Coming full circle: the development, rise, fall, and return of the concept of anticipation in hereditary disease
Date
2009-10-26T18:16:36Z
Authors
Friedman, Judith Ellen
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Abstract
This dissertation examines the history of the creation and development of the concept of
anticipation, a pattern of heredity found in several diseases (e.g. Huntington’s disease and
myotonic dystrophy), in which an illness manifests itself earlier and often more severely
in successive generations. It reconstructs major arguments in twentieth-century debates
about anticipation and analyzes the relations between different research communities and
schools of thought. Developments in cutting-edge medicine, biology, and genetics are
analyzed; many of these developments were centered in Britain, but saw significant
contributions by people working in France, Germany, Switzerland, the Netherlands and
North America.
Chapter one traces precursor notions in psychiatric and hereditarian thought from
1840 to the coining of the term ‘anticipation’ by the ophthalmologist Edward Nettleship
in 1905. Key roles in the following chapters are played by several figures. Prior to World
War II, these include: the neuropathologist F.W. Mott, whose advocacy during 1911-
1927 led to anticipation being called “Mott’s law”; the biometrician and eugenicist Karl
Pearson, who opposed Mott on methodological and political grounds; and two politically
and theoretically opposed Germans – Ernst Rüdin, a leading psychiatrist and eugenicist
who came to reject anticipation, and Richard Goldschmidt, a geneticist who offered a
peculiar Mendelian explanation. The British psychiatrist and human geneticist, Lionel
Penrose, makes a first interwar appearance, but becomes crucial to the story after World
War II due to his systematic dismissal of anticipation, which discredited the notion on
orthodox Mendelian grounds. The final chapters highlight the contributions of Dutch
neurologist Christiaan Höweler, whose 1980s work demonstrated a major hole in
Penrose’s reasoning, and British geneticist Peter Harper, whose research helped
demonstrate that expanding trinucleotide repeats accounted for the transgenerational
worsening without contradicting Mendel and resurrected anticipation as scientifically
legitimate. Reception of the concept of anticipation is traced across the century through
the examination of textbooks used in different fields.
This dissertation argues against established positions regarding the history of the
concept, including claims that anticipation’s association with eugenics adequately
explains the rejection of the notion after 1945. Rejected, in fact, by many eugenicists
from 1912, anticipation was used by physicians until the 1960s.
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Keywords
Eugenics, Medicine, Genetics, trinucleotide repeat disorders, Heredity, Biology, Genetic Anticipation, myotonic dystrophy, Huntington's disease, Fragile X, schizophrenia, Psychiatry, trinucleotide repeat expansion disorders, expanding trinucleotide repeats