What Happens to Science When Model Organisms Become Endangered?

Update (December 12): Following a string of indictments against a smuggling ring, Cambodia will no longer export long-tailed macaques, STAT reports.

Update (November 28): Science reports that the US Department of Justice broke up an operation that had been illegally exporting hundreds of endangered long-tailed macaques (Macaca fascicularis) from Cambodia. The macaques were being falsely labeled as “captive-bred” and were sent to the US for use in biomedical research. Science notes that the indictment may exacerbate ongoing macaque shortages.

Long-tailed macaques (Macaca fascicularis) and southern pig-tailed macaques (Macaca nemestrina) have emerged as important model organisms, especially for research on infectious diseases. While not quite as popular with scientists as their cousin, the rhesus macaque (Macaca mulatta), both species provide unique insights into difficult-to-study viruses, including HIV and SARS-CoV-2. Unfortunately, in July the International Union for Conservation of Nature (IUCN) updated its Red List designations for both species, shifting them from “vulnerable” to “endangered” and putting them three steps away from the final stage of the organization’s seven-step scale, “extinct.” It’s a move that primate experts say is necessary to ensure the animals’ survival in their natural habitats scattered throughout Southeast Asia, but because the IUCN identifies export for the purposes of laboratory experimentation as one of the main threats facing the macaques, biomedical researchers worry that designating the species as endangered could stymie some types of science.

The new designations don’t trigger any immediate changes to primate research, notes University of Washington researcher Charlotte Hotchkiss, the associate director for animal resources at the Washington National Primate Research Center—an institute that conducts both biomedical and conservation-focused macaque research and also maintains a colony of macaques for their own and others’ research, at the behest of the National Institutes of Health (NIH). “Right now, there is no impact, but we are very concerned for the future, and we are trying to figure out the best way to address this,” says Hotchkiss. “One thing I hope we can do is get the message out that we [primate researchers] are important.”

Lauren Gilhooly, a former anthropologist who studied the effects of ecotourism on wild macaque populations but has since left academia, says it’s past time that the plight of the animals receives the same attention as concerns over whether researchers will be able to do their experiments. “I understand the cost-benefit tradeoff [of] lab research with helping humans and treating disease, but we also have to think about the cost-benefit of using nature as a commodity to help humans,” she says.

Vanishing macaques

The idea that macaques are in trouble might seem surprising because they’re typically not hard to find in the Asian countries they’re native to. “There seemed to be some discrepancies between the perception of abundance of longtail macaques and the true abundance of longtail macaques,” says Malene Hansen, a primate researcher and member of the IUCN’s primate specialist group. Hansen, who says she’s documented some of those perceptual discrepancies in her work, is head of the conservation charity The Long-Tailed Macaque Project (a collaboration among researchers who performed the long-tailed macaques’ conservation status surveys for the IUCN Red List, resulting in its reclassification), and she also contributed to the surveys on the pig-tailed macaques. Because macaques have lived among humans for millennia, especially around the borders of towns or settlements in Southeast Asia, people tend to assume that they’re only seeing a small fraction of the macaque populations, with other, more numerous macaque communities living deeper within jungles. “There’s a tendency for everyone to believe that an animal cannot be endangered if you see it,” Hansen says.

Photo of four long-tailed macaques (Macaca fascicularis), two grown and two young, sitting on a rock.

Long-tailed macaques (Macaca fascicularis) in Thailand

But their close association with human society is actually a sign of the danger they face. “Most of the macaque’s world is in what we call anthropogenic environments, which is one of the big reasons we know they’re in trouble,” explains Princeton University anthropologist Augustín Fuentes, whose work contributed to the IUCN reclassifications, adding that the more reclusive populations people often imagine may not actually exist.

“I feel like people like me who have been studying macaques for a while . . . have been saying these things for a long time,” says Gilhooly. “Yes, they’re ubiquitous, but look at the number that are being killed every year, whether it’s traffic accidents, or culling, or being for the pet trades or labs. . . . The rate at which they’re being killed has been high for a while.” Gilhooly adds that macaques haven’t gotten the same attention from conservationists as other animals that find themselves in more dire situations.

And the macaque situation is indeed dire, Fuentes notes. The IUCN estimates that, if things continue as they are now, both species are expected to suffer catastrophic population losses in the coming decades. The organization calculates that approximately 40 percent of the wild long-tailed macaque population has vanished in the last three generations (about 42 years) and over 50 percent of the pig-tailed macaque population has vanished in the last three generations (about 33 years).

“What it means is they are under extreme threat and, if nothing changes, the next three [or] four decades are going to see them go to nothing,” he adds.

I understand the cost-benefit tradeoff [of] lab research with helping humans and treating disease, but we also have to think about the cost-benefit of using nature as a commodity to help humans.

—Lauren Gilhooly

Researchers studying macaque conservation and human-macaque interactions tell The Scientist that one of the chief reasons these animals are disappearing is the ongoing capture and export of these monkeys for the pet trade as well as for lab experimentation, with the US being the primary importer of the animals for research. Long-tailed macaques, for instance, are commonly used in preclinical experiments to test the safety profiles or efficacy of new pharmaceuticals, including vaccines for SARS-CoV-2. Scientists have used pig-tailed macaques as crucial models in HIV/AIDS research because they’re the only macaque species that can be infected by the virus. More recently, the pig-tailed macaque was deemed more useful than other macaque species as models for SARS-CoV-2 infections, as the way the disease presents and progresses in them more closely resembles human COVID-19 than do infections in other macaques.

See “Monkeys Develop Protective Antibodies to SARS-CoV-2”

Tracking down just how many macaques are traded for research (and how that number compares to the number of captive-born or bred macaques used for research) is difficult: Many of the experts who spoke to The Scientist either couldn’t identify clear, accurate numbers or shared data that only covered a portion of the trade. Part of the problem is that recent years’ export data from major exporting countries such as Indonesia are still missing, explains Action for Primates cofounder Sarah Kite, who adds that the data that has been reported likely underestimates the number of wild captures, as traders will often claim that wild-caught macaques were bred in captivity in order to circumvent regulations.

Also, she notes that the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), which monitors international animal exports, doesn’t track domestic trade in a given country, so macaques taken from the wild and used in local research or to establish or replenish breeding farms are not tracked internationally—and within-country data collection can be patchy. Even so, she shared data (backed by CITES database searches) indicating that thousands of live, wild-caught macaques were sent to the US in 2020 alone. The database also shows that exports to the US represent the vast majority of reported live macaque trade.

How the IUCN Red List affects research

The IUCN’s decisions do not in any way force researchers who use macaques in their work to alter course, nor does a species’ status on the organization’s Red List prevent scientists from importing, conducting studies on, or sacrificing it for the purposes of research. So the long-tailed and pig-tailed macaques’ new endangered statuses don’t have much influence over scientists or their academic or private research institutions—unless those scientists or institutions actively decide to change their practices of their own volition.

A photo of a long-tailed macaque (Macaca fascicularis) holding a flowering plant up to its face.

A long-tailed macaque (Macaca fascicularis) at Batu Caves in Kuala Lumpur, Malaysia


“This is based on goodwill,” says Fuentes. The IUCN is essentially “scientists getting together, saying ‘This is where we are,’ hoping the folks in charge of global trade . . . notice and take this seriously.”

Such voluntary changes, experts tell The Scientist, have not yet happened. The global macaque trade continues apace. In fact, demand for macaques destined for laboratories has increased, Hansen says, as researchers scramble to obtain the monkeys necessary for their research in the face of recent transportation restrictions, the Chinese government’s decision to cease macaque exports, and other factors that have led to a shortage of macaque research subjects in the past few years. And researchers in macaque-exporting countries have followed suit, responding to increased demand from foreign countries such as the US by securing more macaques for their own work to make sure they don’t run out, she adds.

While the IUCN listings may not have sway, the international macaque trade is managed and documented by CITES, to which nearly every country in the world belongs. Hansen says that the legal international trade recorded in the CITES database likely represents the tip of the iceberg, given untracked domestic trade and black-market exports. Furthermore, in the US, macaque import, export, and research are regulated by the US Fish and Wildlife Service (USFWS). Any changes in either organization’s policies would have a much more tangible and immediate impact on researchers’ careers than the Red List status updates.

Still, the IUCN assessments are “a foot in the door” that may influence other institutions to impose restrictions on macaque research and trade, says Hotchkiss. “It’s raising the question in people’s minds,” she says.

That’s a concern to Hotchkiss, as she questions the IUCN’s conclusions and says she’d like to find a way to repeal the Red List reclassifications. In particular, she feels that the IUCN hasn’t shared enough data to justify its decisions or to point fingers at exports for biomedical research, suggesting that the CITES database may be inflated by repeatedly counting animals that are exported multiple times. She also feels that the IUCN’s prediction of future population decline is based on speculation rather than data.

“Population changes aren’t always linear,” she notes. “Maybe with habitat loss, you’ve lost some subpopulations. That does not mean you’re on a linear trajectory to zero. . . .We don’t have any of that information.”

Hansen explains that the data on both macaque species that she and her colleagues gathered for the IUCN came from a network of habitat-country researchers who have firsthand experience with macaque populations in their local areas. Responding to questions regarding data availability, she points to the information and works cited in each species’ entry in the Red List, though she adds that much of the data hasn’t been published in academic journals yet because it was gathered so recently. And while she concedes that it’s hard to predict what will happen to long-tailed or pig-tailed macaque populations, the IUCN’s projections that current threats will result in significant population declines in the next few decades stems from the fact that habitat loss and capture has rendered remaining populations small and fragmented, with low levels of genetic diversity and, prior to the surveys by her and her colleagues, little public understanding of the animals’ well-being or status.

“I’m just saying currently it is not sustainable what we are doing,” Hansen says, of the research-driven macaque trade. “This species cannot sustain the pressure.”

How should research on endangered macaques progress?

In general, the researchers who spoke to The Scientist in favor of the IUCN reclassification all say that a better balance ought to be struck between animal and human wellbeing, as far as biomedical research on macaques is concerned. A “human-first approach is what put us in this climate crisis to begin with,” notes Gilhooly, suggesting that the impetus ought to be to use endangered animals in experiments as little as possible.

Fuentes suggests that perhaps federal regulations should be adjusted to raise the bar for approving a study using an endangered macaque “to match the level of risk to the species being engaged,” such that researchers need to jump through a few more hoops to ensure that their work answers an important enough question.

A photo of a long-tailed macaque (Macaca fascicularis) embracing its child.

Long-tailed macaques (Macaca fascicularis) at Batu Caves


In contrast, former-primatologist-turned-advisor for People for the Ethical Treatment of Animals (PETA) Lisa Jones-Engel, who was a member of the IUCN assessment team, says she’d like to see researchers move away from macaque research altogether, suggesting that pharmaceutical toxicity work could be done on tissue cultures or other alternatives.

But studies without animals wouldn’t be as informative, Hotchkiss says. While she says that she expects the number of macaques used in research to decline over time and that she feels there are some current uses where other models could work, there are others for which there are no good alternatives to macaques.

For instance, Hotchkiss argues that mice are too dissimilar to humans for certain types of biomedical research and that labs on a chip don’t offer a full picture of how a human body will respond to “the unexpected effects” of a drug. She offers the example of a toxicity study for an antileukemia drug that she worked on. “You put it in the monkey, and it dropped the white blood cells down, but it also caused liver damage,” she says. “If you’re looking at a kidney drug and it looks good in a kidney on a chip, it’s not going to tell you if it causes liver damage. That’s when you need the whole animals.”

“If anyone is going to do a study in primates, it’s because they think it’s the only possible animal model that will work,” Hotchkiss emphasizes. “That gets more and more [true] each year. Those of us in primate research still believe they are necessary.”

Hansen says that she simply wants better transparency and more communication between scientists that are more conservation-minded and those who work in biomedical labs. “We’re not working on this species to condemn laboratory research, medical research,” she says. “We only work with this species and create this assessment to highlight that there’s an issue. So now, please help us solve it.”

“That’s what I would like for the biomedical researchers to do: to help us solve this, to take responsibility,” she adds, saying that so far, the only outreach she’s received has been from experts working in animal welfare. “It cannot be that we can’t have both. We should be able to both save these two species and save humans. There is a middle ground, there are solutions to be found, and now we need to collaborate [to find them] instead of just yelling . . . old, rehearsed lines at each other.”

Clarification (October 14): The article has been updated to state that Lisa Jones-Engel was a part of the team that proposed the change in Red List status for the two macaque species.

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