A Discovery in Tragedy: Sir Archibald Garrod
It is a nice accolade for us at Barts to lay claim to six Nobel Laureates. But it is little more than that. For if an institution is to legitimately count its Nobel Laureates as a measure of its status, it must do so by turning a blind eye to the many scores of alumni and faculty who were never recognised with such an honour, whether because they lived in the wrong era or achieved excellence in the wrong field. And then there are those who were simply ignored, such as Sir Archibald Garrod.
Sir Archibald Garrod was born in 1857 as the son of Harley Street rheumatologist, Sir Alfred Baring Garrod, himself a famous physician, noted for his discovery of excess uric acid as the cause of gout. Completing his preclinical natural sciences degree at Christ Church, Oxford, Archibald Garrod undertook his medical training at St Bartholomew’s Hospital in the 1880s. It was through his studies, he developed a fascination with chemical pathology, and throughout his career, he would identify a number of rare, inherited diseases through analysis of the urine of patients.
In 1897, as assistant physician at the Great Ormond Street Hospital, Garrod would take the first steps towards making his most famous discovery. A mother arrived at the hospital, distraught as her child’s diapers were inexplicably stained inky black in colour. The child was otherwise well and three years later, the mother would become pregnant again. Working on a hunch, born from the instinct innate to all great scientists, Garrod instructed the nurses on the ward to inspect the diapers of the newborn. Sure enough, they were inky black in colour.
Garrod researched other cases of what he defined as alkaptonuria - so-called due to the accumulation of alkapton (oxidized homogentisic acid) which is then excreted in the urine - realising its prevalence in infants with a family history of consanguineous marriages. Although unaware of the concept of genes at the time, Garrod explained his findings through Mendelian inheritance, identifying an autosomal recessive pattern of inheritance and attributing the disease to enzyme defects within an important metabolic pathway (the breakdown of tyrosine). In 1908, he presented his seminal work to the Royal College of Physicians as ‘Inborn Errors of Metabolism’, ushering in a new era of medicine decades ahead of its time, its significance still to be properly appreciated.
Yet in the midst of these breakthroughs, Garrod’s research was interrupted by the breakout of the First World War. While he was knighted for his wartime services, serving as a consulting physician to the Mediterranean Forces in Malta (again proving that he was a century ahead of his time), he would lose two of his sons in action, with the youngest later passing away due to the Spanish flu.
While his daughter, Dorothy Garrod, would become a renowned Professor of Archaeology at the University of Cambridge, and the first woman to hold an Oxbridge chair, the deaths of his three sons had a profound effect on Garrod, who retreated from the wards and into the laboratory. Upon his return from the Great War, he became a director of a medical unit at Barts but would soon move on to the post of Regius Professor of Medicine at Oxford. His reserved manner was perhaps diametrically opposed to that of his predecessor, the great Sir William Osler, who emphasised the value of clinical training for medical students.
But through his devotion to the pursuit of scientific research, Garrod discovered three other rare conditions, similar in their inheritance and effects to alkaptonuria: albinism, cystinuria, and pentosuria. These diseases were each due to issues with the normal chemical pathways taking place in the body. These four diseases would form Garrod’s tetrad, the subject of his final great thesis, and pioneering the field of ‘inborn errors of metabolism’, findings which would gain prominence as the field of genetics progressed.
But in spite of all his work and discovery of these inherited metabolic disorders, Garrod never received the Nobel Prize in Physiology or Medicine. In 1958, 22 years after his death, half of the honour was awarded to George Wells Beadle and Edward Lawrie Tatum “for their discovery that genes act by regulating definite chemical events”. In his acceptance speech on December 11th 1958, George Wells Beadle would mention Garrod nineteen times, recognising how Garrod was essential to the development of the one gene - one enzyme (later one gene - one polypeptide) hypothesis they first proposed in 1941. “In this long, roundabout way”, Beadle said, “we had rediscovered what Garrod had seen so clearly so many years before. By now we knew of his work and were aware that we had added little if anything new in principle.”
That the full scope of Garrod’s discovery was under-appreciated for so long, until his achievements could no longer be acknowledged posthumously, points to just how capricious the awarding committee of the Nobel Prize may be. But despite the omission, Archibald Garrod can perhaps lie claim to the greatest honour of all, of greater scarcity than even a Nobel Prize. In 2008, although he was a Barts man, the old London Hospital Medical College Building was named after him. To this day, the Garrod Building is a testament to one of our greatest pioneers and continues to serve as the spiritual home of Barts and The London School of Medicine and Dentistry.
(Image Credit: Wellcome Collection. Attribution 4.0 International (CC BY 4.0))
