Volume 94 Issue 32 | pp. 25-26
Issue Date: August 8, 2016 | Web Date: August 3, 2016

Athletes at Rio Olympics face advanced antidoping technology

Officials can now check for long-ago anabolic steroid use, with gene doping tests on the horizon
Department: Science & Technology
News Channels: Analytical SCENE, Biological SCENE
Keywords: biotechnology, doping, gene therapy
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Turkish weight lifter Sibel Özkan was recently stripped of the silver medal she won at the 2008 Beijing Olympic Games after retesting showed that she had doped.
Credit: Newscom
Image of Turkish weightlifter Sibel Ozkan receiving her silver medal.
 
Turkish weight lifter Sibel Özkan was recently stripped of the silver medal she won at the 2008 Beijing Olympic Games after retesting showed that she had doped.
Credit: Newscom

Athletes currently attending the Summer Olympics in Rio de Janeiro may eventually face a new kind of doping test: one that checks whether they have received performance-enhancing gene therapy. According to the International Olympic Committee’s medical and scientific director, Richard Budgett, samples collected in Rio will be tested for gene doping at some point after the games, even though the test won’t be run during the Olympics itself.

Officials want to know whether athletes have been given synthetic DNA that codes for erythropoietin (EPO), a hormone that increases red blood cell production and, consequently, athletic performance, said Carl Johan Sundberg, an exercise physiologist at Karolinska Institute and member of the World Anti-Doping Agency’s gene doping panel. Sundberg explained the technique that Olympic officials plan to use to test for gene doping at the EuroScience Open Forum (ESOF) conference, held July 23–27 in Manchester, England.

Retroactive testing isn’t good news for corrupt athletes. When scientists retested fluid samples from athletes competing at previous Olympics Games, namely Beijing’s 2008 and London’s 2012 Summer Games, many more athletes tested positive for banned substances than with prior analyses. The tests, carried out with improved analytical techniques, revealed that, on average, 8% of the athletes at those two games actually tested positive for banned substances, up from an average of less than 1% observed in past games. The increase is “sensational,” said Arne Ljungqvist, a 1952 high-jump Olympic athlete and former vice president of the World Anti-Doping Agency (WADA), at the ESOF session.

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Busted
When scientists retested athletes’ samples in 2016 with more sensitive methods, they found a higher rate of doping than initially reported.


Note: Not all samples originally tested during the Olympics were retested in 2016. For example, there were 5,051 samples tested in 2012 in London. In 2016, 403 of those were retested.
Sources: World Anti-Doping Agency and Arne Ljungqvist
Credit: WADA and Arne Ljungqvist
A bubble graphic showing the numbers of athletes found to be doping at the Olympics in 2008 and 2012 compared with the number of athletes found to be doping after the fact.
 
Busted
When scientists retested athletes’ samples in 2016 with more sensitive methods, they found a higher rate of doping than initially reported.


Note: Not all samples originally tested during the Olympics were retested in 2016. For example, there were 5,051 samples tested in 2012 in London. In 2016, 403 of those were retested.
Sources: World Anti-Doping Agency and Arne Ljungqvist
Credit: WADA and Arne Ljungqvist

Add these data to other recent doping scandals, and the International Olympic Committee has had its hands full lately. Last month IOC announced that Russian athletes could participate in the Rio Games, despite evidence of sample tampering at the 2014 Sochi Winter Olympics and indications of an entrenched doping culture in the country’s athletic community.

It’s up for debate whether WADA doping labs will eventually find any athletes guilty of gene doping at the Rio Olympics this month. There is no evidence that Olympic athletes are currently undergoing gene doping, Sundberg said. But then again, “the test has never been used before,” he added.

Even so, evidence does exist that at least one corrupt German coach tried to organize gene doping for his athletes more than a decade ago: In a 2006 trial, prosecutors exhibited e-mails written by former German Athletics Association coach Thomas Springstein in which he requested EPO gene doping products from his drug dealer.

Although only a handful of gene therapy procedures to treat disease have been approved by worldwide regulators, WADA started considering the possibility that athletes might abuse gene doping in 2002, and in 2003 it added gene doping to its list of prohibited substances and methods.

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Doping investigators have discovered that long-term metabolites of these banned steroid compounds can survive in athletes’ bodies for months.
Credit: C&EN
Structures of six banned compounds.
 
Doping investigators have discovered that long-term metabolites of these banned steroid compounds can survive in athletes’ bodies for months.
Credit: C&EN

The gene doping test is based on work by Anna Baoutina and colleagues at the National Measurement Institute in Sydney, Australia. The technique relies on the gene that naturally codes for EPO in the human body and the fact that it contains four introns, sequences that get cut out of messenger RNA after the gene has been transcribed. Synthetic EPO DNA inserted during gene therapy is unlikely to have such intron sequences. Gene dopers could be caught if officials scanned blood samples for EPO DNA without these introns.

There’s also a growing doping problem among the general public.

This is not the only strategy proposed for checking athletes for gene doping. Researchers have also designed tests that search for proteins in blood that are unique to the viruses scientists use to transport genes across a cell membrane and then into a genome (Drug Test. Analysis 2012, DOI: 10.1002/dta.1347). Other techniques rely on looking at the sugars decorating the protein that’s been produced from the contraband: For example, EPO is normally produced in the kidney, where it is glycosylated in four different places.

Gene dopers, however, are more likely to inject EPO DNA into muscle, which has different glycosylation pathways. Unusual sugar decorations could act as a smoking gun for gene doping, Sundberg said. In fact, doping labs currently do an analogous test that looks for athletes who have injected bacteria-synthesized EPO directly into their blood, he added. Bacteria decorate EPO differently than humans do, giving testers a way to catch cheaters.

WADA is also funding research to test whether athletes have received gene therapy for growth factor proteins, such as growth hormone and IGF-1, which bolster muscle development. The doping research field is also investigating ways to test for anticipated cell doping in athletes, Sundberg said. Doctors have for a long time transplanted bone marrow stem cells in cancer patients, he said. “In the future, athletes may transplant cells to improve heart and muscle strength and endurance.” And with the advent of the CRISPR/Cas9 technique, athletes could start paying for genetic editing of their own cells. “You might think it sounds like a bit of science fiction, but it might quite soon not really be so,” Sundberg said.

Although researchers are trying to anticipate future doping strategies, steroids are currently still the number one choice for corrupt athletes, Ljungqvist said at ESOF.

The spike in positive doping results that scientists saw when they retested samples from Beijing and London, for instance, can be attributed to steroids. Researchers have made improvements in analytical instruments—primarily mass spectrometers—for detecting contraband compounds, and they’ve discovered so-called long-term metabolites of banned anabolic steroids, including metandienone, oxymetholone, and stanozolol, in athletes’ urine.

In the past, researchers could only detect metabolites of a banned steroid in urine for weeks after the last dose, Ljungqvist explained. “Now that window has been expanded to a couple of months” with the identification of these metabolites that stick around much longer.

After a WADA-accredited laboratory in Cologne, Germany, started testing for long-term metabolites of metandienone, the lab saw a 400% increase in positive doping results (Br. J. Sports Med. 2014, DOI: 10.1136/bjsports-2014-093526).

Though most media attention focuses on doping by professional athletes, there’s also a growing doping problem among the general public, Ljungqvist said.

“Nine-tenths of the iceberg underwater is the doping taking place in recreational sports or by people trying to enhance their body image in entirely unregulated ways,” said doping researcher Mike McNamee from Swansea University to the ESOF delegates.

“It’s not just young men wanting to look like their favorite Hollywood actor. It’s also policemen, firefighters, security personnel, and bouncers,” he said. Although everyone working in doping agrees it’s a huge problem among the general public, there’s no reliable prevalence data, McNamee said. Because it’s not possible to test the general public for contraband drugs—except in Denmark, where doping officials are allowed to test people in public gyms—education is probably the best way to reduce the use of contraband drugs by the general public, McNamee added.

Of course, it’s hard to convince the general public not to use contraband substances if professional athletes caught doping don’t suffer consequences.

“I am one of those who was fooled in Sochi by the Russians,” Ljungqvist told reporters during a press conference at ESOF. “At night, behind my back, [they] were changing samples through a hole in the wall. This is not the first time I was cheated by the Russians. During the Beijing Games, we discovered that female athletes’ urine was exchanged. This deserves some punishment.” When asked about IOC’s recent decision not to ban Russian athletes from participation in Rio, Ljungqvist replied: “In the IOC report, I would have welcomed an explanation about why this penalty wasn’t chosen.” 

The dope on doping
Get the basics on why athletes risk their careers and their health with banned anabolic steroids from our friends at ACS Reactions.


 
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Comments
Gerardo Caballero (Wed Aug 03 17:39:53 EDT 2016)
Antidoping tests are always a step behind doping "novelties", a race impossible to win in the long run. A smoker knows that smoking is harmful to her/his health, so does an athlete that commits doping. And smoking is a much, much bigger public health problem than doping. So, why spend huge human, technological, and financial resources to take care of a health issue that concerns only to privileged athletes? In my opinion it would be more fair and less hypocritical to eliminate doping controls from all sports, and invest the resources thus liberated in research focused on health areas more relevant to the big public.
Robert Buntrock (Fri Aug 05 09:44:47 EDT 2016)
Interesting article. Check a recent New York Times article for more on the eligibility or Russian athletes as of Fri. 7/5/16. Note that there is a fourth, unidentified compound shown last in the The Russian Doping Scandal box. Please identify.
laurenkwolf (Fri Aug 05 13:56:44 EDT 2016)
Hi Bob,
That last compound is trenbolone. There's some (admittedly) small type under oral turinabol that says it was swapped into the cocktail after the 2012 London Games. Thanks for checking!
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