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Facts about the California National Primate Research Center at UC Davis

By Andy Fell on July 30, 2014 in Human & Animal Health

The California National Primate Research Center at UC Davis is one of seven primate research centers supported by the National Institutes of Health. Collectively, the national primate research centers are a unique resource for investigators studying human health and disease, offering the opportunity to study potential cures, treatments, and preventive measures in nonhuman primate models that most closely resemble human responses. Research performed at the CNPRC provides necessary information before proceeding to clinical trials in humans, and has led to new drugs and therapies that benefit human health and quality of life.

The center works with researchers at UC Davis and other institutions that conduct their studies in a nonhuman primate model. The center has four major research areas: Brain, Mind and Behavior; Infectious Diseases; Reproductive Sciences and Regenerative Medicine; and Respiratory Diseases.

Medical advances of the past century, ranging from vaccines to organ transplants to cancer treatment, were made possible by animal research. Animal models allow researchers to study complex systems that cannot yet be reproduced in other ways. Federal laws mandate that animal studies must be done prior to studies in humans, and thus, every new medicine for humans has gone through previous animal studies to ensure safety for human patients.

There are many examples of how research in nonhuman primates has extended our fundamental knowledge of how the human body functions in health and disease. Monkeys are susceptible to an immunodeficiency virus similar to HIV, making them ideal for the study of AIDS and potential vaccines and treatments. Similarities in the central motor pathways between monkeys and humans have led to the development of safe and effective interventions to slow the progress of Parkinson’s disease. Monkeys are the only mammalian animal model with menstrual cycles and hormonal patterns comparable to humans, providing crucial insights into fertility, pregnancy and menopause.

Many serious diseases still threaten our well-being: AIDS, Alzheimer’s disease, cancer, and infectious diseases (such as Zika virus, Dengue Fever and Chikungunya) to name a few. Research toward developing ways to treat and prevent these and other ailments involves the use of animals before the treatments are used in humans, as required by the FDA.

Research conducted with animals is highly regulated at the local, state and federal levels. Ensuring the welfare and humane treatment of animals used in ethically and scientifically sound research is a priority for the team of scientists, veterinarians, animal care personnel and university-based oversight committees. In addition to honoring their ethical obligation, scientists maintain the highest standards of animal care to ensure that research results are scientifically valid.

Publicly-funded scientific research with animals receives rigorous review at many different levels. Proposals for research undergo expert scientific review to evaluate the importance of the research question, the quality of the research approach and investigators, and the likelihood of the project’s success. The scientific review for proposals to NIH occurs through the NIH’s Center for Scientific Review. The process is extremely competitive in order to ensure both the quality and the importance to public health of NIH’s research portfolio. 

Proposals for research with nonhuman animals must also be rigorously reviewed in advance by the federally-mandated Institutional Animal Care and Use Committee (IACUC) at the host institution (for the CNPRC, the IACUC is at UC Davis).  The IACUC includes veterinarians, members of the public, scientists, and others. Their charge is to carefully analyze each research proposal and ensure high standards of animal care and humane treatment, in accordance with federal law.

At the federal level, animal research is overseen by the Department of Agriculture (USDA) Animal and Plant Health Inspection Service Animal Care Unit, and the National Institutes of Health (NIH) Office of Laboratory Animal Welfare. The UC Davis animal care program, including the CNPRC, is accredited by the International Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), an independent group, and is regulated and inspected by the U.S. Department of Agriculture. AAALAC inspections are conducted every 3 years for the entire UC Davis campus, including the CNPRC. UC Davis follows NIH guidelines for the care of laboratory animals and is also inspected by the NIH Office of Laboratory Animal Welfare (OLAW). Following their 2013 inspection, OLAW praised UC Davis for its "outstanding animal care and use program." This multi-level system of oversight ensures the highest standards for humane care and treatment of animals in research.  

For more than 50 years, the CNPRC has ensured the highest quality of animal care and well-being for nonhuman primates and demonstrates leadership in the field of nonhuman primate care, enrichment and social housing. The state-of-the-art research and scientific findings at the Center contribute to the understanding and treatment of human and animal disease and increase knowledge of nonhuman primate behavior, nutrition, development, health, and social networks, leading to further advancements in the level of care provided to laboratory and wild animals worldwide. 

How many monkeys are there at UC Davis and what kind?

  • The CNPRC houses about 4,500 monkeys, mostly rhesus macaques (Macaca mulatta). This species is widespread in Asia, especially in India where they are often found in urban areas, and in China. They can adapt to a wide range of climates. The vast majority of the monkeys at UC Davis are bred on site, with a few obtained from other facilities. No monkeys are obtained from wild populations.

  • Rhesus macaques live in extended family groups consisting of a few males and a number of females. Many of the monkeys at UC Davis live in half-acre outdoor corrals where they can form such family groups and complex social networks.

  • The rhesus macaques at the CNPRC can live to 30-38 years, far longer than their normal lifespan in the wild of up to 19 years. Many of the geriatric animals remain in the outdoor corrals with family members of all ages in the rich social environment of their home community. The aged rhesus colony at the Center provides distinctive opportunities to better understand normal aging changes and to develop new treatments and solutions for age-related health problems.

  • The center also houses a small colony of South American titi monkeys (Callicebus cupreus). There are no chimpanzees or other apes at the center. 

Why are nonhuman primates needed for research?

  • Rhesus macaques are very similar to humans in many ways, both genetically and in organ systems and physiology. This means that these animals are useful models for studying human diseases and conditions.

  • For example, research at the CNPRC has led to advances in our understanding of HIV/AIDS, lung diseases, autism, and of how environmental pollutants can affect the immune system.

  • Researchers also study the family structure and behavior of monkeys living in outdoor corrals to learn more about the behavior of these primates in the wild, and how we can apply that knowledge to understanding our own behavior. Students from across the campus, including those in anthropology, veterinary medicine and animal science, have been able to carry out research projects at the center.

What are some of the key discoveries from CNPRC research?

  • CNPRC researchers helped develop the effective anti-HIV drug tenofovir (Truvada). Due to this work, HIV-infected mothers can give birth to HIV-free infants, and HIV-infected people can live long and healthy lives. Tenofovir has become the key ingredient of successful prophylaxes, and is the most commonly used anti-HIV drug in the world. Truvada was recently approved as the first drug to prevent HIV infection in adults.

  • CNPRC researchers developed and tested a lung surfactant that helps premature infants, born before 28 weeks of gestation, to survive.

  • CNPRC research discovered a link between an infant’s temperament and asthma – research that is leading towards the screening, prediction and prevention of lung disease in children.

  • In a major recent advance, research at the CNPRC defined a link between maternal auto-antibodies and increased risk of a child to develop autism.

  • The lungs of monkeys are similar to those of humans, continuing to grow and develop in the early years of life (unlike those of mice and rats). CNPRC researchers have studied monkeys' lungs by using noninvasive lung function tests to learn how childhood asthma and allergies can develop, and to discover the causes of Chronic Obstructive Pulmonary Disease -- a leading cause of death in Americans.

  • The Center has the capability to study animals throughout their lifespan -- from conception, through adolescence and adulthood, into old age, because monkeys housed at the Center can live much longer than wild animals. This makes possible a wide range of studies with applications in human health, such as alerting us when pollutant exposure during gestation might harm offspring, to finding solutions for Alzheimer's Disease.

Are the monkeys only available to UC Davis researchers?

The CNPRC is a national resource and provides opportunities for research to investigators around the U.S. The CNPRC has 18 core scientists, who hold joint appointments with various departments at UC Davis. The center also hosts around 70 affiliate scientists from UC Davis and other institutions, who work with core scientists on their research projects or conduct independent research. Many affiliate scientists are located in California, but others are located at institutions throughout the world.

Is it possible to use computer models or cell cultures instead of animals?

  • Animal research occurs alongside other types of studies, including human clinical and epidemiological research, as well as alternatives to whole live animal research such as cell cultures and computer simulations.  In fact, consideration of viable alternatives to research with live animals is a basic ethical principle that undergirds the conduct of all research with nonhuman animals. Furthermore, this principle is implemented through a stringent regulatory oversight system that mandates review and approval of such research, at multiple levels.

  • Nonhuman primates are studied when there are no feasible current alternatives to address the research question.

  • UC Davis follows the principles of "reduce, refine, replace:" Whenever possible, researchers must reduce the number of animals needed, refine how experiments are conducted, replace animals with others (e.g. mice instead of monkeys), or replace animal tests with cell cultures or computer models. It is currently not possible to completely replace animal models with computer simulations or cell cultures.

  • Technology can be used to reduce the number of animals required. For example, in collaboration with biomedical engineers at UC Davis, the Center acquired a Positron Emission Tomography (PET) scanner, similar to those used in human medicine, designed specifically for noninvasive imaging of animals. By providing more detailed information from a single animal, the PET machine reduces the number of animals required for certain studies.

Some people claim that “animal tests rarely translate to actual treatments for human diseases.” Is this true?

We should not expect that all, or even most, drugs or vaccines that undergo animal testing will ultimately be used in people. There are many drug and vaccine concepts that seem promising theoretically, but turn out not to work for reasons that cannot be predicted from testing in computer simulations or cell culture. One goal of preclinical animal experiments is therefore to “weed out” approaches that are unlikely to work in humans before they advance to expensive and time-consuming human trials. For example, a vaccine may not promote the right kind, or right strength, of immune responses to protect against viral infection. We don’t understand enough about how the immune system works to predict how it will respond without actually doing the experiment in nonhuman primates. It is neither economically feasible nor ethical to go directly to human testing for every theoretically promising vaccine or treatment.

Humans and monkeys are different, so how can you be sure that results from monkeys will be relevant to people?

  • Monkeys closely resemble humans and provide predictive value for the outcome of human trials. To give just one example from HIV, trials in monkeys clearly showed that “pre-exposure prophylaxis” (PrEP), or treatment of HIV-negative individuals with HIV drugs, is highly effective at preventing infection after exposure to virus. This result paved the way for clinical trials of PrEP in humans that were also extremely effective. The drug Truvada is now approved for use in PrEP, and a main ingredient, tenofovir, was first developed and tested for safety and efficacy at the CNPRC.
  • Overall, animal studies allow us to make detailed longitudinal observations of viruses interacting with their hosts and with the immune system that are not possible in humans. Such studies let us define what kinds of immune responses vaccines might need to elicit, where in the body viruses may replicate, whether viruses can “hide” in tissue reservoirs, whether drugs might be toxic and to what organs, and more.

Why does the CNPRC primarily use rhesus monkeys?

  • Rhesus monkeys, one of the most common species used in biomedical research, share about 93 percent of their genes with humans. They are also widely used because they breed well in captivity. Rhesus monkeys offer many advantages because of their close similarity to humans.
  • Nonhuman primates, including rhesus monkeys, are essential to understand biological functions, study complex human diseases, and address safety of new diagnostics and therapies proposed for human use. They share many important features with humans: similarities in reproduction, development, physiology, immunology, anatomy, genetics, cognition, and social complexity aid in overcoming the roadblocks to new human treatments.
  • Monkeys and humans share many reproductive features including a similar menstrual cycle. Thus, there is an ongoing need for nonhuman primates that parallel the human condition, and within a supportive infrastructure with the necessary expertise to facilitate access and use.

Are monkeys under stress or in pain?

  • All animal research at UC Davis is conducted humanely in strict compliance with the Animal Welfare Act, which governs how laboratory animals are housed, cared for and used in investigational studies. The law requires that any procedures causing more than slight or momentary discomfort be performed using appropriate pain-relieving drugs. It requires the use of anesthesia for surgical and other invasive procedures, the same as with humans.

  • In addition, research with nonhuman primates follows strict regulations to ensure that the animals receive daily enrichment and facilitate psychological well-being through provision of multiple forms of environmental enrichment and social housing.

  • Primate center veterinarians and scientists do everything possible to ensure that animals involved in research projects are comfortable. Veterinarians also provide the animals with routine health care, including biannual physical exams, vaccinations and dental cleaning and care.

How are the animals housed and cared for?

  • The CNPRC has model environmental enrichment and behavior management programs for the benefit of all its animals. Most of these animals live in large half-acre outdoor field corrals, in large natural social groups similar to those found in the wild. The remainder of the animals are housed as pairs in indoor housing, with a small percent housed singly as needed. More about animal care at the CNPRC.

  • Programs provide daily enrichment and facilitate psychological well-being through provision of multiple forms of environmental enrichment and social housing. An important component of this program is to provide social experience for indoor-housed animals, that allows them to spend the daytime hours with another animal – either male or female pairs, or male / female pairs and offspring. The CNPRC Behavior Health Services staff use their extensive expertise and knowledge of the animals’ personalities to accomplish appropriate pairings.

  • State-of-the-art research and scientific findings at the Center contribute to the understanding and treatment of human and animal disease, but also demonstrate leadership in the field of nonhuman primate care, enrichment and social housing. Novel research studies and progressive care increase knowledge of nonhuman primate behavior, nutrition, reproduction, development, health, and long-term social health, leading to further advancements in the level of care provided to captive nonhuman primates worldwide.

  • CNPRC staff and researchers understand that working with animals is a responsibility and a privilege. Their work involves not only a duty to provide a humane environment for the animals, but to minimize the number of animals used, to make their involvement in research as comfortable as possible and whenever feasible to look for alternatives to their use in scientific studies.

  • About half of the center’s approximately 4,500 monkeys live outdoors. They are housed either in half-acre field corrals or conical-shaped “corn cribs.” Outdoor enclosures contain swings, jungle gyms and shelters for the monkeys, as well as supplemental heat during the winter months. Indoor monkeys are housed in cages and paired with another monkey for companionship during the day.

  • In the wild, rhesus monkeys thrive on fruits, seeds, roots, herbs and insects. In captivity, monkeys primarily eat monkey chow, and an array of fresh, seasonal fruit, vegetables and nuts once to twice a week to provide them with variety and to supplement their diet. Outdoor monkeys also forage in the grass for roots, seeds, and insects, and are provided with a daily mixture of seeds and oats scattered in the grass to replicate normal foraging behaviors. Indoor animals also receive seeds, oats, and fresh fruits and vegetables, in addition to monkey chow and specialize enrichment foods.

  • Monkeys are provided the best of veterinary care and living conditions. The center's exemplary Environmental Enrichment Program addresses the physical and social needs of the animals by utilizing appropriate social housing, toys, fresh fruits and vegetables, and activities to encourage and enable expression of species-typical behaviors for the health and well-being of every animal.

  • Animals at the Center receive a twice-daily "welfare check," at which every animal is observed for health issues, however minor. There is a staff of trained veterinarians, specializing in primate medicine, and a fully-equipped hospital on site. CNPRC staff and researchers understand that working with animals is a responsibility and a privilege. Their work involves not only a duty to provide a humane environment for the animals, but to minimize the number of animals used, to make their involvement in research as comfortable as possible and whenever feasible to look for alternatives to their use in scientific studies.

How is animal research regulated?

  • Under federal law, UC Davis receives regular visits by inspectors from the U.S. Department of Agriculture, which is charged with enforcing the federal Animal Welfare Act. USDA inspectors visit both the CNPRC and other animal research facilities at UC Davis.

  • UC Davis follows the National Institutes of Health guidelines for laboratory animal care. The NIH Office of Laboratory Animal Welfare (OLAW) inspected the campus facilities in 2013 and endorsed the program.

  • The campus' animal care program is also accredited by the International Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC). UC Davis is one of more than 770 research institutions and other organizations in 29 countries worldwide that have earned AAALAC accreditation, demonstrating the program commitment to responsible animal care and use.

  • All research studies involving animals must be approved by the campus's Institutional Animal Care and Use Committee (IACUC), which includes public representatives as well as faculty and staff. The IACUC also inspects the facilities every six months. Research involving primates is also reviewed by an internal committee at the Center.

Have there been violations relating to the care of the animals?

  • Throughout its 53-year history the CNPRC has been a leader in quality animal care and is continually making advancements in the care and welfare of captive primates. Its outstanding animal care program has been recognized by OLAW and AAALAC, both organizations with high standards for animal facilities.

  • The USDA conducts regular rigorous inspections of the primate center once to twice per year.  These inspections serve to monitor compliance with all rules and regulations relating to animal care, and to create an environment where animal care technicians provide the best care possible.  The university can be penalized heavily for violations and certain types of infractions can even result in the closure of a facility. 

  • There have been violations at CNPRC in the past, as there have been at every other national primate center. At CNPRC, these violations have involved small numbers of animals and have rarely led to fines. Violations are always rectified and new procedures developed to minimize the chance of recurrence.  

  • The university is committed to the highest ethical and medical standards for the care of its animals. Any violations, as rare as they may be, are dealt with immediately and comprehensively and are promptly reported to regulatory oversight entities. 

  • Through advanced and continuous training, the CNPRC aims to eliminate all violations and maximize the well-being of its animals. The CNPRC also conducts research that aims to improve the quality of life for the animals under its care.

Do monkeys ever escape from the center?

The Center has multiple security measures in place to keep the monkeys safe and all housing facilities are routinely monitored to ensure that the animals are secure. UC Davis reported one event to the USDA in 2011 where some monkeys escaped their primary outdoor enclosure but due to redundant multiple security measures, all were secured on the premises and no animals were harmed. 

Can members of the public visit the monkeys?

  • The CNPRC is a research facility that is not open to the general public.  This is because research on animal behavior often requires minimal contact with humans. Also, humans may carry diseases that can be extremely dangerous to the monkeys, and for research on diseases that may infect humans, it is important to keep those monkeys isolated.

  • All CNPRC employees are subject to annual health screenings to ensure they are not carriers of diseases that are a threat to the monkeys. In addition, the center’s veterinarians, animal care staff, and scientific staff are trained in safety procedures to prevent the transmission of diseases.

Can the diseases being studied spread to the community?

  • Infectious diseases that are studied at the CNPRC are carefully controlled and all personnel are appropriately trained to ensure containment of biohazards.  PPE (personal protective equipment) is worn at all times when around the animals, to ensure protection for the humans and animals. Humans carry infectious viruses and bacteria that can be transmitted to the monkeys, therefore all personnel that work at the CNPRC are screened annually and wear PPE to protect themselves and the monkeys.
  • The CNPRC does not conduct research on diseases such as the Ebola virus or anthrax related studies.

Where do the monkeys come from?

The vast majority of the monkeys are bred on site. The center occasionally acquires a small number of monkeys from other primate breeding facilities. No monkeys are obtained from wild populations.

How is the center funded?

  • UC Davis receives a “base grant” from the NIH that pays for the infrastructure and basic functions of the center, including core research facilities and scientists, and administrative functions. UC Davis has also received NIH grants to pay for specific infrastructure, such as the new Respiratory Disease Center.
  • Specific research projects are usually supported by grants or contracts, either from the NIH, other federal agencies, or in some cases companies that want to test new drugs or therapies prior to their use in humans as required by the FDA.

Media contact(s)

Andy Fell, 530-752-4533, ahfell@ucdavis.edu

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