Embryo Project Encyclopedia Articles

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

The United States Food and Drug Administration, or FDA, published 'General Considerations for the Clinical Evaluation of Drugs,' in September 1977. The document defined acceptable practices for investigators who studied new drugs. Specifically, the document outlined the common clinical trial methods. Clinical trials are studies to test whether a new drug is safe before doctors can prescribe it to patients. Prior to 1977, the Protection of Human Subjects Rule primarily regulated clinical drug trials, but it did not specify who could and could not be included in clinical trials. In the document, the FDA recommended that anyone who could become pregnant be excluded from early-phase clinical trials to minimize risks to a potential fetus. After the FDA published the document, investigators excluded women from clinical trials. The document ultimately prevented women of reproductive capacity from participating in early phase clinical trials, which affected women’s health research.

Charles Knowlton was a physician and author who advocated for increased access to information about reproduction in the nineteenth century in the US. Throughout his early medical education, Knowlton was particularly interested in anatomy and on several instances robbed graves for bodies to dissect. In 1832, Knowlton authored The Fruits of Philosophy, a pamphlet that contained detailed descriptions of the reproductive organs and information on conception and methods to control reproduction. Knowlton circulated his work among his patients until it was republished in Boston, Massachusetts, in 1832. For publishing a book on sex and methods of birth control, Knowlton was convicted of breaking obscenity laws, which prevented the transmission of obscene materials. After his death, social activists Charles Bradlaugh and Annie Besant republished his work in London, England. Knowlton’s writing about sex and birth control allowed individuals to understand and take control of their reproduction and initiated a public discussion about obscenity laws.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.

Sidney Q. Cohlan studied birth defects in the US during the twentieth century. Cohlan helped to discover that if a pregnant woman ate too much vitamin A her fetus faced a higher than normal risk of teratogenic effects, such as cleft palate. A teratogen is a substance that causes malformation of a developing organism. Cohlan also identified the teratogenic effects of several other substances including a lack of normal magnesium and prenatal exposure to the antibiotic tetracycline. Cohlan's experiments with vitamins and other chemicals brought attention to how nutrition and environmental agents adversely affect human pregnancy outcomes.

In 1993, the NIH published the Revitalization Act that established guidelines for minorities’ and women’s participation in clinical research. Before the 1990s, investigators largely excluded women from their research based on the 1979 guidance from the US Food and Drug Administration, or FDA. The FDA urged investigators to exclude any woman who was or could become, pregnant to protect the woman and any developing fetuses from harm. Between 1979 and 1993, several other US governmental agencies urged investigators to increase the number of women in their clinical research to improve the state of women’s healthcare. After Congress passed the National Institutes of Health Revitalization Act, hereafter Revitalization Act of 1993, investigators who used NIH funds for clinical research were required to include both women and minorities in their clinical research. The Revitalization Act established the Office of Research on Women’s Health headquartered in Washington, DC and required investigators to include women in their clinical research, thus improving the quality of women’s health research.

Annie Wood Besant was a social activist who advocated for women’s access to birth control as well as marriage reform, labor reform, and Indian Nationalism in the nineteenth century in England and India. In her early career, Besant was involved in various social and political advocacy organizations including the National Secular Society, the Malthusian League, and the Fabian Society. Besant gave many public lectures and authored various articles in support of secularism, workers’ rights and unionization, and women’s rights. In 1877, Besant and her colleague Charles Bradlaugh republished the pamphlet The Fruits of Philosophy, by Charles Knowlton, on reproduction and contraception. Besant and Bradlaugh were tried for violating the obscenity law that prohibited the publication of obscene material, including sex and contraception. Later in her life, she converted to theosophy and moved to India where she joined the Theosophical Society. In India, Besant campaigned for Indian self-rule and became the president of the Indian National Congress. Besant, through republication of The Fruits of Philosophy and many public lectures and writings on women’s rights, expanded public knowledge of birth control.

Charles Bradlaugh was as a political and social activist in the seventeenth century in England. He held leadership positions in various organizations focused on social and political activism including the Reform League, the London Secular Society, the newspaper National Reformer, and the National Secular Society. Throughout his career, Bradlaugh advocated for better conditions for the working poor, and for the separation of government and religion. The British government prosecuted him numerous times for violating laws prohibiting the publication, sale, and transmission of antireligious, antigovernment, and obscene materials. In 1877, Bradlaugh and another secularist, Annie Besant, republished The Fruits of Philosophy, a pamphlet about contraceptive techniques originally whose author was physician Charles Knowlton. In the nineteenth century, individuals did not have access to information on sex, reproduction, and contraception, as much of society argued such information encouraged immoral behavior. Bradlaugh and Besant were tried for publishing information on sexual anatomy, conception, and methods to control reproduction. Bradlaugh expanded public knowledge of reproduction and contraception, and initiated the process of dismantling the obscenity laws.

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.