‘Game of Thrones’ offers medical lessons in genetics, incest, and infertility

Editor’s note: This post contains spoilers.

As Game of Thrones winds down, and the body count ramps up, one of the plot threads that lives on and on is incest within the royal families.

This season, Queen Daenerys Targaryen and Jon Snow suffered terribly upon learning — only after they fell in love and started sharing a bed — that they really are aunt and nephew.

But by GOT standards, that’s barely related. Even Daenerys’ own parents were brother and sister, and theirs was not the first incestuous relationship in the Targaryen family, which may be how her father earned his nickname, the Mad King. And remember how creepy Daenerys’ own brother was around her back in Season One?

In Westeros, as in most places, incest is taboo. Why else would Jaime Lannister have hurled little Brandon Stark off the castle wall if the kid hadn’t observed Jaime and sister Cersei having sex? Not to mention they were committing adultery.

As for the outcome of their relationship: consider the villainous behavior of their son Joffrey, though it is unclear if his behavior is due to inheriting a recessive disease, or if Cersei simply passed on whatever her evil is. Jaime wasn’t a bad guy. Usually.

Close but not-too-close family relationships seem acceptable in Westeros. Jaime and Cersei, now deceased, were the offspring of Tywin and his first cousin Joanna Lannister, a relationship apparently no one tried to hide. Of course, these cousins also produced Tyrion, a dwarf whose nasty sister considers him an error of nature, but who generally is morally superior to his siblings.

Incest has been taboo for thousands of years and is explicitly banned in the bible (though so are homosexuality and other practices many of us have no problem with today). There are many terrifying tales of incestuous pairings, especially among royalty. Take the famous mythical story of Oedipus who unknowingly killed his father and then married his mother.

But what are the real risks of producing children from incest? Should Daenerys and Jon consult a genetic counselor, should their union survive? And separately, given her history of stillbirth after a curse, can Daenerys even bear children?

Fiction and history aside, there is an increased risk for genetic diseases when two people who share too much genetically have children. The medical term for incest is consanguinity, literally meaning “within blood.”

The biological purpose of sexual reproduction is to create new combinations of genetic material to create offspring. When two similar sets of genes are paired together, there’s a greater chance that a recessive disease, one that wouldn’t ordinarily have a chance to be expressed if it were in only one parent’s genome, comes out.

In European royal families, consanguinity occurred because of a bottleneck effect: They wanted to marry only other royals. With only a small representation of the full diversity of genetic possibilities available, the result was inbreeding. Thus, diseases such as hemophilia and porphyria became overrepresented in this group. Indeed, hemophilia was known as “the royal disease,” with a high percentage of Queen Victoria’s descendants affected.

This is also the reason we see certain diseases appear in populations of genetic homogeneity. For instance, Tay-Sachs disease occurs in Ashkenazi Jews more often, because when you exclusively mate in a smaller genetic pool, small risks become more likely. On the other hand, if you have children with a partner who is the least genetically like you, the chances of recessive genetic diseases are the least likely. Of course, spontaneous mutations can happen to anyone, so genetic diseases are always possible.

The risk of genetic disease in children of incest is most significant among first-degree pairings (brother-sister like Jaime and Cersei or Daenerys’ parents, father-daughter, mother-son) since they may share up to 50 percent of their genetic material. When it comes to first cousins or beyond, the risk lowers since there is only 12.5 percent genetic overlap potential.

Aunt-nephew pairings are not especially risky, but Daenerys and Jon still may share up to 25 percent of their DNA.

Moving on, how about Daenerys’ ability to have children? Daenerys tells Jon, "The dragons are my children. They're the only children I'll ever have — do you understand?" It’s unclear if Daenerys simply believes she cannot carry a child to term or is uninterested in having non-dragon children. That is her right, after all. Must she have to justify her position not to have kids beyond her dragons? Still, let’s consider the possibilities.

Way back, before her dragons were born, recall that Daenerys was pregnant with Khal Drogo’s child. When Khal Drogo is near death, Daenerys pleaded with Mirri Maz Duur, who practiced blood magic, to save him, in exchange for whatever sacrifice necessary. Soon after, Daenerys’ unborn child Rhaego started kicking and she developed pain, ultimately culminating in stillbirth. Was Daenerys cursed? Did she trade away her ability to have children?

It was unclear how far along Daenerys was when she lost her baby. Women can feel fetuses kicking as early as 13 weeks, so if Daenerys had a miscarriage or stillbirth, she must have had a second or third trimester pregnancy loss. All miscarriages can be devastating, but they do not indicate an inability to have future children. In fact, one-fourth of all recognized pregnancies are thought to end in miscarriage (usually very early on), yet the stigma of miscarriage may prevent people from discussing it openly.

Still, late miscarriages are less common, with 1 to 5 percent lost at 13 to 19 weeks, and 0.3 percent at 20 to 27 weeks. The Targaryens supposedly have a higher rate of stillbirths and miscarriages, so it is possible that Daenerys herself carries a genetic disease that predisposes her to pregnancy loss; this includes coagulopathic disorders such as Factor V Leiden, protein S deficiency, and the prothrombin G20210A mutation. Another condition called antiphospholipid antibody syndrome, which is associated with lupus, can also cause repeated or late miscarriages.

Many problems can lead to infertility in women, including endometriosis, polycystic ovaries, and complications from sexually transmitted infections. Curses, however, have not been reported in medical literature.

In the end, there are many options for having children, from adoption (including dragons), surrogacy, and natural childbirth. Should Daenerys want to have more children, she has options, but regardless of her reasons, especially having recently lost at least two adoptive children (her dragons), we should respect her agency in deciding her own future reproductive choices.

Jules Lipoff, M.D., is assistant professor of dermatology at the University of Pennsylvania Perelman School of Medicine.