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The PKU Paradox

A Short History of a Genetic Disease

Diane B. Paul and Jeffrey P. Brosco

Publication Year: 2013

PKU (phenylketonuria) is a genetic disorder that causes severe cognitive impairment if it is not detected and treated with a strict and difficult diet. In a lifetime of practice, most physicians will never encounter a single case of PKU, yet every physician in the industrialized world learns about the disease in medical school and, since the early 1960s, the newborn heel stick test for PKU has been mandatory in many countries. Diane B. Paul and Jeffrey P. Brosco’s beautifully written book explains this paradox. The development of state programs for early detection of and treatment for PKU is deservedly considered a great public health success story. Advocates have traded on this success to urge expanded newborn screening, to defend basic research in genetics, and to confront proponents of genetic determinism. When deployed for these purposes, treatment for PKU is typically represented as a simple matter of adhering to a low-phenylalanine diet. In reality, the challenges of living with PKU are daunting. In this first general history of PKU, a historian and a pediatrician explore how a rare genetic disease became the object of an unprecedented system for routine testing. The PKU Paradox is informed by interviews with scientists, clinicians, policy makers, and individuals who live with the disease. The questions it raises touch on ongoing controversies about newborn screening and what happens to blood samples collected at birth.

Published by: The Johns Hopkins University Press

Series: Johns Hopkins Biographies of Disease


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p. 1-1

Title Page, Copyright Page

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pp. 2-5


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pp. 6-7

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pp. vii-xii

...Disease is a fundamental aspect of the human condition. Ancient bones tell us that pathological processes are older than humankind’s written records, and sickness and death still confound us. We have not banished pain, disability, or the fear of death, even if we die, on the average, at older ages, of chronic and not acute ills...

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pp. xiii-xxii

...Thus, in a lifetime of practice, most physicians will not encounter a single case. Yet, probably every physician in the industrialized world has learned about PKU in medical school, many parents vividly remember the heel-stick test for their newborn, and scientists interested in genetics and metabolism...

List of Abbreviations

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pp. xxiii-xxvi

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Introduction. Pearl Buck, PKU, and Mental Retardation

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pp. 1-9

...Carol had been a beautiful blond and blue-eyed baby; strong and healthy, at first she seemed to develop normally. But she was slow to talk, and her mother began to grow uneasy. Although friends and others whom she informally consulted were reassuring, there were mounting signs of trouble. Carol exhibited...

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Chapter 1. The Discovery of PKU as a Metabolic Disorder

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pp. 10-21

...Borgny Egeland gave birth to her first child, a daughter named Liv, in Norway in 1927. Like Carol Buck, Liv Egeland seemed fine in early infancy but was slow to begin to talk. Consulting the family doctor, this mother, too, was assured there was no cause...

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Chapter 2. PKU as a Form of Cognitive Impairment

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pp. 22-34

...For scientists and clinicians in the early twentieth century, phenylketonuria was a scientific puzzle connecting biochemistry and symptoms; for affected children and their families, phenylketonuria meant living with a cognitive impairment. Before the discovery...

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Chapter 3. Testing and Treating Newborns, 1950–1962

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pp. 35-53

...By the 1950s, scientific medicine offered hope that the medical conditions causing mental retardation could be prevented or cured. The transformation of PKU from an obscure metabolic cause of MR to a new paradigm for the treatment of a genetic...

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Chapter 4. The Campaign for Mandatory Testing

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pp. 54-71

...Universal newborn screening programs are an anomaly in the United States, where medical practice has historically focused on the diagnosis and treatment of individual patients by their private physician, with the role of government generally restricted...

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Chapter 5. Sources of Skepticism

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pp. 72-91

...In the 1960s, when states began mandating newborn screening for PKU, much about the diagnosis and treatment of the disease remained uncertain. For example, a report of a 1966 consensus conference on PKU, sponsored by the US Children’s Bureau, criticized...

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Chapter 6. New Paradigms for PKU

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pp. 92-110

...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...

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Chapter 7. Living with PKU

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pp. 111-139

...The management of phenylketonuria through nutritional therapy is inescapably arduous, given the sheer scale of the required reduction in dietary protein, the centrality of food to our cultural identities and social relationships, and the nature of the body’s...

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Chapter 8. The Perplexing Problem of Maternal PKU

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pp. 140-155

...mid-1960s, “The solution of one problem often begets new ones,” and the history of PKU prevention is a case in point: “The oldest early-treated phenylketonuric girls are now more than ten years of age. Mental retardation due to phenylketonuria is waning as a...

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Chapter 9. Who Should Procreate? Perspectives on Reproductive Choice and Responsibility in Postwar America

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pp. 156-178

...When Savio Woo and his colleagues announced, in 1983, their discovery of the gene whose mutations result in PKU, they titled their paper “Cloned Human Phenylalanine Hydroxylase Gene Allows Prenatal Diagnosis and Carrier Detection of Classical Phenylketonuria...

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Chapter 10. Newborn Screening Expands

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pp. 179-203

...Newborn screening is more than the collection of blood from newborns to detect an unseen malady. It is a complex system of care that includes training of personnel in hospitals throughout the country; collection of individually identified blood spots and...

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Epilogue. “The Government Has Your Baby’s DNA”: Contesting the Storage and Secondary Use of Residual Dried Blood Spots

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pp. 204-212

...In the half-century since the advent of the first blood-spot screening programs for phenylketonuria, fundamental changes have taken place in the context of debates about newborn screening. In the 1960s, there were few commercial interests in newborn screening...

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pp. 213-218

...Nearly two decades have elapsed since Diane Paul began to research the history of PKU. Over such an extended period, one amasses many debts, some of which she might no longer even recall. To anyone inadvertently excluded from the list of those to whom thanks are due, she offers sincere apologies...

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A Note on Sources

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pp. 219-222

...No “biography” of PKU, even a short one, would be complete if it did not pay attention to the lived experience of patients and their families. Indeed, one aim of this book is to provide a more realistic account of life with the disease than readers are likely to encounter in discussions intended for nonspecialists. To that end, between...


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pp. 223-282


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pp. 283-289

E-ISBN-13: 9781421411323
E-ISBN-10: 1421411326
Print-ISBN-13: 9781421411316
Print-ISBN-10: 1421411318

Page Count: 304
Illustrations: 12 b&w illus.
Publication Year: 2013

Series Title: Johns Hopkins Biographies of Disease