Bruce Willis turned tardigrade? A biological perspective of what it means to ‘Die Hard’
Written by Mira White '26
Edited by Yuliya Velhan '25
Colloquially known as water bears, it seems unlikely that tardigrades could belie their modest nickname. Despite a microscopic size and gentle appearance, tardigrades are one of, if not the most, resilient organism on the planet - opposing Bruce Willis’ equally robust character in Die Hard. With the ability to withstand extreme temperatures and radiation , tardigrades have the potential to provide immense insight into redefining cell resilience in humans.
Characterized by an otherworldly appearance, tardigrades have proven how their indestructibility stems from the environment that they inhabit on Earth. The cool and mossy habitat that tardigrades call home dries out multiple times each year , challenging its inhabitants. These organisms become forced to survive in a now arid environment, demonstrating the robustness of the tardigrades’ ability to adapt biologically. This drying has the same potential to damage cells similar to how radiation does: causing shortened DNA fragments, cracked cell membranes, and unfolding proteins . However, because of an extremophile nature, tardigrades have evolved to resist cell degradation.
Throughout the tardigrades' evolutionary development, they’ve refined their cell biology so that their nucleic acids and proteins are shielded from stress-induced damage . The type of protein found to enhance this mechanism, IDPs (intrinsically disordered proteins), more specifically Dsup (damage suppressor)  is capable of binding to DNA and shielding it from harmful oxidative damage.
However, this is not to say that tardigrades stand alone in their possession of IDP proteins, as humans also have them encoded into their DNA. Unfortunately, IDPs are very poorly understood so their true function is unknown . The little we do know about IDPs in tardigrades is that they slow down cellular function as a form of cryptobiosis - a state of inactivity in response to unfavorable environmental conditions. Because this only occurs in specific proteins, the remaining functions are unknown.
In tardigrade-specific functions, the effects of this protein on the organisms’ resilience have been observed with dehydration. The process occurs as such: when the tardigrade begins to dry out, proteins that appear shapeless in water become crisscrossed in drier conditions. These structured protein fibers support the cell membrane that prevents breaking or folding as a result of adverse conditions . Using this knowledge, researchers are looking to use tardigrade biology to create optimized therapies in humans.
The viability of blood platelets in humans is relatively short. Dehydration is an unfortunate circumstance in the donation process, however, by infusing platelets with tardigrade proteins prior to transfusion researchers found that 90% of the platelets remained usable after rehydration . Clinical trials have shown that even when abnormalities occur, the ability of cells to recover is uncompromised. The use of tardigrade proteins poses an exciting opportunity for advancements in regeneration and resilience if able to be replicated.
In comparison to the tardigrade, humans are a fragile species - excluding Willis, naturally. Our cells cannot withstand the same stress that tardigrade cells can. As a result of this, researchers at Harvard Medical School, the University of Washington, and MIT are looking to use IDPs as a basis for creating therapeutic methods to stop cell damage and prevent cell death . The tardigrades' inclination to survive compared to humans poses an ambitious approach to manufacturing cryptobiosis that has never been seen before.
Research at Harvard Medical School by Debora Marks entails a trial-and-error approach with amino acid combinations . The goal of the project is to find the combination that will provide aid to those having suffered traumatic injuries and halt the tissue damage caused as a result. To do so, researchers must create an optimal candidate protein that will be tested, first, in tissues, then organs, and finally animals.
This method of cell therapy is meant to be tried in conditions such as heart attacks or strokes. These medical emergencies, taking place in the heart and brain, are among the most significant when considering oxidative damage or stress.
At Harvard, the computational design of synthetic IDPs  has begun using the application of tardigrade biology to human biology. The group has created amino acid combinations to be tried as candidate proteins on tissues to determine if the proposed damage-halting design is effective. If successful, the project will be escalated in terms of subject efficacy from muscle, vascular, and cardiac tissues to organoids and ultimately animals . The group hopes to find new entry points in the cell making it possible to insert the protein. Should this be found, major developments would be made not only in protein integration but also in protein formation, allowing for the possibility to design proteins, turning millions of years of evolution into decades.
Naturally, some factors inhibit the direct integration of a protein into our cells. Creating a protein that is proposed to be safe and functional in humans must also be able to bypass immune defenses. Proposing a protein that triggers an antibody response is a considerable threat as a candidate can affect many people or a few, hence the desire for a greater understanding of protein formation.
Biopausing compounds offer prolonged mortality in some sense, however, they also offer the opportunity to enhance research efforts about our own mortality. With the help of these optimized compounds, scientists could silence specific proteins during experiments to gauge cell response . Such could be seen in experimental drug pathway trials where IDPs could be used to deactivate a protein to determine how another one behaves in the absence of the first.
Beyond medicine alone, tardigrade research offers insight into space colonization. Because of the enhanced resistance to radiation and extreme temperatures, tardigrade cells, if integrated into plants and animals, could provide a wider variety of species for use in the colonization of space occupancy.
Tardigrades may be a key element in the future for the development of new therapeutics in medicine and space colonization alike. They provide insight into how multicellular organisms can be fabricated to become optimal candidates for much more extreme conditions. Medicinal advancements and space exploration are both promising and demanding so should we succeed in making such advancements, immense achievements would be owed partly to the microscopic tardigrade. As for Willis, his contribution to science is not nearly equivalent to the feats of the tardigrade but rather the feet of humans - fragility demonstrated by the removal of his shoes.
 Pesheva, E. (2019, February 27). Could an extremophile hold the secret to treatment of devastating injuries? Harvard Gazette. Retrieved October, 2022, from https://news.harvard.edu/gazette/story/2019/01/could-an-extremophile-hold-the-secret-to-treatment-of-devastating-injuries/
 Tardigrades could teach us how to handle the rigors of space travel. (2022, July 13). Science News. https://www.sciencenews.org/article/tardigrades-space-travel-survival-humans
 Tardigrade-Tough Applications for Humans. (2020, September 22). Sealevel. https://www.sealevel.com/2020/09/22/tardigrade-tough-applications-for-humans