animal experiments monkeys

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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• Future Perfect

What can caged lab monkeys tell us about free human beings?

Where biomedicine gets it wrong about primate research.

by Garet Lahvis

A friend says they can always tell when you’re hungover. The way you close the cage latch. With so little to do, their attention can focus on those subtle differences in movement: the way it turns, whether it drops all or part of the way.

After easing the latch back open, the monkey climbs down to the concrete floor, past the rolling service station with its cotton swabs, boxes, bottles, and syringes.

Out in the hallway, two caretakers see him crouched against the cinderblock wall, hands pressed against the cream-colored paint, shoulders pulled up, head turned sideways and facing down the corridor, eyes toward them.

Over the past couple of years, experimentation on non-human primates has had a run of bad publicity. In 2020, media attention focused on a federal laboratory that studied the neurobiology of anxiety by scaring monkeys with toy snakes . In November, the US Justice Department indicted members of an alleged “primate smuggling ring” for trafficking and selling wild long-tailed macaques , an endangered species, to biomedical researchers in the US.

Around the same time, attention turned to the Livingstone Lab at Harvard University, where researchers sewed baby macaques’ eyelids shut to investigate how visual deprivation affects brain development. The controversy landed in Science magazine , where scientists debated the ethics of blinding monkeys. I was asked to weigh in. But my questions were different — less about the blinded macaques, and more about the controls staring at their cage walls.

For 16 years, I worked as a professor for medical schools in Wisconsin and Oregon. Both universities had primate centers. I knew about their operations, though I never experimented on primates. Instead, my laboratories mostly studied mice. Our goal was to identify the genetic and pollutant risk factors for autism, a disability that features challenges with social emotions. We never successfully identified any risk factors, but we did discover that mice enjoy one another’s company and have empathy for their pain.

After publishing more than 40 scientific papers, I left academia. In part, I left on principle. I believed that if we experimented on animals, we were obligated not to waste them. I also believed that biomedical scientists were obliged to consider the implications of our own discoveries — like how our animals were responding to their cage environments — so we could do better science. Eventually, I lost faith in the process. I also lost the stomach to confine sentient creatures to tiny cages.

Scientists know that the tight confinement of standard laboratory cages distorts the psychology and physiology of our animal subjects. Yet despite a half-century of evidence, we continue to cage them as if their biology is baked into their genetics. From decades of rodent studies, scientists know that an animal’s brain anatomy and physiology are highly vulnerable to even modest changes in their living environments. Mice housed in standard cages, rather than slightly larger ones furnished with blocks and tunnels for mental stimulation, are more susceptible to drug abuse, genetic modifications, and toxic chemicals. Monkeys, nearly our next of kin, can become so mentally deranged by their cage environments that they no longer resemble healthy humans. They might have more in common with children housed in Romanian orphanages in the 1980s and 1990s, who were so deprived of human contact that they still struggle with lifelong physiological and psychological disabilities .

Can we use mentally damaged animals to model mental health?

Primate experiments have undeniably aided the discovery of treatments for human disease, particularly vaccines and surgical techniques. More than a century ago, for example, scientists collected extracts from the spinal cord of a boy who died of polio, injected them into monkeys, studied how the infection spread, and then developed a vaccine that nearly eradicated polio. Much more recently, primate experiments were useful for developing a brain-spine interface that can restore the ability of people with paralysis to walk .

But these successes have been rare. Part of the problem lies in the question we now ask. Globally, scientists use approximately 100,000 non-human primates at any given time, often to explore highly nuanced questions, like finding risk factors and treatments for mental health challenges — autism, ADHD, schizophrenia, addiction, anxiety, depression, post-traumatic stress disorder. And here, we mostly fail. Most drugs showing extreme promise in animal studies fall short in human trials. We haven’t developed a new category of drugs for treating psychiatric illness in more than 50 years; new psychiatric drugs introduced over the same period have been modified versions of existing drugs.

Scientists also use primates to understand how human-like immune systems respond to infectious diseases — but, like mental health, immunity is also highly sensitive to how the monkeys feel inside their cages.

Housing for monkeys is tight. The standard cage for a rhesus macaque, a common laboratory primate, is about 2.5 feet across, narrow enough for its inhabitant to touch both walls at once. By contrast, their wild relatives can navigate home ranges averaging about 1.5 square miles. Macaques are built to navigate 740 American football fields’ worth of savannah grasslands and forest canopies. Yet inside biomedical labs, they typically get confined to the equivalent of a telephone booth .

Housing situations vary. Some live “singly housed” — a situation that resembles solitary confinement, often for a few months, sometimes for life. Others get “protected contact” — two monkeys separated by a grate that permits fingertips to touch. Others live as “buddies in a cage” — sharing the space of a shower stall until one buddy gets pulled out, often leaving the remaining one stressed and with a depressed immune system for weeks to months depending on his temperament (and, perhaps, how close he felt to his buddy).

In some respects, singly housed monkeys have it better than human inmates in solitary. For instance, they can more easily hear each other vocalize. Some have handheld mirrors to see their neighbors. Many have opportunities to rattle their squeeze bars, the metal poles fixed to the cage’s back walls, used to pull the monkeys forward for procedures like injections and blood draws. But while the United Nations considers more than 15 days of solitary confinement in humans to be torture, research monkeys often get a lifetime — especially if they lose it and assault their buddy in the cage. And although humans in solitary get time each day outside their cell, primates usually don’t get a break.

Studies show that human solitary confinement in prisons can cause depression, anxiety, paranoia, violent fantasies, full-blown panic attacks, hallucinations, psychosis, and schizophrenia. Some incarcerated people also self-mutilate, cutting their wrists and arms, ingesting foreign objects, self-burning, and reopening stitches from prior injuries. Physical symptoms include cardiovascular disease , migraine headaches, back pain, profound fatigue, and deterioration of eyesight.

Likewise, lab monkeys express behaviors that suggest psychological trauma. Among 362 singly housed rhesus monkeys, a study found that 89 percent expressed abnormal behavior. Most were what we call “stereotypies” — repetitive behaviors that serve no purpose, save coping. Some monkeys pace in circles. Others rock or bounce for hours, like idling engines. Some methodically somersault. Others incessantly rattle their squeeze bars. A few spend time in “eye salute,” a euphemism for self-stimulation by sticking fingers into one’s own eye.

My friend tells me he’s seen some monkeys cross the line of no return. Unresponsive to the caretakers interacting with them, they can’t stop rocking, twirling, circling, or twitching. They can’t pull away from the back of the cage. Their eyes no longer make contact.

Up to 15 percent of laboratory monkeys self-mutilate . They might pluck single hairs from their backsides until they turn bright pink, or bang their heads repeatedly against their cage walls, or bite themselves deep enough to require sutures. Unlike their wild brethren, caged macaques often paint the walls with their feces — a substance they can manipulate.

Nearly one-quarter of caged macaques express “floating limb” behaviors. Watch one for long enough and you might see his leg writhe or kick. He might grab his leg as it slowly elevates, seemingly out of control. It might hover behind his back. Or his foot might relentlessly smack the back of his head. He might respond by attacking his leg, as if it were foreign.

Scientists have normalized the idea that their caged primates are healthy

I suspect these behaviors are manifestations of an intolerable allostatic load : a “wear and tear on the body and brain resulting from chronic overactivity or inactivity of physiological systems that are normally involved in adaptation to environmental challenge.” Cramped living spaces deny primates the ability to act on their innate motivations: to seek pleasures, avoid discomforts, and explore complex and changing environments. Oysters don’t need these motivations because they can flourish cemented to a rock. For moving animals, motivations help us make decisions. An innate taste for sugar and salt prompts us to seek the calories and sodium we need to survive. When scientists remove the pleasure center of a rat brain, called the nucleus accumbens, they no longer eat .

Curiosity is also an innate drive. In the wild, animals feel compelled to investigate their environments — where to go, what to eat, with whom to interact — to know their options when their situations change. Scientists leverage an animal’s innate curiosity to study how memory works: Introduce a laboratory mouse to a novel object and a familiar one, and if the rodent remembers the object they encountered before, they’ll spend more time sniffing the unfamiliar one. Since the 1950s , scientists have known that monkeys will solve complex puzzles simply for the challenge of solving the task.

I suspect that, deprived of varied and ongoing challenges to overcome, environments to explore, or a natural range of body movements, caged monkeys — studied because they resemble us — go insane with boredom. Still, I’ve heard scientists insist that these animals are happier in cages because they get food, water, and safety from predators. They’ll tell you laboratory primates get “environmental enrichment,” like a rubber ball stuffed with a treat, a toy dangling from a cage door, a mirror to play with, or snacks scattered on the cage floor. I suppose they get exercise, too. For glutes and biceps, they can rock back and forth or rattle their cage doors. For a cardio workout, they can pace in circles or slam themselves against the cage walls.

Here’s the rub. Scientists must believe that lab animals thrive physically and mentally — not for animal welfare reasons, but to justify our experiments. We need healthy controls, not psychologically broken ones, to benchmark our disease models. And we need the animals used as disease models to be otherwise healthy because we lack the scientific capacity to separate the biology of a nuanced disorder, like autism or ADHD, from confounding factors like the mental damage caused by incarceration.

My qualm with the Livingstone Lab’s experiment, the one that entailed sewing baby monkeys’ eyelids shut, is not primarily ethical but scientific. They claimed that by blinding monkeys, they could gain “insight into evolutionary changes in the functional organization of high-level visual cortex.” But they wrongly presumed that their “healthy” control monkeys, who were denied most visual stimulation save the depleted sensory environment of a steel-gray cage, had normal visual functioning.

By describing what they’re studying as “evolutionary changes,” the researchers lured us into believing the ridiculous — that brain development behind steel bars is not only normal but natural enough to be relevant to evolutionary changes occurring outside the lab. Yet their monkeys experienced no full spectrum of color, no natural movement like the rustling of leaves, and no passing landscape. Like most other primate experimenters, the lab normalized the idea that monkeys naturally live inside telephone booths, not in the vast, dynamic, and aesthetically complex expanses of nature.

What bothers me most is that the scientific community expresses so little concern about whether we’re chasing artifacts of confinement. And for the few of us who ask, the answer is loud with silence.

Can we do better?

Admittedly, scientists are in a fix. Our problem might have begun during the late Middle Ages, about 800 years ago, when Italian philosopher and theologian Thomas Aquinas argued that because animals lacked “rational souls,” they were like machines. Centuries later, René Descartes, a father of modern science, called animals automata , robots driven by reflexes, without thoughts or feelings — like the mechanical men of his era, built to hammer the bells of village clock towers. Armed with this philosophy, scientists tacked dogs to walls and opened them up without anesthesia to learn that the heart, not the liver, pumped blood. Their shrieks and howls were thought of as if they were bells ringing on the hour.

The cruel irony is that the ethical justification for experimenting on animals — that they lack subjective experiences — allowed us to find cogent evidence that they do. Now we’re forced to ignore what we’ve learned from science — so that we can keep doing it.

Rather than envision a new paradigm, scientists have devised arguments to keep things the same, claiming, for example, that we need small cages to control for confounding variables in an animal’s environment. But we routinely accept the inescapable variables inside their confines — sound, lighting, food quality, social situations — that are either impossible or too inconvenient to control. In truth, we use small cages because they afford the cheapest and most convenient way to generate scientific publications.

What could scientists do differently? We could pivot to more helpful alternatives. We could deploy spatially and temporally complex spaces to study smaller organisms under conditions where they might thrive like the free human beings they are meant to resemble. Mice and rats could live in small research barns with varied food and shelter options and penned-in outdoor access, where they could author their own experiences and meet ongoing and unpredictable challenges . Zebrafish, snails, and fruit flies could also get environments complex enough to operate as they might in the wild. Remote technologies could help deliver various drugs and biomolecules to moving animals and help us monitor their responses.

Biomedical research institutions could double down on financially neglected health research programs, like disease prevention. We could expand monitoring of human and wildlife populations for elevated pockets of disease — like cancer, congenital disorders, and mental illness — arising from our exposures to thousands of pesticides and industrial contaminants.

Present-day concerns over “forever chemicals” in our food and drinking water , and the enormous price tag we now face for cleanup, could have been predicted and more easily remediated decades ago, when epidemiologists and chemists found evidence of their presence in humans and wildlife. The elevated prevalence of congenital disorders, endocrine disruption, immune dysfunction, and mental illness found in fish-eating wildlife in pollutant hot spots around the Great Lakes and along the US coasts could be used to identify regional exposures to chemical mixtures that also threaten human health. Why not focus on these issues ? With advanced epidemiological computer modeling, and gene sequencing tools, along with high-efficiency cell culture systems that can test multiple chemicals at a time without the use of animals, we could identify harmful compounds, then remove them. The potential is far greater than whatever we might learn from using rubber snakes to scare mentally enfeebled monkeys.

Many people believe that science differs from blind faith. If that’s true, I wonder how many more rabbit holes we’ll plumb before we see that cage-deteriorated primates don’t resemble free human beings. Perhaps scientists collectively disregard animal subjectivity out of fear of the moral implications of experimenting on other sentient creatures. Or are we blinded by our ambitions for careers and legacies? No matter the cause, we have obligations to the societal trust placed in us. And if we’re 1,000 years overdue for a paradigm shift, let’s hope that today’s young scientists can find the unfettered clarity of sight to make it happen.

The fugitive still cowers in the main hall, cheek and chest pressed against the cinderblock, eyes looking upward, seemingly fixed on the audible ballast of the fluorescent lights. Or the fly circling, then resting, beneath it. He might hear the buzz of both, one against the other, a two-tone that cannot calm the anxiety of being outside that room. Having known only metal walls and the fetid mire of idling bodies, he lacks familiarity with concrete surfaces, unfouled air, and the taking of risks.

The protocol is straightforward. Face the escapee, chest out, shoulders straight, eyes toward his. Wedge open the colony room door. Use push brooms to coax him back into his cage.

The convict returns. They close his cage door. He pivots, then grabs the bars of the door as if he’s now the master, then shakes them violently like he’s trying to get out. He’ll be studied over and over again because he somehow represents us. Maybe he does.

Garet Lahvis was an associate professor and the graduate program director of behavioral neuroscience at Oregon Health and Science University. He is currently writing a book for the University of Chicago Press on his experiences with the limits of science, and of the scientific community, in addressing some of our most pressing biomedical issues. Follow him on X (formerly Twitter) at @GLahvis .

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Our fight against expanded use of monkeys in research heats up

We’re pushing back hard against plans to fund expanded reliance on monkeys in experiments in the U.S., plans that would see even more of these intelligent, curious animals used in outdated and unreliable tests, often at taxpayer expense.   

Instead, we’ve advocated for broader investments in technologically-advanced methods that don’t use live animals and can tell us more about how the human body works—instead of attempting to translate the results of animal experiments to humans.  

The drive to breed, procure and use more monkeys is one of the most alarming trends in contemporary biomedical research . It’s something our colleagues have investigated and it’s something we’re focused on in the public policy arena. In February, we told you about a proposed monkey breeding facility in the small town of Bainbridge, Georgia that, if built, would house up to 30,000 long-tailed macaques, most of whom would be shipped to laboratories to be used in experiments. Thankfully, that proposal is now on hold pending legal action . After we asked Georgia residents to join local citizens and animal advocates in speaking out against the facility, the Development Authority of Bainbridge and Decatur County voted to revoke its approval of a key step for the project and the Decatur County Commission disavowed its approval of terms of the deal, which included $300 million in revenue bonds . 

In response, Safer Human Medicine, the company behind the proposed facility, has said it intends to move forward with the project and has filed a motion seeking a preliminary injunction in the matter. Some Bainbridge residents are suing city and county authorities regarding the process that led to the facility being approved. And for our part, we’re preparing to oppose this and any future such proposals.  

This is a battle we’re also waging in the nation’s capital, and in good news, with the help of more than 60,000 supporters who contacted their legislators, we helped ensure that $30 million in taxpayer dollars specifically designated for expanding the use of monkeys in research and testing was not included in the final funding bill for fiscal year 2024, passed by Congress and signed into law by President Biden on March 23. Even better, the package included increased funding and directives designed to advance non-animal methods and reduce animal testing .   

That said, our fight to move away from experiments on monkeys and other animals is far from over. Congress is considering a request from the National Institutes of Health to include $10 million in taxpayer dollars in the federal budget for fiscal year 2025 to increase breeding and experiments on monkeys above and beyond the millions of dollars already spent on these experiments each year. We need your help to keep the momentum going and stop this second funding request . And we need to do so right away.

Monkeys have historically been used in experiments with the hope of improving human health and safety. But animal testing not only causes immense suffering for animals in laboratories—it also hinders advances in human healthcare. Animal experiments will never be able to accurately tell us what we need to know about the human body, animals often do not have the same diseases as human beings and they do not respond to drugs the same way as we humans do. We’re confident that by continuing to push for replacing monkeys in experiments with sophisticated methods based on human biology, using human cells, tissues and data from humans, we’ll ultimately save not just animal lives, but human lives as well. 

Sara Amundson is president of the Humane Society Legislative Fund. 

Taking Suffering Out of Science

About the author

Kitty Block is President and CEO of the Humane Society of the United States and CEO of Humane Society International, the international affiliate of the HSUS

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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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These 1950s experiments showed us the trauma of parent-child separation. Now experts say they’re too unethical to repeat—even on monkeys.

By Eleanor Cummins

Posted on Jun 22, 2018 7:00 PM EDT

John Gluck’s excitement about studying parent-child separation quickly soured. He’d been thrilled to arrive at the University of Wisconsin at Madison in the late 1960s, his spot in the lab of renowned behavioral psychologist Harry Harlow secure. Harlow had cemented his legacy more than a decade earlier when his experiments showed the devastating effects of broken parent-child bonds in rhesus monkeys. As a graduate student researcher, Gluck would use Harlow’s monkey colony to study the impact of such disruption on intellectual ability.

Gluck found academic success, and stayed in touch with Harlow long after graduation. His mentor even sent Gluck monkeys to use in his own laboratory. But in the three years Gluck spent with Harlow—and the subsequent three decades he spent as a leading animal researcher in his own right—his concern for the well-being of his former test subjects overshadowed his enthusiasm for animal research.

Separating parent and child, he’d decided, produced effects too cruel to inflict on monkeys.

Since the 1990s, Gluck’s focus has been on bioethics; he’s written research papers and even a book about the ramifications of conducting research on primates. Along the way, he has argued that continued lab experiments testing the effects of separation on monkeys are unethical. Many of his peers, from biology to psychology, agree. And while the rationale for discontinuing such testing has many factors, one reason stands out. The fundamental questions we had about parent-child separation, Gluck says, were answered long ago.

The first insights into attachment theory began with studious observations on the part of clinicians.

Starting in the 1910s and peaking in the 1930s, doctors and psychologists actively advised parents against hugging , kissing, or cuddling children on the assumption such fawning attention would condition children to behave in a manner that was weak, codependent, and unbecoming. This theory of “behaviorism” was derived from research like Ivan Pavlov’s classical conditioning research on dogs and the work of Harvard psychologist B.F. Skinner , who believed free will to be an illusion. Applied in the context of the family unit, this research seemed to suggest that forceful detachment on the part of ma and pa were essential ingredients in creating a strong, independent future adult. Parents were simply there to provide structure and essentials like food.

But after the end of World War II, doctors began to push back. In 1946, Dr. Benjamin Spock (no relation to Dr. Spock of Star Trek ) authored Baby and Child Care, the international bestseller, which sold 50 million copies in Spock’s lifetime. The book, which was based on his professional observation of parent-child relationships, advised against the behaviorist theories of the day. Instead, Spock implored parents to see their children as individuals in need of customized care—and plenty of physical affection.

At the same time, the British psychiatrist John Bowlby was commissioned to write the World Health Organization’s Maternal Care and Mental Health report. Bowlby had gained renowned before the war for his systematic study of the effects of institutionalization on children, from long-term hospital stays to childhoods confined to orphanages.

Published in 1951, Bowlby’s lengthy two-part document focused on the mental health of homeless children. In it, he brought together anecdotal reports and descriptive statistics to paint a portrait of the disastrous effects of the separation of children from their caretakers and the consequences of “deprivation” on both the body and mind. “Partial deprivation brings in its train acute anxiety, excessive need for love, powerful feelings of revenge, and, arising from these last, guilt and depression,” Bowlby wrote. Like Spock, this research countered behaviorist theories that structure and sustenance were all a child needed. Orphans were certainly fed, but in most cases they lacked love. The consequences, Bowlby argued, were dire—and long-lasting.

The evidence of the near-sanctity of parent-child attachment was growing thanks to the careful observation of experts like Spock and Bowlby. Still, many experts felt one crucial piece of evidence was missing: experimental data. Since the Enlightenment, scientists have worked to refine their methodology in the hopes of producing the most robust observations about the natural world. In the late 1800s, randomized, controlled trials were developed and in the 20th century came to be seen as the “gold standard” for research —a conviction that more or less continues to this day.

While Bowlby had clinically-derived data, he knew to advance his ideas in the wider world he would need data from a lab . But by 1947, the scientific establishment required informed consent for research participants (though notable cases like the Tuskegee syphilis study violated such rules into at least the 1970s). As a result, no one would condone forcibly separating parents and children for research purposes. Fortunately, Bowlby’s transatlantic correspondent, Harry Harlow, had another idea.

Over the course of his career, Harlow conducted countless studies of primate behavior and published more than 300 research papers and books. Unsurprisingly, in a 2002 ranking the impact of 20th century psychologists , the American Psychological Association named him the 26th most cited researcher of the era, below B.F. Skinner (1), but above Noam Chomsky (38). But the (ethically-fraught) experiments that cemented his status in Psychology 101 textbooks for good began in earnest only in the 1950s.

Around the time Bowlby published WHO report, Harlow began to push the psychological limits of monkeys in myriad ways—all in the name of science. He surgically altered their brains or beamed radiation through their skulls to cause lesions, and then watched the neurological effect, according to a 1997 paper by Gluck that spans history, biography, and ethics. He forced some animals to live in a “deep, wedge-shaped, stainless steel chambers… graphically called the ‘pit of despair'” in order to study the effect of such solitary confinement on the mind, Gluck wrote. But Harlow’s most well-known study, begun in the 1950s and carefully documented in pictures and videos made available to the public, centered around milk.

To test the truth of the behaviorist’s claims that things like food mattered more than affection, Harlow set up an experiment that allowed baby monkeys, forcibly separated from their mothers at birth, to choose between two fake surrogates. One known as the “iron maiden” was made only of wire, but had bottles full of milk protruding from its metal chest. The other was covered in a soft cloth, but entirely devoid of food. If behaviorists were right, babies should choose the surrogate who offered them food over the surrogate who offered them nothing but comfort.

As Spock or Bowlby may have predicted, this was far from the case.

“Results demonstrated that the monkeys overwhelmingly preferred to maintain physical contact with the soft mothers,” Gluck wrote. “It also was shown that the monkeys seemed to derive a form of emotional security by the very presence of the soft surrogate that lasted for years, and they ‘screamed their distress’ in ‘abject terror’ when the surrogate mothers were removed from them.” They visited the iron maiden when they were too hungry to avoid her metallic frame any longer.

As anyone in behavioral psychology will tell you, Harlow’s monkey studies are still considered foundational for the field of parent-child research to this day. But his work is not without controversy. In fact, it never has been. Even when Harlow was conducting his research, some of his peers criticized the experiments , which they considered to be cruel to the animal and degrading to the scientists who executed them. The chorus of dissenting voices is not new; it’s merely grown.

Animal research today is more carefully regulated by individual institutions, professional organizations like the American Psychological Association and legislation like the Federal Animal Welfare Act. Many activists and scholars argue research on primates should end entirely and that experiments like Harlow’s should never be repeated. “Academics should be on the front lines of condemning such work as well, for they represent a betrayal of the basic notions of dignity and decency we should all be upholding in our research, especially in the case of vulnerable populations in our samples—such as helpless animals or young children,” psychologist Azadeh Aalai wrote in Psychology Today .

Animal studies have not disappeared. Research on attachment in monkeys continues at the University of Wisconsin at Madison . But animal studies have declined. New methods—or, depending on how you look at it, old methods—have filled the void. Natural experiments and epidemiological studies, similar to the kind Bowlby employed, have added new insight into the importance of “tender age” attachment .

Romanian orphanages established after the fall of the Soviet Union have served as such a study site. The facilities, which have been described as “slaughterhouses of the soul” , have historically had great disparities between the number of children and the number of caregivers (25 or more kids to one adult), meaning few if any children received the physical or emotional care they needed. Many of the children who were raised in these environments have exhibited mental health and behavioral disorders as a result. It’s even had a physical effect, with neurological research showing a dramatic reduction in the literal size of their brains and low levels of brain activity as measured by electroencephalography, or EEG, machines.

Similarly, epidemiological research has tracked the trajectories of children in the foster care system in the United States and parts of Europe to see how they differ, on average, from youths in a more traditional home environment. They’ve shown that the risk of mental disorders , suicidal ideation and attempts , and obesity are elevated among these children. Many of these health outcomes appear to be even worse among children in an institutional setting , like a Romanian orphanage, than children placed in foster care, which typically offers kids more individualized attention.

Scientists rarely say no to more data. After all, the more observations and perspectives we have, the better we understand a given topic. But alternatives to animal models are under development and epidemiological methodologies are only growing stronger. As a result, we may be able to set some kinds of data—that data collected at the expense of humans or animal —aside.

When it comes to lab experiments on parent-child attachment, we may know everything we need to know—and have for more than 60 years. Gluck believes that testing attachment theory at the expense of primates should have ended with Harry Harlow. And he continues to hope people will come to see the irony inherent in harming animals to prove, scientifically, that human children deserve compassion.

“Whether it is called mother-infant separation, social deprivation, or the more pleasant sounding ‘nursery rearing,'” Gluck wrote in a New York Times op-ed in 2016, “these manipulations cause such drastic damage across many behavioral and physiological systems that the work should not be repeated.”

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• 09 November 2023

This hybrid baby monkey is made of cells from two embryos

• Carissa Wong

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Scientists have produced an infant ‘chimeric’ monkey by injecting a monkey embryo with stem cells from a genetically distinct donor embryo 1 . The resulting animal is the first live-born chimeric primate to have a high proportion of cells originating from donor stem cells.

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Cao, J. et al. Cell https://doi.org/10.1016/j.cell.2023.10.005 (2023).

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Harvard study on monkeys reignites ethical debate over animal testing

Updated on: November 21, 2022 / 12:54 PM EST / CBS/AFP

Mother monkeys permanently separated from their newborns sometimes find comfort in plush toys; this recent finding from Harvard experiments has set off intense controversy among scientists and reignited the ethical debate over animal testing.

The paper, "Triggers for mother love," was authored by neuroscientist Margaret Livingstone and appeared in the Proceedings of the National Academy of Sciences (PNAS) in September to little fanfare or media coverage.

But once news of the study began spreading on social media, it provoked a firestorm of criticism and eventually a letter to PNAS signed by over 250 scientists calling for a retraction.

Animal rights groups meanwhile recalled Livingstone's past work, which included temporarily suturing shut the eyelids of infant monkeys in order to study the impact on their cognition.

"We cannot ask monkeys for consent, but we can stop using, publishing, and in this case actively promoting cruel methods that knowingly cause extreme distress," wrote Catherine Hobaiter, a primatologist at the University of St. Andrews, who co-authored the retraction letter.

Hobaiter told AFP she was awaiting a response from the journal before further comment, but expected news soon.

Harvard and Livingstone, for their part, have strongly defended the research.

Livingstone's observations "can help scientists understand maternal bonding in humans and can inform comforting interventions to help women cope with loss in the immediate aftermath of suffering a miscarriage or experiencing a still birth," said Harvard Medical School in a statement .

The school added it was "deeply concerned about the personal attacks directed at scientists who conduct critically important research for the benefit of humanity."

Livingstone, in a separate statement , said: "I have joined the ranks of scientists targeted and demonized by opponents of animal research, who seek to abolish lifesaving research in all animals."

Such work routinely attracts the ire of groups such as People for the Ethical Treatment of Animals (PETA), which opposes all forms of animal testing.

In its statement, Harvard Medical School said PETA had published content regarding the study on its website that was "misleading and contains factual inaccuracies."

This controversy has notably provoked strong responses in the scientific community, particularly from animal behavior researchers and primatologists, said Alan McElligot of the City University of Hong Kong's Centre for Animal Health and a co-signer of the PNAS letter.

He told AFP that Livingstone appears to have replicated research performed by Harry Harlow, a notorious American psychologist, from the mid-20th century.

Harlow's experiments on maternal deprivation in rhesus macaques were considered groundbreaking, but may have also helped catalyze the early animal liberation movement.

"It just ignored all of the literature that we already have on attachment theory," added Holly Root-Gutteridge, an animal behavior scientist at the University of Lincoln in Britain.

McElligot and Root-Gutteridge argue the case was emblematic of a wider problem in animal research, in which questionable studies and papers continue to pass institutional reviews and are published in high impact journals.

McElligot pointed to a much-critiqued 2020 paper extolling the efficiency of foot snares to capture jaguars and cougars for scientific study in Brazil.

More recently, experiments on marmosets that included invasive surgeries have attracted controversy.

The University of Massachusetts Amherst team behind the work says studying the tiny monkeys, which have 10-year lifespans and experience cognitive decline in their old age, are essential to better understand Alzheimer's in people.

Opponents argue results rarely translate across species.

When it comes to testing drugs, there is evidence the tide is turning against animal trials.

In September, the Senate passed the bipartisan FDA Modernization Act, which would end a requirement that experimental medicines first be tested on animals before any human trials.

The vast majority of drugs that pass animal tests fail in human trials, while new technologies such as tissue cultures, mini organs and AI models are also reducing the need for live animals.

Opponents also say the vast sums of money that flow from government grants to universities and other institutes — $15 billion annually, according to watchdog group White Coat Waste — perpetuate a system in which animals are viewed as lab resources.

"The animal experimenters are the rainmaker within the institutions, because they're bringing in more money," said primatologist Lisa Engel-Jones, who worked as a lab researcher for three decades but now opposes the practice and is a science adviser for PETA.

"There's financial incentive to keep doing what you've been doing and just look for any way you can to get more papers published, because that means more funding and more job security," added Emily Trunnel, a neuroscientist who experimented on rodents and also now works for PETA.

Most scientists do not share PETA's absolutist stance, but instead say they adhere to the "three Rs" framework — refine, replace and reduce animal use.

On Livingstone's experiment, Root-Gutteridge said the underlying questions might have been studied on wild macaques who naturally lost their young, and urged neuroscientists to team up with animal behaviorists to find ways to minimize harm.

"Do I wish we lived in a world where generating this important knowledge were possible without the use of lab animals? Of course!" Livingstone said in her statement . "Alas, we are not there yet."

• Harvard Medical School

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The Silver Spring Monkeys: The Case That Launched PETA

In the summer of 1981, PETA’s founder, Ingrid Newkirk , leafed through the pages of the U.S. Department of Agriculture’s list of laboratories, picked the closest one, and asked her colleague, Alex, to see if he could get inside. He did and began working as a volunteer at the  Institute for Behavioral Research  (IBR). IBR was a federally funded laboratory in Silver Spring, Maryland, now closed down for reasons that will soon become apparent. It was run out of a warehouse by psychologist and animal experimenter Edward Taub, a man with no medical training. There, we found 17 monkeys living in tiny rusty wire cages caked with years of accumulated feces in a dungeon-like room. There was no veterinarian to tend to their serious wounds, and they had a lot of them.

Taub, who also had no veterinary training, nevertheless subjected the monkeys to surgeries in which he severed their spinal nerves, rendering one or more of their limbs useless. By means of electric shock, food deprivation, and other cruel methods, he forced them to try to regain the use of their impaired limbs to pick up raisins from a tray—or else go without food. In one experiment, monkeys were shut inside a converted refrigerator and repeatedly electro-shocked until they finally used their disabled arm, if they could. The inside of the refrigerator was covered with blood. In another experiment, monkeys were strapped into a crude restraint chair—their waist, ankles, wrists, and neck held in place with packing tape—and pliers were latched as tightly as possible onto their skin, including on their testicles.

The trauma of the monkeys’ imprisonment and treatment was so severe that many of them had ripped at their own flesh, and they had lost many of their fingers from catching them in the rusted, jagged cage bars. Workers often neglected to feed the monkeys, and the animals would desperately pick through the stinking urine and fecal waste in trays beneath their cages to find something to eat.

PETA gathered meticulous log notes detailing what was happening inside IBR and secretly photographed the crippled monkeys and their horrendous living conditions. Then, after lining up expert witnesses and showing them around the laboratory at night, PETA took the evidence to the police—and an intense, decade-long battle for custody of the monkeys ensued.

This groundbreaking investigation led to the nation’s first arrest and criminal conviction of an animal experimenter for cruelty to animals, the first confiscation of abused animals from a laboratory, and the first U.S. Supreme Court victory for animals used in experiments. It even led to landmark additions to the Animal Welfare Act—and unrelenting public scrutiny of the abuse that animals endure in experimentation . And IBR closed its doors.

PETA has scored many victories for animals in laboratories since the landmark Silver Spring monkeys case, but tragically, experiments like this still go on. You can help by asking your congressional representatives to divert public money from cruel animal experiments into promising, lifesaving, and relevant clinical and non-animal research.

urge your member of the Legislative Assembly to support a provincewide ban on glue traps!

Please e-mail the owner of Mysterious Circus, William Jaramillo, and politely ask that the circus end its cruel animal acts and focus on the talents of willing human performers instead.

Urge your senator to support S.4810!

As it’s written, House Bill 8467 would support the dying fur industry in the U.S. We need you to help get it killed!

Next week, delegates at the Union of BC Municipalities convention in Vancouver, British Columbia, will be voting on a resolution asking the provincial government to ban the use, sale, and distribution of cruel glue traps, which kill, injure, and permanently disable countless small animals every year. We need your help to get this historic resolution … Read more »

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“Almost all of us grew up eating meat, wearing leather, and going to circuses and zoos. We never considered the impact of these actions on the animals involved. For whatever reason, you are now asking the question: Why should animals have rights? ”

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What is animal testing?

An introduction to animal experiments

What are animal experiments?

An animal test is any scientific experiment or test in which a live animal is forced to undergo something that is likely to cause them pain, suffering, distress or lasting harm. 

Animal experiments are not the same as taking your companion animal to the vet. Animals used in laboratories are deliberately harmed, not for their own good, and are usually killed at the end of the experiment.

Animal experiments include:

• injecting or force feeding animals with potentially harmful substances
• surgically removing animals’ organs or tissues to deliberately cause damage
• forcing animals to inhale toxic gases
• subjecting animals to frightening situations to create anxiety and depression.

Some experiments require the animal to die as part of the test. For example, regulatory tests for botox, vaccines and some tests for chemical safety are essentially variations of the cruel Lethal Dose 50 test in which 50% of the animals die or are killed just before the point of death.

Which animals are used?

A surprisingly, large range of animal species are regularly used in experiments, including wild animals.

Only vertebrate animals (mammals, birds, fish and amphibians) and some invertebrates such as octopuses are defined as “animals” by European legislation governing animal experiments.  Shockingly, in the USA rats, mice, fish, amphibians and birds are not defined as animals under animal experiment regulations. That means no legal permission to experiment on them is needed and they are not included in any statistics.

Animals used in experiments are usually bred for this purpose by the laboratory or in breeding facilities. It’s a cruel, multi-million dollar industry. We believe that all animals are equally important. A dog bred for research is still a dog who could otherwise live a happy life in a loving home.

Some monkeys are still trapped in the wild in Africa, Asia and South America to be used in experiments or imprisoned in breeding facilities. Their children are exported to laboratories around the world. The use of wild-caught monkeys in experiments is generally banned in Europe but is allowed elsewhere.

Horses and other animals such as cows, sheep and pigs are often supplied by dealers and may originate from racing stables or farms for use in animal experiments. The rules preventing the use of stray companion animals like dogs and cats vary from country to country.

Wild animals can be used in trapping and monitoring experiments in the wild, or they may be captured and brought into a laboratory setting for more invasive research, sometimes in the name of conservation.

What are laboratories like?

Laboratories are no place for any animal. They are typically sterile, indoor environments in which the animals are forced to live in cages, pens or Perspex boxes – denied complete freedom of movement and control over their lives. Some animals in laboratories are confined on their own, without the companionship of others.

Our investigations show time and time again that, despite claims by the animal research community, life inside a laboratory is no life at all.

The science relating to animal experiments can be extremely complicated and views often differ. What appears on this website represents Cruelty Free International expert opinion, based on a thorough assessment of the evidence.

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• v.63(2 Suppl 3); 2022 Jun

Ethical considerations regarding animal experimentation

Aysha karim kiani.

1 Allama Iqbal Open University, Islamabad, Pakistan

2 MAGI EUREGIO, Bolzano, Italy

DEREK PHEBY

3 Society and Health, Buckinghamshire New University, High Wycombe, UK

GARY HENEHAN

4 School of Food Science and Environmental Health, Technological University of Dublin, Dublin, Ireland

RICHARD BROWN

5 Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada

PAUL SIEVING

6 Department of Ophthalmology, Center for Ocular Regenerative Therapy, School of Medicine, University of California at Davis, Sacramento, CA, USA

PETER SYKORA

7 Department of Philosophy and Applied Philosophy, University of St. Cyril and Methodius, Trnava, Slovakia

ROBERT MARKS

8 Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel

BENEDETTO FALSINI

9 Institute of Ophthalmology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy

NATALE CAPODICASA

10 MAGI BALKANS, Tirana, Albania

STANISLAV MIERTUS

11 Department of Biotechnology, University of SS. Cyril and Methodius, Trnava, Slovakia

12 International Centre for Applied Research and Sustainable Technology, Bratislava, Slovakia

LORENZO LORUSSO

13 UOC Neurology and Stroke Unit, ASST Lecco, Merate, Italy

DANIELE DONDOSSOLA

14 Center for Preclincal Research and General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca‘ Granda Ospedale Maggiore Policlinico, Milan, Italy

15 Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

GIANLUCA MARTINO TARTAGLIA

16 Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy

17 UOC Maxillo-Facial Surgery and Dentistry, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy

MAHMUT CERKEZ ERGOREN

18 Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Cyprus

MUNIS DUNDAR

19 Department of Medical Genetics, Erciyes University Medical Faculty, Kayseri, Turkey

SANDRO MICHELINI

20 Vascular Diagnostics and Rehabilitation Service, Marino Hospital, ASL Roma 6, Marino, Italy

DANIELE MALACARNE

21 MAGI’S LAB, Rovereto (TN), Italy

GABRIELE BONETTI

Astrit dautaj, kevin donato, maria chiara medori, tommaso beccari.

22 Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy

MICHELE SAMAJA

23 MAGI GROUP, San Felice del Benaco (BS), Italy

STEPHEN THADDEUS CONNELLY

24 San Francisco Veterans Affairs Health Care System, University of California, San Francisco, CA, USA

DONALD MARTIN

25 Univ. Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, SyNaBi, Grenoble, France

ASSUNTA MORRESI

26 Department of Chemistry, Biology and Biotechnology, University of Perugia, Perugia, Italy

ARIOLA BACU

27 Department of Biotechnology, University of Tirana, Tirana, Albania

KAREN L. HERBST

28 Total Lipedema Care, Beverly Hills California and Tucson Arizona, USA

MYKHAYLO KAPUSTIN

29 Federation of the Jewish Communities of Slovakia

LIBORIO STUPPIA

30 Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, University "G. d'Annunzio", Chieti, Italy

LUDOVICA LUMER

31 Department of Anatomy and Developmental Biology, University College London, London, UK

GIAMPIETRO FARRONATO

Matteo bertelli.

32 MAGISNAT, Peachtree Corners (GA), USA

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees’ adoption of the ‘four Rs’ principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.

How to cite this article: Kiani AK, Pheby D, Henehan G, Brown R, Sieving P, Sykora P, Marks R, Falsini B, Capodicasa N, Miertus S, Lorusso L, Dondossola D, Tartaglia GM, Ergoren MC, Dundar M, Michelini S, Malacarne D, Bonetti G, Dautaj A, Donato K, Medori MC, Beccari T, Samaja M, Connelly ST, Martin D, Morresi A, Bacu A, Herbst KL, Kapustin M, Stuppia L, Lumer L, Farronato G, Bertelli M. Ethical considerations regarding animal experimentation. J Prev Med Hyg 2022;63(suppl.3):E255-E266. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2768

Introduction

Animal model-based research has been performed for a very long time. Ever since the 5 th century B.C., reports of experiments involving animals have been documented, but an increase in the frequency of their utilization has been observed since the 19 th century [ 1 ]. Most institutions for medical research around the world use non-human animals as experimental subjects [ 2 ]. Such animals might be used for research experimentations to gain a better understanding of human diseases or for exploring potential treatment options [ 2 ]. Even those animals that are evolutionarily quite distant from humans, such as Drosophila melanogaster , Zebrafish ( Danio rerio ) and Caenorhabditis elegans , share physiological and genetic similarities with human beings [ 2 ]; therefore animal experimentation can be of great help for the advancement of medical science [ 2 ].

For animal experimentation, the major assumption is that the animal research will be of benefit to humans. There are many reasons that highlight the significance of animal use in biomedical research. One of the major reasons is that animals and humans share the same biological processes. In addition, vertebrates have many anatomical similarities (all vertebrates have lungs, a heart, kidneys, liver and other organs) [ 3 ]. Therefore, these similarities make certain animals more suitable for experiments and for providing basic training to young researchers and students in different fields of biological and biomedical sciences [ 3 ]. Certain animals are susceptible to various health problems that are similar to human diseases such as diabetes, cancer and heart disease [ 4 ]. Furthermore, there are genetically modified animals that are used to obtain pathological phenotypes [ 5 ]. A significant benefit of animal experimentation is that test species can be chosen that have a much shorter life cycle than humans. Therefore, animal models can be studied throughout their life span and for several successive generations, an essential element for the understanding of disease progression along with its interaction with the whole organism throughout its lifetime [ 6 ].

Animal models often play a critical role in helping researchers who are exploring the efficacy and safety of potential medical treatments and drugs. They help to identify any dangerous or undesired side effects, such as birth defects, infertility, toxicity, liver damage or any potential carcinogenic effects [ 7 ]. Currently, U.S. Federal law, for example, requires that non-human animal research is used to demonstrate the efficacy and safety of any new treatment options before proceeding to trials on humans [ 8 ]. Of course, it is not only humans benefit from this research and testing, since many of the drugs and treatments that are developed for humans are routinely used in veterinary clinics, which help animals live longer and healthier lives [ 4 ].

COVID-19 AND THE NEED FOR ANIMAL MODELS

When COVID-19 struck, there was a desperate need for research on the disease, its effects on the brain and body and on the development of new treatments for patients with the disease. Early in the disease it was noticed that those with the disease suffered a loss of smell and taste, as well as neurological and psychiatric symptoms, some of which lasted long after the patients had “survived” the disease [ 9-15 ]. As soon as the pandemic started, there was a search for appropriate animal models in which to study this unknown disease [ 16 , 17 ]. While genetically modified mice and rats are the basic animal models for neurological and immunological research [ 18 , 19 ] the need to understand COVID-19 led to a range of animal models; from fruit flies [ 20 ] and Zebrafish [ 21 ] to large mammals [ 22 , 23 ] and primates [ 24 , 25 ]. And it was just not one animal model that was needed, but many, because different aspects of the disease are best studied in different animal models [ 16 , 25 , 26 ]. There is also a need to study the transmission pathways of the zoonosis: where does it come from, what are the animal hosts and how is it transferred to humans [ 27 ]?

There has been a need for animal models for understanding the pathophysiology of COVID-19 [ 28 ], for studying the mechanisms of transmission of the disease [ 16 ], for studying its neurobiology [ 29 , 30 ] and for developing new vaccines [ 31 ]. The sudden onset of the COVID-19 pandemic has highlighted the fact that animal research is necessary, and that the curtailment of such research has serious consequences for the health of both humans and animals, both wild and domestic [ 32 ] As highlighted by Adhikary et al. [ 22 ] and Genzel et al. [ 33 ] the coronavirus has made clear the necessity for animal research and the danger in surviving future such pandemics if animal research is not fully supported. Genzel et al. [ 33 ], in particular, take issue with the proposal for a European ban on animal testing. Finally, there is a danger in bypassing animal research in developing new vaccines for diseases such as COVID-19 [ 34 ]. The purpose of this paper is to show that, while animal research is necessary for the health of both humans and animals, there is a need to carry out such experimentation in a controlled and humane manner. The use of alternatives to animal research such as cultured human cells and computer modeling may be a useful adjunct to animal studies but will require that such methods are more readily accessible to researchers and are not a replacement for animal experimentation.

Pros and cons of animal experimentation

Arguments against animal experimentation.

A fundamental question surrounding this debate is to ask whether it is appropriate to use animals for medical research. Is our acceptance that animals have a morally lower value or standard of life just a case of speciesism [ 35 ]? Nowadays, most people agree that animals have a moral status and that needlessly hurting or abusing pets or other animals is unacceptable. This represents something of a change from the historical point of view where animals did not have any moral status and the treatment of animals was mostly subservient to maintaining the health and dignity of humans [ 36 ].

Animal rights advocates strongly argue that the moral status of non-human animals is similar to that of humans, and that animals are entitled to equality of treatment. In this view, animals should be treated with the same level of respect as humans, and no one should have the right to force them into any service or to kill them or use them for their own goals. One aspect of this argument claims that moral status depends upon the capacity to suffer or enjoy life [ 37 ].

In terms of suffering and the capacity of enjoying life, many animals are not very different from human beings, as they can feel pain and experience pleasure [ 38 ]. Hence, they should be given the same moral status as humans and deserve equivalent treatment. Supporters of this argument point out that according animals a lower moral status than humans is a type of prejudice known as “speciesism” [ 38 ]. Among humans, it is widely accepted that being a part of a specific race or of a specific gender does not provide the right to ascribe a lower moral status to the outsiders. Many advocates of animal rights deploy the same argument, that being human does not give us sufficient grounds declare animals as being morally less significant [ 36 ].

ARGUMENTS IN FAVOR OF ANIMAL EXPERIMENTATION

Those who support animal experimentation have frequently made the argument that animals cannot be elevated to be seen as morally equal to humans [ 39 ]. Their main argument is that the use of the terms “moral status” or “morality” is debatable. They emphasize that we must not make the error of defining a quality or capacity associated with an animal by using the same adjectives used for humans [ 39 ]. Since, for the most part, animals do not possess humans’ cognitive capabilities and lack full autonomy (animals do not appear to rationally pursue specific goals in life), it is argued that therefore, they cannot be included in the moral community [ 39 ]. It follows from this line of argument that, if animals do not possess the same rights as human beings, their use in research experimentation can be considered appropriate [ 40 ]. The European and the American legislation support this kind of approach as much as their welfare is respected.

Another aspect of this argument is that the benefits to human beings of animal experimentation compensate for the harm caused to animals by these experiments.

In other words, animal harm is morally insignificant compared to the potential benefits to humans. Essentially, supporters of animal experimentation claim that human beings have a higher moral status than animals and that animals lack certain fundamental rights accorded to humans. The potential violations of animal rights during animal research are, in this way, justified by the greater benefits to mankind [ 40 , 41 ]. A way to evaluate when the experiments are morally justified was published in 1986 by Bateson, which developed the Bateson’s Cube [ 42 ]. The Cube has three axes: suffering, certainty of benefit and quality of research. If the research is high-quality, beneficial, and not inflicting suffering, it will be acceptable. At the contrary, painful, low-quality research with lower likelihood of success will not be acceptable [ 42 , 43 ].

Impact of experimentations on animals

Ability to feel pain and distress.

Like humans, animal have certain physical as well as psychological characteristics that make their use for experimentation controversial [ 44 ].

In the last few decades, many studies have increased knowledge of animal awareness and sentience: they indicate that animals have greater potential to experience damage than previously appreciated and that current rights and protections need to be reconsidered [ 45 ]. In recent times, scientists as well as ethicists have broadly acknowledged that animals can also experience distress and pain [ 46 ]. Potential sources of such harm arising from their use in research include disease, basic physiological needs deprivation and invasive procedures [ 46 ]. Moreover, social deprivation and lack of the ability to carry out their natural behaviors are other causes of animal harm [ 46 ]. Several studies have shown that, even in response to very gentle handling and management, animals can show marked alterations in their physiological and hormonal stress markers [ 47 ].

In spite of the fact that suffering and pain are personalized experiences, several multi-disciplinary studies have provided clear evidence of animals experiencing pain and distress. In particular, some animal species have the ability to express pain similarly to human due to common psychological, neuroanatomical and genetic characteristics [ 48 ]. Similarly, animals share a resemblance to humans in their developmental, genetic and environmental risk factors for psychopathology. For instance, in many species, it has been shown that fear operates within a less organized subcortical neural circuit than pain [ 49 , 50 ]. Various types of depression and anxiety disorders like posttraumatic stress disorder have also been reported in mammals [ 51 ].

PSYCHOLOGICAL CAPABILITIES OF ANIMALS

Some researchers have suggested that besides their ability to experience physical and psychological pain and distress, some animals also exhibit empathy, self-awareness and language-like capabilities. They also demonstrate tools-linked cognizance, pleasure-seeking and advanced problem-solving skills [ 52 ]. Moreover, mammals and birds exhibit playful behavior, an indicator of the capacity to experience pleasure. Other taxa such as reptiles, cephalopods and fishes have also been observed to display playful behavior, therefore the current legislation prescribes the use of environmental enrichers [ 53 ]. The presence of self-awareness ability, as assessed by mirror self-recognition, has been reported in magpies, chimpanzees and other apes, and certain cetaceans [ 54 ]. Recently, another study has revealed that crows have the ability to create and use tools that involve episodic-like memory formation and its retrieval. From these findings, it may be suggested that crows as well as related species show evidence of flexible learning strategies, causal reasoning, prospection and imagination that are similar to behavior observed in great apes [ 55 ]. In the context of resolving the ethical dilemmas about animal experimentation, these observations serve to highlight the challenges involved [ 56 , 57 ].

Ethics, principles and legislation in animal experimentation

Ethics in animal experimentation.

Legislation around animal research is based on the idea of the moral acceptability of the proposed experiments under specific conditions [ 58 ]. The significance of research ethics that ensures proper treatment of experimental animals [ 58 ]. To avoid undue suffering of animals, it is important to follow ethical considerations during animal studies [ 1 ]. It is important to provide best human care to these animals from the ethical and scientific point of view [ 1 ]. Poor animal care can lead to experimental outcomes [ 1 ]. Thus, if experimental animals mistreated, the scientific knowledge and conclusions obtained from experiments may be compromised and may be difficult to replicate, a hallmark of scientific research [ 1 ]. At present, most ethical guidelines work on the assumption that animal experimentation is justified because of the significant potential benefits to human beings. These guidelines are often permissive of animal experimentation regardless of the damage to the animal as long as human benefits are achieved [ 59 ].

PRINCIPLE OF THE 4 RS

Although animal experimentation has resulted in many discoveries and helped in the understanding numerous aspects of biological science, its use in various sectors is strictly controlled. In practice, the proposed set of animal experiments is usually considered by a multidisciplinary Ethics Committee before work can commence [ 60 ]. This committee will review the research protocol and make a judgment as to its sustainability. National and international laws govern the utilization of animal experimentation during research and these laws are mostly based on the universal doctrine presented by Russell and Burch (1959) known as principle of the 3 Rs. The 3Rs referred to are Reduction, Refinement and Replacement, and are applied to protocols surrounding the use of animals in research. Some researchers have proposed another “R”, of responsibility for the experimental animal as well as for the social and scientific status of the animal experiments [ 61 ]. Thus, animal ethics committees commonly review research projects with reference to the 4 Rs principles [ 62 ].

The first “R”, Reduction means that the experimental design is examined to ensure that researchers have reduced the number of experimental animals in a research project to the minimum required for reliable data [ 59 ]. Methods used for this purpose include improved experimental design, extensive literature search to avoid duplication of experiments [ 35 ], use of advanced imaging techniques, sharing resources and data, and appropriate statistical data analysis that reduce the number of animals needed for statistically significant results [ 2 , 63 ].

The second “R”, Refinement involves improvements in procedure that minimize the harmful effects of the proposed experiments on the animals involved, such as reducing pain, distress and suffering in a manner that leads to a general improvement in animal welfare. This might include for example improved living conditions for research animals, proper training of people handling animals, application of anesthesia and analgesia when required and the need for euthanasia of the animals at the end of the experiment to curtail their suffering [ 63 ].

The third “R”, Replacement refers to approaches that replace or avoid the use of experimental animals altogether. These approaches involve use of in silico methods/computerized techniques/software and in vitro methods like cell and tissue culture testing, as well as relative replacement methods by use of invertebrates like nematode worms, fruit flies and microorganisms in place of vertebrates and higher animals [ 1 ]. Examples of proper application of these first “3R2 principles are the use of alternative sources of blood, the exploitation of commercially used animals for scientific research, a proper training without use of animals and the use of specimen from previous experiments for further researches [ 64-67 ].

The fourth “R”, Responsibility refers to concerns around promoting animal welfare by improvements in experimental animals’ social life, development of advanced scientific methods for objectively determining sentience, consciousness, experience of pain and intelligence in the animal kingdom, as well as effective involvement in the professionalization of the public discussion on animal ethics [ 68 ].

OTHER ASPECTS OF ANIMAL RESEARCH ETHICS

Other research ethics considerations include having a clear rationale and reasoning for the use of animals in a research project. Researchers must have reasonable expectation of generating useful data from the proposed experiment. Moreover, the research study should be designed in such a way that it should involve the lowest possible sample size of experimental animals while producing statistically significant results [ 35 ].

All individual researchers that handle experimental animals should be properly trained for handling the particular species involved in the research study. The animal’s pain, suffering and discomfort should be minimized [ 69 ]. Animals should be given proper anesthesia when required and surgical procedures should not be repeated on same animal whenever possible [ 69 ]. The procedure of humane handling and care of experimental animals should be explicitly detailed in the research study protocol. Moreover, whenever required, aseptic techniques should be properly followed [ 70 ]. During the research, anesthetization and surgical procedures on experimental animals should only be performed by professionally skilled individuals [ 69 ].

The Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines that are issued by the National Center for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) are designed to improve the documentation surrounding research involving experimental animals [ 70 ]. The checklist provided includes the information required in the various sections of the manuscript i.e. study design, ethical statements, experimental procedures, experimental animals and their housing and husbandry, and more [ 70 ].

It is critical to follow the highest ethical standards while performing animal experiments. Indeed, most of the journals refuse to publish any research data that lack proper ethical considerations [ 35 ].

INVESTIGATORS’ ETHICS

Since animals have sensitivity level similar to the human beings in terms of pain, anguish, survival instinct and memory, it is the responsibility of the investigator to closely monitor the animals that are used and identify any sign of distress [ 71 ]. No justification can rationalize the absence of anesthesia or analgesia in animals that undergo invasive surgery during the research [ 72 ]. Investigators are also responsible for giving high-quality care to the experimental animals, including the supply of a nutritious diet, easy water access, prevention of and relief from any pain, disease and injury, and appropriate housing facilities for the animal species [ 73 ]. A research experiment is not permitted if the damage caused to the animal exceeds the value of knowledge gained by that experiment. No scientific advancement based on the destruction and sufferings of another living being could be justified. Besides ensuring the welfare of animals involved, investigators must also follow the applicable legislation [ 74 , 75 ].

To promote the comfort of experimental animals in England, an animal protection society named: ‘The Society for the Preservation of Cruelty to Animals’ (now the Royal Society for the Prevention of Cruelty to Animals) was established (1824) that aims to prevent cruelty to animal [ 76 ].

ANIMAL WELFARE LAWS

Legislation for animal protection during research has long been established. In 1876 the British Parliament sanctioned the ‘Cruelty to Animals Act’ for animal protection. Russell and Burch (1959) presented the ‘3 Rs’ principles: Replacement, Reduction and Refinement, for use of animals during research [ 61 ]. Almost seven years later, the U.S.A also adopted regulations for the protection of experimental animals by enacting the Laboratory Animal Welfare Act of 1966 [ 60 ]. In Brazil, the Arouca Law (Law No. 11,794/08) regulates the animal use in scientific research experiments [ 76 ].

These laws define the breeding conditions, and regulate the use of animals for scientific research and teaching purposes. Such legal provisions control the use of anesthesia, analgesia or sedation in experiments that could cause distress or pain to experimental animals [ 59 , 76 ]. These laws also stress the need for euthanasia when an experiment is finished, or even during the experiment if there is any intense suffering for the experimental animal [ 76 ].

Several national and international organizations have been established to develop alternative techniques so that animal experimentation can be avoided, such as the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) ( www.caat.jhsph.edu ), the European Centre for the Validation of Alternative Methods (ECVAM) [ 77 ], the Universities Federation for Animal Welfare (UFAW) ( www.ufaw.org.uk ), The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) [ 78 ], and The Center for Alternatives to Animal Testing (CAAT) ( www.caat.jhsph.edu ). The Brazilian ‘Arouca Law’ also constitutes a milestone, as it has created the ‘National Council for the Control of Animal Experimentation’ (CONCEA) that deals with the legal and ethical issues related to the use of experimental animals during scientific research [ 76 ].

Although national as well as international laws and guidelines have provided basic protections for experimental animals, the current regulations have some significant discrepancies. In the U.S., the Animal Welfare Act excludes rats, mice and purpose-bred birds, even though these species comprise almost 90% of the animals that are used for research purpose [ 79 ]. On the other hand, certain cats and dogs are getting special attention along with extra protection. While the U.S. Animal Welfare Act ignores birds, mice and rats, the U.S. guidelines that control research performed using federal funding ensure protections for all vertebrates [ 79 , 80 ].

Living conditions of animals

Choice of the animal model.

Based on all the above laws and regulations and in line with the deliberations of ethical committees, every researcher must follow certain rules when dealing with animal models.

Before starting any experimental work, thorough research should be carried out during the study design phase so that the unnecessary use of experimental animals is avoided. Nevertheless, certain research studies may have compelling reasons for the use of animal models, such as the investigation of human diseases and toxicity tests. Moreover, animals are also widely used in the training of health professionals as well as in training doctors in surgical skills [ 1 , 81 ].

Researcher should be well aware of the specific traits of the animal species they intend to use in the experiment, such as its developmental stages, physiology, nutritional needs, reproductive characteristics and specific behaviors. Animal models should be selected on the basis of the study design and the biological relevance of the animal [ 1 ].

Typically, in early research, non-mammalian models are used to get rapid insights into research problems such as the identification of gene function or the recognition of novel therapeutic options. Thus, in biomedical and biological research, among the most commonly used model organisms are the Zebrafish, the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans . The main advantage of these non-mammalian animal models is their prolific reproducibility along with their much shorter generation time. They can be easily grown in any laboratory setting, are less expensive than the murine animal models and are somewhat more powerful than the tissue and cell culture approaches [ 82 ].

Caenorhabditis elegans is a small-sized nematode with a short life cycle and that exists in large populations and is relatively inexpensive to cultivate. Scientists have gathered extensive knowledge of the genomics and genetics of Caenorhabditis elegans ; but Caenorhabditis elegans models, while very useful in some respects, are unable to represent all signaling pathways found in humans. Furthermore, due to its short life cycle, scientists are unable to investigate long term effects of test compounds or to analyze primary versus secondary effects [ 6 ].

Similarly, the fruit fly Drosophila melanogaster has played a key role in numerous biomedical discoveries. It is small in size, has a short life cycle and large population size, is relatively inexpensive to breed, and extensive genomics and genetics information is available [ 6 ]. However, its respiratory, cardiovascular and nervous systems differ considerably from human beings. In addition, its immune system is less developed when compared to vertebrates, which is why effectiveness of a drug in Drosophila melanogaster may not be easily extrapolated to humans [ 83 ].

The Zebrafish ( Danio rerio ) is a small freshwater teleost, with transparent embryos, providing easy access for the observation of organogenesis and its manipulation. Therefore, Zebrafish embryos are considered good animal models for different human diseases like tuberculosis and fetal alcohol syndrome and are useful as neurodevelopmental research models. However, Zebrafish has very few mutant strains available, and its genome has numerous duplicate genes making it impossible to create knockout strains, since disrupting one copy of the gene will not disrupt the second copy of that gene. This feature limits the use of Zebrafish as animal models to study human diseases. Additionally they are rather expensive, have long life cycle, and genomics and genetics studies are still in progress [ 82 , 84 ].

Thus, experimentation on these three animals might not be equivalent to experimentation on mammals. Mammalian animal model are most similar to human beings, so targeted gene replacement is possible. Traditionally, mammals like monkey and mice have been the preferred animal models for biomedical research because of their evolutionary closeness to humans. Rodents, particularly mice and rats, are the most frequently used animal models for scientific research. Rats are the most suitable animal model for the study of obesity, shock, peritonitis, sepsis, cancer, intestinal operations, spleen, gastric ulcers, mononuclear phagocytic system, organ transplantations and wound healing. Mice are more suitable for studying burns, megacolon, shock, cancer, obesity, and sepsis as mentioned previously [ 85 ].

Similarly, pigs are mostly used for stomach, liver and transplantation studies, while rabbits are suitable for the study of immunology, inflammation, vascular biology, shock, colitis and transplantations. Thus, the choice of experimental animal mainly depends upon the field of scientific research under consideration [ 1 ].

HOUSING AND ENVIRONMENTAL ENRICHMENT

Researchers should be aware of the environment and conditions in which laboratory animals are kept during research, and they also need to be familiar with the metabolism of the animals kept in vivarium, since their metabolism can easily be altered by different factors such as pain, stress, confinement, lack of sunlight, etc. Housing conditions alter animal behavior, and this can in turn affect experimental results. By contrast, handling procedures that feature environmental enrichment and enhancement help to decrease stress and positively affect the welfare of the animals and the reliability of research data [ 74 , 75 ].

In animals, distress- and agony-causing factors should be controlled or eliminated to overcome any interference with data collection as well as with interpretation of the results, since impaired animal welfare leads to more animal usage during experiment, decreased reliability and increased discrepancies in results along with the unnecessary consumption of animal lives [ 86 ].

To reduce the variation or discrepancies in experimental data caused by various environmental factors, experimental animals must be kept in an appropriate and safe place. In addition, it is necessary to keep all variables like humidity, airflow and temperature at levels suitable for those species, as any abrupt variation in these factors could cause stress, reduced resistance and increased susceptibility to infections [ 74 ].

The space allotted to experimental animals should permit them free movement, proper sleep and where feasible allow for interaction with other animals of the same species. Mice and rats are quite sociable animals and must, therefore, be housed in groups for the expression of their normal behavior. Usually, laboratory cages are not appropriate for the behavioral needs of the animals. Therefore, environmental enrichment is an important feature for the expression of their natural behavior that will subsequently affect their defense mechanisms and physiology [ 87 ].

The features of environmental enrichment must satisfy the animals’ sense of curiosity, offer them fun activities, and also permit them to fulfill their behavioral and physiological needs. These needs include exploring, hiding, building nests and gnawing. For this purpose, different things can be used in their environment, such as PVC tubes, cardboard, igloos, paper towel, cotton, disposable masks and paper strips [ 87 ].

The environment used for housing of animals must be continuously controlled by appropriate disinfection, hygiene protocols, sterilization and sanitation processes. These steps lead to a reduction in the occurrence of various infectious agents that often found in vivarium, such as Sendai virus, cestoda and Mycoplasma pulmonis [ 88 ].

Euthanasia is a term derived from Greek, and it means a death without any suffering. According to the Brazilian Arouca Law (Article 14, Chapter IV, Paragraphs 1 and 2), an animal should undergo euthanasia, in strict compliance with the requirements of each species, when the experiment ends or during any phase of the experiment, wherever this procedure is recommended and/or whenever serious suffering occurs. If the animal does not undergo euthanasia after the intervention it may leave the vivarium and be assigned to suitable people or to the animal protection bodies, duly legalized [ 1 ].

Euthanasia procedures must result in instant loss of consciousness which leads to respiratory or cardiac arrest as well as to complete brain function impairment. Another important aspect of this procedure is calm handling of the animal while taking it out of its enclosure, to reduce its distress, suffering, anxiety and fear. In every research project, the study design should include the details of the appropriate endpoints of these experimental animals, and also the methods that will be adopted. It is important to determine the appropriate method of euthanasia for the animal being used. Another important point is that, after completing the euthanasia procedure, the animal’s death should be absolutely confirmed before discarding their bodies [ 87 , 89 ].

Relevance of animal experimentations and possible alternatives

Relevance of animal experiments and their adverse effects on human health.

One important concern is whether human diseases, when inflicted on experimental animals, adequately mimic the progressions of the disease and the treatment responses observed in humans. Several research articles have made comparisons between human and animal data, and indicated that the results of animals’ research could not always be reliably replicated in clinical research among humans. The latest systematic reviews about the treatment of different clinical conditions including neurology, vascular diseases and others, have established that the results of animal studies cannot properly predict human outcomes [ 59 , 90 ].

At present, the reliability of animal experiments for extrapolation to human health is questionable. Harmful effects may occur in humans because of misleading results from research conducted on animals. For instance, during the late fifties, a sedative drug, thalidomide, was prescribed for pregnant women, but some of the women using that drug gave birth to babies lacking limbs or with foreshortened limbs, a condition called phocomelia. When thalidomide had been tested on almost all animal models such as rats, mice, rabbits, dogs, cats, hamsters, armadillos, ferrets, swine, guinea pig, etc., this teratogenic effect was observed only occasionally [ 91 ]. Similarly, in 2006, the compound TGN 1412 was designed as an immunomodulatory drug, but when it was injected into six human volunteer, serious adverse reactions were observed resulting from a deadly cytokine storm that in turn led to disastrous systemic organ failure. TGN 1412 had been tested successfully in rats, mice, rabbits, and non-human primates [ 92 ]. Moreover, Bailey (2008) reported 90 HIV vaccines that had successful trial results in animals but which failed in human beings [ 93 ]. Moreover, in Parkinson disease, many therapeutic options that have shown promising results in rats and non-human primate models have proved harmful in humans. Hence, to analyze the relevance of animal research to human health, the efficacy of animal experimentation should be examined systematically [ 94 , 95 ]. At the same time, the development of hyperoxaluria and renal failure (up to dialysis) after ileal-jejunal bypass was unexpected because this procedure was not preliminarily evaluated on an animal model [ 96 ].

Several factors play a role in the extrapolation of animal-derived data to humans, such as environmental conditions and physiological parameters related to stress, age of the experimental animals, etc. These factors could switch on or off genes in the animal models that are specific to species and/or strains. All these observations challenge the reliability and suitability of animal experimentation as well as its objectives with respect to human health [ 76 , 92 ].

ALTERNATIVE TO ANIMAL EXPERIMENTATION/DEVELOPMENT OF NEW PRODUCTS AND TECHNIQUES TO AVOID ANIMAL SACRIFICE IN RESEARCH

Certainly, in vivo animal experimentation has significantly contributed to the development of biological and biomedical research. However it has the limitations of strict ethical issues and high production cost. Some scientists consider animal testing an ineffective and immoral practice and therefore prefer alternative techniques to be used instead of animal experimentation. These alternative methods involve in vitro experiments and ex vivo models like cell and tissue cultures, use of plants and vegetables, non-invasive human clinical studies, use of corpses for studies, use of microorganisms or other simpler organism like shrimps and water flea larvae, physicochemical techniques, educational software, computer simulations, mathematical models and nanotechnology [ 97 ]. These methods and techniques are cost-effective and could efficiently replace animal models. They could therefore, contribute to animal welfare and to the development of new therapies that can identify the therapeutics and related complications at an early stage [ 1 ].

The National Research Council (UK) suggested a shift from the animal models toward computational models, as well as high-content and high-throughput in vitro methods. Their reports highlighted that these alternative methods could produce predictive data more affordably, accurately and quickly than the traditional in vivo or experimental animal methods [ 98 ].

Increasingly, scientists and the review boards have to assess whether addressing a research question using the applied techniques of advanced genetics, molecular, computational and cell biology, and biochemistry could be used to replace animal experiments [ 59 ]. It must be remembered that each alternative method must be first validated and then registered in dedicated databases.

An additional relevant concern is how precisely animal data can mirror relevant epigenetic changes and human genetic variability. Langley and his colleagues have highlighted some of the examples of existing and some emerging non-animal based research methods in the advanced fields of neurology, orthodontics, infectious diseases, immunology, endocrine, pulmonology, obstetrics, metabolism and cardiology [ 99 ].

IN SILICO SIMULATIONS AND INFORMATICS

Several computer models have been built to study cardiovascular risk and atherosclerotic plaque build-up, to model human metabolism, to evaluate drug toxicity and to address other questions that were previously approached by testing in animals [ 100 ].

Computer simulations can potentially decrease the number of experiments required for a research project, however simulations cannot completely replace laboratory experiments. Unfortunately, not all the principles regulating biological systems are known, and computer simulation provide only an estimation of possible effects due to the limitations of computer models in comparison with complex human tissues. However, simulation and bio-informatics are now considered essential in all fields of science for their efficiency in using the existing knowledge for further experimental designs [ 76 ].

At present, biological macromolecules are regularly simulated at various levels of detail, to predict their response and behavior under certain physical conditions, chemical exposures and stimulations. Computational and bioinformatic simulations have significantly reduced the number of animals sacrificed during drug discovery by short listing potential candidate molecules for a drug. Likewise, computer simulations have decreased the number of animal experiments required in other areas of biological science by efficiently using the existing knowledge. Moreover, the development of high definition 3D computer models for anatomy with enhanced level of detail, it may make it possible to reduce or eliminate the need for animal dissection during teaching [ 101 , 102 ].

3D CELL-CULTURE MODELS AND ORGANS-ON-CHIPS

In the current scenario of rapid advancement in the life sciences, certain tissue models can be built using 3D cell culture technology. Indeed, there are some organs on micro-scale chip models used for mimicking the human body environment. 3D models of multiple organ systems such as heart, liver, skin, muscle, testis, brain, gut, bone marrow, lungs and kidney, in addition to individual organs, have been created in microfluidic channels, re-creating the physiological chemical and physical microenvironments of the body [ 103 ]. These emerging techniques, such as the biomedical/biological microelectromechanical system (Bio-MEMS) or lab-on-a-chip (LOC) and micro total analysis systems (lTAS) will, in the future, be a useful substitute for animal experimentation in commercial laboratories in the biotechnology, environmental safety, chemistry and pharmaceutical industries. For 3D cell culture modeling, cells are grown in 3D spheroids or aggregates with the help of a scaffold or matrix, or sometimes using a scaffold-free method. The 3D cell culture modeling conditions can be altered to add proteins and other factors that are found in a tumor microenvironment, for example, or in particular tissues. These matrices contain extracellular matrix components such as proteins, glycoconjugates and glycosaminoglycans that allow for cell communication, cell to cell contact and the activation of signaling pathways in such a way that the morphological and functional differentiation of these cells can accurately mimic their environment in vivo . This methodology, in time, will bridge the gap between in vivo and in vitro drug screening, decreasing the utilization of animal models during research [ 104 ].

ALTERNATIVES TO MICROBIAL CULTURE MEDIA AND SERUM-FREE ANIMAL CELL CULTURES

There are moves to reduce the use of animal derived products in many areas of biotechnology. Microbial culture media peptones are mostly made by the proteolysis of farmed animal meat. However, nowadays, various suppliers provide peptones extracted from yeast and plants. Although the costs of these plant-extracted peptones are the same as those of animal peptones, plant peptones are more environmentally favorable since less plant material and water are required for them to grow, compared with the food grain and fodder needed for cattle that are slaughtered for animal peptone production [ 105 ].

Human cell culture is often carried out in a medium that contains fetal calf serum, the production of which involves animal (cow) sacrifice or suffering. In fact, living pregnant cows are used and their fetuses removed to harvest the serum from the fetal blood. Fetal calf serum is used because it is a natural medium rich in all the required nutrients and significantly increases the chances of successful cell growth in culture. Scientists are striving to identify the factors and nutrients required for the growth of various types of cells, with a view to eliminating the use of calf serum. At present, most cell lines could be cultured in a chemically-synthesized medium without using animal products. Furthermore, data from chemically-synthesized media experiments may have better reproducibility than those using animal serum media, since the composition of animal serum does change from batch to batch on the basis of animals’ gender, age, health and genetic background [ 76 ].

ALTERNATIVES TO ANIMAL-DERIVED ANTIBODIES

Animal friendly affinity reagents may act as an alternative to antibodies produced, thereby removing the need for animal immunization. Typically, these antibodies are obtained in vitro by yeast, phage or ribosome display. In a recent review, a comparative analysis between animal friendly affinity reagents and animal derived-antibodies showed that the affinity reagents have superior quality, are relatively less time consuming, have more reproducibility and are more reliable and are cost-effective [ 106 , 107 ].

Conclusions

Animal experimentation led to great advancement in biological and biomedical sciences and contributed to the discovery of many drugs and treatment options. However, such experimentation may cause harm, pain and distress to the animals involved. Therefore, to perform animal experimentations, certain ethical rules and laws must be strictly followed and there should be proper justification for using animals in research projects. Furthermore, during animal experimentation the 4 Rs principles of reduction, refinement, replacement and responsibility must be followed by the researchers. Moreover, before beginning a research project, experiments should be thoroughly planned and well-designed, and should avoid unnecessary use of animals. The reliability and reproducibility of animal experiments should also be considered. Whenever possible, alternative methods to animal experimentation should be adopted, such as in vitro experimentation, cadaveric studies, and computer simulations.

While much progress has been made on reducing animal experimentation there is a need for greater awareness of alternatives to animal experiments among scientists and easier access to advanced modeling technologies. Greater research is needed to define a roadmap that will lead to the elimination of all unnecessary animal experimentation and provide a framework for adoption of reliable alternative methodologies in biomedical research.

Acknowledgements

This research was funded by the Provincia Autonoma di Bolzano in the framework of LP 15/2020 (dgp 3174/2021).

Conflicts of interest statement

Authors declare no conflict of interest.

Author's contributions

MB: study conception, editing and critical revision of the manuscript; AKK, DP, GH, RB, Paul S, Peter S, RM, BF, NC, SM, LL, DD, GMT, MCE, MD, SM, Daniele M, GB, AD, KD, MCM, TB, MS, STC, Donald M, AM, AB, KLH, MK, LS, LL, GF: literature search, editing and critical revision of the manuscript. All authors have read and approved the final manuscript.

Contributor Information

INTERNATIONAL BIOETHICS STUDY GROUP : Derek Pheby , Gary Henehan , Richard Brown , Paul Sieving , Peter Sykora , Robert Marks , Benedetto Falsini , Natale Capodicasa , Stanislav Miertus , Lorenzo Lorusso , Gianluca Martino Tartaglia , Mahmut Cerkez Ergoren , Munis Dundar , Sandro Michelini , Daniele Malacarne , Tommaso Beccari , Michele Samaja , Matteo Bertelli , Donald Martin , Assunta Morresi , Ariola Bacu , Karen L. Herbst , Mykhaylo Kapustin , Liborio Stuppia , Ludovica Lumer , and Giampietro Farronato

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VA continues ‘approved’ experiments on dogs, cats and monkeys after Congress orders an end to live-animal tests by 2026

A hospital staff member took this 2019 photo of a cat used in experiments at the Louis Stokes Cleveland VA Medical Center. Tests involved placing electrodes in the cat’s bladder and using a device to stimulate urination. The VA in 2024 is seeking to implant wires and sensors in the legs and backs of cats in a separate experiment to test an implant for translating signals from a prosthesis to the nervous system. (White Coat Waste Project)

WASHINGTON — Researchers from the Department of Veterans Affairs will implant pacemakers in the hearts of 54 dogs that will be euthanized at the end of the tests and surgically embed wires and sensors into the backs and legs of cats in separate experiments that the VA plans to conduct on live animals in 2024, according to agency documents.

Though the Department of Veterans Affairs is under order by Congress to phase out live animal experiments using cats, dogs and primates “with limited exceptions” by 2026, the agency continues to support live-animal research at VA facilities across the U.S., according to the VA.

More than 62,000 cats and dogs are in U.S. labs for live animal experiments run by government agencies, colleges and universities, and private companies, according to the Humane Society of the United States, a nonprofit organization that focuses on the welfare of animals.

The VA has been phasing out live animal testing on dogs, cats and primates since 2018.

Terrence Hayes, the VA press secretary, said the agency is assessing a new congressional directive adopted in March to eliminate the live-animal tests “with limited exceptions” within two years.

“VA is reviewing the recently signed fiscal year 2024 appropriations law to ensure any implementation of the new provisions fully meet congressional intent, including using of funding, program requirements and reporting to our congressional partners,” he said.

A provision requiring the VA to end live animal research is part of the Consolidated Appropriations Act, signed into law March 9. The legislation requires the VA to provide a plan for ending the tests within 90 days of the bill’s enactment.

In 2024, the VA’s list of “approved research” on live animals includes two separate experiments using dogs at the Richmond VA Medical Center in Virginia.

The experiments involve implanting pacemakers in the hearts of dogs to induce extra heartbeats that disrupt the regular heart rhythm, causing a sensation of fluttering in the chest. The purpose is to measure deteriorating heart muscle and heart failure caused by the extra heart beats.

The dogs will undergo open heart surgery to implant a pacemaker device and a radio telemetry system. Catheters also will be positioned on the heart surface, according to the project description.

Fifty-four dogs will be used in the experiment, after which “most will be euthanized,” according to VA documents.

Dogs not euthanized will be granted a four-week recovery at which time the pacemakers will be disabled, and the animals further studied. Those dogs also will be euthanized at the conclusion of the tests.

The White Coat Waste Project, a nonprofit watchdog group, said records obtained by the organization under the Freedom of Information Act show no dogs are currently confined at the Richmond VA Medical Center or being used there for heart experiments.

A separate VA experiment using cats is approved for 2024 for the Louis Stokes VA Medical Center in Cleveland for testing the durability of implanted medical devices to stimulate nerve sensation in patients who have undergone amputations.

“New prosthetic technology for amputees can restore natural sensations,” according to the project proposal published by the National Institutes of Health.

Funding through September for the experiments is about $270,000, according to information the VA published on its website.

The experiments involve surgically embedding wires and sensors into the legs and backs of cats, according to documents obtained by the White Coat Waste Project.

The procedures risk paralysis and death in the cats, which is counter to directives by Congress for restricting these types of tests, said Justin Goodman, senior vice president of White Coat Waste Project.

The experiment is to test a miniaturized implant that translates electrical signals from a prosthesis to the nervous system, which could allow veterans who lost a limb to achieve a better sense of balance and motion in digits and joints, Hayes said.

He described the experiments as safe and said the cats will be placed into adoptive homes at the conclusion of the research in six months.

The VA also has approval in 2024 to continue experiments on dozens of rhesus macaque monkeys for measuring treatment outcomes for spinal cord injuries.

The experiment at the VA San Diego Health Care System involves damaging a monkey’s spinal cord in surgical procedures.

The monkey then undergoes “multiple major survival surgeries” along with stem cell therapy to address injuries and observe recoveries.

“Each of these surgeries will add to the body of knowledge we can gain about recovery from spinal cord injury,” according to the project description on the VA website.

“This research is to explore the possibility that neural stem cells can be used to help bridge the damaged tissue and restore communication across the site of the injury,” according to the project description.

The experiment identifies the use of restraint chairs for behavioral testing to force monkeys recovering from spinal cord injuries to use the hand with limited use to perform tasks. The monkeys also are expected to walk on treadmills and retrieve food to improve function, according to the project description.

The experiments using the monkeys are being conducted in conjunction with other agencies including University of California-Davis, which has one of the biggest primate laboratories in the country, Goodman said.

Animals are purchased from breeders licensed to sell dogs, cats, primates and other animals to laboratories for use in live-animal experiments.

Goodman said his organization objects to the VA using taxpayer dollars to purchase animals and submit them to painful experiments. He said animals often are euthanized and dissected at the end of the research, as part of the study.

previous coverage

• VA ordered to end experiments on dogs, cats and primates by 2026

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Laika at 60: What happens to all the dogs, monkeys and mice sent into space?

Stray dog sent into space in 1957 was first living creature to orbit earth, article bookmarked.

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​ Laika’s last moments on earth were spent strapped into a windowless Soviet rocket awaiting lift off.

The stray dog had enjoyed a meteoric rise to fame in 1957, having been plucked from a Moscow street, hastily trained and blasted into space.

That ill-fated mission resulted in Laika overheating and dying five hours into the flight.

But Sputnik 2’s launch – 60 years ago, today – was a defining moment in the history of space exploration; only the second time a spacecraft had been launched into Earth’s orbit, and the first time a living creature had been on board.

While Laika may have been a trailblazer in orbiting the Earth, animals were being employed in the name of space exploration more than a decade earlier.

Russian and American scientists have long used animals to test the limits of their ability to send living organisms into space – and return them unharmed.

The first sent into outer space were fruit flies blasted to an altitude of 68 miles inside a re-fashioned Nazi V2 rocket in 1947.

In the years that followed, Nasa sent several monkeys, named Albert I, II, III, IV, into space attached to monitoring instruments. All of them died.

It was not until the flight of a monkey named Yorick (accompanied by 11 mice) in September 1951 that scientists could claim to have sent a primate into space and returned it back to Earth alive

Following the success of that flight, the experiments became more elaborate. On one mission, two white mice – Mildred and Albert – were placed inside a rotating drum allowing them to float during the period of weightlessness.

Closely watching these tests were Soviet scientists, who began sending mice, rats and rabbits of their own as one-way passengers on low-level orbits.

But to gather the necessary information to design a cabin fit for a human astronaut, they also turned to stray dogs.

On 15 August 1951, Dezik and Tsygan were launched, becoming the first canine suborbital astronauts.

Several more embarked on similar, suborbital flights until stray mongrel Laika – dubbed Muttnik – was picked up from the street and trained for her Earth-orbiting mission.

“It harks back to a time when people knew very little about the space,” Martin Barstow, director of the Leicester Institute of Space and Earth Observation, said of Laika’s mission.

He told The Independent : “They didn’t know if people could survive in space. It was very much a pathfinder.

“It was a precursor to Yuri Gagarin ’s flight [in 1961]. They were testing their capsule technology, testing the oxygen supply, whether or not radiation might have harmed it and whether it could have survived the mission.”

Adilya Kotovskaya, a 90-year-old Russian biologist who helped train Laika, speaking on the 60th anniversary, said: “Those nine orbits of Earth made Laika the world’s first cosmonaut – sacrificed for the sake of the success of future space missions.”

“We chose bitches because they don’t have to raise a leg to urinate which means they need less space than the males,” she told the AFP news agency.

“And [we chose] strays because they are more resourceful and less demanding.”

The first animals to reach outer space and return alive were a pair of dogs – Belka and Strelka – who blasted off on 19 August 1960, returning a day later.

In 1968 the Soviet Union sent a spacecraft to orbit the moon carrying two tortoises, wine flies and mealworms.

Frogs, cats and spiders have followed. But once humans landed on the moon in 1969, the role of animals began to fade.

Attention – and controversy – has only recently returned to the use of animals in 21st century space exploration and in particular, the bid to send humans to Mars.

A major risk to astronauts attempting to reach the red planet is the high level of radiation, so US, European and Russian space agencies have considered testing the effect on monkeys before sending humans to Mars.

Boris Lapin, director of the Sochi Institute of Medical Primatology, said monkeys and humans “have approximately identical sensitivity to small and large radiation doses”.

“It is better to experiment on the macaques, but not on dogs or other animals,” he said.

Professor Barstow said there was “no chance” that dogs would be tested on in future space missions.

The largest creatures in the International Space Station ’s laboratory are likely to be small insects, he said.

“We’re a bit more alert to the nuances of whether or not you should test anything on animals these days.

“And putting animals in space is not a lot different to testing cosmetics on them. When and if you do it, it has to be under controlled circumstances. It is a different era now.

“We know a lot about radiation and how it affects humans and animals. The issue of radiation for a trip to Mars is more about understanding what the doses will be, and testing protection systems and I don’t see why you would need to use animals to test and verify that. We are much more sophisticated in the ways we measure and test that now.”

The Caenorhabditis elegans worm is the latest animal set to reach space, chosen because it has similar nerve, muscle and digestive systems to humans.

The worms will reach the International Space Station in just over a year as part of the Molecular Muscle experiment.

Libby Jackson, human spaceflight and microgravity programme manager at the UK Space Agency, told The Independent the experiment “will look at how these worms age in space and how their muscles are affected by weightlessness”.

“This could help scientists understand the molecular mechanisms responsible for muscle-wasting conditions, such as muscular dystrophy, which could improve the lives of people on Earth,” she added.

Dr Julia Baines, science policy adviser at animal rights group Peta, said: “Animals aren’t astronauts and, unlike human volunteers, can’t give their consent to being the subjects of experiments or to risking their lives on a frightening mission into the unknown.

“Laika, the first animal to be launched into orbit, died from overheating and panic in the tiny spacecraft – all alone and in severe pain.”

In 2010, under mounting pressure from animal rights campaigners, Nasa announced it was shelving a plan to conduct radiation experiments on squirrel monkeys.

The European Space Agency also ruled out further primate tests, saying it did not see “any need or use” for them.

But reports suggest Russia is also moving ahead with plans for primate experimentation.

Nasa argues that without testing in the early days of space exploration, Soviet and American programmes “could have suffered great losses of human life”.

“These animals performed a service to their respective countries that no human could or would have performed,” the agency said.

“They gave their lives and their service in the name of technological advancement, paving the way for humanity’s many forays into space.”

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About Animal Testing

Humane Society International / Global

What is animal testing?

The term “animal testing” refers to procedures performed on living animals for purposes of research into basic biology and diseases, assessing the effectiveness of new medicinal products, and testing the human health and/or environmental safety of consumer and industry products such as cosmetics, household cleaners, food additives, pharmaceuticals and industrial/agro-chemicals. All procedures, even those classified as “mild,” have the potential to cause the animals physical as well as psychological distress and suffering. Often the procedures can cause a great deal of suffering. Most animals are killed at the end of an experiment, but some may be re-used in subsequent experiments. Here is a selection of common animal procedures:

• Forced chemical exposure in toxicity testing, which can include oral force-feeding, forced inhalation, skin or injection into the abdomen, muscle, etc.
• Exposure to drugs, chemicals or infectious disease at levels that cause illness, pain and distress, or death
• Genetic manipulation, e.g., addition or “knocking out” of one or more genes
• Ear-notching and tail-clipping for identification
• Short periods of physical restraint for observation or examination
• Prolonged periods of physical restraint
• Food and water deprivation
• Surgical procedures followed by recovery
• Infliction of wounds, burns and other injuries to study healing
• Infliction of pain to study its physiology and treatment
• Behavioural experiments designed to cause distress, e.g., electric shock or forced swimming
• Other manipulations to create “animal models” of human diseases ranging from cancer to stroke to depression
• Killing by carbon dioxide asphyxiation, neck-breaking, decapitation, or other means

What types of animals are used?

Many different species are used around the world, but the most common include mice, fish, rats, rabbits, guinea pigs, hamsters, farm animals, birds, cats, dogs, mini-pigs, and non-human primates (monkeys, and in some countries, chimpanzees). Video: Watch what scientists have to say about alternatives to animal testing .

It is estimated that more than 115 million animals worldwide are used in laboratory experiments every year. But because only a small proportion of countries collect and publish data concerning animal use for testing and research, the precise number is unknown. For example, in the United States, up to 90 percent of the animals used in laboratories (purpose-bred rats, mice and birds, fish, amphibians, reptiles and invertebrates) are excluded from the official statistics, meaning that figures published by the U.S. Department of Agriculture are no doubt a substantial underestimate.

Within the European Union, more than 12 million animals are used each year, with France, Germany and the United Kingdom being the top three animal using countries. British statistics reflect the use of more than 3 million animals each year, but this number does not include animals bred for research but killed as “surplus” without being used for specific experimental procedures. Although these animals still endure the stresses and deprivation of life in the sterile laboratory environment, their lives are not recorded in official statistics. HSI believes that complete transparency about animal use is vital and that all animals bred, used or killed for the research industry should be included in official figures. See some animal use statistics .

What’s wrong with animal testing?

For nearly a century, drug and chemical safety assessments have been based on laboratory testing involving rodents, rabbits, dogs, and other animals. Aside from the ethical issues they pose—inflicting both physical pain as well as psychological distress and suffering on large numbers of sentient creatures—animal tests are time- and resource-intensive, restrictive in the number of substances that can be tested, provide little understanding of how chemicals behave in the body, and in many cases do not correctly predict real-world human reactions. Similarly, health scientists are increasingly questioning the relevance of research aimed at “modelling” human diseases in the laboratory by artificially creating symptoms in other animal species.

Trying to mirror human diseases or toxicity by artificially creating symptoms in mice, dogs or monkeys has major scientific limitations that cannot be overcome. Very often the symptoms and responses to potential treatments seen in other species are dissimilar to those of human patients. As a consequence, nine out of every 10 candidate medicines that appear safe and effective in animal studies fail when given to humans. Drug failures and research that never delivers because of irrelevant animal models not only delay medical progress, but also waste resources and risk the health and safety of volunteers in clinical trials.

What’s the alternative?

If lack of human relevance is the fatal flaw of “animal models,” then a switch to human-relevant research tools is the logical solution. The National Research Council in the United States has expressed its vision of “a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines”, and science leaders around the world have echoed this view.

The sequencing of the human genome and birth of functional genomics, the explosive growth of computer power and computational biology, and high-speed robot automation of cell-based (in vitro) screening systems, to name a few, has sparked a quiet revolution in biology. Together, these innovations have produced new tools and ways of thinking that can help uncover exactly how chemicals and drugs disrupt normal processes in the human body at the level of cells and molecules. From there, scientists can use computers to interpret and integrate this information with data from human and population-level studies. The resulting predictions regarding human safety and risk are potentially more relevant to people in the real world than animal tests.

But that’s just the beginning. The wider field of human health research could benefit from a similar shift in paradigm. Many disease areas have seen little or no progress despite decades of animal research. Some 300 million people currently suffer from asthma, yet only two types of treatment have become available in the last 50 years. More than a thousand potential drugs for stroke have been tested in animals, but only one of these has proved effective in patients. And it’s the same story with many other major human illnesses. A large-scale re-investment in human-based (not mouse or dog or monkey) research aimed at understanding how disruptions of normal human biological functions at the levels of genes, proteins and cell and tissue interactions lead to illness in our species could advance the effective treatment or prevention of many key health-related societal challenges of our time.

Modern non-animal techniques are already reducing and superseding experiments on animals, and in European Union, the “3Rs” principle of replacement, reduction and refinement of animal experiments is a legal requirement. In most other parts of the world there is currently no such legal imperative, leaving scientists free to use animals even where non-animal approaches are available.

If animal testing is so unreliable, why does it continue?

Despite this growing evidence that it is time for a change, effecting that change within a scientific community that has relied for decades on animal models as the “default method” for testing and research takes time and perseverance. Old habits die hard, and globally there is still a lack of knowledge of and expertise in cutting-edge non-animal techniques.

But with HSI’s help, change is happening. We are leading efforts globally to encourage scientists, companies and policy-makers to transition away from animal use in favour of 21st century methods. Our work brings together experts from around the globe to share knowledge and best practice, improving the quality of research by replacing animals in the laboratory.

Are animal experiments needed for medical progress?

It is often argued that because animal experiments have been used for centuries, and medical progress has been made in that time, animal experiments must be necessary. But this is missing the point. History is full of examples of flawed or basic practices and ideas that were once considered state-of-the-art, only to be superseded years later by something far more sophisticated and successful. In the early 1900’s, the Wright brothers’ invention of the airplane was truly innovative for its time, but more than a century later, technology has advanced so much that when compared to the modern jumbo jet those early flying machines seem quaint and even absurd. Those early ideas are part of aviation history, but no-one would seriously argue that they represent the cutting-edge of design or human achievement. So it is with laboratory research. Animal experiments are part of medical history, but history is where they belong. Compared to today’s potential to understand the basis of human disease at cellular and molecular levels, experimenting on live animals seems positively primitive. So if we want better quality medical research, safer more effective pharmaceuticals and cures to human diseases, we need to turn the page in the history books and embrace the new chapter—21st century science.

Independent scientific reviews demonstrate that research using animals correlates very poorly to real human patients. In fact, the data show that animal studies fail to predict real human outcomes in 50 to 99.7 percent of cases. This is mainly because other species seldom naturally suffer from the same diseases as found in humans. Animal experiments rely on often uniquely human conditions being artificially induced in non-human species. While on a superficial level they may share similar symptoms, fundamental differences in genetics, physiology and biochemistry can result in wildly different reactions to both the illness and potential treatments. For some areas of disease research, overreliance on animal models may well have delayed medical progress rather than advanced it. By contrast, many non-animal replacement methods such as cell-based studies, silicon chip biosensors, and computational systems biology models, can provide faster and more human-relevant answers to medical and chemical safety questions that animal experiments cannot match.

“The claim that animal experimentation is essential to medical development is not supported by proper, scientific evidence but by opinion and anecdote. Systematic reviews of its effectiveness don’t support the claims made on its behalf” (Pandora Pound et al. British Medical Journal 328, 514-7, 2004).

You can help: Sign the global pledge to Be Cruelty-Free

Donate to help animals suffering in labs and other cruel situations, discover more.

Imagine a syringe being forced down your throat to inject a chemical into your stomach, or being restrained and forced to breathe sickening vapours for hours. That’s the cruel reality of animal testing for millions of mice, rabbits, dogs and other animals worldwide.

We’re giving the beauty industry a cruelty-free makeover with a wave of animal testing bans supported by hundreds of companies and millions of caring consumers worldwide.

We all dream of the day when cancer is cured and AIDS is eradicated, but is the continued use of mice, monkeys and other animals as experimental “models” of human disease actually holding us back from realizing the promise of 21st century science?

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Research on monkeys

A large part of the experimental research at KI is carried out in test tubes or cell cultures, for example. Monkeys are only used in animal experiments when other methods or animal species cannot be used. They are mainly used in studies of diseases of the brain, and in experiments for the development of vaccines or treatments of severe infectious diseases.

Animal experiments in Sweden are subject to approval by an ethics board

A large part of the experimental research is done in test tubes or cell cultures, for example, but it is not yet possible to replace all use of lab animals. Animal experiments are needed, for example, to evaluate if treatments and medicines affect other processes in the body.

Using animals in scientific research is strictly regulated and governed by Swedish and EU legislation on animal protection. In order to conduct animal experiments in Sweden, the researcher must first apply for permission from an animal experiment ethics board, which conducts an ethical review of the experiment and weighs the impact on the animals against the public interest of the research. Research representatives and laymen, including representatives from animal protection organisations, sit on the animal experiment ethics boards.

Monkeys’ living environment and social environment

The Astrid Fagræus laboratory (KM-F) at KI where the research on monkeys is done is accredited by the organisation AAALAC International  for its high quality in animal welfare. KM-F houses one of the few facilities in Sweden that are approved to conduct animal experiments according to GLP (Good Laboratory Practice).

Everyone who conducts research or works with animals at Karolinska Institutet - researchers, students and animal technicians – must undergo training and maintain their competence in animal experiment knowledge.

The monkeys are kept in an environment outfitted to meet their needs to express their natural behaviour and socially interact in their group. Read more about our monkeys’ living environment and social environment .

Research at Karolinska Institutet

Monkeys are only used in animal experiments when other methods or animal species cannot be used. This mainly concerns studies of diseases of the brain, and in experiments for the development of vaccines against severe infectious diseases.

Our understanding of the HIV virus and the antiretroviral medicines available today are the result of medical research on animals.

Other examples where research on monkeys was necessary are the development of medicines against certain kinds of cancer and several neurological disorders (Alzheimer’s, Parkinson’s, epilepsi), and in the development of vaccines against, for example, malaria.

Vaccine research

In order to get a complete picture of the interactions between the immune system and a vaccine, and to evaluate if a lasting immunity develops, it is necessary to use monkeys in the research. Their immune system is very similar to the human immune system, which differs in several respects from rodents, for example.

The anatomical similarities between monkeys and humans and the possibility of testing vaccine doses is also a major advantage when evaluating results and drawing conclusions to then continue to clinical trials on humans. The target group for vaccines is most often healthy people, including children. This means that there is an extra precautionary aspect to ensure that the vaccine is both safe and has a protective effect.

Successful vaccine development requires in-depth understanding, both about the gene that the vaccine is intended for and about the immune system. New vaccines are refined in several steps with extensive tests in test tubes, followed by several rounds of tests on smaller animals. Vaccines that show promising results and where potential tests on humans may be motivated are selected for final evaluation in monkeys.

PET camera to study the functions of the brain

In addition to vaccine research, monkeys are also used in research with a so-called positron emission tomography (PET) camera where extensive progress has been made, especially in research on the structure and functions of the brain. This technology is also very important for locating tumours and developing new medications. This is very important research to develop medicines for various neurological disorders, such as Alzheimer’s, Parkinson’s, schizophrenia and other mental disorders.

Genetic databases contribute to the 3Rs

Genetic databases also contribute to the formulation and interpretation of results from vaccine trials, and can at the same time contribute to what is called the 3Rs ( Reduce/refine/replace ). Studies on non-human primates therefore help researchers obtain an important basic understanding of a model that is relevant to hasten vaccine development.

Why Soviets Sent Dogs to Space While Americans Used Primates

Researchers didn’t know how people would react to weightlessness. So they sent animals first.

The cosmonaut ran away a day before his flight. The training had been grueling and confusing. The food was bad. The cosmonaut hadn’t signed up for this at all.

It couldn’t have: It was a dog.

The researchers at the Institute of Aviation Medicine in Moscow rushed to find a replacement. They plucked a stray dog off the street and named it ZIB, a Russian acronym that means “substitute for missing Bobik,” a common name for a small dog. The mutt was placed inside a capsule, strapped to a rocket, and blasted to the edge of space. It returned in one piece.

This historic flight happened in September 1951. The Soviet Union was developing a program to launch men into orbit, and dogs were their test subjects. On the other side of the world, the United States was carrying out similar biomedical research, only with primates, including monkeys and chimpanzees.

Human beings had lived for all of history beneath the cosmic tarp we call an atmosphere, safe from the universe. No one knew how our bodies would react to weightlessness. Some physicians thought basic functions, like swallowing and pumping blood to the heart, would be impossible without the steady tug of gravity.

“We take for granted now that animals and humans can function in space, but back then we knew absolutely nothing,” says Bill Britz, an American veterinarian who worked with the chimpanzees who flew to space in the early 1960s.

The goal for the Cold War rivals was the same: to prove that animals could survive in orbit so that people could, too. But why did the Soviets use dogs, while the Americans used primates?

Read: What would a dog do on Mars?

The story of ZIB illustrates one rather pragmatic reason: Dogs were everywhere. The Moscow streets were crowded with stray dogs—free, if unwilling, volunteers.

The Soviet Union already had a long tradition of using dogs as research participants, says Amy Nelson, a history professor at Virginia Tech who has studied the Soviet space dogs. At the turn of the century Ivan Pavlov’s work with canines uncovered the learning process known as classical conditioning, a reflexive behavior that ties together a stimulus and a response. Pavlov had been studying canine digestion when he noticed that his pup subjects drooled before he even gave them meat, a hint that something had tipped them off that a delicious treat was coming.

Primates were more difficult to acquire. The chimpanzees were brought over from the Congo region in Africa, Britz says. The Air Force, which conducted some of the earliest primate flights before NASA was established in 1958, paid catchers in African nations to collect dozens of young chimps. Many of the test subjects arrived at the headquarters of the program, Holloman Air Force Base in New Mexico, in poor shape. Out of nine veterinarians, eight contracted hepatitis from the chimps. Britz was the only one who didn’t get sick.

The chimps were one to two years old. “They were just like kids,” Britz says. “We would play with them.” He remembers getting a call at home about flickering lights inside one of Holloman’s buildings. When he arrived, he found that one chimp had opened a padlock, escaped his cage, and helped another chimp out of his own. They were running around the lab, flipping light switches, and pulling chemical wipes from their container, one by one, as if they were Kleenex tissues.

American researchers picked primates because of their physiological similarities to humans, according to veterinarians and historians. They wanted chimps for their intelligence, too. The researchers taught the chimpanzees to conduct simple tasks during flight to test another important unknown—whether it was possible to remain conscious and actually do something in weightlessness. The chimps were taught to push levers in a certain sequence, prompted by flashing lights. If they got it wrong in training, they received a mild electric shock to their feet. For correct moves, they were rewarded with banana pellets. During the short flights, the chimps touched the levers from launch to reentry.

Read: Can humans understand chimps?

Dogs couldn’t be expected to manage similar duties, but the Soviets weren’t concerned, Nelson says. Their early cosmonauts would do little piloting. The capsule that carried Yuri Gagarin, the first man in space, was equipped with controls that could be activated from the ground ; manual controls were to be used in the case of an emergency. The first American man to achieve that same space milestone, Alan Shepard, handled dozens of switches, buttons, and levers in his capsule.

Nelson says that the Soviets did consider using primates, particularly monkeys. They visited the circus and asked monkey handlers how the animals might fare in a rocket launch. “And they’re like, ‘No, they’re way too high-strung, they’re temperamental, they’ll succumb to the stress of the experiment,’” Nelson says.

In both countries, the training for the animals was intense, according to Animals in Space , a comprehensive history by Colin Burgess and Chris Dubbs, and might be labeled animal abuse today. The Soviet dogs were restrained in small containers for hours to simulate the confinement of spaceflight. They were exposed to loud banging noises and spun around in centrifuges to mimic the extremes of spaceflight, from launch to landing. On the American side, primates were subjected to similar shakes and sounds, on top of their motor-skills training.

The Americans began their test flights in 1948 with rhesus macaques. The first six died of suffocation, explosions in flight, or upon impact. Britz says the chimpanzees who flew in the early 1960s fared better. He remembers seeing Ham, the first chimp in space, after he was recovered from a successful flight to the boundary where space begins. “He was in such mint condition,” Britz said of Ham, who went on to live in zoos until his death in 1983. Enos, the second and last chimp to fly, survived the journey but died several months later of a bacterial infection that Britz said was unrelated to spaceflight.

The memory of the Soviet space dogs lives on today in a menagerie of merchandise , from T-shirts to nesting dolls, a legacy that glosses over a less charming reality. Laika, the first dog to go beyond the edge of space and complete an orbit of Earth, breathed frantically during launch, her heart racing at triple the normal speed. The Soviets didn’t design the mission for a safe return, and Laika died in space not long after launch, from the excessive heat in the capsule, in 1958.

“The Russians felt very badly about it, especially about Laika,” says Cathy Lewis, a curator in the space-history department at the Smithsonian National Air and Space Museum. “The principal investigator, Oleg Gazenko, who sent Laika up into space, and knowing full well that she was not going to return—before he died, [he said] that was the one thing in his career that he had really regretted.” Before the flight, Gazenko had brought Laika home with him to play with his children, Lewis says.

Read: The Soviet space program was not woke

The Soviet Union stopped launching dogs in the 1960s. The United States ended its primate program around then, too, save for two squirrel monkeys who joined astronauts on a Space Shuttle flight in 1985 (and survived). Britz says the Holloman facility had trained enough chimps for nearly every Mercury astronaut; Ham had been a test run for Shepard, and Enos for John Glenn, the first American to orbit the planet. After Glenn flew and reported that the experience of weightlessness was, actually,  “extremely pleasant,” the chimp program was canceled.

Researchers switched to the animals that were becoming the preferred subject in laboratory study: rodents. These smaller creatures would help answer more complex questions about spaceflight, like how space radiation affects health . “If something changes in one animal, you don’t know if it’s truly representative of the science, but if it changes in 30 mice, you’ve got a pretty good cause and effect,” says Richard Simmonds, a veterinarian who worked at NASA in the early 1970s and oversaw the handful of mice that went to the moon on Apollo 17. “By the time I got there, it was pretty well-determined that flying the animals just to prove the safety of the flight had been done.”

Today, nearly 70 years after that Soviet dog bolted and lived out a life firmly on the ground, scientists continue to send animals into space as research proxies for people. According to NASA, there are some mice on the International Space Station right now, circling the Earth along with the astronauts on board.

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U.s. taxpayers funded chinese labs that carried out grisly experiments on beagle puppies.

The federal government has been paying Chinese labs that carry out animal testing including experiments that involved severing beagle puppies’ spines to study how they would react to such a horrific injury.

The White Coat Waste Project, in a new investigation shared first with The Washington Times, said 28 Chinese labs are approved to receive U.S. taxpayer money for animal testing. Among them are Sun Yat-Sen University and the Chinese Academy of Sciences, which carry out the grisly experiments on beagles.

Video of some experiments, compiled by WCW, shows beagles whose spines had been severed crawling on their front paws with their rears dragging across the ground, unable to move normally on their own.

Puppies as young as a day old were being “sacrificed” in order to obtain bone marrow material, WCW said.

The experiments are supposed to probe the effects of serious spinal cord injuries.

WCW said that while the U.S. government uses those labs for experiments, there is no evidence that the dog tests were directly funded by American taxpayers.

WCW said Pharmaron, another Chinese lab, is spending U.S. taxpayer dollars on dog testing.

Three other U.S.-approved labs are run by WuXi AppTec , a firm that members of Congress have linked to the Chinese military. And two labs are run by the Chinese Academy of Sciences, which the U.S. government has said contributes to the Chinese military.

“It’s disgusting that the Biden-Harris administration is still sending American tax dollars to shady Chinese labs for unnecessary, unethical, and unsafe experiments on dogs and puppies,” said Rep. Nancy Mace, South Carolina Republican. “This needs to stop immediately. They must’ve forgotten what happened in Wuhan.”

That was a reference to U.S. funding that flowed to potentially risky research at the Wuhan Institute of Virology, the lab that some American agencies believe leaked the coronavirus.

WCW was a key player in exposing that funding, and has been a persistent critic of former National Institute of Allergy and Infectious Diseases chief Dr. Anthony Fauci.

WCW said the ongoing funding for Chinese labs isn’t just a moral affront, it’s a security risk.

“Despite Fauci’s gain-of-function disaster that we exposed at the Wuhan animal lab, we’ve uncovered how the NIH is still shipping tax dollars to dozens of other Chinese labs that butcher beagles, poison puppies, threaten public health and compromise national security,” said Justin Goodman, senior vice president at WCW.

The investigation comes a year after the Government Accountability Office, the government’s chief watchdog, found problems in the way the National Institutes of Health manages its research spending abroad.

In particular, GAO said, it’s impossible to say how much U.S. money actually flows to researchers in China and elsewhere because the government doesn’t require recipients of taxpayer money to report on subcontractors who may be abroad.

Some members of Congress have been pushing to end all U.S. government funding for experiments on dogs and cats, whether conducted domestically or abroad.

Lawmakers are also eyeing legislation that would shut down U.S. funding for animal labs in China and other adversarial nations.

Rep. Lisa McClain, Michigan Republican and sponsor of that bill, said it should get a new look after the latest revelations.

“American tax dollars should never go to the Wuhan Lab again or any others in China that pose national security risks,” she said.

Sen. Joni Ernst, Iowa Republican, announced Wednesday that she has introduced legislation to require annual reporting from federal agencies about how much funding they send to Chinese labs.

“It should not feel like herding cats to figure out how many tax dollars are funding batty experiments in Wuhan,” Ms. Ernst said.

The U.S. House earlier this month approved legislation that would ban pharmaceutical firms that receive taxpayer money from working with five Chinese firms, including WuXi AppTec .

That bill passed 306-81 with nearly every Republican and more than half of Democrats in support, with backers saying the firms are too closely tied to China’s military establishment.

WuXi AppTec , on its website, has challenged the legislation, posting news stories that suggest the bill would undermine medical progress in America.

“We adhere strictly to all U.S. laws and regulatory standards,” the firm said.

Correction: This article has been updated to reflect what kinds of experiments are being funded with U.S. money.

• Stephen Dinan can be reached at [email protected] .

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The Moscow Signals Declassified Microwave Mysteries: Projects PANDORA and BIZARRE

National Security Archive Posts Special Declassified Collection on Microwave Transmissions Aimed at U.S. Moscow Embassy, 1953-1979 

Was the Moscow Signal a Historical Precedent for the "Havana Syndrome"?

Project BIZARRE: Pentagon Officials Conducted Radiation Tests on Monkeys, Planned Secret Human Experimentation

Washington D.C., September 13, 2022 - On the 5 th  anniversary of the CIA’s September 13, 2017, decision to pull its agents out of Cuba, after several operatives were stricken with what has become known as the “Havana Syndrome,” the National Security Archive today posted the first of a declassified documentation series on the “Moscow Signals”—a decades-long chapter of the Cold War during which Soviet intelligence bathed the U.S. Embassy in Moscow with microwave transmissions on a daily basis, and, in the late 1950s, penetrated the U.S ambassador’s residence with ionizing radiation. The records published   by the Archive are among those being reviewed by a special, high-level panel tasked by the Biden administration to search for clues into the enduring mystery surrounding cognitive brain traumas experienced by several dozen U.S. intelligence and diplomatic personnel in Havana, and elsewhere, over the last five years.

The CIA announced in late August that it is compensating at least a dozen of its officers and operatives for syndrome-related injuries known as “Anomalous Health Incidents” (AHI).

The documents posted today record Project BIZARRE, the actual—and rather appropriate—codename for a program of radiation experiments conducted on monkeys to determine if the Moscow Signal was intended to degrade the abilities of U.S. personnel to function at the Embassy. Project BIZARRE was a highly classified component of Project PANDORA, a broader research effort undertaken by the Defense Department’s Advanced Research Projects Agency (ARPA) that included evaluating blood samples of U.S. personnel posted in Moscow and surveying medical records of crew members of the aircraft carrier USS Saratoga to determine if exposure to radiation-emitting technology on board produced physiological effects.

“The Soviets have reported in the open literature that humans subjected to low-level (non-thermal) modulated microwave radiation, show adverse clinical and physiological effects,” ARPA official Richard Cesaro reported in a TOP SECRET, September 1967, update on Project BIZARRE. “The ARPA BIZARRE program will establish methods which should permit us to relate the behavior of sub-human primates to man under conditions of microwave exposure. This may require direct testing with humans under controlled conditions.” 

Among the documents posted today is the original TOP SECRET “Justification Memorandum for Project Pandora,” written by Cesaro in October 1965, which stated that the White House had ordered a program of “intensive investigative research” “under the code name project ‘TUMS’’—Technical Unidentified Moscow Signal. The posting also includes a SECRET May 1965 memorandum by ARPA scientist Samuel Koslov which argued that “a program to specifically check the complex Moscow signal waveforms on higher primates should be carried out to supply some data base for possible use in a protest action” against the Kremlin. Titled “Biomedical Phenomena,” the memo was obtained by science historian Nicholas H. Steneck for his groundbreaking 1984 study, The Microwave Debate , but has never been published in full on the Internet before now.

OVERVIEW OF THE MOSCOW SIGNAL

Despite four years of efforts, the multi-million-dollar PANDORA-BIZARRE projects failed to prove the early hypothesis that the Russians deployed the microwave beams to degrade the mental and physical abilities of U.S. Embassy officers to perform their diplomatic and intelligence duties. An initial experiment of modulated microwave beams on a single monkey appeared to show an impact on its behavior. But the test was conducted using the CIA’s inaccurate readings that the power of the beams was .5 to one milliwatt—exceeding Soviet safety levels by a factor of 100. In reality, as the CIA correctly determined in 1967, the power density of the beams was "no greater than .05 mw/cm in the Moscow Signal," a level that was well below U.S. and Soviet safety levels, as ARPA official Cesaro advised in a TOP SECRET update on Project BIZARRE from September 1967. At the corrected levels, he reported, the “modulated microwave radiation did not cause the primate to degrade in conducting his work tasks.”

The findings, according to one CIA scientist working with ARPA, indicated that the beams were not dangerous to U.S. personnel at the Embassy. “I feel confident in stating,” as Joe Johnston reported in September 1967 on Project BIZARRE results, “that, at the power levels reported for TUMS, persons exposed are at no risk of injury.”

Another theory pursued by the U.S. intelligence community suggested that the signal served as a jamming device intended to disrupt U.S. espionage operations that were conducted out of a surveillance shed on the roof of the Embassy building. A third, and prevalent, theory is that Soviet intelligence agencies employed the Moscow Signal to activate, power and/or interpret eavesdropping devices in the walls of the Embassy building. “Defense feels we must bear in mind the possibility that some of the signals are [deleted] for the activation or interrogation of audio devices implanted in the Embassy,” stated a TOP SECRET/SENSITIVE White House memorandum for President Ford in February 1976, drawing on the Defense Department’s evaluation of the microwave beams. [Note: The memorandum to President Ford will be posted on September 15.] 

Numerous such bugging devices were discovered in April 1964, hidden in the walls of at least eleven Embassy offices—including the office of the U.S. Defense Attaché. The realization that Soviet intelligence had penetrated the Embassy and compromised secret U.S. communications set in motion a series of countersurveillance measures and a major focus on the mysterious energy beam directed at the building. U.S. technicians first detected the energy rays in 1953, shortly after the Embassy opened, but only began to actively monitor the radiation rays in the early 1960s. A technician from the State Department’s Bureau of Diplomatic Security, Maclyn Musser, identified them as microwave radiation and reported, in 1963, that the beam was 50 feet across. “More effort should be made to understand the purpose of the microwave signal directed at the Embassy, or failing in this, to stop it,” Jerome Wiesner, the former chairman of the White House Science Advisory Board advised in a SECRET June 1964 memo on “Bugging of U.S. Embassy, Moscow”—the first document posted today as part of the Moscow Signal collection. “It is hard to understand why we have been so unconcerned about it.”

As the declassified documents posted today record, in the mid-1960s, U.S. national security agencies initiated a series of programs, assessments and operations designed to address the microwave beams, codenamed “TUMS”—Technical Unidentified Moscow Signal. (In the mid-1970s, after a second signal was detected, the codename was upgraded to “MUTS”—Moscow Unidentified Technical Signals.) The Pentagon conducted the Project PANDORA and BIZARRE studies. Those included:

Project Big Boy : A set of medical evaluations of the personnel aboard the Navy’s aircraft carrier Saratoga . ARPA, according to one status report, would place “observers aboard the Saratoga to get base line [sic] readings on selected members of the crew.” The purpose of Project Big Boy was to evaluate physical and mental differences between distinct groups of crewmen: veteran members of the crew whose duties exposed them to microwaves generated by radar instrumentation; newer recruits with no history of previous exposure to microwaves; sailors who were detailed above deck; and others below deck. The study produced no discernible evidence of physiological and psychological differences between the test groups.

The Monkey Experiments : Between 1966 and 1969, ARPA teams conducted and contracted for a series of radiation experiments on chimps and rhesus monkeys, compiling data on behavior modification, heart rates, and tissue and blood analysis, among other physiological elements. (Initially codenamed PANDORA, after the first set of experiments, the primate tests were given their own specific codename—Project BIZARRE.) As members of the ARPA team disagreed on whether the tests had produced any conclusive evidence of radiation exposure on health and behavior, the experiments were sent for outside peer review. One review from the RAND Corporation concluded that “the data do not present any evidence of a behavioral change due to the presence of the special signal within the limits of any reasonable scientific criteria.” Another RAND Corp evaluation of a specific set of experiments noted that it had produced “no material…which is scientifically credible” of any impact. In addition, “animal care was not in accordance with good laboratory practice,” the RAND panel reported. “Examination of the data log indicated that of five monkeys’ deaths, three were certainly due to strangulation resulting from poor experimental design of the restraint system.”

Planning for Human Experimentation : Declassified summaries of the meetings of the PANDORA program’s Science Advisory Committee record preparations to go beyond primate experimentation and use unwitting human subjects who would not be aware of the nature of the radiation tests. Subjects for human testing of radiation impact would be secured from Fort Detrick and subjected to radiation exposure over a period of six months, according to the discussion at an April 1969 meeting. “Study should be double-blind with protection of eyes and gonads,” Committee members suggested. “Shielding of testicles is recommended.” Before any such experiments could be performed, however, the PANDORA/BIZARRE program was shut down in 1970.

The State Department also played a role in the TUMS inquiry, commissioning George Washington University’s Human Cytogenetics Research Laboratory to conduct a SECRET study, “Cytogenetic Evaluation of Mutagen Exposure.” The study gathered, coded and analyzed blood samples taken under false pretenses from U.S. personnel posted in Moscow. They were told that the State Department Medical Office was monitoring the spread of Russian viruses. Publicly, the research was given the innocuous title: “The Moscow Viral Study.”

Among other countersurveillance measures that remain highly classified, the CIA monitored the signal and, in 1965, sent a special technician to evaluate security at the Embassy. He recommended installing thin shields on the Embassy windows to block the radiation beams from entering the building—a recommendation that went unimplemented for more than a decade, according to documents obtained by the Associated Press .

U.S. officials also undertook efforts to convince the Soviet leadership to shut off the signal. The first high-level effort took place at a June 1967 superpower summit held in Glassboro, N.J., between U.S. President Lyndon Johnson and Soviet Premier Alexei Kosygin. At a side meeting, Secretary of State Dean Rusk told Soviet foreign minister Andrei Gromyko that “we were very much concerned at an electro-magnetic signal directed at our Chancery building in Moscow.” “We did not know the purpose of this activity,” Rusk said, according to a declassified memorandum of conversation, but the U.S. wanted “the matter to be investigated and the activity stopped.” In response, Soviet ambassador Anatoly Dobrynin suggested that the U.S. was conducting “similar activity” against the Soviet Mission in New York and the Soviet Embassy in Washington. While expressing skepticism at the U.S. claims—which were, in fact, incorrect—that the radiation exceeded Soviet safety standards, Gromyko “indicated he would look into the matter.”

But the daily doses of radiation continued. By mid-1975, U.S. intelligence monitors detected additional, and stronger, signals aimed at the Embassy. Hundreds of diplomats, security and intelligence officers, and their families who lived in the residence section of the Consulate building, were unknowingly exposed to radiation for up to 19 hours a day.

The U.S. ambassador, Walter Stoessel, became the unsung hero of the Moscow Signal saga in the fall of 1975 when he forcefully pushed a reluctant Secretary of State, Henry Kissinger, to pressure the Kremlin to terminate the transmissions and to authorize a classified briefing for the Embassy staff—who had been kept in the dark about the existence of the Moscow Signal. A strictly confidential Embassy staff briefing was scheduled in early February 1976, cancelled, and then rescheduled and held. Sensitive information Stoessel shared with U.S. Embassy personnel immediately leaked to U.S. newspapers, setting off a major scandal in U.S.-Soviet relations. 

AN INCOMPLETE HISTORICAL RECORD

The publicity surrounding the Moscow Signal generated congressional inquiries and hearings and renewed internal U.S. government efforts to halt the transmissions. The National Security Agency eventually sent one of its leading technical officers, Charles Gandy, to Moscow to assess Embassy security and to determine how the microwave beams were being used to intercept U.S. Embassy communications and identify U.S. spies in Russia. Gandy’s investigation became the focus of a recent book, The Spy in Moscow Station,  by former NSA official Eric Haseltine.

But the intelligence operations and assessments produced by the NSA and CIA on the Moscow Signal remain TOP SECRET. “Information on nonbiological testing that followed the discovery of the Moscow signal is still classified,” Professor Steneck noted in his book, The Microwave Debate , which contained several detailed chapters on the microwave beams and the U.S. government response when it was published in 1984. After nearly four decades, almost none of the intelligence community’s records on the Moscow Signal have been released.

Pursuant to demands by Congress, however, the U.S. government did begin to declassify select parts of the history of U.S. efforts to understand and address the Moscow Signal. ARPA declassified some documentation for a 1979 investigation by the Senate Committee on Commerce, Science, and Transportation. Other records were obtained through the Freedom of Information Act (FOIA) by Steneck while researching his book. In the mid-1980s, the Associated Press used the FOIA to obtain several thousand pages of records. An investigative reporter named Michael Drosnin also obtained numerous PANDORA documents under the FOIA but never published the information they contained. Some of the PANDORA documents were eventually posted on a Pentagon website and later used by former Foreign Policy executive editor Sharon Weinberger in her book, Imagineers of War: The Untold Story of DARPA, the Pentagon Agency That Changed the World . The book was excerpted in an article for the Foreign Policy website, “The Secret History of Diplomats and Invisible Weapons,” that noted that the alleged use of a “sound weapon” against U.S. Embassy officials in Cuba “harks back to a Cold War medical mystery” in Russia. Former U.S. diplomats who were exposed to the Moscow Signal in the 1970s—especially those who believe their rare blood cancer illnesses derive from that exposure—have also written about the parallels with the "Havana Syndrome." “It is like ‘déjà vu’ all over again,” said retired diplomat James Schumacher, who was posted in Moscow over 40 years ago and wrote in an article for the American Foreign Service Association titled “Before Havana Syndrome, There Was Moscow Signal.”

The National Security Archive obtained the declassification of phone conversations between Henry Kissinger and Soviet Ambassador Anatoly Dobrynin relating to the Moscow Signal through the FOIA and has located dozens of reports on PANDORA/BIZARRE—along with diplomatic cables and reports relating to the diplomacy with the Kremlin to end the microwave beams—in the files of the National Archives and various presidential libraries. The Archive will continue to use the FOIA to uncover the full historical record on this episode, including the CIA assessments and the still secret records on how Washington and the Kremlin negotiated an end to the microwave transmissions.

Part II of the series,  “The Moscow Signals Declassified: Microwave Diplomacy,”  which records more than ten years of back channel diplomatic efforts to address the radiation beams aimed at the Embassy, will be posted on September 15, 2022. Part III,  “Irradiating Richard Nixon,”  which documents ionizing radiation detected during the Vice President's 1959 trip to Moscow, will be posted the week of September 19th. A supplementary, special collection of documentation on “Moscow Signals Declassified,” will also be posted the week of September 19.

Acknowledgements : The National Security Archive respectfully thanks Nicholas Steneck for his original, groundbreaking research on the Moscow Signal, and for his support and encouragement on this project; and also Louis Slesin for his assistance. Thanks also to Jacqueline Schluger, George Washington University, for research assistance on this posting.

The Documents

National Security Archive, John Prados and Arturo Jimenez-Bacardi, eds., “Understanding the CIA,” Document 14

In the wake of the discovery of 17 Soviet listening devices hidden in the walls of U.S. Embassy in Moscow in June 1964, the chairman of the President’s Scientific Advisory Committee, MIT Provost Jerome Wiesner, conducted a security review of the Embassy. His classified report to Clark Clifford, who chaired the President’s Foreign Intelligence Advisory Board (PFIAB), contains a number of recommendations, among them using headsets and microphones to conduct secure conversations in the building, “inducing masking sounds” into the walls to disable the function of the eavesdropping equipment, and mounting screens to block electromagnetic-reflection surveillance operations. Wiesner also sounds the alarm on the microwave radiation beams that have been bathing the building for a decade: “More effort should be made to understand the purpose of the microwave signal directed at the Embassy, or failing in this, to stop it,” he advised. “It is hard to understand why we have been so unconcerned about it.”

Nicholas H. Steneck personal collection

In one of the earliest arguments in favor of conducting experiments to explain the Moscow Signal, scientist Samuel Koslov of the Defense Department’s Advanced Research Projects Agency (ARPA) sends a memo to the State Department’s security office with a brief overview, based on Soviet scientific literature, of the “possible effects of low level continuous exposure” to radiation on human health. “A possible explanation of the Moscow Signal may reside in an attempt to produce a relatively low level neurophysiological condition among Embassy personnel,” Koslov postulates, while admitting that “the detailed studies of the signal do not give this a high probability of interest.” Koslov insists, erroneously, that “the Soviet irradiation of the Embassy exceeds their own ambient safety level by a factor of 100.” (Initially, U.S. intelligence significantly overestimated the strength of the signal when, in fact, it was well below both Soviet and U.S. safety standards.) He advocates for “a program to specifically check the complex Moscow signal waveform on higher primates” in order to “supply some data base for possible use in a protest action.” Within a few months, ARPA receives authorization to initiate a secret program to test the impact of radiation exposure on the behavior of monkeys.

Drosnin FOIA, DoD Reading Room

ARPA initiates a special research program codenamed “Project PANDORA.” In this memorandum introducing the project, supervisor Richard Cesaro explains that the U.S. Embassy in Moscow has been radiated with low-level electromagnetic beams on a continuous basis for a number of years. In response, the White House has ordered the U.S. Intelligence Board to assure that “intensive investigative research be conducted within the State Department, CIA and DOD to attempt to determine what the actual threat is and stop it.” The code name for the multi-agency efforts is “TUMS”–Technically Unidentified Moscow Signal. But, Cesaro advises, the ARPA contribution “is known as Project PANDORA” and will address “one of the potential threats, that of radiation effects on man.” Cesaro informs the other agencies participating in the project that a “program has been outlined to irradiate a group of primates under carefully controlled conditions simulating the dosages and complex modulation of the threat.” Cesaro adds that, “The trained primates will be carefully observed under varying and controlled irradiated conditions in an attempt to determine if any changes in their behavior or physiological condition can be detected.” Eventually, as ARPA expands its work on the Moscow Signal, the experiments on rhesus monkeys will be referred to as “Project BIZARRE.”

Nicholas Steneck research papers, Gerald Ford Presidential Library

The State Department’s medical office cables the U.S. Embassy in Moscow to advise them of the “Moscow Viral Study” that the department is conducting as a cover story to draw blood from U.S. personnel to research the physiological effects of the Moscow Signal. To identify potential subjects, the Department requests quarterly reports on employees and dependents who are due to return from Moscow to the U.S. for home leave.

The State Department medical office offers George Washington University an 11-month contract to evaluate and code blood samples taken from Moscow Embassy diplomats, employees, and dependents. The project is titled “Cytogenetic Evaluation of Mutagenic Exposure” and will be supervised by Dr. Cecil Jacobson, a George Washington University scientist assigned to the Human Cytogenetics Research Laboratory who is on the PANDORA team. In a reference to PANDORA, a summary of the contract states that the human blood samples may inform experimentation on animals. “Confirmative animal experiments will be undertaken later,” states a summary of the program.

U.S. National Archives, Department of State Records (RG 59), Subject Numeric Files, 1967-1969, BG Moscow 13

During the June 1967 Summit between President Lyndon Johnson and Soviet Premier Alexei Kosygin, U.S. officials issue the first high-level protest of the ongoing microwave signals. At a side meeting between Secretary of State Dean Rusk and Soviet Foreign Minister Andrei Gromyko, Rusk stated that “we were very much concerned at an electro-magnetic signal directed at our Chancery building in Moscow.” Rusk said the U.S. “did not know the purpose of this activity,” but said the U.S. wanted “the matter to be investigated and the activity stopped.” In response, Soviet Ambassador Anatoly Dobrynin suggested that the U.S. was conducting “similar activity” against the Soviet Mission in New York and the Soviet Embassy in Washington. While expressing skepticism at the U.S. claims, Gromyko “indicated he would look into the matter.”

In a special summary to a colleague, the CIA’s representative on Project PANDORA/BIZARRE, Joseph Johnston, records the status of the experiments. He notes that analysis of the “TUMS power levels” has been revised and considerably lowered. There is now “reasonable certainty that the power level is not over 50 microwatts/cm2” but closer to 2 microwatts/cm2 at its average high level. Citing the results of the first test on a monkey (which were conducted when U.S. analysts mistakenly believed the signal was at a higher power level than it was) Johnston notes that there were “pronounced behavioral affects [and] performance decrement.” The impact on behavior, he suggests, was “due to the modulation feature” of the signal, “and not to the energy bearing carrier frequency.” “This very intriguing and important observation in one animal must be pursued,” he advises, and confirmed by an independent laboratory. Johnston emphasizes that “all positive findings of Project BIZARRE were achieved at one half an order of magnitude below the accepted U.S. standard for safe exposure.” Moreover, subsequent experiments at the adjusted lower level of radiation “produced no behavioral effects,” Johnston points out. He concludes: “I feel confident in stating that, at the power levels reported for TUMS, persons exposed are at no risk of injury.”

Ricard S. Cesaro, overseer of the PANDORA/BIZARRE program, sends a “progress report on Project BIZARRE” to the ARPA research and engineering director in September 1967. His report references a series of previous updates on subjecting primates to microwave exposure, as well as a secret CIA memorandum titled “Summary of TUMS Power Density Measurements” which reported that the levels of the microwaves beamed at the U.S. Embassy were considerably lower than previously believed. (They were, in fact, at levels below the Soviet safety standards, and likely not threatening to human health.) [1] “New measurements with ARPA instrumentation of the ‘Moscow Signal’ on site has [sic] now been completed,” Cesaro advises. Using the corrected level, “the recent BIZARRE tests have completed one experiment on primate behavior” that demonstrates “no overt primate performance degradation …” Even so, Cesaro’s memo lays out the argument to go beyond radiation experiments on monkeys and conduct tests on human subjects. “The ARPA BIZARRE program will establish methods which should permit us to relate the behavior of sub-human primates to man under conditions of microwave exposure,” he advises. “This may require direct testing with humans under controlled conditions.”

ARPA official Herbert Pollack reports on a meeting held on the USS Saratoga aircraft carrier with key naval officers to discuss a new PANDORA project. The project will review medical records of the ship’s personnel, and place “observers aboard the Saratoga to get base line readings on selected members of the crew.” The purpose of the study is to evaluate medical differences between distinct groups of crewmen: veteran members of the crew whose duties exposed them to microwaves generated by radar instrumentation; and new recruits with no history of previous exposure to microwaves. At ARPA, the project is code-named operation “Big Boy.”

Document 10

In one of a series of monthly meetings in 1969, Pandora’s scientific-government board reviews its research efforts on the Moscow Signal. The first part of the meeting covers the initial results of project “Big Boy,” the study of the crew of the USS Saratoga . Early tests “were negative,” finding “no significant differences in psychological tests performed on apparently exposed and control groups,” and no “significant differences” in genetic and physical findings. After almost four years of experiments on monkeys, the panel agrees that “there is at present insufficient evidence to draw conclusions” about the potential impact of the Moscow Signal on human behavior. The inconclusive nature of the research reinforces proposals at the meeting to move beyond exposing monkeys to radiation to “develop[ing] a human program.” Subjects for human testing of radiation impact could be secured from Fort Detrick (misspelled as “Ft. Dietrich” in the document) and subjected to radiation exposure over a period of six months, according to the discussion. “Study should be double-blind with protection of eyes and gonads,” the board suggests. “Shielding of testicles is recommended.”

Document 11

The PANDORA officials devote most of this meeting to developing a specific protocol for subjecting humans to radiation tests, addressing the levels of radiation to be used, and the “behavioral aspects of the program.” They also discuss “classification considerations” and “an appropriate cover” story to maintain secrecy around the research, including from the personnel being subjected to the tests. “DOD regards the general line of effort to acquire human-based data on effects of the signal, with appropriate safeguards, as a high priority,” the minutes state. “ARPA believes that the entire effort should be classified for several reasons.” Reflecting the sensitivity around the issue of human testing, according to the minutes “It was urged that DOD provide written security specifications and guide for the program.” (Emphasis in original.)

Document 12

Drosnin FOIA, DOD Reading Room

RAND Corp. scientist Samuel Koslov, the former ARPA official who in 1965 who helped initiate the PANDORA project, assesses the data generated by several years of experiments on the impact of radiation on the behavior of rhesus monkeys. “I am forced to conclude that the data do not present any evidence of a behavioral change due to the presence of the special signal within the limits of any reasonable scientific criteria,” he writes. “There is evidence of behavioral change in some cases but this change could be attributed to a variety of causes or systematic measurement errors all well within the limits of experimental methodology. Evidence of other effects such as EEG, histology, and chromosomal analyses have not accumulated with either adequate detail or control to tell whether effects due to radiation are present.”

Document 13

U.S. National Archives, Record Group 46, Records of U.S. Senate Committee on Commerce, Science and Transportation, 90 to 95th Congress, Project Pandora Folder

In response to a request from the Navy, a panel of experts led by RAND Corporation scientist Samuel Koslov evaluates one of the last Project BIZARRE-type contracts for radiation experimentation on monkeys and rabbits. The panel concludes that the leading experiments to measure the impact of “long-term, low-level chronic exposure of primates” to radiation have produced “no material … which is scientifically credible ….” Among the factors the panel cites are the failure of the Navy to provide proper radiation devices, bad management, poorly trained technicians, and “poor” animal care. “Animal care was not in accordance with good laboratory practice,” the panel reported, citing the death of five of the monkeys. “Examination of the data log indicated that of five monkeys’ deaths, three were certainly due to strangulation resulting from poor experimental design of the restraint system.”

Document 14

In the aftermath of the scandal over the Moscow Signal, and publication of a high-profile article on the subject in The New Yorker magazine by Paul Broduer, several congressional committees investigate U.S. government efforts to address the microwave beams, including the PANDORA and BIZARRE projects at DARPA. In response to a series of questions posed by Representative Warren Magnuson, chairman of the House Committee on Commerce, Science and Transportation, DARPA director George H. Heilmeier transmits this letter providing answers and a general summary of the PANDORA program. Among the details: PANDORA was shut down in March 1970 after almost five years of work; its total costs amounted to $4,615,000. Heilmeier misleads the committee by denying that PANDORA was intended to “probe” the use of microwaves as a form of “mind control.” He also states that DARPA “does not foresee the development, by DARPA, of weapons using microwaves and actively being directed toward altering nervous system function or behavior. Neither are we aware of any of our own forces or possible adversary forces developing such weapons.” In the letter, Heilmeier also announces that meeting minutes of the PANDORA board have been declassified.

Document 15

U.S. Senate Committee Print

Following the scandal of the Moscow Signal, the Senate Committee on Commerce, Science, and Transportation conducts a lengthy review of the documentation on the PANDORA/BIZARRE projects and of various official investigations in an effort to determine the health and safety effects on U.S. personnel who served at the Embassy. This staff report criticizes the official secrecy that kept U.S. personnel in the dark about the ongoing radiation: “Embassy employees were not informed by the State Department of the presence of this radiation throughout the period from its initial discovery until early 1976,” the report notes. “The employees should have been promptly informed of the situation.” At the same time, the report concludes that as of 1979 the medical survey studies on U.S. personnel showed no discernible evidence of impact on health from exposure to the low-level radiation beams. “No convincing evidence was discovered that could directly implicate the exposure to microwave radiation experienced by the employees at the Moscow Embassy in the causation of any adverse health effects as of the time of this analysis,” the Senate inquiry concluded, with the caveat that “it is too early to have been able to detect long-term mortality effects” among hundreds of U.S. personnel exposed to radiation waves between 1953 and 1977.

[1] See also Nicholas Steneck, The Microwave Debate (Cambridge: MIT Press, 1985), 110.