There was a House episode (Season 3 Episode 2 Cane an Abel) about a young boy who was convinced that he was being probed by aliens. Through a series of very House-like (aka "unrealistic") medical twists and turns, House's team finds cells clumped together in different parts of this boy's body, including his brain, that are functioning abnormally and causing his various symptoms. From sequencing the DNA from those cells, House's team finds that those cells have different DNA than the boy's. In the fictional world of House, the doctors were able to quickly create a probe for the foreign DNA, find all the cells that were different and remove them (House does brain surgery!!) also removing the symptoms including the alien hallucinations. This episode is so wildly out of the realm of current medical ability and practice - so much so that I participated in a "Science Fiction TV Dinner" all about the science and "science" found in this episode. You can watch highlight from this discussion, which included Dr. Kenneth Ramos from University of Arizona Center for Precision Medicine (Science Fiction TV Dinner: House M.D. from Science & the Imagination on Vimeo) or listen to the whole podcast here.
However, what I found most interesting about this episode was the fact that the boy had TWO DIFFERENT genomes in his body. Can this actually happen in real life? If so, how??
The answer is yes, and it's called a chimera or chimerism. In mythology, a chimera is a terrifying hybrid animal that's a lion, with a goat head coming out of it's back and a tail with a snakes head on the end. It may be clear that I'm a scientist since I'm sitting here wondering whether all three heads eat and if so, do they all connect to the same or different stomachs.
But I digress... In genetics, a chimera is an organism composed of two distinct sets of cells with two different sets of DNA. As you may remember from other discussions on this blog, DNA is the genetic material that provides the blueprint to make an organism. DNA is also what is passed along to offspring, so that a child has 50% of the DNA from one parent and 50% of the DNA from the other (more about heredity here). This is also why paternity tests work - if the child has 0% of DNA from the father, it's clear that he isn't the father.
So how in the world can a person have two different sets of DNA? Especially since all people start off as one fertilized egg with one set of DNA instructions? There are a few ways:
- Organ transplants or stem cell transplants. That organ or cells (more about stem cell transplants here) come from another person who has entirely different DNA from the transplant recipient. So when a person gets an organ transplant, they become a chimera. This is also true, at least temporarily, for people who have blood transfusions.
- Are you a mother or a person who a mother gave birth to? In that case, you might also be a chimera. This is called fetomaternal microchimerism. Mothers usually have a few cells identical to their children that stay in their body long term. This is often caused by immune cells being transferred back and forth between the mother and the placenta during development. Even 22% of adults were found to still have blood cells from their mother! These cells are really difficult to find - in part because there usually isn't any reason to look for them - but easier if the mother has a boy because then the chimeric cells contain a Y chromosome whereas the mother's cells do not.
- In vitro fertilization (IVF) also has the possibility of resulting in chimeric adults. Since IVF often implants multiple fertilized eggs into the mother, there is an increased possibility of two fertilized eggs fusing - resulting in one human developing into an adult with two sets of DNA.
Let's talk about this last option a bit more because this is what House and Co. blamed as the cause of the child's chimerism, but also because this is really interesting medically and socially. There have been several noteworthy stories about women who, for different reasons, were found to be chimeras. Lydia Fairchild was looking for child support after a divorce, but when DNA tests to prove paternity were requested, it was found that the father was the father, but Lydia wasn't the mother. After numerous traumatic events, including being accusing of trying to commit fraud to obtain benefits and having the birth of her third child observed (to prove that she was that child's mother, even though genetically it didn't appear that the child was), Lydia was lucky. Her lawyer heard about Karen Keegan, a woman in need of a kidney transplant several years earlier, but when testing her three sons for compatibility, the tests indicated that only one was hers. Only by looking at other cells in her body were doctors able to determine that her body contained two sets of DNA - one set was passed on to two of her boys and the other set was passed on the other. Fortunately for Lydia, this discovery prompted DNA testing of members of Lydia's extended family as well as other parts of Lydia's body. This testing showed that Lydia's cervical cells matched her children's and she was able to obtain child support. The media LOVED this. Just an example of the titles for news articles about Lydia and Karen:
However, besides the obvious media hype, chimerism has practical and legal implications. For example, in 2005, cyclist Tyler Hamilton was charged with blood doping because they found another person's blood mixed with his own. He blamed this on chimerism (New York Times article here) where he had chimeric blood cells that had different DNA than the rest of his body. He lost his case 2-1, but it brings up an interesting idea. If everyone knows about chimerism - either through the popular media or TV shows like House - then this could lead to the "reverse CSI effect" where the jury is so aware of the possibility of chimerism that they discard all mismatched DNA evidence blaming it on chimerism.
Besides how strange this all seems, what's even stranger is that more people are probably chimeras that scientists even realize. The only reason we know that Karen Keegan and Lydia Fairchild are chimeras is because scientists were forced to look at them more closely. For the rest of us, we likely won't need a transplant or have alien-probing hallucinations that induce scientists to look at many different parts in our body to see if the DNA is different. And if more of us are chimeras, what does that mean? This is still something scientists will have to figure out.
- Want to hear more about this amazing phenonemon? Check out \this great article from the EMBO journal NPR's RadioLab story Mix and Match featuring Karen Keegan's story.
Dr. Cathy Seiler is the Program Manager for the tissue biorepository at St. Joseph's Hospital and Barrow Neurological Institute. She has her BA in Biochemistry and Molecular Biology from Boston University and PhD in the Biological Sciences from Cold Spring Harbor Laboratory. Her research and teaching focuses on genetics, cancer, and personalized medicine. Find her on Facebook at www.facebook.com/thingsitellmymom