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ABSTRACT

Nothing in biology makes sense except in the light of evolution and nothing in medicine makes sense except in the light of biology. The essay proposes that medicine is a science of the individual and when the experiences that undermine health are ameliorated, the continuing diseases in the population, in individuals, are increasingly likely to have biological explanations: some are Mendelian but most are multifactorial and complex. How we respond to this transition will influence education and practice.

INBORN ERRORS AND CHEMICAL INDIVIDUALITY

It might be claimed that what used to be spoken of as a diathesis is nothing else but chemical individuality. But to our chemical individualities are due our chemical merits as well as our chemical shortcomings; and it is more nearly true to say that the factors which confer upon us our predispositions to and immunities from the various mishaps which are spoken of as diseases, are inherent in our very chemical structure: and even in the molecular groupings which confer upon us our individualities, and which went to the making of the chromosomes from which we sprang.—A. E. Garrod5

The Inborn Error as a Central Theme in Medicine

The Metabolic and Molecular Bases of Inherited Disease is now in its eighth edition. It is an account of the origins and characteristics of diverse diseases, and being a human enterprise, the book has an ontogeny. The chief attribute of this development is the shift from biochemical explanations of pathogenesis to molecular descriptions of abnormality of structure and function, and with it has come a recognition that disease cannot be described simply as a consequence of a chance encounter with an inimical environment. Rather, it is individual variation in homeostatic range and flexibility that differentiates the disease-prone individual. So the ontogeny of MMBID is the history of the integration of genetics and medicine.

The first edition appeared in 1960, with the inborn error as its central theme. The editors advanced their intention to present “the pertinent clinical, biochemical and genetic information concerning those metabolic anomalies which have been grouped under Garrod’s engaging term ‘the inborn errors of metabolism.’”1 They also recognized that the existing list of inborn errors was not exhaustive. This sensitivity to undiscovered disease was extended in later editions to a much enlarged definition of the inborn error, which at the start was limited to enzyme deficiencies. For example, the second edition included defects of serum proteins and of hemostasis, and in the fourth the immune system made its appearance. By the sixth edition 374 disorders were listed, and the definition of the inborn error had been extended to cancer and developmental defects due to chromosomal anomalies.2 So in the face of such a proliferation, logic leads us to the conclusion that the inborn error is a central idea in medicine.

In this vein the ...

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