From “Piss Prophets” to Rabbits A History of the Pregnancy Test

The history of the pregnancy test is a meaningful history embedded in magic, myth, politics, and science. From ancient Egyptian to modern times, the pregnancy test holds a cultural omnipresence that forces women to confront their fertility, femininity, and their future. Today we know that a pregnancy test that detects the human hormone known as human chorionic gonadatropin (hCG) offers the quickest and most accurate result for determining pregnancy. HcG is secreted by the placenta after the fertilized egg implants in the uterus and can be detected in both urine and blood. Urine pregnancy tests are convenient for home use, but a doctor may also opt to test blood as it provides a quantitative hCG number. Both methods are highly accurate and common. Pregnancy tests, however, were not always so accurate or so culturally accepted.
Ancient Egypt Papyri and the First Pregnancy Test
Four thousand years ago, Egyptians developed the first diagnostic test to detect a unique substance in the urine of both women and domesticated animals. Perhaps the most famous Egyptian pregnancy test is the germination test which involves the female urinating onto bags of wheat and barley. The Berlin Medical Papyrus asserts that “if the barley grows, it means a male child. If the wheat grows, it means a female child. If both do not grow, she will not bear at all” (Bayon 1939). When scientists tested this theory in 1963, they found that 70 percent of the time, the urine of pregnant women did promote growth (Tannery 2007). The Berlin Medical Papyrus also suggests that a woman should have her nipples and skin examined for unusual pigmentation, or that she should drink milk from a woman who has borne a son (and if she vomits, pregnancy is confirmed). The Kahun Medical Papyrus, containing 17 fragmentary medical passages, suggests placing a woman in the light of a doorway to determine pregnancy by the color of her skin. It also says to “grasp [a woman’s] fingers in thy hand and grip her arm ...if the veins within her arms beat against thy hand, thou shalt say: she is pregnant” (Bayon 1939). Several of these pregnancy tests reappear in Hippocratic and pseudo-Hippocratic medical practices in various forms.
Hippocratic and Hellenic Schools
Both the Hippocratic (or Coan) and Hellenic pregnancy detection methods are very similar to the Egyptians'. While Hippocratus (460-370 B.C.) may or may not have written the Corpus Hippocraticum, the aphorisms concerning the Greek’s pregnancy tests are considered genuine. As in the Egyptian papyri, one of these aphorisms (Aphorism XLI) suggests giving a woman a type of milky drink (Bayon 1939). Another asserts that a woman is pregnant if there is transference of odor from a perfumed genital wrap to the mouth and nostrils. (Variations of this are also seen in the Talmud.) The Corpus Hippocraticum also contains a section titled “About the Barren Woman,” which discusses various pregnancy tests modified, again, from the Egyptians (Bayon 1939). Hellenic pregnancy tests are essentially identical to Greek practice, and it can be surmised that Egyptian medical practice reached the Romans through Sicilian Greek colonies. Galen (A.D. 129-200 or 216), a prominent physician in Asia Minor (present-day Turkey), accepted the description of Hippocratic pregnancy tests, and his work had a lasting influence on the transference and application of testing in the Middle Ages.
Middle Ages and the "Piss Prophets"
The Middle Ages used perhaps slightly more empirical techniques but, for the most part, pregnancy testing was Hippocratic practice largely stultified by charms and home remedies. Middle Age pregnancy tests can be characterized by an emphasis on urology, or the nonscientific method of visually evaluating urine. Avicenna (981-1031), a Persian Muslim physician, modified the Egyptian germination test by sprinkling sulphur on the urine to see if it would breed worms, and in Europe, physicians who claimed to diagnose pregnancy by the color of urine became know as “piss prophets”(Leavitt 2006). In a 1552 text, pregnancy urine was described as “clear pale lemon color leaning toward off-white, having a cloud on its surface.” Other tests included mixing wine with urine and observing the results. Indeed, alcohol reacts with certain proteins in urine, so this may have had a moderate success rate (Tannery 2007).
Among the many fascinating scholars of this era stands Albert Magnus (1206-1280). His text Secreta mulierum or De secretis mullerium, printed initially at Cologne in 1478 and many times after, says to give a suspected pregnant woman a sweet drink before going to bed; if she complains of pain in the navel in the morning, pregnancy is confirmed. Magnus says that it is important not to tell the woman the purpose of the drink because women are cunning (astutae). In his Deconceptv Et Generatione Hominis et Iis Quae Circa, Jacob Rueff of Zurich modifies Magnus’s test but also adds one of his own. He describes a needle or nettle rusting red or black in a woman’s urine as an indication of pregnancy (Bayon 1553). It is important to keep in mind that during the Middle Ages, physicians thought the body was constituted by the four humors rather than by hormones. Therefore, they would read urine the same way they would read the four natures—by observing how they looked. Still, Egyptian and Greek medical texts are clearly echoed in the Medieval period.
Nineteenth Century Brings Some Progress
Nineteenth century physicians still practiced urology, but tended to bring more rational and scientific approaches to detecting pregnancy. So, “rather than try to determine pregnancy by changes in urine color or how it might mix with alcohol, they focused on the presence of bacteria or crystalline structures as seen through a microscope” (Tannery 2007). While these scholars also studied the actual reproductive systems in more detail, the discovery of hormones was still at least 200 years away. Consequently, for sexually active women, the best method for diagnosing pregnancy remained observing their own physical signs and symptoms. It wasn’t until the late 1800s that physicians began to talk about chemicals or “internal secretions” of certain organs. English physiologist Ernest Starling (1866-1977) named these chemical messengers "hormones".
The 1920s: "The Rabbit Died" Because of Bioassays
After the turn of the century, scientists in several independent European labs began to recognize a hormone that is found only in pregnant woman, which they called hCG. To identify hCG, scientists developed bioassays, or special tests using animals or live tissue. In 1928, German scientists Selmar Aschheim (1878-1965) and Bernhard Zondek (1891-1966) developed the very first bioassay pregnancy test, known as the “A-Z test”, which identified the presence of hCG in urine. To test for pregnancy, a woman’s urine was injected into an immature rat or mouse. In the case of pregnancy, the rat would show an estrous reaction (be in heat) despite its immaturity. This test implied that during pregnancy there was an increased production of the hormone. Maurice H. Friedman (1903-1991) replaced rats with rabbits and would inject urine into the ear veins of a female rabbit (Bayon 1939). If hCG was present, the rabbit ovulated within 48 hours. Unfortunately, the only way to observe this was to kill the rabbit. In the Hogben test developed in 1939, a female African Clawed Toad was injected with urine and if the woman was pregnant, eggs would appear. The bioassay tests were expensive, required the sacrifice of an animal, and were slow, often taking days to get results. The tests were also insensitive when measuring hormone levels to diagnose pregnancy because of the similarity between hCG and another substance, luteinizing hormone (LH). Most bioassays were in fact unable to distinguish between the two hormones except at extraordinarily high rates of hCG (Vaitukaitis 1972).
1960 and the Immunoassay
In 1960, L. Wide and C. A. Gemzell developed the first immunological pregnancy test. Because it used antibodies rather than animals or live tissue in the testing process, this test was an immunoassay rather than a bioassay. The test used purified hCG mixed with a urine sample and antibodies directed against the hCG. In a positive pregnancy test, the red cells clumped, displaying a particular pattern. This test was much faster and cheaper than the old bioassays, but still relatively insensitive, especially for early diagnosis of pregnancy. The problem with this kind of test is that some substances in the urine can give a false-negative or a false-positive test (Viatukaitis 1972). In 1970, the Wampole immunoassay test became available to physicians but it also required test tubes, syringes, and other items that made it unsuitable for home use.
1970 and the Radioimmunoassay
Most doctors in 1970 used the Wampole test, but that was about to change. In the early 1970s, National Institute of Health (NIH) scientists who were working on finding a tumor marker for certain cancers in which hCG was secreted discovered a new method for pregnancy testing. One of the researchers, Judith Vaitukaitis, found that what made hCG different from LH and other hormones was its “beta subunit.” By creating an antibody specific to that subunit, they could develop a test that not only accurately confirmed pregnancy but also identified precise levels of hCG. This was called radioimmunassay. The results were published in the American Journal of Obstetrics and Gynecology in 1972 and immediately became public, paving the way for home pregnancy tests.
Home Pregnancy Tests: From Novelty to Norm
Warner-Chilcott's e.p.t. test would be the first on the market at the end of 1977 and sold for about $10. Still, a woman was required to mix her urine with solutions using test tubes, and the procedure was rather complex, requiring a few hours for the result to appear. Accuracy rates were still questionable and false-negative results were relatively common. With improvements during the 1980s and 1990s, soon the "home chemistry" mixing-mess was replaced with one-step formats in which the test could be contained on a single “strip” on a handheld applicator. Urine would be absorbed through the anti-hCG antibodies and across a control line (color band) that would appear if the test was used properly (Tannery 2007). Different symbols (plus-sign, line, etc.) in the test area of the strip would indicate a result with 10 minutes or so. Newer tests could detect pregnancy around eight to ten days after a woman ovulates.
The home pregnancy test brought about what Susan Leavitt calls the “private little revolution,” but this little revolution was not universally applauded. As a state official insinuates in a 1978 Consumer Report, “There is no reason to buy the e.p.t unless [a woman] doesn’t want to be seen at the health department” (Leavitt 2006), suggesting that only immoral women with something to hide would need a home test. Before Roe vs. Wade, the test was associated with illegal abortion clinics, known as “Jane” in Chicago, or radical groups in California who organized trips to Mexico for abortions. Pharmacy companies tried to change this image by arguing that home pregnancy tests would be a positive addition to the health care field by increasing early prenatal care. Advertisements also started to focus on the pregnancy test as the focal point of a joyful family event.
Today, women have a wide array of testing options. The beginning of the twenty-first century saw digital pregnancy tests along with clinical-style testing strips that are both highly accurate and affordable. Not surprisingly, home pregnancy tests show no sign of going away soon. The privacy, accuracy, and speed of the tests, as well as the rise in expensive fertility treatments and anxious women who have been delaying pregnancy to work, have led to a rapid increase in sales (Leavitt 2006).

-- Posted December 10, 2007

References
Bayon, H.P. 1939. Ancient Pregnancy Tests in Light of Contemporary Knowledge. Proceedings of the Royal Society of Medicine. XXXII:1527-39.
Leavitt, Sarah A. 2006. A Private Little Revolution: The Home Pregnancy Test in American Culture. Bulletin of the History of Medicine. 80.2:317-45.
Tannery, Allison. 2007. A History of the Pregnancy Test or Is the Rabbit in Heat? Accessed: November 18, 2007.
Vaitukaitis, J.L., G. D. Braunstein, and G. T. Ross. 1972. A radioimmunoassay which specifically measures human chorionic gonadotropin in the presence of human luteinizing hormone. American Journal of Obstetrics and Gynecology. 113:751-8.