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The therapeutic techniques that are currently used for Parkinson’s disease and Essential Tremor would not have been possible without fundamental research on monkeys. The cause of Parkinson’s disease was elucidated following the chance finding that Californian drug addicts who injected a home-made compound containing MPTP developed Parkinson’s-like symptoms. Scientists later showed that they could model the disease by giving MPTP to large primates. This enabled them to study how the symptoms manifested and to test new therapies.
Researchers in the UK found that in the primates with Parkinson’s-like symptoms there is overactivity in a part of the brain that controls movement – namely the subthalamic nucleus – and that the overactivity is due to the selective loss of neurones in the substantia nigra that manufacture the chemical messenger dopamine. Scientists were thus able to target specific drugs.
Deep Brain Stimulation (DBS), used worldwide in around 40,000 patients and constraint-induced movement therapy (CI therapy), which effectively strengthens weak limbs are both interventions derived directly from primate research to alleviate Parkinson’s symptoms.
Initial hopes that primates could be used in the development of a Human Immunodeficiency Virus (HIV) vaccine were dashed when it was found that the virus did not cause disease in chimpanzees. However, primates do have their own species-specific immunodeficiency virus, Simian Immunodeficiency Virus (SIV) - they develop an AIDS-like condition and similar nervous system changes, develop dementia and exhibit behavioural changes similar to those seen in HIV-infected patients.
Studies in female primates led to the identification of the mucosal cells that are initially infected during transmission of the virus. The SIV model also confirmed that the virus could be transmitted to newborns that swallow amniotic fluids or breast milk from infected mothers. These discoveries open new opportunities for blocking HIV transmission with drugs, vaccines, or other precautions.
A humanised monoclonal antibody-based therapeutic approach, that in vitro inhibits HIV and SIV replication, has been shown to be safe when administered to rhesus monkeys. For ethical and legal reasons, therapeutics such as these cannot be directly tested in humans in case they provoke a severe reaction, hence they are first administered to primates that have a similar immune system.
Primates are used in a small number of essential studies where only they share a particular biochemical or metabolic pathway with humans or where they model a human disease particularly well. Without the use of primates, it would have been impossible to quickly identify the coronavirus responsible for the SARs outbreaks. Scientists then developed potential SARs vaccines that have provided protection against the disease in animals. Until we can develop other mammals with ‘near-human’ immune systems, primates are invaluable in safety testing potential human vaccines.
Some of the studies carried out on primates are behavioural studies, as monkeys are perceived to share similar emotions and are capable of carrying out similar actions. The vocal behaviour of primates and its underlying neural processes is another area of scientific investigation. Similarly, advances in the understanding of how the primate auditory cortex functions are leading to new hypotheses for the cause of deafness. Thus, researchers can learn about both normal and disordered brain functions underpinning higher cognitive and motor performance by using primates.
Alzheimer’s disease affects more than 18 million people worldwide. It is a chronic debilitating disease that leads to irreversible memory loss, due to selective neuronal cell death and the presence of beta-amyloid plaques and tau protein tangles in specific parts of the brain. Studies in macaque monkeys in the early 1990s led to the identification of the critical regions of the brain essential for cognition and memory and, like humans, ageing monkeys may show evidence of beta-amyloid plaques and lose neurones as they age.
Partial models of Alzheimer’s may also be created by priming monkeys with small amounts of human amyloid – they will develop plaques later whilst still reasonably young. As primates can be trained to perform memory-related tasks that permit the evaluation of changes in cognitive memory and emotional behaviour during ageing, they can be used to evaluate various treatment and prevention strategies. Beta-amyloid vaccines have been tested for tolerability in monkeys and humans and it is hoped that their use will lead to the alleviation of Alzheimer’s symptoms.
Primates are extremely valuable models for understanding malaria pathogenesis, screening anti-malarial drugs and vaccine development. Interestingly, primates do not die from malaria although they may harbour the parasite. The reason why primates resist disease when infected, whereas humans do not, is an important question for researchers to answer. Additionally, the fact that primates can harbour an infection without becoming seriously ill makes them ideal for research into vaccine and drug development.
Primates were and continue to be essential for the development and testing of the oral polio virus vaccine (OPV), also known as the Sabin vaccine, and the Salk vaccine. The OPV consists of several strains of live attenuated virus and the Salk vaccine of ‘killed virus’. Until recently, each lot of vaccines had to be tested on monkeys to ensure that they were safe. However, in the last couple of years the WHO has approved and recommended that a transgenic mouse test for OPV be implemented as an alternative to the monkey neurovirulence test. Humans are not the only mammals to have benefited from the development of a polio vaccine - it has also been used to protect a wild colony of East African colony of chimpanzees from a potential epidemic.
Some female primates menstruate and undergo menopause in the same way as women. The manner in which pregnancy is maintained following fertilisation and implantation of the embryo into the uterus is shared by all primates. Works on primates could help study the key to understanding how the body maintains a pregnancy and how the hormone prolactin, which, if locally active in primate uteri, has an immunoprotective effect. If the key to pregnancy loss is to be found, one must use the primate model alongside normal cultured human uterine tissue. These are just two examples of studies in the area of in vitro fertilisation (IVF) area which could not advance without using primates.
A prehensile tail is the tail of an animal that has adapted to be able to grasp or hold objects. Fully prehensile tails can be used to hold and manipulate objects, and in particular to aid arboreal creatures in finding and eating food in the trees. The prehensile tail is predominantly a New World adaptation, especially among mammals. Many more animals in South America have prehensile tails than in Africa and Southeast Asia. It has been argued that animals with prehensile tails are more common in South America because the forest there is denser than in Africa or Southeast Asia.