The Fevers of Reason. Gerald Weissmann

in Petri et al.: a blotchy, pitted face with a wolf-like rash on the cheeks; recurrent polyarthritis; facial and leg edema; and repeated seizures, nosebleeds, and lethal stroke. Official portraits of Queen Anne show variable joint swellings, obvious facial swelling, and the classic facial rash. Add her obstetrical history, and we arrive at the diagnosis of the antiphospholipid antibody syndrome. The syndrome is often tagged “Hughes syndrome,” after my colleague Graham R. V. Hughes, who described a patient in London with ailments similar to those of Queen Anne. His seminal 1983 article in the British Medical Journal sums up the problem: “Thrombosis, abortion, cerebral disease and the lupus anticoagulant.” Graham Hughes has earned his eponym: it’s fitting that he directs a unit at St. Thomas’ Hospital, down Royal Street and a bridge away from Westminster Abbey, where Queen Anne lies forever.

      Hughes syndrome, which can also occur in the absence of lupus, results from antibodies directed against one’s own cell membranes (phospholipids and/or proteins). Closely related antibodies, the “lupus anticoagulant,” inhibit the coagulation of normal blood; in pregnant women, these autoantibodies induce cascades of injury directed against the mother or products of her womb. A clue to the diagnosis, as in the queen’s case, is a history of fetal loss.

      BEFORE THE REIGN OF QUEEN ANNE (1702–1714), England was torn by religious and family spats that ranged in intensity somewhere between today’s Sunni–Shiite conflicts and intramural White House squabbles. The House of Stuart regained power in 1660 after Cromwell’s Puritan misadventures. Anne’s uncle, Charles II, restored the monarchy, presided over Restoration comedy, and chartered the Royal Society. The second Charles was a middling Protestant, as Anne had been brought up. But next in line to Charles came a very partisan Catholic, his brother, to be James II, who was Anne’s father. After a short three years in power, James was overthrown in 1683 by Anne’s Protestant brother-in-law (and cousin), who became William III. This coup, called the Glorious Revolution of 1688, resulted in permanent exclusion of any Catholic successor. William III became joint monarch with Anne’s elder sister, Mary II, whom he had married—we know the pair from the college in Williamsburg, Virginia, whose name honors them. As a website devoted to British royals puts it, “the marriage survived although all three of her pregnancies were stillborn.” Two sisters, sixteen stillbirths, no heirs? Time for some genomics here.

      Then came the younger sister’s turn: Queen Anne with her own stillbirths, her gout, dropsy, and seizures. But these days her reign is remembered less for disease than for peace and prosperity. The War of the Spanish Succession had broken out on both sides of the Atlantic the year before her coronation. The great powers—England, Austria, and Holland versus France and Spain—fought battles from the Alps to the Canaries, from Jamaica to the Arctic. Handel’s musical tribute to the “great Anna” celebrated her major achievement, the Treaty of Utrecht (1713). The treaty not only established a peace that would last to midcentury but also left Britain in possession of Newfoundland, Nova Scotia, the Hudson Bay Territory, and Gibraltar. Schama had it right—that full partnership of the United Kingdom had become “the most powerful going concern in the world.”

      Anne followed a path set by uncle Charles II as custodian of arts, science, and the commonweal. She was a patron of Christopher Wren, knighted Isaac Newton in Cambridge, and appointed Jonathan Swift the dean of St. Patrick’s in Dublin. By proclaiming the “Statute of Anne” (1710) for the “Encouragement of Learned Men to Compose and Write useful Books,” she established the basis of copyright law in anglophone countries. In the American colonies, her contented subjects commemorated her name and the benefits of her deeds. Annapolis, Maryland, is named for her, as are Cape Ann in Massachusetts and Fort Ann in Washington County, New York. She is remembered for granting an Act of Denization (by which a foreigner obtained legal status) to Luis Gomez, a Jewish refugee from the Spanish Inquisition in 1705. This document allowed Gomez to conduct business, own property, and live freely within the colonies. His mill in Marlboro, New York, is a tourist site today. Among her other acts, deeds, and grants that remain in the news are those 215 acres the queen bestowed on Trinity Church in Manhattan in 1705. The church elders are debating what to do with the $2 billion it’s worth today.

      Not bad for a dozen years of Stuart-ship, and again one wonders what a living heir would have meant.

      TROUBLE CAME WHEN THE HESSIANS FOLLOWED THE STUARTS. Worried over Anne’s afflicted womb, Parliament passed the Act of Settlement (1701), which assured a Protestant line of succession. The nearest skein of that line led to Hanau (Hanover) and the four Georges who ruled from 1714 to 1830. George I, a Hessian who barely spoke English, kept several mistresses; in return, his wife eloped with a Swedish count, who was killed and dumped in a river on George’s order. He then had his young son, George II, arrested for siding with his mother and excluded him from public ceremonies. When his father died of a stroke on one of his frequent trips home to Hanover, George II assumed the British throne and—one generation after Anne’s “lasting peace”—took the country to war again. The issue was settled in 1745, when Bonnie Prince Charlie and his Highlanders were defeated by the redcoats at Culloden. In 1751, George II’s eldest son, Frederick, died suddenly of mysterious injuries (having been struck by a tennis, or possibly a cricket, ball), and the crown passed to George III.

      At age 22, George III became head of the British Empire in 1760. The official website of the British monarchy notes that he is best remembered for provoking American independence and for going mad—adding, “This is far from the whole truth.” Alan Bennett’s popular play and the film made from it, The Madness of King George (1994), revived the story of a nutty monarch crazed by “variegate porphyria.” Modern analyses reject that diagnosis but not its symptoms: blindness, deafness, and madness—episodic bouts of which followed the loss of the American colonies. When his redcoats and Hessian mercenaries were defeated by the Americans, he declared a General Day of Fast in 1778—a gesture understood as pitiful at the time. Horace Walpole (1717–1797) wrote:

       First General Gage commenc’d the war in vain;

       Next General Howe continued the campaign;

       Then General Burgoyne took the field and; and last

       Our forlorn hope depends on General Fast.

      Whether his madness was caused by, or was coincident with, loss of his American colonies remains in doubt. What is certain is that George III blundered into his American quagmire through economic miscalculation. The empire was going broke, thanks to the costs of the successional wars with France and Spain and the expenses of the East India Company, which ran India for the crown. By the 1770s, at a time when there were no income taxes, the United Kingdom required £4 million (£500 million today) simply to service its debt. The answer was to tax items in demand among the more prosperous of the American colonies. George had figured out a solution. In a letter of the early 1780s, he wrote, “While the Sugar Colonies [the Caribbean] added above three millions a year to the wealth of Britain, the Rice Colonies [South Carolina, etc.] near a million, and the Tobacco ones [Maryland, etc.] almost as much; those more to the north [Pennsylvania on up], so far from adding anything to our wealth as Colonies . . . rivalled us in many branches of our industry, and had actually deprived us of no inconsiderable share of the wealth we reaped by means of the others.”

      The answer was clear: impose taxes on sugar, tea, and commercial transaction. The British were sure that those moneymaking rivals would return some of the “not inconsiderable wealth” in the form of taxes. The result of that miscalculation was the American Declaration in Philadelphia of July 4, 1776, which lists in detail a litany of “ . . . the patient sufferance of these Colonies” and explains the “necessity which constrains them to alter their former Systems of Government.”

      We do not know whether a legitimate heir of Queen Anne would have forestalled rebellion in Scotland or revolution in America, but I can imagine a placid Anne or regal Charles on the throne, making sure of “a lasting peace” on both sides of the Atlantic. Without those antiphospholipid antibodies tugging at Anne’s womb, the Georges might have remained in Hesse, and the United States would have a National Health Service, just like Scotland.

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