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  1. H Holzel1
  1. 1Department of Microbiology, Hospital for Sick Children, Great Ormond Street, London WC1, UK

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    Leading the way as the first article in the first issue of JCP in 1947, Bedson wrote a magnificent review of the laboratory diagnosis of virus infections of man.1 He showed a formidable understanding of the then current situation, stating that it was still impossible to say whether viruses were living microorganisms or not. He highlighted the doubt that all the agents grouped together as viruses were “of the same nature.” How right he was. The major group of agents he discussed were the so called large viruses. His descriptions of the clinical picture and means of investigating the “viral causes” of trachoma inclusion conjunctivitis, lymphogranuloma venereum, and psittacosis were so well observed that they remain true today.

    Bedson discussed the different means of viral diagnosis available in 1947. He described the use of specific histological change, virus isolation by use of eggs or animal inoculation, for example the use of monkeys as the only available means of detecting poliovirus. Serological investigations included use of precipitins, agglutination, complement fixation, and the new haemagglutination inhibition test for influenza. He discussed how complement fixation could be used for the detection of variola antigen in the vesicles and crusts of skin lesions and the novel use of red cell agglutination for virus detection. In his final remarks, Bedson emphasised the important part which the laboratory can play “not just occasionally by making special investigations but in an everyday routine way.”

    Taking the role of microscopy further, Madeley in the Origins series in 19972 described the history of electron microscopy (EM) from its origin in Germany in 1934 to its development as a valuable diagnostic tool. The first pictures of viruses, those of plant viruses such as tobacco mosaic virus, were published in 1941. During the following 10 years micrographs of one virus after another appeared. By the 1960s, the use of the electron microscope had progressed to become an integral part of the diagnosis of smallpox. It was purchased for this reason by a considerable number of diagnostic laboratories. With the elimination of the disease in 1976, however, a new role evolved and EM became used for the diagnosis of viral skin lesions such as warts and molluscum contagiosum. Its importance as a diagnostic tool had receded. By the mid 1970s viruses had been identified as the cause of many diseases. In particular, they were thought to be the major cause of common episodes of diarrhoea and vomiting. Madeley described the progress of the recognition of EM as a tool for the diagnosing of viral causes of diarrhoea common in children, both here and in the tropics. By way of Kapikian's use of EM in finding Norwalk agent as the cause of an outbreak of diarrhoea in Ohio in 1972, Madeley led us through Bishop's findings of rotavirus in thin section EM of biopsies from children with possible malabsorption, to the work of Flewett. In 1973, Flewett showed that rotavirus could be seen by EM directly in stool extracts. In his own work in 1975, Madeley used EM to demonstrate the importance of astroviruses and caliciviruses as causative agents of diarrhoea and vomiting, and in the 1980s Caul and Appleton used EM to highlight the importance of a variety of small round structured viruses.

    Madeley wrote of the gradual fall in the use of this expensive piece of equipment in the current climate of cost conscious diagnostic laboratories. He ended by saying that use of EM with a speed of diagnosis some 15 minutes at its best, coupled with its versatility in being able to detect a wide variety of viruses without prior selection, should ensure its continued use.

    A diagnosis of viral infection made, but then what? In his article in 1999 on recent advances in antiviral therapy, Kinchington discusses the range of antiviral treatment now available.3 Drugs for treating HIV infection are discussed and the explanation of their activity at molecular level makes a complex subject interesting for experts and non-experts alike. The arrival of HIV had changed the perception of the importance of the specialist department of virology. It led to an increased activity in antiviral research into novel treatments for other viruses, including hepatitis B and C and the growing herpes virus group. Kinchington expressed the view that future antiviral chemotherapy will be concerned with the search for compounds that can target viral enzymes. He wrote that the identification and cloning of viral genomes is now routine, because of the availability of PCR technology, even when no cell system for growing the virus itself exists. Bedson would have been surprised, or would he?