The specificity of disease

158 Researches in Poliomyelitis T h e laboratory study of poliomyelitis is becoming a separate branch of virology and has its own techniques. A series of five papers, in a recent number of the American ffournal of Hygiene,* deal with two important aspects of poliomyelitis epidemiology and reach significant results. These papers come from Cincinatti University, from the University of Michigan, A n n Arbor, and the last three from the Department of Epidemiology of the Johns Hopkins University. A. B. Sabin and Steigman, in a sense continuing the findings of Nissler in Denmark, studied the outbreak of mild febrile attacks in children lasting three to seven days in Cincinatti in 1947, which were termed " s u m m e r sore t h r o a t " or " s u m m e r grippe," in number estimated as at least 10,000 in the city of 789,000 inhabitants. T h e children were such as would not normally be admitted to hospital but ten children were admitted for investigation of swabs and stools or for antibody. Two had evanescent nuchal rigidity and were positive, three had pleocytosis of C.S.F., and two were positive stool results, whilst of the five who had neither rigidity nor pleocytosis, two had positive throat swabs and stools ; altogether, seven-tenths showed evidence of having immunising subinfections, though the authors do not use that term. T h e virus appeared to be of low virulence to monkeys. Poliomyelitis notifications in Cincinatti were about the usual number for the time of year. Brown and his co-workers in Michigan, during a large outbreak of poliomyelitis in Minneapolis (762 cases) in 1946, similarly admitted cases of mild illness either seen at outpatients or at home, and considered not to be suffering from poliomyelitis. From seven of 20 such out-patients the virus was recovered from stools. From a further seven of 23 cases reported by nurses, and from two of 22 persons reported as well, the virus was also found. These are results during an exceptionally heavy epidemic. T h e last three papers by Bodian, Morgan and Howe, severally or collectively, relate to the classification of virus types, and the experimental investigation of second attacks. There are three main types of virus Brunhilde, with eight sub-types (including Kotter and Frederick), Lansing with three subtypes, and Leon. All had been isolated in the U.S.A. between 1939 and 1946. Kotter virus is mild but the allied Brunhilde is severe. The separation was made by methods of crossneutralisation and of re-infection. I n relation to second infections of monkeys (by intracerebrat inoculation), the existing considerable literature was found to be defective by reason of lack of information as to the identity, or non-identity, of the strains used in the first and second inoculations. As a result of their studies, Bodian and his colleagues find that " paralytic infection confers solid immunity to subsequent intracerebral reinoculation with the same strain, or with any other strain of the same immunological type. T h e immunity thus conferred is reciprocal with respect to viruses belonging to the same type." But with heterotypic viruses for the second inoculation, given at an interval of one to five months, whilst the resulting paralysis might be less severe. With the second inoculation but little, if any, protection was afforded against attack. There is no evidence of any " interference " phenomenon. The Speeitieity of Disease In the Latin version of Hippocrates' Works occurs the phrase quiquid divinum in relation to febrile disorders, meaning something intangible which gave to each its peculiar characteristics. From then to now, and latterly with increasing success, ardent men have chased this illusive specificity. I n his presidential addresst to the Section of Comparative Medicine of the Royal Society of Medicine, Prof. Wilson Smith has added his contribution to knowledge. But he begins with the words " unsolved problems of specificity met us in whatever bacterial or virus infection we chose to investigate." T h e biochemist and immunologist have greatly added to our knowledge of specificity in their study of specific bacterial

* Am. J. Hyg. (1940). ~f Proc. R. So¢. Med. (1949). 42, 1, 11.

PUBLIC HEALTH, May, 1949 antigens and homologous antibodies, their molecular weights and physical characteristics, even their steric configurations, and have presented us with antigenic crystalline molecular individuals, and even a crystalline antibody which is a near globulin. Now, however, the virus and the bacteriophage provide a hot scent, and it is mainly in this field that Prof. Wilson Smith provides the latest news. It is in relation to the reception---or non-reception--of these paratites, which in the simplest cases, as in the phage, are of molecular dimensions, that the advance is most rapid and most specific. A considerable range of new knowledge resulted from the accidental discovery by Hirst that influenza A virus, grown in the developing chick embryo, could cause agglutination of new red ceils, of those of certain other species. Further, it was found that viruses could be eluted from the red cells, their attachment to which caused the agglutination, leaving the cells now inagglutinable. T h e range of viruses so acting was extended, and it was found that the elution depends upon a partial enzymatic destruction of a ceU-surface substrate ; the viral enzyme, so B u m e t has shown, is probably a mucinase, resembling that extracted from cholera vibrios. So erythrocytes have carbohydrates on the cytoplasmic membranes, as well as the tipids previously suspected to be there, the whole forming, perhaps, a carbohydrate-lipid-protein complex. But in this complex the carbohydrate spots can be picked out by the virus and demonstrated by electronmicroscopy, for photographs at a magnification of 30,000 or more, reveal the adsorb.ed viruses scattered discretely over the surface of the red cell. A similar process of adsorption and elution can be shown to occur, with influenza virus, on the cells of the respiratory epithelium. The earliest stage of viral invasion is thus revealed to the eye. T h e strange biological specificity of virus infections, whereby one species of animal host is susceptible, and another is not, a long concealed mystery, is now open to investigation. In the surface configuration of the molecules of the vertebrate cell and its chemical structure, on the one hand, and on the plasticity of the surface configuration and on its enzymic activity on the other, may lie the answer. A similar line of investigation applied to the attack of bacteriophages on bacteria, a highly specific relationship, again as shown by electron microscopy, leads to the belief that whilst many individual bacteriophage may be specifically adsorbed on the bacterial surface, yet only one phage enters the cell. As with the entry of a sperm into an ovum, the door is barred to later comers. How is this accomplished ? T h e question is as yet unanswered.

International Epidemiology and Quarantine The expert committee appointed by the first Health Assembly of the World Health Organisation to study the best means of relieving national public health administrations from the constant menace of epidemic outbreaks of smallpox, typhus, cholera, plague and yellow fever met in Geneva from November 15th-20th last, and a report of its findings is published in the Chronicle of W.H.O. (January, 1949, 3, 1-8). T h e committee first agreed that defensive measures will be needed until eradication of infectious diseases has been successfully achieved and that W.H.O. sanitary regulations should be devised to replace the present international conventions which are held to be awkward and obsolete. Next it was agreed that new regulations should have a preamble showing the respective responsibilities of national governments and of W.H.O., emphasising the principles that (a) accurate and rapid notifications are the basis of measures against international spread and of withdrawal of restrictions as soon as the danger of infection has ceased ; (b) each country should develop its internal resistance, e.g., by sanitation, immunisation and freedom from insect vectors, rather than rely on measures taken on its frontiers ; and (c) measures taken at frontiers should be the m i n i m u m compatible with the situation and those to be specified by W.H.O. should not be exceeded by local health administrations; thus it would be necessary to specify the maximum as well as the m i n i m u m measures applicable. Regarding (a), as increased speed of traffic necessitates increased speed of epidemiological information, the committee