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 VACCINATION AGAINST CHOLERA. 
 
 Delivered in the Examination Hall of the Conjoint Board of the Roijal 
 
 Colleges of Physicians of London and Surgeons of England, 
 
 December 18th, 1895. 
 
 hv 
 
 W. M. HAFFKIXE, ScD 
 
 LONDON: 
 
 Printed at the Office of the British ^Iedical Association, 
 429, .Strand, AV.C. 
 
 1895. 
 
H3 
 
 BIOLOev 
 LIBRARY 
 
Beprinted for the Author from the British Medical Jouhnal 
 December 2lst, 1895. 
 
 A LECTURE - "*'•-•• *••* 
 
 OM 
 
 VACCINATION AGAINST CHOLERA. 
 
 Delivered in the Examination Hall of the Conjoint Board of the 
 
 Royal Colleges of Physicians of London and Surgeons of 
 
 England, December 18th, 1895. 
 
 By W. M. HAFFKINE, Sc.D. 
 
 The PfliNCiPLEs op Prevbntivb Inoculation. 
 Befoeb dealing with my work in India allow me to re- 
 capitulate here the chiei circumstances connected with the 
 problem of preventive inoculation. After experimental 
 medicine had been inaugurated the efforts of bacteriologists 
 remained for a long time concentrated on that classical 
 form of infectious disease, splenic fever, in connection with 
 which the fundamental laws of the new science have been 
 elucidated. It was reserved to Dr. Koch to discover in the 
 formation of spores the means by which the microbe of this 
 disease, when outside the animal body, protected itself 
 against the external world. Shortly after this it has been 
 found that the spores not only preserved the life, but also 
 all specific properties of the microbe, and that it is owing to 
 this circumstance that the bacillus of anthrax is one of the 
 most constant species of schizomycetes known. On the other 
 hand, a great mutability of properties has been discovered in 
 all microbial virus not possessing spores, or in which sporifi- 
 cation is arrested for a certain period. On the bacillus of 
 chicken cholera Pasteur observed for the first time the loss 
 of virulence in a microbe of a high infectious power. Since 
 then it has been found that the virus of every disease, 
 although it remains constant in the nature of the affection it 
 produces, varies without limit in virulence ; that in one and 
 the same specimen this property can be diminished or 
 strengthened by special proceedings, and that in this we 
 have the greatest part of the explanation of the variability 
 of disease in individuals and communities. 
 
 This variation in virulence was familiar to all ob- 
 servers, and from time immemorial has been turned to 
 advantage by the peoples of the East. It is known that the 
 practice of inoculation against small-pox was originated from 
 the observation that there are mild and severe epidemics of 
 the disease, and that people affected in mild years remained 
 imtaune in severe years. At the appearance of a non-fatal 
 epidemic every one wished to get through the disease, and 
 not only did not avoid infected people, but sought their 
 presence and a close contact with them. A practice thus 
 
 M4:0beiiS 
 
arose in Asia to take artificially the infectious stnflE" from 
 mild cases and to communicate it to healthy people. Un- 
 fortunately, very often in a resistent patient a mild semblance 
 of disease conceals an infectious agent of unexpected viru- 
 lence, and such virus, on being transferred to a less resistent 
 subject, produces a terrible attack, not infrequently leading to 
 a fatal epidemiq in the community. In view of this dangerous 
 chairacttir the religious laws of the Hindus, by special regula- 
 tion!?, resjtrtct the practice, and the Government from time to 
 time find themselves under the necessity of instituting legal 
 proceedmgs against those who apply the method. As soon as 
 Jenner ' discovored an attenuated virus, and showed the 
 method of keeping it in the desired strength by passage 
 through the calf, the practice became immediately safe and 
 certain, and the Eastern method has been abandoned in the 
 whole civilised world. 
 
 In the case of small-pox, however, as in the case of rabies 
 or syphilis, the disease is communicated from individual to 
 individual, and the morbid virus is cultivated exclusively in 
 the animal body, under conditions varying little in their cha- 
 racter. The modifying influences become infinitely greater 
 when a virus can grow in a saprophytic form and is exposed, 
 in the interval between visiting animal bodies, to the vicissi- 
 tudes of nourishment, oxidation, light, temperature, which 
 are to be found in the external world. Even microbes, like 
 that of anthrax or tetanus, provided with protective spores 
 do not escape this law, and one finds in Nature their speci- 
 mens presenting a very large scale of modifications ; but there 
 appears to be no limit to variability in infectious virus lead- 
 ing a saprophytic life and deprived of the sporulating faculty. 
 The microbe of cholera is one of the most striking examples 
 of this phenomenon. 
 
 Vabiability of the Choleba Miobobb. 
 When the cholera bacillus was first discovered, eleven years 
 ago, its properties were described with great precision, which 
 helped in concentrating for a long time all studies on well- 
 defined and carefully-chosen specimens, little by little, as 
 the field of investigation grew larger, a number of varieties 
 have been found with characteristics difl"ering so largely as 
 to annihilate almost completely the original description. 
 When we open the intestines of deceased cholera patients 
 and investigate the microbes there, the adopted methods will 
 bring to the surface vibrios in which the external form, in- 
 stead of the characteristic comma or spirillum, will vary 
 between a coccus and a straight thread ; the number and 
 disposition of the cilia, the secretion of acids, the form of 
 growth in broth, will vary ; instead of giving in gelatine a 
 discrete and well-defined figure of liquefaction, the variation 
 will extend from the complete loss of this property to a rapid 
 dissolution of the whole of the medium ; there will be vari- 
 eties which grow luxuriantly in given media, and others 
 which do not grow there at all ; some will be phosphorescent in 
 the dark, and others not ; some will give the indol reaction, 
 and others will be deprived of this property, and so on. The 
 first thing to be done is carefully to select amongst these the 
 most typical specimens, rejecting the others, and then we try 
 their pathogenic power. We shall find such a divergence in 
 strength that the extreme forms will not be believed to be of 
 the cholera species. There will be commas deprived of any 
 
virulence demonstrable on animals, and others which kill 
 the most resistent species. Some will be fatal to a guinea- 
 pig at a dose of too of a culture tube, and others harmless 
 in doses 500 times stronger. The average comma dies 
 out when introduced under the skin to an adult 
 animal ; others will spread in the system and give 
 a fatal septiceemia. The ordinary comma will be with- 
 out effect on birds ; but several specimens have been 
 isolated, and believed to be typical, which easily killed 
 pigeons by hypodermic or intramuscular injection. I believe 
 to be of great value the method worked out by Pfeiffer for 
 comparing all such varieties with one selected as typical, and 
 which he employed for the preparation of an antitoxic serum. 
 This method will be found of efficient help in distinguish- 
 ing specimens of the greatest affinity with the average 
 cholera comma. But once such specimens are selected 
 and their particular properties studied, they begin to 
 change from the first day they are introduced into 
 the laboratory, and no calculation based on these 
 studies is possible. In a case quoted by M. Metchnikoff, 
 the proportion of initial power of the microbe, and the 
 strength it showed at a later trial, was of 75 to 1, the microbe 
 having gradually sunk to Vj of its initial virulence. If, for 
 producing a certain infectious, or preventive, or curative 
 effect, we had to use, in the first days, 1 c.cm. of this culture, 
 later on a dose smaller than 75 c.cm. would be without effect, 
 and the changes of the microbe would certainly continue still 
 further. 
 
 The System followed in India. 
 
 In all operations on men done in India we used ex- 
 clusively living cholera virus, for the reason that sterilised 
 cultures or products of cultures, as a rule, produce an 
 effect of a far shorter duration than living microbes. The 
 symptoms in anticholera vaccination consist in localised 
 swelling and pain in the side, at the seat of injection, 
 and in an attack of fever. The pain is felt only on pressure, 
 and its amount is such as to prevent a soldier from putting 
 on his belt for a couple of days, and a coolie worker from 
 doing work involving bending the body or stretching 
 otherwise the interested tissues. But the intensity of 
 the symptoms and their duration vary in direct proportion 
 with the virulence of the cultures and the doses administered* 
 On the other hand, in all forms of preventive treatment the 
 amount of protection depends on the intensity of reaction 
 produced in the subject. A small dose of a given virus, or 
 else the same dose of a weakened virus, will produce less 
 reaction and afford less protection; a higher dose of the 
 same virus, or the same dose of a stronger virus, produces 
 more reaction and affords a higher and, probably, more 
 lasting protection. 
 
 In the first period of my work in India I adopted ^V of a 
 standard culture, of a given strength, as a dose for an adult 
 person. The reduction of this dose by a small fraction is suffi- 
 cient not to produce in the subject any noticeable reaction at 
 all. Later on, after the first series of observations was collected, 
 I was induced to apply a treatment by increased doses of a 
 stronger vaccine. A series of experiments and observations, 
 for which I am especially indebted to Dr. Arthur Powell in 
 Cachar, have been instituted with this object. It has been 
 
found that with the increase of the doses the amonnt of local 
 pain, and especially that of general discomfort, was propor- 
 tionately increasing, the fever was of a more severe type, and 
 lasted longer, disabling the men for work for four, five, and 
 more days. In Dr. Powell's mind there remained no room 
 for doubt that with the increase of the doses the operation 
 would become fatal to man. The limit of the doses adopted 
 for the strength of the vaccines we used was between ^ and 
 i ot a, culture. 
 
 From this it will be seen that it is a matter of vital im- 
 portance, a sine qua non, in order not to exceed or fall below 
 the intended reaction, to have a method of fixing the pro- 
 perties of this modifiable microbial virus, to keep it at the 
 same degree of activity, and to know exactly the amount of 
 power contained in a given dose. 
 
 The general method worked out for that purpose consists in 
 finding out an animal susceptible to the given virus, and dis- 
 covering the conditions in which the virus can be trans- 
 planted from animal to animal without interruption and 
 without having recourse to artificial media. Jenner's method 
 in its essential features remains intact, and our proceedings 
 correspond exactly to the cultivation of vaccinia from calf to 
 calf, or from vaccinated man to man. The particular difii- 
 culties which were connected with the diseases for which 
 vaccines have been worked out, have been treated in 
 the technical literature, and I believe there is no room for 
 dealing with the matter in the present lecture. The terms 
 virus and vaccine are still used in the same sense as they 
 were used in regard to small-pox. The infectious substance 
 from a subject who naturally fell ill from a disease— a small- 
 pox patient, a rabid dog, a person affected by cholera— is a 
 virus ; the Eastern practice of inoculating small-pox virus 
 against small- pox is variolisation. On the other hand, the 
 substance cultivated under conditions intended to keep the 
 morbid agent at a given and fixed state of virulence, permit- 
 ting the use of it with safety and sure measurement, such 
 as Jenner's calf lymph, or Pasteur's rabies emulsions, is a 
 vaccine, and the application of such substances for preventive 
 treatment is called — following the suggestion of Pasteur and 
 in honour of Jenner who first used the term — vaccination. 
 
 The method which I worked out for the preparation of 
 two cholera vaccines, one weakened and a second one strength- 
 ened, has been described in my previous lecture delivered 
 in this hall three years ago. 
 
 It is the diflFerence between vaccination and variolisation 
 that distinguishes the method which I have applied in India 
 from that tried in Spain by Dr. Jaime Ferran in 1885. Ferran's 
 operations consisted in inoculating vibrios collected from 
 cholera patients. The method employed in India consists in 
 inoculating a vaccine worked out following the proceedings of 
 Jenner and Pasteur. 
 
 The diff'erence between the two operations is such that 
 Jenner's method has survived criticism and the test of a cen- 
 tury's daily application, and has been vastly generalised ; 
 the other method, imitating the inoculation of small-pox 
 virus against small-pox, had to be abandoned on every occa- 
 sion where attempts to apply it were made. At present 
 there is not a single practice, in therapeutics or in pre- 
 ventive medicine, where the use of living virus taken directly 
 from infectious persons, is allowed, whether on individual 
 
subjects, or, still less, in application to whole populations. 
 The attempts made by Toussaint, previously to Pasteur's 
 operations, of inoculating anthrax virus against anthrax, died 
 out without the slightest possibility of practical application. 
 In the treatment against anthrax by Pasteur's method, an ex- 
 cessive attenuation of the first anthrax vaccine, which was per- 
 mitted to fall below the desired amount of virulence, caused 
 on some occasions serious accidents. The neglect to make 
 strict distinction between vaccine and virus was responsible 
 for a disaster which occurred in the inoculation of sheep 
 against anthrax in the south of Russia. The misadventure 
 led to a prolonged suspension of all anthrax inoculations in 
 that country, and partly in Austria-Hungary, and Italy ; but 
 one shudders to think of any similar accident occurring, in- 
 stead of a flock of sheep, in a regiment of men. The attempts 
 at inoculating cholera virus against cholera by Ferran had to 
 be stopped by the Spanish Government, and was disapproved 
 by all commissions sent out to investigate these operations 
 by the Governments of Spain, Great Britain, France, Russia, 
 Belgium, a result which was used as one ©f the arguments, 
 seven years later, by the Government Committee in Russia, 
 in refusing to admit the trial of my method of protection 
 against cholera. On the other hand, vaccination against 
 rabies has been going on these ten years with a marvellous 
 precision, and has been already applied to about 15,000 
 people in France alone ; innumerable flocks of domestic 
 animals are vaccinated yearly in different parts of the world, 
 against anthrax and pig-measles. And now we come to re- 
 cord the results of upwards of 70,000 injections of living 
 bacteria, performed on 42,179 people, without having to re- 
 cord a single instance of mishap or accident of any de- 
 scription produced by our vaccines. 
 
 Indian Expeeiences. 
 
 My actual work in India lasted twenty-nine months, be- 
 tween the beginning of April, 1893, and the end of July, 1895. 
 During this period the anticholera vaccination has been 
 applied to 294 British officers, 3,206 British soldiers, 6,629 
 native soldiers, 869 civil Europeans, 125 Eurasians, and 31,056 
 natives of India. The inoculated people belonged to 98 
 localities in the North-West Provinces and Oudh, in the 
 Punjab, In Lower Bengal and Behar, in the Brahmaputra 
 valley and in Lower Assam. No official pressure has been 
 brought on the population, and only those have been vacci- 
 nated who could be induced to do so by free persuasion. In 
 every locality efforts were made to apply the operation on 
 parts of large bodies of people living together, under identical 
 conditions, in order to compare their resistance in outbreaks 
 of cholera with that of not-inoculated people belonging to the 
 same unit of population. This object has been obtained in 64 
 British and native regiments, in 9 gaols, in 45 tea estates, in 
 the fixed agricultural population of the villages parallel to 
 Hardw^r pilgrim road, in the bustees of Calcutta, in a certain 
 number of boarding schools where the parents agreed to the 
 inoculation of their children, in orphanages, etc. The vast 
 majority of inoculated people lived thus under direct observa- 
 tion of the sanitary and medical authorities of India. 
 
 Cholera broke out in the inoculated localities from 1 to 459 
 days after the operation, and careful statistics of occurrences 
 were immediately collected by the corresponding civil and 
 
6 
 
 military and medical authorities, as well as by myself. The 
 whole number of observations made, as they were at the time 
 when I left India, may be grouped in three categories : (1) 
 the first, containing unsuccessful results, or such in which 
 no conclusion was possible ; (II) the second, with results 
 slightly favourable to the method ; and (III) the third with 
 results satisfactory. 
 
 I. To the first category belong observations made on a series 
 of tea estates in Assam. The coolie workers on these plan- 
 tations live in well-defined isolated bodies, distant from the 
 villages, and not mixed with outside population. The inocu- 
 lated individuals were scattered among the non-inoculated, 
 and shared with them food, water supply, and all other con- 
 ditions of life. In all instances belonging to this category 
 the people had undergone only one part of the preventive treat- 
 ment — namely, were inoculated with first attenuated anti- 
 cholera vaccine given in maximal doses ; the second inocula- 
 tion, with the final vaccine, was applied after the cholera 
 season had ceased. The disease occurred from one to six 
 months after the first inoculation with the following re- 
 sults. 
 
 Adam Tila. 
 657 non-vaccinated had no cases. 
 318 vaccinated had 2 cases (0.63 per cent.) with 1 death (0.31 per cent.). 
 
 Kalacherra. 
 520 non-vaccinated had 4 cases ( 0.77 per ct. ) with 3 deaths ( 0.58 per ct. ) 
 211 vaccinated had l case ( 0.47 per ct. f with l death "l 0.47 per ct. ) 
 
 Chargola. 
 1,007 non-vaccinated had 3 cases (0.30 percent.) with 1 death (0.10 per cent). 
 291 vaccinated had no cases. 
 
 Pallarbund. 
 1,170 non-vaccinated had 2 cases (0.17 per cent.) with 2 deaths (0.17 per ct.). 
 451 vaccinated had no cases. 
 
 LUNGLA. 
 
 2,0.50 non- vaccinated had 3 cases (0.15 per cent.) with 3 deaths (0.15 per ct.). 
 421 inoculated had no cases. 
 
 Burnie-Braes, Loobachekra, Kalaincheeha, and Sandhura. 
 Number of non-vaccinated not stated ; had 11 cases with 5 deaths 
 677 vaccinated had no cases. 
 
 II. To the second category, with results slightly favour- 
 able, belong (a) two observations made on people inoculated 
 with maximal doses of the first vaccine only, cholera occur- 
 ring a short time after the inoculation, and (b) two observa- 
 tions on people inoculated with weak doses of both vaccines, 
 cholera occurring thirteen to fifteen months after vaccination 
 had been applied. 
 
 (o) The 2nd Battalion Manchester Regiment at Dinapore 2 to 6 days after 
 injection of first vaccine only : 
 729 non-inoculated had 6 cases (0.82 per cent.) with 3 deaths (0.41 per 
 
 cent.). 
 193 inoculated, no cases. 
 Degubber Tea Estate, 3h months after inoculation of first vaccine only : 
 228 non-inoculated had 2 cases (0.88 per cent.) with 1 death (0.44 per 
 
 cent.). 
 387 inoculated, no cases. 
 (6) The British troops in Cawnpore, 13 months after inocniation with 
 small doses of botli vaccines : 
 797 non -inoculated had 19 cases (2.38 per cent.) with 13 deaths (1.63 
 
 per cent.). 
 75 inoculated, no cases. 
 The East Lancashire Regiment in Lucknow, 14 to 15 months after inocula- 
 tion with small doses of botli vaccines : . 
 640 non-vaccinated had 120 cases \ 18.75 p. ct. |_with 79 deaths < 12.37 p. ct. 1 
 1.33 vaccinated had 18 cases "( 13.53 p.;ct. ) with 13 deaths") 9.77 p. ct. f 
 
 III. To the third category, with results satisfactory, belong 
 (a) observations on maximal doses of first (mild) vaccine made 
 
on the Karkurie and Kalaln Tea Estates, one to three months 
 after inoculation ; {b) observations on small doses of both 
 vaccines, made on the prisoners of the Gay a Gaol inoculated 
 during an epidemic ; (c) observations on middle doses of one 
 and of both vaccines in the bustees in Calcutta, collected dur- 
 ing a period of 459 days, and finally, {d) the observation made 
 quite lately on the Kassia Hill coolies, from the survey party 
 of the Assam-Burmah Railway. 
 
 (o) Karkurie Tea Estate, 2 to 3 months after inoculation with strong oses 
 
 of first vaccine only: 
 203 non-inoculated had 5 cases (2.46 per cent.) with 2 deaths (0.98 per 
 / cent.). 
 
 709 inoculaced had 1 doubtful case (0.24 per cent.) with l death (0.24 
 
 per cent.). 
 Kalain Tea Estate, 1 to 3 months after inoculation with strong doses of 
 
 first vaccine only : 
 1,375 non-inoculated had 23 cases (1.67 per cent.) with 11 deaths (0.8 
 
 per cent). 
 681 inoculated had 2 cases (0.29 per cent.) with l death (0.15 per 
 
 cent.). 
 
 {b) In the Gaya Gaol the inoculations were for the first time 
 applied in a prevalent epidemic, and very weak doses of re- 
 latively weak vaccines have been used. The gaol con- 
 tained over 400 inmates. After 6 cases with 5 deaths had 
 occurred, a half of the prisoners, including aged and young 
 people, women, children, patients from the hospital, and 
 people afl'ected with premonitory diarrhoea, was inoculated ; 
 the other half, of an exactly similar composition, was left 
 uninoculated. The result was a gradual disappearance of 
 cases and deaths among the inoculated, the diflerence in 
 susceptibility having gradually increased during the period 
 of 10 days necessary for the two vaccines to produce their full 
 effect. 
 
 During the first period of 5 days necessary for the 1st inoculation : 
 210 non- vaccinated had 7 cases t 3.3S per ct. ^with 5 deaths ( 2.38 per ct. ) 
 212 vaccinated had 5 cases 1 2.36 per ct. ( with 4 deaths') 1.89 per ct. ) 
 
 During the second period of 5 days necessary for the 2nd inoculation : 
 197 non-vaccinated had 9 cases J 4.57 per ct. > with 7 deaths j 2.03 per ct. \ 
 206 vaccinated had 3 cases \ 1.46 per ct. (with 1 death ( 0.48 per ct. ) 
 
 During the last 4 days of the epidemic : 
 192 non- vaccinated had 3 cases (1.56 per cent.) with 1 death (0.52 per cent.). 
 201 vaccinated had no cases. 
 
 The total results are as follows : 
 The non-vaccinated half had i 9.90 p.c. \ of cases with ( 4.95p.c. ) of deaths. 
 The vaccinated half had ^3.86 p.c. ) of cases witht 2.41 p.c. (of deaths. 
 
 The treated prisoners showed a reduction of 2.56 times of 
 cases, and of 2.05 times of deaths. I wish to call your atten- 
 tion to the fact that the inoculations had been applied in this 
 instance not before the epidemic, but a week after it had 
 actually broken out, in order to arrest it, and to cure, so to 
 say, the community from the disease. The reduction of 
 deaths by one half will therefore justify the application of 
 the method in all similar conditions, there being up to now 
 no other method known in medicine by which such an efi'ect 
 could be obtained. We shall see directly an instance of the 
 same kind when far higher results have been obtained by an 
 application of stronger doses. 
 
 (c) In the bustees situated round the tanks in Calcutta, where 
 cholera exists in a permanent state, the disease occurred in 
 36 houses with inoculated people. In each of these houses 
 there was one part of the family inoculated and another not. 
 The observations were continued for 459 days, with the fol- 
 lowing results : 
 
During'.the first period of 5 days subsequent to the inoculation with first 
 vaccine cholera occurred in 8 houses : 
 75 non-inoculated had 5 cases (6.66 per cent.), with 3 deaths (4 per 
 
 cent. 
 52 inoculated had 3 cases (5.77 per cent.), with 3 deaths (5.77 per cent). 
 During the second period of 5 days subsequent to the second inoculation 
 cholera occurred in 2 houses : 
 8 non-inoculated had 2 cases (25 per cent.), with 2 deaths (25 per cent.). 
 17 inoculated, no cases. 
 After the 10 days necessary for the preventive treatment had expired, 
 and up to the 45Hth day, the disease visited 26 houses, with the 
 following results : 
 263 non-inoculated had 38 cases (14.45 per cent.), with 34 deaths (12.93 
 
 , percent.) 
 137 inoculated had l case (0.75 per cent), with l death (0.75 per cent), 
 in a child that had not been brought up for the second inocula- 
 tion. 
 Thus, after the expiration of the first 10 days, the inocu- 
 lated members of the affected houses had 17.24 times fewer 
 deaths and 19.27 times fewer cases than the non-inoculated 
 inhabitants of the same houses, and this proportion was 
 maintained up to the 459th day after vaccination. 
 
 {d) The last observation comes from the Brahmaputra valley, 
 where Surgeon-Captain Hare, of the Indian Medical Service, 
 my co-worker during the last eight months of my stay in 
 India, is continuing now the work of inoculation for the 
 Assam Government. Dr. Hare's full account of this observa- 
 tion has not yet reached me, but from a communication of 
 the Health Oflficer of Calcutta, and from the Indian papers, 
 it appears that 350 Khassia Hill coolies had been collected 
 for the survey party of the Assam-Burmah Railway and put 
 under the escort of a detachment of Goorkhas, when cholera 
 broke out amongst them. The largest part of the coolies 
 immediately submitted to the preventive inoculation, the 
 rest remained uninoculated. The result was that among the 
 not inoculated minority there were 34 cases, with 30 deaths ; 
 whereas the inoculated had 4 fatal cases. In this instance, 
 also, the inoculation appears to be applied not as a preventive 
 but as a curative for an existing epidemic, and the result, if 
 the information is complete, has been the reduction of the 
 mortality of more than seven times. 
 
 SUMMABY. 
 
 The following seems to be a summary of the results 
 observed up to now : 
 
 1. In all those instances where cholera has made a large 
 number of victims, that is to say, where it had spread 
 sufficiently to make it probable that the whole population, 
 inoculated and uninoculated, were equally exposed to the 
 infection, in all those places the results appeared invariably 
 favourable to inoculation. 
 
 2. The treatment applied after an epidemic actually breaks 
 out tends to reduce the mortality even during the time which 
 is claimed for producing the full effect of the operation. In 
 the Gay a Gaol, where weak doses of a relatively weak vaccine 
 had been applied, this reduction was to half of the number of 
 deaths ; in the coolies of the Assam-Burmah survey party, 
 where, as far as I can gather from my preliminary informa- 
 tion, strong doses have been applied, the number of deaths 
 was reduced to one-seventh. This fact would justify the 
 application of the method independently of the question as 
 to the exact length of time during which the effect of this 
 vaccination lasts. 
 
 3. In Lucknow, where the experiment was made on small 
 doses of weak vaccines, a difference in cases and deaths was 
 
9 
 
 still noticeable in favour of the inoculated fourteen to fifteen 
 months after vaccination, in an epidemic of exceptional 
 virulence. This makes it probable that a protective effect 
 could be obtained even for long periods of time if stronger 
 doses of a stronger vaccine are used. 
 
 4. The best results seem to be obtained from application 
 of middle dosea of both anticholera vaccines, the second one 
 being kept at the highest degree of virulence obtainable. 
 
 5. The most prolonged observations on the effect of such 
 middle doses were made in Calcutta, where the mortality 
 from the 11th up to the 459th day after vaccination was, 
 among the inoculated, 17.24 times smaller, and the number 
 of cases 19.27 times smaller than among the not inoculated. 
 
 Eesults of Anticholeba Inoculation. 
 
 The evidence accumulated up to now is decidedly in 
 favour of the anticholera vaccination, and my own conviction 
 in the matter is more and more strengthened. The special 
 responsibility, however, which lies on me in this subject 
 forces me to point out that the number of observations is not 
 yet very large, and that it is most desirable that the results 
 obtained should be further confirmed by new and more ample 
 information. At the same time, you will find it, I hope, 
 pardonable on my part if, before finishing the review of the 
 results, I cite the opinion expressed on the subject by 
 the scientist who himself accomplished the first and the 
 most difficult part of the cholera problem, and whose dis- 
 covery was the starting point of the whole of the modern 
 researches on cholera. 
 
 When recapitulating with Professor Koch the data of my 
 report to the Government of India, I said that, in my idea, 
 the results tend to prove the eflicacy of the method, but that 
 I feel necessary to do all in my power in order to confirm 
 them by new observations, I was most happy to learn that, 
 for Professor Koch, the demonstration was already complete ; 
 that he believes the protective power of the method to be 
 established finally by the observations collected in India up 
 to now ; that further perfections and simplifications may be 
 possible, but that the main question at issue, the chief part 
 of the problem, is solved by the facts recorded in the above 
 report. Professor Koch gave his kind permission to quote 
 these decisive conclusions in this Hall and to use the very 
 terms I used, and he added that, in his conviction, the chief 
 struggle against cholera must certainly take place on the 
 banks of the Ganges, in the home of the disease; that this 
 struggle is to be effected by preventive inoculation, and that 
 he sees in the application of this method the way in which, 
 by gradually restricting the area of the extension of the 
 disease, it shall be brought to such a limit when it will 
 become possible to control its prevalence by simple measures 
 of a sanitary police. 
 
 Pbogbamme fob Next Opebations. 
 Allow me now to consider the question whether the new 
 facts brought to light during my absence in India ought to 
 be incorporated into my method of anticholera vaccination. 
 The treatment by antitoxic serum, which by now may be con- 
 sidered as having proved a decided success in diphtheria, 
 could not, unfortunately, be substituted for a preventive vac- 
 cination, its effect being rapidly worn out by the system. 
 According to the observations made up to now, neither the 
 
10 
 
 antidiphtheritic nor an anticholera serum could be ueed for 
 protecting a population against an epidemic lasting more 
 than a few days, not to speak of an endemic prevalence of the 
 disease. The question stands otherwise as regards the 
 possibility of treatment in individuals actually affected with 
 cholera. Although in this particular disease we have against 
 us the great rapidity with ^yhich the symptoms take hold of 
 the system, the antitoxic serum has accomplished in other 
 instances such excellent results that there is every possibility 
 of its being beneficial in the case of cholera also. I intend, 
 therefore, on my return to India, to give, in connection with 
 the physicians of the country and with the help of Professor 
 Pfeiffer from Berlin — who most kindly put at my disposal 
 all his experience in the matter, as well as a supply of 
 a very active antitoxic serum— an extensive trial to this method. 
 
 In case a simple application of the antitoxin serum 
 proves to be insufficient to stop the rapid course of the sym- 
 ptoms, I intend to combine it with intravenous saline in- 
 jections and to prolong in this way the period left for treat- 
 ment. And if in this case also the attempt should fail, j 
 shall try to utilise the new therapeutic for accelerating the 
 effect of my vaccines in a manner which I will characterise in 
 a few words. We have seen up to now that in the places 
 where anticholera vaccination has been applied in a preva- 
 lent epidemic, the total number of deaths was reduced from 
 two to seven times in comparison with the deaths in the 
 non-inoculated, but the eflFect of the treatment was nil in the 
 first four or five days after the first inoculation. There is the 
 possibility that, by injecting a mixture of my vaccines with 
 a powerful antitoxic serum, the mortality may be reduced 
 also in the first days after the treatment, the serum arrest- 
 ing the disease for the time necessary for the vaccines to 
 produce their full efl!"ect. The admixture of antitoxic serum 
 with the vaccines may mitigate the vaccinal reaction, as has 
 been suggested to me by*^ Professor Wright from Netley, and 
 this reduction of reaction may possibly reduce the amount 
 of active protection conferred by the vaccines. A series of 
 experiments have therefore been undertaken in the Netley 
 bacteriological laboratory in order to investigate this impor- 
 tant question. 
 
 Mr. Chairman and Gentlemen,— On the day when I came 
 back from my expedition to India, I found my former chief, 
 M. Pasteur, lying on his bed of death. Whatever might 
 have been his appreciation of the work done in India, there 
 can be only one desire on my part, that all the honour for 
 the results which may possibly come out of my eff"orts, should 
 be referred to him, to his sacred memory. 
 
 To the Government of India, the gentlemen of the 
 Indian and Army Medical Stafi" in India, to Professor Hankin 
 in Agra, Dr. Powell, and especially to Dr. Simpson, the 
 eminent health officer of Calcutta, I address my hearty ex- 
 pressions of gratitude for the assistance they have given me 
 in carrying out my work. I beg these gentlemen, if my 
 present words are destined to reach them, to accept this 
 public acknowledgment that without their most efficient help 
 I would have never been able, with all my individual powers, 
 to accomplish in India the smallest part of the work which 
 has been done. 
 
 I also beg the Chairman and the organisers of the present 
 meeting to accept my best thanks for having given me this 
 opportunity of making the present communication. 
 
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