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The critical role of nonhuman primates in medical research

Nancy Haigwood, Ph.D.
Nancy Haigwood, Ph.D., is director of the Oregon National Primate Research Center and a professor of pathobiology and Immunology in the OHSU School of Medicine.(OHSU/John Valls)

Research with nonhuman primates, or NHPs – monkeys for the most part – has led to critical health advances that have saved or improved millions of human lives. While NHPs account for just one-half of one percent of animals in current medical research, it is no exaggeration to say they are essential to our ability to find cures for cancer, AIDS, Alzheimer’s, Parkinson’s, obesity/diabetes and dozens of other diseases that cause human suffering and death.

Research with monkeys is critical to increasing our knowledge of how the human brain works and its role in cognitive, motor and mental illnesses such as Alzheimer’s, Parkinson’s and depression. This research is also fundamental to understanding how to prevent and treat emerging infectious diseases like Zika and Ebola. NHP research is uncovering critical information about the most common and costly metabolic disorder in the U.S. – type 2 diabetes – as well as the obesity that leads to most cases.

Without NHP research, we lose our ability to learn better ways to prevent negative pregnancy outcomes, including miscarriage, stillbirth and premature birth. This research is also helping scientists to uncover information that makes human organ transplants easier and more accessible, literally giving new life to those whose kidneys, hearts and lungs are failing.

"Research scientists are like detectives solving mysteries. We want to know why. More importantly, we want to save lives" – Nancy Haigwood, Ph.D., director of the Oregon National Primate Research Center and a professor of pathobiology and Immunology in the OHSU School of Medicine.

 

Monkeys are critical to all stages of research

News headlines tout medical breakthroughs. Breakthrough sounds dramatic, and to someone hearing about how the virus that causes polio is being used to put an aggressive form of brain cancer into remission, it is indeed. But as the scientists involved in that cancer research — and research into every other area of medicine — will tell you, breakthroughs might be dramatic, but they are never sudden.

A well-thought-out and structured process is behind virtually every medical breakthrough and the discovery process probably took decades or more. Every step in the process was essential to the next, from basic research to human clinical trials.

Monkeys are often involved at the later stage of the process — what is called translational or applied research. Here all of the knowledge accumulated earlier is applied to specific medical questions such as: Will this vaccine protect a pregnant woman (and her baby) from Zika infection? And is the vaccine likely to be safe? But monkeys also play a vital role in basic science research that can come decades earlier. Basic NHP research in the 1970s helped scientists understand the inner workings of the basal ganglia, the part of the brain that coordinates movement. Those early findings led to the “breakthrough” 30 years later in which deep brain stimulation is used to reduce involuntary movements of Parkinson’s disease.

Regardless of where it occurs in the scientific discovery process, research with monkeys is highly regulated. Scientists use monkeys only when no other research model can provide the required information. While rodents are used extensively and are extremely helpful in answering many basic research questions, their usefulness is limited by differences from primates in their lack of sophisticated brain structures, less developed immune systems and motor skills, and differences in how their metabolism functions, among other traits.

To cite an example, rodent brains are very different from human brains. The rodent lacks the prefrontal cortex specialization that is found in monkeys and humans. This difference limits the applicability of rodent studies in relation to studies of injury in the human brain. Current studies in monkeys are helping to find ways to help wounded soldiers and stroke victims regain their independence after losing limbs or the ability to control them. NHPs are also the only animals that allow quick response and research into emerging viruses, like Zika. What scientists learn about Zika itself, as well as what they learn about the best use of monkeys in Zika studies, they will apply to studies of future emergent diseases. And with recent history as a guide (Zika, Ebola, MERS, SARS, pandemic flu, etc.), we should expect more infectious disease outbreaks in the near future.

Nancy Haigwood, Ph.D., is director and professor at the Oregon National Primate Research Center in the department of pathobiology and immunology, and an adjunct professor in the department of Molecular Microbiology and Immunology at OHSU. Haigwood and colleagues contributed to this vewpoint, which was excerpted from a National Association for Biomedical Research white paper titled, "The Critical Role of Nonhuman Primates in Research."

Partial list of scientific advances linked to research in nonhuman primates

1900-1950s

  • Components of blood and plasma discovered.
  • Ability to diagnose and treat typhoid fever.
  • Modern anesthesia.
  • Mumps virus discovered.
  • Treatment of rheumatoid arthritis.
  • Discovery of the Rh factor, blood-typing knowledge critical for safe blood transfusions.
  • Development of polio vaccine.
  • Development of antipsychotic medication chlorpromazine and its tranquilizing derivatives.
  • Cancer chemotherapy.
  • Development of yellow fever vaccine.

1960s

  • Mapping of the heart's connections to arteries.
  • Development of German measles vaccine.
  • Therapeutic use of cortisone for reducing inflammation and allergy symptoms.
  • Corneal transplants.
  • Development of treatment and prevention of radiation sickness.
  • Development of measles, mumps, and rubella (MMR) vaccine.
  • Discovery of the biochemical cause of depression.
  • Transmissibility of human prion diseases, such as Creutzfeldt-Jacob disease, discovered.

1970s

  • Treatment of leprosy.
  • Procedures to restore blood supply in the brain.
  • Interaction between tumor viruses and genetic material.
  • Understanding of slow viruses, which linger in the nervous system.
  • Understanding of the inner workings of the basal ganglia, the part of the brain that coordinates movement.
  • Discovery of mechanisms of opiate withdrawal and the anti-withdrawal effects of clonidine.
  • Development of cyclosporine and other anti-rejection drugs helpful for organ transplants.

1980s

  • Processing of visual information by the brain.
  • Identification of physiological and psychological co-factors in depression, anxiety and phobias.
  • Treatment of malnutrition caused by food aversion following chemotherapy.
  • Treatment of congenital cataracts and “lazy eye” in children.
  • First animal model for research on Parkinson’s disease, enabling doctors to more accurately research human Parkinson’s disease.
  • Heart and lung transplant to treat cardiopulmonary hypertension.
  • First hepatitis B vaccine.
  • Development of rhesus monkey model for HIV/AIDS.
  • Addition of taurine to infant formulas. Taurine is necessary for normal eye development.
  • First treatment of naturally diabetic NHPs with a hormone-like insulin stimulus that is now in wide use both for diabetes and obesity treatment (GLP-1 agonist).

1990s

  • Estrogen discovered to control an enzyme key to making serotonin, the brain chemical that regulates mood. Represents first step to providing effective medications for depression at the end of the menstrual cycle, and postpartum and postmenopausal depression.
  • Demonstration of the effectiveness of early administration of AZT to prevent or treat HIV infection. Thanks to this, HIV-infected mothers can give birth to HIV-free babies.
  • Demonstration in monkeys of the high efficacy of the HIV drug tenofovir to prevent or treat infection.
  • Lead toxicity studies help U.S. fight childhood lead exposure.
  • Ongoing development of a one-dose transplant drug to prevent organ rejection.
  • First controlled study to reveal that even moderate levels of alcohol are dangerous in pregnancy.
  • Breakthroughs in understanding the mechanisms of puberty and disorders of puberty.
  • Primate embryonic stem cells studied extensively for the first time, advancing efforts to better understand reproduction and genetic disorders.
  • Control of intimal hyperplasia, a complication of coronary bypass surgery.
  • Parent to child lung transplants for cystic fibrosis.
  • NHPs shown to naturally develop diabetes, which is the same disease as in humans, thus opening the path to research for new treatments.
  • Naturally regenerative mechanism discovered in the mature NHP brain, spurring new research toward curing Alzheimer’s and other degenerative brain disorders.
  • Development of anthrax vaccine.
  • Development of life-saving medications for lupus.

2000s

  • Gene that boosts dopamine production and strengthens brain cells used to successfully treat monkeys showing symptoms of Parkinson’s disease.
  • Monkey model developed to study the effects of malaria in pregnant women and their offspring.
  • NHPs are prime model for development of HIV treatments and potential vaccines.
  • Insulin-treated diabetic patients live longer, fuller lives.
  • The most common and debilitating complications of diabetes can now be studied in NHPs.
  • High blood pressure is treated to prevent heart attack, stroke, and kidney failure.
  • Patients can receive hip replacements and are no longer reliant on wheelchairs.
  • People with degenerative eye diseases are able to see more clearly.
  • Better medications improve lives of people with severe depression, bipolar disorder, and other psychiatric illnesses.
  • Better pre- and postnatal care protects children.
  • Earlier diagnoses and better treatments help those with polycystic ovary syndrome, endometriosis, and breast cancer.
  • Improved treatments help more men survive prostate cancer.
  • Secondhand smoke shown to affect prenatal, neonatal and child lung development, cognitive function and brain development.
  • Exposure to wildfire smoke adversely affects development of the immune system.
  • Better understanding of the effects of BPA, a chemical found in plastic, on prenatal development improves health of children and adults.

     

Adapted with permission from: Primate Info Net, National Primate Research Center, University of Wisconsin – Madison: http://pin.primate.wisc.edu/research/discoveries.html

 

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