STAT Wunderkinds discuss high-impact research, resilience, and social justice

Elenoe “Crew” Smith used to faint at the sight of blood. Still, she knew from a very young age that she wanted to help people living with sickle cell disease. Now, as a research director at Vertex Pharmaceuticals, she is working on potential sickle cell medicines.

Smith was in STAT’s 2017 class of Wunderkinds, an annual selection of standout researchers who are launching their careers. She and a Wunderkind from the class of 2020, Altaf Saadi, assistant professor of neurology at Massachusetts General Hospital and Harvard Medical School, spoke at a virtual STAT event Thursday about their journeys in science and medicine — what their work is, what brought them to the field, and what keeps them going.

In her seventh-grade science class, Smith learned about Gregor Mendel’s discovery of genetics, and how certain traits and diseases — such as sickle cell — are inherited. Smith went home from school that day fascinated by the lesson and excited to share it with her family. She wasn’t expecting to hear that she herself was a likely carrier for sickle cell disease.

“Imagine going home from school with this information — learning in school how devastating this disease is,” Smith said. “Lots of people are not expected to live past the age of 50. It’s debilitating, excessive pain, anemia, all these things that go along with the disease. And then to hear, ‘It’s in our family, you are a carrier. This potentially will affect your children and your grandchildren.’ From then, I was kind of like ‘I gotta do something about this.’”

Smith knew that she wanted to work on sickle cell — a disease that causes red blood cells to become misshapen and break down — but also that she was still uncomfortable with blood. An M.D. wasn’t in the cards for her, so Smith went down the research path.

Saadi was also on the fence about a career in medicine. Saadi grew up in an immigrant family and was always interested in social issues, but she didn’t see many paths in neurology that modeled the kind of health justice work she wanted to do. So Saadi decided to carve her own.

Many of Saadi’s research projects are based on her clinical experience. It was because of her clinical evaluations of asylum seekers and refugees that Saadi conducted a systemic review of the global prevalence of traumatic brain injury among forcibly displaced populations.

Other projects of Saadi’s are based on issues outside the clinic. In 2020, Saadi co-authored a report for Physicians for Human Rights about excited delirium, a diagnosis that police departments have used to justify aggressive tactics and deaths in police custody. In an investigation of the medical literature and other artifacts regarding excited delirium, the authors found conflicts of interest and poor scientific evidence. Last year the Bay Area Rapid Transit Police announced that it would stop using the term and cited the report in its decision.

“That really stands out to me because I think it really speaks to the impact that we can have when we make partnerships outside of our academic silos,” Saadi said. “And also when we address, especially as physicians, issues that are not restricted to what we see in the clinic room. There’s so much that affects people’s health.”

Although working with communities that have experienced physical and psychological trauma can be challenging, Saadi said that people undervalue the strength that work can transmit — that is, vicarious resilience.

“When I began doing training around this work, the topic of vicarious trauma came up often,” she said. “It is really challenging being on the receiving end of these stories. But I think something that doesn’t get as much attention as it should is the concept of vicarious resilience. … It is what gives me hope and inspiration in my work.”

Smith said that vicarious resilience is also what motivates her work in sickle cell, a disease that disproportionately affects Black people.

“It’s actually engaging with patients and talking with families who are helping to care for individuals living with sickle cell disease that drives me to do what I do every day,” she said. “Is there something that I could be doing to help make their lives better?”

When Smith was nominated as a STAT Wunderkind in 2017, she was working in the lab of Stuart Orkin researching CRISPR/Cas9 genome engineering for sickle cell. A few weeks ago, Vertex became the first company to seek FDA approval for a CRISPR gene therapy that can eliminate a patient’s sickle cell. Smith, however, has turned her focus to small-molecule therapies, aiming to bring treatments to more people.

“There’s a lot of buzz and excitement about things in the gene therapy space and it’s duly deserved,” Smith said. “There’s a lot of great things happening, and my postdoc work was some of the work that helped to enable some of these new therapies, so I’m very excited about that. But when we’re thinking about areas of the world that are mostly affected with sickle cell disease, like Sub-Saharan Africa, we think about how we’ll be able to bring these types of other complicated and complex therapies to those parts of the world. We have to be realistic about that. And I think that small molecules give us the opportunity to serve a lot more patients. And so that’s where I sit and that’s what keeps me excited.”

Smith said that there has been a positive shift since she joined Vertex Pharmaceuticals six years ago. She initially hesitated to take a position there because she believed that the industry wasn’t dedicated to working on diseases that mostly affect Black people.

“I was hesitant to join because I said, ‘Well, maybe in two years, they’re gonna pack up and go, and I’m not going to have a job doing what I want to do,’” Smith said. “But what I have seen over the last few years is that many more companies have taken an interest in this. And because of that, there’s actually competition in this space. Healthy competition which I think is only going to be beneficial for patients and their families, because people are looking at how we can really help to address this disease.”

You can nominate someone for the Wunderkind class of 2023 before the July 14, 2023, deadline here.