How diseases became "genetic".

Ilana Löwy

doi:10.1590/1413-812320182410.19102019

Abstract

This article examines the origins of the term "genetic disease." In the late 19 and early 20th century, an earlier idea that diseases that occur in families reflect a vague familiar "predisposition" was replaced by the view that such diseases have specific causes, while Mendelian genetics provided then clues to the patterns of their transmission. The genetictisation of inborn pathologies took a decisive turn with the redefinition, in 1959, of Down syndrome as a chromosomal anomaly, then the development of tests for the diagnosis of other hereditary pathologies. At that time, geneticists distinguished "hereditary" diseases that run in families, from "genetic" conditions that are the result of new mutations during the production of egg and sperm cells. In the latter case, the inborn impairment is produced by an anomaly in the genetic material of the cell, but is not hereditary, because it is not transmitted from one or both parents. In the late 20th and early 21st century, new genomic technologies blurred the distinction between hereditary and genetic impairments, extended the concept of genetic disease, and modified the experience of people living with such a disease.

Highlights

Resumo O presente artigo tem o objetivo de examinar as origens do termo “doença genética
The search for “morbid heredity” was intensified in the 19th century. This concept included a multiplicity of causes, such as familial traits (“likes begets likes”) intensified by intermarriage, and alcoholism, tuberculosis, and venereal diseases, especially syphilis
The British psychiatrist George Edward Shuttleworth (1842-1928), author of the textbook, Mentally Deficient Children: Their Treatment and Training, proposed to distinguish between “acquired mental deficiency,” produced by accidents of childbirth or childhood by events such as trauma, a febrile disease or intoxication, and “inborn mental deficiency,” produced before birth by “formative defects”. Shuttleworth included in the latter category conditions such as microcephalus, hydrocephalus, “mongol” feeblemindedness, “cretinism”, and anomalies produced by diseases of the pregnant woman, such as epilepsy, syphilis and eclampsia

Summary

Hereditary diseases before genetics

An interest in traits that children inherit from their parents – the father’s hair, the mother’s eyes – may be as old as civilizations, but interest in diseases that run in families is documented from the 17th century on, when physicians started to systematically record families with an unusual concentration of abnormal traits[1,2]. In the 1940s and 50s, significant portion of experts believed that while a small number of diseases such as PKU or hemophilia correspond to the description of “pure” hereditary conditions that obey Mendel’s laws, the majority of pathologies described as “hereditary” are produced by multilevel interactions between heredity and environment This view became more complex after 1959, following the description of the consequences of the presence of abnormal number of chromosomes (aneuploidy) – and the rise of an important new category of diseases which were “genetic” but not “hereditary”. In the early 1960s, cytogeneticists were able to diagnose chromosomal anomalies in individuals with impairments produced by these anomalies, while biochemists were able to diagnose hereditary conditions such as metabolic diseases, often produced by a lack of an essential enzyme, by displaying the absence of this enzyme in cells of the affected individuals It was not possible, to detect these conditions before birth. The detection of Down syndrome – an inborn impairment which is much more frequent than hereditary metabolic diseases and hereditary diseases of the blood – became the main target of search for genetic anomalies of the fetus and later for population-based screening for such conditions[44,45]

Abnormal development and abnormal genes

Findings

Genetic diseases in the genomic era