ON THE RESULTS WHICH HAVE BEEN OBTAINED BY ANTI-TYPHOID INOCULATION.

651 to know how far statistical canons have in each case been we recognise and state our wants the means of providing for them will be forthcoming. Let us therefore hope that we conformed to, and on the other hand the thoughtful man, may soon see the establishment of this chair so that the other than the professed student of statistics, who may be University to which we belong may maintain her place on the seeking to know what conditions must be complied with before statistical evidence such as that included in Table I. ,crest of the ever-advancing wave of medical science. I have only now, ladies and gentlemen, to congratulate becomes coercive. Let it be noted that the conditions of you in the name of the Senatus upon having reached the statistical perfection are conditions which are practically termination of your academic career and to wish you success unattainable in actual life.. It follows that to exact that only in your future profession. You have become members of no such statistics should be considered as are flawless would be mean university and in taking up your membership you have to exact that all statistical evidence without exception should also assumed the obligation to uphold all that is most worthy be rejected. There is a way out of this dilemma. We shall, as a matter of fact, have reconciled the demands of our of the ancient reputation of your alma mater. In ordinary circumstances I should have concluded my statistical conscience with the demands of practical life This is, however, no ordinary if, after scrutinising and laying bare to ourselves the flaws address with these words. function but one never to be forgotten in the annals of our in our statistics, we in each case appraise the effect of University. For we are assembled here not only for the the flaw upon the cogency of the statistical conclusion customary purpose of admitting to the ordinary degrees, but arrived at. Table II., supplying as it does examples of also that we may confer the highest distinction which it is in nearly every variety of statistical flaw, will provide illustration of the importance of recognising the principle which has our power to bestow upon the chosen representatives of the To you, gentlemen, just been laid down. In the case of the statistics relating British dominions beyond the seas. who have honoured us by accepting this distinction I beg to to the effect of anti-typhoid inoculation in the garrison of tender on behalf of my colleagues, for whom on this occasion India for the year 1900 (Tables I. and II., serial number I am privileged to speak, a cordial welcome into this Uni- 6), there is a confessed error in the enumeration of the versity. Of all the universities of the United Kingdom it is inoculated. That error may, it is estimated, amount to the one which is, perhaps, the most closely connected with "some hundreds." The proper way to deal with this situation is, not to set aside the statistics, but to conour great colonies, receiving on the one hand, as it does, each year an important contingent of students from them and, on sider instead what would be the maximum effect which the other hand, sending out of its best to assist in establish- an error of this particular magnitude is capable of exerting the statistical conclusion. Interpreting the error of ing the new universities which are springing up within the upon " wealthy and populous communities which, on the important some hundreds" in the enumeration of the inoculated in a occasion of the King’s Coronation, are so worthily repre- liberal spirit as an error of 600 one way or the other, the sented by yourselves. Although we recognise that the error in- the enumeration of the group would amount to a 10 representation of your respective countries at that historic per cent. error. This particular statistical conclusion is thus ceremony is the primary purpose of your visit to the mother- seen to be subject to a 10 per cent. error. In relation to the country, we do not ignore the fact that there is another broad issues which we propose here to discuss such an object, not less dear to the heart of every Briton, whether he error is insignificant. It is a matter of quite subordinate inhabit this or the other side of the ocean. It is common interest whether the diminution of mortality in the inoculated knowledge that you are also here for the purpose of was the 4’4-fold diminution which is actually registered, or endeavouring to find means to weld together more securely a 4’8-fold, or only a 4-fold diminution. An even more striking illustration of the importance of for mutual interest and protection the scattered parts of this vast Empire, which are already united by the more senti- working in accordance with this statistical principle is mental ties of blood and of loyalty to the throne. Gentle- afforded by the statistics relating to the garrison of Egypt Here for 1900 (Tables I. and II., serial number 5). men, in that endeavour we devoutly wish you Godspeed ! we have recorded an 18-fold diminution in the incidence of typhoid fever among the inoculated, numbering 700 ON THE RESULTS WHICH HAVE BEEN odd, as compared with the uninoculated taken as some 2600 odd. If we include in the number of the inoculated OBTAINED BY ANTI-TYPHOID those inoculated in the previous year who are specifically INOCULATION. excluded from the statistical returns here in question we arrive at an inoculated strength of about 1000 and obtain With Separate Table (see Supplement). a 25-fold diminished incidence. If, again, waiving the BY A. E. WRIGHT, M.D. DUB., legitimacy of this course, we include among the uninocuPROFESSOR OF PATHOLOGY, ARMY MEDICAL SCHOOL, NETLEY. lated the full number of troops who passed through Egypt in the course of the year in connexion with military THE question of the utility of the process of anti-typhoid movements to South Africa we bring up our uninoculated inoculation has been gradually solving itself by the accumula- strength to some 5000 and obtain only a 13’5-fold diminution of statistical materials. The time would now appear to tion. For settling the broad issue which we have in view in this paper it matters nothing whether we accept the highest be ripe for presenting this material in the aggregate, and for or the lowest of the above figures as representing the considering what is established by it with regard to the diminution in typhoid incidence achieved in the inoculated. results of the inoculations. By the generosity of the proStatistical flaws which make much less impression upon prietors of THE LANCET-a generosity which I desire the imagination than those just considered may, as is shown gratefully to acknowledge-I am enabled to set out here in by a comparison of the conclusions arrived at in Dr. A. a synoptical form all the statistical material which I have Crombie’s two statistical papers, mislead us much more been able to bring together in connexion with the results of seriously. The conclusions arrived at in the first paper are, anti-typhoid inoculation. My cordial acknowledgments as is brought out (Table II., 22) in connexion with the are due also to Sir William Taylor, K. C. B., Director-General, critical examination of this series of statistics, invalidated Army Medical Service, for permission to make use of certain by the younger age and smaller case mortality (vide injra) hitherto unpublished items which have been supplied to me of the inoculated. In the case of Dr. Crombie’s second personally. paper the first of these factors is taken into account with I have arranged the material at my disposal in the form of the result that the conclusion drawn from the comparison two tables. In Table I. I have set out the statistical of the inoculated with the uninoculated falls into line with materials in the form in which those materials were the conclusion which emerges from the aggregate of the originally published or rendered for consideration. Into this statistics embodied in Table I. table I have incorporated, in addition to the number of the The possibility of fallacy in connexion with conclusions inoculated and uninoculated respectively and the number of based on small figures is illustrated in the fact that in some cases and deaths in each group, also certain other data, of the smaller series of statistics here presented the relative such as the period of exposure and the interval which case mortality of the inoculated and uninoculated differs elapsed between inoculation and the presumed exposure to from the relative case mortality of the two groups, as infection. I have also in each case given the authority for deduced from the event of large comparative series of cases. the figures and in the case of already published statistics a The possibility of a similar fallacy suggests itself also in reference to the literature. connexion with certain of the conclusions arrived at in In Table II. I have set out such other facts as seem to me Dr. Crombie’s papers. I refer (a) to the conclusion in essential for the critical study of the statistics. I have had the first paper that the protective effect of inoculation in view here on the one hand the student of statistics seeking has largely disappeared after the expiration of five months ; G 2

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654 to the conclusion that persons who undergo double blc )lood by anti-typhoid inoculation the study of the blood in he typhoid convalescent and the study of the gradual inoculation are rendered more susceptible to typhoid th fever than the uninoculatedand (c) to the conclusion that su success or failure of the process of immunisation in the actual typhoid attack. It is not necessary to insist on the persons over 35 years undergoing the inoculation are simi- ac ur larly rendered more susceptible than the uninoculated.1 irgency of this task. Having said this much by way of preface and illustration of the general principle which I have taken as my guide THE I may endeavour to indicate the general result of the statistics. USE OF THE IPECACUANHA C CLINICAL GENERAL RESULT OF THE STATISTICS. ALKALOIDS. It would be illegitimate to express the results in the BY R. B. WILD, M.D., M.R.C.P. LOND., M. SC. VICT., form of an arithmetical expression representing as the case LEECH PROFESSOR OF MATERIA MEDICA AND THERAPEUTICS IN THE might be the average diminution of the incidence and the Lf OWENS COLLEGE, MANCHESTER. average diminution in the death-rate from typhoid fever in the inoculated. It would be illegitimate to do so because the degree of exposure to infection and the proportion IN a paper published in THE LANCET of Nov. 23rd, 1895, of inoculated to uninoculated are in each case different. p 1274, upon the Pharmacology of the Ipecacuanha Alkaloids p. TMoeMce.—A study of the statistical material will, I suggested the use of the salts of cephaeline or emetine for however, show that in every case except that of the City certain clinical purposes in place of the notoriously unC4 Imperial Volunteers (where the statistical materials at my rl reliable in the galenical preparations of the ipecacuanha root. Since disposal consist only of the bald figures incorporated t] time the new edition of the British Pharmacopoeia has table) and in the case of the staffs of the Portland Hospital that and Imperial Yeomanry Branch Hospital at Pretoria, there b been issued and the liquid preparations of ipecacuanha was at least a two-fold reduction in cases of typhoid fever hhave been standardised to total alkaloids. Considering the In certain cases, notably in those to in the inoculated. d which exist in the relative actions of the two which the statistics designated by the serial numbers 3, 4, differences chief c in the alkaloids, incidence of especially as regards the emetic dose, and 5, 18, and 21 apply, a greater reduction was reduction from a a the wide fever achieved-a also varying very divergence in the relative proportions in typhoid v which these alkaloids may be present in different varieties six-fold to a 28-fold reduction. Case mortality.-Superadded to the diminished incidence cof ipecacuanha root, it is not surprising that in spite of of the disease there is a striking diminution of case tthe standardisation to total alkaloids the galenical preof ipecacuanha are not altogether satisfactory. mortality, as is attested by the extensive statistical materialparations I collected by Dr. R. W. Dodgson (Tables I. and II ,13) and 1Paul and Cownley have shownthat while two samples of iipecacuanha root may each contain about 2 per cent. of more particularly by the accurate and extensive figures furnished by Major C. Birt, R.A.M.C., personally (Tables I. total t alkaloids, in the one (Brazilian) 72’14 per cent. may be and II.. 8) and by the Staffs of the Civil Hospitals (Tables I. Iemetine and 25’87 per cent. cephaeline, and in the other and II., 9, 10. 11, 12, 14) in South Africa. It may be taken <(Columbian) 40’5 per cent. emetine and 56’8 per cent. that in the aggregate the proportion of deaths to cases 4cephaeline, thus reversing the relative proportions of the two among the inoculated is approximately half that among thealkaloids. Since well crystallisable salts of these alkaloids uninoculated. : are easily to be obtained, and at a moderate cost when - DcA-?’
(b)

to

re-emphasise a point already emphasised by me in prein small and convenient, doses for expectorant, depresvious papers2 that there is in connexion with all protective given I have had no opportunity of or emetic purposes. sant, inoculation a risk to be considered. There is the risk that the effect of the alkaloids in dysentery or in anthrax trying in the where resistance is case the (a) patient’s naturally and am not convinced that they have any special diaphoretic low or has been reduced, as is often the case, by a previous action. The alkaloids are always best given by the mouth, attack of typhoid fever ;; (b) in the case where the patient as local irritation is very apt to follow hypodermic injection, is inoculated with a full dose of vaccine in actually infected For the purpose of comparison solutions of the different surroundings ; and (c) in the case where the patient is’ salts were prepared in water and in different strengths of inoculated with an excessive dose or is re-inoculated too Half of each solution was used for clinical pursoon, the system may be left more open to infection the other half was set aside and examined from time to poses, at a period when it stands in need of protection. The time as to its properties and activity. Some of my facts set out in Column VI. of Table II., and possibly solutions havekeeping now been kept for several years and are still of the attention of Dr. some those which have arrested ; it is, however, not advisable to expose them to a strong Crombie, seem to me to indicate the reality of this risk. active light. Cephaeline hydrochloride was soon found to be less It must be the task of the future to try to minimise the risk, suitable for the ordinary uses of ipecacuanha in catarrhal on the one hand, by working out an adequate method of,E conditions and bronchitis than the emetine salts. The emetic standardisation of the vaccine, and, on the other hand, by, action of cephaeline is so powerful that it is very difficult to the with of the in the combining study changes produced regulate the dose so as to obtain any effect at all without nausea and sickness after a few days’ continued use 1 The suggestion that these conclusions may be due to the tallacy off causing small figures is made in the case of conclusion (a) in view of the factt In one case in an adult I found even -, 0 1 th grain every four that the Indian and Egyptian statistics which deal with an aggregate e hours produced nausea and vomiting within three days. At of some 4000 men inoculated in the previous year do not disclose any the same time the effect upon the secretions of the nose and to attack on the part of these men than on the part of greater liability those inoculated during the current year, and in the case of conclusion rsspiratory tract and the depressing action on the pulse were (b), in view of the fact that the larger experience of Colonel H. Cayley, less marked than could be obtained by doses of emetine 1.M.S., and Captain W. A. Ward, R.A.M.C., points (vide " Supple-’- which caused no sickness.. Another reason for preferring incorporated into Table I. in connexion with the mentary facts to cephaeline was that the salts of the latter eighteenth and twenty-fourth series of statistics) to a greater degree to be less stable, since the solutions after a time of protection being conferred by double inoculation. appeared 2 On the Changes Effected by Anti-typhoid Inoculation in thebecome of a brownish yellow colour when those containing Bactericidal Power of the Blood; with Remarks on the Probable emetine and kept under the same conditions were still colourSignificance of these Changes, THE LANCET, Sept. 14th, 1901, p. 715. less. I have not been able to distinguish any difference in the e Notes on the Treatment of Furunculosis, Sycosis, and Acne, by the e Inoculation of a Staphylococcus Vaccine, and generally on the mode of action or keeping properties of the two salts of Treatment of Localised Bacterial Invasions by the Therapeutic Inoculations of the Corresponding Bacterial Vaccines, THE LANCET, March 29th, 1 PharmaceuticalJournal, April 26th, 1896. 1902, p. 874.

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