Moments of Truth in Genetic Medicine

Chapter 6: Jewish Genes: History, Emotion, and Familial Dysautonomia

chapter 6 J E W I S H G E N E S History, Emotion, and Familial Dysautonomia Most genetic diseases are “small.” They affect very few people. They are also often strange and difficult to recognize. Most physicians never see most of the diseases that appear in Victor McKusick’s catalogue, Mendelian Inheritance in Man. Unlike cancer or heart disease or depression, these diseases have a limited effect on everyday medical care. They can be devastating for the individual and family affected, but they are not important, or familiar, or perhaps even worth mapping to the genome. In this chapter I look at one of those diseases, familial dysautonomia, that most physicians will never see and that most genomic scientists initially had no interest in mapping. Indeed, although it might have its origins in a single fifteenth-century mutation, it is a disease that was not clinically visible until the twentieth century. The new antibiotics of the 1940s permitted the very vulnerable infants born with familial dysautonomia (FD) to survive long enough to be noticed and to be differentiated from the mass confusion of infant mortality: FD is a postantibiotic disease, experienced and lived as a result of a new therapeutic technology.1 It is also a disease that may well disappear , also through technological intervention. A genetic test was first developed in 1993, and in early 2001 the gene was found. Prospective parents who are at risk (and the relevant risk factor is Ashkenazi Jewish heritage) can be tested for carrier status, and fetuses can be tested prenatally and aborted if they have the disease. Many parents, physicians, genomic scientists , and others want to prevent the birth of more babies with FD. It could, perhaps, become a disease for which the generation of affected people alive today is the last. It could become a disease only of the twentieth century, ef- florescing from 1940 to the end of the century, then disappearing. And this disappearance, too, will be the result of technology. I want to hold in sight throughout my discussion the notion of a disease both brought into being and (to be) eliminated by social organization and technology. I want the quality of FD as constructed to be central to my narrative , which draws primarily on the scientific texts that defined the disease and explained its meaning. Familial dysautonomia, as an experienced and lived disease, is a product of neuronal anomaly, of sensory dysfunction, of Jewish history, and of biomedical technology. It is a “natural” phenomenon, a splicing mutation, named DYS, in the IKBKAP gene, a mutation that causes a tissue-specific absence of exon 20 in the IKAP protein within the brain. And FD has been sustained and brought into existence by Ashkenazi Jewish reproductive practices. It is also an extremely demanding bodily state for those affected and their families. FD is an amalgam of history, emotion, biochemistry, and medical technology. Familial dysautonomia was noticed because the Ashkenazi population in New York City was dense enough to produce many cases in a relatively short period. In the 1940s, three physicians at Babies Hospital in New York encountered five “puzzling cases.” All these children did not produce tears. They suffered from intense vomiting and experienced skin blotching, sweating , blood pressure instability, and other signs of “disturbances in autonomic function.” In an atmosphere of “continual exchange” within the hospital ’s social network, physicians Conrad Riley, Richard Day, and their colleagues “recognized the similarity between the patients,” and in the spring of 1948 they prepared a report suggesting that all five children had the same condition. The syndrome, described as “bizarre” and “hitherto unrecognized ,” came to be known temporarily as Riley-Day syndrome (Riley 1970; Riley et al. 1949; Brunt and McKusick 1970). That the disorder might be hereditary was considered possible from the beginning. It was present from birth, and all those affected were Ashkenazi Jews and therefore members of a genetically distinct population. In 1954, J E W I S H G E N E S 1 5 7 Riley concluded that the disease was genetic and renamed it familial dysautonomia (Riley, Freedman, and Langford 1954), but it continued to be called Riley-Day syndrome in scientific publications well into the 1970s. Over the next twenty years, more than two hundred cases were reported in the medical literature. By 1964 a reliable diagnostic skin test (a characteristic muted response to...