Chimera

Human chimeras were once thought to be so rare as to be just a curiosity.

But there's a little bit of someone else in all of us, says Claire

Ainsworth, and sometimes much more...

EXPLAIN this. You are a doctor and one of your patients, a 52-year- old

woman, comes to see you, very upset. Tests have revealed something

unbelievable about two of her three grown-up sons. Although

she conceived them naturally with her husband, who is definitely

their father, the tests say she isn't their biological mother.

Somehow she has given birth to somebody else's children.

This isn't a trick question - it's a genuine case that Margot Kruskall, a

doctor at the Beth Israel Deaconess Medical Center in Boston,

Massachusetts, was faced with five years ago. The patient, who we will

call Jane, needed a kidney transplant, and so her family underwent blood

tests to see if any of them would make a suitable donor. When the results

came back, Jane was hoping for good news.

Instead she received a hammer blow. The letter told her outright that

two of her three sons could not be hers. What was going on?

It took Kruskall and her team two years to crack the riddle. In the end

they discovered that Jane is a chimera, a mixture of two individuals -

non-identical twin sisters - who fused in the womb and grew into a single

body. Some parts of her are derived from one twin, others from the other.

It seems bizarre that this can happen at all, but Jane's is not an

isolated case. Around 30 similar instances of chimerism have been

reported, and there are probably many more out there who will never

discover their unusual origins.

While cases like Jane's are the extreme, researchers now think that

there's a little bit of chimera in all of us, and what was once seen

as a biological oddity may serve a vital function. We may owe our

lives to being chimeras.

At first, Jane's case had Kruskall completely puzzled. The original

data came from the tests done to "tissue-type" her and her children.

Such tests are based on a set of genes called the HLA complex, which

encode many different immune proteins, including cell surface

proteins that immune cells use to distinguish the body's own tissues

from foreign material. There are hundreds of different versions, or

alleles, of each HLA gene, and because of this, each person's

combination of alleles is almost unique. But because the genes are

clustered close together on chromosome 6, they tend to be inherited

together in a block known as a haplotype. Everyone inherits two HLA

haplotypes, one from each parent.

Transplant doctors know that the closer the match between two people's HLA

haplotypes, the lower the risk of a transplant between them being

rejected. If you need a transplant, the obvious place to look for people

with a similar haplotype is your close family. Your siblings, for example,

have a 1-in-4 chance of matching yours exactly, while your children will

have at least 50 per cent of your HLA genes.

Confronted with Jane's bizarre test results, Kruskall's team's first line

of enquiry was to take another look at Jane's HLA genes and those of her

immediate family. They identified Jane's haplotypes and dubbed them 1 and

3. They tested Jane's husband too - he had types 5 and 6. And when they

looked at her sons they confirmed that the original tissue-typing was

correct. While all three shared a haplotype with their father, only one

shared one of Jane's. The other two sons had a haplotype of unknown

origin, labelled type 2.

The obvious interpretation was that Jane was not the biological

mother of two of her sons, yet they were all conceived naturally,

so how could this be? One possibility was that both boys were

accidentally swapped at birth, but the chance of this happening twice to

the same family is very small. Add in the fact that both sons share a

haplotype with their father and it becomes a near impossibility.

Stumped, Kruskall sent her data out to colleagues, asking them if

they could make sense of it. Soon researchers around the world were

scratching their heads in bewilderment. "I did get the most amazing

set of explanations," Kruskall recalls. "No one could quite figure it

out." One suggested that Jane had secretly undergone fertility

treatment using donated eggs. Another speculated that Jane and her

husband had got her sister to

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