254 



NATURE 



[Maiy 29, 19 19 



library system, the limitation of the rate, which pre- 

 vents even the most powerful of our corporations 

 spending whatever they think fit for the maintenance 

 and development of their library systems. If there 

 is to be any real reconstruction in the educational 

 system of this country, this obstacle to progress should 

 receive the immediate attention of the Government. 



REGENT RESEARCHES ON CHOLERA.^ 



THE subject I have chosen to speak about to-day 

 is one regarding which probably but little is 

 known outside the medical profession except that a 

 great reduction in the death-rate has been brought 

 about in recent years in perhaps the most justly 

 dreaded disease of India, namely, cholera. I propose 

 to give you a brief account of my prolonged researches 

 extending over more than a decade, and dealing with 

 several distinct problems by means of a variety of 

 methods of research, physiological, physical, and 

 chemical, as I think this work will best illustrate 

 the value of various collateral sciences in medical 

 research. 



The treatment of cholera at the beginning of the 

 twentieth century remained much as it was seventy 

 years before, when Latta and Mackintosh in Edin- 

 burgh in 1831 introduced the plan of injecting large 

 fluantities of normal saline solution into the veins to 

 combat the collapse stage of cholera. This brilliant 

 Idea just failed to be a great discovery because no 

 means were then found of retaining the fluid in the 

 circulation, so that the apparently miraculous imme- 

 diate effect of reviving the patient as one from the 

 dead was usually followed by fatal recurrence of the 

 terrible drain of fluid from the system. At the time 

 I commenced my investigations the method was 

 seldom used, as shown by the fact that a search 

 through the records of the Calcutta European General 

 Hospital from 1895 to 1904 showed no case in whiph 

 large saline intravenous injections were given, while 

 the mortality among ninety-five cases in those nine 

 years reached the appalling figure of 87-4 per cent, 

 indeed, it was generally recognised that once a 

 European patient reached the collapse stage in cholera 

 recovery scarcely ever' took place. 



Recent Researches on the Treatment of Cholera. 



As the first whole-time professor of pathology in 

 Bengal, the home of cholera, who stuck to unlucra- 

 tive research work for any length of time, this fell 

 disease naturallv attracted my attention, but it was 

 not until after the completion of the first edition of my 

 work on fevers in the tropics, the collection of material 

 for which occupied me for twelve years, that I was 

 able to take up serious work on cholera in 1908. I 

 had previously made a number of blood-counts, and, 

 with the help of my friend Major Megaw, had studied 

 in 1906 Latta and Mackintosh's plan of injecting 

 large amounts of normal or isotonic salt solutions — 

 that is, one containing the same proportion of salts 

 as the normal blood, controlling the quantities in- 

 jected by special blood, and blood-pressure examina- 

 tions — in the hope that, with the aid of these modern 

 methods, better results would be obtained. This hope 

 was largely disappointed, as the mortalitv only fell 

 from 59 per cent, during the previous eleven years 

 to e,jq per cent, in 1906, and the method, which is a 

 time-consuming one, was once more abandoned as of 

 little service. 



On thinking the matter over while on furlough, it 

 occurred to me that on the physiological principle 

 that a high salt content tended to retain fluid in the 



1 From the presidential adriress delivered to the Indian Scienc- Congress, 

 Bombay, 1919, by Lt.-Col. Sir Lernard Roeers, F.R.S, 



NO. 2587, VOL. 103] 



blood, it would be worth while to try a stronger salt 

 solution ». and on return from leave with renewed 

 energy at; the end of 1907 I determined to put this 

 theory to the test. Up to that time the strength of 

 salines generally advised in cholera was 06 per cent., 

 although recent physiological text-books have raised 

 the figure for normal saline to 085 per cent. As I 

 wished to give a hypertonic solution — that is, one 

 containing more salt than the normal blood — I doubled 

 the former strength and used a 1-2 per cent, of sodium 

 chloride, or 120 grains to a pint, to which I after- 

 wards added 4 grains of calcium chloride, because 

 physiologists have found the latter salt to be beneficial 

 to the heart. Capt. (now Lt.-Col.) Mackelvie 

 very kindly carried out the hypertonic injections on 

 the cases under his care, while I made a series of 

 observations on the blood, to be related presently. The 

 results may be summarised in a sentence by saying 

 that by using two teaspoonfuls of common salt to a 

 pint of water instead of one, the mortality from cholera 

 was nearly halved. Nothing could well be simpler, 

 vet nearly eighty years had elapsed since salines were 

 first injected intravenously in cholera before the phvsio- 

 logical principle of using a hypertonic instead of an 

 isotonic solution was established. It was at once 

 clear to me that a great advance had been made, which 

 stimulated me to persevere with my investigations of 

 the blood-changes in cholera, so as to place the whole 

 subject on a firm scientific basis. 



The Blood-changes in Cholera as a Basis for the 

 Hypertonic Treatment. 



In the first place, I estimated the amount of 

 chlorides in the blood before and after saline injections 

 in a series of cases, and found that in the most severe 

 cases they might even be below the normal point in 

 spite of the great concentration of the blood, thus 

 establishing a vicious circle and leading to further 

 rapid loss of any isotonic solution injected into the 

 veins. I further established that the hypertonic saline 

 did materially raise the salt content of the blood, and 

 to the greatest extent in recovering cases, which ex- 

 plained both the failure of the former isotonic and the 

 success of the hypertonic solutions. 



Another important point was to estimate the amount 

 of fluid lost from the blood in cholera, so as to ascer- 

 tain if the amount was in proportion to the severitv 

 of the case, and to learn how much salt solution it is 

 necessary to inject to replace the loss. For this pur- 

 pose I centrifuged a few drops of defibrinated blood 

 obtained by pricking the finger-tip in a graduated 

 capillary tube, and measured the volume of the solid 

 corpuscles and of the fluid serum. By comparing the 

 figures obtained with those of normal blood the per- 

 centage of fluid lost from the blood could be estimated. 

 For example, in a severe case only 18 per cent, out of 

 the original 55 per cent, of serum remained, showing 

 a loss of no less than 67 per cent, of the fluid portion 

 of the blood as a result of the copious evacuations. A 

 series of such observations indicated that in mild cases 

 of cholera not showing any serious collapse an average 

 of 35 per cent, of the serum was lost; in collapse 

 cases recovering after the hypertonic saline injections 

 the loss averaged 52 per cent. ; while in extremely 

 severe cases, who were Ibst ih spite of the new treat- 

 ment, the figure averaged no less than 64 per cent., 

 or almost two-thirds of the fluid of the blood. I have 

 seen cases of cholera in which the blood was so thidc 

 that on opening a vein a drop of black blood slowly 

 exuded having the consistency almost of tar — a condi- 

 tion which must rapidly terminate fatally if not 

 quickly relieved. By repeating these estimations im- 

 mediately after several pints of saline had been run 

 rapidly into a vein in collapsed cholera cases, I was 

 able to ascertain the quantities required to restore the 



