After the discovery of hormones in the early 20th century, new methods of pregnancy testing were developed. Some of these involved animal use, but how did the rabbit test work, and when did it get replaced?
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This is an unofficial transcript meant for reference. Accuracy is not guaranteed.
As a child. The first words out of your mouth were you're, not the boss of me. Boss move are the only moves you make and you never have to worry about the boss approving a vacation since wait. What vacation. Europe a business owner born to be your own boss and Amex, can help with finance options for eligible business customers. So you can keep doing what you were made to do. The power backing of American Express, don't do business without terms apply, learn more american express dot com, slash business will continue stuff. You missed in history class from how stuff works, tat come in long winded upon gas and how we try and I'm Tracy. They will then be traced. this weekend, I was hanging out another city with some friends. and I made a joke: referencing the nineteen. Seventy eight movie, the rabbit test data that movie
of it. But I don't think I've ever seen it, but I will tell you a funny story. After I tell you at the movie is about because it evidences the mind of a child and how they process information, so in that movie, which is a comedy directed by the late Great Joan Rivers Billy Crystal stars as a man who gets pregnant and the tight is a joke. Based on me, now outdated practice of using rabbits as part of a medical tests to determine if a woman was pregnant. Now this we came out what you said and seventy eight. So I was seven when a guy- and I member I had said something like I don't know- Turnover- had seen a poster or an ad or something- and I like rabbits like I was excited to see this movie and my siblings, who are all a good bit older than me? Really go? No! That movies duffer you, because of course it was about sex and reproduction. But my perception as a seven year old was that it must be a terrifying horror movies. I didn't know until I was it, One is that it was a girl. I know it's like a scary
life- I thriller, is what I made up in my head well and and based on everything I know of you Holly. I was genuinely astonished when I got this. You mail from you with this out line last night, because it contains a number of things that are just not your bag. Rights like talking about Reno Nancy and analyzing any animal testing there we have a we have our are our opt out. In a moment, but my point in all of them is that I had to head. Mention is moving to friends, and those friends are all a bit younger than my husband, and I are had never heard of the movie and they had never heard of the use of rabbits in pregnancy testing and I was trying explain this to them with my knots Dr Knowledge and their eyes got really big. It may seem to completely incredulous and thought. Maybe I was pulling one over on them so as they well. I know what I want to work on next in it
There's big. I thought everybody knew they don't if you the lesson of podcast, saw bones and you should they again an episode on the history of praying he testing and it mentions the rabbit test very briefly, but it's really more of it Overview of how pregnancy testing has evolved over the centuries, and we are dead, gonna, look really closely at how this particular test and one very like its both were developed in the twentieth century. So you have surmised already, but heads up this episode is going to involve a significant amount of disk of animals being used in medical testing with an outcome of more, I for the animal in most cases of that, knowing that you would rather not hear about, or rather not perhaps, share with younger history of us. You can tap right out of this one yeah yeah. I I still have a whole layer of the price of Blake.
Well, I love sire. I know you do it just seems, like you know, you're lying about the movie coming across a terrifying horror movie. I feel like the subject is like a holly, terrifying, goofy gear. I mean it's not me. It's me having a child now and it doesn't really talk about like any of the actual pregnancy, just the pathology and medical testing riding. That's why it's a little easier for me to dig him and somehow I don't know why I seem to be able to handle this particular discussion of animal
yeah we'll see. I could start crying halfway through. We will see how it goes its. I was different typing it then it is saying it is definitely one of those subjects that is always on like that. The right of first refusal list what I'm thinking of things to talk about today, home pregnancy, test their inexpensive, very common, usually the first way people find out if they are pregnant, go to the store pick one up, but there have and plenty of folk medicine tests that people could try on their own over the years before there were actual working pregnancy tests and for scientific confirmation of that pregnancy. Up until the seventies you pretty much had to go to the doktor. He couldn't just pick up a home test. They use. the urine to test for pregnancy was nothing new at all. It had been part of how people tested for pregnancy for centuries, yet people the intuitive that there was something going on with your and where it was a way to deter,
if someone was in fact carrying a child, but they were not necessary really rooted in science. As they had all things like peeing on green and seeing if it started out and color. So a really major development, took place in nineteen o two, when each starling, who was a physician and W M Bayliss, who was a physiologist, discovered, secretion and see cretin, is a polypi tied that is made up of more than two dozen amino acids. But what is really important is that it was the first hormone ever discovered. Secretion is aid digestive hormone. It has nothing to do specifically with reproduction and styling didn't start using the word hormone for several years: He first introduced it into medical nomenclature in a lecture that he gave at London's Royal College of Physicians in one thousand nine hundred and five titled on the chemical correlation of the functions of the body and in that lecture, Starling defined hormones, as quote the camel
Passengers which, speeding from cell to sell along the bloodstream, may coordinate the activity he's and growth of different parts of the body and from the point where he established the term. All manner of discovery and research in the field of hormones began yet and that still the pretty basic definition that you learn of what a hormone is in school yap at a very basic level. So from the nineteen in teams, a number of researchers were examining the link between hormones and pregnancy. Through the introduction of extracts of human. Santa into other animals. In a variety of laboratory experience, it became clear that there were hormones in the mix that were related to reproduction. All of this sounds so obvious now but of time, I know I think about like those shorthand of how people just a tribute leg, people's urge to you know, have romantic involvement with one another, though this girl hormones, but like at the time. This was like
mind, blowing concept that that was what was driving your romantic interest, death and the hormone that was eventually. denser fide in all of this was Human Korea Monica Granada Turban, which is more commonly known as h, seed g, and that was the hormone that unlocked the door to pregnancy, testing. Sir, just for a little bit of clay but not too much, because I'm not gonna, give you the hard science, because I will miss something up, but Hc G is really for independent molecules which each have their own functions in, which are produced by separate cells, HTTP, is not only used as an indicator of pregnancy. Certain cancers can also be detected based on tests which analyze Hc G content in a person's bloodstream, and if CD is present in women, even when they are not pregnant, although it's a pretty small amount, they don't produce significant amounts unless they are carrying a child, but pregnancy tests are designed. to measure the levels of aid Fiji and once that passes a certain threshold
It is a reliable indicator of pregnancy and nineteen. Twenty six to german doctors, Selma Osh, I'm an Bernhard Zadok developed a pregnancy to that used mice. Their preparation was described, in a nineteen thirty article in the journal, California and western medicine by authors, Herbert M Evans, M D and Miriam E Simpson empty as follows: the more you're in is sent into the laboratory in clean bottles. They meaning or shine ends on deck, recommend the addition of one drop of trees, all per twenty five cubic centimetres of urine. If it is necessary for the sample to be sent by mail, a group of five mice, each wing, sixty eight grey, is used to test each year and specimen, so the mortality rate for mice just to test a single person sample was quite high at that point, but per Evans and Simpson,
this test was far more reliable than any other options and it produced results in as few as for days. It work, because the urine sample, which was injected into very young mice in a specified regiment, was multiple injections over the course of several days would catalogue. Sexual maturation in the mice, if the urine was from a pregnant woman on the fifth day between ninety six than a hundred hours after the start of the injection process, the mice were killed and then necropsies based on an examination of the masses, ovaries doktor could determine if the woman who had. when the urine sample was pregnant. If the ovaries remained mostly small and smooth, the test was negative, but if there was a large bent- and thracian beyond the normal development. It was positive, Our diamonds on deck also developed a variation on this test for cases where someone might more urgently need to know if they were pregnant, although it came at a cost of more mice they use more mice in the experiment and then that they thyself
did them earlier in the sixty to seventy our range passed when they had begun. The testing that larger sample set made up for the shorter testing period We are about to talk about a little variation on the method that they developed, but first we'll pause and have a quick word from one of the sponsors that keeps the show going. This episode of stuff you missed in history class is brought to you by Norton three hundred and sixty with flock. You know there are some real Grinch is out there, but they aren't green. They dont living caves, the tiny dog I'm talking about cyber criminals and identity. Leaves than they would love nothing more than to steal your happy holidays, because the timing We can do a lot more online shopping and browsing and booking travel, and we might not always using the most secure wifi that makes the holiday season just another hunting season for cyber criminals, who were after you're devices and private information. That's why Norton three sixty with lifelike should be on everyone's wish. what is all in one membership for your cyber safety that gives you device security, identity theft, protection
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Other doctors took the work of the german team and the ash items on deck test, which was often abbreviated to just called, be called the aisy tests, and they made flight tweaks to the method for what works best for their laboratory situation and their staff at the University of California at Berkeley. In the late nineteenth twenties, researchers opted to use six rats for the procedure rather than mice, and they stored the urine samples at freezing temperature before injection they. Of course, he did it back up so that the they animals will not go into shock after the injection using rats was actually more cost. Intensive than mice bet. You see, Berkeley had already had an established rat colony for use in their laps. The primary benefit and using rats instead of mice was the fact that all of the rats usually survived the test, at least the injection and sort of incubation portion of the test, but an mouse base testing
ten percent of the rodents died before they reached that day. Five examination state and both tests- the error rate- was quite small between one and two percent and according to data collected in Ash, Ireland's armed Ex lab this test was also quite good. At early detection, there were recorded instances of positive results before any other clinical signs of pregnancy were present, for example, just three to four days after the patient had MR menstrual period. results were most reliable, though in cases of normal pregnancy? So in instances of more problematic situations like a table, pregnancy, the results were according to the door doctors, data slightly less accurate, that's a lot of time and we'll science when diagnostic tests weren't always common practice in western medicine, and they certainly weren't common specifically for women
Surely a lot of doctors felt as though it was extraneous? They trusted their experience and diagnostic abilities to determine if someone was pregnant or not. There was concern that testing labs removed, the relationship and the trust between the doktor and the patient you. This was particularly a problem. in great Britain. I was reading when article that mention that this one particular lab in Edinburgh had started taking me Lynn samples and people were like, but thereby passing their doctors. Jested do a direct thing. There were a lot of a lot of concerns, and this is at a point where there was insurance in Great Britain, but it didn't always cover women and it certainly didn't cover them just wanting to find out if they were pregnant. That was usually only for like an emergency which will talk about. Additionally, most of the time, most women suspect did they were pregnant already and they went to their doktor just to confirm what they already thought in family practitioners use this as evidence that
was not a real need for such tests to become mainstream. In most cases, As there was an urgent medical dean to know if a woman was pregnant health organism, funds and insurance companies where they existed, because insurance didn't really start until the late nineteenth twenties were unlikely to approve coverage for the cost of the test. Testing sample sent through the mail was particularly looked down upon us. We just with alluded to it, was referred to as postal pal the latter. A criticism that still exist today with all the various things that you can test at home, a kind of male away yet, but this test was recognised for its efforts. see and it became more and more commonly administered. Both summer ass and Bernard's on deck were jewish and both of them to leave. Germany I say chose, but they really had to for their lives in nineteen thirty three, as than See party came into power and they left their lag behind in the process
in nineteen thirty one, the landscape for pregnancy testing shifted when a similar tests, so that aisy tasked with introduced at the University of Pennsylvania by Maurice Harold Friedmann and Maxwell, Edward Lapham Friedman, who was born. October 27th, one thousand nine hundred and three in Gary Indiana had been with the University of Pennsylvania. Is a faculty member. Since one thousand nine hundred and twenty eight he had earned his bat. degree Phd M M D at the University of Chicago starting in nineteen nineteen, so he went his undergrad adjust sixteen, so he was still young when he developed the rabbit test and Maxwell Latham, who was born in new faint New York, was just three years older than his collaborator, and he was working at the university hospital at the time and article titled, a simple rapid procedure for the laboratory: diagnosis of early pregnancies than the March nineteen. Thirty one issue a b, the American Journal of Abstention,
I'm gonna, ecology, Friedmann and lap and wrote about their choice to move away from mice for their test, starting with a reference to the aisy test. It said quote. Yet this test, admirable though it is, has some distinct disadvantages, one of which may make it impact call in a laboratory or hospital not closely affiliated with some university or institute to perform those on back ashine test its essential to be in possession of position to command a ready supply of amateur mice. Wang from six grams, if a large breeding colony of mice is not usually available, some difficulty might be encountered in procuring suitable animals at a time assessed as desired. Moreover, even if one had a hand enough of the amateur mice
answer the calculator requirements were given weak and for some reason or other, the number of samples submitted, fell below expectations. The unused animals would soon mature beyond their usefulness so that another group of the amateur animals would have to be gotten Friedmann and lambs test used right Its instead of mice and just as rats were more of a burden to support than mice. Rabbits took a lot effort and resources to keep in a lab setting, but there were some very difficult benefits to rabbits over mice for one it requires only one to two specimens rather than six aside from just the number of creatures harmed. This also just meant one or two necropsies rather than half a dozen, and, unlike my, rabbits only obviously after meeting that meant, they didn't need to use only very young animals with mice. The very young specimens were used to avoid any fears and that might arise. Should a mouse just be developing a natural Esdras cycle which would look pretty similar to a positive result in the
stay as long as they knew the rabbits history and it had been isolated because exposure to other female rabbits could cause Esdras. It could stay viable as a test subject until it was needed aging out of usefulness protesting purposes, but even if around it had not been fully isolated, it could still potentially be use per Friedmann and Lapham quote in case. One has not had opportunity to ice the rabbits for the desired period, and it is found necessary to perform a test. It is safe to use Abbott that has been isolated in the laboratory for only eight or ten days, even if the rabbit income Jim had had coitus just before it was obtained. The corporal Lou of pregnancy or pseudo pregnancy would then be at least eight or ten days old and could not be confused, with the fresh corporal outta or corporate hemorrhagic, produced by the objections of an active urine. Briefly then, one may say
We use all rabbits that are not demonstrably pregnant at the end of three weeks of isolation by also found the rabbits easier to handle, and it was easy to administer injections into the veins of their ears, they could performed than a crop see without the need for a microscope or a magnifying glass, because the results were observable to the naked eye. Rather, the meeting to be met, yeah. That was not the case of mice, where you have to look very closely at their tiny, tiny organs, you could literally just do the accuracy and go up. The Swindon is positive, but big difference was that a rabbit test could be turning in forty eight hours, rather than five days while lap, em and Friedman try to similar method of earlier necromancy that had been used in mice is remember. They had just up the number of mice, used and then did attests doing sort of pattern, recognition at shorter intervals. They act we found the results a lot less reliable.
Try to similar method in rabbits we're about to get into the numbers involved in the research that Friedmann and lap em used to test their rapid method, but first we will take a quick sponsor break Episode is brought to you by bombast. Everybody loves to feel like they are. The super awesome person at the end of the holiday give giving that everyone's like man, you Hold it if you're, giving everybody barber socks as holiday, you're, probably get that a word. One of the things keep for that. I am in love with is their new sesame Street line, and I know I have several friends that would want those I, have really been enjoying wearing their no show socks, because I, where those a lot with low tops and loafers one of those who have their brands but he'll, slides down and ends up wanted up kind of under my art in this not comfortable. That is not a problem with bombast. Did you know that socks Also the number one most requested item in homely shelters, Bomba Sox, are created to change that, because, for every pair you buy bombast donates appear to some I it's one of the things I love about this company, so you could do
good and give fantastic, gives good Obama's dot com, slash history class in it when percent perceived off any purchase during their big holiday sale November. Eighteen three December fifth, B, O Mba S, dotcom, slash history, class for twenty percent of bombast dotcom, slash history, class. to test their approach, the University of Pennsylvania, use. Two hundred and eleven samples three samples were deemed to toxic to use in the test and the special Nature of the toxicity is not described in the friedmann and lack of paper, but a lab in Edinburgh, Scotland, which did quite a lot of pregnancy testing in the nineteen thirty's Described so domes getting samples of urine which were green because the women who had given them had use some sort of chemical means to try to avoid pregnancy, though samples relief
to mice, which was the testing animal that the Edinburgh LAB used. So the test would not work. Friedmann and lap are mentioned as a desire to find a way to handle so called toxic samples. Writing quote vandyck reports that about six percent of the samples submitted were to toxic to be handled and to obviate this difficulty. He has devised a method by which these toxic uriens may be made innocuous. Since the appearance of this paper, we have not encountered a sample with which to test this point major, so that left, a hundred and eight samples for the study and twenty five of those samples were from women who are in their last months of gestation and all of their samples as expected, yielded positive test results. Thirty two of the samples were from women who had gone to the clinic at the university hospital to determine if they were pregnant. Twenty five of them testing positive for pregnancy and the research team was able to track twenty two of those women to further verify that they had been pregnant, although not all of them.
Carried those pregnancies to full term the remaining three did not remain in contact with the study. There were fifty one negative test results from this viable group of a hundred night samples. Two of those samples were from men and Wednesday. Five were for women in the hospital who were known to have been not pregnant at the time of testing, including several with conditions that might clinically present as looking pregnant without a test like they have nausea or their ab demands were swollen. Something like that. Yes, they wanted to include people that they absolutely knew were not pregnant to prove that the tests was accurate in both positive and negative and also people who might be told by doktor. He was just examining them that they were probably pregnant but were, in fact not. Twenty. Four of the negative test results had been for women who had visited the clinic to determine if they were pregnant and the study remain in contact
with eighteen of those patients and they were verified as non pregnant. That left ninety two cases for which the doctors felt they had adequate data for the inclusion in the studies. Statistical analysis and that left them with an error rate of zero. But in their paper, Friedmann and Lapham wrote it is likely that add more material. We might have encountered an error to hear the they were asserting that it was a hundred percent effective all the time of the ninety two that had been that it had been pared down, after they had to leave out the toxic, you're examples and the ones that they lost track of it was a hundred percent accurate. In that data. The Friedman lab test was adopted more readily than its predecessor, the mouse version in part, because the Aisy test had blaze a trail already. So people already had this idea that this test was worthwhile and end was accurate and I'll
Oh for all, the reasons that were laid out in the paper published by Friedman, lap, em, for example, hospital sound it much easier, to set up a lab for a smaller number of rabbits, then huge numbers of mice which they would have to continually be breeding to get workable animals that they could use and testing, even though it was still more expensive to house of rabbit and the reliability of the speedier assessment during necropsy made this test. Much more appealing as well and that's a bit of miss busting, you may have heard the joke. The rabbit died as a shorthand way to say that somebody is pregnant, and this has been a long. The long standing misconception connected to this test. I think
Polly, and I at some point have probably said that I know I have repeated that myths, so apologies to anyone that heard that from my lips you got misinformation. Yet the positive test result was not indicated by the rabbit dying, rabbits had to be euthanize Edna Crop seed, the positives Hesse result was definitely not the cause of the death correct and, while the rabbit test, what more popular than the mouse tests that preceded it. There was another way to test for pregnancy that followed in the nineteen thirty, so not very long after the rabbit test was introduced called the frog test, and this one is used into western medicine by british biologists. Lancelot Hog been didn't, kill the test. Animal Zena puss leave US frogs used in this test. would begin, avi, leaving and dropping eggs quite quickly after being injected with urine that contained h e in the levels consistent with pregnancy. You also sometimes hear this referred to as the blue photo
that species was originally made. Bhutto leave us before the name changed his universe, so these frogs display there whilst a mere hours compared to the days that it took with previous methods of mice and rabbits and the same frog, could be used for repeated testing. Since there wasn't a crop needed to confirm these rules, yeah. This is also one of those things that has possibly lead to some species integration and places. It is not natural for it to exist because it appears at least based on what I read, that this really cause no harm to the frogs whatsoever, and so these I would end up with lots and lots of frogs and eventually they would start letting some go so they originated in South for her and then ended up being let loose outside of labs throughout the western world, which we ve done like invasive species have come up on the show before, but I dont think I have ever heard of invasive pregnancy test rugs
if, in the end they save frogs that have have gone on to retire from being pregnancy testers. They also eventually realised that they could use male frogs as well and they would basically release sperm and they actually had a much faster test results than the female frog, so both both males and females of the species ended up being used. Husband did not get to retain a clear claim to this discovery. While he had apparently suggested that these frogs could be used to detect certain hormones and pregnant women He didn't really land at the idea that the frogs could be used to design a pregnancy test and he did not set up any of the testing around it. It was husband, student, Hillel, Shapiro and Shapiro is reached partner, Harry's weren't steam, who actually took the idea from the erratic all to practical, by designing executing studies with the frogs, of course, the frog test.
Hot on because of its benefits. There were the other options and it was used until the nineteenth sixtys when pregnancy tests or develop the didn't, involve the use of animals at all after that, home kits eventually hit the market in the nineteen Seventys, the first of which was called predictor and which took two hours to offer. a result. These were a lot more convoluted than today's three to just on a stick. If you had the Netflix series glow give seen what one looks like yeah yeah, and I should say that they there were other tests being developed. That did not involve animals before the nineteen succeed, but they just you know, had not reached a level of reliability that they could supplant these animal based testing options and ass for the day. the birth of the rabbit test, Maxwell E lap, I wrote a book titled maternity care in rural communities in Nineteen- thirty, eight so later in that same decade after they introduce the rabbit test. The year before that he had joined the faculty at two Lane University School of medicine, and he actually stayed with two lane until the end of his career
here when he died at the age of eighty three. It was in two Lane University hospital and per his New York obituary during his time as dean of the medical school, he had significantly bolstered the financing of the schools Research programme taking it from thirty thousand dollars to five point five million, and that was basically just through grant money or EAST Friedman me to the Washington DC area and worked for the belts. Phil agricultural Research centre be served in the Army air Force in World war, two as a medical officer and opened a private practice after the war was over specializing in internal medicine. He died cancer and ninety ninety one at the age of eighty seven and one of Doktor Friedman, more famous, quotes regarding the rabbit test was quote it highly reliable, but only more reliable test is to wait. Nine months does seem like a fun place to end Since it is a little bit at to me, it's very fascinating, but it would you know it does get in the animal testing, which is not the most delightful topic, but it's an important part. I feel like a bar sign
EC history, particularly as relates obviously to reproductive medicine and is something that people may be, don't realize that this was something that was That was not only commonplace, but it was also already being considered in terms of animal welfare. I know in great Britain they already have laws in place by the time the mouse test was being used about how animals could be used for medical testing, That was one of the other things that lead to some of the debates around. Whether people should adopt the test it was. It was like yes, but we're harming animals, and you would just realize you're pregnant a couple weeks anyway, right there's. A lot of a lot of interesting layers to it. Kind of evidence is a discussion about animal rights. It was happening I think, earlier than we may be think of
things got well in that conversation connects to something that listeners as Basque us to talk about before, which is that the synthesis of insulin and how that was developed, which is like it's definitely on the very long topic ideal list and also connects to some of those questions about how the ethics of of animals in medicine. I have a son postcard from Barcelona, how nice it is thrown, listener Alex I believe that other name on here is Tare, although I am not positive, it's written very, very tiny and it has been through international mail but my Alex raids dear how we in Tracy hello from Barcelona, my wife traveling Europe to celebrate her finishing her masters degree in graphic design. Congratulations I, meaning to come here since first learning about Le Sagrada Familia and seventh grade. So this is something of a lifelong dream being fulfilled. By the way, I know you to love to shout
Decatur. So I would like thank my middle school spanish teacher. I believe that since let us of error for inspiring this trip and for being an incredible teacher. So yes, of course, always always. My hat is often educators. It was far too. It is timing for me to get to listen to your episode on Francisco Frank a few days before I left, I have always found the spanish civil war very interesting, but have only learned about it through fictional work, such as pans labyrinth and for whom the Bell tolls. I actually got to discuss frame a little bit with a tour guide and a winery and as a cattle he had an interesting perspective as well about power, the Franco regime, banned the Catalan language and suppress the culture anyway. Thank you for the great show, so it's a beautiful it's those what sort of wide postcards and it's a really beautiful prospect on the cigarettes are familiar from inside and it's just absolutely lovely. So thank you. Thank you again. I'm always where do people want to stop while their travelling beautiful places
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