Sir Archibald Edward Garrod
(25 November 1857 – 28 March 1936) was an
English physician
A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
who pioneered the field of
inborn errors of metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substra ...
. He also discovered
alkaptonuria, understanding its inheritance. He served as
Regius Professor of Medicine at the
University of Oxford
The University of Oxford is a collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the world's second-oldest university in contin ...
from 1920 to 1927.
[Rolleston, J. D. (2004]
"Garrod, Sir Archibald Edward (1857–1936)"
rev. Alexander G. Bearn, in ''Oxford Dictionary of National Biography'', Oxford University Press.
Education and personal life
Archibald was the fourth son of Sir
Alfred Baring Garrod, a renowned physician who received his medical degree at the age of 23 and became a professor of medicine at University College, London by the time he was 32. He discovered the abnormal
uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates, such as ammonium acid urate. Uric acid is a product of the metabolic breakdown ...
metabolism associated with
gout
Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...
.
Garrod's father also successfully estimated the weight of crystals he obtained from a known quantity of blood, resulting in what Garrod called “the first quantitative biochemical investigation made on the living human body”. Garrod's eldest brother
Alfred Henry Garrod was a successful ornithologist that named a number of bird taxa and studied specimens from the
Challenger Expedition
The ''Challenger'' expedition of 1872–1876 was a scientific program that made many discoveries to lay the foundation of oceanography. The expedition was named after the naval vessel that undertook the trip, .
The expedition, initiated by W ...
; Herbert Baring Garrod, his other elder brother also had a successful career, both as a barrister-at-law and as a scholar, writing "Dante, Goethe's Faust, and Other Lectures".
Charles Keene, a cousin, frequently visited Garrod's childhood home. Keene was an illustrator for the magazine Punch for over 40 years. Influenced by Keene, Garrod wrote an illustrated booklet called ''A Handbook of Classical Architecture.'' According to Krishna Dronamraju, Garrod displayed an interest in natural history from an early age and was particularly interested in butterflies. At the age of 12, he began collecting them and noted how few female butterflies were present, musing over possible inheritance patterns in mammals.
He was educated at
Marlborough College
Marlborough College is a Public school (United Kingdom), public school (English Independent school (United Kingdom), independent boarding school) for pupils aged 13 to 18 in Marlborough, Wiltshire, England. Founded in 1843 for the sons of Church ...
and
Christ Church,
University of Oxford
The University of Oxford is a collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the world's second-oldest university in contin ...
. He performed poorly at Marlborough, struggling due to his lack of interest in classics, especially Latin prose and grammar. He graduated with a First-class Honours (or a "First") degree in natural science in 1878.
In 1880, he received further medical training at
St. Bartholomew's Hospital
St Bartholomew's Hospital, commonly known as Barts, is a teaching hospital located in the City of London. It was founded in 1123 and is currently run by Barts Health NHS Trust.
History
Early history
Barts was founded in 1123 by Rahere (died ...
in London, where he obtained several scholarships including the competitive Brackenbury Scholarship. Garrod graduated in 1884 and then spent a year studying in Vienna at the general hospital, known as the
Allgemeines Krankenhaus. His experiences in Vienna formed the basis for his 1886 work, ''An Introduction to the Use of the Laryngoscope,'' which was very well received''.'' In 1885 he obtained his
Bachelor of Medicine
Bachelor of Medicine, Bachelor of Surgery ( la, Medicinae Baccalaureus, Baccalaureus Chirurgiae; abbreviated most commonly MBBS), is the primary medical degree awarded by medical schools in countries that follow the tradition of the United King ...
and
Master of Arts
A Master of Arts ( la, Magister Artium or ''Artium Magister''; abbreviated MA, M.A., AM, or A.M.) is the holder of a master's degree awarded by universities in many countries. The degree is usually contrasted with that of Master of Science. ...
from Oxford, and became a member of the
Royal College of Physicians
The Royal College of Physicians (RCP) is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of physicians by examination. Founded by royal charter from King Henry VIII in 1 ...
, London.
He married Laura Elizabeth Smith in 1886. They had three sons and a daughter,
Dorothy Garrod
Dorothy Annie Elizabeth Garrod, CBE, FBA (5 May 1892 – 18 December 1968) was an English archaeologist who specialised in the Palaeolithic period. She held the position of Disney Professor of Archaeology at the University of Cambridge from ...
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
World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, the United States, and the Ottoman Empire, with fig ...
, 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
The Most Distinguished Order of Saint Michael and Saint George is a British order of chivalry founded on 28 April 1818 by George IV, Prince of Wales, while he was acting as prince regent for his father, King George III.
It is named in hono ...
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
Cologne ( ; german: Köln ; ksh, Kölle ) is the largest city of the German western state of North Rhine-Westphalia (NRW) and the fourth-most populous city of Germany with 1.1 million inhabitants in the city proper and 3.6 millio ...
during the great
Spanish flu
The 1918–1920 influenza pandemic, commonly known by the misnomer Spanish flu or as the Great Influenza epidemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case wa ...
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
Great Ormond Street Hospital (informally GOSH or Great Ormond Street, formerly the Hospital for Sick Children) is a children's hospital located in the Bloomsbury area of the London Borough of Camden, and a part of Great Ormond Street Hospi ...
for Children, and Alexandra Hospital for Children with
hip dysplasia
Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it doe ...
. In 1892, he was appointed assistant physician at the Great Ormand Street Hospital. Dronamraju writes, “He was interested in studies of normal and pathological urine, especially in differences of their coloration. It is of interest that his interest in butterflies and flowers in childhood was also related to color differences and biological variation, and it may well have helped to sharpen his perception in this regard.”
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
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
'' (1913), with
Frederick Batten and
James Hugh Thursfield
James Hugh Thursfield FRCP (July 1869 – 20 June 1944) was a British paediatrician. With Archibald Garrod and Frederick Batten he edited '' Diseases of Children'' (1913), and he edited ''Archives of Diseases in Childhood'' (founded 1926). He s ...
.
Alkaptonuria and inborn errors of metabolism
Garrod is best known for his scientific study of inborn errors of metabolism. He developed an increasing interest in chemical pathology, and investigated
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellular ...
chemistry as a reflection of systemic
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...
and disease. This research, combined with the new understanding of
Mendelian inheritance
Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populari ...
, 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.
In the 1890s he collaborated with Frederick Gowland Hopkins, a well-known and respected London physician and biochemist who studied the concept of how vitamins, then known as “accessory factors”, effect dietary health of patients. Under Hopkins's influence and led by his own childhood fascination with color variations, he took particular notice of how the color of urine changed.
In 1897, a mother arrived at the Great Ormand Street Hospital with an infant and a diaper stained brownish-black. Dr. Garrod recorded the family history of the baby and kept tabs on the newborn's growth over the years. He quickly began seeking other patients with the same disorder and found forty cases and read up on the disorder, the first instance of which was noted in 1822.
In 1900, the same mother became pregnant. Once the baby was born, Garrod had nurses closely inspecting the baby's diaper. Sure enough, they noted the appearance of the black urine 52 hours after the baby was born. Garrod subsequently deduced that the condition, alkaptonuria, was innate. Looking at his records, Garrod noticed that alkaptonuria was more likely to occur in the children of first cousins.
Working with William Bateson, Garrod came to understand the pattern of alkaptonuria appearance in children based on Mendelian principles. Once he applied Mendel's concepts to alkaptonuria, he published a paper in 1902 called “The Incidence of Alkaptonuria: A Study of Chemical Individuality”. In the paper, Garrod explains how he came to understand the condition and speculates as to its causes. He cites various case studies and compares alkaptonuria to albinism in how it's inherited.
In his paper, Garrod focuses on the concept of “chemical individuality” without any prior knowledge of what would come to be known as genes. He writes, “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”.
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
Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some ...
characterized by deposition of brown pigment in
joint
A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...
cartilage and
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue ...
. Garrod studied the recurrence patterns in several families, realized it followed an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
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
Homogentisic acid (2,5-dihydroxyphenylacetic acid) is a phenolic acid usually found in '' Arbutus unedo'' (strawberry-tree) honey. It is also present in the bacterial plant pathogen ''Xanthomonas campestris'' pv. ''phaseoli'' as well as in the ...
. 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 Lecture
The Croonian Medal and Lecture is a prestigious award, a medal, and lecture given at the invitation of the Royal Society and the Royal College of Physicians.
Among the papers of William Croone at his death in 1684, was a plan to endow a single ...
s to the
Royal College of Physicians
The Royal College of Physicians (RCP) is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of physicians by examination. Founded by royal charter from King Henry VIII in 1 ...
, entitled Inborn Errors of Metabolism and published the following year. Garrod expanded his metabolic studies to cover
cystinuria
Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduri ...
,
pentosuria, and
albinism
Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino.
Varied use and interpretation of the term ...
. These three inborn errors, along with alkaptonuria are collectively called
Garrod's tetrad
In medicine, Garrod's tetrad is a term named for British physician Archibald Garrod, who introduced the phrase "inborn errors of metabolism" in a lecture in 1908.Archibald E. Garrod. ''Inborn Errors of Metabolism: The Croonian Lectures Delivered Be ...
. 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
Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first residency program for specialty training of phy ...
as
Regius Professor of Medicine at Oxford
The Regius Professor of Medicine is an appointment held at the University of Oxford. The chair was founded by Henry VIII of England by 1546, and until the 20th century the title was Regius Professor of Physic. Henry VIII established five Regius P ...
. He was elected a
Fellow of the Royal Society
Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the judges of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural knowledge, including mathematic ...
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 Royal Society of Medicine (RSM) is a medical society in the United Kingdom, headquartered in London.
History
The Society was established in 1805 as Medical and Chirurgical Society of London, meeting in two rooms in barristers’ chamber ...
.
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
Bernhard Naunyn (2 September 1839 – 26 July 1925) was German pathologist born in Berlin.
Biography
After receiving his degree at the University of Berlin in 1863, he became an assistant to pathologist Friedrich Theodor von Frerichs (1819� ...
, 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
References
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).
*
{{DEFAULTSORT:Garrod, Archibald
1857 births
1936 deaths
19th-century English medical doctors
Knights Commander of the Order of St Michael and St George
Alumni of Christ Church, Oxford
Fellows of Christ Church, Oxford
Fellows of the Royal Society
Alumni of the Medical College of St Bartholomew's Hospital
Regius Professors of Medicine (University of Oxford)
People educated at Marlborough College
20th-century English medical doctors