The Mouse Lady

Maud Slye - The Mouse Lady

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Katie Hafner: Hey Elah, so you have quite the saga for us today, right?

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Elah Feder: Yes, so Katie, usually on the show we feature women who accomplish something great that deserves to be remembered. Sometimes they're women who discovered something important about our world, and the woman that I'm gonna tell you about, she does fall into that category in some really important ways. But I wanted to also give you a heads up that as I started digging into her archives, I realized she got some things very wrong in cases where she really should have known better––in my view––and she just refused to back down. So not a perfect specimen of scientific research, but if we're gonna understand how science works and advances, I think that this woman and many other researchers like her are definitely part of this story. 

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Katie Hafner:  Of course. I mean, let's not forget people get stuff wrong all the time. I think it's gonna be a matter, once you tell me the story, of how egregious her error was, right?

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Elah Feder:  I'm, I'm very excited for you to weigh in on that. 

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Katie Hafner: Okay, so, who are we talking about today? 

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Elah Feder: Her name was Maud Slye, AKA “the mouse lady.” In the 1910s, she was a researcher at the University of Chicago, and she was working with mice to answer a massively important question: what causes cancer?

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Katie Hafner:  Even today massively important.

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Elah Feder: We still don’t have a complete answer to that question, but back in the 1910s, people were really at sea. Why do our own cells—cells that are supposed to be working for us—end up sometimes growing dangerously out of control and working against us, sometimes even killing us.

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In the 1910s, lots of ideas were being thrown around, some with more validity than others. People spoke often of cancer being caused by some kind of “irritation” to the tissues––like you have repeated friction in that area or maybe you’re a chimney sweep and you’re exposed to soot over and over again, and  maybe you develop cancer in that area later on. Another idea: cancer was caused by some kind of germ, which we know now sometimes it can be. Or, this is an interesting idea––I came across this in the newspaper archives––maybe cancer was caused by eating an overly complex diet. This particular writer even noted that cannibals having a very simple diet do not develop cancer very often. So, this particular idea was probably kinda fringe, but I mean, as far as I could tell, a lot of ideas were honestly being entertained because it really was an open question: what causes cancer?

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And then in 1913, this researcher named Maud Slye publishes a report: the first results of what would become a decades-long research project. And her results suggested to Maud that cancer was actually very simple. Cancer was caused by your genes. Just one gene, actually, a cancer gene.

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Katie Hafner: This is Lost Women of Science, I’m Katie Hafner.

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Elah Feder : And I’m Elah Feder, and today, the story of Maud Slye aka the Mouse Lady.

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Katie Hafner: So 1913, Maud Slye, this unknown researcher jumps into the cancer conversation, and says she’s figured some things out - who was she?

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Elah Feder: Okay, Maud Slye, born around 1869 in Minneapolis––Although a lot of sources say 1879, including Maud herself. 

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Katie Hafner: Wait, that-  that's a lot of years.

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Elah Feder: Yeah. It's a 10 year difference. Census records suggest it was 1869, not 10 years later, like she said, but the University of Chicago thinks that this might have been to avoid mandatory retirement. Apparently quite a few people lied about their age for that reason. 

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Katie Hafner: Oh, interesting.

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Elah Feder: Either way, in 1895, Maud, probably in her late 20s, went to college at the University of Chicago. Maud’s parents didn’t have a lot of money, and Maud doesn’t have an easy time for that reason. She has to pay her own way through college, so she gets a job as a part-time secretary for the President of the University of Chicago on top of working on her undergraduate degree.

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Karen Rader:  I can't even imagine how stressful that must have been, and there are lots of reports that talk about the fact that she had a nervous breakdown.

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Elah Feder: Karen Rader is a history professor at Virginia Commonwealth University, and she’s researched Maud’s story. And she says that while we don’t have any details about Maud’s nervous breakdown, we do know that she left her program at University of Chicago and moved away-

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Karen Rader:  -to Woods Hole, Massachusetts, where she had a bunch of relatives because she has descended from a Mayflower family.

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Elah Feder: Going to Woods Hole ended up being very auspicious for her. 

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Karen Rader:  A lot of people were eager to go there because they knew that prominent biologists were gonna be doing research. She didn't go there––I don't think––for that reason. Although we don’t know. We don’t have documentation.

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Elah Feder: Either way, Maud does go there, and her proximity to that hub of biology ends up being critical for what comes next. Maud ended up enrolling at Brown University in Providence, Rhode Island, which is not too far from Woods Hole. She got her bachelor's degree in 1899, and she ended up doing what a lot of educated women did at the time. She taught. 

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She taught at what’s called the Normal School, so a school for teachers in Rhode Island, but she was obviously still spending time in Woods Hole because we know that it was at Woods Hole she met someone who was going to radically change the trajectory of her life. Charles Whitman, have you heard of Charles Whitman? 

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Katie Hafner: I’ve never heard of Charles Whitman, no.

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Elah Feder: Okay, so he was actually the first director of the Woods Hole Marine Biological Laboratory––distinct from the Oceanographic Institution. He was also head of the biological sciences division at the University of Chicago. And he must have been really impressed with Maud because in 1908 he invites her to come back to Chicago to be his graduate assistant and soon, she was doing her own scientific research there.

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Katie Hafner: Okay, so here she’s been a teacher for several years, which is what a lot of women end up doing for the rest of their lives. And then she's suddenly a full-fledged research scientist.

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Elah Feder: Yeah, it’s a big life change.

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Katie Hafner: And what’s she researching?

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Karen Raider:  The genetics of the Japanese waltzing mouse. These mice go in circles, we know now because they have an inner ear defect and she was trying to understand the genetics of that, not knowing that it was an inner ear defect––thinking it was a behavioral problem.

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Katie Hafner:  They're called Japanese- why are they Japanese? And they're waltzing mice? And it's really because they have an inner ear defect, so they're kind of going around in circles,

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Elah Feder: I will note these are going to be bit players in our bigger story, but it- it's a charming beginning. 

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Katie Hafner: And that said to Maud- what did that say to Maud? 

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Elah Feder:  She, I mean, I think for her it was just a model for genetic inquiry. Although I should mention that she doesn't really use the terms “gene” or “genetics” for many years, even though that's exactly what she's studying. And it kind of makes sense 'cause genetics is such a new field at this point. The terms are still in flux. Mendel’s laws of inheritance had been rediscovered in 1900, so just eight years before she starts researching.

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Katie Hafner:  So, remind me who Mendel was. He was a monk slash biology enthusiast. He was the one who famously studied inheritance in peas. Do you remember this from high school biology?

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Katie Hafner: Peas? As in the peas we eat?

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Elah Feder: The peas we eat.  His famous contribution is, I mean, it's massive. He figured out the whole concept of recessive and dominant traits. So, quick refresher, red hair, for example, is recessive, which means if you get a gene for red hair from your dad and a gene for brown hair from your mom, you will have brown hair because brown is dominant to red. Red is recessive, so it’s hidden away, but you still have that red hair gene in you. You can still pass that on to your kids. Mendel worked these concepts out with peas. Huge, huge contribution, but it was forgotten for many, many years. People got that inheritance was a thing. They could see, obviously, family resemblance, but they didn’t understand how this happened. The prevailing theory was that you just blended traits. It was kind of like mixing paint, so you have a parent with dark brown hair and a parent with blonde hair and the kids would be something in between, like a medium brown. But then, it didn’t quite make sense because every once in a while you get two parents with brown hair and they have a red-headed kid. How do you explain that? Well, Mendel’s theory helped to explain that, right.

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Katie Hafner: Got it. So enter Maud…

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Elah Feder: She’s entering genetics at a time where people are finally aware of Mendel again. His work has been unearthed, and its a super exciting time. You’re starting to get how inheritance actually works, but at the same time there are all these unanswered questions. So Maud jumps in, starting with these waltzing mice, but pretty quickly, she changes her focus to cancer. She later told one newspaper it was because one of her Japanese mice developed a breast tumor and she knew then what God wanted her to do. In other words, God wanted her to figure out what causes cancer and if it can be inherited!

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Katie Hafner:  And at the time, was that a radical idea to suggest that it could be inherited, that it could be genetic?

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Elah Feder: Not exactly. There were other ideas that had more traction, but by the time that Maud published her work, people had noticed that cancer seemed to run in some families. Some strains of inbred mice and rats had higher rates of cancer,  so they kind of got that this might be happening, but it was still controversial. I actually found in her archive some hate mail from someone who said like, how dare you suggest that cancer can be inherited? You’re taking all hope away from people.  So not universally accepted, but to a lot of scientists, it was a plausible idea.

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Katie Hafner:  Mm-hmm. So just to recap, this is the early 1900s, and she couldn't exactly sequence genes. So what does she do? 

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Elah Feder:  Okay, so she did what, what Mendel did: she looked at inheritance patterns. This is very hard to do with human beings. Human beings take forever to reproduce, but mice reproduce in just a few weeks. So Maud she started really small. She was given some space in the basement of the University of Chicago ‘s Zoology building. And she just has a handful of mice, but she keeps on breeding them. And soon she had a hundred, a thousand.

Eventually her colony would grow to more than 60,000 mice. 

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Katie Hafner:  All in the same space? In the basement of the Zoology building?

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Elah Feder: They definitely outgrew the Zoology building and by the end she is given a three storey building. Karen Rader, who you heard earlier, she has learned a lot about laboratory mouse colonies, and here’s what she had to say about keeping tens of thousands of mice.

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Karen Rader:  Wow is what I would say about that many mice. Even in the 5,000 range.

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Elah Feder: Mice need a lot. Their cages have to be cleaned all the time-

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Katie Hafner:  Cleaned. I was gonna say that. I used to have a pet rat, as you know––Peanut Butter, my rat––and, oh my goodness, they smell. 

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Elah Feder:  Yeah. Actually, Karen had a story about that. This other mouse research lab, she looked at Harvard, she said that the people who work there-

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Karen Rader: They were essentially incentivized to live in the dormitory there because every time they would go to the lab, they would leave the lab smelling like mouse urine and they didn't want to have to get on the subway and drive eight stops to get home to their apartment.

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Katie Hafner: Because they couldn't wait to get the urine smell off?

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Elah Feder:  And people probably didn't wanna be around them. And then there's just like everything else that mice need.

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Karen Rader:   They have to have enough materials in their cage to be able to burrow.  They have to be fed, but it has to be done in a way that's very sensitive because if you disrupt their nesting, then they won't reproduce. 

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Katie Hafner:  Did she really need 60,000 mice? I mean maybe she was just a little bit crazy and she just couldn’t help herself.

Elah Feder: I don't feel qualified to say the minimum number of mice she needed to answer her questions. But yeah, she devoted her life utterly to these mice in a way that most researchers don't. She moved in directly across the street from her mice, so she'd cut back on travel time. She would skip meals because feeding the mice was so expensive and sometimes she decided to feed them instead of herself.

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Katie Hafner: And yet, she wasn’t raising them as pets. So what did she find?

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Elah Feder: So, Maud had different inbred families of mice. So mice that had shared a lot of genes. And she found that in some of these mouse families almost everyone got cancer. But, in other families, there was no cancer. They seemed totally immune. And when Maud crossed mice from families that got cancer with mice from families that didn’t, the offspring did not get cancer.

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Katie Hafner:  Run that past me one more time and then explain it to me. 

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Elah Feder:  Okay. So you've got some families: lots of cancer. Some families: no cancer. You take a mouse from a cancer family, and another mouse from a no cancer family. You get them to mate, and she found that the offspring did not get cancer.

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Katie Hafner: Interesting, so what does that mean?

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Elah Feder: To Maud this pattern of inheritance looked super familiar. It looked exactly like what Mendel found with his peas. This was her conclusion at the time:  that there was one gene that controlled cancer risk and cancer risk was recessive. F And Maud felt pretty sure that if that was true, she had a plan to save us all from cancer once and for all.

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Katie Hafner: Okay, I am on tenterhooks. How did she plan to do that?

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Elah Feder:  W0e will find out, after the break!

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BREAK

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Katie Hafner:  So before the break, we found out that Maud Slye decided that cancer was recessive and that she had a solution that would save all of us from the scourge of this disease. What was that?

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Elah Feder:  You'll be shocked to learn that her solution was eugenics.

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Katie Hafner:  Uh, wait, let me make sure I heard that right. So, eugenics as in? 

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Elah Feder:  As in, I'm going to give you Maud's version of eugenics, but generally it's, the belief that we can make humanity better by controlling who mates and how.

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Katie Hafner: Aha.  Okay. you've gotta tell me more. This is getting interesting, and maybe even more interesting than all the mice?

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Elah Feder:  Yes. I think you will find it quite interesting. Definitely ethically questionable to say the least. There are different flavors of eugenics and so I'll tell you about Maud's particular version. She thought that people who have cancer in their families should only have babies with people who have no cancer in their families.  And then if we carefully kept track for generations, we could be done with cancer all together, because again if cancer is recessive, we just had to make sure every baby got at least one copy of the good version of the gene, so the dominant anti-cancer version of the gene. And the baby would be safe. Karen Rader again.

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Karen Rader: She was very, um, what's the word? What's the adjective I wanna use? I would say militant, but that's what a lot of women get called, so I’m not gonna-  what I mean is she was very unromantic about it. She wasn’t into sterilization. She wasn’t into barring. But, she had this  very unromantic, sort of single-minded, like, if what I am saying is true, then we should- we should breed it out. We should do it. 

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Elah Feder: In fact, Maud, she poo-pooed romance. She said this a bunch of different ways over the years but basically, she was like, if we humans just mate scientifically, we’d eliminate cancer. And, don’t worry about romance. Romance will sort itself out.  Maud herself, probably worth noting never married, didn't have kids. So maybe that's why she had a sort of cool detachment? We can't say.

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Katie Hafner:  No, we can't say, we can't conjecture, but it- it supports her, her clinical approach. 

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Elah Feder: Mm-hmm. So obviously we can object to Maud’s plan on moral grounds. I don’t want to live in a world where geneticists decide who I’m allowed to reproduce with, but-

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Katie Hafner: Aw, come on

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Elah Feder: [laughs] There’s a certain excitement factor, you know, the roll of the dice, who’s it gonna be?  But, moral objections aside, her plan assumed things about cancer genetics, we now know just are not true. There isn’t just one or two or even three genes––like Maud eventually thought––that are linked to cancer, but hundreds of genes. And most cancers have no known heritable component.

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Raymond Kim:  When we itemize all cancers in general, only about five to 10% are thought to be hereditary, where an inherited genetic change results in the cancer predisposition.

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Elah Feder: Raymond Kim is a medical geneticist at the Princess Margaret Cancer Centre in Toronto. He’s also medical director of their familial cancer clinic. And he explained that each of the known cancer-linked genes are associated with different kinds of cancer, some to multiple kinds.

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Raymond Kim:  For example, BRCA1 is the most well known, and BRCA2 is the sister gene, and those patients are at increased risk of breast, ovarian, prostate, pancreas, cancer. 

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Unlike what Maud believed, these cancer-linked mutations in BRCA or “braca,” they are dominant, not recessive, meaning if you get just one copy of a mutated gene, that is enough to increase your cancer risk. So, Maud’s idea that you could eliminate cancer by making people with cancer in their family reproduce with people with no familial cancer, that wouldn’t work. A parent with the BRCA mutation can pass that risk on to their kids, regardless of who the other parent is. Still, Raymond thinks Maud got a lot right given the limited tools at her disposal back then.

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 Raymond Kim: Of course, hindsight is 20/20. You know, we do know now, where we have the ability to sequence the entire genome that cancer is a little bit more complex, but there are a few areas that she seemed to have hit. 

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Elah Feder: Maud’s research did demonstrate something really important. Cancer risks could be heritable, but skip generations. This is big for this era. So, scientists were very interested in her findings.

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Katie Hafner: And did other scientists see it that way? 

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Elah Feder:  A lot of scientists were blown away. Maud published her first report on her research in 1913, another in 1914, but people seem to really take notice after her third report comes out, in 1915. 

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A month after she publishes that report, the Journal of the American Medical Association publishes an editorial calling her study remarkable and “one of the great contributions to our knowledge of cancer.” A month after that she wins a prize from her university for research in pathology. People really appreciate this- this is big. 

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But not everyone was a fan. So, I got copies of her correspondences from the University of Chicago library. And, I did not expect them to read like this. 

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Katie Hafner: Uh huh, can you read me a couple?

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Elah Feder: Ohhh. At one point, for example, she has a dispute with the American Society for the Control of Cancer––or what we call the American Cancer Society today––because after one of their meetings, they put out a statement that you can't inherit cancer, but you can inherit cancer risk. But, they also reassure people and say that just because your parents had cancer, it doesn't mean that you're necessarily gonna get it. Can you see the problem with this? 

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Katie Hafner:  Can I see the problem? 

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Elah Feder: Yeah.

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Katie Hafner: No. Am I dense?

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Elah Feder: I couldn’t either.  But, Maud was flabbergasted. I mean, how could they put out such an inaccurate, irresponsible statement?  And I think her problem was they were too reassuring about genetics. She wanted eugenics to be promoted. And they were instead advocating for more focus on quote “personal hygiene” and other preventative and curative measures. This conflict, it was totally unnecessary in my view, but that one was actually pretty brief. The really ugly fight- this one started when a researcher speaking at a meeting of the Columbus Academy of Medicine, publicly says he heard from another researcher that someone went to Maud’s lab and asked to see her data, she refused and then she cried. Maud is understandably horrified at this rumor. She squarely denies it. 

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Katie Hafner:  That she cried or that the person went to the lab? 

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Elah Feder: All of it. She denies every part of it. It’s totally understandable that she wanted to find out who exactly said this about her, and have this publicly corrected. But, this feud goes on and on for months, with back and forth letters. There are apologies, denials, but nothing will appease Maud. Reading her correspondences, I got the sense of a person who felt very much under siege, who felt like she had to to fight to the death to defend her honour. And, you know, sometimes she really was attacked unfairly. But there were times I just wanted her to let it go.

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Katie Hafner:  But, as this debate was going on, Elah, was the science advancing?

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Elah Feder:  That's a really good question. science, as we know is not always like a cold, clinical, detached process. Disagreement and wounded egos are part of it. But, these fights I just told you about were about personal grievances, they were about public messaging, they weren’t  about figuring out what was true. The one exception was a feud with someone named Clarence Cook Little.

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He would rise to be a very big name. But, at the time he'd just finished his PhD where he'd been studying coat color genetics.

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Katie Hafner: Coat color genetics?

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Elah Feder: Yeah sorry, in mice.

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Katie Hafner: Oh in mice!

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Elah Feder: Yes!

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Katie Hafner:  Not in the fashion industry. Got it. Got it. Got it. 

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Elah Feder: Yeah, exactly. In any case, he sees Maud’s third report, and he notices that at the top, she gives a quick refresher how a recessive gene works  cause, like, again, this is now something that everybody learns in high school biology, but not then. Right. This was still new information. So, she does that and she decides to give an example of mouse coat color.

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Little, of course, just happens to know a lot about that. He looks at Maud’s example, and he's like, yeah, this is completely wrong.

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And then he calls her out publicly. He writes a letter to the JAMA, saying: hey this Maud Slye is claiming some really weird things about coat color inheritance. She’s not sharing her data. She’s also calling this basic inheritance, but what she’s describing? No, not Mendelian inheritance.

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Katie Hafner: So walk me through her mistake.

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Elah Feder: So her example is with albino mice. Known to be recessive. Maud correctly calls it that. But then when she walks the reader through how it works, what she's describing is just weird. So, you know, normally you get a copy of a gene from your mom and a copy of a gene from your dad, right? 

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Katie Hafner: Mom, dad, gene, gene. Yep. 

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Elah Feder: Yeah. So kids get two copies, one from each parent. What she was describing would only work if some of these mice got two copies from one parent and none from the other. But, she’s calling this basic inheritance. So Little is completely right here. What Maud has written is bizarre. But she wouldn’t  back down. 

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Maud fires back in Science, saying look, you know Mendellian Schmendellian––I’m obviously paraphrasing––I’ve shown that cancer can be passed down through generations, that it can skip generations. You want to call that recessive, dominant, whatever. The point is you can have two mice with no cancer and they can have offspring that has it. These are the points of all this. Little not impressed with this response. And, honestly I wasn’t either

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 And honestly, I thought we might need to cancel the episode when I read this. It made me question if she had any idea what she was doing, but you kind of walked me back from that last time we talked.

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Katie Hafner:  Well, because I think it's interesting to dissect mistakes and just how worked up everybody got about it, but also how defensive she was. 

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Elah Feder: Yeah, it was interesting, but I did not like reading it. I was like, just admit that you're wrong. Just admit that you're wrong.

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Katie Hafner: Right

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Elah Feder: But I did wonder what would've happened- she's a woman in this era, right? And she does not have the same credentials. She doesn't have a doctorate like Little did - though she did get an honorary one later on. She had an undergraduate degree and a lot of informal education.

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Say she did admit she got this wrong, what would've happened, you know, would anyone have listened to her after that? Karen Rader and I talked a bit about this and we didn't get into the specific details of what I just described because I hadn't found it yet. But, we did talk about this overall drag out fight with Little and how Maud handled it.

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Karen Rader:  It is a damned if you do, damned if you don't situation for a woman in science, right? Because if she doesn't defend herself, she looks like she doesn't know what she's doing.

But if she does, then she becomes this, why is she so defensive? Why is she so strident? 

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Katie Hafner: But she was wrong.

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Elah Feder: I know. But, in her defense, apparently whoever accepted this for publication didn’t catch it either. So, maybe people in general were just less familiar with the laws of inheritance at that point. Even biology people.

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In any case, Maud’s choice was to stick to her guns. And, that actually worked out very well for her.  She got a lot of recognition, a lot of praise over the years. You know, she was featured in Newsweek. She got an honorary PhD from Brown. The American College of Physicians  recommended she get the Nobel Prize at one point. And she had the respect of many colleagues.  She eventually rose to the rank of associate professor at the University of Chicago, made it all the way to the mandatory retirement in 1944, with a pension.

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 But more important than the accolades, I think that Maud Slye did make a meaningful contribution. She created this incredible dataset in mice––one that actually didn’t depend on her having a solid understanding of genetics. It really just required her to carefully, accurately document who was related to who and what they died of.

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And, her work helped convince people to take heritable cancer seriously. That’s even something that Clarence Cook Little, despite calling her out, he made sure to credit her for this. 

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Katie Hafner: You consider her a lost woman of science. The fact that I’d never heard of her means absolutely something 

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Elah Feder: If you think about the people we do consider worth remembering, worth teaching kids about, many of them make mistakes. Some were stubborn, arrogant, bigoted, wrong about the science. They might be so flawed that really, we don't like them. But we still talk about them because they had an impact that we think is valuable. And on that score, Maud counts. Convincing people that genetics are important in cancer- that gets people looking for those genes. In Maud's day, knowing cancer ran in your family might have made you feel hopeless. But, today, it means you can get genetic testing, you can get early screening, you can take preventative measures sometimes, maybe even get better treatments. Work like Maud Slye's helped get us here. So yeah, I would say she counts as a lost woman of science for me.

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Katie Hafner: Yeah, I think she does for me too. 

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Elah, thank you so much for telling us about Maud Slye today.

Elah Feder: You’re very welcome!

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Katie Hafner: This episode of Lost Women of Science was funded by the Anne Wojcicki Foundation in honor of her sister, Susan, who died of lung cancer last year. Next week, we'll share Susan Wojcicki's story.

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Anne Wojcicki: We were supposed to go for a walk on a Sunday and she called me and she canceled because she has a hip pain. And, um, you know, I just thought okay you probably exercise too much. But she went to the doctor, where she got an MRI, and it was cancer. 

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Elah Feder: This episode was produced by me, Elah Feder, and hosted by our co-executive producer, Katie Hafner. Deborah Unger is the Senior Managing Producer. Our music was composed by Lizzie Younan. We had fact checking help from Lexi Atiya. Lily Whear created our art. Thank you, as always, to our co-executive producer, Amy Scharf, and to Eowyn Burtner, our program manager. As well as to Jeff DelViscio at our publishing partner, “Scientific American.” 

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If you want to learn more about the history of mice as lab animals, check out Karen Rader’s book Making Mice. 

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We're distributed by PRX. Remember to subscribe so you never miss an episode. For transcripts, please visit lostwomenofscience.org. See you next week!