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Guinea pig (1942)

Hundreds of years of captive breeding by the Andean people of South America, who kept guinea pigs not as pets but as a food source, have made these gentle rodents docile and unperturbed by cages. They were brought to Europe in the 16th Century – Queen Elizabeth I kept one in the royal menagerie – and in Victorian Britain there was a craze for cross-breeding them to show off their varied coats, much like pet dogs.

If ever an animal was misnamed, it is the guinea pig. They are not members of the pig family, neither do they originate from Guinea. These puppy-sized rodents have become a byword for scientific experimentation, even though the lab mouse and lab rat far outnumber them in scientific institutions around the world.

Guinea pigs are extraordinarily sensitive to certain human diseases. It is said that a single Mycobacterium tuberculosis is enough to infect an adult guinea pig, which is one of the reasons why they became the favourite experimental animal of Robert Koch when he began investigating the cause of tuberculosis in the late 19th Century.

One of the most important immunology experiments carried out with the help of guinea pigs was published in 1942 by Karl Landsteiner and Merrill Chase of the Rockefeller Institute for Medical Research in New York. They were investigating the transfer of sensitivity to specific antigens from an immunised guinea pig to another “naïve” animal.

At that time, it was known that it was possible to transfer antibodies from one animal to another to make them sensitive to an antigen. However, when Chase tried to transfer the sensitivity by injecting serum from immunised guinea pigs into non-immunised, naïve animals, he failed. But when he inadvertently used a supernatant fluid that had not been prepared as well as other preparations, the naïve guinea pigs developed the typical skin reactivity indicating that the sensitisation had indeed been successfully transferred.

Perplexed by the result, Chase looked under the microscope and found that the cell-free supernatant was not cell free at all but contained lymphocytes. In effect, he had discovered what is now called cell-mediated immunity, which worked in quite a different way to antibody-mediated immunity. Cell-mediated immunity does not involve antibodies, but rather the activation of cytotoxic T-lymphocytes in response to contact with an antigen. Chase went on to repeat the experiment with M. tuberculosis and concluded that both sets of reactions where due to the presence of lymphocytes. These experiments established the dichotomy of immediate (antibody mediated) and delayed (cell mediated) immune responses.