Gene Doping

Aug 27, 2012
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Considering exogenous EPO will become old news quickly, and athletes and their doctors are presumed ahead of the game. Media reports that this is already happening within cycling and/or other sports. Where is the current doping frontier?

Some elementary reading to get the topic started (via google and google scholar):

The wiki overview:
http://en.wikipedia.org/wiki/Gene_doping

The popular article:
http://www.theatlantic.com/technology/archive/2012/08/by-the-next-olympics-athletes-may-be-getting-routine-gene-doping-tests/260700/

The overview scientific review - reference 10 in above wiki overview (by "Haisma et al, not "Halsma")
http://www.carnevalijunior.com.br/wp-content/uploads/2010/03/dopinggene.pdf

Abstract of a book by Miah widely cited in the field
http://www.jssm.org/vol3/n3/11/v3n3-11text.php
 
Aug 15, 2012
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I posted in another forum literally 7 years ago on this topic. I'm digging up some of my old quotes from that site. Back then, a biotech called Oxford BioMedica developed a viral based gene delivery system for supplying epo to muscles under the control of a hypoxia-specific promoter. The project was shelved, but similar projects could easily exist. The company appears to still be in business, but I see no signs of this product.

-------------------------------------------------------------------------

From the Oxford BioMedica web site ...

"BioMedica has constructed a viral gene delivery vector carrying the human EPO gene under the control of the Company’s hypoxia control element (“HRE”). The HRE senses low oxygen concentrations and will switch a gene on in response. When the oxygen concentration returns to normal the HRE will then switch the gene off providing an exquisite control mechanism for the production of EPO in situ. Repoxygen™ is designed to be delivered by injection into muscle. Here it produces EPO when the underlying anaemia results in low systemic oxygen concentrations. This will lead to the selective increase in the number of red blood cells, which carry oxygen round the body. As the red blood cell count reaches normal levels and the systemic oxygen concentration reaches normal levels, the EPO gene is switched off. No further release of EPO occurs until the patient becomes anaemic once more and the cycle is repeated. In this way the product should allow the patient to maintain a normal red blood cell count, thereby curing the anaemia."

Biomedica dropped the program because of cost, not specifically because the technology doesn't work. They had a HUGE hurdle to overcome in getting funding for a gene therapy trial given the unintended consequences of the French trials for human SCID. Gene therapy, despite these setbacks, will eventually succeed. Investment money will forgive the previous problems and pour new money in over the next 5 to 10 years. In the meantime, there are many labs and small companies working out the kinks through the use of modified viral or even non-viral vectors.

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Here's the paper supporting this work:
 
Sep 29, 2012
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Just finished reading about Jonathan Tiernan-Locke and how he had epstein-barr virus. Same as Mick Rogers.

Started to wonder if there was any chance the Epstein-Barr virus could be used as the carrier for gene doping? Found one mention of its use back in 1999 in mice:
Tsukamoto H; Wells DJ; Brown SC; Serpente P; Strong PN; Drew J; Inui K; Okada S; et al. (1 Jul 1999). Enhanced expression of recombinant dystrophin following intramuscular injection of Epstein-Barr virus (EBV)-based mini-chromosome vectors in mdx mice. GENE THERAPY. 6:1331-1335. Author weblink DOI.
Not saying in any way that this is at all what is going on with these 2 specific riders.

Looks like it could be used though. Safer than e-coli, at a guess.
 
Mar 17, 2012
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To Dear Wiggo: I think it´s possible, no one really knows if the athlete really suffered from EBV, that´s just what is made public, no chance to verify it from outside. Mutated genes could be injected by using virus as a carrier, or even have to, so this could go into the right direction.
There´s no chance to ever directly find out if someone dopes using this method, only chance will be fishing them out via Biological Passport, where the blood values will be suspicious.
Only question is how doctors who treat athletes (or are planning to treat athletes) with genes handle the mid- to long term effects; will they be able to control it, to inhibit the increases of red blood cell numbers? Otherwise, these athletes risk death within few years.

In cycling, it will be the trace of things like Repoxygen which leads to real gene doping, maybe derivates of this are already used. If not, then Oxyglobin for the blood and IGF1 for the muscles are the current limits.
 
The wicked witch is dead. The era of clean cycling has begun. You haven't been paying attention to what the rocket scientists here have been posting for years. I know these "scientists" haven't been working at the various bio medical skunk works labs throughout the world, but when the CLINIC scientists speaks, so shall it be. After all, they've already slayed the biggest monkey on cycling's back preventing drug free competition, human nature. Nanobots are much smaller than monkeys and won't stand a chance against the CLINICS spoken word.
 
Sep 13, 2012
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I have seen a couple of papers suggesting that Gene doping might not be as undetectable as many people appear to think

Although other methods of gene transfer exist and may be
exploited for gene doping, and such methods are yet to be investigated, our results provide encouraging evidence that doping by gene transfer will likely not go undetected at least when skeletal muscle is the target.
Genetic Doping with erythropoietin cDNA in primate muscle is detectable- 2004- Francoise Lasne, Laurent Martin, Jacques de Ceaurriz,Thibaut Larcher,Philippe Moullier, and Pierre Chenuaud

However the paper does allow for saying that more sophisticated methods of genetic doping would be near undetectable. However the authors seem to be unconcerned about the more sophisticated methods.
 
Aug 15, 2012
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Most gene therapy solutions purposefully limit the therapy to a specific organ or body structure. In the case of the Oxford Biomedica product above, they used a type of virus that was non-replicating and would thus require a repeat injection. The consequence with respect to testing is that the virus (and therefore the foreign DNA) will likely not make it into the bloodstream, urine or readily testable bodily fluid and would potentially require a biopsy of the muscle in order to employ PCR or some other DNA-based solution. Obviously this is not feasible. However, considering the sensitivity of PCR, there may be other solutions.
 
Slava101 said:
I have seen a couple of papers suggesting that Gene doping might not be as undetectable as many people appear to think



Genetic Doping with erythropoietin cDNA in primate muscle is detectable- 2004- Francoise Lasne, Laurent Martin, Jacques de Ceaurriz,Thibaut Larcher,Philippe Moullier, and Pierre Chenuaud

However the paper does allow for saying that more sophisticated methods of genetic doping would be near undetectable. However the authors seem to be unconcerned about the more sophisticated methods.
Lasne et al. were able to detect gene doping for EPO because the gene was injected into muscle, and the muscle cells synthesize a version of EPO that is a little different from that synthesized in the normal location, the kidney. But gene dopers are unlikely to focus on EPO, anyway, because that can be detected by the current blood passport system. I.e., if you insert a gene for EPO, you increase your retics and HT, just as you would if you injected EPO directly. Moreover, with gene doping the athlete has much less control over how much EPO is made, and so the possibility of micro-dosing (wrt raising your HT as much as raising levels of any detectable EPO) is made much more difficult. It’s very difficult to predict ahead of time how much of a product will be made even by a defined dose of gene, and this is made still more difficult by not knowing how much of a dose of a gene will reach cells where the gene is actually activated. Every individual is likely to be very different in that respect, as well as the same individual at different time.

However, there are many other genes that could be inserted, for example, enzymes involved in cell metabolism would be prime targets. This would allow the athlete to extract more energy from a given level of oxygen, so there would be no effect on blood passport parameters. There are other potential targets that could boost metabolism without affecting red cell number, e.g., molecules that increase the amount of oxygen off-loaded to cells. But these changes, too, could in principle be detected by the passport approach, though it would require targeting of other parameters, not hematological ones. This is why I think in the long run it will be necessary to have a physiological passport, that is, one based on deviations from a physiological baseline, such as VO2 max, because gene doping could definitely affect parameters like these and it could be very difficult to develop molecular tests for them based simply on what can be measured in blood. That is, while one can measure molecules not involved in oxygen transport, if these molecules are not present to some extent in blood, they are difficult to access, as twisted pairs points out.

Beyond this, there are more direct methods for detecting gene doping. If the gene inserted is known or suspected, one can test for this gene’s DNA. If the gene inserted is not known, it may be possible to detect its vector, that is, the viral DNA that the gene of interest is inserted into. Some studies have suggested enough such DNA would get into the blood for a test based on that, but in other cases it might require a tissue biopsy, which again obviously gets into difficult territory.

Moreover, newer methods of gene insertion don’t involve viral vectors. There is much current interest in using liposomes, essentially fat globules. The gene of interest is put inside the liposome, and when the liposome contacts cells, it is taken up with the gene. The efficiency of the process can be increased by attaching molecules to the outside of the liposome that selectively interact with characteristic molecules on the intended target cells. Then the liposome will preferentially bind to these cells. The liposome components are natural substances, and it would be very difficult to detect this method of gene doping, unless one knew the gene being inserted and could detect it. And note that if the gene is incorporated into the genome of the host cell, it will continue to be synthesized as long as it stays there. Current research suggests that eventually such genes are recognized as foreign and kicked out, but there may be ways of prolonging its stay, so that the athlete could have the benefit of the gene indefinitely.

Another weapon at the gene doper’s disposal is the use of promoters. These turn a gene on or off, determining whether or not it synthesizes its product. Sometimes these promoters can be activated by a simple substance that itself is innocuous and not banned, i.e., vitamin C. So in principle, an athlete could turn the gene on when he wants the product to enhance his performance, and turn it off when out of competition. This would help evade tests based on passport type approaches, though it would not help beat tests based on DNA sequence detection.
 
Epstein Barr

Dear Wiggo said:
Just finished reading about Jonathan Tiernan-Locke and how he had epstein-barr virus. Same as Mick Rogers.

Started to wonder if there was any chance the Epstein-Barr virus could be used as the carrier for gene doping? Found one mention of its use back in 1999 in mice:


Not saying in any way that this is at all what is going on with these 2 specific riders.

Looks like it could be used though. Safer than e-coli, at a guess.
TENNIS PLAYERS:-
Venus Williams disease

Dr Joanne F Shen, an American ophthalmologist at the Mayo Clinic in Arizona who treats the illness,.....said the syndrome was similar to the Epstein Barr virus, a disease that cost former Liverpool and Germany defender Markus Babbel a year of his career.

AND ROGER FEDERER
Some time later, information was released that helped to explain Roger’s early loss. He was sick with mononucleosis which can cause severe fatigue and take quite a while to recover from.

'Robin Soderling has confirmed he will miss Wimbledon as he continues his recovery from glandular fever' . Soderling was under suspicion for some time due to his sudden winning streak.

Andy Roddick reported that one of several blood tests came back positive for mononucleosis. Doctors thought he had probably had the disease for a few months


Jchurch
12-31-2010, 02:13 PM
I believe mono is most likely to be contracted when the immune system is in a weakened state. Given the constant traveling, I would guess that a good deal of players get it while stressed.


http://tt.tennis-warehouse.com/archive/index.php/t-362194.html

DavidGarcia
12-31-2010, 02:13 PM

'No long ago I read a Doctor explaining on an article the relation between the Mono disease and doping on players (in general, he was not referring to any particular sport).

I thought he had a pretty good point plus facts to back it up.'
 
Aug 15, 2012
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EBV, while explored, is not a very popular choice for delivering genes to tissues. Furthermore, I don't know of anyone working on this commercially. Maybe someone can correct me, but this is not a connection I would be suspicious of.
 
Jul 11, 2013
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http://www.businessinsider.com/gene-doping-at-the-olympics-2014-2?IR=T

Giving the thread a bump with this 2014 article but could have been several others...

You reckon some cyclists/other athletes have started experimenting with gene doping?

The world may be about to watch one of its last Olympic Games without genetically enhanced athletes," wrote H. Lee Sweeney, a professor at the University of Pennsylvania School of Medicine.

Time to cherish the old-fashioned athletes of Sochi? It might be too late. Sweeney actually penned that warning a decade ago, in a Scientific American article exploring a little-known practice called gene doping.

In 2004, gene doping was not yet a real risk. But now? The technology has advanced, and authorities have reason to be concerned.

How gene doping works
If you've heard of gene therapy — which aims to cure diseases caused by genetic mutations by injecting cells with healthy DNA — gene doping is the same thing, but with a different end goal.

Theoretically, athletes could inject specific genes — say, those that promote muscle growth — to enhance their physique and performance.

Scientists now understand how genes work well enough that they have created "super mice," whose muscular build, endurance, and speed all far exceed that of normal mice. In one 2008 study, genetically altered mice had "a remarkable degree of hyperactivity" and "could run for up to 5 km, at a speed of 20 m/min without stopping."

That's 25 times farther than normal mice could run at that speed.

The researchers go on to note that the "super mice" were also frighteningly aggressive, and that — perhaps fortunately — it's neither "ethical nor possible" at this point to introduce the same genetic changes in humans. But there are many different kinds of gene doping, and in 2014, some may well be possible in humans.

We can already "rewire" certain genes
"Although one might argue that there is a long way between applying gene doping/therapy to mice and applying it to humans, there are more reasons to make the idea of genetically modified super athletes not so far-fetched," cautioned researchers in a 2009 review in Clinical Biochemistry.

Performance enhancement among elite athletes has already moved beyond simple steroids.

Athletes, apparently including Tour de France riders in the 1990s, have been using a protein called EPO to increase their supply of oxygen-carrying red blood cells, which support the muscles and boost endurance. Since EPO is also made by the body, it was very hard to detect whether athletes were supplementing their natural supply. An effective test has since been developed and authorities can now detect the synthetic form of EPO.

"But ... introducing the EPO gene would result in the body producing its own EPO," writes Tim Franks of BBC News. "Could this be an undetectable way of improving oxygen delivery?" These experimental genetic interventions may be more difficult — even impossible — to detect, since the EPO would be made by the body instead of in a lab. It would be indistinguishable from the EPO healthy people already have.

And anyone, the BBC reports, can now get the EPO gene on the Internet. In gene therapy, this EPO gene would likely be delivered into the genome using a virus that injects the gene into cellular DNA. But geneticist Philippe Moullier told the BBC that athletes may opt for a quick and dirty shortcut: "injecting the purified gene directly into your muscle."

The authors of the review paper in Clinical Biochemistry pinpointed how specific research into genetic targets could unlock a whole list of athletic superpowers — promoting everything from endurance and pain tolerance to speed and strength.

While virtually all of these trials are in rodents, these animal models are the standard in genetic research, as we share much of our genetic material with mice and rats.

Possible — but dangerous
Messing with our genes is no small matter, and both gene therapy to treat diseases and gene doping to enhance performance are a long way off from being safe enough for widespread use in humans.

For example, in 1999, Jesse Gelsinger, an 18-year-old with a liver disease, died days after receiving an experimental gene therapy. The therapy had been deemed safe in mice, monkeys, and even one human, with flu-like symptoms expected as the primary side effect. But in Gelsinger — who some later argued should have been excluded from the trial — the therapy caused an immune overreaction and, eventually, complete organ failure.

In another early trial, children receiving an experimental genetic therapy for a severe immune system disease — so-called "bubble boy disorder" — later developed leukemia.

More than a decade later, scientists are having some luck using gene therapy to treat very specific, rare disorders, like certain kinds of hereditary blindness. Gene therapy for "bubble boy disorder" has since been effective in some patients, too.

Clinical trials are also underway for genetic diseases that cause muscles to waste away — of particular interest to athletes wanting to bulk up. But while such research is advancing quickly, it's not yet market ready.

Even with these small gains, the dangers associated with gene doping are very real. In the late 1990s, when scientists tried giving extra EPO genes to monkeys and baboons, their blood became "so thick," Sweeney wrote, "that it had to be regularly diluted to keep their hearts from failing."

So, are there super-athletes at Sochi?
WDR, a German broadcaster whom The Guardian noted "has a strong track record in investigating doping in sport," has reported that something that seems like a gene doping substance is floating around Sochi.

A scientist reportedly told the WDR correspondent that the substance, called "full-size MGF," "works two times faster than a normal muscle tonic and cannot be detected by the doping authorities."

While we were not able to independently verify WDR's report, Mario Thevis, a forensic chemist at the Center for Preventive Doping Research at the German Sport University Cologne, tested the substance. He confirmed to Science magazine that "full size MGF" contained a "variant of the IGF-1 gene," which "can prompt muscle growth." Using current anti-doping screens, Thevis said, it would be "more or less invisible."

"We were dealing with a highly pure and therefore probably highly dangerous substance," he added.

But are any athletes actually using it?

"There is no conclusive evidence that gene doping has been practiced in sport," noted researchers in the British Journal of Sports Medicine in 2013, but "given that gene therapy techniques improve continuously, the likelihood of abuse will increase."

The World Anti-Doping Agency, responsible for implementing the international standards and tests that aim to keep sports free of artificial enhancements, has officially banned gene doping since 2003. Now they are "devoting significant resources and attention to ways that will enable the detection of gene doping."

The technology that would make gene doping possible is getting there, and scientists are trying to stay one step ahead of athletes. No one can say yet whether they're succeeding.

After all, the Olympics are a once-every-four-years shot. Athletes may have the pressure of an entire country on their shoulders. The technology for gene doping is not widely accessible or reliably effective, and the risks may be great — but that doesn't mean athletes aren't clued in to the possibilities.

Sweeney told the BBC that after conducting mouse studies that used injected genes to promote muscle growth, he was immediately contacted by athletes and coaches — even though the research was in its earliest stages, targeted mainly toward people who were already very ill.

"I hadn't even considered the fact that a young, ultra-healthy individual who's competing at the peak of their career would risk anything," said Sweeney. "But obviously many of them would risk everything."
 
Gene therapy is messy stuff. There's lots of things that can go wrong, especially if you want to insert the DNA into the dopers genome. Unfortunately, scientist have more to gain from helping athletes dope than preventing athletes from doping or helping to catch them.

This is the one thing of doping which I actually find pretty scary. Not because it's cheating in a sport, but because its unnatural on a whole different level
 
I don't think this will be at Rio, or indeed the 2020 games.

For the forseeable future the limit of gene doping will be taking sucessful athletes and getting them into marriages with other successful athelete, and hoping.
(Phinney as a current example)


Simply injecting for EPO into your muscle and expecting it to do something magic is a crackpot idea from someone who doesn't understand cellular biochemistry,

The risk is very real however, and its probably a future battle already lost
 
Mar 13, 2009
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Re:

Catwhoorg said:
I don't think this will be at Rio, or indeed the 2020 games.

For the forseeable future the limit of gene doping will be taking sucessful athletes and getting them into marriages with other successful athelete, and hoping.
(Phinney as a current example)


Simply injecting for EPO into your muscle and expecting it to do something magic is a crackpot idea from someone who doesn't understand cellular biochemistry,

The risk is very real however, and its probably a future battle already lost
ur talkin eugenics. which is a good 80s post punk joy division, but not much chop for test tubing an athlete. the WR athletes, in a hypothetically clean pool, are all mutants, so far off the bell curve. You dont just mix one pro athlete and his genes with another pro athlete and her genes. You need to hit the jackpot, and it is just as likely the jackpot is from jo blo and jenny blo. you need the million pool catchment for the outofthebox athletic predisposition
 
May 28, 2012
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Red Rick said:
Gene therapy is messy stuff. There's lots of things that can go wrong, especially if you want to insert the DNA into the dopers genome. Unfortunately, scientist have more to gain from helping athletes dope than preventing athletes from doping or helping to catch them.

This is the one thing of doping which I actually find pretty scary. Not because it's cheating in a sport, but because its unnatural on a whole different level
It's still challenging to genetically modify living organisms, especially when you only want to change/add gene expression in specific tissue. It requires knowledge about the human genes that influence performance, and knowledge on effective DNA vectors that won't trigger adverse effect such as inflammation or even cancer. Ironically, the most efficient vector viruses for humans are also the ones that are normally harmful to us. Viral vectors are pretty messy, currently they are being used in gene therapy research in humans.

The best chance for effective gene doping is to clone a fertilized oocyte, using f/e a gene that will express itself in muscles. This kind of techniques will also have a low succes rate due to developmental error during pregnancy, but once a genetically modified human is born, without defects and diseases, and with expression of the desired gene, this will mean a breakthrough. I doubt any human has ever been born like that, yet.

So the simpler method, using (viral) vectors, should be the only method that's currently viable. But it's at one's own risk. In research towards gene therapy, the subjects are mostly terminal patients who can only be cured by participating. A case is known of children suffering from immuno-deficiency, that were treated with MLV vectors. This virus is responsible for leukemia-like conditions in mice. Despite the fact that this therapy had quite a high succes rate in treating the immuno-deficiency, some patients developed illnesses as a result of the vector they were treated with. This can be compared to treatment with the Epstein-Barr virus, although I dont know if that has ever been used in treatment on humans.
 
Sep 29, 2012
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Can you recommend a book for dummies to read regarding viral vector genetic modification attempts and strategies?
 
Jun 27, 2009
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twisted pairs said:
I posted in another forum literally 7 years ago on this topic. I'm digging up some of my old quotes from that site. Back then, a biotech called Oxford BioMedica developed a viral based gene delivery system for supplying epo to muscles under the control of a hypoxia-specific promoter. The project was shelved, but similar projects could easily exist. The company appears to still be in business, but I see no signs of this product.

-------------------------------------------------------------------------

From the Oxford BioMedica web site ...

"BioMedica has constructed a viral gene delivery vector carrying the human EPO gene under the control of the Company’s hypoxia control element (“HRE”). The HRE senses low oxygen concentrations and will switch a gene on in response. When the oxygen concentration returns to normal the HRE will then switch the gene off providing an exquisite control mechanism for the production of EPO in situ. Repoxygen™ is designed to be delivered by injection into muscle. Here it produces EPO when the underlying anaemia results in low systemic oxygen concentrations. This will lead to the selective increase in the number of red blood cells, which carry oxygen round the body. As the red blood cell count reaches normal levels and the systemic oxygen concentration reaches normal levels, the EPO gene is switched off. No further release of EPO occurs until the patient becomes anaemic once more and the cycle is repeated. In this way the product should allow the patient to maintain a normal red blood cell count, thereby curing the anaemia."

Biomedica dropped the program because of cost, not specifically because the technology doesn't work. They had a HUGE hurdle to overcome in getting funding for a gene therapy trial given the unintended consequences of the French trials for human SCID. Gene therapy, despite these setbacks, will eventually succeed. Investment money will forgive the previous problems and pour new money in over the next 5 to 10 years. In the meantime, there are many labs and small companies working out the kinks through the use of modified viral or even non-viral vectors.

-------------------------------------------------------------------

Here's the paper supporting this work:
Back in 2004, a friend of mine on the Gold Coast got head hunted by a university in Austin Texas, for the privately funded exploration of gene therapy and manipulation.. We had talked in general terms about her work and she was understandably cagey and guarded in her responses, but implied that there were massive benefits available using this therapy, "open to abuse", as she said....
 
Yeah, I heard about a study where patients with cystic fibrosis were experimentally treated with gene therapy through a viral vector. It initally worked, they had less problems with CF, until they all died of lung cancer.

Don't know the source though
 
Mar 27, 2014
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With the ability to map the human genome and distinguish between different genes triggering different events, which is being used in many areas of research to attack known diseases, it would not be beyond the realms of belief that a medical corporation or a med student looking for a thesis study, my take two gifted athletes and look at what genetically makes them different to the average joe.

If that could be mapped specifically and then corroborated through a larger study. That is where I believe you would end up looking at the genetic modifications we are talking about.

This is already supposedly for sale in some of the clinics around the world for the super wealthy in order to try to make their offspring the best they can possibly be in their generation.

Whether it is actually true or a fraud is anyone's guess and as it is probably illegal in most places at present there is no risk of anyone suing and bringing it to light, Not to mention you wouldn't know if it had worked or not for a few years after the child was born.
 
Aug 15, 2012
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robertmooreheadlane said:
With the ability to map the human genome and distinguish between different genes triggering different events, which is being used in many areas of research to attack known diseases, it would not be beyond the realms of belief that a medical corporation or a med student looking for a thesis study, my take two gifted athletes and look at what genetically makes them different to the average joe.

If that could be mapped specifically and then corroborated through a larger study. That is where I believe you would end up looking at the genetic modifications we are talking about.

This is already supposedly for sale in some of the clinics around the world for the super wealthy in order to try to make their offspring the best they can possibly be in their generation.

Whether it is actually true or a fraud is anyone's guess and as it is probably illegal in most places at present there is no risk of anyone suing and bringing it to light, Not to mention you wouldn't know if it had worked or not for a few years after the child was born.

You mean, like this?


Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis
(translation: some people carry a mutant EPO gene that results in naturally high hematocrit levels)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC46538/pdf/pnas01462-0175.pdf

From the text:
"The clinical condition is so mild that many affected individuals are not themselves aware of any abnormality, nor do they have any sense of illness. The clinical and laboratory findings based on the study of 25 affected and 72 unaffected family members can be summarized as follows (15). Hb is remarkably high: mean male value, 204 g/liter; range, 183-231 g/liter (normal: mean, 154; range, 136-174); mean female value, 191 g/liter; range, 177-200 g/liter (normal: mean, 138; range, 124-153)."

"The proband, a 53-year-old male, whose Hb level has been 200 g/liter or greater since childhood (last
measurement, 236 g/liter), has been one of the best cross country skiers in the world, having won three Olympic gold medals and two world championships."

The skier in question is Eero Antero Mäntyranta.

50% hematocrit level is approximately 165 g/liter Hb.
 
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