The Strange Tale of a Chimera

The Chimera had a serpent’s tail with the head of a lion and a goat on its monstrous body. That was a Greek myth, but real-life chimeras exist. They originate from the blending of cells from two fertilized eggs into a single body.

A chimeric man was identified in California recently after undergoing fertility treatment with his wife. She received intra-uterine insemination (IUI) with his sperm for a gynecological problem: it was successful and they had a son. There was nothing unusual in the case until a routine blood test revealed the boy had a blood type that didn’t match either parent. But how could a third party be involved in his conception? Since there was no doubt that she was his biological mother (no mix-up in the birthing center), the husband opted for a paternity test using a buccal cell sample.

It didn’t match his boy, even after retesting. Had the clinic accidentally mixed up his semen sample with one from another patient going through the service on the same day? Technocuckoldy happens.

The couple’s next stop was the office of a geneticist, before consulting their lawyer.

The geneticist suggested they send saliva samples from both dad and son to a personalized genomics company (23andMe.com). When the data came back the story suddenly changed from alarming to interesting.

The DNA of man and boy was a 25% match, not the 50% expected for normal paternity. Taken at face value, the result suggests the boy was a grandson or a nephew of the man instead of his son. But dad really was his biological parent because when his semen was carefully analyzed 10% of his sperm corresponded exactly to the boy’s DNA. The rest was from an unknown relative! There was a similar mix of origins in the man’s buccal sample, and probably in other parts of his body they didn’t test.

The geneticist deduced that the man was harboring cells originating from a twin brother who had vanished before birth. Dad was a chimera. Cells from his moribund twin had colonized his testicles when they were sharing a womb and became spermatogonia for making sperm after puberty.

Chimerism sounds strange and deeply abnormal, but it is a natural phenomenon. In a few species it is a normal process, even a necessary one. Perhaps the weirdest example is the deep sea angler fish, the one with gaping jaws and a dorsal fin modified like a fishing line that serves as a lure for prey. Those are the females. The males were overlooked for a long time because they are tiny. Instead of mating in a conventional way (perhaps they don’t dare), they become absorbed into a female’s body after fusing with her. It is not a final death for a male because his blood vessels join up with hers, enabling some of his cells to survive, including the all-important sperm cells. The female becomes a chimera after receiving the male fertility transplant, which enables her to be self-fertilized.

Strictly speaking, anyone who receives a transplanted organ or bone marrow from a donor is a chimera. But in mammals most chimeras originate from sharing a placental circulation in pregnancy, and this occurs regularly in marmoset monkeys. In cattle it can have biological consequences.

Freemartin cows were recognized as far back as Ancient Rome because they are sterile, which is bad news for farmers. The 18th Century anatomist John Hunter realized they only occur when a female calf has a twin of opposite sex. Conceived as genetic females, freemartins are affected by hormones carried over from blood circulating in their male sibling. Male fetuses have much higher levels of testosterone and AMH, hormones that masculinize the body and cause the uterus to shrivel.

Cross-circulation rarely causes these effects in other species, although in humans it accounts for some rare intersex abnormalities, and can create nutritional deprivation in a twin with a shared placenta.

We used to make chimeric mice with four genetic parents for tracing cell lineages during development. When an 8-cell embryo from a black x black mated mouse and one from a white x white mating were “unshelled” and fused to make a single large embryo, the pup born after transfer to a surrogate mother was piebald. Chimeric pups were sexually normal with a few exceptions that were either intersexes with a testis and an ovary or had an “ovotestis.” Although fusion was almost 100% efficient in the Petri dish, the shell (zona pellucida) prevents chimerism at early stages of pregnancy in women by covering sticky surfaces that might cause embryos to adhere to each other or dangerously attach to the wall of the fallopian tube during passage to the uterus. Human-animal chimeras are now hot in experimental biology, but that’s another topic.

In Aldous Huxley’s Brave New World, human freemartins created at the Hatchery were not chimeras but made by a purely chemical process. These low caste females were sterile, asexual women with beards. The history of using physical differences to debase or abuse people is old and agonizing, but chimeras have avoided that fate and I have never even heard the name used as an insult. That’s because they generally go unnoticed until a genetic test reveals more than one zygotic origin in the same individual, or a striped pattern of sunburn raises a question of why the skin cells were differentially sensitive to u-v radiation.

Chimeras are more common than we realize, and I even wonder if I am among their ranks. I heard that I had a vanishing twin, although that doesn’t necessarily imply I am like the man at the California clinic who is carrying cells from a deceased fetal twin. Nor is that remote possibility something I worry about, and it wouldn’t give me the creeps even if I had brains cells from a brother or sister fetus. Fetal cell transfer is no more spooky to me than an organ transplant, and a good deal more natural. But the fact of a vanishing twin sometimes causes me to muse how my life would be different if he or she had lived.

Next Post: Mighty Mitochondria

 

About Roger Gosden

British-born scientist specializing in human and animal reproduction & embryology. Academic career spanned from Cambridge and Edinburgh to McGill and Cornell's Weill Medical College in Manhattan where he was Professor & Research Director. Married to Lucinda Veeck Gosden, embryologist for the first successful IVF team in America, he retired early to Williamsburg, Virginia, to write and to recover from 'nature deficit disorder'
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