why and how scientists want to make you part tardigrade

Injecting a key protein from tardigrades into human cells gives them the same kind of metabolic benefits as the hearty extremophiles.

Maybe the most impressive thing about tardigrades, the seemingly indestructible tiny organisms we’ve sent to space and successfully returned alive and well, is their ability to press pause on their metabolism and enter a state of suspended animation called tun. Basically, when things get stressful and the environment is low on water, high on radiation, or temperatures fluctuate to deadly extremes, they curl up into a ball, slow their metabolic rates to 0.01% of what they usually are, and wait for up to 30 years for their surroundings to improve. This is what makes them such amazing survivors. They simply refuse to deal with hostile environments until they have no other choice.

Now, this is very much along the same idea scientists had about human hibernation, or rather, trying to figure out how to get humans to enter a similar state of suspended animation. It would do wonders for victims of stroke, heart attack, and major trauma, as their metabolic and nutritional needs would be almost nonexistent and give doctors more time to do observations, pick the right course of treatment, and get the recovery process underway all before the patient wakes up. Meanwhile, explorers, astronauts, and alpinists facing inclement weather could simply hide in a cave or bury themselves and wait out the dangerous conditions while conserving precious resources.

Weirdly, humans share a genetic lineage with mammals who either hibernate or show the ability to do so under duress, so one would think we should already be doing it on our own. Unfortunately, we can’t go into suspended animation without powerful drugs that interfere with breathing and circulation, and require constant medical supervision to make sure we’ll wake up and still be able to eat solid food, much less remember our own names. But what if there was a natural protein or enzyme we could use instead? Enter tardigrades. Or rather, a protein known as CAHS D, which fights the stresses of extreme desiccation by turning cellular machinery into gel.

getting human cells to act like tardigrades

When cells dry out, critical molecules inside them can unwind, hindering the essential biochemical reactions necessary for life. Cytoplasmic-abundant heat soluble proteins, or CAHS, prevent this by turning these cells into a gel-like bunkers that retain enough water to keep cellular machinery going. How? They form a spiderweb-like structure a lot like a cell’s cytoskeletal filaments, reinforcing the cell against pressure changes of both desiccation and excess water. It’s this group of proteins, along with some DNA protecting relatives called Dsup, or damage suppressants, that make tardigrades so resilient and adaptable.

So, armed with all this information, scientists introduced CAHS D — one of the 300+ heat soluble proteins in question — into human cells and started putting them under stress the same way they would to test the behavior of tardigrade cells. Modified to behave like extremophiles, the cells exhibited the same abilities as tardigrade cells under stress while turning perfectly normal under typical conditions. These are very encouraging results because biology will often throw weird obstacles at seemingly straightforward experiments, so the fact that it played along means we can start to ratchet up the testing.

One of the biggest gotchas here is that CAHS D was introduced to cells living as just cells rather than components in a differentiated organism. That means we can’t say that tardigrade proteins will give us their superpowers, just that if they were to be in our cells, we should be able adapt to more extreme conditions by slowing down our metabolism and reinforcing our cells against environmental stress for at least some notable amount of time. But then again, biology likes to throw wrenches into things that seem to be exciting and highly beneficial, and it’s a very open question whether our background metabolic processes would coexist with these new proteins.

how tardigrades could improve medicine

The ultimate dream would be to insert genes that produce a variety of CAHS proteins used by tardigrades into our DNA using the CRISPR technique, allowing every cell to manufacture them on demand. On top of that, genes for Dsup proteins for DNA repair being added the same way would also allow us to handle massive, sudden bursts of radiation without long lasting damage. We would be able to exist with less water and food, and tolerate bursts of radiation that would lead to much higher risks of cancers today, if not outright kill us. And theoretically, we could also enter a hibernation state under extreme stress and easily shake it off once conditions are nominal.

But those abilities are still very, very far off, and would require significant research on making CRISPR more reliable, selectively bypassing our immune systems, and making sure there won’t be circumstances under which CAHS proteins would gum up cellular work at inopportune times, introducing a new weakness into the human body instead of making it stronger. For now, the proteins are most likely to be best used in creating far more stable and portable versions of blood products, as well as helping preserve tissues and organs for transplantation, extending the time between the donation and viable implantation by putting the cells into hibernation while in transit.

Sure, this may not be super-powered astronauts resistant to radiation navigating the stars one long nap in a skyscraper sized spaceship at a time, but this is a promising beginning of things that may come. As we’ve already noted, nothing worthwhile in biology comes easy or is guaranteed, so it’s possible that we may never be able to apply CAHS proteins to living, breathing humans. Yet, just having a readily available supply of blood products and organs that can wait days for a patient could already save millions of lives by increasing margins for error and delivering them where they couldn’t be made available before. And that’s nothing to sneeze at.

See: Sanchez-Martinez S, et al. (2024) Labile assembly of tardigrade protein induces biostasis. Protein Science 33(4):e4941, DOI: 10.1002/pro.4941

Nakano T, Watanabe K, Masuda K, et al. (2022) Stress-dependent cell stiffening by tardigrade tolerance proteins that reversibly form a filamentous network and gel, PLOS Biology, DOI: 10.1371/journal.pbio.3001780

Hashimoto T, et al, (2017) DNA protection protein, a novel mechanism of radiation tolerance: lessons from tardigrades, Life, Jun 7(2): 26, DOI: 10.3390/life7020026