Mutants (7 page)

Hilda Pröscholdt’s results were published in 1924, but she did not live to see them in print. Halfway through her doctoral degree she married Otto Mangold, one of her fellow students in Spemann’s laboratory, and it is by his name that she is now known. In December 1923, having been awarded a doctorate, she gave birth to a son, Christian, and left the laboratory. On 4 September 1924, while visiting her Swabian in-laws, she spilt kerosene while refuelling a stove. Her dress caught alight, and she died the following day of her burns. She was only twenty-six, and in all ways a product of the Weimar. As a student, when
not dissecting embryos, she had read Rilke and Stefan George, sat in on the philosopher Edmund Husserl’s lectures, decorated her flat with Expressionist prints, and taken long Black Forest walks. She had only really done one good experiment, but it is said by some that had Hilda Pröscholdt lived she would have shared the Nobel Prize that Spemann won in 1935.

E PLURIBUS UNUM?

When Eng and Chang toured the United States they advertised themselves with the slogan, familiar to any citizen of the Republic,
e pluribus unum
– out of many, one. It seemed apt enough, but it was only half the truth. Conjoined twins are clearly, in the first instance, a case of
ex uno plures
– out of one, many.

The similarity of human twins to the conjoined-twin newts made by Hilda Pröscholdt suggests one way how this might happen. All that is needed are two organisers on a single embryo instead of the usual one. Although Pröscholdt doubled the organisers on her newts by some deft, if crude, transplantation surgery, there are much more subtle molecular means of bringing about the same end. The genes that encode the signalling proteins of the organiser – noggin, cerberus, dickkopf and so on – are regulated by yet other ‘master control genes’. The making of two embryos out of one may, therefore, be simply a matter of one of these master control genes being turned on in the embryo where it normally is not. Why this should happen is a mystery – human conjoined twins occur so rarely (about 1 in every 100,000 live births) and unpredictably that there is no obvious way to
find out. Perhaps they are caused by chemicals in the environment: at least one drug (albeit a rare and potent chemothera-peutic agent) has been shown to cause conjoined twinning in mice. Whatever the ultimate cause of conjoined twins, the ‘two-organiser’ theory, while a neatly plausible account of how to get two embryos out of one, is not in itself a complete explanation for their existence. The theory has nothing to say about their essential feature: the fact that they are glued together.

C
ONJOINED TWINS: PARAPAGUS DICEPHALUS DIBRACHIUS
. F
ROM
B.C. H
IRST AND
G.A. P
IERSOL
1893
Human monstrosities.

One man who thought deeply about the conjoinedness of conjoined twins was Étienne Geoffroy Saint-Hilaire. In 1829 Geoffroy was Professor at the Muséum d’Histoire Naturelle, and next to Cuvier (his colleague and bitter rival) the most
important anatomist in France. Geoffroy’s disciple Étienne Serres had written the monograph describing Ritta and Christina Parodi’s autopsy; Geoffroy’s son, Isidore, had organised the event. It is upon Isidore that suspicion falls for having bullied the Parodis into surrendering the corpse.

Geoffroy
père
was one of the most mercurial intellects of his time: almost everything he wrote has a touch of genius and a touch of the absurd. He was one of nature’s romantics: ostensibly a descriptive anatomist, he investigated the devices by which puffer fish inflate themselves, but did not shy away from larger problems, such as the relationships between the ‘imponderable fluids’ of the universe (light, electricity, nervous energy, etc.), his deductive theory of which never saw print. More reasonably, Geoffroy was also keenly interested in deformity. It is in his hands that teratology first really becomes a science.

In 1799 Geoffroy was among the
savants
that Napoleon Bonaparte brought to Egypt in his futile attempt to block England’s route to the East. Geoffroy spent his Egyptian sojourn (cut short by the arrival of the British) collecting crocodiles, ichneumons and mummified ibises. Egypt also gave him a way of making ‘monsters’ to order. Geoffroy was a staunch epigeneticist. If monsters were caused by accidents in the womb, he reasoned, it should be possible to engineer them. Since time immemorial, the peasants of the Nile valley had incubated chicken eggs in earthenware furnaces fired by burning cow-dung. Inspired by this, Geoffroy established a similar hatchery where he systematically abused developing eggs by shaking them around, perforating them, or covering them in gold foil.
The resulting chicks were mostly more dead than deformed, but some had bent digits, odd-looking beaks and skulls, and a few lacked eyes – unspectacular results, but enough to convince Geoffroy that he had definitively slain preformationism.

From monstrous chickens to monstrous humans was an easy leap and, starting in 1822, Geoffroy published a string of papers on deformed infants, which he classified as zoologists classify insects. A child whose head was externally invisible belonged, for example, to the genus
Cryptocephalus
. He realised that his ‘genera’ were not specific to humans: dogs, cats, perhaps even fish, could be deformed in the same way; his classification transcended the scale of nature. A few years later Isidore elaborated his father’s classification into a system that is still, with some modification, used by teratologists today, one in which Ritta and Christina, and children like them, are known as ‘Xiphopages’ to the French and ‘parapagus dicephalus tetrabrachius’ (side-joined, two-headed four-armed) conjoined twins to everyone else.

Étienne Geoffroy Saint-Hilaire’s greatest contribution to teratology was, however, the realisation that deformity is a natural consequence of the laws that regulate the development of the human body. Moreover, looked at the right way, such deformed infants can
reveal
those laws. This, of course, is a very Baconian idea – and in one of his more philosophical tracts the anatomist speaks warmly of the genius of James I’s Lord Chancellor.

Nowhere, for Geoffroy, were those laws more clearly revealed than in conjoined twins. Even before seeing Ritta and Christina Parodi in 1829, he had dissected a number of conjoined twins. Conjoinedness, he argued, was simply a reflection of what
normally happens in a single embryo. The organs of an embryo develop from disparate parts that are then attracted to each other by a mysterious force rather like gravity. The intimacy of conjoined twins is caused by this same force, but misapplied so that the parts of neighbouring embryos fuse instead to one another.

Geoffroy was deeply enamoured of this deduction and, in the positivist fashion of his day, made a law of it:
le loi d’affinité de soi pour soi
– the law of affinity of like for like. In the monograph that Étienne Serres wrote on Ritta and Christina’s dissection, fully the first half is devoted to the
soi pour soi
and a few other laws of Serres’s own devising. Geoffroy regarded the
soi pour soi
as his greatest discovery, and in later years elevated it into a fundamental law of the universe, not unlike Goethe’s notion of ‘elective affinities’ to which it is related. This hubristic vision has ensured that the
soi pour soi
is, today, quite forgotten. This is a pity, since although Geoffroy’s law is unsatisfactorily vague, and wrong in detail, it conveys something important about how human embryos are built. It was the first scientific explanation of connectedness.

CONNECTEDNESS

Eighteen days after conception the embryo is just a white, oval disc about a millimetre long. It has no organs, just three tissue layers and a geometry. Even the geometry is largely virtual: a matter of molecules that have been ordered in space and time, but not yet translated into anything that can be seen without the special stains that molecular biologists use. Within the next ten days all this will have changed. The embryo will be recognisably
an incipient human – or at least some sort of vertebrate, a dog, a chicken or perhaps a newt. It will have a head, a neck, a spinal column, a gut; it will have a heart.

The first sign of all this future complexity comes on day 19 when a sheet of tissue, somewhat resembling the elongate leaf of a tulip, forms down the middle of the embryo above the primitive streak. The leaf isn’t entirely flat: its edges show a tendency to furl to the middle, so that if you were to make a transverse section through the embryo you would see that it forms a shallow U. By the next day the U has become acute. Two more days and its vertices have met and touched in the middle of the embryo, rather as a moth folds its wings. And then the whole thing zips up, so that by day 23 the embryo has a hollow tube that runs most of its length, the nature of which is now clear: it is the beginnings of the mighty tract of nerves that we know as the spinal column. At one end, you can even see the rudiments of a brain.

Even as the nerve cord is forming, the foundations of other organs are being laid. Small brick-like blocks of tissue appear either side of incipient nerve cord, at first just a few, but then ten, twenty, and finally forty-four. Made of mesoderm, they reach around the neural tube to meet their opposite numbers and encase the neural tube. They will become vertebrae and muscles and the deepest layers of the skin. Underneath the embryo the endoderm, which embraces an enormous, flaccid sac of yolk, retracts up into the embryo to become the gut. As the gut shrinks the two halves of the embryo that it has previously divided are drawn together. Two hitherto inconspicuous tubes, one on either side, then unite to make a single larger tube running the length of the embryo’s
future abdomen, an abdominal tube that echoes the neural tube on its back. Within a few days this abdominal tube will begin to twist and then twist again to become a small machine of exquisite design. Though it still looks nothing like what it will become it already shows the qualities that led William Harvey to call it ‘the Foundation of Life, the Prince of All, the Sun of the Microcosm, on which all vegetation doth depend, from whence all Vigor and Strength doth flow’. On day 21 it begins to beat.

The ability of disparate organ primordia to find each other and fuse to form wholes is one of the marvels of embryogenesis. Underlying it are thousands of different molecules that are attached to the surface of cells and are, as it were, signals of their affiliation, that permit other cells to recognise them as being of like kind. These are the cell-adhesion molecules; molecular biologists speak of them as the Velcro of the body: weak individually, but collectively strong. Even so, the fusion of organ primordia is a delicate business. Neural tube fusion is particularly prone to failure. One infant in a thousand born has a neural tube that is at least partly open – a condition called spina bifida. At its most severe the neural tube in the future head fails to close. The exposed neural tissue becomes necrotic and collapses, leaving a child that has the remnant of a brain stem but in which the back of the head has been truncated, as if sliced with a cleaver.

Such anencephalic infants, as they are known, occur in about 1 in 1500 births; they have heavy-lidded eyes that seem to bulge from their heads and their tongues stick out of their mouths. They die within a few days, if not hours, of being born. As the
name suggests, spina bifida is often not just a failure of the neural tube to close, but a failure in the closure of the vertebral column so that instead of being sheltered by bone the nerve cord lies exposed. It is not the only organ prone to this sort of defect. Sometimes the primordia of the heart fail to meet; the result is cardiac bifida, two hearts, each only half of what it should be.

The power of cell–cell adhesion to mould the developing body is startling. In his monograph on Ritta and Christina, Serres describes a pair of stillborn boys who are joined at the head. Oriented belly to belly, their faces are deflected ninety degrees relative to their torsos so that they gaze, Janus-like, in opposite directions. What is remarkable about these children is that each apparent face is composed of half of one child’s face
fused to the opposite half of his brother’s. The developing noses, lips, jaws and brains of these two children have found each other and fused perfectly – twice.