How Were Pregnancy Tests Invented?

Humans have been using urine to test for pregnancy for thousands of years -- with the help of wheat, barley, rabbits, and frogs. Learn how reliable home tests became available in 1978 thanks to immunoassay technology in this episode of BrainStuff, based on this article: https://health.howstuffworks.com/pregnancy-and-parenting/pregnancy/conception/rabbit-pregnancy.htm

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Episode Transcript

Speaker 1 (00:01):
Welcome to brain Stuff, a production of I Heart Radio.
Hey brain Stuff, Lauren Volga Baum Here. When they're in
our human world, rabbits can be interesting pets, a source
of food assistance in classic magicians, stage shows, or animal models,
and laboratory tests. Of course, we hope that in all

(00:22):
of these cases, the rabbits in question are being treated
by the humans in question with the utmost care. But
did you know that from the nineteen thirties to the
early nineteen sixties, lab rabbits were key element in human
pregnancy tests. It's true, and it's even weirder than it sounds,
because it involved injecting those rabbits with human urine. But

(00:45):
let's back up a little here. The basic principles behind
testing urine for pregnancy date back thousands of years and
continue to this day. Historians believe the physicians of ancient
Egypt were the first to discover a method detecting pregnancy
through the study of urine. We've talked about this one
on the show before. By BC or so, ancient Egyptian

(01:08):
women could determine whether they were pregnant by urinating in
two different bags, one filled with barley and the other
with wheat. If the grain and either bags sprouted, it
meant she was expecting fast forward all the way. In
the nineteen sixties, a study found that this is actually
accurate about seventy percent of the time because the elevated
estrogen levels and a pregnant person's urine can promote seed growth.

(01:32):
What wasn't accurate was the attempt to determine the sex
of the child based on which sprouted first, Barley for boys,
wheat for girls. But still not bad and historians think
this marked the beginning of medical urine examination and potentially
laboratory medicine itself. More than three thousand years of urine
examination also called eurro scopy or your analysis have followed,

(01:56):
with varying accuracy. There was a bit of an expose
in the sixty hundreds in London that called out fraudulent
physicians using urine to diagnose pregnancy and lots of other conditions.
The whistleblower referred to these frauds as piss profits. But
urine research continued, and meanwhile, in the late eighteen nineties,

(02:17):
scientists discovered the existence of hormones. A hormone is a
product that sells make to regulate specific cellular activities such
as cell growth and division, and in the nineteen twenties,
scientists pinpointed a specific hormone called human choreonic ganado trop in.
It's also called hCG because that's much easier to say.

(02:39):
This hormone is found almost exclusively in the blood and
urine of pregnant people, though we now know that certain
cancers also produce it in anyone. But intrigued by this
hormones linked to pregnancy, a couple of German researchers set
out to develop a method of testing for hCG in urine.
They decide to exploit the fact that hormones from one

(03:02):
animal can generate biological responses in the bodies of other species,
sort of like those sprouting seeds. They discovered that by
injecting female mice with a pregnant woman's urine, they could
stimulate the mice's ovaries and cause them to go into
heat within a few days. They called this test the
A Z test. Will note here that just as analyzing

(03:25):
urine has a long history and medical science, so too
has the use of animals. While often controversial and hopefully
replaceable by technology in the future. A number of experiments
on animals called bioassays, have led to important breakthroughs in
medical science anyway, during the nineteen thirties, researchers applied the

(03:45):
Azy tests methodology to two other species. In South Africa,
researchers adapted it for use in frogs, inventing the hogbin test.
The frogs would lay eggs if the urine they were
injected with contained hCG. This test was used tens of
thousands of times in the nineteen forties through the nineteen sixties,

(04:06):
and at the University of Pennsylvania Medical School, one Dr
Maurice Friedman made a breakthrough with rabbits similar to mice,
If hCG is present in urine injected into female rabbits,
the urine stimulates changes to the rabbit's ovaries within just
a few days. The hCG basically fools the rabbit's body
into temporarily thinking it's pregnant, and the rabbit's ovaries produced

(04:29):
temporary tissue structures that a researcher can spot. The urine
injection itself didn't harm the rabbit or the mice or frogs,
but unfortunately, the fastest way to check the ovaries of
the mammals was to euthanize and dissect the animal. Thousands
of rabbits were sacrificed every year, to the point that
the rabbit died became a euphemism for saying that someone

(04:51):
was pregnant. The frogs, however, were unharmed and uh reusable.
Luckily for the bunnies, though, The first immuno essay that
could test directly for hCG and a sample of urine
was developed in nineteen sixty. Immuno essays are tests that
use specific molecules called antibodies that can bind onto whatever

(05:14):
type of particle you're looking for in some detectable way.
Maybe it makes the sample clump up, or maybe the
antibody is attached to an enzyme that will change the
color of a test strip from white to blue. And yes,
today's at home COVID tests are also immuno essays. But
it took over a decade to turn this initial discovery

(05:36):
into something really usable for pregnancy testing. It involved a
lot of research and societal changes, including advancements in prenatal
care and the legalization of most abortions at a national
level via the Supreme Court's decision in Roe v. Wade
in ninety three, both of which incentivized being able to
detect pregnancy as soon as possible. At that time, the

(05:58):
best tests available had be sent away to a lab,
and we're only reliable for detecting pregnancy at six weeks
or later. The first home pregnancy test that's more or
less equivalent to the ones we know today was approved
for home use in nineteen seventy six and was on
store shelves by early night. With the sample of urine,
it could display a result within two hours, though it

(06:20):
wasn't as accurate as early as today's tests are. A
Modern pregnancy tests still involved detecting hc G, but have
gotten more sensitive, meaning they can detect smaller amounts of
it sooner in a pregnancy. Okay, a person's body starts
producing hCG when a fertilized egg implants itself, hopefully in

(06:40):
the prepared lining of the uterus. See our previous episode
on how human conception works for more on that, but basically,
under normal circumstances, a person will ovulate about a week
after their last period, and if that ovulated egg is fertilized,
it'll implant about a week after that. A so that's
two weeks into a pregnancy, because pregnancies are calculated from

(07:03):
the end of a person's last period, and that's when
the pregnant body starts producing hCG. The presence and or
levels of hCG in a person's body can be detected
in two ways, via blood test or via urine test.
A blood test is a little more accurate, but also
more invasive. You have to get blood drawn and often

(07:25):
more expensive. You have to go to a medical care
provider to get your blood drawn and send the sample
to a lab. But a blood test can detect the
presence or quantity of hCG in your blood as early
as two to three weeks into a pregnancy, and so
before you would have ever missed your period, though it
can take a day or more to get the lab
results back. A urine test is more common because even

(07:46):
though it's a little less accurate, especially early in a pregnancy,
it's cheaper, can be done anywhere, and the results are
pretty much immediate. These are done by either collecting a
sample of urine and dipping a testing strip into the sample,
or by urinating directly on a testing strip. A urine
test can generally detect the presence of hCG three to

(08:07):
four weeks into a pregnancy, so from slightly before to
right after you would have missed your period, and the
results develop on the strip within a few minutes. These
tests do very a little, so if you're taking one,
just read and follow the instructions, but rest assured that
there will be no rabbits, frogs, or barley involved. Today's

(08:34):
episode is based on the article how can a Rabbit
Tell Me If I'm pregnant? On how stuff works dot
com written by Robert Lamb. Brain Stuff It's production of
I Heart Radio in partnership with how stuff works dot Com,
and it's produced by Tyler Klang. Four more podcasts from
my heart Radio visit the iHeart Radio app, Apple Podcasts,
or wherever you listen to your favorite shows.