Monkeys and
animal research
EU legislation has some of the strictest requirements for the care and use of laboratory animals in the world and it has special and justified emphasis on the care and use of monkeys, also sometimes known as non-human primates (NHPs).Monkeys are the closest species to humans in terms of biological make-up, with a higher degree of sentience than many other species. For this reason, they are rarely used in medical research. However, animals such as mice and rats are not the most suitable models for humans in a number of important areas.
Why are monkeys needed in biomedical research?
The areas of research where monkeys are essential include the function of the brain and its disease, such Alzheimer's or Parkinson's, reproduction and susceptibility to certain infections where human biology is radically different from that of rodents. Research with monkeys also includes advances in transplantation techniques, the role of the Rhesus-factor in blood transfusions, development of in-vitro fertilisation techniques, and advances in stem cell development.
In 2017, the Scientific Committee on Health and Environment Risks (SCHEER), on the request of the EU Commission, published its final report on the need for monkeys in biomedical research, production and testing of products and devices. It recognised that limited use of non-human primates is imperative in particular biomedical research fields, such as immunology and neurodegenerative disease. It also recognised that replacement should be the ultimate goal, but that it is simply not possible at present.
What areas of biomedical research use monkeys?
Regulatory testing
The majority of procedures conducted on monkeys are to understand the toxicity of a new drug before it can be tested in humans/patients. Rats and dogs are the default species for this type of testing, but monkeys must be used if the drug is so specific to humans, that it does not have a pharmacological effect in a rat or a dog. This is the case for many biotechnology-derived drugs such as therapeutic antibodies, oligonucleotides (short DNA or RNA molecules) or gene therapies. Monkeys are also used in the earlier phases of drug discovery, e.g. when a specific receptor - like the one in humans - for a new potential drug, is only present in monkeys.
Vaccine testing
As seen throughout the Covid-19 pandemic, vaccine development often involves monkeys in the final stages of pre-clinical testing, to ensure safety and efficacy of any vaccines before human clinical trials.
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All leading Covid-19 vaccine candidates (Moderna, Oxford/AstraZeneca, Pfizer/BioNTech, J&J) used rhesus macaques during preclinical testing.
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Baboons were shown in a study to be a good model for studying the effects of Covid-19 and comorbidities such as diabetes.
Some other examples from 2020
Research using monkeys plays a vital role in Covid-19 battle
Study uses three types of monkey to understand Covid-19 infection
Basic research
A small number of monkeys are used for basic research and translational/applied research (usually for human infectious disorders and human, nervous and mental disorders). Monkeys are used in a small number of essential studies where only they share a particular biochemical or metabolic pathway with humans, or where they model a human disease particularly well, e.g. atherosclerosis, osteoporosis and hypertension occur naturally in primates, which make them ideal animal models for those diseases.
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Monkeys have played a significant role in research into very serious conditions such as AIDS/HIV. The introduction of the antiretroviral therapy (ART), developed using NHP models, has dramatically reduced the morbidity and mortality of those infected with HIV.
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Research using monkeys has been critical in developing life-changing treatments for Parkinson’s disease. Dopaminergic therapies, deep brain stimulation to reduce tremor, and constraint-induced movement therapy all resulted from research on monkeys.
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Breast cancer drug Herceptin is now not routinely recommended for nursing mothers after primate studies showed that the drug was secreted in breast milk.
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The first theory of the cause of depression was created thanks to research in monkeys, which subsequently lead to the development of antidepressants.
Some other examples from 2020
Potential treatment for Parkinson’s in monkeys
Restoring vision in monkeys
Why is it difficult to replace monkeys in biomedical research today?
Legislation does not allow experimentation on animals if there is a viable non-animal model. Similarly, monkeys cannot be used if there is a viable alternative animal model - monkeys are only used when no other species are suitable. Here are some examples:
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Retinal degenerative diseases
This disease is caused by photoreceptor cell death and is one of the major causes of irreversible vision loss. As only primates (including humans) have a macula, the function centre of the retina, they have a crucial role not only to understand vision loss, but also to restore it. The translation of this from basic research into clinical trials has been successful.
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Neonatal care
Research in baboons, for example, has led to important findings in the lung development of infants and the refinement of the use of lung-ventilation in prematurely born infants. Recently, monkeys have been used to study infections during pregnancy, which seem to be an important factor in the cause of pre-term birth.
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Addiction
The use of monkeys in addiction research has been fundamental for confirming the reinforcing effects of drugs and abuse thanks to primates having similar neurophysiology to humans.
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Toxicokinetics
Monkeys are also used to study toxicokinetics - how quickly a chemical compound will enter the body and what happens to it once it is in the body.
Are monkeys being replaced or their numbers reduced in research studies?
Transgenic mice have been used to replace monkeys in oral polio vaccine safety tests. The polio vaccine utilises live attenuated virus particles and it is essential that each batch of vaccine is tested to ensure that it is safe and does not revert to its infectious virus form on use. Monkeys possess virus receptors similar to those found in humans and were previously used for this. However, mice have now been genetically modified to express human polio receptors.
In some areas of research into brain function, the use of transcranial magnetic stimulation (TMS) with human volunteers has replaced the use of monkeys. TMS can be used to ‘turn off’ activity in specific areas of the brain, temporarily and safely. This can shed light on the function of that region of the brain.
What are the examples of refinement/improvement of the use of monkeys?
Monkeys can be trained to co-operate with being handled and with procedures such as taking blood samples, so that these activities become less stressful for them. They can also be given a varied environment, including being housed in groups and daily foraging opportunities, so that they can express their full range of behaviours.
What is the reason the use of monkeys is increasing in Europe?
The numbers of monkeys used in research are increasing mostly because there are more biotechnology-derived drugs being developed, i.e. drugs that need to be tested in monkeys. For instance, out of 29 drugs that were approved by the US FDA in 2019, five drugs (17%) were biotechnology-derived products and all of those used monkeys to evaluate toxicity. The same trend occurs in Europe. Other factors include, an increase in the number of studies related to neurodegenerative pathologies, oncology, immune-inflammatory pathologies.
There is also an increase in the number of projects using monkeys (despite a likely decrease in the number of animals per project).
Are monkeys bred for research and then not used being rehomed?
The majority of monkeys used in research are humanely killed as an integral part of the experimental procedures. In situations where this is not necessary for the research, or in the case of former breeding animals, or surplus stock, it may be possible to rehome the animals to legitimate sanctuaries as an alternative.
Eu Directive 2010/63/ allows for this, provided certain conditions are met - monkeys should only be rehomed if it is clear that the process will be truly in the best interests of the individual animals and that the new home offers a good quality of life.
Where are the monkeys used for research bred?
It is required that all monkeys used in research are bred for the purpose of research, except in exceptional circumstances, such as disease epidemics. In the EU, no wild-caught monkeys can be used in research, they must be the offspring of animals bred in captivity.
The majority of research primates are imported from facilities in Asia and Africa (e.g. Vietnam and Mauritius) where they are bred in captivity. The use of great apes (chimpanzees, gorillas, orangutans and bonobos), is only permitted for the purposes of research aimed at the preservation of those species and where action in relation to a life-threatening, debilitating condition endangering human beings is warranted.
Why can't there be an immediate ban on the use of monkeys?
In terms of toxicity testing for drugs under development, monkeys are still required, since toxicity cannot be evaluated in alternative animal species. In vitro methods, including micro physiological systems such as organs-on-a-chip cannot yet fully replace those experiments, since they cannot replicate the complexity of an intact organism. If studies in monkeys were banned in the EU, those studies would simply be conducted outside of the EU, since they are required by regulatory authorities around the world to safeguard patients who participate in clinical trials.
New animal models, such as humanised transgenic rodents or pigs, may have the potential to replace the use of monkeys in the future, but they have not been established so far.
For fundamental research, where monkeys are the only species showing physiology/pathology similar to humans (such as many areas of neuroscience) scientific progress come to a halt in Europe.
The SCHEER opinion on the need for monkeys in biomedical research, production and testing of products and devices states that the development of a timetable for phasing-out the use of monkeys is currently impractical, as there are often no other available species that can help answer key questions specific to human health, and non-animal models remain far from replacing monkeys in research.
Banner and image courtesy of: Sanofi.