Abstract
‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’, published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603–606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.
Highlights
The story of this work done by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, was sparked by an unexpected result of skin grafting experiments in twin cattle [1,2]
This research identified immune responses characterized by lymphocyte infiltration of genetically dissimilar grafts as being responsible for rejection in both species, and by implication in others
Subsequent exposure to grafts from the same donor resulted in faster rejection times, a characteristic of immunological memory
Summary
The story of this work done by Peter Medawar (figure 1) and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham (figure 2), was sparked by an unexpected result of skin grafting experiments in twin cattle [1,2]. The alphabetical order of their names in publications was Medawar’s conven- 2 tion and acknowledgement of their team work They found that following the injection of late-stage mouse embryos [13] or neonates [14] of an inbred strain with cell suspensions from another strain, test skin grafts placed on them as young adults were not rejected: a significant proportion of the recipients had been rendered tolerant indefinitely (‘fully tolerant’), accepting the foreign grafts as ‘self’ (figure 4). The earlier experiments leading up to their landmark 1956 paper [13], as well as the subsequent clinical and immunological sides of this scientific story have been tracked down, with great skill, by Daniel Davis in his recent book, The histocompatibility gene [16]
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