Survival of the Sickest: The Surprising Connections Between Disease and Longevity. Jonathan Prince

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      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, because you were less likely to develop frostbite.

      Now imagine that some small group of people had a different response to the cold. Faced with year-round frigid temperatures, their insulin supply slowed, allowing their blood sugar to rise somewhat. As in the wood frog, this would have lowered the freezing point of their blood. They urinated frequently, to keep internal water levels low. (A recent U.S. Army study shows there is very little harm caused by dehydration in cold weather.) Suppose these people used their brown fat to burn that over-supply of sugar in their blood to create heat. Perhaps they even produced additional clotting factor to repair tissue damage caused by particularly deep cold snaps. It’s not hard to imagine that these people might have had enough of an advantage over other humans, especially if, like the wood frog, the spike in sugar was only temporary, to make it more likely that they would survive long enough to reach reproductive age.

      There are tantalizing bits of evidence to bolster the theory.

      When rats are exposed to freezing temperatures, their bodies become resistant to their own insulin. Essentially, they become what we would call diabetic in response to the cold.

      In areas with cold weather, more diabetics are diagnosed in colder months; in the Northern Hemisphere, that means more diabetics are diagnosed between November and February than between June and September.

      Children are most often diagnosed with Type 1 diabetes when temperatures start to drop in late fall.

      Fibrinogen, the clotting factor that repairs ice-damaged tissue in the wood frog, also mysteriously peaks in humans during winter months. (Researchers are taking note – that may mean that cold weather is an important, but underappreciated, risk factor for stroke.)

      A study of 285,705 American veterans with diabetes measured seasonal differences in their blood sugar levels. Sure enough, the veterans’ blood sugar levels climbed dramatically in the colder months and bottomed out during the summer. More telling, the contrast between summer and winter was even more pronounced in those who lived in colder climates, with greater differences in seasonal temperature. Diabetes, it seems, has some deep connection to the cold.

      We don’t know enough today to state with certainty that the predisposition to Type 1 or Type 2 diabetes is related to human cold response. But we do know that some genetic traits that are potentially harmful today clearly helped our ancestors to survive and reproduce (hemochromatosis and the plague, for example). So while it’s tempting simply to question how a condition that can cause early death today could ever confer a benefit, that doesn’t look at the whole picture.

      Remember, evolution is amazing – but it isn’t perfect. Just about every adaptation is a compromise of sorts, an improvement in some circumstances, a liability in others. A peacock’s brilliant tail feathers make him more attractive to females – and attract more attention from predators. Human skeletal structure allows us to walk upright and gives us large skulls filled with big brains – and the combination means an infant’s head can barely make it through its mother’s birth canal. When natural selection goes to work, it doesn’t favor adaptations that make a given plant or animal “better” – just whatever it takes for it to increase the chances for survival in its current environment. And when there’s a sudden change in circumstances that threatens to wipe out a population – a new infectious disease, a new predator, or a new ice age – natural selection will make a beeline for any trait that improves the chance of survival.

      “Are they kidding?” said one doctor when told of the diabetes theory by a reporter. “Type 1 diabetes would result in severe ketoacidosis and early death.”

      Sure – today.

      But what if a temporary diabetes-like condition occurred in a person who had significant brown fat living in an ice age environment? Food would probably be limited, so dietary bloodsugar load would already be low, and brown fat would convert most of that to heat, so the ice age “diabetic’s” blood sugar, even with less insulin, might never reach dangerous levels. Modern-day diabetics, on the other hand, with little or no brown fat, and little or no exposure to constant cold, have no use – and thus no outlet – for the sugar that accumulates in their blood. СКАЧАТЬ