She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (51 page)

Owen, Medawar declared, had discovered a natural animal version of Winkler's botanical monster: “a genetical chimaera.”

When Medawar published his skin-punch experiments in 1951, he didn't dwell much on whether chimeras were limited to cows—thanks to their unusual placentas—or if other animals might become chimeric, too. But two years later, Medawar got a letter from a London scientist named Robert Race announcing what looked like the discovery of the first human chimera.

We know this original human chimera today only as
Mrs. McK. In the spring of 1953, Mrs. McK, then twenty-five years old, went to the Sheffield Blood Transfusion Centre in northern England and donated some blood. Before storing it, the center tested it for Mrs. McK's blood type. They added antibodies to the blood that would make type A blood cells clump together. Some of the cells clumped, but more of them didn't. The blood looked like what you'd get if you blended together type A and type O.

Ivor Dunsford, a doctor at the clinic, assumed there had been a mix-up. Maybe Mrs. McK had gotten a blood transfusion recently. Perhaps she was type O and had accidentally been given type A. But when he looked into the matter, he learned that Mrs. McK had never gotten a transfusion in her life.

Dunsford got in touch with the Medical Research Council Blood Group Unit in London for help. Robert Race, the director of the unit, was the country's expert on blood groups and relished puzzling cases like that of Mrs. McK. Dunsford supplied him with Mrs. McK's blood, and Race replicated the analysis. He ended up with the same result, separating her blood into O and A once more.

In all his years studying blood groups, Race had never seen such a thing.
It reminded him of Owen's discovery of twin cows that had traded blood cells. Eight years had passed since Owen had described the first genetical chimeras, but nobody had ever demonstrated whether humans could end up the same way. Race wrote back to Dunsford, instructing him to ask Mrs. McK if she had a twin.

When Dunsford relayed the question to Mrs. McK, she was startled. Indeed, she did have a twin brother. But he had died of pneumonia when he was three months old.

Race was intrigued by the news. “I suppose Mrs. McK is not obviously a freemartin,” he mused to Dunsford. “Has she been pregnant?”

Race wondered if cells from Mrs. McK's brother had disturbed her sexual development, in the same way that bull calves render their freemartin sisters sterile. It turned out Mrs. McK had a son, and so her ovaries must be in good working order.

Race wasn't put off by the news. He and his colleagues continued to investigate the possibility that Mrs. McK was a chimera. They took more careful measurements of her blood types, and determined that she had two parts O to one part A.

Race then wrote to Medawar about the case. Fascinated by Mrs. McK, Medawar offered the expertise he had gathered studying chimeric cows. He suspected that Mrs. McK was a chimera, too, and thought up a way to test the idea.

Medawar knew that the gene for blood types—the ABO gene—was active not only in red blood cells but in the salivary glands, for reasons that still aren't clear. Medawar suggested to Race that he collect Mrs. McK's saliva and inspect its ABO proteins. They might offer a clue as to which version of the proteins was original to Mrs. McK, and which she had acquired from her brother.

Race's team discovered that her saliva was type O—the same type that made up about two-thirds of her blood. Race now had his answer: Mrs. McK had inherited type O genes from her parents, and then she had acquired some of her brother's type A stem cells in the womb. His cells established themselves in her bone marrow, where they still contributed to her blood supply.

On July 11, 1953, Dunsford, Race, and their colleagues published “A Human Blood-Group Chimera” in the
British Medical Journal. “
In 1916 Lillie wrote: ‘In the case of the free-martin, nature has performed an experiment of surpassing interest,'” they recounted at the end of the report. “No doubt the same could be said of Nature's experiment on Mrs McK, were we able to appreciate more of its implications.”

In later years, Dunsford kept Race up-to-date about Mrs. McK. The fraction of her blood cells that came from her brother slowly declined. When Race would think back on the case, he marveled that he had been able to determine the blood group of a boy who had been dead for a quarter of a century. When we say people are dead, it goes without saying that their cells are dead with them. Parents can cheat death in a way by using a few of their cells to create new lineages of cells, known as children. By these lights it was hard to know quite what to call Mrs. McK's brother. His infant heart had stopped beating after a bout of pneumonia. But by then his stem cells had nestled into his sister's bones months before, and decades later they were still casting off new blood cells.

Medawar dedicated several pages to the ghostly boy in an essay he called “
The Uniqueness of the Individual”:

There is no telling how long Mrs McK will remain a chimera, but she has now been so for twenty-eight years; probably, in the long run, her twin brother's red blood cells will slowly disappear, and so pay back the still outstanding balance of his mortality.

Three years after solving the mystery of Mrs. McK, Race was delighted to discover another pair of human chimeras. If he found enough examples, he said, he might be able “
to lift the phenomenon out of the ‘freak' category.”

As years passed, more chimeras came Race's way. He recorded them in new editions of his book,
Blood Groups in Man
, up till the 1970s. In 1983, another researcher at the Blood Unit, named
Patricia Tippett, followed up with a list of her own. She counted seventy-five cases of human chimeras in
total. Tippett and other researchers suspected there were many more waiting to be discovered. At the time, the best clue that people were chimeras was that they carried two different blood types. But blood type tests were so crude in the 1980s that they would come up negative if one type made up less than a few percent of a person's blood.

In the 1990s, Dutch researchers invented a better test. They designed a collection of fluorescent tags, each of which could grab onto the cells of a certain blood type. They could spot the glowing tags even when a blood type was as rare as one in ten thousand cells. The scientists then used this new method to search for chimeras. They asked hundreds of parents of twins if they'd send blood samples to their lab. Using their new test, they discovered that
8 percent of the twins were chimeras. When scientists looked at triplets, 21 percent contained a pair of chimeras, too.

But these new blood type tests had their limits. If a pair of twins both had O blood, a blood type test cannot tell if they've mingled their cells. By the 2000s, scientists in search of chimeras were moving away from blood types, to DNA itself.

In 2001,
a thirty-year-old woman in Germany discovered she was a chimera while she was trying to get pregnant. For the previous five years, she and her husband had been trying to have a baby. They were fairly certain the problem didn't lie with her biology, because she had gotten pregnant when she was seventeen and had had regular menstrual cycles ever since. A fertility test revealed that her husband had a low level of viable sperm, and so they made plans for IVF.

As a routine check, the woman's doctors took blood samples from her and her husband. They looked at the chromosomes in the couple's cells, to make sure neither would-be parent had an abnormality that would torpedo the IVF procedure. The woman's chromosomes looked normal—if she were a man. In every white blood cell they inspected, they found a Y chromosome.

Given that she had given birth, this was a weird result. And a careful exam revealed that all her reproductive organs were normal. To get a broader picture of the woman's cellular makeup, her doctors took samples of her muscle, ovaries, and skin. Unlike her immune cells, none of the cells
from these other tissues had a Y chromosome in them. The researchers then carried out a DNA fingerprinting test on the different tissues, looking at the women's microsatellites—the repeating sequences that can distinguish people from one another. They found that her immune cells belonged to a different person than her other tissues.

It turned out that the woman had had a twin brother who died only four days after birth. Although he was unable to survive on his own, his cells took over his sister's blood and lived on within her.

As scientists learned more about chimeras, they also realized that there's more than one way to become them. In 1960,
a girl was born in a Seattle hospital with a clitoris so enlarged it looked like a penis. She grew normally for the next two years, when she underwent surgery to have her clitoris reduced. At the time, doctors were beginning to appreciate how hormones given to pregnant women as medicine could alter the development of fetuses, causing them to become hermaphrodites. But when geneticists at the University of Washington gave the girl an exam, they realized that hers was another story.

A few clues struck them at first. One of her eyes was hazel, the other brown. When the doctors inspected the girl's ovaries, they found that the right one was normal, but the left looked more like a testicle.

The Seattle scientists took tissue samples from the girl's skin, her ovaries, and her clitoris. They carefully examined cells from each part of her body, counting up the chromosomes. Sometimes the cells had two X chromosomes. Sometimes they had an X and a Y. In the ovary, they found, all the cells were double X. But everywhere else, the cells were a mixture of XX and XY. When a blood group expert at the university named Eloise Giblett looked at the child's blood, she found a mixture of two types. But the genes for those two types could only have come from her father, not her mother.

Giblett and her colleagues realized that the girl's father had fertilized two of her mother's eggs with two of his sperm cells. One of his sperm cells carried a Y chromosome, the other an X. They also carried different variants for blood types. The two sperm fertilized two of her mother's eggs, and she became pregnant with a pair of fraternal twins. Under most
circumstances, those twins would have gone on to become a brother and sister. But in this particular case, the two embryos fused early on into a single clump of cells. The cells from both twins were still totipotent at this stage, so they could develop into any tissue, given the right signals. Together, they produced a single healthy child.

Today, this girl would be called
a tetragametic chimera—meaning that she arose from four sex cells (gametes) rather than the regular two. Tetragametic chimeras pose an even greater challenge to our conventional notions of heredity than Mrs. McK. Mrs. McK could point to another distinct person as the source of some of her cells. Tetragametic twins start out as two embryos with separate genomes, and then merge entirely. Only one child is born, and there's no other human being to point to. All we can do is trace their intimately mingled cell lineages to their separate sources.

If two embryos of the same sex form a tetragametic chimera, it's much easier for them to go undetected. The cells from the two twins seamlessly merge together
to produce a girl or a boy with ordinary genitals. Only a close inspection of their DNA will reveal their true heredity. And even when the results are clear, people may refuse to believe them.

In 2003, a woman in Washington State named
Lydia Fairchild had to get a DNA test. Fairchild, who was then twenty-seven, was pregnant with her fourth child, unemployed, and single. To get welfare benefits, state law required that she prove that her children were genetically related both to herself and to their father, Jamie.

One day, Fairchild got a call from the Department of Social Services to come in immediately. A DNA test had confirmed that Jamie was the father of the three children. But Fairchild was not their mother.

The Social Services workers began interrogating her, suspecting her of a crime. Perhaps she had stolen the children. Perhaps she was running some kind of surrogate-mother scam. In any case, she must be guilty of welfare fraud. Fairchild was told her children would be taken away and she would go to jail.

Fairchild desperately tried to prove that the children were hers. She gathered their birth certificates, showing she had delivered them in local hospitals. She contacted her obstetrician to vouch for her. “I saw them come out,” her mother later told ABC News. Six decades earlier, Charlie Chaplin couldn't get courts to look at DNA evidence to decide parenthood. Now DNA was the only evidence the courts would accept, and it was telling Fairchild something that couldn't be true. Fairchild's father confessed that despite his trust in his daughter, the tests gave him doubts. “I have always had faith in DNA,” he later said.

Most lawyers did, too, and it took Fairchild a long time to find one willing to ignore the test results and take on her case. He persuaded Fairchild's judge to order two more DNA tests. The new results also ruled out Fairchild as the mother of her children. When Fairchild was rushed to a hospital to deliver her fourth child, a court officer was there to witness the birth. The officer also oversaw a blood draw for a DNA test. The results came back two weeks later. Once again, Fairchild's DNA didn't match her child's. Even though the court officer had witnessed the child's birth, the court still refused to consider any evidence beyond DNA.

It began to look like there was nothing more to be done. The state prepared to put Fairchild's children into foster care and prosecute her for fraud. But then Fairchild's lawyer read about another mother who had been informed that her children were not her own. In Boston, a woman named
Karen Keegan had developed kidney disease and needed a transplant. To see if her husband or three sons were a match, her doctors drew blood from the whole family in order to examine a set of immune-system genes called HLA.