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article: Gene Doping
Old 01-10-2006, 03:15 PM   #1
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Gene Doping:

Recent headlines sweeping across the bodybuilding world identified a so-called "myostatin baby" in Germany. This baby, born with two defective myostatin genes, is already showing significantly more muscle mass than children his age with normal myostatin genes.(1)
For those who have nto yet heard about Myostatin (A.K.A. GDF8), myostatin is a protein produced by the body that prevents muscle growth. To find out more about this mighty gene check out Elzi Volk's article on Myostatin. Though only time will tell, everyone in the sporting world will be watching to see if he will indeed turn out to have a comic-book hero type physique without ever lifting a weight. And if so, will he have enhanced athletic abilities as well?
Speaking of enhanced athletic abilities, the list of drugs an athlete might use to improve his performance is long and diverse. Far from being a modern strategy, doping as a means of increasing performance, is as old as competition itself. Drinks and potions of various kinds have been used for thousands of years in many different cultures in an attempt to improve upon normal human physical capacity. Now, in the 21st century, we enter a new era of performance enhancement. In the lab we call it genetic engineering. In sports, we call it 'gene doping'.(2)


What is Gene Doping
I'm sure most of you are familiar with what a gene is. Basically, a gene is a blue print for a protein. Each cell of your body contains all the genetic blue prints for every protein your body makes. There are estimates of anywhere from 30,000 to 100,000 genes in the human body. Most experts agree that the number is probably closer to 30,000. Each gene can code for one or more proteins. There are an estimated 10 times as many proteins as genes, so you can see how complicated things can get.
The standard definition of "gene doping" is, “the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance. By various means of introducing the desired gene into the body, and athlete can increase the abundance of a desirable protein, or decrease the levels of an undesirable protein. In this way he can enhance important systems and/or pathways in the body and increase his or her physical capabilities.
Despite the complicated nature of the human genome, researchers have already identified several genetic components involved in muscle mass and athletic performance. Muscle mass is the obvious one. As mentioned above, myostatin is a prime target for increasing an athlete's muscle mass. Other ways of increasing muscle mass and strength include IGF-1 and perhaps more specifically, mechano-growth factor (MGF).
Perhaps less obvious but potential areas of gene doping include erythropoietin to enhance the oxygen carrying capacity of the blood, and even Leptin to alter body composition.


How is it accomplished?
One way to hijack a cell's genes is to take a modified virus (i.e. a recombinant adeno-associated virus), directing over-expression of the desired gene. The viral DNA originally in the virus is removed along with anything that might trigger an immune response. DNA coding for the desired protein (e.g. IGF-1, MGF, erythropoietin, leptin, etc) is then put into the virus along with a promoter gene to ensure high rates of transcription. Then you simply "infect" the athlete with the engineered virus.
Other potential methods include:
direct injection of DNA into the muscle;
insertion of genetically modified cells;
introduction utilizing a modified virus.
It sounds simple on paper, but the technology is quite complicated and it has taken many years to get to a point where it can be used effectively.
I'm sure many of you are wondering whether any athlete has successfully altered their genes or not. At this point I would seriously doubt any athlete has even tried it. Most trainers and "gurus" aren't even aware of the technology at this point, let alone the athletes. Unless of course they are ThinkMuscle.com readers in which case they heard about this back in 1998 when I reported on the findings of Elisabeth R. Barton-Davis from the Department of Physiology, University of Pennsylvania School of Medicine. She and her colleagues were able to demonstrate that by injecting a virus modified to infect muscle with the IGF-1 gene, a mouse could live throughout its entire life without losing an ounce of muscle. Not only did they not lose any muscle or strength as they aged, but the mice actually grew muscles that were ~15% larger and stronger than age matched control mice.(3)


Is there anyway of detecting it?
At this point, it's safe to say nobody is gene doping just yet, and even if there were, no one would be the wiser because there is really no means by which to test for it. Nevertheless, in an attempt to stay one step ahead of the inevitable, the World Anti-Doping Agency (WADA) has already asked scientists to help find ways to prevent gene therapy from becoming the newest means of doping or, at least if they can't prevent it, to try to figure out a way to test for it. [Note: See the end of this article for a list of WADA's prohibited substance and methods list.]
Of course, just because you can't test for it yet, doesn't mean you can't get caught. Take for example the current poster boy of the bodybuilding supplement industry, Victor Conte and his so-called (BALCO Labs). Because he seems to have lacked an ethics gene, he and every athlete he has ever worked with is now on the hot seat for accusations of performance enhancing drug use. So, even if an athlete were to find a scientist and lab willing to perform gene doping, you would eventually get caught or at least accused of cheating when the authorities came snooping around. And believe me, after the whole Balco Labs fallout and Victor's plea to start giving names instead of going to jail, the authorities are going to be doing more and more snooping.


Potential side effects
Of course there are “potential” side effects. Any time you mess with your genes, you risk side effects. This is why nature has taken such care to minimize the impact of random mutations by inserting a kill switch, so to speak, into our DNA. When a gene is being read and an error is found is will automatically stop production of that particular protein. If the error in the DNA is bad enough, the cell will literally self-destruct.
However, occasionally the kill switch doesn't work. When the DNA doesn't trigger self-destruction of the cell, the cell often becomes a cancer cell. I think we all have been impacted in one way or another by cancer so there is no need to elaborate on its detrimental effects.
Short of cancer, an athlete will still run the obvious risk of throwing his bodily systems out of whack by jacking up one system over another. In the end, it is likely that athletes would require medications to (normalize) their body after having altered their DNA for athletic competition. As far as the young boy mentioned earlier in this article with the mutated myostatin gene, only time will tell whether he will experience any side effects other than a bodybuilder-esque physique.


Closing Comments
As long as there is athletic competition, there will continue to be competitors that try to cheat. Cheaters don't change, only their methods do. It will be interesting to see how this new method of enhancing the body's physical capabilities plays out. Will scientists soon perfect gene doping? Will the governing powers-that-be be able to keep up with the dopers and expose them? After decades of (doped) World Records will athletes be able to continue to break records without doping of some kind? And finally, will people continue to be entertained by athletes that can no longer achieve new heights of athletic prowess? I guess time will tell.


References:
1. Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004 Jun 24;350(26):2682-8
2. Unal M, Ozer Unal D. Gene doping in sports. Sports Med. 2004;34(6):357-62.
3. Elisabeth R. Barton-Davis*, Daria I. Shoturma, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7
*Structure
 
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Old 01-10-2006, 04:36 PM   #2
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first time to know this kind of gene .. thx man great article :)
 
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Old 10-24-2006, 06:16 PM   #3
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Quote:
Originally Posted by philosopher
Gene Doping:

Recent headlines sweeping across the bodybuilding world identified a so-called "myostatin baby" in Germany. This baby, born with two defective myostatin genes, is already showing significantly more muscle mass than children his age with normal myostatin genes.(1)
For those who have nto yet heard about Myostatin (A.K.A. GDF8), myostatin is a protein produced by the body that prevents muscle growth. To find out more about this mighty gene check out Elzi Volk's article on Myostatin. Though only time will tell, everyone in the sporting world will be watching to see if he will indeed turn out to have a comic-book hero type physique without ever lifting a weight. And if so, will he have enhanced athletic abilities as well?
Speaking of enhanced athletic abilities, the list of drugs an athlete might use to improve his performance is long and diverse. Far from being a modern strategy, doping as a means of increasing performance, is as old as competition itself. Drinks and potions of various kinds have been used for thousands of years in many different cultures in an attempt to improve upon normal human physical capacity. Now, in the 21st century, we enter a new era of performance enhancement. In the lab we call it genetic engineering. In sports, we call it 'gene doping'.(2)


What is Gene Doping
I'm sure most of you are familiar with what a gene is. Basically, a gene is a blue print for a protein. Each cell of your body contains all the genetic blue prints for every protein your body makes. There are estimates of anywhere from 30,000 to 100,000 genes in the human body. Most experts agree that the number is probably closer to 30,000. Each gene can code for one or more proteins. There are an estimated 10 times as many proteins as genes, so you can see how complicated things can get.
The standard definition of "gene doping" is, “the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance. By various means of introducing the desired gene into the body, and athlete can increase the abundance of a desirable protein, or decrease the levels of an undesirable protein. In this way he can enhance important systems and/or pathways in the body and increase his or her physical capabilities.
Despite the complicated nature of the human genome, researchers have already identified several genetic components involved in muscle mass and athletic performance. Muscle mass is the obvious one. As mentioned above, myostatin is a prime target for increasing an athlete's muscle mass. Other ways of increasing muscle mass and strength include IGF-1 and perhaps more specifically, mechano-growth factor (MGF).
Perhaps less obvious but potential areas of gene doping include erythropoietin to enhance the oxygen carrying capacity of the blood, and even Leptin to alter body composition.


How is it accomplished?
One way to hijack a cell's genes is to take a modified virus (i.e. a recombinant adeno-associated virus), directing over-expression of the desired gene. The viral DNA originally in the virus is removed along with anything that might trigger an immune response. DNA coding for the desired protein (e.g. IGF-1, MGF, erythropoietin, leptin, etc) is then put into the virus along with a promoter gene to ensure high rates of transcription. Then you simply "infect" the athlete with the engineered virus.
Other potential methods include:
direct injection of DNA into the muscle;
insertion of genetically modified cells;
introduction utilizing a modified virus.
It sounds simple on paper, but the technology is quite complicated and it has taken many years to get to a point where it can be used effectively.
I'm sure many of you are wondering whether any athlete has successfully altered their genes or not. At this point I would seriously doubt any athlete has even tried it. Most trainers and "gurus" aren't even aware of the technology at this point, let alone the athletes. Unless of course they are ThinkMuscle.com readers in which case they heard about this back in 1998 when I reported on the findings of Elisabeth R. Barton-Davis from the Department of Physiology, University of Pennsylvania School of Medicine. She and her colleagues were able to demonstrate that by injecting a virus modified to infect muscle with the IGF-1 gene, a mouse could live throughout its entire life without losing an ounce of muscle. Not only did they not lose any muscle or strength as they aged, but the mice actually grew muscles that were ~15% larger and stronger than age matched control mice.(3)


Is there anyway of detecting it?
At this point, it's safe to say nobody is gene doping just yet, and even if there were, no one would be the wiser because there is really no means by which to test for it. Nevertheless, in an attempt to stay one step ahead of the inevitable, the World Anti-Doping Agency (WADA) has already asked scientists to help find ways to prevent gene therapy from becoming the newest means of doping or, at least if they can't prevent it, to try to figure out a way to test for it. [Note: See the end of this article for a list of WADA's prohibited substance and methods list.]
Of course, just because you can't test for it yet, doesn't mean you can't get caught. Take for example the current poster boy of the bodybuilding supplement industry, Victor Conte and his so-called (BALCO Labs). Because he seems to have lacked an ethics gene, he and every athlete he has ever worked with is now on the hot seat for accusations of performance enhancing drug use. So, even if an athlete were to find a scientist and lab willing to perform gene doping, you would eventually get caught or at least accused of cheating when the authorities came snooping around. And believe me, after the whole Balco Labs fallout and Victor's plea to start giving names instead of going to jail, the authorities are going to be doing more and more snooping.


Potential side effects
Of course there are “potential” side effects. Any time you mess with your genes, you risk side effects. This is why nature has taken such care to minimize the impact of random mutations by inserting a kill switch, so to speak, into our DNA. When a gene is being read and an error is found is will automatically stop production of that particular protein. If the error in the DNA is bad enough, the cell will literally self-destruct.
However, occasionally the kill switch doesn't work. When the DNA doesn't trigger self-destruction of the cell, the cell often becomes a cancer cell. I think we all have been impacted in one way or another by cancer so there is no need to elaborate on its detrimental effects.
Short of cancer, an athlete will still run the obvious risk of throwing his bodily systems out of whack by jacking up one system over another. In the end, it is likely that athletes would require medications to (normalize) their body after having altered their DNA for athletic competition. As far as the young boy mentioned earlier in this article with the mutated myostatin gene, only time will tell whether he will experience any side effects other than a bodybuilder-esque physique.


Closing Comments
As long as there is athletic competition, there will continue to be competitors that try to cheat. Cheaters don't change, only their methods do. It will be interesting to see how this new method of enhancing the body's physical capabilities plays out. Will scientists soon perfect gene doping? Will the governing powers-that-be be able to keep up with the dopers and expose them? After decades of (doped) World Records will athletes be able to continue to break records without doping of some kind? And finally, will people continue to be entertained by athletes that can no longer achieve new heights of athletic prowess? I guess time will tell.


References:
1. Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004 Jun 24;350(26):2682-8
2. Unal M, Ozer Unal D. Gene doping in sports. Sports Med. 2004;34(6):357-62.
3. Elisabeth R. Barton-Davis*, Daria I. Shoturma, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7
*Structure
amazing!
 
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Old 10-24-2006, 06:16 PM   #4
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Quote:
Originally Posted by philosopher
Gene Doping:

Recent headlines sweeping across the bodybuilding world identified a so-called "myostatin baby" in Germany. This baby, born with two defective myostatin genes, is already showing significantly more muscle mass than children his age with normal myostatin genes.(1)
For those who have nto yet heard about Myostatin (A.K.A. GDF8), myostatin is a protein produced by the body that prevents muscle growth. To find out more about this mighty gene check out Elzi Volk's article on Myostatin. Though only time will tell, everyone in the sporting world will be watching to see if he will indeed turn out to have a comic-book hero type physique without ever lifting a weight. And if so, will he have enhanced athletic abilities as well?
Speaking of enhanced athletic abilities, the list of drugs an athlete might use to improve his performance is long and diverse. Far from being a modern strategy, doping as a means of increasing performance, is as old as competition itself. Drinks and potions of various kinds have been used for thousands of years in many different cultures in an attempt to improve upon normal human physical capacity. Now, in the 21st century, we enter a new era of performance enhancement. In the lab we call it genetic engineering. In sports, we call it 'gene doping'.(2)


What is Gene Doping
I'm sure most of you are familiar with what a gene is. Basically, a gene is a blue print for a protein. Each cell of your body contains all the genetic blue prints for every protein your body makes. There are estimates of anywhere from 30,000 to 100,000 genes in the human body. Most experts agree that the number is probably closer to 30,000. Each gene can code for one or more proteins. There are an estimated 10 times as many proteins as genes, so you can see how complicated things can get.
The standard definition of "gene doping" is, “the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance. By various means of introducing the desired gene into the body, and athlete can increase the abundance of a desirable protein, or decrease the levels of an undesirable protein. In this way he can enhance important systems and/or pathways in the body and increase his or her physical capabilities.
Despite the complicated nature of the human genome, researchers have already identified several genetic components involved in muscle mass and athletic performance. Muscle mass is the obvious one. As mentioned above, myostatin is a prime target for increasing an athlete's muscle mass. Other ways of increasing muscle mass and strength include IGF-1 and perhaps more specifically, mechano-growth factor (MGF).
Perhaps less obvious but potential areas of gene doping include erythropoietin to enhance the oxygen carrying capacity of the blood, and even Leptin to alter body composition.


How is it accomplished?
One way to hijack a cell's genes is to take a modified virus (i.e. a recombinant adeno-associated virus), directing over-expression of the desired gene. The viral DNA originally in the virus is removed along with anything that might trigger an immune response. DNA coding for the desired protein (e.g. IGF-1, MGF, erythropoietin, leptin, etc) is then put into the virus along with a promoter gene to ensure high rates of transcription. Then you simply "infect" the athlete with the engineered virus.
Other potential methods include:
direct injection of DNA into the muscle;
insertion of genetically modified cells;
introduction utilizing a modified virus.
It sounds simple on paper, but the technology is quite complicated and it has taken many years to get to a point where it can be used effectively.
I'm sure many of you are wondering whether any athlete has successfully altered their genes or not. At this point I would seriously doubt any athlete has even tried it. Most trainers and "gurus" aren't even aware of the technology at this point, let alone the athletes. Unless of course they are ThinkMuscle.com readers in which case they heard about this back in 1998 when I reported on the findings of Elisabeth R. Barton-Davis from the Department of Physiology, University of Pennsylvania School of Medicine. She and her colleagues were able to demonstrate that by injecting a virus modified to infect muscle with the IGF-1 gene, a mouse could live throughout its entire life without losing an ounce of muscle. Not only did they not lose any muscle or strength as they aged, but the mice actually grew muscles that were ~15% larger and stronger than age matched control mice.(3)


Is there anyway of detecting it?
At this point, it's safe to say nobody is gene doping just yet, and even if there were, no one would be the wiser because there is really no means by which to test for it. Nevertheless, in an attempt to stay one step ahead of the inevitable, the World Anti-Doping Agency (WADA) has already asked scientists to help find ways to prevent gene therapy from becoming the newest means of doping or, at least if they can't prevent it, to try to figure out a way to test for it. [Note: See the end of this article for a list of WADA's prohibited substance and methods list.]
Of course, just because you can't test for it yet, doesn't mean you can't get caught. Take for example the current poster boy of the bodybuilding supplement industry, Victor Conte and his so-called (BALCO Labs). Because he seems to have lacked an ethics gene, he and every athlete he has ever worked with is now on the hot seat for accusations of performance enhancing drug use. So, even if an athlete were to find a scientist and lab willing to perform gene doping, you would eventually get caught or at least accused of cheating when the authorities came snooping around. And believe me, after the whole Balco Labs fallout and Victor's plea to start giving names instead of going to jail, the authorities are going to be doing more and more snooping.


Potential side effects
Of course there are “potential” side effects. Any time you mess with your genes, you risk side effects. This is why nature has taken such care to minimize the impact of random mutations by inserting a kill switch, so to speak, into our DNA. When a gene is being read and an error is found is will automatically stop production of that particular protein. If the error in the DNA is bad enough, the cell will literally self-destruct.
However, occasionally the kill switch doesn't work. When the DNA doesn't trigger self-destruction of the cell, the cell often becomes a cancer cell. I think we all have been impacted in one way or another by cancer so there is no need to elaborate on its detrimental effects.
Short of cancer, an athlete will still run the obvious risk of throwing his bodily systems out of whack by jacking up one system over another. In the end, it is likely that athletes would require medications to (normalize) their body after having altered their DNA for athletic competition. As far as the young boy mentioned earlier in this article with the mutated myostatin gene, only time will tell whether he will experience any side effects other than a bodybuilder-esque physique.


Closing Comments
As long as there is athletic competition, there will continue to be competitors that try to cheat. Cheaters don't change, only their methods do. It will be interesting to see how this new method of enhancing the body's physical capabilities plays out. Will scientists soon perfect gene doping? Will the governing powers-that-be be able to keep up with the dopers and expose them? After decades of (doped) World Records will athletes be able to continue to break records without doping of some kind? And finally, will people continue to be entertained by athletes that can no longer achieve new heights of athletic prowess? I guess time will tell.


References:
1. Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med. 2004 Jun 24;350(26):2682-8
2. Unal M, Ozer Unal D. Gene doping in sports. Sports Med. 2004;34(6):357-62.
3. Elisabeth R. Barton-Davis*, Daria I. Shoturma, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7
*Structure
amazing!
 
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Old 10-24-2006, 07:38 PM   #5
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Thanks this really clears up some of the questions I had.

Great article!
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