Archibald Garrod
Encyclopedia
Sir Archibald Edward Garrod KCMG
Order of St Michael and St George
The Most Distinguished Order of Saint Michael and Saint George is an order of chivalry founded on 28 April 1818 by George, Prince Regent, later George IV of the United Kingdom, while he was acting as Prince Regent for his father, George III....

, FRS (25 November 1857 – 28 March 1936) was an English
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...

 physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...

 who pioneered the field of inborn errors of metabolism
Inborn error of metabolism
Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...

.

Education and Personal Life

Archibald was the fourth son of Sir Alfred Baring Garrod
Alfred Baring Garrod
Sir Alfred Baring Garrod FRS was an English physician.He was born in Ipswich, the son of Robert and Sarah Garrod.He initially apprenticed at Ipswich Hospital, and later moved to University College Hospital, where he earned his medical doctorate in 1843. Afterwards he was an assistant at West...

, a physician at King's College Hospital
King's College Hospital
King's College Hospital is an acute care facility in the London Borough of Lambeth, referred to locally and by staff simply as "King's" or abbreviated internally to "KCH"...

, who discovered the abnormal uric acid
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 created when the body breaks down purine nucleotides. High blood concentrations of uric acid...

 metabolism associated with gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

.

He was educated at Marlborough College
Marlborough College
Marlborough College is a British co-educational independent school for day and boarding pupils, located in Marlborough, Wiltshire.Founded in 1843 for the education of the sons of Church of England clergy, the school now accepts both boys and girls of all beliefs. Currently there are just over 800...

 and Christ Church
Christ Church, Oxford
Christ Church or house of Christ, and thus sometimes known as The House), is one of the largest constituent colleges of the University of Oxford in England...

, University of Oxford
University of Oxford
The University of Oxford is a university located in Oxford, United Kingdom. It is the second-oldest surviving university in the world and the oldest in the English-speaking world. Although its exact date of foundation is unclear, there is evidence of teaching as far back as 1096...

. 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
Vienna
Vienna is the capital and largest city of the Republic of Austria and one of the nine states of Austria. Vienna is Austria's primary city, with a population of about 1.723 million , and is by far the largest city in Austria, as well as its cultural, economic, and political centre...

 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
Royal College of Physicians
The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...

, London.

He married Laura Elizabeth Smith in 1886. They had 3 sons and a daughter, Dorothy Garrod
Dorothy Garrod
Dorothy Annie Elizabeth Garrod CBE was a British archaeologist who was the first woman to hold an Oxbridge chair, partly through her pioneering work on the Palaeolithic period. Her father was Sir Archibald Garrod, the physician.-Life:Born in Oxford, she attended Newnham College, Cambridge...

.

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
Cologne
Cologne is Germany's fourth-largest city , and is the largest city both in the Germany Federal State of North Rhine-Westphalia and within the Rhine-Ruhr Metropolitan Area, one of the major European metropolitan areas with more than ten million inhabitants.Cologne is located on both sides of the...

 during the great Spanish Flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...

 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
Great Ormond Street Hospital for Children is a children's hospital located in London, United Kingdom...

 for Children, and Alexandra Hospital for Children with Hip Disease.

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
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

 chemistry as a reflection of systemic metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 and disease. This research, combined with the new understanding of Mendelian inheritance
Mendelian inheritance
Mendelian inheritance is a scientific description of how hereditary characteristics are passed from parent organisms to their offspring; it underlies much of genetics...

, evolved from an investigation of a few families with an obscure and not very dangerous disease (alkaptonuria
Alkaptonuria
Alkaptonuria is a rare inherited genetic disorder of phenylalanine and tyrosine metabolism. This is an autosomal recessive condition that is due to a defect in the enzyme homogentisate 1,2-dioxygenase , which participates in the degradation of tyrosine...

) 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
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

 characterized by deposition of brown pigment in joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...

 cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...

 and connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...

. 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 described the nature of recessive inheritance of most enzyme defects. In 1908, the core of this work was presented as the Croonian Lecture
Croonian Lecture
The Croonian Lectures are prestigious lectureships 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 one lectureship at both the Royal Society and the Royal College of Physicians...

s to the Royal College of Physicians
Royal College of Physicians
The Royal College of Physicians of London was founded in 1518 as the College of Physicians by royal charter of King Henry VIII in 1518 - the first medical institution in England to receive a royal charter...

, entitled Inborn Errors of Metabolism and published the following year. Garrod expanded his metabolic studies to cover cystinuria
Cystinuria
Cystinuria is an inherited autosomal recessive disease that is characterized by the formation of cystine stones in the kidneys, ureter, and bladder.-Signs and symptoms:Cystinuria is a cause of persistent kidney stones...

, pentosuria
Pentosuria
Pentosuria is a condition where xylulose presents in the urine in unusually high concentrations.It is associated with a deficiency of L-xylulose reductase....

, and albinism
Albinism
Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...

.These three inborn errors, along with alkaptonuria are collectively called Garrod's tetrad
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....

. In 1923 he summarized these studies in an expanded edition of his best known work, Inborn Errors of Metabolism.

Honors

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
William Osler
Sir William Osler, 1st Baronet was a physician. He was one of the "Big Four" founding professors at Johns Hopkins Hospital as the first Professor of Medicine and founder of the Medical Service there. Sir William Osler, 1st Baronet (July 12, 1849 – December 29, 1919) was a physician. He was...

 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
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...

, and was made an honorary member of the American Association of Physicians, and of the Ärtzlicher 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
Royal Society of Medicine
The Royal Society of Medicine is a British charitable organisation whose main purpose is as a provider of medical education, running over 350 meetings and conferences each year.- History and overview :...

.

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
    Wilmot Herringham
    Sir Wilmot Parker Herringham KCMG CB was a British medical doctor, academic and author. He was one of the first doctors to investigate the effect and treatment of poison gas in World War I.-Life:...

     & W.J. Gow
  • A Treatise on Cholelithiasis, Bernhard Naunyn
    Bernhard Naunyn
    Bernhard Naunyn was German pathologist who was born in Berlin. After receiving his degree at the University of Berlin in 1863, he became an assistant to pathologist Friedrich Theodor von Frerichs...

    , 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

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