Henry VIII: the fault in his blood? (Archive)

Originally posted February 13, 2018.

Grace Hamilton studies the molecular machinery responsible for ensuring that every time a cell divides its genetic material is distributed equally between the two daughter cells. If this process goes awry, the result is cells with an abnormal number of chromosomes–– a hallmark of genetic disease and cancer.

In response to armchair diagnoses of Donald Trump, the American Psychiatric Association enjoined members never to diagnose a patient that they hadn’t personally examined. We can only hope that they will forgive an armchair diagnosis of leader long dead: the infamous Henry VIII.

If you know anything at all about this English monarch, you know that he suffered a surfeit of wives and a dearth of sons. (Only sickly Edward VI outlived his father, and that by a mere 6 years). Countless works of scholarship and fiction, from the Showtime drama “The Tudors” to the Man Booker Prize-winning novel Wolf Hall, depict how the idealistic, athletic, and beloved young monarch ended his life paranoid, cruel, and obese, obsessed with his inability to produce a male heir, taking bloody vengeance on the women who failed to provide him one. Prince Charming became an ogre. Historians, novelists, and showrunners have long sought to explain the gruesome transformation.

Now biologists are taking a stab at it.

Bioarchaeologist Catrina Banks Whitley and medical anthropologist Kyra Kramer published their theory that the fault was not in Henry VIII’s stars but in his blood. On the surface of his red blood cells to be exact.

First published in The Historical Journal (Cambridge University Press), Whitley and Kramer’s theory is that Henry VIII had a rare blood type that caused his sexual partners (they weren’t all wives) to mount devastating immune responses against their own fetuses. 1

Specifically, Henry VIII may have expressed the dominant version of a gene encoding the Kell antigen. Over 90% of Caucasians have only the recessive version of that gene, 2 meaning that the immune systems of Katharine of Aragon and Anne Boleyn would have recognized the protein as foreign when exposed to it during their first pregnancies. When the body detects foreign proteins, the immune system produces antibodies that will specifically target any cell expressing that protein for destruction.

During the second pregnancy of each queen, a legion of antibodies would attack the red blood cells of any fetus expressing the dominant version of the Kell antigen. Loss of its red blood cells starves a fetus of oxygen, causing miscarriage or death soon after birth. After one successful pregnancy each, Katharine and Anne each had multiple pregnancies ending in such tragedy*. In contrast, Bessie Blount and Jane Seymour (Henry’s mistress and third wife, respectively) each provided him with a son during their first known pregnancies. Thus, an inconvenient Kell antigen could explain Henry’s reproductive misfortunes.

It could also explain his rapid physical and mental deterioration during middle age. Whitley and Kramer posit that Henry VIII suffered from McLeod Syndrome, a degenerative disorder caused by a recessive mutation in the Kell blood group system. Symptoms of this disease begin in middle age and include muscle degeneration and psychiatric symptoms. Henry was confined to a wheelchair and displayed “tyrannical psychosis” later in his life. 3 While others have blamed these symptoms on syphilis 4 or a head wound sustained while jousting, 5 Whitley and Kramer attribute them to McLeod’s Syndrome.

Is there any way to test this theory? Since none of Henry’s children had progeny of their own, the only way to be sure would be to exhume his body and perform genetic testing. While this has been done for another English monarch, Richard III, the current royal family seems unlikely to grant permission to exhume Henry VIII any time soon. Desperate to test this clever theory? Too bad. That’s what you get for diagnosing a patient you cannot examine.

*Connoisseurs of Tudor history will note that Mary was not Katharine’s first pregnancy with Henry, which Whitley and Kramer explain by noting that years earlier Katharine may have been pregnant by Henry’s brother Arthur, to whom she was briefly married, or she could have chosen to “seek an alternative sperm donor” for Mary’s father.

Sources

1. Whitley CB, Kramer K. A new explanation for the reproductive woes and midlife decline of Henry VIII . The Historical Journal. 2010;53(4):827-848. doi: 10.1017/S0018246X10000452.

2. Hessner MJ, Agostini TA, Bellissimo DB, Endean DJ, Pircon RA, Kirschbaum NE. The sensitivity of allele-specific polymerase chain reaction can obviate concern of maternal contamination when fetal samples are genotyped for immune cytopenic disorders. Obstet Gynecol. 1997;176(2):327-333. doi: 10.1016/S0002-9378(97)70493-9.

3. Stride P, Lopes Floro K. Henry VIII, McLeod syndrome and Jacquetta’s curse. The journal of the Royal College of Physicians of Edinburgh. 2013;43(4):353. doi: 10.4997/JRCPE.2013.417.

4. Clarke W. Henry VIII and the French pocks; the end of the Tudors. Journal of social hygiene. 1951;37(7):306.

5. Ikram MQ, Sajjad FH, Salardini A. The head that wears the crown: Henry VIII and traumatic brain injury. Journal of Clinical Neuroscience. 2016;28:16-19. doi: 10.1016/j.jocn.2015.10.035.