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change his conclusions as to the origin of cancer, A PRELIMINARY NOTE ON THE SERUMand he did not put them in any dogmatic way.

THERAPY OF SNAKE-BITE. There was room, both for those who held the parasitic theory and those who did not. He

By Frank Tidswell M.B., Ch M., D.P.H., Prinhimself would gladly welcome a proof of that

cipal Assistant Medical Officer of the theory, which would bring hope in the future.

Government, and Microbiologist to the

Board of Health, N.S.W., Sydney. One of the chief authorities cited in favour of the parasitic theory did not contend that he (From the Microbiological Laboratory of the Board of had proved the parasitic nature of the disease

Health, Sydney). of cancer.

Another authority mentioned dealt with yeasts ; but all their experience would lead them to say that such vegetable organisms By the courteous permission of the President did not produce the phenomena of cancer either of the Board of Health, I am enabled to publish locally or in dissemination. Having referred the present preliminary note in anticipation of to other parasites, Professor Allen went on to an official report dealing with the general subsay that with regard to statistics Dr. Verco ject of snake-bite in this State. had pointed out sources of error. Statistics In February, 1894, Phisalix and Bertrand, were very apt to lead one astray. But when, and A. Calmette announced almost simul. for example, one found in these colonies the taneously that animals could be rendered striking fact that women suffered so much less immune to snake venom, and that the blood than men they could not ignore the figures. serum of such animals was possessed of curative The figures for 1900 were not so satisfactory properties. These statements were confirmed as they might be, owing to the noncompletion by the investigations of T. Frazer, an account of the census. In two or three years' time of which was published in the following year. more definite information would be available. Some observations on the same subject were It was to be hoped, however, that steps would made by Sewell and A. A. Kanthack, but its be taken to obtain some united forms of record more recent development is mainly due to the and establish some nomenclature of cancer. researches of Calmette. This able observer has Mr. Coghlan spoke of external cancer, but he carried his labours to the point of elaborating meant accessible cancer, including cancer of and placing upon the market the producnos the throat. Cancer in the face and lips of well-known as Serum Antivenimeux” anglicé males had not increased ; cancer of the breast "antivenine.' in women stood lower than it did 30 years Although this serum is prepared by treating ago. He himself had brought up his figures in a horses chiefly with cobra venom, smaller quansimple way. He hoped the Government Statists tities of other venoms are additionally used, would keep this matter going, and not allow it and Calmette claims that the serum obtained is to drop, and analyse it to the utmost. Then active against the vynoms of all species of they might find the totality of result most snakes. It is specifically stated to have been valuable. With regard to treatment, all must tested against the poisons of the cobra and tribe agreed that immense progress had been meresurus of Asia, the naja haie and cerastes of made ; but they had also to fear whether Africa, the crotalus of America, the bothrops of there had not also been unwisdom, as well as the West Indies, the viper of Europe, and the wisdom in some of the advanced methods that pseudechis (black snake) and hoplocephalus had been used.

(tiger snake) of Australia. Dr. WOLFHAGEN, on behalf of the executive, Partly from a knowledge of differences in moved a hearty vote of thanks to Professor chemical composition and physiological action Allen for the trouble he had taken in preparing between the venoms of different species of such an able paper to open the discussion, and snakes, and partly as the result of practical also to the other gentlemen who had taken experience, this sweeping assertion of the allgreat pains in preparing most interesting and round efficacy of the serum has not received instructive papers.

To the Government Statis- acceptance. As regards Indian serpents, ticians they were also deeply indebted.

Lamb has found that whilst the serum is The motion was passed amid applause. capable of neutralising the effects of cobra

venom, it possesses no potency against daboid The Estate of the late Sir William Mac

Observations made in this country Cormac. --The value of the estate of the late Sir have also failed to support Calmette's contenWilliam MacCormac, Bart, F.R.C.S, formerly Pres. dent of the Royal College of Surgeons of England, has

tion. In some unpublished experiments made been proved at £22,812 5s.6d.

in this laboratory in October, 1896, the seruin

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proved unable to preserve the animals against The horse subjected to the immunisation was tiger snake venom, and similar negative results a sturdy, well-nourished creature, incapacitated were reported by C. J. Martin in August, from ambulance service only by reason of a 1897, this observer then expressing the opinion sprained shoulder, which induced lameness on “That Calmette's conclusions regarding the continued work. Throughout the treatment value of the serum of an animal immunised this animal has remained fat and sleck, his against cobra venom as a protection against general excellent health being only temporarily other venoms are, as they stand, untrue, and disturbed for brief periods after the injections require considerable modification.” Subsequent of venom. experiments performed in this laboratory have, The treatment was commenced on June 7th, unfortunately, only confirmed the view that 1898, by the subcutaneous injection of .0005 Calmette's claim cannot be admitted as regards gramme of the venom. This was repeated in a Australian snake venoms.

week, and a week later the dose was increased There is no need in this place to enter more

to .00075 gramme.

Increments of .00025 at deeply into the explanation of this lack of success each dose were maintained during the first six than to point out that curative serums are months of the treatment, but after that they essentially specific, acting, as a rule, only or only were raised more rapidly: e.g., by.0005(January, effectively against the toxines with which they 1899), .01 (March, 1899), 05 (May, 1889), and have been prepared ; and that, amongst othör .1 (January, 1901,) gramme. The increments things, there are differences between the effects were pretty regularly given, the same dose of cobra venom and tiger snake venom, such as being repeated only on rare occasions when the might serve to explain why a remedy, applicable reaction was more than usually pronounced. to one, proves ineffective against the other. As Between October, 1899, and May, 1900, the already stated, the venom used by Calmette for pressure of other work interfered with regular the preparation of the serum is chiefly cobra treatment, but otherwise the horse was injected

But other venoms are mixed with it, once a week (June, 1898, to April, 1899); and, by consequence, the serum is not strictly once a fortnight (May, 1899, to May, 1900); adapted for the settlenient of this question of and once a month (July, 1900, to January, specificity. It is necessary for this purpose to 1902.) The lengthening of the intervals was possess a serum prepared with one single kind due to the difficulty of collecting the larger of venom, and to test its efficacy against the amounts of venom required as the dose insame and other kinds of venom. Researches creased. This same difficulty has limited the with this object have been carried on in this maximum dosage to :6 gramme, which laboratory during the past three or four years, reached in April, 1901, and which it has not been and have now resulted in the immunisation of possible to more than approximately maintain a horse, and the acquisition of a serum fulfill to date. During the period of 3 years covered ing the conditions just mentioned.

by the treatment the horse has received a total The venom selected for the immunisation of quantity of about 10 grammes of pure tigerthe horse was that of the tiger snake (notechis snake venom. It may, perhaps, be pointed out scutata vel hoplocephalus curtus), this choice that the dose which the horse now bears withbeing determined by the consideration that out effect ( 6 gramme) is about equal to the should an effective serum be obtained it would aggregate yield of 21 or 22 average snakes, and be serviceable in the treatment of the bites of that the total amount received by the horse the most dangerous of our snakes. The venom during the treatment (10 grammes) is about was taken directly from living snakes kept in equal to the amount which would be yielded by the laboratory, the reptiles being made to bite | 333 average snakes. and eject their venom into a watch-glass covered The serum used in the experiments about to with thin rubber sheeting, which the poison be described was obtained at two bleedings perfangs alone penetrate. By this means the formed on May 5th, 1901, and October 9th, 1901. venom is obtained free from saliva and from any The horse was bled in the usual way from the adventitious products which might be squeezed jugular vein by means of a trochar and canor dissolved out of excised glands. The pure nula. The subsequent manipulations up to the venom was thoroughly dried over calcium in distribution of the serum into small sealed dessicators, and preserved in phials for use as tubes are fully described in the general report, required. Venom so prepared has been obtained but need not detain us here. Sutlice it to say, from the ck, brown and tiger snakes, and therefore, that from first to last the serum is from the death adder. For injection the venom entirely preserved from any risk of contamiwas dissolved in 9 per cent. saline solution. nation, and is finally obtained perfectly pure


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and perfectly sterile, and without added antiseptic of any kind.

The efficacy of the serum was tested in the usual way by determining the amount required to neutralise the effects of a known amount of venom upon test animals. The experiments were performed by injecting


of venom and serum into rabbits In order to prevent the misleading inferences which might result from partial neutralisation, the amount of venom given was 10 times the quantity required to kill the rabbits. As the result of a long series of observations, which, indeed, have not yet been carried to finality, it was found that the following quantities represent approximately the smallest doses which on subcutaneous injection could be relied upon to certainly cause the death of the rabbits :

Tiger snake venom, 00005 gramme per kilo of rabbit

Brown snake Death adder Black snake

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⚫0002 ⚫0002 ⚫0006 99

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It will be seen from this table that 4cc. of the serum per kilo. body weight sufficed to protect against the tiger snake venom, whereas ten times this amount, viz., 4cc, failed to protect against the other venoms tested. It is obvious, therefore, that, although an effective serum has been obtained, its action is specific, being operative only against the particular kind of venom used in its production.

From the fact that 4cc. of the serum proved effective against the tenfold lethal dose of 0005 gramme of the venom, it was to be inferred that 04cc. would protect against the single lethal dose of 00005 gramme of the venom. The validity of this inference is demonstrated by the data contained in the following table, expressing the results of two confirmatory experiments in which were used the single lethal dose of venom, and equivalent quantity of


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Kind of Venom.









Venom in grammes.

Serum in cubic centimetres.

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It is therefore concluded that 04cc. of the serum is the quantity which will entirely neutralise the effects of 00005 gramme of tiger snake venom, the two being measured per kilo. of rabbit, and injected subcutaneously immediately after their mixture in vitro.

By a further series of experiments, it was ascertained that this same value for the serum held good when the mixtures were injected directly into the veins of rabbits. As a preliminary, it was necessary to determine the certain minimal lethal dose of venom for this method of administration. The series of experiments performed to this end gave 000005 gramme of tiger snake venom per kilo as the smallest that could be relied upon to cause death after intravenous injection into rabbits. As in the previous experiment, ten times this minimal lethal quantity was used as the


standard dose of venom. It will be observed 1000 times, the efficient quantity of the serum that the minimal lethal intravenous dose of the locally prepared by means of tiger snake venom happens to be one-tenth of the minimal lethal subcutaneous dose; consequently, in making the tests the serum pitted against it

Per Kilo Body Weight. was correspondingly reduced. The following table shows the results obtained by injecting mixtures of .00005 gramme of tiger snake venom and 04 cc. of serum per kilo of the body weight into the jugular vein of rabbits : –

Subcutaneous in-! 1 .00005 04 Died jection of Single 2

.4 Per kilo body weight.




Mode of Adminis.



Result. Venom in

Serum in

Cubic Cec-


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Venom in

Serum in

cubic centimetres.


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From the series of observations just conThat these results apply also when single doses sidered, it will be apparent that whilst the are used is shown by the results expressed in serum prepared in this laboratory with tiger the following table :

snake venom

possesses a high neutralising

potency against this same venom, it utterly Per kilo body weight.

failed to exhibit appreciable protection against

the venoms of the brown and black snakes and No.

that of the death adder. To extend the series of observations, I have forwarded a quantity of the serum to Captain G. Lamb, of the Parel

Laboratory, Bombay, who has kindly consented 1 ·000005 004 Survived.

to test it against the venoms of Indian spakos.

In the meantime, the outcome of the experi3

ments already performed is such as to indicate

that the serum is specific in its action, operative It will be seen, therefore, that the serum is, only against the venom by means of which it at least, no less efficacious when the mixtures was prepared. In view of this issue, it seems are injected intravenously than when they are reasonable to suppose that the value of injected subcutaneously. Taking the two Calmette's serum against cobra venom, and its series of results together, it becomes clear that lack of efficacy against daboia and tiger snake as mixed and tested upon rabbits in the man- venoms are to be explained on the grounds of ner described, :04cc. of the serum possesses the specificity. However much in keeping with power of neutralising the effects of .00005 scientific theories and beliefs, this specificity is gramme of tiger snake venom, irrespective unfortunate from the point of view of practical of the mode in which the mixture is adminis- serotherapy, since there is the prospect that we tered.

need a special serum for each kind of snake. By way of completion, attention may be Whether or not this complication can be called to corresponding experiments performed overcome by immunisation with a judicious with Calmette's serum and tiger snake venoin, mixture of venoms must be left for the future the results of which are shown in the table on to decide. the next column.

In conclusion, it may be pointed out that In these experiments every advantage is given the experimentally ascertained neutralising to the serum by the use of only single lethal potency of the serum prepared in this laboradoses of the venom ; nevertheless the results tory by no means indicates the degree of its failed to indicate the possession of the power possible value for the treatment of tiger snake of even partial neutralisation, although the bite in practice. The establishment of this subcutaneous dose of Calmette's serum reached point is beset with difficulties, and the observa100 times, and the intravenous dose reached tions so far made with respect to it are too



incomplete to permit of any valid inference. may be the means of spreading the disease was However, the work is in progress, and I hope evidently not made easier of solution—at least to be in a position to make some further com for the time. And the question has always been munication upon this subject in the course of a answered in a somewhat uncertain way. The few months.

infective period was supposed to last till the Sydney, April 11th, 1902.

temperature had definitely fallen to the normal

point, till convalescence was established, or till NOTES ON A MILK EPIDEMIC OF TYPHOID.

an assumed ulceration could be supposed to have ILLUSTRATING


healed up finally. Clearly there were THE

certainties in all these respects, and so authorINFECTIVITY.

ities had a way of avoiding positive expressions By James Jamieson, M.D., Health Officer, of opinion on this most important point. As City of Melbourne.

it became known that the bacillus either ceases

to occur in the fæces, or can with difficulty be As is often the case with new knowledge, the detected, it was also clearly shown that it gaining of more exact information about the may remain lodged in the body for quite long intimate nature of the acute infective diseases, periods after recovery from an attack of the seems for a time to bring in almost as much disease. In his Goulstonian lectures, published doubt as certainty. It may be, of course, that in the Lancet in March and April, 1900, Dr. the old supposed certainty was based on real F. Horton-Smith discussed very fully the ignorance, and that the new doubt marks only evidence as to the persistence of the bacillus a temporary halting place on the path of after recovery and notably in the urine. His scientific progress. This is notably true in the own observations showed that the urine may case of diphtheria. For, while exactness has contain the bacilli, in enormous numbers, at been given to diagnosis by the discovery of the least as late as the seventieth day of the bacillus of Læffler, it is also true that in cases disease, and he makes reference to a case in which look like diphtheria clinically, the real which they were believed to have persisted for bacillus may not be found, and further, that several years. His own belief was that seventy the bacillus is not uncommonly discovered days by no means marked the maximum durawhere there are not clinical signs of the disease. tion. In the present state of our knowledge, In respect of prophylaxis the gain is unmis- therefore, we seem to be driven to the opinion takably great.

that the disease is more liable to be spread by With regard to typhoid the present position contaminated urine than by fæcal discharges, is distinctly an interesting one. The relation especially at a late period of an attack, and of Eberth's bacillus to the disease is definitely after apparent establishment of full accepted, although the distinctive characters of convalescence. the organism, as against varieties of the Colon But though observations such as those rebacillus, are not easily definable. It is corded by Dr. Horton-Smith and others carry especially, however, in respect to the duration conviction to a very large extent, it is both of the period of infectivity, that fresh light interesting and important to get evidence of was needed, and has to some extent lately actual infection, as helping to fix the duration come. It is owing largely to the strenuous of the period of infectivity. advocacy of Budd that the doctrine as to the A series of cases occurring among

the spread of infection mainly, if not solely, by customers of a dairy in the City of Melbourne, means of the stools of patients suffering from the supplies some points of interest in this connecdisease came to be almost universally accepted. tion. S.B., the keeper of the dairy was The demonstrated presence of the bacillus in removed to the hospital on 6th December, 1900, the structures of the intestinal wall, and in the on what was considered to be the sixth day of fæcal contents went to establish the contention bis illness. He remained in hospital till the of Budd and his followers, which had been 15th day of January, 1901, the trade having based on practical observation. But difficulties in the meantime been carried on, after prearose, and there came to be agreement among cautions taken, and without any consumers of bacteriologists that, while the bacillus is very the milk having been reported as affected. He frequently discoverable in the fæces at an early went home from the hospital, and declared stage of the disease, it is difficult or impossible that he did no work about the dairy for to identify it at a later period. That being so, several weeks. On the 11th of March the the old question about the length of time first of a series of six cases was reported, the during which the stools of typhoid patients, others occurring in pretty rapid succession,



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