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1CHAPTER II 
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5A SPOONFUL OF SUGAR HELPS THE 
6TEMPERATURE GO DOWN 
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10The World Health Organization estimates that 171 million people have diabetes — and that number 
11is expected to double by 2030. You almost certainly know people with diabetes — and you certainly 
12have heard of people with diabetes. Halle Berry, Mikhail Gorbachev, and George Lucas all have 
13diabetes. It's one of the most common chronic diseases in the world, and it's getting more common 
14every day. 
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16Diabetes is all about the body's relationship to sugar, specifically the blood sugar known as 
17glucose. Glucose is produced when the body breaks down carbohydrates in the food we eat. It's 
18essential to survival — it provides fuel for the brain; it's required to manufacture proteins; it's what 
19we use to make energy when we need it. With the help of insulin, a hormone made by the pancreas, 
20glucose is stored in your liver, muscles, and fat cells (think of them as your own internal OPEC) 
21waiting to be converted to fuel as necessary. 
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23The full name of the disease is actually diabetes mellitus — which literally means "passing 
24through honey sweet." One of the first outward manifestations of diabetes is the need to pass large 
25amounts of sugary urine. And for thousands of years, observers have noticed that diabetics' urine 
26smells (and tastes) particularly sweet. In the past Chinese physicians actually diagnosed and 
27monitored diabetes by looking to see whether ants were attracted to someone's urine. In diabetics, the 
28process through which insulin helps the body use glucose is broken, and the sugar in the blood builds 
29up to dangerously high levels. Unmanaged, these abnormal blood sugar levels can lead to rapid 
30dehydration, coma, and death. Even when diabetes is tightly managed, its long-term complications 
31include blindness, heart disease, stroke, and vascular disease that often leads to gangrene and 
32amputation. 
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34There are two major types of diabetes, Type 1 and Type 2, commonly called juvenile diabetes 
35and adult-onset diabetes, respectively, because of the age at which each type is usually diagnosed. 
36(Increasingly, adult-onset diabetes is becoming a misnomer: skyrocketing rates of childhood obesity 
37are leading to increasing numbers of children who have Type 2 diabetes.) 
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39Some researchers believe that Type 1 diabetes is an autoimmune disease — the body's natural 
40defense system incorrectly identifies certain cells as outside invaders and sets out to destroy them. In 
41the case of Type 1 diabetes, the cells that fall victim to this biological friendly fire are the precise 
42cells in the pancreas responsible for insulin production. No insulin means the body's blood sugar 
43refinery is effectively shut down. As of today, Type 1 diabetes can only be treated with daily doses of 
44insulin, typically through self- administered injections, although it is also possible to have an insulin 
45pump surgically implanted. On top of daily insulin doses, Type 1 requires vigilant attention to blood 
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49sugar levels and a superdisciplined approach to diet and exercise. 
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51In Type 2 diabetes, the pancreas still produces insulin — sometimes even at high levels — but the 
52level of insulin production can eventually be too low or other tissues in the body are resistant to it, 
53impairing the absorption and conversion of blood sugar. Because the body is still producing insulin, 
54Type 2 diabetes can often be managed without insulin injections, through a combination of other 
55medications, careful diet, exercise, weight loss, and blood sugar monitoring. 
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57There is also a third type of diabetes, called gestational diabetes because it occurs in pregnant 
58women. Gestational diabetes can be a temporary type of diabetes that tends to resolve itself after 
59pregnancy. In the United States, it occurs in as much as 4 percent of pregnant women — some 100,000 
60expectant mothers a year. It can also lead to a condition in the newborn called macrosomia — which is 
61a fancy term for "really chubby baby" as all the extra sugar in the mother's bloodstream makes its 
62way across the placenta and feeds the fetus. Some researchers think this type of diabetes may be 
63"intentionally" triggered by a hungry fetus looking for Mommy to stock the buffet table with sugary 
64glucose. 
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66So what causes diabetes? The truth is, we don't fully understand. It's a complex combination that 
67can involve inheritance, infections, diet, and environmental factors. At the very least, inheritance 
68definitely causes a predisposition to diabetes that can be triggered by some other factor. In the case of 
69Type 1 diabetes, that trigger may be a virus or even an environmental trigger. In the case of Type 2, 
70scientists think many people pull the trigger themselves through poor eating habits, lack of exercise, 
71and resulting obesity. But one thing is clear — genetics contributes to Type 1 and especially to Type 2 
72diabetes. And that's where, for our purposes, things really start to heat up. Or, more precisely, to cool 
73down, as you'll see shortly. 
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77there's A big difference in the prevalence of Type 1 and Type 2 diabetes that is largely based on 
78geographic origin. Even though there seems to be a stronger genetic component to Type 2 diabetes, it 
79is also closely related to lifestyle; 85 percent of people who have this type of diabetes are obese. 
80That means it's currently much more common in the developed world because easy access to high- 
81calorie, low-nutrient junk food means so many more people are obese — but it seems clear that the 
82predisposition to Type 2 diabetes exists across population groups. There are higher levels of 
83incidence in certain populations, of course — but even that tends to occur hand in hand with higher 
84levels of obesity. The Pima Indians of the southwestern United States, for example, have a staggering 
85rate of diabetes — nearly half of all adults. It's possible that their historic hunter- gatherer lifestyle 
86produced metabolisms more suited for the Atkins diet than the carbohydrate-and sugar-heavy diet that 
87European farmers survived on for centuries. Type 1 diabetes is different — it is much, much more 
88common in people of Northern European descent. Finland has the highest rate of juvenile diabetes in 
89the world. Sweden is second, and the United Kingdom and Norway are tied for third. As you head 
90south, the rate drops lower and lower. It's downright uncommon in people of purely African, Asian, 
91and Hispanic descent. 
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93When a disease that is caused at least partially by genetics is significantly more likely to occur 
94in a specific population, it's time to raise the evolutionary eyebrows and start asking questions — 
95because that almost certainly means that some aspect of the trait that causes the disease today helped 
96the forebears of that population group to survive somewhere back up the evolutionary line. 
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98In the case of hemochromatosis, we know that the disease probably provided carriers with 
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102protection from the plague by denying the bacteria that causes it the iron it needs to survive. So what 
103could diabetes possibly do for us? To answer that, we're going to take another trip down memory 
104lane — this time measured, not in centuries, but in millennia. Put your ski jackets on; we're looking for 
105an ice age. 
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109until about fifty years ago, the conventional wisdom among scientists who studied global climate 
110change was that large-scale climate change occurred very slowly. Today, of course, people from Al 
111Gore to Julia Roberts are on a mission to make it clear that humanity has the power to cause 
112cataclysmic change in just a few generations. But before the 1950s, most scientists believed that 
113climate change took thousands, probably hundreds of thousands, of years. 
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115That doesn't mean they didn't accept the notion that glaciers and ice sheets had once covered the 
116Northern Hemisphere. They were just happily certain that glaciers moved, well, glacially: eons to 
117descend and epochs to recede. Humanity certainly didn't have to worry about it — nobody was ever 
118going to be run over by a speeding glacier. If massive climate change was going to lead us into a new 
119ice age, we'd have a few hundred thousand years to do something about it. 
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121Of course, there were some contrary voices singing a different tune, but the larger scientific 
122community paid them very little regard. Andrew Ellicott Douglass was an astronomer working in 
123Arizona in 1 895 when he first started cutting down trees to examine them for evidence of any effect 
124from a specific solar activity, called sunspots, that occurs in cycles. He never found that — but he did 
125ultimately invent dendrochronology, the scientific technique of studying tree rings for clues about the 
126past. One of his first observations was that tree rings were thinner during cold or dry years and 
127thicker during wet or warm years. And by rolling back the years, one ring at a time, he discovered 
128what appeared to be a century-long climate change that occurred around the seventeenth century, with 
129a significant drop in temperature. The reaction of the scientific community was a collective "Nah." 
130As far as the climate change community was concerned, Douglass was cutting down trees in a forest 
131with nobody there to hear it. (According to Dr. Lloyd Burckle of Columbia University, not only was 
132Douglass right: the hundred-year cold spell he discovered was responsible for some beautiful music. 
133Burckle says the superior sound of the great European violin makers, including the famous Stradivari, 
134is the result of the high-density wood from the trees that grew during this century-long freeze — denser 
135because they grew less during the cold and had thinner rings as a result.) 
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137More evidence of the possibility of rapid climate change accumulated. In Sweden, scientists 
138studying layers of mud from lake bottoms found evidence of climate change that occurred much more 
139quickly than anyone at the time thought possible. These scientists discovered large amounts of pollen 
140from an Arctic wildflower called Dryas octopetala in mud cores from only 12,000 years ago. 
141Dryas's usual home is the Arctic; it only truly flourished across Europe during periods of significant 
142cold. Its widespread prevalence in Sweden around 12,000 years ago seemed to indicate that the 
143warm weather that had followed the last ice age had been interrupted by a rapid shift back to much 
144colder weather. In honor of the telltale wildflower, they named this arctic reprise the Younger Dryas. 
145Of course, given prevailing thinking, even these scientists believed that the "rapid" onset of the 
146Younger Dryas took 1,000 years or so. 
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148It's hard to underestimate the chilling effect conventional wisdom can have on the scientific 
149community. Geologists of the time believed the present was the key to the past — if this is the way the 
150climate behaves today, that's the way it behaved yesterday. That philosophy is called 
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154uniformitarianism and, as the physicist Spencer Weart points out in his 2003 book The Discovery of 
155Global Warming, it was the guiding principle among scientists of the time: 
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159Through most of the 20th century, the uniformitarian principle was cherished by geologists as the 
160very foundation of their science. In human experience, temperatures apparently did not rise or 
161fall radically in less than millennia, so the uniformitarian principle declared that such changes 
162had never happened in the past. 
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166If you're positive something doesn't exist, you're not going to look for it, right? And because 
167everyone was certain that global climate changes took at least a thousand years, nobody even 
168bothered to look at the evidence in a way that could reveal faster change. Those Swedish scientists 
169studying the layers of lake bottom clay who first postulated the "rapid" thousand-year onset of the 
170Younger Dryas? They were looking at chunks of mud spanning centuries; they never looked at 
171samples small enough to demonstrate faster change. The proof that the Younger Dryas descended on 
172the Northern Hemisphere much more rapidly than they thought was right in front of their eyes — but 
173they were blinded by their assumptions. 
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177by the 1950s and 1960s, the uniformitarian vise started to lose its hold, or at least change its grip, as 
178scientists began to understand the potential of catastrophic events to produce rapid change. In the late 
1791950s, Dave Fultz at the University of Chicago built a mockup of the earth's atmosphere using 
180rotating fluids that simulated the behavior of atmospheric gases. Sure enough, the fluids moved in 
181stable, repeating patterns — unless, that is, they were disturbed. Then, even the smallest interference 
182could produce massive changes in the currents. It wasn't proof by a long shot, but it certainly was a 
183powerful suggestion that the real atmosphere was susceptible to significant change. Other scientists 
184developed mathematical models that indicated similar possibilities for rapid shifts. 
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186As new evidence was discovered and old evidence was reexamined, the scientific consensus 
187evolved. By the 1970s there was general agreement that the temperature shifts and climate changes 
188leading into and out of ice ages could occur over mere hundreds of years. Thousands were out, 
189hundreds were in. Centuries were the new "rapid." 
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191There was a new consensus around when — but a total lack of agreement about how. Perhaps 
192methane bubbled up from tundra bogs and trapped the heat of the sun. Perhaps ice sheets broke off 
193from the Antarctic and cooled the oceans. Maybe a glacier melted into the North Atlantic, creating a 
194massive freshwater lake that suddenly interrupted the ocean's delivery of warm tropical water to the 
195north. 
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197It's fitting that hard, cold proof was eventually found in hard, cold ice. 
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199In the early 1970s, climatologists discovered that some of the best records of historic weather 
200patterns were filed away in the glaciers and ice plateaus of northern Greenland. It was hard, 
201treacherous work — if you're imagining the stereotypical lab rat in a white coat, think again. This was 
202Extreme Sports: Ph.D. — multinational teams trekking across miles of ice, climbing thousands of feet, 
203hauling tons of machines, and enduring altitude sickness and freakish cold, all so they could bore into 
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207a two-mile core of ice. But the prize was a pristine and unambiguous record of yearly precipitation 
208and past temperature, unspoiled by millennia and willing to reveal its secrets with just a little 
209chemical analysis. Once you paid it a visit, of course. 
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211By the 1980s, these ice cores definitively confiremd the existence of the Younger Dryas — a 
212severe drop in temperature that began around 13,000 years ago and lasted more than a thousand years. 
213But that was just, well, the tip of the iceberg. 
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215In 1989 the United States mounted an expedition to drill a core all the way to the bottom of the 
216two-mile Greenland ice sheet — representing 110,000 years of climate history. Just twenty miles 
217away, a European team was conducting a similar study. Four years later, both teams got to the bottom 
218— and the meaning of rapid was about to change again. 
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220The ice cores revealed that the Younger Dryas — the last ice age — ended in just three years. Ice 
221age to no ice age — not in three thousand years, not in three hundred years, but in three plain years. 
222What's more, the ice cores revealed that the onset of the Younger Dryas took just a decade. The proof 
223was crystal clear this time — rapid climate change was very real. It was so rapid that scientists 
224stopped using the word rapid to describe it, and started using words like abrupt and violent. Dr. 
225Weart summed it up in his 2003 book: 
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229Swings of temperature that scientists in the 1950s believed to take tens of thousands of years, in 
230the 1970s to take thousands of years, and in the 1980s to take hundreds of years, were now found 
231to take only decades. 
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235In fact, there have been around a score of these abrupt climate changes over the last 110,000 
236years; the only truly stable period has been the last 11,000 years or so. Turns out, the present isn't the 
237key to the past — it's the exception. 
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239The most likely suspect for the onset of the Younger Dryas and the sudden return to ice age 
240temperatures across Europe is the breakdown of the ocean "conveyor belt," or thermohaline 
241circulation, in the Atlantic Ocean. When it's working normally — or at least the way we're used to it 
242— the conveyor carries warm tropical water on the ocean surface to the north, where it cools, 
243becomes denser, sinks, and is carried south through the ocean depths back to the Tropics. Under those 
244circumstances, Britain is temperate even though it's on the same latitude as much of Siberia. But when 
245the conveyor is disrupted — say, by a huge influx of warm fresh water melting off the Greenland ice 
246sheet — it may have a significant impact on global climate and turn Europe into a very, very cold 
247place. 
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251just before the Younger Dryas, our European ancestors were doing pretty well. Tracing human 
252migration through DNA, scientists have documented a population explosion in Northern Europe as 
253populations that had once migrated north out of Africa now moved north again into areas of Europe 
254that had been uninhabitable during the last ice age (before the Younger Dryas). The average 
255temperature was nearly as warm as it is today, grasslands flourished where glaciers had once stood, 
256and human beings thrived. 
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260And then the warming trend that had persisted since the end of the last ice age kicked rapidly 
261into reverse. In just a decade or so, average yearly temperatures plunged nearly thirty degrees. Sea 
262levels dropped by hundreds of feet as water froze and stayed in the ice caps. Forests and grasslands 
263went into a steep decline. Coastlines were surrounded by hundreds of miles of ice. Icebergs were 
264common as far south as Spain and Portugal. The great, mountainous glaciers marched south again. The 
265Younger Dryas had arrived, and the world was changed. 
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267Though humanity would survive, the short-term impact, especially for those populations that had 
268moved north, was devastating. In less than a generation, virtually every learned method of survival — 
269from the shelters they built to the hunting they practiced — was inadequate. Many thousands of humans 
270almost certainly froze or starved to death. Radiocarbon dating from archaeological sites provides 
271clear evidence that the human population in Northern Europe went into a steep decline, showing a 
272steep drop-off in settlements and other human activity. 
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274But humans clearly survived; the question is, how? Certainly some of our success was due to 
275social adaptation — many scientists think that the Younger Dryas helped to spur the collapse of hunter- 
276gatherer societies and the first development of agriculture. But what about biological adaptation and 
277natural selection? Scientists believe some animals perfected their natural ability to survive cold 
278spells during this period — notably the wood frog, which we'll return to later. So why not humans? 
279Just as the European population may have "selected" for the hemochromatosis gene because it helped 
280its carriers withstand the plague, might some other genetic trait have provided its carriers with 
281superior ability to withstand the cold? To answer that, let's take a look at the effect of cold on 
282humans. 
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286immediately upon his death in July 2002, baseball legend Ted Williams was flown to a spa in 
287Scottsdale, Arizona, checked in, and given a haircut, a shave, and a cold plunge. Of course, this 
288wasn't your typical Arizona spa — this was the Alcor Life Extension cryonics lab, and Williams was 
289checking in for the foreseeable future. According to his son, he hoped that future medical science 
290might be able to restore him to life. 
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292Alcor separated Williams's head from his body, drilled a couple of dime-size holes in it, and 
293froze it in a bucket of liquid nitrogen at minus 320 degrees Fahrenheit. (His body got its own cold 
294storage container.) Alcor brochures suggest that "mature nanotechnology" might be able to reanimate 
295frozen bodies "perhaps by the mid-2 1st century," but they also note that cryonics is a "last- in- first- out 
296process wherein the first-in may have to wait a very long time." 
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298Make that a very, very long time, like. . .never. Unfortunately for Williams and the other sixty-six 
299superchilled cadavers at Alcor, human tissue doesn't react well to freezing. When water is frozen, it 
300expands into sharp little crystals. When humans are frozen, the water in our blood freezes, and the ice 
301shards cut blood cells and cause capillaries to burst. It's not dissimilar to the way a pipe bursts when 
302the water's left on in an unheated house — except no repairman can fix it. 
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304Of course, just because we can't survive a true deep freeze doesn't mean our bodies haven't 
305evolved many ways to manage the cold. They have. Not only is your body keenly aware of the danger 
306cold poses, it's got a whole arsenal of natural defenses. Think back to some time when you were 
307absolutely freezing — standing still for hours on a frigid winter morning watching a parade, riding a 
308ski lift with the wind whipping across the mountain. You start to shiver. That's your body's first 
309move. When you shiver, the increased muscle activity burns the sugar stored in your muscles and 
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313creates heat. What happens next is less obvious, but you've felt the effect. Remember the 
314uncomfortable combination of tingling and numbness in your fingers and toes? That's your body's next 
315move. 
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317As soon as the body senses cold, it constricts the thin web of capillaries in your extremities, first 
318your fingers and toes, then farther up your arms and legs. As your capillary walls close in, blood is 
319squeezed out and driven toward your torso, where it essentially provides a warm bath for your vital 
320organs, keeping them at a safe temperature, even if it means the risk of frostbite for your extremities. 
321It's natural triage — lose the finger, spare the liver. 
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323In people whose ancestors lived in particularly cold climates — like Norwegian fishermen or 
324Inuit hunters — this autonomic response to cold has evolved with a further refinement. After some time 
325in the cold, the constricted capillaries in your hands will dilate briefly, sending a rush of warm blood 
326into your numbed fingers and toes before constricting again to drive the blood back into your core. 
327This intermittent cycle of constriction and release is called the Lewis wave or "hunter's response," 
328and it can provide enough warmth to protect your extremities from real injury, while still ensuring that 
329your vital organs are safe and warm. Inuit hunters can raise the temperature in the skin of their hands 
330from near freezing to fifty degrees in a mater of minutes; for most people it takes much longer. On the 
331other hand, people descended from warm-weather populations don't seem to have this natural ability 
332to protect their limbs and their core at the same time. During the frigid cold of the Korean War, 
333African American soldiers were much more prone to frostbite than other soldiers. 
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335Shivering and blood vessel constriction aren't the only ways the body generates and preserves 
336heat. A portion of the fat in newborns and some adults is specialized heat- generating tissue called 
337brown fat, which is activated when the body is exposed to cold. When blood sugar is delivered to a 
338brown fat cell, instead of being stored for future energy as it is in a regular fat cell, the brown fat cell 
339converts it to heat on the spot. (For someone acclimated to very cold temperatures, brown fat can 
340burn up to 70 percent more fat.) Scientists call the brown fat process nonshivering thermogenesis, 
341because it's heat creation without muscle movement. Shivering, of course, is only good for a few 
342hours; once you exhaust the blood sugar stores in your muscles and fatigue sets in, it doesn't work 
343anymore. Brown fat, on the other hand, can go on generating heat for as long as it's fed, and unlike 
344most other tissues, it doesn't need insulin to bring sugar into cells. 
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346Nobody's written the Brown Fat Diet Book yet because it requires more than your usual lifestyle 
347change. Adults who don't live in extreme cold don't really have much, if any, brown fat. To 
348accumulate brown fat and get it really working, you need to live in extreme cold for a few weeks. 
349We're talking North Pole cold. And that's not all — you've got to stay there. Once you stop sleeping in 
350your igloo, your brown fat stops working. 
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352The body has one more response to the cold that's not completely understood — but you've 
353probably experienced it. When most people are exposed to cold for a while, they need to pee. This 
354response has puzzled medical researchers for hundreds of years. It was first noted by one Dr. 
355Sutherland, in 1764, who was trying to document the benefits of submersing patients in the supposedly 
356healing — but cold — waters of Bath and Bristol, En gland. After immersing a patient who suffered 
357from "dropsy, jaundice, palsy, rheumatism and inveterate pain in his back," Sutherland noted that the 
358patient was "pissing more than he drank." Sutherland chalked the reaction up to external water 
359pressure, figuring (quite wrongly) that fluid was simply being squeezed out of his patient, and it 
360wasn't until 1909 that researchers connected increased urine flow, or diuresis, to cold exposure. 
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362The leading explanation for cold diuresis — the need to pee when it's cold — is still pressure; but 
363not external pressure, internal pressure. The theory is that as blood pressure climbs in the body's core 
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367because of constriction in the extremities, the body signals the kidneys to offload some of the extra 
368fluid. But that theory doesn't fully explain the phenomenon, especially in light of recent studies. 
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370The U.S. Army Research Institute of Environmental Medicine has conducted more than twenty 
371years of study into human response to extreme heat, cold, depth, and altitude. Their research 
372conclusively demonstrates that even highly cold-acclimated individuals still experience cold diuresis 
373when the temperature dips toward freezing. So the question persists: Why do we need to pee when 
374we're cold? This certainly isn't the most pressing question facing medical researchers today — but as 
375you'll soon discover, the possibilities are intriguing. And the answers may shed light on much bigger 
376issues — like a disease that currently affects 171 million people. 
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380let's put aside the delicate subject of cold diuresis and turn to one much more suitable for the dinner 
381table — ice wine: delicious, prized, and — supposedly — created by accident. Four hundred years ago, 
382a German vintner was hoping to squeak just a few more growing days out of the late autumn when his 
383fields were hit by a sudden frost, or so the story goes. The grapes were curiously shrunken, but, not 
384wanting to let his entire harvest go to waste, he decided to pick the frozen grapes anyway and see 
385what would come of it, hoping for the best. He let the grapes defrost and then pressed the crop as he 
386usually did but was disappointed when it yielded just one-eighth of the juice he was expecting. Since 
387he had nothing to lose, he put his meager yield through the fermentation process. 
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389And discovered that he had a hit on his hands. The finished wine was insanely sweet. Since its 
390first, semilegendary, certainly accidental harvest, some winemakers have specialized in ice wine, 
391waiting every year for the first frost so they can harvest crops of frozen grapes. Among the many ways 
392wine is rated, graded, and weighted today, it is measured on a "sugar scale." Typical table wine runs 
393from 0 to 3 on the sugar scale. Ice wine runs from 18 to 28. 
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395The shrunken nature of the grapes is due to water loss. Chemically speaking, it's not difficult to 
396guess why grapes might have evolved to offload water at the onset of a freeze — the less water in the 
397grape, the fewer ice crystals there are to damage the delicate membranes of the fruit. 
398
399How about the sharp increase in sugar concentration? That makes sense too. Ice crystals are only 
400made of pure water — but the temperature at which they start to form depends on what else is 
401suspended in the fluid where the water is found. Anything dissolved in water interferes with its 
402ability to form the hexagonal latticework of solid ice crystals. Average seawater, for example, full of 
403salt, freezes at around 28 degrees Fahrenheit instead of the 32 degrees we think of as water's freezing 
404point. Think about the bottle of vodka some people keep in their freezer. Usually, alcohol is about 40 
405percent of the liquid volume in the bottle; it does a great job of interfering with the creation of ice — 
406vodka doesn't freeze until you cool it down to around minus 20 degrees Fahrenheit. Even most water 
407in nature doesn't freeze at exactly 32 degrees, because it usually contains trace minerals or other 
408impurities that lower the freezing point. 
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410Like alcohol, sugar is a natural antifreeze. The higher the sugar content in a liquid, the lower the 
411freezing point. (Nobody knows more about sugar and freezing than the food service chemists at 7- 
412Eleven who were in charge of developing a sugar-free Slurpee beverage. In regular Slurpees, the 
413sugar is what helps to keep the frozen treat slurpable — it prevents the liquid from completely 
414freezing. So when they tried to make sugar-free Slurpees, they kept making sugar-free blocks of ice. 
415According to a company press release, it took two decades for researchers to develop a diet Slurpee 
416by combining artificial sweeteners with undigestible sugar alcohols.) So when the grape dumps water 
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420at the first sign of frost, it's actually protecting itself in two ways — first, by reducing water volume; 
421and second, by raising the sugar concentration of the water that remains. And that allows the grape to 
422withstand colder temperature without freezing. 
423
424Eliminating water to deal with the cold? That sounds an awful lot like cold diuresis — peeing 
425when you're cold. And higher levels of sugar? Well, we know where we've heard that; but before we 
426get back to diabetes, let's make one more stop: the animal kingdom. 
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430many animals thrive in the cold. Some amphibians, like the bullfrog, spend the winter in the frigid 
431but unfrozen water at the bottom of lakes and rivers. The mammoth Antarctic cod happily swims 
432beneath the Antarctic ice; its blood contains an antifreeze protein that sticks to ice crystals and 
433prevents them from growing. On the Antarctic surface, the woolly bear caterpillar lives through 
434temperatures as low as minus 60 degrees Fahrenheit for fourteen years, until it turns into a moth and 
435flies off into the sunset for a few short weeks. 
436
437But of all the adaptations to cold under the sun — or hidden from it — none is as remarkable as the 
438little wood frog's. 
439
440The wood frog, Rana sylvatica, is a cute little critter about two inches long with a dark mask 
441across its eyes like Zorro's that lives across North America, from northern Georgia all the way up to 
442Alaska, including north of the Arctic Circle. On early spring nights you can hear its mating call — a 
443"brack, brack" that sounds something like a baby duck's. But until winter ends, you won't hear the 
444wood frog at all. Like some animals, the wood frog spends the entire winter unconscious. But unlike 
445hibernating mammals that go into a deep sleep, kept warm and nourished by a thick layer of insulating 
446fat, the wood frog gives in to the cold entirely. It buries itself under an inch or two of twigs and 
447leaves and then pulls a trick that — despite Ted Williams's possible hopes and Alcor's best efforts — 
448seems to come straight out of a science fictiom movie. 
449
450It freezes solid. 
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452If you were on a winter hike and accidentally kicked one of these frogsicles out into the open, 
453you'd undoubtedly assume it was dead. When completely frozen, it might as well be in suspended 
454animation — it has no heartbeat, no breathing, and no measurable brain activity. Its eyes are open, 
455rigid, and unnervingly white. 
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457But if you pitched a tent and waited for spring, you'd eventually discover that little old Rana 
458sylvatica has a few tricks up its frog sleeves. Just a few minutes after rising temperatures thaw the 
459frog, its heartbeat miraculously sparks into gear and it gulps for air. It will blink a few times as color 
460returns to its eyes, stretch its legs, and pull itself up into a sitting position. Not long after that, it will 
461hop off, none the worse for wear, and join the chorus of defrosted frogs looking for a mate. 
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465nobody knows the wood frog better than the brilliant and irrepressible Ken Storey, a biochemist 
466from Ottawa, Canada, who, along with his wife, Janet, has been studying them since the early 1980s. 
467Storey had been studying insects with the ability to tolerate freezing when a colleague told him about 
468the wood frog's remarkable ability. His colleague had been collecting frogs for study and 
469accidentally left them in the trunk of his car. Overnight, there was an unexpected frost and he awoke 
470to discover a bag of frozen frogs. Imagine his surprise later that day when they thawed out on his lab 
471
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474table and started jumping around! 
475
476Storey was immediately intrigued. He was interested in cryopreservation — freezing living tissue 
477to preserve it. Despite the bad rap it gets for its association with high-priced attempts to freeze the 
478rich and eccentric for future cures, cryopreservation is a critical area of medical research that has the 
479potential to yield many important advances. It has already revolutionized reproductive medicine by 
480giving people the opportunity to freeze and preserve eggs and sperm. 
481
482The next step — the ability to extend the viability of large human organs for transplants — would 
483be a huge breakthrough that could save thousands of lives every year. Today, a human kidney can be 
484preserved for just two days outside the human body, while a heart can last only a few hours. As a 
485result, organ transplants are always a race against the clock, with very little time to find the best 
486match and get the patient, organ, and surgeon into the same operating room Every day in the United 
487States, a dozen people die because the organ they need hasn't become available in time. If donated 
488organs could be frozen and "banked" for later revival and transplant, the rates of successful 
489transplants would almost surely climb significantly. 
490
491But currently it's impossible. We know how to use liquid nitrogen to lower the temperature of 
492tissue at the blinding speed of 600 degrees per minute, but it isn't good enough. We have not figured 
493out how to freeze large human organs and restore them to full viability. And, as was mentioned, we're 
494nowhere near the ability to freeze and restore a whole person. 
495
496So when Storey heard about the freezing frog, he jumped at the opportunity to study it. Frogs 
497have the same major organs as humans, so this new direction for his research could prove amazingly 
498useful. With all our technological prowess, we can't freeze and restore a single major human organ — 
499and here was an animal that naturally manages the complex chemical wizardry of freezing and 
500restoring all its organs more or less simultaneously. After many years of study (and many muddy 
501nights trudging through the woodlands of southern Canada on wood frog hunts), the Storeys have 
502learned a good deal about the secrets behind Rana sylvatica's death-defying freezing trick. 
503
504Here's what they've uncovered: Just a few minutes after the frog's skin senses that the 
505temperature is dropping near freezing, it begins to move water out of its blood and organ cells, and, 
506instead of urinating, it pools the water in its abdomen. At the same time, the frog's liver begins to 
507dump massive (for a frog) amounts of glucose into its bloodstream, supplemented by the release of 
508additional sugar alcohols, pushing its blood sugar level up a hundredfold. All this sugar significantly 
509lowers the freezing point of whatever water remains in the frog's bloodstream, effectively turning it 
510into a kind of sugary antifreeze. 
511
512There's still water throughout the frog's body, of course; it's just been forced into areas where 
513ice crystals will cause the least damage and where the ice itself might even have a beneficial effect. 
514When Storey dissects frozen frogs he finds flat sheets of ice sandwiched between the skin and muscle 
515of the legs. There will also be a big chunk of ice in the abdominal cavity surrounding the frog's 
516organs; the organs themselves are largely dehydrated and look wizened as raisins. In effect, the frog 
517has carefully put its own organs on ice, not unlike adding ice to coolers containing human organs as 
518they're readied for transport to transplant. Doctors remove an organ, place it into a plastic bag, and 
519then place the bag in a cooler full of crushed ice so the organ is kept as cool as possible without 
520actually being frozen or damaged. 
521
522There's water in the frog's blood, too, but the rich concentration of sugar not only lowers the 
523freezing point, it also minimizes damage by forcing the ice crystals that eventually form into smaller, 
524less jagged shapes that won't puncture or slash the walls of cells or capillaries. Even all of this 
525doesn't prevent every bit of damage, but the frog has that covered, too. During the winter months of its 
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529frozen sleep, the frog produces a large volume of a clotting factor called fibrinogen that helps to 
530repair whatever damage night have occurred during freezing. 
531
532
533
534eliminating water and driving up sugar levels to deal with the cold: Grapes do it. Now we know 
535that frogs do it. Is it possible that some humans adapted to do it, too? 
536
537Is it a coincidence that the people most likely to have a genetic propensity for a disease 
538characterized by exactly that (excessive elimination of water and high levels of blood sugar) are 
539people descended from exactly those places most ravaged by the sudden onset of an ice age about 
54013,000 years ago? 
541
542As a theory, it's hotly controversial, but diabetes may have helped our European ancestors 
543survive the sudden cold of the Younger Dryas. 
544
545As the Younger Dryas set in, any adaptation to manage the cold, no matter how disadvantageous 
546in normal times, might have made the difference between making it to adulthood and dying young. If 
547you had the hunter's response, for instance, you would have an advantage in gathering food, because 
548you were less likely to develop frostbite. 
549
550Now imagine that some small group of people had a different response to the cold. Faced with 
551year-round frigid temperatures, their insulin supply slowed, allowing their blood sugar to rise 
552somewhat. As in the wood frog, this would have lowered the freezing point of their blood. They 
553urinated frequently, to keep internal water levels low. (A recent U.S. Army study shows there is very 
554little harm caused by dehydration in cold weather.) Suppose these people used their brown fat to burn 
555that oversupply of sugar in their blood to create heat. Perhaps they even produced additional clotting 
556factor to repair tissue damage caused by particularly deep cold snaps. It's not hard to imagine that 
557these people might have had enough of an advantage over other humans, especially if, like the wood 
558frog, the spike in sugar was only temporary, to make it more likely that they would survive long 
559enough to reach reproductive age. 
560
561There are tantalizing bits of evidence to bolster the theory. 
562
563When rats are exposed to freezing temperatures, their bodies become resistant to their own 
564insulin. Essentially, they become what we would call diabetic in response to the cold. 
565
566In areas with cold weather, more diabetics are diagnosed in colder months; in the Northern 
567Hemisphere, that means more diabetics are diagnosed between November and February than between 
568June and September. 
569
570Children are most often diagnosed with Type 1 diabetes when temperatures start to drop in late 
571
572fall. 
573
574Fibrinogen, the clotting factor that repairs ice-damaged tissue in the wood frog, also 
575mysteriously peaks in humans during winter months. (Researchers are taking note — that may mean that 
576cold weather is an important, but underappreciated, risk factor for stroke.) 
577
578A study of 285,705 American veterans with diabetes measured seasonal differences in their 
579blood sugar levels. Sure enough, the veterans' blood sugar levels climbed dramatically in the colder 
580months and bottomed out during the summer. More telling, the contrast between summer and winter 
581was even more pronounced in those who lived in colder climates, with greater differences in 
582seasonal temperature. Diabetes, it seems, has some deep connection to the cold. 
583
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585
586we don't know enough today to state with certainty that the predisposition to Type 1 or Type 2 
587diabetes is related to human cold response. But we do know that some genetic traits that are 
588potentially harmful today clearly helped our ancestors to survive and reproduce (hemochromatosis 
589and the plague, for example). So while it's tempting simply to question how a condition that can cause 
590early death today could ever confer a benefit, that doesn't look at the whole picture. 
591
592Remember, evolution is amazing — but it isn't perfect. Just about every adaptation is a 
593compromise of sorts, an improvement in some circumstances, a liability in others. A peacock's 
594brilliant tail feathers make him more attractive to females — and attract more attention from predators. 
595Human skeletal structure allows us to walk upright and gives us large skulls filled with big brains — 
596and the combination means an infant's head can barely make it through its mother's birth canal. When 
597natural selection goes to work, it doesn't favor adaptations that make a given plant or animal 
598"better" — just whatever it takes for it to increase the chances for survival in its current environment. 
599And when there's a sudden change in circumstances that threatens to wipe out a population — a new 
600infectious disease, a new predator, or a new ice age — natural selection will make a beeline for any 
601trait that improves the chance of survival. 
602
603"Are they kidding?" said one doctor when told of the diabetes theory by a reporter. "Type 1 
604diabetes would result in severe ketoacidosis and early death." 
605
606Sure — today. 
607
608But what if a temporary diabetes-like condition occurred in a person who had significant brown 
609fat living in an ice age environment? Food would probably be limited, so dietary blood- sugar load 
610would already be low, and brown fat would convert most of that to heat, so the ice age "diabetic's" 
611blood sugar, even with less insulin, might never reach dangerous levels. Modern-day diabetics, on the 
612other hand, with little or no brown fat, and little or no exposure to constant cold, have no use — and 
613thus no outlet — for the sugar that accumulates in their blood. In fact, without enough insulin the body 
614of a severe diabetic starves no matter how much he or she eats. 
615
616The Canadian Diabetes Association has helped to fund Ken Storey's study of the incredible 
617freezing frog. It understands that just because we haven't definitively linked diabetes and the Younger 
618Dryas doesn't mean we shouldn't explore biological solutions to high blood sugar found elsewhere in 
619nature. Cold-tolerant animals like the wood frog exploit the antifreezing properties of high blood 
620sugar to survive. Perhaps the mechanisms they use to manage the complications of high blood sugar 
621will help lead us to new treatments for diabetes. Plants and microbes adapted to extreme cold might 
622produce molecules that could do the same. 
623
624Instead of dismissing connections, we need to have the curiosity to pursue them And in the case 
625of diabetes, sugar, water, and cold, there are clearly plenty of connections to pursue.