Developmental Toxicology: 2. History

1
Developmental Toxicology2. History
2
Embryology

• 1885 Wilhelm Roux
• Experimental embryology using amphibians
• 1915 Bridges Morgan genetics of development
• Homeotic genes in Drosophila
• antennaepedia
• 1924 Spemann, Mangold
• Looking for the embryonic organizer
• How is cell fate decided?

3
Early Embryology

• Plato 427-347 BC
• Socrates 384-322 BC
• stages of chick development
• Renaissance
• Volcher Coiter, 1514-176
• chick embryology
• William Harvey 1578-1657
• all animals from eggs
• Anton von Leeuwenhoek 1632-1723
• homunculi in semen
• Caspar Wolff 1738-1794
• morphogenesis
• Friedrich Blumenbach 1742-1840
• vitalism
• Ernst Haeckel 1834-1919
• Ontogeny recapitulates phylogeny.
• Oscar Richard Hertwig (1849-1937)
• observed fertilization in sea urchins

4
Wonders and Monsters

• Pliny the Elder
• The Odyssey
• Tablet of Nineveh, ca 2000 BC
• When a woman gives birth to an infant
• That has no mouth, the mistress of the house will
  die.
• Whose upper lip overrides the lower, the peoples
  of the world will rejoice.
• That has?no right hand, there will be
  earthquakes.

5
Malformations in Art
Velasquez Las Meninas
6
Experimental Embryology

• Experimental embryology
• Wilhelm Roux, 1850-1924
• amphibian embryos
• totipotency
• Hans Spemann and Hilde Mangold
• The dorsal lip of the blastopore and the
  embryonic organizer
• Thomas Hunt Morgan and Calvin Bridges
• Homeotic genes in Drosophila melanogaster

7
Developmental Toxicology --Major Eras

• Experimental embryology 1885 to 1935
• Academic teratology 1935 to 1961
• Warkany
• Wilson
• Tuchmann-Duplessis and aminopterin
• Fraser, Kalter, and genetics
• Regulatory teratology 1961 ----gt
• thalidomide
• Developmental biology 1985 ----gt

8
Academic Teratology

• 1935 Hale - Australian veterinarian
• Pigs without eyeballs
• 1st example of environmental causes of birth
  defect
• 1930s Gregg - Australian ophthalmologist
• Rubella causes birth defects
• 1940s Warkany - experimental teratology
• Dietary deficiencies cause birth defects in
  rodents
• 1940s Radiation causes microcephaly
• 1950s Fraser Fainstat
• Genetics environment interact
• Cortisone-induced cleft palate

9
An In-between Time

• 1950s Aminopterin-induced malformations
• 1961 Lenz identifies thalidomide as teratogen
• 1964 Mintz chimeric mice
• 1984 Grosschedl 1st transgenic mouse
• 1984 McGinnis and Gehring The homeobox
• 180 base pair sequence common to homeotic genes
• 1984 Homeobox found in vertebrates
• 1984 ---gt present Golden age of developmental
  biology