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From open education learners to MIT coders

MIT Digital Learning Lab’s high school interns gain professional experience working on the backend of open online MITx courses. The program emerged after Mary Ellen Wiltrout, PhD '09, digital learning scientist at MIT Open Learning, connected with the executive director and founder of Empowr, a nonprofit that serves low-income communities by creating a school-to-career pipeline through software development skills.

Katherine Ouellette | MIT Open Learning
August 26, 2024

Switching programming languages is not as simple as switching word processors. Yet high schooler Thomas Esayas quickly adapted from Swift to Python during his 2023 internship with the MIT Digital Learning Lab, a joint program between MIT Open Learning and the Institute’s academic departments. One year later, Esayas returns to the Institute for a second internship and as a new undergraduate student.

“I felt thoroughly challenged and learned a lot of new skills,” says Esayas.

Through this remote opportunity, interns gain real-world coding experience and practice professional skills by collaborating on MIT’s open online courses. The four interns from Digital Learning Lab’s 2023 and 2024 cohorts also participate in Empowr, a four-year program for low-income high school students that teaches in-demand software development skills and helps them secure paid internships.

The Digital Learning Lab program emerged after Mary Ellen Wiltrout PhD ’09, digital learning scientist at MIT Open Learning, connected with Adrian Devezin, executive director and founder of Empowr, at a conference about making education more accessible and equitable.

“It was affirming to have someone else see what Empowr is trying to do,” says Devezin about the organization’s goal to strengthen the school-to-career pipeline. “Being able to collaborate was beautiful for me, and more importantly, to the students.”

Building technical skills and self-confidence

The Digital Learning Lab internship empowers students to build confidence in their technical abilities, career skills, and the college application process. Interns assist the lab’s digital learning scientists with their work developing and maintaining online MITx courses at Open Learning across multiple academic areas.

“I found myself always busy with something interesting to work on,” says Esayas.

The interactive open education resources that Esayas produced last summer are now being used in live courses. He also helped find and fix bugs on the platform that hosts the MITx courses.

The internship’s flexible design allows projects to be adapted based on the student’s personal progress and interests.

“The students became co-creators of their educational experiences,” says Wiltrout, noting this is beneficial from a pedagogical standpoint.

Devezin adds, “I definitely saw a big improvement in their problem-solving abilities. Having to switch their mindset to a new language, work in new frameworks, and work on teams solving real problems enhanced their ability to adapt to new situations.”

The students’ also strengthened their professional repertoire in areas such as collaboration, communication, and project management. The 2023 cohort, Devezin says, developed the initiative to help other students and take on leadership roles.

Now that Esayas has completed his 2024 internship, he says, “I’m glad that I got to collaborate with more people and work on more projects. Overall, I’m very happy I was able to return.”

two people smiling, standing in front of a colorful wall.
Adrian Devezin, executive director and founder of Empowr (left), and Mary Ellen Wiltrout, digital learning scientist at MIT Open Learning (right), presented their takeaways from the first year of the MIT Digital Learning Lab internship at the 2024 Open edX conference. Photo courtesy of Empowr.

Learning from both sides

Learning occurred for both students and educators alike. Wiltrout says that the Digital Learning Lab values the opportunity to see the interns’ growth day-to-day and week-to-week, since digital learning scientists rarely follow the trajectory of individual learners who are using the course materials they create. Having instant feedback informs how they can adjust their teaching approaches for various problems.

The positive impact of the Digital Learning Lab internship’s hands-on learning experiences has made Devezin rethink the way he teaches class moving forward, and “the problems I want them to be solving,” he says.

Now, Devezin tries to emulate the real-world experience of working on a project for his Empowr students. Instead of assigning coding exercises where he provides the exact methods to solve the problems, he started asking students to determine the correct approach on their own.

The fact that Wiltrout and Devezin are open to adapting their teaching methods based on student feedback is indicative of a key factor to the internship’s success — active participation in students’ growth. It was mutually beneficial for the students and the educators to have determined stakeholders at both Digital Learning Lab and Empowr.

“A lot of dedicated educators understand that there’s a lot of inequities in education, and we need to come together to solve them,” Devezin says.

The Digital Learning Lab internship shows how open source learning materials can make educational and professional opportunities more accessible. The 2024 cohort has been able to increase their annual household income by an average of 75%, a recent Empowr report revealed. Wiltrout says that the two new Empowr students seem more confident with coding and showed enthusiasm and dedication to their tasks as they also consider colleges.

Wiltrout and Devezin presented their takeaways from the internship’s first year at the 2024 Open edX conference.

“I think it’s important to try making sure that more people are aware of tools and resources that are out there,” Wiltrout says. “Then giving people opportunities where they may not have otherwise had that chance.”

Now, Devezin is thinking about how Empowr students can come full circle with their relationship to open educational materials. He’s asking, “How can I help my students contribute to the open source world to give back to others?”

Alum Profile: Gevorg Grigoryan, PhD ’07

Creating the Crossroads

Lillian Eden | Department of Biology
June 13, 2024

From academia to industry, at the intersection of computation, biology, and physics, Gevorg Grigoryan, PhD ’07, says there is no right path–just the path that works for you

A few years ago, Gevorg Grigoryan, PhD ‘07, then a professor at Dartmouth, had been pondering an idea for data-driven protein design for therapeutic applications. Unsure how to move forward with launching that concept into a company, he dug up an old syllabus from an entrepreneurship course he took during his PhD at MIT and decided to email the instructor for the class. 

He labored over the email for hours. It went from a few sentences to three pages, then back to a few sentences. Grigoryan finally hit send in the wee hours of the morning. 

Just 15 minutes later, he received a response from Noubar Afeyan, PhD ’87, the CEO and co-founder of venture capital company Flagship Pioneering (and the commencement speaker for the 2024 OneMIT Ceremony)

That ultimately led to Grigoryan, Afeyan, and others co-founding Generate:Biomedicines, where Grigoryan now serves as CTO.

“Success is defined by who is evaluating you,” Grigoryan says. “There is no right path—the best path for you is the one that works for you.” 

Generalizing Principles and Improving Lives

Generate:Biomedicines is the culmination of decades of advancements in machine learning, biological engineering, and medicine. Until recently, de novo design of a protein was extremely labor intensive, requiring months or years of computational methods and experiments. 

“Now, we can just push a button and have a generative model spit out a new protein with close to perfect probability it will actually work. It will fold. It will have the structure you’re intending,” Grigoryan says. “I think we’ve unearthed these generalizable principles for how to approach understanding complex systems, and I think it’s going to keep working.” 

Drug development was an obvious application for his work early on. Grigoryan says part of the reason he left academia—at least for now—are the resources available for this cutting-edge work.  

“Our space has a rather exciting and noble reason for existing,” he says. “We’re looking to improve human lives.”

Mixing Disciplines

Mixed-discipline STEM majors are increasingly common, but when Grigoryan was an undergraduate at the University of Maryland Baltimore County, little to no infrastructure existed for such an education.  

“There was this emerging intersection between physics, biology, and computational sciences,” Grigoryan recalls. “It wasn’t like there was this robust discipline at the intersection of those things—but I felt like there could be, and maybe I could be part of creating one.” 

He majored in Biochemistry and Computer Science, much to the confusion of his advisors for each major. This was so unprecedented that there wasn’t even guidance for which group he should walk with at graduation. 

Heading to Cambridge

Grigoryan admits his decision to attend MIT in the Department of Biology wasn’t systematic. 

“I was like ‘MIT sounds great, strong faculty, good techie school, good city. I’m sure I’ll figure something out,’” he says. “I can’t emphasize enough how important and formative those years at MIT were to who I ultimately became as a scientist.”

He worked with Amy Keating, then a junior faculty member, now Department Head for the Department of Biology, modeling protein-protein interactions. The work involved physics, math, chemistry, and biology. The Computational and Systems Biology PhD program was still a few years away, but the developing field was being recognized as important. 

Keating remains an advisor and confidant to this day. Grigoryan also commends her for her commitment to mentoring while balancing the demands of a faculty position—acquiring funding, running a research lab, and teaching. 

“It’s hard to make time to truly advise and help your students grow, but Amy is someone who took it very seriously and was very intentional about it,” Grigoryan says. “We spent a lot of time discussing ideas and doing science. The kind of impact that one can have through mentorship is hard to overestimate.”

Grigoryan next pursued a postdoc at UPenn with William “Bill” DeGrado, continuing to focus on protein design while gaining more experience in experimental approaches and exposure to thinking about proteins differently. 

Just by examining them, DeGrado had an intuitive understanding of molecules—anticipating their functionality or what mutations would disrupt that functionality. His predictive skill surpassed the abilities of computer modeling at the time. 

Grigoryan began to wonder: could computational models use prior observations to be at least as predictive as someone who spent a lot of time considering and observing the structure and function of those molecules?

Grigoryan next went to Dartmouth for a faculty position in computer science with cross-appointments in biology and chemistry to explore that question. 

Balancing Industry and Academia

Much of science is about trial and error, but early on, Grigoryan showed that accurate predictions of proteins and how they would bind, bond, and behave didn’t require starting from first principles. Models became more accurate by solving more structures and taking more binding measurements. 

Grigoryan credits the leaders at Flagship Pioneering for their initial confidence in the possible applications for this concept—more bullish, at the time, than Grigoryan himself. 

He spent four years splitting his time between Dartmouth and Cambridge and ultimately decided to leave academia altogether. 

“It was inevitable because I was just so in love with what we had built at Generate,” he says. “It was so exciting for me to see this idea come to fruition.” 

Pause or Grow

Grigoryan says the most important thing for a company is to scale at the right time, to balance “hitting the iron while it’s hot” while considering the readiness of the company, the technology, and the market. 

But even successful growth creates its own challenges. 

When there are fewer than two dozen people, aligning strategies across a company is straightforward: everyone can be in the room. However, growth—say, expanding to 200 employees—requires more deliberate communication and balancing agility while maintaining the company’s culture and identity.

“Growing is tough,” he says. “And it takes a lot of intentional effort, time, and energy to ensure a transparent culture that allows the team to thrive.” 

Grigoryan’s time in academia was invaluable for learning that “everything is about people”—but academia and industry require different mindsets. 

“Being a PI is about creating a lane for each of your trainees, where they’re essentially somewhat independent scientists,” he says. “In a company, by construction, you are bound by a set of common goals, and you have to value your work by the amount of synergy that it has with others, as opposed to what you can do only by yourself.” 

Taking RNAi from interesting science to impactful new treatments

Alnylam Pharmaceuticals is translating the promise of RNA interference (RNAi) research into a new class of powerful, gene-based therapies. These days Alnylam is not the only company developing RNAi-based medicines, but it is still a pioneer in the field. The company’s founders — MIT Institute Professor Phil Sharp, Professor David Bartel, Professor Emeritus Paul Schimmel, and former MIT postdocs Thomas Tuschl and Phillip Zamore — see Alnylam as a champion for the field more broadly.

Zach Winn | MIT News
May 13, 2024

There are many hurdles to clear before a research discovery becomes a life-changing treatment for patients. That’s especially true when the treatments being developed represent an entirely new class of medicines. But overcoming those obstacles can revolutionize our ability to treat diseases.

Few companies exemplify that process better than Alnylam Pharmaceuticals. Alnylam was founded by a group of MIT-affiliated researchers who believed in the promise of a technology — RNA interference, or RNAi.

The researchers had done foundational work to understand how RNAi, which is a naturally occurring process, works to silence genes through the degradation of messenger RNA. But it was their decision to found Alnylam in 2002 that attracted the funding and expertise necessary to turn their discoveries into a new class of medicines. Since that decision, Alnylam has made remarkable progress taking RNAi from an interesting scientific discovery to an impactful new treatment pathway.

Today Alnylam has five medicines approved by the U.S. Food and Drug Administration (one Alnylam-discovered RNAi therapeutic is licensed to Novartis) and a rapidly expanding clinical pipeline. The company’s approved medicines are for debilitating, sometimes fatal conditions that many patients have grappled with for decades with few other options.

The company estimates its treatments helped more than 5,000 patients in 2023 alone. Behind that number are patient stories that illustrate how Alnylam has changed lives. A mother of three says Alnylam’s treatments helped her take back control of her life after being bed-ridden with attacks associated with the rare genetic disease acute intermittent porphyria (AIP). Another patient reported that one of the company’s treatments helped her attend her daughter’s wedding. A third patient, who had left college due to frequent AIP attacks, was able to return to school.

These days Alnylam is not the only company developing RNAi-based medicines. But it is still a pioneer in the field, and the company’s founders — MIT Institute Professor Phil Sharp, Professor David Bartel, Professor Emeritus Paul Schimmel, and former MIT postdocs Thomas Tuschl and Phillip Zamore — see Alnylam as a champion for the field more broadly.

“Alnylam has published more than 250 scientific papers over 20 years,” says Sharp, who currently serves as chair of Alnylam’s scientific advisory board. “Not only did we do the science, not only did we translate it to benefit patients, but we also described every step. We established this as a modality to treat patients, and I’m very proud of that record.”

Pioneering RNAi development

MIT’s involvement in RNAi dates back to its discovery. Before Andrew Fire PhD ’83 shared a Nobel Prize for the discovery of RNAi in 1998, he worked on understanding how DNA was transcribed into RNA, as a graduate student in Sharp’s lab.

After leaving MIT, Fire and collaborators showed that double-stranded RNA could be used to silence specific genes in worms. But the biochemical mechanisms that allowed double-stranded RNA to work were unknown until MIT professors Sharp, Bartel, and Ruth Lehmann, along with Zamore and Tuschl, published foundational papers explaining the process. The researchers developed a system for studying RNAi and showed how RNAi can be controlled using different genetic sequences. Soon after Tuschl left MIT, he showed that a similar process could also be used to silence specific genes in human cells, opening up a new frontier in studying genes and ultimately treating diseases.

“Tom showed you could synthesize these small RNAs, transfect them into cells, and get a very specific knockdown of the gene that corresponded to that the small RNAs,” Bartel explains. “That discovery transformed biological research. The ability to specifically knockdown a mammalian gene was huge. You could suddenly study the function of any gene you were interested in by knocking it down and seeing what happens. … The research community immediately started using that approach to study the function of their favorite genes in mammalian cells.”

Beyond illuminating gene function, another application came to mind.

“Because almost all diseases are related to genes, could we take these small RNAs and silence genes to treat patients?” Sharp remembers wondering.

To answer the question, the researchers founded Alnylam in 2002. (They recruited Schimmel, a biotech veteran, around the same time.) But there was a lot of work to be done before the technology could be tried in patients. The main challenge was getting RNAi into the cytoplasm of the patients’ cells.

“Through work in Dave Bartel and Phil Sharp’s lab, among others, it became evident that to make RNAi into therapies, there were three problems to solve: delivery, delivery, and delivery,” says Alnylam Chief Scientific Officer Kevin Fitzgerald, who has been with the company since 2005.

Early on, Alnylam collaborated with MIT drug delivery expert and Institute Professor Bob Langer. Eventually, Alnylam developed the first lipid nanoparticles (LNPs) that could be used to encase RNA and deliver it into patient cells. LNPs were later used in the mRNA vaccines for Covid-19.

“Alnylam has invested over 20 years and more than $4 billion in RNAi to develop these new therapeutics,” Sharp says. “That is the means by which innovations can be translated to the benefit of society.”

From scientific breakthrough to patient bedside

Alnylam received its first FDA approval in 2018 for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis, a rare and fatal disease. It doubled as the first RNAi therapeutic to reach the market and the first drug approved to treat that condition in the United States.

“What I keep in mind is, at the end of the day for certain patients, two months is everything,” Fitzgerald says. “The diseases that we’re trying to treat progress month by month, day by day, and patients can get to a point where nothing is helping them. If you can move their disease by a stage, that’s huge.”

Since that first treatment, Alnylam has updated its RNAi delivery system — including by conjugating small interfering RNAs to molecules that help them gain entry to cells — and earned approvals to treat other rare genetic diseases along with high cholesterol (the treatment licensed to Novartis). All of those treatments primarily work by silencing genes that encode for the production of proteins in the liver, which has proven to be the easiest place to deliver RNAi molecules. But Alnylam’s team is confident they can deliver RNAi to other areas of the body, which would unlock a new world of treatment possibilities. The company has reported promising early results in the central nervous system and says a phase one study last year was the first RNAi therapeutic to demonstrate gene silencing in the human brain.

“There’s a lot of work being done at Alnylam and other companies to deliver these RNAis to other tissues: muscles, immune cells, lung cells, etc.,” Sharp says. “But to me the most interesting application is delivery to the brain. We think we have a therapeutic modality that can very specifically control the activity of certain genes in the nervous system. I think that’s extraordinarily important, for diseases from Alzheimer’s to schizophrenia and depression.”

The central nervous system work is particularly significant for Fitzgerald, who watched his father struggle with Parkinson’s.

“Our goal is to be in every organ in the human body, and then combinations of organs, and then combinations of targets within individual organs, and then combinations of targets within multi-organs,” Fitzgerald says. “We’re really at the very beginning of what this technology is going do for human health.”

It’s an exciting time for the RNAi scientific community, including many who continue to study it at MIT. Still, Alnylam will need to continue executing in its drug development efforts to deliver on that promise and help an expanding pool of patients.

“I think this is a real frontier,” Sharp says. “There’s major therapeutic need, and I think this technology could have a huge impact. But we have to prove it. That’s why Alnylam exists: to pursue new science that unlocks new possibilities and discover if they can be made to work. That, of course, also why MIT is here: to improve lives.”