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paleoanthropology, genetics and evolution

gene doping

  • Throwback to earlier dopes

    Tue, 2012-06-19 19:06 -- John Hawks

    In its continuing series of Olympics lead-ups, the Guardian enters this one: "Sports doping, Victorian style". The story covers the great scandal of coca leaf chewing and its effects on the study of protein in muscle.

    Weston's other favourite tonic – which he thought more effective than coca leaves – was Liebig's Extract of Meat. By 1908 this was the familiar household brand Oxo, and Oxo was the official caterer of the 1908 Olympic Marathon. Runners were given it for free, with the organisers' blessing.

  • Gene doping mice

    Sat, 2012-03-17 20:32 -- John Hawks

    Andy Coghlan reports on work using viral vectors to amp up mouse muscles, a form of "gene doping", in New Scientist: "Blood tests won't stop gene cheats".

    Autopsies showed that the extra IGF-1 triggered the production of 10 times more protein than normal in the muscles. Giacca also saw activity soar in genes controlling energy production, contraction of muscles and respiration. Also detectable in the muscle were traces of the virus used to deliver the genes. However, the gene, protein and virus were undetectable in blood or urine from the mice (Human Gene Therapy, DOI: 10.1089/hum.2011.157).

    Writing this sent me looking through my "gene doping" archives. This from 2006, where I reacted to fears that athletes in the Beijing Olympics might be using viral vectors to amp themselves: "Is the dawn of "gene doping" at hand?"

    But there is a total lack of recognition of a basic reality: Somebody who actually could figure out how to genetically enhance an athlete before 2008 probably deserves a Nobel prize! And if they could figure that out, they would be a paid a whole lot more by applying their 'l33t genetic skillz curing osteoporosis or something.

    I mean, even Zorin's doctor had that whole residual-Third-Reich-loyalty keeping him in the game.

    I'm pretty sure that snark will shorten my life a lot more than red meat ever could.

  • Gene-a-dope

    Fri, 2010-02-05 09:37 -- John Hawks

    Science gives us a "policy forum" this week on gene doping. The lead author, Theodor Friedmann, is the chair of the "Gene Doping Expert Group" at the World Anti-Doping Agency.

    The essay describes the current potential of gene doping, and is a good short review. I found the paragraphs on "marketing gene doping" very interesting:

    Athletes are an especially vulnerable population in the marketing of performance enhancement (31). Reputable athletes or coaches with little knowledge of genetics are at a disadvantage in assessing "scientific" claims that appear in advertisements. Marketing is particularly worrisome when the science is still a work in progress, when a person's health can be adversely affected, and when consumer knowledge about genetics is low. Although advertisements promoting products that promise to enhance athletic performance have pervaded the Internet for many years, recently it has become home for advertisements that promote products to "alter muscle genes...by activating your genetic machinery" (32), or that state "your genetic limitations are a thing of the past!" (33) or "Finally, every bodybuilder can be genetically gifted!" (34).

    These are people who make easy targets for nutrigenomics and other questionable areas of "health enhancement." A large number of amateur bodybuilders and fitness enthusiasts create a "gray market" supporting questionable products, and these products themselves support the ecosystem of effective performance enhancement drugs. They also create a lot of biochemical noise for those who want to find new tests for performance enhancers.

    The essay includes a few paragraphs that describe the prospects of future detection of gene doping. It may be very difficult. Detecting some synthetic performance-enhancing agents requires the cooperation of primary producers, who add tracers to their products. Gene doping might enhance performance for periods months or years after the vector is administered, and may not require dosage that would significantly alter isotopic or chemical signatures, even if they contained such tracers. The authors suggest that the incidental biochemical effects of gene doping might enable the identification of a "signature" of such products:

    For instance, exposure of murine myoblasts to IGF-1 has been shown to induce transcriptional and proteomic changes that may eventually constitute a "signature" specific for exogenous IGF-1 exposure (29, 30). Of course, the application of these kinds of global assays would require rigorous validation of a connection with specific doping agents or methods.

    I am very skeptical -- it's likely that the "signature" of a doped individual will not differ appreciably from the normal variability of tissue metabolism, particularly in the subset of high-performance athletes. Still, it may be possible to find one particular tissue type that provides a high-information-content message about normal versus doped processes. I just think that a lot of innocent athletes are likely to get snared in this net as it closes in on clinical validation.

    References:

    Friedmann T, Rabin O, Frankel MS. 2010. Gene doping and sport. Science 327:647-648. doi:10.1126/science.1177801

  • A gene doping summit

    Wed, 2009-01-07 10:42 -- John Hawks

    The AP's Howard Fendrich reports on an American Enterprise Institute conference about gene doping:

    Gather a roomful of anti-doping experts, administrators, academics and athletes alike — something a conservative think tank did Thursday — and there is no consensus as to whether gene doping, thought by some to be the next frontier in Olympic cheating, is at hand.

    Indeed, there isn't even consensus on whether it would be a bad thing.

    The article is not really an in-depth coverage of the issue, but merely trades back-and-forth quotes from various conference participants. It's still interesting, though:

    John Leonard, executive director of the American Swimming Coaches Association, told of conversations he has had with coaches and scientists in China.

    "We are really naive if we are to believe that the Chinese at this point are clean or that they are the only country in the world that is experimenting with genetic enhancement as we speak," said Leonard, who was not a panelist but attended the conference and spoke during question-and-answer periods.

    "There are lots of countries in the world who couldn't care less about doing it safely, and there are lots of athletes who will take the chance that they will die in order to win medals. ... Will the United States have the same viewpoint when we start losing gold medals?"

    The views of the pro-doping people seem to have been well represented, along with Edwin Moses and others who are anti-doping.

  • Is the dawn of "gene doping" at hand?

    Fri, 2006-12-15 13:10 -- John Hawks

    The AP is running this:

    LONDON - Scientists are racing to develop a test to catch athletes who may attempt to boost performance by manipulating their genes.

    The premise is that athletes will use gene therapy techniques, using retroviral vectors, to amp up the expression of certain performance-enhancing genes. So the anti-doping folks want to screen for antibodies:

    At the World Anti-Doping Association, researchers are trying to track the immune traces left by the viruses commonly used in gene doping. Gene transfers are most effectively performed with viruses, which have had any dangerous properties removed. In most cases, viruses tend to leave behind incriminating antibodies.

    This is the same principle that incriminated Floyd Landis' urine samples -- it wasn't the presence of a high testosterone level, it was the presence of an isotopic signature (supposedly) distinctive to synthetic testosterone. (I should mention, I believe Landis is innocent, but his case makes a very convenient example.)

    There is a certain comical aspect to this. The article describes how the anti-doping people are trying to find ways to characterize alterations in expression for "families" of genes:

    Because it is virtually impossible to identify the individual gene altered, researchers are also focusing on the secondary impact such changes would provoke.

    "If you perturb a biological system, you'll get all kinds of changes in the homeostasis to keep it functioning," Friedmann said.

    Friedmann and his colleagues are researching a gene doping test in mice that attempts to identify the molecular changes following a gene mutation.

    "We're finding families of genes that unexpectedly change in response to an alteration at the genetic level," Friedmann said. "Those genes can constitute a molecular signature for the system having been disturbed."

    Now it is undoubtedly true that an attempt to amp up some regulatory gene in order to improve performance will cause changes to the expression of a large network of genes. But I find the article ludicrous for two reasons:

    1. This cascade of changes is, of course, precisely the same kind of effect that systematic training in some sport should inspire compared to ordinary, non-elite athlete people. And we don't have a clue what those changes are at the genetic level! So first, you have to start with a sample of non-elite athletes and see what changes when you train intensively. Those changes will be heterogenous to some extent between different athletes (otherwise, they would all perform the same...). So you have to characterize the normal variability as an outcome of this highly unusual training regime. Only then can you start to assess whether a competitor is "outside the range" of normal variation. The Landis example makes it clear that we aren't at this point yet for ordinary chemical differences -- his testosterone tested high, but not outside the normal range.

    2. The same problems that keep us from finding a good way to identify gene doping also pretty much prevent anybody from applying it. The anti-doping people don't know what genes will be targeted, because it is not at all obvious which genes doping should target. There is no "Olympic athlete HapMap". Heck, we don't even know how to gene dope a horse (Max Zorin notwithstanding), and for horses at least someone would probably absorb the costs of experimentation. These anti-doping people are working on mice, for goodness' sake.

    The article is focused on the Beijing Olympics, with the idea that blood samples will be kept afterward for 10 years, so tests could be developed in the far future to detect current cheating.

    But there is a total lack of recognition of a basic reality: Somebody who actually could figure out how to genetically enhance an athlete before 2008 probably deserves a Nobel prize! And if they could figure that out, they would be a paid a whole lot more by applying their 'l33t genetic skillz curing osteoporosis or something.

    Not to say there aren't candidates -- for instance, suppose you could ratchet down a weightlifter's myostatin to match this kid. It is not too complicated to make it work, it's just that it won't be made to work in the next couple of years. The trickle-down from gene therapy is inevitable, but gene therapy itself is far from being ready yet.

    I mean, really, the reason why any reasonably talented scientist would deal in routine chemical enhancement for athletes is either (a) the black market and need for silence makes it incredibly lucrative compared to treating growth disorders in private practice, or (b) a much-higher-than-usual athlete-wanna-be complex. As soon as we do make some progress on these genetic systems, there will be plenty of doctors standing in line to do it. Just not so many Nobel-prize-worthy scientists. I mean, even Zorin's doctor had that whole residual-Third-Reich-loyalty keeping him in the game.

    Keep in mind, that many of these genetic manipulations will be most effective as interventions early in childhood, maximizing the developmental alteration. A huge shift in gene expression a year before the Olympics will usually be a lot less effective than a small course correction in a five-year-old. And are Olympic anti-doping mavens going to start screening out people because they had a small tweak in HGH when they were toddlers?

    The real theme of the article seems to be an attempt to scare athletes into shying away from gene doping. All the talk about health risks, and changing Mother Nature's blueprints, and whatnot -- they end with a warning that gene transfer may cause cancer by activating oncogenes.

    But really, there are plenty of people who would stand in line to trade 20 years of their lives to win an Olympic medal. And many who think that the current winners are simple beneficiaries of a genetic lottery. As soon as genetic modifications become routine to correct developmental problems, the kids who had them will start coming up through the sports ranks. The way it stands now, the Olympics and other sports venues are staging themselves as some of the last arbiters of "pure" humanity.

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