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Women & Power 2022

‘FemTech’ and a moonshot for menstruation science

Women’s health is understudied and underfunded. An MIT scientist wants to close the health gap.

MIT student Elizabeth E. Brennan (left) and Boston University student Victoria Gonzalez-Canalle work on signs for the Sept. 14 Stand Up and Be Counted rally held at MIT, which Gonzalez-Canalle helped organize.Ceal Capistrano

The morning of September 11, 2001, I arrived at my MIT office, wondering if I would last to teach my afternoon class. About two weeks earlier, I had woken in the night with abdominal pain and a fever, and thought I had food poisoning. After the discomfort continued for days, I’d been tentatively diagnosed over the phone by an urgent care doctor: maybe a burst ovarian cyst, given my history of six prior endometriosis surgeries. “Impossible!” I’d argued.

But the pain intensified, and that morning I found myself on the way to the emergency room. With the terrorist attacks sending shock waves through the nation, the trip to the hospital was surreal — the T was free; the hallways at Massachusetts General Hospital were deserted. Dr. Keith Isaacson, the surgeon treating me for endometriosis, assessed my situation, and recommended a hysterectomy as soon as possible.

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By the fall of 2001, 10 years into my Massachusetts Institute of Technology faculty career, I had become known for research in tissue engineering. I’d collaborated with Dr. Chuck Vacanti to create cartilage in the shape of a human ear on the back of a mouse, an iconic image of tissue engineering. I had collaborated with MIT colleagues to adapt their trademarked 3DP printing process, invented for ceramics, to print synthetic grafts to guide bone tissue regeneration, and cofounded a company that produced these synthetic grafts for patients.

Not long after the hysterectomy, I had an epiphany. Instead of aiming to replace failed organs with lab-made transplants, why not use tissue engineering to create models of human disease, to replace animals in drug development? My lab then invented the Liverchip, a living model of the liver grown inside tiny perforations on a silicon chip, nourished by its own circulatory system. But more importantly, I collaborated with my husband, Doug Lauffenburger, and other MIT colleagues, to found the Department of Biological Engineering to bring the lens of engineering analysis, design, and synthesis to modern molecular life sciences. I was leading development of MIT’s first new undergraduate major in almost 40 years. Although I did not realize it at the time, this new discipline of “biological engineering” provided an essential intellectual foundation for engineering new directions in research on endometriosis.

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A second career-changing epiphany happened in 2007. Susan Whitehead, an MIT Corporation member, invited me to speak at a Museum of Science “Women in Science” lunch series. I was unprepared for her next request: to “emphasize in your talk the ways your work specifically benefits women.” I have nothing, I thought, and wished she had not asked.

But simmering beneath the surface were the elements that would change my career. First, there was the situation with my niece in Atlanta. Caitlin excelled in school, but missed it often due to health problems that started around the time she hit puberty. Her problems — eerily and distressingly identical to those I had in high school — were dismissed by her female obstetrician-gynecologist, who said Caitlin was making it all up to get out of going to school. But a surgeon confirmed she wasn’t. In 2006, at age 16, she was diagnosed with endometriosis.

Then, there was my own situation. After surgery in 2007 revealed I was having an endometriosis recurrence, Dr. Isaacson told me it was about time that I start working with him on finding a new treatment, or even cure, for the disease. I had rolled my eyes — what could a tissue engineer like me do in this space? Plus, it would be professional suicide — the funding scene was dismal. He was quietly insistent. “I operated on a 23-year-old woman today — her tenth surgery for endometriosis,” he said. “We must do better for patients.”

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A question from a student at the Museum of Science event — ”Where do you see your lab in three to five years?” — jolted these disparate puzzle pieces into a coherent vision, and my answer spilled out, “I will have a lab that focuses on engineering new directions in endometriosis research!”

I had just gotten a MacArthur Fellowship and was being asked what “creative” thing I would do next. Endometriosis was an important societal problem, virtually untouched by engineers. But the new discipline of biological engineering was literally made for problems such as endometriosis. As a systemic inflammatory disease, afflicting almost 10 percent of reproductive-age women around the world (translating to almost 200 million women today), and no clear genetic basis, endometriosis was a poster child for demonstrating how engineers searching for new drug targets could use machine learning to analyze scores of immune system proteins in the patients. And living avatars made from patient tissue biopsies in our lab would be part of an exciting new direction for validating those possible new drug targets.

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Soon, we secured a foundation grant to launch the Center for Gynepathology Research in 2009 as a joint effort between MIT and Newton-Wellesley Hospital, where Dr. Isaacson has served as medical director of the hospital’s Center for Minimally Invasive Gynecology Surgery since 2001. My answer to that student’s question was taking shape.


Linda G. Griffith, scientific director of the MIT Center for Gynepathology Research, at her lab.JARED CHARNEY

“We have been quietly dealing with an elephant in the room — bad periods! As a ‘secret illness of women,’ bad periods are a pervasive drain on the lives of roughly 20 percent of women. Yet, they’re rarely discussed in our professional environment,” I wrote along with my colleague Tavneet Suri, an economics professor at MIT Sloan School of Management, in an open letter to the MIT community this September. We were inviting everyone to a series of events that month, to shine a light on the dire need to develop and fund a new field of “menstruation science,” and to bring diverse expertise, including engineers and economists, into gynecological research.

As the Center for Gynepathology Research website explains, endometriosis involves growth of the endometrium (uterine lining) outside the uterus, most often in the abdominal cavity, where it attaches to and sometimes invades organs including the ovaries, bowel, and bladder. This displaced tissue can also “bleed” during normal menstruation, causing inflamed lesions to form and resulting in crippling pain and infertility. Symptoms often begin in early teenage years and can last into menopause. A sister disease, adenomyosis, afflicts about 10 percent of women, yet is often undiagnosed.

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Hormonal therapies that suppress estrogen are the go-to treatment, but don’t work for everyone and can cause unbearable side effects. Surgery to remove lesions is common, and it isn’t unusual for patients to have to go back on the operating table, as Tavneet and I have, when symptoms return.

“I take what I call the Neanderthal approach, which is to either remove or destroy the tissue. However, this is a temporary benefit, not a cure,” Dr. Isaacson told an audience of about 300 people gathered at MIT for our panel discussion. “The answer is trying to understand how the endometriosis got there, why it got there, how it behaves, and what we can do to not only prevent it but treat it better.”

Although gynecological disorders are a significant source of missed work, a constellation of other chronic immune-mediated diseases skews strongly female, including chronic Lyme diseases; migraines and rheumatoid arthritis, which have a 2.5 to 1 female-to-male ratio; and Lupus, at 9 to 1. Like endometriosis, these diseases are not linked to unique genetic markers, and share symptoms including fatigue, pain, and others that make diagnosis difficult and protracted, and development of effective therapies especially challenging. Studies conducted around the world have shown that women miss more work than men do (about seven more days per year in the United States, according to the latest data), because they are sick, in addition to work missed to care for sick children or elderly parents, or for maternity leave.

Yet, existing studies barely scratch the surface of a possible “health gap,” which encompasses the disparity of how sick women and men get during their productive working years from diseases they are more prone to because of their gender. Delayed diagnoses and lack of effective therapies even for patients with the best access to care can contribute to worse outcomes, and these factors are accentuated for lower-income patients. Endometriosis, like many female-skewed diseases, is not strongly linked to lifestyle factors, such as diet and exercise, giving even the most motivated patients a sense of helplessness.

How big is this health gap, and how much does it contribute to the wage gap? I was able to return to work 10 days after my hysterectomy because I had a minimally-invasive procedure, and because many of my job functions can be carried out sitting or lying down. But I’ve still lost a lot of consulting income while sick. I’m lucky: About half of women who have hysterectomies get large abdominal incisions, taking weeks to recover. Unsurprisingly, all of this comes at a huge cost to the economy. By age 60, 1 in 3 women in the United States has had a hysterectomy. For endometriosis alone, estimates from the most recent comprehensive study to be done on the issue, would put today’s cost at about $15,000 per patient, with two-thirds of that due to lost productivity. For the 7 million to 8 million US women who have endometriosis, this translates to a loss of roughly $105 billion annually.

It’s possible that a relative lack of National Institutes of Health funding over decades for women-skewed diseases contributes to a health gap. A 2019 study about the various factors contributing to racial disparities in NIH funding success found that “the [topic word] cluster with the lowest award rate, 7.5%, is characterized by the words ovary, fertility, and reproductive.” A study published last year in the Journal of Women’s Health comparing NIH funding levels for male-skewed and female-skewed diseases revealed that “in nearly three-quarters of the cases where a disease afflicts primarily one gender, the funding pattern favors males, in that either the disease affects more women and is underfunded ... or the disease affects more men and is overfunded.”

More investigation is needed, and Congress — which appropriates the funding for the NIH — can start by considering funding changes for outliers that are either overfunded or underfunded compared with the average.


MIT postdoctoral associate Lauren Pruett prepares devices to grow blood vessels used for modeling endometriosis lesions.JARED CHARNEY

“AI for endo? If only there were data!” This sentiment was among many expressed by protesters carrying signs at our Stand Up and Be Counted (for Women’s Health) demonstration at our September event. There’s enormous interest in “FemTech,” a catch-all term coined in 2016 that sweeps in all forms of technology — software, diagnostics, medical devices, apps, and yes, artificial intelligence — to offer better solutions for women’s health needs. Indeed, there has been a surge in startups to address women’s health problems, with $2.5 billion in capital raised for FemTech through December 9, 2021, according to a February McKinsey report on the FemTech “revolution.”

But FemTech exists on a spectrum: On one end are devices and apps that can be considered a technology push, where no fundamental new science is needed. A cost-effective screening tool for anemia could be deployed in low-resource settings, for example, and would greatly improve diagnosis of fibroids and other treatable conditions characterized by heavy menstrual bleeding. On the opposite end are transformative tools and treatments that would require extensive (and expensive) basic scientific work along with clinical studies — for example, diagnostics for endometriosis and adenomyosis that could distinguish whether a patient has a disease and pinpoint which drugs could work best.

My research at MIT covers the entire FemTech spectrum. I’m in the process of cofounding a company relating to fertility. But it is a technology push, and, like so much technology in this space, addresses infertility downstream, at the point of fertility treatment, rather than upstream, at the point of diseases that cause not only infertility but immense suffering, and lost productivity. We can’t get the full spectrum of FemTech to stay on track without doing some major upgrading of the basic and translational science research infrastructure. This is a frustration I live with daily. Special women’s health programs such as the one sponsored by the Massachusetts Life Sciences Center help, but they are not enough.

We persist by finding creative routes to funding the basic infrastructure. With our first foundation grant, we published papers pioneering a possible molecular classification of endometriosis, stimulating a sea change in favor of the view that it “is not one disease” (patients can be classified into categories on a molecular basis, similar to how we classify breast cancer patients) and identifying a potential non-hormonal drug target. We found an ally in an industry scientist who had independently championed the same target through successful preclinical rodent and baboon trials — only to see a drug treatment hit roadblocks in clinical trials. He encouraged us to find a better way to predict human outcomes of all classes of endometriosis drug therapies if we ever wanted to see this target tested again in humans.

This was a tall order — we needed living human avatars that could represent the biology of different types of patients compared with healthy women. Developing such avatars was beyond the scope of the typical NIH grant, as it required enormous advances in microfluidic device engineering and biomaterials for tissue engineering. We secured funding from a Defense Advanced Research Projects Agency program, requiring us to build a microfluidic platform to interconnect 10 living human organ mimics to live for a month, capable of predicting human drug responses. Leveraging our commercialized Liverchip technology, our team developed useful new technology that the lab now uses to grow endometriosis lesions from patients, and is now starting a joint study with that drug expert to test his new molecules against that target we independently identified years ago.

Is there an advantage to having women lead the charge on these problems? Maybe. When deep knowledge and personal experience are informed by technical expertise, new insights on problems naturally emerge. You’re thinking about the problem all the time. Insights coupled with an insatiable need to slay the dragon that almost got you can drive a relentless, methodical slog to build the required technical infrastructure that draws in additional expertise. Importantly, the technologies we built for endometriosis patient avatars are generically useful for almost any disease-modeling problem. A rising tide lifts all boats — we’re collaborating with Novo Nordisk to apply these technologies and approaches to type 2 diabetes, and with the Fairbairn donor-advised fund to solve the riddle of long-term Lyme diseases.

Yet the need for public awareness of these issues persists. Below the Belt, a new documentary executive produced by Hillary Rodham Clinton, slated for general release in the spring, tells the story of four women slogging through the endometriosis journey. We screened it at our MIT event last month — and it sparked the discussion we had hoped for.

Even in my professional environment, well-respected female colleagues have admonished me, “Don’t say those things, men will think we are weak.” On the day of the post-Trump-inauguration women’s marches, I encountered young women in Harvard Square holding signs reading “Anything a man can do, I can do while bleeding.” I stopped and explained that about 1 in 5 women are so debilitated by menstruation problems that they often miss school or work. “That’s your opinion!” they argued. I call this “period privilege.” It’s what prevented the female OB-GYN from diagnosing my niece, and is especially insensitive in this era of increased awareness of health disparities, such as the earlier onset and more severe, life-disrupting symptoms from uterine fibroids Black women experience.

These were the attitudes society had about breast cancer decades ago; we didn’t talk about it. But then we finally focused on the science, and overcame the squeamishness about mentioning “breasts” by creating a technical language that could be spoken without hesitation by anyone. We need a similar scientific push for menstruation science, and a comfort level with the language that goes with it. It’s time.


Linda G. Griffith is the School of Engineering Professor of Teaching Innovation in the departments of biological and mechanical engineering at MIT. Send comments to magazine@globe.com.