For decades, science maintained an awkward relationship with women as research subjects. Basically, scientists ignored them for logistical and cultural reasons, hoping that studies involving men and male animals would apply to women as well.
Here’s the not-so-surprising twist: That’s actually not how biology works. Sex and gender matter a lot when you’re testing a new drug, trying to identify a disease’s risk factors or hunting for a cure. This gender blind spot has put women’s health at a big disadvantage, but a study published this week in Nature Communications could dramatically change that.
The study debuted a tool its inventors call Evatar (and yes, that’s an intentional nod to the one and only Eve). The device is made up of plastic wells and containers that individually house a mouse ovary and human fallopian, uterine, cervical and liver tissue. It mimics the menstrual cycle through reproductive hormones produced by the ovary. While the miniature reproductive tract can’t bleed, it can prompt the release of an egg from the ovary.
This little marvel of biology and engineering, known as a tissue chip, is no larger than a Kindle.
This 3D culture system is the first of its kind and it effectively gives researchers a tiny lab to test conditions like fertility, the effects of chemical exposure, and how well certain drugs work — and not just in specific experiments overseen by scientists. Instead, the hope is that Evatar will eventually become so common that patients can show up at a doctor’s office and have their own cells cultured in the device to see how their body reacts to a chemotherapy drug for ovarian cancer, a different type of birth control, new treatment for a sexually transmitted disease, or something else entirely.
“This is absolutely a victory for women’s health,” says study co-author, Kelly E. McKinnon, a doctoral candidate at Northwestern University.
As recently as a year ago, says McKinnon, basic research in drug development still predominantly relied on male mice subjects. Now that research incorporates postmenopausal women, which is an improvement yet still leaves many unanswered questions about how drugs affect women of childbearing age.
“We’re really trying to address that gap and come up with a new system.”
“We’re really trying to address that gap and come up with a new system,” says McKinnon.
The gap is an infamous one in medicine and science. Female sex hormones do present their own unique challenges in experiments because they regularly fluctuate, and that’s partly why scientists defaulted to male human or animal study subjects. In the past, there were also ethical concerns about negatively affecting fertility for women of childbearing age, a worry that effectively excluded women from research while men continued to participate.
Even 30 years ago, researchers routinely conducted men-only studies. The groundbreaking research on taking aspirin to prevent a heart attack? That was done in the 1980s with 22,000 male participants. As retired Maryland Sen. Barbara Mikulski once recalled, researchers working on one aging study apparently didn’t include women because there wasn’t a ladies room available for female participants.
It wasn’t until 1994, when Congress passed a law requiring the National Institutes of Health to include women in its clinical studies and analyze results by sex or gender, that things began to change.
Evatar, a collaborative project led by the Woodruff Lab at Northwestern University and funded partly by the NIH, is proof of how far we’ve come in just two decades. Dr. Les Reinlib, program director for the National Institute of Environmental Health Sciences, says the tool has the potential to help scientists understand the interaction between genes and environment as they never have before. For women’s health, it could lead to important revelations about contraception, cancer, and fertility.
“This is a lot closer to the way people are,” Reinlib says of Evatar’s ability to model the female reproductive tract in three dimensions. “It provides cells the opportunity to respond the way they do in nature.”
What it’s not designed to do is become sentient or serve as an artificial womb for a test-tube baby. Evatar’s ovaries and human tissues are not connected to each other as a reconstruction of a woman’s reproductive organs. Instead they are linked via tiny channels that allow the hormones to flow throughout the system. Even though the team mimicked the hormonal response of pregnancy in its experiment, the egg was not transported from the fallopian tube to the uterine tissue. There also isn’t a brain to signal the beginning of ovulation through the pituitary gland — just a researcher jumpstarting the system with doses of reproductive hormones.
The Woodruff lab is working toward using the tool for testing drug toxicity related to female reproductive organs. There also plans to create a male equivalent of Evatar called — wait for it — Adatar.
In the meantime, we get the thrill of waiting to see if Evatar indeed catapults women’s reproductive health and medicine into the 21st century.