DARPA Thinks Tardigrades Could Help Scientists 'Freeze' Injured Soldiers in Time

Tardigrade PLOS
Tardigrades are being studied for their extreme survival abilities. PLOS One

Tardigrades are the only animal known to have survived in the vacuum of open space. They can survive temperatures of up to 304 degrees Fahrenheit, and can withstand being frozen for up to 30 years, as in one documented case.

They can also survive without water for up to a decade by shriveling up and placing themselves in something resembling a state of suspended animation—and it is that trait that has scientists at Harvard Medical School, the University of Washington and MIT interested.

Their research is being funded by the Defense Advanced Research Projects Agency (DARPA), having been awarded up to $14.8 million as part of the Biostasis program in December 2018. The aim of the program is to find a way to extend the "golden hour," the period of time between a traumatic injury and medical intervention. This could apply to a soldier suffering a traumatic injury on the battlefield, someone suffering a stroke or heart attack, or cases of sepsis.

Biostasis interventions would not be a long-term fix; biological processes would return to normal after a short period. But it would buy doctors and medical personnel more time to get the patient the help they need.

Tardigrades offer a promising avenue for this area of research because of their ability to shut down their metabolic processes and enter a state of cryptobiosis, wherein the creature is sort of frozen in time, having slowed down its metabolic processes to almost undetectable levels.

"The idea is that tardigrades have proteins can slow [them down], so that they can survive extreme conditions such as dehydration," Harvard's Pamela Silver, principal co-investigator on the project, told Newsweek. "These are called IDPs: intrinsically disordered proteins. The functions of this class of proteins are under intense recent research, so our results play into the overall picture as well. Our idea is to design proteins that have similar action in human cells and tissues. The notion is that by forming a special state in cells, that the proteins then can become protective. It is of note that our new proteins could prove [to be] a basis for further drug design."

DARPA's involvement in the project was described as a "cooperative agreement" that will last for five years. In that time, the agency's program manager can be involved with and influence how the research develops.

Tristan McClure-Begley, Biostasis program manager, told Newsweek: "Tardigrades are an excellent example of cryptobiotic organisms—that is, creatures that can reversibly enter a state where all outwardly observable signs of metabolic activity are effectively paused under conditions that are essentially incompatible with life … In order to survive extreme environmental challenges and reversibly enter that cryptobiotic state, they actually upregulate the production of certain proteins that have interesting properties, such as the lack of highly ordered structure and the ability to interact with many other proteins and promote vitrification within the organism. This effectively protects the organism's cellular components until such time when conditions are more habitable.

"The discovery of these proteins and their roles in tardigrade survivability serves as good proof of concept for the application of novel unstructured proteins as inducers and supporters of cryptobiotic states."

Current research indicates that tardigrades are able to deploy biochemicals, including proteins and sugar molecules, which protect cells from damage. These disordered proteins—the IDPs—are found across nature, including in humans. However, not all IDPs slow down cellular aging, so first the team must work out the structure of the proteins that helps tardigrades survive extreme conditions. After that, they will need to design a protein that can be turned into a "drug" for human benefit.

This is an extremely complicated task. The sequence of the amino acids that make up a protein determine its shape. The shape then determines its function. What the team has to do is find the right shape from an infinite number of possible amino acid combinations. To do this, researchers are going to use a computer model to run through possible candidates, then test them to rule them out or investigate them further.

"We have a design-build-test cycle where we test many proteins at once," Silver said. "The first step is to use machine learning to design new proteins. Then we will test their ability to preserve activities of proteins. This is followed by cell-based tests for prolonging life under harsher conditions, followed by tests in organoids that mimic tissues and, lastly, in animal models.

"It is important to note that we are developing totally new designer proteins based on what nature has provided. Our 'drug' will be a protein. The proteins need to be delivered to cells—this is another part of the challenge of the project. For example, they could be delivered by a spray onto the wounded area."

Silver said their work had just begun, but was confident in the "exceptional team" involved. Much more research will be needed before it gets to the point of human tests, something the Biostasis program is not funding at this point.

"Any designer peptides they create would be subject to the same preclinical regulatory evaluation for safety that any drug or compound destined for introduction into a human body receives prior to any study designed to test the products in humans," said McClure-Begley, adding that the initial real-world applications could include the preservation of biological products without the need for refrigeration, such as vaccines, blood products and engineered cells.

"This is an example of DARPA funding high-risk research with broader impacts to all people," Silver added.

The end goal of Biostasis is to "add a new class of tools to the human health toolbox" that can protect biological systems from collapse after damage, McClure-Begley said. "Medical professionals already have lots of ways to help the body cope with insult and aid in the elimination of infectious organisms, but we do not currently have any approaches that work by slowing down the types of cascading molecular events that ultimately lead to the collapse of the system.

"Biostasis is fundamental biochemistry research, but our hope is that the direction we're taking and the types of technology being developed will provide new opportunities for improved care in the future."