University of BristolAutoimmune Inflammation Research

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Expect the Unexpected

Sydney Brenner recently gave a public lecture on 'Humanity's Genes' as part of the Colston Research Symposium which I attended. I have been a fan of his since reading the description of his work with Francis Crick on messenger RNA in 'The Eighth Day of Creation' by Horace Freeland Judson. One of his themes was how incomplete the genome is, as a description of an individual. And it was good to hear him use the immune system of identical twins as an argument to illustrate this. It has been a puzzling observation that an identical twin, whose sibling has autoimmune disease, doesn't always develop the same condition, although they are genetically indistinguishable. This gap is usually ascribed to differences in their environments, but the observation also contains a deeper insight, that I first picked up at a talk given by Jonathan Howard. Immune systems evolve in real time, even as individuals are evolving in generational time. This allows the immune system to develop responses to unknown threats and to recognise molecules that have never existed. On the other hand, completely novel threats are likely to be rare, while the onslaught from pathogens that have co-evolved with humans can be likened to an indefinite arms race, with new attacks and defences being added pell mell as we rush through time. I believe that this means that the repertoire which immune responses have to draw on is actually very similar in our hypothetical identical twins, and that is why the selection of that repertoire by MHC molecules has such a profound effect on their susceptibility to autoimmune disease. (You can find a scientific take on this in the Journal of Experimental Medicine (2000) 191, 761-770).

Which brings us to another assertion by Sydney Brenner that caught my attention. 'Mathematics is the art of the perfect. Physics is the art of the optimal. Biology is the art of the just good enough.' The immune system has to be good enough, or we wouldn't be here; but it doesn't have to be perfect: Which is why we need research to understand how to manipulate it, when it targets our own tissues, as if they were infected, and causes autoimmunity.

Lindsay Nicholson.

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