Pick up a wood frog in the middle of Canadian January and feel like a rock. Ice forms crusts on the eyelids. There is no heartbeat, no breathing, no measurable nervous activity, and about two-thirds of the water in your body remains frozen in the spaces between your cells. “For all intents and purposes, this animal is clinically dead,” Shannon Tessier, a researcher at Massachusetts General Hospital, told The Scientist. Then spring comes, the animal thaws and jumps to find a pond as if nothing had happened. That trick is now a research program. What happens inside a frozen frog Freezing begins on the outside. Ice forms on wet leaf litter, touches the frog’s permeable skin, and crawls inside. Within minutes, the liver begins to destroy its glycogen stores and floods the body with glucose, which functions as a natural antifreeze within the cells. Kenneth Storey of Carleton University, who has devoted decades to this animal, sums it up in a review of wood frog physiology: Between 65 and 70 percent of total body water is converted to ice in extracellular masses, and so much water is extracted from cells that organs visibly shrink. Ice can be survived outside of cells. The ice inside is a death sentence. Frogs also store urea, rebuild their cell membranes, and raise antioxidant levels before the first hard freeze, changes that he and Janet Storey cataloged in Physiological Reviews. The populations of the North put more pressure on the entire system. Interior Alaska wood frogs survive temperatures of -16°C, 10 to 13 degrees colder than their Ohio relatives. The work led by M. Clara F. do Amaral attributed the difference to a greater reserve of liver glycogen that is mobilized faster once the ice appears. Why Transplant Surgeons Started Reading Articles About Amphibians Every donated organ follows a clock from the moment it leaves the body. Standard practice is static cold storage, which is about as low-tech as it gets. Korkut Uygun, a chemical and systems engineer who works alongside Tessier at Mass General, put it clearly in the same article: Pack the organ in ice and run to the receiver, and you’ll be counting hours, not days. The schedule means that each transplant is performed as an emergency. Distance kills games. In the United States alone, federal transplant figures place more than 100,000 people on the waiting list, and about thirteen die each day before receiving an organ. If you extend storage from hours to days, the entire business will become logistics rather than a race. That is why a frog that can remain inactive for months attracts everyone’s attention. Borrowing the frog’s antifreeze, glucose in frog concentrations, would poison mammalian tissue, so the researchers turned to 3-O-methyl-D-glucose, a modified sugar that cells absorb but cannot metabolize. Combined with supercooling, which cools the tissue below zero without allowing it to freeze completely, the approach produced a clinical-scale result in 2019. Writing in Nature Biotechnology, Reinier de Vries, Tessier, Uygun and their colleagues maintained five human livers at -4°C and kept them viable for 27 hours, nearly triple the usual window. The National Institutes of Health, which helped fund the work, noted that human livers were previously considered healthy for about nine hours. Letting in ice on purpose The fundamental assumption of cryobiology was that ice is the enemy and should be avoided completely. Tessier’s group challenged that in 2022, reducing whole rat livers to between -10°C and -15°C and keeping them for five days on ice, then recovering them on a perfusion platform. In a report published in Nature Communications, researchers placed the credit squarely on the wood frog, borrowing both the glucose analogue and the animal’s habit of seeding ice in controlled locations so that it forms where it causes the least damage. The storage time increased fivefold. A study, in rodents, without any transplant at the end of it. Since then, that gap has mostly closed. The same partial-freezing approach was applied to a pig kidney in 2025. A team at Mass General preserved it at subzero temperatures for ten days, then rewarmed it and transplanted it into a live pig, restoring kidney function, according to a National Science Foundation-funded preservation center that participated in the trial. Getting warmed up is the hardest part. Getting cold is easy. When it gets hot again, the organs literally break down. Vitrification, which cools tissue so quickly that it hardens in a glass instead of crystallizing, has been around for decades. The sticking point has always been melting: the heat warms up too slowly and ice forms anyway; It heats unevenly and thermal stress splits the fabric. Engineers at the University of Minnesota tackled that problem with iron oxide nanoparticles, launching them through an organ’s blood vessels and then heating them from the inside using alternating magnetic fields. Their 2023 study in Nature Communications describes rat kidneys stored for up to 100 days, rewarmed, rinsed to remove nanoparticles, and transplanted into rats whose own kidneys had been removed. The animals lived. What the frog hasn’t delivered No molecule explains any of this, and that’s the frustrating part. As Uygun sees it, freezing tolerance is not a clever trick, but rather a tightly sequenced set of biological changes that work together. Ice nucleation, sugar loading, membrane changes, metabolic shutdown, and antioxidant defense are activated in order, and a lab has to reproduce enough of that sequence in tissues that never evolved to cooperate. Rasha Al-Attar, a biologist in Tessier’s lab, is testing gene editing to make normal cells better tolerate cryoprotectants. In a paper by Storey in Comparative Biochemistry and Physiology, Al-Attar has argued that the frog works better as a template than a model. The animal has a real advantage over any transplant team. He just has to save himself, once a year, in a body he’s been rehearsing with since the last ice age. A surgeon has to do it on someone else’s liver, on a Tuesday, first. About this articleThis article is for general information and reflection. It is not professional advice. For your specific situation, consult a qualified professional.
