The Inborn Factors in Disease

Garrod, Archibald E.

doi:10.1097/00007611-193106000-00028

Cited by 77 publications

(31 citation statements)

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“…It was proposed, at least in outline, by A.E. Garrod in 1931. In his remarkable book, The Inborn Factors in Disease, he suggested that infectious diseases may have been a major selective force in human evolution and in shaping our biochemical individuality. In 1948, J.B.S.…”

mentioning

confidence: 99%

The Role of Genomics in Studying Genetic Susceptibility to Infectious Disease: Figure 1.

Weatherall

Clegg²,

Kwiatkowski³

1997

Genome Res.

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mentioning

confidence: 99%

The Role of Genomics in Studying Genetic Susceptibility to Infectious Disease: Figure 1.

Weatherall

Clegg²,

Kwiatkowski³

1997

Genome Res.

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“…The role of genetics in response to drugs was first predicted by Sir Archibald Garrod in the early 1930s (Garrod 1931). Pharmacogenetics, as it is known today, originated as a new scientific discipline in the late 1950s by the merging of two older ones: pharmacology and genetics.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Pharmacogenomics of Thiopurine S-Methyltransferase: Clinical Applicability of Genetic Variants

Pavlović¹,

Zukić²,

Nikčević³

2012

Clinical Applications of Pharmacogenetics

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“…Mutations in homeotic genes are now recognized as unitary determinants underlying many complex developmental disorders in plants and animals -and with emerging significance in humans (Boncinelli 1997). It was indeed William Bateson who indicated to Garrod that the pattern of inheritance and frequent consanguinity in pedigrees affected by alkaptonuria immediately suggested transmission of a unitary Mendelian recessive character -thus explaining the nature of the inborn in "errors of metabolism" (Saunders and Bateson 1902;Garrod 1931).…”

Section: William Bateson and His Influence: Treasure Your Exceptionsmentioning

confidence: 99%

Alkaptonuria: Leading to the Treasure in Exceptions

Cox

2011

JIMD Reports

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The brilliant geneticist, William Bateson, a formidable English experimentalist, was the first to recognize the nature of the "inborn" in Archibald Garrod's errors of metabolism. Bateson's advice to young scientists: "Treasure your exceptions!" summarizes much of the vigorous empiricism associated with the study of rare disorders.The first inborn error of metabolism to be so recognized was alkaptonuria, and it is only recently that a proper understanding of this condition as a disease, rather than a biochemical curiosity, has emerged. Abnormal excretion of the reactive tyrosine metabolite, homogentisic acid, not only provides a tangible biomarker of alkaptonuria, but also a focus for detailed mechanistic understanding.Currently, there is no proven treatment for alkaptonuria but emergence of orphan drug legislation internationally has promoted the licensing of nitisinone (Orfadin™) for an equally rare disorder of tyrosine metabolism -hereditary tyrosinaemia type 1. Nitisinone, a triketone competitive inhibitor of a proximal step leading to the formation of homogentisic acid, has potent therapeutic effects in hereditary tyrosinemia and rapidly ameliorates the primary biochemical abnormality in patients with alkaptonuria.Here, we discuss the context in which nitisinone should be further explored for the treatment of alkaptonuria. This exceptional disease is a paradigm case, which opens up unusual opportunities for basic and applied research. In modern times, it also shows how the conflation of orphan drug legislation and the emerging power and commitment of patient organizations can synergize effectively to advance basic research and therapeutic development in ultra-orphan diseases.

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The Inborn Factors in Disease

Cited by 77 publications

References 0 publications

The Role of Genomics in Studying Genetic Susceptibility to Infectious Disease: Figure 1.

The Role of Genomics in Studying Genetic Susceptibility to Infectious Disease: Figure 1.

Pharmacogenomics of Thiopurine S-Methyltransferase: Clinical Applicability of Genetic Variants

Alkaptonuria: Leading to the Treasure in Exceptions

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