Historical review of routes of drug administration Baggellardus, a contemporary of Columbus, observed Indians applying fumigation to the mouth or anus of apparently dead persons and brought the technique to Europe. In the aftermath, during the seventeenth and eighteenth century, scientific societies all over Europe recommended warmth, artificial respiration, rectal fumigation with tobacco smoke, friction, and bleeding for resuscitation purposes. Insufflation of air, tobacco smoke, or vaporized aromatic plants either by mouth, the nostrils, or the rectum was common, stimulants were administered by nasogastric or rectal tubes, and topical application with “spirits of wine, hartshorn, or, which is perhaps the most powerful, the spirits of sal ammoniac” were used. Eventually, tobacco insufflation was abandoned when Brodie in 1811 published his observations that even a dog was easily killed by injection of smoke into the rectum. History of intravenous techniques Bronze syringes had been known since antiquity, when Heron of Alexandria had recommended his pus extractor for injection of fluids. Blood circulation was discovered in 1616 by William Harvey, and in 1656 the British astronomer Sir Percival Christopher Wren (1632 to 1723) first demonstrated intravenous therapy by injecting wine and beer into a dog. He noted that “the opium…did within a short time stupefy, though not kill the dog.” Three other physicians, acting independently of Wren, described intravenous (iv) therapy: Johann Sigismund Elsholtz (1623 to 1688), who infused water into the brachial artery of a drowned woman in 1661, the surgeon Carlo Fracassati (ar. 1630 to 1672), and lastly Johann David Major (1634 to 1693), a medical doctor.