Archibald Garrod

Sir Archibald Edward Garrod was an English physician who pioneered the field of inborn errors of metabolism. He was born on November 25 1857, in London, and died on March 28 1936, in Cambridge.

Archibald was the fourth son of Sir Alfred Baring Garrod, a physician at King's College Hospital, who discovered the abnormal uric acid metabolism associated with gout.

He was educated at Marlborough and Christ Church, University of Oxford. He graduated with an honours degree in natural science in 1880. He received further medical training at St. Bartholomew's Hospital in London. He spent several months of postgraduate study at the Allgemeines Krankenhaus in Vienna in 1884-85. In 1885 he obtained his BM and MA from Oxford, and became a member of the Royal College of Physicians, London.

Over the next 20 years he served on the attending staff of several hospitals in London: Marylebone General Dispensary, West London Hospital, St. Bartholomew's Hospital, the Great Ormond Street Hospital for Children, and Alexandra Hospital for Children with Hip Disease.

He married Laura Elizabeth Smith in 1886. They had 3 sons and a daughter, Dorothy Garrod.

Garrod was a proponent of scientific research as the foundation of medical practice, and published on a variety of diseases and topics throughout his career, including "An Introduction to the Use of the Laryngoscope" (1886) and "A Treatise on Rheumatism and Rheumatoid Arthritis" (1890). He helped found the "Quarterly Journal of Medicine" to provide a forum for more fundamental research into the processes of disease. He helped edit a pediatrics textbook, "Diseases of Children" (1913), with F.E. Batten and Hugh Thursfield.

He developed an increasing interest in chemical pathology, and investigated urine chemistry as a reflection of systemic metabolism and disease. This research, combined with the new understanding of Mendelian inheritance, evolved from an investigation of a few families with an obscure and not very dangerous disease (alkaptonuria) to the realization that a whole territory of mysterious diseases might be understood as inherited disorders of metabolism.

Alkaptonuria is a rare familial disease of organic acid metabolism that is best known for the darkening of urine from yellow to brown to black after it is exposed to the air. In later life, individuals with this disease develop arthritis characterized by deposition of brown pigment in joint cartilage and connective tissue. Garrod studied the recurrence patterns in several families, realized it followed an autosomal recessive pattern of inheritance, and postulated that it was caused by a mutation in a gene encoding an enzyme involved in the metabolism of a class of compounds called alkaptans. He published "The Incidence of Alkaptonuria: a Study in Chemical Individuality" in 1902.

Over the next decade he developed an understanding of the possible nature of inherited diseases of metabolism. He formulated the "one gene, one enzyme" hypothesis and described the nature of recessive inheritance of most enzyme defects. In 1908, the core of this work was presented as the Croonian lectures to the Royal College of Physicians, entitled "Inborn Errors of Metabolism" and published the following year. Garrod expanded his metabolic studies to cover cystinuria, pentosuria, and albinism.

During the First World War Garrod served as medical consultant to the army, primarily in Malta. Two of his three sons were killed in the war and the third died during the great influenza epidemic of 1919.

In 1923 he summarized these studies in an expanded edition of his best known work, [http://www.esp.org/books/garrod/inborn-errors/facsimile/ Inborn Errors of Metabolism] . As it became clearer that he had pioneered a new field of medicine, Garrod was increasingly honored in England and abroad. He succeeded William Osler as Regius Professor of Medicine at Oxford. He was elected a Fellow of the Royal Society, was appointed to the Medical Research Council, and was made an honorary member of the American Association of Physicians, and of the Artzlicher Verein in Munich. 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.

He died at the Cambridge home of his daughter after a brief illness in 1936.

The Canadian Association of Centres for the Management of Hereditary Metabolic Diseases is commonly referred to as the Garrod Association to honor his contributions to the field of inborn errors of metabolism.

Publications

*The Nebulae: A Fragment of Astronomical History (Oxford, 1882)
*An Introduction to the Use of the Laryngoscope (1886)
*A Treatise on Rheumatism and Rheumatoid Arthritis (1890)
*A Handbook of Medical Pathology, for the Use of Students in the Museum of St Bartholomew's Hospital (1894), with Sir W.P. Herringham & W.J. Gow
*A Treatise on Cholelithiasis, Bernhard Naunyn, translated by Garrod (London, 1896)
*Clinical Diagnosis, Rudolf Von Jaksch, edited by Garrod (London, 5th ed., 1905)
*Inborn Errors of metabolism (1909), second edition 1923
*Diseases of Children (1913), with F.E. Batten & Hugh Thursfield
*The Inborn Factors of Disease (1931)

Quotation

*"... scientific method is not the same as the scientific spirit. The scientific spirit does not rest content with applying that which is already known, but is a restless spirit, ever pressing forward towards the regions of the unknown, ... it acts as a check, as well as a stimulus, sifting the value of the evidence, and rejecting that which is worthless, and restraining too eager flights of the imagination and too hasty conclusions." [W.F. Bynum & Roy Porter, eds 2005. "Oxford Quotations" ISBN 0-19-858409-1 241:5.]
*:--Archibald Garrod, "The Scientific Spirit in Medicine: Inaugural Sessional Address to the Abernethian Society", "St. Bartholomew's Hospital Journal", 20, 19 (1912).

References

* [http://www.aim25.ac.uk/cgi-bin/search2?coll_id=7107&inst_id=8 biography (An English archival website with a brief but more detailed biography)]
*"Archibald Garrod and the Individuality of Man", Alexander Gordon Bearn (Oxford, 1993). ISBN 0-19-262145-9
*Bearn AG, Miller ED. Archibald Garrod and the development of the concept of inborn errors of metabolism. "Bull Hist Med". 1979 Fall;53(3):315-28. [PMID 394776]