Sporting a bulbous body, deflated head, and eight tiny caterpillar legs, this creature looks like a toddler’s drawing of a Macy’s Day Parade balloon. But the humble, microscopic tardigrade just might hold the secret to saving countless human lives.
Also known as a “moss piglet” or “water bear” because of its striking appearance, the tardigrade is no stranger to experimentation. In the name of science, researchers have sent water bears to space, zapped them with X-rays, thrown them into a deep freeze, and heated them to extreme temperatures. And to everyone’s amazement, their tardigrade subjects almost always survived, by resorting to their signature move: hibernation.
Experts suggest that these nearly indestructible animals, which are just as at home on a backyard tree as in a sewage treatment plant in Antarctica, might live to see the eventual death of the Sun.
Most organisms that thrive in extreme conditions do so by producing a special sugar called trehalose, which protects them from drying out. Strangely, most tardigrade species lack this sugar. But they do possess cytosolic-abundant heat soluble (CAHS) proteins, which have been found only in water bears and separate them from Planet Earth’s other extremophiles (organisms capable of surviving in extreme environments). University of North Carolina biologist Dr. Thomas Boothby and his colleagues discovered that when tardigrades are deprived of water, their production of CAHS proteins is kicked into overdrive.
In extreme conditions, CAHS proteins create a 3D gel-like network, which protects tardigrades’ other proteins from unfolding and combining with each other—a process that can lead to cell death. Boothby wondered if CAHS proteins could be recruited to protect vulnerable proteins that humans rely on, such as vaccines and blood in blood banks, both of which are protein-based and need to keep cool to stay viable. Medical experts call the temperature-controlled supply chain of vaccines and other protein-based pharmaceuticals the “cold chain.”
New methods that allow for the safe and stable preservation of cells and bioreagents (biological substances like enzymes) are needed, “particularly when delivering drugs and medicine to inaccessible areas, or to areas that lack an infrastructure to maintain the cold chain,” says Dr. Jenny Tenlen, a biologist at Seattle Pacific University who studies tardigrade development. “Because of tardigrades' extreme stress tolerance, they have the potential to provide biological solutions to this problem.” About 90 percent of the cost of vaccination programs in developing countries, Boothby adds, comes from the need to keep vaccines cold.
If tardigrade proteins could protect protein-based pharma, Boothby says, we wouldn’t have to rely on the cold chain to keep vaccines stable. “It might not seem like a big deal to us in a developed world,” he says. “But in other parts of the world, keeping things cold can be a logistical and economic burden.”
Now, Boothby and his team are partnering with Cellphire, a biotech company focused on cell stabilization technology, to apply tardigrade proteins to pharmaceuticals. If successful, this research could make it easier to maintain vaccine supplies in developing countries and military zones, both of which can lack reliable access to refrigeration.
To collect large amounts of CAHS proteins, the team inserts copies of tardigrade genes responsible for making CAHS proteins into bacteria, which are notoriously prolific. “We can grow billions or trillions of bacteria a day and engineer them to make the protein,” Boothby says.
Converting bacteria into human protein factories is nothing new. The pharmaceutical industry uses them to create everything from insulin to cancer-fighting interferon. Safely extracting a desired protein from its engineered bacterial creators is always vital, Boothby explains, as bacteria can produce a toxic substance called an endotoxin. (To ensure its endotoxin cleanup is thorough, Boothby’s team is conducting immune studies in which CAHS proteins derived from the bacteria are inserted into mice.)
Already, Boothby and his team have compared tardigrade proteins’ ability to preserve vaccines to that of FDA-approved protectants. CAHS proteins, they found, protect the proteins within pharmaceuticals about 10 times more efficiently than current methods.
The team’s ultimate goal, Boothby says, is to use CAHS proteins to protect human blood in blood banks. It's a challenge, because our blood is much more complex than the protein-based pharmaceuticals the team is currently working with. Blood is made up of many types of cells, each of which contain different types and ratios of proteins. So, the team will first attempt to use CAHS proteins to preserve each individual kind of cell found in our blood. If they can master this, the researchers hope, they can use CAHS proteins to preserve blood in its complete state.
“The FDA keeps a tap on refrigerated blood for 60 days,” Boothby explains. “After that, you have to throw it out. You can imagine if there are soldiers on patrol, they can’t carry a mini fridge on their back. But, if we can get whole blood at a dry state at ambient or even hot temperatures and soldiers can carry it and someone needs a transfusion, they can just add water and use it.”
Tenlen, who is not involved in the new research, believes Boothby’s preliminary work “provides encouraging evidence” that CAHS proteins can be used to stabilize biological substances under challenging conditions. But, she cautions, Boothby and his team will have to be careful that CAHS proteins don't introduce side effects when used to preserve vaccines and human blood.
If the team does succeed in stabilizing vaccines and human cells, the societal impact—all originating from the blimp-like tardigrade—could be enormous.
“You see these animals do these weird things and produce these materials that no other organism has,” Boothby says. “As I was looking into how tardigrades survive desiccation I started to think about how useful these proteins could be for people… And that’s what we should do, as good citizens of the world: help people.”