Frogs' freezing tricks could benefit humans

Scientists study process for use in transplants

By David A. Fahrenthold

The Washington Post

December 14, 2004

WASHINGTON - This is the way a wood frog freezes:

First, as the temperature drops below 32 degrees, ice crystals start to form just beneath the frog's skin. The normally pliant and slimy amphibian becomes - for lack of a better word - slushy.

Then, if the mercury continues to fall, ice races inward through the frog's arteries and veins. Its heart and brain stop working, and its eyes freeze to a ghostly white.

"Imagine an ice cube. Paint it green," and you've got the wood frog in winter, said Ken Storey, a professor at Carleton University in Ottawa, Ontario. The frog is solid to the touch and makes a mini-thud when dropped.

But it is not dead. When a thaw comes, the frog is able to melt back into its normal state over a period of several hours, restart its heart and hop away, unscathed.

This amazing process of reanimation is being examined by scientists hoping to learn the secrets of the frog and other animals that freeze solid.

The hope is that these apparent Lazarus routines can yield clues for improving human medicine, including better preservation of organs on their way to transplant patients.

"Here's an amphibian that has solved the problem of cryo-preserving its organs - all of them, simultaneously," said Jon Costanzo, a professor of zoology at Miami University in Ohio. "And we haven't been able to do that with one (human organ)."

The wood frog, a 2-inch-long creature with a call like a quack, which lives in woods from Georgia to Alaska. It's very hard to find them frozen in the wild, because they're hidden underground. Other species - spring peeper and the gray tree frog, as well as a few kinds of caterpillars and the babies of the painted turtle -can freeze but lose the ability as they age.

Scientists say these animals'freezing abilities are just extreme reactions to a problem that all cold-climate animals face: periodic blasts of winter chill. Human retirees head to Florida, Chesapeake Bay crabs bury themselves in the mud and most frog species hide out deep underground or underwater.

But not the freezing frogs. Instead, buried just a few inches under dirt and leaves, they welcome the chill. When the soil starts freezing - even if it falls just a couple of degrees below 32 - so do the frogs.

The frogs can survive this process, in which as much as 65 percent of their body water freezes, because their cells are protected by a kind of natural antifreeze.

Scientists say that before winter comes, the frogs eat ravenously, storing a starch in their livers. A freeze triggers their bodies to convert the starch into other compounds, most often glucose, or blood sugar. The frogs become, in essence, extremely diabetic.

The glucose lowers the freezing temperature of water inside the frogs' cells, and because of this, the cells stay liquid, even as ice fills the space around them. This is crucial: If the water inside the cells froze, scientists say, the jagged ice crystals would destroy everything inside, killing the frog.

Medical researchers say they hope to copy these long-term freezing abilities to add hours or even days to the time that human organs can be preserved.

Now, after organs are removed from a donor, they are packed in a special solution and kept on ice. But they can't be frozen because of the damage that ice crystals would do to the cells. Without freezing, the shelf life of these organs can be as much as 48 hours for a kidney and as little as four hours for a heart.

If organs could be preserved longer, it would allow more time for locating an organ recipient and setting up the operation, said Jimmy Light, head of transplantation at Washington Hospital Center.

"It would allow you to have a more prepared patient," Light said. "Now, it's kind of like a fire drill. The bell rings, the clock ticks and you've got to get going."

Other researchers have turned to arctic fish, which manufacture special chemicals to keep from freezing even as the water around them falls below 32 degrees.

Scientists say they don't see any immediate potential for putting an entire human body in a science fiction-style deep freeze; the frogs, after all, don't stay frozen forever.

But just freezing and thawing one human organ would be a major breakthrough.

"If we can translate that into a human heart, then we'll do very well," said Boris Rubinsky, a University of California professor.

Copyright © 1997-2004 Concord Monitor & New Hampshire Patriot.

Copyright © 2004 The Washington Post.

This article posted January 2, 2005.