York, 1886; Richard John Leeper, L. R.C.S. Irel. 1885, L.A.H. Dubl. 1887. Additional qualification registered :--Harry Sydenham Lyons, M.D. Glas. 1885.

HEALTH OFFICERS.-The following appointments have been confirmed:Kowree Shire, North Riding-Samuel Handy Halahan, M.B. Poowong and Jeetho Shire-Murdoch MacKenzie, L.R.C.P., vice William McGee, L.K.Q.C.P., resigned. Wyndham Shire-Charles de Wolfe Heard, L.R.C.P., vice Hector Rath MacLean, M.B. Arapiles Shire, North Riding-Richard Kingston Bird, L.R.C.P., vice Johann August Weber, M.D., resigned.

PUBLIC VACCINATORS.-The following appointments have been made:Max Wall, M.D., Bannockburn, vice James Miller Mackay Muir, M.B., who has left the district; Matthew Lang, M.B., Clunes, vice James Campbell, M.D., resigned; Sidney Plowman, F.R.C.S., Frankston, vice Henry Boase Wilson, M.R. C.S., resigned; Victor Joseph Emanuel Zichy-Woinarski, M.B., West Melbourne, vice Gustave Henry Stephen Zichy-Woinarski, M.B., resigned.

We regret to have to record the death of Mr. S. M. Burroughs, of the firm of Burroughs, Wellcome and Co., Manufacturing Chemists, of London and Melbourne, which took place in London on the 6th inst., the intimation being received by cable by Mr. J. C. Langley, their Australian Manager. Mr. Burroughs, in addition to being a thorough business man, was also very benevolent. He was the first man in England to adopt the eight hours principle in connection with his factory, which he considered to be a decided advantage over the long hours previously prevailing. Quite recently he donated a large sum of money to the Dartmoor Hospital, virtually building and endowing it. He took a lively interest in all philanthropic work, and was closely associated with a number of institutions which were instituted for the emancipation of the masses, his absence from which will cause a gap not easily to be filled.

BIRTHS.

KERR. -On the 2nd February, at Orbost, the wife of James Kerr, M. B., C.M., of a daughter. LAWRENCE. On the 26th January, at Marnoch, Brunswick-street, Fitzroy, the wife of Herman Lawrence, M.R.C.P. E., &c., of a son.

NAPTHINE. On the 11th February, at Ardshaw, Main-street, Stawell, the wife of G. J. Napthine, L.R.C.S. Edin., of a daughter.

WALSH. On the 2nd February, at Wilton, Kew, the wife of W. Butler Walsh, M.D., F.R.C.S.I., of twin daughters.

MARRIAGE.

ARGYLE-LEWIS.-On the 24th January, at Holy Trinity Church, Kew, by the Dean of Melbourne, assisted by the Ven. Archdeacon Herring and the Rev. W. G. Hindley, Stanley Seymour, M. B., M.R.C.S., third son of the late Edward Argyle, of Kyneton, to Violet Jessie, eldest daughter of Thomas Lewis, of Kew.

DEATH.

O'DONNELL. On the 12th February, at Victoria-street, North Melbourne, Eileen, the dearly beloved infant daughter of N. M. and M. A. O'Donnell, aged 15 months.

Contributors of Papers to the Australian Medical Journal can have copies re-printed in pamphlet form by communicating with the Publishers before the issue of the Journal.

THE

Australian Medical Journal

MARCH 20, 1895.

Original Articles.

DIPHTHERIA ANTITOXIN.

By THOMAS CHERRY, M.D., M.S. Melb.

Demonstrator and Assistant Lecturer in Pathology, University of Melbourne.

Whatever may be the ultimate position assigned to antitoxin in the treatment of diphtheria, there can be no doubt that antitoxin itself is one of the most remarkable substances ever discovered. After a virulent broth culture of the diphtheria bacillus has been filtered in order to remove the bacilli, it is found that 2 c.c. of the filtrate is usually sufficient to kill a guinea-pig in twenty-four hours. The fatal result is prevented, and all symptonis of disease are absent if 0001 c.c. of serum is mixed with the dose before injection. That is to say, the serum neutralises 2000 times its own volume of the filtrate containing the toxines. Moreover, when diphtheria has been given to animals by inoculating the bacilli into abraded mucous membranes, so that the conditions of the experiment resemble as nearly as possible those which obtain amongst human beings, the animals may be saved if the injection of the serum is begun early enough. Otherwise, they invariably die in from four to six days. The new treatment therefore stands on a sound scientific basis. It is founded on experimental facts which are admitted by all observers, and which are being daily confirmed in the tests to which the serum is subjected before it is sent out of the laboratories in which it is prepared. In this respect it differs totally from tuberculin. It is significant also that the death rate immediately falls upon the introduction of the serum. This has, I believe, been the experience of every hospital in which it has been tried upon an extensive scale.

With regard to the method of preparing the serum, considerable modifications exist in the details. The bacilli are cultivated at VOL. XVII. No 3.

H

body temperature in alkaline beef broth containing 2 per cent. of peptone. In all cases the broth is kept in a shallow layer in the flask, so as to obtain as free a supply of oxygen as possible, and this is sometimes increased by drawing a current of moist air through the vessel. After a month or six weeks, the broth is very rich in toxin. In Germany the usual plan is to kill the bacilli by adding 5 per cent. carbolic acid to the culture fluid. In France, the broth is passed through a Chamberlain filter, and the clear fluid containing the toxin alone used for injecting into the horse. Most English laboratories follow closely the methods of the Pasteur Institute, but in some cases a satisfactory serum has been obtained by injecting increasing doses of virulent bacilli as well as their products. The general plan of dealing with the horse is the same, whether the carbolised or filtered culture fluid is selected as the means of producing immunity. The doses are small in amount to begin with, and repeated every two or three days, the horse's temperature and weight being carefully noted from day to day. A large dose at the first occasionally kills the horse, but after a week or two his resisting power becomes highly developed. In the course of a month or so he is bled, and the power of the serum tested upon guinea-pigs. When sufficiently rich in antitoxin, he is bled regularly every three or four weeks, the quality of the blood being maintained by repeated small doses of the original injection. Cows and sheep are more susceptible to the diphtheria poison than the horse, and their serum should theoretically have greater antitoxic power, but it has not yet been used outside of laboratory experiments. Since horses have been immunised in large numbers, it has been found that their serum varies considerably in richness, although the animals have all been subjected to precisely the same course of treatment. This fact will perhaps modify a statement made by Roux at the Buda Pesth congress, to the effect that serum obtained by injecting the bacilli is not equal to that obtained by injecting the toxin alone. The dose of the antitoxin serum varies from 2 to 20 c.c. The small dose is that prescribed by German firms, who are believed to concentrate the serum by evaporation in vacuo. In the Paris hospitals 20 c.c. is the routine dose. The injection of nearly an ounce of fluid produces a large swelling under the skin of the abdomen. The serum, however, appears to be quite unirritating. A child six years old takes very little notice of the operation, and complacently strokes the tumour till it

disappears. The discrepancy of dosage is not easy to understand, but Roux appears to have allowed a wide margin beyond the amount necessary to neutralise the toxins probably present in the body. The tendency for the present is for the Germans to increase, and the French to diminish the initial dose. Experiments are being carried on with the view of isolating the active principle from the serum. The latter may be concentrated to dryness without losing any of its properties. The dried serum may then be re-dissolved in sterilised water, and injected in the usual manner. So far, the greatest difficulty to be overcome is the production of a perfectly aseptic serum. The manipulations to

which it is exposed entail great risk of contamination. Up to the present every drop of serum has been used as soon as available, and the low temperature prevailing on the Continent during my visit reduced the risk of invasion by outside germs to a minimum. The bottles of serum, however, occasionally become turbid, and are then unfit for use. Dr. Kossel, of Berlin, who has had perhaps the most extensive clinical experience of the serum, told me that he regards the impure serum as responsible for the rashes and other unpleasant symptoms which have been noted as following upon its use. Transit to Australia, unless the material is kept in a refrigerator, is likely to try its stability to the utmost. In some cases, 5 per cent. carbolic acid is added as a preservative, and serum of three qualities is procurable from Germany.

seen.

The impression which one receives from a short visit to the hospitals is decidedly favourable to the new remedy. In Paris and Berlin, I saw about 200 children in the wards of the various hospitals, and was particularly struck by their bright and cheerful appearance. Many of the faces were pale, but these children seemed comfortable, and dyspnoea and cyanosis were very rarely In Berlin, three of the modern hospitals have provision for a perfect classification of the patients; separate wards exist for the mild, severe, and complicated cases, and for convalescents. At the Hôpital des Enfants Malades, Paris, the patients occupy two wards, one for each sex, with an isolation room for complicated cases. In every case an injection of serum is given upon admission, without waiting for the confirmation of the diagnosis by bacteriological examination. This, however, is immediately set about, so that the result is known by the following day. The urine of every patient is tested for albumin twice a day, and the fullest antiseptic precautions enforced, both with regard to the

wards and every one who enters them. Medical officers, nurses, and visitors are all provided with a special dress. It may of course be objected, that there is no proof as to the severity of diphtheria this year in Europe, and that most of the patients treated by antitoxin would recover in any case. This objection may be met by the facts that, at intervals during November and December, when no serum was obtainable, the hospital mortality at once rose to its former level; and secondly, that the mortality under the serum treatment is lower than the minimum mortality for any corresponding period out of a long series of years. Thus at the St. Josef Kinderspital, Vienna, the present mortality is, 19 per cent., while the average for the last ten years is 51 per cent., with a maximum of 58.7, and a minimum of 38 per cent. The most severe critics are those who attack the remedy on theoretical grounds. Clinical observers who have seen the manner in which the symptoms are relieved and the membranes disappear under its use, admit that there is something in it. No hospital which has tried it during the past twelve months has given it up as a failure.

Before the serum can be used to full advantage in private practice, its scope and the best method of administration require to have been thoroughly tested in a hospital. Isolated cases are of no value from a scientific standpoint. It is of first importance that the injections should be begun at the earliest possible moment, otherwise the vital powers of the body are so much depressed by the diphtheria poison that the tissues are unable to respond to the stimulus of the serum. The dose must be sufficiently large, and local treatment by means of unirritating antiseptics efficiently carried out. Emergencies must be promptly dealt with the moment they arise. The serum has not eliminated tracheotomy or intubation, but the number of cases calling for operative interference is diminishing, and the results are much better than formerly. "Complicated" cases are those which arise from a joint growth of Klebs-Loeffler bacillus and streptococci, and the results of treatment of these are not by any means so good as those of pure diphtheria. These are clinically the malignant cases, and treatment of any kind is often of no avail. Many of them die of septic broncho-pneumonia; yet experimentally, rabbits and guineapigs may sometimes be cured by means of the serum after inoculation with both germs. I think we have grounds for believing. that if a means can be obtained for controlling diphtheria, so as to