United nations shall combine,
To distant climes their sound convey,
That Anna’s actions are divine,
And this the most important day
The day that gave great Anna birth
Who fix’d a lasting peace on earth.
—G. F. Handel, “Ode for the Birthday of Queen Anne” (1713)
George the Third
Ought never to have occurred.
One can only wonder
At so grotesque a blunder.
—E. C. Bentley, “George III,” (1929)
WERE IT NOT FOR LUPUS and the antiphospholipid antibody syndrome, the United States might now have a National Health Service. That’s my conclusion from finding links between the most prominent victim of the syndrome—Queen Anne—and recent debates over Scotland’s secession from England. Anne (1665–1714) was the last of the Stuarts, a dynasty that gave England not only the union with Scotland but also the Royal Society, Isaac Newton, and the copyright law. The “grotesque” Georges who succeeded her led the British to Bunker Hill and Yorktown.
In September 2014, Scots held a referendum on whether to dissolve a partnership that had lasted since Queen Anne presided over the Acts of Union (1707), which established the “united Kingdom of Great-Britain.” As Simon Schama wrote in A History of Britain, Anne saw to it that the United Kingdom, which “began as a hostile merger would end in a full partnership . . . ” Anxious voters were reassured that, after independence, Scots would retain their popular National Health Service. Secession lost out, but Scotland’s first minister had already set Scottish Independence Day as March 24, 2016, to commemorate the anniversary of the Acts of Union and the United Kingdom’s founding mother, Queen Anne. The queen, a childless widow, died in 1714, sickened by what was then diagnosed as gout, dropsy, hemorrhage, and stroke. If poor Anne had produced a Stuart heir, that blundering George from Germany would not have ascended to the throne, and the United States today might have a National Health Service like those in Scotland, Canada, or Australia.
QUEEN ANNE’S LIFE AND THE STUART DYNASTY were undone by systemic lupus erythematosus (SLE) and its harsh companion, the antiphospholipid antibody syndrome, which produces bleeding, clotting, stroke, and obstetrical calamity (Hughes, 1985). Anne and her husband, Prince George Oldenburg of Denmark, sweated out at least seventeen pregnancies from 1684 to 1700 (Table 1): all but one resulted in miscarriages, stillbirths, or infant death. Anne’s longest-surviving child, William, the last Stuart to live at Kensington Palace, died at age 11 after suffering infantile seizures, childhood dyskinesias, and gross hydrocephalus, symptoms now recognized as those of neonatal lupus.
Table 1. Children of Anne Stuart, Queen of Great Britain, and George Oldenburg, Prince of Denmark
| Stillborn daughter 1 Oldenburg b. 12 May 1684, d. 12 May 1684 |
| Mary Oldenburg b. 2 Jun 1685, d. 8 Feb 1687 |
| Anne Sophia Oldenburg b. 12 May 1686, d. 2 Feb 1687 |
| Stillborn child 1 Oldenburg b. 21 Jan 1687, d. 21 Jan 1687 |
| Stillborn son 1 Oldenburg b. 22 Oct 1687, d. 22 Oct 1687 |
| Stillborn child 2 Oldenburg b. ca. Oct 1688, d. ca. Oct 1688 |
| William Henry Oldenburg, Duke of Gloucester, b. 24 Jul 1689, d. 30 Jul 1700 |
| Mary Oldenburg b. 14 Oct 1690, d. 14 Oct 1690 |
| George Oldenburg b. 17 Apr 1692, d. 17 Apr 1692 |
| Stillborn daughter 2 Oldenburg b. 23 Mar 1693, d. 23 Mar 1693 |
| Stillborn daughter 3 Oldenburg b. 21 Jan 1694, d. 21 Jan 1694 |
| Stillborn daughter 4 Oldenburg b. 17 Feb 1695, d. 17 Feb 1695 |
| Stillborn son 2 Oldenburg b. 25 Mar 1696, d. 25 Mar 1696 |
| Stillborn son 3 Oldenburg b. 25 Mar 1697, d. 25 Mar 1697 |
| Stillborn son 4 Oldenburg b. 10 Dec 1697, d. 10 Dec 1697 |
| Stillborn son 5 Oldenburg b. 15 Sep 1698, d. 15 Sep 1698 |
| Stillborn son 6 Oldenburg b. 25 Jan 1700, d. 25 Jan 1700 |
It’s clear that Anne suffered from SLE, a disease that chiefly afflicts women of child-bearing age and their newborns. The queen’s contemporaries describe four clinical features that add up to current criteria for the diagnosis, described 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,
