ARCHIBALD EDWARD GARROD: THE MAN AND HIS TIME ALEXANDER G. BEARN, M.D. NEW YORK
Archibald Edward Garrod was born in London in 1857, the son of Alfred Baring Garrod, Professor of Medicine and Professor of Therapeutics and Clinical Medicine at University College, London. By then, Alfred Garrod also had a fashionable and lucrative West End practice. Earlier, at the age of 28, he had made a name for himself as a medical scientist by discovering that uric acid was increased in the blood of patients suffering from gout. The Garrod family came from Ipswich in Suffolk where Archibald's grandfather, Robert Garrod, had built up a thriving real estate agency. Archibald Garrod was the youngest of three gifted brothers. The eldest, Alfred Henry Garrod, was 11 years old when young Archie was born. Alfred's career got off to a brilliant start, and he is still remembered in zoological circles for his reclassification of birds. He was elected a Fellow of the Royal Society at the age of 32 but died of tuberculosis in the same year. Herbert, eight years older than Archibald, gained an enviable reputation in the humanities. He won the Newdigate Prize for English verse at Oxford with a poem on Charlemagne, and had a most distinguished career. It was a happy circumstance that young Archibald grew up in a household where good talk and good science were the order of the day. Intellectually challenged by this environment, and even to some extent awed by it, he built a reputation that was to exceed that of his older brothers. Archibald began to organize his youthful thoughts on paper at an early age. When he was 10, he wrote a booklet entitled "The Handbook of Clasical Architecture." (Fig. 1). Although it was illustrated in a hesitant and childish hand, it showed surprising attention to precise architectural detail if not to all the tedious conventions of spelling. A few years later he came out with another booklet for home consumption, "The Tiger". In it we can detect a beginning interest in the concepts of heredity: "There has been an instance of a lion being the father and a tigress the mother of cubs. The lion was born in captivity and the tiger From the Department of Medicine, Cornell University Medical College, New York, New York. This paper is an abbreviated version of the Lettsomian Lectures delivered in London on February 9th and 23rd, 1976. 85
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ALEXANDER G. BEARN
FIG. 1. Frontispiece of "The Handbook of Clasical Architecture."
was captured at a very early age. The cub had the head of the lion but the tigerine stripes on the body." After attending a preparatory school at Harrow, Archibald entered Marlborough at the age of 15. His classics master despaired at his slow progress in Greek and Latin, but he collected butterflies, studied the biology of pond life, and generally did well in the sciences. It was clear that science was to be his forte. Young Garrod entered Oxford as a commoner at Christ Church in 1875, and took full advantage of university life; his letters home bubbled with enthusiasm for his courses, and for the laboratory work that he undertook so conscientiously. During his last year at Oxford he was awarded the Johnson Memorial Prize for an essay entitled, "The Nebulae-A Fragment of Astronomical History", a rare book which except for one copy in the British Museum, has all but vanished. In 1878, Garrod got a first in Natural Sciences. He could doubtless have followed his eldest brother in pursuing a distinguished scientific career, but decided instead to follow his father into the medical profession. So he left Oxford for London and entered St. Bartholomew's
ARCHIBALD EDWARD GARROD: THE MAN AND HIS TIME
87
Hospital in 1880; he did well scholastically during his years there, qualifying in 1884. After his graduation, and on his father's advice, Garrod spent a year in Vienna where, enviably nourished by the continental masters, he first learned ofthe laryngoscope and its growing usefulness in medicine. On his return home, he promptly summed up his experiences in a small and very popular book on the medical uses of the laryngoscope. A year later he married Laura, the daughter of Sir Thomas Smith Bart, and the young couple set up house at 9 Chandos Street. There they lived for more than 30 years, bringing up four children, three boys and a girl, in pleasant but not luxurious surroundings. Shortly after his marriage, Garrod joined his father in practice, but it was soon clear that a fashionable West End practice was not his idea of a satisfying medical career. In 1890, he published a treatise on rheumatism and rheumatoid arthritis. Two years later, at the age of 35, he was appointed Assistant Physician to the Hospital for Sick Children, and from then on Garrod retained a special interest in diseases of childhood. In 1904 he was placed in charge of an outpatient department at St. Bartholomew's Hospital restricted to diseases of children. (It was only in 1912, after a long period of waiting for dead men's shoes, that he was appointed to the medical staff of St. Bartholomew's Hospital.) Garrod became interested in chemical pathology early in his career; he struck up a friendship with Gowland Hopkins, one of the most delightful and distinguished biochemists of his day, and began to concern himself with the chemical nature of the pigments that occur in normal and pathological urine. Alkaptonuria, the disease of black urine which is now so closely identified with the name of Archibald Garrod, attracted his attention, and he remained fascinated by it for his entire professional life. Although the disease had been well described by Boedeker in 1859, the exact nature of the black material remained obscure until 1891, when it was found to be a crystallizable acidic compound to which was given the name homogentisic acid. Alkaptonuria is exceptionally rare, but it represented for Garrod a clinical and chemical challenge. In 1889 he reported extensively on 31 patients with the disease; seven of them had not been previously reported; an additional five had been studied by Garrod personally. In his day most physicians thought that alkaptonuria was an infectious disease of the gastrointestinal tract. Homogentisic acid was formed, so it was believed, in the gut by the degradative action of specific microorganisms. Garrod looked carefully for these in the feces of patients with the disease; finding none, he rejected the hypothesis and advanced the alternate suggestion that alkaptonuria might be the consequence of "some erratic metabolism".
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Garrod's interest in the inherited metabolic sports he called inborn errors of metabolism steadily increased. Between 1889 and 1908, when he gave the Croonian Lectures at the Royal College of Physicians, he continued to work closely with Gowland Hopkins. In addition to alkaptonuria, cystinuria, pentosuria, and albinism, came under his clinical and biochemical scrutiny. Garrod's friendship with the botanist William Bateson, was also crucial to his evolving ideas on inborn errors of metabolism. Bateson, with his knowledge of Mendelism, freshly rediscovered in 1900, pointed out to Garrod that consanguinity should be found more frequently than normal among the parents of individuals with an autosomal recessively inherited disease. Garrod followed this lead and specifically inquired about the existence of consanguinity among the parents of his patients. He quickly found that Bateson was right. Garrod's Croonian Lectures were epoch-making, but those who reviewed them for The Lancet and The British Medical Journal were not particularly impressed. They certainly did not for a minute realize that a new era of medicine had opened. Soon after joining the staff of St. Bartholomew's Hospital, Garrod began a serious effort to introduce chemical pathology into the curriculum and to emphasize the importance of both "the laboratory and the ward". In line with his growing interest in medical education, Garrod took special note of Abraham Flexner's reports on medical education which had descended on the academic world as Carnegie Bulletins in 1910 and 1911. Flexner was disturbed by the lack of a scientific approach to clinical medicine in England and had observed that, in this respect, medical education in England and America had lagged behind their German counterpart. Garrod was persuaded by the logic and the essential correctness of Flexner's reports and resolved to do something about the problem. "If it be true that the scientific spirit is not in evidence in the places in which the training of the future members of our profession is carried out," he wrote, "this must be reckoned a grave defect in our British system of education." Because of Garrod's growing interest in recasting medical education in England, he was interested in the Haldane Commission on Medical Education. But then came the first World War. Garrod was gazetted a major and first stationed in London, at the General Hospital in Camberwell. In November 1915 he embarked for Malta where he served as a Consultant Physician until the war ended. Garrod's military career was distinguished, and in 1918 King George V appointed him a Knight Commander of St. Michael and St. George. But the war brought him devastating personal tragedy: his three sons died in uniform. The first two, Alfred Noel and Thomas A. Garrod, a
89 physician, were killed in action. The third and last, Basil Rahere, died in Cologne during the massive influenza pandemic which swept through Europe in the first few month of peace. Garrod's life was never the same; bereaved and broken, he returned to civilian life to pick up the threads of his professional career. He continued to be concerned with medical education and was frequently articulating his abiding concern for a scientific base in clinical medicine. His vision was clear-sighted, his pen compelling, and his campaign successful. One thing he urged ARCHIBALD EDWARD GARROD: THE MAN AND HIS TIME
: t AtCHIAL E GARROD FIG. 2. Archibald Garrod, Regius Professor of Medicine, Oxford, 1920-1927.
90
ALEXANDER G. BEARN
was the creation of medical professorial units in London teaching hospitals, in which the ward and those in the laboratory could work side by side. Small wonder that, when his views were adopted by the Commission, he was asked to head the first medical professorial unit in London at St. Bartholomew's Hospital. Unfortunately for the development of the unit, he had been appointed a bare year when, at the age of 63, an invitation came for him to succeed Osler as the Regius Professor of Medicine at Oxford. (Fig. 2). With some reluctance, for Garrod hated to leave his new post, he accepted the invitation and served out the rest of his professional life in Oxford. Never gregarious, and even less so after the death of his sons, Garrod busied himself at Oxford with his teaching responsibilities, the administration of the University, and the Clarendon Press. Four years after retirement, at the age of 74, Garrod wrote another classic, "Inborn Factors in Disease", an essay on the doctrine of diathesis, in which he outlined his reasons for thinking that disease susceptibility was no more than a reflection of biochemical individuality. After Garrod's retirement as Regius Professor of Medicine at Oxford, he moved to Melton, Suffolk, but soon became weary of the countryside and lack of friends. So he returned to Cambridge, to live with his daughter with whom he spent the rest of his days. He died on March 28th, 1936, in his 80th year, from a coronary thrombosis. REFERENCE BEARN, A. G.: The Lettsomian Lectures on Inborn Errors of Metabolism. 1. Archibald Garrod and the birth of an idea. 2. Present concepts and future directions. Transactions of The Medical Society of London, vol. 92. In press.
Archibald Edward Garrod was born in London in 1857, the son of Alfred Baring Garrod, Professor of Medicine and Professor of Therapeutics and Clinical Medicine at University College, London. By then, Alfred Garrod also had a fashionable and lucrative West End practice. Earlier, at the age of 28, he had made a name for himself as a medical scientist by discovering that uric acid was increased in the blood of patients suffering from gout. The Garrod family came from Ipswich in Suffolk where Archibald's grandfather, Robert Garrod, had built up a thriving real estate agency. Archibald Garrod was the youngest of three gifted brothers. The eldest, Alfred Henry Garrod, was 11 years old when young Archie was born. Alfred's career got off to a brilliant start, and he is still remembered in zoological circles for his reclassification of birds. He was elected a Fellow of the Royal Society at the age of 32 but died of tuberculosis in the same year. Herbert, eight years older than Archibald, gained an enviable reputation in the humanities. He won the Newdigate Prize for English verse at Oxford with a poem on Charlemagne, and had a most distinguished career. It was a happy circumstance that young Archibald grew up in a household where good talk and good science were the order of the day. Intellectually challenged by this environment, and even to some extent awed by it, he built a reputation that was to exceed that of his older brothers. Archibald began to organize his youthful thoughts on paper at an early age. When he was 10, he wrote a booklet entitled "The Handbook of Clasical Architecture." (Fig. 1). Although it was illustrated in a hesitant and childish hand, it showed surprising attention to precise architectural detail if not to all the tedious conventions of spelling. A few years later he came out with another booklet for home consumption, "The Tiger". In it we can detect a beginning interest in the concepts of heredity: "There has been an instance of a lion being the father and a tigress the mother of cubs. The lion was born in captivity and the tiger From the Department of Medicine, Cornell University Medical College, New York, New York. This paper is an abbreviated version of the Lettsomian Lectures delivered in London on February 9th and 23rd, 1976. 85
86
ALEXANDER G. BEARN
FIG. 1. Frontispiece of "The Handbook of Clasical Architecture."
was captured at a very early age. The cub had the head of the lion but the tigerine stripes on the body." After attending a preparatory school at Harrow, Archibald entered Marlborough at the age of 15. His classics master despaired at his slow progress in Greek and Latin, but he collected butterflies, studied the biology of pond life, and generally did well in the sciences. It was clear that science was to be his forte. Young Garrod entered Oxford as a commoner at Christ Church in 1875, and took full advantage of university life; his letters home bubbled with enthusiasm for his courses, and for the laboratory work that he undertook so conscientiously. During his last year at Oxford he was awarded the Johnson Memorial Prize for an essay entitled, "The Nebulae-A Fragment of Astronomical History", a rare book which except for one copy in the British Museum, has all but vanished. In 1878, Garrod got a first in Natural Sciences. He could doubtless have followed his eldest brother in pursuing a distinguished scientific career, but decided instead to follow his father into the medical profession. So he left Oxford for London and entered St. Bartholomew's
ARCHIBALD EDWARD GARROD: THE MAN AND HIS TIME
87
Hospital in 1880; he did well scholastically during his years there, qualifying in 1884. After his graduation, and on his father's advice, Garrod spent a year in Vienna where, enviably nourished by the continental masters, he first learned ofthe laryngoscope and its growing usefulness in medicine. On his return home, he promptly summed up his experiences in a small and very popular book on the medical uses of the laryngoscope. A year later he married Laura, the daughter of Sir Thomas Smith Bart, and the young couple set up house at 9 Chandos Street. There they lived for more than 30 years, bringing up four children, three boys and a girl, in pleasant but not luxurious surroundings. Shortly after his marriage, Garrod joined his father in practice, but it was soon clear that a fashionable West End practice was not his idea of a satisfying medical career. In 1890, he published a treatise on rheumatism and rheumatoid arthritis. Two years later, at the age of 35, he was appointed Assistant Physician to the Hospital for Sick Children, and from then on Garrod retained a special interest in diseases of childhood. In 1904 he was placed in charge of an outpatient department at St. Bartholomew's Hospital restricted to diseases of children. (It was only in 1912, after a long period of waiting for dead men's shoes, that he was appointed to the medical staff of St. Bartholomew's Hospital.) Garrod became interested in chemical pathology early in his career; he struck up a friendship with Gowland Hopkins, one of the most delightful and distinguished biochemists of his day, and began to concern himself with the chemical nature of the pigments that occur in normal and pathological urine. Alkaptonuria, the disease of black urine which is now so closely identified with the name of Archibald Garrod, attracted his attention, and he remained fascinated by it for his entire professional life. Although the disease had been well described by Boedeker in 1859, the exact nature of the black material remained obscure until 1891, when it was found to be a crystallizable acidic compound to which was given the name homogentisic acid. Alkaptonuria is exceptionally rare, but it represented for Garrod a clinical and chemical challenge. In 1889 he reported extensively on 31 patients with the disease; seven of them had not been previously reported; an additional five had been studied by Garrod personally. In his day most physicians thought that alkaptonuria was an infectious disease of the gastrointestinal tract. Homogentisic acid was formed, so it was believed, in the gut by the degradative action of specific microorganisms. Garrod looked carefully for these in the feces of patients with the disease; finding none, he rejected the hypothesis and advanced the alternate suggestion that alkaptonuria might be the consequence of "some erratic metabolism".
88
ALEXANDER G. BEARN
Garrod's interest in the inherited metabolic sports he called inborn errors of metabolism steadily increased. Between 1889 and 1908, when he gave the Croonian Lectures at the Royal College of Physicians, he continued to work closely with Gowland Hopkins. In addition to alkaptonuria, cystinuria, pentosuria, and albinism, came under his clinical and biochemical scrutiny. Garrod's friendship with the botanist William Bateson, was also crucial to his evolving ideas on inborn errors of metabolism. Bateson, with his knowledge of Mendelism, freshly rediscovered in 1900, pointed out to Garrod that consanguinity should be found more frequently than normal among the parents of individuals with an autosomal recessively inherited disease. Garrod followed this lead and specifically inquired about the existence of consanguinity among the parents of his patients. He quickly found that Bateson was right. Garrod's Croonian Lectures were epoch-making, but those who reviewed them for The Lancet and The British Medical Journal were not particularly impressed. They certainly did not for a minute realize that a new era of medicine had opened. Soon after joining the staff of St. Bartholomew's Hospital, Garrod began a serious effort to introduce chemical pathology into the curriculum and to emphasize the importance of both "the laboratory and the ward". In line with his growing interest in medical education, Garrod took special note of Abraham Flexner's reports on medical education which had descended on the academic world as Carnegie Bulletins in 1910 and 1911. Flexner was disturbed by the lack of a scientific approach to clinical medicine in England and had observed that, in this respect, medical education in England and America had lagged behind their German counterpart. Garrod was persuaded by the logic and the essential correctness of Flexner's reports and resolved to do something about the problem. "If it be true that the scientific spirit is not in evidence in the places in which the training of the future members of our profession is carried out," he wrote, "this must be reckoned a grave defect in our British system of education." Because of Garrod's growing interest in recasting medical education in England, he was interested in the Haldane Commission on Medical Education. But then came the first World War. Garrod was gazetted a major and first stationed in London, at the General Hospital in Camberwell. In November 1915 he embarked for Malta where he served as a Consultant Physician until the war ended. Garrod's military career was distinguished, and in 1918 King George V appointed him a Knight Commander of St. Michael and St. George. But the war brought him devastating personal tragedy: his three sons died in uniform. The first two, Alfred Noel and Thomas A. Garrod, a
89 physician, were killed in action. The third and last, Basil Rahere, died in Cologne during the massive influenza pandemic which swept through Europe in the first few month of peace. Garrod's life was never the same; bereaved and broken, he returned to civilian life to pick up the threads of his professional career. He continued to be concerned with medical education and was frequently articulating his abiding concern for a scientific base in clinical medicine. His vision was clear-sighted, his pen compelling, and his campaign successful. One thing he urged ARCHIBALD EDWARD GARROD: THE MAN AND HIS TIME
: t AtCHIAL E GARROD FIG. 2. Archibald Garrod, Regius Professor of Medicine, Oxford, 1920-1927.
90
ALEXANDER G. BEARN
was the creation of medical professorial units in London teaching hospitals, in which the ward and those in the laboratory could work side by side. Small wonder that, when his views were adopted by the Commission, he was asked to head the first medical professorial unit in London at St. Bartholomew's Hospital. Unfortunately for the development of the unit, he had been appointed a bare year when, at the age of 63, an invitation came for him to succeed Osler as the Regius Professor of Medicine at Oxford. (Fig. 2). With some reluctance, for Garrod hated to leave his new post, he accepted the invitation and served out the rest of his professional life in Oxford. Never gregarious, and even less so after the death of his sons, Garrod busied himself at Oxford with his teaching responsibilities, the administration of the University, and the Clarendon Press. Four years after retirement, at the age of 74, Garrod wrote another classic, "Inborn Factors in Disease", an essay on the doctrine of diathesis, in which he outlined his reasons for thinking that disease susceptibility was no more than a reflection of biochemical individuality. After Garrod's retirement as Regius Professor of Medicine at Oxford, he moved to Melton, Suffolk, but soon became weary of the countryside and lack of friends. So he returned to Cambridge, to live with his daughter with whom he spent the rest of his days. He died on March 28th, 1936, in his 80th year, from a coronary thrombosis. REFERENCE BEARN, A. G.: The Lettsomian Lectures on Inborn Errors of Metabolism. 1. Archibald Garrod and the birth of an idea. 2. Present concepts and future directions. Transactions of The Medical Society of London, vol. 92. In press.
