On lawnmowers and lay‐down misères

[Extract] When one of us (A.G.B.) was rather younger than he is today, he acquired the solemn responsibility for mowing the family lawn with a somewhat battered two-stroke motor mower. Each week, he would wheel it out, prime the carburettor and pull the starter cord. Occasionally it would start, but most weeks it would not. Out came the spanners, screwdrivers and a handy hubcap to keep all the bits, as the motor was stripped down and rebuilt. Finally, it would be repaired and the lawn mowed. But a paradox remained, for every time the mower was stripped down and rebuilt, a few pieces were left over: a split washer, a few screws, a nut or a strangely shaped piece of metal that seemed to fit… nowhere. After some years of this treatment, the question had to be asked: How few pieces can a lawnmower have and still run?\ud\udThe contemporary history of experimental models in immunology has taken something of an opposite path. Once the T-cell receptor (TCR) was cloned and the structure of the major histocompatibility complex (MHC)-encoded ligands determined (and that nasty business with I-J swept under the carpet), there was a general feeling that the vertebrate immune system did not need many parts. It should be possible (it was reasoned) to create an experiment that would demonstrate at what point tolerance was induced and what cell or factor was responsible for its production. And so the three pieces of the machine were assembled: TCR; peptide antigen; and restriction molecule. The critical tool in the assembly was the use of transgenic technology