Historical Perspectives

Abstract

It began with Bob Guthrie’s second child. John was mentally retarded. Because of this, Guthrie was stimulated toward research that could prevent mental retardation and other developmental disabilities. In 1957, Guthrie was conducting cancer research at the Roswell Park Cancer Institute in Buffalo, NY. Because of John, Bob and his wife Margaret were very active in the Buffalo chapter of the New York State Association for Retarded Children. As Vice-President of the chapter, he was responsible for the program at the monthly meeting. He had heard that Dr Robert Warner, Director of the newly established Children’s Rehabilitation Center at Buffalo Children’s Hospital, was doing work in developmental disabilities, so he invited Dr Warner to speak about his work at one of the meetings. At the meeting, Dr Warner discussed his work in treating children with mental retardation, some of whom had metabolic disorders. Over coffee after the meeting, Guthrie mentioned his interest in the prevention of mental retardation. As a result of the meeting and especially the discussion after the meeting, the two kept in touch. About a year later, Dr Warner introduced Guthrie to phenylketonuria (PKU). Dr Warner explained that PKU was an inborn error of phenylalanine metabolism that caused mental retardation, but that when these retarded children received a special phenylalanine-restricted diet, not only did their blood phenylalanine levels decrease, but their behavior improved substantially. One problem in administering the diet, Dr Warner explained, was the difficulty with tests required to measure the blood phenylalanine levels for close monitoring of the patients. This persuaded Guthrie to try to produce a simpler method for measuring blood phenylalanine. Guthrie thought such a test might be possible by modifying the Bacillus subtilis or Escherichia coli bacteria assays he was using to screen for different antimetabolites in blood from patients who were …