It seemed like an impossibility. After all, DNA doesn’t lie.
The setting is Alaska. A serious sexual assault has been committed and investigators are trying to find out who the perpetrator is. The evidence they have is sperm, which famously contains DNA.
When the extracted DNA is compared to the criminal justice DNA database, a match is found to a blood sample that was taken from a known criminal. Case closed, right?
Except that when the sexual assault took place, this known criminal was behind bars.
How had he escaped, committed the crime, and returned to jail undetected?
DNA may not lie, but we have to understand its rare eccentricities. To solve this puzzling case, we need to appreciate mythical beasts.
Her own twin
“She was […] in the fore part a lion, in the hinder a serpent, and in the midst a goat, breathing forth in terrible wise the might of blazing fire.” This is how Homer, in his famous tale The Iliad, describes the Chimera. She was a monstrous creature, a hybrid of many animals, ultimately slayed by the hero Bellerophon.
But chimeras do exist outside of Greek myths. The season 4 finale of the television show C.S.I. pointed that out in a somewhat flamboyant fashion by having its criminal proclaim that, “I’m a creature of myth.” He was a chimera, though not the sort with a fire-breathing head. He was a genetic chimera.
We assume that we have a single genetic code in all of our cells, one born of the combination of one half of our father’s DNA and one half of our mother’s DNA. Sperm meets egg, and we get a zygote with a full set of chromosomes. It divides into two, making copies of these chromosomes, and we think that every cell down the line ends up with the same genetic bundle. But there are interesting cases where the developing embryo becomes a sort of chimera.
When twins are growing in the womb, the blood vessels feeding them can connect. In medical terms, this cross-connection is known as an anastomosis. DNA from each twin can thus be exchanged, and these siblings end up with parts of each other.
Another natural way that genetic chimeras can emerge is when two eggs get fertilized by two sperms at the same time, which would normally result in fraternal twins. Sometimes, though, these twins fuse in the womb and become one. Because eggs and semen are known as gametes, and since four of them end up creating a single person, scientists have called this phenomenon “tetragametic chimerism.” More poetically, it has been referred to as “the vanishing twin.”
A tetragametic chimera thus has two main types of cells making up their body. Some cells come from sperm 1 and egg 1, while the rest come from sperm 2 and egg 2. That means these families of cells are genetically different, and because DNA is a blueprint, it can result in interesting physical manifestations. Some will have two-toned skin or differently coloured eyes. Tetragametic chimeras can have what doctors refer to as “atypical genital appearance,” although not all intersex people are chimeras, and not all chimeras are intersex. In fact, when tetragametic chimeras have no idea that they are “creatures of myth,” to put it theatrically, it can make for puzzling discoveries and leave some in legal trouble.
In the late 1990s, a fifty-two-year-old woman named Karen Keegan needed a new kidney due to renal failure, so she and her family—including her children, crucially—were tested to see if a biologically compatible kidney was available. That’s when Keegan was told that she was not the mother of two of her three children.
This was clearly impossible to her, but this uncanny result was not due to a sample mix-up in the lab. Scientists ended up testing all manners of biological specimens from her—her hair, her skin, cells from inside her mouth, even tissue that had been removed from her in the past and preserved—and they found in some of these two different DNA profiles. Her blood had come from one sperm and one egg, but some of her other tissues had a touch of the chimera. With no other tell-tale manifestation of chimerism, Keegan had spent most of her life not knowing that she was probably the result of twins that had fused in early development.
A similar case a few years later was much more unpleasant. Lydia Fairchild was applying for public assistance to help support her family, and testing was required to prove that her children were indeed related to her. Except they were not. DNA testing established that the children were indeed siblings but concluded that she was not their mother. She was accused of attempting to defraud the government through an elaborate surrogacy scheme, and prosecutors even asked that her children be taken away from her and sent to foster care. Fairchild was told to lawyer up, but the attorneys she approached did not want to dispute DNA evidence. After all, DNA doesn’t lie, right?
Finally, a lawyer did take her on as a client and stumbled upon the Keegan case as reported in the New England Journal of Medicine. If Keegan had been a chimera, might Fairchild not be one too? A sample taken from Fairchild’s cervical smear did indeed match her children’s DNA. As ABC News put it, she was “her own twin,” carrying within her two different sets of genes, with one being consistent with her children and creating her eggs, and the other one being inconsistent.
Tetragametic chimerism appears to be rare. At first, the technical difficulties involved in finding these chimeras might have contributed to an underestimation, but given the large number of paternity tests and direct-to-consumer genetic tests regularly done, and the slow trickle of case reports in the scientific literature, it’s unlikely that vanishing twins are commonplace.
There is more than one way of creating a chimera, however. Outside of the quirks of the womb, chimerism can be artificially induced in a medical setting. Have you ever had a blood transfusion? If it contained white blood cells (as red blood cells in mammals lose their DNA as they mature), you temporarily had someone else’s DNA flowing through your veins. You were a momentary chimera. No need to lose sleep over it: your body removed most of these white blood cells from circulation when they got too old.
If you receive a solid organ transplantation—a liver, or heart, or lungs, for example—, you are technically a chimera, as the DNA in the cells of this organ is different from your own, and this chimerism can spread when white blood cells that carried over from the donor during the organ transplant start to circulate. If they attack the recipient’s cells, doctors call this “graft-versus-host disease.”
A bone marrow transplant which comes from an outside donor (often used in cases of blood cancer) will also create chimerism, as the bone marrow is the birthing and nurturing ground for blood cells. Someone else’s bone marrow in you means someone else’s DNA in you, which is carried inside the blood cells that emerge from it. In fact, chimerism can be measured in the lab in order to track the progress of the engraftment and make sure that the cancerous blood cells are no longer detectable and have been replaced by healthy ones made by the graft.
As fascinating as these situations are, there is an even more peculiar, and much more common, form of chimerism. It’s the one that happens during pregnancy.
Your children’s cells inside of you
In 1969, three researchers from the University of California, San Francisco, collected white blood cells from women pregnant with boys and found that some had what appeared to be a Y chromosome. This controversial finding was confirmed by subsequent studies. Cells from the male fetuses were ending up circulating in the mother’s blood supply and, as we would later learn, vice versa.
This phenomenon is common and can begin as early as the first trimester. It affects less than 5% of cells, and as such is not considered complete chimerism. It is known as microchimerism: fetal microchimerism refers to the presence of fetal cells in the mother and maternal microchimerism, to the presence of the mother’s cells in the fetus.
What these cells do, if anything, remains unclear, but some findings point in the direction of non-negligible health effects for fetal microchimerism. The often-touted view is that the presence of fetal cells in the mother, over time, decreases the risk of cancer and increases the risk of autoimmune conditions, like lupus. In keeping with scientists’ obsession with affixing the root “-ome” to the complete collection of certain molecules, like “genome” to refer to all of our genes, the word “microchiome” was birthed. It is possible that this pregnancy-related microchiome interacts with the immune system in such ways as to flag cancerous cells but also to trigger undesired immune reactions, but the truth is, with studies differing so much in their methodology and outcomes, we can call the microchiome beneficial, neutral, or detrimental, depending on our mood. It is quite possible, as the study of biology keeps teaching us, that it can be all three depending on the context.
Given all these different ways of creating human chimeras, what is the overall definition of chimerism? This is an interesting question to contemplate, because it allows us to distinguish chimerism from another, very similar genetic anomaly. Putting aside the mythological lens and replacing it with a genetic one, a chimera is a single organism that is made up of cells from at least two genetically distinct zygotes. The twins who become chimeras in the womb because of their interconnected blood supply, they are distinct zygotes. The vanishing twins, like Karen Keegan and Lydia Fairchild, came about from the fusion of distinct zygotes. And when we look at chimerism induced through medical interventions or pregnancy, there are always clearly two people involved, and thus originally two zygotes: the donor and the recipient, the mother and the child.
When an organism has cells with different genetic codes but they all come from a single zygote, that is called mosaicism. It arises due to mistakes that are made when DNA is copied early on in embryogenesis.
All this talk of genetic anomalies and quirks brings us right back to Alaska. How did a criminal escape from jail to commit sexual assault, only to quickly return behind bars? The answer is simple: he did not.
Medical records are confidential, so the investigators had no easy way of knowing, but after speaking to friends and family members, they found out that the man in jail had received a bone marrow transplant from his brother, who was not in jail. The brother was the sexual assailant. When he had donated his marrow, it was blood cells bearing his DNA that started to spread in his sibling’s bloodstream. From the blood alone, these two brothers were now identical twins. When the marrow recipient was arrested, his blood was collected and its DNA was entered into the database, where it proved a match during the sexual assault case.
It was a swab of his cheeks—and the fact that he physically could not have committed the crime—that exonerated him.
I was sitting in the room when Abirami Chidambaram, then of the Alaska State Scientific Crime Detection Laboratory, presented this fascinating case at a genetics conference in Salt Lake City in 2005. It helped renew my interest in genetics and in its real-world applications.
We often think of inheritance in simple terms: my parents had it, therefore so do I. But the eccentricities of DNA are many. They sometimes create mythical creatures and they make the world a more interesting place.
Take-home message:
- In genetic terms, a chimera is any organism that is made up of cells from at least two genetically distinct zygotes, a zygote being a fertilized egg
- People can be chimeras because they shared blood supply with their twin in the womb; because they are the result of twins fusing in the womb; because they received cells, tissues, or organs from a donor, like a bone marrow transplant; or because they were pregnant
- Cells that belong to the fetus can continue circulating in the mother’s blood for years, and while they may decrease the mother’s risk of cancer and increase her risk of autoimmune diseases, more studies are needed to clarify these associations
