332 TREATMENT OF 8’l’APHYLOCOCCAL INFJICTIONS

preserved when the better endowment of clinicalscience makes it possible for picked men to escapethe burden of practice and to devote themselveswhole-heartedly to the study of their subject.LEWIS’S efforts to make such escape possible for alarger number have been untiring and to someextent fruitful. But for the development of anyfield of work something more than opportunitiesare needed ; men of ability and industry must beinspired to seize the opportunities that are beingdemanded for them, and no better source of

inspiration could be imagined than the accountof the results achieved by full-time workers in theclinical research department of University CollegeHospital.

TREATMENT OF STAPHYLOCOCCALINFECTIONS

THE history of the last ten years in regardto the prophylaxis or treatment of streptococcalinfections along immunological lines has tendedto emphasise the difference between immunityto the invasive activities of a bacterium and tothe toxin, or toxins, that it produces, and hassuggested that the presence in the blood or tissuefluids of a relatively large amount of antitoxinhas little if any effect in protecting the tissuesagainst invasion by a highly virulent organism.Argument from analogy is, however, alwaysdangerous ; and it by no means follows that whatis true of the streptococcus is true of the staphy-lococcus also. Two papers published in our

present issue (and some others that have recentlyappeared) suggest quite clearly that it is not.The reports by D. S. MURRAY and C. E. DOLMANon the results of clinical trials, in London andin Toronto, of staphylococcus toxoid in the treat-ment of recurrent or relapsing infections, suchas furunculosis, acne, and carbuncles, are of morethan ordinary interest both to medical practitionersand to academic immunologists. The former willexamine the figures to form a judgment on theprobable value of the new method of treatmentas compared with those with which they are

already familiar. The latter will value them forthe data they contribute towards the solution ofa perplexing problem, the effect of an antitoxicas opposed to an antibacterial immunity in aninfection in which tissue invasion plays a significantpart. The results recorded emphasise, also, the

necessity, once animal experiment has indicateda line of advance, for carefully controlled trials inman ; since, in this particular instance, it wouldseem that a more effective protection is attainedagainst natural human infections than againstexperimental’infection in the rabbit.The significance of the data recorded by MURRAY

emerges clearly from his tabulated figures. Thereis, of course, the old difficulty of establishingcriteria of cure or improvement that are objectiveand capable of quantitative expression, and itcannot be said that the difficulty has been over-come ; but it will probably be agreed that MURRAY,by adopting the rule of recording " recovery "only when he, the colleague who sent the case for

treatment, and the patient treated were all agreedabout it, has gone some way to ensure an objectiveand conservative estimate of his results. Assessedon this basis, the figures of his eighth table-51 cases recovered, 56 improved, and 9 unaffected,of 116 treated-are distinctly encouraging. Itwould be of great interest if the efficacy of staphy-lococcal toxoid could be compared, in paralleltrials carried out on groups of adequate size, withthat of other therapeutic methods that haveobtained a considerable vogue, as, for instance,treatment with a staphylococcal vaccine or withyeast. Both MURRAY and DOLMAN refer to casesthat had failed to respond to such treatment, butrecovered when treated with the toxoid. Suchscattered instances do not, however, afford anyreal basis for comparison ; nor is it usually possible,by comparing reports on different methods oftreatment, each of which is recorded as exerting abeneficial effect, to form any accurate judgmentas to their relative merits. It is this questionthat actually exercises the mind of the clinicianwhen faced with a patient whom he has to

treat, and it is here that clear and authoritativeguidance would be most helpful. For thosewhose interests lie in mechanisms rather thanresults MURRAY has an interesting story totell. He shows, in agreement with many otherworkers who have e examined this point, thatmost normal persons have some staphylococcalantitoxin in the blood-he gives a mean figureof 0’765 international units per c.cm. measuredas antihaemolysin-and that this amount is not

greatly altered in persons suffering from staphy-lococcal infections other than osteomyelitis. Hismean figures for acne, blepharitis, furunculosis,and carbuncles range from 0’60 unit to 1’03 units,while seven cases of osteomyelitis gave a meanof 11’7 units. His fourth, fifth, and sixth tablesshow that an adequate course of toxoid injectionsinduces a marked rise in antitoxin titre, up to eightor more times its original value ; and the figuresset out in his ninth table afford support for theview that the degree to which this titre is raisedis correlated with the clinical effectiveness of thetreatment. If any criticism is to be made ofMURRAY’S presentation of his figures, it is that thetabulation of the standard errors of his meanvalues would have made their significance moreeasily assessible, and would have conformed to apractice that should, we think, be universal inrecords of this type.

If, in this summary of the data set out in detailon other pages, we have quoted extensively fromMURRAY’S paper and not at all from DOLMAN’S,it is because the latter presents his evidence ina form that makes useful quotation impossibleand assessment of its significance difficult. Hisconclusions, however, are very similar to MURRAY’S,and this agreement is obviously important, thoughhe has made no serious attempt to provide thereader with data on which he can form his own

judgment. Apart from the failure to present thedata in a form that allows of statistical analysis,where such analysis is obviously necessary, there

333ST. GEORGE’S IIOSI’ITAL

is one suggestion in DoLMAN’s paper to whichwe should be inclined to take exception—namely,that staphylococcal toxoid should be preparedfrom several different strains of staphylococcus,and that failure to do this may account for clinicallyunsatisfactory results. There is, so far as we

know, no evidence that such minor qualitativedifferences as exist between the toxins elaborated

by different strains of staphylococci are of

importance in relation to the prophylactic or

curative value of the toxoids prepared fromthem ; and the international unit of antitoxin,which now forms the basis for accurate quantitativework in this field, measures a particular activityof the toxin which appears to be highly correlatedwith its toxic potency for laboratory animals.If we are to progress in such studies as these wemust, adopt some working hypothesis that is inaccord with the existing evidence, and adhere toit until the collection of new data affords reasonfor modification or addition. It is, of course,

possible that toxic components other than thosemeasured by the international unit are of

importance in infection, but their existence andsignificance must be proved, not assumed. Forthe moment it is clearly desirable to approach theproblem as MURRAY has done, by determiningwhether a toxoid that is known to be antitoxino-

genic in terms of the international unit is an

effective therapeutic agent in man, and whetherthere is a demonstrable relation between anti-toxin production and clinical improvement. Withanother criticism applied by DoLMAN to reports ofclinical failures-that no significance can beattached to such findings until it has been shownthat the toxoid employed was possessed of adequateantigenic activity-we are, of course, in entire

agreement. MURRAY’S paper is, as will be noted,a report to the Therapeutic Trials Committeeof the Medical Research Council. He states thatsince his work was begun before the committeedecided to make an official test of staphylococcaltoxoid, his records do not conform exactly to thosedesired. They could, in fact, be improved incertain details. But they mark a very definiteadvance on the way in which evidence of this kindis frequently collected and presented ; and ifthe Therapeutic Trials Committee are able tomaintain and in some ways to improve thisstandard of trying out in the ward or the fieldmethods devised in the laboratory, they willrender a very real service to scientific medicine.

ST. GEORGE’S HOSPITAL

AT the end of last week the treasurers ofSt. George’s Hospital, Lord GREVILLE and LordWINCHILSEA, issued the statement that they wereempowered by a unanimous vote of the board ofgovernors to declare publicly that the work ofrebuilding the hospital would start at once onthe site that it had occupied for 200 years. Thedecision, which has thus been come to with nodissentient voice, had been forecast by most ofthose who knew the difficulties inherent in arrivingat the best of three possibilities-to rebuild on

the original site, to acquire and build on an

adjacent site, or thirdly, to build in another districtwhere the purchase of a suitable site would be lessruinously expensive. A communication from SirGEORGE TURNER, the senior consulting surgeonon the staff of the hospital, was published in thesecolumns on Dec. 22nd, in which the argumentspressing in one or other of these directions wereset out, with the intention to indicate the difficultiesbefore those who advocated the removal of the

hospital. But the obvious fact that the hospitalmust be rebuilt was admitted, and this thetreasurers confirm, pointing to crumbling and shored-up walls, and a lack of space that must cramp alladvance, as complete justification for rebuilding.The statement of the treasurers of the hospital,which is published on p. 345 of this issue, willremove a public impression, which has long beencurrent and which has worked possibly to thedetriment of the institution. It has been held,despite protests and public announcements, thatthose in charge of the finances of the hospitalhave been sitting on a gold mine while allowing,under the eyes of all men, their buildings to fall topieces. The proof is now before us that the condi-tions on which the site is held are such that a salewould leave only a small balance, if any, in favourof the hospital, after the purchase money hadbeen employed in acquiring a site in the neighbour-hood of Hyde Park Corner.The determination to rebuild on the present site

will be welcome to those who are, or who have beenin the past, connected with the institution, but thisnatural sentiment is of no account compared withthe public reaction. And it can hardly be doubtedwhat that reaction will be. There are statistics

estimating how many people pass St. George’sHospital daily in conveyances or on their feet.The figure is enormous, and a substantial proportionof those who pass must have recognised thedrawbacks to the work of the hospital due to thestate of affairs that has recently existed ; yetmany of them also know how splendid that workhas been over two centuries, and, further, that inthe face of grave material difficulties its qualityhas been maintained. Thus the decision whichthe authorities of the hospital have arrived at toremain and to rebuild should command generalapproval, and with that decision a period ofintolerable doubt for the authorities comes to anend and there begins for them a struggle in

hopeful circumstances towards complete rehabil-itation.We learn that a million pounds must be raised to

rebuild, equip, and endow St. George’s and thetask will not be found a light one by those whoare now preparing to undertake it. But publichelp can be safely anticipated. For some time pastthe hospital, in common with similar great charities,has been compelled to plead for help as a routine,and its outward appearance has given force to

its appeals. But cooperation in a great constructiveplan has never been present to the minds of donors,although they have given sporadically and fre-quently. They may have been made aware by theannual statements or by rumours of doings at the