The Genesis and Collapse of Third Millennium North Mesopotamian Civilization H. Weiss; M.-A. Courty; W. Wetterstrom; F. Guichard; L. Senior; R. Meadow; A. Curnow Science, New Series, Vol. 261, No, 5124 (Aug. 20, 1993), 995-1004. Stable URL: hhup//links jstor-org/sici?sici~0036-8075% 28199308207 293 %3A261%3A5124%3C995%3ATGACOT3E2.0,CO%3B2-4 ‘Your use of the ISTOR archive indicates your acceptance of JSTOR’s Terms and Conditions of Use, available at hhup:/www.jstororg/about/terms.html. JSTOR’s Terms and Conditions of Use provides, in part, that unless you have obtained prior permission, you may not download an entire issue of a journal or multiple copies of articles, and you may use content in the JSTOR archive only for your personal, non-commercial use. Each copy of any part of a JSTOR transmission must contain the same copyright notice that appears on the screen or printed page of such transmission, Science is published by American Association for the Advancement of Science, Please contact the publisher for further permissions regarding the use of this work. Publisher contact information may be obtained at bup:/svww jstor.org/journals/aaas.hual. Science (©1993 American Association for the Advancement of Science ISTOR and the ISTOR logo are trademarks of ISTOR, and are Registered in the U.S. Patent and Trademark Office. For more information on JSTOR contact jstor-info@umich.edu, (©2003 JSTOR hupslwww jstor.org/ Thu Oct 9 02:08:28 2003WB ARTICLES The Genesis and Collapse of Third Millennium North Mesopotamian Civilization H. Weiss, M.-A. Courty, W. Wetterstrom, F. Guichard, L. Senior, R. Meadow, A. Curnow ‘Archaeological and sol-stratigraphic data define the origin, growth, and collapse of Subir, the third milennium rain-fed agricuture civilization of northern Mesopotamia on the Habur Plains of Syria. At2200 B.C. a marked increase in aridity and wind circulation, subsequent to a voleanic eruption, induced a considerable degradation of land-use conditions. After {our centuries of urban life, this abrupt climatic change evidently caused abandonment of Tell Lelian, regional desertion, and collapse of the Akkadian empire based in southern Mesopotamia. Synchronous collapse in adjacent regions suggests thatthe impact of the abrupt climatic change was extensive, ‘The origins and early history of southern Mesopotamian civilization, the third mil- lennium B.C. itrigation-based cities and states of Sumer and Akkad, have been a ‘major archaeological rescarch enterprise for the past century (I, 2). Recently, archaco- logical inquiry has returned to two poorly inderstood_ questions that fist attracted attention 50 years ago. The first is the problem of secondary state formation, or ‘when, how, and why the prestate societies of regions adjacent to pristine civilizations were transformed into state-level societies 6-6). The developmental history of Sum- e's northern neighbor, Subir, or Subart, the rainfed cereal agriculture Habur Pains of northeastern Syria (Figs. 1 and 2) (7, 8), provides a means to examine these ques: tions. The second problem is state collapse, cor when, how, and why stable or expanding carly civilizations suddenly disintegrated and, after a period of instability, were re placed by new state organizations, often controlled by new ethnic groups (9, 10). ‘The sudden collapse of the Akkadian em- pire at ~2200 B.C, (11) is the earliest historical example ofthis problem. In this article we present archaeological and climatic data that define four stages for state formation, consolidation, imperializa- tion and collapse of Subir, and its dynamic nteraction with southern Mesopotamia that resulted in the disintegration of the Fr Wess and A Gurow ae wih te Projet, Depriment of Near Ease Languags {Gateatios, Yate University, Now Haven, CT O6S2D~ 7425. Mv. Couty sw Uri do Raerche assoc 723, Caro Natonal de Pochorobe Scere. La Galore diycrioge ef de Gaochimie ecooiue, Univorsis do Part Sus. F-01405 Oreay, W. Water Som ih bo Haverd Botrcal Mau, Car fridge, MAG2ta9.F Gch ew he Cote de Featios Radu, Laborato Mido Caro Na Teno Recherche: Saettave-Cone SEE Bomique, Aver. do Ia Torso, F190 Gir ‘eto Sort the Deparment of Antvoplooy, Unworly of zona. Tutsan AZ 89716 Fe Moadon Is wih he Zooarchaeoigy Labora, Peabody Mr eum, Hara Uniersy, Cambadge, MA 02138. no SCIENCE + VOL. 261 + 20 AUGUST 1995 ‘Akkadian empire. Moch of the data are derived ftom Tell Leilan, one of the three large chitd millennium cities on the Habur Plains (Fig. 3). This site occupied 75 to 100 hectares at maximum size and was dominat- ed by a I5chectare Acropolis that today Fes 201m above plain level. Occupied from the mid-siath millennium B.C., Tell Jan became a major centr in the mid-t Fig. 1. (A) Syr0-Mesopotamia, 2600 to £200085.C, Major urban centers of southern Mesopotamia. (Sumer and Alka) and Habu Pains (Subi), and adjacent anciont toponyins. Arrows indicate tribal pastoral ‘st Amorie (Sumerian MAROU) seasonal ‘onth south transhumance inferred betore Habur hiatus 1 and subsequent move: ‘ment down the Euphrates and Tris food: plains. The Repeller of tho Amonios wallof fortesses was constructed ~ 2054 to 2090, BC. from Badighursaga to Simudar to Control Arnie ifitation. (B) Modem po- Iitcal unis of southwest Asia and location (of Tell Leilan in Syria 995millennium B.C. and the political capital of the region in the early second millenni- um BC. (12, 13) ‘We conducted excavations in eight Tell Leilan horizontal exposures and soundings through stratified deposits, which yielded architectural, ceramic, faunal, and floral data. A series of 26 conventional and ac- celerator_mass spectrometry radiocarbon dates were derived from seed and_ wood ‘samples from the Tell Leilan Acropolis and Lower Town South residential area (Table Tand Fig. 4). In addition we conducted two regional surveys that illuminate regional settlement patterns for the genesis and col- lapse of Subir’s third millennium urban settlement. Additionally, we studied datable, stratigraphic units sealed below chird Tennium occupations within 6-m-deep trenches at six loci at the perimeter of Tell Leilan. The micromorphological and phys- ‘cochemical properties ofthese units define alterations in hydrologic regime and soil ‘conditions diagnostic of significant climatic changes. To correlate geological events and social responses within the archaeological record, we present dated regional socioeco- ‘nomic and climatic data. These data define the major effects of an abrupe climatic change at ~2200 B.C., namely imperial collapse, regional desertion, and large-scale population dislocation. ‘Stage 1—Secondary State Formation From the fist settlement in the sixth rnil- lennium B.C. until the 26th century B.C., Tell Leilan was a small agricultural commu- nity typical of disperse settlements in the rain-fed north Mesopotamian plains (14). During the Tell Leilan Illd period (~2600 to 2400 B.C), settlement patterns on the Habur Plains ‘and the adjacent Assyrian steppe were radically altered with the sud- den emergence of indigenous state-level society, as seen in the large planned city at Tell Leilan and the reorganization of setle- iments across the region. Settlement at Tell Leilan expanded more than sixfold within 200 years; the city grew from a 15-hectare Actopolis-based settlement, to ~100 hect- ares comprising the Tell’ Leilan Lower Town (excavation operations 2, 3, 5, 7, and 8) and extended settlements 0 the ‘west (excavation trench D3) and east (ex- cavation trench E) (Fig. 3). \\\ \ . \ Excavations in the Lower Town South (Operation 5) indicate that this new Tell Leilan settlement was carefully planned on previously unoccupied virgin soil. The set- tlement included a straight. sherd-paved street that was 4.75 m wide. On each side of the street was a mudbrick wal, behind which stood domestic structures that opened only onto alleyways; long wall Perpendicular to the street probably delim- ited residence or property lines. A limited sample of faunal remains (total of 73) from the lowest strata of the Lower Town indi- cates that the inhabitants exploited almost ‘equally pig (33%), sheep and goat (32%), and cattle (29%) during this period. Excavations on the Tell Leilan Acropo- lis reveal tha the simple village economy of the 29h to 27th centuries B.C. was re- placed by a structured economy based on central collection and storage-and-redistr- bution. In an area previously occupied by small-scale domestic architecture, a block of rectangular storerooms (larger than 200 rm?) was constructed. The receipt and dis- tribution of stores was in the hands of a central administration, as reflected in. 188 broken door and jar sealings of clay re- twieved within the storerooms, The eylinder WH Fig. 2. Habur Plains, Norheast Syria, urban settlement system at 2600 0 £2200 B.C. and sites discussed in ne text. Circles indicate probable areas (of agicuture and herding sustaning each city. Diagonal lines are Clovation =500 m above ‘sea level, dotted lines are modern rainfall Medium circles are sites atu 2, ‘sohyets (n millmoters). Large circles are sites of 75 to 100 hectares, SCIENCE + VOL.261 + 20 AUGUST 1995 of 25 to 50 hectares. Small holo circles are Sites less than 10 hectares. Tephra deposits have been retrieved trom Tell Lolan, Tell Bager, Tel Nasran 1, Tell Nasran 2, Abu Hgeira 2, and Abuseal impressions on the sealings are local Subarian-style imitations of the Early Dy- nastic II-Ila iconography of banquet scenes cof contemporary southern Mesopotamia (15). These suggest that northern states ‘emulated southern administrative iconogra- phy to legitimize nascent state administra- tive and redistributive power (16). This north-south cultural contact followed a 300-year period of isolation from each oth- et. The reasons for the period of isolation and the sudden reestablishment of contact remain to be determined. Charred plant remains recovered through flotation suggest that large quanti- ties of cereals were processed nearby in preparation for storage. The flotation sam- ples consisted of cereal processing by-prod- ucts, primarily inedible portions of the ce- real head (number of samples, n = 1867; lume bases, glumes, and rachis segments) of barley (Hordeum vulgare), emmerwheat (Tritictem dicoceum), and durum wheat (Triticum duu), followed by the seeds of field weeds (n = 733), and small quantities of cereal grains (n = 112). This combina- tion of materials matches the by-products of sieving and possible hand-sorting of tradi- tional cereal processing (17). After the Tell Leilan cereals had been threshed and win- nowed in the fields, they were apparently delivered to the Acropolis where they were cleaned before storage. Climatic deterioration during this period conditioned the formation of Subarian states and the southern Mesopotamian role in this process. For at least one century before this period, regular alluviation is documented by massive sandy loam deposits that are intensively bioturbated. The pres- ence of soils with a high moisture content at the wide active flood plain enhanced cereal production in the Tell Leilan region. During period Illd, however, climatic con- ditions are marked by increased seasonality of water discharge, evident by the accumu- lation of coarse textured alluvial deposits that were eroded from the Tur Abdin mountains by torrential rains. More abun- dant pedogenic carbonates in the soil sam- ples and changes in soil structure indicate that soil water reserves became reduced and evapotranspiration increased. The in- creased irregularity in Tur Abdin stream flows suggests that precipitation on the Anatolian plateau was reduced as well. The flow of the Euphrates as far south as Sumer would have declined, but it is difficult to quantify reductions (18-20). This climatic deterioration in northern Mesopotamia may be related to the rapid global aridifica- tion initiated at ~5000 B.P. (21). The centrally administered urban econ- mies and mixed land use strategies that developed in period Illd may have present- ed adaptive advantages by facilitating max- BUNS Fig. 3. Topographic map ‘of Tell Lelian, showing ar- eas of excavation. Con. tour intervals are 1 rm, Leta radocoonoaie —8.c. ets, outnum indus FBoay SRS EER ay Too) ‘lt Babe -“ bbin-Larsa, 1000 or ae ‘ats a Hereppen 2100 a! _ oa 220 ~ A (open :4) ‘kad 22 R mee (Creepenst) 55 Fa0 — om rai 2 E Z2400 161 oe CE ee atu iil 8 & b x00 © eta ii Mare Utan Bit mw ms) doco arpa ZELG| | [om Seen a 6654 zs zoo er fe 0 ia amet ae 000 wv late Uruk Early Foam Fig. 4. Thicd millennium B.C. Southwest Asia chronology. Vertical lines are calibrated ranges + 1.80 in years B.C. of Tell Leiian radiocarbon dates for periods illc through IIb, horizontal lines are calibrated weighted averages, Ebla occupation periods define proto- and early historic chronol ‘ogy for northwest Syria. Leilan ceramically defined periods are subdivided for operation 5 ‘occupation phases. Dates for third millennium historical periods in southern Mesopotamia have ‘an uncertainty of 120 years (67); ED, Early Dynastic, Indus Valley periods are radiocarbon-basec estimates (74) SCIENCE * VOL.261 * 20 AUGUST 1993 997scammers mum agricultural production under. in- creased variability of rainfall (22). The sudden growth of Tell Leilan, Tell Mozan, and Tell Brak, each 75 to 100 hectares, transformed the Habur Plains into an urban landscape dominated by three equidistant centers with approximately equivalent ter- ritorial control extending up to 25 km around each center (Fig. 3). A three-tiered or four-tered hierarchy of settlement opti- mized agroproduction and transport in the Tell Leilan region (23). These changes in sertlement and political organization at Tell Leilan were part of a regionwide process of state formation and urbanization. Centers such as Tell Mozan, Tell Leilan, Tell al- Hawa, Nineveh (Ninua), and Tell Taya, developed 50 to 80 km apart, at locations where rainfall and soil fertility were most favorable. In the south, Sumer was also trans- formed simultaneously by interaction with Subir. The first Sumerian palaces appeared at this time, in the late Early Dynastic If to Early Dynastic Illa periods, in at least seven ‘major cities. The transition from temple to secular rule marked a radical realignment of intemal political structures, and was per- haps in part a response to reductions in Euphrates stream flow. The model for this transition may have derived from Sumerian contact with Subir (24).. ‘Stage 2—Consolidation of State Power ‘The consolidation of a complex state admin- istration in the cities of Subit is marked at Tell Leilan during the Ila period (~2400 to 2300 B.C) by the construction of a 2-mewide defensive wall around the Tell Lean Acrop- oli, its storerooms, and administrative build- ings, and by the appearance of numerical notations, based on circles and vertical lines, upon the’ rims of large cereal storage vessels (6). State organizational change in this period is also documented by retirement of fine craft ‘incising on ceramics, which is labor-inten- sive, and the fist appearance of mas-pro- duced ceramics. Horse, mul, or lange onager are documented in the contemporary Lower Town South street. These animals were prob- ably used for wheel-irawn transport of the cereal harvest (25). During this period the military power of the Subarian countryside was apparently united and could have joined with forces from states in southwestern ran (Elam) and the central Euphrates region ‘(Mari in attacking Sumer, which was domi- nated by one city, Lagash (26). Stage 3—Imperialization From approximately 2300 to 2200 B.C. (period IIb) southern Mesopotamia was united under the rule of Sargon of Akkad 998 USER OT EB EES and his dynastic succesors. Akkadian rule imperialized irrigation-based agricultural production in southem Mesopotamia and expanded into adjacent rain-fed agriculture regions where production could also under- go intensification, Documents and monu- ments retrieved from Tell Brak indicate that the Akkadians controlled Tell Leilan and Tell Moran through their imperial em- placement at Tell Brak (23, 27). Five fea- tures of Akkadian control have been iden- tified at Tell Lelan during period Mb: 1) Population redistribution from sites apparently nucleated within Tell Leilan (28) seems to have been directed at remov- ing local second-level centers and elites from the administration of production. Vil- Tages appear to have been maintained in Table place to sustain imperialzed production. A. similar patter of settlement during the ‘Akkadian period is documented at Tell al-Hawa, 80 km to the east of Tell Leilan 9). 2) Plant remains recovered from floors in houses and courtyards in the Lower Town South consist primarily of weed seeds and some cereal grains, with small quanti- ties of the inedible portions of the cereal head, and chaf. Seeds (n= 2112) were 9.6 to 61 times as abundant as chaff fragments (n= 304) in hearth, floor, oven, and courtyard contexts. Lower Town South hhouseholds, therefore, received precleaned cereal stores, probably as labor ration pay- ments in the Akkadian imperial system G0). |. Toll Lellan period Illc-lib radiocarbon dates and calibrated dates (years B.C.) Lower Town eS South (operation 5, OpS) samples are carbonized seeds retrieved from foation, Weighted ‘averages indicated below each group. Bota, Beta Analytic, Miami, Florida: N, Nishina Merexil Toyo, K; National Museum, Copenhagen; AA, University of Arizona AMS Faeity, Tucson; Lab. ro. laboratory number; and Op, operation, Multiple dates reflect several possible caibrations. Caliba tion was with CALIB 2.0 by the Univesity of Washington. Date ri (years BP. = 1 SD) es (0p8, phase 4 (Lelan tb terminal) A-8859 3805 = 75 2281 ‘88.0661 3610 = 75 2010 ‘AAT201 3825= 65 2203 AN T2O2 3885 = 65 2464, 2420, 2402 2274, 2248, 2206 (0p8, phase 5 (Letan Mlb midale) A709 3960 = 80 2470 AA7208 3780 = 70 202 AATO21 745 = 60 2189, 2164, 2143 aa7024 3315 + 65 2a6t AA7200 3855 = 65, 2339 2s18 (0p, phase 6 (Lean ib intial) AA7020 ‘3935 + 65, 265, An7028 4005 = 65, 2566, 2540, 2501, 4-720, 3905 = 60 258 267 0p8, phase 7 (Lelan lla) AA T022 4020:= 65, 2578, 2885, 2606 AN 7003 40202 60 2573, 2585, 2506 AAT025 3040 = 60 266 AA-7026 3360= 60 2864 (Op! str 14 (Acropolis Leian lla) (72) ks1s3 3870 = 100 Kst55. 4070 = 85 Ks156 4090 = 85 K5157 41402 85, (0p! str 15 (Acropolis terminal Leilan Il) (72) Ks154 3850 = 85 aaa K5158 4060 70 287 (Opt str 20 (Acropolis Lelia Ile) (14) 010-177 4090 = 70, 2853-2615 Beta-3099 4060= 60 2587 N-3a97 3e70= 85 2483 N-3898 4070= 70 298 2585 SCIENCE * VOL. 261 + 20 AUGUST 19933) Stacked kiln wasters from period IIb document production of standard-size 0.33, 1. and L.S-lter vessels. These vessels, and their nonwaster rim and base sherd equiva: lents only occur during this period at Tell Leilan. These observations suggest that they were used to distribute Akkadian standatd ined worker rations of barley and oil, which have been documented epigraphically (31). 4) A city wall was constructed for the first time. The rock-hard calitic virgin soil was excavated to depths of 0.5 to 1-5 m, then two concentric walls of mud brick, @ casemate, were set into these excavations. The inner and outer walls were 8 m wide; a riddle wall, perhaps a walkway between the two, was I_m wide. On the northern side of the city, where a natural depression and rise afforded protection, an earthen rampart was constructed by excavating a 10-m-wide by 10-m-deep ditch and then rmounding the excavated virgin soil. A city wall was also constructed at Ninua (Nin- eveh), the regional center on the Tigris River 150 km east southeast of Tell Leilan, where a son of Sargon established Akkadian control (32). 5) As part of the Akkadian roorganiza tion of production, and in response to the continuing reduction in water discharge and siltation that began in period Id, ‘water courses were stabilized by channeliza tion and repeated clearing. These construc~ tions may aso reflect Akkadian expertise in canal management developed in southern Mesopotamia. In trench D chis water man- agement is recorded within a 4-m sequence of repeated entrenchments into caleic vit gin soil, embankments of large basalt blocks, and masses of water-borne silt and pebbles that were cleared from the channel ‘on the western side of Tell Leilan. Occupations during the late Akkadian petiod at Tell Leilan, Tell Brak, and other dly-farming sites, as well as late Akkadian petiod texts from dry-farming sites and sites in Sumer, document a thriving imperial ‘economy sustaining long-distance trade and ‘construction of monumental buildings and massive agricultural projects (33, 34). Ake kadian military power bolstered distant im- perial fortresses and regularly repressed local rebellions (35). The imperialism of this period created the ideology of economic, ethnic, and regional unification that legit {mized all subsequent Babylonian and As- syrian imperial structures (36) The occurrence within anthropic soils of trenches B, C, D, and E of well-structured loam with minor signs of hydric erosion, aeolian influence, and moderate biological activity indicate climate of marked sea sonal contrast similar to the present, al: though better developed calcic horizons suggest that temperatures were slightly warmer. Thus, for the ~100-year period of Akkadian imperialization, plitico-military control of the Habur Plains was accompa nied by agricultural intensification and ap propeation under eonltions of gradual en- ronmental degradation that began in pe- lod Id. Stage 4—Collapse: Desertification and Desertion ‘At approximately 2200 B.C. the Akkadian- dominated period Ib occupations of Tell Leilan and Tell Brak. were suddenly aban- doned. The subsequent remnant occupation at Tell Brak was limited to one-half the area formerly occupied (37). At Tell Leilan, an ‘cccupational hiatus extending until reoccu- pation, historically dated at the beginning of period I (~1900 to 1728 B.C.) (38), has been documented at each sounding in the site (operations I to 8) (Fig. 5). Similar abandonments are evident at almost all ex ccavated sites of this period across the Habur and Assyrian Plains, including the excavat- ced sites of Chagar Bazar, Arbie, Germayit Mohammed Diyab, Tell Bideri, Kash’ keashuk, Abu Hgeira 1, Melebiya, Tell Taya, SCIENCE * VOL. 261 * 20 AUGUST 1995 NSH and Tepe Gawra (39). Surface surveys across the Habur Plains have failed to identify any ceramic assemblages for this period. Surface reconnaissance of Tell al-Hawa to the east of Tell Leilan also indicates an occupational hiatus (40). To the west, in the adjacent Balikh drainage, Tell Chuera and Jidle were abandoned, Hammam et-Turkman’s occu- pation was reduced, site occupation in the northern Balikh drainage was reduced by 36%, and settlements along the Euphrates north of Bireik were redaced or abandoned 41). The extant epigraphic documentation, from southern Mesopotamia suggests that ‘only remnant occupations refasined at Urk- ish (Tell Mozan) and Ninua (Nineveh) (42). We label this abandonment period “HHabur hiatus 1." ‘Abnupe climatic change. Habur hiatus 1 coincides with an abrupt environmental change recorded within a well-defined stra- tum found at Tell Leilan trench B, opera- tion 5 (Lower Town South), and operation 8, Study of thin sections from this stratum reveals a rapid evolution in depositional conditions that can be divided into three phases. Fig. 5. Toll Lollan, operation 8 south stratigraphic section, stratig: raphy and sampling. Scale is 2m [Numbers role tothe following: 1 Lean period 1 surtace; 2, Habur hiatus 1; 3, Lelan period ito surfaces; and 4, cate virgin sol at 2600 BCThe base of phase 1 is a 0.5-cm-thick layer of weakly altered fine silt-sized volean- fc glass with a few potasic feldspars, phy- toliths, and rounded calcitic sand-sized pel- lets, stratified and sealed in the last floor of period IIb in operation 8, lot 29, geology sample 203 (Fig. 5). This deposit is aeolian and was finely fragmented by human tram- ling on an open-air surface. Subsequently, in all three loci, the fine silt-sized voleanic slass fragments were mixed with caleitic clay loam derived from surrounding mud- brick construction collapse. This mixing ‘occurred during the early abandonment of the site when soil moisture was suficient to maintain earthworm activity and to alter slightly the voleanie ash, and when rainfall, was high enough to disintegrate mudbrick constructions. Climatic conditions during this phase were thus broadly similar to those before the tephra fall Phase 2 is represented by a 20-cm-thick accumulation in each locus (for example, ‘operation 8, lot 29, geology sample 204) of arey, well-ounded, sand-sized pellets, and loose, silt-sized, calcitic silt and abundant, very fine fragments (5 10 25 um) of weakly weathered volcanic glass with abundant, fine slt-sized phytoliths. These sedimentary features are characteristic of both local strong wind deflation and long-distance ae- olian transport. Evidence for reduced earth- ‘worm turbation of anthropic soils scarce slaking crusts fragmented by dessication, absence of pedogenic carbonates, and only 1 minor colluvial contribution, indicate simultaneous reduction of rainfall and oc- casional erosion at a bare soil surface by violent rainstorms. Both soil and sediment features may be evidence of the establish- Sek Fig. 6 (left. Tel Lelan collapse, phase 1: operation 8, botiom of lot 29, ‘geology sample 203, Calotie sit rch in finely fragmented st-sized tephra fragments, phyolths, charcoal, and rounded, sanc-sizd pallets of ye: lowish-brown and giey calcareous sol al of windblown origin. Accum ying on the upper part ‘of ‘eccupation floor (Tell Leian Ii) in operation 8. Length is 0.87 mm Fig. 7 (eight). Abu Hera 2, layer lla (270 to 300 em), Moderately sorted lation of aeolian sediment 1000 ment of marked aridity induced by intensi- fication of wind circulation, and an appat cent increase of dust veil frequency com- pared to present-day conditions. Phase 3 is a clearly defined unit of rain- driven primary and secondary mudbrick wall collapse in the ditch fill of trench B (I m of yellowish-brown compact unit), in the Low- er Town South (80 cm of loose, heteroge- neous, yelowish-brown to grey unit), and in operation 8 (geology samples 205 and 206; 40 cm of loose, yellowish-brown unit). Wind-blown sand:sized pellets and voleanie sass, observed within thatched-roof remains that are abundant in the fills, were trapped on the roofs during phases 1 and 2 before they collapsed. The Tell Leilan voleanic sass fragments (Fig. 6) are sle-sized (5 to 25, um) particles and are mixed with calcitic ‘dust. Their pale yellow color, low birefin- ‘gence, and diffuse contours indicate chemi- cal weathering induced by an increase of oil moisture during this phase. Alteration of volcanic ash, by pedogenic proceses under alkaline conditions is confirmed by the wide range of compositions of glass-like particles by electron microprobe analysis. Increase in earthworm activity, abundance of slaking ‘rusts, and occurrence of pedogenic carbon- ates formed in situ, all mark the augmenta- tion of soll moisture, a reestablishment of marked dry-wet seasonal contrast, a lessen- ing of heavy rainstorms and a progressive soil stabilization, ‘The absence of a marked tephra layer associated with windblown dustin the deep horizons of surface soils of the Tell Leilan region is noe surprising. Under present-day type climatic conditions, voleanic glass in corporated in soils weathers rapidly (43) ro-hialus SCIENCE * VOL. 261 + 20 AUGUST 1993 anu windblown pellets merge into the sil fine mas (4). A well-defined stratigraphic uni similar to those of Tell Leilan hints phase 2 ar also been observed at the Sppermost part of three archaeological sites, in the environs of Tel Leilan. A layer of windblown calcitic dust rch in voleante ash fand fine phyolths seals Halt period (3900 B.C.) occupation layers at Tell Bager, Ubid period (~4500 B.C.) occupa tion layers at Tell Naan 2, and Ura period (~3000 B.C.) occupation layer at Tell Nasran 1. The excelent preservation of layers of windblown dosti these specific Iocations can be explained by the redeced effects of postedepoitional distance on fchacologial sites in comparison to str- face sil on the flood plain. Some coarse sand layers of acolian. origin consist of silesied volcanic gles particles and potas- sium feldspar phenoeryts, clearly voleenie in origin, enbeddel in «pale plow, toe tropics ie ground sues The lowe aor phological resemblance of these particles withthe fetores marking Tell Leiln occu ation histus phase {and the overall char- Acterscs of the straiaraphic unit suagest that they relate tothe same ard event. “The regional elects of the ~2200 B.C. arid phase are alo. documented by soi Statgraphic data collected at Abu Hgeia 2 (Table 2) and Abs Har, 15 km northwest of Hasseke and 50 ki vouthwest of Tell Leilan. Voleuic los ane fine sands were cbrered in a sephonsich deposit at the bottom of a Jnrdeep tench excavated at the foot of Abu Heeira 2 (Fig. 7). Stat graphic unit [at Abu Higeita 2 is correlated with the terminal occupation of Abu Hageira T level 2, also an Akkadian period-Tell sand including subrounded sand-sized volcanic oh ‘cent) associated with wellvounded sand-sized pellets of calcitic sit {revish brown) and yelowish-brown subangular, coarse sand-sized ‘aggregates of calc loamy so This facies characterizes the intial stage Othe abeuptcimatic change recorded at the bottom ofthe Abu Hgetra 2 tronch when winds of moderate intensity started to defate soils simuta ‘neously withthe fl of voleanic ash. Length is 0.87 mm.Leilan Ib occupation (45). The intensifica- tion of the wind subsequent to the tephe layer is clearly defined at Abu Hieira 2 by the I-m accumulation (soil units Ia, IIb, Ic) of fine sand-sized pellets derived from aeolian deflation of the surrounding soils. ‘This layer accumulated in less chan 500 years on the basis of chronostratigraphic correla- tion. A similar windblown calcitic loam with abundant slt-szed tephra particles was also observed at Abu Hafur 2 situated along the same seasonal stream as Abu Hgeira 2, 2 Jem farther south. The aeolian unit overlies a caleic horizon correlated with Tell Leilan period Il environmental conditions and is sealed by Mitanni (~1500 B.C.) occupation levels. The similarity in the degradational sequence of ate chind millennium landseapes suggests that che tephra layers at Tell Leilan and Abu Hgeira 2 are products of the same ‘ruption. ‘The diference in size between voleanic particles observed at Tell Leilan ‘able 2. Abu Hgeira 2: pedo-sedimontary faces. Cale, calcareous; ab, abundant; com., common. and Abu Hgeira 2 could be explained by dliferential regional dispersion coincident with strong wind turbulence. ‘Tephra analyses. Glass sherds from the Abu ‘geira 2 layer (ample T9-43) display a hy- ‘dacitic composition indicating derivation fom a potasium-ich calcalkaline voleano. Their major element and trace element com. Position was compared to samples from the TTth-century B.C. Santorini eruption, the conly ash-producing eruption known ia the ‘Mediterranean basin during the second mil Tennium, which dispersed tephra over a large area of Asia Minor, up to regions close to the ‘Habur Plains (46, 47). Differences in major clement composition and in Th/Ta ratio rule ‘out a Minoan origin for the Abu Hieire 2 tephra (47) (Tables 3 and 4). Comparison with the few available trace element data from Anatolian volcanic rocks (48) suggest chat ‘Anatolian volcanoes were the source forthe Habur Plains ash (Table 4). Cale-alkaline volcanic centers, such as Nemrut and Karacilag, ae situated only a few hundred Jilometers from the Habur Pain. Potsic voleanie centers are also known in the Ana- tolian-Caucasian area, but the chronology of their activity during the Holocene is uncer- tain (49). ‘The Tell Leilan occupational hiatus and Hiabur hiatus 1, therefor, coincide with an episode of tephra fall, followed by an abrupe ard phase marked by intensification of wind circulation that seems to match, in duration and amplitude, a major short-term climatic change (50). The reinstallation of climatic conditions similar to those before the tephra fall preceded reestablishment of Habur Pains sedentary human occupation in the 19th cen- tury B.C. Outside of the historical record, major volcanic eruptions have been documented by proxy dating evidence ofered by tree rings and Greenland ice cores (51-53). The Unt (Characteristics Environment Corelaion| Basal aata ‘Occupation floor, statiied cutural debris ‘Nuzl ware-Mitanni period =1500 8. V.010 106m Gale foam, fine priamaté etructuce, ab, ‘Stable soll, vegtated, reduced winds, ‘pedogenic carbonato, high biological activity seasonal ainfall similar to present IV: 10010 140.6m Cale. loam with gravel lenses, calcio nodules Unstable eol, surface runof, degraded Early 2nd vegetation rnllonsium 8.6, I 14010 200 em Cale. loam, weak prismatic structure, lw Weak sol stably, heavy rains, surface “19008. biological actvly, rare pedogen runof, reduced soil moisture, moderate| carbonates, ab. crusts, ab. windblown winds Pseudosands le: 200 0.240 cm Well-soted, well-rounded calc. pseudosands, _Stiong winds, sltaton aeolian transport, Lan collapse, ab, crusts, i heavy rain spell, degraded vegetation phase 3 ib: 240 to 270 em Fine pseudosands, volcanic glass, ayBsum, Suspension aoolan transport horizontal’ Lean colapse, ‘calcitic loam, ab, sedimentary crusts ‘winds, heavy ain spell, degraded phase 2 vegetation lla: 270 0 200.6m Well sorted, wellrounded windblown, “Tpha fal saation aeolian transport, Lean collapse, ‘pseudosands, voleanic glass, calctic loam, Reavy rain spells, degraded vagetaion Phase 1 2b. sedimentary crusts £2200 86. 1,900 t0 370m Massive calcareous loam, well-developed Moderately stable sol, moderato winds, Lean tb ‘pedogenic carbonates, moderate biological Reavy rain spolls ‘actviy, com. pseudosands, com, sedimentary crusts 2900 8.6. ‘Table 9. Major element composition of Minoan tephra ia easter Mecltor- ranean cores in weight percent. For MD.90020 (35°17 53N, 26°12 46, 11620 m dopth, sample taken from 28.5 to 27.5 cm, size interval for glass sherds is 63 to 250 um. For TRI-172-22, data trom (47), Minoan refers to lass sherds of Minoan age from marine cores (72). T2-46 refers to Abu Hgoira 2 sample. Analyses made on individual gids sherds with a scanning electron microscope, coupled wth an enetay dispersive xray spectiomoter (analyses performed: at 15 KV, 0.3 NA on 20° tO 60-am= ‘ar9as for 100 seconds). Slandars deviation (2a) n parenthesis, Total ton ‘expressed as FeO" Coe NSO, ALO, KO N&O MgO Cad_—*TIO,—-MnO.FAO” CH P s Moe0e2014-=«73:38°=«1368 4S 028196 «SAO? «205 ~~ ~«OOSSCta (082 18) 11) 27) 1 112) (008) (030) 19) (008) .09) qaie22 10 «78021361337, 49912 kT 2s ore 017 47 021) 1 48) O13) O15) O14) 1S) 25) 13) ON. OI Moen? 41725) 137) 149028 SS 19 5 = (1) 4 2) (00 1) 1) on 19.43 18 7598 1328 445499008076 1818 (©5832 O14 031) (008) OT) (008) 08) 23) (.OH 0.6) O14) SCIENCE ¢ VOL, 261 + 20 AUGUST 1995 1001average global temperature signal of volcanic ‘eruptions may, however, be undetectable for all but the langest eruptions (54), and the proxy dating is incomplete (53, 54). The ice core record has one major sulfurtich peak, cof unknown origin, at the end of the third millennium B.C, (4040 10 years ago) (63). The voleanic eruption documented at Tell Leilan, however, probably occurred ~100 years'earlier, may not have been a major sulfurrich eruption, and should not necessarily corelate with 2 well-defined sig- nal in the proxy record. The Anatolian trce-ring record has only one to four samples for the petiod 2200 to 2000 B.C., a number sufficient for the positive identification of neither a voleanic event nor abrupe climatic change. These tree ring data do, however, suggest a. 200-year-long period of climatic instability culminating in reduced and irreg- ‘ular ring growth forthe period 2055 to 2043 £37 BC. (55). ‘The abrupt increase in aeolian deflation and aridity (from phases 1 to 2) following the tephra fll (phase 1) raises the question of the causative linkage between the two events. ‘The climatic effect of volcanic erupeions are well documented (56). Several lines of evi- dence, however, suggest that the late third ‘millennium Habur Plains climatic change ‘may not be a direct response to volcanic activity: (@) Its duration, approximately 300 years, as estimated by the Tell Leilan radio- carbon and historic record, differs consider- ably from the briefer modifications of global climate induced by volcanic eruption (51). (ii) Our data suggest that atmospheric insta Dilley caused by air warming in addition to attenuated seasonality and extended atidity persisted during this period. This regional trend is apparently not consistent with the slobal cooling caused by at aerosol forcing, although the range of possible local cfecs isnot yt defined (57). (i) A dust veil persisted fr several decades, long ater the fall ‘of the voleanic ash that occurred at the beginning of the event. Comparison. with ‘modem circulation patterns (58) suggests that ‘8 major modification ofthe climatic boundary conditions has to be invoked for explaining ‘maintenance of air warming and strong zonal winds during phase 2 (59). A northward position of the polar jet would explain weak- ened cyelogenesisin Mediterranean and Near Ease regions, A stronger subtropical jet might als have been responsible for more intensive circulation of northerly winds synchronous with a weakened monsoon in the Indian subcontinent. Land-Use Effects of the Abrupt Climatic Change Phase 2 desertification, identified as in- ‘creased aridity, intensified wind turbulence, and increased’ dust veil, i interpreted «0 1002, have significantly reduced soil moisture re- serves, increased aeolian loss of soils, and reduced ground visibility. Therefore, we hhypothesize that phase 2 coincides with conditions of low agricultural productivity During Habur hiatus 1_we estimate that the intensively surveyed Tell Leilan region suffered a net loss of ~182 hectares of built-up ste area, or a displacement of be- ‘weer ~14,000 and ~28,000 persons with- in 15 km of Tell Leilan (22). Displacement ofthe to four times that numberof persons is suggested by equivalent abandonments along Habur Plains western drainages. Syn- chronously, we hypothesize that the scason- ally transhumant populations of the Habur Plains were also displaced as the plains were no longer the summer alternate to their winter foraging along the banks of the Eu- phrates (60). Comparison with archacologi- cal data from southern Mesopotamia suggests thatthe desertification and desertion of the Habur Plains between ~2200 and. 1900 B.C. engendered the collapse of the Akka- dian empire, and the attendant displace- ‘ment of Hurtian, Gutian, and Amorite pop- ulations into southem Mesopotamia. Initially, the desertification caused the abandonment or reduction of northern setle- ‘ments such as Tell Leilan, Tell Brak, and ‘Mohammed Diyab, on the Habur plains, and the collapse of the Akkadian economy that was dependent in pare upon imperialized ag- riculture throughout the ran-fed lands adja- cent to southem Mesopotamia (61)- The abandonment displaced the sedentary Hur- rian-speakers of Subir (62). Gutians, perhaps fiom the Diyarbakr plains adjacent to the Habur Plains, were also displaced by this abrupt climatic change, and eventually seized control of the collapsed imperial core (63). ‘Amorite populations, formerly seasonally ‘ranshumant, moved down the Euphrates and ‘Tigris banks, and force the succeeding Ur ll dynasty to ‘construct the Repeller of the ‘Amaorites wall (6). These populations, how- ever, continued to immigrate into southem villages (65) at the same time that southern irrigation agriculture was sufering ftom re- duced flow of the Euphrates (66, 67). While the Ur III dynasts were able to extend some politcal contol afar north as Assur, they did rot reestablish contol over the Habur and ‘Assyrian plains (68) because these regions were not efficiently productive for southern imperialization during this period. "The abrupe climate change that gener- ated Habur hiatus 1 and the asociated ‘Akkadian-Guti-Ur II collapse are synchro ‘hous with climate change and collapse phe- ‘nomena documented in the Aegean, Exypt, Palestine, and the Indus (69). The reoceu pation of the Habur Plains in the 19th ‘entury B.C. and the sudden emergence of centralized Amorite control of the plains under Shamshi-Adad at Tell Leilan was SCIENCE * VOL. 261 * 20 AUGUST 1993 cevidently facilitated by the amelioration of climatic conditions documented by the phase 3 soil-stratigraphic data at Tell Lelan. and the subsequent return of Amorite, sed- Table 4. Concentrations of race elements in a Minoan ash layer rom a marine core, a sample from Abu Hgewa 2 and comparison with trace clement ratios in volcanic rocks from Turkey Fr marine core MD-90820, samples consisted of 80 mg of purified glass sherds. Sample 1 ‘was fom a dopih of 265 lo 27.5 om. sample 2 ‘was ftom a depth of 3210 33 cm. Gass sherds are from the 63- 10 125-ym size fraction. The 79-43 sample consisted of 50 mg of purfiod ‘lass sherds from the 80- to 150um size Traction, Neviron activation was caried out by activation analysis: eration with an epiher- mal netron ux of 10"* cm? ¢~" for 12 hours In ‘Ca tubes or 60 minutes in quartz tubes. Exper- Imonts wore performed atthe Centre cEtudes Nucléaies of Saclay, France; samples wore ‘counted using @ 80-cr? Ga detector BEN and ‘GSN rock standards were rom the CRPG (Nan- ‘oy, France), Ta the new adopted value for this ‘element in GSN is 2.578 ppm. Analytical proci- sion is +1036 for Ag, S, 2s, Cr, Ni, and 5% for ‘ther elements. For comparson, we present ‘data fom easter Anatola lavas having a sub- ‘duction signature (73): 16 analyses trom Ararat strict yielded @ TWTa rato of 8.53 and 27 ‘analyses fom the Kars plateau yielded a THTa fato of 10:2 When Ta data were not avaiable, they have ben calculated from the equation Ta ‘= (No/16). Units expressed in parts per millon ‘excopt foc Ag and Au, which are in parts por billion, Th/Ta, La/Eu, and Eu/Yb ratios caleu- lated from average data of marine core MD- ‘90920 samples 1 and 2. MO-90820 Tes ent 7 2 v 538 528 7.06 Th 16721708245 z 201 302 139) it 787 773 3.98 Ta 0937 oes ar Ba 498 503 398 sr 101 102 2a Gs 268 270 7A Ab 940 our 185 8 0.30 03 os or 8 8 13 Co 33 57. 17 N 18 23 86 Se 77 78 2 la 265 265 2B Ge 537 535 536 No 3.96 Sm 482 472 31 Bs ogi og 030 1 078 = 071 Oa Yo 449 453 257 Ww 045 rs 249 2.95 Mo 279 206 Br 126 a 49 80 129 a ‘a7 55 Twa 179 108 Lae 231 mar Fuy> 020 015,entary and seasonally transhumant exploi- tation of the Habur Plains (70). 1 a 18 18 2B REFERENCES AND NOTES McC. Adar, Heatand of Cites (Uv. of Chicago Press cage, 108), ih fess, 7 Mesncane Boats VG, Child, Mar Makes Himsa Now American UUs, New Yr, 281). pp 186-142 ‘AL dina The Advert o he Ea of Townships fn honor Mesopotamia (Bl Leon the Net ‘nds, 1985). 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M Wess Ed (out Ques, Calle, Un fe King, #990), pp. 71-108, Sten and P Wanemaer, Mas: Arpt Sol Cont Arent. J-7 (eippl). 8 (180), Wie, Nour. Asyrit Bréves Un 4, (1992) 4G Marque, Lee Palas -Mésopotaions {Gone Pars’ 1067. Wels. Ae ‘Shao! 96, 703 (108 (2) pp. 187-18, [igh upper P2 oath mum cow igh fr buccal occucal boasth ~23 rer) froma hy acu male equ. Te abv ape rtocane cecal engh 93), the presence fe oso as wo ae thereat pe 31 a8 es a. ar 2. 2. a 46 a fe of te ooh suggest tat thi foo may be tram Equus cabal, poss Hom alge rule bral onoge (Eouishams baobab fot ema dorky. Sibi, Das Atsumerichen Bau und Wen- Schon Tal |. nsfvten aus Lagash (Sener, Wiesbaden, 1982) pp. 14,150. ‘A. Catognot| and M. Bonoch. Now. Asset ‘roves Ua 2,50 (192) B.Lyonnet, Gah, Nov. Assy. Bréves Uti 1.74 (0990, 1. tinson, tag 52 8 (1900) Pow Raatouton Assy 7, 7 (1990), The Ulnar Town Sou ip fas assenblage (7 = $128 epecmane derited at sto gen) doce ‘2k oplayatlorng recescarly rated to A adlanmperalzaton Shoop, goat and PQ pe ‘dominate, as in cotemporry urban ad Town ‘ee in ror and outer. Mesopotamia, From phaso Sto phase 4 he a stiorert he folate Fequency of ig rose form 47 to 63%. Ot {he ageabie pig ror, 86% dori ro fants ‘oF juveniles, suggesting that igs wore tacod Daman for moat Two compe shatters ot Fewbar o young pigs suapest hat pie wore Bang kot in the Lower Town Url aq 47,190 (1908): M_ Pow, Ro ‘SockonAsnya 7,487 (190), Senor and Wis, Crentexoress Pas) 2.10 (1082). Blain, Siem Vande, A Ani 88, (4993) PSxtoacn, Amu Archagol. 98, 305 (1980, 18. Rostra 39,31 (197), Acmnaion ‘29d Uso of nstunal Lar Sargon Surat (Gages, Copanhngon, 1062), A Woserhol ‘ts Simons and Ol Akkadian Texsin Pade a Pan of Capea Copan Mi Liverar. Ed, Akkac The st Emre (Sargon. Pack ay peo) Tacobeen, Ach Orontrsoh 26 1 (1978). Pp. 5-60 In (11); Wesorhol, in Power and Propaganda A Sympesum an Ancient Emates, MOT" Larsen, £4 VAkaderisk, Copestagen, 1979). pp 107-123, NM Mslonan, rag 8, 2 (1847, Oates, it 48 ‘79 186" Tol Lian period |e astocsed with he Sham StivAdad rooocupabon ofthe Rabu Pare and {stabs olan a Yogionsl acer Igratve cere (9), (Chagar Bazar M Mallonan, rag 1 (199) 4°51 (197; Goma MNiowan, x29 118, ‘At Me Malowen, i. p17, Mobs Diab: (20). Tel Sdn P. Pate, Damazorer I 3, $986, Kashasuk:C. Brenque, in LE Irate 6.1 Tampa, 0. Rou Es. (eet, Mla, 1906), pp. 69-171; Abu gata LL Math an CMa, Aton. Forsch 18.247 (1092). Moe feb M Lebeau. acca 6 1 (1985) Tel ‘aye J. eado, 12935, 12 (1979), Tepe Gama: Parada ands, Basham. n Chrnalogis in OS Word Archacoogy. Eich, Ea (Un of On aps Press, Cncago, 1902) p18 Wicat B Tucker tJ. Wikegon, ag 61, 18 (hao) be, poe atCrvera:U Mecngat Cozens, Reaewton As ‘yr 4,460 (1079). Ie: M ahowan ra 8 1 (a). alan H. Cavers, teas, Unw of ‘Amatercar, Arstrdar (1981. pp. 197-200 ‘ran Rujak Tou Wikesn, Tou and County In Soueas Anata (Un. cf Chicago Prose Chicago, 1000, p. 108, Malaya: M. renapane Fealeon Asso 8,47 (190), Wels, Mar, 272 (1985) D. Eazard and G. Farber, (6), p. 224: Wht, J. Cureton ‘Sud 28173 (1982, C. Wicks, Drew Vostok (Grown) 5, 225 (188) 0. Calo, Rew ASS 4,120 (000) WG. Welomakor and T. Wakaaui, Gooderme 32,21 (1088). Cook A Waren, A. Goud, Desert Gooner hotogy (iver Catoge, London, 1853) Cart, Onant excess 28 (1001. (6 Douras and Papazoglu, Nate 267, 22 (i6'D' Strley ara Shang. 320, 733 SCIENCE * VOL.261 * 20 AUGUST 1993, «. gas or NTE (1986); 0. G. Suvan, be 899, 852 (1988, Guna ta, 968, 610 (1985). {1A Poaree et a, Vesna Oeahorm Fs. 4 12 (1900), Fbocart eral, Geol Mag. 112 349 (178) ¥ "irae Votan! Geotor, Aes. 4,6 (100) Wan Zeit and S. Bota [Lo Vagetaton ofthe Near Eat (Rocher. Wista- on, 1001) suggen a redaing of Lake Van palon oor [ET Dopens HK Wong, 8. Kemps, ‘Geol Rundech 73, 701 (1064) whieh rest ‘olan event ted at 4627 and 07 yore 290 (urcabated) NA Memarn Cimae: Histon, Pesceny anc Preictbiy, Mo Ranpine 2a Ede (Van Nestand, enol, New York, 1887). pp. S36 260, in Pago ENSO Racorda LO ad Macha, Ede. (ORSTOM-CONCYTEO, “Lina 1902) pp. 201-206 DM: yo, uot Fes. 7,125 i002. VC. Lene and KK Fiachboeck, Nate 907, 121 (1088)°M. GL Baile and LA. FL Maro, tc 882 344 (108) LA Sexton, Guat. Fs'3467 (18), Sd Jomngen ea, Natire 950, 11 (1002. LA Seusen, Guat ae 37.190 kunt, Sues in onar Gag Mt “Mane, T- Ozgig,€. Porada, Eos. (Trash Historical Sooty, Arar, 1003) pp. 371-374 RS Bradley, Chr, Change 1,321 (1888) (1), FM Bul, Volcanoes of heart (un ot Tras regan oo, Sut, Pale PalasocimatoPalsaosco 88, 277 (000; Pre at, Scenon 59,1 (1903) TMC L gay and G. Famer, Easton Meck Tetanoen Fogo i Later Proto... Br, EL m_ Acnaea! ep. it. Sr. 188, Odor 1362). pp. 3-29. In (9h. 173 Haracan Arorte speaking tibes are docu ‘ented nis, seasonal pation bogieing at Te50 BC. s00 Meee Les Titus Amaritoe Mar (Unw- of Fret, Froburg. Germany, ‘0, Weis and MA Coty (3 EGate Hurans ana Subanan (Un. of Ch ago Pres, Cheage, 044). pp. 2-1 dak Darand in Lz Gredlation des Bens, des Porson oe, des laas dare Paco Oren Ancien, Charan ana F searnbs, Eas. (eons Ro: ‘herce sr lee Chetan, Pars 02), p 125. {Gutum might be oes inmate north oo abu Pan or Dyarbai lara uago tom () "he Guban population er cull legacy rornart thera a0 lea the Ton contay BC. Wd Firlsten, J Cunarm Stad 2, 95 (1966) and (ibis fener, serifed ae vary asthe 40h Contry B.C. wih Yoararaz, the wesier pat ot tho Habur Plans .'O. Havnin, Poaenkon ‘Assyrol 8,25 (1980) (9) Wicks 2: Asso! 80,54 (1970, McC. Adame, (2. pp 18 ae 151-152, (20): Joes, SungrleglalStuces in Hanar {1 Teshl Jacobson 8. Usborman. Ea (Un {t ricago Press, Cheago, 1079) p60; T. Gor. {1 Soe Bean Hit Ont 23,1 (1979) 4 Cuno Tom Suc 96,211 (1084); H, acto Labor {nto Arion Near East M. A'Powel Ea (Nor Kean Gnontal Sooty, New Haven, CT 1987) p "25. Thee are no ean acs artis forth et ha ofthe Uri yeasty ‘The historical chronology ofthis pasod has an reotaity of 120 year oes. Brkran Mh ALL Opparhaim, Arion Mesopotamia (Uni of ‘Cheago Fees, Chicago 1977) p 3. P-ubor Ie From Ancient Omens to Statisical Mechanics. SU Borggron and F.Galdton, Eas, (Une ‘iy of Copenhagen, Copennagen, 1087), pp. 31a] tena a figh chronology fe the UF ‘ymastyand-a mde chonogy fo he acces ‘Son of Sorgen, Sterkator In The Organization of Power. As cts of ureaucracy nthe Ancor Noa’ Est Ghson and A Baggs, Eos, (Un. of Chca96 ross, Cheage, 1987), pp. 15.34, ‘Regean Foran, Tho Tug of tho Ey Hllaces: Disturbances in East Cota and Sutnarn ropoe Towards the En othe Early fronzo Age (Pham, dorerod, Sneon, 1002: Pace: AD, Crown Noa East Sud 31, S12 (1972, Schos (Gre. Archacel Rep. In Set, 527, ‘Gerd, 180), op 247-255 Egyp:B. Ball Am ‘Archaeol 78,1 (1971): Buse Ear yas Guteaer sn Eoyet (Unw. of Cheago Press, heap, 1976, 8 38\F Hassan, Sooo 212 $142 1981) 0: Canna. in Popiaion Growth Aniropeiogeal lpteators: 8. Spear Ed (asachusots Insthae of Testraiogy, Cam Bridge 1972) pp. 78-10, Inu Re Mughal, Pak ‘Achaso! 2, 88 (990). Sater, 9 Cer. 70. (53). Charon, n Mcaianea Babylonia, Buran and JF. Kupper, Es (Eons Recher ‘he sures Calzaton, Par 1985) pp. 51-88. 171, SRebnacn and H Wis ne Ong of Nah ‘Chaeaton. H. Wels, Ea. (Yale Un: Praas, New Haven, CT. n pres) 72. KIN. Federman and © N. Garey, Gut. Res 18, 10 (1980), 73 Fitmocertie al, Gaal Mag. 112 349 (1975 Kale, J ValeanatGaoterm Fes, 21 (1065) E Aya, Los Lavos a Quatoraie ce Capoadoce Torque): Vacenaogiea! Pérobge, Mamare DEA (Clamon-Ferand. Unverty Crmont Franc France, 1860): p188 1 (45) 14, J Shafer and. chtansn, fis Arche Top 2117 (1080) G. Passa, Arras ew. A tropa 1,261 (1860) Shaler, nChronaggies ‘novo ea Fic Ea (Us oF Ghieago Press, Chicago, 1902 vol Tp. 5 75, Wo ark he Otecorte-General of Anus, Damascus and especialy Abe Aes dA Antisense Oligonucleotides as Therapeutic Agents—Is the Bullet Really Magical? C. A, Stein and Y.-C. Cheng Because ofthe specificity of Watson-Crick base pairing, attempts are now being made to se oligadeoxynucleotides (oligos) in the therapy of human disease, However, for a successful outcome, the oligo must meet at least six criteria: () the oligos can be syn- thesized easily and in bulk; the oligos must be stable in vivo; ) the oligos must be able toenter the target cell (i) the oigos must be retained by the target cell () the oligos must be able to interact wit their cellular targets; and (vi) the oligos should not interact in a rnon-sequence-specific manner with other macromolecules. Phosphorothioate oligos are ‘examples of oligos that are being considered for clinical therapeutic trials and meet some, but not all, ofthese criteria. The potential use of phosphorothioate oligos as inhibitors of Viral replication is highlighted. kis the idea of specificity that provides the underlying allure of oligodeoxynucle- otide technology (Fig. 1). Standard eyto- toxic chemotherapy for conditions such as neoplastic disease is fraught with systemic toxicity. The ratio of the toxie dose to the therapeutic dose is relatively low, which reflects the large numberof cellular cargets aifeeted hy the chemotherapeutic agent and the agents inability to distinguish between normal and diseased cells. In theory, this problem can be solved by taking advantage of the specificity c fereed by Watson-Crick base pair forma- tion, if an appropriate target ean be iden tified. For example, an oligo of more than 15 to 17 nucleotides in length would have a unique sequence relative to the entire hhuman genome. In principle, a suitable oligo should be able to interfere, ina ‘EA Sianie nie Deparment ot wedne, Gaurba ‘nies, New Yore NY TOI32.Y-C. Cheng nhs Deparimert of Pharmacclogy, Yala Unrest, Now Hoven CT 05810 sequence-specific manner, with processes such as the translation of mRNA into protein (1). Ifthe synthesis of that protein {sa requirement for cell growth or, alter natively, for intracellular viral replication, then these processes would be slowed by the antisense agent. Furthermore, the property of complementarity may also be used to inhibit other physiologic processes in addition to mRNA translation; for ex- ample, oligos targeted to donor-acceptor sites for splicing pre-mRNA inhibit hu- man immunodeficiency. virus-type 1 (HIV-1) replication (2). In addition, ol {gos complementary to genomic DNA can. interact with it, by means of Hoogsteen base pairing in the major groove, to form a triple-helical structure. Investigators have inhibited transcription in tissue culture by inducing triple helix formation, and sev- eral examples are given below. Phase I clinical trials of oligos, designed to evaluate the toxicity of these compounds in cancer patients, have already com- SCIENCE + VOL.261 + 20 AUGUST 1993 ‘Bourn for asitance, ae well as M Must, A fb Ghat Mt Lat, an & Roum fh ino Hoi. Wo avo gato to Hende at Tell olan, ‘Tel Barham. Gotan ‘Sih. acd Do Gir fo hospitality and Heldworkpatipabon Research at Tells Calan, Sager, Nasran, aed Nasran Ia supported by ne National Science Foundaton grants BNS-8408217 aed BNS-8913490), ho Natoral Erowment fete Hurraites (grants NEH RO-21489.87 and AO: 2199089), and Leon Levy The overly ard Reymond Sacer Foundation, end The Oula Foundalon Oala om Abu Pera and Ass Hote wero calleetod curing an atchaslogial survey direciedby B.Lyonnet rd supported by th French hts of Foreign Aare we thank Suleiman. Marin, and A Heche for ta Steiay, fer assistance wih router actvaton anaes. menced. A phosphorothioate (PS) oligo complementary to tie p53 mRNA has been administered to a patient with chemother- apy-refractory acute myelogenous leukemia G). Another crial that has been proposed lfor a methylphosphonate (MP) oligol is phase T-Il trial in patients with chronic ‘myelogenous leukemia. The trial. design calls for patients to receive transplants of autologous oligo-purged marrow (4) after they receive standard chemotherapy and radiotherapy. Requirements for the Therapeutic Use of Oligos The use of antisense oligos as therapeutic agents presupposes that six criteria can be satisied The oligos can be synthesized easily and in bulk. The development of phosphoramidite chemistry by Caruthers and co-workers and its elaboration into an automated technol- ogy (5) have greatly enhanced the ease with which oligos are synthesized and conse- quently their availability. Methods for large-scale oligo synthesis are being com- mercially pursued (6). Although the cost has been dramatically reduced, the final cost to the consumer ofa “treatment” with ‘oligo has not been determined. “The oligos must be stable in vivo. This precludes the use of phosphadiester (PO) ‘oligos as therapeutics because serum and Intracellular nucleases (both endo- and exo- nucleases) will degrade them (7). For the past decade, significant effort has been ex- pended by synthetic chemists to develop rnuclease-resistant oligos. Perhaps the great- est successes in doing so have been achieved with the PS (8) and MP oligos (©), which can be synthesized with relative ‘The oligos must be able to enter the target cell. The ability of oligos to penetrate the cell membrane and the mechanism of en- tance ate critical considerations in devel-