Nerd Na­tion

Jenny Ni­cholls ex­plores some bizarre quirks of hered­ity.

North & South - - Contents - By jenny ni­cholls

TO AN­CIENT GREEKS, the chimera was a spit­ting, snarling, fire-breath­ing fe­male patch­work of scary an­i­mals, with a goat thrown in for good mea­sure. “A thing of im­mor­tal make,” wrote Homer, “not hu­man, lion-fronted and snake be­hind, a goat in the mid­dle, and snort­ing out the breath of the ter­ri­ble flame of bright fire.” She ap­par­ently lived in Ly­cia ( part of mod­ern- day Turkey).

This might seem a long way from the De­part­ment of So­cial Ser­vices of­fice in Wash­ing­ton State, USA, where a solo mother was sum­moned af­ter ap­ply­ing for wel­fare in 2003. The in­cred­i­ble story of Ly­dia Fairchild – an Amer­i­can chimera and a liv­ing tes­ta­ment to the tricks hered­ity plays on us – is re­counted in a new book by US science writer Carl Zim­mer, She Has Her Mother’s Laugh: the Pow­ers, Perver­sions and Po­ten­tial of Hered­ity (Macmil­lan, $40).

On the sur­face, Fairchild, at 27, seemed about as far from a fire-breath­ing snakegoat hy­brid as you could get. Preg­nant with her fourth child, she found her­self in need of state sup­port af­ter she broke up with her chil­dren’s fa­ther. State law in Wash­ing­ton re­quired a DNA test to prove her chil­dren were hers. A for­mal­ity, she thought.

When the re­sults came back, they as­tounded ev­ery­one who knew her. Fairchild’s ex, Jamie, was con­firmed as the fa­ther of her three chil­dren – but Fairchild her­self had no ge­netic link to them. De­spite the ev­i­dence of the ob­ste­tri­cian and Fairchild’s mother, who’d seen her grand­chil­dren be­ing born, two fur­ther tests repli­cated the find­ings.

To Fairchild’s hor­ror, the De­part­ment of So­cial Ser­vices threat­ened to foster out her chil­dren, and charge her with wel­fare fraud.

Her story be­came noth­ing short of sur­real af­ter she gave birth to a fourth child un­der the beady gaze of a court of­fi­cial, who watched as nurses drew blood from the in­fant for a DNA test. The re­sults came back two weeks later: her DNA did not match the baby a court of­fi­cial had seen be­ing born.

Un­for­tu­nately for Fairchild, the court gave more weight to DNA ev­i­dence than to the tes­ti­mony of those present at the birth. Her preg­nancy was not enough to prove moth­er­hood. So­cial Ser­vices pre­pared to charge her with fraud.

WHEN WE take a cheek swab of cells and send it to a Dna-test­ing com­pany, we make the same as­sump­tion the US So­cial Ser­vices made in Fairchild’s case: that ev­ery cell in our body con­tains the same genome. Our DNA is the same, whether it comes from cells in our blood, our brain or our kid­neys, right?

Fairchild’s lawyer heard of a case in Bos­ton which echoed the ex­pe­ri­ence of his client. When 52-year- old re­nal pa­tient Karen Kee­gan needed a sec­ond kid­ney trans­plant, her fam­ily was tested for com­pat­i­bil­ity. To ev­ery­one’s as­ton­ish­ment, she was told the test proved she could not be the bi­o­log­i­cal mother of two of her three sons. The hos­pi­tal even sug­gested she might have stolen the two boys as babies.

Lynne Uhl, a trans­fu­sion medicine spe­cial­ist at Beth Is­rael Dea­coness Med­i­cal Cen­tre in Bos­ton, wasn’t buy­ing it. “We knew this woman very well and knew with­out any doubt that she was the mother of these kids. That prompted us to look more care­fully for an ex­pla­na­tion for this find­ing.”

Uhl and her team be­gan test­ing other kinds of tis­sue be­long­ing to Kee­gan. They checked her hair fol­li­cles, cheek swabs and old stored tis­sue sam­ples from ear­lier mi­nor sur­gi­cal pro­ce­dures.

Bingo. Kee­gan, it tran­spired, was made up of two dif­fer­ent kinds of cells, each with their own DNA, as if two peo­ple had fused. This is, in fact,

pre­cisely what hap­pened.

In science- speak, Kee­gan was a “tetraga­metic chimera”: the re­sult of two fe­male non-iden­ti­cal twins who be­came one early in their de­vel­op­ment. One twin gave rise to all her blood, but only some of her eggs. The son cred­ited to her de­vel­oped from one of them. Her other boys be­gan as eggs from the other twin’s cell lin­eage, con­tain­ing the other twin’s DNA.

UHL AND HER team agreed to test Fairchild’s tis­sues. The first tests were un­promis­ing. DNA from Fairchild’s hair, saliva and skin didn’t match her chil­dren’s. And then Uhl tested cells from a cer­vi­cal smear. These re­vealed the bizarre truth: Fairchild was also a chimera. Her twin may have only ever ex­isted as a bunch of cells – but, fer­tilised by a dif­fer­ent sperm to the sperm that led to Fairchild, those gave rise to the lin­eage that pro­duced her eggs. The tran­sient twin was the bi­o­log­i­cal mother of her chil­dren.

“The sto­ries of Ly­dia Fairchild and Karen Kee­gan both ended hap­pily,” writes Zim­mer. “But they left the women with haunting ques­tions not only about their fam­i­lies but about them­selves. Fairchild’s eggs, cervix and per­haps some other tis­sues in her body all had a direct ge­netic link to her chil­dren. But what of the rest of her body. Was she partly their aunt, too? As for Kee­gan, were her sons half-broth­ers to each other, with two sis­ters for their moth­ers?”

It took 16 months for the case against Fairchild to be dis­missed. With­out the help of Kee­gan’s doc­tors, she would have gone to jail and, even worse – lost her chil­dren. Her at­tor­ney, Alan Tin­dell, had his own views about a sys­tem which put such im­pla­ca­ble faith in DNA. “Peo­ple go to death row be­cause of DNA tests,” he said. “Peo­ple are re­leased from death row be­cause of DNA tests.”

WE HAVE KNOWN about hu­man chimera since 1953, when a young woman recorded in med­i­cal his­tory as “Mrs MCK” do­nated a pint of blood in Eng­land. It turned out to be a mix of type O and type A.

When Mrs MCK told sci­en­tists about a twin brother who died of pneu­mo­nia at three months, they (even­tu­ally) re­alised his stem cells had en­tered her body in the womb and set up shop in her bone mar­row. There, they pro­duced enough type A blood to make her blood­stream a cock­tail of two parts O to one part A. If Mrs MCK and her twin had shared a blood type, her chimerism would not have been dis­cov­ered.

We now know that chimeras are hardly rare. In fact, you might well be one your­self – al­though prob­a­bly in a less dra­matic sense than Mrs MCK, Fairchild or Kee­gan.

The pla­centa, it turns out, is leakier than we once thought. An un­born child’s cells of­ten cross into their mother, where they may pro­duce a lin­eage of cells with their DNA that lasts for days, weeks or even years. If the woman gets preg­nant again, these cells, as well as her own, can cross the pla­centa into her new fe­tus.

To find out how com­mon this is, US re­searcher Diana Bianchi tested women with sons to find out how many had tis­sue with their son’s Y chro­mo­somes. She ex­cluded women who had ever re­ceived a blood trans­fu­sion or had an or­gan trans­plant. Bianchi found fe­tal cells with Y chro­mo­somes in six of the eight moth­ers she tested. “One of the women with Y chro­mo­somes had a 27-year-old son,” writes Zim­mer, “mean­ing his cells had re­mained es­tab­lished in her body for more than a quar­ter- cen­tury.”

In the years since Bianchi’s pa­per was pub­lished in the Pro­ceed­ings of the Na­tional Academy of Sciences jour­nal in 1996, re­searchers have found that more than half of moth­ers carry fe­tal cells decades af­ter their preg­nan­cies. And ac­cord­ing to a re­cent es­ti­mate, says Zim­mer, 42% of us carry cells con­tain­ing our mother’s DNA.

But surely a few alien cells wouldn’t af­fect our health? “Fe­tal cells don’t sim­ply mi­grate around their mother’s bod­ies,” says Zim­mer. “They sense the tis­sue around them and de­velop into the same types of cells.” One US sci­en­tist, Lee Nel­son, has spec­u­lated this might ex­plain why women are more prone to au­toim­mune dis­eases. For­eign fe­tal cells, he hy­poth­e­sised, might trig­ger a woman’s im­mune sys­tem into at­tack­ing her own tis­sues. Al­though re­search ap­pears to bear this idea out, Zim­mer re­mains cau­tious about the link. One of the strengths of his book is his re­luc­tance to over-egg re­search, and his fa­mil­iar­ity with the peer-re­viewed pa­pers he writes about – ev­ery study has its foot­note.

And, any­way, be­ing a chimera might also be a good thing. Bianchi found a woman with goitre, which had de­stroyed her own thy­roid cells. Oddly, the gland was still se­cret­ing healthy amounts of thy­roid hor­mone. The gland, it turned out, was stuffed with her son’s cells. The ev­i­dence, writes Zim­mer, pointed to an amaz­ing con­clu­sion.

“A fe­tal cell from her son had wended its way through her body to her dis­eased thy­roid gland. It had sensed the dam­age there and re­sponded by mul­ti­ply­ing into new thy­roid cells, re­gen­er­at­ing the gland.”

In an­other case, a woman’s liver had been rav­aged by hep­ati­tis C. Years be­fore, she’d had a preg­nancy ter­mi­nated. In­cred­i­bly, her aborted son’s cells, still bear­ing the Y chro­mo­some of the fa­ther, came to the res­cue by re­build­ing an en­tire lobe of her liver.

And what does this all mean for sur­ro­gate moth­ers? They may well end up con­nected to the child they bear, in ways they didn’t imag­ine.

BUT WE DON’T need to be a mother to have, in some bod­ily nook or cranny, traces from a ghostly twin who be­queathed us their stem cells.

Charles Bok­lage, a de­vel­op­men­tal bi­ol­o­gist who has stud­ied chimerism for more than two decades, ex­plains: “About one- eighth of all con­cep­tions and about one- eighth of live births are ‘twins’ – the ma­jor­ity of whom are born alone with­out a live twin. About one in eight of ev­ery­body walk­ing around is a twin who was born sin­gle.”

Hered­ity, says Zim­mer – and this is the over­ar­ch­ing theme of his book – can surge and com­min­gle in strange ways, blow­ing back­wards and side­ways like a strange eddy of wind, or a river cur­rent flow­ing the wrong way. +

We have known about hu­man chimera since 1953, when a young woman known to med­i­cal his­tory as “Mrs MCK” do­nated a pint of blood in Eng­land.

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