10.07.15 6:20 PM ET

DNA At the Fringes: Twins, Chimerism, and Synthetic DNA

DNA tests are thought to be conclusive proof—of crime, of family relation—but in some cases, our genetic material acts in mysterious ways.

Plenty of things can go wrong in DNA testing in a run-of-the-mill case. Problems with interpreting the sample, determining the right match probabilities, and ensuring the integrity of the sample and the evidence collection and testing process are everyday, ordinary kinds of issues that may arise. But, of course, sometimes the extraordinary occurs.

Forensic DNA testing is to some extent a field of frontiers. Researchers continue to probe how our DNA works, filling the pages of science journals with their new discoveries. Technologists constantly refine the instruments used to conduct DNA testing, enhancing speed and sensitivity. Forensic DNA testing takes advantages of some of these advances as they occur, but it does not have frictionless adaptability. For instance, the government has built an enormous DNA database around a specific kind of DNA test, and sunken costs prevent laboratories from instantly converting to the latest in testing instrumentation.

But cutting-edge science still crops up in the criminal justice system, typically inspired by the exigencies of an individual case. One such example livening up the otherwise predictable environs of an American criminal court include issues related to chimeras.

In 2003, 26-year-old Lydia Fairchild applied for public assistance in the state of Washington. She had two children already, and a third child on the way. Washington law required that Fairchild submit  a DNA sample for the entire family to prove relatedness and to pursue paternal support if appropriate. Those tests confirmed her partner’s paternity, but revealed something unthinkable to her: She was not the children’s biological mother. Lab reports had excluded her genetically as a possible mother.

Officials called her into the office and badgered her with questions. As she continued to insist she had borne all her kids, they accused her of fraud and threatened to have the children removed by child services. Panicked, Fairchild went home and rummaged for photos and birth certificates as proof, even enlisting the support of the doctor who had delivered the children. She requested retests, but they, too, confirmed that she was not the mother.

When her third child was born, a court officer was present to witness the birth and an immediate DNA test. When those results, too, showed that Fairchild was not the mother, she was suspected of being some kind of unconventional surrogate.

Fairchild sought legal assistance but attorneys turned her down, viewing the DNA tests as conclusive proof. Finally, attorney Alan Tindell agreed to take the case. He believed Fairchild’s story, and so he tried to get to the bottom of the mystery. He found his answer in the New England Journal of Medicine. There, doctors told the story of Karen Keegan, a Boston woman in need of a kidney transplant. Her entire family had undergone tests to find a match; the testing revealed that her two sons were not her own.

Treating it as a “medical mystery,” doctors probed further. They took samples from different parts of Keegan’s body, and even dredged up some old tissue from her thyroid that had been removed in the past. That old thyroid solved the case—it contained DNA that was different from the other parts they had sampled, and that matched her sons’. The study also referenced two other known cases of the kind. Tindell asked for similar testing of Fairchild, which likewise ultimately revealed that she was in fact her children’s mother.

In the decade since the Fairchild and Keegan discoveries, scientists have learned more about their conditions. The notion that a person’s DNA might not be stable, or rather that more than one genetic profile might be present in an individual, is loosely labeled “chimerism.” In Greek mythology, Chimaera was the hybrid offspring of two monsters, one of whom was Echidna, herself half-woman, half-snake. This powerful imagery has even fueled a British play about motherhood, microbiology, and genetic puzzles.

Chimeras can come about in several ways, summarized by one commentator as “transfusion, transplantation, or inheritance.” Put simply, chimeras can result from a person’s receiving a blood transfusion or organ transplant, from the passage of DNA between a mother and fetus while the child is in utero, and from the spontaneous dissolution of what had been two zygotes into a single embryo, as it turned out happened in the Fairchild case.

One common source of chimerism may be blood transplants and transfusions. It should come as no surprise that injecting blood from one individual into another, or transplanting one person’s organs into the body of another, will result in the donor’s genetic profile showing up in a DNA test. Although red blood cells do not contain DNA, transfusions that contain white blood cells or platelets may readily transfer DNA. Although such transfers in general are temporary, more lasting traces may be seen.

In the case of bone marrow, transplants may result in wholesale replacing of a recipient’s DNA with the donor’s DNA, particularly older, aggressive forms that destroy the recipient’s DNA entirely. For instance, in a sexual assault investigation in Alaska in 2005, police typed a semen sample and found a match in their DNA database. The suspect, however, had an alibi—he was incarcerated at the time of the offense. Upon further investigation, investigators learned that the incarcerated man had a brother who had donated bone marrow to him years earlier. But because the recipient’s skin cells had not yet been contaminated by the donor’s DNA, a simple check swab removed all suspicion from the accused.

A second source of chimerism, known as microchimerism, is actually quite common, and stems from the free passage of fluids between a pregnant woman and her fetus. Researchers now believe that these cells may actually aid in maternal health. A recent study of 272 Danish women showed that in nearly two-thirds of them, the male Y chromosome was present in their blood. Amazingly, a 2005 study tested 120 women who had never given birth to sons, and found traces of male DNA in 21 percent of them. Scientists believe these traces are the result of fetal cells that “migrate all over a mother’s body, becoming part of the heart, the brain, and blood.”

Although the highest percentage of microchimerism was found in women who had induced abortions, a significant number of women who had only had daughters or had no children at all also showed signs of male DNA. Any woman who has recently become pregnant may have learned of this phenomenon firsthand. Invasive genetic tests, such as amniocentesis and chorionic villus sampling (CVS), have now largely been supplanted by a simple blood draw at ten weeks, which can test for major genomic defects in the fetal cells floating within maternal blood.

The final form of chimerism—the one that led to the confusion in the Fairchild and Keegan cases—is known as tetragametic chimerism. Tetra, meaning “four,” refers to the creation of two zygotes from four cells (two eggs and two sperm), rather than one zygote from two cells (one egg and one sperm) as is typically the case. This condition is characterized by the idea of the “vanishing twin”: instead of producing twins, those two zygotes fuse into one. In Keegan’s case, for instance, researchers determined that her blood cell contained one DNA line, whereas her other tissues (such as mucous membranes, skin, and hair) were a mixture of two different cell lines. This form of chimerism can arise in both women and men, as the “collapsed twin” can occur in either gender.

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The precise scope and extent of chimerism is still a topic of considerable research. Some forms are fairly readily ascertainable—such as those acquired through transfusions or transplants—even if the precise scope of the chimeric effects of such activity is still unknown. Inherited forms of chimerism are much harder to gauge. In addition, chimerism is most easily measured when the sex of one line differs from that of the other. That is why researchers focus largely on finding evidence of Y chromosomes in females—because the Y chromosome is distinctly male, and thus easily stands out against the woman’s own double-X chromosomes. In contrast, traces of a foreign Y profile in a male, or a foreign X profile in a female, may be less readily uncovered.

Estimates of inherited chimerism range wildly, from as many as 1 in 2,400 persons in the population, to 10 percent, to as much as 50 to 70 percent. One 2014 report in the American Journal of Medical Genetics stated that “chimerism in humans is not as rare as previously thought, although it has been studied only recently.” Some scientists predict that chimerism rates are even likely to rise as a result of assisted reproduction techniques that implant multiple embryos, without all those embryos’ resulting in live births. In such cases, the shadow profiles of those vanished embryos may show up in genetic traces in their siblings’ blood.

It is also hard to project precisely how chimerism could play out in a criminal investigation. For the most part, many forms of chimerism may leave only a bare trace of the foreign cells in the body, so that ordinary sampling is unlikely to pick them up. On the one hand, if a suspect leaves a chimeric profile at the crime scene (say, a blood sample from a person who received a transfusion), it may appear that two persons committed the crime instead of one. If a suspect is known, and the chimeric condition endures, tests may show that this suspect has the unusual combined pattern and result in a pretty powerful match. But if a suspect is unknown, DNA analysts may attempt to pull apart two profiles to find two different “contributors,” and it is not hard to imagine that a search in an enormous national database might then lead to an accidental match. Or what appears to be a triallelic pattern, or low-level contamination or “noise,” may in fact mask chimerism.

Similarly, highly sensitive testing methods, such as low copy number testing, may result in a DNA profile emerging from the chimeric cells of an individual. Again, this could result in the exclusion of a known suspect who seems to have a different DNA profile when tested. But that profile, too, may turn up an accidental match when run through a database trawl. Recall that the likelihood that two people share the same DNA profile is much different than the probability that a DNA sample will match a person who has been picked at random.

Law enforcement should stay alert to the possibility that a match could result from fortuity of this kind, unusual as such scenarios are, especially since just how uncommon they are remains a matter of some dispute. Some have warned that chimerism may “undermine the very basis of the forensic DNA system.” Others conclude that “considering the nature and type of chimerism and the implications of each type for forensic identity testing, it should be clear that the fears about chimerism are exaggerated.” At this point, it seems only time will tell.

This is an adapted excerpt from INSIDE THE CELL: THE DARK SIDE OF FORENSIC DNA. Reprinted with permission from Nation Books.