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Painful Endometriosis Could Hold Clues To Tissue Regeneration, Scientist Says

May 13, 2021
Originally published on May 13, 2021 5:22 pm

It's estimated that one in 10 women experience endometriosis during their reproductive years, a condition where cells that line the uterus go rogue by moving to other organs, taking root and spreading there, leading to terrible pain. Many women who have the disorder struggle to be properly diagnosed.

As Linda Griffith, a top biological engineer at MIT, relates in a recent New York Times article by Rachel Gross, it was years before she knew why she was experiencing exceptionally heavy periods and debilitating pain.

"I was told it was normal. I was told that I was under stress ... [that] I was rejecting my femininity," Griffith says now.

When a doctor finally diagnosed her with endometriosis in the late 1980s, Griffith says, "I was relieved to know that finally somebody found something wrong with me — because I knew something was wrong."

Her treatment involved hormone therapy and multiple surgeries, including a hysterectomy. Her personal experience, Griffith says, has informed her research, as she's come to see the study of the endometrium as a great way to unlock some of the mysteries of tissue regeneration.

Griffith first became famous in the science world for her work in grafting living tissue shaped like a human ear onto the back of a mouse — an achievement that's helping tissue engineers figure out the rich mix of factors needed to grow skin and cartilage for human transplant. In 2009, she co-founded the MIT Center for Gynepathology Research, where she broadened the scope of her work to include endometriosis.

"The regeneration of the endometrium is weirdly not studied as much as it should be," she says. "But it's fascinating because you get about a centimeter of growth of tissue that has beautifully formed blood vessels, an immune system, all of the structures of the tissue — over a period of about two weeks."

To understand endometriosis and find better treatments, she says, society needs to become more comfortable addressing women's reproductive health in general.

"It is not acceptable in society really to talk about your period," she says. "There's many period problems: Heavy menstrual bleeding, fibroids, all of these kinds of things. You just don't talk about your period. So that has to change."


Interview highlights

On the remarkable qualities of the cells of the endometrium, which is shed each month when a women gets her period and which then regenerates

There's very rapid cell growth. There's no scarring in a normal individual, and understanding that might help us with heart regeneration and other kinds of wound healing. ... There's also an enormous influx of different kinds of immune cells throughout the cycle we don't really understand: Are immune cells migrating in from blood? Are they proliferating in place? We know that certain kinds of immune cells in the uterus are very different than elsewhere in the body. So there's a lot of fascinating things that orchestrate this beautiful event every month going on under the direction of these hormones.

Linda Griffith received a MacArthur "Genius" Fellowship in 2006 for her work in tissue engineering.
Melissa Blackall/www.melissablackall.com / National Academy of Engineering

On what is happening in the body with endometriosis

We don't know exactly what causes it, but what we find in patients is that the lining of the uterus, the endometrium, is found growing outside the uterus. It can grow on the lining of the abdomen. It can invade the bladder, it can invade the bowel. It can land on the ovaries and cause a big cyst. When it causes symptoms and it's found growing there, we call it endometriosis.

On why endometriosis can be so painful

We don't know all of the reasons. There's a lot of speculation around why it causes so much pain. It could be because there's inflammation that comes from leaking blood every time the woman has her period. The little lesions that are growing in the abdomen also can bleed. They cause the blood vessels to become very leaky. And whenever you have an accumulation of blood, you get inflammation. This can send signals for pain.

Think about it: When you even just get a paper cut, it hurts, right? Now imagine that you have a whole bunch of those all over the inside of your body. It's going to hurt for the same reasons and more. If you have something like a blister that goes on and you're continually irritating it, it's going to hurt. Later, when the disease progresses, you can get distortion of the internal organs. The ovary may spin out of place. This can pull on a nerve all the time. So it's like you're constantly, constantly being kicked or something, because that nerve is being pulled all the time by the distortion of the organs that comes from scar tissue that builds up and glues things together.

On the notion of "period privilege," and how it can prevent women from being diagnosed with endometriosis

When you even just get a paper cut, it hurts, right? Now imagine that you have a whole bunch of those all over the inside of your body. - Linda Griffith

Some women just don't understand that other women could have these terrible, terrible things happening, because they themselves don't experience those symptoms. "Period privilege," as I'm calling it, could be active or passive. Passive is just they don't think about it and they kind of find it hard to believe. But active — and I encountered this a lot — is women saying, "It can't be that bad." And some of these women are gynecologists, like the one who treated my niece who had endometriosis, and the gynecologist told my sister my niece was making everything up. So I think period privilege is one of those things where women who don't have menstrual problems don't believe the women who do. Either just they don't think about it, or they actively say, "Don't talk about it," because it makes women look weak.

On the prevailing theories about how endometrial tissue migrates

There's potentially a lot of different ways it could happen. There are theories that during [fetal] development you have migration of cells from the neural crest and you get cells migrating all over the body to their respective ultimate positions. And sometimes [with] the cells moving along in a train, some cells fall off the train. And then when you go through puberty, the cells that fell off the train are sitting there and they can develop into the endometrium or other tissues. So that is a probable cause in some women — that they had a developmental issue.

There's also a lot of evidence that in ... people who are in their 20s or 30s, that menstrual tissue, instead of all going out the cervix as it should, it goes out the fallopian tubes. And this happens in all women. When you have women undergoing surgery during their periods, you can find menses in the abdominal cavity. So it happens in all women. But what we don't know is why in some women it may not be cleared away by the immune system as it should. There are about 10% of women who have endometriosis. So why that tissue wouldn't be cleared away, we don't exactly know. Is it something strange about their endometrium? Is their endometrium very aggressive or is it something strange about their abdominal cavity? Is the immune system weak or not proper or is it fertile ground for the endometrium?

On why she initially hid her disease from her colleagues

I was diagnosed in 1988 and joined the faculty in 1991. ... That was at a time when the premier endocrinology textbook — I had to teach endocrinology at Harvard Medical School at the time — it had a tiny chapter, two or three pages, on endometriosis and it said: "The typical patient is a nulliparous [never given birth] white woman in her late 30s who's highly educated and has an anxious personality." The textbook said that. [In] 1991.

We call that a diagnosis bias. Because the people who would get diagnosed were the people who had resources and who would be persistent and had access to care.

We know endometriosis affects all different races, all different [societies] around the world — everybody has about the same incidence of endometriosis. So to get back to why didn't I study it? I just didn't want to think about it. At that time, you didn't talk about gynecology. You still don't talk about it if you have a gynecology disease and you're an engineering professor or any kind of science professor. So I hid. I had elaborate rituals — how I ran my life — to hide the fact that I had a gynecology disease. Nobody really knew it. You just didn't talk about it.

Amy Salit and Kayla Lattimore produced and edited the audio of this interview. Bridget Bentz, Molly Seavy-Nesper and Deborah Franklin adapted it for the Web.

Copyright 2021 Fresh Air. To see more, visit Fresh Air.

TERRY GROSS, HOST:

This is FRESH AIR. I'm Terry Gross. My guest, Linda Griffith, first became famous in the science world for her work in grafting living tissue shaped like a human ear onto the back of a mouse. Now she's doing groundbreaking research into endometriosis, a condition in which tissue from the endometrium, the lining of the uterus, migrates to other organs and grows there. It can be very painful, especially when a woman is menstruating. Endometriosis has been seen as a women's issue, with little research devoted to solving its mysteries. But in a recent New York Times profile, Rachel Gross - no relation - described Griffith as reframing endometriosis as a key to unlocking some of biology's greatest secrets, like tissue regeneration, scarless wound healing and immune function.

Griffith started doing this research because she has endometriosis. And like most women who are plagued by it, her pain was treated dismissively by doctors. And it took years to get an accurate diagnosis. Her treatment required multiple surgeries. In 2009, she co-founded the MIT Center for Gynepathology Research. In 1994, she was instrumental in creating MIT's biological engineering department and in helping recruit Dr. Doug Lauffenburger to head it. After working together in the lab and getting to know each other, they fell in love and got married. They were jointly awarded the Bernard M. Gordon Prize for creating the discipline of biological engineering. That came with an award of half a million dollars. She's also a recipient of a MacArthur Fellowship, the so-called Genius Award. Her research has implications for understanding and treatment of inflammation and many diseases.

Linda Griffith, welcome to FRESH AIR. Before we get to the science, let's start with what endometriosis is. Would you describe what happens in the body?

LINDA GRIFFITH: So we don't know exactly what causes it. But what we find in patients is that the lining of the uterus, the endometrium, is found growing outside the uterus. It can grow on the lining of the abdomen. It can invade the bladder. It can invade the bowel. It can land on the ovaries and cause big cyst. And it causes symptoms. There's debate about whether it's a disease if it doesn't cause symptoms because some patients have this growing, and they experience no pain or other symptoms. But when it causes symptoms and it's found growing there, we call it endometriosis.

GROSS: Why does it cause so much pain?

GRIFFITH: Again, we don't know all of the reasons. There's a lot of speculation around why it causes so much pain. It could be because there's inflammation that comes from leaking blood. Every time the woman has her period, the little lesions that are growing in the abdomen also can bleed. They cause the blood vessels to become very leaky. And whenever you have an accumulation of blood, you get inflammation. This can send signals for pain. Think about it. When you even just get a paper cut, it hurts, right? Now imagine that you have a whole bunch of those all over the inside of your body. It's going to hurt for the same reasons and more. If you have something like a blister that goes on and you're continually irritating it, it's going to hurt. Later, when the disease progresses, you can get distortion of the internal organs. The ovary may spin out of place. This can pull on a nerve all the time. So it's like you're constantly, constantly being kicked or something because that nerve is being pulled all the time by the distortion of the organs that comes from scar tissue that builds up and glues things together.

GROSS: You had pretty debilitating pain, right?

GRIFFITH: I had terribly debilitating pain, terribly debilitating pain, first during my period when I was younger as a teenager. And then as I got older, because I had such advanced - they call it fibrosis, that excess scar tissue, things were stuck together. And I would be in constant pain all the time until I had surgery to remove some of the scar tissue. And then the whole process would start again.

GROSS: Wow. Where are you now in terms of endometriosis?

GRIFFITH: So I had nine major surgeries. I had a hysterectomy when I was just about 40 and then two recurrences after the hysterectomy, both marked by intense, intense pain. And then right after I had my ninth surgery for endometriosis, I was diagnosed with triple-negative breast cancer and underwent aggressive chemotherapy. And ever since then, I've not had any more symptoms of endometriosis. Whether it was the chemotherapy or whether it was that last surgery, I really don't know.

GROSS: Wow.

GRIFFITH: But it's been 11 years.

GROSS: So one in 10 women have endometriosis. That's a lot of women. But you don't hear that much about it. If one in 10 women have it, you'd think that everybody would be talking about it. Is - do women who have it consider it just, like, too personal or too embarrassing to talk about because it has to do with menstruation?

GRIFFITH: So this is a can of worms. There's many forces that contribute to lack of awareness. So first of all, it is not acceptable in society, really, to talk about your period. There's many period problems, heavy menstrual bleeding, fibroids, all of these kinds of things. You just don't talk about your period. So that has to change - more dialogue. And it's - I see it among younger women. But also, there's something - and I'm just going to hypothesize this - of period privilege. Some women just don't understand that other women could have these terrible, terrible things happening because they themselves don't experience those symptoms.

Period privilege, as I'm calling it, could be active or passive. Passive is just they don't think about it. And they kind of find it hard to believe. But active - and I encounter this a lot - is women saying, it can't be that bad. And some of these women are gynecologists, like the one who treated my niece who had endometriosis. And the gynecologist told my sister my niece was making everything up. So I think period privilege is one of those things where women who don't have menstrual problems don't believe the women who do. Either just - they don't think about it. Or they actively say, don't talk about it because it makes women look weak.

GROSS: It usually takes years for women to be diagnosed with endometriosis. It took years for you to be diagnosed. What had doctors told you before that?

GRIFFITH: Well, they - doctors would often try to talk you down from the symptoms that you had. So I was told it was normal, that I was under stress. I was always under stress, you know? I was rejecting my femininity was a diagnosis I got when I went to Berkeley, so many things that were not making sense to me because it was being gaslit, because I - you know, I really couldn't get out of bed. And I bled so much. You know, you have the tampons. You have the junior, the regular, the plus, the super plus. You know, you'd think a super plus should do it. But three super plus, and I'd still be bleeding after an hour, you know? So you would tell the doctor these things. And they just didn't register. And I was diagnosed completely accidentally. I was told I was going in for outpatient surgery, and I'd go to work the next day. I didn't even wake up until the next day.

GROSS: What were you going into surgery for?

GRIFFITH: So I ended up having an image of pain that I could, like - somebody said this is not normal. And it had to do with my inability to turn around and answer a phone in the laboratory where I was a graduate student. And I'm like, yeah, it's not normal that I can't turn around and answer the phone because I'm in so much pain. So I went to the doctor every month for six months. They sent me for an ultrasound. They said I had a cyst. They said they would drain the cyst. It was just a very simple procedure. No one ever mentioned endometriosis. Anesthesia wasn't so great in 1988. So I woke up the next day and discovered I had a huge incision with staples. And the doctor told me I had endometriosis and explained what it was.

GROSS: Has there been any treatment for endometriosis besides occasional surgeries in which scar tissue is cut away and if the organs have become kind of glued together because of the tissue that's growing, the surgery can kind of unglue them together? But so beyond these surgeries, is there any treatment?

GRIFFITH: Well, I was put on birth control pills when I was 14. So birth control pills, some kind of hormone suppression, are the first line treatment. And a lot of women respond to those. Others don't respond or have side effects that are intolerable. They can cause terrible depression. Back then, they told you having a baby would cure it or make it better, which we know isn't true for the majority of women. But there was a drug called danazol, which is an anabolic steroid that was coming into use at the time. And for me, that was a miracle drug. I took that drug. I gained 20 pounds in two months, became very, very strong. I could run three miles in 18 minutes, beat guys at arm wrestling and all kind of stuff. But I had no pain when I was taking that drug. But I also took drugs that caused menopause. I took a whole bunch of different drugs, and the only one that really worked for me was the anabolic steroid.

GROSS: Let me reintroduce you here. If you're just joining us, my guest is Linda Griffith, co-founder and co-director of the MIT Center for Gynepathology Research. One of the diseases she's researching is endometriosis, which she has. We'll be right back. This is FRESH AIR.

(SOUNDBITE OF SOLANGE SONG, "WEARY")

GROSS: This is FRESH AIR. Let's get back to my interview with Linda Griffith, a biological engineer who helped graft living tissue in the shape of an ear onto the back of a mouse. Now she's researching endometriosis, inflammation, the connection between the digestive system and the brain, research that could lead to breakthroughs in the treatment of many diseases. One of the diseases she's focusing on is endometriosis, which she has.

It's really a kind of remarkable disease in the sense that, like how does tissue from the uterine wall migrate to other organs and grow there? That just sounds strange.

GRIFFITH: It is very strange, isn't it? And there's potentially a lot of different ways it could happen. There's theories that during development, you have migration of cells from the neural crest and you get cells migrating all over the body to their respective ultimate positions, and sometimes the cells moving along in a train, some cells fall off the train. And then when you go through puberty, the cells that fell off the train are sitting there, and they can develop into the endometrium or other tissues. So that is a probable cause in some women, that they had a developmental issue. There's also a lot of evidence that in more older women, people who are in their 20s or 30s, that menstrual tissue, instead of all going out the cervix as it should, it goes out the fallopian tubes. And this happens in all women. When you have women undergoing surgery during their periods, you can find menses in the abdominal cavity. So it happens in all women.

But what we don't know is why in some women it may not be cleared away by the immune system as it should. There are about 10% of women who have endometriosis. So why that tissue wouldn't be cleared away, we don't exactly know. Is it something strange about their endometrium? Is their endometrium very aggressive? Or is it something strange about their abdominal cavity? Is the immune system weak or not proper or is it fertile ground for the endometrium?

GROSS: You know, the uterine lining is remarkable in and of itself. The uterus sheds its lining every month when a woman is menstruating and then a new lining grows. So what are the remarkable qualities of the tissue of the endometrium, the uterine lining? And then how do those remarkable qualities translate when they migrate to an organ where they don't belong?

GRIFFITH: So the regeneration of the endometrium is weirdly not studied as much as it should be. But it's fascinating because you get about a centimeter of growth of tissue that has beautifully formed blood vessels, an immune system, all of the structures of the tissue, over a period of about two weeks. So there's very rapid cell growth. There's no scarring in a normal individual. And understanding that might help us with heart regeneration and other kinds of wound healing to go better. But what's remarkable about it is the cells are proliferating very fast and the fibroblasts, or cells that form the support structures for the tissue, undergo this remarkable bifurcation in their fates. Some of them become what we call decidual cells that plump up and get ready to receive that embryo. And other ones go into what we call senescence, meaning they're aging and dying, and they make a lot of support structures to help get the embryo in. Stem cells - there's evidence that stem cells are found near the top of the layers of cells. You know, we think a lot about epithelial stem cells in the intestine as being very protected down in the crypts. In the endometrium, they're right there on the front lines, evidence suggests, waiting for this baby to be implanted.

So the mysteries of this - there's also an enormous influx of different kinds of immune cells throughout the cycle or they may be proliferating in place. We don't really understand. Are immune cells migrating in from blood? Are they proliferating in place? We know that the certain kinds of immune cells in the uterus are very different than elsewhere in the body. So there's a lot of fascinating things that orchestrate this beautiful event every month going on under the direction of these hormones.

GROSS: You were initially reluctant to devote a lot of your research to endometriosis, even though you have it. Why were you initially reluctant?

GRIFFITH: Many reasons. First of all, the kind of engineering I do - when I first was diagnosed, it wouldn't have been possible to really make headway in endometriosis because I didn't have particular skills to contribute. You know, I was diagnosed in 1988 and joined the faculty at MIT in '91. And I'll point out, that was at a time when the premier endocrinology textbook - I had to teach endocrinology at Harvard Medical School at the time - it had a tiny chapter, two or three pages, on endometriosis. And it said, the typical patient is a nulliparous white woman in her late 30s who's highly educated and has an anxious personality. The textbook said that - 1991. And we call that a diagnosis bias because the people who would get diagnosed were the people who had resources and who would be persistent and had access to care. Right?

And so we know endometriosis affects all different races around the world. Everybody has about the same incidence of endometriosis. So to get back to why didn't I study it, I just didn't want to think about it. At that time, you didn't talk about gynecology. You still don't talk about it if you have a gynecology disease and you're an engineering professor or any kind of science professor. So I hid. I mean, I had elaborate rituals, how I ran my life to hide the fact that I had a gynecology disease. Nobody really knew it. You just didn't talk about it.

GROSS: So many women have endometriosis. You have it. You were initially reluctant to devote your research to endometriosis, even though you have it. Why were you reluctant? And I'm wondering, too, if being a woman at a time when women were considered maybe a little bit less-than in the science world, if you were concerned that that would kind of emphasize that you were a woman (laughter) and make it harder to get taken seriously.

GRIFFITH: I think certainly talking about gynecology diseases and admitting you had one at that time was awkward. Not many people would understand it. Not even women understood it. But also at the time that I started my faculty career, the tools in biology weren't available for engineers to really make sense out of how it all worked together. Those tools developed over my faculty career. As I got tenure, full professor, and became a very successful member of the National Academy, I felt much more comfortable in my accomplishments, but also because of all the directions I'd taken linking engineering to modern molecular life science - helping start a new department, educating students at this interface - all the sudden there was the time to do it. So it was a reluctance because I needed to keep that part of my life separate from my professional life when I was younger. But also the tools weren't there. I helped create the tools. I really did. And my husband, who works close with me, helped create those tools, and now we're very happy to be able to apply them.

GROSS: What's an example of a tool that you helped create that you now use in your research?

GRIFFITH: So tool may be a little bit of a facile word to use. I would say a whole compendium of different approaches. Some of them are computational. So biologists often will identify new molecules and new ways of doing things. So Phil Sharp, my colleague on a project I have now, discovered a whole new way that information is transferred inside of cells and won the Nobel Prize. So individual pathways and molecules and phenomenon biology are discovered by biologists. But how everything works together, how a cell can physically crawl across an interface, that's something that engineers can describe if they know what the components of the system are. How does it all work together? That's what engineers are great at.

And so one kind of tool is simply being able to put together all the individual component parts of a biological system and predict how it will behave because you think of not just pathways, but networks. You think, how do cells communicate with each other? How do they communicate with their neighbor? How do they communicate across the whole body? And you build models, different kinds of mathematical models. So this whole field of what we might call systems biology and computational biology involves understanding information flow inside a cell, between cells, between different organs in the body.

So you're very familiar probably with using animals to model human diseases. And animal models are very important. They help us generate hypotheses. But they're not humans. So my research focuses on, how do we use different kinds of biomaterials and little flow devices, little reactor systems - how do we use these to grow mimics of human tissue? Because you need, at some level, to study the human tissue because it is different than the mouse tissue. We've cured endometriosis in a lot of mice and a lot of baboons. And the same drugs don't work in humans.

And so my job is, how do we make a little model of the patient in our lab so that we take her tissue, bring it to the lab and grow a little version of what's wrong with her and study it? There's a lot of engineering in that.

GROSS: If you're just joining us, my guest is Linda Griffith, co-founder and co-director of MIT's Center for Gynepathology Research. That means gynecological diseases. We'll talk more about some of the breakthrough research she's done after we take a short break. I'm Terry Gross, and this is FRESH AIR.

(SOUNDBITE OF BRAD MEHLDAU, KEVIN HAYS AND PATRICK ZIMMERLI'S "GENERATRIX")

GROSS: This is FRESH AIR. I'm Terry Gross, back with Linda Griffith. She's a biological engineer who co-founded and directs the MIT Center for Gynepathology Research. Its main focus is endometriosis, a disorder in which tissue from the endometrium, the lining of the uterus, goes rogue and migrates to other organs, typically causing a lot of pain, particularly during menstruation.

This and other research she's conducting can lead to breakthroughs in our understanding of regenerative tissues and how organs communicate with each other. It could also result in treatments for a range of diseases and medical problems, from Parkinson's to bone grafting.

I am not a scientist. And hearing you talk about this, I just find it so remarkable that there are all these different kinds of cells and enzymes and hormones and so on that talk to each other in ways that we have no idea about but that you're discovering. And all that communication that happens in the body is just remarkable. And I suppose that that's why you're taking what you describe as a systems approach, not to just - looking at individual cells, but looking at the whole system of how one kind of cell, one kind of hormone and one kind of organ - how they all communicate.

GRIFFITH: Exactly, and in fact, when I first started working on endometriosis, I didn't know that much about gynecology organs and the peritoneal cavity. And it was a lot of work to learn about these things when I already had a very, very active research program in bone regeneration, liver, the intestine, etc. But what I - what I find is, looking on the bright side, all of these influence the functions of the uterus. And so there's of course tremendous interest in the gut microbiome - what you eat, how it affects the microbes in your gut - because that affects your immune system.

We did a collaboration with a colleague in Brazil to look at the microbiome and how it might be related to different kinds of endometriosis. And there's many other people studying these directions. We've built a little model of the human colon that can grow those really oxygen-sensitive bacteria together with cells from patients so that we can now start to look at how different bacteria influence the immune system in the gut because we know that something involving that could be related to how the uterus is functioning.

The gut actually controls a lot of hormone metabolism, steroids - you know, your sex steroids, if you take birth control pills - all of these things, the gut is participating. And of course, all the blood that leaves the gut goes to the liver. So everything's connected in an immunological sense, in a metabolic sense and in a nervous sense. And so studying all of these things really helps us build the full picture.

GROSS: Because you had endometriosis, you ended up studying endometriosis and co-founding the MIT Center for Gynepathology Research. You also had breast cancer. And the treatment of breast cancer depends on the type of breast cancer you have, and determining the type depends on looking for certain markers in the tumor. But your tests were ambiguous. Apparently, your tumor was kind of partly one type and partly another type, so it was very difficult to figure out which treatment to get.

Are there things that you've learned from having breast cancer and from trying to understand what was going on from a patient point of view that you were able to apply to your research?

GRIFFITH: Oh, absolutely. I was diagnosed with breast cancer right after Keith Isaacson and I and Doug Lauffenburger, my husband, started the center. And it was like, you know, I can't believe this. And - but it was an aha moment also because I had a 3-centimeter tumor. And the - Eric Winer, my oncologist, didn't say, oh, you have a 3-centimeter tumor; here's what we're going to do. He said, first, you're triple-negative, but, oh, you have an unambiguous HER2. And I had to decide...

GROSS: Those are two different types of cancer - of breast cancer.

GRIFFITH: Yeah. So there's different types, and there's three markers that they typically use - estrogen receptor, progesterone receptor and a growth factor receptor, HER2. And in endometriosis, we had been treating patients - how big their lesions are, how many they have, where they are - that's how patients were staged.

And it was - it is equivalent to saying, you know, you have a 3-centimeter tumor, and that's going to get your treatment. No, I had a very aggressive chemotherapy regimen because there were no targeted therapies. So I had a very aggressive - because it's known that triple-negative has typically not-good outcomes, etc. So the prognosis was gated by those molecular markers and the treatment by those molecular markers, not just by the size of the tumor.

So we reasoned 10% of women have endometriosis. There's got to be molecular subtypes. And so that was the hypothesis we set out on. And our first really big paper - our first two big papers, explored that hypothesis and opened up the field to think about the ways that we can do molecular classification of patients.

Now, we're not there yet to treat patients on the basis of these classifications the way we do for breast cancer. But we've certainly gotten other people to think along those lines. It's not one disease. It's not a disease where the size of your lesions dictate everything. There's molecular subtypes, and we really need to be able to figure them out.

GROSS: Are there new treatments on the horizon for endometriosis?

GRIFFITH: So there are. You know, there's - so I'll say it's a - it's an interesting landscape. There's a drug that causes menopause that I took - and I had terrible side effects, as do a lot of women - called Lupron. And there's an oral-pill version of that, which also basically shuts off steroid hormone production, so you go into menopause. But the pill lets you kind of titrate it. So is it totally deep, dark menopause, or is it a little bit menopause? And that has been effective for some patients, but it's not effective for everyone.

So I think what we're trying to do in my research is understand, how do women respond to various levels of different hormones? Like the endometrial tissue itself, you can shut off all the estrogen in the body, but it will make its own estrogen from other things. And so this is what I actually am trying to study in my NIH work is, how is it that this endometrial tissue when it's trapped can make its own estrogen when you deprive it of estrogen from everywhere else in the body?

And in my case, I had progression of the disease when I was taking this menopause drug. I had terrible side effects, and I had progression of the disease. And so we don't know a lot about what these cells are doing to make the estrogen themselves when they're stuck somewhere deep in the body. So the new drugs - I think new drugs have to target inflammation, and these just have not really gotten into the clinic yet.

GROSS: Can you think of an example where something a patient told you led you to some kind of breakthrough or some kind of new understanding?

GRIFFITH: So I'm a member of several Facebook patient-support groups, and I monitor what people are posting about. So there are comorbidities that you get with endometriosis, and one of them is called Ehlers-Danlos syndrome. And it's a constellation of different things that make connective tissues behave strangely so that you're often double-jointed. You can bend your, you know, arm back or your fingers back. And it has to do with how the proteins in your skin and your bones and ligaments and so on are processed. And there's a very high incidence of endometriosis in these patients.

So getting back to the point where I said endometriosis is not one disease and we want to look for molecular subtypes, this is a fascinating thing because it points us to potential things going on with extracellular matrix, these proteins that provide the support - physical support for our tissues as contributing to how the disease starts and how it progresses. So we're actually studying this in the lab, and it's because people were posting on Facebook groups. And I didn't know what it was, and their posts led me to look into it. And then a family member - extended family member had Ehlers-Danlos and just understanding what they go through helped me now study the disease in a different way.

Breakthrough - I don't know. But I think, again, science is often incremental. I know journalists always want the breakthrough, but it's a series of - it's - it can be very, very tedious to get the science right. You've got to put a lot of little pieces together to make the whole picture.

GROSS: Let me reintroduce you here. My guest is Linda Griffith, the co-founder and co-director of the MIT Center for Gynepathology Research, and one of the diseases she's researching is endometriosis, which she also has. We'll be right back. This is FRESH AIR.

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GROSS: This is FRESH AIR. Let's get back to my interview with Linda Griffith, a biological engineer who helped grow tissue in the shape of a human ear onto the back of a mouse. Now she's researching endometriosis, inflammation, the connection between the digestive system and the brain and the uterus - research that could lead to breakthroughs in the treatment of many diseases. One of the diseases she's focusing on is endometriosis, which she has.

In the early part of your career as a professor and as a researcher, you pretty much did not tell your science colleagues or the scientific community that you were suffering from endometriosis, but at some point, you came out about it. And I think that was the point where you also had started doing research on it, and it became a really important issue for you. And you wanted to talk about how endometriosis was an incredible scientific opportunity to study and that it could lead to all kinds of understanding of other - of other medical issues.

So - but what was it like for you to discuss what most women consider a very personal issue, menstruation and a menstrual-related disease, with the public and with the scientific community?

GRIFFITH: I got a lot of courage from Padma Lakshmi, actually, who founded a center with her surgeon, Tamer Seckin.

GROSS: And she - she's a famous chef and TV host.

GRIFFITH: Yes, she's a famous chef and TV host. And I didn't know who she was, except I read an article about her in Newsweek where she did an interview. And she said she wanted to go on a college tour. I cold-called her. I wrote my lab. I said, does anybody know who Padma Lakshmi is? 'Cause I don't watch a lot of TV. And people wrote me back and said, oh, my God. Are you going to have Padma Lakshmi? I'll help host. You know, and everybody knew who she was, of course.

So she had the courage to go out and really tell her story and put the time and effort in to start a foundation. And her foundation fostered a lot of communication among scientists and clinicians and with the lay public. And that gave me the courage to jump off that deep end myself. She came to MIT. She had standing-room-only - huge crowd for her talk when we launched the center. And she's been back to MIT. We have all kinds of discussions about nutrition.

You know, I think the fact that she went before me - and also I was a full professor, and I was a MacArthur Fellow. So there were some comforts I had at that stage of my career that made it a lot more feasible.

And another thing - and I think this is a very important thing to say - I really am unhappy with how people - some people have painted a picture of how terrible it is for women in science. MIT participated in this. I've had a fabulous career in science. It's an amazing career for women. The men who supported me, mentored me have been amazing. Many of my colleagues and I at MIT didn't have any of these things that you read about in the press or very few of them. It's a place that you control your destiny. You write your narrative. You get to work on amazing problems with fabulous colleagues.

So I think another opportunity was to give another dimension to what the experiences of women in science. It's a place where you can conquer the things that are hurting women, which I think is a very important message, that science is such an amazing career for women.

GROSS: So I think it's time to talk about the ear mouse - the so-called ear mouse. And I want you to describe, first of all, what the mouse looked like when you were done growing tissue in the shape of a human ear on the back of a mouse - just, like, that's so surreal just to think about it. What did it look like?

GRIFFITH: It looked like a human ear growing on the back of a mouse. It's the outer part of the ear, not the part that does hearing. And it appeared on "South Park" and on Hallmark greeting cards. And most people have seen some kind of depiction of it, but it pretty much looked like the shape of a human ear but just growing out of the back of the mouse.

GROSS: What - like, if you can, describe in the simplest terms how you managed to do that, you and the other scientists who you were working with.

GRIFFITH: The project was motivated by a plastic surgeon who treats children, and he would need to replace the outer part of the ear. And the typical way to do it was with a prosthetic rubber device that would get infected. So he wanted to grow natural tissue there in some way. A colleague had shown if you take a degradable suture and put cells derived from cartilage onto the suture, they would form cartilage tissue if you put it beneath the skin of a mouse. So the idea was they needed a degradable polymer scaffold that you could put cells on and would look like an ear so the cells could form...

GROSS: Wait, wait, I'm going to stop you right there. What is a polymer scaffold? Just so we can visualize it in our minds.

GRIFFITH: So what had been shown is that you could take a polymer degradable suture and put cells on it, but you needed something actually in the shape of an ear that had pores in it that the cells could be put into so they would be able to grow and form a tissue. So what my contribution was, was to figure out how do we shape this material that's normally in a suture into the shape of a human ear so that it has these holes in it that cells can be put into so they'll form the tissue? My job was to make it into the shape of a human ear.

GROSS: So did you build, like, a model of an ear so that the cells could grow around that model and have the right shape?

GRIFFITH: So what we did is I found a company that could make something like felt out of the same material that sutures were made out of. And I used the rubber - silicone rubber ear as a mold, and I could put the felt on there and glue the felt into that shape with another biomedical polymer that degrades, and it would hold the shape of the ear. So we used a mold to shape this polymer felt glued together with another polymer and would hold the shape of an ear. Then when you put the cells on it over a couple of months, they would turn into cartilage tissue, and the polymer would degrade away in the presence of water. So you got a piece of cartilage in the shape of an ear.

GROSS: So are there practical applications of that, I mean, since a mouse doesn't need an ear on its back, that was just an experiment, a very surreal one? But what are the practical applications for treating disease or just for plastic surgery?

GRIFFITH: So there are - as in science, nothing is completely linear. First of all, the molding process was not easily transferred to manufacturing. So I got involved with the creation of three-dimensional printing, which was invented at MIT by colleagues in mechanical engineering and material science. And I became a co-inventor to apply these to tissue engineering. And we ended up taking three-dimensional printing into the clinic for making scaffolds to regenerate bones. And it could be used for cartilage. We didn't. But others continue to do work in this area. After that big initial demonstration you could do it, I moved on to other things, like liver and so on. But it went into the clinic. So you can make cartilage in various shapes by using that approach. And there have been patients treated with cartilage made that way in the clinic.

GROSS: There's something very science fiction about the whole idea of the ear on the back of the mouse. Are there other things that you've done that are, like, as surreal or science fiction-y (ph) as that?

GRIFFITH: I feel like what we're doing now, which is growing little models of human organs and tissues that have blood vessels permeating through them that we can pump fluid through and watch in our microscopes, I feel that that's pretty surreal. We can grow a patient's endometrial tissue in 3D and contact it with these blood vessels. We're looking at how hormones change the permeability of these vessels. When I look at these things in the microscope, I really feel like it's science fiction in a way. We can - we're able to grow the bacteria in the colon that do the fermentation of fiber. And we can watch it go from what is, you know, the poopoo space, you know, the pooping space into the bloodstream space across a patient's tissues. I mean, it's wild.

We measure these things, and you're like, wow, you know. We're mimicking things that are super complicated that go on in humans. And we can measure all this stuff in the lab where we can perturb it in ways that we're not going to do in people. So I go in my lab, and almost every day, I feel like it's science fiction because we're building little models of humans. It's one thing to do something in a mouse, but hardly ever does it translate to a human when you do it in a mouse. What we're trying to do in lab is actually build the humans so that we can really directly translate to patients and study them and then translate to them.

GROSS: Well, Linda Griffith, thank you so much for your research, and thank you so much for coming onto our show. It's been a pleasure.

GRIFFITH: Thank you, Terry, for having me. And thank you on behalf of all the women who are suffering from these diseases.

GROSS: Linda Griffith is the co-founder and co-director of MIT's Center for Gynepathology Research and a pioneer in the field of biological engineering. After we take a short break, TV critic David Bianculli will review the new comedy series "Hacks" about the clash in sensibility and lifestyle between two women comics of different generations. It stars Jean Smart. This is FRESH AIR.

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