bacteriology at the lister institute

2
172 BACTERIOLOGY AT THE LISTER INSTITUTE of a particular cestrogen on a particular organ we can be guided only by assays made on that organ in mice of the same inbred strain to which the hormone has been given in identical conditions. Even then our prediction cannot be exact, because of the different individualities within the same strain. The bearings of these remarks are manifold. One example will suffice-the failure of triphenyiethylene to cause mammary cancer in Strong A mice, though cestrone has this action. As the authors say, had triphenylethylene been tested on Strong A and CBA mice only it would have been regarded as incapable of producing mammary cancer. COUNTERACTION OF FATIGUE WITH VITAMINS GERMAN science and medicine are affected by the Nazis’ cultivated neglect of truth. Some of their papers would be interesting if true but are so openly vulnerable to criticism that it is remarkable that they should be published, in the German medical press, by people of recognised position. Prof. Theo. Morell of Berlin has recently published a paper on counteracting fatigue by giving vitamins. Two fasting young men were made to take exercise on a fixed bicycle, and their energy output was measured when they had and when they had not received tablets of "vitamultin" containing dextrose, vitamin C, vitamin B1 and compounds of nicotinamide, the total amount given being unstated. The effect in increasing energy output was striking, and since all the substances given are implicated in carbohydrate meta- bolism and oxidation-reduction processes it is highly plausible that this should be so. Prof. Morell, however, neglected to make any control experiments with dummy tablets. The two subjects reported a comfortable feel- ing as soon as the tablets got inside their stomachs and . their output of energy immediately increased; this the observer called the suggestive stimulation (Suggestiv- schub). The energy output soon dropped but rose again after 15 minutes in what is described as the absorption stimulation (Resorptionschub). When one subject was treated with vitamins and the other not, the energy output was equivalent to cycling 42’7 and 26-7 kilometres respectively in H hours. Whether energy output was really promoted by the vitamins or whether the young men simply pedalled away as good Nazis should to attain the result known to be desired is uncertain, but Prof. Morell accepted the evidence as sufficient for him to recommend strongly that " vitamultin" should be supplied to airmen and drivers of motor vehicles when called upon to make long sustained efforts. The claim should perhaps be examined. BACTERIOLOGY AT THE LISTER INSTITUTE THE outbreak of war had an unfortunate paralysing effect on our organised medical research, more par- ticularly on the work of the special institutes in London whose staffs were dispersed to the various sectors or to emergency public-health laboratories throughout the country. The Lister Institute, with the exception of its biochemical and biophysical departments, shared in the general exodus, but it had at Elstree a country home for its bacteriological staff, the division of nutrition was accommodated at Cambridge, while individual members of the staff found refuge in other research institutes. As a result, the latest annual report bears little imprint of disorganisation. It is impossible to comment adequately on the institute’s widespread researches in bacteriology, nutrition and biochemistry, much of which has already been discussed in these columns, and this year only the bacteriological work will be reviewed. 1. Dtsch. med. Wschr. April 12, 1940, p. 398. The bacteriological division under the direction of Sir John Ledingham together with the serum (Dr. Amies) and the vaccine lymph (Dr. McClean) departments at Elstree have produced a large volume of work, part academic like the interesting and intricate studies of A. S. McFarlane and his colleagues on the chemical and physical properties of vaccinia virus, but much of it with a topical application. Virus work has been concentrated on vaccinia. The results obtained by McClean, in con- junction with Dr. R. G. Henderson of the London County Council’s staff, on the inoculation of children intra- and sub-cutaneously with elementary body suspensions of vaccinia virus prepared from sheep strongly indicated that, with the vaccine, used immunity resulted only if cutaneous vesicles were produced. Thus, if secondary infection from superficial ulceration of the vesicles-per- haps the main objection to vaccinia-is to be avoided, proliferation of the virus in the skin or subcutaneous tissues is needed, and from rabbit experiments it seems possible that virus may be adapted to such growth. Of bacteriological work the studies of D. W. Henderson and P. A. Gorer on the synergic effect of antitoxin and sulphapyridine in the treatment of experimental gas gangrene and the similar studies of Amies on the treat- ment of experimental meningococcus infection have already been discussed in these columns. An important advance in the production of antityphoid serum has been made by the substitution of acetone-killed cultures, in which the Vi and 0 antigens are preserved intact, to replace the use of living cultures. Dr. Felix with Miss R. M. Pitt has continued his studies on the antigens of S. typhi and has shown that the Vi antigen has more than a directly toxic effect-as is maintained by 0rskov and Kauffmann-for it protects the 0 antigen against natural or immune 0 antibody and thus guards the whole bacterial cell against the opsonising activities of the serum. In view of the work of Craigie and Yen on the subdivision of S. typhi into a number of distinct types according to their phage-sensitivity, Felix and Pitt have tried, unsuccessfully, to demonstrate serological differ- ences in strains of S. typhi corresponding to their phage- sensitivity-a result, as is remarked, very reassuring from the viewpoint of antityphoid’ inoculation and serum therapy. Dr. Schutze is conducting experiments in guineapigs on simultaneous immunisation against diphtheria and pertussis, and has reached some con- clusions on the toxicity and virulence of B. pesti.s as a result of tests with unenveloped variants of the bacillus. Investigation of the " diffusing factor " elaborated by certain bacteria and tissues, in which McClean has been a pioneer, has taken an interesting turn from the dis- covery by Chain and Duthie at Oxford that purified extracts of the substance from mammalian testes have a strong mucolytic activity. Following up this work, McClean has shown that purified bacterial filtrates also contain this mucinase which is antigenic and specific for each bacterium. Seminal fluid has been found by other workers to contain the mucolytic enzyme by means of which the spermatozoa penetrate the plug of mucus in the cervical canal, and this is doubtless the explanation for its abundance in the testes. Coordinated studies on the changes that occur in the serum of horses during immunisation are being carried out with the ultra-centri- fuge and the electrophoresis apparatus ; they have shown that the x and 13 globulins are especially associated with the antitoxic value of the serum. The preparation of refined antitoxins by the peptic digest method is being further investigated by Dr, Knight. In the field of experimental pathology Dr. Gorer has been working on the genetic factors concerned in tumour transplanta- tion, while there are references in the report to studies on the metabolism of fat and on kidney function in the rat and to Professor Ledingham’s work on the relation- ship of the sex-hormones to the Foh-Kurloff cell in the guineapig. AT 2.30 P.M. on Friday, Aug. 16, at the British Post-- graduate Medical School Lieut.-Colonel St. J. D. Buxton and Mr. H. L. C. Wood will give a demonstration of plaster technique. Applications for tickets should be addressed to the dean of the school, Ducane Road, London, W.12. °_

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172 BACTERIOLOGY AT THE LISTER INSTITUTE

of a particular cestrogen on a particular organ we canbe guided only by assays made on that organ in mice ofthe same inbred strain to which the hormone has beengiven in identical conditions. Even then our predictioncannot be exact, because of the different individualitieswithin the same strain. The bearings of these remarksare manifold. One example will suffice-the failure oftriphenyiethylene to cause mammary cancer in Strong Amice, though cestrone has this action. As the authorssay, had triphenylethylene been tested on Strong A andCBA mice only it would have been regarded as incapableof producing mammary cancer.

COUNTERACTION OF FATIGUE WITH VITAMINS

GERMAN science and medicine are affected by theNazis’ cultivated neglect of truth. Some of their paperswould be interesting if true but are so openly vulnerableto criticism that it is remarkable that they should bepublished, in the German medical press, by people ofrecognised position. Prof. Theo. Morell of Berlin hasrecently published a paper on counteracting fatigue bygiving vitamins. Two fasting young men were made totake exercise on a fixed bicycle, and their energy outputwas measured when they had and when they had notreceived tablets of "vitamultin" containing dextrose,vitamin C, vitamin B1 and compounds of nicotinamide,the total amount given being unstated. The effect inincreasing energy output was striking, and since all thesubstances given are implicated in carbohydrate meta-bolism and oxidation-reduction processes it is highlyplausible that this should be so. Prof. Morell, however,neglected to make any control experiments with dummytablets. The two subjects reported a comfortable feel-ing as soon as the tablets got inside their stomachs and

. their output of energy immediately increased; this theobserver called the suggestive stimulation (Suggestiv-schub). The energy output soon dropped but rose againafter 15 minutes in what is described as the absorptionstimulation (Resorptionschub). When one subject wastreated with vitamins and the other not, the energyoutput was equivalent to cycling 42’7 and 26-7 kilometresrespectively in H hours. Whether energy output wasreally promoted by the vitamins or whether the youngmen simply pedalled away as good Nazis should toattain the result known to be desired is uncertain, butProf. Morell accepted the evidence as sufficient for himto recommend strongly that " vitamultin" should be

supplied to airmen and drivers of motor vehicles whencalled upon to make long sustained efforts. The claimshould perhaps be examined.

BACTERIOLOGY AT THE LISTER INSTITUTE

THE outbreak of war had an unfortunate paralysingeffect on our organised medical research, more par-ticularly on the work of the special institutes in Londonwhose staffs were dispersed to the various sectors or toemergency public-health laboratories throughout thecountry. The Lister Institute, with the exception of itsbiochemical and biophysical departments, shared in thegeneral exodus, but it had at Elstree a country home forits bacteriological staff, the division of nutrition wasaccommodated at Cambridge, while individual membersof the staff found refuge in other research institutes.As a result, the latest annual report bears little imprintof disorganisation. It is impossible to commentadequately on the institute’s widespread researches inbacteriology, nutrition and biochemistry, much ofwhich has already been discussed in these columns,and this year only the bacteriological work will bereviewed.

1. Dtsch. med. Wschr. April 12, 1940, p. 398.

The bacteriological division under the direction of SirJohn Ledingham together with the serum (Dr. Amies)and the vaccine lymph (Dr. McClean) departments atElstree have produced a large volume of work, partacademic like the interesting and intricate studies ofA. S. McFarlane and his colleagues on the chemical andphysical properties of vaccinia virus, but much of it witha topical application. Virus work has been concentratedon vaccinia. The results obtained by McClean, in con-junction with Dr. R. G. Henderson of the London CountyCouncil’s staff, on the inoculation of children intra- andsub-cutaneously with elementary body suspensions ofvaccinia virus prepared from sheep strongly indicatedthat, with the vaccine, used immunity resulted only ifcutaneous vesicles were produced. Thus, if secondaryinfection from superficial ulceration of the vesicles-per-haps the main objection to vaccinia-is to be avoided,proliferation of the virus in the skin or subcutaneoustissues is needed, and from rabbit experiments it seemspossible that virus may be adapted to such growth. Ofbacteriological work the studies of D. W. Hendersonand P. A. Gorer on the synergic effect of antitoxin andsulphapyridine in the treatment of experimental gasgangrene and the similar studies of Amies on the treat-ment of experimental meningococcus infection havealready been discussed in these columns. An importantadvance in the production of antityphoid serum has beenmade by the substitution of acetone-killed cultures, inwhich the Vi and 0 antigens are preserved intact, toreplace the use of living cultures. Dr. Felix with MissR. M. Pitt has continued his studies on the antigens ofS. typhi and has shown that the Vi antigen has more thana directly toxic effect-as is maintained by 0rskovand Kauffmann-for it protects the 0 antigen againstnatural or immune 0 antibody and thus guards the wholebacterial cell against the opsonising activities of theserum. In view of the work of Craigie and Yen on thesubdivision of S. typhi into a number of distinct typesaccording to their phage-sensitivity, Felix and Pitt havetried, unsuccessfully, to demonstrate serological differ-ences in strains of S. typhi corresponding to their phage-sensitivity-a result, as is remarked, very reassuring fromthe viewpoint of antityphoid’ inoculation and serumtherapy. Dr. Schutze is conducting experiments inguineapigs on simultaneous immunisation againstdiphtheria and pertussis, and has reached some con-clusions on the toxicity and virulence of B. pesti.sas a result of tests with unenveloped variants of thebacillus.

Investigation of the " diffusing factor " elaborated bycertain bacteria and tissues, in which McClean has beena pioneer, has taken an interesting turn from the dis-covery by Chain and Duthie at Oxford that purifiedextracts of the substance from mammalian testes havea strong mucolytic activity. Following up this work,McClean has shown that purified bacterial filtrates alsocontain this mucinase which is antigenic and specific foreach bacterium. Seminal fluid has been found by otherworkers to contain the mucolytic enzyme by means ofwhich the spermatozoa penetrate the plug of mucus inthe cervical canal, and this is doubtless the explanationfor its abundance in the testes. Coordinated studies onthe changes that occur in the serum of horses duringimmunisation are being carried out with the ultra-centri-fuge and the electrophoresis apparatus ; they have shownthat the x and 13 globulins are especially associated withthe antitoxic value of the serum. The preparation ofrefined antitoxins by the peptic digest method is beingfurther investigated by Dr, Knight. In the field ofexperimental pathology Dr. Gorer has been workingon the genetic factors concerned in tumour transplanta-tion, while there are references in the report to studieson the metabolism of fat and on kidney function in therat and to Professor Ledingham’s work on the relation-ship of the sex-hormones to the Foh-Kurloff cell in theguineapig.

AT 2.30 P.M. on Friday, Aug. 16, at the British Post--graduate Medical School Lieut.-Colonel St. J. D. Buxtonand Mr. H. L. C. Wood will give a demonstration ofplaster technique. Applications for tickets should beaddressed to the dean of the school, Ducane Road,London, W.12. °_

173JN ENGLAND NOW

In England NowA Running Commentary by Peripatetic Correspondents

PATHOLOGISTS are like dictators who deal with humanmaterial but whose contact with human beings is lessthan that of the local dustman. Since we started to runthe local blood-transfusion service, however, we are meet-ing people, speaking to them as doctor to patient andglorying in a relationship which, momentarily at least,cloaks us in omniscience. And we are all as pleased asPunch about it. The relief from a repression which usedto manifest itself only in the phrase " the clinical folk sayso but, well ... " has been immense and we are all newmen. No longer does the shadow of being just membersof an ancillary service thwart our lives. We are littleclinical maestros ourselves, and we’ve lots to say aboutthe number of apparently normal people with mildthyrotoxicosis, and we can and do discuss the treatmentof collapse in blood-donors. Yes, we work from hell tobreakfast just to prove that we can make a real successof a real doctor’s job.

One thing that strikes every doctor and must havestruck many laboratory folk afresh is the faith andconfidence the public puts in those whose names happento be on the medical register. vVe’ve noticed it parti-cularly among our country donors, farmers, shepherdsand woodmen. They come to have their blood groupedwithout the faintest idea of what is to be done and oftenone of them will say : " Do you think I’ll be able to castmy peats next week doctor ? " ; or " I’ve still ten acresof turnips to hoe, so be canny." It is a pleasure to workin those country places with the scent of clover-fields andthe broad accents of country folk drifting through openwindows. We’ve had a lot of fun out of it too. Oncewe went to do blood-grouping at a village where theladies had prepared a bedroom with spotless white sheetson the floor and walls and stripped the bed as for a majorobstetrical operation. There was the schoolmistresswhose democratic principles made her fly to her own,doctor to have her group AB blood changed to somethingmore common, and the robust policeman whose bloodhad been thinner than water since the Boer War when hedrank himself drunk for a week. These people surpriseus by their willingness to help and in one village of lessthan 4000 people there are now well over 200 volunteerdonors. In the city the response has been about as goodbut townspeople know a great deal more about medicinethan countryfolk, whose experience of doctors is oftenlimited to the two essential visits in one life-time.We’ve also been blood-grouping in several unmentionableplaces and nothing has been more pleasant than to dis-cover the competence of sick-room staffs in the services.We’ve heard London dance-band musicians, miners anddockers arguing with understanding about the physiologyof the kidney. We’ve had less contact with the officersbut the picture of a pilot wearing the D.F.C. with barwho nearly fainted when we pricked his finger is areminder that courage may go with a distaste for us andour kind.

* * *

Some time ago we had our’first serious air-raid when.the hospital services worked well and the transfusionteam gave its first bottles of blood for civilian air-raidcasualties. There were little snags, of course, and we’velearned how to correct them. One debatable pointwhich arose from this baptismal raid was whether, whenthere are few people injured they should be taken to first-aid posts at all. The trouble is how are we to know howmany injured there will be. But obviously the sooner’shocked and wounded people are in hospital and the lessman-handling they get the higher their chances ofrecovery. In mass raids the first-aid posts will get theiropportunity, but with all our available facilities would itnot be easier to transfer a small number of casualtiesimmediately to the hospitals ? At least, this was thefeeling in the tea-room where we now talk a good deal lesshigh politics and more common medicine.

. * * *

Yesterday I walked over with a friend to see the localConscientious Objector. He is a man of 25, of well-to-doparents who came down here some years ago to lead asimple life, paint rather quaint pictures, keep a shop in

the village, and grow a beard. He has recently beenexcused by the local tribunal from military service onreligious grounds. He is married and has children. Wefound this biblical figure working in his lovely garden.I talked with him and was impressed by his charming,almost boyish, frankness, and at the same time by adignified composure. We admired his flowers and hispaintings, we bought from his shop, and went home.I asked my friend if he knew anything of his earlierhistory. " Oh, he was at X," naming a public school," but was so unhappy there that he left when he wassixteen. He told me he magnified some illness to getout of it." One could guess at the whole story now,the retreat from the turmoil of the public school, fromurban conditions, from the very idea of army service,each time because his little force with its simple equip-ment was in danger of being annihilated or split up,each time the process being rationalised on health orreligious grounds, which I suppose corresponds to

" previously prepared positions " ; retreats not fromreality, but from the more tiresome forms of it. We etalked on and both of us had little doubt that if thisman had been forced into the army he would have brokendown and very likely have spent the rest of his life inthat penultimate retreat of all-a state of schizophrenia.There must be a lot of C.O.s who save the Governmentany amount of expense by becoming C.O.s.Yet we are all guilty of little withdrawals from the

unpleasant at times, often quite unconsciously. I oncemade an almost Newtonian discovery which illustratesthis. I was living with a lot of other men and we allshared a bathroom. Each of us used to shave and baththere every morning. Some had hot baths and somecold, and I always knew which water was running inbecause the hot-water tap used to make little explosivenoises which interrupted the sound of flowing water.I used to lie in bed and time them. Then I made thisremarkable discovery: although the cold-bath menwere in the bath for a much shorter time than the hot-bath men, as deduced from the splashing noises, theywere in the bath-room longer. What happened wasthat with the grim reality of the cold bath ahead of themthey lingered, pondered, and dawdled over their shaving.

* * ** * *

I was drinking lager in a bar full of working men whenHitler’s peace speech came over the air. There was abreathless and béaming silence ; no-one wanted to miss aword. " They might be listening to Jack Warner," theold waiter whispered in my ear ; he had come in fromthe dining-room, regardless of his hungry charges. Ilooked round at the pleased faces of Hitler’s enemies, butI thought the waiter had got it wrong. Their faces didnot show the intelligent amusement accorded to Mr.Warner-they wore the indulgent smiles reserved forDonald Duck in one of his rages.

* * *

Whatever the paucity of information that comes tothe hospital with a patient, there is invariably aninsatiable quest for reports about him. All the case-papers go as a matter of course to records office andpersonal notes from the doctor in charge of the case tothe medical officer of his unit, but there is in addition aconstant quest from all sorts of sources, often long afterthe patient has left the hospital and his case-sheets havegone to their rightful home. When the patients areallies, the quest for information appears to be greaterthan ever. Sometimes we are asked to send lists,sometimes someone is sent to collect information andvery often both things happen about the same time forthe same set of patients. The more varied the national-ities concerned, the greater the number of seekers afterinformation and the greater the difficulty of disposing ofthe patients, for many deities have to be consulted andthere is universal reluctance to see a dispersal of ewelambs that makes administration and ultimate returnto units more difficult ; nor is it always desirable to sendallies of too many hues to the same auxiliary hospital.Once when it was considered necessary by our Frenchcolleagues to take back to their native land as many menas quickly as possible a doctor arrived unexpectedlywith a lorry one evening and said he desired to takeaway with him in an hour thirty men to join a ship whichwas sailing for France early the following morning. He