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 (now Emory) 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

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.”

 

February 23, 2021

Is gene editing the answer scientists have been looking for to eliminate diseases such as HIV?  

A research team at Temple University and Tulane National Primate Research Center (TNPRC) has focused  on removing DNA from viruses, one of the main ways  a virus survives treatments. Now, they’ve seen promising results  that may lead to a cure for HIV.  

The team has employed CRISPR technology, best described as “molecular scissors,” which can precisely cut and remove specific segments of DNA. When attached to a mild adeno-associated virus, these gene editing shears can be sent into the body to cut and remove  DNA from viruses, including HIV.  

They tested this on nonhuman primates infected with  simian immunodeficiency virus (SIV), a disease genetically similar  to HIV, and observed that the  gene editing molecules were able to enter SIV viral reservoirs in the lymph, spleen, bone marrow and brain to prevent the cells from making new virus within these reservoirs. 

Within just three weeks, the new treatment had eliminated nearly two-thirds of the virus that had managed to resist the antiretroviral therapy (ART) many HIV patients receive.  

Andrew MacLean, PhD, one of the principal investigators of the research project and associate professor of microbiology and immunology at TNPRC, views this as evidence a cure for HIV is a real possibility. 

“This is an important development in what we hope will be an end to HIV/AIDS,” MacLean said. “The next step is to evaluate this treatment over a longer period to determine if we can achieve complete elimination of the virus, possibly even taking subjects off of ART.” 

Co-corresponding author also includes Dr. Binhua Ling, one of the principal investigators of the research and previous associate professor of microbiology and immunology at TNPRC. Ling is currently an associate professor at Texas Biomedical Research Institute. 

A potential cure for HIV is just the beginning though. These “molecular scissors” will likely play a role in future efforts to cure diseases currently receiving treatments to make them manageable.  

The results are indeed promising, but the work of the NPRCs is never over. They will continue searching for the causes, preventions, treatments and cures leading to longer, healthier lives worldwide. Learn more about our HIV-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.

November 10, 2020

Could a recent discovery about the body’s natural defenses be a stepping stone toward combating kidney-related health issues? Scientists say yes.

Macrophages are a type of white blood cell central to the immune system that detect and engulf harmful pathogens, like viruses, bacteria and fungi, serving as helpful scavengers to fight infections. They also cause or suppress inflammation and secrete molecules that allow communication between different cell types, all of which provide a healthy immune response in fighting infection and disease.

Scientists have long known the origins of different types of macrophages found in the brain, gut, heart and liver. The origins of those found in kidney tissue, however, are not as well understood. Until now, researchers hadn’t known if these macrophages had traveled from elsewhere in the body or if they were produced during embryonic development. As it turns out, both theories are correct.

In a recent study, Tulane National Primate Research Center (TNPRC) scientists Xuebin Qin, PhD, professor of medicine, and Fengming Liu, PhD, assistant professor of microbiology and immunology, made a new discovery about renal (kidney) macrophages that fundamentally changes the understanding of how these cells populate.

Using a new rapid cell ablation (destruction) technique created by Qin, the team discovered that in a mouse model, half of renal macrophages originate during the embryonic state and the other half derive from bone marrow. They also showed that embryo-derived renal macrophages have a stronger immune response than their bone marrow-derived counterparts. 

“These findings advance our current understanding of tissue-resident macrophages and may lead to promising new directions for the development of new therapeutics for kidney diseases,” explained Qin.

The implications of this discovery are important because while the kidneys help control the volume of blood in the body and maintain the proper concentrations of proteins and electrolytes, they are also subject to infection and disease. The role of macrophages in clearing any infection and supporting kidney function could prove key to future treatments of kidney disease and even infectious diseases that are associated with kidney failure, like human immunodeficiency virus (HIV) and coronavirus (COVID-19).

NPRC scientists across the country are working to combat infectious diseases through a variety of research projects. You can learn more about NPRC’s infectious disease studies at this link, as well as coronavirus-specific studies at 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 26, 2020

Protecting against three diseases at once may seem improbable, but a recent study has produced a vaccine which may do just that.

In a joint collaborative effort involving Tulane National Primate Research Center (TNPRC), the National Institutes of Health and the U.S. Army, researchers have developed the first vaccine that provides complete protection against three types of equine encephalitic viruses in nonhuman primates.

There are no existing vaccines or treatments against Western, Eastern and Venezuelan equine encephalitis, all of which are spread by mosquitoes. During summer months when mosquitos increase, horse populations are particularly susceptible to fatal infection. Transmission from horses to humans can occur via mosquitoes and can cause serious illness and death in vulnerable populations like the elderly and children.

Using nonhuman primate and mouse models of aerosol infection, the study showed that the trivalent virus-like particle (VLP) vaccine induced an immune response and provided complete protection from all three viruses. The response was strong enough to effectively block the neurological effects of infection, which is normally present with any of the three viruses.

Chad Roy, PhD, director of Infectious Disease Aerobiology and Biodefense Research Programs at Tulane, said one reason this finding is significant is because of its possible influence on the field of bioweaponry. These encephalitic viruses are possible bioterrorism agents because of their potential to be aerosolized, underlining the need for a vaccine in the event of an attack.

“These findings are an important milestone in the development of a vaccine that could be employed in the event that these viruses are ever used in a deliberate release,” noted Roy.

Of course, the vaccine could also be used to prevent or slow the natural spread of equine encephalitic viruses.

“This is a significant step, not only in protecting human populations from possible threats of bioterrorism, but also protecting both animals and humans from natural vector-borne disease transmission,” said Vicki Traina-Dorge, PhD, associate professor of microbiology and immunology at Tulane.

As the global climate warms and human and animal populations increase, mosquito-borne infectious diseases have greater potential to spread. These vaccines could be highly useful in protecting global populations from both natural and man-made outbreaks.

April 2, 2020

In the midst of the novel coronavirus (COVID-19) outbreak, scientists at the National Primate Research Centers (NPRCs) have initiated research programs to better understand and diagnose as well as develop potential treatments and vaccines for the disease. NPRC animal colonies will be key in moving SARS-CoV-2 infection/COVID-19 research from cell models to studies in whole living systems so researchers can determine treatment safety and effectiveness.

Since the virus began to spread at the end of 2019, more than 3 million people have been infected worldwide as of April 28, 2020, with numbers growing daily. The coordinated efforts of the scientific community will be crucial to slow the spread of COVID-19, lower the risk of transmission and treat those who have the disease.

NPRC COVID-19 Research

Several of the NPRCs have made public announcements that research is under way, including California NPRC, Southwest NPRC, Tulane NPRC and Wisconsin NPRC. Others, including Oregon, Washington and Yerkes NPRCs, are also beginning research, and Oregon and Yerkes are accepting applications for COVID-19 pilot projects, which facilitate research collaborations and provide important preliminary data.

California NPRC researchers have already isolated, characterized and cultured COVID-19 from a patient treated at UC Davis, the first community-acquired case in the U.S. Next, they plan to make diagnostic tests in-house.

The Southwest NPRC scientists are proposing research projects to establish a nonhuman primate model to study the development and transmission of the disease, test new detection methods and partner with others in the scientific community.

At Tulane NPRC, researchers plan to create a nonhuman primate model to study the disease’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations. The scientists are aiming to answer many questions, including why older individuals are more susceptible to complications and death from COVID-19.

In Wisconsin NPRC researchers have developed a coalition of scientists to combat the disease, drawing heavily from their firsthand experience during the Zika virus outbreak in 2016.

Yerkes NPRC researchers have begun initial research, and the center’s goals include understanding immunity and antibody response to SARS-CoV-2, and developing diagnostics, key reagents, antiviral therapies and vaccines.

COVID-19 Research Safety

The NPRCs are well-positioned to conduct SARS-CoV-2 infection/COVID-19 research because of our expertise in infectious diseases and collaborations internally at each NPRC as well as across NPRCs and with colleagues worldwide. Also, we can conduct such research safely in our Biosafety Level 3 (BSL3) facilities specifically designed to keep personnel, the research and the environment safe. Examples of BSL3 safety features include additional training and oversight for employees, directional air flow and filtered ventilation systems, and specialty equipment to contain the virus isolates used in the research and to decontaminate the lab space and research equipment and supplies.

News Stories about NPRC COVID-19 Research

Recent news articles by STAT News, Bloomberg, The Scientist and ABC News provide more information about the NPRC studies and the critical role of research with animals.

As we have more information to share about NPRC COVID-19 research, we’ll post information at NPRC.org/news and tweet from @NPRCnews. In the meantime, here are a few helpful COVID-19 resources we’re following.

 

March 21, 2020

At the NPRCs, our focus is conducting research and caring for our irreplaceable animal colonies so we can help people and animals live healthier lives. In the midst of the global COVID-19 pandemic, we are prioritizing our research to focus on developing diagnostics, preventions and treatments for this novel disease.

As we work to combat this health crisis, we also want to help keep you informed about the latest developments. Below are some of the resources we are following. These organizations are on the front lines of combatting COVID-19 and are frequently sharing crucial information regarding public health, personal guidelines and coronavirus research.

Centers for Disease Control and Prevention (CDC)
https://www.cdc.gov/coronavirus/2019-ncov/index.html
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

World Health Organization
www.who.int/emergencies/diseases/novel-coronavirus-2019

National Institutes of Health
https://www.nih.gov/health-information/coronavirus

In addition, we want to provide resources to help address any mental health and emotional well-being concerns COVID-19 brings for you and your loved ones:

CDC’s Recommendations for Managing Anxiety and Stress
https://www.cdc.gov/coronavirus/2019-ncov/prepare/managing-stress-anxiety.html

National Alliance on Mental Illness
https://www.nami.org/About-NAMI/NAMI-News/2020/NAMI-Updates-on-the-Coronavirus

Just for Kids: A Comic Exploring the New Coronavirus
https://www.npr.org/sections/goatsandsoda/2020/02/28/809580453/just-for-kids-a-comic-exploring-the-new-coronavirus

The NPRCs are working closely with our collaborators worldwide to address COVID-19. Look for updates from us at NPRC.org and @NPRCnews.

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