by Bill Hayes
King George III was likely never fed such savory dishes when he was ill. Rather, according to historians, he was often straitjacketed, tied to a bed or chair, and subjected to a varying regimen of vomits, purges, blisterings (the placing of hot coals on the skin in order to draw “bad humors” to the surface), cuppings, bloodlettings, and leechings. Heaven help the king. Perhaps some degree of solace can be found, however, in the fact that the last three forms of treatment would have, in theory at least, helped the ruler. While anemia can be relieved through adding blood, removing blood will quickly reduce the level of porphyrins in circulation. In fact, some types of porphyria are currently treated through phlebotomy, the modern-day counterpart to bloodletting, as is the more common hereditary blood disease, hemochromatosis, in which a dangerous excess of iron in the blood must be decreased through regular blood draws. (A curious side note: Once this heme-heavy blood is collected, it’s routinely destroyed, even though—assuming the donor with hemochromatosis is otherwise disease-free—its iron-richness is exactly what many ER patients need.)
Four of King George’s sons are believed to have had porphyria, including the heir apparent, George IV, whose wife (a first cousin) and daughter, Charlotte, were also afflicted. It’s quite possible the illness later led to Princess Charlotte’s death during childbirth at age twenty-one (her son was stillborn), a tragedy that precipitated a regency crisis: The king, who by this point was blind, enfeebled, and nearly eighty, now had no legitimate heir beyond George IV. Moving swiftly, he arranged marriages for his three eldest sons, and each produced a child in the year 1819, one of whom, Victoria, would be crowned queen of England at age eighteen. Although Victoria, who also married a first cousin, Albert, was spared porphyria, she introduced another devastating blood disease into the British royal family, one that would eventually taint the ruling houses of Spain, Germany, and Russia: hemophilia.
TEN
Shemophilia
BLOOD NATURALLY SEPARATES. REMOVED FROM THE constant “stirring” of the circulatory system and collected in, say, a test tube, blood settles into our tricolor hematological flag, amber, white, and red. The band at the top is plasma, the liquid in which the cells of the blood are normally suspended. Next is the narrowest stripe and the palest, a blend of white cells and platelets. And beneath these, the bog of burgundy-colored red cells, the heaviest of which, the deep red, almost black corpuscles laden with waste, have sunk like sediment at the bottom of a pond. Curiously, what some would call the defining quality of blood—its redness—does not in fact contain the defining quality of humanness, DNA; red cells are “dumb” cells, devoid of a cellular “brain,” a nucleus.
The color blue is not part of the mix, although the long-lived phrase blue blood deserves a little deconstruction. Its etymology begins with sangre azul, a term that arose out of a medieval case of xenophobia. During the Moorish occupation of Spain, members of the oldest and staunchly Christian families of the Castile region claimed they were superior for never having intermarried with the darker-skinned Muslim invaders of their country. The proof of their blood’s purity was as near as a forearm. A Castilian need only point to the tributaries of blue visible through his or her white skin. What they called sangre azul we’d now call an optical effect, deep purple blood seen through pale purplish veins seen through an epidermal scrim.
By the time blue blood crossed into the English language in the 1830s, concurrent with the beginning of Queen Victoria’s reign, it had shed the racial connotation and become synonymous with society’s upper crust. Within this rarefied meringue of British blue-bloodedness were further distinctions: the gentry class, the aristocracy, and, at the top, the royal family. Royalness, too, had its own degrees. To be of “morganatic blood,” for example, meant that one of your parents was of pure royal extraction—that is, “of the blood,” the bluest of the blue—and the other was not. Perhaps your mother and father had married not as a dynastic stratagem but out of love—what folly! Entering into a morganatic marriage came with a price: the forfeiture of your children’s right to succession. Compared to other sovereigns of her era, Queen Victoria was far more accepting of such unions. A sterling example of this magnanimity came in the spring of 1866. When informed that an obscure Austrian prince wished to marry one of her cousins, Victoria dismissed the many objections regarding the gentleman’s unequal birth and gave her full blessing. What’s more, upon first laying eyes on this tall, strapping man, the queen saw not the penniless military officer but a solution to a problem, one the prince’s physical presence brought to the fore. What the queen would never admit publicly was her deep concern about the quality of her family’s blood, made, as she described it, “so lymphatic,” generation after generation, by all “that constant fair hair and blue eyes.” Prince Teck was all things but with jet-black hair and dark good looks. Shortly after meeting him, the queen wrote to her eldest daughter, Vicky, a lifelong confidante, who was grown with fair-haired children of her own and ensconced as the crown princess of Prussia. Oh, Victoria lamented, “I do wish one could find some more black eyed Princes or Princesses for our Children!”
It’s hard to imagine Vicky’s reaction as she read the rest of her mother’s words, which, in just a handful of sentences, move from despair to envy to a rising franticness (note how even the underscorings escalate): “I can’t help thinking what dear Papa [the queen’s deceased husband] said—that it was in fact a blessing when there was some little imperfection in the pure Royal descent and that some fresh blood was infused.” Here the queen paused for a moment, asking her daughter to excuse this “somewhat odd letter,” before diving back in: “It is not as trivial as you may think, for darling Papa—often with vehemence said: ‘We must have some strong dark blood.’ ”
This letter reads as if a mother’s intuition had sharpened in grandmotherhood, but at the time Victoria would’ve had no idea of the troubles to come. The hemophilia that would eventually touch sixteen family members had, in 1866, manifested solely in Victoria’s youngest son, thirteen-year-old Leopold. A strange aspect of the disease is that while females carry the defective gene that prevents proper clotting, in general only males develop the disorder. In other words, it stays hidden in a woman until it shows up in a son. By scanning Queen Victoria’s family tree, medical historians have established that two of Leopold’s five sisters, Alice and Beatrice, were carriers. There’s also no doubt that his mother introduced hemophilia into the royal bloodline.
How Victoria got it is something of a puzzler. Tracing back her ancestry, no red branchings of the disease appear, which leads to three possibilities. The traditionally held view is that it was caused by a spontaneous mutation (this occurs in about 30 percent of hemophilia cases). Second, that, against the odds, Victoria’s mother, maternal grandmother, maternal great-grandmother, and so on were carriers whose sons never suffered the disorder. Or, third, the most sensational possibility, that Victoria was illegitimate. Genetics has fueled this particular speculation. Given that every daughter of a male hemophiliac (and a normal female) is a carrier, perhaps then, as a pair of British scientists postulated in the mid-1990s, Edward, Duke of Kent, was not her biological father. (As a Newsweek headline blared, “Was Queen Victoria a bastard?”) Well, maybe, maybe, and maybe, although I’m leaning toward (1), spontaneous mutation.
To her dying day the queen refused to believe that the disease came from her side of the family. It is also considered unlikely that she was ever fully briefed on the cause and patterns of the disorder, even though a fairly sound clinical description had been established at the dawn of the nineteenth century. In Leopold’s early childhood, no obvious flags went up. He was her most “delicate” son, Victoria admitted, born tiny, and less graceful than his three older brothers. She blamed his frequent bruising on clumsiness and, in her ignorance of Leo’s true condition, was ofttimes impatient and critical. Sickly, pallid, and frail, the boy was an embarrassment. At the time of his fifth birthday, though, a family walk, a skinned knee, and a cut
that would not stop bleeding forced Victoria to face the reality that her son was a “bleeder.” With that, the queen made an emotional turnaround, and a well-intended overprotectiveness set in. She drafted an all-staff bulletin of sorts regarding her son. Forthwith and henceforth, all active play with other boys would be denied the lad, and “all the essentially English notions of ’manliness’ must be put out of the question.” His tutor must never leave Leo unattended, and a long list of activities became restricted. But of course, tell a child “don’t” and he’ll naturally be tempted to “do.” When Leopold was eight, to cite one example, he somehow managed to ram a steel pen through the roof of his mouth.
Leopold, age nine, with his mother, Queen Victoria, April 1862
Stitches didn’t work well for a hemophiliac because, obviously, they just introduced more holes. The alternative was cauterizing, a method that essentially melted closed a wound, using either a caustic substance or a red-hot brand. I can only hope that Leopold was well anesthetized when this treatment was inflicted. When Victoria described this incident in a letter to her daughter Alice, her words seemed to stumble, as if numbed: “The fear was—the bleeding could not be stopped and then—you know he could not have lived.”
That Leopold survived into his early thirties is medically remarkable. Most bleeders in his day never made it into adolescence. In fact, individuals with severe hemophilia faced a similar mortality rate well into the 1960s. To answer definitively why Prince Leopold lived as long as he did, however, would require something that simply no longer exists: a sample of his blood. With it, a modern hematologist would be able to find exactly what was missing. Without it, a good guess is still possible. But first, some basics are in order.
The simplest way to describe coagulation is to say it’s a complex process in which blood turns from a liquid to a solid. As many as twenty different blood proteins take part in this coordinated effort—what one scientist with a touch of the poet named “the clotting cascade.” Thirteen of these blood proteins are called factors, and a deficiency of any one results in a different clotting or bleeding disorder. To picture the prevalence in the general population, imagine a twenty-thousand-seat sports stadium filled to capacity and split evenly between the sexes. Four hundred attendees, men and women alike, would have the most common bleeding disorder, von Willebrand’s disease, in which a deficiency of the von Willebrand factor keeps platelets from clumping properly at the site of an injury. Just two attendees, men only this time, would have hemophilia A, or classic hemophilia, which is caused by a lack of factor VIII. To find a single gentleman with hemophilia B, two additional stadiums are needed (one in thirty thousand men have this deficiency in factor IX). Now on to a bigger challenge. To find a woman with classic hemophilia, one should probably scrap the whole stadium idea and consider instead the entire population of the United States. One in one hundred million citizens is this rarest of the rare, a female hemophiliac. Its infrequency in women is simply a matter of genetics, the female XX versus the male XY. The recessive gene for hemophilia rides the X chromosome. In a female, if one X is defective, the other can normally compensate. It would take the pairing of two defective X’s for the condition to develop.
In males, the first sign of a serious bleeding disorder often comes when a baby boy is circumcised, a danger that has been recognized since ancient times. In the Babylonian Talmud, the collection of Jewish rabbinical laws written between the third and sixth centuries, it was declared that a newborn son would be excused from circumcision if two brothers had previously died from the procedure. From a modern standpoint, this law calls to mind a common misconception that should be stanched forthwith: that a hemophiliac with, say, a minor wound will never stop bleeding. The lack of factor VIII or IX doesn’t mean your blood won’t ever coagulate; the woodwinds may be absent, so to speak, but the orchestra still plays. Other components of the clotting cascade continue to do their job. The problem is, you clot more slowly and hence bleed longer. How long depends largely upon how much clotting factor is present in your blood. Analyses of blood can calculate the speed of your clotting as well as pinpoint which factor is deficient and in what quantity. A person with mild hemophilia, for instance, will have, at best, only half the clotting activity of a healthy person. By contrast, in severe hemophilia, the amount is less than one one-hundredth of normal. Once these calculations are determined, treatment is fairly straightforward, at least in theory. You simply inject or infuse the missing substance. And of course the earlier in a person’s life that these levels are assessed, the better.
Regarding Leopold, it is possible to piece together details of his condition through his words, for the young man’s personal correspondence lays bare his suffering. A well-understood medical consequence of severe hemophilia is spontaneous internal bleeding into the joints and muscles, which balloon with blood, becoming excruciating and crippling. Leopold clearly had this. In a letter to his sister Louise begun June 6, 1870, he barely got past the “Dearest Loo” before having to stop, so fierce was the pain. He couldn’t continue until four days later: “. . . At this moment I am in agonies of pain; my knees get worse daily and I get more desperate.” Despite the limited relief offered by the treatments of the day—bed rest, ice packs, and, only as a last resort, morphine—Leopold, seventeen at the time, leavened his note with a bit of gallows humor. “If this continues long I shall soon be driven to Bedlam [by which he meant the loony bin], where I shall be fortunately able to terminate a wretched existence by knocking out my brains (if I have any) on the walls; that is the brightest vision that I can picture to myself as a future. . . .”
Signed, “Your wretched brother, Leopold.”
If humor helped him rise above the pain, an intense pursuit of academics also provided an escape. By this point in his life, the Scholar Prince, as he would be known, had become well versed in Shakespeare and fluent in several languages. Over his mother’s objections, Leo attended Oxford University, the first in the family to do so. His gumption is all the more remarkable when you factor in that he also had epilepsy. After graduation he became one of the queen’s most trusted political advisers, gaining the title Duke of Albany. At the same time, he wanted to establish a life for himself apart from his mother and longed to marry. In 1882, at age twenty-nine, Leopold made both himself and the queen happy by wedding Princess Helena of Waldeck, sister of the Dutch queen. The happiness would last just two years. Shortly before the birth of his second child, Leopold took a spill—what for a healthy person would’ve merely meant a bump on the head. He died a few hours later from a brain hemorrhage. Upon receiving the news of her son’s loss to hemophilia, Queen Victoria, now sixty-five, set down in her journal three devastated words, “Am utterly crushed.”
At this stage of her reign, Victoria was becoming known to the world as “the Grandmama of Europe,” so called because so many of her children and grandchildren had married heirs to thrones throughout the Continent. The Grandmama of Europe was also the hands-on grandmama of six grandchildren, in whose raising she’d taken an active role since her daughter Alice’s passing from diphtheria in 1878. When these children approached marrying age, she did more than matchmake. As with many of the other royal marriages she’d helped broker, these unions would expand the family power base. They would also spread hemophilia geographically. In 1888 granddaughter Irene was married to a first cousin, Prince Henry, thus bringing hemophilia into Prussia. In 1894 granddaughter Alexandra was married to Czar Nicholas II, tainting the Russian imperial family, the Romanovs. The 1885 marriage of Victoria’s youngest child, Beatrice, also bears noting here, for it brought the stain into the German royal bloodline. A daughter of this union would then go on to introduce hemophilia into the blue blood of Spain. Closest to home, Leopold’s daughter would perpetuate the family legacy in her marriage to a British nobleman.
From a medical historian’s perspective, the damage wrought by Queen Victoria’s gene was grim: three affected children, six grandchildren, and seven great-grandchild
ren. Ten male sufferers and six known female carriers. Only late in life were her eyes opening to the depth of the devastation. “Our poor family,” she wrote privately, “seems persecuted by this awful disease, the worst I know.”
As disease names go, I have to wonder what in the world Dr. Johann Schönlein was thinking when he came up with hemophilia back in the early 1800s, a term translating from the Greek as “love of blood.” I have it on good authority that affection has nothing to do with it. Aggravation is more like it, according to Christine Pullum, a dry-humored Louisianan who is one of those rarest of the rare, a woman with classic hemophilia. An acquaintance had introduced me to Christine, age sixty-six. I reached her by phone at her home in Lafayette, where she, a retired administrative assistant, lives with her husband of thirty-six years, Doyle, a former junior high school math teacher.
With so few cases of female hemophilia A on record, it would be a stretch to call any one instance typical. Still, experts say it most likely would manifest in a daughter born of a male hemophiliac and his carrier wife. Not so with Christine. “Our family didn’t have the usual pattern,” she told me. “I got it directly from my daddy.” In a genetic fluke, the good X chromosome she got from her mother failed to compensate for the defective one, making Christine what’s called a symptomatic carrier. Her two sisters are also carriers but have never been symptomatic. The shared disease between Christine and her father created a unique bond. Throughout her childhood, he would tell her that their hemophilia could be traced back to the czars of Russia, referring, I gathered, to the doomed Romanov family, all of whom—Nicholas, Alexandra, Olga, Tatiana, Marie, Anastasia, and Alexis—were assassinated in 1918 in the wake of the Russian Revolution. Christine has never seen any documentation of this tie, she acknowledged, and I had to admit I couldn’t see how this branch fit onto the Romanov family tree. Even so, it sounded like a sweet way to make a daughter with a scary disease feel special.