The Parasitic Theory of the Etiology of Carcinoma. BT ROSWELL PARK, A. M., M. D., BUFFALO, N. Y., Professor of Surgery, Medical Department, University of Buffalo *, Attending Surgeon, Buffalo Qeneral Hospital, etc. BEPRIHTED FROM Neto STortt JHetifcal journal for March 4, 189S. Reprinted from the New YorJc Medical Journal for March 1893. THE PARASITIC THEORY OF THE AETIOLOGY OF CARCINOMA.* By ROSWELL PARK, A. M., M. D., BUFFALO, N. Y., PROFESSOR OF SURGERY, MEDICAL DEPARTMENT, UNIVERSITY OF BUFFALO ; ATTENDING SURGEON, BUFFALO GENERAL HOSPITAL, ETC. In any discussion on cancer the question of its aetiology should always take precedence of that concerning its treat- ment, since the latter, to be both rational and effective, should be based upon the former. It is not my purpose at present to consider the numerous theories put forward in time past to explain its essential cause, but rather to invite vour attention to a resume of the latest and perhaps most fascinating explanation offered as to the prime cause of this dreadful malady. Just who is entitled to the credit of having first ad- vanced the hypothesis of its parasitic origin it would be hard to tell, but to two English surgeon-pathologists, Hutchinson and Paget, we are largely indebted for having advanced the a 'priori plausibility of such a view. In a * Read before the Medical Society of the State of New York at its eighty-seventh annual meeting. Copyright, 1893, by D. Appleton and Coswant, 2 THE PARASITIC THEORY OF memorable address some years ago the latter called atten- tion to the parasitic origin of most of the xylomata or woody tumors seen on so many trees, and ventured the pre- diction that an analogous parasitic origin would ere long be determined for many of the tumors met with in the ani- mal kingdom. That we now have a class of infectious granulomata, acknowledged by all, is not yet sufficient realization of such a prophecy. Virchow recognized as early as 1847 certain peculiar bodies noted in and between carcinoma cells, which he then supposed to be evidences of degeneration. Their true na- ture was not made out till 1888, when they were identified as belonging to the sporozoa, although he himself later (Virchow’s Archiv, Bd. xxxiii) suggested the possibility of their being psorosperms. Inasmuch as the present paper deals mainly with these organisms, it will be proper to stop here a moment to re- hearse a few statements concerning their nature and place in the animal kingdom. First of all, they are distinctly not bacteria, which are vegetable organisms, but belong to the protozoa or unicellular animal forms. The Gregarinidce are included in the suborder Endo- plastica and subclass Sporozoa, according to Leuckart, and are described as having ovoidal or spheroidal bodies, some- times with a segmental constriction, occasionally with one end beaked and carrying horny spines. They consist of a dense ectosarc and a softer endosarc, containing an endo- plast but no contractile vacuole. They are all essentially parasitic. They have neithe* oral aperture nor pseudopodia. They contain granular protoplasm with nucleus and nucleo- lus, and vary in size even up to a centimetre in diameter. The Coccidia form another subclass of the Sporozoa, are quite similar to the foregoing, but have a micropyle at one end. THE AETIOLOGY OF CARCINOMA. 3 According to another classification, the Sporozoa or Cj/tozoa are divided into four subclasses, as follows: Gre- garinidea (by some held to include the coccidia); Coccidi- idea or Microsporidia; Myxosporidia; Sarcocystidia or Sarcosporidia. But minutiae of classification aside, it is enough for our present purposes that the bodies in question are exceeding- ly minute forms of unicellular animal life. In 1878 Rivolta (Dei parassiti vegetali, Turin, 187S) and Bollinger (Vir- chow’s Archiv, Bd. lviii) recognized their parasitic nature and identified them as Gregarince ; and they gave to the lesions found in fowls and pigeons which so closely resem- ble molluscum the suggestive name epithelioma gregarino- sum. In 1880 Nedopil, Ilerisson, and others thought to characterize miliary carcinomatosis as an infectious disease. Neisser, in a study of molluscum contagiosum ( Vierteljahr- schft. f. Dermatol., 1888, xv, 553), distinguished between their'spores and better developed stages. lie only studied them in sections, his culture and inoculation experiments failing. He found them in greatest number in affected tis- sues, but also in uninjured cells and adjacent tissues. L. Pfeiffer described, also in 1888 (Zeitsch/t. f. Hygiene, 1888, iii, 3, and iv, 422), certain bodies met with in two cases of general carcinosis and one of sarcoma of the breast, and regarded them as belonging to the Sporozoa. He found them in the epithelial cells of a fresh, warm melanotic growth, and, studying their developmental stage, saw that it resembled closely the spore formation of the Micro- sporidia. (See also Die Protozoen als Krankheitserreger, Jena, 1890.) Darier, in 1889, observed certain bodies which he be- lieved to be coccidia in a hitherto undescribed skin disease to which he gave the name psorospermose folliculaire vege- tante (Annales de derm, et de syph., 1889, No. 7), and later, THE PARASITIC THEORY OF 4 with Wickham (Ctrlbl. f. path. Anat., i, 682), he attrib- uted Paget’s disease of the nipple to a coccidiuin which in- vades the skin. It would certainly seem as though, provided Paget’s disease of the nipple is a factor in the production of cer- tain mammary cancers, and that it is a true psorosper- mosis, the best conditions for a study of the parasitic nature of cancer would be met with in cases of dis- ease. Hutchinson, Jr. [Trans, of the Path. Soc. of London, xli, 1890, 214), and Wickham (Archives de m'ed. experimentale, 1890, i, 1 ; Annales de dermat. et de syph., 1890, i and ii) have both studied the matter carefully, the latter with seven cases. Wickham describes three stages of the disease after invasion: 1. Thickening and disorganization of the epidermis and inflammation of the corium. 2. Elevation of the horny cells, lively escape of leuco- cytes which crowd aside the epithelial cells, proliferation of the rete mucosum, and the epithelium of the sweat, seba- ceous, and milk glands, and Anally extensive infiltration of the cutis. 3. Stage of true carcinomatous growth from both the superficial and glandular epithelium. In the beginning the parasites appear with or without nuclei, later surround themselves with a double membrane, while the contained protoplasm differentiates itself into a number of granules, and thus is formed what he calls a sporiferous cyst. These he found not only in the epider- mis, but also in various gland ducts and in the pearly bodies. In spite of failure to cultivate or inoculate, Darier and Wick- ham did not doubt their parasitic as well as their pathogenic character, and felt that under their influence not only epi- thelioma but other forms of carcinoma might develop. THE AETIOLOGY OF CARCINOMA. 5 Malassez and Albarran found in two epitheliomata of the jaw peculiar bodies having striking resemblances to the coccidiaso often found in the livers of rabbits (Soc. de biol., April, 1889), and Vincent bad a similar experience (Annales de micrographie, 1890, ii, p. 10). Thoma found in the nuclei of many cancer cells peculiar bodies so different from other human cells that he consid- ered them parasitic and thought they might be encapsulated coccidia (Fortschrit. d. Med., 1889, p. 413). Sjorbring, of Lund (ibid., p. 529), studied their life history and found free extracellular as well as intra- cellular and spore forms, and called attention to their re- semblances to the organisms which produce pebrine in silk- worms. Steinhaus examined thirty cancers from various sources, sometimes finding these bodies, sometimes not, but consid- ered them parasitic when present (Virchow’s Archiv, Bd. cxxvi, p. 533). Hacke described in 1890 four cases of cancer in which he found coccidia in and among the cells, varying in size from two to fifty microns, the smaller intracellular the larger extracellular, spherical, encapsulated, the capsule very highly refractive. Within the cell they often appeared as in a vacu- ole, owing to the shrinking of the surrounding protoplasm during hardening. As they grew they seemed often to fill and destroy the cell (Soc. de biol., Nov. 8, 1890). Van Heukelom, of Leyden, studied some two hundred tumors, and came to conclusions essentially those of Thoma and Sjorbring (Ctrlbl. f. path. Anat., 1890, p. 704). But these views were not accepted without lively dis- pute. Russell, Piffard, Schiitz (Microscopische Carcinombe- funde, Frankfort, 1890), Torok, and Tommasoli, among oth- ers, after minute study claimed that these so-called coccidia were only altered cells, simple masses of chromatin, products 6 TIIE PARASITIC THEORY OF of degeneration, etc. Ivlebs made implantation experiments without success, and these bodies underwent no change or increase. Duplay and Cazin, finding no such changes as they thought coccidia in their evolution should evince, con- cluded these bodies to be of degenerative origin and to re- sult not only from cells hut from mitoses. Ribbert made a most exhaustive study (Deutsche med. Woch., 1891, p. 1179) of cell inclusions in cancer, and con- cluded that his results did not permit his acceptance of the parasitic theory, and therefore held to the degenerative view of their nature. Ramsay Wright [Ctrlbl.f. allgem. Path., 1890, No. 11) and Russell [Brit. Med. Jour., 1890, p. 1297), while not so opposed to the parasitic view, referred these bodies to the saccharomyces. Moreover, the latter found among them certain granules which have an affinity for fuehsin, the so- called “ fuchsin bodies” (Fuchsinophile), which are also to be found in other pathological and normal tissues. Cornil (Journal de Vanat. et de physiol., 1891, No. 1) and Idansemann (Virchow’s Archiv, Bd. cxxiii, p. 356, 1890) think it possible to mistake for coccidia or their spores va- rious stages of karyokinetic cell division. Stroebe (Ziegler’s Beitrage, 1891, xi, lift. 1) and Stein- haus (Ctrlbl.f. allgem. Path., 1891, No. 2) feel compelled to admit the sporozoan nature of these bodies, but are not convinced that they are the true cause of cancer. Sudakewitsch (Wratsch, 1891, No. 49) decides that “a carcinomatous growth of epithelium in man, as well as in other animals, may follow the immigration of parasites belonging to the Sporozoa” [Med. Mews, Jan. 7, 1893, p. 20). While all these studies concerning coccidia were in prog- ress the bacteriologists wrere by no means idle. Even in 1887 Scheurlen published his address on the aetiology of THE .ETIOLOGY OF CARCINOMA. 7 cancer (Deutsche med. Woch., 1887, No. 48, p. 1033) and described a small spore-bearing bacillus, slightly motile, easily stained, bleached by alcohol, but shown by Gram’s method and its spores by the ordinary stains. He found that it grew on agar, on potatoes, and in broths. This ba- cillus was difficult to find in sections, and its spores were found in only about one cover-glass preparation of cancer juice out of three. He also described the appearance of the spores in Unstained preparations in words which almost make one who reads them now think he mistook coccidia for spores. Hut he cultivated his bacillus and injected it into the mammary glands of dogs and found,„as a result, tumors whose most notable characteristic was cell prolifera- tion. His claim to priority, by the way, was hotly contested by Freire (Deutsche med. Woch., 1888, No. 1, p. 14). In a discussion following the reading of Scheurlen’s pa- per, A. Fraenkel expressed himself as believing that cancer wras a parasitic disease, but that its prime cause might be- long to a class of organisms then little or not at all known, and not bacteria. In a critique on the so called cancer bacillus Baumgar- ten makes some very sensible remarks, which should be carefully noted by those interested in the subject (Jahres- bericht der Mikroorganismenlehre, 1887, iii, p. 273). He holds that cancer, like all true tumors, is an abnormal con- dition of original embryonal elements, according to views enunciated by Cohnheim, and that, according to these, there is neither need nor room for a bacillus. He argues that we have as rrtuch reason to expect, e. g., a teratoma ba- cillus. Or, supposing that this theory be held only to con- cern a certain number or proportion of cases, he still re- gards the hypothesis as untenable, since it has no analogies either in pathological mycology or parasitology. For, so 8 THE PARASITIC THEORY OF far as we know, he maintains, all other micro-organisms cause, instead of cell and tissue proliferation, rather exu- dative inflammation and tissue necrosis, the later prolifera- tion being protective when present. I may, perhaps, be permitted here to digress for a mo- ment to give an illustration of the way in which Cohnheim’s views may be made to suit any purpose. The writer of an editorial in a recent number of the Journal of the American Medical Association (Jan. 14, 1893, p. 49) epitomizes them to this effect: that they constitute a theory that “ tumors are due to exaggerated growth of primary remnants of em- bryonal folds gone astray in various parts of the body,” and states that it has been severely criticised by enthusiastic believers in the parasitic origin of carcinoma, although so good a bacteriologist as Baumgarten, as just stated above, falls back on it as an a -priori argument against this origin. But this same writer goes on to say that it has been shown that embryonal folds exist in all inulticellular organisms, and that, consequently, invertebrates would theoretically be just as liable to various forms of tumors as the higher animals ; “ but such a thing as carcinoma has never been de- scribed in the inferior animals rip to the present time, although they are very liable to parasitic tumors of various kinds." (Italics mine.) Here he shows a lamentable lack of knowl- edge, since veterinary and pathological records and mu- seums are full of instances such as he denies, while that prince of comparative pathologists, J. Bland Sutton, has described numerous specimens which have come under his own observation. Hence the force of such argument is at once lost. Scheurlen’s position was also speedily attacked from other quarters—by Senger, A. Pfeiffer, van Ermengem, Rosenthal, Sanquirico, and Sanarelli (Biforma med., 1888) —all of whom insisted that his cancer bacillus was widely THE ETIOLOGY OF CARCINOMA. 9 diffused and harmless, while Rosenthal showed that it frequented the nipples of healthy women and young girls. Schill, who worked at this subject for six years, ob- served something which he described as consisting of two colored (stained) points connected by a hyaline body, which he found in large numbers in various cancers, and which he cultivated and considered a fungus (Deutsche med. Woch., 1887, No. 48, p. 1034). A little later Nepveu (Gazette hebdom. de med. et de chir., 1888, No. 18) found all sorts of organisms in breaking down and ulcerating cancers; and Hauser (M'unchener med. Woch., 1888, No. 12) and Markara (Deutsche med. Woch., 1888, No. 31) contested Scheurlen’s hypothesis on patho- logical grounds. Scheurlen, however, rejoined (Deutsche med. Woch., 1888, No. 30), with the aid of Francke, Lampiasi-Rubino, and Magalhaes, and fought for the acceptance of his con- tentions, hut apparently in vain, since to-day they are nearly forgotten. Fatichi (II bacillo di Scheurlen e un saprofita della pelle, Firenze, 1889) cultivated from skin of normal individuals a bacillus which morphologically, in cultures, and in every other way, resembled Scheurlen’s. It is also identical with Bordoni-Uffreduzzi’s Bacillus epider- midis. On the other hand, Koubassoff professed, in 1890 ( Ctrlbl. f. Bakteriol., vii, 317), to have found in cancerous tumors a bacillus different from Scheurlen’s, which, when implant- ed in animals, caused disseminated nodules, histologically resembling cancer, and final death. No one seems to have confirmed his researches. Balance and Shattuck (Proc. of the Royal Soc., xlviii, 1890, p 392) reported only failures to find any organism in cancers (also Brit. Med. Jour., 1887, Oct. 29, p. 929). Since 10 TI1E PARASITIC THEORY OF 1890 scarcely an article has appeared on the subject of can- cer bacilli, and the attention of all workers in this field seems to have been concentrated on the Sporozoa which are alleged to cause the disease. Inasmuch as everything now points in their direction, it will be worth while to refer briefly to methods for their detection. Pieces of cancer tissue should be preserved in Flemming’s solution, which seems to cause the organisms to appear to better advantage. The stain which gives the best result is the so-called Ehrlich-Biondi triple stain, whose formula is simple, but whose happy combination seems diffi- cult. The directions given are to dissolve— Methyl green 0’5 in distilled water.. . . 100; Acid fuchsin 0*5 in distilled water. ... 40; Orange 2'0 in distilled water *.. 200. These solutions to be mixed and filtered before use. Sec- tions are left in it for twelve hours, then washed, dehy- drated, cleared, and mounted. With this stain the nucleus of the cancer cell becomes green, the protoplasm orange-red, the nucleus of the parasite red, and its protoplasm light- blue. Working with it, Puffer, Walker, and many others have not hesitated to pronounce the included bodies to be true parasites. At a meeting of the London Pathological Society held December 20, 1892 (Lancet, December 31, 1892, p. 1496), Jackson Clarke described a case of epithelioma of the nose which abounded in unmistakable psorosperins. To be sure, coccidia with stain-resisting capsules were not found, but every other stage of rabbit’s coccidia was represented. The idea of degeneration was negatived by beautiful nuclear figures and by clear evidence of biological processes. Con- jugation and amoeba formation were observed. Many large psorosperins lay within the epithelial cells, whose capsules were seen to possess perfect radial striation. lie called at- -THE .ETIOLOGY OF CARCINOMA. 11 tention to the fact that most writers had failed to distin- guish the amoebae from leucocytes, and stated that the amoeboid stage of the parasite’s eyclic existence afforded the key to the malignancy of cancer. He had found clear evidence of the following processes : 1. A single psorosperm, or one formed by conjugation of two, becomes changed by formation of a reticulum which extends outward from the nucleus till it fills the whole cell. 2. The reticular plasmodium, usually surrounded by a capsule, consisting of the dead and distended host cell, breaks up into rounded segments which keep the reticular structure, and stain faintly purple with acid hsematoxylin. 3. Within some of these daughter psorosperms fine filaments of chromatin appear. By breaking up of the same, amoeboid cells are set free, which multiply by division and are distinguished from leucocytes by treatment with acid haematoxylin. 4. These amoeboid bodies make their way in vast num- bers into connective-tissue spaces*-beyond the epithelial part of the growth. In passage they separate epithelial cells and thus facilitate epithelial down-growth and detach- ment of small groups of cells. A considerable degree of inflammation is caused by this tissue invasion, with results similar to those seen in inflammatory papilloma (e. g., mu- cous tubercles)—i. e., extension of epithelial growth, new formation of vessels, etc. 5. Later most of the amoebae disappear and the resultant inflammation subsides. A small proportion enter epithelial cells and can there be detected, with care, even in their non- nucleated stage. Those that remain are by this time the somewhat familiar intracellular psorosperms, most abun- dant in and about cell nests. Arriving at a certain stage, the cycle is renewed and a fresh extension of growth takes 12 THE PARASITIC THEORY OF place, sometimes with detachment of venous or lym- phatic emboli and resulting metastasis. Clarke insisted that the cyclic life of these parasites and their reaction on the tissues could account for all the phenomena of cancer. He remarked further that these amoeboid sporozoa were identical in structure with some of the plasmodia met with in ague. The cyclic cause of the disease corresponds with the cyclic life of the parasites. From a psorospermosis of the spleen and lymph nodes it is but a step to leucocythae- mia and sarcoma. In a cystic scirrhus he had found the cream-like contents of the cyst to consist wholly of amoe- boid psorosperms. Apart from the mystery of the path (and source) of infection, the nature of the disease is now revealed. During the discussion following Clarke’s remarks Mr. Shattuck said that though the former had described one cycle of growth in man, it was quite possible to have another and differing cycle outside the human organism—e. g., in rabbits, where the appearances were often different. He himself inclined to the view held by Metschnikoff. We can not infect lower animals with cancer from human be- ings, hut are seeking now how to cultivate the parasite and then inoculate animals with it. Instances of successful inoculation are at present as rare as the occurrence of cysti- cercus in man. That indefatigable worker, Metschnikoff, has recently taken part in this discussion by an argument entitled Re- marks on Carcinomata and Coccidia (Revue generate de sciences pures et appliquees ; Jour, of the Am. Med. Assoc., loc. cit.). He states that these so-called parasites have the greatest analogy with the coccidia; he contrasts carcinoma with coccidiosis of rabbit liver, and sees between them many points of striking similarity. Coccidiosis is an infectious THE AETIOLOGY OF CARCINOMA. 13 parasitic disease, not contagious, its lesions nodular in ar- rangement, composed of proliferating epithelium of biliary ducts, the cells containing the parasites or Sporozoa whose rble is now not denied. So, too, epithelioma is character- ized by epithelial proliferation ; is not contagious, is nodu- lar, and its cells contain peculiar bodies which certainly present most accurate resemblances to Sporozoa, and he concludes the researches reported to be sufficiently reliable to serve as a starling point for new studies. The most elaborate contribution to the subject is that of Podwyssozki and Sawtschenko, of Kiev, entitled Para- sitism in Cancer, with Description of Certain Parasitic Organisms found in Cancerous Tumors (Ctrlbl. f. Bak- teriol., 1892, xi, pp. 493, 532, 559). In their monograph they have considered at length the history of the subject. They also call attention to the fact that a multitude of analogies offer where epithelial proliferation is due to the irritation produced by parasites—e. g., besides the changes in the rabbit’s liver due to the Coccidium oviforme, the le- sions in the intestinal mucosa of many animals, with inflam- matory infiltrate and neoplastic growths caused by the Coc- cidium perforans. (Full details of these and similar lesions are to be found in L. Pfeiffer’s Die Protozoen als Krank- heitserreger.) To even summarize their most interesting paper would be to exceed the limits of this one ; but some of their statements must be here epitomized or quoted. For example, this : “ The more pronounced the intensity of car- cinomatous proliferation, the more numerous the mitoses in the cancer cells ; the softer the tumor and more marked its tendency to degeneration, the greater the number of parasitic organisms in its cells. They are best to be found in medullary growths, and especially in those of the breast; in epitheliomata of the lips and face they do not abound.” 14 TIIE PARASITIC THEORY OK They studied these sporozoa in more than twenty cases of miscellaneous cancers, and looked carefully to find in them the same biological characteristics that are found in bodies whose protoplasmic life history is unquestioned, such as evidences of cell division, holding that the dispute concerning their true nature, as illustrated by the papers of Steinhaus and Stroebe, was due to the failure of previous investigators to produce convincing evidence thereof. They find the sporozoa either inside the cells or in the in- tervening lymph spaces, and furnish some beautiful chromo- lithographic reproductions of their specimens. These bodies consist of cyst-like cells (sporocysts) with semilunar nuclei, which undergo fission, their progeny escaping and becom- ing disseminated by the lympli paths. They consider it probable that the parasites display a symbiosis or commensalism with the epithelial cells. They leave open the question of just what part the coccidia play in the aetiology of cancer, declining to express convictions until inoculation experiments with cultures shall be made possible. (The experiments of Delepine, Brit. Med. Jour., May, 1891, make it probable that this happy day is not far off.) That we have here to do with a true parasitism they do not doubt. Or, to put it in their own words, “ In a question of such extreme difficulty, so acknowledged by zoologists and specialists, as the determination of species of sporozoa, it will be the most sensible thing to ‘go slow’ (zuruckhalten); for the immediate present it is enough if we can ascribe them their proper place.” Finally, Foa, of Turin, described and figured, in August of last year (Ctrlbl. f. Bakteriol., 1892, xii, No. 6. p. 185), certain bodies found in and about cancer cells which stained with hsematoxylin and showed marked variations in size and configuration, whose evolutionary phases, appearances, segmentation, and behavior to stains all stamped them as parasites. He, however, hesitated to insist that their pres- ence was more than accidental. Foa’s publication, in which he criticised some of Pod- wyssozki’s statements, has provoked a very recent rejoinder from the latter, in which he reiterates his former statements and views, and promises further corroborative evidence in the near future (ibid., No. 16, p. 551). Herewith is concluded a necessarily incomplete, because brief, summary of our present knowledge bearing on one of the most important topics now or ever before our profes- sion. W hile the parasitic theory is by no means new, the facts which tend to substantiate it are of very recent dis- covery—so recent, in fact, that it would be unseemly to ac- cept them as all-sufficient. Obviously they can but consti- tute a mere foundation upon which we may hope to build. The other all-important yet subsidiary topics of the geo- graphical distribution of cancer, and the influence of sex, age, part involved, civil and sanitary condition, injury, heredity, state of nutrition, and of preceding benign growth, must be constantly borne in mind. Many apparent contra- dictions must be explained, many conflicting statements reconciled. The proper position for the real student, it would seem to me, is in the middle ground, between skepticism on the one hand and credulity on the other, working and waiting for the light that we have great reasoff to eagerly expect, and probably from the direction indicated in the course of this paper. For my own part, I can not help feeling that we are on the eve of great discoveries in this matter, partly, perhaps, because I have for years had a growing conviction that can- cer—and syphilis, too—were parasitic diseases, due to either unfamiliar or yet unknown organisms, and that some new technical method, or some new application of old methods, THE AETIOLOGY OF CARCINOMA. 15 16 THE ./ETIOLOGY OF CARCINOMA. would ere long furnish the key to the mystery. Whether we have been recently supplied with this by the investiga- tors quoted above is as yet uncertain, though probable. IIow anxiously impatient, yet sanguine, I am you may bet- ter appreciate when you recall that my home is (in western New York) in a limited area, where the death-rate from cancer is greater than in any other part of our continent. REASONS WHY Physicians Should Subscribe FOR The New York Medical Journal, Edited by FRANK P. FOSTER, M. D., Published by D. APPLETON & CO., 1, 3, & 5 Bond St 1. 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