The PKU Paradox: A Short History of a Genetic Disease

Chapter 6. New Paradigms for PKU

92 CHAPTER SIX New Paradigms for PKU F F F The remarkable improvement for individuals with phenylketonuria treated early in life led to many interpretations of the “PKU story.” For human geneticists, screening and treatment represented a vindication of Lionel Penrose’s prediction in the 1940s that the metabolism in PKU would someday be manipulated and, by extension, that other inherited disorders would turn out to be treatable.1 In the words of Charles Scriver (who had studied with Penrose), treatment for PKU “changed the paradigm. Genetics is something you can’t do anything about. Wrong. Genetics is something you can do something about and here’s the example.”2 Through the 1960s, however, PKU programs also served as a paradigm in at least two other, at the time, more prominent ways: as a means to prevent mental retardation through the application of scientific medicine and as a novel public health program based on collecting, testing, and storing biological material obtained from an entire population. In the former case, PKU was presumed to be merely one of many metabolic disorders that would be discovered and treated to reduce the prevalence of MR; in the latter, universal newborn screening served as an unprecedented example of the role of the state in improving the health of individual citizens . Much like the example of polio vaccination campaigns in New Paradigms for PKU 93 the 1950s, the experience with PKU in the 1960s solidified the US focus on laboratory medicine as the key to improving health.3 Over time, the “PKU paradigm” was increasingly identified with the geneticists’ interpretation of the PKU story as proof that “genetic” ought not be equated with “fixed.” As an exemplar of genetic malleability, PKU was increasingly invoked in the service of new agendas: in various iterations of the “nature-nurture” debate , it illustrated the flaws of genetic determinism, and in the discourse of biomedicine, it symbolized the value of genetic screening and the unique contribution of genetic research to the improvement of clinical outcomes. Indeed, wherever the point about plasticity is made, and to whatever ultimate purpose, it is likely to be illustrated by the successful alteration of the course of PKU. Before PKU could serve as a model of effective intervention in a genetic disease, however, its being an inherited disease had to be emphasized to a much greater degree than had been the case in the 1960s, when most state screening programs were established.4 Of course, it had been recognized since the 1930s that PKU was an autosomal recessive trait, but in the 1960s, the nature of PKU as a disease transmitted in the genes from one generation to another had little salience for the politicians, parent advocates, and others involved in the campaign to legislate screening for the disease . Discussing the case of cystic fibrosis, Keith Wailoo and Stephen Pemberton note that in the 1960s and 1970s, “neither families nor experts emphasized the ‘genetic’ features of the disease. To be sure, they understood it to be a ‘hereditary’ disorder, but this way of thinking did not capture what they saw as its fundamental biological underpinnings.”5 Similarly, while popular articles on PKU testing almost always noted that the disease was hereditary and occasionally described its recessive mode of transmission, the focus was elsewhere: on the ability to prevent mental retardation resulting from at least one cause and on the possibility that a similar approach would prove effective against other disorders causing MR. That the devastating effects of the disease had far 94 The PKU Paradox more salience than its etiology is reflected in the state legislative hearings on mandatory testing, where the hereditary nature of PKU received virtually no attention. None of the statutes establishing NBS programs even mentioned genetics. According to a 1975 National Academy of Sciences (NAS) report, interviews and transcripts of legislative hearings indicated that, at the time, most lobbyists and public officials involved in the process were responding to claims that screening would prevent MR and hence spare parents suffering and save taxpayers money. “There was little recognition of the implications for public policy, or for the impact on individuals who were screened, of the fact that PKU is a genetic disease.”6 But the implications of PKU being a genetic disease would not have been obvious at the time most NBS programs were established . A majority of US states had launched screening...