Teratogen

Teratogens are substances that produce neurological and physical malformations in developing human fetuses. The word comes from the Greek teras, meaning "malformation" or "monstrosity." Certainly, ever since the first malformed baby was born, people have wondered what causes birth defects. Most early explanations referred to mystical forces: the influence of celestialbodies, divine intervention, even conception during the woman's menstrual period. The theory of maternal impression was widely accepted from the seventeenth to the early twentieth centuries. According to this concept, a specific, strong impression on the mother during pregnancy would produce a corresponding specific birth defect in her child; for instance, a mother who was startled by a hare might give birth to a child with a harelip.

During the nineteenth and early twentieth centuries, however, a number of researchers showed that exposure of animals (such as chickens and fish) to certain physical and chemical substances would produce birth defects in their offspring. While a few medical investigators conducted studies that showed similar effects in mammals, the scientific community as a whole embraced the concept that a woman's placenta acted as an impenetrable barrier preventing harmfulsubstances from reaching the unborn child. This belief was shattered by thethalidomide tragedy.

Thalidomide, a synthetic developed by Chemie Grunenthal, was hailed as a "wonder drug" which enduced a sound sleep with no hangover effect the following morning and no fatal effects in overdose cases. Its use spread rapidly acrossCanada and Europe after its introduction in West Germany in 1958, and was considered so safe it was dispensed over the counter rather than by prescription. In 1959, twelve infants were born in West Germany with severe deformities--a very rare condition called phocomelia, in which the arms and legs developedinto stubs resembling a seal's flippers. No link to thalidomide was considered, even after 83 more cases were reported in 1960. (Cases of such birth defects eventually climbed to 5,000 in Germany and 10,000 worldwide.)

In September 1960, the American drug firm William S. Merrell submitted to theFood and Drug Administration (FDA) an application to market thalidomide in the United States. The application, considered routine, was given to anew FDA employee, Dr. Frances Kelsey (1914-), who was expected to approve it within the usual sixty days. Kelsey, however, became concerned about some of the effects of thalidomide, repeatedly postponing approval while asking Merrell for further information. Meanwhile, cases of phocomelia continued to mount in Europe. Finally, in November 1961, a Hamburg pediatrician named Widukind Lenz, established that the mothers of many of the infants with severebirth defects at his clinic had taken thalidomide. The link was confirmed byDr. William McBride in Australia and, by the end of November, thalidomide waswithdrawn from the market. Early in 1962, Dr. Helen Taussig of Johns HopkinsUniversity, traveled to Europe to investigate the phocomelia situation and,upon her return, she publicly warned American physicians about the dangers ofthalidomide and urged the FDA to ban the drug. Media publicity galvanized public opinion, and a new, landmark law was passed in 1962 mandating much stricter procedures for testing and marketing all drugs. (Bendectin, an antinausea drug also marketed by Merrell, was voluntarily withdrawn by the firmfrom the market following several lawsuits claiming the drug caused birth defects, even though scientific evidence at the trials and subsequent laboratorytests could not confirm this.)

However, with dramatic proof of the potential effects of teratogens, investigations exploded and a wide variety of substances have now been shown to havethe ability to produce birth defects. These include cocaineand crack cocaine--which cause severe problems including premature birth, low birth weight,physical defects, death at birth, and babies addicted at birth; alcohol--which can cause Fetal Alcohol Syndrome, mental retardation, and other defects; hormones (testosterone taken during pregnancy results in male genitalia on a female baby); doses of vitamin A above 8,000 IU per day and vitamin Aderivatives such as isotretinoin and etretinate cause multiple congenital malformations; and many other substances including--but certainly not limited to--central nervous system-active drugs, aspirin,caffeine, cigarette and other types of smoke, food additives, pesticides, herbicides, toxins in the workplace, and viruses such as rubella Virtuallyall drugs, including illegal, prescription, and over the counter drugs, haveteratogenic possibilities. Researchers have found that damage depends upon the stage of pregnancy during which the fetus is exposed to the teratogen, duration of exposure, and the nature of the substance. For the first two weeks,the developing embryo is relatively impervious to teratogens; from then untilthe end of the second month, the rapidly developing organs and body parts are vulnerable to severe malformations from exposure to harmful substances; after that, teratogens can interfere with fetal growth, body function, and braindevelopment.

In the early 1990s concerns were raised about the effect of teratogens on sperm. Studies have linked fathers' exposure to a number of substances--especially lead, pesticides, organic solvents, and heavy metal fumes--to birth defects in their offspring. Research continues in this area.

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