Celebrating 5 decades of the Newborn screening project
Genes, the building blocks of heredity, are passed from parent to child. A genetic disorder is a disease caused by a mutation in one gene, multiple genes, a combination of gene mutations and environmental factors, or by damage to chromosomes, which are the structures that carry genes. Our understanding of genetic disorders has vastly increased in the last few decades. With advancement in understanding a disease, our efforts to come up with proper diagnosis and treatment for a disorder have also increased.
Phenylketonuria (PKU), a metabolic genetic disorder, was the first amongst several genetic disorders to be diagnosed in newborn children. PKU is inherited in a recessive way, i.e., both parents must pass on the defected gene to the offspring. PKU is characterized by mental retardation due to a deficiency in phenylalanine hydroxylase, an enzyme necessary to metabolize the essential amino acid phenylalanine to tyrosine. Without phenylalanine hydroxylase, phenylalanine is converted to phenylpyruvic acid. In PKU patients, phenylpyruvic acid accumulates and becomes toxic to the brain, leading to developmental defects and mental retardation. Thus, an early detection of PKU can dramatically improve an individual’s quality of life.
We owe the early detection of PKU and several other disorders to the efforts of one microbiologist, Dr. Robert Guthrie. In 1947, Dr. Guthrie’s second son, John, was born mentally handicapped and the cause of his condition was not diagnosed. This motivated him to devote his career to mental retardation research. It was the diagnosis of his niece with PKU that brought Dr. Guthrie’s attention to the treatable causes of mental retardation. In 1960, he developed a test a screening test for PKU. He incubated a culture of bacteria, Bacillus subtilis, on agar in the presence of a chemical that blocks the supply of phenylalanine, preventing the bacteria that require the amino acid from growing. When blood soaked filter paper discs are placed on the agar, the presence of phenylalanine overcomes the growth inhibition due to the lack of phenylalanine, allowing the determination of excess phenylalanine to be made based on the amount of bacterial growth.
In 1961, a field trial of newborn screening for PKU began in the US on nearly one million infants using the Guthrie Test, and in 1963 Massachusetts became the first state to implement the screening program. Within two years, 400,000 infants had been tested from 29 states, resulting in 39 positive cases of PKU. Newborn screening for PKU identified an incidence of almost one in 10,000 births in the United States. By 1967, PKU screening in all newborns was mandated in 37 states, and today, all 50 states have such laws.
Dr. Guthrie’s test still forms the basis of PKU testing, however the originally used filter paper is now replaced with an infant heel stick. Today, newborn screening for genetic diseases has become a part of infant health care in the United States. The program has grown tremendously in recent years and now all states must screen for at least 21 disorders by law, while some states test for 30 or more. As this year marks the golden jubilee since the first newborn screening test was performed in the US, we must recognize the revolution that the screening program has brought in healthcare and be grateful for the efforts that scientists constantly put in, often spending late hours in the lab in trying to resolve a clinically relevant problem that might positively influence the lives of thousands, just like Dr. Guthrie’s experiment did.
- R. Guthrie, The introduction of newborn screening for phenylketonuria. A personal history, Eur. J. Pediatr. 155, 1996.
- R. Guthrie, Blood screening for phenylketonuria, JAMA. 178, 1961.