Teratology as a science was born in the 1920s and 30s, when the birth of malformed piglets from mothers fed an experimental diet high in fat or deficient in vitamin A elicited the shocking realization that the conceptus was not, as had been believed, in a privileged and highly protected position when within the mother’s ‘impervious womb,’ but was susceptible to environmental conditions with potentially serious effects. All of these piglets suffered a variety of malformations, predominantly, lack of eyes. [3]
Subsequent evidence came to light over the next two decades and a correlation was estabilished between children born with birth dfects and maternal Rubella infection in 1941 and with environmental mercury contamination in 1956.[3]
James Wilson originally proposed a set of "Principles of Teratology" in 1959, the year before he helped to found the Teratology Society. Wilson's principles were formulated after thalidomide tragedy. They become a fundamental for teratological studies with drugs and other factors that may disturb fetal development. By 1977, these Principles were presented in a more definitive form in Wilson and Fraser's Handbook of Teratology. Wilson's Principles have continued to guide scientific research in teratology, and they are widely used in teaching. Recent advances in our knowledge of the molecular and cellular bases of embryogenesis serve only to provide a deeper understanding of the fundamental developmental mechanisms that underlie Wilson's Principles of Teratology.
It is postulated that susceptibility to teratogen depends on the genotype and developmental stage of the conceptus. Teratogenic agents act in specific manner on developing cells and tissues. The exposition depends on the agent's nature and availability. Manifestations of deviant development depends on the dosage and exposure frequency. In case of abnormal development the final manifestations include death of embryo or fetus, malformation, growth retardation and functional disorder.[5] Wilson's Principles have continued to guide scientific research in teratology, and they are widely used in teaching.
- Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
- Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. There are critical periods of susceptibility to agents and organ systems affected by these agents.
- Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
- The access of adverse influences to developing tissues depends on the nature of the influence. Several factors affect the ability of a teratogen to contact a developing conceptus, such as the nature of the agent itself, route and degree of maternal exposure, rate of placental transfer and systemic absorption, and composition of the maternal and embryonic/fetal genotypes.
- There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
- Manifestations of deviant development increase in frequency and degree as dosage increases from the No Observable Adverse Effect Level (NOAEL) to a dose producing 100% Lethality (LD100).[4]
 .jpg) Pictures of babies affected by Thalidome during the 1960s. | The Thalidomide Tragedy of the 1960sThalidomide was one of the greatest cases in history of a drug disaster tragedy being caused by animal research.Thalidomide was a widely used drug in the late 1950s and
early 1960s for the treatment of nausea in pregnant women. It became apparent
in the 1960s that thalidomide treatment resulted in severe birth defects in
thousands of children. Though the use of thalidomide was banned in most
countries at that time, thalidomide proved to be a useful treatment for leprosy
and later, multiple myeloma. [6] In fact when the link between human foetal abnormalities and
thalidomide was established (through clinical observation), the world-wide
explosion of animal testing, using a large range of species, proved very
difficult to duplicate the abnormalities. The massively increased use of test animals following the
thalidomide tragedy only served to dupe the public, encouraging it to keep
consuming animal tested drugs.[7]
|
