MIT Research News' Journal

Taking on gender gaps in health care and technology

When Alicia Chong Rodriguez first toured the MIT campus as a high school student, she was so impressed by everything she saw that she still remembers excitedly phoning her mom back home in Costa Rica, calling collect from a pay phone in the student center.

“It’s the first time I was faced with the fact that people create the things that we use,” says Chong, who has always been interested in technology and computers. “I felt like I could do that too.”

Chong’s life has taken many twists and turns in the years since, but she is finally back at MIT as a master’s candidate in the inaugural class of the Integrated Design and Management Program. There, she is using her electrical engineering skills to combat cardiovascular disease in women, while also encouraging and inspiring young Latinas to pursue careers in technology.

Journey to MIT

Chong, who grew up in San José, Costa Rica, describes her family as very international, and she always assumed she might attend college elsewhere. After visiting MIT, her interest in technology spurred her to fill out an application, but she realized the timing wasn’t right for her family to take on the financial cost. Instead, Chong spent two years studying at the Instituto Tecnológico de Costa Rica before traveling to Mexico to earn her bachelor’s degree in electronic and computer engineering at Tecnológico de Monterrey. It was during her undergraduate courses, where there would often be two or three women in a class of 40, that Chong was faced with the stark reality of gender inequality in engineering.

“Before that I thought we all have opportunity to study whatever we want now,” she says. “But there's a lot of bias, and I started understanding it and learning more about it, and becoming really interested in these issues.”

Chong banded together with her fellow women in engineering and started a group called Mujeres en Tecnología (Women in Technology) or MenTe, to help them motivate and empower each other. The group quickly gained momentum — the members began visiting local high schools, inviting interesting guest speakers to campus, and even attending international conferences.

After college, Chong returned to Costa Rica, where she spent six years working in engineering roles at tech companies Teradyne, Inc. and HP Networking. She knew she wanted to return to school but was unsure of what she wanted to study until she came across a three-month summer program that caught her attention.

“I found this program at Singularity University [in Silicon Valley] that mixes technology with social impact,” she says. “I saw people who were using technology to solve world problems, and that was really interesting.”

Around the same time, Chong discovered MIT’s newly minted program in Integrated Design and Management (IDM) and decided to apply. She was accepted to both programs on the same day, and it was during her summer at Singularity University that she uncovered a passion she is now pursuing at MIT: health care.

Tackling an invisible problem

While at Singularity, Chong was shocked to learn that cardiovascular disease affects one in three women worldwide, and mortality rates continue to climb as women are frequently misdiagnosed or not treated.

“There's a lot of things about the physiology of women we don't know yet,” says Chong. “There's a data gap. So there I could combine my passion for gender issues and the technical challenge of creating a medical device for this purpose.”

Chong and four of her classmates began thinking about body sensors that could be used for data collection on cardiovascular health, and came up with a seemingly obvious solution: a bra with built-in sensors.

“It just makes so much sense,” she says. “You wear the bra every day, you will never forget to put it on, it's so comfortable, you don't have to think about it. It's located in a clever part close to getting the signals of the heart.”

The team launched a startup called Bloomer Tech (named after women’s rights advocate Amelia Bloomer), and during her first year at MIT Chong put her electrical engineering skills to work developing prototypes. The idea is simple: Medical-grade sensors, integrated into the bra as washable, flexible circuits, monitor heart activity and communicate to a smartphone application via Bluetooth. The app transforms the information into a format that is accessible to the patient and her doctor, allowing convenient, long-term monitoring. Bloomer Tech will first market the bras for women who have already had one cardiac episode, and support them with technology tools as they undergo life changes.

Chong is currently working on her third prototype and recently realized she can use the power of social media to help improve her design.

“We have decided to dig deeper into what patients really want and design it with the patients,” says Chong. “There are super-huge communities of heart disease survivors on Facebook, so we want to ask them to help us. We want to provide them the data that matters to them the most.”

Along the way, Chong has met many people at MIT who have helped her with various aspects of Bloomer Tech, from app creation to narrowing down her target demographic. She has also been part of several programs through the MIT Science and Technology Initiatives (MISTI). A MISTI Seed Grant sent her to Peru, where she organized workshops on cardiovascular health, with the support of Pratik Shah, her professor in an engineering health course she took in the fall. The grant also allowed one of her cofounders to come to MIT. MISTI also provided support for Chong to visit a heart research institute in India and participate with the MIT Media Lab Camera Culture Group as a mentor at the Emerging Worlds, Innovating for Billions event in Nashik, India, and to learn about mass production and scaling in the new MIT Kickstart program in Hong Kong and Shenzhen.

Empowering the next generation

Even in the midst of launching a startup and working on a master’s degree, Chong hasn’t lost sight of what started her on this journey — the gender inequality she noticed as an undergraduate in Mexico. Chong realized that there are many Latinas in tech at MIT, so she applied, along with Colombian IDM student Maria Fernanda Tafur, for a student life grant through the Office of the Dean for Graduate Education to fund an MIT chapter of MenTe. First, the group members are connecting women on campus to each other through a dinner series; next, they aim to connect them to organizations in Latin America devoted to encouraging girls to pursue careers in tech.

“There's a lot of role models here, and sometimes, in Chile or in Mexico or in Costa Rica, [girls] don't know that there's a graduate student or an undergrad doing these cool things at MIT,” says Chong. “I think it's a matter of just connecting the dots.”

In Costa Rica, Chong also is part of the nonprofit organization Ideas en Acción that launched a 12-week program called MenTe en Acción, for 15- to 19-year-old girls in communities at social risk. Through the program, girls build a mobile app with MIT App Inventor and are exposed to different technology careers, while learning about leadership, entrepreneurship, and female empowerment.

Lately, Chong has garnered a lot of attention for her work, ranging from invitations to speak at conferences, to a cover story for Revista Perfil (the Costa Rican equivalent of Glamour), a turn of events she describes as amazing, if slightly surreal, and one that propels her forward in her work.

“Sometimes I feel like everything is happening so fast, it's so cool, it matches so well, I still can't believe it,” she says. “Right now, I'm learning so much, and getting excited all the time, and meeting a lot of cool people. It has been a wonderful experience.”

Recording analog memories in human cells

MIT biological engineers have devised a way to record complex histories in the DNA of human cells, allowing them to retrieve “memories” of past events, such as inflammation, by sequencing the DNA.

This analog memory storage system — the first that can record the duration and/or intensity of events in human cells — could also help scientists study how cells differentiate into various tissues during embryonic development, how cells experience environmental conditions, and how they undergo genetic changes that lead to disease.

“To enable a deeper understanding of biology, we engineered human cells that are able to report on their own history based on genetically encoded recorders,” says Timothy Lu, an associate professor of electrical engineering and computer science, and of biological engineering. This technology should offer insights into how gene regulation and other events within cells contribute to disease and development, he adds.

Lu, who is head of the Synthetic Biology Group at MIT’s Research Laboratory of Electronics, is the senior author of the new study, which appears in the Aug. 18 online edition of Science. The paper’s lead authors are Samuel Perli SM ’10, PhD ’15 and graduate student Cheryl Cui.

Analog memory

Many scientists, including Lu, have devised ways to record digital information in living cells. Using enzymes called recombinases, they program cells to flip sections of their DNA when a particular event occurs, such as exposure to a particular chemical. However, that method reveals only whether the event occurred, not how much exposure there was or how long it lasted.

Lu and other researchers have previously devised ways to record that kind of analog information in bacteria, but until now, no one has achieved it in human cells.

The new MIT approach is based on the genome-editing system known as CRISPR, which consists of a DNA-cutting enzyme called Cas9 and a short RNA strand that guides the enzyme to a specific area of the genome, directing Cas9 where to make its cut.

CRISPR is widely used for gene editing, but the MIT team decided to adapt it for memory storage. In bacteria, where CRISPR originally evolved, the system records past viral infections so that cells can recognize and fight off invading viruses.

“We wanted to adapt the CRISPR system to store information in the human genome,” Perli says.

When using CRISPR to edit genes, researchers create RNA guide strands that match a target sequence in the host organism’s genome. To encode memories, the MIT team took a different approach: They designed guide strands that recognize the DNA that encodes the very same guide strand, creating what they call “self-targeting guide RNA.”

Led by this self-targeting guide RNA strand, Cas9 cuts the DNA encoding the guide strand, generating a mutation that becomes a permanent record of the event. That DNA sequence, once mutated, generates a new guide RNA strand that directs Cas9 to the newly mutated DNA, allowing further mutations to accumulate as long as Cas9 is active or the self-targeting guide RNA is expressed.

By using sensors for specific biological events to regulate Cas9 or self-targeting guide RNA activity, this system enables progressive mutations that accumulate as a function of those biological inputs, thus providing genomically encoded memory.

For example, the researchers engineered a gene circuit that only expresses Cas9 in the presence of a target molecule, such as TNF-alpha, which is produced by immune cells during inflammation. Whenever TNF- alpha is present, Cas9 cuts the DNA encoding the guide sequence, generating mutations. The longer the exposure to TNF-alpha or the greater the TNF-alpha concentration, the more mutations accumulate in the DNA sequence.

By sequencing the DNA later on, researchers can determine how much exposure there was.

“This is the rich analog behavior that we are looking for, where, as you increase the amount or duration of TNF-alpha, you get increases in the amount of mutations,” Perli says.

“Moreover, we wanted to test our system in living animals. Being able to record and extract information from live cells in mice can help answer meaningful biological questions,” Cui says. The researchers showed that the system is capable of recording inflammation in mice.

Most of the mutations result in deletion of part of the DNA sequence, so the researchers designed their RNA guide strands to be longer than the usual 20 nucleotides, so they won’t become too short to function. Sequences of 40 nucleotides are more than long enough to record for a month, and the researchers have also designed 70-nucleotide sequences that could be used to record biological signals for even longer.

Tracking development and disease

The researchers also showed that they could engineer cells to detect and record more than one input, by producing multiple self-targeting RNA guide strands in the same cell. Each RNA guide is linked to a specific input and is only produced when that input is present. In this study, the researchers showed that they could record the presence of both the antibiotic doxycycline and a molecule known as IPTG.

Currently this method is most likely to be used for studies of human cells, tissues, or engineered organs, the researchers say. By programming cells to record multiple events, scientists could use this system to monitor inflammation or infection, or to monitor cancer progression. It could also be useful for tracing how cells specialize into different tissues during development of animals from embryos to adults.

“With this technology you could have different memory registers that are recording exposures to different signals, and you could see that each of those signals was received by the cell for this duration of time or at that intensity,” Perli says. “That way you could get closer to understanding what’s happening in development.”