Deborah Green1 has just made a life-or-death decision — and she isn’t happy about it. “We have two cancer drugs in development and we had to choose which one would move up to the next level,” she says. “We made our choice, but you can’t help wondering how many lives might have been saved by the other one.”
The choice made by Green, the head of animal testing compliance for one of the world’s biggest pharmaceutical companies, is one increasingly being made by biomedical researchers across the world — but not because of financial constraints, ethical considerations or scientific limitations.
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It is all because of a shortage of monkeys.
On almost every continent, pharmaceutical research is being undermined by a dearth of primates caused by an export ban introduced by China last year to restrict the spread of Covid-19. It’s a measure that was initially welcomed in the West, but which is now being seen as an existential threat to biomedical research in the UK, Europe and the US.
Scientists fear that unless this shortage is addressed, the West will become dangerously reliant on China to test new treatments for heart disease, cancers and neurological disorders. More worryingly, come the next global pandemic, the ability to affect which vaccines are approved — and how quickly — could lie firmly in the hands of the Communist Party of China.
“It isn’t too dramatic to say that this could be the beginning of the end for biopharmaceutical research in the West,” says Green. “I believe China’s long-term aim is to become the world leader in the sector, the place you will have to go to if you want to test your products. But you have to ask yourself whether you want China to be in control of such an important part of our lives — and to have access to so much of our intellectual property.”
The past 12 months have well demonstrated China’s growing influence on the West. But while attention has been focused on Covid-19, Huawei’s involvement in the UK’s 5G rollout and the threat to democracy in Hong Kong, its impact on Britain’s research sector has slipped under the radar.
Despite protests from critics, the testing of drugs and treatments on “Non-Human Primates” (NHPs), as scientists call them, cannot be replaced by computer modelling. It remains a requirement for many new drugs — including the Oxford-AstraZeneca and Pfizer-BioNTech Covid-19 vaccines — before trials can be allowed in humans.
In 2019, 2,015 new NHPs were used in experiments in the UK. Only 220 of them were not imported; most being bred under licence at a government breeding facility at Porton Down in Wiltshire. Some 1,154 came from breeding centres in Africa, largely from the island of Mauritius. And 782 came from Asia — roughly 75% of which came from China.
So when, in January last year, China imposed a ban on the export of all animals, the flow of a sizeable number of NHPs — roughly a quarter of those needed in the UK — was suddenly switched off. But that was only the beginning. British researchers also carry out a significant portion of their research through companies in other, worse-hit countries. And as a result, they have been left scrambling around to find the animals they need to complete their research.
US biotech companies were especially hard-hit. The US relies on China for 60% of its monkeys — some 35,000 a year — and because most of the big pharma companies are multinational, shortages in one area have resulted in bottlenecks in others, including the UK. Desperately in demand, the average price of the animals most-often used — rhesus macaques, cynomolgus macaques and marmosets — has doubled to $10,000 in the past year.
Kirk Leech, executive director of the UK-based European Animal Research Association, which represents contract research organisations (CROs) — private labs that conduct animal research on behalf of pharmaceutical companies — has seen rare cases of desperate firms paying $30,000 a-head for monkeys.
“As China is the primary source of NHPs purpose-bred for scientific purposes, this ban has had a dramatic impact on both the supply and the cost of NHPs around the world and the ability of researchers to access the animals essential for the development of new vaccines and medicines,” he says.
“This export ban is a clear and present danger to human health, creating obstacles to, and additional expenses for, the development of vaccines and therapeutics, including for Covid-19. The Pfizer-BioNTech vaccine relied on preclinical data generated by BioNTech in Germany, using rhesus macaques. The Oxford-AstraZeneca vaccine and the Janssen vaccine have also relied on preclinical testing with NHPs for safety and efficacy.”
In the event of another global health crisis like the one we are experiencing, he warns, the repercussions could be severe: “Imagine a new pandemic; we would need a global response, we would need vaccine research and we would need to use NHPs. If shortages grow worse due to China’s actions, UK researchers would not be able to respond as they have to the Covid-19 pandemic. That is a real fear.”
Surely, then, the answer is simply to breed more monkeys outside China? In the long-term, that certainly seems to be the solution. But for at least half a decade, numbers will remain finite. More important, decisions to increase breeding could, counter-intuitively, make matters worse.
“The problem is we can’t simply increase the numbers of monkeys we have for sale,” one major Mauritian breeder told me, on condition of anonymity. “For every 100 breeding females, only around 60 babies are produced, and they are usually sold at two years. In order to increase the numbers, we would have to hold back females for breeding instead of selling them, and that would add to the shortage.
“We would have to hold them back for a further three years until they were mature enough to breed, and a female will produce only one baby every 18 to 20 months. A monkey generation [the time it takes for an animal to be born, reach adulthood and procreate] is five years, so that’s a whole generation taken out until numbers can be increased.
“Since the Chinese export ban, we’ve been receiving calls from researchers all round the world begging for monkeys. Some people sound desperate, but there’s nothing we can do in the short term.”
But if the situation is so potentially-damaging to the UK’s life sciences, why isn’t the research sector issuing dire warnings over its future — or lack of one?
According to senior industry insiders, there is a two-pronged reluctance to publicly debate the problem. First is the memory of violent demonstrations against the animal research sector at the turn of the century, when staff at Huntingdon Life Sciences (HLS) in Cambridgeshire were targeted by extremists. Brian Cass, managing director of HLS was beaten outside his home by three men; the company’s marketing director, Andrew Gay, was temporarily blinded in a chemical spray attack; and the homes of workers and contractors were firebombed.
Violent animal activism has since all but evaporated. Yet memories endure of its peak in 2006, when extremists dug up the body of Gladys Hammond, a member of the family which ran Darley Oaks in Staffordshire, a farm which bred guinea pigs for the research industry. Three people who “ransomed” the body in return for the farm halting its business were jailed for 12 years each, but the fear of attracting such levels of violence and hatred remain.
Second, and more significantly, there is concern among CROs that if it became public knowledge that they were being affected by primate shortages, their pharmaceutical clients might turn elsewhere — probably China.
Only one CRO in the UK was prepared to comment publicly, yet anonymously, saying the Chinese ban “will result in global demand exceeding supply and what initially began as a US issue will also negatively impact the European research sector. The lack of access to NHPs due to the China ban will create obstacles to the development of vaccines including for Covid-19 and therapeutics globally.”
Leech — who represents the CROs, as well as pharmaceutical companies, private researchers and some universities — has called upon the British government and the European Commission to demand China lifts the ban, arguing it is in breach of World Trade Organisation General Tariffs and Trade rules. He says importing countries had bio-safety arrangements in place within a month and that the ban could have been lifted by then. The UK and European Commission say they are conducting internal discussions but have not yet agreed to act.
As for why China would deliberately starve the US and Europe of such a vital resource, I twice asked the Chinese Embassy in London to address the accusation that its actions were designed to undermine research in the West, but it failed to reply.
It is worth noting, however, that such allegations about China’s quest for pharmaceutical dominance are nothing new. In 2016, David Cyranoski, writing for the journal Nature, was granted access to the Yunnan Key Laboratory of Primate Biomedical Research near Kunming in south west China. In his article “Monkey Kingdom”, he described a research nirvana where animal rights activism doesn’t exist and bureaucracy presents no obstacles.
“With support from central and local governments, high-tech primate facilities have sprung up in Shenzhen, Hangzhou, Suzhou and Guangzhou over the past decade,” he wrote. “These centres can provide scientists with monkeys in large numbers, and offer high-quality animal care and cutting-edge equipment with little red tape.”
He described how “many [researchers] have since sought refuge for their experiments in China… Some of the Chinese centres are even advertising themselves as primate-research hubs where scientists can fly in to take advantage of the latest tools, such as gene editing and advanced imaging.”
Finally, and with estimable prescience, Cyranoski concluded: “With China fast becoming a global centre for primate research, some scientists fear that it could hasten the atrophy of such science in the West and lead to a near monopoly, in which researchers become over-reliant on one country for essential disease research and drug testing.”
Deborah Green agrees. “When you look at China’s stated intentions for their industry, there have been a number of moves that seem intended to drive research towards it,” she says. “That’s everything from their control over lab supplies, PPE, research animals and so on. You can look at what China is spending on pharmaceutical research and development. The US is the biggest investor in this sector but China is now very close, and that number has gone from a very low number to rivalling that of the US in a very short time.”
“This all adds up to a reason to believe that China is trying to take control of this sector,” says Green. “Between the moves to push research towards China, and the animal rights activity in Europe and the US, we are going to see a continuing diminishing of research in the western world and a shift of it towards China. There are already researchers from major academic institutions in the US, and Europe sending their primate work to China. It’s cheaper, there is less regulation and they have the capacity to do it.”
But if major institutions and drug companies start sending highly advanced and hugely sensitive research to be advanced in China, isn’t this a risk every bit as great as that posed by Huawei, whose role in Britain’s 5G infrastructure is now being blocked by the UK government?
“I think this all presents serious issues when you look at China’s attitudes to intellectual property (IP), in that it has a very poor record on respecting IP rights,” says Green. “There is a great risk in taking the products that we develop and sending them over there for testing”
One solution, she says, would be for Western governments to help to create the infrastructure to breed NHPs. “These animals can’t simply be bred anywhere,” she admits. “They need sub-tropical conditions because ideally from a welfare point of view, they should be raised outdoors in large spaces. But where this is possible in parts of the United States and southern Europe, a bit of government protection from animal rights activists would be welcome. In the meantime, we’re hanging on, but we’re losing by inches.”
And if the West does lose, it seems there will be only one winner: China.