Nonhuman primates are used to test experimental drugs and vaccines before they enter human trials, and to probe fundamental questions about the aging brain and infectious diseases. Nationally-funded primate research centers maintain domestic colonies for biomedical research, but about 30,000 are imported each year to meet demand.

Cambodia has emerged as the largest international source of monkeys used in U.S. research, after China stopped exporting primates during the pandemic. Imported monkeys must meet various international and U.S. regulatory requirements. The investigation into Cambodian monkeys centers on the question of whether they were bred in captivity, as permits stated.

In November, eight people, including two Cambodian government officials, were indicted on charges of allegedly capturing wild long-tailed macaques from national parks and protected areas and falsifying permits, due to a shortage of monkeys at the breeding facilities. As the investigation continues, shipments of primates from Cambodia have been paused.

The disruptions come on top of an already strained supply of laboratory monkeys in the United States. Five years ago, a National Institutes of Health study predicted that future demand for nonhuman primates was likely to outstrip supply.

Then the coronavirus pandemic landed and demand soared, as monkeys were needed to test coronavirus vaccines and therapeutics. At the same time, China stopped exporting monkeys, so U.S. suppliers had to scramble to find new sources, shifting much of their business to Cambodia.

“So this has been coming to a head for a while, and the covid pandemic certainly exacerbated it,” said Lyric Jorgenson, acting director of NIH’s Office of Science Policy.

Many different sectors of the biomedical research community use monkeys in research, and they rely on different sources. NIH funds a domestic network of National Primate Research Centers that house about 20,000 monkeys. These are self-sustaining breeding colonies that provide animals primarily for NIH-funded research.

Contract research organizations, such as Charles River Laboratories International, Inotiv and Laboratory Corporation of America, provide primates to drug companies as well as academic and government scientists and they rely on multiple sources, including international suppliers.

The Centers for Disease Control and Prevention and the U.S. Fish and Wildlife Service declined to provide numbers on how many primates are imported into the United States. A Freedom of Information Act request was not responded to immediately. According to PETA, the country brings in about 30,000 primates each year.

On Feb. 22, Charles River Labs disclosed that it had received a subpoena related to shipments of monkeys from Cambodia and had voluntarily suspended future shipments until they could develop a new protocol that has the U.S. government’s blessing. The company’s shares fell 10 percent that day.

“With regard to Cambodia, where 60 percent of the animals come from, we are all at least temporarily foreclosed from bringing new animals in and utilizing them on studies in the United States,” James C. Foster, chief executive of Charles River Labs, said during an earnings call last week. “This is an industry issue, a relatively profound one, because drugs aren’t going to move through preclinical [stages] and into the clinic.”

Research analysts at investment bank Evercore estimate that, given the supply decrease, Charles River will raise its prices on nonhuman primates this year to $33,000 each, up from $22,000 last year and just $2,500 in 2019.

In the wake of the announcement, animal activists called for an even broader investigation into Charles River and its customers. They reject the idea that there is a shortage of monkeys and argued that the high prices the animals can now command is creating incentive for people to capture wild monkeys.

“The allure for the amount of money that’s now available to catch these monkeys … the folks are going to do it. They’re just going to do it as long as the demand remains, and the price remains at this point,” said PETA senior scientific adviser Lisa Jones-Engel.

Charles River said the company is committed to ensuring its operations comply with laws and regulations globally, and that it was critical to work with the government to resolve the concerns in Cambodia. “The U.S. biopharmaceutical industry and the patients who need new treatments and cures are counting on us,” the company said in a statement, adding that any concerns regarding its practices “are without merit.”

Charles River was just the latest company to come under scrutiny in the DOJ investigation. In June 2021, two companies that later became subsidiaries of Inotiv received subpoenas regarding their primate imports, following up on grand jury subpoenas each had received in 2019, according to a securities filing. Inotiv has said its main supplier of nonhuman primates was criminally charged in November with illegally importing the animals from Cambodia.

Inotiv brought in $140 million from selling Cambodian monkeys in 2022, a quarter of its revenue, and the company’s stock lost half of its value the day after DOJ announced the indictments.

Inotiv said that it would establish new procedures before importing more primates from Cambodia, adding that lawfully securing animals bred for research there was “imperative for the support of critical pharmaceutical development activities in the United States.” Earlier this month, Bob Leasure, chief executive of the Indiana-based company, said that Inotiv had been able to determine that some monkeys imported from Cambodia were “purpose bred” — not illegally smuggled from the wild — and resumed shipping them to customers.

Laboratory Corporation of America, which also supplies primates to biotech and pharmaceutical customers, said earlier this month that delays in procuring primates will hit its revenue by $80 to $100 million early in the year. The company said nonhuman primates make up less than 2 percent of its revenue, and it has reached agreements with additional primate vendors.

The expected price increases and delays will have downstream effects. For example, academic researchers and smaller biotech companies that use contract organizations may be less able to absorb the price hikes.

“We’re looking at it as an acute stress upon a chronic situation,” said R. Paul Johnson, director of the Emory National Primate Research Center, which maintains a breeding colony with about 3,400 monkeys. The center has four tiers of priority, supplying animals to researchers funded by the National Institutes of Health before other government-funded scientists, foundations and finally pharmaceutical companies.

Skip Bohm, chief veterinary medical officer and associate director of the Tulane National Primate Research Center, said that it is a struggle to even meet the demand from the first priority tier.

“The first thing to recognize is there may not be enough animals or resources to get to the bottom of that list,” Bohm said. The waiting time for NIH-funded researchers who get first priority “can be three months, or up to a year or more depending on the type of animal.”

Part of the challenge is that long-term planning is essential for biomedical research involving primates, because resources can’t be increased overnight to respond to an emergency like a pandemic. Emory’s Johnson gave the example of rhesus macaques, a key animal used in scientific research, that breeds seasonally in the fall and gives birth in the spring. Mature animals are often needed for experiments, and females may be needed to continue sustaining the population.

“The process of breeding rhesus macaques requires a long-term investment. Decisions we make now won’t have an impact for four to five years from now,” Johnson said.

But it’s equally important to make sure that there isn’t a wasteful surplus of the animals, NIH’s Jorgensen said.

The National Academies of Sciences, Engineering and Medicine is currently conducting a review of the state of science for primate research, including examining questions about how to reduce reliance on animals. A report is expected to be released this summer.

In the short-term, the interruptions stemming from investigations into Cambodian suppliers may be par for the course in an industry that has had to scramble repeatedly to find new sources of animals or work around supply disruptions. Over the years, major airlines have stopped carrying the animals, for example.

“It’s not like there’s this massive sea change in ability to do preclinical work that’s just happened today,” Jon Miller, an Evercore analyst, said on the firm’s podcast. He said it will probably take a couple of years for the backlog to fully resolve itself.

“In the meantime,” he said, “we shouldn’t expect new drug pipelines to suddenly come to a screeching halt because of this issue.”