Friday, August 2, 2013

Mutants: On the Form, Varieties, and Errors of the Human Body by Armand Marie Leroi

WARNING:  If discussions of sexual anatomy disturb you, please skip paragraphs 16-18.

I really enjoyed this “popular science” book—in a sense, it was very like the territory covered by Bondeson, and like Bondeson, Leroi comes from a science background. However, where Bondeson is (I think) a practicing consultant as well as a university lecturer, (I think) Leroi’s background at Imperial College (at least when he wrote the book) was more clinical research-based.  Bondeson, too, is more interested in the narrative and “characters,” and while Leroi has an excellent humanist wit, there is something a bit less approachable, a bit darker, about the way he builds up his argument.   Though I struggled with some of the higher science, I did learn a lot about subjects that, as a non-scientist, I could never dream to grasp without Leroi’s guidance. 

Leroi’s argument is that we are all, in lesser or greater degrees, mutants of the perfect human genome.  We don’t know who that person is—“Who among us has the genome of genomes, the one by which all other genomes will be judged?”—and in a sense, it doesn’t matter.  The book is about exploring the degrees that make us less perfect that the model human being.  Most mutations, he points out, destroy meaning—these are called “loss-of-function” mutations.  This is why you can examine mutation as being less perfect than the ideal or normal example of the type.  Thus it seems the X-Men are the exception to the rule . . .  Leroi even comments that “red hair is not good for anything at all,” pleasing, no doubt, all those ginger-haters out there.  “Whether a given genetic sequence is a mutation rather than a polymorphism hinges on two issues:  its global frequency and its usefulness.”  Red hair, he concludes, is neither frequent enough nor useful enough to be considered a polymorphism. 

There is still something slightly sleazy about the “common” fascination with “freaks,” and something still slightly elevated about examining them from the scientific viewpoint.  At least, I think so, and I believe that quality informs why Leroi put one of the daughters of Petrus Gonsalvus, a hairy family (with hypertrichosis) originally from the Canary Islands, on the cover (she has a pleasing aspect and inside the book, Leroi compares her to a friendly cat).  (On the back cover is a painting of a pair of female conjoined twins with long red hair, which Leroi comments are rather beautiful.)

In fact, Leroi seems rather taken by twins.  He spares a few sentences for my “favorite” pair of conjoined twins, the Biddenden Maids, but misses out others like the Tocci Brothers.  Anyway, he uses Ritta-Christina Parodi (born in 1829) to illustrate his main points (twins known as xipophages in France and parapagus dicephalus tetrabrachius elsewhere).  As in the case of their unfortunate countrywoman Caroline Crachami, Ritta-Christina’s body was acquired for science by dubious methods.  Leroi is more careful about stating fact than Bondeson, whose authoritative authorial voice made the vagaries of science seem safely corralled.  Leroi tells us that current scientific research suggests that conjoined twins are considered nearly always monozygotic—originating from a single egg fertilized by a single sperm (monozygotes also account for identical twins—one embryo that has accidentally split into two).  Conjoined twins share a single placenta and a single amniotic sac; separate twins share a single placenta but each usually has an amniotic sac of its own.  It is quite interesting to know, as well, that while 50% of separate monozygotic twins are female, 70% of conjoined twins are female.

Perhaps the two-but-one relationship of conjoined twins (upon which we, as individuals in individual bodies, can only speculate upon) lends itself to poetry.  Parasitical twins, however, do not.  “Some forty cases have been described of children who have dwarfed and deformed parasites growing from their palates . . . In 1860 a child was born in Durango, Mexico, who had a parasite growing from his mouth to which two others were attached.”  Teratomas, such as one described in a Roman woman in a recent edition of Archaeology Today, are tissue that are masses of hair, teeth, bone and skin.  “A Dutch child born in 1995 had the remains of twenty-one foetuses (as determined by a leg count) embedded in its brain.”  Frankly, this makes me both incredibly grateful to have been born as well-formed as I was, and furthermore makes me less likely to attempt to have children.  Leroi gives no explanation for what causes parasitical twins—probably because no one knows for sure.  Now, who has ever watched the Doctor Who TV Movie and wondered at the likelihood of a fictional hospital in San Francisco destroying the evidence of a patient—who died on the operating table, so they think—having two hearts?  It was always going to look like a fairly moronic and cynical thing to do, but even more so in light of Kartagener’s syndrome, the earliest known example being of an old soldier who died at Les Invalides in 1688.  “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 around.”  Meaning, they have a heart on the right side (but, unlike the Doctor, no mirror image on the left side). 

Leroi is very keen—as a clinical researcher would be—on animal-based lab experiments and their insights into human mutants.  Some of the experiments seem excessive, even for the time they were performed in—Hilda Pröscholdt’s fascinating experiments with newts in the 1920s, for example, were able to produce “conjoined-twin newts, oriented belly to belly,” by transplanting a piece of blastopore lip, which seemed to have the power to instruct a whole new creature.  (Though contrast this with Étienne Geffroy Saint-Hilaire’s attempt in the early 19th century which rather lacked subtlety:  “If monsters were caused by accidents in the womb, he reasoned, it should be possible to engineer them . . . he systematically abused developing eggs” in the Nile Valley hatcheries “by shaking them around, perforating them, or covering them in gold foil.”)  One luckless salamander “had a leg amputated twenty times—and grew it back each time.”          

Like a scientific journal article beginning with its literature review, Leroi begins his treatise on mutants by surveying teratology. Partly this is to trace societal attitudes toward mutants and highlight how difficult it can be to diagnose cases retrospectively (that does not prevent him from trying.  He makes a good case for the Monster of Ravenna, born March 1512 and starved to death by order of Julius II, to have been a child born with Roberts’ Syndrome[1]).  Some examples are too obscure to pinpoint.  The Monster of Cracow, born in 1540, “with barking dogs’ heads mounted on its elbows, chest, and knees” died “declaiming ‘Watch, the Lord cometh.’”  Leroi finds a great deal of beauty and sometimes even sympathy in the heretofore-categorized-callousness of our ancestors; for example, Sir Thomas Browne wrote Pseudodoxia epidemica, or, enquiries into very many received tenets and commonly presumed truths (1646) and Religio medico (1642).  Browne sees “the works of nature—all of them, even the most deformed—as the works of God, and if they are the work of God then they cannot be repugnant.”  Furthermore, Leroi has great sympathy for Charles I as he witnessed experiments into the biology of deer; “England lost a monarch with a taste for experimental embryology, a thing not likely to occur again soon.”

I’d heard it long claimed that the origins for the Cyclops of Homer’s myth were from prehistoric elephantoid skulls on Mediterranean islands such as Crete; it’s been a long time since anyone suggested to me that Cyclopic people existed.  However, as Leroi has found out, “the ease with which fetuses become cyclopic is frightening.”  It has to do with the fusing of what should be bisected; it happens in animals as well as humans; “the single eye of a cyclopic child is the external sign of a disorder that reaches deep within its skull,” in fact, to the two halves of the brain.  By starting from cyclopic embryos, Leroi demonstrates the ways in which mutants of all stripes can be made from varying doses of retinoic acid from vitamin A.  He cites a 1932 experiment, “when a sow at a Texas agricultural college that had been fed a vitamin A-deficient diet gave birth to eleven piglets all of which lacked eyeballs.”  Furthermore, too much retinoic acid can causes problems. 

Leroi often takes surprising starting points to eventually work his way around to a scientific principle or breakthrough.  For example, a small marble statue from the ruins of Herculaneum of the god Pan raping a nanny goat brings him to discuss supernumerary ears, because these are common in goats and show up occasionally in humans; the sculptor, whoever he was and whatever his propensities, knew enough about goats to depict both Pan and the rape victim with them.  A girl in 1858 displayed just such appendages and when they were amputated, they were found to be ears (though not functioning ears, of course).  This is an example of homeosis, “in which one part of a developing embryo becomes anomalously transformed into another.”  Extra ribs are surprisingly common—one in every ten adults has them (no less frequently in women than in men!). 

Although, as we said earlier, the majority of mutations are “loss-of-function,” life often seems to find a way, such as with a group of people colloquially known as Cleppies (nothing to do with, as I first surmised, the Blue Fugates of Kentucky).  Here, too, is Leroi pulling story from disparate sources that seem, at first, to have nothing to do with the subject at hand.  The Cleppies’ legend begins in 1685 in Wigtown, Scotland, where two religious dissenters, Margaret McLaughlin and Margaret Wilson, were drowned in the River Bladnoch.  A man named Bell was said to shout at them as they perished, “Clep down among the partens and be drowned!”  Bell’s descendents, then, were said to be cursed with “claws” instead of hands—they were known as the Cleppie Bells.   A family living in London in 1908, possibly related to the Bells of Wigtown, possessed “hands moulded from birth into a claw-like deformity.”  Now called ectrodactyly, the children of the family wrote, drew, did needlework, and most other tasks; some of the parents were cab drivers and bootmakers[2].  Mammals, as Leroi states, have a good ability to compensate for lack of limbs. Since we’ve just mentioned the Blue Fugates, “it is impossible to keep a good myth down.  In the mid-1980s two South African journalists claimed that they had stumbled across a whole tribe of two-tod people in the darker reaches of the Zambezi.  Now websites assert that that Wadoma worship a huge metal sphere buried in the jungle and rare, in fact, extraterrestrials.”    Our fingers and toes, meanwhile, are formed by cell death—much as water might carve shapes into rock.  We don’t know why, however, most vertebrates have less than five digits per limb. 

Willem Vrolik occurs somewhat earlier than the discovery of the Wadoma, his collection being bought by the University of Amsterdam at the turn of the twentieth century.  “In a fine display of Dutch rationalism they have decided that all who wish to do so should be allowed to see the worst for themselves,” unlike, for example, the Gordon Museum at King’s College, upon which uneducated gawking is frowned.  “And the worst is terrible indeed.  Arrayed in cabinets, Vrolik’s specimens are really quit horrifying.  The gaping mouths, sightless eyes, opened skulls, split abdomens and fused or missing limbs seem to be the consequence of an uncontainable fury” or Eddie Campbell’s illustrations for From Hell, perhaps.  “Many of the infants that Vrolik collected were stillborn.  A neonate’s skeleton with a melon-like forehead is a case of thanatophoric dysplasia; another whose stunted limbs press against the walls of the jar in which he is kept has Blomstrand’s chonododrodysplasia.  There is a cabinet containing children with acute failures in neural tube fusion.  Their backs are cleaved open and their brains spill from their skulls.  Across the gallery is a series of conjoined twins, one of which has a parasitic twin almost as large as himself protruding from the roof of his mouth.  And next to them is a specimen labelled ‘Arcadia amorphous,’ a skin-covered sphere with nothing to hint at the child it almost became except for a small umbilical cord, a bit of intestine, and the rudiments of a vertebral column.”             

I don’t think I’ve seen a specimen with “Arcadia amorphous,” but I have seen, in specimen jar, the foot of someone who suffered from elephantism.  Leroi, however, doesn’t believe that Joseph Merrick suffered from elephantism; he prefers PTEN protein deficiency which causes Proteus syndrome.  An illustrative example, though not of Proteus syndrome but fibrodysplasia ossificans progressiva, was Harry Eastlack.  He “requested that his skeleton be kept for scientific study, and today it stands in Philadelphia’s Mütter Museum.  Bound in extra sheets, struts, and pinnacles of bone that ramify across the limbs and ribcage, this skeleton is, in effect, that of a forty-year-old man encased in another skeleton, but one that is inchoate and out of control.” 

There isn’t room for Leroi to discuss every kind mutant manifestation, so the second half of the book focuses on disorders that have affected a relatively large number of people over the ages.  Achondoplastics like Joseph Boruwlaski—a celebrated dwarf of the European courts—continue growing into their twenties, long after most people have stopped, and suffer from a growth hormone failure.  Giants like Charles Byrne also suffer from hormone problems; his pituitary gland was the size of a small tomato.  Did P.T. Barnum know he was cloaking tragedy with fairy tale fantasy when he publicized the wedding of Tom Thumb and Lavinia Warren in the 1870s?  “Should a foetus inherit two copies of the achondroplasia mutation (by virtue of having two achondroplastic parents) it, too, will die shortly after birth with all the symptoms of thanatophoric dysplasia.” 

One is tempted to suppose, however, that man proved infinitely more cruel than nature in the case of the Ovitz Family, who had pseudoanchondroplasia.  The patriarch Rabbi Ovitz “was renowned for his wisdom and compassion,” and his ten children, seven of whom had pseudoanchondroplasia, became a jazz troupe after his death in order to support themselves.  Yoshko Moskovitz “wrote to his sister that he had met a woman, small in size, but well-endowed with talent, wisdom, and industriousness.”  He and Elizabeth Ovitz soon married.  However, when the family was forced to Auschwitz, “they paid for survival by being given starring roles in [Josef] Mengele’s bizarre and frenetic programme of experimental research. . . . As with all he did, he reasons for doing so remains unfathomable.” 

One group of people who we think of as rooted in the past are castrati.  From drawings we know they were tall and somewhat oddly shaped.  We know anecdotally that they suffered from kyphosis, symptomatic of osteoporosis.  We can be fairly sure that they never went bald and never had prostate cancer.  “Testes, then, are not only the source of hormonal signals that regulate gender; they are also the source of at least one hormone that in late adolescence instructs bones to seal their growth plates and so cease growth.”  Therefore, in 1994, a Cincinnati man’s hormonal problems were corrected when he sought medical help:  he had been 5’10” on his driving license and at the age of 28, had shot up to 6’8.”  There was a mutation in his estrogen receptor.  The last Chinese court eunuch, however, was only buried in 1996 (along with his testicles preserved in a jar, as the Khanum threatens to do to Erik in Susan Kay’s Phantom).

If we can’t relegate eunuchs (or people with eunuch-like symptoms) to the past, nor can we people with indeterminate physiological genders.  Through the example of Alexina Barbin, who in 1857 became an assistant teacher in a girls’ school and began an affair with another young schoolmistress, Leroi gives quite a tour-de-force on proving all that you think you know about sexual organs is wrong.  “Alexina was a hermaphrodite.  Medicine may have recognized hermaphrodites, but not so the law or society.  A choice had to be made, and those ovoid bodies [the doctor discovered in Alexina] decided it.”  Alexina became, to all intents and purposes, a man, a male pseudohermaphrodite, writing an autobiography before killing himself.  Leroi comes to a stunning conclusion:  the vagina is unique to females:  it has no male equivalent.  If you think that sounds like an obvious statement, think again. 

For example, female spotted hyenas are female pseudohermaphrodites, in which the pathological has become normal.  They copulate and give birth through the clitoris (painfully, I might add)! Renaldus Columbus in 1559 “discovered” the clitoris, which he called the “Sweetness of Venus,” but placed it in the uterus.  If we accept that the clitoris is part of a larger structure called the vestibular bulbs, the anatomical corollaries between male and female make more sense.  For example, by day 28 after conception, the human embryo has for small limb buds and a tail, and a small bump between the lower limb buds.  This is soon surrounded by two sets of folds, one inside the other.  This bump eventually makes all of our external genitalia.  Differences only appear by day 63—in the male, the genital tubercle expands and becomes the penis; in the female, it remains small and the labia minora and labia majora form around it. 

If this is all that stands in the way of, on the one hand, making the embryo female and on the other, making it male, it seems less remarkable that some fetuses get “caught in between.”  For example, in testosterone synthesis mutations, usually the effect is in making the foetus female at birth; the symptoms are only picked up at puberty when the girl fails to menstruate.  “The combination of feminine looks and male height means that women without testosterone receptors are often strikingly attractive.  In the 1950s at least one French woman with defective testosterone receptors made a living as a catwalk model.”  

Leroi is also quite interested in hair.  As I said, he is slower than Bondeson to diagnose hypertrichosis languinosa for people like Petrus Gonsalvus or Schwe-Mong or Maphoon (and doesn’t mention Julia Pastrana, possibly because she doesn’t fit the languinosa phenotype).  But, because baldness is close to Leroi’s heart (if his author’s photo is anything to judge by J), he tries to get to the bottom of male pattern baldness, which affects 20% of American men in their 20s, 50% of 30-50 year-olds, and 80% of 80-year-olds.  “Balding is truly a white man’s burden.”   He discusses two quite interesting studies:  one from 1999, in which a married pair of scientists excised a piece of dermis from his scalp and put it on a hairless region under her arm, thus proving that the dermis “has a voice, one that tells the epidermis:  ‘make follicles here.’”  The second study was done by James Hamilton in 1942, featuring 54 eunuchs, some of whom had been born without testes, some of whom had been castrated as boys out of medical necessity (inguinal hernias, etc), and, Leroi suspects, some of whom were “mentally retarded men who had been castrated as boys in Kansas medical institutions, a legacy of eugenic programmes that ran in the United States until the 1960s.”  “Women who acquire, for whatever reason, abnormally high levels of testosterone not only grow beards but tend to go bald as their baldness genes, hitherto silent, manifest themselves.”

The last chapter treats aging as a disease and that we mutate physically and mentally with old age.  Leroi highlights Alexander Graham Bell’s eccentric idea to create a race of gerontocrats (ie, a database where the longest-lived recorded their children who should then marry and reproduce with other lineage from long-lived groups in order to make humans live to Biblical ages).  This scheme “was visionary and only slightly mad.”  There is evidence, however, that these gerontocrats would have an ever-dwindling fertility.  So would it be worth it?  “The only reliable way to extend the general physiological life of a mammal is to give it no more than two-thirds of the daily calories that it wants.”  Again, though, is it worth it?  “A thousand calories is about the minimum number needed to sustain the life of an average-sized man, though not enough to sustain his sex drive (or, to judge by pictures, his sex appeal).”

Mutants was an absolutely fascinating read, and I applaud its author.      

[1] “It seems likely that it was simply a child who was born with a severe, rare, but quite unmysterious genetic disorder . . . That, at least, would account for the limb and genital anomalies, if not the two serpents on its waist and the supernumerary eye on its knee.” 
[2] I saw a woman with ectrodactyly just the other day in a London theatre.