Archibald Garrod

Archibald Garrod
Born	(1857-11-25)25 November 1857 London
Died	28 March 1936(1936-03-28) (aged 78) Cambridge
Nationality	English
Known for	alkaptonuria
Awards	Fellow of the Royal Society
Scientific career
Fields	medicine
Institutions	University of Oxford

Sir Archibald Edward Garrod KCMG FRS (25 November 1857 – 28 March 1936) was an English physician who pioneered the field of inborn errors of metabolism. He also discovered alkaptonuria, understanding its inheritance. He served as Regius Professor of Medicine at the University of Oxford from 1920 to 1927.

Education and personal life

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 College 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 Bachelor of Medicine and Master of Arts from Oxford, and became a member of the Royal College of Physicians, London.

He married Laura Elizabeth Smith in 1886. They had three sons and a daughter, Dorothy Garrod a British archaeologist who was the first woman to hold an Oxbridge chair, partly through her pioneering work on the Palaeolithic period.

First World War

During the First World War, Garrod served as medical consultant to the army, primarily in Malta and in 1918 was appointed Knight Commander of the Order of St Michael and St George in recognition of his wartime services.

Two of his three sons were killed in action during the war, Thomas Martin Garrod aged 20 in 1915 and Alfred Noel Garrod aged 28 in 1916. In 1919, his third son Basil Rahere Garrod died, aged 21, in Cologne during the great Spanish Flu pandemic.

Professional career

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, Great Ormond Street Hospital for Children, and Alexandra Hospital for Children with Hip dysplasia.

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.

Alkaptonuria and inborn errors of metabolism

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 alkapton. 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 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.These three inborn errors, along with alkaptonuria are collectively called Garrod's tetrad. In 1923 he summarized these studies in an expanded edition of his best known work.

Honours

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 in 1910, was appointed to the Medical Research Council, and was made an honorary member of the American Association of Physicians, and of the Ärztlicher 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.

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.

Death

He died at the Cambridge home of his daughter after a brief illness in 1936, and is buried in Highgate Cemetery, London.

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.

— Archibald Garrod, Archibald Garrod, "The Scientific Spirit in Medicine: Inaugural Sessional Address to the Abernethian Society", St. Bartholomew's Hospital Journal, 20, 19 (1912)

Bibliography

• 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]