In my last column (“The Problem with Proteins”), I described the problem with protein folding. Today I wanted to describe one of the major efforts underway to solve this problem. And believe me, this really is a group effort. This effort uses a process called Distributed Computing.
Labs at Stanford University, the University of Pittsburg, the University of California at San Francisco, Notre Dame, California State University Long Beach, and the Mediterranean Institute for Life Sciences in Croatia use computers around the world to model and predict protein folding. It is a method of computer processing that runs different parts of a program, or different sets of data for the same part of the program, simultaneously on more than one computer. These individual computers, working at the same time on different parts of the same project, then share their results. This results in much greater computing power than any individual computer can provide.
Okay, so these labs use computers around the world to do the work. What work? What are these computers solving?
Computers are often used to model possible ways for a protein to fold. They can run through the innumerable possible folds and configurations for a given stretch of amino acids in a step-by-step process. At each step, it can analyze how likely it is that the protein folds in that way, based on biophysical and biochemical criteria. Step-by-step, the computer can work its way through from the raw amino acids to what is the most physically likely structure for that sequence. This takes a lot of computing power.
One standard modern computer can simulate how a protein will fold in a nanosecond (that’s 1 billionth of a second) in one day. That’s 1 billionth of a second of folding done in 1 day of work. Unfortunately, proteins fold on an average of around 10,000 nanoseconds. That would take 10,000 days for one computer to analyze a protein from start to finish. Alternatively, if you could link 10,000 computers and have them all run different parts of the prediction, you could finish in 1 day! (I know which method I’d prefer.)
Okay, so by coordinating all of these computers around the world, we can dramatically speed up the predictions and modeling of protein folding. Why is this helpful? Scientists hope that this will allow them to discover the "first principles" of protein folding. Knowing these first principles will allow them to (a) predict what final shape any given protein sequence will ultimately form, (b) make artificial proteins that form a certain shape and thus perform a certain task, and (c) determine why some proteins in our bodies dramatically misfold with dire consequences. There are numerous examples of how misfolding proteins cause human disease, including Huntington's diseases, Alzheimer's disease, and the prion disease Creutzfeldt-Jakob. Figuring out why these diseases are associated with dramatically misfolded proteins is one of the major goals of many protein folding scientists in the world.
If you are interested in checking out the software involved in this project, or even adding your computer to their work, you can read more about them at:
http://folding.stanford.edu/
Tuesday, October 30, 2007
Thursday, October 25, 2007
The Problem with Proteins
Proteins are one of the basic building blocks of life. They are the workhorses that accomplish most of the physiology of every cell, including DNA replication, cell division, energy production, metabolism, and degradation of cellular waste, to name a few examples. There are multiple thousands of different proteins in each cell, and each one is distinct from every other by virtue of its shape.
Wait, what do you mean, a protein’s shape? Well, proteins are much like keys. They have a very specific 3-dimensional structure, which must be maintained for them to do their jobs. A protein shaped for one job will not work for another job, just as a key for one lock will not open a different one. And if a protein gets warped out of shape, it will no longer work properly, much as a bent key will no longer open its lock. We know how keys get their shape – go to any home improvement store and you can see the key-making machine. But how do proteins get their shape?
Would it surprise you to learn that this simple sounding question is actually one of the biggest unsolved questions plaguing biologists today? How proteins achieve their final shape is referred in science circles to the problem of protein folding. And it is a thorny problem indeed.
To understand why this is such a tough question, let’s talk first about how proteins are made. Imagine that you have lots of different beads that you can string together to make a necklace. These beads are connected together end-to-end, and each necklace that you make will look different from each other depending on which beads you choose. Proteins are the same way. The beads are called amino acids; there are 20 standard amino acids in your cells that can be strung together to make thousands of different proteins. The standard amino acids are all different from each other by several biochemical criteria. Some are large, others are small. Some have positive charges, and others have no charge at all. Some are really simple, and others are very complex. Whatever their characteristics, these amino acids are strung together by a “machine” in the cell called the ribosome. Once the amino acids are connected together, though, the process of making the protein is only halfway done .
Now that the protein is in its raw form, it must fold itself into the final 3-dimensional shape. The final shape is enormously complex, usually comprised of different substructures within the overall shape. The final shape directly depends on the linear string of amino acids. But the big question is this: how does the protein know how to do this? How does it know how to take this end-to-end string of different amino acids and twist, turn, fold and bond to itself in such a way as to form the final, complex structure?
Here’s what we know about protein folding:
1. We know that the folding of a protein will depend largely on its amino acids. Let me give you a few examples. Amino acids can be hydrophobic (“water-fearing”) or polar (“water-loving”). Hydrophobic amino acids do not like contact with water, while polar ones prefer a watery environment. Hydrophobic amino acids, therefore, like to be tucked away into the inside of the protein, where there is no water. Polar amino acids like to be on the surface of the protein, where they will encounter water a lot. Another example depends on the size of the amino acids. Some are extremely bulky, and simply cannot fit into tight pockets. They must be folded in a place with lots of room. Thus the structure of a protein is limited by the physical properties of its amino acids.
2. We know that there are several kinds of folds, or substructures, that proteins can adopt in their overall structure. To understand this, imagine the engine of a car. It has an overall structure. But the individual parts of the engine (the transmission, the cooling system, the fuel injection) have their own shapes, as a subset of that larger structure. The same is true with proteins. Proteins can have some part of themselves fold into an alpha helix (kind of like a slinky), while others fold into a beta sheet (like an accordion fan). These smaller bits then fold together in larger structures to form the overall protein shape.
3. We know the structures of many different kinds of proteins. These have been determined experimentally (and this is actually a problem that I will talk about below).
4. We know that proteins can fold extremely quickly (sometimes as fast as a millionth of a second).
That sounds great, right? Yes, but there are also lots of things we don't know about protein folding. Here are some examples:
1. We cannot predict what the final shape will be of a given stretch of amino acids. So far, the only way we can know the structure of a protein is to solve it biophysically. This is done mostly with x-ray crystallography. But this is difficult, expensive, and doesn’t always work. As a result, we do not know the structure of the majority of the innumerable proteins in the world.
2. We do not know what steps most proteins take to form the final shape. It is a multi-step process, and requires the help of lots of other cellular machinery. But most of those steps are a mystery.
3. We don’t know why some proteins fail to fold properly. In fact, sometimes they misfold so badly that the only thing that cell can do is destroy them and start over.
4. We don’t know how to take a predetermined shape and artificially produce a protein to fold into that shape. This is really the converse of problem number 1. We cannot predict a structure based on certain amino acids, nor can we predict amino acids to give a certain structure.
5. We don't know how on earth proteins fold so fast.
The biggest problem facing protein folding experts right now is problem #1. We simply are unable to predict what a protein will look like, even if we know its sequence of amino acids. This is actually a pretty big problem for molecular biologists. We know lots of protein sequences. But we'd be able to conduct much better research if we knew what shape that protein adopted. Again, imagine a protein to be like the engine of a car. If a mechanic needs to fix the engine, simply having a list of the parts that engine contains won't be much help. He needs to know what the engine looks like to have any success.
Okay, I’ve given you the problems we have with protein folding. The good news is that there are lots of scientists working to solve these very problems. And now that I ’ve laid the groundwork for the problem, I’ll come back to this in another post and discuss how some scientists are trying to solve these problems.
Wait, what do you mean, a protein’s shape? Well, proteins are much like keys. They have a very specific 3-dimensional structure, which must be maintained for them to do their jobs. A protein shaped for one job will not work for another job, just as a key for one lock will not open a different one. And if a protein gets warped out of shape, it will no longer work properly, much as a bent key will no longer open its lock. We know how keys get their shape – go to any home improvement store and you can see the key-making machine. But how do proteins get their shape?
Would it surprise you to learn that this simple sounding question is actually one of the biggest unsolved questions plaguing biologists today? How proteins achieve their final shape is referred in science circles to the problem of protein folding. And it is a thorny problem indeed.
To understand why this is such a tough question, let’s talk first about how proteins are made. Imagine that you have lots of different beads that you can string together to make a necklace. These beads are connected together end-to-end, and each necklace that you make will look different from each other depending on which beads you choose. Proteins are the same way. The beads are called amino acids; there are 20 standard amino acids in your cells that can be strung together to make thousands of different proteins. The standard amino acids are all different from each other by several biochemical criteria. Some are large, others are small. Some have positive charges, and others have no charge at all. Some are really simple, and others are very complex. Whatever their characteristics, these amino acids are strung together by a “machine” in the cell called the ribosome. Once the amino acids are connected together, though, the process of making the protein is only halfway done .
Now that the protein is in its raw form, it must fold itself into the final 3-dimensional shape. The final shape is enormously complex, usually comprised of different substructures within the overall shape. The final shape directly depends on the linear string of amino acids. But the big question is this: how does the protein know how to do this? How does it know how to take this end-to-end string of different amino acids and twist, turn, fold and bond to itself in such a way as to form the final, complex structure?
Here’s what we know about protein folding:
1. We know that the folding of a protein will depend largely on its amino acids. Let me give you a few examples. Amino acids can be hydrophobic (“water-fearing”) or polar (“water-loving”). Hydrophobic amino acids do not like contact with water, while polar ones prefer a watery environment. Hydrophobic amino acids, therefore, like to be tucked away into the inside of the protein, where there is no water. Polar amino acids like to be on the surface of the protein, where they will encounter water a lot. Another example depends on the size of the amino acids. Some are extremely bulky, and simply cannot fit into tight pockets. They must be folded in a place with lots of room. Thus the structure of a protein is limited by the physical properties of its amino acids.
2. We know that there are several kinds of folds, or substructures, that proteins can adopt in their overall structure. To understand this, imagine the engine of a car. It has an overall structure. But the individual parts of the engine (the transmission, the cooling system, the fuel injection) have their own shapes, as a subset of that larger structure. The same is true with proteins. Proteins can have some part of themselves fold into an alpha helix (kind of like a slinky), while others fold into a beta sheet (like an accordion fan). These smaller bits then fold together in larger structures to form the overall protein shape.
3. We know the structures of many different kinds of proteins. These have been determined experimentally (and this is actually a problem that I will talk about below).
4. We know that proteins can fold extremely quickly (sometimes as fast as a millionth of a second).
That sounds great, right? Yes, but there are also lots of things we don't know about protein folding. Here are some examples:
1. We cannot predict what the final shape will be of a given stretch of amino acids. So far, the only way we can know the structure of a protein is to solve it biophysically. This is done mostly with x-ray crystallography. But this is difficult, expensive, and doesn’t always work. As a result, we do not know the structure of the majority of the innumerable proteins in the world.
2. We do not know what steps most proteins take to form the final shape. It is a multi-step process, and requires the help of lots of other cellular machinery. But most of those steps are a mystery.
3. We don’t know why some proteins fail to fold properly. In fact, sometimes they misfold so badly that the only thing that cell can do is destroy them and start over.
4. We don’t know how to take a predetermined shape and artificially produce a protein to fold into that shape. This is really the converse of problem number 1. We cannot predict a structure based on certain amino acids, nor can we predict amino acids to give a certain structure.
5. We don't know how on earth proteins fold so fast.
The biggest problem facing protein folding experts right now is problem #1. We simply are unable to predict what a protein will look like, even if we know its sequence of amino acids. This is actually a pretty big problem for molecular biologists. We know lots of protein sequences. But we'd be able to conduct much better research if we knew what shape that protein adopted. Again, imagine a protein to be like the engine of a car. If a mechanic needs to fix the engine, simply having a list of the parts that engine contains won't be much help. He needs to know what the engine looks like to have any success.
Okay, I’ve given you the problems we have with protein folding. The good news is that there are lots of scientists working to solve these very problems. And now that I ’ve laid the groundwork for the problem, I’ll come back to this in another post and discuss how some scientists are trying to solve these problems.
Wednesday, October 24, 2007
The best time for sleeping
I just spent an interesting few days at the annual meeting of the National Association of Science Writers. At the meeting, we learned a lot about a wide range of topics, not the least of which was science. I was fortunate enough to have lunch one day with a sleep researcher from Washington State University. And, if you recall from some of my previous posts, I think that sleep is a really fascinating scientific topic! One thing I learned from this sleep scientist is that everyone has an optimal time of the day in which to fall asleep. This depends largely on your circadian rhythms.
I bet that you've heard of circadian rhythms before - but do you know what they really are?
Circadian rhythms are 24-hour (roughly) cycles that occur in the physiology of all living beings - animals, plants, and even bacteria. Human circadian rhythms are those cyclical changes that occur in our bodies during a 24 hour period. The rhythms are controlled by something called the superchiasmatic nucleus (or SCN), which is a pair of structures in your brain about the size of a pinhead. The SCN, containing around 20,000 neurons, sits in the brain just above where your optic nerves cross. Different levels of light that hit your eyes are translated into a signal for the SCN, which then regulates multiple physiological processes. These processes mostly relate to the sleep/wake cycle - body temperature, blood pressure, brain activity and hormone secretion. In particular, when it gets dark, our brains signal the secretion of melatonin, a hormone that makes us feel sleepy.
Now, while our circadian rhythms are regulated by the light/dark cycle around us, they do not absolutely require it! Animals kept in total darkness for an extended period of time will have what is called a "free running" rhythm - the rhythm is still there, it's just not dependent on light levels. In fact, blind subterranean mammals (such as blind mole rats) maintain their endogenous clocks without any external stimulus. (That's good news for those of us who live far enough north that the winter months have significantly more darkness than daylight.)
Even for blind rodents living in the dark, circadian rhythms help determine the optimal time for an organism to go to sleep. And since everyone's circadian rhythm is different from everyone else, so is their best sleep time. How do you determine what your ideal bedtime is? The answer is called a sleep latency test.
A sleep latency test is based on the premise that, as you get sleepier, the amount of time it takes you fall asleep decreases. If you were to lay down in a dark room with nothing to do, eventually you will fall asleep. How long it takes you to do so is called your sleep latency. If you are wide awake, it will take you a long time; if you are sleepy, it won't take very long at all. Your ideal bed time is that time of day when you have the shortest sleep latency. If you try to fall asleep before then, it will take you a longer time. Interestingly enough, if you stay awake past that point, it will also take you longer!
If you want to find out your ideal time to sleep, this sleep scientist said that conducting a sleep latency test is very easy to do (though you need someone to help you). For a few nights, go to bed at different times (8:00pm, 9:00pm, 10:00pm and 11:00pm, for example). Have someone monitor you to see how long it takes you to fall asleep. Whenever you fall asleep the fastest is the closest optimal bed time for your circadian rhythm. Of course, this test must be done when you are not sleep deprived, or that will skew the results. (If you're tired enough, it may not matter what time you lie down, you might go right to sleep regardless!)
I believe that I know roughly my optimal bed time, but I would be interested to try this to see whether I'm right or not. Does anyone else want to try it?
I bet that you've heard of circadian rhythms before - but do you know what they really are?
Circadian rhythms are 24-hour (roughly) cycles that occur in the physiology of all living beings - animals, plants, and even bacteria. Human circadian rhythms are those cyclical changes that occur in our bodies during a 24 hour period. The rhythms are controlled by something called the superchiasmatic nucleus (or SCN), which is a pair of structures in your brain about the size of a pinhead. The SCN, containing around 20,000 neurons, sits in the brain just above where your optic nerves cross. Different levels of light that hit your eyes are translated into a signal for the SCN, which then regulates multiple physiological processes. These processes mostly relate to the sleep/wake cycle - body temperature, blood pressure, brain activity and hormone secretion. In particular, when it gets dark, our brains signal the secretion of melatonin, a hormone that makes us feel sleepy.
Now, while our circadian rhythms are regulated by the light/dark cycle around us, they do not absolutely require it! Animals kept in total darkness for an extended period of time will have what is called a "free running" rhythm - the rhythm is still there, it's just not dependent on light levels. In fact, blind subterranean mammals (such as blind mole rats) maintain their endogenous clocks without any external stimulus. (That's good news for those of us who live far enough north that the winter months have significantly more darkness than daylight.)
Even for blind rodents living in the dark, circadian rhythms help determine the optimal time for an organism to go to sleep. And since everyone's circadian rhythm is different from everyone else, so is their best sleep time. How do you determine what your ideal bedtime is? The answer is called a sleep latency test.
A sleep latency test is based on the premise that, as you get sleepier, the amount of time it takes you fall asleep decreases. If you were to lay down in a dark room with nothing to do, eventually you will fall asleep. How long it takes you to do so is called your sleep latency. If you are wide awake, it will take you a long time; if you are sleepy, it won't take very long at all. Your ideal bed time is that time of day when you have the shortest sleep latency. If you try to fall asleep before then, it will take you a longer time. Interestingly enough, if you stay awake past that point, it will also take you longer!
If you want to find out your ideal time to sleep, this sleep scientist said that conducting a sleep latency test is very easy to do (though you need someone to help you). For a few nights, go to bed at different times (8:00pm, 9:00pm, 10:00pm and 11:00pm, for example). Have someone monitor you to see how long it takes you to fall asleep. Whenever you fall asleep the fastest is the closest optimal bed time for your circadian rhythm. Of course, this test must be done when you are not sleep deprived, or that will skew the results. (If you're tired enough, it may not matter what time you lie down, you might go right to sleep regardless!)
I believe that I know roughly my optimal bed time, but I would be interested to try this to see whether I'm right or not. Does anyone else want to try it?
Wednesday, October 17, 2007
Those red hot chili peppers (no, not the band)
Are you a fan of spicy food, or do you steer clear of anything with spicy zest to it? I used to be reluctant to order anything remotely spicy in Thai restaurants, I would not cook with any peppers other than bell peppers, and merely the thought of deliberately adding cayenne pepper to my chili made my eyes water! However, over the last several years, my tolerance for spicy food has increased significantly. In that time, I’ve grown more familiar with a variety of peppers, many of which are now used regularly in my cooking. Ranging from jalapenos to habaneros, pepperocinis to scotch bonnets, and chilis to cayennes, peppers are arguably the biggest source of spiciness in the food that we eat.
So here’s a question for you - do you know why peppers are spicy?
The main culprit in the spiciness of peppers is a compound called capsaicin (pronounced kap-say-sin). Actually, capsaicin is a type of capsaicinoid. There are several capsaicinoids in pepper plants (which, incidentally, belong to the genus Capsicum). Capsaicin is the most abundant (accounting for about 70% of the total capsaicinoids), followed by dihydrocapsaicin (which makes up around 20%). There are also three minor related compounds (with fairly complex names), which total approximately 10% of the capsaicinoid load. Both capsaicin and dihydrocapsaicin are about twice as potent as the 3 minor compounds in terms of irritation. They are particularly strong against mucous membranes, including your mouth, nose and eyes. That means that, when you eat a pepper and your mouth burns, your eyes water, and your nose runs – you have mostly capsaicin to thank.
Capsaicin is produced by pepper plants at glands located at the junction of the placenta and the pod wall. (That’s the white “ribs” that run down the inside of a pepper.) As the peppers develop, it gets dispersed unevenly throughout the pepper, becoming heavily concentrated in the seeds. The seeds themselves do not produce capsaicin, but they are a major storage point for it. (So if you ever want to eat a pepper but don’t want all the spice, simply remove the seeds and the white ribs. That won’t get rid of all the spice, but it will eliminate most of it.) Capsaicin itself is not used as a metabolite for the plants, but it is theorized to be useful as a defense mechanism. Mammals generally will not eat peppers, presumably because they don’t like it when their mouths hurt! The peppers are eaten mostly by birds. For birds, capsaicin is an analgesic rather than an irritant - in other words, it acts as a pain killer, not a pain producer. It does them no harm, allowing them to pass the seeds through and deposit them for plant dispersal.
Capsaicin is an interesting molecule. For one thing, it is incredibly stable. It is unaffected by either cold or heat, and retains its spicy potency despite cooking or freezing. That means that you cannot cook the spiciness out of peppers. Another interesting fact is that capsaicin is not very soluble in water, but it is soluble in oils, fats and alcohols. Have you ever eaten something really spicy, then tried to quench the burning by drinking water? I bet it didn’t work. That’s because capsaicin does not dissolve well in water, so drinking water will not wash it off your tongue. You’d be better off drinking a glass of milk, which contains casein, a fat-loving compound that dissolves capsaicin much like soap dissolves grease.
Pure capsaicin is an incredibly powerful compound. At a cellular level, an exposure to capsaicin triggers calcium ions to flood into the affected cell, ultimately triggering a pain signal to the next cell. This is very similar to what happens during a thermal burn. A single milligram (which weighs 1/1000th as much as a paperclip) would be enough to blister the skin on your hand. When pure, it can only be handled by chemists wearing full body protection, including a closed hood to prevent the inhalation of the powder. Lloyd Matheson, a pharmaceutical chemist from the University of Iowa was reported to have once inhaled pure capsaicin accidentally; according to him, “It’s not toxic, but you wish you were dead if you inhale it.” Capsaicin also features prominently in pepper spray, which is a strong irritant for all of the mucous membranes on your face (eyes, nose, mouth, and respiratory system.)
But don’t worry. There isn’t enough capsaicin in peppers to be dangerous – only spicy! The spiciness of peppers is measured in terms of Scoville Heat Units, which is parts per million of capsaicinoid content. At the extremes of the scale are pure capsaicin and bell peppers. Pure capsaicin has a Scoville Heat Unit score of 16 million, while bell peppers have a score of 0. Here are the scores of other common peppers:
Habaneros: 100,000 – 300,000
Scotch Bonnets: 100,000 – 250,000
Thai Peppers: 50,000 – 100,000
Cayenne Peppers: 10,000 – 30,000
Jalapenos: 2,500 – 5,000
Pepperocinis: 100 – 500
As I said, I’ve gradually been increasing my tolerance for spiciness. Of course, I’m not munching on habanero peppers for an afternoon snack, but I can handle jalapenos, cayenne peppers, and even very small levels of Thai peppers. Of course, now that I know how potent Scotch Bonnet peppers are, I may have just reached my limit on the peppers I’m willing to try!
So here’s a question for you - do you know why peppers are spicy?
The main culprit in the spiciness of peppers is a compound called capsaicin (pronounced kap-say-sin). Actually, capsaicin is a type of capsaicinoid. There are several capsaicinoids in pepper plants (which, incidentally, belong to the genus Capsicum). Capsaicin is the most abundant (accounting for about 70% of the total capsaicinoids), followed by dihydrocapsaicin (which makes up around 20%). There are also three minor related compounds (with fairly complex names), which total approximately 10% of the capsaicinoid load. Both capsaicin and dihydrocapsaicin are about twice as potent as the 3 minor compounds in terms of irritation. They are particularly strong against mucous membranes, including your mouth, nose and eyes. That means that, when you eat a pepper and your mouth burns, your eyes water, and your nose runs – you have mostly capsaicin to thank.
Capsaicin is produced by pepper plants at glands located at the junction of the placenta and the pod wall. (That’s the white “ribs” that run down the inside of a pepper.) As the peppers develop, it gets dispersed unevenly throughout the pepper, becoming heavily concentrated in the seeds. The seeds themselves do not produce capsaicin, but they are a major storage point for it. (So if you ever want to eat a pepper but don’t want all the spice, simply remove the seeds and the white ribs. That won’t get rid of all the spice, but it will eliminate most of it.) Capsaicin itself is not used as a metabolite for the plants, but it is theorized to be useful as a defense mechanism. Mammals generally will not eat peppers, presumably because they don’t like it when their mouths hurt! The peppers are eaten mostly by birds. For birds, capsaicin is an analgesic rather than an irritant - in other words, it acts as a pain killer, not a pain producer. It does them no harm, allowing them to pass the seeds through and deposit them for plant dispersal.
Capsaicin is an interesting molecule. For one thing, it is incredibly stable. It is unaffected by either cold or heat, and retains its spicy potency despite cooking or freezing. That means that you cannot cook the spiciness out of peppers. Another interesting fact is that capsaicin is not very soluble in water, but it is soluble in oils, fats and alcohols. Have you ever eaten something really spicy, then tried to quench the burning by drinking water? I bet it didn’t work. That’s because capsaicin does not dissolve well in water, so drinking water will not wash it off your tongue. You’d be better off drinking a glass of milk, which contains casein, a fat-loving compound that dissolves capsaicin much like soap dissolves grease.
Pure capsaicin is an incredibly powerful compound. At a cellular level, an exposure to capsaicin triggers calcium ions to flood into the affected cell, ultimately triggering a pain signal to the next cell. This is very similar to what happens during a thermal burn. A single milligram (which weighs 1/1000th as much as a paperclip) would be enough to blister the skin on your hand. When pure, it can only be handled by chemists wearing full body protection, including a closed hood to prevent the inhalation of the powder. Lloyd Matheson, a pharmaceutical chemist from the University of Iowa was reported to have once inhaled pure capsaicin accidentally; according to him, “It’s not toxic, but you wish you were dead if you inhale it.” Capsaicin also features prominently in pepper spray, which is a strong irritant for all of the mucous membranes on your face (eyes, nose, mouth, and respiratory system.)
But don’t worry. There isn’t enough capsaicin in peppers to be dangerous – only spicy! The spiciness of peppers is measured in terms of Scoville Heat Units, which is parts per million of capsaicinoid content. At the extremes of the scale are pure capsaicin and bell peppers. Pure capsaicin has a Scoville Heat Unit score of 16 million, while bell peppers have a score of 0. Here are the scores of other common peppers:
Habaneros: 100,000 – 300,000
Scotch Bonnets: 100,000 – 250,000
Thai Peppers: 50,000 – 100,000
Cayenne Peppers: 10,000 – 30,000
Jalapenos: 2,500 – 5,000
Pepperocinis: 100 – 500
As I said, I’ve gradually been increasing my tolerance for spiciness. Of course, I’m not munching on habanero peppers for an afternoon snack, but I can handle jalapenos, cayenne peppers, and even very small levels of Thai peppers. Of course, now that I know how potent Scotch Bonnet peppers are, I may have just reached my limit on the peppers I’m willing to try!
Monday, October 15, 2007
The useless parts of human bodies
Have you ever had your wisdom teeth removed? I have – all 4 of them. I was 18, and my dentist was concerned that my jaw was too small to handle these extra teeth butting their way in, so – bam! – out they came. It was not a pleasant experience. I’m glad that I had them all out at the same time, so that I don’t ever have to go through it again! Of course, the reason I could have them pulled out like that is that wisdom teeth don’t seem to have a purpose. For modern humans, all indications are that they are totally useless. Of course, they may have been a useful part of our jaws thousands of years ago, but that usefulness is (apparently) long gone.
Interestingly enough, wisdom teeth are not the only seemingly useless parts of our bodies. There are 2 other well-known pieces of anatomy that fall into this category of uselessness – the tonsils and the appendix. In fact, not only are all 3 of these body parts apparently pointless, they can be a lot of trouble. Tonsils are often infected and inflamed. When wisdom teeth become impacted, they can damage other teeth or cause gum infection or bone damage. And appendices can become inflamed, requiring rapid removal by surgery to reduce the risk of the infection turning lethal. So surgeons remove these things routinely. And people live just fine without them. So, they’re useless, right?
Maybe not. It turns out the appendix may have a purpose after all. In October, scientists at Duke University’s medical school announced a theory about the possible job of the appendix. They suggest that the appendix is a back-up storage system for intestinal bacteria.
It turns out that our intestines are chocked full of bacteria – in fact, your body contains more bacteria cells than your own body cells! Most of these bacteria (which are also referred to as “bugs”) are helpful, and in fact are essential for you to digest your food. However, there are certain diseases that can wipe out the flora from your digestive system – diseases such as cholera and amoebic dysentery. These diseases are characterized by severe diarrhea, which quickly flushes out the friendly bugs residing in your gut. If that happens, your digestive tract needs a way to rapidly recover those helpful bacteria. Enter the appendix. The authors of the report argue that the appendix serves as a safe-house for intestinal bugs, allowing them to survive in an offshoot of the intestines that would be protected from the intestinal ravages of severe diarrheal diseases. (The location of the appendix is consistent with this hypothesis. It is a small, finger-shaped structure located near the beginning of the large intestine.)
In the western world characterized by dense populations, we don’t have much of a need for this function of the appendix. Cholera and amoebic dysentery are rarely (if ever) encountered in western society anymore. But even if we were to contract some disease that wiped out our intestinal flora, we could rapidly pick them up again from the people we encounter every day. (Yes, the bugs can be shared.) However, in areas of the world where cholera could devastate entire regions of people, this job of the appendix could be very relevant. In fact, here is a curious fact – in less developed societies in the world, the rate of appendicitis is much lower than in first-world countries. That would be consistent with the fact that people in regions exposed to severe diarrheal diseases must rely more on their appendix than do those who live elsewhere.
On a related note, I found some interesting facts about appendices in other animals. It turns out that appendices are large and very functional in animals whose diets consist mainly of vegetative matter. This includes koala bears (who have perhaps the longest appendix of any animal in the world), opposums, kangaroos, rabbits and zebra. The diet of these animals is very dense in cellulose. Cellulose is the main component of the cell walls of plants, and it is very difficult to digest. Our digestive systems cannot make the enzyme needed to break cellulose apart, so we are actually unable to digest cellulose at all. (It simply goes through our systems.) The appendices of animals that eat a lot of plant matter house a specialized set of bacteria that secrete the enzyme to digest the cellulose that they eat. Without this bacteria, these animals would simply be unable to digest most of what they've taken in.
I guess that means it would be pretty serious for a koala bear to get a case of appendicitis!
Interestingly enough, wisdom teeth are not the only seemingly useless parts of our bodies. There are 2 other well-known pieces of anatomy that fall into this category of uselessness – the tonsils and the appendix. In fact, not only are all 3 of these body parts apparently pointless, they can be a lot of trouble. Tonsils are often infected and inflamed. When wisdom teeth become impacted, they can damage other teeth or cause gum infection or bone damage. And appendices can become inflamed, requiring rapid removal by surgery to reduce the risk of the infection turning lethal. So surgeons remove these things routinely. And people live just fine without them. So, they’re useless, right?
Maybe not. It turns out the appendix may have a purpose after all. In October, scientists at Duke University’s medical school announced a theory about the possible job of the appendix. They suggest that the appendix is a back-up storage system for intestinal bacteria.
It turns out that our intestines are chocked full of bacteria – in fact, your body contains more bacteria cells than your own body cells! Most of these bacteria (which are also referred to as “bugs”) are helpful, and in fact are essential for you to digest your food. However, there are certain diseases that can wipe out the flora from your digestive system – diseases such as cholera and amoebic dysentery. These diseases are characterized by severe diarrhea, which quickly flushes out the friendly bugs residing in your gut. If that happens, your digestive tract needs a way to rapidly recover those helpful bacteria. Enter the appendix. The authors of the report argue that the appendix serves as a safe-house for intestinal bugs, allowing them to survive in an offshoot of the intestines that would be protected from the intestinal ravages of severe diarrheal diseases. (The location of the appendix is consistent with this hypothesis. It is a small, finger-shaped structure located near the beginning of the large intestine.)
In the western world characterized by dense populations, we don’t have much of a need for this function of the appendix. Cholera and amoebic dysentery are rarely (if ever) encountered in western society anymore. But even if we were to contract some disease that wiped out our intestinal flora, we could rapidly pick them up again from the people we encounter every day. (Yes, the bugs can be shared.) However, in areas of the world where cholera could devastate entire regions of people, this job of the appendix could be very relevant. In fact, here is a curious fact – in less developed societies in the world, the rate of appendicitis is much lower than in first-world countries. That would be consistent with the fact that people in regions exposed to severe diarrheal diseases must rely more on their appendix than do those who live elsewhere.
On a related note, I found some interesting facts about appendices in other animals. It turns out that appendices are large and very functional in animals whose diets consist mainly of vegetative matter. This includes koala bears (who have perhaps the longest appendix of any animal in the world), opposums, kangaroos, rabbits and zebra. The diet of these animals is very dense in cellulose. Cellulose is the main component of the cell walls of plants, and it is very difficult to digest. Our digestive systems cannot make the enzyme needed to break cellulose apart, so we are actually unable to digest cellulose at all. (It simply goes through our systems.) The appendices of animals that eat a lot of plant matter house a specialized set of bacteria that secrete the enzyme to digest the cellulose that they eat. Without this bacteria, these animals would simply be unable to digest most of what they've taken in.
I guess that means it would be pretty serious for a koala bear to get a case of appendicitis!
Tuesday, October 9, 2007
What do you call that?
The geoduck. Large. Long-lived. Tasty. Weird. And native to where I live.
Odds are, unless you live in the Pacific Northwest somewhere, you’ve probably never heard of a geoduck. I’d never heard of them, until I moved to the Puget Sound! Geoducks are native to the Pacific coast of the northern US and Canada, primarily concentrated in Washington State and British Columbia. In fact, there are an estimated 109 million of them in the Puget Sound area! That makes this creature the single most abundant organism in the region. So you’re probably wondering – what on earth is a geoduck?
“Geoduck” is, in my opinion, one of the most confusing words in the English language. It is properly pronounced “gooey-duck.” And these things aren’t ducks at all! They are large saltwater clams, which are also known as king clams or elephant trunk clams. Geoducks are actually the largest saltwater burrowing clam in the world. If you were to go dig a geoduck out of the sand, you would probably find one weighing somewhere between 1 and 3 pounds. However, there are tales of geoducks reaching upwards of 20 pounds. (That’s a lot of clam.)
Geoducks are burrowing clams, and you will find them buried in sandy areas around bodies of salt water. (They are also buried beneath the sediment underneath the surface of the water, too. In fact, they have been observed at depths of 360 feet in the Puget Sound.) About 50 days after they begin their lives, they begin digging down into the sediment at a rate of 1 foot per year. Once they reach about 3 feet below the ground, they generally stop digging, and remain at that level for the rest of their lives. They eat and breathe through their siphons, which protrude up through the sediment to the surface. Through one hole in the siphon, they suck in water (from which they extract plankton and oxygen), then spit the remaining water back out through a different hole in the siphon.
Interestingly enough, the geoduck is one of the longest-living creatures in the region. It has an average life span of 146 years, and the oldest geoduck on record was around 160 years old! In a previous column (“the small animal, short life phenomenon”), I discussed how the average longevity of mammals correlates with body size. For the most part, small mammals live short lives, while large mammals live long ones. For reasons that scientists do not understand, that correlation only holds true for mammals. Reptiles, amphibians, birds and insects all play by their own rules when it comes to average lifespan.
For example, here are the average size and lifespan of a few non-mammals:
Oriental Fire-bellied toad: <0.1 pounds / 11-14 years
American Alligator: 1300 pounds / 50-65 years
African Grey Parrot: 1-1.5 pounds / 50-70 years
Ostrich: 250 pounds / 50-70 years
Alligator Snapping Turtle: 200 pounds / 50 years
Tarantula: 0.1 pounds / 10-30 years
If you notice, there is really no correlation between how big these animals are and how long they live, and that is certainly true for the geoduck. Their lifespan is roughly comparable to that of a blue whale, which is hundreds of times larger. Scientist speculate that the reason for the geoduck’s long lifespan is because they live a very low-stress, easy lifestyle. They have relatively few predators, though sea otters, dogfish, and starfish will sometimes attack them. And, of course, humans love them.
Washington state is home to a large and growing industry of geoduck aquaculture (worth 80 million dollars a year), primarily because the large meaty siphon can be sold for upwards of $30 a pound in Asia. It is extremely popular in Hong Kong and Japan, where it is eaten either raw (sashimi style) or cooked in a fondue-style hot pot.
Of course, given what they look like, I don’t know if I’d ever be brave enough to eat one raw.
Odds are, unless you live in the Pacific Northwest somewhere, you’ve probably never heard of a geoduck. I’d never heard of them, until I moved to the Puget Sound! Geoducks are native to the Pacific coast of the northern US and Canada, primarily concentrated in Washington State and British Columbia. In fact, there are an estimated 109 million of them in the Puget Sound area! That makes this creature the single most abundant organism in the region. So you’re probably wondering – what on earth is a geoduck?
“Geoduck” is, in my opinion, one of the most confusing words in the English language. It is properly pronounced “gooey-duck.” And these things aren’t ducks at all! They are large saltwater clams, which are also known as king clams or elephant trunk clams. Geoducks are actually the largest saltwater burrowing clam in the world. If you were to go dig a geoduck out of the sand, you would probably find one weighing somewhere between 1 and 3 pounds. However, there are tales of geoducks reaching upwards of 20 pounds. (That’s a lot of clam.)
Geoducks are burrowing clams, and you will find them buried in sandy areas around bodies of salt water. (They are also buried beneath the sediment underneath the surface of the water, too. In fact, they have been observed at depths of 360 feet in the Puget Sound.) About 50 days after they begin their lives, they begin digging down into the sediment at a rate of 1 foot per year. Once they reach about 3 feet below the ground, they generally stop digging, and remain at that level for the rest of their lives. They eat and breathe through their siphons, which protrude up through the sediment to the surface. Through one hole in the siphon, they suck in water (from which they extract plankton and oxygen), then spit the remaining water back out through a different hole in the siphon.
Interestingly enough, the geoduck is one of the longest-living creatures in the region. It has an average life span of 146 years, and the oldest geoduck on record was around 160 years old! In a previous column (“the small animal, short life phenomenon”), I discussed how the average longevity of mammals correlates with body size. For the most part, small mammals live short lives, while large mammals live long ones. For reasons that scientists do not understand, that correlation only holds true for mammals. Reptiles, amphibians, birds and insects all play by their own rules when it comes to average lifespan.
For example, here are the average size and lifespan of a few non-mammals:
Oriental Fire-bellied toad: <0.1 pounds / 11-14 years
American Alligator: 1300 pounds / 50-65 years
African Grey Parrot: 1-1.5 pounds / 50-70 years
Ostrich: 250 pounds / 50-70 years
Alligator Snapping Turtle: 200 pounds / 50 years
Tarantula: 0.1 pounds / 10-30 years
If you notice, there is really no correlation between how big these animals are and how long they live, and that is certainly true for the geoduck. Their lifespan is roughly comparable to that of a blue whale, which is hundreds of times larger. Scientist speculate that the reason for the geoduck’s long lifespan is because they live a very low-stress, easy lifestyle. They have relatively few predators, though sea otters, dogfish, and starfish will sometimes attack them. And, of course, humans love them.
Washington state is home to a large and growing industry of geoduck aquaculture (worth 80 million dollars a year), primarily because the large meaty siphon can be sold for upwards of $30 a pound in Asia. It is extremely popular in Hong Kong and Japan, where it is eaten either raw (sashimi style) or cooked in a fondue-style hot pot.
Of course, given what they look like, I don’t know if I’d ever be brave enough to eat one raw.
Thursday, October 4, 2007
Boo!
In my last column (“when sleep goes awry”), I wrote about a sleep disorder called narcolepsy. I mentioned that there are several well-known videos of narcoleptic dogs collapsing without warning in the middle of playtime. Watching those videos made my mind think back to another kind of animal that I’ve heard sometimes collapses without warning, and I wanted to investigate it further. The animal? The fainting goat.
Fainting goats have gone by many names over the years, including Tennessee goats, nervous goats, stiff-leg goats, wooden-leg goats, and Tennessee scare goats. All of these names are reflective of the fact that these guys (a) originate from Tennessee and (b) have the unfortunate tendency to fall over when startled. When spooked or surprised, the muscles in their legs become as stiff as a board, resulting in the goat falling on its side, as if in a dead faint. (In animals less severely affected, though, they don’t actually fall over. They just stand there on unbending legs, looking really awkward.) Mind you, the goat has not really fainted, since it is fully conscious - it just can’t move its muscles! After 10-15 seconds, the muscles will relax enough to let the goat walk, albeit stiffly at first. Once the stiffness has worn off, though, they walk and run just like any other goat. (To see a picture of what they look like when they’ve fallen over, check out: http://agonline.com/runningbird/goats.asp. It’s a good illustration of a goat that has fainted in the midst of ones that haven’t.)
This may sound similar to what I described for a narcoleptic/cataplectic attack, but it is actually something different. Fainting goats suffer from a muscle condition called myotonia congenita. Myotonia congenita occurs in many animal species, including humans. It is a disease of the cells in skeletal muscles, preventing normal muscle contraction and expansion. Let’s take a look at how muscle cells work to understand what’s going wrong in these poor goats.
When muscles expand and contract, they do so in a coordinated fashion, regulated by the flow of ions in and out of the muscle cells. Ions are electrically charged atoms due to the fact that they have unequal numbers of protons (conferring positive charge) and electrons (conferring negative charge). Ions are essential for life – there are literally thousands of cellular processes regulated by them. Ions used by your cells include sodium, potassium, calcium, magnesium, zinc and chloride; because they are so important, their movement and levels are carefully controlled. Muscle contraction and expansion requires a tightly regulated flow of chloride and calcium ions through dedicated ion channels that sit in the membranes of the muscle cells. These channels act like tunnels through the barriers of the cell, letting only their designated ions through. There are many such barriers in a cell, including the outer membrane (separating cell from non-cell) and organelle membranes (enclosing numerous compartments within the cell). One important compartment in muscle cells is called the sarcoplasmic reticulum. The sarcoplasmic reticulum is a major storage compartment of intracellular calcium (a positively charged ion).
When your skeletal muscles receive a signal to contract (the signal coming from the nervous system), calcium channels in the membrane of the sarcoplasmic reticulum allow a rush of calcium to flow from the sarcoplasmic reticulum to the interior of the cell (the cytoplasm). The calcium allows the proteins that control muscle contraction to work. When the contraction is finished, the cells must have some way of balancing out the positive charge in the cytoplasm – if they don’t, the contraction would not end! There are 2 ways to achieve this balance. First, a different set of channels pump the calcium back into the sarcoplasmic reticulum. And second, there is a counterbalancing inrush of chloride ions. Chloride, being negatively charged, cancels out the remaining positive charge conferred by the calcium. This balance of electrical charge in the cell keeps the muscles from contracting abnormally.
(It’s important to emphasize that what I’m talking about here is skeletal muscle. There are actually 3 different kinds of muscles in your body – skeletal, cardiac and smooth. Both cardiac and smooth muscles contract and relax involuntarily, while skeletal muscle function can be both voluntary and involuntary. The muscles differ in their organization and mechanism of action, and what I’ve written above is specific for skeletal muscle.)
Okay, back to the goats. Fainting goats have a genetic defect in the chloride channel in their skeletal muscles. This mutation - in a gene called CLCN1 - results in chloride channels with an abnormal shape – as a result, they cannot properly control the flow of chloride in or out of the muscle cells. If the goat is startled, it will contract its muscles to run or jump away. Once the muscles are contracted, though, they cannot be relaxed as normal because the chloride ions are not flowing properly. The result - their muscles remain contracted abnormally long. And tightly contracted leg muscles equates to falling over. Eventually, the calcium ions causing the contraction get pumped back into the sarcoplasmic reticulum in the goat’s muscle cells, which is why they are able to move again after a while.
I do want to emphasize that this condition is painless and harmless to the goats. While it makes them easier prey for goat-eating predators like coyotes, if properly protected, they suffer no ill effects from their condition. The only muscles affected are the skeletal muscles, not their hearts or digestive muscles. In fact, if anything, these goats tend to be slightly more muscular than their unaffected counterparts.
Of course, only a goat could tell you whether being buff would make up for the embarrassment of falling over every time you were startled.
Fainting goats have gone by many names over the years, including Tennessee goats, nervous goats, stiff-leg goats, wooden-leg goats, and Tennessee scare goats. All of these names are reflective of the fact that these guys (a) originate from Tennessee and (b) have the unfortunate tendency to fall over when startled. When spooked or surprised, the muscles in their legs become as stiff as a board, resulting in the goat falling on its side, as if in a dead faint. (In animals less severely affected, though, they don’t actually fall over. They just stand there on unbending legs, looking really awkward.) Mind you, the goat has not really fainted, since it is fully conscious - it just can’t move its muscles! After 10-15 seconds, the muscles will relax enough to let the goat walk, albeit stiffly at first. Once the stiffness has worn off, though, they walk and run just like any other goat. (To see a picture of what they look like when they’ve fallen over, check out: http://agonline.com/runningbird/goats.asp. It’s a good illustration of a goat that has fainted in the midst of ones that haven’t.)
This may sound similar to what I described for a narcoleptic/cataplectic attack, but it is actually something different. Fainting goats suffer from a muscle condition called myotonia congenita. Myotonia congenita occurs in many animal species, including humans. It is a disease of the cells in skeletal muscles, preventing normal muscle contraction and expansion. Let’s take a look at how muscle cells work to understand what’s going wrong in these poor goats.
When muscles expand and contract, they do so in a coordinated fashion, regulated by the flow of ions in and out of the muscle cells. Ions are electrically charged atoms due to the fact that they have unequal numbers of protons (conferring positive charge) and electrons (conferring negative charge). Ions are essential for life – there are literally thousands of cellular processes regulated by them. Ions used by your cells include sodium, potassium, calcium, magnesium, zinc and chloride; because they are so important, their movement and levels are carefully controlled. Muscle contraction and expansion requires a tightly regulated flow of chloride and calcium ions through dedicated ion channels that sit in the membranes of the muscle cells. These channels act like tunnels through the barriers of the cell, letting only their designated ions through. There are many such barriers in a cell, including the outer membrane (separating cell from non-cell) and organelle membranes (enclosing numerous compartments within the cell). One important compartment in muscle cells is called the sarcoplasmic reticulum. The sarcoplasmic reticulum is a major storage compartment of intracellular calcium (a positively charged ion).
When your skeletal muscles receive a signal to contract (the signal coming from the nervous system), calcium channels in the membrane of the sarcoplasmic reticulum allow a rush of calcium to flow from the sarcoplasmic reticulum to the interior of the cell (the cytoplasm). The calcium allows the proteins that control muscle contraction to work. When the contraction is finished, the cells must have some way of balancing out the positive charge in the cytoplasm – if they don’t, the contraction would not end! There are 2 ways to achieve this balance. First, a different set of channels pump the calcium back into the sarcoplasmic reticulum. And second, there is a counterbalancing inrush of chloride ions. Chloride, being negatively charged, cancels out the remaining positive charge conferred by the calcium. This balance of electrical charge in the cell keeps the muscles from contracting abnormally.
(It’s important to emphasize that what I’m talking about here is skeletal muscle. There are actually 3 different kinds of muscles in your body – skeletal, cardiac and smooth. Both cardiac and smooth muscles contract and relax involuntarily, while skeletal muscle function can be both voluntary and involuntary. The muscles differ in their organization and mechanism of action, and what I’ve written above is specific for skeletal muscle.)
Okay, back to the goats. Fainting goats have a genetic defect in the chloride channel in their skeletal muscles. This mutation - in a gene called CLCN1 - results in chloride channels with an abnormal shape – as a result, they cannot properly control the flow of chloride in or out of the muscle cells. If the goat is startled, it will contract its muscles to run or jump away. Once the muscles are contracted, though, they cannot be relaxed as normal because the chloride ions are not flowing properly. The result - their muscles remain contracted abnormally long. And tightly contracted leg muscles equates to falling over. Eventually, the calcium ions causing the contraction get pumped back into the sarcoplasmic reticulum in the goat’s muscle cells, which is why they are able to move again after a while.
I do want to emphasize that this condition is painless and harmless to the goats. While it makes them easier prey for goat-eating predators like coyotes, if properly protected, they suffer no ill effects from their condition. The only muscles affected are the skeletal muscles, not their hearts or digestive muscles. In fact, if anything, these goats tend to be slightly more muscular than their unaffected counterparts.
Of course, only a goat could tell you whether being buff would make up for the embarrassment of falling over every time you were startled.
Monday, October 1, 2007
When sleep goes awry
In a previous entry (“Zzzz….”), I talked about sleep – why we need it, what happens when we don’t get it, and how the sleeping habits of animals across the world compare to our own. Having delved into what constitutes normal patterns of sleep, I wanted to know about what happens when sleep goes awry. If sleep is such an important part of our biology, why do some people have so much difficulty with it?
The term “sleep disorder” encompasses a wide variety of sleeping problems. Sleep disorders can be grouped into 4 main categories: dyssomnias, parasomnias, proposed disorders, and medical/psychiatric disorders. Of these, dyssomnias and parasomnias are the most prevalent. Dyssomnias are disturbances in the timing, amount or quality of sleep. Common dyssomnias include: insomnia, narcolepsy, restless leg syndrome, sleep apnea, jet lag and shift-work sleep disorder. Parasomnias interfere with the transitions between sleep stages, and include: sleepwalking, sleep talking, sleep terrors, bedwetting and teeth grinding. While much work is being done on many of these different sleep disorders, one in particular has been extensively studied in terms of its biological cause. This condition is called narcolepsy.
Narcolepsy is a sleep disorder that affects almost 150,000 people in the US (about 1 in 2,000 people). It is a neurological condition characterized by excessive daytime sleepiness and abnormal REM sleep. (Remember, REM sleep is that stage in our sleep cycles when our brains are active but our bodies are inactive.) A narcoleptic often becomes so drowsy that they will fall asleep wherever they are, irresistibly and without warning. There are additional manifestations of narcolepsy, including sleep paralysis (inability to talk or move upon waking), hypnagogic hallucinations (auditory or visual hallucinations while falling asleep or waking up) and cataplexy (a sudden episode of muscle weakness that is triggered by strong emotions). While symptoms of excessive daytime sleepiness, sleep paralysis and hypnagogic hallucinations are sometimes seen in people who are not narcoleptic (usually people who are extremely sleep deprived), cataplexy appears to be exclusive to narcolepsy.
Narcoleptics who are having an attack of cataplexy is a truly unusual thing to watch. There are several fairly well known videos of narcoleptic dogs, including Rusty the narcoleptic daschund and several from the Stanford Center for Narcolepsy. Typically, the dogs in the videos are playing and seemingly having a great time, then suddenly their knees buckle and give way and their necks and jaws go slack. The dogs fall down and become paralyzed for a period of time, during which all of their reflexes are lost. After some time, they recover with no ill effects, and resume their previous activities.
So why does this happen? I’ve said it before, and I’ll say it again – it’s not fully understood. Sleep researchers have shown that over 90% of narcolepsy with cataplexy is caused by defective signaling from 2 related chemicals in the brain. These chemicals – hypocretin-1 and hypocretin-2 – regulate activity in the hypothalamus, the part of the brain that regulates sleep and appetite. Scientists have shown that the inherited form of narcolepsy in dogs is caused by genetic mutations that make their brains unable to respond to hypocretin-1 and hypocretin-2. In humans, it appears that the chemicals are physically absent, because the cells that make the hypocretins are mysteriously missing. The current thinking is that those cells have been killed off by the body’s own immune system. But why that happens is still unknown, as is what causes narcolepsy without cataplexy.
I guess I shouldn’t be surprised that there are so many ways that sleep can go awry, as well as the fact that we don’t really understand why yet. After all, sleep is an enormously complicated part of the brain, and it integrates a huge number of different factors of genetics and environment. It’s amazing that our brains and our bodies handle it as well as they do.
The term “sleep disorder” encompasses a wide variety of sleeping problems. Sleep disorders can be grouped into 4 main categories: dyssomnias, parasomnias, proposed disorders, and medical/psychiatric disorders. Of these, dyssomnias and parasomnias are the most prevalent. Dyssomnias are disturbances in the timing, amount or quality of sleep. Common dyssomnias include: insomnia, narcolepsy, restless leg syndrome, sleep apnea, jet lag and shift-work sleep disorder. Parasomnias interfere with the transitions between sleep stages, and include: sleepwalking, sleep talking, sleep terrors, bedwetting and teeth grinding. While much work is being done on many of these different sleep disorders, one in particular has been extensively studied in terms of its biological cause. This condition is called narcolepsy.
Narcolepsy is a sleep disorder that affects almost 150,000 people in the US (about 1 in 2,000 people). It is a neurological condition characterized by excessive daytime sleepiness and abnormal REM sleep. (Remember, REM sleep is that stage in our sleep cycles when our brains are active but our bodies are inactive.) A narcoleptic often becomes so drowsy that they will fall asleep wherever they are, irresistibly and without warning. There are additional manifestations of narcolepsy, including sleep paralysis (inability to talk or move upon waking), hypnagogic hallucinations (auditory or visual hallucinations while falling asleep or waking up) and cataplexy (a sudden episode of muscle weakness that is triggered by strong emotions). While symptoms of excessive daytime sleepiness, sleep paralysis and hypnagogic hallucinations are sometimes seen in people who are not narcoleptic (usually people who are extremely sleep deprived), cataplexy appears to be exclusive to narcolepsy.
Narcoleptics who are having an attack of cataplexy is a truly unusual thing to watch. There are several fairly well known videos of narcoleptic dogs, including Rusty the narcoleptic daschund and several from the Stanford Center for Narcolepsy. Typically, the dogs in the videos are playing and seemingly having a great time, then suddenly their knees buckle and give way and their necks and jaws go slack. The dogs fall down and become paralyzed for a period of time, during which all of their reflexes are lost. After some time, they recover with no ill effects, and resume their previous activities.
So why does this happen? I’ve said it before, and I’ll say it again – it’s not fully understood. Sleep researchers have shown that over 90% of narcolepsy with cataplexy is caused by defective signaling from 2 related chemicals in the brain. These chemicals – hypocretin-1 and hypocretin-2 – regulate activity in the hypothalamus, the part of the brain that regulates sleep and appetite. Scientists have shown that the inherited form of narcolepsy in dogs is caused by genetic mutations that make their brains unable to respond to hypocretin-1 and hypocretin-2. In humans, it appears that the chemicals are physically absent, because the cells that make the hypocretins are mysteriously missing. The current thinking is that those cells have been killed off by the body’s own immune system. But why that happens is still unknown, as is what causes narcolepsy without cataplexy.
I guess I shouldn’t be surprised that there are so many ways that sleep can go awry, as well as the fact that we don’t really understand why yet. After all, sleep is an enormously complicated part of the brain, and it integrates a huge number of different factors of genetics and environment. It’s amazing that our brains and our bodies handle it as well as they do.
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