medical research monkeys

On this page

• Which monkeys are used in scientific research?

Why are monkeys used in research?

• Why do some monkeys have cranial implants?

Where do research monkeys come from?

How are the monkeys looked after?

The future of research in monkeys, what the experts think.

• What types of research are monkeys used in?

Areas of research that have relied on monkeys

Which monkeys are used in scientific research .

The most commonly used monkeys in medical research are: Rhesus macaques  (Macaca mulatta);  Cynomolgus macaques  (Macaca fascicularis); and  Common Marmosets  (Callithrix jacchus).

The order of primates can be broken down into three groups: apes; Old-World monkeys; and New-World monkeys. Macaques belong to the Old-World monkeys and are native to South and Southeast Asia. Marmosets are New-World monkeys, native to South America. Although the great apes (Orangutans, Chimpanzees, Bonobos, Gorillas) are our closest relatives, using a great ape in any regulated procedure is banned under UK legislation.

The next-closest ape species to humans are the Old-World monkeys. Humans share around 94% of their genetic code with macaques, and 91.7% with marmosets. This is compared to 85% genetic similarity between humans and rodents , making primates both physically and genetically the most useful comparison to humans in the animal kingdom.   

Each year, around 2,000 – 3,000 primates are involved in experiments in Great Britain. This makes up 0.1% of the animals used in research .  

Because Old-World monkeys are anatomically, physiologically, and genetically so similar to humans, they can be useful models for human disease.  Macaques and marmosets have similar brains, muscle structure and reproductive and immune systems to humans. This means research with monkeys can provide results which are more relevant to humans compared to information obtained from mice or rats. 

Roger Lemon, retired Professor of Neurophysiology at the Institute of Neurology, UCL, goes even further and says:

“I am absolutely certain that our knowledge of the human motor system would be very poor indeed without the wealth of neuroanatomical and neurophysiological studies carried out in monkeys.” 

Monkeys are complex animals with complex needs, for example needing larger enclosures, additional enrichment, and social housing.  Monkeys are very intelligent and sensitive animals, which is why they are protected by stricter regulations than other species and can only be used when it is absolutely necessary.

Why do some research monkeys have cranial implants?

Cranial implants or head posts are implanted into the monkey's skull whilst the animal is under anaesthetic. Implants must be monitored daily to ensure that wound healing is not impaired and no infection has arisen. Surgical aftercare such as pain relief is always given when needed.

Where do research monkeys come from?  

In Great Britain, it is prohibited to conduct experiments on wild-caught monkeys due to the impact that capture and subsequent experiments have on their wellbeing, as well as the increased risk of disease transmission. 

As a result of this, all monkeys involved in experimental procedures in Great Britain are either F1 generation (captive offspring of wild-caught individuals) or F2+ (offspring of captive individuals). Where possible, F2+ generation individuals are used instead of F1 individuals. You can see the numbers of F1 and F2+ individuals used in animal research in Great Britain in 2022 in the Statistics of scientific procedures on living animals, Great Britain: 2022 (Section 3.1.3).  

A key source of cynomolgus macaques for research is breeding centres in Asia and Africa, including colonies in Mauritius, where macaques are non-native and are considered an invasive species and agricultural pest. Macaques that would otherwise be culled to control the population are bred to produce offspring that can be used in research.

In Great Britain, there are several establishments which are licensed to breed macaques solely for research purposes, for example, the Medical Research Council’s Centre for Macaques (CfM). 

Animal welfare is a legal and ethical responsibility for everyone who works with research animals. In the UK, lab animals are cared for by animal technicians who have undergone extensive training on the care and welfare of animals in a laboratory setting.

Within the lab, senior animal technicians and Named Animal Care and Welfare Officers (NACWOs) are responsible for each animal’s health and wellbeing and are not involved in the research. Animal technicians spend every day with the animals observing them, ensuring they are experiencing as little suffering as possible, and enriching their lives with activities that mimic the natural behaviours that would be displayed in the wild, for example foraging.

All research establishments in the UK must have a veterinarian on call 24 hours a day in case of emergencies.

Housing 

Primates are highly intelligent and social animals, and require large enclosures that allow individuals to walk, climb, swing and leap. Housing is designed to suit the unique biology of each species. For example, wild marmosets spend most of their time in trees and so their housing is made with this in mind: complex vertical structures like bridges, swings and perches above human head height are key to ensuring that marmosets can express their natural behaviours. To learn more about marmoset housing, click here . 

Macaques, however, use floor space more, so ground-based structures are important as well as vertical spaces. To learn more about macaque housing, click here . 

Both macaques and marmosets are highly social, living in multi-male, multi-female groups in the wild . To allow for natural social interactions, macaques are housed in pairs or social groups, and marmosets are housed in family groups. Animals may be isolated under rare circumstances, for example, if they are recovering from an illness or surgery and need to be quarantined or if being in a social group poses a danger to them.

Enrichment 

Enrichment can also be structural (e.g. swings, climbing apparatus and water tanks), food-related (e.g. food puzzles and foraging) or other sensory stimuli (e.g. smells and sounds).  

A prime example of enrichment for monkeys is spreading food, such as grains or dried fruit, around the home cage. (see video ). This encourages the monkeys’ natural foraging behaviour and keeps them occupied for long periods of time.  

Learn more about the enrichment used for marmosets on the University of Stirling’s marmoset care website.  

Learn more about the enrichment used for macaques on the NC3Rs macaque website or head to the macaque holding room 1 of the  University of Oxford lab tour to find out more about enrichment. Visit the food preparation room to find out more about how food is prepared for macaques. 

Training 

In order to minimise the stress caused by captivity and research procedures, monkeys need to have a good relationship with their keepers. One of the ways that this is achieved is through positive reinforcement training. Training helps to reduce stress by putting the ball in the animal’s court. By rewarding desired behaviours, the animal learns to associate those behaviours with rewards, and is therefore more motivated to complete those tasks. 

“We are finding that these monkeys can learn these tasks very quickly within their natural environment. It’s sort of like enrichment. It’s an interesting, fun game for them to play,” explains Professor Andrew Jackson, of Newcastle University. 

Training also removes the need for some procedures to be performed. For example, taking blood used to require the animal to be anaesthetised, but now animals are trained to present their arms or legs for injections (see video ). This is much less stressful for the individual animal and the animal carers. 

Prof Jackson describes how this is approached at Newcastle University: “We want to see how much of the training we can actually do within the animals’ natural environment, so within the home cage where the monkeys live. We have developed a system that we can attach to the front of the cage, and the animals are free to come into this system and perform a simple task.” 

Check out the training pages of the NC3Rs website for more information about training research animals. 

Head to the Main Corridor Exit of the  University of Oxford lab tour to hear more about how they train macaques for experiments. 

Learn more about training animals to move to desired locations at the MRC Centre for macaques . 

The use of monkeys in research remains controversial and has been the subject of vigorous campaigning by animal rights groups in the past. Many independent and expert enquiries such as the Weatherall Report have concluded that there is a strong case for using monkeys to advance scientific and medical knowledge and to assess the safety of new medicines. The use of monkeys, like other animals, should only be undertaken when there is no alternative, and should be subject to careful regulation. 

Most research monkeys are macaques or marmosets. They are used in relatively small numbers (they make up around 0.1% of research animals) but they have been important in many major medical advances, for example, the polio vaccine, life support systems for premature babies, and deep brain stimulation for Parkinson’s disease.

Currently, the main areas of primate study are infectious diseases to develop vaccines and treatments for HIV/AIDS and malaria. Monkeys are also used in neuroscience to better understand the brain and treat conditions ranging from Alzheimer’s disease to schizophrenia. They are important in research into reproduction, fertility and foetal development, and they are also used in the safety testing of new medicines and vaccines. 

In 2017, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) released an updated opinion on the use of primates in research. Here is what they said: 

“The use of non-human primates remains necessary for certain types of research, but when their use is required to be determined on a case to case basis and only if no viable alternatives are available it is essential to adopt the highest standards of non-human primates housing and husbandry and to follow best practice in the conduct and refinement of scientific procedures.”

The topic of using monkeys was the subject of the Weatherall Report in 2007. At the time the government’s Chief Scientific Advisor, Sir David King FRS, said: 

"Although rare, the use of primates in medical research and testing is invaluable, as an essential aspect of work which provides the best hope for breakthroughs in important areas such as neurodegenerative disorders and for aspects of immune and reproductive functions."  

MRC press release responding to the Weatherall Report, June 2007. 

"There is a strong scientific case for the carefully regulated use of non-human primates where there are no other means to address clearly defined questions of particular biological or medical importance."  

Weatherall Report: The use of non-human primates in research, December 2006: 

"Primates have been used in research aimed at understanding how complex brains work, as their neurological development and higher cognitive functions are very similar to humans … Animal [primate] disease models were also used for research on hepatitis C, and polio."  

Nuffield Council on Bioethics, The ethics of research using animals, May 2005:

"... for certain experiments there are no alternatives to the use of non-human primates. Such experiments may be needed, for example, during the development of drugs and vaccines for prevention and cure of disease such as AIDS, TSE1, malaria, and influenza".  

European Commission Scientific Steering Committee (SSC), The Need for Non-Human Primates in Biomedical Research, April 2002: 

"Many significant advances in modern medicine have been based on research involving primates."    

What types of research are monkeys used in?  

Monkeys have been used to study many different areas of human and animal disease. They have been essential in research into neurological disorders such as Parkinson’s disease, reproductive disorders, understanding how vision works, and the development of vaccines.  

Like humans, monkeys see in colour and have binocular vision , which is why they have been used to better understand how humans process visual information from the 3D environment. 

Rhesus macaque monkeys were vital in the race to develop an effective vaccine against SARS-COV-2, the virus that causes COVID-19. Monkeys were used to identify the most promising candidates for vaccines and ensure that they were safe enough for human volunteers to take in the large-scale clinical trials that took place. 

Marmoset monkeys are predominantly used for research into Parkinson’s disease. Since the accidental discovery of MPTP, a substance that destroys a part of the brain and causes the symptoms of Parkinson’s, MPTP is used to induce the symptoms of Parkinson’s in marmoset monkeys. This has helped scientists explore new treatments for Parkinson’s disease.

More examples of how monkeys are used in research are listed in our iBook:  Primates in Medical Research . 

Alzheimer's disease

Like Parkinson’s, Alzheimer’s is a neurodegenerative disorder, meaning that it involves the progressive loss of nerve cells in the brain over time. In the case of Alzheimer’s, this is thought to be caused by the build-up of material called amyloid plaques around the nerve cells, and tangles of fibres within the cells, reducing their function and connectivity.

There are several animal models of Alzheimer’s disease, mostly rodents but also monkeys. Monkeys are essential in this research as drugs developed using only rodent models show a much lower efficacy when translated to human trials.

Monkeys have a shorter lifespan than the typical human. Most monkey species live for 20-25 years, although some can reach 40 and others only live to 12. Because monkeys have a shorter lifespan than humans, researchers can more easily investigate the process of brain ageing and how diseases progress over time.

More about primates in Alzheimer’s research

22/09/2017: Dr Mark Dallas Reddit Ask Me Anything

06/07/2018: Alzheimer’s Researchers win 2018 Brain Prize

26/05/2021: Can you give a brain organoid Alzheimer’s?

08/11/2022: The animal research behind a new Alzheimer's drug

Between December 2019 and August 2023, the World Health Organisation estimates that Covid-19 killed a minimum of 6.9 million people.

The outbreak of Covid-19 resulted in the world’s first pandemic on a global scale and an unparalleled response from the scientific community. For the first-time, scientists across the world mobilised to tackle the same issue at the same time – preventing and treating Covid-19.

Animal research in various species was critical to the rapid development of a Covid-19 vaccine but none more so than monkeys, whose immune response so closely resembles our own. Rhesus macaque monkeys were irreplaceable during the search for a Covid-19 vaccine as they were one of the only animals that responded to SARS-Cov-2 in a comparable way to humans.

Each of the vaccines approved for use against Covid-19 in the UK was tested on monkeys before being given to human volunteers in clinical trials.

A 2022 study from Imperial College London looked at the global impact of vaccines in the first year of the Covid-19 pandemic. Using mathematical models and data on excess deaths from 185 countries and territories, they concluded that 19.8 million out of a potential 31.4 million Covid-19 deaths were prevented worldwide.

The pandemic may be over, but research into new treatments, more effective vaccines, and the long-term impacts of Covid-19 on the body continues. In addition to this, new ways of preparing for future pandemics are being created to reduce the suffering that diseases like Covid-19 cause.

See our Covid-19 page for more.

More about primates in Covid-19 research

Oxford Astrazeneca vaccine timeline

11/02/2023: Inhalable SHIELD protects lungs against COVID-19 .

01/04/2022: Long-term effects of COVID-19 shown in rhesus macaques

08/12/2021: COVID-19 research must go on

18/10/2020: Primate role in COVID-19 vaccine research

07/05/2020: Remdesivir trials effective against coronaviruses in animals and humans

18/03/2020: Warning signs of the coronavirus: why we knew about it and couldn't stop it

Heart disease

According to the World Health Organisation, heart disease is the leading cause of death in the world . In the UK, heart disease kills around 460 people each day.

Monkeys are ideal models of heart disease , not only because of their genetic and physiological similarities to humans, but also because key aspects of heart disease in humans, such as atherosclerosis, high cholesterol and diabetes, also occur naturally in monkeys. The fact that these occur naturally means that environmental risk factors for heart disease can also be studied, allowing us to look at the causes of heart disease.

Primate research has also played a role in the development and further evaluation of drugs which aim to reduce the risk of heart disease, for example statins.

More about primates in heart disease research

03/07/2023: Researchers measure chimpanzee heart rates through facial movements

23/02/2021: Preclinical Study Shows Safety, Efficacy, and Durability of Lowering LDL-Cholesterol Levels Long-Term in Non-Human Primates

06/07/2018: Heart disease research in primates 2018

02/07/2018: Stem cells restore function in primate heart-failure study

Human immunodeficiency virus ( HIV ) is a virus that attacks particular types of cells in the immune system, leading to much weaker defences against disease or infection. The development of disease in a person with HIV is called AIDS.

Although primates do not suffer from HIV, they show AIDS-like symptoms caused by a closely related virus called simian immunodeficiency virus (SIV). Studies in macaques have led to advancements in our knowledge of how the body’s immune system responds to HIV/SIV, and how to combat the disease through anti-viral treatments and vaccines.

While a cure for HIV has not been identified, combinations of drugs have been identified from studies in primates that have been shown to restore the immune defences of HIV patients.

Visit our researching disease page for more information about HIV/AIDS .

More about primates in HIV research

UAR update: Primate briefing number one

25 years of primate research and HIV

01/03/2019: Human diseases are threatening chimpanzees

06/07/2018: HIV advances made in 2018

09/03/2018: New hope for HIV vaccine found in monkey trials

24/03/2016: Giving antibodies to infant macaques exposed to HIV-like virus could clear the infection

26/02/2010: HIV vaccine ready for trials

MERS , or Middle East respiratory syndrome, comes from MERS-CoV, a coronavirus that occurs in dromedary camels. This zoonotic disease has made the jump to humans several times.

Compared to Covid-19, MERS has a higher mortality rate, but it is much harder to transmit between humans. There is currently no vaccine available for MERS.

Current research aims to develop vaccines to help protect people from this disease. Many of the pre-clinical trials for MERS vaccines involve macaques or marmosets which respond to the disease in a similar way to humans.

More about primates in MERS research

30/07/2015: New vaccine to fight MERS in macaques

Motor and sensory research

One aspect that sets monkeys apart from other animal models is the way in which their bodies move, and the way in which the brain communicates to the muscles in the arms and hands. This is an important characteristic when studying afflictions like paralysis and their treatment.

Transcript of an Interview with Professor Andrew Jackson about macaques in movement research.

Like humans, Monkeys have binocular vision (i.e. two eyes facing forwards) as well as many parts of the eye that are also present in humans. This makes them extremely useful in vision research. One area of importance is where vision is completely lost due to the death of cells that process incoming light. The affected part of the eye, called the macula, which is only present in humans and other primates, means that monkeys are the only suitable model for these diseases.

Additionally, the genes that cause these diseases are also present in monkeys, meaning that we can investigate the genetic and environmental factors that contribute to these diseases, as well as targeted treatments to restore eyesight.

Neuroscience

One of the areas where primates are of unique importance to medical research is in studying the brain. While certain aspects of other organs can be replaced by non-animal technology, there is currently no way of studying brain function without the use of animals.

As Chris Petkov, Professor in Comparative Neuropsychology at Newcastle University puts it:

“Many of these technological improvements allow us to glimpse at the human brain. But it is only that: a glimpse. Although one might think that animal research might become obsolete thanks to these machines, the understanding of the human brain and the neurosurgeries performed today relied on and still rely on information gathered by primate neuroscience.”

Primates are key to this research due to the similarity of human and primate brains. Our brains are similar in size (relative to body mass) have the same physiological regions and show similar levels of connectivity compared to other animals. As a result, primates have helped to advance our knowledge of numerous conditions, including Parkinson’s disease, Alzheimer’s and stroke. Some major conditions are explained further below.

More about Primates in Neuroscience

06/07/2022: Why are animal studies important in neuroscience research?

04/06/2021: Why do we need to use animals in neuroscience research?

UAR article: “ The importance of non-human primates in neuroscience ”

25/07/2011: Primate research overview

Check out some neuroscience labs in “Animal holding room 2”, ‘Behavioural testing room”, “Behavioural testing control room” and “MRI room” at the University of Oxford lab tour .

Parkinson's disease

Parkinson’s disease is characterised by the loss of dopamine-producing nerve cells in a part of the brain named the substantia nigra . Parkinson’s sufferers experience involuntary shaking, slow and uncontrolled movement, and stiffness, which becomes progressively worse over time. As such, Parkinson’s is categorised as a neurodegenerative condition.

There are several ways in which monkeys are used to study Parkinson’s disease, from naturally occurring ageing monkey models, to genetic modification. Perhaps the most unique and famous technique involves the use of the chemical MPTP, which creates parkinsonian-like symptoms.

Primate models have been instrumental in understanding the brain areas involved with the disease, and the surgical and non-surgical treatments for Parkinson’s. For example, monkeys were used to better understand the process of deep brain stimulation, where an electrical current is used to stimulate specific parts of the brain continuously ( click here to see this in action ). Ultimately, work in primates led to more precise stimulation, and a more effective treatment of symptoms.

More about primates in Parkinson’s research

Check out our video explaining Marmosets in Parkinson’s research

Reproduction

Several primate species have similar reproductive biology to humans, including menstruation and menopause. As a result, primate research has been essential for the study of pregnancy loss, infertility, ovarian and uterine disorders.

For example, researchers have found that conditions like endometriosis occur naturally in rhesus macaques. Research in these animals has led to advances in treatments of the disease, including monthly antibody injections that reduce inflammation and endometrial tissue formation.

Macaques are also an important model of human menopause as they undergo the same hormone changes as humans and respond similarly to hormone replacement therapy.

Visit our disease pages for more information about Endometriosis and premature babies .

More about primates in reproductive research

29/08/2023: Contributions of animal research (including baboons) to womb transplants .

31/05/2023: Creation of mock embryos in cynomolgous monkeys .

22/03/2019: Advances in fertility restoration in children with cancer.

05/02/15: 3 person IVF and the monkeys that made it possible.

28/08/09: Monkeys with two mums may eradicate mitochondrial disorders

Animals such as mice, rats, and monkeys have been used to study auditory processing.

Monkey models for auditory processing are exceptional because of the anatomical similarities in brain structure between monkeys and humans. Studies in macaques, squirrel monkeys and marmosets have been key to our understanding of how loud noises affect hearing.

Xenotransplantation

Animals have been used extensively to study and perfect the transplantation of organs from one species to another, known as xenotransplantation. In a bid to address the increasing shortage of human organs, scientists have been perfecting xenotransplantation through work in different animal species, including monkeys.

The Guardian: Baboon survives for six months after receiving pig heart transplant

20/01/22: Pig to human heart transplants: how did we get here?

More on transplantation .

Zika virus was brought to public attention by the outbreak in 2015-16 in South and Central America, although the disease was identified for the first time in 1947 in a rhesus macaque in Uganda. As the disease naturally occurs in macaques and other primates, they represent a key source of information regarding Zika’s basic biology and the immune response to the virus.

Research in primates has advanced our knowledge of the effects of the virus on the body’s tissues, which are now known to persist for months after infection. In addition to this, primate research has played a major role in our understanding of the damage that the virus inflicts on developing babies in the womb.

Read more about the disease on animalresearch.info

More about primates in Zika research

06/07/2018: Zika research advances made in 2018

21/03/2018: Zika: Monkeys, Mice and Mosquitoes

Watch our videos 

Parkinson's disease patient demonstrates his brain implant     Marmosets in medical research     Macaques in medical research  

Related Links 

Weatherall Report The use of non-human primates in research       EC SSC Report: The Need for Non-Human Primates in Research    Nuffield Council on Bioethics report: The ethics of research using animals    NC3Rs guidance: Non-human primates      European Scientific Committee on Health and Environmental Risks (SCHER) opinion on primate research (January 2009)  

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Ethics of Medical Research with Animals

Using Monkeys to Understand and Cure Parkinson Disease

Research with nonhuman primates is essential to medical progress and will still be necessary for the foreseeable future. Almost all research scientists agree that animal research is critical to understanding basic biology, discovering new treatments for human (and animal) diseases, and maximizing the safety of new medicines while minimizing their harm to humans. All but two of the Nobel prizes in medicine awarded over the last one hundred years have depended on animal research, [1]  and the list of modern medicines, vaccines, and other treatments, as well as basic science discoveries, is so extensive that it could not be adequately covered in even a huge volume. [2]  Increases in average life span in the last century are the result of improved public health measures, and many diseases may be related to lifestyle choices. But animal research has contributed to understanding these factors and to the development of vaccines and lifesaving treatments. The philosophical debate regarding the benefits and moral costs of animal research has also filled many volumes by ethicists and philosophers. The major arguments against the use of animals in medical research have been explicitly refuted by a few brave scientists, [3]  as well as implicitly by the vast majority of the working biomedical science community.

My contribution to this discussion is to provide a personal perspective on my decision if, when, and how to use monkeys in research experiments on Parkinson disease. I do not claim to speak for all scientists. Many of them prefer not to speak on this issue because people with strongly held opposing beliefs have been willing to engage in distortion of the facts, violence, and intimidation as a way of advancing their views. Universal and unequivocal support for animal research is reflected in collective statements by all of the major medical and scientific organizations, which state, in summary, that the benefits to humans are worth the cost of some animals, as long as humane animal welfare guidelines are met.

I have great empathy and respect for animals, but I also accept the fact that the careful selection and use of animals in experiments to  understand biology or to improve medicine is justified, even though this often represents a significant harm to them.

What are the criteria for conducting research on monkeys? There must be a potential scientific or medical benefit of the research, and useful knowledge from the monkey research should be likely and unobtainable from alternative approaches. Basic research to understand diseases is ultimately as important as research with specific treatment goals. Rodents and other mammals are excellent models of many physiological processes and diseases in humans, but the central nervous system and higher brain functions are sufficiently different that monkey experiments are often essential for progress with neuropsychiatric and brain-related problems. Parkinson disease represents a research problem for which monkey studies can be justified. It is a poorly understood and often fatal disease affecting millions of people worldwide for which there are only palliative treatments. We know that a small population of neurons in the brain that produce the neurotransmitter dopamine dies prematurely, leading to the signs and symptoms of the disease, which include resting tremor, slow movement, rigidity, postural instability, and other motor problems. L-Dopa, a drug that increases dopamine concentrations in critical brain areas, mitigates many of the motor problems, but unfortunately does not always control all the symptoms. The drug also has diminished effects over time and often causes unacceptable side effects, such as hallucinations or incapacitating, abnormal movements.

A number of models are useful to understand the disease and test potential therapies. They include cells in a culture dish, genetically modified fruit flies, and rats with dopamine systems destroyed by a neurotoxin to induce some signs of Parkinson disease. But each of these models has limitations and may not predict results in humans. The brain systems responsible for dopamine function that underlie Parkinson disease differ between rats and humans. The rat model responds consistently to some drugs that have effects against Parkinson disease in patients, but it also responds to other drugs that have no effect. [4]  A different compound, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was tested in rats and was not found to have any deleterious effects, although when tested in patients, it made them worse. It was later discovered that MPTP actually destroys dopamine neurons in humans and monkeys and reproduces nearly every reported effect of Parkinson disease in monkeys. [5]  Accidental exposures of humans to MPTP simulate Parkinson disease almost completely, confirming that monkeys exposed to MPTP are a reasonable model for studying the condition in humans.

Possibly better animal models are being developed as a result of new knowledge about several genes associated with Parkinson disease. At the present time, however, the monkey with MPTP-induced Parkinson disease is the best model we have and can predict benefits and side effects of new treatments. The species of monkey we use, Clorocebus sabaeus , is not endangered in the West Indies, and its closely related “parent” species, Chlorocebus aethiops , is widespread in Africa, with an estimated population in the millions.

Finally, there are considerable data supporting the main hypothesis of my work—that the dopamine neurons destroyed by Parkinson disease (or experimentally by a neurotoxin) could be replaced by neurons derived from fetal brain tissue, stem cells, or gene manipulations that would lead to therapeutic dopamine release and symptom relief. [6]  We don’t know, however, whether the cells would survive, develop, and connect properly in an adult brain affected by Parkinson disease. It is necessary, therefore, to test potential therapies in an animal model that simulates the conditions of the disease as closely as possible. [7]

When should the research be done? The first steps in research with animals should begin with the simplest animals that are appropriate. There are economic—and, some would say, moral—reasons that experiments should progress with models up the phylogenetic scale where possible. Extensive neural tissue transplantation studies were first done in rodents, showing that cells survived. Monkeys should not be used without knowing the results from studies in simpler biological systems, although, as in the case of MPTP, rodent studies do not always predict what would happen in monkeys or humans.

For cell replacement therapy, using dopamine precursor cells derived from fetal brain tissue, stem cells, or from other adult cell sources such as skin, it is important that the potential treatment be well characterized. We should know what types of cells they are and what they become in culture, what genes and proteins they express, how neurons are activated electrophysiologically, and what neurotransmitters and other chemicals they release. Then they should be tested in the best Parkinson disease model to see if they survive a new environment, what cells they become, where they go, and if they relieve the signs and symptoms of the disease.

The fact that monkeys are genetically closer to humans than are rats increases the probability that predictions from monkey experiments will be correct. But this closeness also makes their use of greater concern. At some point after enough research has been done in monkeys, humans also have to be studied to find out the potential benefits and harms of the treatment. The fact that this is so does not diminish the importance of what is learned from the animal experiments. Far more harm would be done to humans if the animal experiments were not done first. When, exactly, enough preliminary research has been done to move to human trials is often a controversial point, and scientists tend to argue for more animal and safety studies.

How should the research be conducted? When animal use is necessary, it should be carried out humanely and with concern for the comfort, general health, and well-being of the animals by scientists and staff who are qualified and trained to do the work successfully. These concerns have been codified in the Animal Welfare Act and the Guide for the Care and Use of Animals in the United States and in similar documents in other countries. Scientists, physicians, and veterinarians drafted these regulations not only for the well-being of the animals, but because they are necessary to ensure that research with the animals is valid. Animals are provided with veterinary care, cages that are large enough for them to move about, adequate food and water, an environment free of pain and with minimal stress, and conditions that are as natural as possible for their species. Proper anesthetics are used for procedures that might cause pain, along with analgesics thereafter. At the end of experiments, animals often must be killed to harvest tissues such as brain specimens that provide critical outcome measurements. These “sacrifices” are done humanely, using the same drugs that a veterinarian uses to put cats and dogs to sleep. If there are exceptions to any of these guidelines, such as research on pain, or the withholding of palliative treatments, these must be justified scientifically. The study plan and procedures must be reviewed and approved by an independent committee of experts for each institution that is constituted and operates according to rules that eliminate conflict of interest to ensure that the plan is properly carried out and the animals are cared for.

The best experimental designs should be used, with random assignment of treatment groups, controls for as many variables as possible, and blinding of evaluations to eliminate investigator bias. The fewest animals should be used that are necessary to accept or reject the study hypothesis according to the method that modern science uses to make progress. [8]   The reality is that most experiments conducted in accordance with the scientific method could be described as failures, but this does not mean that they are without value. They rule out important negatives that lead to incremental knowledge and then, often after many years, to a successful new treatment. When new discoveries are made, they have to be replicated. That is not a “waste of animals” or duplication of effort, but how modern science works. Independent replication is how we confirm what is true. I have summarized the conditions for the use of monkeys in the table.

Moral and ethical issues. The morality and necessity of medical research with animals are linked with the ethics of human research and medical practice. The ethical prescriptions and proscriptions as outlined in the Declaration of Helsinki in 1964 (and modified through 2008) [9]  require a number of practices, many of which have been codified into the laws of many countries and are regulated in the United States by the Food and Drug Administration. These guidelines prescribe that humans should not be exposed to unknown risks or to risks without potential benefits. This usually requires that substances and potential treatments be tested in animals for efficacy and safety. It is certainly true that animal research does not predict human responses perfectly. This depends upon how accurate the animal model is and how similar or identical the particular animal system used is to humans. So research on human subjects is also always necessary. It is often necessary to do new animal experiments after human clinical trials to improve understanding or resolve problems before arriving at the most successful therapy.

Could “alternatives” lead to the same or better results? Groups opposed to animal research often argue that computer models and other alternatives to animals could make animal experiments unnecessary. Alternatives to animal use are clearly desirable and researchers eagerly adopt them when they become available. But at this time we do not have good alternatives to replace the animal models in use.  A computer might be able to model a disease in some respects if we knew everything possible about it, and if the computer had all of the necessary capacities of an animal (the ability to move and to simulate the abnormal movement in Parkinson disease). But we do not have that knowledge, and to get it requires that we study animals.

Conditions for Using Monkeys for Biomedical Research

• The research should address a significant basic science or potential therapeutic question for humans or monkeys.
• Preliminary research should be done to support and justify the experimental approach proposed.
• Some research should have been done in nonprimate species to gather preliminary data and, if possible, to test the experimental design.
• There should be research findings to support differences between other potential animal models and monkeys or humans that would therefore support the study of monkeys and the inferiority of other animal models or alternatives to animals.
• The potential benefits of the research should be evaluated against the potential risks to the primate subjects.
• The species of monkeys used should be justified, and the use of endangered or threatened populations avoided without special justification.
• The number of monkeys used for the research should be justified and minimized.
• All animal welfare regulations should be followed, with special importance placed upon species-typical behaviors and environments unless exceptions are scientifically justified.

The drug industry and academic and government scientists are highly motivated for economic and ethical reasons to replace animal research if possible. Animals are expensive, experiments often take a long time, and the necessary sample of animals that must be studied is often not clear. Finally, the experiments often fail to predict the results in humans. New strategies are being adopted that are an improvement over animal experiments, such as gene arrays for toxicology studies (see “No Animals Harmed: Toward a Paradigm Shift in Toxicity Testing,” in this volume) or stem cells taken from humans with a disease to be studied in cell cultures (“disease in a dish”). None of these advances, however, resulted from targeted efforts to find “alternatives,” but from excellent basic science. Many of these alternatives depended upon animal experiments for their development or will depend on them for validation of results.

The suggestion by critics of animal research that scientists persist in animal experiments despite valid and viable alternatives is an ill-informed and intellectually and ethically insulting attack on the major scientific professional organizations, the National Institutes of Health, the Centers for Disease Control and Prevention, the U.S. Department of Agriculture, and most research universities and institutes. I do not know a single scientist who takes pleasure in inflicting pain or injury on animals. I, for one, have known and cared about all kinds of animals starting with my childhood experiences on my grandmother’s farm with cows, horses, sheep, pigs, chickens, and other domestic animals (that are often treated horribly with today’s industrialized farming conditions). I have been very attached to pet dogs and cats, and I had a monkey living in my house with my family for two years. I also have observed and interacted with numerous other animals in their native habitats and work for their conservation and protection. I have great empathy and respect for them, but I also accept the fact that the careful selection and use of animals in experiments to understand biology or to improve medicine is justified, even though this often represents a significant harm to them.

Moral status of animals. I do not accept the idea that all living creatures have equal moral status, but rather that they have graded value according to their genomic similarities with us. In this view, highly intelligent, sentient creatures such as great apes, monkeys, dolphins, whales, and elephants have relatively high moral status. We have responsibilities because of our intelligence and power to interact with all animals with kindness and compassion. We also have the responsibility to understand and cure disease in our own species and others if possible, while inflicting the least amount of harm to both humans and animals. Basic science and research for new treatments are both essential for this process. Research with monkeys aided in the development of deep brain stimulation,with benefits for some Parkinson disease patients so far, but we have more work to do for the cure. [10]  If the use of monkeys leads to the cure of Parkinson disease for the 500,000 people in the United States (and millions more around the world), some of whom suffer, suffocate, and die each year, it is an acceptable moral price to pay. These are your parents, grandparents, brothers, sisters, and possibly yourself. And Parkinson disease is just one of many horrible and incurable diseases that remain to be conquered with the aid of research with animals, including monkeys.

D. Eugene Redmond, Jr., is professor of psychiatry and neurosurgery at the Yale University School of Medicine. He has published extensively on his team’s effort to cure Parkinson disease using cell replacements, beginning with fetal brain cells and more recently using stem cells in monkeys. His research interests are in restoring the damaged brain and spinal cord, using cellular replacements, and gene therapy. He has worked extensively with nonhuman primates on studies of anxiety, drug addiction, schizophrenia, cognition, Parkinson disease, spinal cord injury, and amyotrophic lateral sclerosis.

• 1. Foundation for Biomedical Research, http://www.fbresearch.org/TwoColumnWireframe.aspx?pageid=128, accessed September 30, 2012. ↵
• 2. Ibid. ↵
• 3. J.H. Comrow and R. Dripps, Jr., “Scientific Basis for Support of Biomedical Science,” Science 192 (1976): 105-111; P.M. Conn and J.V. Parker, “The Animal Research War,”  Federation of American Societies for Experimental Biology Journal 22, no. 5 (2008): 1294-95; N.E. Miller, “The Value of Behavioral Research on Animals,” American Psychologist 40, no. 4 (1985): 423-40; N.E. Miller, “The Morality and Humaneness of Animal Research on Stress and Pain,” Annals of the New York Academy of Sciences 467, (1986): 402-4; D.L. Ringach, “The Use of Nonhuman Animals in Biomedical Research,” American Journal of the Medical Sciences 342, no. 4 (2011): 305-313. ↵
• 4. M.E. Emborg, “Nonhuman Primate Models of Parkinson’s Disease,” Institute for Laboratory Animal Research Journal 48, no. 4 (2007): 339-55; J.R. Taylor et al., “Behavioral Effects of MPTP Administration in the Vervet Monkey: A Primate Model of Parkinson’s Disease,” in Toxin-Induced Models of Neurological Disorders, A.J. Nonneman and M.L. Woodruff, eds. (New York: Plenum Press, 1994), 139-74. ↵
• 5. Emborg, “Nonhuman Primate Models of Parkinson’s Disease,” 339-55. ↵
• 6. A. Björklund and U. Stenevi, Neural Grafting in the Mammalian CNS (Amsterdam, the Netherlands: Elsevier Science Publishers, 1985); L.M. Björklund et al., “Embryonic Stem Cells Develop into Functional Dopaminergic Neurons after Transplantation in a Parkinson Rat Model,” Proceedings of the National Academy of Sciences U.S.A. 99, no. 4 (2002): 2344-49; D.L. Choi-Lundberg et al., “Dopaminergic Neurons Protected from Degeneration by GDNF Gene Therapy,” Science 275 (1997): 838-41; H. Lui et al., “Generation of Induced Pluripotent Stem Cells from Adult Rhesus Monkey Fibroblasts,” Cell Stem Cell 3, no. 6 (2008): 587-90; I. Mendez et al., “Dopamine Neurons Implanted into People with Parkinson’s Disease Survive without Pathology for 14 Years,” Nature Medicine 14, no. 5 (2008): 507-9; M.J. Perlow et al., “Brain Grafts Reduce Motor Abnormalities Produced by Destruction of Nigrostriatal Dopamine System,” Science 204 (1979): 643-53; D.E. Redmond, “Cellular Replacement Therapy for Parkinson’s Disease—Where Are We Today?” Neuroscientist 8, no. 5 (2002): 457-58; D.E. Redmond, Jr., et al., “Cryopreservation, Culture and Transplantation of Human Mesencephalic Tissue into Monkeys,” Science 242 (1988): 768-71; D.E Redmond, Jr., et al., “Behavioral Improvement in a Primate Parkinson’s Model Is Associated with Multiple Homeostatic Effects of Human Neural Stem Cells,” Proceedings of the National Academy of Sciences U.S.A. 104, no. 29 (2007): 12175-80;  E.Y. Snyder et al., “Multipotent Neural Precursors Can Differentiate toward Replacement of Neurons Undergoing Targeted Apoptotic Degeneration in Adult Mouse Neocortex,” Proceedings of the National Academy of Sciences U.S.A. 94, no. 21 (1997): 11663-68; M. Wernig et al., “Neurons Derived from Reprogrammed Fibroblasts Functionally Integrate into the Fetal Brain and Improve Symptoms of Rats with Parkinson’s Disease,” Proceedings of the National Academy of Sciences U.S.A. 105, no. 15 (2008): 5856-61. ↵
• 7. Redmond, Jr., et al., “Behavioral Improvement in a Primate Parkinson’s Model Is Associated with Multiple Homeostatic Effects of Human Neural Stem Cells.” ↵
• 8. Ringach, “The Use of Nonhuman Animals in Biomedical Research.” ↵
• 9. World Medical Association Declaration of Helsinki—Ethical Principals for Medical Research Involving Human Subjects, October 2008, http://www.wma.net/en/30publications/10policies/b3/. ↵
• 10. T. Wichmann et al., “Milestones in Research on the Pathophysiology of Parkinson’s Disease,” Movement Disorders Journal 26, no. 6 (2011): 1032-41; “Parkinson’s Patient Speaks Up,” http://www.youtube.com/watch?v=uMaCiuapAW0, uploaded April 29, 2010, and accessed September 30, 2012. ↵

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• NEWS EXPLAINER
• 16 November 2023
• Clarification 17 November 2023

How wild monkeys ‘laundered’ for science could undermine research

• Gemma Conroy

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In 2019, immunologist Jonah Sacha purchased a shipment of monkeys for his research into infectious diseases. But while conducting preliminary chest X-rays, Sacha found one monkey that stood out for all the wrong reasons: it had latent tuberculosis (TB), meaning it was carrying the bacterium that causes TB.

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doi: https://doi.org/10.1038/d41586-023-03533-1

Updates & Corrections

Clarification 17 November 2023 : The text has been modified to make clearer that Jonah Sacha had purchased research animals that were captive-bred.

Warne, R. K., Moloney, G. K. & Chaber, A-L. One Health 16 , 100520 (2023).

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Science behind cloning monkeys is helping advance medical research

The first rhesus monkey to be successfully cloned after many failed attempts has raised concerns among animal welfare groups

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Researchers in China have successfully cloned the first rhesus monkey, a species widely used in medical research because of its physiological similarity to humans.

The monkey, named Retro, is now more than three years old and is "doing well and growing strong", according to Falong Lu, one of the authors of the study published in the journal Nature Communications .

It marks the first successful cloning of the rhesus monkey, and was achieved "using a slightly different approach from the conventional technique" used to clone Dolly the sheep in 1996, as well as other mammals such as long-tailed macaques , the first primates to be cloned, said Nature .

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How did scientists create Retro?

The technique used to create Retro builds upon the pioneering work that led to the creation of Dolly the sheep nearly 30 years ago, known as somatic cell nuclear transfer (SCNT). 

This method involves reconstructing "an unfertilised egg by fusing a somatic cell nucleus (not from a sperm or egg) with an egg in which the nucleus has been removed", explained CNN .

Since Dolly, scientists have cloned various mammalian species, such as pigs, cows, horses and dogs. But the process has a low success rate, with only a small percentage of embryos transferred into surrogates resulting in viable offspring.

Expanding on previous successful work with macaque monkeys, the research team developed a modified version of the SCNT technique to clone the rhesus monkey. 

After hundreds of failed cloning attempts the scientists realised that, in the early cloned embryos, the outer membrane that forms the placenta did not develop properly. 

To address this, they used a technique called inner cell mass transplantation, involving placing cloned inner cells into a non-cloned embryo. This technique allowed the cloned embryos to develop normally.

The team rigorously tested the refined technique, utilising 113 reconstructed embryos, of which 11 were transferred to seven surrogates, ultimately resulting in just a single live birth: Retro.

What are the implications of the new research?

One of the big potential implications is that it could speed up drug testing in the future. That's because genetically identical animals – of the kind produced by cloning – give like-for-like results, providing greater certainty in drug trials.

Animal welfare charity the RSPCA has deep concerns about the research, arguing that there is "no immediate application" for the study. "We are expected to assume that human patients will benefit from these experiments, but any real-life applications would be years away and it is likely that more animal 'models' will be necessary in developing these technologies," the group told the BBC .

Professor Robin Lovell-Badge, of the Francis Crick Institute in London, is an advocate of animal research where the benefits to patients outweigh the suffering of animals. He told the BBC he had similar concerns. "Having animals of the same genetic make-up will reduce a source of variation in experiments. But you have to ask if it is really worth it," he said. ''The number of attempts they had is enormous. They have had to use many embryos and implant them into many surrogate mothers to get one live born animal.''

He added that it was difficult to draw conclusions about the success of the technique when it had resulted in only one live birth. "You need at least two, but preferably more," he said.

Does it mean we're closer to cloning humans?

Cloning human beings in the near future remains highly unlikely. Most scientists find the idea of human cloning highly controversial and unethical. The team that created Retro explicitly stated that human cloning is "completely unacceptable", and refused to speculate on any future uses for their research in this area.

Speaking to CNN, Dr Lluís Montoliu, a research scientist at the National Centre for Biotechnology in Spain, who wasn't involved in the research, said that the result demonstrated two things. "First, it is possible to clone primates. And second, no less important, it is extremely difficult to succeed with these experiments, with such low efficiencies," he said.

He added that the low success rate of the process showed that "not only was human cloning unnecessary and debatable, but if attempted, it would be extraordinarily difficult and ethically unjustifiable."

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Is it time to end biomedical experiments on monkeys?

Some researchers argue testing on primates is both unethical and irrelevant, but vaccine developers and others say it saves human lives — and the pandemic is their latest example, niranjana rajalakshmi • february 11, 2022.

Confining monkeys in small cages instead of their natural forest environment changes the results of experiments, some researchers say. [Credit: Wikimedia Commons]

Chimpanzee justice, roni jacobson • november 19, 2012, the monkey in the mirror, mary beth griggs • january 19, 2011, the end of biomedical research on u.s. chimps may imperil their wild brethren, mark d. kaufman • february 17, 2017.

In 2015 , the National Institutes of Health banned experiments on chimps, our closest genetic relatives . But that hasn’t ended tests on other primates, despite never-ending criticism from both ethicists and some researchers. 

This is the kind of research that Pfizer and Moderna relied on to get their COVID-19 vaccines to the market as soon as possible. Tests on rhesus macaques were important in speeding along the process, says Matthew R. Bailey , president of the Foundation For Biomedical Research . “To argue that primate research should not be conducted is itself unethical. It means you’ve delivered a death sentence to a lot of people who are depending on that research to save their lives,” he says.

But other animal experts, including several who formerly worked in research facilities, think it’s time to consider an outright ban on all monkey experiments. Noting that experimenting on chimps and other large apes is already banned in most countries , including the U.S., they argue that the monkeys in medical experiments suffer physically and psychologically. That raises not only ethical concerns but also scientific ones, since research monkeys living in a lab are more restricted in their movement than are monkeys that are free to roam.

In justifying the phase-out of chimp testing, NIH Director Dr. Frances Collins stated that “ new scientific methods and technologies have rendered their use in research largely unnecessary.” However, Collins has also said that continued testing on monkeys and other primates is vital to improving human health – even though chimps are actually much closer to humans than monkeys. We share almost 99% of our DNA with chimpanzees, compared to just 93% with rhesus monkeys . 

“It’s deeply illogical,” asserts Lisa Jones-Engel , a former primate scientist at the University of Washington who is now a consultant to People for the Ethical Treatment of Animals (PETA). “It’s just about money. Monkeys are smaller and cheaper than chimpanzees. There are more of them available in the wild. It has nothing to do with scientific or ethical relevance.”

The cost associated with buying and maintaining chimps was one of the factors that influenced the NIH to ban chimpanzee testing, according to Dr. Larry Carbone , a former university veterinarian in San Francisco who is now an independent animal welfare consultant. “Chimps will cost you $100,000, and you spend $100 a day to house them”, he says. On the other hand, a rhesus monkey costs about $7,000, and just $15 to $20 per day to house and feed, Carbone adds. 

Ultimately, the NIH concluded that “chimps are not useful enough” to justify the expense and the regulatory complications, since chimps are also an endangered species, unlike rhesus macaques, Carbone says.

No one knows exactly how many monkeys are used in research projects in the U.S. because the private companies that do much of the testing don’t have to disclose that information, according to Carbone. However, a 2019 federal report  puts the total at more than 68,000. Even so, there was a monkey shortage when the COVID vaccine research was at its peak — one that still continues. “The shortfall of monkeys began in 2018 and their overall demand increased when the pandemic struck”, says Sheri Hild , an NIH program director for primate research. 

The strongest case for continuing to use monkeys in experiments is for research on diseases like HIV and Ebola : diseases that monkeys are known carriers for . “The immune systems between humans and monkeys are so similar. That allows the testing of new treatment interventions,” says Caroline Pereira Bittencourt Passaes , who studies HIV-induced inflammation in rhesus macaques at the Pasteur Institute in Paris. “Giving HIV vaccines directly to humans would be a disaster,” she says. 

But even in HIV research, monkeys are not an ideal experimental model for humans. For one thing, they tend to get less severe HIV infections than humans, making it more difficult to design appropriate drugs and vaccines.  

Opponents of monkey testing, like Jones-Engels, extend this argument, claiming that “95% of drugs and treatments that work in animals, including monkeys, actually fail in humans.”. However, the NIH says the 95% failure rate applies to the entire drug discovery process, not to the animal tests that occur just before the human clinical trials. 

COVID-19 vaccines are the latest reason most biomedical researchers continue to defend monkey experimentation. In a recent statement , a network of seven primate research centers argued that monkey tests were essential for getting fast approval for the Pfizer and Moderna mRNA vaccines, as did a group of European researchers . Both companies tested their vaccines in monkeys and found they could induce SARS-CoV-2 antibodies. 

Monkey testing was important in the development of the COVID treatments and vaccines because the SARS-CoV-2 cellular receptor in humans is more similar to the one in monkeys than in other lab animals such as mice, according to the Pasteur Institute’s Passaes. “Monkeys have given a very valuable contribution to all these preclinical studies of drugs, monoclonal antibodies and of course, vaccines to fight COVID pandemic.”

But there was a dark side to some of that COVID-19 research, according to Jones-Engel. She says some monkeys used in the research were captured in forests in India and Bangladesh instead of being bred in captivity. “That is completely antithetical to best practices in the scientific community,” she says. “These monkeys were not bred for experiments. They were not specific-pathogen-free. How do you expect the results to be accurate?” For India’s COVAXIN  vaccine, for example, authorities allowed researchers to capture 30 rhesus monkeys from the wild. 

Primatologists point out that monkeys in cages are very different from their wild cousins, which inevitably affects experimental outcomes. “Some primates can walk for 50 kilometers a day, and they cannot do that in any lab. That’s a very big limitation,” says Constança Carvalho , a biologist at the University of Lisbon. 

Wild monkeys not only range widely, they also engage in a variety of mind-stimulating behaviors, everything from gouging holes in tree trunks and cracking open nuts to being curious like humans . Restricting their movement and suppressing their natural instincts in the lab setting makes some scientists doubt the accuracy of research conducted on them.

“Housing animals with large brains in cramped cages has a powerful effect on their physiological and neurological systems”, says John P. Gluck , a retired primatologist at the University of New Mexico who now works on animal welfare issues. “Practically, primate models are not as good as we once thought and that has a lot to do with how we house them.” This could be relevant for vaccine studies, since at least one study has shown that separating young monkeys from their families and housing them indoors affects their immune system .

If monkeys are used at all for research, Carvalho thinks that they should be treated the same way as humans. “You need to have someone appointed to be in charge of defending the best interests of that particular animal, in the same way you have someone responsible for a child. And this is not what is done in labs.”

Operators of primate research labs, however, say critics are misrepresenting conditions at some facilities. At the California Primate Research Center , for example, most monkeys are housed outdoors with their families, says  Kent Pinkerton , who is a scientist there. Outdoor monkeys “are happy with each other,” he adds, “and it’s not just one monkey with its offspring — it’s a colony.”

Opponents of monkey research cite the rise of alternative ways to model how humans may respond to experimental drugs, including  3D-printed human tissues and organoids and even organs on chips . Most of those tools, however, are still being developed and are not ready for widespread use yet.

And even when they are ready for prime time, alternative techniques like organs on chips can only be complementary tools to animal models, according to Hild, the NIH program director for primate research. “They definitely cannot be viewed as replacements for a whole organism,” she says. “They are just refinements that help in reducing animal usage in research.”

Even critics like Gluck acknowledge that ending primate testing overnight would slow down drug development — for the simple reason that the use of animals is such an ingrained tradition in biomedical research. “If all the primate research centers were emptied in the middle of a pandemic like this, it would have slowed down vaccine development, because that’s the way we think,” Gluck says, “even if it’s inferior thinking.”

About the Author

Niranjana Rajalakshmi

Niranjana Rajalakshmi is a veterinarian from South India. After a master’s in veterinary microbiology, she has combined her subject matter expertise with her fervor for storytelling and transitioned as a science journalist. From the three seasons of her city – summer, summerer, and summerest – she thinks moving to NYC will add at least one more season to her life and more flavor to her writing. Niranjana enjoys cooking, singing, and feeling nostalgic about her furry patients.

Experimenting on other species is fundamentally flawed because while they are like humans in their ability to feel pain and suffer, their physiology differs significantly from humans’. That’s why drugs that have passed animal tests with flying colors have sickened and even killed humans. Testing drugs on animals is as unnecessary as it is cruel. A prime example is the development of COVID vaccines. To expedite the process, the FDA and NIH allowed potential COVID vaccines to go to human clinical trials without first being tested extensively on animals. If they had required the usual years of animal tests, we still might not have an effective vaccine available.

YES YES YES! There are kinder and more accurate research methods available that take advantage of cutting-edge technology instead of cutting into animals.

It’s good to see this being written about, but the article needed some additional vetting. For instance: “But even in HIV research, monkeys are not an ideal experimental model for humans. For one thing, they tend to get less severe HIV infections than humans, making it more difficult to design appropriate drugs and vaccines.”

Monkeys are immune to HIV. Monkeys used in HIV research are infected with a different retrovirus called SIV (Simian Immunodeficiency Virus.) So, a different species being infected with a different virus is claimed to be HIV research.

I think that it is barbaric to experiment on any animals. How could any human experiment on any animal knowing the pain and suffering is going to be inflicted on that animal. This is something that needs to stop.

Yes let’s let’s end this!!!! Please! Hard to see these monkey suffering!

Yes shut down these labs. How can a human being do this. It’s barbaric. A person that does this has no soul or feelings.

A big thank you to the author of this article. How can we respect or believe the medical researchers for being so cruel to animals!! I agree their motivation is purely money and trying to win a prize. Leave the animals to live their lives free of human cruelty. People fighting for animal rights deserve a huge prize.

I wish someone would let people know that the monkey videos are staged and the monkeys were abused and most are dead, Kaka and Deim ones, multi pages fooling people thinking they are good people and treat Kaka like family, someone please make an article about what happen.

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Research monkey shortage undermines US readiness, panel says

FILE - River, left, and Timon, both rhesus macaques who were previously used in medical research, sit in an outdoor enclosure at Primates Inc., in Westfield, Wis., on May 13, 2019. The sanctuary is a 17-acre rural compound where research animals can live their remaining years when their studies are done. A report released on Thursday, May 4, 2023, says a shortage of monkeys available for medical research undermines U.S. readiness to respond to public health emergencies. (AP Photo/Carrie Antlfinger, FILE)

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There’s a shortage of monkeys available for medical research and the U.S. should expand its breeding programs rather than rely on international suppliers to solve it, an influential scientific advisory panel said Thursday.

Studies using nonhuman primates, especially monkeys, have been critical to lifesaving medical advances – including creating vaccines against COVID-19 – because of their similarities to people. The U.S. funds colonies at national primate centers but supplies were tight and more animals were regularly imported even before the pandemic.

Then China, once a leading supplier, ended exports of research monkeys in 2020, as scientists everywhere needed more for coronavirus studies. And last fall, the U.S. filed charges to stop a Cambodian smuggling ring accused of shipping endangered wild monkeys in place of those bred for research, further constraining supplies.

Thursday’s report examined only research funded by the National Institutes of Health, deemed key to responding to public health emergencies — not drug company or other publicly or privately funded research with monkeys.

The nation’s preparedness is undermined by having to depend on imports of these animals, which are especially important for infectious disease research and neuroscience, said a panel of the National Academies of Sciences, Engineering and Medicine. Highlighting that vulnerability, the U.S. experienced a 20% drop in imports of one species, cynomolgus macaques, when China suddenly stopped shipping.

The panel also called for more development of alternatives to monkey testing — and in the meantime urged better scientific collaboration to make the best use of each research animal.

“If the U.S. is to produce high-impact biomedical research and have a research infrastructure capable of responding to the next public health crisis, now is the time to strengthen the systems we need for nonhuman primate research,” said committee chairman Dr. Kenneth Ramos of Texas A&M University.

Use of animals in biomedical research, especially nonhuman primates, is controversial. Under pressure, the NIH already retired chimpanzees, humans’ closest relatives, from invasive research but has maintained there’s still need for monkeys. Nonhuman primates represent 0.5% of all the animals used in biomedical research in the U.S., the report said.

In a survey of NIH-supported researchers, the National Academies panel found 64% reported challenges in getting nonhuman primates required for their work, including increased wait times and cost. In 2021, the National Primate Research Centers had such a shortage of monkeys never used in previous studies that it couldn’t meet two-thirds of researcher requests, the report said.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

The Hastings Center

Bioethics Forum Essay

Primates in medical research: a matter of convenience, not sound science.

In Beaverton, Oregon, in one of seven National Primate Research Centers, a rhesus macaque sits in a cage awaiting her fate in an Alzheimer’s disease experiment. She is one of more than 100,000 monkeys–regarded by some neuroscientists as key to understanding dementia–forcibly separated from her family, traded as a commodity, and scheduled to die in a laboratory in the U.S. What are the current and future potential uses of nonhuman primates in research? The National Academies of Sciences, Engineering, and Medicine is examining this question.

Experiments on animals date back to at least 6 BCE when ancient Greek physicians, culturally forbidden from cutting open human bodies, turned to nonhuman bodies. By the 17th century, philosopher and scientist Francis Bacon asserted that the dissection of living animals could “sufficiently satisfy” as a substitute for human experiments. Although nonhuman primates have been dissected for ages, the systematic inclusion of nonhuman primates in research began in the last century .

After the Second World War, revelations of human research abuses led to the establishment of guidelines for the conduct of research with humans, such as the Nuremberg Code and the Declaration of Helsinki. By 1979, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, appointed by the U.S. Congress, published The Belmont Report , which laid ethical foundations for 20th century human research protections. The Belmont Report centered on the principle of justice and the importance of avoiding the selection of human research subjects based on convenience, accessibility, or manipulability.

While it was well-intentioned and rightly protected vulnerable populations, such as children and imprisoned persons, The Belmont Report encouraged a shift to research involving nonhuman primates and other animals. This shift has resulted in unresolved moral and scientific problems that can now only be addressed by another paradigm.

Today, unlike in the 17th century, scientists easily recognize the truth in the saying “mice lie and monkeys exaggerate,” which points to a well-known problem in biomedical research: using nonhuman primates and other animals in research fails more often than it succeeds. Approximately 90 percent of new investigational drugs–drugs that appear safe or effective in monkeys and other animals–fail to be safe and/or effective in humans. Nearly 100 percent of the drugs developed for Alzheimer’s in decades of research have failed . As researchers at the Oregon National Primate Research Center in Beaverton wrote in 2021, “in the rhesus macaque model of aging, all four major hallmarks of [Alzheimer’s disease]—significant cognitive decline, amyloid beta plaques, p-tau tangles, and neuronal death—do not reach the pathological levels of clinical [Alzheimer’s disease].” In other words, these monkeys do not develop Alzheimer’s disease.

If researchers were to extend The Belmont Report’s principle of justice to nonhuman primates and other animals, they would perhaps acknowledge that the continued use of these animals is a matter of convenience, accessibility, and their vulnerability to coercion rather than a matter of sound science. The translational failures of science discount lives that are utterly thrown away in experiments that we have good reason to expect will fail. Animals are treated like disposable equipment rather than as conscious, living, feeling beings.

Translational failures also harm humans—those who will face the risks of human experiments based on animal research and those who will continue to wait for medical treatments that are promised but not delivered. The translational failures of biomedical research are not just a scientific problem, but a moral problem—a failure to recognize the value of both nonhuman and human lives.

Failures to transform medical research are propelled by institutional biases and by limitations in transparency and in accountability for spending trends—all of which are complicated by long-standing relationships between the pharmaceutical industry, academia, and government. This network of influence has contributed to a shift away from health research and planning that was historically focused on the public interest to research priorities that are now largely driven by profit margins. Many stakeholders within the industry-academia-government complex have an interest in animal research remaining the norm. The National Primate Research Centers are a notable example.

Nonetheless, public pressure does from time-to-time break through and cause policy makers to reevaluate the norm. For example, in 2011, following a request from the U.S. Congress and the National Institutes of Health, an Institute of Medicine  Committee on the Use of Chimpanzees in Biomedical and Behavioral Research concluded that most current uses of chimpanzees in research were unnecessary. Chimpanzees are humans’ closest living relatives, yet chimpanzee experiments are still viewed as unreliable and unnecessary. A growing number of physicians and scientists realize that evolutionary and individual differences within and across species impede the translation of animal research findings to humans—even for animals who are so like us.

This year, in response to a request from Congress and the NIH, the National Academies of Sciences, Engineering, and Medicine (comprising the former IOM) is again examining the use of nonhuman primates in research. But rather than asking if monkeys should be used in research, the NIH’s mandate to the NASEM committee leaves that important question off the table. To protect the status quo, the committee is comprised of individuals entrenched in primate research, and the only members to disclose conflicts of interest are those with an interest in nonanimal methods.

But the status quo isn’t working, as decades of science demonstrate. Across the US, the families of the estimated six million people living with Alzheimer’s disease—and the physicians treating them—are desperate for answers. They know the suffering Alzheimer’s can cause, and they want more effective prevention and treatment strategies.

As Thomas Insel, the former National Institute of Mental Health director, explained in his book Healing , we need to shift from relying on reductionist models of disease to looking at what patients, families, and communities living with various forms of psychiatric and neurological illness experience and need. This shift, overturning the status quo, requires investing in ethically designed studies that center on patients and population-based interventions, as well as on science that is centered on human biology and systems. Such a shift requires recognizing the failure of 17th century ideas, and reimagining and modernizing biomedical research to meet the real needs of patients and the demands of justice.

Hope Ferdowsian, MD, MPH, is an associate clinical professor at the University of New Mexico School of Medicine, and president and CEO of Phoenix Zones Initiative. @HopeFerdowsian

L. Syd M. Johnson, PhD, is an associate professor at the Center for Bioethics and Humanities and a clinical ethics consultant at Upstate Medical University in Syracuse, N.Y. @LSydMJohnson

Hastings Bioethics Forum essays are the opinions of the authors, not of The Hastings Center.

Thanks, team for this reawakening call to end this vice, more resources need to be channeled to research on IT modeling as a replacement for the use of primates in biomedical research. #Animal lives matter #Animals too deserve another chance to live

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January 24, 2018

First Primate Clones Produced Using the “Dolly” Method

The success with monkeys could ignite new ethical debates and medical research

By Dina Fine Maron

This is a photograph of Hua Hua, one of the first monkey clones made by somatic cell nuclear transfer.

Qiang Sun and Mu-ming Poo  Chinese Academy of Sciences

Meet Zhong Zhong and Hua Hua—healthy newborn monkeys and the first primate clones produced via the same method that made Dolly the sheep two decades ago.

The advance at a lab in China edges scientists closer to a future in which they could create large numbers of genetically identical monkeys to serve as models for human diseases and other conditions. This could help researchers unravel complex questions, including how environmental factors may fuel common human cancers.

Primate research ethics could, however, limit such research. “It’s a cost-benefit analysis,” says Kevin Sinclair, a developmental biologist at the University of Nottingham who was not involved with the latest cloning work. “If you have a population of nonhuman primates that are genetically identical, that’s a really, really powerful model to study human disease, underlying mechanisms and potential cures. But it has to be done on a case-by-case basis to justify doing that.” Many countries, including the U.S., have strict guidelines on primate research due to ethical concerns about experimenting on our close genetic relatives. For example, U.S. government biomedical research on chimpanzees is effectively over, and all lab chimps are being slowly retired.

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Scientists at the Chinese Academy of Sciences’ Institute of Neuroscience, in Shanghai, published a report on their two primate successes Wednesday in Cell . The cloning technique they used, called somatic cell nuclear transfer (SCNT), involves swapping the nucleus of a donor cell into a fertilized egg that has been purged of its own chromosomes. The egg will then contain an exact copy of the donor’s genome, and if it is implanted into a surrogate mother, the eventual offspring will be a clone. More than 20 other species, including pigs and dogs, had already been successfully cloned using SCNT. And numerous studies of animals produced by this method indicate they are as healthy as their noncloned cousins.

Making this process work in primates has been tough. When researchers previously tried using the “Dolly” approach on monkeys it produced fetuses—but no pregnancy that lasted beyond 80 days. The main obstacle, the Institute of Neuroscience researchers wrote, was likely that transferred nuclei were not properly programmed to support embryonic development. So this time the Chinese team deployed two critical enzymes that removed genes’ epigenetic memory of being somatic cells (cells that make up tissues and organs). This extra step allowed development to proceed, says stem cell expert Alan Trounson, an emeritus professor at the Hudson Institute of Medical Research in Australia who was not involved in the new research. The success rate was still extremely low. But as scientists adjust their methods they could create dozens of clones in the near future, he notes.

Researchers have managed to clone nonhuman primates in the past couple of decades using other techniques, including a similar nuclear transfer method that relies on embryonic stem cells instead of somatic cells. But using SCNT is a major advance because it would likely be easier to use and reproduce in large numbers. It could also be more successfully coupled with CRISPR gene-editing techniques for future research on specific diseases or genetic mutations, the Institute scientists wrote in their paper.

This approach to cloning could eventually help save endangered primates, Sinclair says. In situations where habitat destruction has left only a small number of primates, he adds, researchers could obtain somatic cells from body tissue and freeze it for storage in gene banks. But this would require further scientific progress, because the recent Chinese SCNT work was successful using fetal cells—not adult cells, which can be more difficult to reprogram.

Aspects of monkey SCNT will also need to be improved before the technology can be used to produce primates for research, experts caution. “From a scientific standpoint the advances here are significant. But from a practical, immediate utilization perspective there are still some technical issues that exist,” says Jon Hennebold, chief of the division of reproductive and developmental sciences at the Oregon National Primate Research Center who was not part of the work. “The pregnancy rate and the live birth rate were not at a level that would allow this to be done on some wide scale. You would also have to have expertise in assisted reproductive technologies, reproductive physiology—and a large cohort of donors. And all those things are limiting with this current technology.”

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Future Vaccines Depend on Test Subjects in Short Supply: Monkeys

Veterinary techs distribute food every morning to more than 5,000 monkeys at the Tulane University National Primate Research Center outside New Orleans. Credit...

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By Sui-Lee Wee

Photographs and Video by Bryan Tarnowski

• Feb. 23, 2021

Mark Lewis was desperate to find monkeys. Millions of human lives, all over the world, were at stake.

Mr. Lewis, the chief executive of Bioqual, was responsible for providing lab monkeys to pharmaceutical companies like Moderna and Johnson & Johnson , which needed the animals to develop their Covid-19 vaccines. But as the coronavirus swept across the United States last year, there were few of the specially bred monkeys to be found anywhere in the world.

Unable to furnish scientists with monkeys, which can cost more than $10,000 each, about a dozen companies were left scrambling for research animals at the height of the pandemic.

“We lost work because we couldn’t supply the animals in the time frame,” Mr. Lewis said.

The world needs monkeys, whose DNA closely resembles that of humans, to develop Covid-19 vaccines. But a global shortage, resulting from the unexpected demand caused by the pandemic, has been exacerbated by a recent ban on the sale of wildlife from China, the leading supplier of the lab animals.

The latest shortage has revived talk about creating a strategic monkey reserve in the United States, an emergency stockpile similar to those maintained by the government for oil and grain.

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The Emergence of Mpox: Epidemiology and Current Therapeutic Options

Samriddhi ranjan.

1 College of Public Health, George Mason University, 4400 University Drive Fairfax, Fairfax, VA 22030 USA

Kanupriya Vashishth

2 Advance Cardiac Centre Department of Cardiology, PGIMER, Chandigarh, 160012 India

3 NGO Praeventio, Tartu, Estonia

Hardeep Singh Tuli

4 Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207 India

Associated Data

This document includes citations for all the data that were analysed throughout the literature review.

The world recently witnessed the emergence of new epidemic outbreaks like COVID-19 and mpox. The 2022 outbreak of mpox amid COVID-19 presents an intricate situation and requires strategies to combat the status quo. Some of the challenges to controlling an epidemic include present knowledge of the disease, available treatment options, appropriate health infrastructures facilities, current scientific methods, operations concepts, availability of technical staff, financial funds, and lastly international policies to control an epidemic state. These insufficiencies often hinder the control of disease spread and jeopardize the health of countless people. Also, disease outbreaks often put a huge burden on the developing economies. These countries are the worst affected and are immensely dependent on assistance provided from the larger economies to control such outbreaks. The first case of mpox was reported in the 1970s and several outbreaks were detected thereafter in the endemic areas eventually leading to the recent outbreak. Approximately, more than 80,000 individuals were infected, and 110 countries were affected by this outbreak. Yet, no definite vaccines and drugs are available to date. The lack of human clinical trials affected thousands of individuals in availing definite disease management. This paper focuses on the epidemiology of mpox, scientific concepts, and treatment options including future treatment modalities for mpox.

Introduction

Amidst the COVID-19 pandemic, another public health concern emerged as a potential threat to afflict people globally, i.e. an abrupt increase in the incidence of mpox (monkeypox) cases. Indeed, starting from mid-May 2022, cases of human mpox have significantly risen in several non-endemic countries worldwide, leading to the declaration of the ongoing outbreak of mpox as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in July 2022 [ 1 , 2 ]. Mpox disease is caused by the mpox virus (MPXV), a double-stranded DNA virus from the Orthopoxvirus genus, belonging to the Poxviridae family [ 2 , 3 ]. The same genus includes the variola virus, a known causative agent of smallpox [ 2 ]. Genetically, MPXV is identified with two types of clads. Clad I, also known as Congo Basin clad, is mostly clustered in the Central-South Cameroon region till DRC. Infections from this clad are more severe with case fatality rates (CRF) > 10%. Clad II also referred to as West African clad, commonly distributed in western Cameroon to the Sierra Leon area, is further divided into sub-clad groups as IIa and IIb (also now referred to as clad III) having a CRF < 1% [ 4 , 5 ]. Overall reported human case fatality rates (CFRs) range between 3.6 and 10.6% in the endemic regions [ 2 ]. In the current 2022 outbreak, clad IIb was predominant [ 6 , 7 ]. To date, the exact animal reservoir for the mpox virus (MPXV) has remained unknown. However, few native African rodents (Gambian giant rats) and squirrels are suspected to be natural reservoirs of the virus. Common species which were frequently infected with MPXV are squirrels, Gambian giant rats, strip mice, dormice, and primates [ 8 ].

Emergence of Mpox

The first outbreak of mpox was reported in 1958 in a group of 10 captive monkeys at the Statens Seruminstitut, Copehengan, Denmark, and Centre d’Enseignement et de Recherches de Medecine aeronautique, Paris. No human infection was reported in individuals who were in close contact with infected monkeys. Subsequently, the mpox outbreak occurred for the first time in humans between 1970 to 1971 [ 9 ]. The first case was reported in a 9-month-old boy residing in a remote village of the Democratic Republic of Congo (DRC), admitted to a local hospital suspected of smallpox infection. Samples from infected individuals were sent to the WHO Smallpox Reference Center, Moscow, revealing mpox infections in virus isolates [ 10 ]. When inspected from family, monkeys were part of the diet, and their skins were also processed in this area. However, no other cases including secondary infections were reported in the community. Nonetheless, seven more cases were reported during this time period [ 9 ]. The World Health Organization in 1967 took the initiative to collaborate with laboratories to conduct cooperative studies. This was to conduct serological surveys, identify mpox outbreaks, and determine the natural foci of the virus. However, these surveys failed to state any major findings and concluded mpox is not a widespread disease and can exist only in the local environment [ 9 ]. Ever since, there has been a subsequent upsurge of mpox cases, mostly recorded in the DRC province. Approximately, 80% of the cases were reported in this region from the years 1970–1997 [ 11 ]. For the past five decades, DRC is the most affected country with mpox; no other country had reported an mpox outbreak to such an extent [ 12 ].

The initial mpox outbreak that was reported in DRC mostly affected children below 10 years of age. A slight male predominance was observed in the systemic review conducted by Beer and Rao [ 11 ]. Most of the initial outbreaks occurred among individuals living in small rural areas or residing close to humid evergreen tropical forests or individuals commonly involved with bushmeat hunting [ 11 ]. Geographically, the spread of infection from 1970 to 2003 concentrated in the Central and Western parts of Africa (Table 1). Countries which frequently reported infections were Cameroon, the Central African Republic, Gabon, Sierra Leone, Liberia, Nigeria, and Cote d’Ivoire, yet greater outbreaks were mostly detected in DRC [ 13 ]. An active surveillance programme was carried out by WHO between the years 1981 to 1986 reporting total confirmed cases of 338 and 33 deaths, an almost 20 times rise in the reported case after the surveillance [ 10 , 11 ]. A slight drop in the incidence of disease was observed between the period of 1993–1995. But soon after, DRC witnessed a major outbreak from 1996–1997 [ 13 ]. A total of 511 cases were recorded with a surge in secondary transmission rates of up to 78% and a fatality rate between 1 and 5% [ 10 , 13 ].

In 2003, the mpox outbreak occurred for the first time in the USA, outside the African continent. The index case was a 3-year-old girl, bitten by an infected prairie dog, imported from Ghana along with other African rodents to the USA [ 14 ]. A total of 71 cases were reported, including both suspected and laboratory-confirmed cases, as per the CDC report [ 15 ]. During the period of 2005, mpox was registered for the first time in the dry savannah region of Sudan. Overall, 40 cases both suspected and confirmed were recorded. In this outbreak, a change in the genomic structure of MPXV was observed as compared to the MPXV traditionally reported in DRC suggesting the adaptability of MPVX in dry regions from humid evergreen tropical forests [ 10 ]. In the year 2018, mpox travelled for the first time to the UK and was reported in the European continent. Only two cases were registered, in individuals, which had a travel history to Nigeria [ 16 ]. Nevertheless, with the advent of 2022, the world saw a major outbreak of mpox (Table ​ (Table1 1 ).

Decade-wise spread of mpox across different countries between 1970 and 2020 9,10

Mpox Outbreak 2022

Mpox is endemic in Central and West Africa, where hundreds of cases were detected annually for many years, acquired mostly from wild animals and most rarely from infected humans [ 1 , 3 ], which results in a sporadic spillover of cases in humans as observed in the MPVX endemic regions [ 5 ]. However, in the 2022 outbreak of mpox, most of the cases were reported in non-endemic countries like N. America, S. America, and Europe (Fig.  1 ) [ 17 ]. Although the origin of the 2022 outbreak is still unknown, it is highly likely that the initial infection has been imported from an endemic country, allowing the circulation of the virus through close physical contacts among humans [ 1 , 18 ]. For the first time, mpox was documented with transmission chains in countries which had no immediate contact with Central or Western Africa [ 19 , 20 ]. This suggests a probability of undetected MPXV circulating in the local population in the outbreak-hit regions causing disease transmission in humans [ 17 ]. Being a DNA virus, mpox is more stable in nature and may have possibly evolved as a potent virus causing infections in humans in the due course of time [ 17 ]. Daniel et al. reported 6–12 times higher mutation rates in mpox as previously estimated [ 6 ]. Human to human transmissibility of mpox has also evolved in these decades [ 21 , 22 ]. Vertical infection of mpox has been also reported. Pregnant mothers infected with mpox had miscarriages during the first trimester of pregnancy [ 6 ]. Perinatally acquired mpox infection was registered in a 9-day year old neonate as well [ 23 ]. Transmissibility of infection within the family especially from parents to children have also been stated to increase [ 20 , 22 ]. The degree of transmissibility of the diseases, popularly known as R 0 , reported in the 1980 for mpox was 0.83. However, in the 2022 outbreak, the R 0 reported was 1.1–2.4 [ 21 , 24 ]. Pan et al. suggested the increase in the R 0 is due to decreased immunity of individuals due to the absence of smallpox immunization and high contact rates of infection in the MSM community [ 6 ].

Countries reporting mpox historically vs countries reporting an mpox outbreak as recorded in an early March 2023 report by CDC 19

As per the WHO, till 17 March 2023, the total confirmed cases for mpox were 86,601, with 1265 probable cases reported with 112 deaths. Globally, 110 countries were affected by mpox so far (Fig.  2 ) [ 20 ]. Approximately 34.7% of cases were reported in America, the worst affected country [ 20 ]. Majority of the infection occurred through household contacts (43%) and by sexual encounters (43%) [ 20 , 22 ]. Commonly affected individuals were young males who were not vaccinated against smallpox and have had sex with men. There was a slight male predisposition, with the median age reported as 34 years (IQR: 29–41). Around, 98% of individuals who were infected were either gay or bisexual, among which 41% of the people were HIV infected [ 4 ].

Mpox number of cases and deaths recorded in early March 2023 across the continent as per the report by CDC 19

On 23 July 2022, mpox was declared a public health emergency by the Public Health Emergency of International Concern (PHEIC), depicting a risk of international spread, along with significant international coordination to control the disease [ 25 ].

Clinical presentation of this disease includes three distinct phases, i.e. incubation, prodrome, and rash [ 2 ]. The incubation period can last for 3 to 20 days with the median being 7 days followed by the prodrome phase that is characterized by lethargy, myalgia, headache, fever, and lymphadenopathy which may last up to 5 days (Fig.  3 ) [ 2 , 4 , 18 ]. Lymphadenopathy is one of the critical features of the progression of the disease and often reported before the development of skin lesions [ 18 ]. Fever is usually followed by multiple papular, ulcerative, and vesiculopustular skin lesions [ 4 ], which progress from macules to papules, vesicles, pustules, crusts, and lastly scab, presenting for up to 4 weeks [ 2 , 18 ]. In 95% of the cases, skin lesions appears [ 4 ]. Common anatomical sites for skin lesions were anogenital with approximately 73% of cases followed by trunk, arms or legs, face, and eventually palms and soles, only accounting for 10% of the cases. Lesions developed contain infectious virus particles, through which the infection can be transmitted directly with human contacts [ 2 ]. Secondary complications include pneumonia, encephalitis, keratitis, gastroenteritis, sepsis, and secondary bacterial infections, affecting mostly patients with a previous diagnosis of HIV infection [ 2 , 4 , 5 ].

Common features reported in mpox infection 4

Current Treatment Modalities and Prevention

The strategy for the prevention and treatment of mpox is very similar to the treatment of Orthomyxovirus infection [ 26 ]. The 2022 outbreak revealed the urgency to control the spread of mpox as it has caused a potential threat in many countries [ 27 ]. Presently, there is no definitive cure for mpox infection, mild symptoms are manageable, and further complications can be avoided in patients with mpox with the help of supportive care [ 28 , 29 ]. Studies have depicted that patients with mild symptoms recover without any treatment [ 30 – 32 ]. Treatment options available for smallpox are also effective in the treatment of mpox, as the clinical presentation of mpox and smallpox is very similar. These include the vaccinia vaccine, vaccinia immune globulin (IVG), and antiviral agents such as cidofovir, tecovirimat, and brincidofovir [ 32 ]. Furthermore, CDC recommends the use of the potential treatment options should be done depending upon the severity of the cases and for serious emergency cases, as the current drugs pose severe adverse effects, and their therapeutic efficacy is still uncertain [ 33 ]. Antiviral drugs are a choice of treatment in immunocompromised patients, in patients with complicated lesions, in pregnant women infected with mpox, in breast-feeding women, and in the paediatric population [ 34 ]. Tecovirimat is the first line of action antiviral recommended for the treatment of smallpox; it works by inhibiting the viral envelope protein, thereby blocking the final steps of virus maturation and release from infected cells, inhibiting the spread. As per the CDC guidelines, emergency access use of tecovirimat is allowed for compassionate use, for the treatment of Orthopoxvirus infections, such as mpox [ 35 , 36 ]. Cidofovir and its oral analogue brincidofovir are commonly approved drugs for the treatment of smallpox; both act by inhibiting viral DNA polymerase. Different studies have evaluated the effect of brincidofovir against Orthopoxvirus infections [ 37 ]. Studies done by Lanier et al. and others on the effect of cidofovir and brincidofovir have been evaluated for mpox with some success [ 34 , 37 ]. As per the recommended guidelines by CDC, preexposure smallpox vaccination has been advised for veterinarians, monkeypox contacts, healthcare workers caring for mpox patients, researchers, and field investigators [ 38 ]. Prior immunization with the smallpox vaccine has demonstrated some proven protective effects against mpox due to the cross-protective immunity provided by the smallpox vaccine. Furthermore, the severity of clinical manifestations is also reduced [ 39 ]. Currently, three available smallpox vaccines with the US national stockpile, i.e. JYNNEOSTM, ACAM2000, have been licenced (2007) for smallpox, the most recent being Aventis Pasteur Smallpox Vaccine (APSV) which could be potentially used for mpox on a case-to-case basis, under an investigational new drug (IND) protocol. JYNNEOSTM, a third-generation and live viral vaccine, is produced from the modified vaccinia Ankara-Bavarian Nordic [ 40 – 42 ]. Licenced in 2019, JYNNEOSTM is an attenuated non-replicating orthopoxvirus. It is now indicated for both smallpox and mpox prevention for adults. Further, ACAM2000, a second-generation vaccine constituted of live vaccinia virus, under the emergency access ACAM2000 is allowed for mpox during the outbreak. Researchers have demonstrated that these vaccines can be used as pre- and post-treatment options, i.e. either in preventing the infection and the disease or in ameliorating the infection and disease [ 34 , 43 , 44 ]. Studies have demonstrated that pregnant women, children less than 8 years of age, and immunocompromised patients should be given antiviral treatment than vaccination. These vaccines, although approved, have shown some local and systematic side effects such as fever, muscle pain, vaccinia, abdominal and back pain, fatigue, headache, lymphadenopathy, etc. [ 42 – 44 ]. Researchers have also highlighted the need for maintaining appropriate social barriers such as avoiding close contact with affected individuals, avoiding contact with skin lesions of individuals infected with MPXV, etc. [ 44 – 46 ]. Vaccinia immune globulin intravenous (VIGIV) is a choice of treatment in case of severe infection with mpox, though there is a paucity of data about its effectiveness in treating mpox. VIGIV is also under SNS and can be administered under investigational new drugs held by CDC [ 29 , 30 , 47 – 49 ]. Therefore, the treatment options and the repurposing of vaccines need to be considered on a case-to-case basis depending on the severity of cases and the immune state of patients [ 50 ] (Fig. ​ (Fig.4 4 ).

A Symptoms and B mechanism of action of mpox antiviral therapy: cidofovir, brincidofovir, vaccinia immune globulin, and tecovirimat [ 50 ] 

Key Fundamental Findings of the Narrative Review

Some major key findings related to mpox are as follows: mpox was solely endemic to the region of DRC [ 11 ]. There has been a slow and steady increase in mpox cases which has adapted itself to develop into the current outbreak. Secondly, the 1996–1997 DRC outbreak highlighted the increase in secondary transmission rates of mpox, potentially getting adapted to spread in the human population [ 13 ]. Thirdly, the MPXV had adapted to thrive itself from the humid evergreen regions to the dry savannah region of Sudan, as observed in the 2005 outbreak, thus further demonstrating its environmental adaptability to flourish [ 10 ]. Lastly, international travel and commerce have given a wider chance for the disease to spread as reported in the 2003 and 2018 outbreaks of mpox in the USA and the UK [ 14 , 16 ]. All these above factors have led to the 2022 outbreak of mpox, affecting every continent across the globe (Fig.  5 ).

Global spread of mpox in 2023 outbreak 19

Most of the consistent outbreak guidelines available from WHO or CDC only account for people with a high risk of exposure; these guidelines are based on the best available evidence which is based upon risk–benefit analysis and other factors [ 51 ]. Available drugs for the treatment of choice are also limited and lack evidence-based studies in humans [ 29 , 30 , 48 ]. This depicts an extensive need to increase the sustainable funding option to enhance our understanding of the development of new drugs and vaccines to curtail the spread of mpox.

Implication in Future Research

The environmental, behavioural, and social reasons behind the 2022 mpox outbreak remain unknown to date [ 1 ]. A deeper understanding of mpox genetics and biochemistry is essential to control its outbreak. It is currently unclear how mpox is closely related and linked to the viral strain that is primarily found in western Africa, as well as the potential routes of rapid transmission. To further understand the immune defence mechanisms against MPXV, more research is needed on the human systemic and mucosal immune responses. As DNA viruses are more adept to correct mutations; therefore, it is unlikely that the mpox virus will suddenly change during human transmission [ 24 , 52 ]. It is yet unknown, whether vaccinations and earlier infections have given the population immunity. Additionally, exploratory studies are required to pinpoint the precise mpox virus reservoir, understand how the virus spreads naturally, and determine the causes of the present increase in cases across several nations. Currently, no potent drugs are available and limited evidence-based studies are being conducted for the treatment of mpox [ 29 ]. Most of the available choices of treatment are discussed in this paper (Fig.  6 ). Therefore, it becomes essential to investigate the domain of natural products with antiviral properties. This provides alternative treatment options, to prevent human to human spread of infection and restrict virus amplification in the host organisms. There is a recent increased interest among the scientific community to look into the numerous bioactivities of structurally unrelated natural compounds [ 53 , 54 ]. Plant-derived polyphenol resveratrol has beeb shown to significantly suppress replication of MPXV affecting probably the viral DNA synthesis and inducing a comparable effect to the well-characterized Orthopoxvirus inhibitor, i.e. cytosine-1-β- d -arabinofuranoside (AraC) [ 55 ]. Due to the pleiotropic action of natural compounds and lack of systemic toxicity, plant-derived agents may represent target compounds to be explored in future clinical trials to enrich the drug arsenal against Orthopoxvirus infections. Parallel to this, early detection of infected patients who are potentially capable of transmitting the infection is also crucial, pointing to the need for improved diagnosis (particularly in atypical clinical presentations and asymptomatic cases), and better availability of molecular tests. Besides, such continual efforts of preclinical scientists and pharmaceutical companies, availability of health infrastructures, and medical staff are of critical importance—a situation still aggravated by the ongoing COVID-19 pandemic. A high-risk patient population is possibly in danger of mpox nosocomial transmission and deserves more attention. Therefore, it is crucial to administer the proper supportive care [ 24 ]. Consequently, it is necessary to improve genomic sequencing capabilities to identify the mpox viral clade(s). The primary necessities are to combat the spread of mpox while dealing with the ongoing COVID-19 pandemic and to include suitable and timely information campaigns for people at risk. It is challenging to create an evidence-based classification of drug safety and effectiveness having a brief history of mpox. Further studies on various animal models, which may affect medication exposure, are also encouraged. The focus of larger research should be on identifying the patients who are most at risk for consequences from mpox infection as well as the best timing for initiating and completing antiviral therapy.

Different treatment modalities in mpox

The emergence of new diseases is one of the incessant threats which mankind can face. Persistent interference between the environment and humans creates an opportunity for new infections to evolve. Over 75% of the pathogens, which are newly emerging, are zoonotic in nature [ 56 ]. Several diseases like HIV/AIDS, Nipah, SARS, and Ebola including mpox have recently appeared. International travel and commerce and human behaviour often help disease to spread [ 56 ]. With the first emergence of mpox in 1958, little is still known about its reservoir host and vector of the disease. Despite repeated outbreaks of mpox over the past years, it has failed to gather scientific attention. There is a lack of understanding of mpox transmission dynamics and disease evolution. In the areas endemic to mpox, regular disease surveillance is lacking. This also includes the need to promote funding for capacity building required for surveillance of the disease, research activities, and testing facilities [ 17 , 57 ]. The role of central bodies like the World Health Organization plays a major role in controlling such outbreaks. However, non-compliance to guidelines and regulations by health agencies like WHO severely impacts the control measures [ 25 ]. Boosting vaccine development and effective drug development is essential to prevent future outbreaks. In addition, new plant-derived products could be further developed and can be promoted as they potentially have lesser side effects for mpox treatment.

Abbreviations

Author Contribution

SR, KV, and KS: conceptualization and writing; HST: editing and proofreading. All authors reviewed the manuscript.

Data Availability

Compliance with ethical standards.

Not applicable.

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The authors declare no competing interests.

This article does not contain any studies with human or animal subjects performed by any of the authors.

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December 18, 2014

Crows join human, apes and monkeys in exhibiting advanced relational thinking

by University of Iowa

Crows have long been heralded for their high intelligence - they can remember faces, use tools and communicate in sophisticated ways.

But a newly published study finds crows also have the brain power to solve higher-order, relational-matching tasks, and they can do so spontaneously. That means crows join humans, apes and monkeys in exhibiting advanced relational thinking, according to the research.

Russian researcher Anna Smirnova studies a crow making the correct selection during a relational matching trial.

"What the crows have done is a phenomenal feat," says Ed Wasserman, a psychology professor at the University of Iowa and corresponding author of the study. "That's the marvel of the results. It's been done before with apes and monkeys, but now we're dealing with a bird; but not just any bird, a bird with a brain as special to birds as the brain of an apes is special to mammals."

"Crows Spontaneously Exhibit Analogical Reasoning," which was published December 18 in Current Biology , was written by Wasserman and Anna Smirnova, Zoya Zorina and Tanya Obozova, researchers with the Department of Biology at Lomonosov Moscow State University in Moscow, Russia, where the study was conducted.

Wasserman said the Russian researchers have studied bird species for decades and that a main theme of their work is cognition. He credits his counterparts with a thoughtful and well-planned study.

"This was a very artful experiment," Wasserman says. "I was just bowled over by how innovative it was."

The study involved two hooded crows that were at least 2 years old. First, the birds were trained and tested to identify items by color, shape and number of single samples.

Here is how it worked: the birds were placed into a wire mesh cage into which a plastic tray containing three small cups was occasionally inserted. The sample cup in the middle was covered with a small card on which was pictured a color, shape or number of items. The other two cups were also covered with cards - one that matched the sample and one that did not. During this initial training period, the cup with the matching card contained two mealworms; the crows were rewarded with these food items when they chose the matching card, but they received no food when they chose the other card.

Once the crows has been trained on identity matching-to-sample, the researchers moved to the second phase of the experiment. This time, the birds were assessed with relational matching pairs of items.

These relational matching trials were arranged in such a way that neither test pairs precisely matched the sample pair, thereby eliminating control by physical identity. For example, the crows might have to choose two same-sized circles rather than two different-sized circles when the sample card displayed two same-sized squares.

What surprised the researchers was not only that the crows could correctly perform the relational matches, but that they did so spontaneously—without explicit training.

"That is the crux of the discovery," Wasserman says. "Honestly, if it was only by brute force that the crows showed this learning, then it would have been an impressive result. But this feat was spontaneous."

Still the researchers acknowledge that the crows' relational matching behavior did not come without some background knowledge.

"Indeed, we believe that their earlier IMTS (identity matching-to-sample) training is likely to have enabled them to grasp a broadly applicable concept of sameness that could apply to novel two-item samples and test stimuli involving only relational sameness," the researchers wrote. "Just how that remarkable transfer is accomplished represents an intriguing matter for future study."

Anthony Wright, neurobiology and anatomy professor at the University of Texas-Houston Medical School, says the discovery ranks on par with demonstrations of tool use by some birds, including crows.

"Analogical reasoning, matching relations to relations, has been considered to be among the more so-called 'higher order' abstract reasoning processes," he says. "For decades such reasoning has been thought to be limited to humans and some great apes. The apparent spontaneity of this finding makes it all the more remarkable."

Joel Fagot, director of research at the University of Aix-Marseille in France, agrees the results shatter the notion that "sophisticated forms of cognition can only be found in our 'smart' human species. Accumulated evidence suggests that animals can do more than expected."

Wasserman concedes there will be skeptics and hopes the experiment will be repeated with more crows as well as other species. He suspects researchers will have more such surprises in store for science.

"We have always sold animals short," he says. "That human arrogance still permeates contemporary cognitive science."

Journal information: Current Biology

Provided by University of Iowa

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Health agencies scramble to prepare for new mpox strain

by Ariel Cohen, CQ-Roll Call

State and federal health agencies are gearing up to respond to a new strain of mpox—the virus formerly known as monkeypox—if the new strain spreads to the United States.

But this time, they are doing so with fewer resources.

Both an mpox public health emergency declaration and federal pandemic preparedness law were still in effect in 2022, the last time the U.S. faced a widespread mpox outbreak. That gave the federal government and state health departments more resources and flexibility than it has now to deal with an outbreak.

Last month, the World Health Organization declared a public health emergency of international concern, the highest alarm under international health law, over the new mpox strain. The strain, known as clade 1b, has been rapidly circulating in central Africa and has been detected in Sweden and Thailand.

The new strain differs from the 2022 world outbreak of the clade IIb mpox strain, which U.S. officials treated with two doses of the JYNNEOS mpox vaccine . Much like the COVID-19 vaccines, the mpox shot JYNNEOS prevents severe infection, hospitalization and death from mpox, but doesn't fully prevent transmission, according to the Centers for Disease Control and Prevention.

Clade 1b is endemic in the Democratic Republic of Congo, and the strain is more widespread than any other outbreak. Clade 1b usually causes a higher percentage of people with mpox to get severely sick and die, compared to clade IIb, according to the CDC.

While clade 1b has not yet been detected in the U.S., state and federal health officials are gearing up for what could be a potentially worse outbreak than in 2022 by leaning on the lessons it learned two years ago.

"It's a different ballgame than in 2022, in some ways that are better and in some ways that are TBD," Jen Kates, senior vice president and director of global health and HIV policy at KFF, said. She noted that public health jurisdictions today are already armed with mpox vaccines and treatments, unlike in 2022.

Budgeting for vaccines

The State Department says it's been preparing for clade 1b's emergence in the U.S. since December 2023 through increased monitoring of wastewater and other surveillance systems. But access to public health surveillance systems has waned since the COVID-19 public health emergency ended.

And the 2022 mpox public health emergency allowed the federal government to more easily free up resources to produce and distribute vaccines to high-risk groups at no cost.

The federal government ended the emergency declaration in 2023, but JYNNEOS vaccine maker Bavarian Nordic privatized the vaccine earlier this year. Now states must order it on the commercial market. State health officials said the budget is more of a concern now that vaccines are privatized.

Crystal La Tour Rambaud, the manager of the vaccine preventable disease program of the Pima County Health Department in Tucson, Ariz., said that between the mpox vaccine and the new RSV vaccine, costs are adding up.

"It's just added a lot onto the plate in just a couple years, where the budget hasn't changed significantly," La Tour Rambaud said.

As a result, the Pima County Health Department is reassessing whom they offer free vaccinations to, and in some cases, only offering free shots to the uninsured. Insured individuals can get vaccinated at commercial pharmacies, she said.

Under the current structure, those with public or private insurance can access the mpox shots without any cost barrier, because the CDC's vaccine advisory panel has recommended the vaccine.

But the only way uninsured adults can get the shot at no cost is if their jurisdiction has used federal funds to purchase the vaccines.

Raynard Washington, the director of the public health department in Mecklenburg, N.C., said the department has been able to use some of STD and HIV funds for mpox response, but are still stretched too thin.

The pandemic preparedness law expired in September 2023, but Congress extended seven provisions of that law via the March government funding bill until the end of 2024. This included policies to help activate personnel during a public health emergency, among others.

The CDC recommends health departments report all mpox cases to the CDC within 24 hours and promote vaccination in their communities. Under a declared public health emergency, the government can waive certain authorities to streamline disease reporting, sending funds to jurisdictions, for example.

Even though there is no public health emergency in effect now, Washington said that in Mecklenburg, "overall, the system is probably better prepared now than we were in 2022" because they've dealt with mpox before. Public health departments already have vaccines on the ground and people in the community who have been vaccinated.

The Mecklenburg health department is pushing for the reauthorization of the federal pandemic preparedness law as well as giving CDC the authority it needs to collect data, from both health care systems and laboratories so it could share that information to jurisdictions.

But because there is a new strain of mpox , it's possible they'll have to change their response.

"We might be starting back at ground zero again, depending on how this all plays out," Washington said.

2024 CQ-Roll Call, Inc., All Rights Reserved. Distributed by Tribune Content Agency, LLC.

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Mpox in South Africa: All you need to know about the disease and its prevention

The Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) Africa Hub, hosted by the SAMRC, has led discussions with key stakeholders and funders within the GloPID-R funders network. These discussions have primarily focused on gathering real-time information on the Mpox outbreak in the Democratic Republic of Congo (DRC) before the declaration as a public health emergency of concern. The results of these engagements led to an evidence briefing document compiled by GloPID-R Africa, alongside the Pandemic PACT programme, which was shared with the European & Developing Countries Clinical Trials Partnership (EDCTP) to guide funders on necessary interventions to curb the spread of Mpox.

“Through these strategic engagements, the SAMRC is better positioned to understand and address research priorities, with the Africa Hub playing a pivotal role in identifying gaps in the response to the outbreak,” says Dr Duduzile Ndwandwe, a Specialist Scientist leading the Vaccine Implementation and Pandemic Preparedness research at Cochrane South Africa, a research unit within the SAMRC.

Furthermore, Cochrane South Africa is also involved in an initiative to compile evidence with other partners on the continent. This evidence will support the National Immunisation Technical Advisory Groups (NITAGs) in making informed recommendations regarding the public health response and the introduction of vaccines across the African region.

“With these initiatives, the SAMRC is poised to ensure a coordinated and effective response to the Mpox outbreak, grounded in the latest scientific research and public health best practices. Our objective is to ensure that every individual has access to critical information necessary to curb the spread of this disease. While vigilance remains vital, it is equally important that we respond with calm, informed actions rather than succumbing to panic or misinformation," says Dr Ndwandwe.,

South Africa has reported 24 Mpox cases and three deaths as of 5 August 2024, with the majority of cases occurring between 8 May and 6 July 2024. The epidemiological profile of cases reported in South Africa mirrors those of the global MPXV clade II outbreak, primarily affecting young males. The Democratic Republic of the Congo (DRC) and other affected African countries are currently grappling with severe Mpox outbreaks, with the DRC having reported over 14,000 cases and 524 deaths. Currently, a total of 12 African countries have reported Mpox outbreaks this year, with nine experiencing active outbreaks.

The situation in the DRC is particularly concerning due to rapid human-to-human transmission, new modes of transmission, and the impact on vulnerable populations, including children under 15 years old who represent the majority of deaths.

In South Africa, Dr. Sandile Buthelezi, Director-General of Health, has established an Incident Management Team (IMT) focused on clinical interventions, surveillance, communication, and port health. National and provincial plans and budgets are being developed to coordinate an effective response.

The Africa Centres for Disease Control and Prevention (CDC) declared a public health emergency of continental security, marking the first time this declaration has been used. The declaration empowers the Africa CDC to coordinate the response and mobilise resources, including an Incident Management Team to support affected countries. The World Health Organization (WHO) also declared the Mpox outbreak a Public Health Emergency of International Concern (PHEIC), emphasising the need for a globally coordinated response. The WHO has developed a regional response plan, anticipating that $15 million is needed for surveillance, preparedness, and response. So far, $1.45 million has been released from the WHO Contingency Fund for Emergencies, with ongoing appeals for donor support.

The shortage of medical countermeasures remains a major concern, with Africa CDC calling for international solidarity.

The continent currently needs 10 million vaccines but only has 20,000. However, several initiatives are underway to support affected African countries, including a $10 million donation from USAID, along with 50,000 vaccines, a partnership agreement with the European Commission’s Health Emergency Preparedness and Response Authority (HERA) and Bavarian Nordic for 215,000 vaccine doses, and WHO’s Emergency Use Listing (EUL) process to increase vaccine access.

“While the situation is serious, Africa CDC and WHO maintain that there is no need for travel restrictions at this time. The focus remains on educating the public, ensuring access to vaccines, and coordinating a robust international response to contain the outbreak and prevent further spread,” says Dr Ndwandwe.

For more information:

• Mr Tendani Tsedu Head of Corporate and Marketing Communications: South African Medical Research Council Cell: 082 945 1980 e-mail: [email protected]  
• Dr Duduzile Ndwandwe Specialist Scientist: Cochrane South Africa Email: [email protected]

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