Louis Isaac Woolf (born 1919 in London, England; died 2021 in Vancouver, Canada)^[1] was a British biochemist who played a crucial role in the early detection (via neonatal screening) and the treatment of phenylketonuria (PKU).

Early career

Woolf was born in London, England, on 24 April 1919. He studied chemistry at University College London (UCL) and was awarded a PhD in 1945. In 1947, he was awarded an ICI research fellowship at the Hospital for Sick Children at Great Ormond Street, London, working on inherited metabolic disorders with a focus on amino acids.^[2]

The idea that PKU should be treated with a low-phenylalanine diet was being put forward by doctors in the 1930s; however, isolating this amino acid source was difficult for scientists.^[3] His vision of using activated charcoal filtering to deplete phenylalanine from casein hydrolysate laid the groundwork for future dietary interventions,^[4] which he researched in the late 1940s and early 1950s.^[2]

The first successful trial of this diet involved collaboration with Horst Bickel, John W. Gerrard and others. This occurred in 1951, resulting in significant clinical improvement in a young patient. Woolf's contributions, along with others, marked a significant shift from considering PKU as untreatable to a condition with potential treatment possibilities. These led to the proposal of dietary treatment for PKU, involving a low-phenylalanine diet, despite facing scepticism and professional challenges, including the belief that PKU was not treatable due to its genetic nature.^[5]

In 1957, Woolf and colleagues recommended mass screening for PKU using a ferric chloride test on newborn urine samples. They emphasised the importance of early diagnosis and treatment, proposing screening at 21 days after birth.^[2]

In 1958, Phenistix was first used for PKU screening. This was adopted in various locations, including the United Kingdom and the United States, where screening programmes which emphasise early detection and treatment were adopted. In 1966–1967, Woolf's screening methods were adopted in Spain, with a pilot program in Granada.^[2]

Woolf moved to Vancouver in 1968, where he joined the University of British Columbia and continued research on phenylalanine biochemistry and metabolic diseases. His work extended beyond PKU to include a wide range of inborn errors of metabolism, including: galactosaemia, phenylketonuria, leucinosis (maple syrup urine disease), valinaemia, isovaleric acidaemia, β-methyl-crotonylglycinuria, propionic acidaemia, hyperprolinaemia, citrullinaemia, d- and l-methylmalonic acidaemias, non-ketotic hyperglycinaemia, arginosuccinic aciduria, types I and II hyperammonaemia, hyperargininaemia, homocystinuria, histidinaemia, cystinosis, hyperlysinaemia, saccharopinuria and ornithinaemia.^[2]

In 1979, Woolf discussed the variants of PKU, including cases with blood concentrations of phenylalanine below typical PKU levels, and the consequences of interrupting a low-phenylalanine diet in later childhood.^[2]

References