B

Data on Nonhuman Primate Use in NIH-Supported Biomedical Research

This appendix serves as an accompanying resource to the major findings presented in the body of the report, specifically Chapter 3, on the current landscape of intramural and extramural research using nonhuman primates (NHPs) supported by the National Institutes of Health (NIH). It summarizes data from various stakeholders on NHP supply, investigator demand, impacts of NHP shortages, and future priorities for NHP models in NIH-supported biomedical research. The data presented below are grouped topically, where applicable. Appendix A provides an accounting of the committee’s data-collection methodology.

RESEARCH FACILITIES REPORTING NHP USE IN 2021

U.S. Department of Agriculture (USDA) data compiled from reports submitted annually by research facilities in the United States were the most complete data available to the committee on NHP use, although these data do not provide information on funding source (e.g., whether the research using NHPs was NIH supported), number of studies, species, research domain, or origin and ultimate destination of animals. Therefore, these data should be reviewed with the understanding that the numbers presented do not reflect NHP holding and use in the specific context of NIH-supported research. Despite these limitations, the USDA data provide a foundation for understanding the general distribution of NHP holdings and use in the United States over time, and these data can be categorized by stakeholders, some of which are largely or entirely supported by NIH (e.g., National Primate Research Centers [NPRCs]).

Table B-1 shows the distribution of NHPs across major stakeholders¹ in fiscal year (FY) 2021 and is grouped by stakeholder type. The 34 facilities listed account for nearly 93 percent of the 113,502 NHPs reported as held or used to USDA in FY2021. This table shows the

NOTES: These facilities are listed in alphabetic order within their respective stakeholder categories and represent those research facilities that reported 400 or more NHPs held or used in fiscal year (FY) 2021. The Children’s Hospital of Philadelphia reported more than 400 NHPs onsite in FY2021 but is not included on this table as it does not fit into these major stakeholder categories. These 34 facilities account for nearly 93 percent of all NHPs held or used for research purposes in the United States in FY2021 (113,502 NHPs).

^a These facilities hold NIH awards that involve the holding or use of NHPs for NIH intramural or extramural research purposes.

^b These facilities host an NIH-supported breeding colony. In some cases, not all NHPs reported to USDA by the facility are supported by NIH funds, as these facilities also receive funding for domestic breeding and research from other sources.

SOURCE: USDA, 2021.

TABLE B-2 U.S. Department of Agriculture (USDA) Annual Report Holding and Use Data from All Facilities with 400 or More Nonhuman Primates (NHPs)

NOTE: This table includes the 35 facilities holding or using 400 or more NHPs per fiscal year; facilities are listed from most to least total NHPs reported to USDA.

^a “Total NHPs held” describes the number of animals being bred, conditioned, or held for use in teaching, testing, experiments, research, or surgery but not yet used for such purposes (USDA, 2021).

^b “Total NHPs used” describes the number of animals upon which teaching, research, experiments, or tests were conducted, regardless of whether or not pain was inflicted. This number does not include those animals held, bred, or conditioned for research but not yet used (USDA, 2021).

^c “Total NHPs” describes the number of NHPs reported to be held, bred, or conditioned for research purposes but not yet used, and the number of NHPs used for research purposes in the identified fiscal year.

* Denotes an academic institution (excluding NPRCs and National Resources).

** Denotes a contract research organization or commercial NHP supplier.

SOURCE: USDA, 2021.

Table B-3 lists all facilities reporting fewer than 400 NHPs to USDA in 2021 and the number of animals held versus used for research purposes. Unlike Table B-2, which lists the major research facilities with 400 or more total NHPs reported to USDA and includes many CROs, suppliers of NHPs, and pharmaceutical and biotechnology companies, the research facilities listed in Table B-3 represent a higher proportion of academic institutions with most using a small number of NHPs. The 67 academic institutions in this table make up nearly 45 percent of all facilities reporting NHP use to USDA, but report just 3.7 percent of all NHPs held or used. Because of the limitations of available databases, the proportion of these academic institutions with investigators holding active NIH awards for NHP research is unknown.

TABLE B-3 U.S. Department of Agriculture Annual Report Holding and Use Data from Facilities with Fewer than 400 Nonhuman Primates (NHPs)

NOTE: This table includes the 114 research facilities reporting fewer than 400 NHPs in FY2021 and is ordered by facility from greatest to fewest total NHPs.

^a “Total NHPs held” describes the number of animals being bred, conditioned, or held for use in teaching, testing, experiments, research, or surgery but not yet used for such purposes (USDA, 2021).

^b “Total NHPs used” describes the number of animals upon which teaching, research, experiments, or tests were conducted, regardless of whether or not pain was inflicted. This number does not include those animals held, bred, or conditioned for research but not yet used (USDA, 2021).

^c “Total NHPs” describes the number of NHPs reported to be held, bred, or conditioned for research purposes but not yet used and the number of NHPs used for research purposes in the identified fiscal year.

* Denotes an academic institution.

** Denotes a contract research organization or commercial NHP supplier.

SOURCE: USDA, 2021.

NHP RESOURCES FOR BIOMEDICAL RESEARCH

The following tables and figures support content in the section on NHP availability in Chapter 3. It should be noted that the supporting data presented do not focus exclusively on the supply of animals available and used only for NIH-supported research, as noted in the sections that follow.

NHP Importation

The Centers for Disease Control and Prevention (CDC) tracks all NHPs imported into the United States, regardless of whether they are being transported for use in research or for nonresearch use. Therefore, while the numbers presented below include all NHPs imported into the United States for research use, they may also include a minority of NHPs brought in for other purposes (e.g., for zoos or wildlife parks). The CDC does not maintain a database

Tables B-6 and B-7 detail importation trends by country of origin and species by country of origin, respectively, and illustrate the major shift in countries supplying NHPs to stakeholders in the United States. Table B-6 shows a sharp increase in animals imported from Cambodia and Mauritius, which corresponds with the sudden decrease in animals originating from China. Table B-7 details these trends at a species level. These data show that the countries of origin for imported cynomolgus macaques have shifted since FY2020. Although China was previously a major supplier of cynomolgus macaques to the United States, following the Chinese exportation ban in early 2020 the number of cynomolgus and rhesus macaques imported from China dropped to zero. In FY2021, imports of cynomolgus macaques originating from Cambodia, Vietnam, and Mauritius greatly increased. As compared to FY2020, FY2021 also saw increases in importation of capuchin and squirrel monkeys from Guyana. Chapter 3 describes the impacts of these changes in importation patterns and risks associated with the reliance of biomedical research on imported NHPs.

TABLE B-6 Number of Nonhuman Primates Imported, by Country and Fiscal Year (FY)

*Smuggled spider monkeys seized at the U.S.-Mexico border.

NOTE: Due to data limitations these numbers represent NHPs imported for a variety of purposes and do not represent animals imported exclusively for biomedical research use.

SOURCE: CDC, 2023.

TABLE B-7 Number of Nonhuman Primates Imported by Species, Country, and Fiscal Year (FY)

*Smuggled spider moneys seized at the U.S.–Mexico border.

**Other imported species varied by year but commonly included colobus monkeys, siamangs, DeBrzazz’s monkeys, geladas, saki monkeys, spider monkeys, emperor tamarins, bushbabies, and orangutans.

NOTE: Due to data limitations these numbers represent NHPs imported for a variety of purposes and do not represent animals imported exclusively for biomedical research use.

SOURCE: CDC, 2023.

NHP Resources at NPRCs and National Resources

As described in Chapter 3, NPRCs and National Resources receive funding from NIH’s Office of Research Infrastructure Programs (ORIP) to maintain NHP resources for NIH-supported biomedical research. These facilities house a range of NHP species, some of which are actively bred in domestic breeding colonies. The data presented in the tables that follow originate from information provided by the seven NPRCs and four National Resources following a committee request for information, as well as from USDA (see Appendix A).

Table B-8 shows the change in the number of NHPs reported held or used by the seven NPRCs to USDA between FY2015 and FY2021. When reviewing changes across all NPRCs, the total number of NHPs reported to USDA increased by just over 3 percent between FY2015 and FY2021, while the number of NHPs held but not used for research increased by

TABLE B-8 Comparison of Fiscal Year (FY) 2015 and FY2021 Nonhuman Primate (NHP) Holdings and Usage Data Reported by National Primate Research Centers (NPRCs) to the U.S. Department of Agriculture (USDA)

SOURCE: USDA, 2015, 2021.

nearly 28 percent, and the number of NHPs used for research purposes decreased by over 25 percent over the same time. However, when examining the data at the center level, there is no clear pattern of change. The data reported by the Wisconsin NPRC show a decline in the number of NHPs held and an increase in the number of NHPs used in research over this 6-year period. While the actual reasons for these shifts are not known, it is possible that NHPs originally included in breeding colonies had been shifted to research use. The reported values from the California NPRC showed a decrease in the number of NHPs held and in the number of NHPs used over these 6 years, although the reasons for these dual reductions are not clear, nor is it clear which change came first based on the data available. Lastly, the Tulane, Southwest, Oregon, Washington, and Emory NPRCs each showed an increase in the number of NHPs held; however, the Tulane and Oregon NPRCs reported an increase in the number of NHPs ultimately used in research, while the Southwest, Washington, and Emory NPRCs recorded a decrease in NHPs used over the same period. Again, because of limitations in the data available from USDA, the context underlying these changes is unknown.

Based on information provided by the NPRCs as summarized in Table B-9, 12 species of NHPs are currently held or used at NPRC facilities. Of these, rhesus and cynomolgus macaques are reported to be held or used at every center. Other species were reported by a smaller number of sites (1–3 NPRCs), suggesting that they are models used for fewer areas of research. Table B-10 shows the seven species reported as currently held or used by the four ORIP-supported National Resources. These tables do not report which species are being bred in colonies at NPRCs and National Resources.

TABLE B-9 Nonhuman Primate Species Held or Used at National Primate Research Centers (NPRCs), Fiscal Year 2021

SOURCE: NPRC Information Request, 2022.

TABLE B-10 Nonhuman Primate Species Held or Used at National Resources Supported by the National Institutes of Health Office of Research Infrastructure Programs, Fiscal Year 2021

NOTES: These data may include NHPs not directly supported by Office of Research Infrastructure Programs funding. Additionally, these facilities may also hold or use other NHP species that were not reported in the facilities’ responses to the committee’s information request.

SOURCE: National Resources Information Request, 2022.

Annual Production from Breeding by Species

NPRCs and National Resources receive NIH support to maintain domestic colonies of NHPs for biomedical research use. Table B-11 shows the eight species with annual production from domestic breeding, as reported by the NPRCs to the committee. More than 3,500 NHPs were produced from breeding colonies at NPRCs in FY2021, and of these, nearly 85 percent were rhesus macaques. The corresponding data from National Resources can be found in Table B-12 and show that more than 1,300 NHPs were produced in FY2021 from breeding colonies managed by National Resources. As with the data reported by the NPRCs, most (76 percent) of the NHPs bred by National Resources were rhesus macaques.

TABLE B-11 Reported Number of Nonhuman Primates Produced Annually at National Primate Research Centers, by Species, Fiscal Year 2021

Annual Production from Breeding by Facility

Tables B-13 and B-14 list the number of NHPs produced at the NPRCs and National Resources in FY2021. These numbers do not include all NHPs produced for biomedical research use (they do not include numbers from NIH intramural facilities and breeding colonies outside the seven NPRCs and four ORIP-supported National Resources). As previously noted, NPRCs report an annual production of more than 3,500 NHPs annually, and National Resources report more than 1,300. Of the NPRCs, the Wisconsin NPRC produced the greatest number of NHPs, followed by the California NPRC. The Caribbean Primate Research Center accounts for more than half of NHPs produced by the National Resources in FY2021.

TABLE B-13 Total Number of Nonhuman Primates Produced Annually at National Primate Research Centers (NPRCs), Fiscal Year 2021

SOURCE: NPRC Information Request, 2022.

TABLE B-14 Total Number of Nonhuman Primates Produced Annually at National Resources, Fiscal Year 2021

NOTE: These data may include NHPs produced by breeding colonies not directly supported by Office of Research Infrastructure Programs funding.

SOURCE: National Resources Information Request, 2022.

INVESTIGATOR DEMAND FOR NHPs IN NIH-SUPPORTED RESEARCH

The tables and figures in this section support content in the Chapter 3 section on investigator demand for NHP resources. These data were collected from NIH-supported NHP researchers via a survey and from NPRCs, National Resources, and NIH via information requests (see Appendix A for data-collection methodology). The section begins with details on NHP researcher survey responses and subsequently provides data on NHP researcher sourcing practices and demand by research domain and NHP species. A copy of the survey sent to investigators and complete reporting of the frequency of responses by question are included in Appendix E.

NHP Researcher Survey Demographics

A total of 1,431 researchers were contacted with an invitation to complete the committee’s survey on NIH-supported investigator perspectives on and experiences with using NHPs in biomedical research. A total of 273 investigators responded (19.1 percent); three of these respondents reported incomplete data regarding their NIH awards (i.e., answered few questions). A total of 535 awards were reported by respondents² with an average of two NIH research project grants per investigator (min = 1, max = 9). Institutions in which responding investigators carry out their research can be found in Table B-15. More than half (56 percent) of respondents included in the data analysis reported their affiliation as an “other academic center,” which represents facilities that are not an NPRC, a National Resource, or an academic center with an NHP breeding colony. Domains in which responding investigators conduct NHP research can be found in Figure B-1. Behavioral and systems neuroscience was the most reported research domain by responding investigators, followed by HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome), viral infectious disease (non-HIV/AIDS), and visual system research.

TABLE B-15 Responding Investigators by the Primary Institution in Which They Carry Out Their Research

NOTE: Table generated from responses to Question 113 from the NHP Investigators Survey.

SOURCE: NHP Investigators Survey, 2022.

TABLE B-16 Active National Institutes of Health Awards Using Nonhuman Primates (NHPs) as Reported by NHP Researchers Responding to the Committee’s Survey, by Species and Source

NOTES: Total awards column may not reflect the sum of numbers in each row because some awards obtained the same species of nonhuman primates from multiple sources. Contingency table generated from unique awards (n = 506) reported by respondents to both Questions 5 and 11 from the NHP Investigators Survey. NPRC = National Primate Research Center.

SOURCE: NHP Investigators Survey, 2022.

TABLE B-17 Enrollment Status by Award as Reported by Nonhuman Primate (NHP) Researchers Responding to the Committee’s Survey

NOTES: Late enrollment included any award receiving NHPs after the planned enrollment date. Contingency table generated from award data reported by respondents to both Questions 9 and 10 from the NHP Investigators Survey.

SOURCE: NHP Investigators Survey, 2022.

NPRCs provide animals for use by investigators at their facilities and for use at external research facilities (e.g., an academic center that does not have a breeding colony on-site and requires marmosets for an NIH-funded study). Numbers of NHPs provided to NIH-funded investigators for use at a facility external to the NPRC varied by NPRC and year but generally were lower in FY2020 and FY2021 relative to the FY2018 and FY2019 numbers (Table B-18). The number of NHPs provided to external investigators for research carried out at the NPRC was lower in FY2019 and FY2020 relative to FY2018 numbers but in FY2021 increased above the FY2018 numbers (Table B-19). Data provided by the responding National Resources did not yield any clear trends in the provision of NHPs to external investigators conducting research at the National Resource facility or at a different location (Tables B-20 and B-21). It appears that the distribution of animals by the Caribbean Primate Research Center is the major driver in increasing provision of NHPs for research at external facilities and for a decline in the number of animals made available for use for research conducted within the center.

TABLE B-18 Numbers of Nonhuman Primates Provided by National Primate Research Centers (NPRCs) to National Institutes of Health–Funded Researchers for Research Conducted at an External Facility, Fiscal Years (FY) 2018–2021

SOURCE: NPRC Information Request, 2022.

TABLE B-19 Numbers of Nonhuman Primates Provided by National Primate Research Centers (NPRCs) to External National Institutes of Health–Funded Researchers for Research Conducted at the NPRC, Fiscal Years (FY) 2018–2021

SOURCE: NPRC Information Request, 2022.

TABLE B-20 Numbers of Nonhuman Primates Provided by National Resources to National Institutes of Health–Funded Researchers for Research Conducted at an External Facility, Fiscal Years (FY) 2018–2021

SOURCE: National Resources Information Request, 2022.

TABLE B-21 Numbers of Nonhuman Primates Provided by National Resources to External National Institutes of Health–Funded Researchers for Use in Research Conducted at the National Resource Facility, Fiscal Years (FY) 2018–2021

SOURCE: National Resources Information Request, 2022.

Needs for specific NHP characteristics, as well as external pressures (e.g., infrastructure and logistical issues), were found to be factors associated with poor accessibility of NHPs by NIH-supported investigators. Certain characteristics of investigators’ requests for animals from NPRCs and National Resources were noted by these stakeholders as contributing to longer wait times for animals (Table B-22). Particularly, all NPRCs and National Resources indicated that the need for a specific age of the requested NHPs was associated with longer wait times for animals. Sex and specific genotypes of requested NHPs were also commonly reported by NPRCs and National Resources as factors associated with increased wait times. Factors commonly reported by NPRCs and National Resources as impediments to meeting researcher demands for NHPs (Table B-23) included issues related to NHP housing, sufficiency of funding, and the time required to expand breeding colonies. These factors and challenges are described in Chapter 3.

TABLE B-22 Nonhuman Primate Demographics and Characteristics Associated with Increased Wait Times for Investigators as Reported by National Primate Research Centers (NPRCs) and National Resources

* “Other” characteristics noted as associated with long wait times by responding NPRCs include viral infection status (n = 4), animal size and weight (n = 1), and pregnancy status (n = 1). Among responding National Resources, the single “other” response noted was viral status (n = 1).

SOURCES: NPRC Information Request, 2022; National Resources Information Request, 2022.

TABLE B-23 National Primate Research Center (NPRC) and National Resources Perspectives on Challenges to Meeting Researcher Demand for Nonhuman Primates

*“Other” challenges reported by responding NPRCs included staffing challenges (n = 4) and research infrastructure challenges (research equipment and nonhuman primate caging) (n = 2). Among responding National Resources, the single “other” response noted staffing challenges (n = 1).

SOURCE: National Resources Information Request, 2022; NPRC Information Request, 2022

As indicated earlier, in Table B-17, NIH-supported researchers experienced challenges with timely enrollment of NHPs in their studies. Among investigators responding to the committee’s survey and reporting issues with accessing NHPs, 72 percent associated these challenges with shortages of NHPs meeting specific demographics required for their study protocols, and 50 percent faced challenges accessing NHPs from their preferred source (see Table B-24). More detail about these challenges and associated impacts on NIH-supported research can be found in Chapter 3.

TABLE B-24 Challenges Associated with the Timely Enrollment of Nonhuman Primates (NHPs) as Reported by NHP Researchers Responding to the Committee’s Survey

* Other issues reported as write-in responses related to challenges with obtaining NHPs were similar to those provided as options for the survey and included lack of availability of nonhuman primates with needed characteristics, delays related to COVID-19, limitations in NIH funding, available space, and staffing issues, among others.

NOTES: Table generated from responses to Question 115 from the NHP Investigators Survey. Respondents were able to select more than one challenge.

SOURCE: NHP Investigators Survey, 2022.

Demand for NHPs by Research Domain and Species

NPRCs, National Resources, NIH-supported investigators, and NIH institutes, centers, and offices were asked to consider areas for future demand for NHPs (see Figure B-2 and Tables B-25 and B-26). The most commonly listed domains generally overlapped across stakeholders and indicated existing and future demand for NHP models in neuroscience research, infectious disease, aging and aging-related diseases (such as Alzheimer’s disease and related disorders), and regenerative medicine. More information about priority research domains for current use and future NHP investment across these stakeholders is described in Chapter 3.

TABLE B-25 National Primate Research Center Predicted Future Demand for Nonhuman Primates by Research Domain

NOTE: Respondents were able to select multiple priority research domains.

SOURCE: NPRC Information Request, 2022.

TABLE B-26 National Resources Predicted Future Demand for Nonhuman Primates by Research Domain

NOTE: Respondents were able to select multiple priority research domains.

SOURCE: National Resources Information Request, 2022.

No available, comprehensive data sources describe the number of NHPs used in NIH-supported research or how NHPs are used across different research domains. Table B-27 shows the distribution of NHPs used in active NIH awards across research domains as self-identified by investigators who responded to the committee’s survey. The greatest number of NHPs used were reported for NIH awards associated with HIV/AIDS, behavioral and systems neuroscience, behavior and psychological research, reproductive health, and viral infectious diseases (besides HIV/AIDS). It should be noted that investigators were able to select more than one domain per

TABLE B-28 Projected Future Needs for Nonhuman Primate (NHP) Species among Researchers Responding to the Committee’s Survey Who Anticipate Using NHPs in the Next 5 Years

NOTES: Table generated from responses to Question 118 from the NHP Investigators Survey. A total of 258 respondents responded to the question and were able to select more than one species in response.

SOURCE: NHP Investigators Survey, 2022.

NPRCs were prompted similarly to provide projections for future increases and decreases in researcher demand for NHP species (Table B-29) and identified high-demand species similar to those identified by the investigators responding to the committee’s survey. Six of seven NPRCs indicated that demand for certain species will increase, and of the six NPRCs that responded to this question, all projected increased demand for rhesus macaques.

TABLE B-29 National Primate Research Center (NPRC) Projections for Change in Researcher Demand, by Nonhuman Primate (NHP) Species

SOURCE: NPRC Information Request, 2022.

Openness Practices in NHP Research

Investigators who responded to the committee’s survey were asked to provide their experiences with engaging in various openness practices aimed at improving scientific rigor. Of the 263 researchers who answered the survey question, 81 percent indicated that they were engaged in the sharing of data in its raw or aggregate form upon the submission of a manuscript for publication. Other actions reported by respondents included actions to increase the transparency of study design and analysis (74 percent), the sharing of research materials (60 percent), and sharing of code or other analytic methods (50 percent) (Table B-30). These data suggest that interest in engaging in openness practices for the benefit of rigor are widespread.

TABLE B-30 Openness Practices for Scientific Rigor among Nonhuman Primate Researchers Responding to the Committee’s Survey

*The “other” responses included the publication of results in peer-reviewed journals, tissue sharing, studies that combine research groups across multiple centers, and the use and sharing of standardized written methods and transparent data documentation, among others.

NOTES: Table generated from responses to Question 122 from the NHP Investigators Survey. A total of 263 unique investigators responded and were able to select more than one response. ARRIVE = Animal Research: Reporting of In Vivo Experiments.

SOURCE: NHP Investigators Survey, 2022.

PATHOLOGY, TISSUE ARCHIVES, AND RESOURCE SHARING

The seven NPRCs and four National Resources were asked to provide information on their tissue-archiving and resource-sharing practices. Responses varied across institutions in terms of the proportion of decedent NHPs undergoing necropsy examinations, the types of examinations performed, and the length of time tissues were archived. While all NPRCs

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