On Drawing Lessons from the History of Newborn Screening for PKU

1. On Drawing Lessons from the History ofNewborn Screening for PKU Diane B. Paul New England Consortium of Metabolic Programs November 6, 2009

2. ACKNOWLEDGMENTS • The National Institutes of Health (NHGRI) for support of my research on the history of newborn screening • The staff of the Metabolic Clinic at Children’s Hospital Boston for their advice and consistent encouragement • Those professionals who agreed to be interviewed and sometimes re-interviewed about the history of their field and those patients who shared their experiences of living with PKU for generosity both with their time and insights

3. Pearl S. Buck (1892-1973)

4. Louis Woolf, PhDDesigned first usable lo-pro product for PKU(slide courtesy of Neil R.M. Buist, MD)

5. Horst Bickel, MD First to use the PKU treatment proposed by Louis Woolf (slide courtesy of Neil Buist MD)

6. Willard (Bill) Centerwall with Robert Guthrie (slide courtesy of Neil Buist, MD) Gibbs & Woolf were also doing this in Cardiff UK

8. Robert Guthrie (1916-1995) In 1961, microbiologist Robert Guthrie and his lab technician Ada Susi developed a simple and inexpensive screening test that could be administered before the newborn had been discharged from the hospital.

9. Obtaining blood for testing by sticking the heel of the newborn

11. A fifty cent test spared this baby from spending his life mentally retarded But only in Massachusetts, New York, Louisiana, and Rhode Island is the test legally required…. Advertising Council Campaign for PKU testing

12. State Medical Societies • Ideologically opposed to state intervention • Fearful of malpractice suits (Only organized opposition to mandated screening)

13. Samuel P. Bessman(photo courtesy Edward R.B. McCabe, MD, PhD)

14. American Academy of Pediatrics Statement on Compulsory Testing (1967) “Failure to achieve expected health benefits as a result of premature and injudicious legislation may do irreparable harm to the orderly development of mass screening techniques for the early identification of disease and undermine public support of further research. . . . At this time, the American Academy of Pediatrics favors neither the extension of current compulsory legislation nor passage of new legislation for the compulsory testing of newborn infants for the presence of congenital metabolic disease.”

15. Metabolic Researchers/Public-Health Community Concerns about unknowns: • Accuracy of the Guthrie test • Optimal level of blood phenylalanine • Proportion of individuals testing positive actually at risk of MR • Possible harm from unneeded or overtreatment • Duration of treatment • Efficacy of treatment • Effect on fetus during pregnancy of treated women Concerns about focus on detection Concerns about process: Guthrie’s mode of publication and direct appeals to politicians and the press Concerns about use of law to conscript research subjects

16. Phenylketonuria and Allied Metabolic Diseases. Proceedings of a Conference held at Washington, D.C. April 6-8-1966. From Summary, John A. Anderson, Kenneth F. Swaiman: “Legislation has been enacted in a large number of States to screen newborn infants for phenylketonuria. The general public, and indeed most of the medical profession, were led to believe that screening tests for hyperphenylalaninemia are indeed tests for phenylketonuria. This is not true. . . . [W]e have already experienced the practical effect of such legislation which has included public pressure for a specific therapy at a time when competent medical investigators are not in agreement on criteria for diagnosis, natural course of the disease or optimal therapy or diagnosis” (p. 238).

17. Sen. Hillary Clinton with former Buffalo Bills’ quarterback Jim Kelly Press Conference, University of Buffalo, Sept. 2006

18. Comments Submitted by Hunter’s Hope Foundation to the Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children “While we respect the ‘efficacious treatment’ element for diseases to be included in the uniform panel, we believe that this type of criterion may not be the most appropriate one for newborn screening as affected families may find treatment essential that is not yet deemed efficacious. …we also must highlight our concern over the ‘well understood natural history’ aspect of the ACMG report as many of the conditions are rare for which there are, and or, will be tests. For conditions like these a well-understood natural history would be best achieved with early detection, standardized follow-up and shared data.” May 8, 2005

19. TO THE: SECRETARY’S ADVISORY COMMITTEE ON HERITABLE DISORDERS AND GENETIC DISEASES IN NEWBORNS AND CHILDREN “ALL NEWBORNS MUST HAVE ACCESS TO APPROPRIATE AND EFFECTIVE SCREENING PROGRAMS” MAY X, 2005 Thank you for the opportunity to address this committee…. The reason I am writing is because… (Your personal story goes here) … While funding is essential it is only one barrier currently holding up progress in the expansion of newborn screening programs. Our family supports the uniform screening panel outlined by the HRSA commissioned ACMG report, yet additionally we believe the following are needed: The development of a set of national screening minimum standards that would ensure uniformity in access to newborn screening services at all points of entry … Development of a procedure for the expansion of the core and secondary panels Including a re-evaluation of the “efficacious treatment” and natural history for inclusion The establishment of nationwide minimum standards will create uniformity of access in a newborn screening system that is currently unbalanced. Please, our children deserve a better newborn screening system!

20. Letter Responding to Request for Public Comment on ACMG Report Maternal and Child Health Bureau Health Resources and Services Administration 5600 Fishers Lane Rockville, MD 20857 I strongly feel that newborns should be screened for every disorder or genetic defect possible. Signature