Attitudes towards experimenting on monkeys are diverging

IN 2014 A GERMAN animal-rights group called SOKO Tierschutz planted a caretaker in the laboratory of Nikos Logothetis, a neuroscientist working at the Max Planck Institute in Tübingen. The infiltrator secretly filmed around 100 hours of lab work over six months, some of which was later broadcast on German television. The footage showed monkeys with metal plugs grafted into their skulls—ports which researchers used to probe and study their brains. One vomits on camera, apparently as a result of damage done to blood vessels in its brain while electrodes were inserted.

The impact was immediate and lasting. Around 800 people massed outside Dr Logothetis’s lab, demanding an end to his work with monkeys. He was called a monster and a murderer. He and his family received death threats. He faced charges (which were dismissed) of breaking German animal-welfare laws. So in 2020 he announced that his laboratory would move to China. He is building a new research facility in Shanghai, working with Mu-ming Poo of the Institute of Neuroscience, one of China’s leading brain researchers, who was on the team responsible for first cloning a genetically modified primate in 2018. Dr Logothetis is packing up his Tübingen lab.

Research on primates—mostly macaque monkeys—is increasingly unpopular in Europe and America. The EU has promised that it will reconsider rules about the use of monkeys in research every five years. It wants to end all animal research at an unspecified point in the future. American lawmakers are trying to pass the Humane and Existing Alternatives in Research and Testing Sciences Act. It would encourage scientists funded by the National Institutes of Health, the country’s largest funder of biomedical research, to move away from reliance on animals. In both Europe and America the number of monkeys in research has been flat or falling for the last five years.

And yet in East Asia, particularly China and Japan, the volume of research carried out on monkeys is growing. Most of this has been driven by creating and expanding domestic primate-research programmes. Leading institutions such as the Shanghai Institute of Neuroscience focus on breeding monkeys whose genomes have been modified in order to make their physiology more like humans’ and so more useful for studying human diseases.

This kind of genetic modification of research animals is common around the world in biomedical research, but is almost exclusively carried out on mice. No American or European laboratory maintains a line of genetically modified monkeys, but several Chinese and Japanese laboratories do. And since monkeys’ brains are far more like human ones than those of mice, transgenic monkeys will probably serve as a better model for studying neurological disease than transgenic mice. While such experiments remain beyond the pale in many countries, China and Japan are racing ahead.

Campaigners argue that no animal should be used for research because they cannot give informed consent. Julia Baines, who works on science policy at People for the Ethical Treatment of Animals (PETA), an animal-rights group, suggests that all animals, including primates, can be replaced in biomedical research by a combination of in vitro studies (carried out in Petri dishes and test tubes without relying on living creatures), computer simulations and consensual human trials.

Others, such as researchers at the Centre for Alternatives to Animal Testing at Johns Hopkins University, advocate replacing animal experimentation where that seems possible and refining how it is used where it does not.

Monkeys make up just one in every 2,000 lab animals, according to Stefan Treue, a neuroscientist who works on them at the University of Göttingen in Germany. But they generate by far the most controversy. The social nature of their lives and their intelligence—which is why they are so useful for research—also help explain why such experiments are so troubling. Research which relies on them is simultaneously more valuable and more ethically fraught than research on other creatures. Neuroscientists in particular consider monkeys irreplaceable.

The brain is so poorly understood that looking at its activity in living creatures is the only way to fathom how it works, says Dr Treue. Dissecting dead brains produces only limited information. Brains only really make sense when active. Few humans would volunteer to have electrodes implanted in their brains. The consent of any who did would be suspect.

Allyson Bennett, a psychologist at the University of Wisconsin-Madison, also argues for experiments on monkeys based on the value of pure science—research with no set goal. She cites Vittorio Erspamer, a physiologist working in Italy in the early 1930s. He was curious about the properties of chemicals found in the intestines of rabbits and frogs. In studying them he discovered serotonin.

Didn’t see that coming

Drugs that regulate the body’s production of serotonin nowadays treat various depressive disorders, improve the lives of millions and help prevent thousands of deaths. Erspamer, however, had no interest in depression or anxiety. It was decades before his discovery became the foundation for such treatments.

The list of medical advances which rest on animal experimentation is long, but Dr Bennett points to one in particular that could not have happened without monkeys: prosthetic limbs which “talk” to the brain, known as neural prosthetics. The brains of non-human primates are sufficiently similar to ours to allow for a prosthetic developed on monkeys to be used by humans. They are still rare, but prototypes have restored the power to interact with the physical world to people who have lost the use of their own limbs.

China is becoming the global centre for the kind of neuroscience that uses monkeys. And the stakes are getting higher. Neurological disorders are the world’s second-leading cause of death after heart disease. Conditions such as Parkinson’s disease, Alzheimer’s and dementia are becoming more burdensome as the world gets greyer. Meanwhile technology companies hope that an understanding of the brain can help them build cleverer software. Generals think advances in neuroscience can help them build better weapons.

The pandemic has bolstered China’s position. In February 2020 China’s government banned the export of all wild animals in an effort to tamp down the wildlife trade that is thought to be a vector for the zoonotic spillover of pathogens such as SARS-CoV-2, the virus that causes covid-19. Exceptions for research are subject to the government’s approval. Until recently the majority of monkeys used in America were imported from farms in China. But export controls have created shortages (see chart).

“China holding onto its primates fits into a long-term strategy it announced in 2015: the China 2025 policy,” says Kirk Leech of the European Animal Research Association. Understanding the brain was one of the key areas of scientific research for that policy. To achieve it, China needs more monkeys. Dr Treue says China has decided that research primates are a strategic resource. Exports are unlikely to revert to their previous levels.

This leaves Europe and America in a bind. The farms in China are well respected by the research community. Alternative suppliers from Vietnam and Cambodia operate in a way that is closer to grabbing wild monkeys out of their natural habitat. This is both more traumatic for the animal and less useful for research, as the health and age of such animals varies. Increasing the harms and reducing the usefulness of any research exacerbates the ethical dilemma of using monkeys.

Meanwhile, even as it keeps all of its farmed monkeys in its own country, Chinese neuroscience is expanding at such a pace that even domestic labs are experiencing shortages, according to Mr Leech. While researchers and campaigners in America and Europe battle over whether any sort of primate research is permissible, China and Japan are racing ahead.

The Institute of Neuroscience in Shanghai is the largest buyer of the Neuropixel, a new brain probe. These are easier to install in animals’ brains than the kinds currently used. The institute bought 3,000 of the probes when they were released to install in macaque monkeys. This would have allowed it to gather neurological data on an unprecedented scale. The probe also offers a path to less invasive research than older, bigger electrodes, though the harm done by putting sensors into a brain will always be considerable.

Erika Sasaki at the Central Institute for Experimental Animals in Kawasaki near Tokyo has developed a line of genetically modified marmosets, a small monkey native to South America. She and her collaborators at the RIKEN Centre for Brain Science, also in Japan, are creating a 3D atlas of the marmoset brain to map both the higher cognitive functions unique to primates (humans included) and the neurodegenerative diseases that disrupt them.

Drifting apart

Diverging attitudes towards scientific research on monkeys have three consequences. America and Europe may find themselves outsourcing the creation of knowledge that relies on research methods they consider unethical. In future they may have to choose between relying on the fruits of that knowledge, such as treatments for neurological disorders, and rejecting them in principle. The UN’s World Health Organisation estimates that neurological disorders affect at least a billion people worldwide. Treatments for such conditions almost certainly involving some neuroscientific research on monkeys will become increasingly valuable.

Competition for control of the supply chains may sharpen. The pandemic has exposed the significance of Chinese supply chains for producing a range of medical equipment and supplies. If cutting-edge neuroscience becomes concentrated in China, new companies and medical treatments will emerge there too. Many governments are already wary of plugging Chinese-made networking equipment into their phone networks; they will probably be queasy about bunging vital Chinese-made probes into their citizens’ brains.

Probing the workings of the brain is a 21st-century equivalent to exploring the farthest reaches of the planet. The results will not only teach humans about their own minds but will also help them design artificial intelligence—a separate but connected field in which competition between countries has become fierce. If such scientific knowledge is largely produced in China and Japan, it will become ever harder for others to catch up, should they decide they wish to do so. ■