THIS ARTICLE ORIGINALLY APPEARED IN BLOOMBERG ON SEPTEMBER 28, 2022.
Beijing’s ban on macaque exports—needed to test vaccines and other lifesaving drugs—could give its pharma industry an edge.
Swedish scientist Karin Lore used to depend on China to keep her laboratory running. A professor at Stockholm’s Karolinska Institutet, Lore studies the immune system’s interaction with vaccines, and safety tests on monkeys are a critical part of her research. But after Covid-19 hit, Beijing halted exports of primates central to her work amid concerns that live animals could contribute to the virus’s spread. More than two years later, monkeys from China are in increasingly short supply, leaving Lore and scientists around the world struggling to complete their research.
“I can see some studies will never be done,” Lore says. An executive at a Western pharmaceutical company, who wasn’t authorized to speak publicly and asked not to be identified, backs her up, saying the shortage has already led to delayed production of some compounds and stalled decisions about drug development. The ban and rising medical research demands have had a “knock-on effect on global supply” that has raised the pressure on the few primate suppliers outside China, the UK government said in June.
Of all the bottlenecks sparked by the pandemic—computer chips, toilet paper, even bicycles—the shortage of primates used in medical research is among the most consequential. Drug researchers depend on the animals to help determine how new compounds will affect humans. So China’s export ban is reverberating globally, making the work of scientists trying to develop treatments for everything from the next coronavirus variant to Alzheimer’s disease and tuberculosis even harder—and possibly giving the Asian nation an edge in developing its own medicines.
With the shortage has also come a spike in costs: Average prices have more than doubled since just before the pandemic, Lore says, to about €11,500 ($11,000) per animal. One research industry executive says it’s worse in some cases, rising to more than $35,000 per primate at times. For now, Lore says, her lab has postponed some of its projects, including work on new vaccines for malaria and rabies.
“Already, prices were so high,” she says. “This is just making it even tougher.”
Researchers who use monkeys argue that there aren’t many substitutes for what are referred to as “nonhuman primates,” or NHPs, animals whose physiology and DNA are so similar to humans’ that testing on them is essential to meeting safety requirements of regulators such as the US Food and Drug Administration. Despite protests from animal-rights groups, monkeys and other primates “serve as critical animal models for many research areas, including infectious diseases; social, cognitive, and behavioral research; reproductive biology; regenerative medicine; aging and neuroscience research,” the National Institutes of Health’s office of research infrastructure programs said in a 2018 report.
China began breeding cynomolgus monkeys—also known as long-tailed macaques—for scientific research in 1985, with exports starting five years later. For years, the comparatively cheaper cost of breeding monkeys in China helped make the nation the leading exporter of captive-bred macaques used in scientific research.
But starting in 2013, China’s forestry ministry, which regulates the trade in primates, said the demand from domestic research institutes and local pharmaceutical companies would be prioritized over exports. That still offered enough animals to help meet global demand, but then came Covid. And while Beijing’s initial trade ban was based on Covid worries, some researchers suspect the continuing restriction may have more to do with geopolitics and President Xi Jinping’s interest in building up China’s pharmaceutical industry.
“Biomedical research is in a position now where you have a couple of world superpowers—the US, China, and Europe—all vying for the same or similar pool of resources,” says Matthew Bailey, president of the National Association for Biomedical Research in Washington. About 60% of the 30,000 monkeys imported into the US were from China before the pandemic, he says, and the suspension of exports “has just created an incredible amount of uncertainty about the supply chain.”
With the US and China at a standoff over issues including Taiwan, trade tariffs, and human rights in Xinjiang, the trade in primates has gotten far less attention. Yet Beijing’s dominant role in monkey supplies provides leverage similar to Washington’s control of advanced semiconductors or the Kremlin’s power over Europe’s natural gas supply, says Stefan Treue, professor at the University of Gottingen and director of the German Primate Center.
“The Chinese could have long ago started again to export animals,” Treue says, conceding that Beijing’s initial ban made sense, given the lack of knowledge at the time about Covid’s spread. But now, he says, “there’s a strategic, global competition for biomedical research,” and China may want to keep all the advantages it can.
The US is responding. President Joe Biden on Sept. 12 signed an executive order outlining a strategy to boost domestic biomanufacturing and reduce reliance on China for new medicines, chemicals, and other products. He’s also sought to boost funding for America’s primate research centers.
“There are not enough NHPs at present to support both pandemic research and all the existing NIH research for which NHPs are necessary,” the National Institutes of Health said in a statement accompanying Biden’s fiscal year 2022 budget request.
Even before Covid hit, the NIH was warning about a shortage, but concern in Washington spiked early in the pandemic, which exposed America’s dependence on China for even basic medical gear, including gowns and masks.
As China’s pharmaceutical industry grows—companies there had revenue of about 3.4 trillion yuan ($475 billion) in 2021, up about 19% from a year earlier, according to state media—firms in the niche business of breeding monkeys see opportunities. Hong Kong-listed WuXi AppTec Co. in 2019 acquired a Guangdong, China-based breeder of more than 20,000 monkeys. Rivals Joinn Laboratories China Co., Frontage Holdings Corp., and Pharmaron Beijing Co. have been expanding, too, investing in new breeding facilities and spending hundreds of millions of dollars buying up local competitors.
“Grabbing monkeys means grabbing customer orders,” the Global Times, the Chinese Communist Party’s English-language newspaper, said in June.
Sinolink Securities, a Chengdu, China-based brokerage, said in a June report that there’s still “a lot of room for growth’’ in the industry. The Kunming Institute of Zoology is finishing work on a facility that will be China’s largest for primates, able to hold 5,000 monkeys, the journal Science reported on Sept. 20. That could help with a 5 billion-yuan brain research project that China recently launched and which will rely on nonhuman primates for a critical part of its work, according to Science.
Yet Beijing’s suspension of trade in live animals has hurt some Chinese companies. Long-tailed macaques aren’t native to China, so the country relies on imports from Southeast Asia to keep its breeding colonies fresh, says Sarah Kite, co-founder of Action for Primates, a global advocacy group.
In June, Beijing adjusted its rules to allow imports of animals, including monkeys, for reproductive purposes, a change that should help improve supply as the breeding population expands and exports eventually resume. Because of the time required for newborn animals to grow mature enough for researchers to use, though, China’s supply of commercial monkeys will not change significantly in the next three to four years, according to Sinolink.
Of the 240,000 monkeys raised for research purposes in China last year, only about 30,000 met the right age and other criteria to make them suitable research candidates, according to state media. Chinese scientists used 28,000 of them, highlighting how small the potential export population is even if the ban is revoked.
“Now, because the demand for lab monkeys has surged, there are challenges with sourcing,” Zhang Guodong, who helped set up WuXi AppTec’s large animal pharmacology team, said in a July 19 webinar.
The decline in Chinese exports is putting more strain on the system in the US, where the federal government operates seven National Primate Research Centers with about 20,000 macaques, marmosets, baboons, and other animals. The centers maintain breeding colonies, and while they have some of the long-tailed macaque variety that used to come from China, their primary focus is on rhesus macaques, a different species.
Some institutions are turning to new suppliers such as Cambodia and the Indian Ocean island nation of Mauritius, which has a large population introduced centuries ago. But that’s raised other concerns given that long-tailed macaques this year were listed as “endangered” by the International Union for Conservation of Nature, which said the species is expected to experience “at least a 50% decline in the coming three generations.”
Animal-rights activists worry that the strong demand is leading unscrupulous traders to target monkeys from the wild rather than those raised in captivity, according to Lisa Jones-Engel, a senior science adviser for People for the Ethical Treatment of Animals. “There’s this monkey laundering that’s going on,” she says. PETA on July 27 called on the US Centers for Disease Control and Prevention to suspend imports “so that wild populations can recover.”
In a bid to prevent researchers from getting hooked on wild-caught monkeys, the European Union will, starting in November, require all member states to use only NHPs that come from animals bred in captivity or “sourced from self-sustaining colonies.” The UK said in June that while the more than 1,700 primates its researchers and institutes used in 2020 met that criteria, China’s ban makes continuing to meet that standard harder.
Animal-rights groups have also targeted the transport of primates, scoring some success in pressuring airlines to stop carrying monkeys. Most major carriers now refuse to fly NHPs for research. One of the last major holdouts, Air France, said in June that it, too, would stop.
Nakissa Sadrieh, a senior adviser for new alternative testing methods at the FDA’s Center for Drug Evaluation and Research, said at a conference in August that the shortage of NHPs should spur efforts to “rethink nonclinical development strategies,” an approach that animal-rights activists—who want to go further—would still embrace. Yet for now, telling scientists not to use NHPs is “not really an option,” says the German Primate Center’s Treue. “The reason to do primate experiments is because there are no alternatives.”
The controversy around animal testing and the continuing shortage of research primates may make global researchers more likely to do more of their development in China—despite concerns about intellectual-property protection there. Sirnaomics Ltd., a Gaithersburg, Md.-based drug developer, has a research center in the eastern Chinese city of Suzhou, near Shanghai. Having the option of doing research in China provides an advantage because starting a trial with monkeys takes less time than in the US, according to Chief Executive Officer Patrick Lu. But with more researchers competing for Chinese monkeys, Sirnaomics is taking no chances.
“We can work with our Chinese counterparts over there. It is easier, and there’s a shorter waiting time,” Lu says. “If you start a request from a US company to do such a study, usually you have to wait six months, even nine months. In China, they can give us something in three months.” —With Riley Griffin
(Feature image credit: CHUNYIP WONG / E+ / Getty Images)