21st Century Olympic Doping

An illustration of swimmers, one of them in the lineup is a giant.

Gene editing for performance enhancement may not be the Tokyo cheat, but we asked the experts how far off it might be.

The 2020 Summer Olympics in Tokyo, finally set to kick off this week, have already been upended. After waiting an additional year to qualify, Games athletes will now compete in largely empty venues in an event sparked not by the running of a torch, but a series of closed-door ceremonies. Meanwhile, athletes hope to avoid joining a growing number of competitors who have tested positive for COVID-19 since arriving in Tokyo. Victors will accept gold medals passed to them on trays. Even the specter of cheating has evolved. As technologies like CRISPR leap ahead, a newer threat looms, unsteadily: gene doping.

The World Anti-Doping Agency (WADA) recently barred U.S. track star Shelby Houlihan from the Olympic trials after she tested positive for steroids—which Houlihan blamed on a pig organ meat burrito. The agency also banned sprinter and gold medal favorite Sha’Carri Richardson after she tested positive for THC. In addition to those traditional banned substances, WADA has long banned genetically modified cells and alterations of genome sequences or gene expression “by any mechanism,” including gene editing, silencing, and transfer technologies. WADA has yet to detect gene doping in any athlete; a spokesperson pointed to the agency’s ability to store samples for up to 10 years for potential reanalysis. This is no idle threat.

“Precedent shows when WADA has gone back to samples from previous Olympics, they have picked up doping in some form or another with numerous athletes,” says Diana Bowman, a law professor and expert on the governance of emerging technologies at Arizona State University. But the problem with gene doping is that it’s not clear how athletes would use it, what might happen if and when they do, and how it would be detected. 

“The rules will always lag the technology in terms of regulatory frameworks,” Bowman says. “Across all times with sport, individuals were willing to take risks to push the boundaries and to either outright cheat or break boundaries in a way that was advantageous to them.” Governments, she notes, have also been to blame for enabling pervasive, organized doping through state-sponsored programs.

Mainstream biomedical researchers have focused on therapeutic uses of gene editing to ameliorate disease and improve human health, with strides forward, for instance, in correcting a mutation that causes sickle cell disease and successfully editing liver cells in six patients with a rare, fatal nerve disorder. They’ve also created techniques like base editing, which replaces single base pairs (as opposed to larger chunks of DNA) and prime editing, a search-and-replace technique that only requires cutting a single strand of DNA. 

Greg Neely, a functional genomics expert at the University of Sydney in Australia, believes that CRISPR is the most likely avenue for near-future gene doping. “In my experience with mice and cells, it’s much easier to use CRISPR-Cas9 to turn off a gene than it is to use base or prime editing to specifically and precisely recode a nucleotide.” Still, he says that inefficiencies among these techniques—only a fraction of cells will incorporate a given gene-edited change introduced via CRISPR, base editing or prime editing—make it tough to predict future gene doping methods.

So, are athletes gene doping at this year’s Olympics? For Neely, who believes gene doping and even the ethical quandry of embryonic editing are on the way for future Olympians, the answer is still no. Mario Thevis, a doping prevention researcher at the German Sport University Cologne, recently developed a test for gene doping in mice that can detect the presence of Cas9, a protein used in CRISPR, for up to eight hours. And he’s not ready to rule out the possibility that athletes are already using CRISPR for doping in Tokyo.

“Technically, these gene-editing strategies are available and could be misused in an attempt to illicitly improve athletic performances,” Thevis says. “Obviously, a series of known and unknown risks would be associated with this, but the tool[s] to conduct such manipulations are presumably at hand already today.”

A picture of Sha'Carri Richardson celebrating after winning her 100-meter running Olympic trial.
Sha’Carri Richardson, who was recently banned from the Tokyo Olympics after testing positive for THC. AP Photo/Chris Carlson

How gene doping would work

Neely says that gene editing could be used to alter blood progenitor cells to induce an increased production of red blood cells—or to change the oxygen affinity of hemoglobin proteins in those cells—and therefore increase blood oxygen levels, essentially achieving the same result as injecting the banned substance erythropoietin. Another theoretical gene doping possibility is that CRISPR could be used to suppress myostatin, a muscle cell growth inhibitor. There is no evidence that any athlete has ever done either of those, and at present, neither would be an easy or guaranteed way to gain advantage. Worse, any gene editing raises the possibility of unpredictable (and irreversible) harms to athletes.

For example, while scientists know that people born with myostatin mutations tend to be more muscular, that’s based on naturally occurring genomes in which 100 percent of cells have the same genes. In a gene-doped athlete, however, only a fraction of gene-edited cells would have the desired genetic material. Instead, the athlete would have blood or tissue with mosaicized cells, Neely says, which specific and potentially invasive testing (depending on the type of cell edited) could reveal. Finally, our bodies are a delicate balance. Even if we could target the genes responsible for a desirable trait and edit them with a high level of efficiency, we have no idea how the body would respond. 

“There is a great deal of speculation about the possible advantages of gene editing for athletic ability without much attention to its possible risk,” says Hank Greely, a Stanford professor and author of the book CRISPR People: The Science and Ethics of Editing Humans

“Genes are complicated and, as far as we can tell, most of them do many different things,” Greely says. “That a particular variation produces strong bodies in cattle or dogs—or even, in the one case I know of, where a child was born with the mutation—does not mean they will produce the same, or even roughly similar, effects on an adult human. Or that they will not cause serious health problems.” Adding to these difficulties, Josef Penninger, a molecular immunologist at The University of British Columbia, says, “Even if you have a targeted gene, it is not so easy. For most enhancements, [you] probably have to change ten, twenty genes at the same time.”

“The only thing you can do is hope the characters of the people who are steering the ship across uncharted seas are decent.”

There are larger ethical quandaries on the horizon, too. Bowman points out that the promise of gene editing in medicine also raises questions about fairness, as many athletes could not afford experimental CRISPR treatments. This is a parallel to an athletic world in which, Greely says, some athletes are already born with genetic variations that enhance performance. But gene doping would advantage athletes from wealthier nations by giving them artificial access to those same genes in the same way they are already potentially advantaged because of specialized diets, training regimens, elite coaches and trainers, altitude training, etc. 

Genetic editing is not limited to adults, and embryonic editing could produce gene-doped Olympians whose alterations may be undetectable. If procedures could be done safely (and avoid unwanted, off-target genetic changes), the resultant babies would appear as if they were born with those genes naturally, according to Neely. Unlike gene editing in adult athletes, embryonic changes would be passed through generations with unpredictable outcomes for their offspring—and future generations

“We evolved as a fine-tuned balance, and strongly switching things can cause disastrous outcomes. A thousand years from now, we may have mutated out of something that we really actually needed and didn’t know it,” Neely says, pointing to the need for regulations. Meanwhile, Bowman predicts that a spotty patchwork of regulations governing gene editing will emerge, in which some nations ban it, and others regulate it in varying ways, potentially allowing less-regulated nations to play host to those seeking to push legal and scientific boundaries. University of Chicago bioethicist Laurie Zoloth sees things more optimistically, pointing to protective norms that develop across scientific communities. “People pull back and come to a sensible discussion. This creates norms, so even if there are not international laws, there are international norms.” Still, she says, “When you’re dealing with a total unknown, the only thing you can do is hope the characters of the people who are steering the ship across uncharted seas are decent.” 

But the very existence of a policing agency like WADA would suggest decency alone is not enough to prevent a well-funded athlete from trying to gain an unnatural advantage ahead of competition. Let the Games begin.

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