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