Can synthetic biology usher in the next generation of anti-doping measures?

This article originally appeared in SynBioBeta

By Embriette Hyde

It’s no secret that sports suffer from doping, the use of banned substances that enhance athletic performance. From Lance Armstrong being stripped of his Tour de France titles to Russia’s doping scandal during the 2014 Winter Olympics in Sochi, no sport seems to be left untouched by athletes driven to cheat by the need to retain sponsorships, by coaches that need wins to keep their jobs, or simply by the need to put food on the table. And despite the devastating losses associated with being caught doping, athletes — and their coaches — continue to do it.

While most people probably think of steroids and grotesquely muscled bodybuilders when they think about doped-up athletes, performance-enhancing substances are much broader than that — and in most cases you can’t tell just by looking at someone that they’ve taken a performance-enhancing drug.

An imperfect system, an elegant solution

Many athletes get away with doping, sometimes for years, sometimes for their entire careers. To determine whether an athlete has taken a banned substance, a blood or urine test is typically performed. These tests are quite expensive, rendering it impossible to perform them for each and every athlete in a competition. And, many substances have been developed to disappear from the bloodstream within a few hours, making them undetectable by the time the test is administered. Or, they may be present at concentrations too low to be detected by a standard urine test. In an age where banned substances are becoming increasingly optimized to evade detection, we are in sore need of new detection methods that can keep up.

Enter biosensors.

Biosensors are analytical devices that can be used to detect chemical substances. They combine a biological component — such as microorganisms, antibodies, or nucleic acids — with a physicochemical detector, which produces light, electricity, luminescence, or some other signal upon interaction with the substance of interest. Biosensors have been used for a variety of applications, from detecting heavy metal contamination of drinking water, drug residues in foods, to one application we’re all probably quite familiar with: blood glucose levels. And with the advent of synthetic biology techniques, ultra-specific, ultra-sensitive biological components are becoming ever easier to engineer.

One lab in Queensland, Australia, is intimately familiar with biosensors. Diabetics around the world can thank the Alexandrov laboratory at the University of Queensland for their point-of-care glucometer strips, a type of biosensor that has made checking blood glucose levels as quick and easy as tying your shoes. Now, the Alexandrov lab is working to re-engineer the glucometer strip to recognize a different class of targets: performance-enhancing drugs.

Using synthetic biology to detect the doping of today

The premise is simple: re-engineer the enzyme that responds to glucose in the blood into an easily modifiable platform enzyme that can be rapidly modified to recognise just about any target molecule you can think of. In a recent blog post, Alexandrov lab postdoc Jason Whitfield explained the process this way:

“In nature, enzymes and other proteins have a function called ‘allostery’ where the activity of the enzyme can be turned on or off depending on the environmental conditions … synthetic biologists … saw in this the possibility of synthetic allostery, which would allow us to control the activity of an enzyme for a purpose of our choosing. Essentially, they built a molecular on/off switch into the enzyme that can be activated by another molecule, such as a steroid or growth factor. So now, using an almost identical system to the glucometer, we are able to measure a completely different target substance.”

With this approach, testing athletes for banned substances could be as easy — and cheap — as testing blood sugar levels. Point-of-care type detection methods like this would make it much easier to enforce anti-doping measures and may prove a stronger deterrent to athletes who currently bet on the low odds of detection offered by current methods and testing strategies.

Using synthetic biology to detect the doping of tomorrow

Yet if history has taught us anything, it is this: the truly motivated will always find a way — and elite athletes have a sort of reputation for being willing to do anything to get the competitive edge. Synthetic biology — the toolset that may improve detection of today’s doping — may also prove the secret weapon toward creating the next generation of athletes. For example, CRISPR and other gene-editing tools may be attractive options for encoding athletic advantage into one’s genome. Or, industrial fermentation could yield high levels of pure substances impossible to extract from their natural sources, as is the case with some cannabinoids.

But not only may synthetic biology approaches help create the doping strategies of tomorrow, they may also be the best tool to detect them. CRISPR-based methods have already been developed to trace cell lineages; could they or other techniques be used to detect gene edits? Or, could living cell biosensors, like those designed to target pathogens or tumor cells, instead be engineered to search out banned substances? Perhaps they could also deliver new drugs to block the activity of the performance enhancing substance, rendering it useless — in essence, leveling the playing field.

For now, the future of synthetic biology in athletic performance is unclear. Indeed, CRISPR is years away from being capable of adding performance-enhancing genetic material to the human genome, facing both scientific and ethical challenges. But one thing is certain: synthetic biology has provided us with a useful tool set that we can put to work today. While novel detection methods may not eliminate the usage of banned substances completely, we may soon enter an era where doping is the exception, rather than the norm.