Research Interests
Guthrie became interested in causes and prevention of mental retardation after his son, John, was born disabled in 1947. Despite his work in the field, the cause of his son's disability was never diagnosed. In 1958, Guthrie's 15-month old niece was diagnosed with phenylketonuria (PKU), a condition in which the body cannot metabolize phenylalanine. Untreated PKU results in irreversible neurological damage. After the discovery of PKU as a cause of mental retardation, Horst Bickel and colleagues discovered that it could be treated successfully with a diet low in phenylalanine. The main drawback in successful treatment of PKU was the delay in identifying affected individuals. The common test for PKU at the time was mixing urine with ferric chloride. The excess phenylpyruvic acid in the urine of an individual with PKU would produce a bright green colour when reacting with the ferric chloride. Infants do not excrete high enough concentrations of this compound to give a positive test result, thus delaying their diagnosis, and allowing irreversible damage to take place. Guthrie's disabled son had driven his interest in causes of mental retardation, the diagnosis of his niece with PKU turned his attention to preventable causes. Others working with children who had PKU asked Guthrie to focus on a test that would allow for earlier identification, before irreversible damage had taken place.
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