58 Scientific American, April 2019
tale of shark bites at a scottish pub has led us to some new ideas
about rebuilding broken bodies. In the early 2000s American gene ticist
Michael Zasloff of Georgetown University had traveled to the University
of St. Andrews to give a talk about several natural antibio tics found in
animal skin. After the lecture, he and some of the university scientists
went for a drink, and one of them, a marine biologist, began to talk
about how dolphins were frequently savaged by sharks, sustaining some
bite wounds 45 centimeters long and 12 centi meters deep. But remarkably the dolphins healed
up in weeks, with no signs of infection.
Zasloff was struck by this swift recovery from terrible inju-
ries, and he could not get the conversation out of his mind. He
spent the next several years reading reports about bitten dol-
phins and talking to marine biologists who studied these ani-
mals. In 2011 he published a letter to the Journal of Investiga-
tive Dermatology entitled “Observations on the Remarkable
(and Mysterious) Wound-Healing Process of the Bottlenose
Dolphin.” He noted that the dolphins did not seem like they
were simply patching torn flesh with a scar, which produces dif-
ferent kinds of cells, but instead might be actually regenerating
the damaged tissue. And soon after that, he called one of us.
Strange, at the time president of the MDI Biological Laboratory,
was pushing the institution to investigate natural and synthetic
compounds that stimulated regeneration, and Zasloff thought
some of the antibiotics he had found in animal skin might also
foster this kind of regrowth. Anything that helped the body re -
place or restore cells destroyed by disease or injury would be a
major medical boon.
Six years after that phone call, the three of us (Yin, Strange
and Zasloff ) have shown that a natural antibiotic called MSI-
1436, originally identified by Zasloff in a small shark, dramatical-
ly stimulates several types of damaged organs to regrow in zebra
fish and prompts heart muscle to regenerate in mice. The com-
pound appears to release some molecular “brakes” holding back
a tissue’s natural ability to regenerate after sustaining damage. In
mice that have a condition that mimics muscular dystrophy in
people, it appears to slow down muscle degeneration. We are still
experimenting in animals and have not shown these effects in
humans, but MSI-1436 has an important advantage over the
legion of drug candidates that look good in test tubes but fail in
people: it has already been shown to be safe.
In 2007 this compound was tested in humans as a potential
treatment for obesity and type 2 diabetes because it improves
cell sensitivity to insulin. The studies, regulated by the U.S. Food
and Drug Administration, demonstrated that MSI-1436 was well
tolerated at high doses and did not harm patients. But because
the drug comes as a liquid that needs to be injected every day, it
was unlikely to be popular with patients who already had alter-
IN BRIEF
Stem cell treatments grab many headlines
about healing and regrowing body parts but
have had minimal success.
A compound called MSI-1436 may be more prom-
ising, animal experiments show. It takes the brakes
off the body’s natural ability to regenerate cells.
The molecule, originally intended as a diabetes and
obesity medicine, was successfully tested for safety
in people—a big head start in drug development.
A
Biologist Kevin Strange, CEO of Novo Biosciences,
is a former president of the MDI Biological Laboratory
(MDIBL) in Bar Harbor, Me.
Viravuth Yin is the chief scientific officer at
Novo and an associate professor at MDIBL.
