|MEDICAL HISTORY PAGE
|Year : 2013 | Volume
| Issue : 1 | Page : 42-43
Sir Archibald Garrod
K Varadaraj Shenoy, P Thara, M Sharmila
Department of Paediatrics, Fr. Muller Medical College, Kankanady, Mangalore, Karnataka, India
|Date of Web Publication||20-May-2013|
K Varadaraj Shenoy
Department of Paediatrics, Fr. Muller Medical College, Kankanady, Mangalore - 575 002
Source of Support: None, Conflict of Interest: None
When the history of inborn errors of metabolism is written, the name that will be mentioned foremost is that of Sir Archibald Garrod, who through his pioneering work on Alkaptonuria laid a solid foundation for this evolving specialty of medicine in the early years of the 20 th century. This article gives a brief overview of his work and his accomplishments of his career.
Keywords: Alkaptonuria, inborn error of metabolism, biochemical genetics
|How to cite this article:|
Shenoy K V, Thara P, Sharmila M. Sir Archibald Garrod. Muller J Med Sci Res 2013;4:42-3
Sir Archibald Garrod
"Scientific method is not the same as scientific spirit. The scientific spirit does not rest content with applying what is already known but is a restless spirit ever pressing forward toward the regions of the unknown………."
Sir Archibald Garrod is today widely acknowledged as the father of "inborn errors of metabolism" for his pioneering work on elucidating the biochemical basis of Alkaptonuria.
Garrod was born in 1857 in London, the youngest son of Sir Alfred Garrod, a professor of Medicine at University College London who was the first to detect the presence of uric acid in patients with gout and thus became the first person to perform a quantitative biochemical investigation on human beings. Garrod studied astronomy at Oxford University from where he graduated with first class honors in natural science in 1880. Following in his father's footsteps he started his medical training in St Bartholomew's Hospital in London. He also spent some time in Vienna continuing his medical study at Allgemeines Krankenhaus. During this time he published a book on the laryngoscope. In 1885, he graduated in medicine from the University of Oxford. Soon afterwards he joined the staff of St Bartholomew's Hospital, became casualty physician and subsequently assistant physician in 1903. He was also a visiting staff at the West London Hospital and the Alexandra Hospital for children with hip disease. He was appointed physician at the Hospital for Sick Children at Great Ormond Street in 1899. He was promoted as full physician at Bart's in 1912. During the First World War he was appointed as the consulting physician to the Mediterranean forces in Malta where he worked till the end of the war. For his services during the war he earned a Knight commander of St. Michael and St. George. After his return, he became the head of a new unit at Bart's but within a year he was nominated Regius Professor of Medicine at Oxford succeeding Sir William Osler. 
He married Laura Elizabeth Smith in 1886 and they had three sons and a daughter. Two of his sons were killed in the First World War and he lost his third son due to the Spanish flu.
In the 19 th century medicine was essentially dealing with infection and morbid anatomy. During the first part of the 20 th century exciting discoveries in biochemistry, physiology, microbiology led to the concept of elucidating the pathogenesis of disease. It was at this time that Garrod first propounded his theories of the biochemical basis of disease based on his work on families suffering from Alkaptonuria. His first paper "the incidence of Alkaptonuria: A study in chemical individuality" published in 1902 dealt with the relation between an abnormal accumulation of a chemical and the resultant clinical phenotype. At that time the word inborn error of metabolism was not yet coined, however, in his series of Croonian lectures given to the Royal College of Physicians London in 1908 he made several significant observations: (1) Several disease of chemical abnormality in the metabolic pathways (alkaptonuria, pentosuria, cystinuria, albinism) had a hereditary basis. (2) Evidence of a block in a normal metabolic pathway. (3) Congenital onset of these metabolic problems. He arrived at these conclusions based on his extensive studies, which were both patient and laboratory based. Thus, he became one of the first to link an abnormality of a missing enzyme in a metabolic pathway to a defect in the genetic makeup of the individual. In this, he was probably influenced by the work of Gregor Johann Mendel whose pioneering work on inheritance of traits was being rediscovered by the scientific community. Garrod's hypotheses did not catch on among the medical fraternity initially but eventually helped unify the fields of medicine biochemistry and the emerging specialty of genetics. 
He subsequently published these findings in the form of a book under the historic title "the inborn errors of metabolism" in 1909. When the one gene one enzyme hypothesis was enunciated by Beadle and Tatum in 1941, Garrod's inborn errors got more recognition and the link between biochemical abnormalities and genetic causes was firmly established. Thus, belatedly Garrod gained recognition for predicting such a connection. Garrod published a second edition of "inborn errors of metabolism" in which he discussed two new entities - congenital steatorrhoea and congenital porphyria. His third book "inborn factors in disease" was published in 1931. In this monumental work Garrod broke new ground in the field of genetics by proposing that inborn factors in disease which he called diathesis are responsible for complex familial disorders that did not have an overt pattern of inheritance. Garrod is also credited with having written a book "a treatise on rheumatism and rheumatoid arthritis" (1890) and helped edit a pediatrics textbook on diseases of children (1913). He helped found the Quarterly Journal of Medicine to provide a forum for fundamental research in to the processes of disease. 
As it became clear that Garrod had pioneered a new field of medicine, he was honored in England and abroad. He became Regius professor of medicine in Oxford University and was elected a fellow of The Royal Society of Medicine. He was also appointed to the Medical Research Council of England. He was made an honorary member of the American Association of Physicians. He received honorary degrees from the universities of Aberdeen, Dublin, Glasgow, Malta, and Padua. In 1935, he was awarded the gold medal of the Royal Society of Medicine. The Canadian association of centers for the management of hereditary metabolic diseases is commonly referred to as the Garrod association to honor his contributions in the field of inborn errors of metabolism.
Garrod was described by his colleagues as quiet, courteous and a little reserved, with a fine judgment of good work in others. He was universally respected and liked but too gentle and honest to demand attention. He died at the Cambridge home of his daughter after a brief illness in 1936. 
The contribution of Garrod to furthering the science of genetics was not appreciated in his lifetime. However, the tremendous discoveries made in the field of genetics have conclusively proved Garrod's remarkably accurate predictions regarding heritability of metabolic disorders. It can be said that Garrod was far ahead of his time.
| References|| |
|1.||Scriver CR. Garrod′s Croonian Lectures (1908) and the charter ′Inborn Errors of Metabolism′: Albinism, alkaptonuria, cystinuria, and pentosuria at age 100 in 2008. J Inherit Metab Dis 2008;31:580-98. |
|2.||Childs BD, David Valle Sanchez GJ. The inborn error and biochemical individuality. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. Metabolic and Molecular Basis of Genetic Disease. New York: Mcgraw Hill; 8 th ed. 2001. p. 155-65. |
|3.||Available from: http://www.wikipedia.org. [Last accessed 2013 Jan 10]. |
|4.||Available from: http://www.hharp.org/library/gosh/doctors/archibald-edward-garrod.html. [Last accessed 2013 Jan 12]. |