First came the Schwarzenegger mice. Then a German track coach tried to get his hands on Repoxygen.
And thus began discussion about gene doping in sport.
Lee Sweeney, a scientist at the University of Pennsylvania, created the well-muscled “Schwarzenegger mice” by inserting a gene into their cells that signals the body to make more muscle. Sweeney’s research aims to create new therapies for muscles degenerating from age or diseases such as muscular dystrophy. Soon after the news about the mice broke in 1998 Sweeney was inundated with calls from people connected to sport. He says that one junior college football coach wanted him to gene-dope his entire team. Sweeney told The Daily Beast he refused.
A few years later, Thomas Springstein, a prominent German coach, attempted to get an experimental gene therapy to use on his athletes. Repoxygen, as it was known, was intended to insert a gene that would increase endurance by boosting production of red blood cells. By 2006 Springstein was on trial for giving illegal substances—performance enhancing drugs—to a minor including a 16-year-old girl. There is no evidence he ever found any Repoxygen. In any event, commercial development on it was abandoned. But there seems little doubt that he’d have tried it on athletes in his care if he had.
“Gene doping,” like the more familiar doping with anabolic steroids and other drugs, relies on using biomedical technologies to enhance an athlete’s performance. However, with gene doping, rather than swallowing a pill or injecting a drug, you’re targeting the genome itself—the instruction kit that tells your body, among other messages, which hormones to make and when. It’s helpful to know that many of the drugs athletes use are hormones—synthetic anabolic steroids, erythropoietin (EPO) and growth hormone, for example.
Following decades of frustration and a number of deaths, the FDA has now approved three gene therapies, the most recent to treat a rare genetic mutation that can cause blindness. The first approval, which required a scientific judgment that the benefits outweighed the risks, came just last year.
The same technology powers both gene therapy and gene doping. If and when gene therapies that build muscle or increase endurance become available, the people who peddle enhancement drugs to athletes will surely do the same with gene therapies. A 2008 report from Beijing claimed that Chinese scientists were selling gene doping for $24,000. But the headline was misleading: they proposed to use stem cells, not genetic manipulation. In any event, the stem cells likely would have been no more effective at enhancing performance.
We can think of genes as sentences—the fundamental unit of meaning in the genetic language. That language has only four letters, A, C, G and T; every word has precisely three letters. But the genes, the genomic sentences, can be of Faulknerian length. In gene therapy/doping, the gene is packaged inside a tiny vessel intended to deliver its payload to your cells. The most common delivery system at this time is an adeno-associated virus or AAV, a small virus unlikely to provoke an immune response. Previous exposure to AAV viruses is very common in humans but there is little evidence that AAV causes any human diseases. (A report just published makes it clear, however, that AAV is not risk-free. Three monkeys and three piglets were injected with a high dose of AAV in a study to develop a treatment for motor neuron diseases. The researchers observed “severe toxicity occurred in both NHPs and piglets.”) We can think of the successful “delivery” of new genetic sequence via AAV as editing the collection of sentences—genes— that constitute your genome. The “story” your genome would now tell is different from the one you were born with.
When the goal is to treat a serious disease, we can justify modest, proportionate risks in the human research trials necessary to prove the therapy works; likewise, we weigh the benefits and the risks in deciding whether to use this or any other therapy for this patient. When the goal is to boost an athlete’s strength, speed or stamina, the calculation must be different. How do we justify exposing young athletes—make no mistake, the “experimental subjects” are likely to be young, some may be children—to very risky interventions? What weight if any should we give any potential “benefit” in enhanced performance that would be measured in fractions of seconds or inches? Does the remote possibility that such an enhancement could some day mean the difference between victory and second place change our moral assessment?
Despite these powerful ethical stop signs some people will try to sell what they claim is gene doping to athletes. Much of what is being peddled is likely to be something else. (Steroids are a good guess.) Nor is whatever “gene doping” athletes might use today likely to help them perform better. If an athlete is naïve or foolish enough to try underground “gene doping” I hope they’re getting a placebo instead. That way, at least the risks aren’t so awful.
It’s worth noting that anti-doping scientists are on the case. Remnants of the AAV delivery system can be detected. Furthermore, the genes inserted into our cells aren’t identical to our own, and that difference can be picked up by sequencing the gene, which is becoming increasingly cheap and easy to do. It turns out that the sentences in our natural genes consist of fragments called “exons”—phrases— interspersed with other stretches of DNA called “introns.” An unnatural intron-free gene would be evidence of gene doping.
Gene therapy is finally a reality. People will try to sell what they’ll claim is gene doping to athletes, even in the absence of solid evidence that it’s safe and it works. Expect buzz about gene-doped athletes in Pyeongchang; the likelihood that any medals will be affected in 2018 is close to zero.