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Published On May 23, 2019

BASIC RESEARCH

Beyond Cold Storage

A metabolic slowdown would press pause on the body until surgeons can repair damage. How close is it to becoming a reality?

Science fiction authors popularized the idea of suspended animation, an ageless kind of sleep useful for voyages between stars. But its close cousin, biostasis—a slowing of biological processes in the body—is very much a topic of current research, with practical applications. If emergency responders could slow cell metabolism in a trauma patient, for instance, they might gain extra minutes to save a life.

Previous biostasis efforts have mostly relied on lowering body temperature—a process at work when you place ice on a new wound—which can be effective. But techniques that require cold can be hard to implement on a battlefield or in other locations where critical injuries happen. So DARPA, a research arm of the U.S. Department of Defense, recently put out a call for new approaches to biostasis that can function at room temperature.

“DARPA would like a way to stabilize soldiers in the field, to literally slow time down until they can get someone who has been injured to a distant site for medical care,” says Donald Ingber, director of the Wyss Institute for Biologically Inspired Engineering at Harvard University. The Wyss Institute will receive up to $23 million over five years for biostasis research, and its scientists are pursuing several promising leads.

Certain compounds, including the gas hydrogen sulfide, have been shown to slow metabolism in mice by reducing oxygen consumption at a cellular level. (Cells rely on oxygen to convert nutrients into energy.) But studies of how hydrogen sulfide affects larger animals have been inconclusive. The gas is also extremely dangerous. “Any time you suppress metabolism you basically make a poison,” says Richard Novak, co-principal investigator of biostasis research at the Wyss Institute. The trick is to manage the concentration of such a compound so that it slows metabolism without stopping it entirely, he says.

Other Wyss researchers are looking for chemical alternatives that might have a similar effect on metabolism. A team led by Jim Collins at MIT is using machine learning to screen chemical libraries for likely compounds. This application of artificial intelligence has helped identify other drugs, including promising antibiotics and cancer treatments. “There may be an existing molecule that fits the bill and may already be FDA-approved for another purpose,” Ingber says.

Wyss researchers are also looking at hibernation, a natural process in some mammals that is similar to biostasis. The scientists are analyzing changes in the animals as they enter and exit this state, pinpointing the biological pathways involved and then testing drugs that act on those pathways. Cold itself is probably the most significant force in slowing metabolism in hibernating animals, Novak says, adding, “But there is a question of cause and effect. To what extent is the cold stimulating a pathway that we can induce chemically with a small molecule that doesn’t require cold?”

Another model in nature is the microscopic tardigrade. These organisms can freeze to almost absolute zero and even survive in the vacuum of space. Roger Larken Chang, a researcher in systems biologist Pamela Silver’s lab at Harvard, which is also receiving DARPA grant funds, manages a team working to design synthetic variants of a special class of molecules called intrinsically disordered proteins (IDPs) that are produced by certain organisms, including tardigrades and other extremophiles.

Some IDPs can slow or pause cellular activity and protect against an array of environmental stresses. Chang’s team aims to deliver these proteins directly to cells without genetic intervention. “We’re breaking new ground on a difficult-to-study class of proteins,” Chang says. “These proteins have diverse functions setting them apart from almost all we know about how other proteins work.”

Finding a safe, effective approach to inducing biostasis in humans won’t happen quickly. The effects of any therapy must be reversible and gradual, avoiding abrupt changes. “Imagine going from 60 mile per hour on the interstate to going backwards in a side street,” Novak says. Drug candidates will be tested in computer simulations, tissue culture, laboratory models of human tissue and model organisms.

Even if biostasis doesn’t lead to interstellar travel, Ingber expects the research will find broad applications in medicine and beyond. “At the most basic level, we’re looking at how you slow down biological molecules,” he says. “That could lead to new chemicals that would let us store and transport biologic drugs, cell therapies and tissues and organs without cooling them. It could allow us to keep food fresh without refrigeration. This grant is really the ultimate DARPA project—first you write the science-fiction story, and then you get the money to make the real thing.”