Book Excerpt from p53

In Chapter 12, "Of Mice and Men," author Sue Armstrong recounts the point at which researchers moved from working with p53 in tissue culture to studying the gene in animal models.

Written bySue Armstrong
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BLOOMSBURY SIGMA, FEBRUARY 2015In the long history of p53, huge amounts of data have been generated by scientists poring over little scraps of tissue and clusters of cells in test tubes and Petri dishes—specimens that have been coaxed and manipulated in super-controlled environments. “These [systems] are easy and convenient, but they’re not the real world,” says David Lane, co-discoverer of the gene in 1979, sounding a note of caution. “The more I look at p53, the more I realise that in the real world it’s operating at a very different level and in a different sort of way.” Tissue culture itself puts cells under stress and p53 into a state of alert, he says, and rather than studying the difference between active and inactive protein, what most researchers are in fact studying is the difference between very active and moderately active protein. Experiments using animal models tell a story that’s different and a lot more subtle.

Recognition of this fact lies behind one of the legendary stories of p53 research, and it involves David Lane and his friend and colleague, Peter Hall, both working at Dundee University at the time. The Year was 1992. The two scientists had been sharing a pint in a local Pub at the end of a busy day, and mulling over the crucial question of whether p53 responds to cellular stress in real life, as it does in tissue culture in the lab. They knew others were asking the same question and that competition to find answers was hot. They knew too that they faced a forest of paperwork to obtain Home Office permission for animal experiments, and their frustration at the prospect of inevitable delay ...

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