转基因的奥运会运动员？

转基因的奥运会运动员？
Genetically Modified Olympians?

Gene doping
基因兴奋剂

On the eve of the Beijing Olympics, we examine the prospect of athletes using gene therapy to enhance their performance—and of catching them if they try.

奥运会日益临近，我们分析参赛运动员使用基因治疗技术提高他们运动成绩的可能性，如果运动员真这样做了，我们能抓住他们么？

FOR as long as people have vied for sporting glory, they have also sought shortcuts to the champion’s rostrum. Often, those shortcuts have relied on the assistance of doctors. After all, most doping involves little more than applying existing therapies to healthy bodies. These days, however, the competition is so intense that existing therapies are not enough. Now, athletes in search of the physiological enhancement they need to take them a stride ahead of their opponents are scanning medicine’s future, as well as its present. In particular, they are interested in a field known as gene therapy.

只要人们在竞技体育中追求荣誉，他们同时就会寻求通往冠军领奖台的捷径。通常情况下，找到这些捷径依赖于医生的帮忙。毕竟兴奋剂的使用大多数只不过是把现有的治疗技术应用于健康的运动员。然而，现在的体育竞争太激烈了，以至于即使使用当前的治疗技术都不足以帮助运动员获胜了。现在那些想通过提高生理条件来战胜对手的运动员，除了想依赖目前的医疗技术外，也开始寻觅医疗领域的新突破。这些运动员尤其对基因疗法感兴趣。

Gene therapy works by inserting extra copies of particular genes into the body. These extra copies, known as “transgenes”, may cover for a broken gene or regulate gene activity. Though gene therapy has yet to yield a reliable medical treatment, more than 1,300 clinical trials are now under way. As that number suggests, the field is reckoned to be full of promise.

基因疗法的工作原理在于把特定基因的额外拷贝植入到体内。这些叫做“转基因”的额外拷贝能覆盖损坏的基因或者调节基因活动。虽然基因疗法还没有产生可靠的治疗效果，但是目前仍有超过1300多个的临床试验在进行之中。这个庞大的数字仿佛表明基因疗法的前景一片美好。

As far as sport is concerned, the top transgene on the list, according to Jim Rupert, an anti-doping expert at the University of British Columbia, is the gene for erythropoietin. EPO, as it is known for short, is a hormone that regulates the production of red blood cells. It is already available as a drug (it was one of the first products of biotechnology companies in the late 1980s), and it has been used widely in endurance sports such as long-distance cycling. But if an athlete’s body could be stimulated to make more of it that would—from the athlete’s point of view—be better than taking it in drug form.

来自英属哥伦比亚大学的反兴奋剂专家吉姆•鲁珀特说，就体育运动而言众多基因中最受关注的是红细胞生成素基因。红细胞生成素（简称EPO）是一种调节红细胞生成的荷尔蒙。EPO作为一种药品目前在市场上有售（它是上个世纪80年代后期生物技术公司的第一批产品），有人已经在一些耐力体育项目，诸如越野自行车中使用这种药品。但是从运动员的角度看，如果运动员的身体能通过刺激来生成更多的EPO的话，那么这种刺激的方式比服用做为药品的EPO好。

No dopes
禁止服用兴奋剂

The reason is that EPO, like most performance-enhancing drugs, is banned. However, bans work only when they are enforced, and that requires a test which can distinguish synthetic EPO from the natural hormone made by an athlete’s body. At the moment, this is possible. The EPO from a biotechnology company’s vats has a slightly different chemical structure from the natural sort. But the evidence suggests that EPO produced as a result of gene therapy will be far harder to distinguish.

这是因为EPO和其它许多兴奋剂一样是违禁药品。但是，禁令只有执行以后才生效，这就要求进行兴奋剂的检测。通过检测人们能把合成的EPO与运动员自身产生的天然荷尔蒙区别开。目前人们能做到这一点。生物技术公司制造的EPO与天然的EPO在化学结构上有一些细微的差别。但是，有证据表明通过基因疗法生产的EPO很难与天然的EP 区别开来。

In fact, EPO doping may already have happened. In 2006, during the trial of Thomas Springstein, a German coach accused of doping his underage charges, it transpired that Repoxygen, an experimental gene-therapy product containing the gene for EPO, was already making the rounds on the black market. Repoxygen causes a controlled release of EPO, but only when the body senses a lack of oxygen. Or at least it does so in mice.

实际上，服用EPO兴奋剂的事件可能已经发生过。在2006年审判托马斯•斯普林斯廷（一名德国教练，被控让由他负责的未成年人运动员服用兴奋剂）的案件中，人们就知道兴奋剂Repoxygen（一种含有EPO基因的处于试验阶段的基因疗法产品，）已经流入黑市。兴奋剂Repoxygen能可控释放EPO，但这仅仅是在身体缺氧的时候，至少对于老鼠来说情况是这样的。

Whether black-market Repoxygen has won any races is unknown. But several other genetic therapies being tested in mice also look as if they may interest the sort of men and women who feel their athletic performance needs a little boost.

黑市上的兴奋剂Repoxygen是否帮助运动员赢得过比赛现在还不得而知。但是其它几项正在以老鼠为实验对象的基因疗法，看起来能引起希望靠兴奋剂提高成绩的运动员的兴趣。

Like EPO, vascular endothelial growth factor spurs red-blood-cell formation and thus helps to supply tissues with oxygen. The gene that encodes this protein is the subject of several medical studies, and is thus a prime candidate for sporting use.

跟EPO 一样，血管内皮生长因子促使红细胞的形成从而帮助组织供血。该蛋白质编码基因是目前几项医学研究的对象，该基因也很可能在将来成为基因兴奋剂。

IGF-1 is also a growth factor—though it promotes brawniness in muscle rather than the production of blood cells. Inject the gene that encodes it into a particular muscle and you can affect that muscle and no other. Such specificity might be of interest to people like tennis players and javelin throwers. Meanwhile, a gene called MSTN encodes a protein called myostatin, which limits rather than enhances muscle development. In this case, therefore, the doping is designed to switch the gene off. The result is what have been nicknamed “Schwarzenegger” mice.

IGF-1也是一种生长因子，但是它的作用是强健肌肉而不是产生血细胞。如果把该生长因子的基因注入到特定的肌肉里，那么它只能影响该特定肌肉而不会影响其它的肌肉。网球和标枪运动员对这种专一性可能会感兴趣。另外，一种叫做MSTN的基因编码肌抑素蛋白质，这种蛋白质限制而不是增强肌肉的生长。因此在这种情况下，服用兴奋剂的目的是关闭MSTN基因。这样的基因疗法应用到老鼠之后，就会得到昵称为“施瓦辛格”老鼠。（译者注：施瓦辛格，好莱坞影星，以其健壮的肌肉著称，现任加州州长）

Once brawny muscles have been acquired, whether licitly or illicitly, other genes might then be used to tune their activity. Tweaking PPAR-delta, for instance, alters the way muscles obtain their energy. The individual fibres that comprise a muscle can run in one of two modes. In slow-twitch mode they burn fat, and are less prone to fatigue. In fast-twitch mode they burn sugar. That makes them prone to fatigue, but is useful for delivering short bursts of power. Both modes are valuable to athletes, but in different types of event. The ability to make muscle fibres specialise in one mode or the other would thus be of great benefit to unscrupulous coaches. PPAR-delta controls the switch.

一旦获得了强健的肌肉（不管是合法还是不合法），其它的基因就可以用来调整肌肉的活动方式。比如对PPAR-delta稍加改变后，它就能改变肌肉获取能量的方式。组成肌肉的肌纤维有两种活动模式。在慢速伸缩模式下，肌纤维燃烧脂肪获取能量，在这种模式下肌肉不易疲劳。在快速伸缩模式下，燃烧糖，虽然在这种模式下肌肉易疲劳，但有利于获得爆发力量。这两种肌纤维活动模式对于运动员来说都是有利的，只是针对不同的体育赛事而已。如果能使肌纤维专门用于某一种模式下，这对于那些想使用兴奋剂的不诚实的教练来说将具有极大的好处。PPAR-delta可以到达这样的控制目的。

Finally, animal studies on the genes for natural pain-killers called endorphins suggest that these could be used to limit the perception of pain—another desirable trait for athletes. That might consign the adage “no pain, no gain” to the history books.

最后，天然止痛剂（内啡肽）基因的动物实验表明这些基因能降低动物对疼痛的感受能力，对运动员来说这又是一大好处。所以“不劳而获”这句谚语可能要进入历史书本了。

There is thus a lot of potential. And although—the Springstein incident aside—there is no evidence that any of these techniques have made their way into real athletes, the authorities are taking no chances.

看起来基因兴奋剂的使用是很有可能的。虽然目前还没有证据表明这些技术已经在运动员身上使用（斯普林斯廷事件除外），但是国际反兴奋剂组织对于基因兴奋剂不愿冒任何的风险。

The World Anti-Doping Agency (WADA), sensed several years ago which way the wind was blowing. In 2003 it issued a proclamation banning “the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance”. It followed this by putting its money where its mouth was. Since much of gene doping’s allure derives from its alleged undetectability, WADA committed $7.8m—a quarter of its research budget for 2004-07—to 21 projects intended to develop ways of detecting it. Now another $6.5m is up for grabs.

国际反兴奋剂组织（WADA）几年前就发觉了基因兴奋剂的动向。在2003年该组织发布了一项禁令，禁止“非治疗性使用能提高运动员成绩的基因、基因组分/细胞”。发布禁令后，该组织随后就展开了实际行动。因为基因兴奋剂的诱惑在于其不易被检测出来，所以WADA向承担研发检测兴奋剂方法的21个研究项目拨出780万美元（其2004—07研究预算的四分之一）。现在该组织又拨出了650万美元的研究经费。

Broadly, there are two ways of spending this money usefully. The direct approach focuses on improving ways of detecting differences between truly natural and “therapeutically enhanced” proteins or, failing that, on detecting the “vector” used to inject the transgenes into the places where they will operate. Such vectors are often particular sorts of virus.

一般来说，有两种检查兴奋剂的方法。直接法集中于提高检测真实蛋白质与“治疗性提高”蛋白质之间的差别的方法。如果这个不灵，就集中于检测“载体”，这些“载体”用来把转基因植入所需要的地方。这些载体经常是一些特定的病毒。

The indirect approach seeks second-hand signs of the transgene or its vector. Viruses, for example, may produce a characteristic immune response that can be detected. Meanwhile the transgenes themselves may alter the body’s proteome (the set of proteins active in it at any given time) or its metabolome (a list of all the by-products of the chemical reactions that go on in each cell). Changes to either of these “-omes” can, in principle, be detected in blood or urine. What is needed are points of comparison. This requires working out the typical “biosignatures” of elite sportsmen as a group, or indeed of each individual, as a baseline.

间接方法寻求找到转基因或者其载体的二手信号。举例来说，病毒能产生出一种能被检测到的特征免疫响应。另外，转基因本身可以改变身体的蛋白质组（在任何时候体内的一组活性蛋白）或者代谢组（在每个细胞中进行化学反应后的一组副产品）。原则上讲，蛋白质组或者代谢组的改变可以在血液和尿液中检测出来。这时所需要的是对比点。这就要求得到一组优秀运动员或者实际上每个运动员的典型的“生物签名”来作为基准。

Testing times
考验的时候

Whether gene doping will make its debut in Beijing remains to be seen—or perhaps not, if it is as hard to detect as its protagonists hope. Theodore Friedmann of the University of California, San Diego, who heads WADA’s Gene Doping Panel, reckons it probably won’t happen this time. He does not think there is, yet, a form of gene therapy that could easily be used to enhance performance. As for Dr Rupert, he says, “I would be surprised. But I have been surprised before.” It would be ironic if the first successful application of gene therapy were to people who are among the fittest on the planet. But it is possible.

基因兴奋剂是否会在北京奥运会上初次亮相还有待证实。如果它们正如使用兴奋剂的运动员所希望的那样难以检测出来，或者我们将看不到它们的初演。来自加利福利亚大学圣迭戈分校的西奥多•弗里德曼是国际反兴奋剂组织基因兴奋剂小组的主任，他认为本届奥运会可能不会出现基因兴奋剂丑闻。他认为目前还没有一种基因疗法可以很容易地用来提高运动员的成绩。鲁珀特博士说，“如果本届奥运会出现基因兴奋剂，我会感到吃惊。但是我以前是被兴奋剂丑闻震惊过的。”如果基因疗法的首次成功应用是在这个地球上那些最健康的人身上，这将是个讽刺。但是这是可能的。（编辑：胡慧）

（英文原文来自The Economist 《经济学人》http://www.economist.com）