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.¹⁶ This constitutes some direct evidence for the existence and activity of P. falciparum on the periphery of the Mediterranean world already in the fourth millennium . Further research into ancient biomolecules (especially DNA) from human skeletal remains excavated on archaeological sites in southern Europe offers the best prospect of obtaining direct evidence for P. falciparum malaria in Europe in prehistory.¹⁷ There was clearly some contact between Egypt and ¹⁴ M. T. Gillies in Wernsdorfer and McGregor (1988: i. 455) expressed the view that mosquito flight range is a property of the environment, not the species, depending on the availability of breeding sites and food, but it is clear that they generally do not fly far; Garrett-Jones (1962); Halawani and Shawarby (1957) on malaria in Egypt in recent times.

¹⁵ Angel (1966); Borza (1979), Zulueta (1987: 200), Sallares (1991: 275–7), Stuart-Macadam (1992), Grmek (1994), Corvisier (1994: 299–303), and Larsen (1997: 30–40) all agree that porotic hyperostosis does not necessarily indicate malaria.

¹⁶ R. L. Miller et al. (1994); Cerutti et al. (1999). cf. Marin et al. (1999).

¹⁷ The problem with trying to detect ancient proteins is that antibody reactions depend on the conformation of proteins. Since protein conformation would be expected to degenerate over time, it is not clear what degree of specificity could be expected in any particular antibody reaction with degraded proteins. G. M. Taylor et al. (1997) unsuccessfully tried to amplify ancient DNA from one of the same individuals studied by R. L. Miller et al. (1994), namely the Gurna mummy dating to c. 700 . There are many possible explanations for this failure. Similarly C. Plowe, reported in Parasitology Today, 14 (1998: 9) expressed scepticism about the results obtained by R. L. Miller et al. (1994). Consequently further research is need-32

Evolution of malaria

Greece at least as early as the Early Bronze Age in the third millennium . The most striking illustration of this contact was the construction of the small-scale imitations of Egyptian pyramids at Hellenikon and Ligourio in the Argolid in Greece, which Pausanias passed on his travels much later. Consequently it is quite possible that P. falciparum could have been transmitted directly from Egypt to Greece at that time.¹⁸

However, there is another, even earlier, possibility. The Neolithic period commenced in Europe with the introduction of agriculture by human populations from the Near East, according to the generally convincing arguments presented in the monumental book by Cavalli-Sforza and his colleagues, a very important contribution to knowledge.¹⁹ Agriculture—specifically the cultivation of cereals and legumes—first developed in the general vicinity of modern Israel, Jordan, and Syria. These regions in antiquity certainly included some significant areas of wetlands, along the Mediterranean coast and in the Jordan valley, which harboured amphibious animals as large as the hippopotamus and permitted the cultivation of aquatic plants like papyrus. In more recent times, until they were drained, these wetlands were intensely malarious.

Similarly in antiquity Josephus described as pestilential in summer the air of the Great Plain around Lake Tiberias and the Dead Sea.²⁰ Consequently the earliest Neolithic farmers lived in a region that included some environments that were extremely favourable for malaria.²¹ This consideration supports Angel’s hypothesis that ed to confirm their results. Sallares and Gomzi (2001) discussed the problems in applying immunological tests to ancient materials. However, the results of the studies in molecular evolution cited earlier based on comparisons of modern DNA sequences make it extremely likely in any case that P. falciparum was present in Egypt by the fourth millennium , since such research does not suffer from the same technical problems as research on ancient biomolecules. Schiff et al. (1993) described the Para Sight test.

¹⁸ Theocharis et al. (1997) and Pausanias 2.25.6 on the Greek pyramids.

¹⁹ Cavalli-Sforza et al. (1994).

²⁰ Josephus, de bello Iudaico 4.8.2, ed. Bekker (1855–6): ƒkpuroıtai d† ¿r6 qvrouß tÏ ped≤on, ka≥ di’ Ëperbol¶n aÛcmoı perivcei nos*dh tÏn åvra (The plain is burnt up during the summer season, and extreme drought makes the air unhealthy).

²¹ Tacitus Histories 5.6–7 also described the Dead Sea region as pestilential with bad air: lacus immenso ambitu . . . gravitate odoris accolis pestifer (a lake with a huge circumference . . . whose oppressive smell brings pestilence to the local inhabitants). Hirsch (1883: 202) noted that malaria affected extensive regions near the Dead Sea in the nineteenth century, as well as the Bekaa valley in Lebanon at an altitude as high as 1200 metres (cf. Leeson et al. (1950) ). Fisher (1952) made the interesting observation that mosquitoes are carried up to the Bekaa valley by rising air currents which regularly occur in that region; Amadouny (1997); Filon et al. (1995) extracted ancient DNA showing the presence of b-thalassaemia from human skeletal Evolution of malaria

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all the three species of human malaria under consideration, including the most dangerous, P. falciparum, were carried to Europe inside the bodies of the very first Neolithic farmers. The diagnosis of thalassaemia, a human genetic disease that confers some resistance to malaria, in the skeleton Homo 25 (a male sixteen or seventeen years old) from the PPNB (Pre-Pottery Neolithic B) village of Atlit Yam (now submerged off the coast of Israel) supports the idea that malaria was already active in the Levant at the dawn of agriculture.²² Given that the climate in the Neolithic period was actually exceedingly favourable to it, whether P. falciparum would have survived in new environments in southern Europe depended, as was noted earlier, on whether it encountered species of mosquito that were capable of acting as efficient vectors. Only a minority of the European species of Anopheles mosquito are good vectors for malaria.

This problem leads on to the fourth pillar of the late-introduction theories, namely the question of the possible refractoriness of mosquitoes to infection with P. falciparum. Experiments were performed using samples of A. labranchiae, originating from

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