The PKU Paradox is a book about the history of phenylketonuria (PKU), an autosomal recessive heritable metabolic disorder whose sufferers possess a defective enzyme that fails to metabolize the amino acid phenylalanine. Phenylalanine accumulation, if not diagnosed in newborn babies, produces – by a mechanism which still remains elusive – irreversible brain damage and consequent learning and behavioural difficulties. Standard accounts hail the PKU story, its first description, its diagnosis and its dietary treatment as the perfect synthesis of a genetic and an environmental approach to disease management. PKU thus is presented as a successful case of genetic medicine, one that, because of the possibility of intervention, represents a paradigm shift in medical thinking.

However, as Diane Paul and Jeffrey Brosco make explicit in the preface of this book, PKU is an extremely rare genetic disease (hence the paradox), so rare that ‘in a lifetime of practice most physicians will not encounter a single case’ (p. xiii). So how, they ponder, has such a relatively rare genetic condition, one that affects only one in fifteen thousand individuals in the US, become the focus of so much attention?

Paul and Brosco's book shows that key to this generalized attention has been the construction of a particular account of PKU, one that has been made possible not only because of its presentation as a success story, and therefore as a guiding model for other genetic diseases, but also because of the productive interaction it has had with other developments (in particular in the US), such as (i) the expansion of research funding on genetic diseases from the 1950s onwards, (ii) a growing momentum for implementation of state policies on mental disability and (iii) the merging of parent groups into wider associations aiming to protect the mentally disabled.

Without denying two central claims of the standard account – namely the benefits of the screening programs and subsequent dietary management in preventing for many the onset of the disease – Paul and Brosco's book provides a richer and more detailed picture of the PKU story than the standard account offers. They not only disclose the many intricacies at play among scientists and physicians, US state politicians (many with mentally disabled children in their families) and family support groups, but also show the many transitions that the PKU story has been part of in general, and in the US in particular. In effect, the paradoxical PKU story is intimately linked to the transformation of eugenics into genetic medicine; the shift in the social conceptualization and location of care for the mentally disabled (from the private to the public sphere); the emergence from the early 1960s of parent groups to lobby states for the appliance of universal screening of babies (the authors offering an important glimpse at one key aspect of the history of lobbying in the US); the impact of new biotechnological developments, such as genetic engineering in the 1970s, that shifted the relevance of diseases from their aetiology to their genetics; and, finally, issues of reproductive decision-making and consent for the future use of archived blood samples.

The PKU Paradox challenges a key claim of the standard account, that the condition was well managed by a screening which was swiftly routinized as a result of the appliance of a straightforward test (the Guthrie test) and an even more straightforward dietary plan based on the absence of phenylalanine in foodstuffs. Paul and Brosco show that, in spite of the lack of a full understanding of the biochemistry of the disease and the uncertainties about the timing of using a restrictive diet – two issues that were contested by many scientists and physicians from the 1960s onwards – the PKU case was by then conceptualized as successful.

The PKU Paradox rests on twenty years of research into the history of the disease by Paul. Many of the main themes discussed in it are found in work she has previously published. However, this book is far from being just a rehearsal of the conclusions reached in all of her previous works – not only because it includes Brosco's contribution on issues of mental disability, but also because it contains in-depth discussion of new issues, such as what it means to live with PKU in general and with a PKU restrictive diet in particular, the distressing consequences of maternal PKU (a condition created by the success of the screening programs), and the issue of the history of the regulation of reproductive choices in the post-war United States.

The PKU Paradox is a significant book for readers interested in understanding the many factors and intricacies involved in the history of diseases, in particular genetic diseases. It is also a precious exemplar for history-of-medicine students and others looking to develop the skill of writing clearly and succinctly whilst making timely use of extensive and well-placed references in support of sound argumentation. The PKU Paradox is an illuminating book, for it provides a compelling argument against the simplistic and persistent view that genetic diseases are fixed in the lab. Instead, it proposes a complex contextual history, not only a more persuasive one, but also one that provides a model for comprehensive study of other diseases, genetic or not.