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

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.”

 

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 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 18, 2020

For some, a summer internship is merely a stepping stone into their career. But for Brendan Creemer, a junior biology major at Portland’s Lewis & Clark College, a recent summer internship meant so much more.

Creemer has Usher syndrome, a genetic disorder that causes progressive vision loss and deafness. He spent much of the summer in the laboratory of the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) with neuroscientists Martha Neuringer, PhD and Trevor McGill, PhD, working on a method to improve the ability to use stem cells as a possible treatment for the disorder.

For more than 40 years, Neuringer has taken on high school and college summer interns, but Creemer is the first intern to live with the often-debilitating symptoms of Usher syndrome.

“I’ve been working for many years on retinal diseases and potential therapies without that personal connection,” said Neuringer, a professor in the Division of Neuroscience at the ONPRC and research associate professor of ophthalmology in the OHSU School of Medicine. “It’s all the more motivation when you know what it’s like for someone facing this.”

Creemer sought out the internship after learning about the research through the OHSU Casey Eye Institute.

“You have that choice to either give up and assume everything is hopeless or choose to take action and not only help yourself but others around you as well,” he wrote of his experience.

Creemer’s summer project focused on a key issue for stem cell therapies: rejection of transplanted cells. When stem cells are delivered as therapies for any health issue, they are perceived as “non-self” by the recipient and attacked by the immune system. Creemer analyzed a possible method to suppress the immune system in rodents, which was then tested to see if it enhanced the survival of retinal stem cell transplants.

“It makes it so much more palpable and real when you see how someone deals with their limitation and overcomes it,” Neuringer said. “It was a perfect match.”

The scientists at the NPRCs across the country are focused on solving myriad genetic disorders. Discover more of our latest research here.

July 8, 2020

Children born to HIV-positive mothers are susceptible to contracting the disease themselves, but scientists at Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) have new evidence suggesting that newborn infection may be entirely preventable.

The researchers successfully demonstrated, in a non-human primate model, that a single dose of an antibody-based treatment given after virus exposure can prevent HIV transmission from mother to baby, provided that dose is given at the correct time. 

The study found that rhesus macaque newborns did not develop the monkey form of HIV (known as SHIV), when they received a combination of two antibodies 30 hours after being exposed to the virus. This is the first time a single dose of broadly neutralizing antibodies given after viral exposure has been found to prevent SHIV infection in nonhuman primate newborns.

However, when the antibody treatment was delayed until 48 hours after exposure, half of the baby macaques developed SHIV, even when given four smaller doses of the same antibody. 

Previous research by this group has shown that four doses of antibodies started 24 hours after exposure also prevented SHIV infection, and the current ONPRC study suggests that a three-week course of antiretroviral therapy given after virus exposure could also prevent HIV transmission to newborns.

“These promising findings could mean babies born to HIV-positive mothers can still beat HIV with less treatment,” said Nancy Haigwood, PhD, ONPRC director and a professor of pathobiology and immunology at the OHSU School of Medicine.

Antibodies aren’t toxic and can be modified to last a long time in the body, which reduces treatment frequency. This means antibody treatments may also help prevent negative side effects from the drug combination currently given to infants born to HIV-positive mothers.

Next, ONPRC scientists plan to see if different antibodies, or a combination of antibodies and antiretroviral therapy, could be even more effective. They also hope to find out whether the antibodies actually eliminate HIV or only prevent it from replicating.combination. This suggests that there is a 30-hour limit for the successful use of antibodies to prevent HIV transmission to newborns.

June 11, 2020

Scientists have made one more step toward the treatment and cure of multiple sclerosis (MS) by developing a compound that successfully promotes the regeneration of the protective myelin sheath around nerve cells.

In a recent study, scientists at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) described successfully testing the compound in mice, and they have already started to apply it to a rare population of macaque monkeys who develop a disease that is similar to MS in humans.

“I think we’ll know in about a year if this is the exact right drug to try in human clinical trials,” said senior author Larry Sherman, PhD, an OHSU professor in the Division of Neuroscience at the primate center. “If it’s not, we know from the mouse studies that this approach can work. The question is, can this drug be adapted to bigger human brains?” 

The discovery arrives after more than a decade of research following a 2005 breakthrough by Sherman’s lab. In that study, scientists discovered that a molecule called hyaluronic acid (HA), accumulates in the brains of patients with MS. The researchers then linked this accumulation of HA to the failure of cells called oligodendrocytes (which generate myelin) to mature. 

Myelin forms a protective sheath covering each nerve cell’s axon—the threadlike portion of a cell that transmits electrical signals between cells. Damage to myelin is associated with MS, stroke, brain injuries and certain forms of dementia like Alzheimer’s disease. Delay in myelination can also affect infants born prematurely, leading to brain damage or cerebral palsy. 

Other studies led by the Sherman lab have shown that HA is broken down into small fragments in multiple sclerosis lesions by enzymes called hyaluronidases, and these fragments send a signal to immature oligodendrocytes to not turn on their myelin genes. 

There is currently no cure for MS, but an international team of researchers led by OHSU has been working to develop a compound that neutralizes the hyaluronidase in the brains of patients with MS and other neurodegenerative diseases. This will ideally revive the ability of progenitor cells (descendants of stem cells that differentiate, or change, into specific cell types) to mature into myelin-producing oligodendrocytes and regenerate myelin sheath. 

The ONPRC macaque study describes a modified flavonoid—a class of chemicals found in fruits and vegetables—that does just that. The compound, called S3, reverses the effect of HA and promotes functional remyelination in mice. 

“It’s not only showing that the myelin is coming back, but it’s causing the axons to fire at a much higher speed,” Sherman said. “That’s exactly what you want functionally.”

The next phase of research involves testing, and possibly refining, the compound in macaque monkeys who carry a naturally occurring version of MS called Japanese macaque encephalomyelitis. The condition, which causes clinical symptoms similar to multiple sclerosis in people, is the only spontaneously occurring MS-like disease in nonhuman primates in the world. 

Researchers at the ONPRC and other NPRC locations are consistently making breakthrough discoveries to help treat and eradicate MS and other neurological diseases. Learn more about the latest findings here.

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.

 

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