Marine Biological Laboratory. (Photography by Daniel Cojanu)

Natural connection

Joining forces with the Marine Biological Laboratory, the University formalizes its long-standing links to a venerable scientific destination.

At the Marine Biological Laboratory, neurobiologist Jennifer Morgan studies how sea lampreys recover from spinal cord injury, a regenerative marvel and mystery. Within three weeks of injury, the sea lampreys typically regain the ability to move, at first in irregular fits and starts. As the weeks pass, their improvement continues until, about three months after a spinal transection, it’s hard to distinguish a previously injured animal from an uninjured one.

Plotted on a graph, it’s impressive progress. Witnessed in the tanks shelved in Morgan’s lab, where she rakes the sand with a plastic tool to stir the burrowing fish, it’s astonishing. They lurch out of the sand and propel themselves through the water, undulating like Michael Phelps after pushing off the wall of a pool.

Morgan points out a slight kink near one sea lamprey’s head, the faintest hitch in its otherwise fluid motion, and the only visible evidence of recent trauma. To the naked eye, an uninjured animal in the same tank has no apparent physical advantage. “You actually have to video them,” Morgan says, “and measure quantitatively things like swimming speed,” which the injured fish never fully regain.

Sea lampreys are vertebrates with genetic similarities to humans, so the level and consistency of their recovery is especially tantalizing. Analyzing brain and spinal cord tissue at different stages of the healing process, researchers can identify what genes are expressed to understand the neurobiological mechanisms driving regeneration.

“Because the recovery is so stereotypical, now we can start to do manipulations that might improve it, make it go faster,” Morgan says. “Or we can perturb pathways that might inhibit regeneration and make it go slower, so that we know that pathway is important.”

Data indicates relevant activity in genes related to neuron growth and to the immune system. “The goal is to say, OK, what’s the recipe that gets you good regeneration?” Morgan says. “What’s happening in an animal that doesn’t recover very well, like a mouse? And make that comparison.”

Morgan explores those questions at the Eugene Bell Center for Regenerative Biology and Tissue Engineering, where she is associate director. Part of the Marine Biological Laboratory (MBL), the Bell Center recently added to the web of connections developing between the Woods Hole, Massachusetts, institution and the University of Chicago since they formed an affiliation in 2013.

In July a $3.5 million gift from the Millicent and Eugene Bell Foundation endowed the Eugene Bell Professorship in Tissue Engineering. The position will be based at the University’s Institute for Molecular Engineering with the faculty member directing a research project at the Bell Center as well.

Also this past summer, seven College students and recent graduates worked at the MBL as part of Career Advancement’s Metcalf Internship Program for UChicago undergraduates. They budgeted to hire five Metcalfs, but Joel Smith, the MBL’s associate director of education, says several of the students’ research proposals were of such high quality that they were “impossible to distinguish between.” Additional funding allowed eight to be hired, although one could not participate.

The students were, in a sense, experimental subjects themselves, offering the first inklings of the ways UChicago undergraduates could be assimilated into the MBL’s array of programs. Mostly, though, they were participants. Smith describes the lab’s philosophy as “teaching science by doing science,” and that’s just how the Metcalf students learned.

On her first day, Clara Kao, ’17, used tweezers under a microscope to remove zebrafish embryos from their eggs. She had never worked at such a tiny scale before. “I was dizzy for a while,” Kao says, but that eventually faded into a different kind of heady feeling. “Afterwards, I was like, ‘Wow, I actually did something today.’”

Kao works with Jonathan Gitlin, the Bell Center director and the MBL’s deputy director of research and programs, to study what happens when zebrafish are put into a state of suspended animation, or hibernation. A pediatrician, Gitlin became interested in the subject as a resident when he treated a six-year-old girl whose mother jumped off a bridge with her in a snowstorm, plunging them into an icy river. Pulled out 48 minutes later, the mother died, but the child lived. “Her heart rate,” Gitlin says, “was ten when I arrived.”

She needed several surgeries, but the role that a drastic cellular slowdown could play in survival stayed with Gitlin. Heart attack survivors, for example, experience a phenomenon called stunned myocardium. “The heart cells at the time of that event just stop,” he says. “And they wait.”

His scientist’s intuition and his physician’s imagination merged in a basic research question with hopeful medical implications. “How does a cell turn way up or way down its metabolism, its metabolic rate?” Gitlin says. “A great way to think about this is, the old physiologists used to call this turning down to the pilot light.”

Could children suffering from brain cancer have cells put into suspended animation—“stunned brain”—to prevent damage from aggressive treatment of the tumor? Could such a process better preserve organs for patients who are waiting for a transplant?

Turning the pilot light up and down in zebrafish allows for genetic testing to understand the cellular processes that keep the animals alive in and out of the induced torpor. “You take away all the oxygen. You put them in an environment called anoxia. Everything stops,” Gitlin says, pausing for a few beats, as if to mimic the state. “Then if you come back with the oxygen 30 hours later and add it in, everything starts right back up again. The heart starts beating again. The blood starts flowing.”

Scientists appear to experience a similar phenomenon during the bustling summer months at the Marine Biological Laboratory. Many visit from academic institutions around the world. They talk about shedding administrative burdens and returning to the source of their inspiration.

Hearts start beating, blood starts flowing, and a dormant passion for research reawakens.

Woods Hole, Massachusetts, sits on the shoulder blade of Cape Cod’s flexed arm. A historic whaling, fishing, and shipping port, Woods Hole is also a venerable scientific destination, its rocky coastline dotted with research institutions, including the Marine Biological Laboratory, which dates to 1888. Each summer the migratory biologists arrive.

They don’t come on vacation, but there’s an unmistakable air of relaxation even amid the blur of activity during summer’s brief window. Wearing shorts, T-shirts, and sandals, they drift between lectures—popular daily offerings, sometimes filling the auditorium to overflowing—and labs, lost in thought or conversation.

“One of my favorite things about being here,” says Metcalf Intern Medha Biswas, ’16, “is that there’s so much intellectual stuff going on,” even beyond her own summer project with UChicago neuroscientist William Green. The curious stuff through the open doors of other labs, for example, into which everyone feels free to wander to peek at other people’s work. “Just come over and we’ll show it to you,” Biswas says, describing the prevailing sentiment.

Days start early and end late, often at the Captain Kidd restaurant and bar, which serves as a de facto conference room for impromptu meetings that last long after office hours. In that accelerated—even a little bit overextended—environment, a virtuous cycle of research gathers momentum in Woods Hole.

“They just go on a data binge over three months, and then they spend a year or so analyzing, and then they discover things,” says Shalin Mehta, a microscopist in the cellular dynamics program. “And then they come back with new questions, which comes from the data they have taken previously.”

Like the questions researchers ask, and like the marine and terrestrial creatures they study to answer them, the programs at the MBL are diverse. The summer courses are perhaps the institution’s most distinctive offering. In 1892 Jacques Loeb, one of several early UChicago faculty members whose names adorn MBL buildings, founded the flagship physiology course.

This summer there were seven graduate-level full submersion courses in subjects such as embryology, microbial diversity, and neurobiology. Each course has 20 to 24 students, who come from all over the world, paying $5,625 in tuition this summer—costs that their home institutions, scholarships, grants, and need-based aid help reduce.

Over six to eight weeks, they embark into territory that, for some, is entirely unfamiliar. About half of the students in this summer’s physiology course, for example, had physics and math backgrounds.

To study motor proteins isolated from squid—as well as the microbes in plaque scraped from their own teeth—students first assembled microscopes during a “boot camp” that began the course. Then they “caught” their own squid from a tank in the MBL’s Marine Resources Center, which collects and maintains more than 200 organisms for scientific use.

“What a great introduction to biology,” says physiology course codirector Wallace F. Marshall, a biochemist at the University of California, San Francisco, “to actually have a whole squid that you fish out of the water with a net.” It might take a while to wash off the ink that the animal sprays in self-defense, but the students can wear it as a mark of field experience that, Marshall notes, even many trained biologists never have.

Fishing for squid or building microscopes together creates a camaraderie that makes the daunting workload more manageable. Not that the hundreds of scientists and students who flock to Woods Hole for the summer want to spend fewer hours in the lab.

Labs close on Sundays for enforced rest, but relaxation is also a prominent part of the institution’s DNA. Students make time to outdo each other with costumes and floats of varying biological correctness for the Woods Hole Fourth of July parade. “My kids call it the nerdiest parade in the world,” UChicago’s Green says.

Professional and personal interests merge in the labs too. In the neural systems and behavior course, a hum that sounds like an industrial fan comes from the drone of fruit flies the students are studying. Later, when a huge screen at the front of the room broadcasts the World Cup, Germany’s win over Brazil generates the biggest buzz.

Creative science germinates in that casual atmosphere. Intellectual inhibition disappears. “Both in the courses and in the research there’s a lot more freedom to try new things, to think of ideas, to talk to people, to meet new people,” says Ron Vale, a professor of cellular and molecular pharmacology at the University of California, San Francisco, and a Howard Hughes Medical Institute investigator.

Vale and Columbia University’s Michael Sheetz were two of three recipients of the 2012 Lasker Basic Medical Research Award for their work on kinesin, a motor protein that they and colleagues discovered in squid as MBL collaborators in the 1980s. A graduate student at the time, Vale says the breakthrough “probably wouldn’t have happened anywhere else.”

Also a former physiology course director, Vale praises the MBL’s structural advantages. Around him in the lab, principal investigators from seven different institutions, along with graduate students and postdocs, work in floating clusters over microscopes and computer screens, as if dramatizing his description of an environment that creates “collisions between people.”

Summer’s precious few months bring a rush of scientific interactions, making the MBL a hothouse of ideas. “The system heats up here to a boil,” Vale says, “and the pot is stirred in ways that often don’t happen at your home institution.”

For about 125 researchers, like Gitlin and Morgan in the Bell Center, the Marine Biological Laboratory is home.

Another resident scientist, Julie Huber, who is associate director of the Josephine Bay Paul Center, studies microbes in the deep ocean. Below a depth of a few hundred meters, human understanding about the ecosystem and the life it supports fades into darkness. “It’s this big habitable volume that we know very little about,” says Huber, who has spent her career on a deep dive into the subject.

On one oceanic voyage about eight hours from Samoa in the western Pacific, she was among the first people ever to witness an undersea volcano erupt. With a robotic camera sending images to a live video feed on board, Huber and a group of geologists, geophysicists, and chemists thrilled to a sight nobody had seen in four billion years of such eruptions on the ocean floor. “The cooks are coming out of the kitchen, the captain’s calling down from the bridge,” Huber says. “People are running outside to see if you could see any bubbles on the surface.”

The eruption occurred a mile deep, so there were none, but that didn’t flatten the champagne fizz everyone on the ship felt. One geophysicist told Huber that he had seen his holy grail and could now retire.

For Huber, there was even more of interest on the screen than the spewing volcano itself. “The magma’s 1,200 degrees Celsius or higher, and you look a few meters away and there’s these little shrimp feeding on microbial mat. So life, very often, can find a way,” she says. “The fluids at the erupting volcano, the pH is like battery acid, and yet there’s life.”

Over the past decade Huber and colleagues who worked on the International Census of Marine Microbes were amazed to discover the sheer scope of undersea life. In the mid-2000s, a developing technology called next-generation sequencing—a new way of generating huge amounts of genomic data—offered a vastly more effective method of determining what microbes are present in seawater samples, including some of Huber’s from the deep ocean. “I knew there was a lot more than I could see with the other methods,” she says. “So we tried it and when we first got our data back, it just blew us all away. We were like, wait, that can’t be right.”

They spent months combing through a quantity of data they were not accustomed to handling. Poring over the results, they identified and ruled out one potential error after another until they were confident enough to publish. “This roller coaster went up and down,” says Mitchell Sogin, a Distinguished Scientist in the Bay Paul Center who codirected the census. Led by Sogin, their paper identified an enormous population of marine microbial types that they called the Rare Biosphere.

The population of interested scientists only went up as the research progressed. “People who were funded to do other projects were spending time because it was intellectually interesting,” Sogin says. “And that’s characteristic of what goes on.”

Drawing on what Smith, the associate director of education, calls a “critical density” of scientific talent and technology, the MBL’s pooling of resources is part of its historic philosophy. “We have laid the principle of cooperation at [the MBL’s] foundation,” as the lab’s second director, Frank R. Lillie, PhD 1894, put it, “and we have attempted to build it into every one of our activities.”

Adding to that foundation, last year the University of Chicago and the Marine Biological Laboratory created the Frank R. Lillie Research Innovation Awards as one of the affiliation’s first initiatives. Lillie was a student under Charles O. Whitman, the Marine Biological Laboratory’s founding director in 1888 and the University’s first zoology chair. Lillie went on to become zoology chair himself and then biological sciences dean, in addition to serving as MBL director from 1908 to 1925. In all he spent 55 consecutive summers in Woods Hole.

Despite connections dating back to the founding of both institutions, UChicago and the MBL had no official relationship until 2013. The benefits of establishing a partnership were mutual.

Struggling like many research institutions in a difficult economic climate, the MBL needed support that the University could provide, including expanded access to grant money, fundraising experience, and reduced operational costs. It remains a separate entity, registered in Massachusetts as a 501(c)3 nonprofit and led by president and director Joan Ruderman, who helped shape the partnership and will step down at the end of her term this fall. The laboratory has a $76 million endowment, a $47.4 million operating budget, and about 250 employees.

Under the affiliation, the director reports to University president Robert J. Zimmer, who also serves as chair of the MBL board of trustees. UChicago professor Neil Shubin is the senior adviser to the president and to the vice president for research and national laboratories for the affiliation.

Similar to the management of Argonne and Fermilab, the MBL relationship broadens the scope of the University’s research and educational potential, particularly in biological and environmental sciences. As Shubin noted last year, the affiliation offers UChicago scientists “the means to develop academic programs otherwise not possible.”

It’s hard to tell what Rachel Folz, SB’14, likes most about her Metcalf Internship: charting elevations in the field on an experimental salt marsh, or plotting the results with geographic information systems mapping software.

“We have a very high-tech instrument that we use to measure the elevation,” Folz says. She’s kidding. “It’s like a bucket on a crate.”

Her mentor, Ivan Valiela, a Distinguished Scientist at the MBL Ecosystems Center, comes to the equipment’s defense. Folz tried a more advanced technique, he says, but it produced an unacceptable level of uncertainty. She wisely adjusted and learned a scientific lesson in the process. “That you just have to be very skeptical to test things,” he says, “and then you use the technique—although it might sound very inexpensive and low tech—that works.”

“And it works so well,” Folz adds.

Folz and her fellow Metcalf Intern in Valiela’s lab, Caroline Owens, ’15, banter back and forth with Valiela. He jokes with Folz, who pointed out the poison ivy she also has to show for her work on the marsh, that identifying the plant and avoiding it are two different things.

He’s also protective of their work and its importance. Owens opens a large spreadsheet—“it’s like a blanket,” Folz says—showing land-use data around Waquoit Bay originally compiled in the 1990s. “We need to know how changing land cover in the watershed has affected the concentration of nitrogen in the bay,” Owens says, a task that will eventually require boat trips to collect samples.

For now, with current land-use information from the local tax assessor, she brings Valiela’s original spreadsheet up to date. Using that data and information about changing precipitation since 1990, she can then run simulations estimating the effects of both factors on nitrogen entering the bay.

“That’s pretty exciting,” Valiela says. “So we’re going not only from the millimeter scale that she’s working on in the salt marsh to the global scale of changing precipitation regimes in North America.”

Just using the GIS software for the first time, transforming raw data into visual order, excites the students. “It’s really fun,” Owens says.

“It’s cool, yeah,” Folz echoes, before displaying the grid where she plotted the elevations, bringing into digital relief the contours she could only sense on foot.

Whether referring to technology or to the natural processes it helps reveal, “cool” is a word heard often around the MBL, and maybe nowhere more than Roger Hanlon’s lab. Hanlon studies cephalopods—cuttlefish, squid, octopus—and their stunning capacity to camouflage themselves.

In a video he took on a Caribbean dive, an octopus appears like a ghost from a bushy green rock where it had been invisible. Reversing the video in slow motion, Hanlon points out a dark circle appearing around one eye. “This is like electric skin,” he says, referring to the chromatophore organs that trigger a complete visual transformation in a quarter of a second.

It’s not just color that changes. To conceal itself against the ragged background, the octopus also alters the contours of its skin. Even knowing its location from multiple viewings and video speeds, it’s impossible to distinguish from the rock. “So now the animal has changed its appearance optically,” Hanlon says, “but also its physical three-dimensional texture.”

Metcalf Interns Andrea Rummel, SB’14, and Lyda Harris, AB’14, help him collect and chart the images that illustrate those mechanisms. Rummel, for example, works with a new camera Hanlon developed with the National Science Foundation, which captures colors beyond the spectrum of human vision in order to see what the animals, including cephalopod predators, see.

Trade-offs for the technological benefit of putting so much color into every pixel include bulk, a manual-focus lens with no zoom, and a limited depth of field from only one F-stop. “It’s photography in the 1850s, no kidding,” Hanlon says, but it allows for advanced science. “Andrea will be really, in this case, on the cutting edge of being able to use an instrument that no one’s ever had before.”

Hanlon’s project highlights another MBL resource: technology developed in sync with research objectives. Amy Gladfelter, an associate professor of biological sciences at Dartmouth College and an MBL summer investigator, offers an example of how that happens.

Last year Hari Shroff, an optical imaging specialist from the National Institutes of Health, worked with MBL students and scientists to create a device suited to the complex particulars of cell biology. “He came and built a very specialized microscope and had many people come in and throw whatever critter it is on it and, in response to the biologists, fine-tuned this instrument,” Gladfelter says.

Prototypes like Shroff’s, along with models already on the market that are not within the budgets of many institutions, are available at the MBL. That equipment helps attract top researchers who, in turn, help make the technology more efficient and effective. “You just don’t get that,” Gladfelter says, “hardly anywhere else in the world.”

Maximizing the potential of advanced microscopy also requires computational capacity, a particular strength she believes UChicago brings to the affiliation. Gladfelter envisions blending those complementary assets into what she and colleagues are calling a “collaboratorium” to accelerate science and technology together—a year-round research destination that “takes advantage of this historical strength in biology and microscopy of the MBL and then the computational power of Chicago.”

Hanlon mentions another benefit UChicago offers the MBL: “access to students.” Exactly how undergraduates, in particular, can contribute to and benefit from the relationship remains an open question. A committee led by Shubin has been exploring the possibilities. Retreats in Chicago and Woods Hole over the past year allowed the new colleagues to begin comparing notes.

Hiring Metcalf interns, who helped fill the MBL to overflowing this summer, was one step. During the academic year there’s room to spare. That unoccupied space and time offers several options, Ruderman says, including “the possibility of giving something that we call a quarter abroad in Woods Hole.”

It could be modeled after, or even incorporated into, the laboratory’s existing Semester in Environmental Science program that attracts undergraduates from multiple colleges and universities. Curricular and logistical wrinkles still need to be ironed out, but the learn-by-doing culture will be central to any MBL-based education for UChicago students.

Students there don’t solve textbook problems with predetermined answers. Instead, as Ruderman puts it, they see “what’s muddy and how the questions change,” gathering original data and following evidence to their own conclusions.

Organic geochemist Maureen Conte, a deep ocean researcher and mentor to Metcalf Intern Shaunae Alex, SB’14, recalls a research assistant coming to understand why Conte responded “I don’t know” to so many of his questions. “He said, ‘It’s really frustrating, and then one day I realized, that’s what research is about, you don’t know what you’re doing.’” Conte says. “That’s perfect. I think that’s a totally different skill from what you learn in the classroom.”

Valiela agrees. To him, it’s not data-gathering equipment or analytical software that opens minds and widens eyes; it’s the previously unknown truth revealed in every fragment of information students unearth. “Nobody in the history of humankind has seen those results before. You found something about reality that nobody has ever seen,” he says. “It seems to me that’s a transcendental step in education.”