1
1248 model as this Fund to acquire new knowledge by study on short-lived animals in order to economise time and money. Another reason for the restriction of the main endeavours of the Imperial Cancer Research Fund to the experimental study of cancer under laboratory conditions-and this restriction has not escaped criticism-is the fact that the whole group of tumours which can be transmitted speci- fically without the intervention of living cells can only be studied at present in the domestic fowl. A further use for experimental animals in cancer research isin trying out suggested lines of treatment I The executive committee regard the publication of new methods of treatment which have not fulfilled the expectations of their authors and of sufferers from the disease as one of the most discouraging features of the world-wide activity in cancer research during the last ten years. They believe that a more extended and critical utilisation of the methods and material made available by experimental cancer research, before advancing to the crucial, time- consuming experiments on man, would not only be the means of avoiding much unnecessary human suffering, but would accelerate progress. This sug- gestion should be followed up. The early work done under the auspices of this Fund proved conclusively that the new growths occurring spontaneously in animals correspond with those arising in human beings ; and later work, in these laboratories and elsewhere, has left no doubt that cancer artificially produced progresses to a fatal issue if left untreated. It seems a plain duty, therefore, to study by preliminary trial on animals any new method of treatment before offering it for clinical application. BACTERIOPHAGE IN CHOLERA. ADDITIONAL information on the use of bacterio- phage in the treatment of cholera has been sent us from India since the publication of our leading article on Sept. 20th. The work which Prof. d’Herelle began under the auspices of the Indian Research Fund Association has been carried on for a period of three years, now nearly expired, by his pupil and successor in this particular field, Dr. Igor Asheshov. In the period Jan. 1st to Sept. 1st, 1929, Asheshov addressed himself more especially to the laboratory side of this work, and his results 1 are of considerable interest, not only from their bearing upon the immediate practical problem, but from the light they throw upon certain aspects of bacteriophage behaviour. The main fact elucidated by Asheshov and his colleagues is that at least three strains of bacterio- phage are necessary for effective and complete lysis of a culture of cholera vibrios. Three such types, named A, B, and C, will, as a rule, accomplish this end. The failure of permanent lysis is, as is well known, due to the emergence of " secondary " resistant cultures from a growth which is under the destructive influence of the bacteriophage. These fft’ata44-tA strains may, however, be susceptible to another strain of bacteriophage, and by the applica- tion of this principle Asheshov has selected his three types. These are complementary in their action, in that the secondary cultures resulting from the action of A are susceptible to B ; but only partially so, since a second secondary culture will arise, which, in its turn, may be extinguished by C. This looks like selective action upon a heterogeneous population. The strains differ amongst themselves in other 1 Asheshov, I. N., Asheshov, I., Khan, S., and Lahiri, M. N. : Ind. Jour. Med. Res., 1930, xvii., 971. characters ; thus, while A acts rapidly the duration ot its effect is short and secondary cultures soon make their appearance. It is, moreover, somewhat liable to loss of virulence and only active against smooth vibrios, and it seems never to reach so high a concentration in media as do the other two strains. These are more polyvalent in action, lysing both rough and smooth strains and acquiring a high con- centration in media. The C strain is less dramatically lytic than either the A or B. In the presence of all three types, Asheshov states that lysis is usually complete, unless the bacteriophages are of low virulence. As an outcome of these experiments it is to be noted that the preparation of a suitable bacteriophage is not as simple as has been widely represented, and that many of the important races are much less stable, and more delicate in cultiva- tion, than was formerly appreciated. Efforts are, accordingly, being directed to the establishment of a mixture of bacteriophages which would be at the same time polyvalent in action, rapid in producing lysis, and stable in solution. In regard to, treatment, Asheshov and his colleagues do not take up the position indicated in our leading article. They say : " we cannot do away with saline and alkaline infusions.... We continue our experi- ments in the treatment because we strongly believe that with the modification of our bacteriophage cultures the results will be improved. However, we think that the main role of the bacteriophage will be not in the treatment of cholera, but in its prevention." This is a weighty pronouncement in the face of d’Herelle’s statement that " the administra- tion per os of cultures of bacteriophages possessing a high virulence for the cholera vibrio constitutes the specific treatment of Asiatic cholera." 2 Further, the belief that this agent should be exclusively administered by the mouth has evidently been abandoned, since Asheshov states that he is experi- menting with intravenous injections with encouraging results. The work of Asheshov bears the stamp of care and caution. If he finally succeeds in establishing the position of the bacteriophage in reference to cholera- which with different reports has varied from that of an almost unfailing specific to that of an inert substance- he will have rendered India no small service. A MEMORIAL TO GEORGE VIVIAN POORE. THE National Homecroft Association is proposing to erect a memorial to Dr. George Vivian Poore, whom they regard as an advocate of homecrofting, although he did not use that name for it. Poore certainly deserves to be remembered, for in many ways he was a remarkable man, whether considered as physician, clinical teacher, author, or sanitarian. At his best there was something compelling about his light-hearted brilliance. Of slight build and delicate physique he possessed a voice with which he filled the largest room with ease, and his after-dinner speeches and other public utterances were long remembered by those who heard them. He was a clear and learned exponent of the principles,of forensic medicine, lecturing on the subject at Charing Cross and later being professor of medical jurisprudence at University College. At both the medical schools to which he was attached he was a pioneer in the study of medical electricity, but it was by his work as a practical sanitarian that he was best known. His contributions on matters like the hygiene of the street, 2 Indian Med. Res. Memoirs, 1930, No. 14.

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Page 1: BACTERIOPHAGE IN CHOLERA

1248

model as this Fund to acquire new knowledge bystudy on short-lived animals in order to economisetime and money. Another reason for the restrictionof the main endeavours of the Imperial CancerResearch Fund to the experimental study of cancerunder laboratory conditions-and this restrictionhas not escaped criticism-is the fact that the wholegroup of tumours which can be transmitted speci-fically without the intervention of living cells can

only be studied at present in the domestic fowl. Afurther use for experimental animals in cancer

research isin trying out suggested lines of treatment IThe executive committee regard the publication ofnew methods of treatment which have not fulfilledthe expectations of their authors and of sufferersfrom the disease as one of the most discouragingfeatures of the world-wide activity in cancer researchduring the last ten years. They believe that a moreextended and critical utilisation of the methods andmaterial made available by experimental cancer

research, before advancing to the crucial, time-

consuming experiments on man, would not only bethe means of avoiding much unnecessary humansuffering, but would accelerate progress. This sug-gestion should be followed up. The early work doneunder the auspices of this Fund proved conclusivelythat the new growths occurring spontaneously inanimals correspond with those arising in human

beings ; and later work, in these laboratories andelsewhere, has left no doubt that cancer artificiallyproduced progresses to a fatal issue if left untreated.It seems a plain duty, therefore, to study bypreliminary trial on animals any new method oftreatment before offering it for clinical application.

BACTERIOPHAGE IN CHOLERA.

ADDITIONAL information on the use of bacterio-

phage in the treatment of cholera has been sent usfrom India since the publication of our leadingarticle on Sept. 20th. The work which Prof. d’Herelle

began under the auspices of the Indian ResearchFund Association has been carried on for a period ofthree years, now nearly expired, by his pupil andsuccessor in this particular field, Dr. Igor Asheshov.In the period Jan. 1st to Sept. 1st, 1929, Asheshovaddressed himself more especially to the laboratoryside of this work, and his results 1 are of considerableinterest, not only from their bearing upon theimmediate practical problem, but from the light theythrow upon certain aspects of bacteriophage behaviour.The main fact elucidated by Asheshov and his

colleagues is that at least three strains of bacterio-phage are necessary for effective and completelysis of a culture of cholera vibrios. Three such

types, named A, B, and C, will, as a rule, accomplishthis end. The failure of permanent lysis is, as is wellknown, due to the emergence of "

secondary "

resistant cultures from a growth which is under thedestructive influence of the bacteriophage. These

fft’ata44-tA strains may, however, be susceptible toanother strain of bacteriophage, and by the applica-tion of this principle Asheshov has selected his threetypes. These are complementary in their action,in that the secondary cultures resulting from theaction of A are susceptible to B ; but only partiallyso, since a second secondary culture will arise, which,in its turn, may be extinguished by C. This lookslike selective action upon a heterogeneous population.The strains differ amongst themselves in other

1 Asheshov, I. N., Asheshov, I., Khan, S., and Lahiri, M. N. :Ind. Jour. Med. Res., 1930, xvii., 971.

characters ; thus, while A acts rapidly the durationot its effect is short and secondary cultures soonmake their appearance. It is, moreover, somewhatliable to loss of virulence and only active againstsmooth vibrios, and it seems never to reach so higha concentration in media as do the other two strains.These are more polyvalent in action, lysing bothrough and smooth strains and acquiring a high con-centration in media. The C strain is less dramaticallylytic than either the A or B. In the presence of allthree types, Asheshov states that lysis is usuallycomplete, unless the bacteriophages are of lowvirulence. As an outcome of these experimentsit is to be noted that the preparation of a suitablebacteriophage is not as simple as has been widelyrepresented, and that many of the important racesare much less stable, and more delicate in cultiva-tion, than was formerly appreciated. Efforts are,

accordingly, being directed to the establishment ofa mixture of bacteriophages which would be at thesame time polyvalent in action, rapid in producinglysis, and stable in solution.

In regard to, treatment, Asheshov and his colleaguesdo not take up the position indicated in our leading

article. They say : " we cannot do away with salineand alkaline infusions.... We continue our experi-ments in the treatment because we strongly believethat with the modification of our bacteriophagecultures the results will be improved. However,we think that the main role of the bacteriophagewill be not in the treatment of cholera, but in its

prevention." This is a weighty pronouncement inthe face of d’Herelle’s statement that " the administra-tion per os of cultures of bacteriophages possessinga high virulence for the cholera vibrio constitutesthe specific treatment of Asiatic cholera." 2 Further,the belief that this agent should be exclusivelyadministered by the mouth has evidently beenabandoned, since Asheshov states that he is experi-menting with intravenous injections with encouragingresults.The work of Asheshov bears the stamp of care and

caution. If he finally succeeds in establishing theposition of the bacteriophage in reference to cholera-which with different reports has varied from that of analmost unfailing specific to that of an inert substance-he will have rendered India no small service.

A MEMORIAL TO GEORGE VIVIAN POORE.

THE National Homecroft Association is proposingto erect a memorial to Dr. George Vivian Poore,whom they regard as an advocate of homecrofting,although he did not use that name for it. Poore

certainly deserves to be remembered, for in many wayshe was a remarkable man, whether considered as

physician, clinical teacher, author, or sanitarian.At his best there was something compelling about hislight-hearted brilliance. Of slight build and delicatephysique he possessed a voice with which he filledthe largest room with ease, and his after-dinnerspeeches and other public utterances were longremembered by those who heard them. He was aclear and learned exponent of the principles,of forensicmedicine, lecturing on the subject at Charing Crossand later being professor of medical jurisprudenceat University College. At both the medical schoolsto which he was attached he was a pioneer in thestudy of medical electricity, but it was by his work asa practical sanitarian that he was best known. Hiscontributions on matters like the hygiene of the street,

2 Indian Med. Res. Memoirs, 1930, No. 14.