WASHINGTON — Nonhuman primate research supported by the National Institutes of Health is critical to the nation’s ability to respond adequately to public health emergencies and carry out high-impact biomedical research — but gaps in the systems that support research using these animal models are undermining the U.S. biomedical research enterprise and national health emergency readiness, says a new National Academies of Sciences, Engineering, and Medicine report.  

Nonhuman primates include any primate species except humans — for example, rhesus macaques, baboons, marmosets, or African green monkeys. Nonhuman primates can be valuable for answering certain research questions because of their genetic, anatomic, physiologic, and behavioral similarities to humans. A ban on exporting research animals enacted by China in 2020 coupled with increased research demands for nonhuman primates following the emergence of COVID-19 have exacerbated an ongoing shortage in the number of animals available for NIH-supported research.  

The report says the U.S. needs to prioritize expansion of domestic nonhuman primate breeding programs. Relying on importing these animals from other countries is unsustainable, and dependence on international sources undermines the security of the nation’s biomedical research enterprise. Creating a national plan for allocating and expanding the number of nonhuman primates available for research is necessary — and should encompass financial, physical, and personnel resources, as well as a centralized tracking system to enable a data-driven approach, says the report. 

Without decisive action, the ability of NIH-supported investigators to conduct studies that require nonhuman primates will become more a function of access to these animals than a concerted response to public health priorities, the report says. The core tenet of NIH’s work — that the most meritorious research should receive the highest priority — will be threatened. 

Some research approaches that use in vitro or in silico models in place of animals, also called new approach methodologies, may complement or reduce reliance on nonhuman primates, says the report, as they can replicate some of the complex cellular interactions and other functions that occur in vivo and for which nonhuman primates are used to answer specific research questions. New approach methodologies, however, are currently limited in their ability to study all the complex interactions that occur within the bodies of humans and animals. The report says there are no alternatives that can fully replace nonhuman primates at this time.  

“If the U.S. is to produce high-impact biomedical research and have a research infrastructure capable of responding to the next public health crisis, now is the time to strengthen the systems we need for nonhuman primate research — including resource tracking, having an adequate domestic supply of these animals, and further development of new approach methodologies,” said Kenneth S. Ramos, chair of the committee that wrote the report and assistant vice chancellor for health services for the Texas A&M University System. 

Nonhuman Primates in NIH-Supported Research  

Nonhuman primates represent a small proportion, estimated at half of 1 percent, of all the animals used in U.S. biomedical research. When warranted, research using these animals allows scientists to understand health and disease, pursue discovery, and investigate new treatments and vaccines. Scientists choose which model they use — animals or otherwise — based on the scientific question at hand.  

Research using nonhuman primates has contributed to human health advances that have improved and saved countless lives, says the report. Medical breakthroughs such as treatments for Parkinson’s and sickle cell disease; drugs to prevent transplant rejection; and vaccines for COVID-19, Ebola, polio, and measles have all been enabled by research that relies on nonhuman primates.  

The report says the need for nonhuman primates in specific areas of NIH-supported research — including neuroscience and neurodegenerative disorders, infectious diseases, immunotherapy, reproduction, aging, and chronic inflammatory diseases — is likely to increase in the coming years. It is likely that macaques will remain in high demand, and the need for marmosets will likely increase. 

Impact on Biomedical Science 

In a survey of NIH-supported researchers conducted by the committee, 64 percent of respondents reported challenges with obtaining nonhuman primates for their research. In 2021, two-thirds of researcher requests for macaques that have not been used in a previous study could not be met by the National Primate Research Centers. Researchers also face increased wait times for animals, and costs have risen 10 percent to 200 percent for a single animal, depending on the species.   

Base funding for the National Primate Research Centers and other NIH-supported institutions that manage domestic nonhuman primate breeding populations has also declined over time, and budgetary shortfalls have limited the ability of institutions to expand their breeding programs and infrastructure at a level sufficient to meet research needs. However, the report says that there is currently a window of opportunity to bolster existing infrastructure, while cynomolgus macaques, marmosets, African green monkeys, and other nonhuman primate species remain accessible from other countries and can be imported to establish domestic breeding programs. Domestic breeding provides greater control over the health and well-being of the animals and characteristics such as age, prior use in research, and social and genetic backgrounds, all of which can improve the quality of the research data, says the report. 

Need for Increased National Coordination and Strong Stewardship  

The report concludes that inadequate coordination of research programs at the national level contributes to missed opportunities for efficient use of the limited number of nonhuman primates available for research. The development and implementation of a national plan for nonhuman primate research resources would help ensure the availability of these important research models to meet the nation’s public health needs. 

It is incumbent upon researchers and NIH to make the best use of each animal through cooperative efforts, data sharing, purposeful planning, and data-driven care and management methods, the report says. NIH has no central structure for tracking the number of nonhuman primates required to meet current and future research needs, and therefore no way at present to implement a strategic management plan. 

Recent advances in genomics, bioinformatics, imaging, digital biomarkers, extended reality, and artificial intelligence have the potential to augment the scientific knowledge that can be gained from studies using nonhuman primates, though additional investments will be needed to expand use of these approaches. 

Opportunities for New Approach Methodologies  

Continued development and validation of new approach methodologies is critically important to support further advances in biomedical research, the report says. This may reduce the need for, enhance the utility of, and mitigate shortages and costs of nonhuman primate models in the future.  

In vitro models, which use cell and tissue cultures and have been revolutionized by advances in stem cell technologies, are widely used to complement nonhuman primate models and, for some toxicology applications, have reduced reliance on them. However, they cannot currently replicate the full complexity of a living organism’s physiological systems or be used to model behavior.  

In silico models use quantitative and computational methods such as artificial intelligence and machine learning to model biological systems and are useful for screening compound libraries to identify high-priority drug candidates to advance nonhuman primate studies. In silico models are limited by the availability of the data that can be put into them but have the potential to help design new experimental approaches, and to reduce reliance on nonhuman primates for research.  

Advancing new approach methodologies will require planning and support for studies to demonstrate their performance. The report says some regulatory agencies such as the U.S. Food and Drug Administration have indicated that they are supportive of the use of these new methods for regulatory decision-making once they have been validated or qualified. A strategy for using new approach methodologies in conjunction with nonhuman primate models and investment in opportunities for collaboration between researchers using nonhuman primates and those developing alternatives will be needed to reduce barriers to their adoption. 

The study — undertaken by the Committee on the State of the Science and Future Needs for Nonhuman Primate Model Systems — was sponsored by the National Institutes of Health. 

The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, engineering, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. 

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