Survival of the Sickest: The Surprising Connections Between Disease and Longevity. Jonathan Prince
sugar-free blocks of ice. According to a company press release, it took two decades for researchers to develop a diet Slurpee by combining artificial sweeteners with undigestible sugar alcohols.) So when the grape dumps water at the first sign of frost, it’s actually protecting itself in two ways – first, by reducing water volume; and second, by raising the sugar concentration of the water that remains. And that allows the grape to withstand colder temperature without freezing.
Eliminating water to deal with the cold? That sounds an awful lot like cold diuresis – peeing when you’re cold. And higher levels of sugar? Well, we know where we’ve heard that; but before we get back to diabetes, let’s make one more stop: the animal kingdom.
Many animals thrive in the cold. Some amphibians, like the bullfrog, spend the winter in the frigid but unfrozen water at the bottom of lakes and rivers. The mammoth Antarctic cod happily swims beneath the Antarctic ice; its blood contains an antifreeze protein that sticks to ice crystals and prevents them from growing. On the Antarctic surface, the woolly bear caterpillar lives through temperatures as low as minus 60 degrees Fahrenheit for fourteen years, until it turns into a moth and flies off into the sunset for a few short weeks.
But of all the adaptations to cold under the sun – or hidden from it – none is as remarkable as the little wood frog’s.
The wood frog, Rana sylvatica, is a cute little critter about two inches long, with a dark mask across its eyes like Zorro’s, that lives across North America, from northern Georgia all the way up to Alaska, including north of the Arctic Circle. On early spring nights you can hear its mating call – a “brack, brack” that sounds something like a baby duck’s. But until winter ends, you won’t hear the wood frog at all. Like some animals, the wood frog spends the entire winter unconscious. But unlike hibernating mammals that go into a deep sleep, kept warm and nourished by a thick layer of insulating fat, the wood frog gives in to the cold entirely. It buries itself under an inch or two of twigs and leaves and then pulls a trick that – despite Ted Williams’s possible hopes and Alcor’s best efforts – seems to come straight out of a science fiction movie.
It freezes solid.
If you were on a winter hike and accidentally kicked one of these frogsicles out into the open, you’d undoubtedly assume it was dead. When completely frozen, it might as well be in suspended animation – it has no heartbeat, no breathing, and no measurable brain activity. Its eyes are open, rigid, and unnervingly white.
But if you pitched a tent and waited for spring, you’d eventually discover that little old Rana sylvatica has a few tricks up its frog sleeves. Just a few minutes after rising temperatures thaw the frog, its heartbeat miraculously sparks into gear and it gulps for air. It will blink a few times as color returns to its eyes, stretch its legs, and pull itself up into a sitting position. Not long after that, it will hop off, none the worse for wear, and join the chorus of defrosted frogs looking for a mate.
Nobody knows the wood frog better than the brilliant and irrepressible Ken Storey, a biochemist from Ottawa, Canada, who, along with his wife, Janet, has been studying them since the early 1980s. Storey had been studying insects with the ability to tolerate freezing when a colleague told him about the wood frog’s remarkable ability. His colleague had been collecting frogs for study and accidentally left them in the trunk of his car. Overnight, there was an unexpected frost and he awoke to discover a bag of frozen frogs. Imagine his surprise later that day when they thawed out on his lab table and started jumping around!
Storey was immediately intrigued. He was interested in cryopreservation – freezing living tissue to preserve it. Despite the bad rap it gets for its association with high-priced attempts to freeze the rich and eccentric for future cures, cryopreservation is a critical area of medical research that has the potential to yield many important advances. It has already revolutionized reproductive medicine by giving people the opportunity to freeze and preserve eggs and sperm.
The next step – the ability to extend the viability of large human organs for transplants – would be a huge breakthrough that could save thousands of lives every year. Today, a human kidney can be preserved for just two days outside the human body, while a heart can last only a few hours. As a result, organ transplants are always a race against the clock, with very little time to find the best match and get the patient, organ, and surgeon into the same operating room. Every day in the United States, a dozen people die because the organ they need hasn’t become available in time. If donated organs could be frozen and “banked” for later revival and transplant, the rates of successful transplants would almost surely climb significantly.
But currently it’s impossible. We know how to use liquid nitrogen to lower the temperature of tissue at the blinding speed of 600 degrees per minute, but it isn’t good enough. We have not figured out how to freeze large human organs and restore them to full viability. And, as was mentioned, we’re nowhere near the ability to freeze and restore a whole person.
So when Storey heard about the freezing frog, he jumped at the opportunity to study it. Frogs have the same major organs as humans, so this new direction for his research could prove amazingly useful. With all our technological prowess, we can’t freeze and restore a single major human organ – and here was an animal that naturally manages the complex chemical wizardry of freezing and restoring all its organs more or less simultaneously. After many years of study (and many muddy nights trudging through the woodlands of southern Canada on wood frog hunts), the Storeys have learned a good deal about the secrets behind Rana sylvatica’s death-defying freezing trick.
Here’s what they’ve uncovered: Just a few minutes after the frog’s skin senses that the temperature is dropping near freezing, it begins to move water out of its blood and organ cells, and, instead of urinating, it pools the water in its abdomen. At the same time, the frog’s liver begins to dump massive (for a frog) amounts of glucose into its bloodstream, supplemented by the release of additional sugar alcohols, pushing its blood sugar level up a hundredfold. All this sugar significantly lowers the freezing point of whatever water remains in the frog’s bloodstream, effectively turning it into a kind of sugary antifreeze.
There’s still water throughout the frog’s body, of course; it’s just been forced into areas where ice crystals will cause the least damage and where the ice itself might even have a beneficial effect. When Storey dissects frozen frogs he finds flat sheets of ice sandwiched between the skin and muscle of the legs. There will also be a big chunk of ice in the abdominal cavity surrounding the frog’s organs; the organs themselves are largely dehydrated and look wizened as raisins. In effect, the frog has carefully put its own organs on ice, not unlike adding ice to coolers containing human organs as they’re readied for transport to transplant. Doctors remove an organ, place it into a plastic bag, and then place the bag in a cooler full of crushed ice so the organ is kept as cool as possible without actually being frozen or damaged.
There’s water in the frog’s blood, too, but the rich concentration of sugar not only lowers the freezing point, it also minimizes damage by forcing the ice crystals that eventually form into smaller, less jagged shapes that won’t puncture or slash the walls of cells or capillaries. Even all of this doesn’t prevent every bit of damage, but the frog has that covered, too. During the winter months of its frozen sleep, the frog produces a large volume of a clotting factor called fibrinogen that helps to repair whatever damage might have occurred during freezing. Eliminating water and driving up sugar levels to deal with the cold: Grapes do it. Now we know that frogs do it. Is it possible that some humans adapted to do it, too?
Is it a coincidence that the people most likely to have a genetic propensity for a disease characterized by exactly that (excessive elimination of water and high levels of blood sugar) are people descended from exactly those places most ravaged by the sudden onset of an ice age about 13,000 years ago?
As a theory, it’s hotly controversial, but diabetes may have helped our European ancestors survive the sudden cold of the Younger Dryas.
As the Younger Dryas set in, any adaptation to manage the cold, no matter how disadvantageous in normal times, might have made the difference between making it to adulthood and dying young. If you had the hunter’s response, for instance, you would have an advantage in gathering food,