In 1961, a telephone rang in Robert Guthrie's laboratory in Buffalo, New York. His sister-in-law, Mary Lou Doll, was calling to tell him that her daughter had just been diagnosed with phenylketonuria, the inherited disease Guthrie had spent years trying to catch early enough to treat. The diagnosis was accurate. It also arrived too late: by the time the standard urine test for the disease turned positive, the child's brain had already been damaged beyond repair.
Phenylketonuria leaves the body unable to break down phenylalanine, an amino acid in ordinary protein; the excess builds up in the blood and, left unchecked, damages a developing brain. The Norwegian physician Asbjørn Følling had identified the disease in 1934 by testing a child's urine for a chemical reaction that turns green in the presence of ferric chloride. A newborn only a few days old, before any symptom could prompt a doctor to test at all, rarely excretes enough of that chemical for the test to register. By 1953, researchers had a diet, low in phenylalanine, that could prevent the brain damage entirely, provided it started in the first weeks of life. No test existed that could find the disease that early.
Guthrie was a microbiologist, not a pediatrician. Through the 1950s he built bacterial assays to screen potential cancer drugs at Buffalo's Roswell Park Memorial Institute. In 1957, the pediatrician Robert Warner asked him for a faster way to monitor blood phenylalanine in his own phenylketonuria patients, who otherwise had their blood shipped to a laboratory in California for every test. Guthrie adapted his bacterial method to phenylalanine within days: a disc of blood-soaked filter paper, laid on a culture plate seeded with bacteria that only phenylalanine would let grow. After his niece's late diagnosis in 1961, he pushed the method further, blotting a few drops of blood directly from a newborn's heel onto the same filter paper, early enough to answer the question before any clinical sign of the disease existed to look for.
The federal Children's Bureau funded a trial of the heel-prick test across twenty-nine states and roughly four hundred thousand infants; it found phenylketonuria in about one birth in ten thousand. In 1963, Massachusetts became the first state to require the test by law for every infant born there; the state's own public-health laboratory, under Robert MacCready, had already been running the screening before Guthrie could persuade anyone elsewhere that it was worth doing. Guthrie met resistance from the medical profession and struggled even to get his method published in a medical journal; parents, meanwhile, were pressing their own legislators to require the test. By the 1970s, screening newborns for phenylketonuria was routine across the country.
The old urine test had never been dishonest. It would have found the same disease in the same child, eventually. A fact that arrives after the harm it describes has already happened has not stopped being true; it has simply stopped being useful. What Guthrie changed in Buffalo was not whether phenylketonuria could be found. It was whether it could be found before it had already won.