Then & Now

Over the MDI Bio Lab’s 125 years, thousands of investigators have passed through its seaside quarters, creating a kaleidoscope of knowledge about the innermost workings of life. They’ve focused the lens of comparative biology on dozens of animal models, from albatross to zebrafish. They’ve peered into countless worlds, making significant contributions to marine physiology, developmental biology, toxicology, transport and nephrology. And there is a detectable throughline of fascination with one field of inquiry that’s coming on strong in biomedical science today: regeneration, and the animals that do it well. A trio of books in the office library of MDI Bio Lab investigator James Godwin, Ph.D., documents some high points: Thomas Hunt Morgan’s Regeneration of 1901, Richard J. Goss’s Principles of Regeneration of 1969, and Charles E. Dinsmore’s History of Regeneration Research of 1991.

“These are some of the incredible researchers in the field who have actually lived and breathed, shed blood, sweat and tears right here on campus,” Godwin says. “A lot of the concepts, the foundational knowledge on regeneration that we build upon, were established here.”

Morgan spent the summer of 1909 at the Harpswell Laboratory, the first home for what is now MDI Bio Lab. He was already known for cataloguing types of animal regeneration and demonstrating that the mechanics of regeneration are instrumental to understanding embryogenesis and development. It’s unclear whether he focused on regeneration in Harpswell — he later won a Nobel Prize for rather different work linking chromosomes and heredity. But Morgan did propose research that led another young biologist of the era, Max Morse, to regeneration studies in Harpswell. Morse sampled Casco Bay’s waters for the hydrozoan Tubularia cocea — stalky marine animals that can regenerate whole organisms from severed parts. His 1909 article, Autotomy of the Hydranth of Tubularia found that when a polyp detached from its colony, cells disorganized and proliferated at its base, creating precursor conditions for regeneration. That opened a long, if fitful, history of discovery in regeneration to be nurtured at the Laboratory, both in Harpswell and Mount Desert Island.

Midcentury Momentum

In the late 1950s and early 1960s, Brown University researcher Richard J. Goss spent seven summers on the MDI campus. Goss was a pioneering investigator, responsible for new insights on the regulation of cell proliferation, the re-patterning of de-differentiated cells, and seminal research on how deer repeatedly regenerate their antlers. At MDI Bio Lab, a focus on killifish fins led to his finding that regeneration of a lost part almost always requires innervation — that is, communication with a minimum number of nerve fibers.

In 1969, Goss published Principles of Regeneration, now a classic primer for the field. “He was an incredibly generous guy,” recalls Charles “Chuck” Dinsmore, Ph.D., who studied with Goss while he was a Ph.D. candidate at Brown University. Encouraged by Goss, Dinsmore in the 1970s and 1980s brought his own regeneration studies to MDI. In those “early years of wonder” Dinsmore made some key findings about amphibian regeneration, including important differences in how remaining muscle and skin cells influence a salamander’s replacement of a lost limb, versus a lost tail.

Powerful New Tools for Discovery

Dinsmore published A History of Regeneration Research in 1991. Today, he’s a bit in awe of the biotech tools at the fingertips of MDI Bio Lab’s investigators, such as automated gene-editing, bioinformatics and “multi-omic” cell analysis. “My direction was micro-anatomy, morphological stuff,” he says. “And then you leap into the 21st century with these guys: molecular genetics and systems biology, the extraordinary technologies for visualizing things.” Prayag Murawala, Ph.D., is deploying big-data tools and 3D microscopy to take an ever more refined look at the same mechanics Dinsmore scrutinized at the tissue level. He says work with transgenic axolotl salamanders — champions of regeneration — is catching up to advances with mice and zebrafish. “Axolotl lagged behind,” Murawala says. “We are refining and improving these tools.”

But Murawala adds that the fundamental questions remain the same: “How does an embryo develop into an organism?” he asks. “Why do some organisms regenerate when others don’t?” Godwin has questions too: “Where in the evolutionary tree did regeneration begin to fade? Do mammals have latent regenerative abilities that can be recovered or enhanced?” He is designing new biotech tools to carry forward his earlier insights about the unexpected roles macrophages and T cells play in regeneration in axolotls and, ultimately, in mammals like us. In collaboration with scientists at Vanderbilt University, Godwin is using macrophagetargeted nano-particles to control gene transcription and expression in real time.

“These new tools give me the ability to turn off any gene specifically inside a macrophage,” he says. “Nobody has yet been able to untangle the exact flavor of macrophage that is compatible with regeneration. That is what we are doing right now.”

Godwin adds that his most recent research suggests that signature groups of salamander genes could be used to engineer enhanced human macrophages and promote scar-free healing. He says that the MDI Bio Lab’s 125-year commitment to imaginative research using atypical models is a hallmark of its unique value to science — and human health. It’s work he is confident will continue to produce transformative biomedical discoveries, including therapies that will help human beings heal and even regenerate damaged organs and limbs.

“It allows us to tackle all these fundamental questions from different angles,” Godwin says. “And that’s a legacy, right? That’s a legacy that other places don’t have.”