The Fevers of Reason. Gerald Weissmann

to the journals and found a recent report by George Whipple and Frieda Robscheit-Robbins that dogs made anemic by repeated bleeding could be restored to health by being fed huge quantities of uncooked liver. If it worked in dogs, why not in humans?

      The first patients to whom Murphy fed slightly cooked liver were patients with pernicious anemia. One of these patients was an old woman who had recently become cranky and obstreperous, but whom, after a mighty contest of wills, Murphy cajoled into taking her daily ration of half a pound of liver. Murphy described his everlasting “surprise” that not only did her red blood cells respond to a week or so of this cumbersome regimen, but also that she was relieved of her mental symptoms. She soon reverted to her former, agreeable self. Eventually, his lucky observation of her mental improvement persuaded Murphy that the active factor in liver must work not only in the marrow but also elsewhere in the body. Iron alone could not do the trick.

      By May 1926, Minot and Murphy had treated each of forty-five patients with half a pound of liver a day. Soon Minot persuaded a young biochemist, E. J. Cohn, to make a liver extract, which would be rich in the anti–pernicious anemia factor. The extract briskly revved up red cell production by the marrow and cured the disease as readily as raw liver. Indeed, it remained the primary treatment for pernicious anemia until Alexander Todd isolated and named vitamin B₁₂ in 1948. It was among the first miracle drugs to cure a hitherto fatal disease.

      Ironically, Whipple’s dogs had not suffered from pernicious anemia—they had iron-deficiency anemia caused by repeated bleedings, and their response was due to the iron present in massive doses of liver. Whipple’s error and Minot’s luck led directly to the first Nobel Prize in Physiology or Medicine awarded for work in the United States.

      There’s more to the Minot story, and it touches on Mello’s conversation with Adam Smith of the Nobel Foundation. Like Mello’s young daughter, Minot suffered from what we would now call type I diabetes: he was gravely ill when he made his great discovery. A strapping six-footer, Minot had developed a severe case of diabetes, and by 1922 his weight had dropped to 120 pounds. As luck would have it, Charles Best and Frederick Banting in Toronto, following the approach of John Macleod (Medicine and Physiology, 1923) had prepared the first useful batches of insulin. Minot was in the initial group of patients treated with the hormone by Eliott Joslin, the first American specialist in diabetes. One Nobel led to another: had insulin not been discovered, vitamin B₁₂ might have been a distant dream. It’s what Robert Hooke predicted in 1665 when the Royal Society began its assault on “not precisely Knowing”: “By this means they find some reason to suspect that those [phenomena] confessed to be occult, are performed by the small machines of Nature.”

      THE NAMES OF FIRE AND MELLO are now up there with those of Minot and Murphy, carved in stone on that pink granite slab behind a New York museum. More likely than not, some other kid from the neighborhood will point up at those names and start to wonder about what it takes to discover the new.

       6.

       Lupus and the Course of Empire

       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