[Image above] Example of a frozen wood frog in winter. Credit: Jan Storey, U.S. National Science Foundation
We all know that the early bird gets the worm, but have you heard that the frozen frog gets to thaw?
Wood frogs are the only type of frog found north of the Arctic Circle, but they also live throughout forests in the United States in Alaska and the northeast region. Like other amphibians, they reside in woodlands and wetlands and are prey to snakes, snapping turtles, racoons, foxes, coyotes, and even birds.
Every spring, wood frogs resume their lives earlier than other frogs because they do not hibernate in frozen bodies of water. Instead, the wood frog has the unique ability to freeze and thaw itself completely unharmed on land in a process similar to vitrification.
Vitrification is the full or partial transformation of a substance into a glass or glass-like state. The vitrification of nuclear waste is a well-known application among materials scientists. But this process is also commonly used in fertility treatments to freeze human eggs because it takes place quickly and so avoids water crystallization, which can damage the eggs’ cell structure.
Vitrified eggs can remain frozen indefinitely without undergoing a decline in quality. If larger bulk systems, such as kidneys and the liver, could be similarly frozen, it could revolutionize the organ transplant industry.
As of March 2024, there are more than 103,000 people in the U.S. on the organ transplant waiting list, but just over 46,000 organ transplants took place in 2023. This discrepancy is due in part to the small window of viability for organs. Currently, whole organs can be transported through hypothermic bio preservation without causing damage to the tissue or cells, but the organs typically last for hours instead of days or weeks. If the shelf life of organs can be extended, then more organ transplants can occur.
Deep freezing could potentially keep organs viable for months, maybe even years. Unfortunately, studies on the vitrification of bulk organs have faced difficulties with preventing crystallization during rewarming. So, finding ways to work with rather than avoid crystallization may be a better approach to the deep freezing of organs. That’s where the wood frog comes in.
The wood frog has adapted to a gradual freezing process as the seasons change, which provides it ample time to protect its cells during ice nucleation and before the full onset of freezing. Even though it will show no sign of a heartbeat, brain function, or physical movement during the cold, lengthy sabbatical,1 it can successfully thaw in the spring and live to hop another day.
The freezing process starts when the wood frog hunkers down under leaf litter and debris on the forest floor instead of hibernating underwater like other frog species. These frogs, like other amphibians, absorb water through their skin, which means that when ice crystals form on the outside of the wood frog as temperatures drop, the crystals also form beneath their skin. The ice then forms sheets between the muscles and the skin, encasing vital organs of the abdominal cavity, bladder, brain ventricles, and eye lenses.2
As the ice forms inside the wood frog, its glucose levels start to rise and mix with urea stored in the frog’s blood, acting as a protectant for the frog’s cells to help prevent intracellular fluids from freezing. The outside of the wood frog is then frozen while the cells inside remain intact, ensuring that the frog can warm up in the spring without any damage. The video below demonstrates how the wood frog undergoes the freezing process.
Credit: Smithsonian Channel, YouTube
This miraculous feat of the wood frog has not gone unnoticed. Papers such as this one explain how the wood frog’s freeze-tolerance can serve as a model for researchers to replicate the process with human organ transplants. If successful, this frog-inspired deep freeze process may help close the gap between the number of viable organs and those in need of a transplant.
References
1 Al-attar, Rasha, and Kenneth B. Storey, “Lessons from nature: Leveraging the freeze-tolerant wood frog as a model to improve organ cryopreservation and biobanking,” Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2022, 261: 110747.
2 Rubinsky, B., et al, “1H magnetic resonance imaging of freezing and thawing in freeze-tolerant frogs,” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 1994, 266(6): R1771-R1777.
