Why do researcher investigate primates?
Monkeys are used in animal research only if a particular phenomenon cannot be studied on any other species of animal, such as mice, fish or fruit flies. In the course of evolution, similar structures and functional principles have developed in the brains of monkeys and humans. Such structures and principles are not present in other mammal groups. Neuroscientists can therefore only research complex cognitive functions relating to perception, attention, memory formation and awareness on monkeys.
Because they are biologically so similar to humans, the potential for applying research results to humans is very high. They are therefore used primarily for the final drug safety tests on new medicines before they are used on humans. Moreover, scientists use monkeys to study important fundamental questions on how a healthy organism functions or how to cure fatal illnesses (e.g. Ebola) or severely debilitating disorders (e.g. Alzheimer’s). Monkeys therefore play an important role as laboratory animals in infection research and in the neurosciences.
In order to treat neurodegenerative diseases in future, it is important to understand first of all the neural basis of normal cognitive processes, as it is only by doing this that the pathological mechanisms can be systematically investigated. Despite enormous progress in recent decades, our knowledge of the brain is still far from complete, especially when it comes to the higher cognitive functions. Much of what we know is based on studies conducted on relatively simple brains. However, this information is only of limited benefit if we want to understand and treat neurological and psychiatric disorders that are based on complex interactions between the different parts of the brain. Monkeys are currently the only model that can be used to systematically study the relationships between the activity of individual neurons and higher cognitive functions.
The animals most frequently used in brain research are the long-tailed macaque (Macaca fascicularis) and the rhesus macaque (Macaca mulatta). More recently, marmosets have also been used with increasing frequency. This is because they exhibit complex social behaviour and many cognitive functions that are similar to those exhibited by humans. Research is conducted less frequently on the three-striped night monkey (Aotus trivirgatus) and the callitrichid (Callithrix). In 2015, 0.1 percent of all laboratory animals in Germany were monkeys (2,424). Scientists used 17 percent of monkeys (412) for academic research. The remaining 83 percent were used by industry primarily for prescribed safety tests.
Medical progress through primate research
As laboratory animals, monkeys have already provided important findings for medicine. The rhesus factor incompatibility in a mother's blood and in the blood of her unborn children was discovered as a result of studies conducted on rhesus macaques, hence the name. The vaccinations that prevent polio, measles, yellow fever and Hepatitis B are all based on research that was carried out on monkeys. The treatment of diabetes patients with insulin was researched on monkeys, as was the treatment of patients with leprosy and rheumatoid arthritis. The development of stem cell technology, on which so many hopes are based today, can also be traced back to work with monkeys.
Deep brain stimulation for Parkinson's patients
The development of a new treatment for Parkinson's patients is a compelling example of the successful implementation of findings from research conducted on rhesus macaques. In deep brain stimulation as it is known, electrodes are placed in damaged areas of the brain to electrically stimulate the areas. This can alleviate certain symptoms of the disease, which cannot be treated or can no longer be treated pharmacologically. [Link zum Video]. Efforts are also currently being made to treat certain obsessive-compulsive disorders, pathological obesity and some forms of depression using deep brain stimulation if these conditions do not respond to the available medications. However, this method is still relatively untested and is not free of side effects. In order to be able to minimize these side effects, scientists are also studying exactly how deep brain stimulation works on monkeys.
Research has been ongoing for some time now on a new method in which the spinal cord rather than the brain is stimulated with electrodes. These studies are currently taking place on rats. However, before the results can be transferred to humans, they must be researched on monkeys.
Primates used as a model in dementia research
Monkeys are one of the few species of animal that, like humans, can develop Alzheimer's disease. Studies on long-tailed macaques have shown that they develop protein deposits in the brain, largely similar to those that occur in humans. The corresponding protein that develops in mice and rats, on the other hand, is very different to the one that develops in humans. Researchers can therefore study long-tailed macaques and possibly other monkey species much more effectively to see if they develop these protein deposits in the brain and, more importantly, investigate how they can be prevented.
Primates used as a model in Huntington's disease
Patients with Huntington's suffer from the progressive destruction of an area in the brain that is important for controlling movement and basic mental functions. The brain cells in this area are destroyed by an aberrant protein (Huntingtin), which is formed as a result of a defect in the corresponding gene. The physical symptoms include impairment of the emotions, muscle control, including facial expressions, and ultimately brain function as a whole – the final stage is dementia. This is another disorder that may be better explained using monkeys rather than mice or rats. Genetically modified macaques with a mutated form of the Huntingtin protein in the brain form protein deposits like those that occur in Huntington's patients. The symptoms of the disease are also similar in monkeys and humans. Further research on these animals could therefore lead to new forms of treatment for this currently incurable disease.
Brain-machine interfaces for patients with locked-in syndrome
Certain brain injuries lead to what is termed locked-in syndrome. It causes patients to lose their ability to communicate – whether this is through language, facial gestures or gesticulation. This condition occurs even though the patient is fully conscious and aware of everything around them. The only option for enabling patients to have a minimum of contact with their environment is based on the development of brain-machine interfaces. With this technology, brain activity is extrapolated via electrodes and converted via a computer into signals, which can then be used to control keyboards or robotic arms. To date, the best results have been obtained with implanted electrodes although the conversion of signals into appropriate movements was previously optimized in research on monkeys. Now, patients who are completely paralyzed can regain a certain autonomy in this way. They learn how to move robotic arms using their brain activity and thus to guide food to their mouth or execute keyboard commands in order to write. Efforts are of course also made to extrapolate brain activity from the surface of the head non-invasively using EEG electrodes in order to spare the patients an operation. Unfortunately, as already mentioned, the spatial resolution of this minimally invasive procedure is too low to decipher more complex commands.
In future, these neuroprostheses are expected to be available not only to patients with locked-in syndrome and patients who are completely paralyzed for other reasons. It will, however, also be used for patients who have lost limbs so that they can regain movement using prostheses that are controlled directly by the brain. To this end, neuroscientists are investigating the signals in the motor centres of the brains of macaques.
Brain-machine interfaces in paraplegia
In 2016, for the first time ever, researchers in Switzerland managed to mobilize paralyzed monkeys quite normally by 'wirelessly' transmitting the corresponding brain activity to the spinal cord. Each of the rhesus macaques, whose back right leg was paralyzed, was fitted with a microchip in its brain. The microchip records the activity of neurons in the region that controls movement of the back right leg. In the activity pattern that is recorded, a computer recognizes in real time the intention to walk and sends the relevant signals to a stimulator. This activates the neural circuits in the spinal cord, which control the rhythmic muscle activities involved in walking – a finely tuned tensing and relaxing.
The animals were actually able to use their paralyzed leg again without any training. The researchers' aim is to use this technology one day to enable paraplegic patients to regain control over their legs. For this reason also, technical components that have already been approved for clinical tests were used in this research.