Thursday, February 28, 2019

The Strange Tale of Pregnancy and Heredity: Chimerism


The term chimera is derived from classical Greek mythology in which there was a beast containing a body made up of parts of three different animals.  The term chimera has come to be used to refer to any animal that consists of parts from more than one animal.  This seemingly bizarre occurrence turns out to be rather common in nature with we humans being no exception.  This recently discovered fact is only one of the many revelations provided by Carl Zimmer in his fascinating book She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity.

Zimmer tells the story of a woman from Washington state, Lydia Fairchild, who in 2003 filed for welfare benefits.  She had three children and was pregnant with a fourth.  She was required to have a DNA test to verify that she was the mother of her children.  The test results indicated that her husband was the father of her children, but she was not the mother.  The state officials suspected that she was guilty of at least welfare fraud if not of having kidnapped the children.  She was being threatened with the loss of her children and jail time.  None of her records or personal references helped because the DNA test was deemed infallible.  When she delivered her fourth child the state sent a witness to observe the event and to get a DNA sample from the child.  Again, the DNA results indicated that Lydia could not be the child’s mother.  Even though a state witness observed the birth, the DNA tests were still treated as being incontrovertible.

Fortunately for Lydia, her legal representation heard about a similar case in Boston where a woman named Karen Keegan needed a kidney transplant and had her three sons and husband tested for acceptability as donors.  The DNA studies indicated that her husband was the father of the sons, but she couldn’t possibly be the mother of two of them.  Again, she was suspected of foul play, but this time the doctors involved decided to look further for an explanation.  They acquired as many tissue examples from Karen as they could and discovered that her organs contained two separate pedigrees, as if she had been the product of two separate fertilized eggs instead of one.  Both Karen and Lydia are what would come to be known as a tetragametic chimera. 

In pregnancy, more than one egg can be fertilized at a time.  If two are fertilized they would normally develop into fraternal twins.  In some cases, the two fertilized eggs can merge very early in development.  If the embryos are of the same sex, the merger is difficult to recognize, if of different genders, the sexual development can be abnormal.

“Tetragametic twins start out as two embryos with separate genomes, and then merge entirely.  Only one child is born, and there is no other human being to point to.  All we can do is trace their intimately mingled cell lineages to their separate sources.”

Consider Karen Keegan’s development.

“The cells of one twin gave rise to all her blood.  They also helped to give rise to other tissues, as well as some of her eggs.  One of her sons developed from an egg that belonged to the same cell lineage as her blood.  Her other two children developed from eggs belonging to the lineage that arose from the other twin.”

This form of chimerism is rare, but common enough that physicians now know to consider it when genetic anomalies appear.  It is rather astonishing that a single person can essentially be constructed from two different people and continue to function normally.  Isn’t our immune system designed to attack cells that are not our own?  How does it deal with two classes of cells?

We now know that there is much more common form of chimerism that can occur during pregnancy that does not require the merging of embryos.  Embryos develop in the placenta.  There is a barrier that can transmit nutrients and other molecules from the mother’s blood to support the embryo’s development.  But there is supposed to be no transmission of cells.  Over a century ago it was discovered that transmission of cells could occur, but it was not until the 1960s that it became clear that this transmission was a common occurrence during pregnancy.  It would take another thirty years before it was realized that these cells, transmitted in both directions, mother to embryo and embryo to mother, could live for a very long time and could become an active participant in bodily functions.  This form of chimerism came to be called microchimerism. 

“Their research has revealed that all pregnant women have fetal cells in their bloodstream at thirty-six weeks.  After birth, the fraction drops, but up to half of mothers still carry fetal cells in their blood decades after carrying their children.”

“Very often, a mother’s cells will infiltrate their children’s bodies, where they can endure and grow long after her death.  According to one estimate, 42 percent of children end up with cells from their mothers.”

It gets even more complicated when a mother has multiple pregnancies.  Cells from a son who was born can then be transferred from the mother to a subsequent daughter.  One study detected this occurrence, and it was not particularly rare.  Males have an X chromosome and a Y chromosome.  Females have two X chromosomes instead.  Women should not have any Y chromosomes in their bodies.  If they do, it is evidence of a transfer that occurred from another human entity.

“At the University of Copenhagen, scientists got blood samples from 154 girls ranging in age from ten to fifteen.  They cracked open the cells in the blood and searched them for Y chromosomes.  In 2016 they reported that twenty-one girls—more than thirteen percent—had them.”

Searching for Y chromosomes in women is a simple way to determine how long these cells persist.

“Lee Nelson, a rheumatologist at the Fred Hutchinson Cancer Research Center, and her colleagues examined the cadavers of fifty-nine women who died, on average, in their seventies.  In 63 percent of the women, the scientists found Y chromosomes in their brains.”

Zimmer also notes that given this propensity for microchimerism, the practice of utilizing a surrogate mother to carry a couple’s child is no longer as simple as it once seemed.  The surrogate can inherit cells from the fetus and the fetus may no longer become the genetically simple child that the parents assume.

Given that this form of chimerism is so common and that it can persist indefinitely, what might its effects be?  It is known that women are more susceptible to autoimmune diseases.  Could this be because females, as mothers, will generally be subjected to higher concentrations of foreign cells than a male who will only encounter them once?  Once again, scientists looked for evidence of Y chromosomes in females suffering from the autoimmune skin disease scleroderma.

“Nelson and Bianchi found that women with scleroderma had far more fetal cells from their sons than did the healthy women.  Other scientists who carried out similar studies got the same results for a number of other diseases.  These findings aren’t definitive proof that microchimerism made these women sick, however.  It was also possible that the diseases came first, and the fetal cells only later flocked to the diseased tissues where they could multiply.”

And then there are these observations which suggest that having these fetal cells acquired in pregnancy can be beneficial.

“In another woman, Bianchi discovered that an entire lob of her liver was made up of Y-chromosome bearing cells.  Bianchi was even able to trace the paternity of the cells to the woman’s boyfriend.  She had had an abortion years before, but some of the cells from the fetus still remained inside her.  When her liver was damaged later by hepatitis C, Bianchi’s research suggested, her son’s cells rebuilt it.”

“It is also possible that fetal cells help mothers fight cancer.  In 2013, Peter Geck of Tufts University and his colleagues looked for cells with Y chromosomes in the breast tissue from 114 women who died of breast cancer and 68 women who died of other causes.  Fifty-six percent of the healthy samples had male fetal cells in them.  Only twenty percent of the cancerous tissue had them.  Geck speculated that fetal cells swooped into the niches of breast tissue that are good for proliferating cells.  Those may be the same niches cancer cells need to find in order to grow into tumors.”

What is startling about this topic is that this notion of humans as chimera is so new, and the knowledge about the consequences of this phenomenon is so inadequate.  Who knows what else we might yet learn about ourselves?  Occasionally, we hear of “miracles” occurring where no medical explanation is possible.  Perhaps they are not so much miracles as indications that the human body is still too complicated for us to understand.


The interested reader may find informative the following articles based on information found in Zimmer’s book:









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