Dr. Jessica Whited's office is sunny, with a large window overlooking one of the busiest streets in Boston's Longwood Medical neighborhood. It's a new building—the lab moved there in February of 2017—with expansive lab space and plenty of new tech, but an old-fashioned chalkboard dominates one wall. A chalk sketch of a spiky salamander leg, surrounded by labels and notes, proclaims her expertise: the Whited lab studies limb regeneration in axolotls, which are rare, neotenic salamanders that can regrow their limbs after amputation or injury.

Whited herself is as sunny as her office, with the scientist's classic, contagious enthusiasm about her work. She's been the principal investigator of her lab at Harvard Medical School since 2013.

"It's a really rewarding career," she says. "Every day I'm puzzled about why we can't get certain things to work." Life in the lab is challenging, and there are certainly frustrations. "[But] we're probing secrets of life on earth that literally no person knows the answer to."

Finding regeneration

Whited hasn't always been fascinated by salamanders. Her undergraduate degree was in biology and philosophy; when she chose the former for her career, she also chose MIT to do her PhD, specifically so she could work with Dr. Paul Garrity.

"He was working on axon guidance when I met him, which was super hot in the late 1990s," she says. "People were just starting to unravel the molecular cues for how axons are guided around in space." She continued to work with Garrity throughout her degree, studying the problem in fruit flies, and ended up taking on a side project in neuronal architecture. While investigating the maintenance of neuronal structures, she discovered a fly phenotype that disassembled its neuronal structure after development was complete.

"That got me thinking about, OK, what happens after development?" she says. "And that got me thinking a little bit about tissue injury, homeostasis, and even just about molecules that keep things in the right place … That's actually what got me interested in regeneration, even though it wasn't a regeneration project."

Since the decision of where to go for a postdoc was a hugely important one, she decided to take a broad approach. "I literally got out my undergraduate biology textbook, and I read through it, and I was like, what are still the huge questions?'" she remembers. "And I had this little bit of a nugget of a thought about going in to something about repair, or homeostasis, or maybe stem cells.

"I stumbled on the figure with the starfish. It had lost one of its arms, and it had the tiny arm in that place; it was depicting the regeneration of the starfish arm. And I thought: well, this is a huge question that we still don't know the answer to. How do you grow huge structures back? Not just replacing some cells that are lost during normal animal functioning, but replacing a whole arm or a whole leg or a whole tail."

She decided to write to Dr. Cliff Tabin, an expert in limb development at Harvard Medical School who had worked on limb regeneration earlier in his career. "I thought that I could write him and just see what he would say. I literally sent him a paper letter … I mailed it from Cambridge to Boston." His response came quickly and enthusiastically. "He was secretly hoping to find someone to take up the salamander project again—someone gullible enough!"

Gullibility and bravery are possibly the same thing, in Whited's case. Salamander limb regeneration is tough, risky work—the axolotls' generation time is long, and their genome isn't fully mapped.

"As it turned out, [Cliff] had a few people, maybe three let's say, take a stab at working on the axlotls at his lab, but they all just became frustrated with the slow pace and all the animal work," Whited explains. There are a great many challenges involved with keeping the animals alive and healthy; vertebrate care is tightly regulated, and the tank systems available for their care are generally not custom-made for them, so they require a lot of aftermarket tweaking. This process has been made easier, she says, by Will Ye, the animal husbandry technician she recently recruited from the New England Aquarium. "We'd be in such trouble without Will," she says, laughing. "He never picks a pipette up. He's in the axolotl room 90% of his time building stuff." But the care and keeping of the axolotls is a constant process—one that often keeps people in the lab long after business hours.

Life outside the salamander lab

Work-life balance is always a hurdle for scientists, but it's even more challenging for those with partners and children. "I'm thinking about [work] from the moment I wake up. That's just life," Whited says. "I think about it when I'm lying in bed at night. I search my phone under the covers for PubMed and stuff like that."

This is both more and less difficult for her because her husband is not a scientist. "A lot of scientists marry scientists, and then they know the struggle," she laughs. "But my husband is not a scientist at all … for him, when it's fun time, it's fun time. That is challenging. The science is just always there, and I can't turn it off, and I don't even want to turn it off. But that can be frustrating for other people."

The benefits of a layman partner are undeniable, however. Her husband's logistics career is home-based, and the support system they've built from their different schedules enables a less stressful life than might be expected from a PI with twin eight-year-old boys. Though she admits to habitually staying up to do lab work after the rest of the family goes to bed, she has plenty of non-salamander-related interests to pursue: arts, gardening, baking, and a variety of outdoor activities, including hanging out with the boys (Ashton and Oakley, named after trees) and playing with the family's two cats (Midnight and BatKitty). Her answer to the ubiquitous question for women in science—how to balance the kids and the lab—is encouraging.

"I have so much freedom here," she says. "In the end, the professor job is actually really quite flexible, because your time is mostly your own … it is actually not a bad career for a woman who has kids, because even if it's a small ship, you're running it. It hasn't happened, but if an emergency happened and I had to cancel lab meeting, who's going to stop me, you know? We're canceling lab meeting."

"You want to mix in some bravery"

The lab meetings in question involve four graduate students, three postdocs, three technicians, and "a small army" of undergraduates. "The sweet spot for me is about 10 people that are here full time," Whited says. The business of managing those people, getting the best out of them, and helping them succeed seems to occupy the largest part of her mental energy at the moment; the night before our interview, for example, she was up late into the night editing an abstract for her first PhD student's thesis defense.

"The hardest part of it is honestly the feeling of being responsible for the people in the lab," she says. "The question is, how do you get the most out of each individual personality type?" This is a learned skill as much as anything, and one that she ascribes to her experience in Tabin's lab. "He was really good at figuring out personalities and what makes each person tick," she explains. "Different things motivate different people, and people have different levels of risk that they're willing to take."

Taking risks is one reason Whited is where she is today. She and her lab have gotten to this point, she says, "through a lot of grit and determination and just not being afraid to do something that we knew was going to be a ton of work and super frustrating." That's what she tends to recommend to young researchers as well.

"I would say don't be afraid to tackle something that you think is almost too hard," she advises. "You could take a project that was obviously going to work, and you'd get a great paper out of it and everything, but if it's just very straightforward and very cookbook, then you would easily be perceived as the pair of hands in that equation. And I think there's something to be said for other types of approaches … you want to mix in some bravery. Especially if you want to start your own lab," she adds, "people are also looking for future growth in that area."

Back to the chalkboard

Future growth is very much the focus of the Whited lab at the moment. A variety of new and ongoing projects—a test of the limits of limb regeneration, a search for the transcripts made by wound epidermis, and a gene-discovery project using single-cell profiling, just to name a few—are revealing new and interesting information and possibilities for future research. Whited is optimistic about where that research will eventually lead, though those ideas haven't quite been sketched on her office chalkboard yet.

"Everyone can appreciate, 'Oh, [salamanders] can do this amazing thing that people can't do,'" she says. "People call it a model for regeneration, but it's not that we're using mice to model a human disease, because it's intractable in a human and unethical to do the experiments. It's kind of the opposite."

"We need to understand why they do it, because otherwise we're missing an opportunity to figure out how limbs can regrow. And it just follows, to me, that that information is of course going to inform future approaches in regenerative medicine."