Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient IQ in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.

Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess intake of vitamin A and retinoids by pregnant women often results malformations to fetuses' skulls, faces, limbs, eyes, central nervous system. Additionally, doctors often use derivatives of vitamin A, known as retinoids, as medicine to treat a number of skin conditions and carcinomas, the most common form of human cancers.

Thalidomide, a drug capable of causing fetal abnormalities (teratogen), has caused greater than ten thousand birth defects worldwide since its introduction to the market as a pharmaceutical agent. Prior to discovering thalidomide's teratogenic effects in the early 1960s, the US Food and Drug Administration (FDA) did not place regulations on drug approval or monitoring as it later did. By 1962, approximately 20,000 patients in the US had taken thalidomide as part of an unregulated clinical trial before any actions were taken to stop thalidomide's distribution. Due to thalidomide's effects on fetuses, both nationally and abroad, the US Congress passed the 1962 Kefauver-Harris Amendments to the 1938 Food, Drug, and Cosmetic Act. These amendments imposed guidelines for the process of drug approval in the US and required that a drug be safe as well as effective before it could be approved and marketed. Thalidomide also influenced the FDA's creation of pregnancy categories; a ranking of drugs based on their effects on reproduction and pregnancy. Thalidomide motivated the laws on regulating and monitoring drugs developed in the US and by the FDA in the twentieth and twenty-first centuries.

This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.