Elixir of life: In vino veritas.

T he wine grape, Vitis vinifera, is a member of the Vitaceae, a family of vigorous, climbing, woody plants that live in the Northern Hemisphere. The plants are illadapted to tropical climates, and thus never crossed the equator (except those transported by humans, which are cultivated in Argentina, Chile, Australia, South Africa, and other regions in the Southern Hemisphere). The genus Vitis consists of some 48 species distributed between 30° and 50° latitude north throughout all continents from Japan to the western United States. Only one species, V. vinifera, is native to Europe and the Near East, 12 species are native to Asia, and 35 are native to North America. Two subspecies of V. vinifera are V. vinifera vinifera, the domestic table and wine grape, and its wild relative, V. vinifera sylvestris. Several thousands of cultivars, often known as “varieties,” of V. v. vinifera are known. In PNAS, Myles et al. (1) have characterized genome-wide patterns of genetic variation in several hundred cultivars of V. v. vinifera and 59 of V. v. sylvestris. They show that V. v. vinifera was domesticated from V. v. sylvestris in the Near East and have identified parent–offspring and sibling connections, most of them first-degree relationships, between some well-known varieties. The relationships are often surprising. Wild grapes dangle in clusters that are small compared with cultivated grapes but are strikingly beautiful and must have attracted early human gatherers because they are sweeter and juicier than other fruits, and thus desirable as food and drink. Cultivation of grapes likely started in the Paleolithic before human gatherers discovered the food value of grass seeds and started cultivating cereals. A gatherer of grapes would surely preserve the surplus clusters by hanging them or storing them in a nook or vessel, where oozing juice would quickly ferment. Sooner or later, the juice would be tasted and wine discovered. This is more or less how the discovery and use of wine are recorded in early mythologies. The earliest extant work of literature, the Sumerian Epic of Gilgamesh, tells of Gilgamesh’s lover Ishtar, a wine goddess, and of Siduri, a temple harlot who teaches civilized manners to the wild woodsman Enkidu and introduces him to wine drinking. In Persian mythology, King Jamshid loved grapes and stored them in jars to have a supply available throughout the year. He once found a jar in which the juice that had oozed from ripened grapes had a sour rather than sweet taste. He put the jar aside, thinking that it might be poisonous. A harem lady discovered otherwise and told her secret to the king. Cultivation of the grape and the making of wine are associated with the Syrian demigod Danel and his daughter Pagat. The snake goddess Renenutet of Egypt presides over the vintage of grapes (2). In the Bible, the earliest experience of wine is attributed to Noah. The ninth chapter of Genesis tells how, after the Flood, Noah “planted a vineyard: and he drank of the wine, and was drunken.” The earliest archaeological evidence of cultivated grapes comes from grape pips and occasional skin and wood remains found in the southern Caucasus and dating from the Neolithic, about 9,000 y old (3). The oldest evidence of wine is from a jar dated 7,400 to 7,000 y ago, from the foothills of the Zagros Mountains near where present-day Iran meets Turkey and Iraq. The jar, located at the University of Pennsylvania Museum, has residues of tartaric acid and resin from the terebinth tree. Tartaric acid occurs in large amounts only in grapes among natural products, and terebinth resin was a wine preservative used all over the ancient Near East for millennia. Archaeological evidence indicates that wine making extended south and west from the Near East to Lower Mesopotamia and Egypt, where numerous varieties were cultivated as early as 4,500 y ago, and later to Crete, Greece, Rome, and throughout Europe all the way to Spain (3). The wild grapevine V. v. sylvestris ranges from Central Asia to Spain and from the Crimea to Northwest Africa. Domestication could have happened anywhere in this enormous area and more than once, but archaeological, viticultural, and genetic evidence strongly suggests that it occurred only once, in the northern parts of the Near East (1, 3, 4). Wine and table grape varieties are propagated by cuttings or buds from preexisting vines. The first vine of a given variety is the only one that grew from a seed, the outcome of a cross between two parents. All vines of a given variety are clones, genetically identical except for occasional somatic mutations that may have occurred since the variety was isolated. Over the past 200 y, grape breeders have performed cross-pollinations between selected parents to develop different varieties. All classic wine varieties predate deliberate cross-pollination, however, and none originated from a controlled cross. The charters of the American colonies of Virginia and the Carolinas specify the goal of making wine, taking advantage of the abundance of grapevines. The settlers soon discovered that native grapes gave wines with foxy or other unlikable tastes, however. Plantings of V. vinifera as early as 1619 failed because of vine disease. Thomas Jefferson lived in France in 1784– 1789 as resident US minister to the French government and became a wine connoisseur, particularly of Bordeaux vintages. As an enthusiastic practitioner of scientific farming, he embarked in 1807 on an ambitious planting program of some 300 vines from 24 European varieties. He anticipated that grapevines, like so many other crops, would flourish in the fertile soil and climate of Virginia. Jefferson’s vineyard experiment failed spectacularly at first. It failed again each of the six times he tried it. He never learned that what killed his vines was black rot and the Phylloxera root louse. Junipero Serra and his Franciscan missionaries were somewhat more successful in the drier California climate. V. vinifera was planted in 1769 near San Diego and then further north, all the way to Sonoma, where the first vineyard was planted in 1805. Wine-making in California was revolutionized in the early 1850s by the Hungarian Agoston Haraszthy. Haraszthy had the wisdom or good luck to plant dry slopes, with no possibility of irrigation, on 560 acres that he had acquired in 1857, not far from San Francisco. He wrote a manual on planting and wine making; in 1861, Fig. 1. The J-shaped relationship between wine drinking and risk for death (7).