Owing to their uncanny similarities with human beings, non-human primates (NHPs) have a small but important role in basic and translational biomedical research particularly when it comes to neuroscience. NHPs have delivered fundamental knowledge about how the human brain functions, which has directly led to the development of valuable therapies that have dramatically improved the lives of human patients.
For example, damage to the brain from stroke, accident, or disease can sometimes cause the patient to lose control of their body, perhaps leaving them with a severely shaking hand or twitching arm. These movements are exhausting and leave the afflicted person unable to lead their previous life.
Work with monkeys showed that directly stimulating certain parts of the body with tiny electrical currents could switch these movements off. This allowed people to be fitted with ‘brain pacemakers’, with dramatic improvements to their situation. You can see this very clearly in this video interview with Mike Robbins.
Neuroscience is a fascinating field in which breakthrough technology developments are materialising at a rapid pace. Machines are built to assist the human brain so prosthetics can gain feeling and paralysed patients can walk again. Those machines also help scientists study and understand the brain. However, research using NHPs faces serious ethical and welfare considerations.
Imaging the brain
Functional magnetic resonance imaging (fMRI) takes pictures of the brain to watch how neural circuits work in real-time. PET, or positron emission tomography, creates images of the brain by tracking radioactive molecules. Transcranial magnetic stimulation (TMS) allows doctors to stimulate neural circuits in psychiatric patients to alleviate their symptoms. Advances in genetic engineering have even led to technologies that enable scientists to control neural circuits using light.
“Many of these technological improvements allow us to glimpse at the human brain. But it is only that: a glimpse. Although one might think that animal research might become obsolete thanks to these machines, the understanding of the human brain and the neurosurgeries performed today relied on and still rely on information gathered by primate neuroscience,” explains Chris Petkov, Professor in Comparative Neuropsychology at Newcastle University.
NHP work informs patient conditions
The way deep brain stimulation affects the brain still remains quite mysterious. Sometimes it works, but sometimes it doesn’t so there is a lot of interest in trying to visualise the impact of this stimulation on the brain. To do so, researchers use fMRI scanners, but it can be challenging and there are safety issues for patients. The same goes for PET scans that require the use of radioactive tracers. Primate work really sets the stage so that any observations using those techniques can give reliable results and be done safely in human patients.
“The work in patients was made possible in large part from the research with NHPs. There are many examples where the primate work has informed or continues to inform patient work, explains Chris.
As a system neuroscientist, Chris mainly focuses on helping patients that have communication and language problems known as Aphasia, caused by strokes, epilepsy, brain degeneration or other conditions. The language network is quite extensive in the brain. What that means, is that when a disorder affects the brain, chances are the language network will be affected.
“Whenever possible, we use imaging and monitoring techniques to study the human brain directly. But some information about how the brain works remain unattainable with studies only in humans. That is where work in animals becomes inevitable.”
Non-human primate research is heavily regulated
Of course, neuroscientific work in primates is heavily and rigorously regulated and is never taken lightly. When working with humans, Chris respects guidance and standards set by the Helsinki Declaration which was established by the World Medical Association many years ago and keeps getting refined. There are equivalent sets of rules and principles for animal research included in the Basel Declaration. It is required to abide by the 3Rs: Replace, Reuse, Refine, and Chris does all three:
“Ethically we use the smallest number of primates to produce publishable results. Typically, one animal is not enough, but in neuroscience two or three NHPs can be sufficient. The sample size is not determined by an individual but by the number of neurons recorded or the amount of data produced,” explains Chris.
“Whenever possible according to the experimental protocol, we conduct all experimental steps with the same individual and are often overpowered with the sample sizes in each individual.”
Using two animals helps establish that the results are not just a fluke in any animal. However, ethically, it is difficult to use more animals to determine the confidence with which this result is likely to be extrapolated to more animals. However, global initiatives now exist to pool worldwide data. Primate neuroscientists are sharing their data to increase sample sizes. Some neuroimaging initiatives now have information from over 1000 animals, and some questions can now be answered with data collected from hundreds of animals, without more animals being used.
Implementing the 3Rs in non-human primate research
Part of reducing work in primates is finding alternative animal models to work with. It isn’t always an easy task, but scientists are working harder than ever to find corresponding cognitive tasks in primates and rodents for example. Chris explains:
“It is important to develop tasks that rodents might struggle with, but primates and humans can do, and then establish correspondence so that the work in rodents is as relevant as possible. We are a laboratory that never makes the assumption that the primate or rodent work is going to be a good model for the human condition. We go the extra distance to conduct the necessary comparative work to know one way or the other.”
This has meant that although humans are the only species to use language, the researchers were able to find appropriate animal models, in particular NHP models, for language-related conditions, by showing that the animals respond to mini languages or artificial made-up languages.
Chris adds: “However, some cognitive tasks are just not as well developed in the same way with monkeys, considering their natural behaviour and capabilities. One obviously can’t use monkeys unless you develop a corresponding task, which might mean that the new task needs to be tested in humans as well to level the playing field. Human and monkey brain are strikingly similar. Many times when we’ve thought that there would be a striking discordance in the brain system with humans, we’ve been surprised in how much correspondence the studies have shown.”
Working with non-human primates means caring for the non-human primates too
The advantage of using non-human primates is that they can be taught lots of things, which can find application for the scientific protocols but also for the welfare of the animals.
For example, Chris and his team gradually, step by step, teach the animals to stay still and calm in the MRI machine which can be noisy and frightening, much like they would help dementia or older patients get used to the device.
“We help the animals get used to the situation and we do things as we would in humans, including insulating their ears. As one example, we developed a helmet system, with funding from the National Centre for the 3Rs, inspired by a helmet used to treat cancer patients with radiotherapy in one of the hospital in Newcastle. We have also conducted several animal welfare studies with monkeys and have published quite a few papers on aiming to advance animal welfare.”
Chris concludes: “We care about the animals. We do our best to meet the highest standards of welfare and to continue to improve the conditions for the animals. Working with non-human primates is difficult. Sometimes the public does not appreciate that we’re not just doing research to satisfy scientific curiosity, we aim to help people and help to advance biomedical science. Findings in NHPs have played and continue to play a tremendous role in patient care, particularly when it comes to neuroscience. The ethical and regulatory regulations are in place to make sure that the work with non-human primates is scientifically important, valid, done to the highest ethical and welfare standards and is as relevant for advances in human patients as much as possible. Our research with nonhuman primates and human patients aims to help people suffering from brain disorders.”
Last edited: 15 December 2022 14:41