ABSTRACT
Garrod presented his concept of 'the inborn error of metabolism' in the 1908 Croonian Lectures to the Royal College of Physicians (London); he used albinism, alkaptonuria, cystinuria and pentosuria to illustrate. His lectures are perceived today as landmarks in the history of biochemistry, genetics and medicine. Garrod gave evidence for the dynamic nature of metabolism by showing involvement of normal metabolites in normal pathways made variant by Mendelian inheritance. His concepts and evidence were salient primarily among biochemists, controversial among geneticists because biometricians were dominant over Mendelists, and least salient among physicians who were not attracted to rare hereditary 'traits'. In 2008, at the centennial of Garrod's Croonian Lectures, each charter inborn error of metabolism has acquired its own genomic locus, a cloned gene, a repertoire of annotated phenotype-modifying alleles, a gene product with known structure and function, and altered function in the Mendelian variant.
Subject(s)
Metabolism, Inborn Errors/history , Albinism/history , Alkaptonuria/history , Carbohydrate Metabolism, Inborn Errors/history , Cystinuria/history , History, 20th Century , History, 21st Century , Humans , London , Pentoses/urineSubject(s)
Alkaptonuria/history , Alkaptonuria/complications , Genetics, Medical/history , History, 19th Century , History, 20th Century , Humans , Hyperpigmentation/etiology , Hyperpigmentation/history , London , Lumbar Vertebrae/diagnostic imaging , Radiography , Spinal Osteophytosis/diagnostic imaging , Spinal Osteophytosis/etiology , Spinal Osteophytosis/historyABSTRACT
Clinical disorders have intrigued the human mind for thousands of years. Many are enshrined in history as 'medical curiosities'. This report is a tribute to one of the greatest minds of modern genetics and medicine, Sir Archibald Edward Garrod (1857--1936), who brought forward the scientific study of inborn errors of metabolism. Garrod's concept of 'chemical individuality' with no awareness of 'genes' more than 100 years ago is an amazing example of futuristic thinking. His own words reflect this, 'Owing, as I believe, to their chemical individuality different human beings differ widely in their liability to individual maladies, and to some extent in the signs and symptoms which they exhibit'. The concept of chemical individuality is here to stay. Garrod has also provided insight into a number of scientific concepts and modern thinking.
Subject(s)
Metabolism, Inborn Errors/history , Molecular Biology/history , Alkaptonuria/history , England , History, 19th Century , History, 20th Century , Humans , Metabolism, Inborn Errors/geneticsSubject(s)
Alkaptonuria/genetics , Alkaptonuria/history , Dioxygenases , Genes, Recessive/genetics , Oxygenases/chemistry , Oxygenases/genetics , Alkaptonuria/enzymology , Alkaptonuria/urine , Cloning, Molecular , Crystallography, X-Ray , History, 20th Century , Homogentisate 1,2-Dioxygenase , Humans , Mutation/genetics , Nobel Prize , Oxygenases/metabolism , Protein ConformationSubject(s)
Alkaptonuria/history , Dioxygenases , Alkaptonuria/enzymology , Alkaptonuria/genetics , Aspergillus nidulans/genetics , Aspergillus nidulans/metabolism , History, 20th Century , Homogentisate 1,2-Dioxygenase , Humans , Oxygenases/genetics , Oxygenases/metabolism , Phenylalanine/metabolism , Tyrosine/metabolismSubject(s)
Alkaptonuria/genetics , Alkaptonuria/history , Alkaptonuria/epidemiology , Female , History, 20th Century , Humans , MaleABSTRACT
Osler's immediate successor as Regius Professor at Oxford was Archibald Garrod (1857-1936), the founder of biochemical genetics. Like Mendel's, Garrod's concepts and discoveries were late in gaining wide currency and had in effect ot be rediscovered by Beadle and Tatum and by the students of biochemical individuality in the 1950s and 1960s. I have attempted to show that Garrod's predecessor Regius also contributed to medical genetics--not to its theoretical roots, to be sure, but certainly in an important way to the nosology of genetic disease.
