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a b
AUTHORS: Jeffrey P. Brosco, MD, PhD, and Diane B. Paul, PhD
a
Department of Pediatrics, University of Miami Miller School of Medicine, Miami,
Florida; and bUniversity of Massachusetts Boston, Boston, Massachusetts;
Museum of Comparative Zoology, Harvard University, Cambridge,
Massachusetts.
Address correspondence to Jeffrey P. Brosco, MD, PhD, Department of
Pediatrics, University of Miami Miller School of Medicine, PO Box 016820, Miami,
FL 33101. E-mail: jbrosco@miami.edu
Accepted for publication Sep 24, 2013
KEY WORDS
history, phenylketonuria, newborn screening, genetics
ABBREVIATIONS
NBS—newborn screening
PKU—phenylketonuria
doi:10.1542/peds.2013-1441
hopes of finding a simple medical like to test for conditions that are much Breakfast
Kid cereal, 6 tbsp 30
cure, despite the relatively small im- less treatable than PKU or that may Banana, 6-in section 30
pact of PKU and similar conditions on provide no direct medical benefit at all Orange juice, 4 oz 15
the prevalence of intellectual disabil- to the child. Moreover, the dried blood Phenyl-free formula, 6 oz 0
Lunch
ity in the late 20th century.3 spots collected from millions of new- Vegetarian vegetable 60
In the 1970s and 1980s, PKU took on new borns, representing an unselected soup, 1/2 can
roles as an exemplar in the nature- population, have become a valuable re- Saltine crackers, 2 30
Lettuce, shredded, 15
nurture debates and as a resource for source for researchers. But these po- 1/2 cup
advocates of genetic testing.2 PKU is a tential clinical and research practices, French dressing, Free
genetic condition that is highly treatable which would seem to require specific 2 tbsp
Fruit cocktail, 3/4 cup 15
if infants receive a diagnosis at birth and informed consent from parents, are not
Phenyl-free formula, 6 oz 0
are placed on a diet low in phenylala- easy to harmonize with a legal frame- Snacks
nine, an essential amino acid found in all work and hospital routines that date Popsicle Free
Sucker, 1 Free
dietary proteins. That an environmental from the 1960s.2
Apple, 1 medium 8
intervention could dramatically alter the The regularity with which PKU was and Phenyl-free formula, 6 oz 0
course of a genetic disorder made it an is invoked in the service of divergent Dinner
Rice, cooked, 4 tbsp 60
attractive example both for critics of agendas is intriguing and prompts an Green beans, cooked, 15
genetic determinism, who employed it in obvious question: How well does this 3 tbsp
both the genetics of IQ and sociobiology ubiquitous PKU success story accord Jelly gelatin, 6 tbsp 30
Phenyl-free formula, 6 oz 0
controversies, and for enthusiasts for with reality? Accounts of PKU diagnosis Kool-Aid, 4 oz Free
genetic screening, who traded on the and treatment in the nonspecialist lit- Total 278
“large store of goodwill and ethical erature rarely mention any diagnostic From Kaufman M, Nardella M. A teacher’s guide to PKU.
credit” accumulated by NBS to legitimate Texas Department of Health. 1985. Available at: www.pkuil.
complications, treatment challenges, or org/TeachersGuide.pdf. Accessed October 2, 2013
genetic screening programs more gen- imperfect outcomes. The authors of
erally.4 Foes of genetic determinism and a recent Nature article, for example,
promoters of genetic tests have not assert that treatment of newborns with way one strand of the history of PKU
generally been political bedfellows, and PKU and other metabolic and immu- follows the contours of the discovery of
indeed, are often at odds; yet both find nologic disorders “is often as simple as insulin: the famous breakthrough of
support for their positions in the history diet change.” 5 A common analogy has scientific medicine does indeed save
of PKU. been to insulin, as in a 1964 New York lives and reduce morbidity, but only
In the 1990s and 2000s, PKU served as Times report on the new law mandat- through the arduous and uncertain
the paradigmatic example for advo- ing PKU testing: “The disability can be path of living with a chronic condition.7
cates eager to expand NBS. Twenty-first detected by a simple blood test and can In the end, PKU will always be remem-
century NBS programs can potentially be corrected by a special diet in much bered as the first condition for which
identify dozens of conditions, and the same way as diabetics are enabled newborns were screened. This dramatic
proponents of expansion continue to to lead normal lives by the use of in- success is rightfully celebrated as a
use PKU to underscore the value of sulin.”6 It turns out that PKU is indeed major victory for modern medicine. But
screening infants for disease. How- like type 1 diabetes, though not as the the continuing value of PKU in policy
ever, advocates inherit not just the Times writer intended. As anyone with debates is explained by the paucity of
goodwill generated by the success of either a personal or professional in- more powerful examples of the success
treatment of PKU, but also the chal- terest in diabetes (or PKU) knows, of modern scientific medicine in pre-
lenges arising from the fact that NBS therapy for these conditions involves a venting intellectual disability, altering
programs were established a half- lifelong struggle with personal behav- the course of genetic disease, or dra-
century ago in specific historical con- iors and medical management. The matically changing outcomes through
ditions that do not necessarily obtain diet allows extremely limited choices NBS. Despite great promise over the last
today. For example, NBS programs are (Table 1) and interferes with the social 50 years, there have been precious few
almost everywhere de facto or de jure and cultural aspects of eating. In this victories in these realms comparable to
the success of testing and treatment of nih.gov/2000/2000phenylketonuria113html. Practice. Oxford and Herndon, VA: Bios Sci-
PKU. That is why it continues even today htm. Accessed October 2, 2013 entific Publishers; 1997:107–117
to serve as an exemplar for diverse 2. Paul DB, Brosco JP. The PKU Paradox: A Short 5. Fan HC, Gu W, Wang J, Blumenfeld YJ, El-
History of a Genetic Disease. Baltimore, MD: Sayed YY, Quake SR. Non-invasive prenatal
constituencies.
Johns Hopkins University Press; 2013 measurement of the fetal genome. Nature.
3. Brosco JP, Mattingly M, Sanders LM. Impact of 2012;487(7407):320–324
REFERENCES specific medical interventions on reducing 6. Dales D. Infant PKU Tests Made Mandatory.
1. National Institutes of Health. Phenylketon- the prevalence of mental retardation. Arch New York Times. April 25, 1964:31–32
uria: screening and management. NIH Con- Pediatr Adolesc Med. 2006;160(3):302–309 7. Feudtner C. Bittersweet: Diabetes, Insulin,
sensus Statement Online; 2000 October 16– 4. Clarke AJ. Newborn screening. In Harper PS, and the Transformation of Illness. Chapel Hill,
18;17(3):1–27. Available at: http://consensus. Clarke AJ, eds. Genetics, Society, and Clinical NC: University of North Carolina Press; 2003
This essay was adapted from The PKU Paradox: A Short History of a Genetic Disease by Diane B. Paul and Jeffrey P. Brosco. Published by The Johns Hopkins
University Press, 2013. Reprinted by permission of the publisher.
JPB obtained funding, made substantial contributions to study design and interpretation of results, and collaborated in drafting the manuscript. DBP obtained
funding, created study design, carried out archival research and structured oral interviews, made substantial contributions to interpretation of results, and
collaborated in drafting the manuscript.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Dr Brosco received support from the HRSA/MCHB Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children
(subcontract number 06-C210-01) and an Arsht Distinguished Ethics Faculty Award at the University of Miami (2012-14). Dr Paul received support from the National
Institutes of Health, grant 1R03HG003730-01 (2005-2007). Funded by the National Institutes of Health (NIH).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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