MDI lab takes heart in regenerating tissue

Kevin Strange says he almost turned around before crossing the Trenton Bridge — a natural divide between Down East Maine's more populous areas and the solitary outpost of Bar Harbor — for a job interview. But the man who would become the first full-time director of the Mount Desert Island Biological Laboratory drove on, saying he sensed a lot of potential to do novel biomedical science at the small lab.

In 2009, he left behind a position as full professor and anesthesiology chair at the Vanderbilt University School of Medicine to take over MDIBL. He is now rebuilding the lab into a center for regenerative biology, a hot scientific discipline that might one day be applied to essentially self-heal hearts and other wounded tissues.

Indeed, in mid-February the 115-year-old lab spun off its first company, Novo Biosciences Inc., which will develop an experimental compound taken from dogfish sharks that potentially could heal wounds. Strange is CEO of the new company, which will be based at MDIBL in Salisbury Cove. Researcher Voot Yin is chief scientific officer.

"When I came here, I saw the beginnings of a core infrastructure. What appealed to me was the diversity of animal models being used to address biological questions," says the salt-and-pepper-bearded Strange. Leaning forward, he emphasizes his plans for the lab, which he described as "very primitive" in 1994 when he studied there for a summer. "I geared the lab toward regenerative biology as I looked at what made sense, given our history, and what made us unique."

Strange had previously researched C. elegans, a microscopic roundworm, and found that it fit into the work being done at MDIBL with other primitive organisms such as zebrafish and sea urchins. Those lower life forms can help cut costs on basic research on animals, he adds, and allow researchers to essentially move up the food chain of model organisms as their work progresses. Nearby Jackson Laboratory (see Mainebiz, Nov. 12, 2012) breeds and uses mice for research, and the two labs have some collaborations.

Strange says MDIBL is the only such small lab in the world that is focusing its scientists on regenerative biology, which he calls a key area of 21st-century medicine that will look at how humans harness their innate healing processes. MDIBL has 10 full-time research faculty, and plans to bump that up to about 15 over the next five to seven years, Strange says.

"The lab needs to take a big directional change, which demands that we use diverse model systems," he explains. "But we want to remain small and focus on regenerative and aging biology."

The days when scientists used reductionism, which tries to understand complex things by breaking them down into their parts, are over, Strange says. It is now necessary to use integrative biology, which pulls together different techniques and disciplines to take a more holistic approach to research.

"We look for scientists who are nonreductionist in their thinking, and for people who are willing to take a risk," he says. "We need a vibrant academic environment that is not an ivory tower."

MDIBL researchers also collaborate with other institutions. For example, one staff scientist works with the nearby College of the Atlantic, and there are active cooperative efforts on aging and protein damage with Jackson Lab.

The power to self-heal

The lower organisms used by MDIBL can do things humans cannot, namely regrow tissues, organs and even limbs to repair and replace damaged body parts. Strange says that while there has been a focus on stem cells, a big part of the research on regeneration was missing.

"Why not study the zebrafish and salamanders?" he says. "They have a tremendous capacity to replace and regenerate just about any organ. And the zebrafish doesn't use special genes to regrow body parts. It uses the same genes we do."

The lab is studying why these pathways are inactive in humans.

Voot Yin, a Ph.D. and assistant professor at MDIBL, is studying heart disease in a zebrafish by removing part of the heart tissue, which the animal then regrows while its immune system degrades dead and damaged heart tissue. The challenge is to understand why the zebrafish can regenerate the tissue, while a human, with the same genetic tools to potentially do the remodeling, cannot.

"These genes are present in mice and in humans," Yin explains. "But while the mechanism is present, it is not activated."

The zebrafish will fully regenerate the cut-out parts every time to their healthy function and form. Yin says the zebrafish's body seems to know what's damaged and can essentially reboot its system from the time it was healthy, much as a computer can be rebooted to get rid of errors. The regeneration works only with damaged tissue; normal aging and disease will eventually kill the zebrafish. Also, its ability to repair decreases with age.

Watch: Zebrafish grows back damaged fin in 14 days

Yin says other researchers have looked at the first three days of life in a mouse, during which the animal can heal itself. On the fourth day of its life, that ability is diminished, and it is gone after one week. Yin says it still isn't clear what happens to essentially turn off the self-heal mechanism after the third day. The main differences between a three-day-old mouse and a one-week-old mouse are the composition of its heart and its genetic makeup. It also isn't clear how and why the human mechanism turns off, and how to turn it back on to regenerate damaged tissue naturally.

"The global goal of regenerative medicine is to coax the body to repair itself in a natural fashion," he says. "You and I have all the equipment in our body for it to repair itself. We hope that by surveying different species that do this naturally, that we can identify the self-healing circuit. If this is such a powerful process, why have we lost it in evolution?"

Yin says his lab's work focuses on understanding the fundamental processes of disease and regeneration, and on identifying potential chemicals to alleviate the disease. The compound identified from the dogfish, which is the original focus of the startup company, helps control part of the body's immune response, and has already been shown to have twice the growth and cell activity of current regeneration. For example, the part of a fish fin that is removed during experimentation will regrow to the exact size and function as before the damage, but do so twice as fast as a fin without the compound treatment.

That makes the compound a promising candidate for wound healing. It could mean soldiers wounded in battle might be healed more quickly, he says. The idea is for the chemical compound to target a specific gene that will stimulate the body's natural mechanism to heal.

"I look at biomedical problems and then to nature," says Yin. "Animals perfected the art of repair and regeneration, and they've done it for hundreds of years. I want an organism to tell me what's important. We are looking at the process of regeneration in a natural setting as an entire system." Applications in which humans will benefit from regeneration still are, optimistically, five to 10 years out, Yin says.

MDIBL got the compound from a colleague of Yin's who worked at the lab as a seasonal researcher. The colleague, a surgeon, has his own company with two compounds that he wanted to try in regeneration.

Strange says MDIBL's spinoff company, run by a core group of people, is trying to raise money from venture capitalists, federal Small Business Innovation Research grants, industry and elsewhere. MDIBL's board of trustees unanimously approved the formation of the company, which has one small private investment to cover early business expenses.

"We're looking to raise $300,000 to $400,000 to understand the molecule better," Strange says.

If the compound proves promising, the lab intends to license it rather than conduct the costly Phase 2 and 3 clinical trials to ready it for human use. Such licenses represent a new revenue stream for the lab, he says.

Year-round research

Founded in 1898 as the Tufts Summer School of Biology at South Harpswell by Professor J.S. Kingsley, the lab's earliest faculty and students studied comparative anatomy and the embryology of marine species collected from Casco Bay. In 1921, conservationist George Dorr offered a 200-acre farm in Salisbury Cove to the lab. Dorr, along with John Rockefeller Jr. and Charles Eliot, who together created Acadia National Park, felt Mount Desert Island was an ideal location for a marine biology lab. Since the 1800s, it had been a haven for naturalists and artists. Kingsley agreed to move, and the entire Harpswell lab was packed onto a boat and sailed to Salisbury Cove.

The lab was expanded on 250 acres and renamed MDIBL in 1921. A summer student -- C.C. Little -- eight years later founded The Jackson Laboratory.

Throughout most of the 20th century, MDIBL operated as a summer research institute. In 1998, it transitioned to a year-round research institution, and the next year it had a $750,000 budget. In 1999, it got $600,000 of a $10 million allocation from the state of Maine general fund, which MDIBL's director of development Jerilyn Bowers called a defining moment for the lab.

In 2001, it established a federally funded partnership among Maine institutions to make the state more competitive in attracting federal money for scientific research. The project, called the Maine Idea Network for Biomedical Research Excellence, connects MDIBL with The Jackson Laboratory and 10 Maine colleges and universities. The program has received $50 million in funding from the National Institutes of Health to date.

"The program aims to enhance biomedical research and research programs," says Patricia Hand, administrative director of MDIBL. "We share resources and expertise with 11 other institutes."

The general INBRE program has been launched in 23 states and Puerto Rico. A recent regional project with New Hampshire, Vermont, Rhode Island and Delaware involves building a cyber infrastructure so the institutes in those states can collaborate on bioinformatics research training.

In 2008, MDIBL started its most recent growth spurt by opening a 15,000-square-foot lab with green building technology.

The total annual budget of MDIBL increased nine-fold over the past 10 years, and the number of year-round employees has grown from nine to 50. More than $80 million in federal grants have been generated since 1999. Bowers says the lab is gearing up for a major fundraising effort to support a $35 million expansion over the next five to seven years. She expects most of the money to come from philanthropy, as well as relationships with industry.

Strange is quick to point out that federal funding is harder and harder to get.

"We had a program grant to [National Institutes of Health] one year ago for $13 million that was approved for funding," he says. "But we need to revise and resubmit it, as there isn't a [federal government] budget yet."

Right now, the government is continuing at 2012 funding rates, and if no budget is passed, no new programs will be funded.

"We are looking to venture capitalists," Strange says, referencing the spinoff company. "It's part of the new model on how we move basic discovery to the next level."

Lori Valigra, a writer based in Harrison, can be reached at editorial@mainebiz.biz.

Editor's note: This story was changed to more accurately reflect the connection between MDI Lab and the founding of The Jackson Laboratory.

Read more

RockStep Solutions moves into MDIBL

MDI Bio Lab researcher IDs two drug candidates for chemo side-effect