Enhancing athletic performance on a genetic level

​Doping is always a hot topic at the Olympics. One day, we may never again have to ban the entire Olympic team from Russia, not because athletes won't be doping, but because they will be gene doping and be able to completely avoid detection. The World Anti-Doping Agency (or WADA) is trying to stay a step ahead.

What is gene doping?

Gene doping can mean a few things but ultimately it means reversibly or irreversibly changing how your body works by changing how the genes in your body are used or expressed.

WADA calls it: the non-therapeutic use of cells, genes, genetic elements or modulation of genetic expression having the capacity to enhance performance.

In fact, WADA has been talking about how to detect and deter athletes from gene doping for years now, and recently had a meeting in Montreal about considering asking all athletes to have their entire genome sequenced prior to competition.

How is it done?

It isn't done, at least not that we know of, but the technologies exist in certain forms. If you want to alter your genes then there is something called gene therapy. It's a medical intervention for genetic diseases. When you are born with a mutation in your genes that makes you sick, it aims to restore the normal function of that gene.

This medical research has been around for a while and has seen fits and starts of success but the idea is to use this technology for non-therapeutic enhancement of athletic performance, instead of fixing grave genetic disease.

Gene therapy is done in two main ways: called in vivo and ex vivo.

The first strategy is to inject a patient, or athlete in this case, with a virus that carries a chunk of DNA that is going to enter the target cells of the body – the muscle, for instance, in an athlete – and deliver a modified form of DNA that will provide some competitive advantage. There are lots of complications when trying to do this which is why it isn't common practice medically….yet.

There's also ex vivo. This involves taking cells from the patient, growing and genetically modifying those cells in the lab then reintroducing these new and improved cells back into the patient. Again, lots of hurdles but with some successes as well, with some types of genetic diseases being cured with this strategy.

What kind of genes are being modified?

There are quite a few genes that we know of that can improve athletic performance. Again, a lot of this basic scientific research has been done to be medically relevant it just also may have a more sinister application in athletic performance.

One gene that works in mice to create so called "marathon-mice" is a gene called PPAR delta. It was introduced in mice in 2004 and allowed them to increase their Type I and Type II muscle fibres. That meant they could run twice as far as their littermates — an obvious advantage for anyone in endurance sports.

There's also IGF-1 (insulin-like growth factor 1). This gene could be modified and introduced to help heal muscle. It was first used in gene therapy in mice to try to cure Duchenne's muscular dystrophy and also helped mice maintain muscle tone and fitness into old age. But this one may also increase your chances of cancer.

And there's EPO – the drug Lance Armstrong was using, as well as many cross-country skiers in past Olympics. That's detectable if you just take a dose of it, but if you modify the genes for it and increase its potency or natural levels then it skirts below the detection systems.

Are any of these gene doping techniques detectable?

Effectively no. There may be a few ways to detect the leftovers of the gene therapy procedure but it will be exceedingly hard to prove.

That's why WADA is considering whole genomic sequencing of athletes in order for them to enter into the world competition stage. It used to be too cost-prohibitive for anyone to consider having a reference for each athlete but now it's about $100 per genome, so it's economically feasible. 

But is it worth it? That depends. Some of the researchers who have done these experiments on mice have admitted to being approached by non-Olympic athletes looking for a boost. But it's so far away from being safe in humans that the question is: Who is even doing it?

There is one new technique that would be entirely undetectable – that's the CRISPR/Cas9 system. This is a permanent modification to the DNA sequence that is like a search, cut and paste editing tool on your computer editing software. This technique has been tried on some human embryo cells in China, with disputed results, and has been used in all kinds of research animals to show its potency. This is gene replacement in a totally new way than traditional gene therapy.

At some point should we just throw our hands up and say, "Let the floodgates of doping open?"

That's the question isn't it?

If CRISPR/Cas9 genome modification is ever found to be doable and safe in humans there is almost no way to ever catch a cheat. You'd have to get a sample of their DNA before they even become competitive athletes, when they are kids, to have some reference sample so you can tell if any changes have been made in adulthood.

I'm presuming no one would irreversibly change the genetics of a child before they even show athletic potential and I hope that is safe to assume.

The thing is that doping technology has always stayed one step ahead of detection, but it has only stayed one step ahead. So if CRISPR/Cas9 modification of the genome in humans becomes possible and is done by athletes, we can only hope the minds at WADA are just years or even months away from catching the cheaters. Now with retroactive punishments it's still possible to catch a cheat even if it takes a while to catch up.