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Rhesus macaque monkey (1932)

This small, old-world monkey can be found widely distributed in the wild, from Afghanistan to Indo-China. It often lives close to human settlements, frequently taking advantage of its “cheeky chappie” nature by begging or stealing food.

Its genetic proximity to humans has also made it a popular experimental animal. When scientists talk of “primate studies”, more often than not they mean experiments carried out on the rhesus macaque. And in immunology one of the most famous animal models involving the rhesus monkey is known as experimental autoimmune encephalomyelitis – a standard animal model for multiple sclerosis in humans.

By the early 1930s, scientists were well aware that certain vaccines, such as those against rabies, smallpox or measles, could occasionally result in damage to a person’s central nervous system, causing paralysis. Some thought it may be due to the viral element of the vaccine not being properly inactivated to render them harmless. But Thomas Rivers, a young virologist at the Rockefeller University in New York, thought differently.

Rivers had known from published studies that injecting rabbits with foreign brain tissue could also cause paralysis. In addition, he was also aware that rabies vaccine can contain brain extract. So he and his co-workers set about designing a series of studies to test whether emulsions and extracts of rabbit brain would cause paralysis when injected into rhesus macaques. He was also on the look-out for any loss of the fatty myelin sheath that surrounds the nerve cells of the brain and spinal cord – something that had also been observed previously and noted as “demyelinating lesions”.

Starting in 1932, he injected an emulsion of normal rabbit brain into rhesus monkeys and after six months found that they had become ataxic, or slightly unsteady on their feet. Sometime later the monkeys started to tremble, became weak in the legs and eventually so immobile they had to be put down.

When Rivers analysed their brain tissue under a microscope he found evidence of demyelinating encephalitis. Further work showed that the injections of rabbit brain tissue had effectively triggered the monkey’s own immune system to attack and destroy the myelin of its central nervous system.

Rivers and his team had found the first evidence of an autoimmunity where the body’s own antibodies target and destroy nerve cells, or more specifically the myelin sheaths surrounding them. This is precisely what happens in multiple sclerosis. Rivers had discovered, with the help of rhesus macaques, “experimental allergic encephalomyelitis”, later re-named “experimental autoimmune encephalomyelitis” (EAE). It is now the standard experimental model for understanding multiple sclerosis in humans.

Rivers was later to write: “To me, it’s a profound biological phenomenon to learn that the tissues of a person or animal can create antibodies that will result in disease or death of that person or animal.”

The rhesus monkey also lends its name to the rhesus blood type first discovered in 1937 – although its significance only became apparent in 1940 (see Anti-D). The name “rhesus” was given to them by a French naturalist Jean-Baptise Audebert, who said it has no meaning and does not refer to the Greek mythological king, Rhesus of Thrace.