INTERNATIONALJOURNAL OF SYSTEMATICBACTERIOLOGY, Jan. 1981, p. 82-87 Vol. 31, No. 1 0020-7713/81/010082-06$02.00

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Microevolutionary Change in the Human Pathogenic Treponemes: an Alternative Hypothesis DON BROTHWELL Institute of Archaeology, London WCl, England

Recent evidence from both archaeology and biology suggests that the taxonomy of the human pathogenic treponemes may be more complex than previously thought. An alternative evolutionary tree for the treponematoses is suggested.

During the past 50 years there has been grow- dum, is involved. Hackett (9),on the other hand, ing interest in the ecology of the human patho- considers the same range of evidence and as a genic treponemes. Not only have they been clas- result supports the following classification: Tre- sified on clinical evidence into a number of spe- ponema pallidum Schaudinn (1905)-venereal cies, but also theories as to their evolution since and endemic , pertenue Cas- Pleistocene times have been put forward. Evi- tellani (1908)-; “Treponema carateum” dence over the past decade, from both archae- Brumpt (1939)-. (Note: Names in quota- ology and biology, now seems to demand a re- tion marks are not on the Approved Lists of consideration of the microevolution of trepo- Bacterial Names [Int. J. Syst. Bacteriol. 30:225- nemes (or “treponemata”) of this kind. 420, 19801.) A variant of the latter classification For perhaps three or four centuries, syphilis is suggested by Hardy (ll),who accepts that the has been a subject of considerable epidemologi- differences between endemic and veneral syph- cal and clinical interest (16). Since 1905 (20), ilis are equally deserving of specific (or subspe- when was incriminated as cific) distinction, and therefore he would seem the causative agent of syphilis, the taxonomy to accept “T. endemicurn” (or “T. pallidum of the microorganisms producing the human endemicum”) as the causative agent of endemic treponematoses has slowly attracted attention. syphilis. Whichever side is taken in this debate, As Hudson (13) points out, the generic name of course, most authors accept that the taxon- Spirochaeta was earlier preferred by some med- omy of these pathogens can only be tentative, ical biologists, but after some controversial ex- and perhaps significant steps will be made when changes (19, 23), Treponema was accepted as in vitro cultures of these varieties are eventually properly in accord with taxonomic principles, studied. However, this does not mean that hy- although the American Medical Association did potheses concerned with the microevolution of not seem to give it official recognition in their these treponemes should not be advanced. journal until 1943. Moreover, whether the four treponemal patho- The treponematoses are comprised of four gens considered here are worthy of species, sub- distinct clinical entities: venereal syphilis, en- species, or varietal status, their evolutionary re- demic syphilis, yaws, and pinta (9,13-15). These lationships remain basically the same. But what divisions are made on pathological and clinical is their relationship to space and time? evidence rather than on any taxonomic relation- Previous evolutionary schemes. Although ships of the organisms themselves (Table 1). Hudson (13,14) and others have commented on Even electron microscopy has so far failed to the apparent association between the syphilis, reveal structural differences, although these yaws, and pinta treponemes and climatic-cul- pathogenic treponemes can be distinguished tural factors, Hackett (9) alone has constructed from others by having pointed ends with three a workable evolutionary tree for these microor- flagella inserted subterminally in a row (12). ganisms. Minor alternatives to the same basic Failure so far to demonstrate differences of eco- scheme are shown in Fig. 1, hypothesis A being logical significance in the microorganisms iso- preferred by Hackett on evidence available to lated in these four disease groups has resulted in him in 1963. On this overall medical information, differences of opinion as to whether more than he suggests that the pinta form was the fust one species is involved. Hudson (13), in partic- variant evolving from a basal treponemal stock ular, has argued that only one species, T.pal& (representatives of which do not occur in most 82 VOL. 31,1981 NOTES 83

TABLE1. Clinical characteristics of the four treponematoses (modified from Hackett [9]) Endemic Venereal Yaws Character Pinta s-mhilis smhilis Usual source of treponemes Skin anywhere Skin anywhere Buccal mucosa Genital and mucosal lesions Size of infectious area Large Large Small Small Duration of Infectiousness of individ- Many years A few months A few months A few months ual lesions Infectiousness of patients, Many years 3-5 yr 3-5 yr 3-5 yr including infectious re- lapses Latency" Absent Characteristic Characteristic Characteristic Lesions: Initial, site Exposed skin Skin of legs Mouth? Genital Generalized skin, extent Extensive Extensive Limited Moderate Genital, occurrence Unusual Scanty Scanty Frequent Buccal mucosal, occur- Absent Scanty or Moderate Scanty rence absent Palmar and plantar hyper- Absent Frequent Scanty Scanty keratoses, occurrence Bone, occurrence Absent Moderate Moaerate Scanty Juxta-articular nodules, Absent Frequent scanty scanty occurrence Heart, brain, and other Absent Absent Scanty and Moderate viscera, occurrence mild, or absent Congenital transmission Absent Absent Absent Present Age group for most infec- Children Children Children Adults tions " Latency in a communicable disease is a stage in its course in which there is evidence of such as seroreactivity but no clinically detectable active lesions. modern populations). By further mutation and fit both clinical and archaeological information divergence, yaws organisms evolved in humid, now available. Paleopathological discoveries in warm environments, and then endemic syphilis the last 10 years related to the question of tre- evolved from yaws as a means of adapting to ponemal microevolution and dispersal have been arid, hot climates. Venereal syphilis is seen as a principally as follows. late culmination of microevolutionary change, (i) Osteological evidence in the Marquesas linked with climatic change, decreasing endemic islands, Borneo (3), and Tonga (13) suggesting syphilis, denser settlement, more clothing, and infection by one or more varieties of Treponema perhaps even changing sexual behaviour. Will- confirms the previous claim of a yaws type of cox (24, 25) echoes this view in that he sees disease in the Marianas islands (229, and it now treponemal divergence occurring sequentially as looks certain that early Southeast Asian popu- a result of mutation and the selection of a path- lations had gradually extended the treponeme ological state best suited for the continuing range into the central Pacific. transmission from host to host in the particular (ii) Further studies on Amerindian skeletons environment. from North and Central America have estab- Some years ago, modification of Hackett's lished beyond reasonable doubt that treponeme original changes in the spatial distribution of the varieties in the Pre-Columbian New World (5) treponematoses through time seemed to me (2) included one which produced bone lesions dis- to be essential, as various archaeological discov- tinctive of a treponematosis. As some of these eries were casting some doubt on the interpre- cases are from arid zones in Mexico (4) and tations arrived at purely by extrapolating back Arizona (and also probably Peru) (26), trepone- into time from modern clinical evidence. Further mal differentiation was clearly adapting here to archaeological evidence leads me to suggest that hot and dry as well as to more humid climates the time has arrived for at least a consideration (as experienced by the Illinois and Florida Amer- of alternative hypotheses concerning trepone- indians) (17). Moreover, this also seems to dem- mal evolution, especially if they would seem to onstrate that pinta was not the only early New 84 NOTES INT, J. SYST.BACTERIOL.

HYPOTHESIS A HYPOTHESIS B

FIG. 1. Hypotheses A and B, as suggested by Hackett (9), to explain the microevolution of human pathogenic treponematoses.

World treponeme variety, and from the valley of modification of previous hypotheses is possible, Tehuacan in Mexico (1) there is clear evidence if not desirable. of a bone-changing treponematosis at least 2,200 From clinical evidence, it is established that years ago. To me, this is a very important point four main pathogenic varieties of Treponema which so far has not been considered in relation affect humans today. The probable Pleistocene to treponeme evolution. isolation of populations in such areas as New (iii) Although the Aswan project in Egypt and Guinea and Australia and the development in Nubia has resulted in large numbers of extra these communities of yaws-endemic syphilis dis- skeletons being available for study, there still eases suggest that some form of treponematosis remains no evidence of early treponemal disease has affected humans since at least late Pleisto- in Africa. cene times. If treponemes were carried into the (iv) Large numbers of skeletons continue to Americas by early Paleo-Indian groups (rather be excavated in northern Europe, and there is than having had a trans-Pacific entry into the still no evidence of treponemal disease until late New World), then again a Pleistocene antiquity medieval times (circa A.D. 1200 to 1500). A recent is suggested. On available archaeological evi- excavation at the site of the medieval church of dence, treponemes causing bone changes were St. Helen-on-the-Walls in York (J. Dawes, per- certainly present in eastern Asia by about A.D. sonal communication) would appear to substan- 500 and in the New World by 200 B.c., if not tiate other evidence from Chichester that, prior much earlier. It could be argued that the absence to Columbus, a bone-changing treponeme had of skeletal evidence of treponematosis in Africa arrived in northern Europe. might indicate that the less devastating condi- Discussion. Taking this new information in tion, pinta, was the only one affecting these conjunction with what is known of the biology communities until quite later on, but the alter- of modern treponemes, it would seem that some native one of an absence of pathogenic trepo- VOL. 31,1981 NOTES 85 nemes is equally likely. This argument similarly external area of the body. Even with T.pallidurn applies to Europe. If the pinta variant had been the skin offers an optimum temperature for the well distributed in parts of the Old World, it retention of infectivity (21). Further adaptive would seem to me very surprising if some, per- advantages of “T.carateurn” are that it is spread haps more isolated, groups of people did not by direct contact and possibly by an insect vec- display it today. I make this point because it tor and that it often establishes itself in child- seems relevant to the proper construction of an hood. alternative hypothesis concerning treponemal Experimental evidence is also relevant here. microevolution. It is possible that the pathogenic rabbit trepo- Turning to the New World, it is no longer neme, 7’. paraluis-cuniculi, has evolutionary possible to disclaim the occurrence of Pre-Co- links with the human varieties being discussed. lumbian treponematosis of a kind which left In view of this, it is interesting to note that, clear evidence in bone pathology (as defined by unlike the other three types, “T. carateurn” Hackett’s guidelines [lo]). As varieties of produces no infection in rabbits (ll),a fact Treponerna eventually existed in populations which might suggest a greater evolutionary dis- occupying both hot and humid as well as arid tance from T.paraluis-cuniculi. environments, there seems a case for accepting As far as the New World is concerned, then, the evolution of T. pallidurn and perhaps even I suggest that one can reasonably postulate the T.pertenue strains, although this is not to sug- occurrence in Pre-Columbian times of three gest that these early variants need be identical treponemes. In view of the present eastern Asian with the modern yaws-syphilis varieties studied evidence, it does not seem necessary to suggest mainly in non-Amerindian communities. As far independent evolution of all three forms but as the distribution of these parasites is con- rather to derive a basal T.pertenue/T. pallidurn cerned, it is significant that they clearly overlap stock from the areas which were to people the that of “T. carateurn” (pinta). In the case of Americas. This would explain the occurrence of Mexico, it is difficult to argue that pinta does bone-changing treponematosis in some Amerin- not extend into zones represented by the earlier dian communities of North America, well out- finds. A further point, and one which has been side the range for pinta. After this initial intru- neglected, is that “T.carateurn” occurs in com- sion of treponemes, there could have been 10,000 munities populated by those who are by no years or more of independent microevolution, means simply “remote jungle people” as is usu- with the eventual emergence of pinta as a tre- ally implied. Much of the area which is impor- poneme most adapted to survival in humans but tant in the evaluation of pinta was at the fore- with minimum damage to the host. front of cultural changes in the Americas. This In the Old World, with different human pop- same region was involved in the development of ulations and environmental factors, “T. cara- early agricultural societies and later of densely teurn” did not evolve. Instead, with the expan- populated and advanced empires. sion of the Classical World, the widening of trade It is thus difficult to avoid, from this New horizons, and eventually the Holy Wars, the World evidence, the need to construct an alter- treponemes were transferred beyond their nat- native hypothesis for the evolution of the path- ural ranges and met further adaptive challenges. ogenic human treponemes. Figure 2 gives a ten- It was for this reason that syphilis was late tative alternative to Hackett’s evolutionary tree. intruding into Europe, and the as yet rare me- It will be seen that the major difference is in dieval skeletal evidence suggests that changes positioning “T.carateurn” (pinta) as a final stage were demanded of the endemic form if it was to in the treponemal sequence rather than in a survive in northern cultures and climates. The basal position. As pinta has restricted distribu- adaptive strategy was to concentrate on adults tion in Amerindian groups and as it is found in and to rely on genital contact or congenital areas where advanced early societies have oc- transmission. curred and where evidence of bone-changing Conclusion. Prior to European voyaging in treponematosis has been found, it seems impor- late medieval times, then, there would appear to tant to view the condition in relation to these be evidence of three treponemes in both the Old other factors. The facts that the pinta treponeme World and the New World, with two forms being mainly causes skin lesions and is especially char- shared by both. It could be that the long period acterized by a long period of (but probably not of separation of some treponemal stocks led to great) infectiousness do not contradict this further microevolution, even if marked clinical scheme. One could argue, in fact, that “T. car- differences are not yet known. It may be signifi- ateurn” had become the most specialized form, cant in this respect that immunological differ- and at the same time more ideally host adapted, ences in these treponemes are now being noted in becoming so localized in the cooler, more at an intraspecific level (ll),and certainly this 86 NOTES INT. J. SYST.BACTERIOL.

FIG. 2. Alternative evolutionary tree for the treponematoses as suggested in this paper.

casts doubt upon the value of the present species care. Similarly, I appreciate information from Jean Dawes of names T. pallidum, T. pertenue, and cara- the York Archaeological Trust relating to late medieval Brit- “T. ish treponematosis. I should also like to record that, in the teum.” As Fig. 2 suggests, there may be six lines past, I have greatly benefited from information and encour- of Treponema which have been separated over agement from E. H. Hudson. The hypothesis presented here time and space, but how long yaws in New was discussed at a seminar in the Sub-Department of the History of Medicine at University College London during Guinea (7) and Africa (8) has undergone sepa- 1978, and I am grateful for the encouraging responses from rate evolution, or endemic syphilis in South- colleagues. west Asia (14) and Australia (9),remains to be seen. And what earlier varieties have been com- REPRJ” REQUESTS pletely replaced? Clearly, the taxonomy of the Address reprint requests to: Institute of Archaeology, 31- human pathogenic treponemes may be more 34 Gordon Square London, WClH OPY, England. complex than previously thought. Species names seem less importnat at this stage than attempt- LITERATURE CITED ing to relate the clinical and archaeological data 1. Anderson, J. W. 1967. The human skeletons, p. 91-113. In D. S. Byers (ed.), The prehistory of the Tehuacan with a satisfactory evolutionary scheme. Valley, vol 1. Environment and subsistence. University of Texas Press, Austin. I thank Arturo Romano of the Mexican National Museum 2. Brothwell, D. R. 1970. The real history of syphilis. Sci. of Anthropology for support and help in studying the impor- J. 6:27-33. tant collection of ancient treponematosis specimens in his 3. Brothwell, D. R. 1976. Further evidence of treponema- INT. J. SYST.BACTERIOL. NOTES 87

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