Some of Sydenham’s most vivid writings are those describing the onset, pain, and progress of gout, a disease also known as podagra. Sydenham confessed that he had endured the agonies of gout for 34 years without discovering anything useful about its nature or treatment. Many physi- cians, especially those who suffered from gout, considered the condition incurable. In its typical form, the disease announced itself by intense pain in the big toe. Victims were told that it was better for their ‘‘bad humors’’ to accumulate in a peripheral joint rather than in vital interior parts of the body. For the miseries of gout, stone, and chronic hematuria (which Sydenham bluntly referred to as ‘‘a great pissing of blood’’), his only antidote was opium and more opium. Until the twentieth century, little could be added to Hippocrates’ observations that gout generally attacked young adult males, while sparing women and eunuchs. Victims of the disease were thought to be wealthy men who indulged themselves in heavy wines, rich foods, excessive sexual activity, and those with an ‘‘unhappy hereditary ten- dency.’’ Seneca said the disease had ‘‘Bacchus for its father and Venus for its mother.’’ Today, primary gout is described as an inherited dis- order of purine metabolism, which results in the accumulation of uric acid. Secondary gout is a condition apparently caused by noxious chemi- cals, such as lead and various drugs. Seventeenth-century microsco- pists depicted crystals teased from a gouty joint: these crystals were eventually identiﬁed as uric acid. In 1847, Sir Alfred Baring Garrod (1819–1907), an eminent London physician and professor of medicine, noted an elevated level of uric acid in the blood of victims of gout; uric acid levels were not elevated in patients with other forms of arthritis or rheumatism. In addition to developing tests for gout, Garrod correctly suggested that gout might be caused by the inability of the kidney to excrete uric acid or an increase in the formation of this chemical, and that acute attacks of gout might be the result of the precipitation of sodium urate in the affected joints. Gout attacks are not fatal, but they are so painful that some vic- tims have been driven to suicide. An attack usually begins with intense pain in the great toe, chills, shivers, restlessness, and fever. Eventually, gout cripples the major joints and results in the chronic torment of kidney stones. Sometimes, Sydenham observed, the stones killed the patient ‘‘without waiting for the gout.’’ Living with fear, anxiety, and pain, the victim’s mind ‘‘suffers with the body; and which suffers most’’ even the long-suffering Sydenham could not say. The only comfort Sydenham had to offer his fellow victims was the thought that gout ‘‘kills more rich men than poor, more wise men than simple.’’ Nature, Sydenham believed, balanced her accounts by giving those she had favored an appropriate afﬂiction in order to produce a mixture of good and evil. Gout was the disease of kings, emperors, admirals, and philosophers. Despite Sydenham’s belief that gout reﬂected divine justice, the alleged relationship between gout and wealth and wisdom is simply an artifact of historical interest in the medical problems of the rich and famous and general indifference to the anony- mous victims of disease who suffered the torments of gout without bene- ﬁt of medical or biographical attention. Still, the list of distinguished victims of gout is so impressive that the British psychologist Henry Havelock Ellis (1859–1939) thought the disease was associated with genius. The victims of gout included Erasmus, Francis Bacon, William Harvey, Benjamin Franklin, Joseph Banks, Tobias Smollett, Edward Gibbon, Benjamin Disraeli, and Joseph Conrad. Lord Chesterﬁeld said that ‘‘gout is the distemper of a gentleman, rheumatism .. . of a hack- ney coachman.’’ Franklin, who wrote a witty ‘‘Dialogue’’ between him- self and the gout, also suffered from kidney stones. He concluded that ‘‘the Gout is bad, and .. . the Stone is worse.’’ Comforting himself with the idea that those who lived long and well must expect to encounter some diseases, Franklin reﬂected that there were maladies far worse than kidney stones and gout. Still, the torments of gout and stone drove him to seek out dubious remedies, including a good dose of ‘‘Jelly of Blackberries.’’ Physicians traditionally attacked the gout with bleeding, sweating, purges, cathartics, emetics, diuretics, blisters, massage, and cauter- ization. From his own experience, Sydenham could testify that none of these methods worked any better than ancient Roman charms and incan- tations. Abstinence in diet and drink was advisable, but in Sydenham’s experience: ‘‘If you drink wine you get gout—if you do not, gout gets you!’’ In 2004, scientists actually corroborated the traditional belief that alcohol consumption increases the risk of developing gout. Sydenham would be surprised to learn, however, that beer is more likely to lead to gout than liquor, or wine. Unfortunately, Sydenham failed to appreciate the value of colchicum, the one remedy that could have mitigated his sufferings. Colchicum, a crude extract of the autumn crocus, was used in many traditional purges. The Doctrine of Signatures provided a tenuous link between colchicum and gouty arthritis by associating the shape of the ﬂower with that of the crippled arthritic hand. Although colchicum was reputed to have aphrodisiac properties, it also caused unpleasant side effects, including stom- ach irritation, nausea, and death. Colchicum generally produced dra- matic relief from the pain of gout, as demonstrated by the success of the secret remedies of various quacks and empirics. By the eighteenth cen- tury, physicians had joined the quacks in recommending colchicum for the relief of gout. The mechanism by which colchicine, the active ingredient in colchicum, relieves gout attacks is still obscure. Colchicine was ﬁrst isolated in 1820 by Joseph Pelletier (1788–1842) and Joseph Bienaime´ Caventou (1795–1877), who are considered the founders of alkaloid chemistry. In addition to its therapeutic virtues, colchicine is invaluable to cell biologists and horticulturists, because it arrests mitosis (cell division) at metaphase. In plants this can cause polyploidy (increase in chromosome number), leading to the production of new varieties.