Forty years ago today, the United States Environmental Protection Agency (EPA) banned commercially manufactured polychlorinated biphenyls (PCBs), acting on evidence of their extreme environmental persistence and toxicity.

Five years before the April 19, 1979, ban, New Scientist published “US losing fight against PCBs – a new cancer risk?”, referencing its 1973 article by Allen and Norback (Vol. 57, p. 289) about changes in nonhuman primates at the Wisconsin Regional Primate Research Center exposed to PCBs.

“As far as the monkeys are concerned, the potential of PCB carcinogenicity is there,” senior author James Allen of the center’s experimental pathology unit stated in the article.

These early research findings were also described in the Summer 1973 issue of Primate Record, the Wisconsin center’s newsletter at the time. The narrative describes how three months of exposure to PCBs at 300 parts per million (ppm) in the animals’ diets resulted in liver enlargement, facial swelling, hair loss and gastritis of the type associated with cancer.

By that time, industrial accidents had at least twice contaminated human food supplies with up to 3,000 parts per million of PCBs. Levels of 28 ppm in milk and 35 ppm in certain fish had also been reported. In previous PCB studies with rats, liver enlargement was the only major reaction.

Quoting Allen, the final paragraph of the newsletter reads, “The discrepancy in clinical findings between the rat and monkey subjects in PCB tests again points to the inadequacy of testing drugs and chemicals only on organisms distantly related to man before certifying them as safe for humans…”

In 1975, the EPA cited the Wisconsin Primate Center team’s findings at its National Conference on Polychlorinated Biphenyls in Chicago. And in 1978, a paper by James Allen et al, published in Pharmacology Biochemistry and Behavior, fully described the toxic effects of PCBs on nonhuman primate health and pregnancy.

While no single study led to the landmark ban, several peer-reviewed studies like the monkey study contributed to the building body of evidence that PCBs cause cancer and other serious health problems. Today, these harmful chemicals are no longer produced in the United States.

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Pictured above are PCB cleanup operations on Wisconsin’s Fox River circa 1989.

Photo credit: Wisconsin Department of Natural Resources

In August 2018, Texas Biomedical Research Institute President and CEO Larry Schlesinger, MD named Deepak Kaushal, PhD, the new Director of the Southwest National Primate Research Center (SNPRC).

Dr. Kaushal joined SNPRC in January 2019, succeeding the retiring Robert Lanford, PhD As Director of SNPRC, Dr. Kaushal will be responsible for leading a national scientific resource funded by a $40 million National Institutes of Health grant and a team of nearly 150 scientists, veterinarians and animal care professionals.

Dr. Kaushal joins SNPRC after his tenure as Director of the Center for Tuberculosis Research within the Tulane National Primate Research Center (TNPRC) in Covington, La., and Professor in the Department of Microbiology and Immunology at Tulane University School of Medicine in New Orleans.

“We are excited Dr. Kaushal will be joining the Texas Biomed and SNPRC team,” Dr. Schlesinger said. “He is a world-renowned researcher whose focus in tuberculosis and HIV, specifically using nonhuman primates in TB research, is a natural fit with the Institute’s long-term vision of becoming the world leader in infectious disease research.”

Dr. Kaushal brings more than 25 years of experience working to eradicate tuberculosis, which kills more than two million people worldwide each year. Using the macaque nonhuman primate model, Dr. Kaushal’s lab tests new vaccine candidates and new drugs against the disease. A major focus of his research is to study the synergy between TB and HIV-AIDS.

“The opportunity to work in San Antonio is tremendous,” Dr. Kaushal said. “The community has a strong health science center and medical school, a network of higher education that fuels the engine of a research enterprise, strong non-profit organizations such as the Southwest Research Institute and is a vibrant, multicultural city. This is a place where technology, industry and supported research in infectious diseases can grow.”

A Bill and Melinda Gates Foundation supported researcher, Dr. Kaushal brings a portfolio of about $25 million in grant funding to SNPRC and Texas Biomed. He has authored more than 94 journal publications that have been published, are in press, in review or in revision and has presented at more than 66 scientific conferences worldwide.

He holds a PhD in biochemistry and microbiology from the University of Delhi in India and is a member of the Infectious Diseases Society of America, the American Society for Biochemistry and Molecular Biology, the Bill and Melinda Gates Foundation Collaboration for TB Vaccine Discovery (CTVD), the Bill and Melinda Gates Foundation working group on Nonhuman Primate Models and the AIDS Clinical Trials Group (ACTG).

November 6, 2018 marks the 20th anniversary of the seminal paper “Embryonic stem cell lines derived from human blastocysts,” published in Science. The paper documented a breakthrough that occurred when University of Wisconsin-Madison and WiNPRC scientist James Thomson, VMD, PhD, developed a technique to successfully isolate and culture human embryonic stem cells from patient-donated, lab-fertilized embryos.

Thomson was successful again in 2007 when he became the first to grow induced pluripotent stem cells. Induced pluripotent stem cells behave similarly to embryonic stem cells with their source being genetically reprogrammed mature cells, such as skin cells. Thomson derived this type of cell with WiNPRC scientist Junying Yu, publishing again in Science.

Scientists predicted both of these cell types could someday be useful for drug discovery and transplant medicine. Today, those predictions are coming true.

Embryonic and induced pluripotent stem cells can become virtually any cell in the body. Scientists and doctors study these cells and their derivatives to learn more about basic biology and genetic origins of disease. They also use them for cell, tissue and organ transplant studies, as well as for pharmaceutical testing and studying the effects of environmental toxins on human cells and tissues.

Both types of stem cells, which Thomson and other NPRC scientists advanced from rodents to nonhuman primates and then to humans in the 1990s, are already in early clinical trials for macular degeneration, spinal cord injury, heart disease, ALS and more. There are currently 27 clinical trials around the world involving embryonic stem cells and their derivatives. Another 42 trials involve the use of induced pluripotent stem cells.

These discoveries underscore the importance of basic science and are excellent examples of how basic science can lead to applied science, clinical trials, entrepreneurship and expanding business and industry. Globally, the market for products related to stem cell discoveries is projected to reach more than $270.5 billion by 2025, according to a 2017 Transparency Market Research report.

A whole new era of science and medicine sprung from those early 1990s discoveries with nonhuman primates. The NPRCs continue to advance research in both human and nonhuman primates involving embryonic stem cells, induced pluripotent stem cells, tissue-specific (adult) stem cells and gene editing of both stem cells and mature cells. We look forward to the cell and regenerative medicine discoveries that are still to come!

Dr. Nancy Haigwood, director of the Oregon National Primate Research Center, discusses the launch of nprc.org, the public-facing website of the seven National Primate Research Centers, in this podcast from Oregon Health and Science University. The website’s goal, she says, is to give the general public information about research at the NPRCs that is “helping humans live longer, healthier lives.”

Researchers from the seven National Primate Research Centers have joined six Nobel Laureates and a growing contingent of America’s scientific community in signing a letter that acknowledges the importance of animal research as well as transparency. The letter calls upon “our country’s research institutions – large and small – to embrace openness. We should proudly explain how animals are used for the advancement of science and medicine, in the interest of the health and wellbeing of humans and animals.”

“We fully support the goal of helping the public understand and trust the research process,” says John Morrison, PhD, director of the California National Primate Research Center. “All seven NPRCs engage in community and educational outreach to provide information about our research as well as the care of our animals.”

USA Today printed the letter and signatures June 20.

Top 10 Research Accomplishments at the NPRCs

The National Primate Research Centers (NPRCs) have played a crucial role in some of the most important medical breakthroughs of the past 50 years. NPRC research with nonhuman primates (NHPs) is highly regulated, provides unique insights not available with other models and often precedes clinical trials in humans. This list highlights 10 of the most significant, recent NHP research breakthroughs that are helping people across generations and the world live longer, healthier lives.

1. COVID-19 – The emergence of SARS-CoV-2 in 2019 was one of the greatest public health crises in American history, and NPRC researchers were crucial in the effort to address it. Results from NHP studies on transmission routes, pathogenicity and genetics of the virus, in addition to decades of research on other mRNA viruses, such as HIV, informed the design of human clinical trials and the safe and effective vaccines we have today. Furthermore, the two lead vaccines that have been given to tens of millions of U.S. nationals were both tested in nonhuman primates for safety, immunogenicity and efficacy, including one (Pfizer) at an NPRC (the Southwest NPRC). Several next generation vaccine candidates and therapeutics are currently being pre-clinically tested at different NPRCs.
2. HIV/AIDS – The emergence of HIV/AIDS in the early 1980s was one of the greatest public health crises in American history, and NPRC researchers were crucial in the effort to address it. Results from NHP studies on the ability of pre-exposure dosing of antiretroviral medicines to prevent infection with SIV or SHIV (the primate versions of HIV) informed the design of subsequent human clinical trials, which provided clear evidence that such pre-exposure dosing was effective in preventing infection.
3. Emerging Infectious Diseases – One of the most potent viruses to infect humans, Ebola is intensely studied by infectious disease researchers who work with NHP models to develop preventive vaccines and novel therapies. The disease course in macaques and marmosets is very similar to that in humans, and new vaccines and therapies have been tested in these animals. When Zika was identified in Brazil in 2015 and associated with severe birth defects, the infectious disease expertise of NPRC researchers was at the forefront of the scientific community’s response and early understanding of the disease’s pathology. Researchers are also working to 1) identify antiviral drugs that are effective against Zika in lab cultures and then test these drugs in NHPs; and 2) determine if and how Zika infection in pregnant animals results in defects of the fetal central nervous system.
4. Tuberculosis – TB kills approximately 2 million human beings each year. NPRC researchers have developed robust NHP models of the various presentations of the human TB syndrome, including those that permit the evaluation of the pathological granuloma, TB latency, TB/HIV co-infection and novel vaccine and therapeutic candidates, some of which are advancing to human trials.
5. Parkinson’s disease – Parkinson’s disease is a progressive neurodegenerative disorder that produces motor symptoms, such as tremor, walking difficulty and muscle stiffness, as well as many non-motor problems. NHP research led to an innovative surgical procedure called deep brain stimulation (DBS), which uses an implanted, battery-operated device to deliver electrical stimulation to specific brain areas that control movement. This blocks the abnormal nerve signals that cause the symptoms of Parkinson’s disease. NHP research also contributed to the development of autologous stem cells as a potential therapy for Parkinson’s and other neurodegenerative diseases. In 2007, researchers transformed skin cells from humans and monkeys into induced pluripotent stem (iPS) cells, and subsequently transformed the monkey iPS cells into dopamine neurons. Because transplanted neurons are able to differentiate into multiple different neural cell types and provide long-term increases in dopamine-producing neurons, such cells can be used to partially restore motor function in people who have Parkinson’s disease.
6. Brain-machine interfaces – This therapy combines neural recordings, computer representations of movement and robotics to allow monkeys and humans to manipulate their environments without the use of their arms. This research, which is dependent on NHPs, holds great promise for people who are paralyzed or who have suffered brain damage from stroke. Researchers have developed a brain-machine interface that enables monkeys to control robot arms with brain activity coded through a computer.
7. Huntington’s disease – Although the genetic defect responsible for this neurodegenerative disease is well known, the specific mechanisms by which the mutation induces the condition are not as well understood. NPRC researchers have developed a transgenic NHP model of Huntington’s disease by introducing a portion of the mutant human gene responsible for Huntington’s into fertilized macaque eggs. The result is transgenic animals that reproduce many of the key features of Huntington’s disease.
8. Stem cell research – This pioneering discovery, which NPRC scientists advanced from rodents to NHPs and then into humans in the 1990s, is already in early human clinical trials for macular degeneration, spinal cord injury, heart disease, ALS and more. There are approx. 30 clinical trials around the world involving embryonic stem cells and their derivatives. At least 40 trials involve the use of induced pluripotent stem cells. Pluripotent stem cell research has ushered in a new era of science and medicine that is dramatically expanding our options for pursuing cures and treatments.
9. Transplantation – NPRC researchers have developed a novel approach to suppressing immune responses to kidney transplants. The technique involves creating a fusion protein of a molecule that is involved in the stimulation of T cells, which sometimes reject transplanted tissue. This research paved the way for successful human clinical trials and FDA approval of belatacept, the first new transplant drug since 1999.
10. Mitochondrial disease – No treatment or preventive measures exist for this group of devastating human disorders, which present shortly after birth and can affect multiple organ systems to cause diabetes, deafness, blindness, dementia or epilepsy. Mitochondrial replacement therapy, or correcting dysfunctional mitochondria in the egg of a woman who previously delivered a child with mitochondrial disease, offers her the chance to have a typically developing child. NPRC researchers were the first to establish this process in NHPs by demonstrating the feasibility of replacing mitochondrial DNA in an egg with donor mitochondria from another egg, followed by in vitro fertilization and the development of typically developing offspring.

Updated February 2022

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Photo credit: Wisconsin National Primate Research Center