The Compatibility Gene by Davis Daniel M

Author:Davis, Daniel M.
Language: eng
Format: epub
Publisher: Oxford University Press, USA
Published: 1987-03-21T16:00:00+00:00

7

Missing Self

Klas Kärre would later chair the committee that decides the Nobel Prize in Physiology or Medicine, but in 1981, while writing his PhD thesis, he was less secure. Trying to summarize his observations in the last chapter of his thesis, he was puzzled by some data that didn’t seem consistent with the prevailing ideas about how the immune system worked. Kärre – described by his PhD supervisor, Rolf Kiessling, as soft-spoken, eloquent and slightly absent-minded1 – thought about the problem a lot. Others had come across the same discrepancies but just didn’t think them particularly important. What often distinguishes the great from the everyday scientists is their ability to think lucidly about observations that don’t fit with contemporary paradigms. As Leonard Cohen sings, ‘There is a crack in everything, that’s how the light gets in.’2

Once again, experiments in transplantation were at the heart of the matter. Recall that a transplant is rejected whenever it has proteins detected as non-self which cause an immune attack. But there was an exception to this rule – first observed in the 1950s by George Snell, working in the Jackson Laboratory, Maine, USA, a small, independent non-profit research institution. He discovered a situation in which transplants would be rejected even when they didn’t have non-self proteins.

To understand the mystery – to think about it deeply like Kärre did – we need to consider the genetics of the inbred mice used in Snell’s experiments. Inbred mice are obtained by successive breeding between siblings (or parents and their offspring) over long periods.3 Offspring from two different types of inbred mice are called the F1 hybrid. Not the cutest of baby names, it stands for Filial 1 hybrid and is a widely used genetic term to describe offspring from different strains of animals or plants. For example, a mule is the F1 hybrid of a male donkey and a female horse. That is, a mule came about when a donkey and horse mated rather than being a species that evolved through gradual changes in an ancestor of all three animals.

The importance of inbreeding here is that all the mice from one inbred population have identical compatibility genes – the normal diversity being wiped out by the inbreeding. Usually, there are different compatibility genes on each strand in the double-helix shape of our DNA. On one strand of the helix there are genes inherited from the mother and on the other strand there are genes from the father. This gives us, for example, two versions of the HLA-A gene. But, because inbred strains of mice have the same compatibility genes on each strand of their DNA, there’s no variation in what they pass on to their children. And – crucial to the transplantation mystery – F1 hybrids inherit all of the compatibility genes found in their parents. So F1 hybrids should be able to accept transplanted tissue from either parent.

But here’s the mystery: Snell found this to be true for skin or organs like kidneys – these can

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