Why experiments with primates?
Experiments on monkeys are generally considered when it is not possible or not permitted to use other methods. These are cases in which the research must come as close as possible to the conditions in the human body, but research on humans is not possible for ethical reasons, among others. It is forbidden to conduct risky studies on humans. National and international laws regulate research on humans, for example the Swiss Human Research Act or the of Helsinki, which states that research on humans should be based on animal experiments if necessary. However, the welfare of the animals must be considered.
Examples of this required proximity to humans include neurological problems (blindness, paralysis, Parkinson's or Alzheimer's disease), special viruses that only affect primates (e.g. Zika, Ebola), development of sensory or motor prostheses, medicines and vaccinations (e.g. Covid-19), etc.
What successes have been achieved thanks to experiments on primates?
The examples below show experiments on primates that have led to therapeutic medical use in humans. These experiments could not be tested directly on humans for ethical and legal reasons. In these cases, experiments on monkeys were necessary so that sick and injured humans could be treated. And who knows which therapies, after successful implementation in human medicine, could one day also be used to treat domestic animals.
Neurology – Paraplegia
In 2016, a report caused a stir that in an experiment macaques were able to walk again after spinal cord damage. What sounded like science fiction became reality: an electrode transplanted into the brain sends those signals to another implant that are important for the movement of the muscles in the leg. The animal or – after introduction into human medicine – human patient was able to move his legs again. Why does this work? In the case of a nerve injury in the spinal cord, the normal connections between brain and muscle are severed, the signal for movement from the brain no longer reaches the muscles: the patient is paralysed. With electronic prostheses, however, the injury in the spinal cord can be bridged, the signals from the brain reach the muscle again, and the patient is able to consciously move again.
Following the experiments on monkeys, this therapy was also applied to paralysed humans in the hope that they too would be able to learn to walk again. In 2018, the news was published that patients, some of whom had been dependent on wheelchairs for years, were able to take their first steps again thanks to the stimulation provided by the implants – still with the help of crutches and a rollator, but without a wheelchair.
The interaction between brain and muscles is very complex. It is no use stimulating the brain at random. Imagine you want to bend the leg, but the muscle extends, or the wrong muscle is moved. You have to know precisely which signals to give to make walking possible. This can be recorded much more precisely in monkeys than in a rat, for example. However, this paraplegia treatment was only able to be successful because it was possible to first study the normal function of the brain and the nerves in basic research on animals. Based on these findings it was in the end possible to use the treatment on humans without putting more strain on the patients than they already had due to their injuries. That is why experiments on macaques were and are indispensable for the success of this therapy in humans.
People who have severe hearing problems due to non-functioning hair cell receptors in the inner ear can benefit from so-called cochlear implants, which stimulate the cochlea by means of electrical impulses. These inner ear implants, thanks to which many deaf babies are able to learn to hear and speak, were developed in experiments on cats and guinea pigs. Cats have particularly sensitive auditory senses, and their auditory system is anatomically similar to that of humans. Furthermore, cats and guinea pigs hear in a similar frequency range as humans. For the more targeted transmission of electrical signals, researchers at the German Primate for example are genetically modifying the nerve cells so that they can be stimulated by light signals instead of electrical current. To this end, researchers are also conducting experiments on monkeys, as only primates have a similar anatomy and communicate with similar sounds. The aim is to further develop the implants so that patients can better hear melodies, pitches, and speech.
Blind people can no longer perceive optical signals because of missing information from the optic nerve, the eye, or the brain. A prosthesis that would bridge these interruptions can restore vision to a certain degree. Studies on monkeys have already shown that with the help of such prostheses, electrical stimulation in the visual cortex of the brain successfully produces correct optical images. This was later repeated in humans. No other animal species was suitable for these studies because only primates have a highly developed visual system and are also anatomically similar enough to humans. Like humans, they have forward-facing eyes and high-resolution vision. Furthermore, only the Old World monkeys, which include the macaques, have so-called trichromatic vision like humans, i.e. three different types of cones as colour receptors in the retina. Therefore, a translation of studies on these animals to humans is incomparably more reliable than for any other animal species. There are currently clinical trials underway that aim to use visual prostheses in humans: https://clinicaltrials.gov/ct2/show/NCT03344848, https://clinicaltrials.gov/ct2/show/NCT03326336
As early as 2012, researchers were able to help a person suffering from the "locked-in" syndrome learn to move a robotic arm with the help of brain electrodes. With locked-in syndrome, the affected persons can neither move their bodies nor express their needs through speech. They cannot communicate with the outside world and are literally locked inside their bodies. Test subjects had electrodes responsible for muscle movement in the body implanted into their brains. These electrodes register brain signals and transmit them to external computers. These converted the signals into movements of a robotic arm. The arm responded to the commands right/left and down/up. With this tool, the test person was able to think of a movement he or she would like to perform. The brain produced the corresponding signals and through the connection with the computer and the robotic arm, the person was able to move the robotic arm by "thought" and thereby lift a drinking bottle to their mouth, and the test person was able to drink a sip of water independently for the first time in 15 years.
The same would presumably be applicable to quadriplegic patients. The principle that this activation from a robotic arm works through conscious brain signals was also first demonstrated in macaques before it was applied to humans. This example shows that the implementation from basic research to preclinical research to the implementation in the clinic is often a long journey: It took a good 40 years from the beginning of the research to this moment.
Regeneration of nerve tissue in paralysis
The human brain has a limited ability to regenerate damaged tissue or neuronal circuits. In the 1980s, with the help of experiments on mice, factors were discovered that are responsible for this limited growth of new nerve cells. One of these factors is Nogo-A. Researchers subsequently developed antibodies to block this inhibition. This made it possible, for example, to stimulate blood vessels in injured parts of the spinal cord to grow again. The mice showed significant improvements in motor function after the intervention.
Rats which had been trained to run on a treadmill were also able to move on the treadmill again after a spinal cord injury when they had been treated with a Nogo-A inhibitor. Muscle spasms were also prevented and bladder function control – a serious problem in paralysed people – was improved.
Regeneration of the nerve tract could be restored in macaques, and fine motor skills of hands could be improved. This is important for a complete recovery from a spinal cord injury in impaired people and can only be studied in primates, because they are able to grasp a tool with precision. This development of anti-Nogo-A – especially the involvement of primates – to a large extent took place in Switzerland.
The treatment of paralysed patients with anti-Nogo-A antibodies has already successfully passed phase I clinical trials, i.e. the tests of effect and possible side effects. Now (as of 2022), clinical trials are in phase II, where they test efficacy in freshly injured, quadriplegic patients. This study is being conducted in various for people with spinal paralysis, including in Switzerland.