WEBVTT - The Rabbit Test 0:00:01.120 --> 0:00:04.080 Welcome to Stuff you missed in History Class from how 0:00:04.120 --> 0:00:13.360 Stuff Works dot com. Hello, and welcome to the podcast. 0:00:13.400 --> 0:00:17.079 I'm Holly Frying and I'm Tracy d Wilson. So Tracy. 0:00:17.200 --> 0:00:19.239 This weekend, I was hanging out in another city with 0:00:19.320 --> 0:00:23.319 some friends. UM, and I made a joke referencing the 0:00:24.239 --> 0:00:27.120 movie The Rabbit Test. Do you know that movie? I 0:00:27.200 --> 0:00:29.080 know of it, but I don't think I've ever seen it. 0:00:30.280 --> 0:00:32.159 I will tell you a funny story after I tell 0:00:32.159 --> 0:00:35.280 you what the movie is about, because it evidences the 0:00:35.360 --> 0:00:37.839 mind of a child and how they process information. So 0:00:37.920 --> 0:00:40.280 in that movie, which is a comedy directed by the 0:00:40.360 --> 0:00:43.720 late great Joan Rivers, Billy Crystal stars as a man 0:00:43.840 --> 0:00:46.560 who gets pregnant and the title is a joke based 0:00:46.600 --> 0:00:49.880 on the now outdated practice of using rabbits as part 0:00:49.880 --> 0:00:53.040 of a medical test to determine if a woman was pregnant. Now, 0:00:53.120 --> 0:00:54.959 this movie came out, like I said, in seventy eight. 0:00:55.040 --> 0:01:00.000 So I was seven when it huh out, And I remember, Um, 0:00:59.840 --> 0:01:02.240 I had said something like I don't know if I 0:01:02.240 --> 0:01:04.240 had seen a poster or an ad or something, and 0:01:04.280 --> 0:01:06.320 I was like rabbits, Like I was excited to see 0:01:06.360 --> 0:01:09.240 this movie and my siblings, who are all a good 0:01:09.240 --> 0:01:11.040 bit older than me. We're like, oh, no, that movie 0:01:11.080 --> 0:01:13.360 is not for you, because of course it was about 0:01:13.800 --> 0:01:17.480 sex and reproduction. But my perception as a seven year 0:01:17.520 --> 0:01:19.920 old was that it must be a terrifying horror movies. 0:01:21.120 --> 0:01:22.920 I didn't know until I was in my twenties and 0:01:23.000 --> 0:01:26.679 it was a comedy. I was like, no, it's like 0:01:26.680 --> 0:01:28.880 a scary sci fi thriller, is what I made up 0:01:28.880 --> 0:01:31.840 in my head. Well, and and based on everything I 0:01:31.880 --> 0:01:35.480 know of you, Holly, I was genuinely astonished when I 0:01:35.520 --> 0:01:38.480 got this email from you with this outline last night, 0:01:38.920 --> 0:01:41.800 because it contains a number of things that are just 0:01:41.880 --> 0:01:46.080 not your bag, right, like talking about you know, pregnancy 0:01:46.160 --> 0:01:49.000 and um um, and I'm going to get to the 0:01:49.200 --> 0:01:51.640 animal testing things and we have a we have our 0:01:51.840 --> 0:01:56.480 our our opt out discussion in a moment. But my 0:01:56.640 --> 0:01:58.800 point in all of this is that I had had 0:01:58.840 --> 0:02:01.080 mentioned this movie to friends, and those friends are all 0:02:01.400 --> 0:02:04.480 a bit younger than my husband and I are, and 0:02:04.520 --> 0:02:06.560 they had never heard of the movie, and they had 0:02:06.680 --> 0:02:10.079 never heard of the use of rabbits in pregnancy testing. 0:02:10.600 --> 0:02:13.040 And I was trying to explain this to them with 0:02:13.120 --> 0:02:16.280 my not scientific knowledge and their eyes got really big 0:02:16.320 --> 0:02:19.040 and they seemed completely incredulous and thought maybe I was 0:02:19.080 --> 0:02:22.200 pulling one over on them. So, um, I was like, well, 0:02:22.240 --> 0:02:24.760 I know what I want to work on next, and 0:02:24.800 --> 0:02:28.600 it's this Because I thought everybody knew, they don't. Uh. 0:02:28.639 --> 0:02:30.960 If you also listen to the podcast saw Bones and 0:02:31.040 --> 0:02:34.360 you should, they indicated an episode on the history of 0:02:34.360 --> 0:02:37.480 pregnancy testing, and it mentions the rabbit test very briefly, 0:02:37.560 --> 0:02:40.360 but it's really more of a broad overview of how 0:02:40.880 --> 0:02:44.400 pregnancy testing has evolved over the centuries, and we are 0:02:44.440 --> 0:02:47.240 instead going to look really closely at how this particular 0:02:47.280 --> 0:02:50.040 test and one very like it both were developed in 0:02:50.040 --> 0:02:52.960 the twentieth century. So you may have surmised already, but 0:02:53.120 --> 0:02:56.639 heads up, this episode is going to involve a significant 0:02:56.639 --> 0:02:59.880 amount of discussion of animals being used in medical testing, 0:03:00.800 --> 0:03:04.359 with an outcome of mortality for the animal in most cases. Um, 0:03:04.400 --> 0:03:06.080 So if that is something that you would rather not 0:03:06.120 --> 0:03:09.400 hear about or rather not perhaps share with younger history buffs, 0:03:09.720 --> 0:03:13.080 you can tap right out of this one. Yeah. Yeah, 0:03:13.280 --> 0:03:18.119 I still have a whole layer of surprise of like, well, 0:03:18.160 --> 0:03:21.000 I love science, I know you do. It just seems 0:03:21.040 --> 0:03:22.919 like you know you're talking about the movie coming across 0:03:22.960 --> 0:03:25.600 as a terrifying horror movie. I feel like the subject 0:03:25.760 --> 0:03:29.239 is like a holly terrifying horror movie. Yeah. No, I 0:03:29.280 --> 0:03:34.079 mean it's not me. It's not me having a child, 0:03:34.760 --> 0:03:37.120 and it doesn't really talk about like any of the 0:03:37.160 --> 0:03:40.480 actual pregnancy, just the pathology and medical testing. So I 0:03:40.480 --> 0:03:44.080 think that's why it's a little easier for me to 0:03:44.960 --> 0:03:48.119 dig in on. And somehow I don't know why I 0:03:48.200 --> 0:03:52.080 seem to be able to handle this particular discussion of 0:03:52.120 --> 0:03:55.920 animal testing. Yeah, we'll see. I could start crying halfway through. 0:03:56.040 --> 0:03:58.680 We'll see how it goes. It's always different typing it 0:03:58.720 --> 0:04:01.000 than it is saying it. But definitely one of those 0:04:01.040 --> 0:04:03.960 subjects that is always on, like the right of first 0:04:04.000 --> 0:04:06.840 refusal list what I'm thinking of things to talk about. So, 0:04:08.640 --> 0:04:13.560 uh today, Home pregnancy tests they're inexpensive, very common. Usually 0:04:13.600 --> 0:04:15.800 the first way people find out if they are pregnant 0:04:16.040 --> 0:04:18.520 just go to the store and pick one up. But 0:04:18.720 --> 0:04:21.760 there have been plenty of folk medicine tests that people 0:04:21.839 --> 0:04:24.080 could try on their own over the years before they 0:04:24.080 --> 0:04:29.800 were actual working pregnancy tests and for a scientific confirmation 0:04:29.839 --> 0:04:32.080 of that pregnancy. Up until the seventies, you pretty much 0:04:32.080 --> 0:04:34.160 had to go to the doctor. You couldn't just pick 0:04:34.240 --> 0:04:37.400 up a home test. The use of urine to test 0:04:37.440 --> 0:04:39.960 for pregnancy was nothing new at all. It had been 0:04:40.000 --> 0:04:44.400 part of how people tested for pregnancy for centuries. Yeah, 0:04:44.640 --> 0:04:47.600 people had intuited that there was something going on with 0:04:47.839 --> 0:04:51.640 urine where uh it was a way to determine if 0:04:51.680 --> 0:04:54.040 someone was in fact carrying a child, But they were 0:04:54.080 --> 0:04:58.000 not necessarily rooted in science. Always they involved things like, 0:04:58.440 --> 0:05:02.599 you know, peeing on grain and see if it turned color. 0:05:03.760 --> 0:05:07.120 But a really major development took place in nineteen o 0:05:07.240 --> 0:05:11.320 two when E. H. Starling, who was a physician, and W. M. Bayliss, 0:05:11.320 --> 0:05:15.960 who was a physiologist, discovered secreton. And secreton is a 0:05:16.040 --> 0:05:18.520 polypeptide that is made up of more than two dozen 0:05:18.600 --> 0:05:22.080 amino acids. But what is really important is that it 0:05:22.120 --> 0:05:27.560 was the first hormone ever discovered. Secreton is a digestive hormone. 0:05:28.200 --> 0:05:31.680 It has nothing to do specifically with reproduction and Starling 0:05:31.720 --> 0:05:35.160 didn't start using the word hormone for several years. He 0:05:35.200 --> 0:05:38.560 first introduced it into medical nomenclature and a lecture that 0:05:38.640 --> 0:05:41.880 he gave at London's Royal College of Physicians in nineteen 0:05:41.920 --> 0:05:45.520 o five titled on the Chemical Correlation of the Functions 0:05:45.560 --> 0:05:49.320 of the Body, and in that lecture, Starling defined hormones 0:05:49.440 --> 0:05:53.080 as quote the chemical messengers which, speeding from cell to 0:05:53.160 --> 0:05:57.280 sell along the bloodstream, may coordinate the activities and growth 0:05:57.360 --> 0:06:00.240 of different parts of the body. And from the point 0:06:00.240 --> 0:06:04.080 where he established the term, all manner of discovery and 0:06:04.160 --> 0:06:07.360 research in the field of hormones began. Yeah, and that's 0:06:07.360 --> 0:06:10.200 still the pretty basic definition that you learn of what 0:06:10.240 --> 0:06:13.760 a hormone is in school. Yeah, at a very basic level. 0:06:14.600 --> 0:06:18.360 So from the nineteen teens, a number of researchers were 0:06:18.520 --> 0:06:22.039 examining the link between hormones and pregnancy. Through the introduction 0:06:22.160 --> 0:06:25.599 of extracts of human placenta into other animals in a 0:06:25.640 --> 0:06:28.440 variety of laboratory experience, it became clear that there were 0:06:28.480 --> 0:06:32.080 hormones in the mix that were related to reproduction. All 0:06:32.120 --> 0:06:35.080 of this sounds so obvious now, but at the time, 0:06:36.160 --> 0:06:38.560 I know, I think about like the shorthand of how 0:06:39.040 --> 0:06:44.000 people just attribute like people's urge to uh, you know, 0:06:44.080 --> 0:06:46.800 have romantic involvement with one another, they'll just go hormones. 0:06:47.160 --> 0:06:50.000 But like at the time, this was like mind blowing 0:06:50.120 --> 0:06:53.640 concept that that was what was driving your romantic interest. Yeah, 0:06:53.720 --> 0:06:56.680 And the hormone that was eventually identified in all of 0:06:56.720 --> 0:07:00.640 this was human choreonic gonadotropin, which is more commonly known 0:07:00.720 --> 0:07:04.359 as hCG, and that was the hormone that unlocked the 0:07:04.400 --> 0:07:07.360 door to pregnancy testing. So just for a little bit 0:07:07.360 --> 0:07:10.920 of clarity, but not too much, because I'm not going 0:07:10.960 --> 0:07:12.760 to give you the hard science because I will miss 0:07:12.800 --> 0:07:16.320 something up. But hCG is actually four independent molecules which 0:07:16.360 --> 0:07:19.080 each have their own functions in which are produced by 0:07:19.120 --> 0:07:23.360 separate cells. hCG is not only used as an indicator 0:07:23.400 --> 0:07:26.640 of pregnancy. Certain cancers can also be detected based on 0:07:26.760 --> 0:07:31.200 tests which analyze hc G content in a person's bloodstream. 0:07:31.680 --> 0:07:34.560 And hCG is present in women even when they are 0:07:34.600 --> 0:07:37.280 not pregnant, although it's a pretty small amount. They don't 0:07:37.320 --> 0:07:40.760 produce significant amounts unless they are crying a child. But 0:07:41.040 --> 0:07:44.120 pregnancy tests are designed to measure the levels of hCG 0:07:44.680 --> 0:07:47.400 and once that passes a certain threshold, it is a 0:07:47.480 --> 0:07:52.720 reliable indicator of pregnancy. In six two German doctors Selma 0:07:52.840 --> 0:07:57.600 Asheim and Bernhard Zondeck developed a pregnancy test that used mice. 0:07:58.200 --> 0:08:01.080 The preparation was described in a nine team thirty article 0:08:01.160 --> 0:08:05.600 in the journal California and Western Medicine by authors Herbert M. Evans, 0:08:05.760 --> 0:08:10.200 m d. And Miriam E. Simpson, m D. As follows 0:08:10.760 --> 0:08:14.840 the morning urine is sent into the laboratory and clean bottles. 0:08:15.000 --> 0:08:18.679 They meaning Ashaim and Zondeck recommend the addition of one 0:08:18.920 --> 0:08:22.520 drop of tri cresal per twenty five cubic centimeters of 0:08:22.720 --> 0:08:24.720 urine if it is necessary for the sample to be 0:08:24.760 --> 0:08:28.040 sent by mail. A group of five mice each wing 0:08:28.120 --> 0:08:31.360 six to eight grahams is used to test each urine specimen. 0:08:31.840 --> 0:08:35.160 So the mortality rate for mice just to test a 0:08:35.200 --> 0:08:38.480 single person sample was quite high at that point, but 0:08:38.760 --> 0:08:42.119 per Evans and Simpson, this test was far more reliable 0:08:42.120 --> 0:08:45.200 than any other options, and it produced results in as 0:08:45.240 --> 0:08:48.840 few as four days. It worked because the urine sample, 0:08:48.920 --> 0:08:52.360 which was injected into very young mice in a specified regiment. 0:08:52.400 --> 0:08:54.800 It was multiple injections over the course of several days 0:08:55.280 --> 0:08:58.760 would catalyze sexual maturation in the mice if the urine 0:08:58.800 --> 0:09:02.040 was from a pregnant woman. On the fifth day, between 0:09:02.080 --> 0:09:05.160 ninety six hundred hours after the start of the injection process, 0:09:05.200 --> 0:09:08.120 the mice were killed and then the crop seed based 0:09:08.120 --> 0:09:12.240 on an examination of the mice's ovaries, doctor could determine 0:09:12.280 --> 0:09:14.800 if the woman who had given the urine sample was pregnant. 0:09:15.320 --> 0:09:18.880 If the ovaries remained mostly small and smooth, the test 0:09:18.960 --> 0:09:22.480 was negative, but if there was enlargement and maturation beyond 0:09:22.600 --> 0:09:25.880 the normal development, it was positive. Ash I'man's on Deck 0:09:26.080 --> 0:09:29.200 also developed a variation on this test for cases where 0:09:29.240 --> 0:09:32.160 someone might more urgently need to know if they were pregnant. 0:09:32.559 --> 0:09:35.520 Although it came at a cost of more mice, They 0:09:35.600 --> 0:09:38.280 used more mice in the experiment and then that they 0:09:38.360 --> 0:09:42.920 dissected them earlier in the range past when they had 0:09:42.920 --> 0:09:46.080 begun the testing. That larger sample set made up for 0:09:46.120 --> 0:09:48.880 the shorter testing period. We are about to talk about 0:09:48.920 --> 0:09:51.600 a little variation on the method that they developed, but 0:09:51.679 --> 0:09:53.840 first we'll pause and have a quick word from one 0:09:53.880 --> 0:10:04.960 of the sponsors that keeps the show going. Other doctors 0:10:05.080 --> 0:10:07.760 took the work of the German team and the Asheim 0:10:07.840 --> 0:10:10.360 Zondeck test, which was often abbreviated to just called be 0:10:10.440 --> 0:10:13.440 called the AZ test, and they made slight tweaks to 0:10:13.480 --> 0:10:16.800 the method for what worked best for their laboratory situation 0:10:16.840 --> 0:10:20.480 and their staff at the University of California at Berkeley 0:10:20.520 --> 0:10:23.800 in the late nineteen twenties, researchers opted to use six 0:10:23.920 --> 0:10:26.880 rats for the procedure rather than mice, and they stored 0:10:26.920 --> 0:10:30.240 the urine samples at freezing temperature before injection. They of 0:10:30.280 --> 0:10:32.920 course heated it back up so that the animals were 0:10:32.960 --> 0:10:36.920 not going to shock after the injection. Using rats was 0:10:36.960 --> 0:10:40.199 actually more cost intensive than mice, but you see, Berkeley 0:10:40.240 --> 0:10:43.160 had already had an established rat colony for use in 0:10:43.200 --> 0:10:46.640 their laps. The primary benefit and using rats instead of 0:10:46.679 --> 0:10:49.200 mice was the fact that all of the rats usually 0:10:49.200 --> 0:10:53.200 survived the test at least the injection and sort of 0:10:53.240 --> 0:10:56.320 incubation portion of the test, but in mouse based testing, 0:10:56.360 --> 0:10:59.440 fift of the rodents died before they reached that day 0:10:59.480 --> 0:11:02.680 five exam a nation stage, and both tests the error 0:11:02.760 --> 0:11:05.720 rate was quite small, between one and two percent, and 0:11:05.760 --> 0:11:09.839 according to data collected in Ashiman Zondex lab, this test 0:11:09.960 --> 0:11:14.000 was also quite good at early detection. There were recorded 0:11:14.040 --> 0:11:17.679 instances of positive results before any other clinical signs of 0:11:17.720 --> 0:11:20.839 pregnancy were present, for example, just three to four days 0:11:20.960 --> 0:11:24.640 after the patient had missed a menstrual period. Results were 0:11:24.679 --> 0:11:28.040 most reliable though in cases of normal pregnancy, so in 0:11:28.040 --> 0:11:32.199 instances of more problematic situations like a tubal pregnancy. The 0:11:32.360 --> 0:11:36.600 results were, according to the German doctor's data, slightly less accurate. 0:11:36.880 --> 0:11:39.360 This was at a time in medical science when diagnostic 0:11:39.400 --> 0:11:42.840 tests weren't always common practice in Western medicine, and they 0:11:42.880 --> 0:11:46.920 certainly weren't common specifically for women. Additionally, a lot of 0:11:46.960 --> 0:11:50.120 doctors felt as though it was extraneous. They trusted their 0:11:50.160 --> 0:11:53.800 experience and diagnostic abilities to determine if someone was pregnant 0:11:53.880 --> 0:11:57.319 or not. There was concerned that testing labs removed for 0:11:57.400 --> 0:12:01.160 the relationship and the trust between the doctor and the patient. Yeah, 0:12:01.160 --> 0:12:05.560 this was particularly a problem UM in Great Britain. I 0:12:05.600 --> 0:12:08.600 was reading one article that UM mentioned that this one 0:12:08.640 --> 0:12:12.200 particular lab in Edinburgh had started taking mail in samples 0:12:12.200 --> 0:12:14.840 and people were like, but they're bypassing their doctors just 0:12:14.920 --> 0:12:19.079 to do a direct thing. Um. There were a lot 0:12:19.120 --> 0:12:20.720 of a lot of concerns. And this is at a 0:12:20.720 --> 0:12:23.280 point where there was insurance in Great Britain, but it 0:12:23.520 --> 0:12:27.240 didn't always cover women, and it certainly didn't cover them 0:12:27.280 --> 0:12:29.200 just wanting to find out if they were pregnant. That 0:12:29.280 --> 0:12:32.720 was usually only for like an emergency, which we'll talk about. Additionally, 0:12:32.760 --> 0:12:35.800 most of the time most women suspected they were pregnant 0:12:35.840 --> 0:12:38.800 already and they went to their doctor just to confirm 0:12:38.880 --> 0:12:42.319 what they already thought. And family practitioners used this as 0:12:42.360 --> 0:12:44.600 evidence that there was not a real need for such 0:12:44.600 --> 0:12:48.199 tests to become mainstream. In most cases, unless there was 0:12:48.240 --> 0:12:51.200 an urgent medical dean to know if a woman was pregnant. 0:12:51.200 --> 0:12:55.480 Health organizations and insurance companies where they existed, because insurance 0:12:55.880 --> 0:13:00.199 didn't really start until the late nineteen twenties, were unlikely 0:13:00.280 --> 0:13:03.559 to approve coverage for the cost of the test. Testing 0:13:03.600 --> 0:13:07.000 samples sent through the mail was particularly looked down upon 0:13:07.160 --> 0:13:09.640 us we just sort of alluded to. It was referred 0:13:09.640 --> 0:13:14.360 to as postal pathology. That's a a criticism that still 0:13:14.360 --> 0:13:16.240 exists today with all the various things that you can 0:13:16.240 --> 0:13:19.280 test at home and kind of mail away. But this 0:13:19.360 --> 0:13:22.040 test was recognized for its efficacy and it became more 0:13:22.040 --> 0:13:26.160 and more commonly administered. Both Selmer Asheim and Bernard Zondeck 0:13:26.240 --> 0:13:29.079 were Jewish, and both of them chose to leave Germany. 0:13:29.080 --> 0:13:31.160 I say chose, but they really had to for their 0:13:31.160 --> 0:13:34.640 lives in nineteen thirty three as the Nazi Party came 0:13:34.679 --> 0:13:37.640 into power, and they left their lab behind in the process. 0:13:38.360 --> 0:13:41.920 In thirty one, the landscape for pregnancy testing shifted when 0:13:41.920 --> 0:13:44.840 a similar test to the A Z test was introduced 0:13:44.880 --> 0:13:48.320 at the University of Pennsylvania by Maurice Harold Friedman and 0:13:48.400 --> 0:13:54.000 Maxwell Edward Lapham. Freedman, who was born on October three 0:13:54.000 --> 0:13:57.240 and Gary, Indiana, had been with the University of Pennsylvania 0:13:57.280 --> 0:14:00.959 as a faculty member since he had earned his bachelor's 0:14:00.960 --> 0:14:04.000 degree PhD and m d at the University of Chicago 0:14:04.080 --> 0:14:06.840 starting in nineteen nine, so he went into his undergrad 0:14:06.880 --> 0:14:09.800 at just sixteen, so he was still quite young when 0:14:09.800 --> 0:14:13.079 he developed the rabbit test, and Maxwell E. Lapham, who 0:14:13.120 --> 0:14:15.640 was born in newfe New York, was just three years 0:14:15.679 --> 0:14:18.040 older than his collaborator, and he was working at the 0:14:18.120 --> 0:14:21.720 university hospital at the time. And an article titled a 0:14:21.800 --> 0:14:26.160 Simple Rapid Procedure for the Laboratory Diagnosis of Early Pregnancies 0:14:26.200 --> 0:14:30.359 in the March issue of the American Journal of Obstetrics 0:14:30.400 --> 0:14:34.040 and Gynecology, Friedman and Lapham wrote about their choice to 0:14:34.080 --> 0:14:36.800 move away from mice for their test, starting with a 0:14:36.840 --> 0:14:39.840 reference to the as test, It said quote Yet this 0:14:39.960 --> 0:14:43.960 test admirable, though it is has some distinct disadvantages, one 0:14:44.000 --> 0:14:46.800 of which may make it impractical in a laboratory or 0:14:46.880 --> 0:14:51.080 hospital not closely affiliated with some university or institute. To 0:14:51.280 --> 0:14:55.040 perform the zondek Asheim test, it's essential to be in 0:14:55.360 --> 0:14:58.160 in a position to command a ready supply of amateur 0:14:58.240 --> 0:15:02.480 mice weighing from sixt grahams. If a large breeding colony 0:15:02.520 --> 0:15:05.480 of mice is not easily available, some difficulty might be 0:15:05.560 --> 0:15:08.880 encountered in procuring suitable animals at a time as test 0:15:08.920 --> 0:15:13.400 as desired. Moreover, even if one had at hand enough 0:15:13.400 --> 0:15:16.560 of the immature mice to answer the calculated requirements for 0:15:16.600 --> 0:15:18.840 a given week, and for some reason or other the 0:15:18.920 --> 0:15:23.560 number of samples submitted fell below expectations, the unused animals 0:15:23.600 --> 0:15:26.960 would soon mature beyond their usefulness, so that another group 0:15:27.000 --> 0:15:29.960 of the immature animals would have to be gotten. Freedman 0:15:30.040 --> 0:15:33.320 and Lapham's test used rabbits instead of mice, and just 0:15:33.360 --> 0:15:35.840 as rats were more of a burden to support than mice, 0:15:36.440 --> 0:15:39.280 rabbits took a lot more effort and resources to keep 0:15:39.280 --> 0:15:42.760 in a lab setting. But there were some very significant 0:15:42.760 --> 0:15:46.440 benefits to rabbits over mice. For one, it required only 0:15:46.520 --> 0:15:50.400 one to two specimens rather than six. Aside from just 0:15:50.480 --> 0:15:53.440 the number of creatures harmed. This also just meant one 0:15:53.520 --> 0:15:57.480 or two necropsies rather than half a dozen, and unlike mice, 0:15:57.680 --> 0:16:01.120 rabbits only ovulate after mating. That meant they didn't need 0:16:01.200 --> 0:16:04.680 to use only very young animals. With mice, the very 0:16:04.680 --> 0:16:07.680 young specimens were used to avoid any confusion that might 0:16:07.720 --> 0:16:11.640 arise should Amounse just be developing a natural estrous cycle, 0:16:11.680 --> 0:16:14.120 which would look pretty similar to a positive result in 0:16:14.160 --> 0:16:17.360 the testing. As long as they knew the rabbit's history 0:16:17.400 --> 0:16:21.280 and it had been isolated because exposure to other female 0:16:21.360 --> 0:16:24.440 rabbits could cause estrus, it could stay viable as a 0:16:24.440 --> 0:16:27.720 test subject until it was needed, instead of aging out 0:16:27.760 --> 0:16:31.280 of usefulness for testing purposes. But even if a rabbit 0:16:31.320 --> 0:16:34.680 had not been fully isolated, it could still potentially be 0:16:34.840 --> 0:16:38.920 used per Friedman and Lapham quote. In case one has 0:16:38.920 --> 0:16:42.240 not had opportunity to isolate the rabbits for the desired period, 0:16:42.800 --> 0:16:45.640 and it is found necessary to perform a test, it 0:16:45.800 --> 0:16:48.200 is safe to use a rabbit that has been isolated 0:16:48.240 --> 0:16:52.000 in the laboratory for only eight or ten days, even 0:16:52.040 --> 0:16:54.760 if the rabbit in question had had coitus just before 0:16:54.760 --> 0:16:58.320 it was obtained. The corporal lutilla of pregnancy or pseudo 0:16:58.320 --> 0:17:01.640 pregnancy would then be least eight or ten days old 0:17:01.800 --> 0:17:04.479 and could not be confused with the fresh corporate lutia 0:17:04.640 --> 0:17:09.560 or corporal hemorrhagica produced by the injections of an active urine. Briefly, 0:17:09.640 --> 0:17:12.399 then one may safely use all rabbits that are not 0:17:12.480 --> 0:17:15.760 demonstrably pregnant at the end of three weeks of isolation. 0:17:16.200 --> 0:17:19.359 Pathologists also found the rabbits easier to handle, and it 0:17:19.400 --> 0:17:23.120 was easier to administer injections into the veins of their ears. 0:17:23.160 --> 0:17:26.000 They could perform the necropsy without the need for a 0:17:26.080 --> 0:17:30.040 microscope or a magnifying glass because the results were observable 0:17:30.080 --> 0:17:33.000 to the naked eye rather than needing to be magnified. Yeah, 0:17:33.040 --> 0:17:34.560 that was not the case with mice or you had 0:17:34.600 --> 0:17:37.800 to look very closely at their tiny, tiny organs. You 0:17:37.800 --> 0:17:40.399 could literally just do the necropcy and go yep, this 0:17:40.480 --> 0:17:44.159 one is positive. But the big, big difference was that 0:17:44.280 --> 0:17:46.880 a rabbit test could be turned around in forty eight 0:17:46.880 --> 0:17:50.560 hours rather than five days. While Lapham and Friedman tried 0:17:50.600 --> 0:17:53.360 a similar method of earlier necropsy that had been used 0:17:53.359 --> 0:17:55.520 in mice, as you remember, they had just up the 0:17:55.600 --> 0:17:59.400 number of mice used and then did a test doing 0:17:59.440 --> 0:18:02.840 sort of pattern recognition at a shorter interval. They actually 0:18:02.880 --> 0:18:05.920 found the results a lot less reliable when they try 0:18:05.960 --> 0:18:08.760 a similar method in rabbits. We're about to get into 0:18:08.760 --> 0:18:11.879 the numbers involved in the research that Freedman and Lapham 0:18:12.000 --> 0:18:14.440 used to test their rabbit method, but first we will 0:18:14.480 --> 0:18:25.080 take a quick sponsor break. To test their approach, the 0:18:25.200 --> 0:18:28.840 University of Pennsylvania team used a hundred and eleven samples. 0:18:29.520 --> 0:18:32.679 Three samples were deemed too toxic to use in the test, 0:18:33.200 --> 0:18:36.200 and the specific nature of the toxicity is not described 0:18:36.280 --> 0:18:38.920 in the Freedman and lap of paper, but a lab 0:18:38.920 --> 0:18:41.480 in Edinburgh, Scotland, which did quite a lot of pregnancy 0:18:41.520 --> 0:18:45.800 testing in the nineteen thirties, described sometimes getting samples of 0:18:45.960 --> 0:18:49.200 urine which were green because the women who had given 0:18:49.240 --> 0:18:51.680 them had used some sort of chemical means to try 0:18:51.680 --> 0:18:55.080 to avoid pregnancy. Those samples were lethal to mice, which 0:18:55.080 --> 0:18:57.600 was the testing animal that the Edinburgh lab used, so 0:18:57.640 --> 0:19:01.080 the test would not work. Freedman and Lapa mentioned as 0:19:01.280 --> 0:19:04.040 a desire to find a way to handle so called 0:19:04.119 --> 0:19:07.560 toxic samples. Writing quote zon Deck reports that about six 0:19:07.640 --> 0:19:10.760 percent of the samples submitted were too toxic. To be handled, 0:19:10.840 --> 0:19:13.919 and to obviate this difficulty, he has devised a method 0:19:13.920 --> 0:19:17.840 by which these toxic urines may be made innocuous. Since 0:19:17.880 --> 0:19:20.359 the appearance of this paper, we have not encountered a 0:19:20.400 --> 0:19:23.920 sample with which to test this procedure, so that left 0:19:23.920 --> 0:19:27.560 a hundred and eight samples for the study, and twenty 0:19:27.560 --> 0:19:29.520 five of those samples were from women who were in 0:19:29.560 --> 0:19:32.480 their last months of gestation, and all of their samples, 0:19:32.520 --> 0:19:36.600 as expected, yielded positive test results. Thirty two of the 0:19:36.640 --> 0:19:38.840 samples were from women who had gone to the clinic 0:19:38.880 --> 0:19:41.760 at the university hospital to determine if they were pregnant. 0:19:42.240 --> 0:19:45.399 Twenty five of them tested positive for pregnancy, and the 0:19:45.440 --> 0:19:47.800 research team was able to track twenty two of those 0:19:47.800 --> 0:19:50.960 women to further verify that they had been pregnant, although 0:19:51.000 --> 0:19:54.119 not all of them carried those pregnancies to full term. 0:19:54.200 --> 0:19:57.400 The remaining three did not remain in contact with the study. 0:19:57.760 --> 0:20:00.760 There were fifty one negative test results from this viable 0:20:00.800 --> 0:20:04.080 group of a hundred eight samples. Two of those samples 0:20:04.080 --> 0:20:07.800 were from men and were from women in the hospital 0:20:07.840 --> 0:20:10.199 who were known to have been not pregnant at the 0:20:10.200 --> 0:20:13.800 time of testing, including several with conditions that might clinically 0:20:13.920 --> 0:20:17.120 present as looking pregnant without a test, like they had 0:20:17.240 --> 0:20:21.480 nausea or their abdomens were swollen, something like that. Yes, 0:20:21.520 --> 0:20:24.040 so they wanted to include people that they absolutely knew 0:20:24.080 --> 0:20:27.120 were not pregnant to prove that the tests was accurate 0:20:27.160 --> 0:20:30.320 in both positive and negative and also people who might 0:20:30.359 --> 0:20:33.879 be told by a doctor who was just examining them 0:20:34.119 --> 0:20:36.439 that they were probably pregnant but were in fact not. 0:20:36.920 --> 0:20:39.680 Twenty four of the negative test results had been for 0:20:39.800 --> 0:20:42.080 women who had visited the clinic to determine if they 0:20:42.080 --> 0:20:45.280 were pregnant, and the study remained in contact with eighteen 0:20:45.320 --> 0:20:48.360 of those patients and they were verified as non pregnant. 0:20:48.720 --> 0:20:51.320 That left ninety two cases for which the doctors felt 0:20:51.320 --> 0:20:54.000 they had adequate data for the inclusion in the study 0:20:54.040 --> 0:20:57.440 statistical analysis, and that left them with an error rate 0:20:57.520 --> 0:21:01.160 of zero. But in their paper Forman and Lapham wrote, 0:21:01.240 --> 0:21:03.679 it is likely that if we had more material, we 0:21:03.760 --> 0:21:07.440 might have encountered an error or two. Yeah, they were 0:21:07.480 --> 0:21:09.600 not asserting that it was a percent effect of all 0:21:09.600 --> 0:21:12.479 the time, um, but of the ninety two that had 0:21:12.520 --> 0:21:15.560 been that it had been paired down to after they 0:21:15.720 --> 0:21:19.159 uh had to leave out the toxic urine samples and 0:21:19.240 --> 0:21:22.520 the ones that they lost track of it was accurate 0:21:22.680 --> 0:21:26.239 in that data. The Freedman Lapham test was adopted more 0:21:26.320 --> 0:21:29.359 readily than its predecessor, the mouse version, in part because 0:21:29.359 --> 0:21:32.120 the asy test had blazed a trail already, so people 0:21:32.160 --> 0:21:35.280 already had this idea that this test was worthwhile and 0:21:36.680 --> 0:21:40.320 was accurate, and also for all of the reasons that 0:21:40.359 --> 0:21:43.080 were laid out in the paper published by Freedman and Lapham. 0:21:43.160 --> 0:21:46.159 For example, hospitals found it much easier to set up 0:21:46.160 --> 0:21:49.000 a lab for a smaller number of rabbits than huge 0:21:49.080 --> 0:21:51.560 numbers of mice, which they would have to continually be 0:21:51.640 --> 0:21:55.160 breeding to get workable um animals that they could use 0:21:55.160 --> 0:21:58.359 in testing, even though it was still more expensive to 0:21:58.520 --> 0:22:02.040 house a rabbit, and the reliability and the speedier assessment 0:22:02.080 --> 0:22:05.399 during necropsy made this test much more appealing as well. 0:22:05.880 --> 0:22:08.199 And as a bit of myth busting, you may have 0:22:08.320 --> 0:22:11.040 heard the joke the rabbit died as a shorthand way 0:22:11.080 --> 0:22:13.200 to say that somebody is pregnant, and this has been 0:22:13.200 --> 0:22:18.000 a long a longstanding misconception connected to this test. I 0:22:18.040 --> 0:22:20.800 think both Holly and I at some point have probably 0:22:20.840 --> 0:22:23.439 said that I know I have repeated that myth, So 0:22:23.520 --> 0:22:25.800 apologies to anyone that heard that from my lips. You 0:22:25.920 --> 0:22:30.800 got misinformation. Yeah, the positive test result was not indicated 0:22:30.800 --> 0:22:34.400