Robert Guthrie, father of newborn screening

Dr. Robert Guthrie introduced the newborn screening test for phenylketonuria (PKU), a fatal disease in young children, in the early 1960s in the US for the first time. While the use of Guthrie’s filter paper for taking blood samples from the heel in newborn screening is well-known to many laboratorians today, many people are unaware of the story of Dr. Guthrie’s first newborn screening test.

Dr. Guthrie was born in Marionville, Missouri, in 1916 and grew up in Minnesota. He earned a medical degree in 1942 and a Ph.D. in bacteriology from the University of Minnesota in 1946. For the first 12 years of Dr. Guthrie’s career, he was a cancer scientist at the Roswell Park Institute in Buffalo, New York. During this time, Dr. Guthrie’s second son, John, was born with mental retardation in 1947, and his 15-month-old niece was diagnosed with PKU in 1958. According to Dr. Guthrie himself, it was the birth of his second son that inspired him to pursue research aimed at preventing mental retardation and developmental disabilities. It was the birth of his niece that drew his attention to the curable causes of mental retardation.

By 1957, Dr. Guthrie had become very active in the Buffalo local chapter of the State Association for Retarded Children. Dr. Guthrie invited Dr. Robert Warner, director of the newly established Pediatric Rehabilitation Center at Children’s Hospital Buffalo, to speak at the organization’s monthly meeting. Dr. Warner’s work in treating children with developmental disorders attracted the attention of Dr. Guthrie. In subsequent meetings with Dr. Warner, Dr. Guthrie discussed his interest in preventing mental retardation due to inherited metabolic disorders. Dr. Warner and Dr. Mitchell Rubin, chief of pediatrics at Children’s Hospital, eventually convinced Dr. Guthrie to transfer from the Cancer Institute to Buffalo Children’s Hospital in 1958. At Dr. Rubin’s suggestion, Dr. Guthrie began developing a new method for monitoring phenylalanine levels. By modifying bacterial tests he had used in his cancer research, he developed a technique for monitoring PKU.

While this test was developed to monitor the phenylalanine level in the blood of children treated with a low-phenylalanine diet, it soon became evident that it could be used as a screening mechanism to prevent delayed growth and retardation in patients. PKU used. The original experiment used filter paper soaked in serum, and this method had some difficulties. Dr. Guthrie realized that filter paper can be utilized to take blood samples from the baby’s heel and implemented this work.

PKU screening using this method was first conducted in 1960 to test children for mental retardation at Newark State School. Children’s blood samples were collected on filter paper (Guthrie paper), and the level of phenylalanine was tested with the bacterial inhibition method designed by Dr. Guthrie. The test successfully identified all previously confirmed cases of PKU, as well as four previously undiagnosed cases by urine screening. In 1961, Dr. Guthrie’s lab began receiving filter papers containing blood samples from infants in two Jamestown hospitals. As demand grew, Dr. Guthrie received funding from the United States Children’s Bureau to conduct national newborn screening for PKU. This funding provided Dr. Guthrie with the resources to establish a small factory next to Buffalo Children’s Hospital and provide the materials needed to perform the PKU screening test. Within two years, 400,000 newborns from 29 states were tested, and this resulted in the identification of at least 39 cases of PKU. Newborn screening for PKU has shown that approximately one in 10,000 babies in the United States has the condition. The important thing is that with this new screening method, all cases of PKU disease have been identified. This method provides the possibility of treatment for all identified patients.

Influenced by Dr. Guthrie’s successes and efforts, the National Association for Retarded Children lobbied in the mid-1960s for mandating PKU screening. In 1967, 37 states passed laws mandating PKU screening for all newborns. Today, all 50 US states have enacted such laws. The most significant achievement of PKU screening in infants is that it raises the question of whether other diseases can be prevented through similar early detection methods. It soon became clear that the answer to this question was yes, and by the late 1960s, newborn screening for genetic diseases became part of neonatal health care in the United States. Most newborn screening programs in the United States now use tandem mass spectrometry (MS/MS) as the primary tool for blood spot analysis. The list of diseases detected by newborn screening continues to expand today, and cystic fibrosis has recently been added to the list of conditions screened for by most states.

Dr. Robert Guthrie died on June 23, 1995, at the age of 78. He lived with his wife for 53 years and had six children. Today, the expanded newborn screening programs based on the blood collection system invented by Dr. Guthrie for the early detection of metabolic diseases continue to be a cornerstone for improving the health of children in the United States and worldwide.