Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 175 ON THE MODES OF PRODUCTION OF "RICKETTSIA"-BODIES IN THE LOUSE. By H. M. WOODCOCK, D.Sc.LoND. . Fellow of University College. (Con~inued from p. un.) "RICKETTSIA "·BODIES FROM NORMAL LICE. As I pointed out in my previous paper [16], there was no reason to doubt, on my view of the nature of "Rickettsia" -bodies, that such would be found to occur, at any rate occasionally, in normal lice, "uninfected " with the virus of either typhus or trench-fever. A box of lice, obtained as stated in my introductory. paragraph, was fed ori myself daily without intermission (and usually twice daily) for over a month. D~ring this period, the fine gauze, through the meshes of which the lice bit, was only once renewed, and each covering became considerably. soiled with the excreta. The bites proved- very irritating to me and a certain amount of scratching was unavoidable, so that now and again excoriation and bleeding occurred. Apart from this, however, I have not experienced the slightest inconvenience from the effects of these lice feeding on me. I desire to take this opportunity of thanking Dr. Arkwright very much for valuable hints and assistance in regar~ to keeping and feeding the lice. Tfte clean, unused box was started with ten or eleven lice, including both males and females. Eggs were laid, and in due time the young lice' hatched out and in their turn fed. By about the middle of the third week all the original lice had died off and only small or medium-sized ones, of the new generation, were present. My whole object was, of course, to confirm the statements already made by various workers that normal, healthy lice do contain "Rickettsias," and to see what these would prove to be like. Hence, for the most part, I contented myself with making preparations regularly from samples of the mass~excreta, shaken out of the box. On each occasion, all the loose excreta were removed. Three or four smears were thus made at a time, sometimes at daily intervals, at others ·every two or three days. Now and again, smears were made of the gut-contents of individual lice, and some of these also proved positive, thus placing beyond doubt that the bodies in question did come from the gut of the lice. After the event, I see that more information .on one or two interesting points could have been gained had I followed a few individual lice separately, throughout the life-history. "Rickettsia "-bodies, of one or more of the types to be described, were found in one or more of the smears made, on every occasion except the first time, when I took extremely little material and fOUlid nothing which I Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 176 The Production of "Rickettsia" -bodies in the Louse could regard as definite, and once during the period when the original lice were nearly all dead and the new generation'very young. I cannot say certainly that every louse would show the bodies, therefore, though I think it most probable that they all would, at one period or another. I have the impression'that very young' lice do not show them at first. Towards the end of the month, there were many more adult lice in the box (from twenty-five to thirty at least), than at the start, and the" Rickettsias" were much more readily found in the smears..This was probably because the . excreta were more abundant and mote material was put on each slide. . POFtions of the dry excreta were allowed to fall out.of the lid of the box (by gentle tapping), into droplets of salt-citrate 'solution or tap-water on the slide, and were then well rubbed about and broken up as much as possibl~' with a needle. I found that it made no difference whether salt-citrate or tap-water was used. The drop was spread out a little and then allowed to dry tho];oughly, being afterwards fixed in absolu~e alcohol for ten minutes and stained in the usual ma.nner. The preparation was not otherwise treated in any way, my object being to see what was present in the excreta, in as natnrala form as possible. That some blood in a condition very little altered is passed in the 'fmces, is apparent from the fact that, invariably, some yellow hfPmoglobin-like substance is dissolved out, from the small, almost black particles of excreta,\ when these are moistened by the water . .But the pigmentiferous residue of the. comple'tedigestion is preserved unaltered. . The general appearance of the smears, when examined, varies considerably, this being, again, dependent on the stage to which the digestion had been. carried in the case of the particular sample of hmmatogenous material forming the preparation. If the digestion was practically complete, scarcely anything but pigmentiferous masses and clumps of grains, of all variety (as described in the first section above) would be present. If, on the other hand, hmmatogenous material in an earlier stage of digestion had been also excreted and formed part of the sample, altered blood, still recognizable as such, would be found. Red corpuscles~ amorphous masses of hmInoglobin, resulting from a quantity of corpuscles having had their envelope dissolved and running together, black masses, and the same separating out .into pigment grains-all these stages occur. ·And there is one important point to note. The more the preparation indicates that the sample of excreta consisted of blood in an early stage 6f digestion, the less' likelihood. is there of finding "Rickettsias." Conversely, the more the smear consists of well-defined pigment-grains the greater the number of clumps of such bodies. In my preparations I have not found any bacteria, and I must confess I regar,d the gut-contents of the louse as being, practically speaking, sterile. . The I ' Rickettsia" -bodies are always in cluinps or aggregations; sometimes very dense, but at other times more scattered, having possibly been separated a little in making the preparation. They can never be found Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 177 H. M . Woodcock FIG. 20. FIG. 21. ,. FIG. 22. 12 FIG. 23. Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 178 The Production of "Rickettsia" -bodies in the Louse dispersed or isolated more or less uniformly in any particular area; and I think this itself is an argument against their being hving micro-organisms. Not infrequently, a clump of bodies is in close relation with a pale, bluestaining lragment of cell-cytoplasm, which has been desquamated and is undergoing autolysis (such as is seen at c, figs. 21 and 23.) The ,. Rickettsias" are not actually in this cytoplasm, but lying in contact with, or lIear to it; part of a cluster may be in contact, the rest separate. Further, very often clumps of .f Rickettsias" occur in company with pigment-grains, some of which, at least, are of tbe same form and size. At other times, in dense c1umps, pigmentiferous JDasses are seen in the midst of them. (In the figures, R = "Hickettsia "-bodies, p = pigment, or pigmentiferous masses.) rrhe Rickettsias" are most usually coccoid, or diplococcal in [arill U (figs. 20 to 22), tbougb sometimes caeca-bacillary, or even like slender bacilli (fig. 17). Occasionally I have observed markedly bipolar forms, and also ring-forms; sncb also occnr io the trench-fever type. But there is noL Lhe remarkable polymorpbism in the case of these normally produced bodies in the louse that is seeu in such forms as pTowazeki, 1"ocha·lim.ce, and lectula,·ii of the bed-bug. The great majority of the bodies have a relatively limited range of form, in which respect they rnuch more closely resemble quintana and, again, melophagi of the sbeep-ked, as I observed this latter type. As regards their size, the coccal forms are mostly from 0·4 to 0·6,. in diameter, while the diplococcal ones average 0·9,. to 1·0,. by 0·4,.. BacilliLry forms Iliay be t1 little longer, up to 1·2,. m length (fig. 17), tbough fine, narrow ones, less than ]·0,. long, also occur. The colour is generally reddish-lilac to lilac, on the whole distinctly more lilac than is the case with the "Rickettsias" in Brumpt's smears; in other words, the tint much mme resembles that of quintana than of, for instance, prowazeki. In brief, this type, lllust be regarded, in my opinion, as corresponding to ped·iculi of other observers, which is admittedly very like the trenchfever form. I do not think it can be doubted that we are dealing with an extremely similar type of body in the two cases. Absolutely identical, we should not expect them to be, because one is abnormal, the other is not. And if there is a distinction, I consider it is that the size of the majority of the normally occurring forms is a trifle larger than the average size of the trench-fever forms. because there is not the same relative proportion of minute forms (I say average, because it must be remembered that there is quite a considerable range of size in the trenchfever bodies). This means, I would say, tbat in the pathological condition, where the breaking·down process of the bmmatogenous material is going lOne or two photoll1icrographs of "Rickettsia !I.bodies actually on such fragments werc taken, but owing to the blue-stained cytoplasm forming the background, the general result was not good. so that these were among those eliminated, Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com H.M. Woodcock 179 on wholesale, the ultimate physical disintegration of the residual material tends to be carried to a further extent. And a similar explan:;ttion applies to prowazeki and rocha-limaJ (cl. my figs. of the latter). With the illuminating -transitions between the pigment-grains and "Rickettsia "-bodies, illustrated above, to ghide me, I have had no difficulty in ascertaining that, in the case of these bodies in normal lice, the great majority of the clusters are produced by a corresponding modification in the pigment. Naturally, in a pathological state (as in the case of rocha-limaJ), where this production of" Rickettsias " is occurring en masse in the gut, it is far easier to obtain such transitional st:;tges in ample number. Nevertheless, in the present case also, clear indications can be obtained when carefully -looked for. I have already mentioned that there is frequently an intimate association in occurrence between the two things. And between definite blackish or brownish pigment-grains on the one hand, and equally definite lilac " Rickettsias " ::m the-other, there are usually several granules which one cannot assuredly place in either category-blackish with a tint of purple in, or reddish-lilac, with a tint of brown in, as the case may be; i.e., the same change is taking place, on a miniature scale, of course, that I described above, in the consideration of .Brumpt's smears. Such intermediate forms are commonly to be observed in places such as those shown in figs. 21 to 23. Speaking generally, it is in the case of small clumps of definitely formed and separated pigment-grains that the further alteration occurs. But, occasIOnally, the "Rickettsia "-bodies are found in connexion with a large, amorphous mass of hrematogenous material, as shown, for instance, in fig. 20. The greater part of this mass 1 is brownish-green, altered hremoglobin, in which the pigmentiferous residue is gradually becoming defined, as digestion and -absorption goes on. The dark, central part consisted mainly of such pigmentiferous granules. And every possible gradation can be seen in the change in colour of these elements; greenish-black (the earliest stage), almost black, ditto, with a tint of purple, deep lilac, and, ultimately, at the periphery (especially at the upper and left-hand sides), typical lilac to reddish-lilac" Rickettsia "-bodies. A very similar position, it may be added, of "Rickettsia "-bodies in relation to dark, hffimatogenous material has been noted in trench-fever smears. Fig. 17 gives a good example of the transformation of narrow, rod-like pigment-grains into cocco-bacillary or bacillary" Rickettsias." The arrow, p, on the right, indicates a clump of closely applied, blackish pigment-rods. The arrows p, on the left, point to similar grains, but yellowish-brown in colour, and in the case of one to which the lower arrow points, definitely segmented into a double or diplococcal form. The rest of the little bodies are lilac "Rickettsias." Compare, similarly, the pigment-grains and the 1 The right-hand portion has been omitted in the figure, in order to get the" Rickettsias " more sharply focused. Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 180 The Production of "Rickettsia "-bodies in the Louse " Rickettsias " in figs. 18 and 19. One or two of the pigment grains here (that, namely, to which the arrow pI, indicating a lit.tle clump, immediately points, in both figures), show an interesting feature, a slight but distinct trace of bipolarity. The two ends am slightly deeper in colour than the central portion. And I have seen "Rickettsia "-bodies manifestly corresponding to these. Now and· again I have found little clumps of "Rickettsia "-bodies, of fairly regular oval arrangement, which I regarded as having resulted from karyolysis. But, from my observations, I should say that the production of definite" Rickettsias " by this particular method is not, for some reason or other, nearly so marked a feature, normally, as it is, for instance, in mites. GENERAL CONSIDERATIONS. On the other hand, I never observed a corresponding alteration in the pigment in the smears of mites I examined. And I think this difference is an important one and stands in relation with the fact that, in the mite, the pigment-production is intracellular, i.e., it is the end product of the intracellular blood-digestion (vide my previous paper); whereas, in the louse, all the pigment is produced extracellularly. Another point is that there is a very much greater range of form and size of the pigment-grains in the latter type of digestion than in the former. The inference is, therefore, that the digestion of the hoomatogenous material is performed, somehow, differently by the intracellular ferment in the one case and by that poured out of the cells into the lumen, in the other. In the mite, the autolysis of desquamated and breaking-down cells has no further influence, apparently, on the endogenously formed pigment-grains, which are simply liberated and dispersed. But I think that when the pigment-grains in the louse happen to come under the influence of the autolytic (?) enzyme of such cells, further alteration does occur. And this is my explanation of the mode of origin of the mostly sparse and small clumps of "Rickettsia "-grains in the normal louse. I consider that they result when pigment-grains have been in close contact with such disintegrating cells, some of them, perhaps, temporarily adherent to cell-fragments (vide also above, p. 178). Hence their occurrence in any particular louse, at any particular time is largely fortuitous and dependent on whether such autolytic action of broken-down cells happens to have been at work. Probably by careful searching, a few instances could be found in most lice, if the excreta were examined on two or three successive days; though, in' the case of young lice, with new, healthy cells, one might not at first find themuntil some cells became effete and were desquamated. I think that the change brought about by this further digestion is manifest, at any rate in one respect, in the separation of the iron from the proteid constituent of the pigment (or from a part of it). These normal " Rickettsia "~bodies, therefore, represent proteid material of. pigment- Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com H. M. Woodcock 181 grains, which have lost their iron. Clumps of I< Rickettsias," whose posItion on the slide had been noted, were de-stained and then submitted to the iron-test, both by the short method (as above) and by the long method, with absolutely negative result. Further, clumps of minute granules, in a fresh unstained smear, closely resembling neighouring fine granules of yellowish-brown pigment, but which I regarded as "Rickettsias" from the fact that they were colourless, were treated with acidified, dilute methyl-green, and they still remained quite colourless. The smear was then fixed in absolute alcohol and stained with Giemsa, and these colourless clumps proved to be the usual" Rickettsia" -bodies. Lastly, another stained smear, with marked "Rickettsias," was decolorized and then stained with iron-hffimatoxylin. A little smear of blood was also added on the slide to control the differentiation, which was purposely not carried far. 'l'he nuclei of the leucocytes were left deeply stained, a large proportion of the corpuscles were still black, and so was most of the hffimatogenous material and pigment. But the "Rickettsias" were either quite unstained or else (in a few cases) very faintly coloured, probably with a trace of bluish Giemsa still left in, and were hardly distinguishable; the result must certainly be regarded as negative. These observations eliminate, of course, the presence of iron or chromatin in these bodies and afford, practically, proof, I consider, that they are not organisms (vide also Woodcock [15]). Moreover, my findings entirely agree with the clear demonstration of Nicholson [10] that the" Rickettsias " of Rocky Mountain spotted fever do not stain with iron-hffimatoxylin. Now, I myself do not think there can be any reasonable doubt that the bodies I have described in this paper from Brumpt's smears and my own, are the same type of thing as the other known louse" Rickettsias " and produced in what is essentially the same manner. It follows, therefore, that, whether we consider q~lintana, rocha-limaJ or prowazeki, these bodies, in so far as they are produced by abnormal digestion of the hffimatogenous material (i.e., practically entirely in the first-named and very largely in the other two) also represent the residual proteid material after the iron has been removed. 1 Then does this explanation of the nature and mode of origin of these elements imply that those met with in infective lice have no causal relation with the respective diseases? Not at all; on the contrary, indeed, I regard what I have found as constituting still further evidence in favour of my view that these diseases are due to pathogenic enzymes. I have considered this view fully in my former paper, so that I propose only to add here a few remarks bearing on this new point. I think the biology of the blood-digestion (if I may so put it) is a most important factor III the question. Normally, as we have seen, both in the mite and in 1 Of course, in the case of karyolysis, they will result from a corresponding degradation of the chromatin, and breakdown of the general nuclear material. Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 182 The Production of " Rickettsia" -bodies in the Louse the louse,· most of the iron of the ingested hremoglobin is execreted in the form of pigment. In the louse, the only iron which appears to be assimilated is that obtained from the relatively small proportion of the corpuscles which are digested intracellularly.l Evidently, the iron of the hremoglobin taken in as its food is vastly in excess of the normal requirements of the louse. Next, as regards the pathological change in this blood-digestion, as found, say, in infection with typhus fevE:r or Rocky Mountain spotted fever. 2 In man a noteworthy characteristic is increased hrematophagy on the part of the vascular endothelial cells. Now, as I have previously shown [14], the specialized macrophages of endothelial cell-type are able normally to exercise hremetaboly and assimilate the products of digestion in a relatively complete manner, incorporating the iron in their own protoplasm; the only manifest residual product being the platelet granules. On my view,- the pathogenic enzyme is one which induces this mode of behaviour on the part of the related endothelial cells of capillaries, etc. It is most likely, I think, that such cells are not normally hrematophagic and plateletproducers to any extent 3 (as are megakaryocytes and large mononuclears, for instance). In the above diseases, however, these cells are stimulated to produce a hremetabolic enzyme, capable of digesting on similar lines the ingested blood. Nevertheless, the cell condition is somehow different from that of the normalmacrophages, because the affected cells also undergo active proliferation. To put the matter in a nutshell, these endothelial cells are assimilating and using iron to a much greater extent than £s customary. I may add that, although such serious systemic disturbance results, yet I do not consider that the divergence from the normal type of hremetaboly is anything like so marked in these endothelial cell diseases as it is, for example, in the hrematophagias of ectodermic epithelial cells such as hydrophobia and smallpox where, from the point of view· of the cell, the digestion is entirely unsuccessful, only Negri-bodies, Guarnieribodies and so on resulting from the abnormal effort.If we turn now to the louse we find, I think, that an entirely comparable 1 In the case of the mite, this function appears to be restricted to those particular cells which ingest chiefly the nuclei of the red cells, etc., taken in, and of course no pigment is formed. 2 The alterations in connexion with the cells of the vascular tissue in trench-fever do not appear to have been yet ascertained. 3 The reason, I think, that it is extremely doubtful if this occurs normally is just because the production of platelets would involve prior hffimatophagy, and this seems most unlikely to take place in the case of the. thin and stretched-out endothelial cells, constituting the lining of the smaller vessels and capillaries_ Moreover, platelet-production on any scale, implying, as it would, the abstriction of platelet-cytoplasm from large, overgrown cells, would almost certainly lead to blocking and thrombosis; such does not occur normally, of course, but, on the other hand, is distinctly in evidence as a result of the abnormal behaviour of the cplls in ty~us. To suggest the endothelium as an important source of platelets would strike me now as utterly unreasonable and illogical; and, indeed, I will confess that, if anyone made such a suggestion I, personally. should be very much inclined to doubt whether he really knew a platelet, let alone its mode of origin! Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com H. M. Woodcock 183 pathological action is occurring. The cells are producing a pathogenic enzyme which so digests the blood that the iron is not manifestly eliminated in pigment grains. My inference is that this is the same enzyme which is produced by the endothelial cells, and that it is digesting the blood wholesale in such a manner that the iron tends to be separated in some other compound and the excretory residue is in the form of "Rickettsias," the ultimate minute type of which bears a suspiciously close resemblance to a platelet granule. That there is no great difficulty in the way of such an occurrence happening will be understood, I think, if my view that the autolytic ferment produced by these desquamated cells in the course of their own natural breakdown is itself capable of separating the iron from the pigment and leaving" Rickettsia "-bodies is right. Are the cells of the louse able to assimilate this additional iron material? We must bear in mind the wonderfully delicate differences in these blooddigestive enzymes and in the exact mode of the blood-digestion. There is a rich field here for the biochemists to cultivate. Even the normal intracellular digestion of the louse must be in some way different from that of· macrophages, becausfl nothing like platelet-granules (or" Rickettsias ") are left over in the cytoplasm. And the products of what may be called the platelet-producing cell type of blood-digestion, even if the cells of the louse are capable of assimilating them, may not be (and apparently are not) in the long run so suitable for the welfare of ·the cells. Again, the normal extracellular digestion is, of cour)'!e, manifestly different. Now I do not know whether the same type of cell is able to perform both these types of normal digestion. However this may be, I think that both types-intracellular and extracellular-are replaced by the pathological kind in those cases where, in addition to extracellular" Rickettsia "-bodies, wefind also iDtracellular types. And it looks as if an attempt were made by the cells to assimilate and utilize the products of the abnormal intracellular digestion, at least, because of the marked increase in size (hypertrophy) of such cells (cf. especially Wolbach, Todd and Palfrey's figures [10]. Nevertheless, in the end the cell is overcome and we find karyolysis and general breakdown. On the . other hand, in trench-fever where intracellular " Rickettsias " are, at all events, extremely rare, and the cells do. not appear to be injuriously altered, it would seem that the normal intracellular type of digestion is not affected; and in this case probably the cells do not assimilate the iron-containing product of the abnormal extracellular digestion. This will naturally be of slightly different character (because, on my view, the ferment· virus is different) from that resulting frOID both types of the digestion in typhus, etc. It is probably much more closely akin to the auto-digestion phenomenon with which is associated the "pediculi" -type of "Rickettsias." Stress has been laid on the fact that a louse does not become itself infective for at least five to eight days after it has fed upon a trench-fever patient, as being important evidence in favour of the view that a micro~ organism is the rotiological agent, which has at first to multiply and develop Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 184 The Production of " Rickettsia" -bodies in the Louse in the body of the louse. But, equally on my view, a certain time will have to elapse while the pathogenic enzyme is being increased in amount from the minute quantity originally imbibed, adsorbed to the platelets. The more cells that are stimulated to produce this enzyme, the greater of course it will be in amount and the more blood will be abnormapy instead of normally digested, with ever-increasing production of " Rickettsia "-bodies. This view affords, equally, an explanation of why " Rickettsias " are not met with at first. And, in the early days, when they are beginning to appear, but as yet in small numbers, the chances against a successful infection are correspondingly high. It may be thought that I have endeavoured to build up a somewhat . elaborate edifice of function upon a foundation of microscopical appearances; still, the above seems to me the most reasonable and logical interpretation not only of my own observations but of those of others I have indicated. And in this connexion I would quote the following passage from a review by Delezenne (Bull. Inst. Pasteur, 21, ] 923, p. 825) of the great treatise on hmmatology recently published by Jolly: "Que l'etude microscopique des tissus puis se, it l'egal des autres procedes d/investigation utilises par le physiologiste, servir it interpreter le fonctionnement, nul ne peut en douter. C'est, faut-il rappeler, ce que comprit le premier Claude Bernard, lorsqu'orientant son eleve Ranvier vers les recherches microscopiques, il le preparait it poser de fa<;on magistrale les premiers fondements de l'histo-physiologie." I have been led to think there is a tendency among certain physiologists of to-day to treat microscopical anatomy as of negligible utility. I hope I am wrong, because, if they do take that view, they are decidedly to blame! Lastly, I have only a few words to add about the most recent efforts of certain continental workers to establish a true micro-organism as the cause of typhus (e.g., Barykin and Kritsch [3J, Weigl [12J). I confess to a feeling of amazement at Weigl's. hypothesis. Apparently, he regards Plotz's bacillus, strains of Weil's proteus-X, Barykin's Microbion and R. pl'owazeki as all being forms or variants of the specific causal organism. Truly, a hypothesis of desperation! And I gather that Kuczynski also connects the X-strains with R. prowazeki. But, if the "Rickettsias are not living organisms, these views are necessarily dissolved. Barykin and Kritsch pin their faith to something they call JJficrobion typhi exanthematic'i, which, it is interesting to note incidentally, they found in seven per cent of their healthy, control lice! These authors say that " Microbion" cannot be identified with any micro-organism yet found in typhus, with the possible exception of" R. prowazeki "-a significant doubt! From the description and figures, I am strongly inclined to think the authors were dealing with a form of " Rickettsia."1 Their principal reason 11 Since this was written, I see that, in a review of Barykin and Kritsch's paper by A." (Trap. Dis. Bull., 20, No. 8, August, 1923, p. 661), the reviewer also says: "Indeed, except that it" (Microbion) "is amenable to cultivation, it agrees in all parti. culars with that Rickettsia" (Le., " R. prowazeki "). 1 "A~ Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com H. M.Woodcock 185 for regarding" Microbion" as a micro-organism is because they were able to cultivate it in: a special "Organ brei," consisting chiefly of splenic, or brain-tissue. Oh! these tissue-media, I do think they are responsible for a lot of erroneous conclusions! I have myself little doubt that the pathogenic enzyme was causing breakdown of the hremoglobin and cell-lysis, with the usual end-result ofbacteriomorphic granules, of one kind or another (cf., my reference to Kuczynski's " cultivation" of R. prowazeki in my previous paper, p. 259). I will merely quote here from M'Leod and Bevan-Brown (Journ. Pathology, 22, 1918, p. 79): "It is perhaps worth while mentioning here that, in the course of the careful examination of these cultures" [which were blood-cultures from trench-fever !] "a phenomenon was observed which, so far as we have noticed, has not received much attention. We draw attention to it because it serves to emphasize the caution necessary in accepting as evidence of bacterial growth various forms which appear in culture-media that contain animal tissues undergoing autolysis. The phenomenon consists in the appearance of granules in, the red corpuscles which take a deep stain with fuchsin or with stains appropriate for moulds." The authors thought they were dealing with bodies simulating moulds, but their figures suggest irresistibly to my mind atages in the (artificial) production of "Rickettsia "-like- bodies from the blood undergoing lysis or digestion by the pathogenic enzyme. And I think the same explahation will apply to the" Mt·crobion" appearing in Barykin and Kritsch's " cultures." The evid~nce that the "Rickettsias" represent, or indicate the virus of trench-fever and typhus-fever is, to my mind, strong-very strong indeed in the case of trench-fever. And if this is true for the one, there can be little doubt it is true also for the other diseas~. The valuable experimental work which Arkwright and the late A. Bacot were able to carry out in Cairo [1] points unmistakeably in this direction. Even Weigl (l.c.) wrote: "Auf Grund der Ergebnisse der Rickettsienforschung miissen wir die Rickettsia prowazeki als die Form des Fleckfiebererregers in der Laus ansehen. Diese wohlbegriindete Annahme scheint endlich durchgedrungen zu sein." Now, the pathogenic "Rickettsias" are certainly, I think, solely products of abnormal hremetaboly and karyolysis of the diseased cells. Does not this almost inevitably imply, therefore, that the actual virus is an abnormal hcemetabolic enzyme? REFERENOES. [1] ARKWRIGHT and (the late A.) BACOT. "Investigations of the lEltiology of Typhus Fever, especially undertaken for the Egyptian Government in the Public Health Laboratories, Oairo," Brit. Journ. Exper. Path., iv, 1923, 70. [2J Idem., idem., and DUNCAN. "The Association of Rickettsia with Trench Fever," Journ. of Hygiene, xviii, 1919, 76. [3] BARYKIN and KRITSCH.' "Microbio1'/, typhi exanthematici (der Fleckfiebererreger), " Arch. Schiffs. Tropenhyg., xxvii, 1923, 49. (4] BRUCE. "Trench Fever. Final Report of the War Office Trench Fever Investigation Oommittee," Journ. of Hygiene, xx, 1921, 258. Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com 186 The Production of " Rickettsia" -.bodies w the Louse [5] BRUMPT. "Au sujet d'un parasite (Rickettsia prowazeki) des poux de l'homme, considere, it tort, comme l'agent causal du typhus exanthematique," Bull. Soc. path. exot., xi, 1918, 249. [6] BYAM (with otbers). "Trench Fever," London: Frowde, and Hodder and Stougbton, 1919. [7] COWDRY. "The Distribution of Rickettsia in the Tissues of Insects and Arachnids," Jour. Exper. Med., xxxvii, 1923, 431. [8) M'LEOD and BEVAN· BROWN. "The Technique of Blood-culture," Jom·n. Path. Bact., xxii, 1918, 74. [9] MELLo. "Some Researches on Rickeitsias and tbe lEtiologyof Typhus Fevers," Journ_ Trop. Med. and Hyg., xxvi, 1923, 24 (January 15). [10] NICHOLSON. "A Cytological Study of the Nature of Rickettsia in Rocky Mountain Spotted Fever," Journ. Exper. Med., xxxvii, 1923, 221. [11] NOLLER. "Zur Ziichtung des Schaftrypanosomas und der Schafiausrickettsia aus dem Schafblute," Berl. Thierarztl. Woch., 1923, No. 18 (Sonderabdr.). [12] WEIGL. "Die Beziehungen der X-Stamme zur Rickettsia prowazeki," ZeitschT. Hyg., xcix, 1923, 302. [13] WOLBACH, TODD and PALFREY. "The Etiology and Pathology of Typhus," Intern. League of Red Cross Socs., Geneva, 1922. [14] WOODCOCK. "Introduction to the Study of Hrematophagy," JOURNAL OF THE ROYAL ARMY MEDICAL CORPS, xxxvii, 1921, 321, 418. [15] Idem. "Are the Active Principles of Filter·passing and 'Ultra-microscopic' Viruses Living Organisms or Enzymes?" Op. cit., xxxix, 1922, 243. [16] Idem. '" Rickettsia' -Bodies as a resulfl of Cell-digestion or Lysis," op. cit., xl, 1923, 81, 241. EXPLANATION OF FIGURES. FIGS. 17 to 23.-" Rickettsia "-bodies from the excreta of normal lice. FIGS. 17 to 19, and 23.-Illustrating transitions between pigment-grains and" Rickettsia"bodies. R," Rickettsia "-bodies ; p, pigmentiferons masses and grains; Plo :6gs. 18 and 19, pigment. grain with distinct indication of bipolarity, the two ends being more deeply coloured; c, fig. 23, fragment of desquamated cell-cytoplasm. FIGS. 20 to 22. -Coccal and diplococcal forms of "Rickettsia "-body and their relation to the pigment. (Lettering as above.) Downloaded from http://jramc.bmj.com/ on June 17, 2017 - Published by group.bmj.com On the Modes of Production of ''Rickettsia''-Bodies in the Louse H. M. Woodcock J R Army Med Corps 1924 42: 175-186 doi: 10.1136/jramc-42-03-02 Updated information and services can be found at: http://jramc.bmj.com/content/42/3/175.c itation These include: Email alerting service Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article. Notes To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
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