by Kelsey Tyssowski
figures by Olivia Foster
Let me look at your pee, and I’ll tell you your future.
For over 3000 years, women wondering if they’ll be mothers have heard some variation of this phrase. In the first known pregnancy tests, ancient Egyptian women urinated on barley or wheat seeds: quickly sprouting seeds indicated pregnancy. While this may sound like pseudoscience, several modern studies have shown that it works pretty well, correctly identifying 70-85% of pregnancies.
The ancient Egyptians were certainly onto something, as modern pregnancy tests work in much the same way: they detect a hormone in urine. But it’s still taken thousands of years of scientific progress to get us from peeing on seeds—and waiting a week to see if they sprout—to the fast, convenient pregnancy tests found in all pharmacies today.
“Piss Prophets”: Early history of the pregnancy test
Although it’s not intuitive that analysis of urine would be the key to pregnancy detection, most historical pregnancy tests have, for unknown reasons, focused on just that (Figure 1). In Europe, starting in the Middle Ages, “Piss Prophets” claimed to be able to predict pregnancy with a variety of bizarre urine tests. They believed that pregnant women’s urine would rust a nail, change the color of a leaf, or be home to tiny, living creatures. Based on what we know today, it’s unlikely that any of these tests were actually able to correctly detect pregnancy.
However, the first of the modern tests that could accurately detect pregnancy was no less bizarre. This test was developed in 1927 by German scientists, Aschheim and Zondek. They found that injecting a pregnant woman’s urine into sexually immature female mice would cause the mouse’s ovaries to grow and produce eggs.
What’s so Special About Pregnant Women’s Urine?
If you’re like me, you’re now left with a burning question that you probably weren’t expecting to ask today: why does a pregnant lady’s pee make a juvenile mouse ovulate?
The short answer is that the urine of pregnant women has a unique blend of hormones (Figure 2). A woman (actually, anyone with a uterus, though throughout the article I’ll refer to women) becomes pregnant when an egg released from her ovary is fertilized by sperm. This fertilized egg then starts growing into an embryo and releases a hormone called hCG (a.k.a. human chorionic gonadotropin), which builds up in a woman’s body during early pregnancy. Like all hormones, hCG sends a signal. hCG’s particular job is to tell the uterus to stop the woman’s regular menstrual cycle and prepare itself for pregnancy.
Since hormones are excreted into the urine after they’re done sending their signals, the urine of pregnant women has hCG in it, whereas the urine of anyone who is not pregnant does not. hCG, it turns out, makes mice ovulate, allowing Aschheim and Zondek’s test to detect pregnancy. Since the invention of this test, all modern pregnancy tests have focused on detecting hCG.
But why does hCG make young mice ovulate? hCG is very similar to another hormone called luteinizing hormone. In humans and in mice, luteinizing hormone stimulates the ovaries to release an egg every month of the menstrual cycle, and hCG can mimic that signal. Aschheim and Zondek’s test worked because the level of hCG in the urine of pregnant women is much higher than that of luteinizing hormone in non-pregnant, ovulating women: there’s never enough luteinizing hormone in urine to make a mouse ovulate.
Mice, Rabbits, and Frogs: Animal-based pregnancy tests
Although Aschheim and Zondek had developed an accurate test, it wasn’t exactly simple, especially compared to the drug store tests available today. They had to inject five mice per woman and wait about a week before getting the result. And even then, they could only detect the high levels of hCG that women have starting around 2 weeks after a missed period. In addition, the use of so many animals made it so that the test was expensive and relegated it to a few labs that received shipments of urine through the mail.
Today, women can know that they are pregnant as soon as 10 days after conception—a few days before a missed period—using tests they can buy for less than $10 in any drug store. But up through the 1930s, women had to wait until at least a month after conception, visit a doctor, mail her urine to a lab, and then wait at least another week to get the result of the test. Unsurprisingly, pregnancy testing in this era was not routine, used only by those who were wealthy or needed to know if they were pregnant for medical reasons.
The juvenile mouse test was slightly improved in 1931 by an American doctor, Maurice Freidman, who swapped juvenile mice for adult rabbits, which were easier to inject.
However, a test using frogs, developed the British scientist Lancelot Hogben, marked the pinnacle of these animal tests. Frogs lay eggs, so they don’t need to be killed or dissected to assess ovulation and could therefore be reused, lowering test costs. This test also gave results faster: within twelve hours. The frog test increased the availability of pregnancy testing, but it still required shipping urine to a select number of frog labs.
Tens of thousands of frogs were injected with urine throughout the 1940s-1960s, but pregnancy testing in this era was still not the norm. Most labs would only test urine sent by a doctor, meaning that women had to rely on their doctors to get tested. And many doctors—and health insurance companies—would only grant a woman a test if she had some urgent medical reason that she needed to know she was pregnant. Most women instead relied on morning sickness and sore breasts as early clues to their pregnancy, not visiting a doctor to confirm until months after conception.
Blood and Test Tubes: The pee-on-a-stick precursors
This all changed in the 1960s when scientists began to develop pregnancy tests that didn’t require the use of live animals and could therefore be done in doctor’s offices. At first, these tests had similar sensitivity for hCG, but by the early 1970s, Drs. Vaitukaitis, Braunstein, and Ross had developed a test that could detect pregnancy just 2-3 weeks after conception—on the first day of a missed period. These new tests used antibodies.
Antibodies are molecules that recognize and stick to other molecules. In their usual job, they’re sticking to the molecules of bacteria or viruses to alert the immune system to these invaders. In pregnancy tests, however, scientists engineered antibodies that recognized and stuck to hCG. Armed with these hCG antibodies, the urine of pregnant women, and, strangely enough, sheep’s blood, we had a new pregnancy test.
To perform the test, scientists attached hCG to the outside of the sheep’s blood cells, decorating the blood cells with hCG. They then mixed these blood cells with the other test components: hCG antibodies and urine.
Based on the way that antibodies stick to hCG and to each other, the hCG-decorated blood cells would clump if they were mixed with the urine of a woman who was not pregnant. On the other hand, if the blood cells and hCG antibody were mixed with the urine of a woman who was pregnant, the blood cells would not clump. So by looking at the clumpiness of the blood cells, doctors could tell if a woman was pregnant (Figure 3).
These and other, similar antibody-based tests could give doctors results in a few minutes to hours and finally made pregnancy testing mainstream. At first, women still had to visit their doctor to get a pregnancy test.
But that, too, changed in the 1970s (1971 in Canada, 1977 in the US) when the first at-home pregnancy test hit the market, using this same blood-and-antibody technology. This test looked like a kid’s chemistry kit, including test tubes, droppers, dried capsules of sheep’s blood cells, and hCG antibody serum. Success in completing the test required carefully following a 10-step process all while keeping the test tubes in a place free from vibrations for two hours. But if used correctly, it was 97% accurate for a positive result and 80% accurate for a negative one. And for the first time, a woman could confirm that she was pregnant without ever contacting a doctor.
Pee on a Stick: The birth of the modern pregnancy test
Since the 1970s, at-home pregnancy tests have become the norm, with about 20 million sold per year in the US alone. Current stick tests, which were developed in 1988, are much easier to use, don’t involve sheep’s blood or test tubes, and are still extremely accurate: about 99% for a positive result. But they are doing the same thing we’ve been doing for thousands of years: detecting hormones in women’s urine. Modern pregnancy tests still use hCG antibodies, but instead of interacting with hCG-decorated blood cells, the antibodies interact with dye-activating molecules. These dye-activating molecules are what causes the blue line, or other symbol, to appear on positive pregnancy tests.
Women today usually find out that they’re pregnant just after (and sometimes before) missing a period in the comfort of their own bathroom without the involvement of a doctor. But as recently as the 1950s, women could not definitively confirm pregnancy until they started to noticeably gain weight or feel the fetus move—several months into the pregnancy. And until the 1970s, women relied on doctors to tell them that they were pregnant.
The development of the pregnancy test was not just a feat of scientific advance, but also allowed for a cultural revolution. The at-home pregnancy test became available a time when women were fighting back against the male-dominated medical establishment, trying to learn more about their health and their bodies. And it granted women more information about and control over their bodies. Women could use this information as they liked, without pressure from a doctor: they could decide for themselves to get a safe, early abortion or start prenatal care.
As a woman who is grateful for this cultural advance, I want to say thanks to the first person who thought, “I bet I can tell if she’s pregnant by looking at her pee.”
Kelsey Tyssowski is a graduate student in the Department of Genetics at Harvard Medical School. She is also a former editor-in-chief of the SITN Blog. You can find her on Twitter: @kelseytyss.
For more information:
- A Thin Blue Line: a pregnancy test history put together by the NIH
- An academic article about the science and culture of animal-based pregnancy tests
- An excellent, but hard-to-access, academic review article about the history of the pregnancy test, and a less-descriptive, but similar, open-access article
- An article in The Atlantic that describes the history of the pregnancy test from a more historical perspective
- A video explaining the science behind modern pregnancy tests
24 thoughts on “Pee is for Pregnant: The history and science of urine-based pregnancy tests”
I was told that during war time pregnate women’s urine was collected and used in the production of aspirin, is there any truth to this? Since there was shortages of many things people would get creative and find alternative choices that would give acceptable results. This would of been in the Montreal Quebec area or surrounds.
Woman’s urine doesn’t have the ingredients to become aspirin. from what I have read.
Aspirin is easily derived from the bark and branches of the Willow (Salix )
“…Willow, shrubs and trees of the genus Salix, family Salicaceae, mostly native to north temperate areas and valued for
… . Salicin, source of salicylic acid used in pain relievers, is derived from certain willows. All species have …”
“Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated.”
Native Americans historically drank willow bark tea (tisane) to relieve headaches.
i am unaware of this, it may have been used as a home remedy but who knows. may people would boil willow bark and make a tea to obtain ASA. chemical component of asprin
thanks for sharing this interesting info
Just watching the comedy series “The Great” and wanted to know if there was any truth in the series use of wheat stems to determine if a woman was pregnant… interesting to read that there is… although it clearly won’t sprout flowers immediately as in the series!
I also watched the series “The Great” and landed here – HUZZAH!
HUZZAH! AND THEN GLASS SMASHING 😉
Huzzah! Science! 😊
I have been injected with a pregnant womens pee n lost 30 pounds, now im lookin for a doctor that does it.
Dunno where you can get pregnant human pee for injection, but have you heard of the hormone medication “PREMARIN”?
is the source, according to a show I watched in my teens….
“Women could use this information as they liked, without pressure from a doctor: they could decide for themselves to get a safe, early abortion or start prenatal care.” The development of science can make people’s living better, especially for women and children.
More information about Pregnancy in Vietnamese: https://youmed.vn/tin-tuc/tips-suc-khoe/mang-thai/
I used the very first version of the “One Step” urine test when I was 18 years old and just graduated from high school. I remember that it took a long time, like hours I think. You had to look in this plastic box like thing and it had a small tube of a few drops of urine and something that reacted when the urine was added, then formed a brown ring or circle. I lived a half hour from the nearest Planned Parenthood Agency where you could get a confidential pregnancy test. In those days your parents kept pretty close tabs on you and my mother saw the charge for the long distance charge when I tried to call for an appointment. I lied and to her I called for my cousin, then bought the One Step. It was accurate. My first baby is now 41 years old an RN and a grandma!
Still I haven’t understood that, How Egyptians used to know whether the baby is boy or girl by the help of pee of pregnant women?
because they believed if the barley spouted it was a boy and wheat for a girl. It’s not true – they both will sprout for either sex, but they will sprout.
So how are plants affected by regular urine vs hcg containing urine? Can urine with hcg be used to imrove plant growth? Like natural fertilizer?
Woah very good blog and very informative. I absolutely love this site. Thanks!
Well researched and written! Glad to read what was happening behind the shocking headlines
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In the Middle Ages the mid wife induced an abortion by feeding the women fermented , mouldy rye . Sometimes the woman would abort ,sometimes she would die . Fermented rye causes the uterus to contract. It’s ergot ,which can cause hallucinations , uterine contractions ,and death
The development of science can make people’s living better, especially for women and children.
Signs of a successful pregnancy can appear as early as 1 week after conception or a few weeks after the missed period. Specific signs of pregnancy often include:
Missing your period is a common and relatively accurate sign of pregnancy. However, other reasons such as stress, being overweight or medical conditions like Polycystic Ovarian Syndrome can also cause missed periods.
Breasts that are softer or more sensitive than usual are an early sign of pregnancy. However, it can be a symptom of PMS or breast problems.
An elevated basal temperature can be the first sign of pregnancy, right before a positive pregnancy test. Basal temperature is the temperature upon waking and is not affected by hormones or daily activities.
More : https://vietmecgroup.com/me-va-be/co-dau-hieu-mang-thai-nhung-thu-que-1-vach
Good post. Science can make living better!
Thanks for the sharing!
The development of science can make people’s living better, especially for women and children.