The Prophet and the Frog: A short history of pregnancy testing
What did people use to uncover conception before they peed on test sticks? Why, they peed on plants, in jars, and in animals, of course!
Pregnancy has always been a big deal, and finding out whether or not you were pregnant was a useful fact to know. Unfortunately, for the longest time humans lacked the necessary science to prove a woman’s body was with child by methods other than visual. This naturally left much to be desired.
Fortunately, people weren’t that off base when it came to understanding their bodies. They correctly surmised that the answer lay in a woman’s urine millennia before we could prove it, even if all they had going for them was what we would today characterize as folk medicine and superstition. Armed with their ways, the methods they came up with were downright silly and strange, but also ingenious and inventive.
The Ancient world: Egypt
An ancient Egyptian lady had many different and relatively easy options. One text calls upon a woman to be laid on the ground and be given sweet beer. Should she vomit, she was pregnant. The amount of times she vomited told her how many children she would bear. Owing to the damage to the medical papyrus in question, other ingredients (experts suspect a ‘potion’ of various and probably vile ingredients was used) may have been involved, so we shouldn’t jump to conclusions that the Egyptians habitually encouraged potentially pregnant women to drink until their bodies couldn’t take it anymore.
Later on, during the Middle Kingdom around the halfway mark of the second millennium BCE, things had improved to the point where an inquirer simply sprinkled a flask or bag filled with a mix of dates, grains, and sand with urine and noted if the grain grew. Easy. Doubly helpful was the tests compatibility with male urine in determining if he was sterile or not.
A third method was to place a clove of garlic inside a woman’s vagina and see if her breath smelled the next morning. The ancient Egyptians believed the birth canal connected to the esophagus, and so the logic went that a fetus in the belly would block the passage of any aroma. Hence, garlic breath indicated there was no blockage, hence no baby, and all involved could breathe easily.
The basic rubric of examination of plant or cereal growth watered by urine wasn’t limited to the ancient Egyptians. It was widely practiced around the Mediterranean and beyond by many different peoples. For example, the renowned Roman physician Galen (a pretty influential guy that was ancient medicine’s answer to Aristotle) outdid the accuracy of the Egyptians by claiming to be capable of not only predicting pregnancy but the sex of the baby. All it required was urinating in two holes, each seeded with either barley or wheat, and seeing what grew first: barley signaled a boy, and wheat predicted the girl. If neither sprouted, the woman wasn’t pregnant. What happened if twins were on the way? What if both grew? What if it happened that neither grew but a baby still came out? Awkward.
Urine played a prominent role through the middle ages and the early modern period when it came to diagnosing physiological conditions. Uroscopy, or the study of urine, became an elaborate process practiced in medieval Europe and the Middle East, even as its history stretched back millennia. Very bright people wrote legitimate texts on the topic, no doubt owing to the fact that urine was plentiful and easily replenished, and hence easily studied, and could reveal health issues like diabetes or kidney problems. Everything about urine – its taste, colour, smell, consistency – could tell the experts something about a paying customer’s body. Perhaps disparagingly, the learned men of the 17th century dubbed these individuals ‘piss prophets’.
Pregnancy prediction was just another skill for these urine diviners. The story of Notke the Stammerer illustrates this well. Notke was a 9th century monk in St. Gall, Switzerland asked to test a certain duke’s urine. What he didn’t know was that the duke, perhaps suspicious of the man, gave him the urine of a pregnant lady of the court. Not one to be fooled, Notke managed to make the correct pronouncement and declared the duke’s pregnancy nothing short of a miracle. Sufficiently impressed (or merely gracious at being beaten at his game), the duke rewarded him. Apocryphal or not, this suggests that uroscopy was practiced by a diverse number of individuals hailing from diverse occupations. Undoubtedly, owing to their better understanding of their own bodies and perhaps a finer sense of discretion, women must have played a very large party in it, too. It also illustrates the complicated relationship between these piss prophets and prophetesses and the public. Notke and his kind were both supported by enthusiastic believers and denounced by critics who protested what they saw as the fraudulent preying on the naïve.
Approaching modernity: Victorian era and bioassays
Flash forward to slightly more modern times. The scientific method as applied to medicine was on the way to becoming established. People were tinkering in the lab, analyzing the body, breaking down its components. In the 1830’s, French scientists supposedly discovered kyestein (Greek for ‘early pregnancy’), a white cakey layer formed on the standing urine of pregnant women. These were explained in several ways, from microorganism blooms to pronouncements that it was casein, a protein component of mammalian milk. Whatever the reason, the so called ‘kyestein pellicle’ test never caught on. Short of a medical text or two from the 1860’s, it fell in to unknown obscurity.
Animals as intermediates
The first instance of pregnancy bioassays, or the usage of other organisms in the study of substances and chemicals, concerns two German gynocologists, Selmar Aschheim and Bernhard Zhondek, and their collaboration in figuring out the human endocrine system. In studying the biology of pregnancy, their search isolated a certain hormone called human chorionic gonadotropin (hCG).
HCG functions as a sort of intermediary between the ovarian follicule and the uterus during ovulation, when the follicle splits off in to an egg and a substance called the corpus luteum. This corpus luteum secretes the hormone progesterone which causes the lining of the uterus to thicken in readiness for a fertilized egg. If fertilization does not occur, the corpus luteum wastes away and, with it, the uterine lining. This is what is expelled when a woman menstruates.
However, if the egg is fertilized, hCG causes the corpus luteum to continue progesterone secretion, which in turn causes further change in the uterine wall. It becomes ever more packed with blood vessels and eventually ends up turning in to the specialized placenta that will nourishment the fetus; the umbilical cord that once connected your bellybutton to the uterus was anchored in the placenta. HCG is thus an early cog that pushes several levers in the process of constructing a baby.
This is where the first test subjects – mice – came in. As they are placental mammals with similar biologies to our own, Aschheim and Zhondek correctly reasoned that exposing mice to hCG would create detectable physiological changes. Accordingly, they injected mice with urine several times a day over several days and inspected the consequences. If the ovaries had changed, the woman in question possessed hCG and was certifiably pregnant.
Unfortunately this meant the end of the mouse, since the quickest way of examination involved dissection. Taking the time and effort to perform gentler procedures which would have spared the mouse’s life was deemed overly time consuming and unnecessary.
The process, marketed as the A-Z test, became a standard for nearly half a century, and gained the euphemistic moniker of the ‘Rabbit Test’ when rabbits were found to be quicker indicators. “The rabbit is dead” became a colloquial response to a positive test result, and the A-Z test had an impressive 98% accuracy rate.
Yet there were serious drawbacks. One was the length of time necessary for a result. Like now, customers wanted things done quickly back then, too. Another was that the A-Z test never easily accessible or mass producible. Many people had rabbits, but few wanted to open one up each time they had a suspicion to assuage. Another problem with using animals was that in many cases the urine of certain people proved too toxic and concentrated, leading to their deaths. It had to be diluted to keep the animal alive, but this dilution lowered the sensitivity of the test and led to a prevalence of both false negatives and false positives.
Like with all things, science was working towards something better. By the 1940’s general testing had found Xenopus Laevis, a species of African clawed frog favoured in experiments because of the ease with which it could be studied and manipulated in the lab. The presence of human hCG caused the frog to lay eggs within eight to twelve hours (unlike the rabbit test, which took up to two days), eliminating the need to dissect the creature. Several years later, a species of toad cut the wait time down to a mere two to five hours.
Less bloody and shorter than your average Lord of the Rings trilogy, there was still one major issue. Even the best bioassays were only sensitive enough to detect hCG concentrations several weeks after conception. This was an annoying limitation that needed to be solved.
Beyond animals: Immunoassays
The answer lay in fashioning an ultrasensitive test that could directly pick up the faintest whiffs of what was to come. These were immunoassays.
As their name suggests, immunoassays are different than bioassays in that they use specialized biological molecules such as antibodies to specifically bind to a target – in this case, hCG – and announce their presence. Because they are tasked with the critical job of correctly classifying ally from foe, foreign from native, the immune system proved to be perfect tool for detecting the subtlest body chemistry. By creating a chain that magnified the detection and altered the way the results were expressed, it was possible to announce the end of the process by something as visually appealing as a colour change. Companies invested in this innovation, miniaturized it, and packaged it for cheaper until it eventually led to the home pregnancy kit. What began with chamber pots decipherable only by professionals ended as a litmus test encased in plastic and intelligible to one and all. A revolution in reproductive control for women and their families was ushered. The rest is history.
So what’s happened since then to some of the main players in our story?
Home pregnancy kits are ubiquitous and relatively accurate.
Rats and rabbis are still used in testing, but not for pregnancy. I think.
Piss prophecy is no longer a lucrative specialization.
African clawed frogs have gone on to bigger and better things. They were the first vertebrate to be cloned all the way back in 1958 (Dolly the sheep was the first mammal to be cloned), and they were blasted in to orbit aboard space shuttles to test the effects of space on reproduction and embryo development. Domestically, they’ve become intrepid and destructive explorers: after the demise of the A-Z test the frogs were released into North American ecosystems, only to proliferate wildly and wreak havoc with the native fauna.
The ancient Egyptian urine method was finally put to the test in the early 1960’s by researchers who reported, amazingly enough, that in at least one case study urine from a pregnant woman did help with plant growth. Go figure.
To date, nobody has attempted to predict twins with barley and wheat.