Chimera Among Us

During my undergraduate and medical school days, I learned about a peculiar instance in which one particular organism would have two distinct genetic lines, made possible by specific embryonic conditions which I will heretofore describe. The possibility of this occuring was extremely interesting to me at the time, however, I did not pursue any further thought about the implications of chimerism until very recently, when I viewed a program on TLC (The Learning Channel) about a very peculiar story concerning chimerism. Here I will describe chimerism, its implications for our justice system, and a very interesting story which prompted a case report article in The New England Journal of Medicine.
In ancient Greece, a chimera was a mythological being consisting of a mix between a lion, a goat, and a snake. In biological terms, a chimera is any animal which has a combination of two or more distinct genetic lines. Although chimeras can result from a variety of different mechanisms, the most interesting example of how a chimera is formed is when two embryos, each with their very own genetic makeup, fuse together to form one embryo very early in the stages of embryonic development. This, to me, is absolutely amazing. Chimeras occurring naturally are thought to be pretty rare, and can occur in many different species. Chimeric mice are created artificially for biological research purposes, because their two distinct genetic codes can be "tracked," so to speak.
In a human, a chimera could occur when two fertilized eggs (i.e. non-identical, fraternal twins) fuse together in the blastocyst stage, when they only consist of 8-16 cells or so. However, unlike siamese twins, which in certain cases consist of two embryos fusing together a little later in development, and then are born as two people who are attached at some point in their body, chimeras consist of two embryos which fuse and then are born as ONE person. In other words, that one baby is made up of two fraternal twins, and thus two different genetic codes! For example, the person's heart may be encoded by DNA from one of the embryos, and their liver from the other embryo. Or, some organs may be derived partially from one embryo and partially from the other embryo, thus resulting in one organ being derived from two distinct cell lines. Even more amazingly, chimeras are known in which the brain (and some other organs) are derived from a female, yet the person externally looks like a male. How unusual would it be to have a woman's brain trapped in a man's body!?! The combinations that can occur in chimeric organisms are almost endless, depending upon how early the fusion takes place, and which cells from each embryo are destined to create a particular tissue or organ. Chimeras which are created in this manner are tetraploid organisms, meaning they are one organism derived from two sperm and two eggs.
You can see the potential problems with this. What if a male embryo (XY) fuses in the womb with a female embryo (XX) to form one person? Well, that particular chimera will sometimes become a hemaphrodite, with both male and female sex organs, each differentiating from the male or female genetic codes, which are both contained in that one person.
Human chimeras can look very strange indeed. I have seen a picture of a chimeric baby which had had both a black person and a white person as parents. One of the embryos which had fused must have been white, and the other black, as the resulting baby had a line running completely down the middle of its body in which one half of the baby was black, and the other white. Chimeras which are obvious by looking at them externally in this manner are pretty rare. But what if chimeras exist in which it was impossible to tell if they are a chimera just by looking at them? And what if these chimeras exist all over the place, and the only way to tell if that particular person is a chimera or not is to run extensive genetic testing in order to detect the two different genetic codes that are present? Well, what I am about to describe to you may open up a whole new world.
This is the story of Karen Keegan, a chimera. She never knew she was a chimera until she was an adult with three grown sons. If you saw her on the street, you would never know anything was "wrong" or "different" about her. All of that changed when Mrs. Keegan developed a kidney condition known as focal sclerosing glomerulonephritis, which would require a kidney transplant. Mrs. Keegan and her three sons subsequently underwent genetic testing for the transplant, to see if one of her sons could be a donor. The results of the genetic testing were very peculiar indeed. Although one of her sons was a genetic match, the tests performed revealed that Mrs. Keegan could not have possibly been the mother of her other two sons!
Since Mrs. Keegan obviously remembered giving birth to these two sons, she knew that there had to be some sort of biological reason as to why the genetic testing persistently revealed that she was not their mother. It subsequently took researchers almost 2 years to find answers, and the answer was that Mrs. Keegan was a chimeric person. They tested many different organ samples looking for the other genetic code that would match her two sons, and luckily, her second genetic line was finally found within a thyroid nodule which had previously been excised and stored. Her thyroid gland had been derived from a different genetic line of cells than her blood. Testing on this sample revealed that Mrs. Keegan was indeed related to her two sons. Mrs. Keegan is now a known case of human chimerism, and she can safely say, "I am my own twin!"
The story of Lydia Fairchild is even crazier, and interestingly intermingles with the story of Karen Keegan. Lydia Fairchild was the mother of two children when her story began several years ago. She had applied for welfare benefits, and in the application process, a DNA test was administered by the county to determine both maternity and paternity of her two children. The DNA test revealed, similarly to Mrs. Keegan, that she could not possibly be the mother of her two children. Although Ms. Fairchild was not as lucky. The county threatened repeatedly to take her children away, and she was accused of welfare fraud. A second test was performed, and the results did not change. This was very distressing for Ms. Fairchild, as she knew that she had given birth to her children and that they were indeed hers. But nobody believed her.
During this time, no lawyer would obviously take her case, because Ms. Fairchild had the almighty proof of DNA evidence working against her, and since DNA doesn't lie, nobody thought that she was the mother. Theories and speculation came that perhaps the children were from Ms. Fairchild's sister, since further testing had revealed that the two children were related to Ms. Fairchild's parents (the children's maternal grandparents). Then, in an ironic twist of fate, Ms. Fairchild became pregnant again by the same father as her first two children, in the middle of the court processes and appeals in which the county was attempting to obtain custody of her children. This was her chance to prove that she was not a fraud.
When it came time to deliver her third baby, court officials were by the bedside, bearing witness to the whole labor and delivery. When Ms. Fairchild's baby was born, a DNA test to prove maternity was again performed. The result? Ms. Fairchild, by evidence of DNA, could not possibly be this baby's mother. Even the courts at this point admitted that something was afoot. A lawyer finally agreed to take Ms. Fairchild's case, and in doing so, he ran across a case report in the May 16, 2002 issue of The New England Journal of Medicine, Vol. 346: 1545-1552. The title of the report: "Disputed Maternity Leading to Identification of Tetragametic Chimerism." The subject of this report? Mrs. Karen Keegan. Ms. Fairchild was tested in a similar vein, and she was found also to be a chimera, and her second genetic line was found to match her three children's. The county subsequently let her keep her children.
The implications of chimerism on the use of DNA evidence in our justice system are astounding, as evidenced by this particularly unusual story. Can DNA evidence be trusted? How many unknown chimeric fathers have been denied paternal rights to their own children because their DNA were not a match? We may never know. Again, chimerism usually only comes to the forefront if the chimeric organism appears unusual physically and externally. But Karen Keegan and Lydia Fairchild look completely normal, and in Karen Keegan's case, it took almost 2 years to find her second genetic line. A chimera's blood, hair, and other testable samples may be from one cell line, whereas the other cell line may be very difficult to find, being intermingled in lower percentages in certain organs, or consisting of a whole organ which would have to be sampled by invasive biopsy.
Based on this, it is difficult to know how many chimeras there really are among us. You or I may be a chimera, and we would never know until the day we die, unless our DNA is tested and subsequently disputed. Unless the incidence of this strange twist of nature is known, we may never know the utter impact it has on our trust in DNA evidence. As more and more civil and criminal cases rely upon genetic information, perhaps more and more chimeras will be brought to the surface.