Last year, season 3 of Orphan Black introduced a line of genetically male clones to its tale, and with them came a scary new twist in the Orphan Black biology. How scientifically realistic is this weird new development? Well, something like it does happen in the real world -- but only with fruit flies, not humans. Spoilers for season 3 of Orphan Black ahead...
Orphan Black has introduced a strange new bioweapon: semen that causes women to become infertile after sexual intercourse. Allow us to explain.
In the Orphan Black mythos, there are two known lines of clones: The genetically female Leda clones and the genetically male Castor clones. (There is actually one male Leda clone, Tony, who is transgender, but for the sake of this piece, I'll be generalising and referring to the Leda clones as female and the Castor clones as male.) Both sets of clones have something very important in common: a synthetic genetic sequence that made the cloned fetuses viable in the womb. Unfortunately, it's caused horrible health problems for both lines of clones.
Now things get complicated on Orphan Black pretty quickly, so here's a breakdown of what the show tells us about the genetic condition afflicting the Leda and Castor clones:
- In the Castor clones, the genetic sequence results in a prion disease, in which a misfolded protein causes other proteins to misfold. On a few occasions, Cosima likens it to Creutzfeldt-Jakob disease, which in humans is associated with the major prion protein (PrP). In cows, PrP is associated with bovine spongiform encephalopathy, better known as mad cow disease.
- This prion disease attacks the brain of Castor clones, causing rapid neurological degeneration. It's pretty horrifying.
- In most of the Leda clones, the genetic sequence results in an autoimmune disorder that attacks the lungs and uterus. Nearly all of the Leda clones are infertile, and many suffer from a terminal respiratory illness.
- But this is the really scary part: When one of the Castor clones has unprotected vaginal intercourse with a woman, he can transmit his misfolded proteins to his sexual partner. Many of the women who have had sex with the Castor clones subsequently develop a fever and their ovaries rapidly degenerate, rendering them infertile. Granted, it doesn't kill the women the same way the prion and autoimmune diseases kill the Castor and Leda clones, but someone has decided this would make a really neat superweapon. Gross.
A genetic illness that can be passed through sexual contact? This is some pretty freaky stuff. But is it remotely plausible? We turned to our own Throb editor (and expert on reproductive anatomy) Diane Kelly, plus Norman Johnson, an adjunct research professor at UMass Amherst who specialises in genetics and evolution, for help separating the scientific wheat from the pseudoscientific chaff.
"So, genetic illnesses are usually the result of mutations," Kelly explained. "And the mutations change the sequence of amino acids that make up the protein, so they don't fold right, or the site where they're supposed to grab onto other proteins is malformed. Or sometimes you get a mutation that knocks a protein out altogether." According to the US National Library of Medicine's Genetic Home Reference, between 10 and 15 per cent of all cases of prion disease in humans are the result of a mutation in a gene known as PRNP (PRioN Protein) gene. Here's how the Genetic Home Reference describes prion diseases:
In people, these conditions impair brain function, causing changes in memory, personality, and behaviour; a decline in intellectual function (dementia); and abnormal movements, particularly difficulty with coordinating movements (ataxia). The signs and symptoms of prion disease typically begin in adulthood and worsen with time, leading to death within a few months to several years.
That's pretty consistent with what we see happen to the Castor clones, although their decline is rapid. They go from high functioning to babbling and unable to control their movements in a matter of days.
And Johnson adds that it is certainly possible that a specific genetic sequence would affect the Leda and Castor clones differently. In the real world, we do see genetic sequences have different effects on different sexes, and some of those differences can be quite drastic. "Sometimes, a given genetic variant can increase fitness in one sex and decrease it in the other," he explains. "That pattern is called sexual antagonism." In this case, we're not seeing sexual antagonism, since neither the male and female clones are exactly thriving here, but we are seeing the same sequence having different effects along sexual lines.
But the big question is whether a genetic condition can result in a sexually transmitted pathogen, and that's where things veer from plausible science into science fiction. "The unprotected sex thing suggests that we should limit ourselves to the proteins in semen. (And there are many.)" Kelly says. "And they're all proteins that have to be coded in the guy's DNA. So very occasionally you hear about women who have allergic reactions to the proteins in their partner's semen.... So, if you're passing bodily fluids from one person to another, there's a really rare chance that the recipient will have a allergic reaction to the fluid donor. But we're pretty robust, and that's rare."
In the context of Orphan Black, though, we're not talking about an allergic reaction; we're talking about a protein that attacks women's ovaries. Even getting out of the realm of what we actually observe in nature and into the realm of speculative science, Kelly has a hard time imagining that it's possible. "Maybe if the proteins are on the sperm?" she wonders momentarily. "But sperm don't usually get that far. They don't live long enough."
However, if we're talking about insects instead of humans, that's a different story. Johnson notes that, in some insects, the seminal proteins of the males can be toxic to the females. "In some insects, notably Drosophila flies [also known as fruit flies], males pass on various proteins in the seminal fluid. These proteins affect the female nervous system causing them to be more reluctant to mate again and more willing to lay eggs. As a byproduct, these proteins reduce the lifespan of the mated female flies." He points to a July 2013 paper published in Ecology and Evolution as a recent example of an attempt to understand the role of the Drosophila melanogaster seminal fluid protein Acp62F in postcopulatory sexual selection. Fortunately, he says that he's not aware of a similar example of toxic seminal proteins in mammals.
Johnson also offers interesting side note on Drosophila and their toxic seminal proteins: In 1999, the Proceedings of the National Academy of Sciences journal Evolution published a study by Brett Holland and William Rice on the toxicity of seminal proteins in Drosophila melanogaster. The researchers forced the fruit flies to reproduce under "strict, life-long monogamy" for 47 generations. They found that the male fruit flies that resulted from these generations of monogamy had seminal proteins that were less toxic to their female mates than those in the "promiscuous" control group.
The study suggests that when there is no chance for a female fruit fly to re-mate with another male, there is no reason for evolution to select for the more toxic seminal fluid proteins -- in fact, those more toxic proteins would be selected against, because the female fruit fly would produce more eggs in the long run without those toxins. The seminal toxins are something of a weapon -- a weapon to prevent other males from breeding. In Orphan Black, the forces behind Castor imagine that they could use the Castor protein to render the enemy population infertile, a chilling way to end wars within a single generation.
Perhaps these fruit flies provided an inspiration for Orphan Black's current story line, but can we comfortably declare humans who transmit ovary-destroying seminal proteins something that stretches the limits of believability? "Dear god, yes," says Kelly. "But then, they started with a massive human cloning operation."