Ozempic and Wegovy, medications that have become increasingly popular this year due to their weight loss effects, were both tested on a monkey species listed as endangered, according to a National Geographic analysis of public drug label disclosures maintained by the U.S. Food and Drug Administration.
The two drugs are among the highest-profile products that relied on long-tailed macaques—a Southeast Asian species that was designated as endangered by the International Union for Conservation of Nature (IUCN) last year. The listing was due in part to the animal’s use in biomedical research, the expert body wrote.
Known for its body-length tail, white underbelly, and greyish or brown fur, the animal is the top primate imported into the United States.
In 2022 alone the U.S. imported almost 32,000 of the animals according to a report published by the National Academies of Science, Engineering, and Medicine in May. More than half of these two-foot-tall monkeys came from Cambodia, the report said, while others were sourced from Mauritius, Vietnam, and Indonesia.
That data comes even as controversies have besieged the monkey shipment industry—and exports from Cambodia in particular. Criminal allegations from the U.S. government, revealed in an unsealed indictment last year, charge that thousands of supposedly lab-bred monkeys were plucked from the wild and passed off as animals bred in captivity.
Many of the macaques sourced from elsewhere are also wild-caught, including almost 4,000 shipped from Mauritius in 2021 and another 2285 from the country in 2020, according to a global trade database maintained by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), which regulates such cross-border trade.
Now the monkey industry is at a public inflection point, with heightened scrutiny due to the IUCN endangered status decision, ongoing criminal and civil investigations from the U.S. government on monkey trafficking, and new U.S. legislation that was signed into law last year that removes mandatory requirements for new pharmaceuticals to be tested on animals.
Moreover, there’s a new push from a cadre of animal welfare groups, led by People for the Ethical Treatment of Animals, to get the species listed under the U.S. Endangered Species Act. If granted, that protected designation could complicate efforts to continue testing on the species at all—as it once did for chimpanzees.
In April, the groups submitted a petition to the U.S. Fish and Wildlife Service asking for the animal to be awarded a threatened or endangered species status under that U.S. law and the agency is now required to issue its initial response this month.
Lisa Jones-Engel, a former primate scientist at the University of Washington and current senior science adviser at PETA, says the issue is urgent. “As a primate scientist whose entire career was devoted to studying the movement of infectious disease between humans and non-human primates, I know the only scientific, ethical and public health choice is to immediately end the export and import of non-human primates,” she says.
But the recent National Academies report concluded, among other things, that there’s no viable replacement for testing with primates. It said imports were unsustainable, but there should be a heightened investment in more domestic breeding of the animals.
Kenneth Ramos, the National Academies committee chair, says that primate research remains essential, particularly when close parallels to humans are a priority. That’s because biomedical studies that require interactions with multiple organs are best done with animal models, he says.
In the years ahead, he adds, “as methodologies continue to advance, reductions and even replacements of [primates] and other animal model systems may be possible.”
A human stand-in
With physiology similar to our own, the monkeys are often used by pharmaceutical companies as human stand-ins to test reproductive side effects or potential harms to a fetus, as they were with Ozempic, Wegovy, and the popular asthma drug Tezspire. They’re also the top primate species used in toxicology testing.
Until now, the animals have been “readily available” and easy to work with, and there’s a lot known about them due to that widespread use, says John Pippin, who directs academic research and education for the nonprofit Physicians Committee for Responsible Medicine, which signed the PETA petition.
Yet that widespread use in lab testing and research in the U.S. and elsewhere, alongside factors including habitat loss and hunting, have led to a 40 percent population decline in Southeast Asia the past four decades, according to the IUCN.
“The research industry needs to become accountable for the effects of their actions on wild nonhuman primate populations,” it wrote in the species endangerment finding.
Pippin, whose group opposes animal experimentation, says that the time to move away from animal research has already arrived. Domestic breeding of the monkeys won’t solve research problems since animal results often do not successfully translate to humans, he says, and human tissue samples, organs on a chip, and stem cells are already available alternatives.
What’s more, the conclusions from some of the past long-tailed macaque research itself may be up for debate since the genetic backgrounds of the animals may have been far more varied than advertised.
Charges of alleged global monkey trafficking
In November 2022, international monkey shipments made headlines because top wildlife officials at one the world’s top suppliers of the monkeys, Cambodia, was accused of trafficking in the species. U.S. officials arrested a top Cambodian wildlife official, Masphal Kry, on his way to a global wildlife summit and also indicted another Cambodian official.
The U.S. Attorney’s Office for the Southern District of Florida alleged that he and his boss were part of a long-running international primate smuggling ring that represented wild-caught monkeys as captive-bred. Kry, according to the U.S., allegedly personally delivered wild-caught monkeys to a facility that passed them off as captive-bred and also received payments for his involvement in the smuggling scheme.
The case has continued to have ripple effects across the monkey research business, with contract research organizations (CROs) like Charles River Laboratories and Inotiv publicly acknowledging that they’re feeling the strain from this and other related monkey investigations with potential implications for future monkey sourcing.
These companies supply and sometimes conduct testing on a variety of animals. Charles River, for example, had control of 16,000 primates last year, according to its 2022 annual Animal Welfare Act filing.
Public filings to the U.S. Securities and Exchange Commission provide some insights: In 2022, Charles River said that Cambodia was its top monkey supplier and that the Justice Department (DoJ) and Fish and Wildlife Service (FWS) had commenced an investigation into the company’s conduct regarding several monkey shipments from Cambodia, and on February 2023 the company received a grand jury subpoena requesting certain documents related to such investigation.
The criminal investigation, according to the company, is also occurring “in parallel to a civil investigation” being undertaken by those same agencies. The company believes that the concerns raised about its conduct are “without merit” and says it’s fully cooperating with the government investigations.
It said in its SEC filing that it’s also voluntarily halted its Cambodia shipments until the company and FWS “can agree upon and implement additional procedures to reasonably ensure” that its shipments from Cambodia are truly lab-bred.
They’re currently still caring for a shipment of Cambodia-sourced monkeys that was denied clearance to the U.S., a Charles River spokesperson told National Geographic in a statement.
Both FWS and DOJ declined to comment for this article.
A reliance on contract research organizations
Meanwhile, Inotiv, which calls itself the world’s “largest and most trusted” supplier of primates, stated last year that employees at its “principal supplier” in Cambodia had been charged with violating U.S. law by conspiring to illegally import non-human primates.
Eric Kleiman, a researcher with the Animal Welfare Institute, notes that Inotiv’s also purchased major subsidiaries in recent years, increasing consolidation of the industry and making it harder, he believes, to track alleged legal and animal welfare issues of contract research organizations.
Among them: Envigo, a November 2021 acquisition, had received a grand jury subpoena in June 2021 for an ongoing investigation related to the “procurement of non-human primates from foreign suppliers for the period January 1, 2018 through June 1, 2021,” according to its SEC filings. The company says it’s been fully cooperating and will continue to cooperate with this investigation.
Separately, Gary Tucker, the longtime vice-president at Orient—a January 2022 acquisition—was prosecuted and pleaded guilty in August 2021 to knowingly and willfully “making a materially false, fictitious, and fraudulent statement and representation” to FWS agents during an international criminal wildlife trafficking investigation. Court documents in that case suggest that he’d lied and said that there isn’t record-keeping of the inspections he conducted at macaque captive-breeding facilities in southeast Asia. Inotiv purchased the company about five months later.
A huge industry
The business in long-tailed macaques is a lucrative one, with shipments of the live animals worth more than $1 billion between 2010 and 2019. Last August, a U.S. government official testified at a public meeting that its vendors said unborn monkeys are even being purchased as “futures.”
Novo Nordisk, the maker of both Ozempic and Wegovy, said in a statement to National Geographic that the company does rely on external contract research organizations to supply its monkeys.
But its monkeys didn’t come from Cambodia, the statement said: “For years, Novo Nordisk has ensured that all [nonhuman primates] used for research come from audited and approved sites in two countries, Vietnam and Mauritius.” It declined to comment on which CROs it’s used.
In response to National Geographic’s detailed questions on their monkey testing and sourcing, AstraZeneca and Amgen—the two pharmaceutical companies behind Tezspire—referred us to their online statements about their animal testing policies. AstraZeneca’s said it relied on contract research organizations to supply animals for more than 55,000 studies last year.
Animal testing, AstraZeneca’s online statement also said, is a “small but vital part of the process of bringing new medicines to patients.” Amgen stated in a similar online statement that it seeks to reduce animals in research wherever possible.