April 27, 2021

Did you know the rhesus macaque is the most widely studied nonhuman primate in biomedical research? The U.S. research colonies of rhesus macaques were founded primarily with animals imported from India decades ago and with the addition of Chinese-origin rhesus macaques over time. A deep understanding of their evolution and genetics is key to recognizing the origins of human traits and identifying disease genes of value to improving human health.

Rhesus macaques at the seven National Primate Research Centers (NPRCs) are key in the discovery and development of new and robust models of human disease and in evaluating the effect of genetic variation on experimental treatments prior to human clinical trials.  

In a recent publication in Science that detailed researchers’ use of advanced sequencing technology and analysis of more than 850 macaques across the seven NPRCs, researchers present a complete reference genome for the rhesus macaque. “In particular, we can now finally tackle some of the more complex regions of the genome and begin to understand how new genes evolve including the processes that have shaped them,” says University of Washington genome sciences professor and senior author in the paper, Evan Eichler, PhD.

In addition, the study identified animals that naturally carry potentially damaging genetic mutations, allowing researchers to better understand genetic variation and susceptibility to diseases of relevance to humans. So far, the findings reveal thousands of naturally occurring genetic variants (mutations), including those in genes linked to Autism Spectrum Disorder and other neurodevelopmental disorders in humans, such as SHANK3.

Jeffrey Rogers, PhD, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor College of Medicine and co-author of the paper explains, “Rhesus macaques are important for studies of conditions ranging from infectious disease (including COVID-19) to neuroscience, cancer and reproductive biology. A high-quality reference genome can aid researchers who are looking to understand the causes of various illnesses or aiming to develop treatments.”

The study is a great example of a broad collaboration across the NPRCs and other research centers in the U.S. that will continue to make a difference in human health. By identifying rhesus macaques that carry naturally occurring mutations, NPRC and other researchers are now able to examine biobehavioral traits associated with mutations. The researchers can also follow the monkeys’ offspring, and, in some cases, actually create new breeding groups to generate animals with specific genetic mutations and phenotypes. 

“This new information will lay the foundation for us to create naturally occurring models of human genetic diseases,” says Paul Johnson, MD, director of the Yerkes NPRC. “The development of these new models could have a profound impact on our ability to translate research in animal models into treatments and cures in people,” he continues.

To learn more about NPRC advances in genetics and genomics, explore additional research here

April 20, 2021

Alzheimer’s disease (AD) affects more than 5.5 million Americans per year. This staggering prevalence makes it a high-priority disease for researchers to develop better treatments and even a cure. Researchers at California’s National Primate Research Center (CNPRC) are among those pursuing answers and believe the disease actually begins decades before the first signs of cognitive decline are triggered. 

Until recently, testing has primarily been done on transgenic mice that express a human version of amyloid or tau proteins, but these studies have proven to be difficult to translate into new medications for the human population. In contrast, nonhuman primate (NHP) models may yield new treatments by providing a closer biological link between the laboratory and clinic. 

“Humans and monkeys have two forms of the tau protein in their brains, but rodents only have one,” said Danielle Beckman, postdoctoral researcher at the CNPRC and first author on the paper. “We think the macaque is a better model, because it expresses the same versions of tau in the brain as humans do.”

Beckman and her team recommend adding an intermediate step for translational research: “If we can test therapies that work in mouse models prior to investing millions or billions of dollars into clinical trials, we really think it’s going to make an impact in having a new drug on the market. I think we really need to be open about new animal models for diseases.”

Visualization of biomarkers in the brain of NHP models may provide the key into the progression of Alzheimer’s disease. So far, teams have monitored signs of neuron death and performed positron emission tomography imaging. The effects of neurodegeneration were observed rapidly; within three months, end-stage tangles were present. And within 6 months, the progress of neurodegeneration increases markedly.

While it is still unknown whether the treated animals will present the full spectrum of Alzheimer’s Disease, including severe cognitive impairment, the initial observations have set the stage for the next steps in testing tau‐based therapeutics for AD patients. Research with monkeys is again proving critical to finding answers that can improve millions of lives worldwide. 

To learn more about the work happening at our research centers around the country, visit this link

March 3, 2021

Scientific discovery is an ongoing process that takes time, observation, data collection and analysis, patience and more. At the NPRCs, our recent COVID-19 research is an example of the ongoing basic science process — how current research builds on previous discoveries and how discoveries help improve human health. This article from the National Institutes of Health (NIH) explains why basic science, such as the NPRCs conduct, is important and how taking time, as long as it takes, is a necessary part of scientific discovery.

Discoveries in Basic Science: A Perfectly Imperfect Process

Have you ever wondered why science takes so long? Maybe you haven’t thought about it much. But waiting around to hear more about COVID-19 may have you frustrated with the process.

Science can be slow and unpredictable. Each research advance builds on past discoveries, often in unexpected ways. It can take many years to build up enough basic knowledge to apply what scientists learn to improve human health.

“You really can’t understand how a disease occurs if you don’t understand how the basic biological processes work in the first place,” says Dr. Jon Lorsch, director of NIH’s National Institute of General Medical Sciences. “And of course, if you don’t understand how the underlying processes work, you don’t have any hope of actually fixing them and curing those diseases.”

Basic research asks fundamental questions about how life works. Scientists study cells, genes, proteins, and other building blocks of life. What they find can lead to better ways to predict, prevent, diagnose, and treat disease.

How Basic Research Works

When scientists are interested in a topic, they first read previous studies to find out what’s known. This lets them figure out what questions still need to be asked.

Using what they learn, scientists design new experiments to answer important unresolved questions. They collect and analyze data, and evaluate what the findings might mean.

The type of experiment depends on the question and the field of science. A lot of what we know about basic biology so far has come from studying organisms other than people.

“If one wants to delve into the intricate details of how cells work or how the molecules inside the cells work together to make processes happen, it can be very difficult to study them in humans,” Lorsch explains. “But you can study them in a less complicated life form.”

These are called research organisms. The basic biology of these organisms can be similar to ours, and much is already known about their genetic makeup. They can include yeast, fruit flies, worms, zebrafish, and mice.

Computers can also help answer basic science questions. “You can use computers to look for patterns and to try to understand how the different data you’ve collected can fit together,” Lorsch says.

But computer models have limits. They often rely on what’s already known about a process or disease. So it’s important that the models include the most up-to-date information. Scientists usually have more confidence in predictions when different computer models come up with similar answers.

This is true for other types of studies, too. One study usually only uncovers a piece of a much larger puzzle. It takes a lot of data from many different scientists to start piecing the puzzle together.

Building Together

Science is a collective effort. Researchers often work together and communicate with each other regularly. They chat with other scientists about their work, both in their lab and beyond. They present their findings at national and international conferences. Networking with their peers lets them get feedback from other experts while doing their research.

Once they’ve collected enough evidence to support their idea, researchers go through a more formal peer-review process. They write a paper summarizing their study and try to get it published in a scientific journal. After they submit their study to a journal, editors review it and decide whether to send it to other scientists for peer review.

“Peer review keeps us all informed of each other’s work, makes sure we’re staying on the cutting-edge with our techniques, and maintains a level of integrity and honesty in science,” says Dr. Windy Boyd, a senior science editor who oversees the peer-review process at NIH’s scientific journal of environmental health research and news.

Different experts evaluate the quality of the research. They look at the methods and how the results were gathered.

“Peer reviewers can all be looking at slightly different parts of the work,” Boyd explains. “One reviewer might be an expert in one specific method, where another reviewer might be more of an expert in the type of study design, and someone else might be more focused on the disease itself.”

Peer reviewers may see problems with the experiments or think different experiments are needed. They might offer new ways to interpret the data. They can also reject the paper because of poor quality, a lack of new information, or other reasons. But if the research passes this peer review process, the study is published.

Just because a study is published doesn’t mean its interpretation of the data is “right.” Other studies may support a different hypothesis.

Scientists work to develop different explanations, or models, for the various findings. They usually favor the model that can explain the most data that’s available.

“At some point, the weight of the evidence from different research groups points strongly to an answer being the most likely,” Lorsch explains. “You should be able to use that model to make predictions that are testable, which further strengthens the likelihood that that answer is the correct one.”

An Ever-Changing Process

Science is always a work in progress. It takes many studies to figure out the “most accurate” model—which doesn’t mean the “right” model.

It’s a self-correcting process. Sometimes experiments can give different results when they’re repeated. Other times, when the results are combined with later studies, the current model no longer can explain all the data and needs to be updated.

“Science is constantly evolving; new tools are being discovered,” Boyd says. “So our understanding can also change over time as we use these different tools.”

Science looks at a question from many different angles with many different techniques. Stories you may see or read about a new study may not explain how it fits into the bigger picture.

“It can seem like, at times, studies contradict each other,” Boyd explains. “But the studies could have different designs and often ask different questions.”

The details of how studies are different aren’t always explained in stories in the media. Only over time does enough evidence accumulate to point toward an explanation of all the different findings on a topic.

“The storybook version of science is that the scientist is doing something, and there’s this eureka moment where everything is revealed,” Lorsch says. “But that’s really not how it happens. Everything is done one increment at a time.”

 

January 15, 2021

Autism Spectrum Disorder (ASD), which impacts communication and interaction abilities, affects 1 in every 54 children in the United States. In order to understand the biological basis of these types of human disorders, scientists must turn to translational animal models—research with animals that closely reflects the same processes in humans.    

Until now, there hasn’t been an effective way to identify which animals were ideal candidates for ASD research. But Kate Talbot, PhD, and her colleagues in the Neuroscience and Behavior Unit at the California National Primate Research Center (CNPRC) have optimized a screening tool—based on an ASD diagnostic tool used in humans—to do just that.  

ASD is classified by the National Institute of Mental Health as a developmental disorder that affects communication and behavior. It is a spectrum disorder, which means autism can present differently in symptoms and severity across individuals. This variability is part of what makes treatment of ASD more complicated. Rather than a primary treatment for ASD, doctors and patients have to work together to develop specific treatment programs.  

Talbot pointed out that studying disease biology directly in ASD patients is difficult in other animal models because they fundamentally lack the complex social cognitive abilities that are impaired in people with autism. But there is a subset of rhesus monkeys within the natural population illustrating low-social behavior similar to what is observed in humans with ASD. The difficult part is identifying enough of these animals early in their development to conduct the necessary translational research. 

Talbot and her team made a breakthrough in that area. The original macaque social responsiveness scale (mSRS) was a 36-item observation-based instrument similar to the Social Responsiveness Scale originally developed for human children. The mSRS was developed using a relatively small sample mostly composed of females, but due to the sample size and the fact that ASD is a particularly male-biased disorder (four males for every one female), the mSRS was difficult to translate to the human screening tool.  

Talbot and colleagues refined the mSRS by applying it to hundreds of male rhesus macaques across their development. They could then compare experimenter responses to the questionnaire directly to behavioral data collected on the animals throughout their lives. Now, the revised tool can determine with 96% accuracy which monkeys qualify as particularly low-social animals compared to their peers.   

“This instrument will be indispensable for advancing the field’s understanding of the developmental trajectory of core autistic symptomology in rhesus and other macaque monkeys, and it can be used as a primary outcome measure in fast-fail preclinical therapeutic testing efforts,” Talbot explained. 

Understanding autism and other neurological conditions is a primary goal of NPRC research. Find out more about our ASD-related studies by visiting this link.  

December 15, 2020

Research with animals is crucial to improving human and animal health. Animals in research provide unique insights not available with other scientific models, and they help scientists determine safety and effectiveness of preventions, treatments and cures. During the COVID-19 pandemic, animals in research have been especially important in accelerating the development COVID-19 vaccines as well as better diagnostics and additional treatment options.

At the NPRCs, we’re helping fill a critical role in halting COVID-19 by leading NIH-funded studies at our centers. We’re also participating in the public-private partnership ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) to develop treatments and vaccines by sharing our knowledge, resources and animals, including conducting preclinical studies with NPRC monkeys for some of the leading industry vaccine candidates.

Scientific collaboration is especially important during a pandemic when time is of the essence and, in this case, animal resources are limited. At the onset of the pandemic, monkey importation was halted, putting increasing demands on the NPRC animal colonies, which were already limited in quantity and availability. The NPRCs account for only 1 in every 5 nonhuman primates (NHPs) used in U.S.-based research, so the limited supply at a time of high demand impacts NPRC COVID-related studies as well as pre-pandemic studies under way at the NPRCs and those in planning stages.

The NPRCs remain dedicated to our other areas of study, including research into HIV/AIDS and other infectious diseases, the neurosciences, cardiovascular and respiratory health, genetics and transplant medicine. 

We are also committed to meeting the future needs of animals for NIH-funded research. This is why the NPRCs support establishing a strategic reserve of NHPs to be used in times of national health crises. We are already growing our on-site breeding colonies when time, space and funding permit, strategically assigning animals to research protocols, harmonizing across centers for efficient use of animals and increasing rigor and reproducibility to facilitate collaboration and consistency across research labs. These strategic steps now further position the NPRCs for the translation of our research advancements from cell and animal models to humans, and are indicative of our commitment to help people across generations and the world live longer, healthier lives. 

To learn more about the NPRCs’ ongoing efforts to combat COVID-19, visit this page.

Editor’s Note, 2/22/21: The New York Times covered the research monkey shortage in today’s issue. Read the story here.

November 24, 2020

Talking about animals in research may not be part of everyday conversations – unless you work in research, are learning more about it or want to stop it. But if everyone knew how critical animals have been in 2020 to fast-track a safe and effective COVID-19 (coronavirus) vaccine, would that change?

Earlier this year, the National Institutes of Health (NIH) called upon the National Primate Research Centers (NPRCs) – as NIH has for HIV/AIDS, Ebola, Zika and other infectious disease threats – to identify animal species for studying the SARS-CoV-2 virus and developing safe and effective vaccines to block it.

The NPRCs went to work and within a few months had discovered how valuable nonhuman primate models (NHPs), especially macaques, are for studying SARS-CoV-2. The NPRCs found the virus infects rhesus, pigtail and cynomolgus macaques, so these animals were included in research programs that resulted in several vaccine candidates in the pipeline by summer’s end. In addition, other key models for SARS-CoV-2, such as mice and hamsters, contributed to the broadening knowledge of how best to tackle the disease in humans. This rapid pace of discovery was possible due to the NPRC researchers applying their expertise fighting other viruses, especially HIV/AIDS.

As with those other viruses, the NPRC researchers closely studied SARS-CoV-2 transmission routes and pathogenesis – this time focusing on the respiratory virus’ activity in the lungs and its impact on cells, tissues and organs. The researchers also conducted detailed genetic studies on the virus to help pharmaceutical researchers use pieces of the virus’ genetic code to fashion vaccine candidates and test them for safety and effectiveness in macaques.

Translating the biomedical research findings into the human population requires going from up to a few dozen monkeys in research to thousands of human volunteers in clinical trials; for COVID-19, more than 200,000 volunteers have enrolled in four promising clinical trials. As announced in November 2020, the Moderna and Pfizer mRNA vaccines tested on rhesus macaques were more than 90 percent effective in preventing COVID-19 in widespread (Phase 3) human clinical trials and are now on track for emergency FDA approval.

Research with animals connects these vaccines with other SARS-CoV-2 scientific advancements just as it has made connections among NPRC HIV/AIDS studies, the results from which facilitated the rapid pace to COVID-19 discoveries. Improving human and animal health – that’s what NPRC research with animals does, and that’s worth talking about any day.

Learn more about research with animals scientific advancements here.

September 29, 2020

Cardiovascular disease is one of the leading causes of death in the United States, and it has many possible causes. One of the most well-known risk factors is hyperlipidemia, which presents as a high level of lipids, like triglycerides or cholesterol, in the blood. Scientists and doctors are still looking for effective ways to reduce cardiovascular risk from hyperlipidemia—and according to new research, fish oil may be part of the solution.

Recently, a team including Peter Havel, DVM, PhD, of UC Davis and the California National Primate Research Center (CNPRC) found that targeting a protein known as angiopoietin-like protein-3 (or ANGPTL3) could be helpful for managing cardiovascular disease.

In the study, the scientists gave 59 male rhesus macaques flavored, fructose-sweetened beverages daily in addition to their regular diet. A subset of macaques also received a whole fish oil supplement. The fructose supplementation allowed researchers to model symptoms of metabolic syndromes seen in humans, including insulin resistance and hyperlipidemia. This model also rapidly increased levels of triglycerides and certain lipoproteins in the blood, mirroring human risk factors for cardiovascular disease.

The results showed ANGPTL3 levels increased simultaneously with lipid levels in monkeys fed a high-sugar diet. It was also found that inhibiting the production of ANGPTL3 resulted in lower levels of several lipids and lipoproteins in circulation, which suggests the protein could be a helpful therapeutic target. What’s more, the researchers found that increases in the protein and lipids in the blood could be prevented if the animals were also provided with the fish oil supplement.

While the exact mechanisms remain unknown, Havel hopes to clarify in future studies exactly how components of fish oil influence ANGPTL3 production and circulating lipid levels. Understanding this could help scientists develop new interventions for the prevention and treatment of cardiovascular disease.

Heart health is incredibly important, which is why NPRC scientists are actively conducting research on cardiovascular diseases and treatments. Learn more about their breakthrough discoveries by visiting this link.

September 28, 2020

The seven National Primate Research Centers (NPRCs) are participating in SciFest All Access 2020. This is the virtual answer to the postponed USA Science & Engineering Festival, which is recognized as the nation’s top science and engineering festival for K-12 students, college students, educators and families. Happening now through Oct. 3, registered participants can visit the NPRCs in the “Exhibit Portal, Health & Medicine Zone II.”

The NPRC booth includes links to NPRC.org, our collective website, as well as individual web pages for the seven centers. All pages are filled with educational resources and links to help you learn more about our research, the scientific advancements we’re making and the care we provide our research animals. Direct access links to these seven pages are provided below.

NPRC representatives will be “on site” at SciFest All Access answering questions registered participants submit via the “Ask a Question” link in the booth. We’re also answering questions participants email us at nprcoutreach@gmail.com.

You can learn even more about the NPRCs’ research to improve human and animal health by visiting NPRC.org and following us on Twitter at @NPRCnews.

We look forward to joining thousands of students, educators and families at this year’s SciFest All Access!

SciFest All Access NPRC Web Pages

California NPRC

Oregon NPRC

Southwest NPRC

Tulane NPRC

Washington NPRC

Wisconsin NPRC

Yerkes NPRC

August 24, 2020

Note: The NPRCs will update this blog with our latest COVID-19 news.

Since beginning COVID-19 research in early 2020, NPRC researchers have made encouraging progress in efforts to better understand, diagnose, prevent and treat this novel disease. We’re committed to conducting and enabling research to end this global pandemic and to providing information so the public has ready access to our scientific results.

Our most recent COVID-19 news includes: 

  • April 13, 2021: Wisconsin NPRC scientists explore the shifts in the genetic material of COVID-19 to expand the viral genome sequence
  • February 25, 2021: Southwest NPRC helps people understand COVID-19 variants in this TX Biobytes podcast with virologist Dr. Jean Patterson
  • February 23, 2021: The New York Times features NPRC COVID-19 research in this story (Note: may require log in)

Below is even more information about our extensive and collaborative COVID-19 research:

Diagnostics:

Prevention:

Treatments:

Additional NPRC COVID-19 News:

Bookmark this page so you can easily return here for the latest NPRC COVID-19 research information. We’ve also compiled a list of resources here and provided links to previous NPRC COVID-19 news and national media stories here.

August 12, 2020

As scientists continue to make progress in the fight against human immunodeficiency virus (HIV), a recent discovery suggests that certain other microbes may play a role in how the body responds to vaccination.

According to researchers at the California National Primate Research Center (CNPRC) at the University of California, Davis (UC Davis), microbes living in the rectum could alter the effectiveness of experimental HIV vaccines.

Evidence from human and animal studies with other vaccines suggests supplements containing the bacteria Lactobacillus can boost antibody production, while treatment with antibiotics can hamper beneficial immune responses, according to Smita Iyer, assistant professor at the UC Davis Center for Immunology and Infectious Diseases and School of Veterinary Medicine. 

Iyer and her team specifically sought to learn if microbes living in the rectum and vagina—sites of HIV transmission—interacted with an experimental HIV vaccine similar to the HVTN 111 vaccine currently in early stage clinical trials in humans. According to Iyer, a vaccine that produces antibodies at the mucosal membranes where infection takes place is thought to be crucial.

The team studied rectal and vaginal microbes from rhesus macaques before and after they were vaccinated. While vaginal microbes did not show much difference before and after vaccination, rectal microbes did, with certain bacteria decreasing after vaccination. 

Furthermore, the amounts of the common gut bacteria Lactobacillus and Clostridia in the rectum correlated positively with the immune response. Animals with high levels of either Lactobacillus or Clostridia made more antibodies to certain HIV proteins, the researchers found. Prevotella bacteria showed the opposite pattern: High levels of Prevotella were correlated with weaker immune responses.

It’s not clear what the mechanism could be for some bacteria to boost local immune responses in a specific site in the body, Iyer said. However, targeting these bacteria could help scientists get the best possible performance out of vaccines that do not induce a particularly strong immune response, as is the case with HIV vaccines.

The NPRCs are actively conducting HIV/AIDS research across the country. Discover more ways our scientists are making progress against this disease in the ongoing pursuit of a cure.

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