Leonardo's Foot

by Carol Ann Rinzler

  Today, genetic investigators, sensitized by the thalidomide disaster, routinely look for a link between birth defects and known teratogens (from the Greek word teras meaning monster and genesis meaning creation)—drugs or chemical agents, including the more than 4,000 chemicals in a single cigarette; some studies, including one from University College London in 2011, suggest that deformed limbs and clubfoot are more common among children born to mothers who smoke while pregnant.

  And that brings us to our most essential influence, the place where our lives and all our physicalities originate: our chromosomes and genes.

  In 1958, French pediatrician and geneticist Jerome Lejeune (1926–1994) identified a chromosomal anomaly—an extra copy of chromosome 21—as the cause of Down syndrome, the first congenital defect to be conclusively linked to a genetic error. Lejeune’s discovery affected both science and culture. It led inevitably to similar discoveries regarding a wide range of congenital abnormalities, which led inevitably to effective prenatal testing. But it also became what you might call the modern version of the Roman Decemvirs’ Table IV, a decree by which to justify the selective abortion of fetuses with birth defects.

  Lejeune, a practicing Catholic, was appalled. In 1972, at a United Nations conference that included delegates who endorsed the idea of selective abortion, Lejeune charged that “here we see an Institute of Health turning itself into an institute of death.” That evening, he telephoned his wife to say, “This afternoon I lost my Nobel Prize.” He was right. Despite his many honors and the magnitude of his discovery, Lejeune was never nominated for a Nobel. However, on February 19, 2004, at the 10th General Assembly of the Pontifical Academy for Life in Vatican City, Cardinal Fiorenzo Angelini, President Emeritus of the Pontifical Council for Health Pastoral Care, announced the beginning of the beatification process of Lejeune, who had been the group’s first president. According to his daughter, he would have considered that a more than fair trade.

  Long before Gregor Mendel unraveled the mystery of heredity and Lejeune identified the chromosome for Down syndrome, people knew that putting two superior animals together was likely to produce superior offspring. In The Republic, Plato himself proposed using the same method to breed superior people: “You have in your house hunting-dogs and a number of pedigree cocks … do not some prove better than the rest? Do you then breed from all indiscriminately, or are you careful to breed from the best? And, again, do you breed from the youngest or the oldest, or, so far as may be, from those in their prime? And if they are not thus bred, you expect, do you not, that your birds and hounds will greatly degenerate? And what of horses and other animals? Is it otherwise with them? … How imperative, then, is our need of the highest skill in our rulers, if the principle holds also for mankind? … the best men must cohabit with the best women in as any cases as possible and the worst with the worst in the fewest, and that the offspring of the one must be reared and that of the other not, if the flock is to be as perfect as possible.”

  And for those who might have missed the message, Plato said it straight out: “The offspring of the inferior, and any of those of the other sort who are born defective, they will properly dispose of in secret, so that no one will know what has become of them. That is the condition of preserving the purity of the guardians’ breed.”

  Plato was not the only one concerned with maintaining the purity of the ruling class; the Spartans’ laws regarding infants with birth defects were also aimed at racial purity. By the end of the nineteenth century, the leaders of the nascent eugenics movement believed they had discovered a reliably scientific justification for selective breeding in Charles Darwin’s newly popular theory of natural selection and his open distaste for institutions to protect the disabled. “We civilised [sic] men,” Darwin wrote in The Descent of Man, “do our utmost to check the process of elimination; we build asylums for the imbecile, the maimed and the sick…. Thus the weak members of society propagate their kind.”

  Soon, this unpleasant view of the disabled made it possible for supporters of eugenics to establish a firm footing in Britain and the United States. In 1910, Winston Churchill (1874—1965) wrote to then Prime Minister, Herbert Henry Asquith (1852–1928) that the “unnatural and increasingly rapid growth of the Feeble-Minded and Insane classes, coupled as it is with a steady restriction among all the thrifty, energetic and superior stocks, constitutes a national and race danger which it is impossible to exaggerate. I am convinced that the multiplication of the Feeble-Minded, which is proceeding now at an artificial rate, unchecked by any of the old restraints of nature, and actually fostered by civilised conditions, is a terrible danger to the race.” Then Churchill went even further. He decided that reviving the nineteenth century theory of segregated institutionalization for life was too expensive a solution. Instead, he advocated for forced sterilization, a “simple surgical operation so the inferior could be permitted freely in the world without causing much inconvenience to others.”

  Ever mindful of their “special relationship” with the British, eugenicists in the United States moved ahead expeditiously to endorse Churchill’s “remedy.”

  In 1907, Indiana became the first state to enact a law that made sterilization mandatory and marriage illegal for mentally handicapped people in state custody. Two years later California followed suit and was soon joined by other states. The Race Betterment Foundation, founded in 1911 in Battle Creek, Michigan, by members of the Kellogg family of cereal fame, underwrote three conferences on “race betterment.” The Galton Society, founded in New York City in 1918 to counter the inclusive American Anthropological Association, endorsed the superiority of the Nordic race.

  But the intellectual underpinnings of the American campaign came primarily from the Eugenics Records Office (ERO) at Cold Springs Harbor in New York (1910) and the American Eugenics Society (1926), both financed with donations from such philanthropic luminaries as John D. Rockefeller Jr. and the Rockefeller Foundation; Mary Harriman, the widow of railroad tycoon E.H. Harriman; George Eastman of Eastman Kodak; and the Carnegie Institution for Science.

  To counter those who questioned the constitutionality of the procedure, the ERO’s director, Harry Hamilton Laughlin (1880–1943), wrote a “Model Eugenical Sterilization Law,” the basis for a law passed by the Commonwealth of Virginia in 1924. Three years later, in Buck v. Bell, a case involving a seventeen-year-old woman believed at the time to be mentally handicapped, who was the daughter of a mentally handicapped mother and was herself the mother of a mentally handicapped daughter, the U.S. Supreme Court declared the Virginia Eugenical Sterilization Act constitutional. “We have seen more than once that the public welfare may call upon the best citizens for their lives,” Oliver Wendell Holmes, Jr. (1841–1935), whose obviously splendid genes guaranteed him a nicely long life, wrote for the majority: “It would be strange if it could not call upon those who already sap the strength of the State for these lesser sacrifices, often not felt to be such by those concerned, in order to prevent our being swamped with incompetence. It is better for all the world if, instead of waiting to execute degenerate offspring for crime or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind. The principle that sustains compulsory vaccination is broad enough to cover cutting the Fallopian tubes. Three generations of imbeciles are enough.” Pierce Butler (1866–1939) of South Carolina, the sole dissenting associate justice in the eight-to-one decision, declined to write an opinion.

  After that, sterilization programs sprung up like weeds across the country. At the high (or low) point, as many as thirty states had such laws affecting the mentally ill and even persons convicted of such petty offenses as stealing a chicken. Between 1907 and 1981 the surgery was performed on an estimated 65,000 mentally ill Americans; the state of North Carolina alone sterilized more than 7,000 people, most of whom were women whom state and local officials considered to be, for one reason or another, unfit to raise children. The program was officiall
y disbanded in 1977. In 2010, the governor set up an office to locate victims as a prelude to compensation. The North Carolina State House of Representatives endorsed a bill to award $50,000 to persons who had been sterilized. If passed, it would have made North Carolina the first state in the country formally to compensate victims of a eugenics program, but it was killed by the State Senate on June 20, 2011.

  Under his own model law, Laughlin, an epileptic, was himself a candidate for forced sterilization. There is no indication that he ever volunteered for the procedure. On the contrary, in 1936, he was awarded an honorary degree from the University of Heidelberg for work described as supportive of the “science of racial cleansing,” leading the Nazis to applaud the American eugenicists as allies. Laughlin, whom one biographer described as “among the most racist and anti-Semitic of early twentieth-century eugenicists” does not seem to have objected.

  Others did. The German atrocities in the service of racial purity dramatically altered the view of eugenics in the United States, continuing a reversal that began in 1942 when the U.S. Supreme Court overturned an Oklahoma law because it targeted some low-level criminals while excluding the more polite, but equally guilty white collar miscreants: “[S]crutiny of the classification which a State makes in a sterilization law is essential,” the Court wrote, “lest unwittingly, or otherwise, invidious discriminations are made against groups or types of individuals in violation of the constitutional guaranty of just and equal laws.” Although the Nixon administration broadly increased funding for the voluntary sterilization of poor Americans through the Medicaid program (many believe that the majority of these operations were involuntary), there was no turning back. In 1981, the state of Oregon performed the last legal forced sterilization in the United States.

  The conundrum of selective abortion, however, is still with us, as is the question of what constitutes an abnormality incompatible with an acceptable life.

  In Great Britain, late abortion (after twenty-four weeks), is currently legal only in cases of “serious risk to life of the woman or severe fetal abnormality.” Church of England cleric Joanna Jepson, who was successfully treated in her late teens for a congenital anomaly that set her upper jaw so far out in front of her lower jaw that her teeth could not meet, has long campaigned against aborting fetuses with cleft palate. In 2003, she went to the High Court of Justice, which hears important civil cases in Britain, to argue that terminations based on a clubfoot were illegal because it was not a “serious disability.” Three years later, The Sunday Times of London published figures from the British Office for National Statistics showing that more than twenty women had obtained late-term abortions after scans revealed they were carrying a fetus with a clubfoot. Jepson announced herself appalled that women were “under pressure to abort … in a situation where there is a treatable problem such as clubfoot.”

  The issue of acceptable disability remains—to say the least—contentious. But Lejeune’s discovery of Trisomy 21 dramatically quickened and expanded the search for problematic genes, sometimes with positive results for the human foot.

  Geneticists now know, for example, that polydactyly (extra toes and/or fingers) is carried as an autosomal dominant trait, an effect that occurs even if the fetus inherits a problematic gene only from one parent (a recessive trait requires a copy of the gene from both parents). Webbing of the toes or fingers, failure of the digits to separate normally around the sixth to eighth week of pregnancy, is also an autosomal dominant trait.

  As for clubfoot, even before there were measured studies, people understood that clubfoot, like some other abnormalities, might “run in families.” All you had to do was look at your friends and neighbors to see that if one member of a clan had a clubfoot, another family member somewhere in the generations, might also have one. But scientists prefer to nail down their theories with numbers; in 1912, Alfred Ehrenfried (1880–1951) of Children’s Hospital in Boston produced the first set for clubfoot. Toting up five years’ worth of statistics on 232 young patients in the hospital’s orthopedic outpatient department and excluding those whose clubfoot occurred after paralysis or an injury, Ehrenfried was able to identify a family relationship for nearly one in seven cases, an incidence of 14 percent. Two years later, when the number of patients had risen to 342, the incidence of a family history among patients with talipes equinus varus (the foot turned down and in toward the other foot) was 100 percent.

  Today it is understood that about one in four people with clubfoot have a relative with the same deformity. Parents who have already given birth to a child with a clubfoot have a 10 percent risk of giving birth to a second child with the deformity. If one monozygotic (from one egg, i.e., identical) twin has a clubfoot, the odds of the other twin’s having the problem is about one in three versus one in thirty-three for nonidentical twins. Although Ehrenfried found no clubfeet among his “colored” patients, modern population studies show that the incidence of clubfoot differs markedly among ethnic groups. Clubfoot is most common among Polynesians (Hawaiians and Maoris) for whom the incidence is seven per 1,000 live births, and least likely among the Chinese for whom the incidence is about one for every 3,000 live births.

  Regardless of race or ethnicity, clubfoot is twice as common among boys as among girls. About 20 percent of all cases of clubfoot are associated with other genetic defects such as distal arthrogryposis (contracted joints that make it difficult to move the hands and feet), congenital myotonic dystrophy (progressive muscle wasting), spina bifida, and Trisomy 18 (an extra copy of the chromosome that is linked to low birth weight, a small head with a small jaw and low-set ears, mental retardation, clenched hand, and undeveloped fingernails).

  Clearly, something in our DNA has gone amiss here.

  But what? Which gene is to blame?

  A normal human cell has forty-six chromosomes. Half of the chromosomes are provided by the mother via her egg and half by the father via his sperm. The chromosomes occur in pairs, so naming them is easy: All you need is the ability to count to twenty-three. Genes are an exponentially different matter. Together, the twenty-three human chromosomes hold as many as 25,000 genes, each with its special individual role to play in the development of mind and body. To name them, you need to know what they do. For example, Pitx1 is the abbreviation for a gene whose official name is paired-like homeodomain 1. This gene contains a sequence (homeodomain) of DNA that affects the development of a particular part or parts of the body. The Pitx1 gene, located on human chromosome 5, is also found in other animals as well as plants and fungi. In each species, the gene regulates patterns of anatomic development, including the symmetry of the left and right sides of the organisms. It is not easy to spot an asymmetry caused by a problem with the Pitx1 gene in mushrooms or daffodils, but if something goes wrong with a vertebrate’s Pitx1, the results are likely to be painfully obvious.

  In the mid-1990s, geneticists at the Howard Hughes Medical Institute in California identified a link between Pitx1 and hind limb development in mice. Repeated studies show that mutated or missing Pitx1 genes result in shorter hind leg bones and missing toes in the rodents, deformed wings in chickens, and pelvic abnormalities in manatees and sticklebacks (also known as sticklefish, varieties of small fresh- and seawater fish distinguished by spines along the top).

  In 2008, researchers at the Washington University School of Medicine in St. Louis found evidence of a similar genetic link in human beings. For us, Pitx1, which activates TBX4, a gene on chromosome 17 that regulates the acquisition of two hind limbs, is vital to the development of a normal leg.

  The Washington University team’s report in The American Journal of Human Genetics was based on their study of a Pitx1 mutation among members of an Iowa family with a history of malformations of the lower leg. In this one large family, at least eighteen of thirty-five relatives had one or more specific limb deficiencies or deformities such as a missing lower leg bone (tibia), extra toes, and/or a clubfoot. Interestingly, five women in the clan who carried the gene
did not develop any deformities, which suggests a male susceptibility. Two years later, the same Washington University team defined irregularities on chromosome 17 in people with isolated clubfoot (not associated with other abnormalities). In 2011, they were able to confirm the link between a mutation in one region of the Pitx1 gene and clubfoot. “Much remains to be identified regarding both the genetic and mechanistic aspects of this condition,” they said, but “this discovery opens up the possibility of clinical genetic testing for patients with familial isolated clubfoot and provides important insight into the developmental pathway responsible for human limb birth defects.”

  But not solutions for fixing them.

  In 1981, University of California pediatric surgeon Michael Harrison, now the Director Emeritus, Fetal Treatment Center, Division of Pediatric Surgery, and Professor Emeritus of Surgery, Pediatrics, Obstetrics, Gynecology and Reproductive Sciences at the University of California at San Francisco (UCSF), performed the first open surgery on a fetus. His book, The Unborn Patient: Prenatal Diagnosis and Treatment (1984), literally created the specialty of fetal surgery. Today, the technique is an accepted treatment for a handful of congenital abnormalities such as a malformed heart, tracheal atresia (an abnormal windpipe), a narrowing or obstruction of the urinary tract, a pulmonary lesion such as a cyst that makes breathing difficult, a disorder of the spinal cord such as spina bifida, or a cleft lip and/or palate, all problems that modern technology may diagnose before the baby is born.

  A clubfoot is not on this fearsome list. A foot, after all, is only a foot; even when bent it is serviceable. But a clubfoot is a deformity, and all deformities have effects—although not necessarily the ones you might expect.

  Health care professionals are sometimes surprised that parents of children with what is considered a minor problem, such as a clubfoot, evince the same shock, anger, guilt, and depression as parents whose children are born with far more debilitating abnormalities. A team of geneticists at the University of Aberdeen, Royal Children’s Hospital in Scotland and Bournemouth University in England says the experience is real. In 2011, the doctors interviewed fifteen families of children born with a clubfoot. Their report in The International Journal of Orthopaedic and Trauma Nursing captured the fears of parents who face financial and psychological problems along with the worry that their children will suffer from being “different.”