Tuesday, December 11, 2012

Mitochondria I: Ice baths and 2,4 Dinitrophenol

Lichen, Hitler, and A Winters Night Dream

The Nazis hold a special place in the western psyche and not from atrocity alone. The Khmer Rouge murdered nearly three million in the nineteen seventies and in some ways the Cambodian genocide was more brutal than the holocaust, yet few in the western world can identify Pol Pot from a photograph. Everyone knows Hitler. The Nazis were unabashed racists and the unrepentant murderers of women, babies, and the disabled. The truly terrifying aspect that keeps goose-stepping deep into our collective unconscious is their incorruptibility. The Nazis were ideologues; no matter how twisted and sadistic their actions, these people were doing what they believed was right. The unfaltering faith the Nazis held towards their ideology doesn't absolve or even mitigate.Rather, it illustrates the power of a master orator to manipulate, be it a pastor, a teacher, or Hitler.
Of course, the Nazi belief system can't be attributed to Hitler alone. Although nearly everyone points a finger to our misunderstood misogynist friend Nietzsche, he wasn't an antisemite and he shunned nationalism. The most defining influences weren't philosophical, but rather biological. The murdering of groups considered undesirable wasn't anything new, but it had never previously been presented as a reputable science. The Nazi ideology incorporated a hierarchic form of “scientific” racism and a corresponding plan to better the world through selective breeding and selective euthanasia. The man behind all of this was the Marque De Sade of Kazan, Kostantin Mereschkowsky.
Konstantin Mereschkowsky
Konstantin was a late 19th century Russian biologist who specialized in the study of lichen. Most post-Darwinian biologists of the time emphasized mutualism and sought a biological basis for human cooperation, but Konstantin opposed this. He was amongst the earliest to broach ideas of racial hygiene and present them as a science. Isolated, these ideas aren't enough to condemn; particularly since prejudice was a social norm. But Konstantin was so much more than a small-minded antisemite. He aspired to be the savior of all humanity. He preemptively wrote instruction manuals for disciples who never came and admonished the castration of all with Jewish blood as the only path to world peace. He was given his “Marque” moniker in Saint Petersburg after he was discovered to be both a pedophile and a rapist. He considered his greatest contribution to mankind to be his novel, “A Winter Nights Dream,” which described a fascist eugenic utopia, and popularized the notion that racial superiority is based in science. Strangely, his claims regarding racial hygiene were far less contested than those he made as a biological researcher.
As a lichenologist, Konstantin was fascinated by the idea of symbiosis. A lichen consists of two organisms from different taxonomic kingdoms which rely upon each other so heavily they function as one. The fungus component provides a safe, homeostatic environment while the photosynthetic partner soaks in sunlight and assembles the sugars both will feast upon. Genetically, a fungus is more similar to humans than plants. While the sun-loving partner is often an algae, at times lichen go beyond even an inter-kingdom symbiosis. Some Lichen consist of a fungus and a cyanobacteria. Bacteria isn't even in the same domain as fungi. Bacteria is classified as a Prokaryotic, which means “before the nut,” whereas fungi are Eukaryotes or “good nuts.” There are many differences between organisms of these domains such as cell wall composition and DNA structure, but the most striking difference is that Eukaryotic cells have membrane bound organelles inside such as a nuclei.
Konstantin figured that if lichen arose from a symbiotic union between two organisms, then perhaps Eukaryotes arose from the symbiosis of two or more simpler cells. This Endosymbiotic Theory is now widely accepted and it turns out that the little power-plant organelles called mitochondria even have their own DNA. It's thought that some ancient little bacteria was engulfed by a larger cell and once inside, this little bacteria managed to continue living and reproducing. Discontent with scraping out a living as a mere intracellular parasite, this bacteria changed and became a specialist at squeezing out every last drop of energy from a fuel source.
Jews & Money: The Story of a Stereotype” identifies the “Jews are Greedy” stereotype as foundational to antisemitism. This is interesting in light of the fact that Judaism places more emphasis on generosity and honesty in business dealings than any other of the world's great religions. Mitochondria don't have these moral inhibitions and spend their entire lives consumed by avarice. Konstantin Mereschkowsky was never a savior. His ideas certainly didn't advance us any closer to a utopia. The one good lesson that Konstantin gave us is the understanding that we owe our very existence as multicellular organisms to the cooperation between a Goy cell that learned to get along with a little Jew cell.

Zeppelins and the Cities of the Sky

The oldest successful aircraft were hot-air balloons. The first documented flight took place in 1709, 

although some speculate that the Chinese and perhaps even the Nazca culture of Peru were using hot-air balloons far earlier. The underlying principle is simple: Hot-air in a balloon has less density than the ambient air without and thus weighs less. Once the vehicles total weight is less than that of the air it displaces, the balloon floats off into the sky. Buoyancy can also be achieved using lighter than air gasses such as helium or hydrogen. The world's first airline was the “German Airship Travel Corporation” which used enormous Zeppelins and successfully carried over 34,000 passengers prior to World War I, and this same corporation provided the first transatlantic passenger flights of any kind following the war. 
The great spire of the Empire State Building was initially designed as a terminal for such craft; however, it proved too dangerous due to updrafts. Dirigibles such as the Zeppelins are highly efficient at carrying both passengers and cargo, and the decline in their use was primarily due to a few highly publicized accidents such as the Hindenburg.
Cloud Nines
      American engineer and futurist Richard Buckminster Fuller, proposed taking the principle of lighter than air flight much, much further. Fuller is famous for his design and construction of immense geodesic domes, such as the “Spaceship Earth” structure at the EPCOT center.  The advantage of these dome structures is that if designed properly, using a principle Fuller called “Tensegrity”, the durability of the structure actually increases as it's scaled to larger sizes. Fuller proposed the construction of geodesic spheres with a mile diameter. By heating air within by a mere few degrees to provide bouyancy, these “Cloud Nines” would be able to float through the sky with entire cities of people within. The most amazing part? It would have worked.
      When the size of an object increases the surface area of the object decreases relative to the volume. To find the surface area of a cube we square the length (L2) and multiply by six. To find the volume, we cube the length (L3). A 1mm cube has a surface area of 6mm2 and a volume of 1mm3. An 8mm cube on the other hand has a surface area of 384mm2 and a volume of 512mm3. The volume of a sphere relative to its surface area scales up even faster. It's easy to see that a very large balloon requires less effort to get off the ground than a smaller one because it displaces so much more ambient air and has less actual surface relative to its contents. Buckminster Fuller's Cloud Nines could easily house thousands along with all the accoutrement necessary for life.
White Blood Cell and Bacteria
The Surface-to-volume ratio has implications at a microscopic scale as well. Organisms such as bacteria are always very small, typically only a few micrometers in length. They are incredibly diverse in how they acquire energy. Many feed on sunlight, others on the organic compounds of other organisms. Some can even produce energy from inorganic substrates such as Iron or Sulfur. 
They are all restricted in size though because they require enough surface area to collect their energy source. As a bacteria increases in size, the surface area of its cell wall becomes inadequate to supply the volume within.
This limitation became moot with the rise of our friend the mitochondria. Mitochondria increase the energy yield from fuels in some cases by more than an order of magnitude. The most common pathway used by 
 bacteria to produce ATP (The energy of all life) is glycolysis. This pathway breaks down one glucose molecule and yields a paltry 2 ATP. The cells of plants and animals also use glycolysis, but then use the other products of the pathways, pyruvate and NADH in further pathways which yield an addition 36 or so ATP. Due to this vastly increased yield, Eukaryotic cells can be one hundred times as large and weigh a thousand times as much. 
Thomargarita Namibiensis - Largest known Bacteria
Xenophore - Largest known Single Celled Eukaryote

The largest known bacteria, Thiomargarita namibiensis was discovered in ocean sediment from the continental shelf of Namibia and can grow to a whopping 750 micrometers. This is astounding enormous for a bacteria; it can even be seen with the unaided eye. Of course it pales in comparison to the largest single-celled eukaryote, Xenophyophore, which lives 6 miles beneath the ocean and grows as large as 20 centimeters. 20 cm is 7.9 inches... almost 2 inches longer than the average penis according to a 2007 study. Bacteria may not have penis  envy, but I'm sure they hang their heads in the gym shower when the protists swim by with big ol' mitochondria flopping about.

Hibernating Bears and Babies

Neonates are at particulate risk from hypothermia. As we explored above, the surface area of a smaller organism is much greater relative to its volume regardless of whether we are discussing cells or bears; thus, newborns lose heat at a phenomenal rate. Once again, it's mitchondria that save the day.
Mitochondria are found in all human cells, but are particularly abundant in Brown Adipose Tissue (BAT). Large deposits of BAT are found in newborns and in animals that hibernate because it functions to produce heat through a process called non-shivering thermogenesis. A mitochondria has both an inner and an outer membrane. Hydrogen ions get pumped into the space between. They want to escape from the inter-membranous space due to strong chemical and electrical gradients. Enzymes harness this energy in order to make ATP--the energy of life.
 The mitochondria of BAT functions differently though due to the protein Thermogenin. When activated, these thermogenin channels allow the ions to escape rapidly. No ATP is yielded, but large amounts of heat are produced. BAT was previously thought to be active only in hibernating animals and infants, but a 2009 study using PET Scans revealed that BAT deposits remain in the upper chest and necks of adults.
 Previous studies hadn't taken into account that these cells have a very low metabolic function unless exposed to cold and thus wouldn't uptake the contrast. A later study comparing the enzymatic activities of Northern Finnish men who worked outdoors with men who worked indoors confirmed this. Active BAT was found only in the men who worked outside in the cold.
Cells use glucose to produce ATP preferentially. Glucose is first broken down, and then some of the products of that reaction are used by mitochondria. When ATP demand is higher than what can be supplied by glucose, mitochondria can use a process called beta-oxidation to break down lipids to make ATP. In the case of BAT, it's full steam ahead. The system which pumps the hydrogen ions into the inter-membranous space works at full capacity trying to create a concentration gradient, but the ions just keep slipping back out making heat. These studies have also shown that thermogenin activity after exposure to cold remains increased for three days, and the increased metabolic rate of these cells can still be detected for up to three weeks. BAT uses fatty acids so quickly that additional fatty acids are recruited from the large lipid reservoirs of “normal” white adipocytes. BAT quite literally burns fat and at a phenomenal rate.

Ice Baths and Fat Loss

One way we can harness the metabolism boosting power of BAT is with ice baths. Ice baths are cheap and easy but can be quite uncomfortable. My experiences have been glowing overall, but it's important to discuss a few misconceptions. For one, there is little evidence that ice baths prevent delayed onset muscle soreness from exercise. Some swear by it, but the studies are overall inconclusive. Also, ice baths don't cause acute 
weight loss anymore than one can expect to lose a few pound from a single session on a treadmill. While cold exposure does up-regulate the metabolic activity of BAT, it causes a temporary decrease in overall metabolism. In fact, it's used medically for exactly that reason. After cardiac arrest, therapeutic hypothermia has been shown to improve neurological outcomes because it decreases cellular activity and oxygen use. So acutely, it slows down one's metabolism, but provides a longer term increase. One big proponent of ice baths is author Tim Ferriss, who presented it amongst a few other weight loss technique on the Doctor Oz show. I like this guy Ferris. He tried for a twenty second explanation of how ice baths and 
For real Oz?
 cold assist in weight loss before Dr. Oz took over and dropped the ball. Oz went off on a tangent using a short ladder and a tall ladder as a metaphor for how a lower body temperature will cause you to immediately burn lots of calories to stay warm, which is totally inaccurate. The best part was watching Ferriss strive not to roll his eyes.
Because thermogenin activity is most increased for three days following cold water immersion, two baths a week is adequate to get the full effect. Taking an ice bath is simple. One buys a couple of bags of ice from the nearest store, dumps them into a tub, fills the tub and gets in. Each step does have a few additional considerations:

 Getting your ice
  Bags of ice are actually quite pricey depending on where you go. One convenience store near me sells five   
pound bags of ice for 3 dollars each. If I buy four per bath, and take two ice baths a week, this equates to around ninety six dollars a month, around triple the price of a gym membership. Most refrigerators are equipped with an ice maker, but it's actually quite a lot of work to keep dumping the bin or trays into a bag. The option that I've found most effective is the use of square, one gallon Crystal Geyser jugs of water. I can fit ten of these into my freezer at once, they are reusable, and far cheaper than the little blue ice packs. They even have handles. The only disadvantage I've found is that it takes longer for the water to cool adequately. I have to wait around ten minutes before climbing into the bath. Because I travel for work, I've also found the giant ice makers at hotels to be effective, although you do get some funny looks after filling up the same cooler two or three times.

     Filling the tub
    The amount of ice one uses depends on the temperature sought. Few studies used temperatures lower than 50 degrees F. I sure wish I'd known that the first few times, as I started out by nearly packing myself in ice. You don't need to be Professor Sugarman to take ice baths. In fact, some studies suggest that a merely cool bath is equally effective with temperatures as high as 75 degrees F. I've tried both, and I personally feel that a colder bath imparts a greater increase in metabolism. I feel hungrier, better, more alive following a really cold immersion, but of course these feelings are in no way quantitative. A cheap kitchen thermometer (Advertising Potential Here) should cost you around twenty dollars, and you can find out if your experience matches mine. 

     Getting In
    I've read about people using booties and rubber straps and such to avoid frostbite, but I haven't found it necessary. The objective isn't to suffer, so it's completely acceptable to wear a t-shirt and boxers. These will prevent direct exposure to the ice blocks which float at the top of the water. Some studies say the most important part is lowering the core body temperature, while others claim that it's peripheral cooling specifically near the upper chest, shoulders and back that are of the utmost importance. This distinction is important because it determines how long one remains in the bath. Peripheral cooling takes around ten minutes whereas those seeking to drop their core temperature often remain submerged as long as twenty. I have only used the twenty minute regimen at this point and can't comment on whether it's any better than ten. If anyone sets out to compare these variables I'd love to hear about it. If one is attempting to drop their core temperature, the goal shouldn't be lower than 95 degrees F. 90-95 is considered to be mild hypothermia which can result in various types of sympathetic nervous system symptoms such as an increase in blood pressure, heart rate, and difficulty breathing. Those predisposed to cardiac problems should at the very least consult their physician if not forgo cold water immersion altogether. There are a lot of other conditions and factors that make dropping one's body temperature a bad idea, ranging from asthma to sickle cell anemia. If you have any medical conditions, you should probably speak with your physician prior to trying... well pretty much anything. 

    Expected Outcomes
The immediate effects to expect include shivering, an increase in heart rate, and significant peripheral vascular constriction. Your hands and feet will likely get a bit numb and depending on how cold the water is, you may have a decrease in muscle coordination and movement can become labored. If so, it's time to get out. You're likely dropping your temperature too far. I find ice baths are best performed after an extended workout. The cold decreases inflammation and swelling and overall feels great. Ice baths are great at decreasing pain from an injury. Although research hasn't shown a decrease in delayed onset muscle soreness related to working out, there have been a few studies which have shown a decrease in recovery time needed between training sessions.
The long term effect we're seeking is of course an increase of one's overall metabolic rate. Unfortunately, I haven't been able to find a single study on the long-term effects of repeated cold water immersion. I've read a variety of claims which range from losing a few pounds a month to as much as five pounds a week. The problem is that we have no way of assessing the variables. For example, I have always lost a good amount of fat while on a regimen that included ice baths; however, I also find myself eating better so that all that coldness isn't wasted. The most objective information that can be ascribed to periodic cold water immersion is a 2009 study, which found that cold activated BAT exhibits an increase in glucose uptake by a factor of 15. The amount of BAT varies from one individual to another so we can't equate this to a total amount of calories burned. It's certain though that by activating our brown adipose tissue reservoirs to use 15 times as much glucose in a process that results in heat rather than being stored, one can lose a few pounds each week. 

A More Explosive Path to Weightloss: 2,4, Dinitrophenol

"Whatever happens, the flame of the French resistance must not be extinguished and will not be extinguished.

During the Battle of Montcornet, commander Charles De Gaulle led a unit of 85 tanks into battle against the German 1st Panzer division. De Gaulle's forces consisted of two models of tank. The Char D2 had a small engine, a weak transmission, and its tendency to overheat created a constant demand for maintenance. The older Char B1 tank was well armored and reliable, but because it had originally been designed as a self-propelled gun, it was slow and consumed its fuel quickly. The considerably larger German forces consisted of the robust Panzer IV, and yet after the battle De Gaulle had lost a mere 23 tanks to the Germans' 100. This was one of the only French successes against the Germans during the Battle of France, and De Gaulle was promoted to Brigadier General. He escaped to Britain during the occupation and gave a speech broadcast throughout Europe proclaiming that both the Germans and the French puppet government would be crushed. He became the leader of the French Resistance and was considered the leader of the French government in exile.
De Gaulle was also nearly intolerable in his dealings with both the British and the United States. He insisted on retaining full freedom of action on behalf of the French even when faced with having ally support cut. De Gaulle knew something that the Germans had overlooked: A good proportion of the French, men and women alike, were just as patriotic, proud, and haughty as De Gaulle himself, and they knew how to make bombs.
Prior to even World War One, the French had a significant munitions manufacturing industry. 
2,4 Dinitrophenol
At one facility which manufactured the explosive 2,4 Dinitrophenol (DNP), a number of workers died after exposure to the compound. They had some startling symptoms such as highly elevated body temperatures, profuse sweating, and had experienced a rapid loss of weight over a few weeks to the point of excessive thinness. It turns out that DNP can function in a manner very similar to the thermogenin proteins in brown adipose tissue. It allows the ions within the mitochondrial intermembranous space to escape and produce heat. In the case of DNP though... it's in all of your mitochondria, in all of your cells. Incredible amounts of heat can be produced. In cases of excessive exposure, the eyeballs glaze over with cataracts, body temperature can 
 rise to over 115 degrees F, and the body cooks from within even after brain death. Does this sound promising to you? Through the 1930s DNP was marketed as an aid to weight loss. It works better than anything being marketed today and used conservatively DNP can strip fat from the obese and give them a beach body in as little as a month. This may sound like one of the unrealistic sales pitches that air right before the color test pattern, but it's all 100% percent true. The downsides of DNP are that it's illegal to ingest, can be very uncomfortable to use, and did I mention it can kill you?
If one were, and I'm in no way promoting or suggesting a person should ever consider such a potentially deadly augment to one's metabolism... but if one were to take DNP, there is one other benefit: immunity to the cold. DNP causes such a drastic increase in heat production that one can easily run nude through the woods in a snow storm. Imagine the look on the ski lift attendant's face when you're wearing a pair of running shorts to go night boarding. Yes, this is how much heat your body generates.
Availability and Dosage
2,4, DNP isn't all that difficult to get. There are restrictions, and it's not legal if intended for ingestion. It can be purchased from a chemical supply house rather easily in small quantities. I'm not going to post a link to any in this case because if you don't already have experience ordering from chemical supply houses then I doubt your ability to safely measure out the appropriate amounts.
The doses most bodybuilders use range from 200mg to 500mg three times a day. You'd definitely want an accurate high quality scale to measure it out as the distance between therapeutic and lethal isn't very high with DNP. DNP isn't metabolized quickly and the time it takes differs from one person to another, so serum levels continue to increase over time even with a steady dose. Those who use DNP often advise a 2-3 week cycle. There haven't been too many DNP related deaths in the last twenty years, although there have been a significant number of hospitalizations. The two deaths that stand out were non-weight lifters who got their DNP from Mexico and didn't know what they got themselves into. Neither realized how severe the consequences can be and lied upon admittance to the emergency room. The physicians didn't have enough information to treat them and so they died. This is quite a different outcome from the weightlifters who realized they were having a problem, went to the hospital and calmly told the physician that they had taken too much 2,4 Dinitrophenol and needed the muscle relaxant Dantrolene to prevent malignant hyperthermia.
I'll admit that upon first researching DNP I was pretty fascinated, and I considered trying it, but after further consideration I realized that it didn't fit my personal criteria. DNP can help a person lose weight rapidly but comes with a lot of potential long-term problems. Those who take DNP are primarily interested in looking good, and while I can certainly appreciate aesthetics, the amount of risk I'm willing to venture is much lower than for other augments that expand one's capabilities. Perhaps one day, if I ever have the opportunity for a trip to the arctic, I'd give it a try for the purpose of cold tolerance. Cold water immersion, on the other hand, causes the same weight loss safely. Being at a healthy weight can extend one's life, is aesthetically pleasing, and has even been shown to positively effect cognitive ability. As such, ice baths are an augmentation worthy of consideration.

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