The immune system is charged with the task of recognizing and destroying a host of foreign and dangerous agents, but what prevents it from attacking any cells and tissues that belong to its host? The breakthroughs awarded the 1960 Nobel Prize in Physiology or Medicine revealed how self-discrimination is learned at the biological level, through a process that was predicted by Sir MacFarlane Burnet and proven experimentally by Peter Medawar.

Burnet was fascinated with observations made by the biologist Ray Owen regarding immune defences in young animals. Of particular interest was the discovery that non-identical twin cattle happily carry an additional set of red blood cells from their siblings, which they acquired through a shared placenta in the womb. Weaving these findings into a general hypothesis, Burnet proposed that an organism is not pre-programmed to distinguish its own cells from others, as had been widely assumed. Instead, there is a gradual learning process throughout embryonic life, in which the immune system is exposed to some form of self-defining molecules that are present on the host’s cells. If his concept, which he called immunological tolerance, was true, Burnet predicted that this could be induced or acquired by introducing foreign tissues to an embryo at the right time. Tricked into remembering these tissues as belonging to its own body, the organism would not reject the tissues if it encountered them later on in life.

Medawar was investigating the role that the immune system plays in skin graft rejection, but as it turned out he provided the key experimental findings that supported Burnet’s predictions. Unaware of the cattle-twin findings, Medawar and his colleagues found to their surprise that skin grafts exchanged between twin calves were almost always accepted, whether twins were genetically identical or not. Learning about Burnet’s concept and Owen’s findings, Medawar successfully showed that mouse embryos receiving cells from a different mouse strain accepted skin and tissue grafts from that strain later on in life, while rejecting grafts from any other strain. Demonstrating that immunological tolerance could be acquired in animals has offered the exciting possibility that this phenomenon could somehow be exploited in humans to influence the outcome of tissue and organ transplants.