Teratology as an empirical science has been around for millennia and encompasses the study of abnormal structural development. Conjoined twins have been depicted in marble statuary dating to 6500 BC (Warkany, 1983), and Egyptian wall paintings of human cleft palate and achondroplasia date to 5000 years ago. The origin of mythological creatures including the Cyclops and sirens may have been observations of malformed infants (Thompson, 1930; Warkany, 1977). Hippocrates and Aristotle thought that physical agents such as uterine trauma or pressure could cause birth defects. Aristotle also believed that maternal impressions and emotions could affect the developing fetus, and advised pregnant women to gaze at beautiful art to enhance their child's beauty. This idea is historically present in diverse cultures, and we now understand that maternal stress or depression during pregnancy can be deleterious (Dunkel Schetter and Tanner, 2012).
In the 16th and 17th centuries, scientific theories of causation of birth defects emerged. In 1651, William Harvey expounded the theory of developmental arrest, which posited that malformations resulted from incomplete structural development. An example was “harelip,” a congenital malformation in humans that represents a normal but usually transient embryonic stage. In the early 19th century, Saint-Hilaire produced malformed chick embryos by subjecting eggs to physical trauma or toxic exposures. Later in the 19th century, Dareste produced various malformations in chick embryos using chemical and physical agents including heat shock. Dareste found that timing was more critical than the type of insult in influencing the type of defect that resulted (Dareste, 1877, 1891). Many of the great embryologists of the 19th and 20th centuries, including Loeb, Morgan, Driesch, Spemann, and Hertwig, performed teratological experiments using various physical and chemical probes to deduce principles of normal development.
With the rediscovery of Mendel's laws in 1900, it was accepted that some birth defects were hereditary. Bateson (1894) studied animal variations as a means to elucidate evolution, suggesting that inheritance of variations was a means of speciation. He described human birth defects including polydactyly and syndactyly, supernumerary cervical and thoracic ribs, duplicated appendages, and fused kidneys. A genetic basis of birth defects was further supported by studies of inborn errors of metabolism in the early 20th century.
In the 1920s through 1940s, a variety of environmental conditions and exposures were proven to perturb development in avian, reptilian, ﬁsh, and amphibian species. Yet, at that time, mammalian development was thought to be protected from environmental conditions by the mother's body. That idea was refuted when Hale (1935) produced anophthalmia, cleft palate, and other malformations in offspring of pigs by feeding a vitamin A deficient diet. Beginning in 1940, Josef Warkany and co-workers performed a series of experiments demonstrating that maternal dietary deﬁciencies and other environmental factors could perturb intrauterine development in rats (Warkany and Nelson, 1940; Warkany and Schraffenberger, 1944; Warkany, 1945; ...