Mutants (8 page)

C
ONJOINED TWINS: CEPHALOTHORACOILEOPAGUS
. F
ROM
É
TIENNE
S
ERRES
1832
Recherches d’anatomie transcendante et pathologique.

The diversity of ways in which conjoined twins can be attached to each other seems to depend on the position of the developing embryonic discs relative to each other as they float on their common yolk sac and when they contact. The embryonic discs that gave rise to Ritta and Christina were side by side, and fused some time after closure of the vertebral column but before formation of the lower gut. In the case of the twins with fused faces the embryonic discs were head to head. The most extreme form of conjoined twinning is ‘parapagus diprosopus’, in which the fusion is so intimate that the only external evidence of twinning is a partly duplicated spinal column, an extra nose and, sometimes, a third eye. At this point all debates over individuality become moot.

Conjoined twins grade into parasites, infants that live at the expense of their siblings. The distinction is a matter of asymmetry. When the young Italian Lazarus Colloredo toured Europe in the 1630s he was celebrated for his charm and breeding even as his brother, John Baptista, dangled insensibly from his sternum. In the late 1800s an Indian boy, Laloo, displayed his parasite, a nameless, headless abdomen with arms, legs and genitals, in the United States. In 1982, a thirty-five-year-old Chinese man was reported with a parasitic head embedded in the right side of his own head. The extra head had a small brain, two weak eyes, two eyebrows, a nose, twelve teeth, a tongue and lots of hair. When the main head pursed its lips, stuck out its tongue or blinked its eyelids, so did the parasitic head; when the main
head ate, the parasite drooled. Neurosurgeons removed it. Certain parts of the developing body seem especially vulnerable to parasitism, among them the neural tube, sternum and mouth. Some forty cases have been described of children who have dwarfed and deformed parasites growing from their palates. And parasites may themselves be parasitised. In 1860 a child was born in Durango, Mexico, who had a parasite growing from his mouth to which two others were attached.

Teratomas may be an even more intimate form of parasitism. These are disordered lumps of tissue that are usually mistaken initially for benign tumors, but that after surgery turn out to be compacted masses of differentiated tissue, hair, teeth, bone and skin. They have been traditionally blamed on errant germ cells. Unlike most of the body’s cells, germ cells have the potential to become any other cell type, and it is supposed that occasionally a germ cell that has wandered into the abdomen will, perhaps by mutation, start developing spontaneously into a disordered simulacrum of a child. It is now suspected that some teratomas are, in fact, twins that have become fully enclosed within a larger sibling, a condition known trenchantly as ‘
foetus in foetu
‘. A Dutch child born in 1995 had the remains of twenty-one foetuses (as determined by a leg count) embedded in its brain.

LEFT-RIGHT

There is one more thing that Ritta and Christina can tell us, and that is how we come to have a left and a right. We tend to think of ourselves as symmetrical creatures and, viewed externally, so
we are. To be sure, our right biceps may be more developed than their cognates on the left (
vice versa
for the left-handed minority), and none of us has perfectly matched limbs, eyes or ears, but these are small deviations from an essential symmetry. Internally, however, we are no more symmetrical than snails. The pumping ventricles of our hearts protrude to the left sides of our bodies. Also on the left are the arch of the aorta, the thoracic duct, the stomach and the spleen, while the vena cava, gall bladder and most of the liver are on the right. Christina’s viscera were arranged much as they are in any of us (except for her liver, which was fused with Ritta’s). Ritta’s viscera, however, were not. They were the mirror-image of her sister’s.

C
ONJOINED TWINS: SITUS INVERSUS VISCERA
. R
ITTA AND
C
HRISTINA
P
ARODI
. F
ROM
É
TIENNE
S
ERRES
1832
Recherches d’anatomie transcendante et pathologique.

This condition, known as situs inversus, literally ‘position inverted’, is common in conjoined twins, as it is rare in the rest of us (who are situs solitus). Not all conjoined twins are situs
inversus, but only those that are fused side to side (rather than head to head or hip to hip). Even among side-to-side twins situs inversus is only ever found in the right-side twin – ‘right’ referring to the twins themselves not the observer’s view of them – and then only in 50 per cent of them. This last statistic is intriguing, for it implies that the orientation of the viscera is randomised in right-side twins. It is as if nature, when arranging their internal organs, abandons the determinism that rules the rest of us, and instead flips a coin marked ‘left’ or ‘right’.

In recent years, much has been learned about why our internal organs are oriented the way they are. One source of information comes from those rare people – the best estimates put them at a frequency of 1 in 8500 – who, despite being born without a twin, have internal organs arranged the wrong way round. The most famous historical case of singleton situs inversus was an old soldier who died at Les Invalides in 1688. Obscure in life – just one of the thousands who, at the command of Louis XIV, had marched across Flanders, besieged Valenciennes and crossed the Rhine to chasten German princelings – he achieved fame in death when surgeons opened his chest and found his heart on the right. In the 1600s Parisians wrote doggerel about him; in the 1700s he featured in the
querelle des monstres
debate; in the 1800s he became an example of ‘developmental arrest’, the fashionable theory of the day. Were he to appear on an autopsy slab today, he would hardly be famous, but would simply be diagnosed as having a congenital disorder called ‘Kartagener’s syndrome’.

It is a diagnosis that allows us to reconstruct something of the
old soldier’s medical history. Although the immediate cause of his death is not known, it certainly had nothing to do with his inverted viscera. He was, indeed, in all likelihood oblivious to his own internal peculiarities. Although he was quite healthy (dying only at the age of seventy-two), he probably never fathered any children, and his sense of smell was also probably quite poor. We can guess these things because inverted viscera, sterility and a weak sense of smell are all features of men with Kartagener’s.

That the association between these symptoms was ever noticed is surprising, for they seem so disparate, and even after the syndrome was first defined in 1936 the causal link between them remained elusive for years. But in 1976 a Swedish physician
named Bjorn Afzelius found that a poor sense of smell and sterility are caused by defective cilia – the minute devices that project from the surfaces of cells and wave about like tiny oars. Cilia clear particles from our bronchial passages, and the tail that drives a spermatozoon to its destination is also just a large sort of cilium. Each cilium is driven by a molecular motor, a motor that in people with Kartagener’s syndrome does not work. As children, for want of beating cilia to clear the passages of their lungs and sinuses they have chronic bronchitis and sinusitis – hence the poor sense of smell. As adults, the men are sterile for want of mobile sperm. At the heart of the ciliary motor lies a large protein complex called dyenin. It is made up of a dozen-odd smaller proteins, each of which is encoded by its own gene. So far Kartagener’s syndrome has been traced to mutations in at least two of these genes, and it is certain that others will be found.

K
ARTAGENER
’
S SYNDROME
. D
ISSECTED INFANT SHOWING SITUS INVERSUS VISCERA
. F
ROM
G
EORGE
L
ECLERC
B
UFFON
1777
Histoire naturelle générale et particulière.

But it is the situs inversus that is so intriguing. Afzelius noted that not all people with Kartagener’s syndrome have inverted viscera: like conjoined twins, only half of them do. He suggested, insightfully, that this implied that cilia were a vital part of the devices that the embryo uses to tell left from right – but what their role was he could not say. Only in the last few years has the final link been made – and even now there is much that is obscure. It all has to do with (and this is no surprise) the organiser.

I said earlier that the organiser is a group of mesodermal cells located at one end of the embryo’s primitive streak. Each of these cells has a single cilium that beats continually from right to left. Collectively they produce a feeble, but apparently
all-important, current in the fluid surrounding the embryo, an amniotic Gulf Stream. This directional movement, and the cilia whose ceaseless activity causes it, is the first sign that left and right in the embryo are not the same. The mechanism, which was only discovered in 1998, is wonderfully simple and, as far as is known, is used nowhere else in the building of the embryo. What the cilia actually do is unclear; the best guess is that they concentrate some signalling molecule on the left side of the embryo, rather as foam accumulates in the eddies of a river.

This model (with its Aristotelian overtones) is frankly speculative, but it makes sense in the light of what happens next. Shortly after the organiser forms, genes can be seen switching on and left and right in the cells that surround it. They encode signalling molecules that transmit and amplify the minute asymmetries established by the organiser’s beating cilia to the rest of the embryo. One might call it a relay of signals, but that suggests something too consensual. It is more like a hotly contested election. In democracies left and right battle for the heart of the
polis
; so it is in embryos as well.

There is a lovely experiment that proves this. If the various signals that appear early in the embryo’s life on either side of the organiser are indeed involved in helping it tell left from right, then it should be possible to confuse the embryo by switching the signals around. As usual, this is a hard trick to do in mammal embryos, but not that difficult in chickens. By gently cutting open a recently-laid egg and so exposing the embryo as it lies on its bed of yolk, it is possible to gently place a silicone bead soaked in
‘left-hand’ signal on its right (or to place a bead soaked in ‘right-hand’ signal on its left). Either way, the asymmetry of the embryo’s signals is destroyed. And so too, it becomes apparent shortly thereafter, is the asymmetry of the chicken’s heart. Where once it always fell to the left, it now has an even probability of falling to either side. The resemblance of this randomisation to that found in people with Kartagener’s syndrome and in conjoined twins is surely no coincidence. Indeed, it is thought that Ritta’s inverted heart was caused by just such a scrambled molecular signal. When the girls were nothing more than primitive streaks lying side by side, each strove to order her own geometry. But in Ritta’s case this effort was confounded by signals that swept over from her left-hand twin. The molecular asymmetries upon which her future geometry depended were abolished, and from that point on the odds were fifty–fifty that her heart would be placed the wrong way round.

In 1974 Clara and Altagracia Rodriguez became the first conjoined twins to undergo successful surgical separation. Since then, the birth of each new pair – Mpho and Mphonyana (b.1988, South Africa), Katie and Eilish (b.1989, Ireland), Angela and Amy (b.1993, USA), Joseph and Luka (b.1997, South Africa), Maria Teresa and Maria de Jésus (b.2002, Guatemala), to name but a few – has been the occasion of a miniature drama in which surgeons, judges and parents have been called upon to play the part of Solomon. Surgical advances nothwithstanding, had Ritta and Christina Parodi been born today they could not have been separated. But they would surely have lived. Somewhere in America, Brittany and Abigail
Hensel, twins even more closely conjoined than they, have recently turned twelve.