Views And Reviews

BBC2 Horizon: “Death Wish” 7 February Genes that fail in their duty?

BMJ 1994; 308 doi: (Published 05 February 1994) Cite this as: BMJ 1994;308:421
  1. J Goldman

    In an era when science consists too often of armies of researchers using similar techniques to pursue almost identical objectives, it was refreshing to be reminded in this Horizon programme that real advances in biology and medicine start often enough as embryonic ideas in the mind of just one person - ideas which attract little attention or even ridicule from the cognoscenti of the day. Such of course was the fate of Semmelweiss when he proposed in the last century that bacteria transmitted from person to person might be a potent cause of disease, and such might have been the fate of Andrew Wyllie and Alastair Currie had not the current revolution in molecular biology gone some considerable way to proving the merit of their theory.

    Stated as simply as possible, Wyllie was fascinated by the possibility that malignant disease might be due not so much to unrestrained proliferation of rogue cells as to the fact that their scheduled death might be aberrantly prevented. More than 20 years ago he proposed that many cells in the body were programmed to die quite normally when they had completed their assigned tasks, and together with Alastair Currie he coined the term “apoptosis” to describe this programmed cell death. There must be a gene or genes that control this programme, and cancer is then simply a failure of the apoptosis gene to perform its duty. Horizon portrayed this concept graphically as cells that died inexplicably in tissue culture and by reference to the occasional patient whose malignant disease regressed spontaneously.

    Explaining the issues to non-scientists in 30 minutes of television viewing was not easy. Wyllie came across as a sincere Scottish scientist of the old school who could not quite believe the luck that had brought him fame and his ideas acceptance relatively late in life; the central core of the programme was a talk he was giving to a lay audience who must have been baffled by some of the technical concepts that were presented. Indeed, if they had expected to come away understanding clearly the pathogenesis of cancer, they were certainly disappointed. The link between cancer in the clinic - whether apparently cured or eventually fatal - and programmed cell death was not instantly obvious.


    * Human cancer cells: squamous carcinoma (left), leukaemia (centre), and epithelial carcinoma (right)

    Visually the programme moved with some speed, and must have confused the more casual viewer. We saw multiple telephone calls; time lapse cinematography of moving cells, innumerable pictures of microscopes and test tubes, and, rather incongruously, nematodes and arthropods making their serpentine way across photocopies of seminal scientific papers. We were introduced cursorily to oncogenes which in different circumstances can stimulate cell proliferation or apoptosis, and tumour suppressor genes, such as p53, which is mutated in a wide variety of human tumours and is involved in one very rare form of familial predisposition to cancer (Li-Fraumeni syndrome). Again, the non-specialist might have been forgiven for stifling a yawn.

    One message did, however, come across loud and clear. The revolution in cell and molecular biology continues to gain momentum and the enthusiasm of the front line workers was quite remarkable. It was refreshing to see senior scientists - Wyllie, Currie (who, sadly, has died since the programme was made, see BMJ 29 January, p336), Raff, and others - so obviously excited by their chosen profession and readily able to transmit this excitement to their younger colleagues. If all the intricacies of the molecular aspects of programmed cell death were not conveyed with crystal clarity (and there are still many more mysteries than solutions) the programme may at least have persuaded some of its viewers that biological research is a fascinating career for life. This alone would have been a worthy achievement.

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