MONKEY WRENCH

Zhao Shengli, Party secretary of the China Laboratory Primate Breeding and Development Association, told NewsChina that the price for one lab monkey soared from 15,000 yuan (US$2,308) in the second half of 2016 to 62,000 yuan (US$9,542). “It’s really hard to find a lab monkey no matter the price,” Zhao said. 　

With Covid-19 raging around the world for more than a year, international competition for vaccine development is fierce, and primates for testing vaccines and medications are scarce. 　

Non-human primates are the ideal lab animal for research in life sciences. Other common lab animals include mice, rabbits, dogs, ferrets, hamsters, ravens, or even fruit flies. Primates are the most pricey and complex species for lab experiments, and are used for research in the fields of viruses, diseases, developmental biology and neuroscience. More importantly, those animals are vital in the development of new drugs for preclinical trials – those that take place before drugs move on to human trials. 　

A challenge for scientists everywhere is the urgent need to develop new vaccines and drugs, but lab monkeys are a scarce resource. 　

The strict requirements for experimental animals not only ensure the quality of research, but also prolong the supply cycle of experimental monkeys. However, lab monkeys are not available on demand. Monkeys usually take five years to mature, and it may take up to eight years before the first offspring of the breeding monkeys can be sold. “This is the main reason why we have a lab monkey shortage now, and the one that we’ll get three to five years from now,” Zhao said. 

Zhang Yuchao, secretary-general of the Primate Breeding Association, told our reporter there is a reserve of some 240,000 lab monkeys in China. Excluding underage monkeys and breeding monkeys, there are around 100,000 in the reserve. 　

Pre-clinical trials of new drugs make up the greatest domestic demand for lab monkeys, using some 25,000 monkeys a year, mainly long-tailed macaques. Wang Jufeng, senior vice-president of Pharmaron Pharmaceutical in Beijing, told NewsChina that 70 to 80 percent of new drugs need monkeys for pre-clinical trials, while 20 to 30 percent of small molecular drugs, or chemical synthetic drugs, use monkeys for pre-clinical trials. 　

In general, pre-clinical trials use two species to determine which animal is more sensitive to the drug. Common choices are rodents, such as rats or mice, and animals like monkeys, dogs or piglets. “If both dogs and monkeys meet the test conditions, clinical trials will definitely choose dogs because they are cheaper,” Wang said. “Although the price for lab beagles is also rising to around 3,000 to 4,000 yuan (US$461-615), it’s still only 7 percent of the price for a lab monkey.” 　

The number of monkeys used in drug preclinical trials varies. On average, 40 monkeys are needed for 28 days of repeated dosages, and about 20 more are needed if drug metabolism tests are required. The rapid development of the biomedical industry is undoubtedly driving demand. According to official statistics, the number of new drug clinical trial applications processed by the Center for Drug Evaluation of National Medical Products Administration (NMPA) increased from 494 in 2014 to 983 in 2019. 　

According to Li Qin, chief scientist of the Primate Breeding Association, lab monkey use increased from 7,000 in 2013 to nearly 30,000 in 2019. Since 2017, the number of lab monkeys grew by some 10,000 per year, most of which were used in drug development and safety assessments. 　

There are other reasons for the shortage. Xiong Wanhua, founder of the Primate Breeding Association, told NewsChina that the long-tailed macaque, although accounting for up to 80 to 85 percent of total lab monkey use in China, is a non-native species imported from Southeast Asia. After the 2008 global financial crisis, the export industry for lab monkeys was affected. The stock of lab monkeys in China grew steadily and reached nearly 300,000 in 2013, a record high. This led to the suspension of monkey imports that year. 　

In 2015, drug supervision reforms that sped up approval processes and trial result evaluations resulted in explosive growth of domestic drug research and development. Lab monkey use also soared, which quickly depleted stocks. In addition, because of the import ban, monkey farms faced aging stocks and dropping fertility rates. In late 2018, the State approved some imports to monkey farms, but these were halted by the outbreak of Covid-19. 　

On January 26, 2020, China’s State Administration of Market Supervision along with other departments issued the “Notification on Prohibiting Wildlife Transactions,” requiring that “all places where wild animals are kept shall be isolated and all wild animals shall be strictly prohibited from sales or movements [of live animals].” Both imports and exports of lab monkeys were stopped too. 　

Zhao Shengli said supply of lab monkeys became a problem in 2018, when the price increased to a level beyond what most scientific research groups could afford. The Primate Breeding Association receives many complaints from researchers over the shortage of lab monkeys and the high prices. 　

“We’ve had to adjust or cut down research projects according to our existing animal stocks to minimize the use of lab animals,” said Niu Yuyu, vice president of the Laboratory of Primate Biomedical Research (LPBR), Institute of Primate Translational Medicine at KUST. Niu told NewsChina that demand for monkeys increased significantly after 2015. 　

From January 26 to June 29, 2020, the Primate Breeding Association has helped provide 3,551 lab monkeys from member organizations for research relating to Covid-19. “Each major scientific research institute has a limited number of lab monkeys, and sales of monkeys were forbidden during the pandemic. So a research group can only buy lab monkeys from farms after it obtains approval from the Ministry of Science and Technology indicating its research is related to Covid-19,” Zhang Yuchao said. 　

Apart from the upsurge in domestic demand for lab monkeys, global research of stem cells and gene editing also requires experimentation on primates. Applications to use monkeys are much more complex than for other lab animals such as dogs or rodents, and require approval from ethics committees. 　

Before conducting experiments, monkeys are kept in specialized institutions with professional care. According to Wang Xiaohua, an anesthesiologist from Xuanwu Hospital of Capital Medical University in Beijing, apart from the costs of labor, utilities and care services, the average pre-pandemic cost for one lab monkey ranged from 50,000 yuan (US$7,695) to 100,000 yuan (US$15,390), including purchase price and feeding. 　

“The high cost of lab monkeys is mainly due to the high costs of the professionals who care for them. The veterinarian is the interpreter for a lab animal, translating the animal’s behavior to ensure research quality and animal welfare,” Li Qin said. For example, mouse movements mean different things. If its whiskers are back, it feels cold, erect ears signal excitement and flat whiskers signify pain. During an experiment, a veterinarian makes observations many times a day, and each time it costs from hundreds of yuan up to thousands. 　

While the long-tailed macaque is not indigenous to China, it came to dominate the research market because it is smaller, and thus eats less and uses up less materials in safety assessments, which reduces costs, Li Qin said. 　

Globally, the US is the world’s largest lab monkey user. According to statistics from the US Department of Agriculture, more than 74,000 monkeys were used in 2017, a record year for lab monkey use. In the past, the US relied on India to supply long-tailed macaques, but India stopped exporting monkeys in 1978 due to religious objections, animal protection and other reasons. As a result, the US looked to Southeast Asia for its supply. Soon afterwards, the Chinese monkey farming industry replaced Southeast Asia, making China the world’s largest supplier of primates for lab experiments. Guangxi Zhuang Autonomous Region is a key area for lab monkey supply. 　

There are 48 lab monkey farms in China, located in Guangdong, Guangxi, Yunnan, Sichuan, Hubei, Jiangsu and Beijing. In the current market, according to Zhang Wen, a monkey farm can make up to 1 billion yuan (US$154 million) on average a year, although he did not give precise figures on the number of monkeys sold. 　

Beijing, Shanghai and Guangzhou, where universities and hospitals are concentrated, use the most lab monkeys in China. 　

“The Yangtze River Delta region has the most intact industrial chain for the lab monkey farming industry,” Zhang Wen said. 　

An insider with 17 years in the monkey farming industry who spoke under condition of anonymity said that the current suspension of exports has forced international buyers to turn to Southeast Asia, which may trigger development of the region’s monkey breeding industry. Once companies in Southeast Asia and other countries receive capital and mature technology, lab monkey production is likely to catch up in a few years and challenge China’s monkey breeding industry. 　

Also, no one knows whether countries where the long-tailed macaque originates will restrict exports to China and constrain the industry’s continued boom in China. “That’s why we’re now calling on authorities to lift the lab monkey import ban,” Zhang Yuchao said. 　

“Lifting the import ban is the fastest way we can think of to address the shortage of lab monkeys,” said Li Qin, adding that allowing imports of lab monkeys that domestic companies paid for in 2019 but were halted by the pandemic is another urgent issue. 　

“Otherwise, foreign suppliers will charge far more for looking after the monkey than the price of the lab monkey itself. It will be a net loss for the monkey farms.”