
considering any future plan for placement, maintenance, and use of chimpanzees in research
in response to a new, emerging, or reemerging disease that could represent a national security
risk to the United States.
Recommendation SP9: In light of evidence suggesting that research involving chimpanzees
has rarely accelerated new discoveries or the advancement of human health for infectious
diseases, with a few notable exceptions such as the hepatitis viruses, the NIH should
emphasize the development and refinement of other approaches, especially alternative animal
models (e.g., genetically altered mice), for research on new, emerging, and reemerging
diseases.
Review Process for Future Proposals to Use Chimpanzees in NIH-Supported Research
Part of the Working Group’s charge was to advise on a review process for considering whether
the potential future use of chimpanzees in NIH-supported research is scientifically necessary and
consistent with the IOM principles. The Working Group’s recommendations regarding the
establishment of an independent oversight committee and review process are as follows:

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Oversight Committee Independence and Expertise
Recommendation RP1: The NIH should replace the Interagency Animal Models Committee
with an independent Oversight Committee for Proposals Using Chimpanzees in NIHsupported Research (Oversight Committee) to advise on the proposed use of chimpanzees in
research. The current Interagency Animal Models Committee is not considered independent
from other individuals and bodies that review and approve grant applications to the NIH,
contains no members of the public, and thus does not fully meet the spirit of the IOM
principles and criteria.
Recommendation RP2: The Oversight Committee should be separate from extramural
initial review groups, intramural scientific program personnel, and Institute or Center
directors. In addition, the Oversight Committee’s reviews should take place after the standard
reviews and approvals by these entities. The Oversight Committee’s reviews will focus on
whether the proposed research is consistent with the IOM principles and criteria for the use
of chimpanzees in research.
Recommendation RP3: The Oversight Committee should be comprised of individuals with
the specific scientific, biomedical, and behavioral expertise needed to properly evaluate
whether a grant, intramural program, contract, or other award mechanism supporting research
using chimpanzees complies with the IOM principles and criteria.
Review Process
Recommendation RP4: Investigators seeking NIH funding to conduct research using
chimpanzees must explain in their application how their proposed research complies with the
IOM principles and criteria. This supplemental information must address all of the questions
posed in the decision-making algorithm in this report and provide sufficient detail for
consideration by the Oversight Committee. This information is in addition to the vertebrate
animal section and/or applicable animal study protocol. The NIH might wish to develop a
form or other suggested template for investigators to use for this purpose.
Recommendation RP5: To ensure that the scientific use of chimpanzees is justified, the
animal numbers and group sizes must be statistically justified before the NIH approves any
proposed research project involving the use of chimpanzees.
Recommendation RP6: Investigators need not include supplemental information on
chimpanzee use for proposals involving the following, and these proposals will be exempt
from Oversight Committee review:
 The use of any biomaterials, including pathological specimens, collected and/or stored
prior to submission of the research proposal,or as part of a research grant or contract that
has undergone Oversight Committee review and approval, or as part of regular veterinary
(health) examinations;
 Other observational or non-interventional studies, such as behavioral observations in the
wild that do not result in contact or otherwise interfere with the chimpanzees being
observed; or
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

Noninvasive collection of samples from the wild in a manner that does not result in
contact or otherwise interfere with the chimpanzees during the collection.

Placement of Oversight Committee Review
Recommendation RP7: The Oversight Committee review should take place after the Center
or Institute director approves a proposal so that the key elements of the review are publicly
accessible to the extent allowable by federal regulations. The Oversight Committee should
review all requests for grants, contracts, intramural projects, and third-party projects rather
than establishing a separate review process for each mechanism. Funding of an award for
research involving the use of chimpanzees that has received an Institute or Center director’s
approval will be conditional and subject to the subsequent evaluation by the Oversight
Committee.
Recommendation RP8: The Oversight Committee will base its reviews on the supplemental
information provided by investigators on how the proposed research complies with the IOM
principles and criteria and all relevant documents (including animal study protocols and grant
applications) required to make informed determinations for all funding requests (grants,
contracts, and intramural projects) and other requests to use chimpanzees (e.g., third-party
projects).
Recommendation RP9: The Oversight Committee will determine whether each application
meets or does not meet the IOM principles and criteria based on the votes of a majority of all
voting members. At its members’ discretion, the Oversight Committee may vote on whether
different components or parts of an application meet or do not meet the IOM principles and
criteria.

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Overview and Organization of the Report
This report provides two brief introductory sections and four chapters that address the charge of
the Working Group on the Use of Chimpanzees in National Institutes of Health (NIH)-Supported
Research.
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Section 1 provides background information on the use of chimpanzees in NIH-supported
research and introduces the principles and criteria of the Institute of Medicine’s (IOM’s)
Committee on the Use of Chimpanzees in Biomedical and Behavioral Research.
Section 2 describes the creation, charge, and activities of the Working Group.
Section 3 describes the process that the Working Group used to develop an
implementation plan for the IOM principles and criteria and defines the term
“ethologically appropriate physical and social environments,” a key term used in the IOM
principles and throughout this report.
Section 4 offers the Working Group’s recommendations regarding the future of currently
funded research projects using chimpanzees.
Section 5 addresses the number of chimpanzees that might be needed for NIH-funded
research in the future and the placement of these animals. This section also addresses
whether chimpanzees are likely to be needed to study new, emerging, and reemerging
diseases.
Section 6 provides recommendations and implementation guidance pertaining to the
review process for considering whether the potential future use of chimpanzees in NIHsupported research is scientifically necessary and consistent with the IOM principles and
criteria.

In some cases, the Working Group made specific recommendations regarding critical aspects of
chimpanzee environments. The Working Group developed these quantitative recommendations
using a range of inputs, including Working Group members’ expertise, interviews of experts
with knowledge of wild and captive chimpanzees, published information about the behavior of
wild and captive chimpanzees, and consideration of practical constraints pertaining to
chimpanzee management and facilities.
This overview is followed by a glossary of terms used in this report. The appendices include the
Working Group member roster and biographies; list of consultants; schedule of Working Group
activities; summary of expert interviews conducted by the Working Group; summary of public
input in response to NIH requests for information on the use of chimpanzees in research; and a
white paper on the use of chimpanzees for research on new, emerging, and reemerging diseases.

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Glossary of Terms Used in this Report
Acquiescence: voluntary participation in an activity based solely on positive reinforcement
training and not involving forced participation or engagement by coercion. According to this
definition, animals choose whether to participate or not based on their own volition.
Behavioral research: research that involves the study of overt actions; underlying psychological
processes such as cognition, emotion, temperament, and motivation; and biobehavioral
interactions.
Biomedical research: a broad area of science that seeks ways to prevent and treat diseases that
cause illnesses and death in people and in animals. Biomedical researchers study biomedical
processes and diseases with the ultimate goal of developing effective treatments and cures.
Chimpanzee Health Improvement Maintenance and Protection (CHIMP) Act: an act,
signed by the President on December 20, 2000, to amend the Public Health Service Act to
provide for a system of sanctuaries for retired chimpanzees that are no longer needed in federally
funded research.
Chimp Haven is Home Act: an act, signed by the President on December 26, 2007, to amend
the Public Health Service Act and modify the CHIMP Act by terminating the authority to
remove retired chimpanzees from the sanctuary system for research purposes.
Committee on the Use of Chimpanzees in Biomedical and Behavioral Research (also
referred to as “IOM Committee”): committee formed by the IOM and the National Research
Council to review the current use of chimpanzees in NIH-funded biomedical and behavioral
research that is needed for the advancement of the public’s health.
Comparative genomics: a field of biological research in which the genome sequences of
different species (such as humans, mice, and chimpanzees) are compared. These comparisons
allow researchers to identify regions of similarity and difference, shedding light on the structure
and function of human genes and supporting the development of new strategies to combat human
disease.
Council of Councils: a federal advisory committee established by the NIH Reform Act of 2006,
passed by Congress in December 2006 and signed into law by the President in January 2007. The
Council advises the NIH Director and other delegated officials on matters related to the policies
and activities of the Division of Program Coordination, Planning, and Strategic Initiatives.
Culture of care: concept embraced by the Working Group that should be promoted in
ethologically appropriate environments. In a culture of care, chimpanzees are managed in a
manner that engenders respect and mutually positive human-animal relationships.
Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI): a
component of the NIH whose mission is to identify emerging scientific opportunities, rising

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public health challenges, and scientific knowledge gaps that merit further research. DPCPSI
oversees the NIH Chimpanzee Management Program.
Emerging diseases: include outbreaks of previously unknown infectious diseases or known
diseases whose incidence or geographic range is increasing in humans.
Ethologically appropriate physical and social environments (also referred to as
“ethologically appropriate environments”): captive environments that do not simply allow but
also, importantly, promote a full range of behaviors that are natural for chimpanzees.
Ethologically inappropriate environments: environments that do not provide the complexity
and stimulation that chimpanzees need, such as environments that house smaller groups of
animals and have only moderate complexity or in which chimpanzees are managed through the
use of squeeze cages and frequent darting or tranquillization for holding or experimental
purposes.
Federal sanctuary system: the sanctuary system created in compliance with the CHIMP Act to
provide lifetime care for federally owned retired chimpanzees that are no longer needed for
research.
Institute of Medicine (IOM): an independent, nonprofit organization that works outside of
government to provide unbiased and authoritative advice to decision makers and the public.
Interagency Animal Models Committee: chartered by the NIH in 1989 to provide oversight of
all federally supported biomedical and behavioral research involving chimpanzees.
Invasive research: according to the Standards for a National Chimpanzee Sanctuary System,
research that causes more than momentary pain, distress, fear, discomfort, injury, or other
negative modalities to a chimpanzee, including any procedure that enters or exposes a body
cavity.
Minimally invasive research: any research that inflicts little or no harm and that minimizes pain
and distress.
National Institutes of Health (NIH): an agency of the U.S. Department of Health and Human
Services that is the primary U.S. government agency responsible for biomedical and healthrelated research.
National Primate Research Centers (NPRCs): provide facilities, animals, and expertise for
investigators using nonhuman primates for biomedical research. NPRCs are supported in part by
the NIH.
New, emerging, and reemerging diseases: new infectious diseases or diseases of infectious
origin whose incidence in humans has increased within the past two decades or threatens to
increase in the near future.

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NIH-owned chimpanzees: chimpanzees directly owned by the NIH.
NIH-supported chimpanzees: chimpanzees not owned by the NIH but supported through NIH
awards, such as grants and contracts.
Nonhuman primates: all nonhuman members of the order Primates, including monkeys,
chimpanzees, orangutans, gorillas, gibbons, apes, baboons, marmosets, tamarins, lemurs, and
lorises.
Noninvasive research: research that involves minimal physical and mental harm, pain, distress,
and disturbance to the chimpanzee and the social group in which the chimpanzee lives.
Reemerging diseases: known diseases that have reappeared after a significant decline in
incidence.
Research-active chimpanzees: NIH-owned or -supported chimpanzees used for current research
projects.
Research-inactive chimpanzees: NIH-owned or -supported chimpanzees not currently used for
research but that might be used for new projects that meet the IOM principles and criteria.
Retired chimpanzees: chimpanzees that live permanently in the federal sanctuary system and
cannot be removed from that system.
Temporary housing conditions: conditions needed to hold animals for between 24 hours and 21
days, such as standard indoor-outdoor run cages, outdoor geodesic housing structures, and small
outdoor corrals.
Transitional housing conditions: an interim solution that is not intended for long-term housing
of chimpanzees under any circumstance and should only be approved after detailed plans for
achieving ethologically appropriate physical and social environment conditions have been
formalized.
Veterinarian: a licensed, graduate veterinarian with demonstrated expertise in the clinical care
and welfare of nonhuman primates (preferably chimpanzees) and who is directly responsible for
the routine clinical care of the animal(s) in question.
Working Group on the Use of Chimpanzees in NIH-Supported Research: created on
February 1, 2012, within the Council of Councils of the NIH and charged to provide advice on
the implementation of the principles and criteria in the IOM report, Chimpanzees in Biomedical
and Behavioral Research: Assessing the Necessity.

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Section 1. NIH-Supported Chimpanzee Research and Institute of
Medicine Principles and Criteria
The National Institutes of Health (NIH), part of the U.S. Department of Health and Human
Services, is the nation’s medical research agency. The mission of the NIH is to seek fundamental
knowledge about the nature and behavior of living systems and to apply that knowledge to
enhance health, lengthen life, and reduce the burdens of illness and disability. To fulfill this
mission, the NIH sponsors research throughout the world and in its own laboratories.
Some research activities supported by the NIH involve the use of animal models to study
important biomedical and/or behavioral conditions, and the agency devotes additional resources
to caring for and housing animals used in research. The use of animals in research has enabled
scientists to identify new ways to treat illness, extend life, and improve health and well-being.
NIH-Supported Research Involving Chimpanzees
In limited circumstances, the NIH has funded research involving chimpanzees. Chimpanzees’
close genetic proximity to humans makes them a uniquely valuable species for studying certain
human conditions; they have provided exceptional insights into human biology and behavior. For
example, this research has:
 Contributed significantly to the development of the hepatitis A and B vaccines in use
today. These vaccines are usually given to children and, since 1991, the number of
hepatitis B cases in children under age 15 years has declined by 98 percent. The rate of
new hepatitis A infections in the United States dropped by more than 92 percent between
1995 and 2008.
 Identified the hepatitis C virus, which has led to improved public health measures,
increased the safety of blood donations, and led to the development of emerging therapies
(Choo et al. 1989).
 Determined that dietary salt is a major causative factor in elevated blood pressure
(Denton et al., 1995).
 Developed monoclonal antibodies approved by the U.S. Food and Drug Administration
for use in treating lymphomas and other cancers and establishing that certain in vitro
differentiated immune cells can serve as vehicles for cancer immunotherapy (Larsson et
al., 2004).
NIH-funded research involving chimpanzees has ranged from studies of infectious agents,
hepatitis, and HIV/AIDS to studies of learning, cognition, and mental health conditions. Today,
however, new methods and technologies developed by the biomedical community have provided
alternatives to the use of chimpanzees in several areas of research.
Except for brief surges in research to explore new hypotheses, the NIH estimates that researchers
proposed using approximately 100 chimpanzees for biomedical research sponsored by the NIH
each year, on average, throughout the 1990s. The average number proposed for biomedical
research increased to approximately 200 chimpanzees per year in the 2000s. For behavioral
research, the NIH estimates that researchers proposed using slightly more chimpanzees than for
biomedical research during these periods.
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Although the NIH funds more chimpanzee research than any other federal agency, only a very
small proportion—less than one tenth of one percent—of active NIH projects involve
chimpanzees as of January 22, 2013. In a recent review of awarded projects involving
chimpanzees, the NIH identified 30 projects that were actively using chimpanzees between May
and December 2012. These projects involved biomedical, behavioral, or comparative genomics
research using chimpanzees or used NIH funds to pay for the care and housing of chimpanzees.
Additional details about these projects are available in Section 4 of this report.
Committee on the Use of Chimpanzees in Biomedical and Behavioral Research
Members of the public, Congress, and some scientists have inquired about the continued need for
the NIH to sponsor biomedical and behavioral research that uses chimpanzees. Some contend,
for example, that chimpanzees are not suitable models in many cases for studies of human
disease or that research can accomplish its aims without using this animal model (Institute of
Medicine [IOM], 2011). However, other experts point out that research using chimpanzees has
made critical contributions to public health, including the development of the Sabin polio
vaccine and the identification of the hepatitis C virus, and this research is necessary to improve
our understanding of certain diseases and conditions (Nature, 2011).
In December 2010, U.S. Senators Jeff Bingaman (D-NM), Tom Harkin (D-IA), and Tom Udall
(D-NM) asked the National Academies to analyze the current and future need for the use of
chimpanzees in biomedical research. That same month, the NIH commissioned a study by the
IOM of the National Academies to assess whether chimpanzees are or will be necessary for
biomedical and behavioral research.
In response to the NIH request, the IOM collaborated with the National Research Council to
form the Committee on the Use of Chimpanzees in Biomedical and Behavioral Research (IOM
committee). The IOM committee’s task was to review the current use of chimpanzees in NIHfunded biomedical and behavioral research that is needed for the advancement of the public’s
health.
To accomplish its task, the committee was to (IOM, 2011, p. 13):
 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. If biomedical research questions
are identified:
 Describe the unique biological/immunological characteristics of the chimpanzee
that made it the necessary animal model for use in the types of research;
 Provide recommendations for any new or revised scientific parameters to guide
how and when to use these animals for research; and
 Explore contemporary and anticipated behavioral research questions to determine if
chimpanzees are necessary for progress in understanding social, neurological, and
behavioral factors that influence the development, prevention, or treatment of disease.

13

2011 IOM Report: Principles and Criteria
In addressing its task, the IOM committee explored contemporary and anticipated future
alternatives to the use of chimpanzees in biomedical and behavioral research that will be needed
for the advancement of the public’s health. The committee collected information for its analysis
by holding three 2-day meetings, including two public information-gathering sessions. In
addition, the committee met by conference call, solicited public comments, examined the current
availability and use of chimpanzees, and reviewed the scientific literature.
The IOM issued a report, Chimpanzees in Biomedical and Behavioral Research: Assessing the
Necessity, summarizing the committee’s findings on December 15, 2011 (IOM, 2011). In its
report, the committee identified three principles to serve as the basis for its criteria for assessing
the use of chimpanzees in biomedical and behavioral research (IOM, 2011, pp. 26–27):
1. The knowledge gained must be necessary to advance the public’s health;
2. There must be no other research model by which the knowledge could be obtained, and
the research cannot be ethically performed on human subjects; and
3. The animals used in the proposed research must be maintained either in ethologically
appropriate physical and social environments or in natural habitats.
The committee developed separate sets of criteria for assessing the necessity of using
chimpanzees for biomedical research and for comparative genomics and behavioral research:
Biomedical research (IOM, 2011, pp. 67–68): The National Institutes of Health should limit
the use of chimpanzees in biomedical research to those studies that meet the following three
criteria:
1. There is no other suitable model available, such as in vitro, nonhuman in vivo, or other
models, for the research in question; and
2. The research in question cannot be performed ethically on human subjects; and
3. 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.
Animals used in the proposed research must be maintained either in ethologically
appropriate physical and social environments or in natural habitats. Biomedical research
using stored samples is exempt from these criteria.
Comparative genomics and behavioral research (IOM, 2011, p. 69): The National Institutes
of Health should limit the use of chimpanzees in comparative genomics and behavioral
research to those studies that meet the following two criteria:
1. Studies provide otherwise unattainable insight into comparative genomics, normal and
abnormal behavior, mental health, emotion, or cognition; and
2. All experiments are performed on acquiescent animals, using techniques that are
minimally invasive, and in a manner that minimizes pain and distress.

14

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.
The IOM committee concluded that “while the chimpanzee has been a valuable animal model in
past research, most current use of chimpanzees for biomedical research is unnecessary” (IOM,
2011, pp. 66–67). However, the IOM committee also stated that the following areas might
continue to require the use of chimpanzees: some ongoing research on monoclonal antibody
therapies; research on comparative genomics; and noninvasive studies of social and behavioral
factors that affect the development, prevention, or treatment of disease. The committee was
unable to reach consensus on the necessity of using chimpanzees to develop a prophylactic
hepatitis C virus vaccine. Although the committee encouraged the NIH to continue to develop
non-chimpanzee models and technologies, it acknowledged that new, emerging, and reemerging
diseases could present challenges that might require the use of chimpanzees.
NIH Response to the IOM Report and Creation of the Working Group
On December 15, 2011, Francis S. Collins, M.D., Ph.D., Director of the NIH, accepted the IOM
committee recommendations and announced that the NIH was developing a plan for
implementing the IOM committee’s guiding principles and criteria.1 On December 21, 2011, Dr.
Collins announced that the NIH would not fund any new or other competing projects (renewals
and revisions) for research involving chimpanzees and would not allow any new projects to go
forward with chimpanzees2 until the NIH issues further policy implementing the IOM’s
recommendations. The NIH subsequently clarified that the NIH would accept for peer review
competing applications proposing the use of samples obtained from chimpanzees on or before
December 15, 2011—the date on which the NIH accepted the IOM committee’s
recommendations.3 The NIH released this clarification in response to investigator concerns that
the NIH policy might prohibit investigators from using stored samples from chimpanzees in
research—an area of research that the IOM committee explicitly exempted from its criteria.
In addition, as part of its plan for implementing the IOM committee’s guiding principles and
criteria, the NIH created the Working Group on the Use of Chimpanzees in NIH-Supported
Research within the NIH Council of Councils on February 1, 2012. The NIH Council of
Councils provides advice to the NIH Director and other appropriate delegated officials on
matters related to the policies and activities of the Division of Program Coordination, Planning,
and Strategic Initiatives. The Division oversees the NIH Chimpanzee Management Program.

1

Statement by NIH Director Dr. Francis Collins on the Institute of Medicine report addressing the scientific need for
the use of chimpanzees in research: http://www.nih.gov/news/health/dec2011/od-15.htm.
2
National Institutes of Health. NOT-OD-12-025: NIH Research Involving Chimpanzees:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-025.html
3
National Institutes of Health. NOD-OD-12-116, Clarification to the Interim Agency Policy, NIH Research
Involving Chimpanzees: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-12-116.html

15

Section 2. Working Group on the Use of Chimpanzees in NIHSupported Research
Working Group Charge
On February 2, 2012, the NIH charged the Working Group on the Use of Chimpanzees in NIHSupported Research to provide advice on the implementation of the recommendations made by
the IOM committee in its report, Chimpanzees in Biomedical and Behavioral Research:
Assessing the Necessity (IOM, 2011). The NIH asked the Working Group to prepare a report for
consideration by the Council of Councils addressing the following elements of the Working
Group’s charge:
 Developing a plan for implementation of the IOM’s guiding principles and criteria;
 Analyzing currently active NIH-supported research using chimpanzees to advise on
which studies currently meet the principles and criteria defined by the IOM report and
advising on the process for closing studies if any do not comply with the IOM
recommendations4;
 Advising on the size and placement of active and inactive populations of NIH-owned or
-supported chimpanzees that may need to be considered as a result of implementing the
IOM recommendations; and
 Developing a review process for considering whether potential future use of the
chimpanzee in NIH-supported research is scientifically necessary and consistent with the
IOM principles.
Working Group Leadership and Subgroups
Co-Chairs and Members
The NIH selected two members of the Council of Councils, Daniel H. Geschwind, M.D., Ph.D.,
and K.C. Kent Lloyd, D.V.M., Ph.D., to serve as co-chairs of the Working Group and oversee all
Working Group activities. In consultation with the co-chairs, the NIH selected members of the
Working Group with expertise in research involving chimpanzees, chimpanzee behavior and
conservation, veterinary medicine, infectious diseases, and biomedical ethics. The Working
Group’s membership roster, member biographies, and consultants roster are available in
Appendix A, Appendix B, and Appendix C, respectively.
Lists of the Working Group’s meetings and field trips are available in Appendix D. At least one
NIH employee attended all Working Group meetings.
Subgroups
The Working Group created four subgroups, described in Table 1, to fulfill its charge. Three of
the subgroups consisted only of Working Group members. Due to the highly specialized topics
4

The Working Group has not participated in any NIH decisions regarding funding of grants, contracts, or other
awards.

16

addressed by the Emerging Diseases Subgroup, that subgroup sought input from expert
consultants. The Colony Management Subgroup interviewed experts on ethologically appropriate
environments and on the size and placement of chimpanzees (see list of experts interviewed and
a summary of interviews in Appendix E). The Colony Management, Emerging Diseases, and
Process Review subgroups prepared draft documents summarizing their deliberations and
recommendations. All Working Group members reviewed these documents, and this report
incorporates final versions of these documents.
Table 1: Subgroups of the Working Group on the Use of Chimpanzees in NIH-Supported
Research
Subgroup
Colony
Management
Subgroup

5
6

Members and/or Consultants
Beatrice Hahn, M.D.
Daniel Povinelli, Ph.D.5
Stephen Ross, Ph.D.
Patricia Turner, M.Sc., D.V.M., D.V.Sc.

Emerging
Diseases
Subgroup

Alan Barrett, Ph.D.
L. Bill Cummins, D.V.M.6
Frederick A. Murphy, D.V.M., Ph.D. 6
Mark Slifka, Ph.D.6
Lee Thompson6

Process
Review
Subgroup

Daniel Povinelli, Ph.D.
R. Alta Charo, J.D.
Daniel H. Geschwind, M.D., Ph.D.

Project
Review
Subgroup

All Working Group members

From February to September 2012 only
External expert

17

Responsibilities
 Evaluate and make recommendations
on the size and placement of colonies
of chimpanzees
 Draft recommendations on the IOM’s
principles regarding “ethologically
appropriate environments” for
chimpanzees
 Determine whether the use of
chimpanzees is necessary to study
emerging diseases or develop medical
countermeasures
 Identify the circumstances under
which chimpanzees should be used for
emerging disease research
 Evaluate whether one set of
metrics/standards could be developed
for both biomedical and
behavioral/cognitive studies involving
chimpanzees
 Assess and make recommendations
regarding the process for determining
the future need to use chimpanzees in
research
 Review active NIH research involving
chimpanzees
 Advise on the process for closing
studies that do not comply with IOM
recommendations

Timeline of Major Activities
The timeline for the creation of the Council of Councils Working Group on the Use of
Chimpanzees in NIH-Supported Research and its major activities is provided in Table 2.
Table 2. Timeline of Creation of Working Group and Major Working Group Activities
Activity

Date

Council of Councils approves creation of the Working Group
The NIH officially charges the Working Group
The NIH publishes requests for information in the NIH Guide for Grants
and Contracts and the Federal Register
Working Group provides updates to Council of Councils

Working Group presents its final report to the Council of Councils

February 1, 2012
February 2, 2012
February 10 and February
23, 2012, with responses due
by April 10, 2012
June 5, 2012
September 5, 2012
October 29, 2012
January 8, 2013
January 22, 2013

Public Input
To inform the deliberations of the Working Group, the NIH issued two requests for information
(RFIs) seeking public input on issues pertaining to the NIH’s implementation of the IOM
committee recommendations. The NIH published the RFIs in the NIH Guide for Grants and
Contracts7 on February 10, 2012 and in the Federal Register8 on February 23, 2012. In these
notices, the NIH asked for recommendations regarding the core areas of the Working Group’s
charge. The NIH received 110 comments in response to the two RFI notices. A summary of the
comments is available in Appendix F. The Working Group members reviewed the responses to
the RFI notices and took them into consideration when they developed the recommendations in
the current report.
Updates to the Council of Councils
The Working Group co-chairs provided four updates to the Council of Councils between
February 2012 and January 2013. During the publicly open sessions on June 5, 2012, and
September 5, 2012, the Council of Councils assessed the Working Group’s progress and offered
feedback. The co-chairs delivered additional updates during closed sessions on September 5,
2012, October 29, 2012, and January 8, 2013, to provide Working Group recommendations on
currently awarded research projects involving chimpanzees. The Working Group’s
recommendations regarding these projects are summarized in Section 4 of this report.
7

Request for Request for Information (RFI): Input into the Deliberations of the Council of Councils Working Group
on the Use of Chimpanzees in NIH-Supported Research: http://grants.nih.gov/grants/guide/notice-files/NOT-OD12-052.html
8
Request for Request for Information (RFI): Input into the Deliberations of the Council of Councils Working Group
on the Use of Chimpanzees in NIH-Supported Research: http://www.gpo.gov/fdsys/pkg/FR-2012-02-23/pdf/20124269.pdf

18

Section 3. Ethologically Appropriate Physical and Social
Environments: A Key Concept in the IOM Principles
Background
A key component of the Working Group’s charge was developing a plan to implement the IOM
committee’s principles and criteria. This effort involved convening subgroups with appropriate
expertise to fulfill the Working Group’s charge (described in Section 2 above), identifying
subgroup responsibilities (also described in Section 2), and identifying key questions that needed
to be answered to fully address the charge and to enable the NIH to implement the IOM
committee’s principles and criteria.
One of the key questions that the Working Group identified was how to define the term
“ethologically appropriate physical and social environments,” which the IOM committee used in
its guiding principles. This term lacked generally accepted definitions in the IOM report and
other literature. The Working Group therefore identified the characteristics of ethologically
appropriate social environments and ethologically appropriate physical environments to develop
a definition of “ethologically appropriate physical and social environments.” This section
describes the process that the Working Group used to identify those characteristics, its definition
of “ethologically appropriate physical and social environments,” and recommendations to assist
the NIH in operationalizing this concept. This section also addresses additional issues related to
captive environments, including chimpanzee management, the distinctions between ethologically
appropriate and inappropriate environments, and temporary and transitional housing.
Ethologically Appropriate Physical and Social Environments for Captive Chimpanzees
In its 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the
Necessity, the Committee on the Use of Chimpanzees in Biomedical and Behavioral Research
indicated that chimpanzees used in research should be maintained in either ethologically
appropriate physical and social environments or in natural habitats, based on the goal of
imposing “minimal physiological and psychological harm to the animals” (IOM, 2011, p. 28).
The IOM committee suggested that certain environments for chimpanzees accredited by the
Association for Assessment and Accreditation of Laboratory Animal Care International would be
suitable for future housing of chimpanzees being maintained for research purposes. However,
neither the IOM committee nor any other agency—including the Association of Zoos and
Aquariums, Council of Europe, and the U.S. National Research Council—has defined the
concept of an ethologically appropriate physical and social environment for captive
chimpanzees.
The Working Group was charged with advising the NIH on how to implement the IOM
committee’s recommendations. The Working Group therefore needed to provide a working
definition of ethologically appropriate physical and social environments for chimpanzees
referred to in the IOM principles pertaining to the future use of chimpanzees in biomedical and
comparative genomic and behavioral research.

19

The Working Group concluded that a captive environment can be considered ethologically
appropriate when it does not simply allow but also, importantly, promotes a full range of
behaviors that are natural for the species. In the tradition of modern ethology, the behavioral
repertoire of free-ranging wild chimpanzees is used as the model, or gold standard, toward which
facility management should aspire when developing captive environments.
The application of ethologically appropriate conditions to the maintenance of captive
chimpanzees is further complicated by the fact that this Working Group report deals solely with
chimpanzees maintained in captivity for research purposes. Although captive chimpanzees that
are permanently retired and unavailable for research might well be maintained in ethologically
appropriate physical and social environments, the NIH asked the Working Group to provide
advice only on conditions for chimpanzees actively engaged in research protocols and for
chimpanzees that are research inactive,or not currently participating in research.
The Working Group promotes a holistic and performance-based approach to creating an
ethologically appropriate environment for captive chimpanzee management. Defining the full
range of physical and social components that are critical for chimpanzee well-being would be
challenging, and generating definitive, empirically based data for each program element would
be nearly impossible. Thus, the Working Group’s intent is to provide a framework for all
significant parameters that constitute an ethologically appropriate physical and social
environment for captive chimpanzees. In addition to physical and social characteristics, these
parameters include factors related to animal management.
The environment and behavior of wild chimpanzees must be understood before determining how
to recapitulate the most important aspects of the natural behavioral repertoire of chimpanzees in
captive settings. The following subsections describe the environmental and behavioral features of
chimpanzees’ natural habitat along with the Working Group’s recommendations based on these
features.
Social Environments
The most critical component of ethologically appropriate physical and social environments is the
social environment. Chimpanzees in the wild live in large fission-fusion communities of up to
150 individuals, and constantly changing smaller subgroups of individuals break off and
periodically rejoin the primary group (Wrangham, 1979; Goodall, 1986; Chapman et al., 1995).
A core of adult males, which form the primary hierarchical structure of the community,
dominates these groups. A less well-defined hierarchy exists among females (Pusey et al., 1997).
Wild chimpanzee communities are composed of mixed-sex, mixed-age groups of related and
unrelated individuals, with a range of inter-animal relationships. All of the animals in each group
are familiar with one another. Chimpanzees’ social systems are more complex and dynamic than
those of most primates. These social systems are likely the basis for many of the high-level
cognitive and behavioral complexities that have evolved in this species (Humphrey, 1976;
Dunbar, 1998; reviewed in Hopper et al., 2012).
It is impossible to recreate the full and dynamic complexity of the social environment of wild
chimpanzees. However, some sanctuaries have had considerable success in forming large, stable
20

social groups of more than 25 individuals. These groups almost always have a strong multi-male
hierarchy. Although this hierarchy is variable over time, it makes up the long-term leadership
structure in the group.
The degree to which a dynamic fission-fusion system is possible in research settings is unclear;
however, important elements of fission-fusion social grouping have been successfully replicated.
Captive environments that provide opportunities for clusters of animals to completely separate
themselves spatially from others are essential. These features allow individuals to better selfregulate daily social and “political” interactions. In addition, multiple groups have been
maintained at a single facility, with management facilitating regular inter-mixing of groups to
replicate fission-fusion society. Whether implemented on a smaller scale (in-group separation) or
in the context of larger, multi-group socialization (management-facilitated mixing), the
functional elements of social choice are not only practically viable but are also highly desirable
and necessary for creating an ethologically appropriate social environment for chimpanzees.
Recommendation EA1: Chimpanzees must have the opportunity to live in sufficiently
large, complex, multi-male, multi-female social groupings, ideally consisting of at least 7
individuals. Unless dictated by clearly documented medical or social circumstances, no
chimpanzee should be required to live alone for extended periods of time. Pairs, trios, and
even small groups of 4 to 6 individuals do not provide the social complexity required to
meet the social needs of this cognitively advanced species. When chimpanzees need to be
housed in groupings that are smaller than ideal for longer than necessary, for example,
during routine veterinary examinations or when they are introduced to a new social
group, this need should be regularly reviewed and documented by a veterinarian* and a
primate behaviorist.
* In this context, the Working Group defines a “veterinarian” as a licensed, graduate veterinarian with
demonstrated expertise in the clinical care and welfare of nonhuman primates (preferably chimpanzees) and
who is directly responsible for the routine clinical care of the animal(s) in question.

Physical Environments
The natural habitat of wild chimpanzees in equatorial Africa consists primarily of densely
forested jungle, although some topographical variation exists. Chimpanzees spend approximately
half their day off the ground (as high as 66 ft [20 m]), foraging within forest canopies for food
and other resources (Doran, 1996). Daily travel is an essential aspect of chimpanzee life and the
average home range extends from 4 miles (7 km) to more than 12 miles (20 km) (Nishida, 1987;
Newton-Fisher, 2003). Food acquisition is not the only motivation for ranging because adult
males spend considerable time patrolling the borders of their extensive territories to prevent
intrusion from neighboring, unrelated chimpanzee communities (Mitani and Watts, 2005). Thus,
natural chimpanzee environments are expansive and composed of a variety of foliage, substrates,
and assorted topography, all of which provide a wide range of behavioral and locomotor
opportunities.
Even the most ambitious captive environments are unlikely to achieve the sheer size and
complexity of the natural African chimpanzee environment. The key aspects of natural habitats
that represent critical components of an ethologically appropriate physical environment for this
21

species include space, climate, and height of the primary living space (defined as the
environment with which chimpanzees have direct and immediate contact).
Extant research suggests that providing opportunities for captive chimpanzees to form subgroups
and choose potential social partners is important (Clark, 2011) and that large and complex spaces
facilitate species-typical behaviors (Bowen, 1980; Clarke et al., 1982; Aureli and de Waal, 1997;
Videan and Fritz, 2007; Ross et al., 2010; Ross et al., 2011). The space available to captive
chimpanzees should be large enough to support their complex social structures and sufficiently
dense to allow functional subgrouping behaviors. More specifically, spaces should be large
enough for chimpanzees to demonstrate their natural tendencies to range, travel, patrol, and
separate from their social group completely when necessary.
Recommendation EA2: The density of the primary living space of chimpanzees should
be at least 1,000 ft2 (93 m2) per individual. Therefore, the minimum outdoor enclosure
size for a group of 7 animals should be 7,000 ft2 (651 m2).
The climate should be amenable to year-round outdoor access by animals. Although natural
habitats of wild chimpanzees vary to some degree in temperature, humidity, and precipitation,
this variability is considerably less than that of most temperate regions in North America. Ample
evidence also suggests that providing outdoor access to chimpanzees confers significant
behavioral benefits (Videan et al., 2005; Baker and Ross, 1998).
Similarly, captive environments should recapitulate, as much as possible, the complexity of
natural environments to stimulate the full range of foraging, ranging, manipulation, tool-use, and
socio-cultural behaviors of wild chimpanzees (Pruetz and McGrew, 2001). Natural outdoor
environments are not recommended for aesthetics or rote replication of chimpanzee habitat.
Rather, climate represents an important element of the natural, outdoor environments in which
this species evolved and is also important for animal health (McGrew et al., 1981).
Recommendation EA3: Chimpanzees must be housed in environments that provide
outdoor access year round. They should have access to natural substrates, such as grass,
dirt, and mulch, to enhance environmental complexity.
Physical environments should be constructed to fully accommodate the natural arboreal nature of
the species. Wild chimpanzees spend approximately half their waking hours above the ground
foraging, nesting, ranging, and interacting. Captive chimpanzees show a clear preference for
elevated spaces, preferentially selecting them over areas that are closer to the ground (TraylorHolzer and Fritz, 1985; Goff et al., 1994; Ross and Lukas, 2006; Ross et al., 2011). Although an
artificial, constructed climbing apparatus can replicate the functionality of these behavior
patterns, a natural forest habitat provides additional important elements, including shade,
foraging opportunities, visual hides, and humus and other forms of natural ground cover.
Artificial structures cannot fully replicate these variable and complex environmental elements,
especially for the range and size of the spaces described. Thus, ethologically appropriate
environments are large enough to provide sufficient opportunities to range, form subgroups, and
travel. Ideally, these environments are composed of natural substrates, including forests and
other terrains, to replicate the complexity of wild chimpanzee habitats.
22

Recommendation EA4: Chimpanzees should have the opportunity to climb at least 20 ft
(6.1 m) vertically. Moreover, their environment must provide enough climbing
opportunities and space to allow all members of larger groups to travel, feed, and rest in
elevated spaces.
Animal Program Management Considerations
Additional animal program elements that must be considered for appropriate captive chimpanzee
management include enrichment programs, training programs, human interactions, and
individualized care.
Enrichment Programs
Enrichment programs for captive chimpanzees should be formulated to address the range of
natural behaviors of this species and ensure appropriate psychological and cognitive stimulation.
Wild chimpanzees spend the majority of their waking hours foraging for food, and they feed on
hundreds of different fruits, foliage, roots, shoots, and stems as well as insects, birds, and small
mammals. In addition to fulfilling nutritional needs, daily foraging provides opportunities for
physical activity, environmental exploration, and cognitive engagement.
Recommendation EA5: Progressive and ethologically appropriate management of
chimpanzees must include provision of foraging opportunities and of diets that are varied,
nutritious, and challenging to obtain and process.
A key element of chimpanzee ethology is the strong motivation to build new arboreal nests every
night in which to sleep. Extant research has shown that chimpanzees benefit from complex
substrates and provision of nesting materials (Chamove et al., 1982; Brent, 1992; Baker and
Aureli, 1997).
Recommendation EA6: Chimpanzees must be provided with materials to construct new
nests on a daily basis.
Chimpanzees are highly cognitively adept animals, and in the wild, they use this intelligence in a
number of ways. Appropriately complex physical and social environments provide a wide range
of cognitive challenges. However, elements that provide additional problem-solving
opportunities, such as puzzles and tool-use tasks, are necessary to satisfy their inquisitive
personalities. Allowing chimpanzees to make meaningful choices concerning all aspects of their
daily lives is an important component of species-appropriate management. Meaningful choices
can include selecting between types of foods, choosing whether to spend time indoors or
outdoors, and determining the types of social groupings and activities in which to participate.
Recommendation EA7: The environmental enrichment program developed for
chimpanzees must provide relevant opportunities for choice and self-determination.

23

Animal Training Programs
The use of positive-reinforcement training to facilitate necessary veterinary treatment or aspects
of research has measurable behavioral and physiological benefits (Laule et al., 2003; Lambeth et
al., 2006; Laule and Whitaker, 2007; Perlman et al., 2010). The IOM committee recommended
that chimpanzees engaged in research protocols be acquiescent. The Working Group defines
“acquiescence” as voluntary participation in an activity based solely on positive reinforcement
training and not involving forced participation or engagement by coercion. According to this
definition, animals choose whether to participate or not based on their own volition.
Recommendation EA8: Chimpanzee management staff must include experienced and
trained behaviorists, animal trainers, and enrichment specialists to foster positive human–
animal relationships and provide cognitive stimulation. Given the importance of
trainer/animal ratios in maintaining trained behaviors, a chimpanzee population of 50
should have at least 2 dedicated staff members with this type of expertise. Positive
reinforcement training is the only acceptable method of modifying behaviors to facilitate
animal care and fulfillment of management needs. Training plans should be developed
for each animal, and progress toward achieving established benchmarks should be
documented.
Human Interactions
Interactions with caregivers, behaviorists, veterinarians, and scientists are an inevitable part of
captive chimpanzee life. Ensuring that these relationships do not unnecessarily degrade a
chimpanzee’s living conditions is essential. The Working Group has embraced the concept of a
culture of care that should be promoted in ethologically appropriate environments. In a culture of
care,chimpanzees are managed in a manner that engenders respect and mutually positive human–
animal relationships. In some cases, this approach might not be the most convenient means of
accomplishing an activity or task for the human involved. Environments in which caregivers or
others represent negative or threatening stimuli have a negative impact on chimpanzees and are
not ethologically appropriate.
Recommendation EA9: All personnel working with chimpanzees must receive training
in core institutional values promoting psychological and behavioral well-being of
chimpanzees in their care. These institutional core values should be publicly accessible.
Individualized Animal Care
It is widely accepted that chimpanzees are capable of exhibiting a wide range of emotions;
expressing personality; and demonstrating individual needs, desires, and preferences. Although
the Working Group’s recommendations regarding ethologically appropriate physical and social
environments for chimpanzees are geared toward the majority of captive individuals, these
environments must also meet individual physical and social needs.
An appropriate management environment is one that assesses, defines, and addresses individual
chimpanzee needs and preferences in the context of providing opportunities for individuals to
24

meet their species-typical needs. In some cases, chimpanzees might have underlying physical
infirmities or social or behavioral maladjustments that make them better suited to living in a
smaller group than those recommended above. As long as such management decisions are due to
exceptional individual needs rather than institutional, research, or management requirements or
convenience, these strategies might be within the scope of ethologically appropriate physical and
social environments. Individuals with exceptional social, psychological, behavioral, or physical
needs probably do not represent ideal research subjects.
Recommendation EA10: Chimpanzee records must document detailed individual animal
social, physical, behavioral, and psychological requirements and these requirements
should be used to design appropriate individualized chimpanzee management in the
captive research environment.
Additional Considerations
Although chimpanzees might require personalized environments in exceptional circumstances or
due to individual needs, the aforementioned recommendations reflect ethologically appropriate
physical and social environment conditions that apply to all NIH-owned and NIH-supported
chimpanzees maintained in captivity for research purposes. This section makes clear the
distinction between ethologically appropriate and ethologically inappropriate physical and social
environments and discusses the application of ethologically appropriate conditions to temporary
or transitional housing.
A. Ethologically appropriate environments are those that meet the full range of physical,
social, and management characteristics described above. Chimpanzee groups are large
and complex, and they feature a core of multi-male leadership. Spaces are large enough
to promote subgrouping, and chimpanzees have near-constant access to outdoor areas in
which they can:
a. Range widely in an enclosure that permits some degree of subgroup partitioning from
main groups, exploration, and territoriality;
b. Climb high, with numerous opportunities to travel, forage, and nest off the ground;
c. Use nesting materials that are provided daily;
d. Engage in diverse learning opportunities, including the ability to use complex
naturalistic materials, substrates, and foliage, and opportunities to develop and use
tools;
e. Make meaningful choices concerning their environment and living conditions;
f. Forage widely among varied sources; and
g. Form positive human–animal relationships within a management culture that
embraces individualized care while minimizing adverse stress for chimpanzees in all
aspects of their lives.
Ethologically appropriate physical and social environments should be available to house
NIH-owned and NIH-supported research-active and research-inactive chimpanzees
within 3 to 5 years.

25

B. Ethologically inappropriate environments are those in which the aforementioned
components of complexity and stimulation are not available. Environments that house
smaller groups of animals and have only moderate complexity are not acceptable for
long-term housing of chimpanzees. Similarly, environments in which chimpanzees are
managed through the use of squeeze cages and frequent darting or tranquillization for
holding or experimental purposes are not acceptable for long-term housing of
chimpanzees.
Examples of ethologically inappropriate housing for long-term housing of chimpanzees
include the provision of only standard indoor-outdoor run cages, outdoor geodesic
housing structures, and primarily indoor environments. These housing systems, on their
own, do not have the characteristics of ethologically appropriate environments and must
not be used to house chimpanzees on a long-term basis.
C. Temporary housing conditions that do not have all of the above characteristics of
ethologically appropriate housing might be required for captive chimpanzees used for
certain active research protocols. Temporary housing conditions might be necessary to
conduct biomedical research that meets the IOM committee's criteria but requires shortterm containment or periods of close observation or in other exceptional circumstances.
Likewise, some medical treatments or behavioral management initiatives might require
housing chimpanzees outside of ethologically appropriate environments for short periods
of time. Examples of such events include preventive health examinations and related
sedation as well as noninvasive and voluntary cognitive testing.
The Working Group defines “temporary housing conditions” as those needed to hold
animals for between 24 hours and 21 days. Examples of temporary housing conditions
include standard indoor-outdoor run cages, outdoor geodesic housing structures, and
small outdoor corrals.
Chimpanzees should spend as little time as possible in these housing conditions and
should continue to be socially housed. Efforts should be made to provide indoor-outdoor
housing for the duration of a study. Prolonged housing in ethologically inappropriate
environments (e.g., for months) should not be permitted, especially if the main
justification is human convenience or cost.
D. Transitional housing conditions that do not have all of the above characteristics of
ethologically appropriate environments might be required for the next 3 to 5 years to
accommodate current NIH-owned and NIH-supported research-active and researchinactive chimpanzees until ethologically appropriate primary living spaces become
available. Transitional housing conditions might include outdoor corrals or outdoor
geodesic housing structures.
Transitional housing conditions are by definition an interim solution. These conditions
alone are not intended for long-term housing of chimpanzees under any circumstance and
should only be approved after detailed plans for achieving ethologically appropriate
physical and social environment conditions have been formalized.
26

When chimpanzees are housed in transitional housing conditions, every attempt should
be made to provide the animals with daily access to the outdoors and to improve their
primary living spaces and animal program management. These transitional environments
should comply with the recommendations provided in this report to the extent possible.
The IOM committee stipulated that all chimpanzees used in biomedical and in
comparative genomics and behavioral research must be maintained in ethologically
appropriate physical and social environments. Transitional housing therefore provides an
interim solution for the approval of new grants and contracts, but only within a strict 5year time limit.

27

Section 4. Review of Currently Active NIH-Supported Research Using
Chimpanzees
The Working Group used its definition of “ethologically appropriate physical and social
environments,” described in the previous section, to help fulfill its charge of determining
whether currently active NIH-supported research projects using chimpanzees comply with the
IOM principles and criteria. This section describes the process the Working Group used to
evaluate currently active projects and summarizes the recommendations regarding continuing or
ending the projects that the Working Group delivered to the Council of Councils.
The Working Group was also tasked with providing advice on the process for closing any studies
that do not comply with the IOM principles and criteria. For any studies that the Working Group
recommended to “end,” the NIH is in the best position to work with the scientist, resource
director at the facility that maintains the chimpanzees in question, and other relevant parties to
ensure that the scientific value of the research is preserved.
Review Outcomes
The Working Group reviewed 30 projects that involve the use of NIH-owned or NIH-supported
chimpanzees. For each project, the Working Group determined whether to continue the study,
end the study, or conditionally approve the study to continue. The guidance for these
recommendations is as follows:


Continue: These projects comply with all IOM principles and criteria and the Working
Group recommended that the NIH continue to support these projects until the end of the
current project period.



End: These projects do not comply with some or all of the IOM principles and criteria,
and the Working Group recommended that the NIH phase out these projects in a way that
preserves the value of the research already conducted and avoids an unacceptable impact
on the animals.



Conditionally approved to continue: One of the IOM principles is that the chimpanzees
must be housed in an “ethologically appropriate” environment. At the time that the
Working Group reviewed the active NIH projects, the group had not formally identified
the characteristics of ethologically appropriate environments. Working Group members
therefore recommended that projects that met all of the other IOM principles and criteria
be “conditionally approved to continue.” “Conditionally approved to continue” indicates
that a currently active project may continue until the end of the current project period
(e.g., next competitive renewal) but is not eligible for a no-cost-extension or other means
to extend the original project term. Continued maintenance, husbandry, welfare, and
veterinary care of chimpanzees are at the discretion of the NIH as and until suitable,
ethologically appropriate environments become available. Finally, if the principal
investigator elects to submit a competitive renewal application for the project, that
application will be reviewed under the guidance—including the definition of
“ethologically appropriate environments”—that the NIH establishes for the use of
28

chimpanzees in research. The Working Group made provisions for interim housing for
chimpanzees (see Section 3 above) so that new grants and contracts can be approved, but
with a strict cap of 5 years.
The Working Group classified most of the 30 projects that it reviewed into one (or both) of the
two categories suggested in the IOM report—(1) biomedical research and (2) comparative
genomics and behavioral research—and determined whether each of these projects complied
with the IOM criteria for that category of research. For projects that fit neither category, the
Working Group determined whether the research complied with the IOM guiding principles.
Biomedical Research: The Working Group reviewed 9 biomedical research projects on
immunology, bioterrorism, infectious agents, or hepatitis. The Working Group
recommended conditional approval to continue for 3 projects involving immunology and
infectious agents (e.g., hepatitis) and that the NIH end the other 6 projects.
Comparative Genomics and Behavioral Research: The Working Group reviewed 13
comparative genomics or behavioral research projects. The behavioral projects addressed
cognition, perception, communication, development, motor control, altruism, memory, or
brain structure and function. The Working Group recommended continuing or
conditionally approving to continue 8 projects. Six of these projects involved behavioral
research on some combination of chimpanzee cognition, perception, memory, learning,
altruism, development, or brain structure and function. Two of the projects were
comparative genomics/proteomics studies. The Working Group recommended ending the
remaining 5 projects.
Colony Housing and Care Projects: The Working Group reviewed 8 projects involving
chimpanzee colony housing, care, and maintenance or related support services. The
Working Group classified these projects as biomedical research or behavioral or
comparative genomics research if the project focused on supporting research (i.e.,
performed procedures required by a research protocol). The Working Group
recommended conditional approval to continue for 7 of these projects, including all
necessary veterinary care for the health of these chimpanzees, and recommended ending
procedures to support research in 3 of these 7 projects. The Working Group
recommended ending 1 project involving chimpanzee colony housing, care, and
maintenance.
Working Group Recommendations on Currently Active Projects
The Working Group presented its recommendations on the 30 projects it had reviewed to the
Council of Councils during closed-session meetings on September 5, 2012, 9 October 29, 2012,10
and January 8, 2013. The Council of Councils accepted all of the Working Group’s
recommendations. Table 3 summarizes the Working Group’s recommendations.

9

September 5, 2012, meeting: http://www.gpo.gov/fdsys/pkg/FR-2012-08-10/html/2012-19712.htm
October 29, 2012, meeting: http://www.gpo.gov/fdsys/pkg/FR-2012-10-03/pdf/2012-24270.pdf

10

29

Table 3: Working Group Recommendations to the NIH Council of Councils Concerning
Continuation of Current NIH-Funded Research Involving Chimpanzees
Working Group Recommendations

Total
Numbers of
Projects
Considered

Continue

Conditionally
Approved to
Continue

End

Recommendations

 Conditionally
Biomedical
research

9

0

3*

7*

approved to
continue for 3
projects involving
immunology and
infectious agents
 End 6 projects

 Continue or
Comparative
genomics
and
behavioral
research

13

2**

7**

5

conditionally
approved to
continue for 6
behavioral research
and 2 comparative
genomics/proteomics
studies
 End 5 projects

 Conditionally

Colony
housing and
care

8

0

7

†

4

†

approved to
continue for 7
projects
 End 1 project and
the research
component of 3
conditionally
approved projects

*The Working Group recommended conditionally approving part of 1 biomedical research project and ending the
other portion of the project. This project is included in the totals in both the “Conditionally Approved to Continue”
and “End” columns.
**The Working Group recommended continuing part of 1 comparative genomics and behavioral research project
and conditionally approving another part of that project. This project is included in the totals in both the “Continue”
and “Conditionally Approved to Continue” columns.
†
The Working Group recommended conditionally approving to continue parts of 3 colony housing and care projects
and ending the research portions of these projects. These projects are included in the totals in both the
“Conditionally Approved to Continue” and “End” columns.

30

Section 5. Size and Placement of Research-Active and ResearchInactive Populations of NIH-owned and NIH-supported Chimpanzees
This section provides an overview of chimpanzees owned or supported by the NIH and the
Working Group’s assessment of the future need to use chimpanzees in NIH-supported research
(including research on new, emerging, and reemerging diseases). This section also offers
recommendations regarding the size and placement of chimpanzees required for future research
supported by the NIH. The Working Group members based their recommendations regarding the
size of the chimpanzee population needed for research in part on currently active NIH-supported
projects (described in Section 4 of this report). The Working Group members also considered the
advice they received from content experts and current research facility administrators to develop
their recommendations on population size.
Background
As of October 23, 2012, NIH owns and supports the care and maintenance of 670 chimpanzees,
of which 451 are currently designated as either research active or research inactive. These
chimpanzees live at the Michale E. Keeling Center for Comparative Medicine and Research
(Bastrop, Texas), Southwest National Primate Research Center (San Antonio, Texas), and the
Alamogordo Primate Center (Alamogordo, New Mexico). An additional 109 NIH-owned
chimpanzees have been designated as retired and are living in the federal sanctuary system
facility at Chimp Haven (Keithville, Louisiana). Another 110 chimpanzees residing at the New
Iberia Research Center (New Iberia, Louisiana) were designated as ineligible for biomedical
research on September 21, 201211, and will be moved to the federal sanctuary. Finally, NIH
supports research projects using 91 chimpanzees living at the Southwest National Primate
Research Center (San Antonio, Texas) that the NIH does not own. This information is
summarized in Table 4.

11

NIH plans to relocate its chimpanzees from New Iberia to the Federal Sanctuary System:
http://www.nih.gov/news/health/dec2012/od-18.htm

31

Table 4. Census of NIH-Owned and NIH-Supported Chimpanzees, as of October 23, 201212
NIHNIH-Owned Supported
and
but Not
Supported
Owned
Total
Research Chimpanzees at Research Facilities
(research-active and research-inactive
chimpanzees)
Michale E. Keeling Center for Comparative
Medicine and Research, The University of
167
0
167
Texas M.D. Anderson Cancer Center, Bastrop,
TX
*Southwest National Primate Research Center,
Texas Biomedical Research Institute, San
24
91*
115
Antonio, TX
Total at Research Facilities
191
91
282
Research Chimpanzees at Research Reserve
Facility (research inactive)
169
0
169
Alamogordo Primate Facility, Alamogordo, NM
Total Research Chimpanzees
Retired Chimpanzees
Chimp Haven, Inc., Keithville, LA
New Iberia Research Center, The University of
Louisiana at Lafayette, New Iberia, LA
Total Research and Retired
Chimpanzees

360

91

451

109**

0

109

110***

0

110

579

91

670

*Owned by Southwest National Primate Research Center and supported with funds from the NIH
**Chimpanzees retired under the CHIMP Act to the federal sanctuary system
***Designated as permanently ineligible for biomedical research on September 21, 2012, and to be retired over the
next 12-15 months: http://www.nih.gov/news/health/dec2012/od-18.htm

The Working Group was charged with determining the size and placement of NIH-supported
chimpanzees in the context of the IOM principles and criteria (IOM, 2011). Two primary factors
influence any consideration of the size and placement of these chimpanzees: (1) the estimated
future need for this population and (2) the ability of current and planned environments to develop
the characteristics of ethologically appropriate physical and social environments that are defined
in Section 3 above.
Future Need for Chimpanzees in Research
First, it is clear from the 2011 IOM report that in most current invasive research, the use of
chimpanzees is not essential. In fact, the IOM committee specifically notes that only a narrow
12

Costs for Maintaining Humane Care and Welfare of Chimpanzees, October 23, 2012:
http://dpcpsi.nih.gov/orip/cm/chimpanzee_maintenance.aspx

32

range of studies meets its criteria for biomedical research relevance and continuation. From the
IOM report:
Most current use of chimpanzees for biomedical research is unnecessary… (pp. 66–67)
The present trajectory indicates a decreasing scientific need for chimpanzee studies due to
the emergence of non-chimpanzee models and technologies. (p. 67)
The IOM committee identified only two areas of invasive research in which the use of
chimpanzees might be valuable: continued development of monoclonal antibodies and
development of a prophylactic hepatitis C virus vaccine (although the IOM committee did not
reach consensus on the latter). The IOM committee also left open the possibility that research on
new, emerging, or reemerging diseases might require the use of chimpanzees.
Predictions of Future Need Based on the Use of Chimpanzees in Current Research
Using the criteria for biomedical and comparative behavioral and genomic research defined in
the IOM report, the Working Group evaluated all projects currently funded by the NIH that
involve chimpanzees. Details on this process and the Working Group’s recommendations are
provided in Section 4 of this report. The Working Group concluded that 6 of 9 biomedical
research projects using 81 of 93 chimpanzees did not meet the IOM criteria. The Working Group
recommended ending these projects while ensuring that the scientific value of the research is
preserved.
The Working Group’s recommendations regarding active NIH-funded biomedical research
projects demonstrate that the need to use chimpanzees in invasive biomedical research has
diminished substantially. Assessments of the size of future research chimpanzee populations
must reflect this fact. Furthermore, it appears to be likely that over time, the amount of invasive
biomedical research on chimpanzees will diminish to such an extent that all research-active and
research-inactive chimpanzees could be retired.
The Working Group found it more difficult to determine the future need for minimally invasive
research that inflicts little or no harm on chimpanzee subjects. Currently, several investigators
are using approximately 300 chimpanzees for comparative genomic and behavioral research.
This research includes passive behavioral studies (that do not require any intervention with the
chimpanzee group) and investigations of chimpanzee cognition, chimpanzee health, and
genomics. Although unable to quantify the future demand for noninvasive research on
chimpanzees, the Working Group was able to conditionally approve to continue several projects
involving comparative genomics or behavioral research involving 290 chimpanzees. The
Working Group agreed that the need to use chimpanzees in this type of research is not negligible
and opportunities for such research should be made available to the scientific community.
Nonetheless, the Working Group concluded that maintaining a large reserve colony of
chimpanzees for minimally invasive research is not necessarily justified because many of these
NIH research needs could be met in nontraditional research settings, such as accredited
sanctuaries and zoos, as long as such settings provide ethologically appropriate physical and

33

social environments. The Working Group thus recommended that the NIH re-examine
programmatic priorities in these areas of research.
Predictions of Future Need Based on the Assessments of the Emerging Diseases Subgroup
The Working Group engaged a panel of experts in infectious diseases and laboratory biosafety
(Emerging Diseases Subgroup) to provide advice on the number of chimpanzees, if any, needed
to address new, emerging, and reemerging diseases or unanticipated threats to human health. The
full report of the Emerging Diseases Subgroup is in Appendix G.
The IOM committee highlighted the many human health benefits gained from previous and
currently ongoing biomedical research using chimpanzees (IOM, 2011). The committee
acknowledged the difficulties of predicting or forecasting the future need for the chimpanzee as
an animal model and human surrogate. Nevertheless, due in part to the emergence of nonchimpanzee models and technologies, the committee determined that the need for chimpanzee
studies would decrease, but likely not be entirely eliminated, in the future. Specifically, the
committee recognized that “…a new, emerging, or reemerging disease or disorder may present
challenges to treatment, prevention, and/or control that defy non-chimpanzee models and
technologies and therefore may require the future use of the chimpanzee” (IOM, 2011, p. 67).
In its deliberations, the Emerging Diseases Subgroup affirmed the findings of the IOM
committee regarding the future use of chimpanzees in biomedical research on infectious
diseases, namely that the NIH should limit the use of chimpanzees in biomedical research to
studies that comply with the IOM principles and criteria. In addition, the subgroup made the
following observations about issues not addressed by the IOM committee report:
 As of January 22, 2013, approximately 75 percent of emerging infectious diseases are of
zoonotic origin, and about 25 percent of these diseases derive from nonhuman primate
host species (Woolhouse and Gowtage-Sequeria, 2005; Jones et al., 2008).
 Scientific evidence has demonstrated that infectious diseases can be transmitted from
chimpanzees to humans and vice versa (Jones et al., 2008; Köndgen et al., 2008;
Schaumburg et al., 2012).
 Historical scientific evidence indicates that chimpanzees could be an animal reservoir and
zoonotic source of a new, emerging, or reemerging human infectious disease.
 How often an “emergent” event will take place and whether a response to such an event
would involve the use of chimpanzees is impossible to predict.
 The number, ages, and sexes of chimpanzees required for a definitive infectious disease
study would depend on many parameters, including the purpose of the model’s use.
 Infectious disease research in chimpanzees would probably not be considered unless an
episode of direct transmission from chimpanzees to humans was clearly demonstrated or
a response to an “unknown unknown” (a novel emerging disease and/or bioterrorism
agent for which all other approaches to develop prevention and control strategies have
failed) required the use of chimpanzees.
 Infectious disease research would warrant the use of chimpanzees only in unique and rare
situations (e.g., a new, emerging disease of exceptional lethality that threatens the public
health).

34












Chimpanzees do not play a role in discovery-phase infectious disease research, except in
studies on a very small number of infectious agents (e.g., hepatitis viruses).
Even for highly virulent Ebola and monkeypox viruses, significant research and human
health advances (e.g., drug development and vaccines) have been achieved using smaller
animal models.
To the Working Group’s knowledge, all infectious disease research studies conducted on
chimpanzees in the last 20 years have been survival experiments involving nearly
exclusively animal biosafety level 2 (ABSL2) infectious agents (e.g., hepatitis B,
hepatitis C, and HIV).
To the Working Group’s knowledge, the NIH has never supported any research
employing chimpanzees under higher biocontainment-level (i.e., ABSL3 or ABSL4)
conditions.
In some very rare cases of research on infectious diseases that present an exceptional
threat to public health (e.g., an “unknown unknown”), the theoretical possibility of
needing to use chimpanzees in the highest biocontainment-level (i.e., ABSL 4) facilities
exists. However, none of the ABSL4 facilities in the United States is designed to
accommodate research on chimpanzees, and substantial planning, time, and financial
resources would be necessary to create such capability.
Current federal regulatory guidelines prohibit the return of animals used in ABSL3 or
ABSL4 studies to lower biocontainment-level conditions (e.g., to an ABSL2 facility or
sanctuary) (Centers for Diseases Control and Prevention, 2009).
There is no compelling scientific reason to maintain a sufficiently large reserve
population of chimpanzees suitable and/or available for infectious disease research, even
in the case of a national emergency.
Alternative animal models (e.g., mice, rats, hamsters, guinea pigs, and other nonhuman
primates) are currently and increasingly used and developed to study emerging infectious
diseases. The availability of these models will continually raise the scientific bar for
justifying the use of chimpanzees.

Ethologically Appropriate Physical and Social Environments
The ability of current or planned facilities to provide the conditions of ethologically appropriate
physical and social environments is an additional factor to consider when determining the
placement of NIH-owned and NIH-supported chimpanzees. “Ethologically appropriate physical
and social environments” is a new and previously undefined term. For this reason, it is unlikely
that all existing housing environments in current research facilities will provide all of the
characteristics of ethologically appropriate environments that the Working Group recommends.
Substantial financial resources will probably be needed to physically alter facilities to create
fully ethologically appropriate environments. In addition, significant changes to animal program
management will probably be needed.
Colony Size and Placement Recommendations
Given the highly diminished need for chimpanzees as research subjects for invasive biomedical
research, the Working Group proposes the following recommendations:

35

Recommendation SP1: The majority of NIH-owned chimpanzees should be designated
for retirement and transferred to the federal sanctuary system. Planning should start
immediately to expand current facilities to accommodate these chimpanzees. The federal
sanctuary system is the most species-appropriate environment currently available and
thus is the preferred environment for long-term housing of chimpanzees no longer
required for research.
Recommendation SP2: A small population of chimpanzees should be maintained for
future potential research that meets the IOM principles and criteria. Based on an
assessment of current research protocols and interviews with content experts and current
research facility administrators, this colony is estimated to require approximately 50
chimpanzees. The size and placement of this colony should be reassessed on a frequent
basis (approximately every 5 years) to ensure that such a colony is still actually needed
and that the animals are not overused.
Recommendation SP3: This small chimpanzee colony should be maintained at a facility
that has the characteristics of ethologically appropriate physical and social environments
described in this report. Thus, plans should be made now to ensure that ethologically
appropriate physical and social housing conditions will be available within 3 to 5 years.
Maintaining the chimpanzee colony at a single facility could be advantageous to
minimize costs and maximize management flexibility.
Recommendation SP4: The demographic constitution of this small chimpanzee colony
is important to maximize its utility for research. Ideally, the colony should be age and sex
stratified, have an approximately 50:50 sex ratio, and be composed primarily of animals
that are healthy and younger than 30 years. At least half of this population should be
physiologically naïve to infection (e.g., hepatitis or HIV). When this colony is formed,
best practices should be used for maintaining current social groupings, whenever
possible, to minimize adverse stress.
Recommendation SP5: The NIH should review its funding priorities for comparative
behavioral, cognitive, and genomics studies using chimpanzees. The NIH should consider
targeting funding for low-burden projects that can be conducted in nontraditional
research settings that can maintain ethologically appropriate environments or projects that
use materials collected during routine veterinary examinations.
Recommendation SP6: The NIH should not support any long-term maintenance of
chimpanzees intended for research on new, emerging, or reemerging diseases in animal
biosafety level 2 or greater biocontainment-level facilities.
Recommendation SP7: The NIH should not, on its own, revitalize breeding strategies to
derive a population of chimpanzees for any research, including for new, emerging, or
reemerging disease research.
Recommendation SP8: The NIH should collaborate with other federal agencies (i.e.,
Centers for Disease Control and Prevention and Food and Drug Administration) and
36

departments (i.e., Department of Defense and Department of Homeland Security) when
considering any future plan for placement, maintenance, and use of chimpanzees in
research in response to a new, emerging, or reemerging disease that could represent a
national security risk to the United States.
Recommendation SP9: In light of evidence suggesting that research involving
chimpanzees has rarely accelerated new discoveries or the advancement of human health
for infectious diseases, with a few notable exceptions such as the hepatitis viruses, the
NIH should emphasize the development and refinement of other approaches, especially
alternative animal models (e.g., genetically altered mice), for research on new, emerging,
and reemerging diseases.

37

Section 6. Review Process for Future Proposals to Use Chimpanzees
in NIH-Supported Research
The final element of the Working Group’s charge was to develop a review process for
considering whether the potential future use of chimpanzees in NIH-supported research is
scientifically necessary and consistent with the IOM principles and criteria. In developing this
process, the Working Group considered the IOM guidance on this topic, its experience reviewing
currently active NIH-supported research using chimpanzees, and its assessment of and
recommendations regarding ethologically appropriate physical and social environments
(described in Section 3 of this report).
This section summarizes the IOM committee’s guidance regarding the review of research
applications for NIH-funded research and a new NIH committee to review future requests to the
NIH involving the use of chimpanzees for research. This section also includes recommendations
regarding the composition and responsibilities of this committee as well as the process that the
committee should use to review research applications.
IOM Guidance
The IOM committee provided a policy rubric for assessing the need for chimpanzees in
biomedical, comparative genomics, and behavioral research and recommended developing an
independent committee to review applications for NIH-funded research using chimpanzees
(IOM, 2011). From the IOM report:
The committee believes that assessment of potential future use of the chimpanzee would
be strengthened and the process made more credible by establishing an independent
oversight committee that uses the recommended criteria and includes public
representatives as well as individuals with scientific expertise, both in the use of
chimpanzees and alternative models, in areas of research that have the potential for
chimpanzee use. (p. 70)
The committee cannot predict or forecast future need of the chimpanzee animal model
and encourages use of the criteria established in this report when assessing the potential
necessity of chimpanzees for future research uses. (p. 66)
…the NIH should evaluate the necessity of the chimpanzee in all grant renewals and
future research projects using the chimpanzee model based on the committee’s criteria.
(p. 69)
Oversight Committee Composition
Although the IOM committee recommended that the NIH evaluate the need to use chimpanzees
in grant renewals and future research projects based on the committee’s principles and criteria,
the IOM committee was not asked to provide plans for implementing this guidance. The
Working Group therefore provides recommendations regarding the composition of the Oversight
Committee for Proposals Using Chimpanzees in NIH-supported Research (Oversight
38

Committee) and outlines a process for the Oversight Committee to use in reviewing applications
to NIH for research involving chimpanzees.
Recommendation RP1: The NIH should replace the Interagency Animal Models
Committee with an independent Oversight Committee for Proposals Using Chimpanzees
in NIH-supported Research (Oversight Committee) to advise on the proposed use of
chimpanzees in research. The current Interagency Animal Models Committee is not
considered independent from other individuals and bodies that review and approve grant
applications to the NIH, contains no members of the public, and thus does not fully meet
the spirit of the IOM principles and criteria.
Recommendation RP2: The Oversight Committee should be separate from extramural
initial review groups, intramural scientific program personnel, and Institute or Center
directors. In addition, the Oversight Committee’s reviews should take place after the
standard reviews and approvals by these entities. The Oversight Committee’s reviews
will focus on whether the proposed research is consistent with the IOM principles and
criteria for the use of chimpanzees in research.
Recommendation RP3: The Oversight Committee should be comprised of individuals
with the specific scientific, biomedical, and behavioral expertise needed to properly
evaluate whether a grant, intramural program, contract, or other award mechanism
supporting research using chimpanzees complies with the IOM principles and criteria.
A majority vote based on the full committee membership will be necessary to determine whether
a project complies with the IOM principles and criteria. The Oversight Committee should have
an odd number of members and should have no fewer than nine experts in at least the following
key areas.
1. The Oversight Committee should include at least one scientific domain expert from each
of the following categories:
a. Expert in infectious disease (e.g., virology or immunology);
b. Neuroscientist with expertise in cognitive and behavioral research in humans or
nonhuman primates to determine a project’s likelihood of providing otherwiseunattainable insights into behavior, mental health, emotion, or cognition; and
c. Geneticist or evolutionary biologist with expertise in comparative genomics, genetics,
and/or evolution.
In some cases, at least one additional scientific domain expert will be needed on an ad
hoc basis to assess and determine the necessity of using chimpanzees in the proposed
research if the committee’s standing members lack such expertise. The expert(s) should
also have sufficient content knowledge to assess whether alternative models to the
chimpanzee are available. Based on the current research using chimpanzees, ad hoc
members might include, for example, virologists with expertise in hepatitis C virus as
well as experts in transgenic animal models and in vitro systems.

39

2. Licensed, graduate veterinarian(s) with demonstrated expertise in the clinical care of
nonhuman primates, preferably chimpanzees, should assess the health, care, and welfare
of chimpanzees to be used in the proposed research and assess and determine the
potential short-term and long-term health risks of the proposed studies13 for the
chimpanzees.
3. Primatologist(s) or individual(s) with similar demonstrated expertise in primate, and
preferably chimpanzee, behavior should assess and determine the short-term and longterm impact of the proposed research plan on the behavioral needs of chimpanzees. These
experts should also assess the quality of the interactions between the chimpanzees and the
facility’s research and care staff described in the proposals. In particular, these experts
should determine the extent of positive reinforcement training that the chimpanzees have
received (and continue to receive) to voluntarily participate in aspects of the research
project so as to ensure chimpanzee acquiescence.
4. A bioethicist or individual(s) with bioethics expertise and experience as an institutional
review board (IRB) member should assess whether the proposed research could be
conducted ethically in humans instead of chimpanzees. Such assessments would not
require the investigators to develop a comparable protocol for their research in humans or
to obtain IRB approval of their proposal for chimpanzee research.
5. Statistician(s) should assess and determine the validity of the statistical analysis and
interpretations used to calculate the numbers and use of chimpanzees in the proposed
research.
6. At least two persons representing community interests and concerns who have not been
directly involved in animal use for research, teaching, or testing but are able (or
competent) to apply the IOM criteria to assess the necessity of using chimpanzees in the
proposed research.
7. Non-voting NIH official(s) ex officio should advise on process issues and provide
documents and/or relevant information as needed.
Review Process
Distinction Between Biomedical, Comparative Genomics, and Behavioral Research
The Working Group found that the distinction in the IOM report between biomedical research
and comparative genomics and behavioral research is challenging to implement in reviewing
applications. For example, this distinction imposes a potential dichotomy between mental
functioning and the functioning of components outside the central nervous system, and this
13

A determination by the Oversight Committee that a study could be conducted in human subjects does not imply
that the NIH has approved the proposal’s plan for protecting human subjects. Investigators who choose to propose
human studies in place of chimpanzee studies need to revise and resubmit their proposal, including documentation
of applicable institutional review board approval.

40

dichotomy is not warranted based on current scientific understanding. More specifically, because
many mental disorders affect the brain, research on comparative cognition (such as the origins of
language or social behavior that are related to a variety of neuropsychiatric or developmental
conditions) can and should be construed as basic biomedical research. The same is true of
research in evolution and comparative genomics. Furthermore, implementation based on this
dichotomy would require that less invasive, and potentially less harmful, behavioral research on
chimpanzees meet the standard of acquiescence (first mentioned on p. 6 of the IOM’s 2011
report and defined by the Working Group in the glossary in this report) that in the current IOM
rubric would not be applied to biomedical research, even though most biomedical research is
more invasive.
The Working Group suggests avoiding the distinction between biomedical and behavioral and
comparative genomics research and that all research on chimpanzees follow the same decisionmaking algorithm process, as guided by the IOM principles and criteria. The basic process in all
cases involves an initial scientific assessment that includes a determination that:
 The knowledge gained is necessary to advance the public’s health or will lead to
otherwise unattainable insight into comparative genomics, normal and abnormal
behavior, mental health, emotion, or cognition;
 There is no other suitable animal model available, such as in vitro, nonhuman in vivo, or
other models, by which the knowledge could be obtained; and
 The research in question cannot be performed ethically on human subjects.
Process to Apply for Research Using Chimpanzees
Recommendation RP4: Investigators seeking NIH funding to conduct research using
chimpanzees must explain in their application how their proposed research complies with
the IOM principles and criteria. This supplemental information must address all of the
questions posed in the decision-making algorithm in this report and provide sufficient
detail for consideration by the Oversight Committee. This information is in addition to
the vertebrate animal section and/or applicable animal study protocol. The NIH might
wish to develop a form or other suggested template for investigators to use for this
purpose.
Recommendation RP5: To ensure that the scientific use of chimpanzees is justified, the
animal numbers and group sizes must be statistically justified before the NIH approves
any proposed research project involving the use of chimpanzees.
Recommendation RP6: Investigators need not include supplemental information on
chimpanzee use for proposals involving the following, and these proposals will be
exempt from Oversight Committee review:
 The use of any biomaterials, including pathological specimens, collected and/or
stored prior to submission of the research proposal, or as part of a research grant or
contract that has undergone Oversight Committee review and approval, or as part of
regular veterinary (health) examinations;

41




Other observational or non-interventional studies, such as behavioral observations in
the wild that do not result in contact or otherwise interfere with the chimpanzees
being observed; or
Noninvasive collection of samples from the wild in a manner that does not result in
contact or otherwise interfere with the chimpanzees during the collection.

Review Considerations
If the proposed research passes the initial scientific assessment, the Oversight Committee will
determine whether the research can be conducted in ethologically appropriate environments (see
Section 4 of this report for a discussion of ethologically appropriate physical and social
environments).
The IOM committee recommended assessing whether “the benefits gained from research on
animals are sufficient to outweigh the harms caused in the process” to determine whether the use
of chimpanzees in research is justified (IOM, 2011, p. 15). To guide the process of balancing
human health interests and chimpanzee well-being, the Working Group offers several major
considerations. The purpose of the research is to achieve a specific benefit—an improvement in
human health. Thus, determining what the research is designed to learn and the likelihood that
this information will lead to an improvement in human health is important. However, making
such a determination is particularly challenging for basic science research, such as genomic,
evolutionary, or cognitive research, whose aim is to produce general knowledge of as yet largely
unpredictable value to public health. For this reason, determinations of the benefits of basic
research should be based on whether the research will lead to otherwise unattainable insight.
The severity and duration of potential physical or psychological harm (in the form of discomfort,
deterioration in social status, or injury) to chimpanzees and the probability that the harm will
occur must be assessed. For the review process that the Oversight Committee will use, the
Working Group defined this concept as the “burden” on the chimpanzees. Invasive interventions
typically impose higher burdens than noninvasive ones, and biomedical research might impose a
significant burden more frequently than behavioral and genomic studies. However, the Working
Group found that these research categories are all imperfect proxies for the real concern, which is
the actual burden on the chimpanzees.
If an experiment has benefits that greatly outweigh its burdens, it might be approvable but not
until the protocol has been examined to determine whether the benefit-to-burden ratio can be
further improved by, for example, making additional efforts to keep the chimpanzees
comfortable or to shorten the duration of the intervention. The benefits should be reasonably
maximized and burdens reasonably minimized.
Decision-Making Algorithm
1. Does this research use chimpanzees?
a. If no, end of survey.
b. If yes, continue to Q2.
42

2. Does this research use only previously collected biospecimens, including blood, tissue, or
any materials collected postmortem? Does the research solely involve the observation of
animals in their native, natural habitat? Is the research limited to noninvasive sample
collections (e.g., of fecal, urine, or sperm plug specimens) in a manner that does not
result in contact or otherwise interfere with the chimpanzees during the sample collection
process?
a. If the answer to any of these questions is yes, end of survey. This work is not under
the purview of the Oversight Committee.
b. If the answer to all of the questions is no, continue to Q3.
3. Is the purpose of this research primarily to improve the health and well-being of
chimpanzees?
a. If yes, the investigator must provide an explanation that will be reviewed by the
committee. In this explanation, the investigator must demonstrate that the
chimpanzee’s use is in the best interest of the chimpanzee and addresses the mission
of the NIH. Such an explanation is not necessary for standard-of-care or
compassionate use of treatments.
b. If no, continue to Q3c.
c. Is the purpose of this research for the benefit of humans?
i. If yes, proceed to Q4.
ii. If the purpose of this research is not for the benefit of humans or chimpanzees,
chimpanzee research is not permitted.
4. Are other suitable models, such as in vitro, nonhuman in vivo, or other models, available
for the research in question?
a. If yes, chimpanzee research is not permitted.
b. If no, proceed to Q5.
5. Can the research in question be performed ethically14 on human subjects with the
prospect of achieving comparable results?
a. If yes, chimpanzee research is not permitted.
b. If no, proceed to Q6.
6. Will forgoing the use of chimpanzees for the research in question significantly slow or
prevent important advancements in genomics; evolutionary theory; human behavioral,
cognition, or emotions research; or important advances in the prevention or treatment of
life-threatening or debilitating human conditions?

14

One characteristic that the Working Group suggests using to answer this question is whether the research on
humans would be potentially approvable by an institutional review board.

43

a. If no, chimpanzee research is not permitted.
b. If yes, proceed to Q7.
7. Will physical, psychological, and emotional burdens on the chimpanzees be limited by
minimizing the number of chimpanzees used, the duration of the experiment, and the
discomfort of the procedures and by performing the work on acquiescent chimpanzees
that have been trained to present for blood draws or anesthesia or to participate in the
research and can do so voluntarily?15
a. If no, chimpanzee research is not permitted.
b. If yes, proceed to Q8.
8. Are the remaining physical, psychological, and emotional burdens on the chimpanzees
outweighed by the possible benefits to humankind and to science?
a. If no, chimpanzee research is not permitted.
b. If yes, proceed to Q9.
The matrix below (Figure 1) provides a framework for balancing burdens on
chimpanzees and potential benefits of research.

Figure 1. Burden-Benefit Matrix

15

Evidence of voluntary participation is that each chimpanzee has the opportunity to choose not to participate at any
given time.

44

The Working Group defined “lowest or minimal burden” studies as noninvasive or
observational studies that cause little or no discomfort or stress in chimpanzees. Such
studies might involve acquiescent participation in a study on cognition following positive
reinforcement training or simple observation of behavior. Research involving only
samples that are routinely obtained (e.g., leftover blood or urine) while an animal is under
anesthesia for routine veterinary examinations also fall into this category.
“More than minimal burden” studies involve more potential risk or invasiveness, as
reflected by the extent of pain, distress, fear, discomfort, or injury. Examples include
studies involving voluntary separation of chimpanzees from their social group for a short
time; any procedure that requires general anesthesia; any procedure that prolongs routine
anesthesia during routine veterinary examinations; and intravenous injections or repeated
blood sampling in non-anesthetized, acquiescent animals. Such research does not impose
a high burden or risk, but it imposes more than the lowest level of burden.
“High burden” studies include most biomedical research involving measurable distress
or physical alteration. Examples include those that result in the prolonged separation of
chimpanzees from their social group (ethologically inappropriate environments as
defined in Section 3 of this report); inoculation with an infectious agent; exposure to
pharmaceutical agents or chemicals; food or water deprivation; or surgical procedures
such as biopsies, laparoscopy, or prolonged physical restraint.
Using the burden-benefit matrix, investigators could easily show that studies in the
bottom left box meet the IOM criteria because these involve a lowest or minimal burden
and a high benefit. Protocols in the bottom row of boxes might meet the criteria because
they have the potential to offer high benefit (colored in green, “likely to meet criteria” or
“might meet criteria”), but as the burden increases, these studies will only be permissible
if their clear human health benefits also increase. Hence, basic cognition, evolution, or
genomic studies involving a high burden would not be allowable because although their
scientific benefit might be high, this benefit does not outweigh the degree of burden on
the animal (colored in red, “not acceptable”). Experiments with the lowest or minimal
burden and low benefit also would not likely meet the criteria because they are not
scientifically justified (colored in red, “unlikely to meet criteria”). Studies with more than
minimal burden but moderate benefit could be acceptable because the perceived benefit
might depend partially on their outcomes, which cannot be predicted a priori (colored in
yellow, “might meet criteria”). Examples of current studies that might fall into this latter
category are certain cognitive or comparative evolution studies involving neuroimaging.
9. Will the animals used in the proposed research be maintained in either ethologically
appropriate physical and social environments or transitional housing (based on the
characteristics discussed in Section 3 above) or in natural habitats?
a. If no, chimpanzee research is not permitted.
b. If yes, the IOM criteria for the use of chimpanzees in NIH-funded research have been
met.

45

The determinations of the Oversight Committee that proposals (or parts of them) meet or do not
meet the IOM principles and criteria should be transmitted to the Federal Advisory Committee
Act committee assigned by the NIH Director to consider the Oversight Committee’s
determinations (see below).
Placement of Oversight Committee Review
Information pertaining to a research proposal’s review is kept confidential until the NIH Director
or the director of the relevant NIH Institute or Center makes the final award decision. Doing so
protects privileged information. The Working Group therefore offers the following
recommendations.
Recommendation RP7: The Oversight Committee review should take place after the
Center or Institute director approves a proposal so that the key elements of the review are
publicly accessible to the extent allowable by federal regulations. The Oversight
Committee should review all requests for grants, contracts, intramural projects, and thirdparty projects rather than establishing a separate review process for each mechanism.
Funding of an award for research involving the use of chimpanzees that has received an
Institute or Center director’s approval will be conditional and subject to the subsequent
evaluation by the Oversight Committee.
Recommendation RP8: The Oversight Committee will base its reviews on the
supplemental information provided by investigators on how the proposed research
complies with the IOM principles and criteria and all relevant documents (including
animal study protocols and grant applications) required to make informed determinations
for all funding requests (grants, contracts, and intramural projects) and other requests to
use chimpanzees (e.g., third-party projects).
Recommendation RP9: The Oversight Committee will determine whether each
application meets or does not meet the IOM principles and criteria based on the votes of a
majority of all voting members. At its members’ discretion, the Oversight Committee
may vote on whether different components or parts of an application meet or do not meet
the IOM principles and criteria.

46

Section 7: Conclusion
This report by the Working Group on the Use of Chimpanzees in NIH-Supported Research
provides 28 recommendations to the Council of Councils, a federal advisory committee of the
NIH. The report completes the task of the Working Group, which was to advise the NIH on
implementing the recommendations of the IOM report, Chimpanzees in Biomedical and
Behavioral Research: Assessing the Necessity (IOM, 2011), by addressing the following fourpoint charge:
 Developing a plan for implementation of the IOM’s guiding principles and criteria;
 Analyzing currently active NIH-supported research using chimpanzees to advise on
which studies currently meet the principles and criteria defined by the IOM report and
advising on the process for closing studies if any do not comply with the IOM
recommendations;
 Advising on the size and placement of active and inactive populations of NIH-owned or
-supported chimpanzees that may need to be considered as a result of implementing the
IOM recommendations; and
 Developing a review process for considering whether potential future use of the
chimpanzee in NIH-supported research is scientifically necessary and consistent with the
IOM principles.
In developing its recommendations, the Working Group solicited and reviewed public
comments, considered the scientific use of chimpanzees in the 30 currently funded projects that
involve chimpanzees, obtained advice from 11 external experts, and conducted field trips to 7
facilities that care for and house chimpanzees. These experiences gave the Working Group an
informed view of three important perspectives: members of the public with considerable interest
in this topic, scientists conducting research using chimpanzees, and facilities and staff that care
for the chimpanzees on a daily basis.
The Working Group is pleased to have responded to each element of its charge and presents this
report as its final deliverable. In submitting this report to the NIH Council of Councils on
January 22, 2013, the Working Group concludes a series of activities thoughtfully conducted to
facilitate NIH’s implementation of the IOM recommendations.

47

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Acknowledgements
The Council of Councils Working Group on the Use of Chimpanzees in NIH-Supported
Research expresses its sincere appreciation to James M. Anderson, M.D., Ph.D., NIH Deputy
Director for Program Coordination, Planning, and Strategic Initiatives, for his guidance and
leadership as the Working Group engaged in this year-long process. Members of the Working
Group acknowledge the support provided by the following NIH team members: Lora Kutkat;
Betina Orezzoli, M.B.A.; James A. Smith, PMP; Hannah Kim; Carmel Scharf; and Deborah
Berlyne, Ph.D. The Working Group thanks the staff of the chimpanzee housing facilities that
hosted the Working Group’s field trips and the many consultants who provided expert advice.
The Working Group benefited from the feedback and support of the NIH Council of Councils,
the advisory committee to which the Working Group reports.
Members of the Working Group appreciate the opportunity to have been part of this important
effort and hope that its efforts facilitate NIH’s implementation of the IOM recommendations
regarding the use of chimpanzees in research.

52

Appendix A: Working Group on the Use of Chimpanzees in NIHSupported Research Membership Roster
Daniel H. Geschwind, M.D., Ph.D. (co-chair), Gordon and Virginia Distinguished Professor of
Neurology, Psychiatry and Human Genetics; Director, Center for Autism Research and
Treatment, Semel Institute and Program in Neurogenetics, Department of Neurology, University
of California, Los Angeles
K.C. Kent Lloyd, D.V.M., Ph.D. (co-chair), Associate Dean for Research and Graduate
Education and Professor of Anatomy, Department of Anatomy, Physiology and Cell Biology,
School of Veterinary Medicine; Director, Mouse Biology Program, University of California,
Davis
Alan D. Barrett, Ph.D., Director, Sealy Center for Vaccine Development; Professor, Department
of Pathology; Professor, Department of Microbiology and Immunology, University of Texas
Medical Branch
R. Alta Charo, J.D., Associate Dean for Academic Affairs; Warren P. Knowles Professor of Law
and Bioethics, University of Wisconsin Law School
Beatrice H. Hahn, M.D., Professor of Medicine and Microbiology, Perelman School of
Medicine, University of Pennsylvania
Stephen Ross, Ph.D., Director, Lester E. Fisher Center for the Study and Conservation of Apes,
Lincoln Park Zoo
Patricia Turner, M.Sc., D.V.M., D.V.Sc., Professor, Department of Pathobiology, Ontario
Veterinary College, University of Guelph
Members Who Participated in the Working Group for a Partial Term
The following Working Group members did not complete their terms on the Working Group.
They did not participate in writing or reviewing the draft report and, therefore, they have not
expressed an opinion about the final report:
Stanley Lemon, M.D., Professor of Medicine, School of Medicine, University of North
Carolina*
Daniel J. Povinelli, Ph.D., Professor, Department of Biology; James S. McDonnell Centennial
Fellow, University of Louisiana**
Charles Rice, Ph.D., Maurice R. and Corinne P. Greenberg Professor in Virology, The
Rockefeller University***
*Dr. Lemon was a member of the Working Group between February and June 2012.
**Dr. Povinelli was a member of the Working Group between February and September 2012.
***Dr. Rice was a member of the Working Group between February and June 2012.

53

Appendix B: Biographies of Members of the Working Group on the
Use of Chimpanzees in NIH-Supported Research
Daniel H. Geschwind, M.D., Ph.D., is the Gordon and Virginia MacDonald Distinguished
Professor of Neurology and Psychiatry and Human Genetics at the University of California, Los
Angeles (UCLA) School of Medicine. Dr. Geschwind obtained an A.B. in psychology and
chemistry from Dartmouth College and an M.D./Ph.D. from Yale School of Medicine prior to
completing his internship, residency, and postdoctoral fellowship at UCLA. He joined the UCLA
faculty in 1997 and has published over 250 research papers in the field of neurogenetics. Dr.
Geschwind’s work integrates population genetics, functional genomics, and bioinformatics with
basic and clinical neuroscience to understand neuropsychiatric disease pathogenesis and
accelerate treatment development. In addition to his research, Dr. Geschwind is active on
numerous scientific advisory and editorial boards and is a former member of the National
Institute of Mental Health Scientific Advisory Council. He received the Derek Denny-Brown
Neurological Scholar Award from the American Neurological Association in 2004 and the
Scientific Service Award from Autism Speaks in 2008, and he is a member of the IOM.
K.C. Kent Lloyd, D.V.M., Ph.D., is Associate Dean for Research and Graduate Education and
Professor of Anatomy in the Department of Anatomy, Physiology and Cell Biology in the School
of Veterinary Medicine at the University of California, Davis (UCD). Dr. Lloyd is a clinical
veterinarian and research physiologist with expertise in targeted conditional mutagenesis of the
laboratory mouse and physiology of the mammalian gastrointestinal tract, with special emphasis
on mechanisms of enterogastric reflexes. As Director of the UCD Mouse Biology Program, Dr.
Lloyd conducts research, teaching, and services using genetically altered mice. Dr. Lloyd is also
an instructor in the veterinary and graduate curriculums, teaching renal and gastrointestinal
physiology of monogastrics and ruminants to medical, veterinary, and graduate students and
genetic manipulation of the mouse embryo to undergraduate and graduate students. Dr. Lloyd
received his D.V.M. from UCD in 1983 and completed his Ph.D. in 1992 at UCLA. From 1993
to 1995, he was Assistant Professor of Medicine and Physiology at UCLA, and he was
subsquently a visiting scientist at the European Molecular Biology Laboratory in Heidelberg,
Germany, from 1994 to 1996. He has been at UCD since 1997.
Alan D. Barrett, Ph.D., is Director of the Sealy Center for Vaccine Development, Professor of
Pathology, and Professor of Microbiology and Immunology at the University of Texas Medical
Branch. He obtained his B.S., M.S., and Ph.D. in arthropod-borne viruses (arbovirology) from
the University of Warwick (1975–1983), followed by a postdoctoral fellowship at the London
School of Hygiene and Tropical Medicine (1983–1985). Subsequently, he was Lecturer, Senior
Lecturer, and Head of the Molecular Microbiology Research Group at the University of Surrey
(1985–1993). Dr. Barrett is Chair of the Scientific Advisory Panel of the Singapore
Environmental Health Institute and is a member of several national and international scientific
advisory groups, including World Health Organization (WHO) advisory groups on dengue,
encephalitis, and yellow fever vaccines; the Virus Diseases Panel of the Military Infectious
Diseases Research Program; and the Scientific Organizing Committee of the Annual Global
Vaccine Congress. He is an associate editor for Vaccine and has been the author or coauthor of
more than 234 research papers, reviews, and book chapters.

54

R. Alta Charo, J.D., is the Warren P. Knowles Professor of Law and Bioethics at the University
of Wisconsin (UW) at Madison, where she is on the faculty of the Law School and the Medical
School’s Department of Medical History and Bioethics. She obtained an A.B. in biology from
Harvard University in 1979 and a J.D. from Columbia University in 1982. Professor Charo also
serves on the faculty of the UW Masters in Biotechnology Studies program and lectures in the
M.P.H. program of the Department of Population Health Sciences. She has served on the UW
Hospital clinical ethics committee and the university’s Institutional Review Board and Bioethics
Advisory Committee. Professor Charo serves on the expert advisory boards of several
organizations focused on stem cell research, including the Juvenile Diabetes Research
Foundation, WiCell, and the Wisconsin Stem Cell Research Program. In 1996–2001, Professor
Charo was a member of President Clinton’s National Bioethics Advisory Commission. Since
2001, she has been a member of the National Academy of Sciences (NAS) Board on Life
Sciences, and she serves as liaison to or member of several NAS and IOM committees working
in research ethics, public health ethics, and stem cell policy.
Beatrice H. Hahn, M.D., is Professor of Medicine and Microbiology in the Division of
Hematology/Oncology at the University of Pennsylvania Perelman School of Medicine. She is a
microbiologist recognized for her work deciphering the primate origins of the human AIDS
viruses HIV-1 and HIV-2 and the malaria parasite Plasmodium falciparum. She is known
particularly for developing noninvasive methods to study the evolution, biology, natural history,
and zoonotic potential of infectious agents in wild-living endangered primates, especially
chimpanzees and gorillas. Dr. Hahn was born in Munich, Germany, and became a U.S. citizen in
2007. She received an M.D. from the University of Munich in 1981 and a doctorate in medicine
in 1982, and she performed postdoctoral studies at the National Cancer Institute from 1982 to
1985. Hahn was a faculty member at the University of Alabama in Birmingham for 26 years,
where she served as Co-Director of the Center for AIDS Research. In 2011, she joined the
Departments of Medicine and Microbiology at the University of Pennsylvania. Dr. Hahn is a
fellow of the American Academy of Microbiology, a member of the IOM, and a member of the
National Academy of Sciences.
Stephen Ross, Ph.D., is Director of the Lester E. Fisher Center for the Study and Conservation
of Apes at Lincoln Park Zoo in Chicago. In this role, he directs a multidisciplinary team focused
on advancing the knowledge of ape biology, improving the care and management of captive
apes, and conserving and protecting wild ape populations. He holds a B.Sc. from the University
of Guelph, an M.A. from the University of Chicago, and a Ph.D. from the University of
Copenhagen. He has studied chimpanzee behavior for more than 17 years in a range of settings,
including research centers, sanctuaries, and zoos. After joining Lincoln Park Zoo in 2000, Dr.
Ross played a primary role in the design of the award-winning Regenstein Center for African
Apes. In 2002, he was selected as Chair of the Chimpanzee Species Survival Plan®, a multiinstitutional effort to manage the population of chimpanzees living in accredited zoos in North
America. Dr. Ross founded Lincoln Park Zoo’s Project ChimpCARE in 2009 to assess the
housing and management of privately owned chimpanzees (pets and performers) to facilitate
policy changes that will benefit this population.

55

Patricia Turner, M.Sc., D.V.M., D.V.Sc., is Professor of Pathobiology and Program Leader of
Graduate Studies in Laboratory Animal Science at the University of Guelph. She also manages
the campus laboratory animal diagnostic pathology core and provides consultative laboratory
animal pathology services. Her research interests include infectious diseases of laboratory
animals, the influence of the environment on laboratory animal behavior and disease
susceptibility, and anesthesia and analgesia of laboratory animals. Dr. Turner has a B.Sc. in
biochemistry from McMaster University, an M.Sc. in pharmacology from Dalhousie University,
a D.V.M. from Ontario Veterinary College, and a D.V.Sc. in comparative pathology from the
University of Guelph. Following postdoctoral work at McGill University, Dr. Turner was
Director of Animal Care Services and Assistant Professor of Pathology at Queen’s University.
She was subsequently a toxicology team representative in preclinical safety testing at WarnerLambert and Pfizer. Dr. Turner is a Diplomate of the American College of Laboratory Animal
Medicine and the American Board of Toxicology. In 2007, she was the inaugural recipient of the
North American Animal Welfare Award, cosponsored by Procter & Gamble and the Humane
Society of the United States. She is President of the Association of Primate Veterinarians.
Biographies of Members Who Participated in the Working Group for a Partial Term
Stanley Lemon, M.D., is Professor of Medicine at the University of North Carolina. He received
his undergraduate degree in biochemical sciences from Princeton University and his M.D. with
honors from the University of Rochester. He completed postgraduate training in internal
medicine and infectious diseases at the University of North Carolina at Chapel Hill and is board
certified in both internal medicine and infectious diseases. From 1977 to 1983, he directed the
Hepatitis Laboratory at the Walter Reed Army Institute of Research. Dr. Lemon joined the
faculty of the University of North Carolina School of Medicine in 1983, serving first as Chief of
the Division of Infectious Diseases and then Vice Chair for Research in the Department of
Medicine. In 1997, Dr. Lemon moved to the University of Texas Medical Branch as Professor
and Chair of the Department of Microbiology and Immunology. He served as permanent Dean of
Medicine from 2000 to 2004. Dr. Lemon's personal research interests relate to the molecular
virology and pathogenesis of the positive-stranded RNA virus responsible for hepatitis C.
Daniel Povinelli, Ph.D., is Professor of Biology at the University of Louisiana in Lafayette. He
received his undergraduate degree from the University of Massachusetts at Amherst and his
doctorate from Yale University. He joined the faculty of the University of Louisiana in 1991. He
was awarded a $1 million James S. McDonnell Centennial Fellowship in 1999 and named one of
“20 Scientists to Watch in the Next 20 Years” by Discover magazine in 2000. Dr. Povinelli's
primary interests are in characterizing the evolution of higher-order cognitive functions in the
great ape/human clade (humans, chimpanzees, gorillas, orangutans).

56

Charles Rice, Ph.D., is the Maurice R. and Corinne P. Greenberg Professor in Virology at The
Rockefeller University. Dr. Rice received his Ph.D. in biochemistry in 1981 from the California
Institute of Technology, where he was subsequently a postdoctoral research fellow from 1981 to
1985. Before he joined The Rockefeller University in 2000, Dr. Rice spent 14 years on the
faculty of the Washington University School of Medicine. Dr. Rice is Executive and Scientific
Director of the Center for the Study of Hepatitis C, an interdisciplinary center established jointly
by The Rockefeller University, NewYork-Presbyterian Hospital, and Weill Cornell Medical
College. Dr. Rice is a member of the National Academy of Sciences.

57

Appendix C: Consultants to the Working Group on the Use of
Chimpanzees in NIH-Supported Research

Bruce M. Altevogt, Ph.D., Senior Program Officer, Institute of Medicine
Jeffrey P. Kahn, Ph.D., M.P.H., Robert Henry Levi and Ryda Hecht Levi Professor of Bioethics
and Public Policy and Deputy Director for Policy and Administration, Berman Institute of
Bioethics, Johns Hopkins University
Jay R. Kaplan, Ph.D., Professor of Pathology (Comparative Medicine) and Anthropology, Wake
Forest School of Medicine; Director, Wake Forest University Primate Center
Stanley Lemon, M.D., Professor of Medicine, School of Medicine, University of North Carolina
at Chapel Hill
Charles Rice, Ph.D., Maurice R. and Corinne P. Greenberg Professor in Virology, The
Rockefeller University
Robert Sapolsky, Ph.D., John A. and Cynthia Fry Gunn Professor of Biological Sciences,
Neurology and Neurological Sciences, Stanford University

58

Appendix D: Schedule of Meetings and Field Trips of the Working
Group on the Use of Chimpanzees in NIH-Supported Research
Face-to-Face Meetings and Teleconferences
February 2, 2012: Bethesda, Maryland
February 24, 2012: Teleconference (WebEx)
April 4, 2012: Teleconference (WebEx)
May 14–15, 2012: Los Angeles, California
July 2, 2012: Teleconference
August 1, 2012: Chicago, Illinois
September 20, 2012: Teleconference
October 5, 2012: Teleconference
October 18, 2012: Teleconference (WebEx)
November 13, 2012: Teleconference
November 27, 2012: Alamogordo, New Mexico
December 11, 2012: Teleconference
December 20, 2012: Teleconference
December 27, 2012: Teleconference (WebEx)
January 8, 2013: Teleconference (WebEx)
January 11, 2013: Teleconference (WebEx)

Presentations by Working Group Co-Chairs to the Council of Councils
June 5, 2012: Bethesda, Maryland
September 5, 2012: Bethesda, Maryland
October 29, 2012: Teleconference (WebEx)
January 8, 2013: Internet-assisted review
January 22, 2013: Bethesda, Maryland

Field Trips
The Working Group conducted several field trips to chimpanzee facilities (listed below) to
observe and better understand the environments in which the animals are housed. These
experiences helped Working Group members develop their definition of ethologically
appropriate environments.
May 25, 2012: New Iberia Research Center, The University of Louisiana at Lafayette, New
Iberia, Louisiana
May 26, 2012: Chimp Haven, Inc., Keithville, Louisiana
August 1, 2012: Lincoln Park Zoo, Chicago, Illinois
November 26, 2012: Southwest National Primate Research Center, Texas Biomedical Research
Institute, San Antonio, Texas
November 26, 2012: Michale E. Keeling Center for Comparative Medicine and Research, The
University of Texas M.D. Anderson Cancer Center, Bastrop, Texas
November 27, 2012: Alamogordo Primate Facility, Alamogordo, New Mexico
December 4, 2012: Save the Chimps Sanctuary, Fort Pierce, Florida
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Colony Management Subgroup Meeting
August 2, 2012: Chicago, Illinois

Emerging Diseases Subgroup Meeting
December 7, 2012: Houston, Texas

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Appendix E: Summary of Expert Interviews
To assist with their deliberations concerning ethologically appropriate physical and social
environments and size and placement recommendations for captive research chimpanzees,
Working Group members conducted field trips to all facilities housing NIH-owned and
-supported chimpanzees as well as sanctuaries housing chimpanzees that had been retired from
research, entertainment, and private ownership. In addition, members of the Working Group’s
Colony Management Subgroup conducted a series of interviews with international experts in the
care and use of chimpanzees:
 Linda Brent, Ph.D., President and Director, Chimp Haven, Inc.
 Kathleen Conlee, Vice President, Animal Research Issues, The Humane Society of the
United States
 Lisa Faust, Ph.D., Vice President of Conservation and Science, Lincoln Park Zoo,
Chicago, Illinois
 Paul Honess, Ph.D., Director of Animal Behaviour, Welfare, and Research, Bioculture
Group, Mauritius/United Kingdom  
 Sarah Long, M.S., Director, Population Management Center, Lincoln Park Zoo, Chicago,
Illinois
 Elizabeth Lonsdorf, Ph.D., Adjunct Scientist, Lester E. Fisher Center for the Study and
Conservation of Apes, Lincoln Park Zoo; Assistant Professor, Department of Psychology,
Franklin and Marshall College
 Tetsuro Matsuzawa, D.Sc., Director, Primate Research Institute, Kyoto University
 Steven Schapiro, Ph.D., Associate Professor, Michale E. Keeling Center for Comparative
Medicine and Research; Section Chief, Primate Behavior and Environmental Enrichment,
The University of Texas M.D. Anderson Cancer Center
 John L. VandeBerg, Ph.D., Chief Scientific Officer, Texas Biomedical Research Institute;
Director, Southwest National Primate Research Center
 Richard Wrangham, Ph.D., Ruth B. Moore Professor of Biological Anthropology,
Harvard University; Co-Director, Kibale Chimpanzee Project
 Stuart Zola, Ph.D., Director, Yerkes Regional Primate Research Center
This appendix summarizes these interviews.
Ethologically Appropriate Physical and Social Environments
Without exception, the experts that the subgroup consulted indicated that the most important
factor for chimpanzee well-being is the ability to live and act as part of a large, complex, multimale, multi-female social group. To maintain these social structures and provide sufficient
physical and cognitive stimulation, animals should be maintained within large, complex, outdoor
primary living spaces with abundant vertical and horizontal dimensions for climbing and other
forms of exploration, foraging, and ranging.
Ethologists and other experts cited conditions at Gombe National Park in Tanzania, where one of
the densest populations of chimpanzees live, as a possible starting point for calculating
appropriate spaces. Here, the population density is approximately 0.39 square miles (0.35 km2)
per chimpanzee. Chimpanzee densities at large North American sanctuaries range from 25 to 30
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animals per 3–5-acre (12,000 to 20,000 m2) range. The experts consulted recognized that
developing such large spaces would be impractical in most (if not all) captive research settings
and that more practical densities of 1,000 to 10,000 ft2 (93 to 930 m2) per chimpanzee would be
more feasible, while still maintaining the ability of animal groups to appropriately range and
form subgroups.
Although the experts agreed that naturalistic settings are not necessarily required for chimpanzee
housing, these settings are less expensive to develop and maintain than artificial settings, and
they provide a far greater range of multisensory stimulation and complexity. Functional
simulations, such as artificial structures to mimic ant or termite mounds, might be added to
encourage tool use and other cognitive skills development and to augment the captive physical
environment.
The ethologists and other experts interviewed also emphasized the importance of management
considerations for captive chimpanzees. Managing captive chimpanzees through the use of
positive reinforcement training was cited as a critical means of reducing adverse stress for these
animals in research and other captive settings. Furthermore, because of the importance of longterm social bonding in chimpanzees, best management practices preserve stable social groupings
whenever possible.
Size and Placement of Future Captive Research Chimpanzees
When asked to comment on the optimal group size for captive research chimpanzees, the
scientists consulted indicated that ideally, groups should consist of at least 10 to 30 members and
that larger group sizes provide more optimal cognitive stimulation for animals. The most
important limiting determinant for group size is the amount and complexity of primary living
space offered to chimpanzees. Based on these discussions, it was apparent that even if less than
25 to 30 chimpanzees are required annually for long-term invasive biomedical research projects,
it might be necessary to hold more chimpanzees in a research facility to ensure their optimal
psychological well-being. The experts also consistently recognized that noninvasive comparative
behavioral and genomic research projects could be conducted using chimpanzees held in
accredited sanctuary or zoo settings. The CHIMP Act (described in the glossary at the beginning
of this report) permits these types of research in the federal sanctuary system.
There was no consensus regarding the specific numbers of chimpanzees required for biomedical
versus comparative behavioral or genomic research. Some experts indicated that no chimpanzees
are required and that all research-active and research-inactive animals should be immediately
retired to a federally owned sanctuary. Other experts indicated that if chimpanzees were
available for research and research funds were available from the NIH, there would be no
difficulty in finding suitable projects. Importantly, it was unclear whether those interviewed
believed that these new projects would be consistent with the IOM principles and criteria.
Despite this, all of those interviewed indicated that, in their opinion, the use of chimpanzees in
research has declined significantly in the past decade. This was an interesting comment that is
not supported by data because the number of projects using chimpanzees that the NIH has
funded over the past 30 years has remained relatively constant, with sporadic increases in project
62

numbers from time to time (IOM, 2011, Figure 1, p. 22). Finally, several experts recognized that
because of the long breeding span of chimpanzees and the broad age range of current researchactive and research-inactive animals, it would not be necessary to breed chimpanzees to maintain
sufficient numbers for research for at least 10 years.

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Appendix F: Summary of Public Input from NIH Requests for
Information
In February 2012, the National Institutes of Health (NIH) issued two requests for information
(RFIs) seeking public input into the deliberations of the Council of Councils Working Group on
the Use of Chimpanzees in NIH-Supported Research. The purpose of the RFIs was to obtain
broad input on issues underlying NIH’s implementation of the recommendations made by the
Institute of Medicine (IOM) in their report Chimpanzees in Biomedical and Behavioral
Research: Assessing the Necessity and subsequently accepted by the NIH. The first opportunity
for public input was published in the NIH Guide for Grants and Contracts on February 10, 2012,
as Notice number OD-12-052 (NOT-OD-12-052). An identical, second request was published in
the Federal Register on February 23, 2012 to reach out to members of the public not typically
reached through the NIH Guide for Grants and Contract. The comments received in response to
both RFIs are summarized below.
One-hundred ten (110) comments were received in response to the RFIs. Twenty-three (23)
comments were submitted on behalf of organizations while eighty-seven (87) were prepared on
the submitter’s behalf, or “self.” Fifty-six (56) respondents submitted identical information (i.e.,
a form letter). The remaining fifty-four (54) comments were considered unique and were
summarized.
RFI Comment Topic #1: Developing a plan for implementation of the IOM’s guiding principles
and criteria
Respondents expressed considerable support for the IOM process, the recommendations that
resulted, and the NIH’s immediate acceptance of the criteria and principles for the use of
chimpanzees in research. Commenters agreed that the use of chimpanzees in biomedical and
behavioral research should be governed by an additional set of standards, and the reliance on
chimpanzees in research should be reduced and, if possible, eliminated altogether. Differences of
opinion surrounded the proposed timing to reduce their use. Some suggested immediately
ceasing all research involving chimpanzees, stating that this animal model is entirely
unnecessary and/or has been replaced by other methods. Others proposed to continue using
chimpanzees to study specific conditions permitted by the IOM report and phase out areas of
research where the chimpanzee is not necessary. It was universally accepted, however, that the
housing for any chimpanzee, whether used in research, inactive, or retired, be consistent with the
highest standards of care and living environments. Others believed that the Working Group
should consider the ethical implications of research using chimpanzees.
Some respondents suggested that the Working Group’s charge also include the option for
chimpanzee retirement. Because the Working Group was charged with advising on the size and
placement of active and inactive populations of NIH-owned or -supported chimpanzees that may
need to be considered as a result of implementing the IOM recommendations, the size and
placement of retired animals is outside the purview of the Working Group. However, given the
number of commenters that raised retirement as a concern and interest, those remarks are
summarized in RFI Comment Topic #3.

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Some commenters encouraged the Working Group to consider the financial, personnel, and other
resources would likely be needed to implement the recommended oversight process, funding for
alternative in vivo and in vitro models, and costs to implement recommended care and housing
standards. To the extent that certain types of research would continue, respondents noted that
budget support would be needed to address the bolstered psychological and physical welfare of
the animals. Several commenters proposed that stopping research with chimpanzees would
enable the NIH to divert those resources toward alternative models. Commenters also urged the
Working Group and the NIH to increase investments in finding alternatives to the chimpanzee
model.
RFI Comment Topic #2: Factors to consider in reviewing currently active NIH-supported
research using chimpanzees to advise on which studies currently meet the principles and criteria
defined by the IOM report and advising on the process for closing studies if any do not comply
with the IOM recommendations. For example: criteria to assess “minimally invasive”
procedures for comparative genomics and behavioral research and “ethologically appropriate”
physical and social environments; criteria to balance phasing out of the existing research
without causing “unacceptable losses to research programs” or an unacceptable “impact on the
animals.”
Ethologically Appropriate
The IOM report states, “The animals used in the proposed research must be maintained either in
ethologically appropriate physical and social environments (i.e., as would occur in their natural
environment) or in natural habitats.” Due to the uncertainty of the term “ethologically
appropriate” environments, the NIH requested input on how to assess such environments.
Respondents universally were supportive of the concept of “ethologically appropriate”
environments to more fully enhance the physical and psychological needs of chimpanzees.
Commenters discussed the applicability of existing standards set forth by the Animal Welfare
Act and various housing and environment practices as enforced by accrediting entities. Many
stated, however, that “ethologically appropriate” sets a higher bar for chimpanzee habitats than
existing laws and/or regulations.
Concerns surrounding the term “ethologically appropriate” pertained mainly to it lacking a
definition and that, as a new concept, may not be fully represented in the terminology or site visit
standards of the accrediting organization, the Association for Assessment and Accreditation of
Laboratory Animal Care International (AAALAC), or the agency charged with federal oversight,
the U.S. Department of Agriculture (USDA). Many commenters stressed the importance of
defining and operationalizing “ethologically appropriate” because, by itself, the concept is
subjective. Rather than provide a definition for “ethologically appropriate,” several respondents
instead proposed a range of characteristics to help resolve ambiguity surrounding the term.
Suggestions included:
 Accreditation from AAALAC and registration with USDA
 Environments that facilitate foraging and nesting behavior, traveling, climbing, and
brachiating
 Enrichment programs that support chimpanzee problem-solving behaviors

65









Social housing that supports the social needs of captive chimpanzees, including
conspecific social partners
Socially compatible grouping with a minimum group size of at least three chimpanzees to
more closely approximate the size of wild chimpanzee communities; pair housing when
an animal does not do well in a group
Space for subgrouping behavior, i.e., fission-fusion social rhythm of chimpanzees
Inside and outside housing with daily access to outside environment
Environment free of threats or a spatial opportunity to escape threats
Mixed-age and -gender groups

Another commenter suggested that the Working Group consider AAALAC accreditation as
sufficient evidence that appropriate environments are provided.
Minimally Invasive and Acquiescence
With respect to comparative genomics and behavioral research, the IOM recommended that “All
experiments are performed on acquiescent animals, using techniques that are minimally invasive,
and in a manner that minimizes pain and distress.” Some commenters proposed that the Working
Group defer to the definition of invasive research as written in the proposed draft of the Great
Ape Protection and Cost Savings Act, which states: “The term ‘invasive research’ is defined to
include any research that may cause death, injury, pain, distress, fear, or trauma to a great ape.”
Some respondents characterized invasivity as including methods to induce sedation, surgeries,
implantation or attachment of devices, removal from “ethologically appropriate” environments
or natural habitats for research purposes, and removal of blood or tissues other than what is
necessary during prescribed examinations or procedures to monitor or maintain the health and
well-being of the chimpanzee. Another respondent proposed to align the concept of invasive
procedures with the Animal Welfare Act’s definition of major surgery, i.e., invading a body
cavity. Minimally invasive procedures, in general, would be those conducted in human medicine
on an outpatient basis.
Others suggested that “minimally invasive” could be described as a procedure that does not
permanently alter the anatomy or physiology of the chimpanzees, such as blood collection,
imaging procedures, and behavioral studies. It was suggested that some limits be placed on
sedation, including the number of times a chimpanzee can be anesthetized per year for research
purposes, the duration of sedation, and scheduling tests requiring anesthesia to coincide with the
annual exam. Some suggested that certain laboratory tests could be minimally invasive and
conducted on acquiescent animals if the chimpanzee voluntarily presented for blood draws and
accepted injections for anesthesia—something that would benefit both the annual veterinary
check-ups and imaging studies, for example.
RFI Comment Topic #3: Factors to consider when advising on the size and placement of active
and inactive populations of NIH-owned or -supported chimpanzees as a result of implementing
the IOM recommendations. For example: ways to address capacity issues that would accompany
an increase in “inactive” animals; factors to consider in transitioning the animals that are newly
inactive; how many and what would be the characteristics of animals held in reserve for future
research, if any; the number of animals needed to maintain a viable number of research naïve

66

animals but also genetic and social stability and sufficient diversity for unanticipated research
needs.
For purposes of this summary, the NIH clarifies that “active” means the chimpanzees are needed
for current research projects that fit the IOM criteria. In comparison, “inactive” means the animal
is not currently needed for research but may be needed for new projects that fit the IOM criteria.
“Retired” means the chimpanzee is no longer needed for research.
Research “Active”
Some respondents remarked that all chimpanzees should be retired immediately and not held in
reserve for future research. Others were supportive of a limited number of “inactive” animals and
diminishing numbers in “active” status. In the limited circumstances when chimpanzee use
would be permissible, it was suggested that NIH-funded investigators take steps to increase the
quality of life of laboratory-housed animals by working with organizations that specialize in
these matters. In addition, it was recommended that facilities housing chimpanzees for
biomedical research should document animal-specific plans that limit the prolonged and repeated
use in research protocols and specify plans for their retirement. In addition, ongoing and regular
review of the research should be conducted to assess alternative methods or models that may
have emerged since the last approval.
Research “Inactive”
Respondents largely were unsupportive of keeping a reserve of chimpanzees available for
research; however, some were amenable to an “inactive” population if a plausible need exists
and if the laboratory environment can be made more akin to the chimpanzees’ natural habitat, in
effect, “ethologically appropriate.” See “Future Research.”
Retirement from Research
Some commenters recommended the creation of a committee to oversee, in a transparent fashion,
the retirement of chimpanzees from NIH-funded research. Respondents encouraged the Working
Group to recommend a national chimpanzee management system unaffiliated with the NIH to
oversee the transition of chimpanzees out of medical research laboratories and into sanctuaries.
Responsibilities of this committee would include determining which chimpanzees are eligible for
retirement based on predefined criteria, such as:
 Age of chimpanzee
 Medical and psychological status
 Number of years in research
 Anticipated medical and social needs after retirement that could affect the place of
retirement
Proponents of retirement mostly advocated for moving chimpanzees to sanctuaries that are
inspected by the U.S. Department of Agriculture and accredited by AAALAC. Most commenters
lauded the sanctuary environment as a model ethology for the chimpanzee, providing ready and
often unrestricted access to a foraging and forest environment, social groupings, and
opportunities to exercise decision making (making choices). However, some voiced concerns
about the staffing and infrastructure currently available to care for animals with chronic
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conditions (e.g., HIV and advanced diabetes) and other special health and housing needs. Others
expressed concerns about insufficient capacity in existing sanctuaries to house a considerable
influx of newly retired animals, and new facilities would be needed to house chimpanzees retired
from research and relocated to sanctuaries. Others expressed confusion over which federal laws
and regulations apply to sanctuaries.
Several commenters expressed dissatisfaction with the option of retiring the chimpanzee “in
place” (i.e., in the laboratory environment) versus retirement to a sanctuary largely due to
concerns that the laboratory enclosures would not be “ethologically appropriate.” Others
expressed that laboratory facilities, to the extent that they are not currently “ethologically
appropriate,” could take steps to improve the housing and well-being of the chimpanzees. This
approach could be an alternative to retiring the animals to a sanctuary. Some contended that the
veterinary and diagnostic capabilities of the research laboratories are superior to those of
sanctuary environments and could offer better health care to aging and possibly ill chimpanzee
populations.
Future Research
The IOM report suggested that a “new, emerging, or reemerging disease or disorder may present
challenges to treatment, prevention, and/or control that defy non-chimpanzee models and
available technologies.” The NIH asked for input on the number and characteristics of animals
held in reserve for future research, if any, and the number of animals needed to maintain a viable
number of research naïve animals but also genetic and social stability and sufficient diversity for
unanticipated research needs. To the extent that a reserve colony is needed, it was suggested that
retaining animals with breeding potential (e.g., proven breeder, good mother, mother reared,
socially housed) would help maintain a self-sustaining population. It was suggested that one
small colony, possibly ages 10 to 20 years old, should be retained for a brief period (e.g., five
years). Other commenters separately suggested that the requirements for conducting invasive
research mirror those of the Chimpanzee Health Improvement and Maintenance Protection Act
(P.L. 106-551)—that is, they should offer a public comment period and mandate Department of
Health and Human Services Secretarial approval for such research.
In contrast, many commenters stated that no future research on chimpanzees is necessary, and,
therefore, holding a reserve population for future research is similarly unnecessary. If all
chimpanzees owned by the NIH are retired, one commenter suggested that chimpanzees owned
by private entities (not the NIH) could be made available for future research.
Several respondents remarked that some sanctuaries permit scientists to utilize excess specimens
collected from annual veterinary check-ups and necropsy tissue for research. In addition,
observational research reportedly can be conducted at some sanctuaries. The Working Group
was asked by one respondent to consider allowing researchers liberal access to sanctuary
populations of chimpanzees for specimen and behavioral research, should it recommend retiring
some animals to sanctuaries.
RFI Comment Topic #4: A review process for considering whether potential future use of the
chimpanzee in NIH-supported research is scientifically necessary and consistent with the IOM
principles. For example: factors to consider in determining whether other models (e.g., in vitro,
other in vivo) would be a “suitable model” for answering the research question; research areas
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where alternative model development is recommended; whether the NIH should have a plan to
maintain a minimal population of federally-owned chimpanzees and input on the design of the
plan; circumstances under which chimpanzees should be considered as a model for “a new,
emerging, or reemerging disease or disorder that may present challenges to treatment,
prevention, and/or control that defy non-chimpanzee models and available technologies";
characteristics of the oversight committee responsible for reviewing future research proposals
and determining whether they are consistent with the IOM criteria and whether they can be
conducted.
Review Committee for Future Research
The IOM report recommended that “the assessment of the necessity of the chimpanzee in all
grant renewals and future research projects would be strengthened and the process made more
credible by establishing an independent oversight committee…” Several commenters proposed
characteristics of the oversight committee responsible for reviewing future research for
compatibility with the IOM criteria. Suggestions included developing a process that is
transparent (i.e., open to the public and/or having a public comment period), able to be
completed quickly, have committee membership composed of individuals without a personal or
institutional conflict of interest, and have membership representing the following disciplines:
 Laboratory animal veterinarian for chimpanzee-specific medical and behavioral needs
and to advise on the likely health effects of the research during and after the study
 Primatologist to advise on chimpanzee colony size and maintenance
 Bioethicist and member of an institutional review board to provide input on the ethics of
conducting the proposed research in humans
 Public health official to advise on whether foregoing the use of chimpanzees in research
would result in significant delays in making medical advances for life-threatening or
debilitating conditions
 Statistician to advise on the statistical power of the number of animals proposed for use
 Technologists and other experts in alternative methods and models
 Virologist to advise on hepatitis C virus biology
 Immunologist with expertise in monoclonal antibody development
 Social scientist/neuroscientist for insights into whether proposed behavioral research
would provide unattainable insights into behavior, mental health, emotion, or cognition
 Geneticist specializing in comparative genetics and transgenic models
 Patient advocates representing areas of research proposed for study
 Member of the public
Another respondent recommended having a chimpanzee institutional animal care and use
committee (IACUC) at the national or regional level to oversee their research use. Some
commented that the existing NIH scientific peer review process could serve to review research
applications proposing to use chimpanzees in research because the vertebrate animal section of
grant applications could contain the requested details. As an outcome of these reviews, one
commenter suggested that if an application is denied because alternatives exist, the investigator
may need options for learning how to utilize the alternative model or method.

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Alternatives
Respondents were universally supportive of exploring alternative methods for studying diseases
and conditions and emphasized the importance of continuing to study, develop, and commit
resources to finding alternatives to the chimpanzee model. Several commenters who discussed
alternatives also remarked that the development of new or novel methods might be hampered by
continuing to use chimpanzees in research, suggesting that there would be little incentive to find
alternatives so long as the chimpanzee model is available. Others posited that suitable alternative
models are already currently available and should obviate the need for any further research using
chimpanzees, even in the areas the IOM suggested were appropriate to continue. Several
commenters suggested making available to researchers and the review committee a reference list
of suitable alternatives to the chimpanzee model.
Other Comments
Some respondents debated the conclusions of the IOM report with respect to the hepatitis C virus
and monoclonal antibodies, asserting that chimpanzees are not a good model of human disease
and existing alternative methods and models obviate a role for chimpanzees in research. Others
stated that chimpanzees cannot give informed consent and, therefore, should not be used in
research. In contrast, several others presented comments strongly favoring the use of
chimpanzees to study the hepatitis C virus, for example, and offered additional rationale as to
why this research should be continued.
One commenter disagreed with the NIH Guide Notice announcing the policy on NIH research
involving chimpanzees (NOT-OD-025), suggesting that the NIH should accept and review grant
applications proposing to use chimpanzees in research pending the establishment of the formal
oversight process. This commenter suggested that not allowing grant application reviews in the
interim penalizes the investigator seeking NIH funding.
Several comments were largely supportive of research involving stored biological samples,
specimens collected passively from the chimpanzee habitat (e.g., feces), specimens resulting
from annual veterinary check-ups, and observational research where no interaction with the
chimpanzee takes place. One commenter was opposed to obtaining new material for research
without scientific justification as to why the existing and stored materials are unsuitable.

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Appendix G: White Paper on the Use of Chimpanzees in New,
Emerging, and Reemerging Diseases Research
Executive Summary
The five-member Emerging Diseases Subgroup of the Working Group (WG) on the Use of
Chimpanzees in NIH-Supported Research was charged with advising the WG on whether and
how chimpanzees will be needed in the future for research involving infectious diseases. The
Subgroup reaffirmed Recommendation 1 in the Institute of Medicine/National Academy of
Sciences (IOM) report by the Committee on the Use of Chimpanzees in Biomedical and
Behavioral Research (IOM, 2011). This recommendation states that the National Institutes of
Health (NIH) should limit the use of chimpanzees in biomedical research to those studies (1) for
which there is no other suitable model available for the research in question; (2) the research in
question cannot be performed ethically in human subjects; and (3) 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. With
regard to infectious disease research, the IOM Committee considered only two research areas
that might be necessary, hepatitis C virus vaccine research and the “unknown-unknown” (i.e., a
lethal new, emerging, or reemerging infectious agent or a novel bioterrorism agent for which all
other approaches to develop prevention and control strategies have failed, an exception also
referred to as the “safeguard clause”).
Scientific rationale for using chimpanzees in infectious disease research. The Subgroup agreed
that only in a unique and rare situation would infectious disease research warrant use of
chimpanzees. This would have to be a case in which the public health need outweighed the
issues involved in using chimpanzees in high biocontainment (i.e., animal biosafety level
[ABSL] 3 and 4 laboratories) facilities. It was presumed that only a new, emerging disease of
exceptional lethality would warrant any chimpanzee use. Following a decision that chimpanzee
use would be warranted, several practical questions come into focus: (1) the availability of
chimpanzees that are suitable research subjects, (2) the availability of staff trained in both
chimpanzee veterinary care and high biocontainment research, (3) appropriate ABSL3 and/or
ABSL4 facilities that could be used for such work, (4) chimpanzee usage and biosafety
regulations that would allow such work, and (5) the substantial financial resources required for
such research. This scenario would be predicated on evidence that the new emerging disease
could not be adequately studied in other experimental animal species or by using conventional
microbiological/virological laboratory techniques. There has been full agreement that
chimpanzees would not be used for discovery-phase research and that the need might only arise
in downstream research (e.g., in pathogenesis/pathophysiology research required for preclinical
vaccine or drug development research).
High biocontainment facility considerations. There never has been any research employing
chimpanzees under high biocontainment (ABSL3, ABSL4) conditions. In the case (rare as it may
be) of a naturally occurring outbreak or bioterrorism event involving an unknown-unknown,
several options would have to be considered since none of the current high biocontainment
facilities were designed to house chimpanzees. (1) An existing ABSL3/4 facility that is in close
proximity to a chimpanzee research facility might be adapted for use. (2) NIH could, in
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partnership with a federal ABSL4 facility, build modifications so as to house chimpanzees. This
would be most feasible if the federal facility were still in a planning phase at the time of the
decision. The Subgroup was only aware of one such facility, the new U.S. Army Medical
Research Institute for Infectious Diseases (USAMRIID) BSL4 facility at Fort Detrick, Maryland.
(3) NIH could build a new ABSL4 facility specifically designed to house chimpanzees. Since all
high biocontainment facilities are designed around the number and size of animals that are to be
housed, this option would yield the best facility. This is by far the most expensive option, as
BSL4 construction costs are currently estimated to be approximately $6,100 per net square foot,
and annual operating costs are 16% of construction costs. Maintaining unused laboratory
facilities is impractical and cost-prohibitive, so this option would have to include plans for
alternative interim use of the chimpanzee laboratory. (4) NIH could choose to take no action,
given that the need to use chimpanzees in high biocontainment facilities is very unlikely.
Availability of research chimpanzees. Clearly, options 1–3 above assume that research
chimpanzees would be available at the time of a national emergency. There are no active
breeding programs at any of the five U.S. national chimpanzee research facilities. Decisions
made regarding the need for chimpanzees for the described purposes would determine whether
or not there will be chimpanzees available for use in timely fashion, should the need arise. If the
recommendations of the IOM Committee are accepted in full, in the near future, all invasive
medical research using chimpanzees supported by NIH funds would end, with the two exceptions
already cited. This would bring the United States into a consistent regulatory framework with the
European Union and other countries. Hence, it is likely that there would not be any research
animals in reserve, even in the case of a national emergency in which the “safeguard clause”
would allow the use of chimpanzees
Overview of Activities and Conclusions of the IOM Committee in Chimpanzees in
Biomedical and Behavioral Research: Assessing the Necessity Regarding Emerging Diseases
When a new or emerging infectious disease is suspected, a complex continuum of prevention and
control activities may be called into action, but, given financial and resource constraints,
decisions must be made and priorities set. The full continuum (sometimes called the “discoveryto-control continuum”) comprises many activities and resources, which may be divided into
investigative and interventional (or translational) phases (Murphy, 1998). NIH’s role, through its
intramural and extramural programs in this discovery-to-control continuum, typically begins
immediately after a novel dangerous pathogen has been identified, but this is a complex subject
with many variables. The sequence of events is typically as follows: (1) identify the pathogen,
usually by genomic sequencing, to determine if it is new or related to any known pathogen; (2)
determine whether existing knowledge from a known pathogen can be bridged to the new
pathogen; (3) use sequence data to develop diagnostic tools; (4) isolate the pathogen and
undertake in vitro studies; (5) undertake modeling studies in parallel with non-chimpanzee
animal studies; and (6) determine if animal models are needed to study pathogenesis or develop
drugs and vaccines, and ensure that the model recapitulates the disease observed in humans.

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Three guiding principles were developed by the IOM Committee on the Use of Chimpanzees in
Biomedical and Behavioral Research:
1. The knowledge gained must be necessary to advance the public’s health.
2. There must be no other research model by which the knowledge could be obtained, and the
research cannot be ethically performed on human subjects.
3. The animals used in the proposed research must be maintained either in ethologically
appropriate physical and social environments or in natural habitats. (It was understood in
general that high biocontainment research is not “ethologically appropriate.”)
The scientific rationale for using chimpanzees in infectious disease research was discussed at
length by the IOM Committee. It is recognized that chimpanzees do not play a role in discoveryphase infectious disease research. There are several reasons for this: (1) over the years,
chimpanzees have proven to be quite resistant to many pathogens, whereas in discovery research,
the need is for animal models that are relatively susceptible to infection with the infectious agent
of concern; (2) there is an early need to use large numbers of susceptible animals to measure
many variables quantitatively; and (3) we have high confidence in modern molecular biological
technologies for agent discovery and initial agent characterization. If chimpanzees are needed for
research with an unknown-unknown, it would be in later-stage investigations of the disease
outbreak, such as for pathogenesis research during vaccine/drug preclinical development. The
likelihood of needing chimpanzees for research on an unknown-unknown is unknown but
presumed to be very low since in all of the zoonoses identified to date, a suitable animal model
other than a chimpanzee has been identified.
In general, the mantra for dealing with new, emerging, or reemerging infectious diseases is “we
cannot predict, but we can prepare” (Nancy Cox, Director of the World Health Organization’s
World Reference Center for Influenza at the Centers for Disease Control and Prevention [CDC],
personal communication to Frederick A. Murphy). Seventy-five percent of human pathogens
have been zoonotic, and 9 out of 10 naturally acquired diseases in the last 20 years have been
zoonotic. As noted in the IOM report, Learning from SARS: Preparing for the Next Disease
Outbreak (Knobler et al., 2004), we must anticipate the emergence of new zoonoses. The
strategies for containing known zoonoses will serve as models for containing new, unknown
ones. It is in this context that the need for housing chimpanzees in a high biocontainment facility
must be considered. The question of where NIH falls in the universe of responsibilities to
respond to any particular emerging infectious disease threat does not lend itself to a simple
answer. There are lessons from how disease outbreak events have been managed historically.
Indeed, NIH has played a major role in many such investigations. Today, we may say that the
Department of Homeland Security deals with threat assessments, the CDC is responsible for
responding in the field to emerging pathogen threats, and the Food and Drug Administration
(FDA) approves vaccines and drugs for intervention. NIH’s portfolio of intra- and extramural
programs encompasses a wide range of activities that cut across the missions of all the other
agencies; lead responsibility within the biomedical research realm; and major responsibilities
extending into areas of education, training, international field research, and countermeasure
development.

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If it is decided by NIH to respond to the IOM Committee’s report on the use of chimpanzees in
biomedical and behavioral research with the development of a new high biocontainment
chimpanzee facility, perhaps, given the strategic decision to build the “National Interagency
Biodefense Campus” in Frederick, Maryland, there is an opportunity for a partnership between
NIH and USAMRIID to construct a common facility. Given that NIH already has its Integrated
Research Facility on that campus and that the new USAMRIID facility is still in the design
phase, there is a sense of practicality in this notion.
In Europe, the special situation of needing to use chimpanzees for emerging infectious disease
research is covered in a “safeguard clause” in European Union regulations (Article 55 of
Directive 2012/63/EU of the European Parliament and of the Council; September 22, 2010). The
likelihood of needing to use this clause for dealing with a lethal disease caused by an unknownunknown pathogen is difficult to assess. Since the safeguard clause has never been employed and
European Union documents do not go into exhaustive detail, it is not known if the clause could
be practically implemented for short-term use (up to months), much less for longer-term research
(years).
1. Are all emerging diseases caused by infectious agents and do all emerging infectious
diseases “emerge” from animal reservoirs?
The term “emerging disease” may refer to any disease, infectious or not, but in common usage it
has been limited to infectious diseases, as first used by Joshua Lederberg and his colleagues in
the seminal IOM report, Emerging Infections: Microbial Threats to Health in the United States
Lederberg et al., 1992). Although the term might best be limited to diseases whose incidence has
increased within the past two decades and to diseases that threaten to increase in the near future,
in some contexts, it has been extended to all but the most endemic infectious diseases. To date,
approximately 75% of emerging infectious diseases have been zoonotic in origin, and about 25%
of these derive from nonhuman primate host species. The zoonotic transmission pattern involves
transmission to humans from an ongoing reservoir life cycle in animals or arthropods without the
permanent establishment of an independent life cycle in humans. It is useful to distinguish this
pattern from “species jumping” transmission (i.e., host range extension) where initial
transmission to humans is from a reservoir life cycle in animals, followed by the establishment of
a new life cycle in humans that no longer involves an animal reservoir.
It is impossible to predict how often an “emergence” event will take place and whether or not it
would involve chimpanzees. Many human pathogens originated in animals (e.g., measles virus,
influenza viruses). Products of animal origin may also serve as sources for zoonotic or speciesjumping pathogens. Many animal species have been involved in the emergence of human
infectious diseases. Wild (e.g., bats, rodents) as well as domestic (e.g., horses, cats) and food
(e.g., poultry, cattle) animals have been implicated.
Both NIH and CDC have lists of “priority emerging pathogens” that are periodically reviewed
and are subject to revision in conjunction with federal partners. The role of the National Institute
of Allergy and Infectious Diseases (NIAID) is to conduct and support research designed to learn
as much as possible about new or emerging infectious agents and the infections they cause in
order to develop tools for identification, diagnosis, treatment, prevention, and control of such
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pathogens. In recent years, NIAID has moved toward a broad-spectrum approach for
translational research to advance each of these areas; this research often incorporates
sophisticated genomic and proteomic technologies, including novel animal model technologies.
2. Would chimpanzees be expected to be an animal reservoir for human infectious
disease?
Possibly. Chimpanzees are infected with many bacterial, viral, fungal, and parasitic agents that
may be transmitted to humans. Fifty-two infectious agents of humans have been identified in
chimpanzees according to the Global Mammal Parasite Database (17 protozoa, 13 helminths, 16
viruses, 5 bacteria, and 1 fungus; Cooper et al., 2012), but there are other examples suggesting
that the database is not yet complete. Two important considerations are the possibility of
transmission of infectious agents to humans via the bush-meat trade in Africa and the proven
transmission of nonhuman primate viruses to staff in primate centers.
The most notable example of viral host species jumping is the SIVcpz virus that moved from
chimpanzees to humans to become HIV-1. There are several other examples of transmission of
pathogens from chimpanzees to humans, including monkeypox (BSL3), Ebola virus (BSL4), and
several respiratory pathogens. Significantly, chimpanzees have not been directly exposed to
highly virulent infectious pathogens for the development of drugs and vaccines, even in the case
of Ebola and monkeypox viruses; rather, smaller animal models have been used.
3. What is possibility of a human pathogen “jumping” to chimpanzees, and could such a
pathogen then jump back to humans in a more virulent form?
There is evidence for human pathogens jumping to chimpanzees. However, the evidence that
infectious diseases in chimpanzees can jump to humans makes this an important question. A
respiratory disease, suspected of having been transmitted by humans to wild chimpanzees in the
Tai National Park in the Côte d'Ivoire, involved endangered chimpanzee populations, which have
suffered dramatic population declines from pathogens shared with humans, including respiratory
syncytial virus and human metapneumovirus (Köndgen et al., 2008). In another study examining
serum from 14 captive chimpanzees in Japanese primate research institutes, antibodies against 29
of 61 human pathogens tested were detected at high or low prevalence in the chimpanzees
(Kooriyama et al., 2013). Drug-resistant human Staphylococcus aureus has been detected in
sanctuary-housed chimpanzees and among veterinarians working in the sanctuaries (Schaumburg
et al., 2012). Data from a longitudinal analysis of measles antibody responses in 45 non-human
primate care workers for a period of up to 26 years (Amanna et al., 2007) demonstrated that virus
jumping does occur. All of the subjects worked at the Oregon National Primate Research Center.
There were spikes in antibody titers in four samples from 1999 during an outbreak due to a
primate paramyxovirus in the nonhuman primate colony. The antibody spikes identified in these
four human subjects appear to represent uncharacterized simian paramyxovirus infections that
cross-reacted with measles antigens in the serological assays. Fortunately, the infections were
inapparent and there was no indication of human-to-human spread. This is not the first time that
viruses have spread from nonhuman primates to humans; there are a number of cases in which
this has happened in the past. For example, in 1966, there were outbreaks of tanapox virus that

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occurred in three primate centers in the United States, and some animal handlers were infected
through skin abrasions (Downie and Espana, 1972).
4. Can you predict how often an “emergence” event would take place?
No. We cannot predict how often an emerging infectious disease episode might occur. We never
have done so in the past, and it is unlikely we would in the future, even with modern methods.
We should expect the unexpected and be prepared. Modeling studies are now being used to
assess emergence, and evolutionary biologists are using phylogenetic host specificity to help us
understand why some parasites or microbes are shared among primates (Cooper et al., 2012).
The idea of “pathogen flow” from humans to monkeys, and possibly from monkey to monkey,
including wild apes, is being considered and investigated (Nunn and Hare, 2012). Whether such
“flow” might result in a future emerging infectious disease event, as humans continue to
encroach on wildlife habitats, remains to be seen. “Hotspot” maps can be generated to show the
evolutionary relationship between pathogen sharing and divergence time between primate
species; these maps highlight regions where the risk of disease transfer between wild primates
and from wild primates to humans is greatest (Pedersen and Davies, 2009). The authors suggest
Central Africa and Amazonia as potential future hotspots for cross-species transmission events
between wild primates, due to the presence of diverse, closely related primate species. In
addition, hotspots for host shifts to humans are most likely in the forests of Central and West
Africa, where humans come into frequent contact with wild primates. It has been suggested that
these areas are also most likely to sustain a novel epidemic due to their rapidly growing human
populations. However, such studies also have critics, who contend that they lack geographic
precision, at least at present.
The rise in ecotourism is also providing environments for increased interactions among humans
and wildlife. At present, we have little evidence regarding the potential importance of this trend.
The response to an episode of disease stemming from ecotourism may well be driven by severe
morbidity and mortality rates, given the high cost of surveillance and control strategies.
History has shown that it is likely that some emerging disease or biodefense threats will be
unexpected and caused by a new or emerging pathogen. Current modeling efforts are skewed
toward predicting outbreaks of known pathogens and are not very good at predicting events
caused by an unknown-unknown infectious agent. As stated above, no emerging disease threat
has ever been accurately predicted.
5. How would chimpanzees be used in an emerging disease scenario?
Small animal models (i.e., mice, rats, hamsters, guinea pigs, rabbits, and nonhuman primates)
would normally be tested first, and then research might potentially move to nontraditional
laboratory animals, such as ferrets or livestock, depending on the source or circumstances of the
outbreak. Priorities for using different animal host species would likely be identified based on
analogies to similar pathogens that have been studied in the past. For example, an emerging
disease episode caused by a new orthopoxvirus would likely call for experiments in small
rodents, rabbits, or macaques. Unless the episode involved direct chimpanzee-to-human spread,
it is unlikely that chimpanzees would even be considered. The exception might be an emerging
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disease in wild chimpanzees that threatened the survival of the species in the wild; planning for
such an intervention is ongoing in West Africa.
Chimpanzees are our closest biological relative among the nonhuman primates, and they share a
close evolutionary and physiological relationship. In the past, this was the basis for rationalizing
that chimpanzees must be valuable models for human diseases. For example, it was thought that
the ability to infect chimpanzees with HIV-1 might be critical for developing an understanding of
the basic biology of the disease and for drug and vaccine development. The same was also true
for hepatitis B and C, again in the context of the era. However, after testimony from many
experts, the IOM Committee concluded that with the exception of hepatitis C vaccine research,
advances in medical science and technologies have obviated the need for chimpanzee research.
As stated above, the other exception is the unknown-unknown, and the Emerging Diseases
Subgroup concurred with this conclusion, again based on unpredictable practicality of usefulness
and not on the genetic and physiologic relationship between humans and chimpanzees.
6. How many animals of what sex and age would be needed for infectious disease research
in chimpanzees under high biocontainment conditions?
Most emerging infectious diseases of clinical relevance infect both males and females equally, so
either sex of animals could likely be used. The age range called for would depend on
susceptibility and would be model specific. In humans, an inverse bell curve exists for most
viruses (flu, measles, varicella zoster virus, smallpox, etc.), with the very young and the elderly
being more susceptible than young adults.
The number of animals needed would depend on the frequency with which a disease causes
pathology or clinical presentation of interest such as rash, fever, illness, death, etc. For example,
yellow fever virus has a high mortality rate (up to 20% in humans and up to 100% in rhesus
macaques), whereas other closely related flaviviruses, such as dengue viruses, have a mortality
rate of approximately 0.1% in humans and are not typically lethal in macaques. In the latter
example, a different measure of infection is needed (such as immunological host response
measures), and still, because of individual variation, large numbers of monkeys are often needed
to provide statistically significant data. In a 1973 study that has been widely accepted in
developing a working immunological correlate for protective immunity following yellow fever
vaccination, 68 monkeys were required (Mason et al., 1973). In another study confirming that
neutralizing antibody is both necessary and sufficient for protective immunity against lethal
monkeypox infection, 23 monkeys were used (Edghill-Smith et al., 2005). These examples serve
to demonstrate that large numbers of chimpanzees might be needed for any study, especially a
study of the immunological response, such as a vaccine efficacy study.
In conclusion, there is no set number of animals that would be required for a definitive study; it
really depends on the model’s purpose, but many experiments in animal models are only
valuable when a rather large number of animals is employed.
7. What is the timeframe for responding to an emerging disease?

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If all other animal models fail and a decision is made that chimpanzees are needed to resolve key
issues in dealing with a deadly new or emerging infectious disease, the call would be for urgent,
immediate use. As time passes and ongoing research indicates a need for chimpanzee use, events
may rapidly escalate, leading to a timeframe that can only be met by having all resources,
facilities, animals, and personnel at the ready. This reality and the dilemma it presents are
explained in more detail elsewhere in this document.
8. Is there a need for a chimpanzee model for emerging diseases or would other models
suffice or be at least as good?
There are many animal models that are used to study emerging infectious diseases, with rodents
(mice, rats, hamsters, guinea pigs) being most commonly used. Examples of non-standard small
animals include deer mice, prairie dogs, gerbils, and many others. Today, genetically deficient
mice (e.g., SCID, AG129, STAT1 KO) and genetically modified mice (e.g., humanized mice)
play an ever-increasing role. Nonhuman, non-chimpanzee primates that are used in research
include macaques (e.g., cynomolgus, rhesus, Japanese) and other African, Asian, and South
American monkey species. Each species differs in susceptibility to different infectious agents
(e.g., simian varicella virus, simian immunodeficiency virus). One would have to decide where
chimpanzees fit into the overall project and at what point they would be used. For pathogenesis
models, it may be possible to make analogies with human autopsy data.
New animal models are being developed continually. There has been a shift away from
traditional models and toward models employing highly manipulated animals. Nevertheless,
pathogenesis studies still require animal models. Persistent, chronic, and recrudescent diseases
pose unique challenges and require even more sophisticated manipulations of animals as models.
For rare but serious diseases, product-driven studies may need to consider the FDA Animal Rule.
This greatly raises the expectations for the applicability of animal model studies and would raise
expectations about the true value of data from chimpanzee experiments. For example, the
combination of animal and strain of pathogen used would likely be selected so that lethality
occurred in untreated animals but not in treated animals. If a decision were made to use
chimpanzees, it might be necessary to use staged experiments with smaller numbers of animals
per study along with data accumulated from multiple studies. Whether the FDA Animal Rule
would accommodate this is unknown.
9. Are other animal models in development that would change the potential need in 5
years, 10 years, or beyond?
Yes, there will always be new models, and they may be developed by testing different pathogens
in different species of hosts, as mentioned previously. Mouse models will be developed based on
genetic crossing or genetic engineering that will provide new potential for allowing pathogen
replication and pathogenesis. Examples of these new strains include knock-in mice with human
receptors for specific viruses, knock-out mice with higher susceptibility to infection, humanized
mice, and xenotransplanted mice as well as any number of combinations derived by breeding
different genetically altered mice. In addition, new non-human primate models and other nonmurine animal models are being developed.
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10. Could animals be retrieved from a sanctuary or must they be ready for immediate use
in a research facility?
No. Chimpanzees for future infectious disease research would have to be held in research
facilities that can provide optimal veterinary care and behavioral training to support research
activities.
It should be noted that Chimp Haven (Keithville, Louisiana) is the only NIH-supported
sanctuary. The Chimpanzee Health Improvement Maintenance and Protection Act of 2000 [PL
106-551 (HR 3514)] originally specified that animals could be returned to research in case of a
health crisis, but in 2007, the Chimp Haven is Home Act [PL 110-170 (S 1619)] was passed and
prohibits chimpanzees retired from medical research to be returned to laboratories. Even if the
prohibition against the removal of chimpanzees from the sanctuary were eliminated, there would
be factors to consider when returning chimpanzees from sanctuary populations to active
research. First, research animals must be very well characterized in terms of health histories and
current physiological status. It would need to be verified that the chimpanzees brought from
sanctuaries are routinely characterized for health-related characteristics as they are in research
facilities.
Secondly, the chimpanzees in sanctuaries would need to be trained in routine research-related
procedures as they are in research facilities. The chimpanzees maintained in research facilities
are subjected to daily training, so they cooperate with routine research-related procedures.
Training in research-related procedures includes sedation, oral and injectable dosing, and
presentation of body parts for examination. Chimpanzees are also trained for urine donation and
transfer between indoor and outdoor enclosures. This training minimizes the stress associated
with participation in studies and maximizes the quality of research data generated from the
animals. Training also maximizes the safety of routine research procedures both for the
chimpanzees and their human caretakers.
There are arguable advantages to maintaining chimpanzees for future research needs at research
facilities, if such a decision is made. Because they are already on site, the chimpanzees are
immediately available for research and are not subjected to trauma associated with removal from
one facility, transportation to a new facility, and integration into a new facility. Furthermore,
chimpanzees in research facilities are fully characterized for research, facilitating their selection
for research protocols. Finally, and very importantly, research chimpanzees are accustomed to
animal care staff, research staff, and standard research procedures.
11. Could a research facility in the United States undertake studies with chimpanzees
under high biocontainment (ABSL3 and/or ABSL4) conditions?
a. Veterinary Perspective
To date, no research involving chimpanzees in high biocontainment conditions has ever been
done in the United States. If such studies were undertaken in a high biocontainment facility, a
minimum of 8 weeks would be required to get standard operating procedures in place for the care
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and use of chimpanzees in high biocontainment conditions. If chimpanzees were being
transported from another facility, there could be an additional 30-day minimum quarantine
period. Animals would also need to be acclimated and psychologically evaluated before being
put into high biocontainment facilities.
If chimpanzees were to be used in any research on an unknown-unknown or a unique
bioterrorism threat agent, proactive laboratory assessment of “background flora” (i.e., infectious
agents endemically or episodically present in chimpanzees) would be necessary, and this would
require additional resources. In the past, these issues have plagued nonhuman primate research,
but these important considerations have often been ignored by the scientific community. In
contrast, laboratory mice are tested regularly for all known murine viruses and microbes to
insure that they are “pathogen free.”
b. Biocontainment Perspective
None of the high biocontainment facilities that currently exist in the United States were designed
for use with chimpanzees. The design process for high biocontainment facilities includes a user
scientific committee to review the appropriate animal models that will be used in the facility,
instrumentation needed, decontamination systems that will be used, and other similar
considerations. There is also input from the peer-review process, in which the size and numbers
of animals to be used are set historically for the design of the building. There are also numerous
safety and security regulations from national bodies.
Recent design processes for high biocontainment laboratories operated by NIH, the Department
of Homeland Security, and the Department of Defense established the maximum weight of
primates that could be used as 8 to 10 kilograms, appropriate for the upper size of an adult rhesus
macaque. It was noted that a chimpanzee at birth weighs approximately 2 kilograms, an adult
female weighs approximately 30 to 40 kilograms, and a full-sized adult male can weigh up to
150 kilograms. Large animals require larger caging (at least 25.2 square feet for animals over 10
kilograms); this requirement can be overruled by attending veterinarians and the Institutional
Animal Care and Use Committee if there is a critical emergency. The maximum size of the
animal rooms within the current ABSL3 and ABSL4 biocontainment facilities is approximately
300 square feet. These configurations also determined the size of all the supporting scientific and
biocontainment equipment (including caging) that is/will be used in the facilities (e.g., imaging
equipment for a 10-kilogram animal). One also has to be sensitive to the fact that if chimpanzees
are brought into an existing high biocontainment facility, all other studies would likely cease,
including critical experiments already in progress.
12. What facilities would be needed to undertake studies with chimpanzees under high
biocontainment conditions?
Decisions made regarding the size and number of animals that will be housed in a
biocontainment facility affect both biocontainment and scientific considerations. From a
biocontainment design perspective, the sizes of the rooms and numbers of animals that will be
used determine the barrier decontamination capabilities of the facility (i.e., autoclaves, passthrough fumigation chambers, dunk tanks); breathing air capacities in the BSL4 suites; heating,
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ventilation, and air conditioning capabilities in the BSL3 and BSL4 facilities; effluent and
carcass disposal systems and procedures; and animal watering systems. The size and number of
animals also determines the size of imaging equipment (MRI, PET scanner), aerobiology
equipment, and Class III aerobiology isolation equipment; the size and equipment in the
necropsy, procedure, and surgical suites; storage capabilities; and the dimensions and design of
animal caging.
ABSL3 facilities intended to house chimpanzees should be designed at a minimum to comply
with the standards set forth in the U.S. Department of Agriculture ARS-242.1 manual (U.S.
Department of Agriculture, 2012). These standards provide the necessary personnel and
environmental protection required for BSL3 agents on NIAID’s List of Emerging and
Reemerging Diseases, which includes Category A, B, or C priority pathogens. ABSL4 facilities
should have similar designs to the facilities currently available in the world for the support of
agricultural programs. The facilities in Winnipeg (Canada), Gelong (Australia), and Madrid
(Spain) have large-animal rooms, but these rooms are small and are not suitable for chimpanzee
work. All of the barrier support in these facilities is designed for livestock, and carcass/waste
disposal systems are robust enough to handle animals the size of chimpanzees. ABSL4 facilities
are purpose built, and one cannot upgrade an ABSL3 facility to create a ABSL4 facility.
Facilities that house chimpanzees should have holding/acclimation and quarantine facilities (that
are ABSL2 certified) separate from the high biocontainment facility, which reduces costs since
there are different building requirements for ABSL4 facilities. Cage storage is also a major
consideration, even if collapsible caging is used. From engineering and facility perspectives, it is
a significant scientific and financial venture to consider using chimpanzees in emerging
infectious disease research.
In the case of an unknown-unknown pathogen, it would be difficult to distinguish between
ABSL3 and ABSL4 conditions for chimpanzee experiments, so one should assume that ABSL4
containment is required.
The number of animals used per study depends on the disease; however, for an individual
experiment involving four chimpanzees in high biocontainment conditions at any one time,
rooms should be at least 1,000 square feet in size to accommodate the cleaning and manipulation
of squeeze-back panels in the cage system. Two such independent rooms would be considered
ideal, as this would enable active ABSL4 work with four animals while the next four animals
were being acclimated to the ABSL4 environment. Once ready, the active room can be cleaned
and decontaminated while the second group undergoes active studies. Alternatively, a separate
BSL2 room within the ABSL4 facility could be used to hold the four animals waiting to go into
active studies in the ABSL4 laboratory. The facility should be constructed with an independent
chemical shower, suit room, body shower, and clean change area. There should be an adjoining
procedure/necropsy room equipped with a biological safety cabinet, necropsy and procedure
table large enough for a chimpanzee, and an autoclave large enough to process the carcasses and
the panels of the collapsible caging. It should be emphasized that the above example is
hypothetical as there has been no research employing chimpanzees under high biocontainment
conditions and none of the current ABSL4 facilities was designed to house chimpanzees.

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13. Could animals be returned to a sanctuary after the studies have been completed?
Chimpanzees could not be returned to a sanctuary given current guidelines and requirements that
animals used in ABSL-3 or -4 experiments must be euthanized at study end. ABSL3 and ABSL4
nonhuman primates held in ABSL3 facilities have been repurposed and have been held for other
ABSL3 experiments, but they never leave biocontainment.
There was discussion as to whether or not it would be possible to bring animals out of ABSL3 or
ABSL4 housing. With appropriate markers of viral clearance (PCR and neutralizing antibody)
followed by an appropriate safety period, animals could be sanitized in decontamination rooms
and moved to BSL2+ containment housing for a further monitoring period. There would be
major considerations for a decontamination procedure for bringing a chimpanzee out of high
biocontainment housing as it would have to be validated; would only work for acute, shortduration diseases; and would have to be approved by regulatory agencies. It is considered very
unlikely that the regulatory agencies would approve such protocols based on current regulations.
It is more likely that other non-chimpanzee models would be available, as there are good
nonhuman primate models for all known pathogens.
Taking an animal into an ABSL4 facility is considered terminal—all experiments require animal
euthanasia at study end. The time an animal spends in an ABSL3 or ABSL4 facility is usually
minimal because these facilities are so expensive to operate.
The Subgroup discussed whether the United States should invest in an ABSL3/4 facility for
chimpanzees, given that this type of research has never done before and current high
biocontainment facilities were not built to undertake chimpanzee studies. Resolution of this
question would have to involve further discussion by experts and policy authorities. If a high
biocontainment laboratory were to be built, plans would need to be made to maintain the facility.
These laboratories are extremely expensive to run regardless of whether they are empty or in use.
The construction costs for ABSL4 facilities are approximately $6,100 per assignable square foot
and there are additional support facilities and security facilities that add to core construction and
commissioning costs. It takes a minimum of 5 years to build an ABSL4 facility from scratch.
Annual maintenance costs are 16% of construction costs. Maintenance requires highly skilled
mechanics and engineers.
Other facility-related issues involve (1) the equipment and staffing requirements that must be in
place, (2) the funding priority for such “stand-by” research resources, (3) the costs of long-term
maintenance of facilities, and (4) regulatory and oversight authority. The U.S. Department of
Defense, Department of Homeland Security, and Department of Health and Human Services may
be involved with chimpanzee research, but it is not at all clear which federal agencies (e.g., the
CDC, NIH, USAMRIID) would be in charge of or willing to maintain stand-by facilities. Given
that these agencies have different missions, consideration of which agency might provide the
best leadership might depend on whether the use of chimpanzees involves pathogen discovery or
downstream vaccine/drug development research.
Historically, most nonhuman primate experiments performed at ABSL4 or ABSL3 facilities have
been of very short duration (i.e., weeks), whereas many chimpanzee protocols carried out at
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ABSL2 facilities last for months or years (e.g., hepatitis B and C research). Scientists in the
United States have no experience with longer-term research employing chimpanzees in high
biocontainment facilities and certainly no experience in the intermittent use of such a facility
when the need arises. In addition, all animal infectious disease experiments done at ABSL3 and
ABSL4 facilities involve euthanasia of all subject animals. The public response to this
requirement for experiments involving chimpanzees must be considered. All chimpanzee
experiments done in the last 20 years have been survival experiments involving BSL2 infectious
agents, and most animals have been used for multiple protocols (e.g., HBV, HCV, HIV-1);
funding for these experiments has included the cost of lifetime care.
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Emerging Diseases Subgroup Members
Alan D. Barrett, Ph.D. (Chair)
Director, Sealy Center for Vaccine Development; Professor, Department of Pathology;
Professor, Department of Microbiology and Immunology
University of Texas Medical Branch, Galveston, Texas
L. Bill Cummins, D.V.M.
Special Advisor to the Director
Southwest National Primate Research Center, Texas Biomedical Research Institute, San
Antonio, Texas
Frederick A. Murphy, D.V.M., Ph.D.
Professor, Department of Pathology
University of Texas Medical Branch, Galveston, Texas
Mark K. Slifka, Ph.D.
Professor, Oregon Health Science University; Senior Scientist, Oregon National Primate
Research Center, Beaverton, Oregon
Lee Thompson
Assistant Professor (retired)
Department of Pathology
University of Texas Medical Branch, Galveston, Texas
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