The unwinding of the unipolar, US-dominant paradigm continues to fracture the globe across important economic fault lines. Amid the rapidly shifting geopolitical landscape, we are witnessing great nations jostle for control of important natural resources to power the engines of progress. We can see this dynamic clearly illuminated by a close examination of the market for rare ear- sorry no… it’s lab monkeys??
Indeed, one of the most fascinating little pockets of the healthcare economy is the market for non-human primates (NHPs) for clinical research. NHP prices are sky rocketing, and upon close examination, we can see that this market is a microcosm of multiple macrotrends reshaping the US economy:
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The fragility of a globalized supply chain reliant on foreign imports
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A shifting global balance of power in critical innovation sectors
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A race to leverage technology (and yes, AI!) as a strategic off-ramp from foreign dependency
To accompany this post, I’ve created an interactive timeline tracing the evolution of NHP usage in clinical research – check it out here.
In Vivo Veritas
Before commencing clinical trials on humans, pharmaceutical companies typically conduct tests in two animal species to assess safety and toxicity.
Preclinical safety testing typically includes studies in one rodent and one non-rodent species. The choice of species often depends on how closely the animal’s biology mirrors our own. For example, NHPs are commonly used in biologics research where a close approximation to humans on genetics, anatomy, physiology, and immunology is vital.
Biologics are large, complex, and difficult to characterize molecules created through multistep biologic processes… These new treatments for cancer, autoimmune disease, heart disease, infectious disease, post-transplant organ rejection, and genetic disorders depend upon animals closely related to [humans] … Therefore, it is only currently possible to assess the safety and efficacy for biologics intended for human patients in other (non-human) primates.
Source: Charles River Laboratories
NHP research spans diverse therapeutic areas, each category utilizing various subsets of primates (with cynomolgus macaques and rhesus macaques being the most common).
At first glance, the scale of NHPs in clinical research seems small – of the 14 million vertebrate animals used in research in the US, NHPs represent just 0.5%, of which private industry accounts for ~50% of the usage. But NHPs have an outsized impact on clinical development – of the >17,000 individual products in the US R&D pipeline, an estimated 56% of them have used or will require the use of NHPs during their development.
NHP markets have been tightly indexed to overall investment in scientific research and biopharma development. When industry funding and research activity increases, demand for NHPs climbs. When funding dries up, demand falls. However, supply can’t pivot in lockstep with demand. Breeding colonies take 5-10 years to establish, reproductive cycles take 12-18 months, there is typically 1 offspring per cycle, and it can take years for NHPs to reach sufficient maturity for research use. Demand moves in financial quarters; supply is stuck on biological time.
This structural mismatch creates significant baseline vulnerability to volatile price swings. But over several decades, a death by a thousand cuts would make those swings increasingly extreme.
The Blurst of Times
Monkeys have been used in clinical research for over a century. By the turn of the 20th century, they were already becoming central to polio research. In 1908, Karl Landsteiner and Erwin Popper demonstrated that monkeys could model human polio transmission via spinal cord injection from a child who died of the disease. The following year, several groups successfully demonstrated monkey-to-monkey transmission of polio. From the onset, research with NHPs exhibited both the promise and the burdens of the practice:
Simon Flexner had infected monkeys with polio, but researchers in the 1920s were unsuccessful infecting rabbits, mice, guinea pigs, dogs, cats, pigs, chickens, sheep, goats, and calves. Until Charles Armstrong succeeded in infecting cotton rats in the late 1930s, monkeys were the only laboratory animals that polio researchers could use. Researchers’ reliance on monkeys to conduct polio research substantially increased the cost; monkeys averaged about $8 each through the 1930s, and each monkey could be used only once.” John R. Paul observed that “the great majority of universities and private research institutions were unable to furnish the expensive facilities, technical assistance, and the supply of monkeys which were so necessary at that time for poliomyelitis research.
Source: “Basil O’Connor, the National Foundation for Infantile Paralysis and the Reorganization of Polio Research in the United States, 1935–41.” Journal of the History of Medicine and Allied Sciences
Researchers today might lol at that price point (~$150 today adjusted for inflation), but the cost burden of NHP research was clearly an obstacle even then. Nonetheless, without an alternative, imports climbed steadily through the 1920s. By 1931, the trade had grown large enough to appear in annual government reports for the first time. Within a decade, the number of rhesus monkeys imported for research would triple.
Persistent demand for Indian rhesus monkeys was driven largely by a significant cost advantage (~$10/monkey from India vs. say $75/monkey from Puerto Rico). However, supply was precarious. Monkeys hold deep religious significance for Hindus in India, so any perceived mistreatment could threaten to choke off supply – a fragility that would soon surface. As the 1947 Partition of India unfolded, American researchers found themselves contending with an odd predicament:
[via State Department inquiries]: “There is a possibility of an interruption in the supply of monkeys from the United Provinces because the trappers are all Moslems and there has been a large movement of Moslems out of the province in consequence of the communal riots in and around Delhi. The influx of Hindus into the area from Pakistan has contributed to the confusion and has served to make the Moslem trappers nervous about the continuation of their activities because of the Hindu veneration for the monkey.”
Source: “Between Simians and Cell Lines: Rhesus Monkeys, Polio Research, and the Geopolitics of Tissue Culture” by Tara Suri
It wouldn’t be the last time that religious concerns threatened the supply of research primates.
Still, demand kept climbing. In the late 1940s, a large-scale polio typing effort required some 20,000 monkeys to confirm that there were three strains of the virus. Jonas Salk’s vaccine breakthrough further accelerated demand, as monkey kidney tissue was essential to its production. By 1955, the US moved to formalize its import/export relationship with India to secure access to a supply chain that American science had come to depend on.
“T. T. Krishnamachari, Commerce and Industry Minister, told Parliament last week that the United States was likely to release polio vaccine by the middle of this year and for this purpose 100,000 monkeys were required … the monkeys cost $35 each… the monkeys are sacrificed after twenty-eight days.”
Source: New York Times – April 14, 1955
The agreement had an interesting caveat: the Surgeon General would have to certify that imported monkeys would be used solely for medical research or polio vaccine production – explicitly prohibiting their use in atomic research.
Oops! It turns out they were.
When reporting in the 1970s revealed that the Air Force had been testing the effects of radiation exposure on monkeys over the preceding decades, activists like Shirley McGreal brought this to the attention of Indian authorities. Exports of monkeys to the US were swiftly banned in 1978.
Meanwhile, domestic production of NHPs was still in its infancy. Congressional appropriations established what would become the National Primate Research Centers in the early 1960s, but funding was directed mostly to research activities rather than large-scale breeding. So when India closed the door, the US had no meaningful domestic alternative to fall back on.
At this point, the NHP market bifurcated. Academics continued to rely on rhesus monkeys but struggled to source supply as NIH-funded breeding centers slowly ramped up production. Meanwhile, the biopharma industry pivoted to cynomolgus macaques from Indonesia, the Philippines, and Mauritius. These nations filled the vacuum left by India, but only temporarily. They would soon be eclipsed by a behemoth.
Crouching Tiger, Hidden Monkey
In 1985, China established breeding programs for cynomolgus monkeys and began exporting in 1990. Within a decade, China was producing tens of thousands of macaques for export per year.
China also emerged as the default logistics hub for exports of NHPs bred elsewhere. In 2001, approx. 7,000 macaques of Indonesian and Vietnamese origin were shipped to the US via China, as conservationist pressure had forced most airlines to stop transporting primates; Chinese carriers stepped into the gap.
With inherent cost advantages and superior logistics, China soon became the dominant exporter of research macaques.
As it consolidated its grip on NHP supply, China’s goals around clinical research were far more ambitious. From the 2000s onward, China made a deliberate push to become a global player in biotechnology innovation. But 2015 marked a genuine inflection point. China adopted a sweeping set of reforms to supercharge its domestic biotech industry, increasing the number of regulatory reviewers and slashing timelines to achieve clinical trial approval from two years to 60 days. In the following years, domestic clinical trials doubled and drug approvals skyrocketed:
As US researchers grew increasingly reliant on China, which had grown to represent two-thirds of NHP imports, Chinese domestic demand was surging, increasing from 7,000-8,000 NHPs in 2013 to 30,000 in 2019.
Then, in 2020, COVID nuked the NHP market.
Bored Ape Research Club
Ironically, as the pandemic took shape, the hyper-volatile market for digital monkey NFTs turned out to be a surprisingly apt metaphor for the real thing.
At the onset of COVID, China moved to ban the export of macaque monkeys.
US researchers scrambled to find other suppliers. At first, Cambodia filled the market gap left by China and quickly became the new number one supplier to the US. But in 2022, scandal struck as Cambodia was identified as the hub of an international primate smuggling ring, in which wild cynomolgus macaques were being falsely labeled as captive-bred and illegally exported. Cambodian macaque supply shut off almost as quickly as it had rushed on to the scene.
That left Mauritius as the lead horse. But Mauritius has limited breeding supply; to fulfill demand, wild monkeys are trapped at scale for export. This has spawned a cottage industry:
For some locals, capturing monkeys is a way to remove animals that can bite and tear up yards; villagers can also earn up to $200 for allowing Bioculture to set up a trap on their property.
Source: Science (AAAS)
While researchers and industry tout Mauritius as a lifeline for scientific progress, this supply remains fragile. Like India, monkeys hold deep religious significance in Mauritius. Public sentiment could close the door to exports just as quickly.
Where does this leave us today? The supply of NHPs is on tenuous footing. The US has not shown meaningful appetite to build NHP breeding capacity. In fact, the Trump administration has signaled a strong interest in reducing NHP testing – recently, the CDC announced it would end its internal monkey research program. At the same time, China has demonstrated that it intends to reserve its NHP supply for its domestic biotech industry.
According to our checks, China’s move to shut down its NHP export business was done in an attempt to gain competitive advantage over the supply of NHPs and to drive increased drug development business in China.
Source: Mizuho Capital Markets – CRL Initiation Report
Subscale domestic production and limited access to foreign supply mean that the US is one supply shock away from a preclinical research emergency.
The US was never going to out-breed China on NHPs – China’s cost advantages and ethical calculus are insurmountable. Rather, the strategic off-ramp from reliance on this brittle supply chain will require doubling down on areas where the US does have structural advantages – world class technical talent and capital markets that reward technological innovation. And now, a vision for credibly diminishing dependence on NHP testing is coming into focus.
No More Monkeys Jumping on the Bed!
The FDA recently published a roadmap of promising alternatives to animal models – “New Approach Methodologies” (NAMs) – spanning organ-on-chip models, AI/ML toxicity platforms, and other advanced computational modeling approaches. Each approach tackles different pieces of the preclinical puzzle, from modeling how drugs move through the body to predicting immune responses before molecules ever reach a living subject.
Taken together, these approaches represent a potential reinvention of preclinical research – faster, cheaper, more predictive of human outcomes, and not dependent on a supply chain that other countries can turn off.
For its part, the FDA is outlining an aggressive path for adoption of these new methodologies:
In the long-term (3-5 years), FDA will aim to make animal studies the exception rather than the norm for preclinical safety/toxicity testing… Ultimately, the vision is that no conventional animal testing will be required … instead, a comprehensive integrated NAM toolbox (human cell models + computational models) will be the new standard.
Source: FDA New Approach Methodologies Report
Taken literally, this feels like an unrealistic timeline. While these technologies have shown promise, there are legitimate scientific obstacles that will constrain adoption. Many proposed methodologies struggle to capture the full complexity of physiology and how biological systems interact over time.
A key issue is that current NAMs typically offer insights into single cells or organs, failing to capture the complex interactions among multiple organs or the systemic effects of a drug across the whole body. For instance, organoids, which are 3D cell cultures that mimic key organ functions, do not have a vascular system that can replicate whole-organ physiology. While progress is being made, replicating the full complexity of human physiology—encompassing systemic drug distribution, metabolism, and immune responses—continues to be a substantial scientific and engineering hurdle.
Source: McKinsey
There is also the harder problem of the “unknown unknowns.” NHP studies are routinely credited with catching things researchers were not looking for – safety signals that current NAMs may not be designed to detect. Garnering institutional trust could take a long time.
The most likely path forward is NAMs gradually incorporated alongside, not replacing, animal testing. If these technologies prove out to be reliable proxies at scale, the sunsetting of NHP testing will eventually move from aspiration to reality.
The insiders are taking the over. Charles River Laboratories, which takes painstaking effort to emphasize that it is investing millions of dollars in alternatives to NHP research, announced a $510mm deal in January to vertically integrate a Cambodian NHP producer.
“The demand continues to increase, so we want to have control of supply” – CEO of Charles River on the acquisition of K.F. (Cambodia) Ltd.
Monkey Business
I find myself reflecting on two recent anecdotes.
Late last year, a truck transporting rhesus monkeys from Tulane overturned in Mississippi. The local Sheriff’s Department put out a notice that the primates were infected with hepatitis, herpes and COVID. They were not (the Sheriff later blamed this misinformation on the truck driver).
Nonetheless, this led to a weekslong primate hunt. Hearing that disease-riddled lab animals were set loose in their community, the citizens of Mississippi literally took up arms.
Then there is the saga of Punch, a baby Japanese macaque at the Ichikawa Zoo in Japan, which captivated the internet (and me) this month. Little Punch-kun was abandoned by his mother and struggled to socialize with the other macaques. Footage of the other monkeys bullying Punch went viral. The zookeepers gave Punch a stuffed orangutan (specifically a DJUNGELSKOG from IKEA) which he ran back to and snuggled for comfort.
The staggering difference between these two stories feels like an extreme example of the Identifiable Victim Effect – thousands of macaques used in research are a statistic, Punchy is a tragedy.
I’m convinced that continued advancements around NAMs will eventually make testing on live non-human primates obsolete. Probably not on the FDA’s five year shot clock, but eventually.
When the day comes that biopharma companies and other researchers can fully transition to these alternatives, it will bookmark a chapter in history in which we subjected non-human primates to testing that we will almost certainly look back on as barbaric.
We’ll say it was necessary – the advancements enabled by NHP research have saved millions of lives, and will probably go on to save millions more. But it will be hard not to wince.