1. Monkeys: The Key to Innovative Drug Development
Monkeys, specifically species such as Cynomolgus monkeys and rhesus monkeys, play a pivotal role in the field of innovative drug development as ideal stand-ins for human subjects. Owing to their high physiological and genetic similarity to humans, these primates are broadening applications in preclinical research.
Compared to rodents like rats and rabbits, experimental monkeys exhibit higher corporeal and genetic resemblance to humans, capable of being infected by almost all diseases and viruses that affect humans. This compatibility significantly bolsters the precision of preclinical trials carried out using experimental monkeys.
From the 1960s, preclinical trials for human drugs were conducted solely using rats, a practice that led to disastrous outcomes. For instance, Thalidomide, a drug initially approved for treating morning sickness in pregnant women after rat trials, resulted in over 10,000 newborns in more than 30 countries developing tragically short or deformed limbs due to the drug's side effects. The incident underlined the vast genetic difference between rats and humans.
To prevent such tragedies, governments worldwide elevated the standards for drug clinical trials. In the US, the FDA now requires a potential drug or vaccine to be tested on both rodents (like rats or mice) and non-rodent animals (such as dogs and monkeys) before entering the clinical stage. China, too, mandates that all new drug R&D must rely on valid conclusions derived from non-human primates before transitioning into clinical studies.
Since this enforcement, experimental monkeys have been an indispensable component in any new drug development process. Furthermore, due to the relatively low conservation of target points in large-molecule biopharmaceuticals and vaccines, small-molecule pharmaceutical trials often use mice models, leading to less satisfying match rates with human bodies. This propels experimental monkeys to be the first choice for large molecule drug preclinical trials.
According to estimates, a biopharmaceutical's preclinical study requires at least 60 experimental monkeys, with a toxicity study involving repeated doses over 28 days needing approximately 40 monkeys. If a drug metabolism study is also conducted, an additional 20 monkeys are required.
However, not all monkeys qualify for becoming experimental subjects. Given the high standards of scientific experimentation, strict artificial breeding is necessary to control the microbial and parasitic load on experimental monkeys and ensure a clear genetic background or origin. Wild monkeys necessitate human intervention and at least two generations of breeding before being considered as experimental subjects.
Furthermore, similar to humans, monkeys have a long reproduction cycle. Sexual maturation takes around 4 years from birth, pregnancy, and gestation need half a year, and usually, only one offspring results per pregnancy. Offsprings must be at least 3 years old before they can be used for experiments. The long growth cycle and slow reproduction speed make it challenging to augment the experimental monkey supply in a short timeframe, positioning them as strategic resources akin to microchips.
(The geographic distribution of primates today compared with that during the two warmest times of the past 55 million years: the Eocene Climatic Optimum, and the mid-Miocene Climatic Optimum. )
In the past, wild monkeys from Southeast Asia were primarily exported to China. Nowadays, countries like Korea and Japan have joined in the scramble for monkey resources while monkey source countries like Cambodia and Vietnam have noticeably strengthened their management over experimental monkey exports.
Owing to the dearth of wild monkey resources, Europe and the US are the biggest consumers of experimental monkeys worldwide. Recognizing the strategic significance, the US designated experimental monkeys as strategic resources as early as 2002. It houses about 35,000 primates, including 25,000 experimental monkeys in seven national primate research centers funded by the National Institutes of Health (NIH). Additionally, it imports more than 30,000 experimental monkeys every year.
Having a vital grip on the development of innovative drugs, experimental monkeys are thus irreplaceably critical healthcare strategic resources.
2. The impact of COVID-19 and monumentum in experimental monkey demand
The COVID-19 outbreak underscored the strategic value of experimental monkeys. The pandemic triggered a surge in the demand for vaccine and COVID-19 drug development. In 2021 alone, China registered 3,358 clinical trial projects. Assuming a conservative estimate that only 1,000 of these projects require experimental monkeys, with each project needing 60 monkeys, the annual demand reaches 60,000 experimental monkeys.
China is the world's largest breeder and exporter of experimental monkeys. Each year, we import wild monkeys from Southeast Asia, cultivate experimental monkeys, and export them to advanced countries like the US. However, affected by the pandemic, the ban on wildlife trading in China on January 26, 2020, halted the import and export of experimental monkeys. This abrupt interruption impacted the global capacity of experimental monkey breeding.
Apart from the pandemic factor, the fast development track of large molecule drugs and new pharmaceutical techniques within the global biopharmaceutical industry over recent years also played a significant part in the mushrooming demand. These developments mandate the usage of experimental monkeys for drug safety and efficacy assessments.
For CXO companies, the more experimental monkey resources they possess, the easier it is to seize market dominance. They can even monopolize these resources as strategic assets. However, after the pandemic, the volume of COVID-19 vaccine and drug development fell. The domestic monkey prices dropped significantly, impacting CXO companies that previously high-stocked monkeys.
3. Controversies and the Future
Experimental monkeys play a critical role in the pharmaceutical industry as ideal substitutes for human subjects. They are widely used in preclinical research due to their physiological and genetic similarity to humans. In contrast to rodents, experimental monkeys exhibit a higher degree of similarity to humans, allowing for more accurate preclinical testing.
In the past, drug development relied heavily on rodent testing, leading to tragic outcomes such as the thalidomide tragedy. To avoid such incidents, governments worldwide have raised the standards for preclinical drug trials. For example, the FDA now mandates testing on both rodents and non-rodent animals, including monkeys, before entering clinical trials. In China, reliable conclusions derived from non-human primates are required for new drug development before progressing to clinical research.
Experimental monkeys have become an essential component of drug development since then. They are particularly crucial for the preclinical evaluation of large molecule drugs, as their genetic makeup aligns more closely with humans compared to small animal models.
However, not all monkeys can be used as experimental subjects. Strict breeding and control measures are necessary to ensure clear genetic backgrounds and minimize microbial and parasitic load. Wild monkeys require human intervention and multiple generations of breeding before being considered for experiments.
The slow reproductive cycle and long maturation period of monkeys pose challenges in increasing their supply rapidly. This scarcity, coupled with the growing demand for experimental monkeys, has resulted in a global shortage and a significant increase in prices.
The COVID-19 pandemic further highlighted the strategic value of experimental monkeys. The increased demand for vaccine and COVID-19 drug development led to a surge in the need for experimental monkeys in clinical trials. China, being the largest breeder and exporter of experimental monkeys, faced supply chain disruptions due to the ban on wildlife trading.
The sudden shortage of experimental monkeys caused prices to skyrocket within a short period. While domestic prices have gradually decreased since the pandemic subsided, international prices remain high, creating a significant price gap. This gap has led to a shift in CRO orders to China, favoring CXO companies with access to experimental monkey resources.
Controversies surrounding animal testing persist, with ethical concerns and debates regarding the use of live animals for experimentation. The pressure from animal protection organizations has led to the closure of monkey farms and restrictions on transportation.
Advancements in alternative technologies, such as artificial intelligence, organ-on-a-chip systems, and organoids, aim to reduce reliance on animal experimentation. These emerging fields hold promise for replacing traditional animal models. Organ-on-a-chip technology, for example, uses microfluidics to replicate the physiology of human organs and can be used for drug safety and efficacy testing.
While the eventual replacement of animal testing may still be on the horizon, experimental monkeys remain indispensable resources in the short term. Continued research and development of alternative technologies will pave the way for a future with reduced reliance on animal experimentation.
