How Mamadou Sakho Fell Victim To Drug Testing’s Gray Areas

On March 17, 2016, Liverpool played Manchester United to a 1-1 draw in the second leg of the Europa League quarterfinals, a result good enough to send Liverpool to the semis. After the match, Liverpool's starting centerback Mamadou Sakho was called for a doping control test, which is fairly routine. The sample was sent to the lab at the German Sport University Cologne, a World Anti-Doping Agency (WADA)-accredited facility widely regarded as one of the best in the world.

Fast forward almost a year to the present day. Sakho, who was a regular for Liverpool in 2016 and was on the shortlist for a call-up to the French national team for the Euros that summer, has barely played since. He hasn't featured for Liverpool since that Europa League quarterfinal, and was loaned out to Crystal Palace at the January transfer deadline. He made his first start for Crystal Palace on February 26, three weeks shy of a year since his last club game. Over the summer, France's manager Didier Deschamps said he would not call Sakho up for the Euros despite a slate of injuries at centerback, Sakho's position. If he did, Deschamps said, then he would have "no respect for the players I selected."

What exactly did Sakho do to make his career tank so rapidly?

If you follow European soccer, you probably know that the sample Sakho submitted after that March 17 match tested positive for performance enhancing drugs. You may faintly recall hearing that the charge was later dismissed for some reason. But unless you're a die-hard Liverpool fan or a fervent chronicler of doping cases, you probably never heard why.

Sakho's case is an example of how doping charges are rarely the black-and-white, good versus evil dichotomy they're portrayed to be. You probably never heard much about Sakho's case because it's hard to make sense of it. Sometimes, doping cases are messy.

On April 22, more than a month after the test, Sakho was informed that his sample tested positive for Higenamine, according to the UEFA disciplinary body report which detailed the case. Higenamine is a naturally-occurring compound found in several plants native to Asia—partially Japan and China—but it can also be artificially produced and is found in over the counter supplements. Six days later, UEFA opened disciplinary proceedings against Sakho for violation of the UEFA Anti-Doping regulations, which adhere to WADA standards, including WADA's list of prohibited substances.

But Higenamine was not explicitly named in WADA's 2016 banned substance list. In the notification, UEFA told Sakho that the violation occurred because WADA's prohibited list includes all beta2-agonists, which can be found in asthma inhalers, and that Higenamine is a beta2-agonist.

WADA doesn't name every single banned substance on the prohibited list because it would create an easy avenue for athletes to circumvent WADA's testing. Enterprising chemists and doctors could simply design new drugs that aren't technically on the WADA banned list but are chemically similar and achieve all the same goals as a banned substance. This is, after all, precisely what BALCO's lab did. Instead, WADA bans a type of compound and all "similar substances."

The problem is that from time to time a substance comes to the forefront which falls into a chemical gray area. "It is difficult to assess when 'similar' is 'similar enough,'" said Olivier De Hon, manager of scientific affairs for Anti-Doping Netherlands. "So it will be necessary to decide on the prohibited status on a case-by-case basis (or at least a substance-by-substance basis)."

Sports lawyer Howard Jacobs, one of the world's foremost experts on anti-doping cases, was part of the team that represented Sakho. Jacobs acknowledged in a phone conversation with VICE Sports that cases like BALCO proved the necessity of the "related substances" clauses in the banned list, but also says they only make sense in designer drug cases. He argued that there's no reason a substance like Higenamine, a natural compound known by researchers around the world for some time, should fall under the classification. "If it's a substance they [WADA] know about," Jacobs said, "they ought to list it."

The probable reason why WADA declined to list Higenamine specifically is because it wasn't an issue until relatively recently. De Hon said his first encounter with the substance was in April 2013 when it came to his attention as the main ingredient in an "infamous nutritional supplement." That was around the time JACK3D entered the popular news cycle for its controversial ingredient DMAA, a stimulant with the effect somewhere between high doses of caffeine and low doses of amphetamines. In 2012, the company behind it released a related pre-workout product called JACK3D Micro which focused less on stimulants, replacing DMAA with Higenamine to increase oxygen and blood flow during workouts.

Still, as of 2016 and Sakho's positive test, the WADA banned list wasn't clear on Higenamine. Section 3, on beta2-Agonists, only read:

"All beta-2 agonists, including all optical isomers, e.g. d- and l- where relevant, are prohibited."

This is where Sakho's case gets exceptionally strange. Simply as a scientific point, the panel couldn't determine whether or not Higenamine is a beta2-Agonist at all—or whether it had performance-enhancing effects.

In UEFA's decision on Sakho's case, the review panel wrote that, "it is clearly not possible for anyone—laboratory, disciplinary body, football player or otherwise—to know whether or not Higenamine is a prohibited substance just by reading WADA's prohibited list."

Sakho's team commissioned expert testimony from two scientists: Professor Richard Bloomer of the University of Memphis and Nobel Prize-winner Professor Brian Kobilka of Stanford University. Kobilka's testimony addressed Higenamine's status as a beta2-Agonist. The science behind it is complicated, but, according to Mike Morgan, another highly-regarded sports lawyer specializing in anti-doping cases who led the Sakho legal team, Kobilka found that Higenamine has not been studied very extensively. Many of the studies on Higenamine have been done on rodents, and most determined that Higenamine is a beta1-agonist, which is not banned by WADA. A 2008 study on rodents raised the possibility that Higenamine is also a beta2-agonist, but added the caveat that this effect was "extremely weak," as Morgan put it. Kobilka's final conclusion: no proper study has been done on humans which can definitively say that Higenamine acts as a beta2-Agonist. Kobilka declined to comment on his testimony.

The other expert, Richard Bloomer, told VICE Sports his testimony regarded Higenamine's supposed performance-enhancing benefits. He has written two papers on the subject which found Higenamine is comparable to "moderate doses of caffeine" which is not banned by WADA.

Based on UEFA's findings, the expert's testimony obviously had an impact. "It is not clear that Higenamine has been proven to be a beta-2 Agonist," the panel wrote, before going even further to note that the scientific evidence it collected "cast significant doubt on the classification of Higenamine as a beta-2 Agonist."

When I asked Jacobs what Sakho—who asked his medical advisor if he could take the supplement containing Higenamine and was given the all-clear—could have done to recognize Higenamine as a beta2-Agonist and therefore a banned substance, Jacobs replied, "There's no way he could have gotten a definitive answer."

As Jacobs put it, "Nobody except WADA seemed to believe Higenamine is a beta2-Agonist."

In fact, even the director of the lab testing Sakho's sample didn't know the answer. In his testimony to the UEFA panel, Dr. Hans Geyer stated that he had to check with WADA if Higenamine was actually a prohibited substance. (Geyer did not respond to several VICE Sports attempts to contact him, but Morgan said that Geyer had been familiar with Bloomer's work on the subject.) The panel called the mere fact that Geyer had to check with WADA about Higenamine's status "telling."

As part of their scientific review, the panel also consulted with Dr. Martial Saugy of the Lausanne laboratory, another respected WADA-accredited lab, who contributed three key points to the review. (Quick aside: it's worth noting that Saugy is a controversial figure himself, although the particulars have no clear ramifications on the Sakho case. The Lausanne lab was found to have destroyed 67 samples provided by Russian athletes before London 2012. USADA also alleged that Saugy helped Lance Armstrong beat EPO tests. Saugy has denied wrongdoing on both cases.)

First, Saugy expressed significant doubt that Higenamine is, in fact, a beta2-Agonist, the entire premise for Sakho's positive test. Second, he "questioned the steps that WADA has taken to reach its conclusion" that Higenamine was a beta2-Agonist, alleging that WADA went through none of the four required administrative steps to add a substance to the banned list. Third, and perhaps most damning, he informed the panel that his lab in Lausanne and, indeed, a majority of WADA-accredited labs don't even test for Higenamine.

That is to say, if Sakho's sample had been sent to his lab instead of the Cologne lab, he never would have tested positive and none of this would have ever happened.

Saugy's pointed criticisms of WADA are specifically noteworthy because the Lausanne lab is an important cog in retroactive testing conducted in the 10 years after each Olympics. The Lausanne lab receives the vast majority of samples which will be tested at a later date. To have the director of that lab criticize WADA, Morgan said, was "unusual." But, Morgan added, it wasn't just Saugy; the Cologne lab director also was very "frank" about his views as well.

The UEFA review panel didn't hold back. "Frankly, the CEDB [Control, Ethics and Disciplinary Body] struggles to understand the value of a code which lacks universal enforcement," it concluded. "A code, for example, where different laboratories are looking for different things…From a strictly legal point of view, this is not robust."

On June 30, one week before the hearing, Sakho's team submitted to evidence their expert testimonies by Bloomer, Kobilka, and the two lab directors, as well as two additional pieces of evidence. One was a PowerPoint presentation hosted on WADA's website by Dr. Audrey Kinahan, the chair of the Prohibited List Expert Group. The presentation, from a 2014 WADA Therapeutic Use Exemption Symposium, covered which beta2-Agonists are banned and in what quantities. The presentation did not mention Higenamine, even on the final slide titled "All Other beta2-Agonists."

Along with the PowerPoint, Sakho's lawyers also submitted the minutes from an April 25, 2016 Institute of National Anti-Doping Organizations (iNADO) meeting, the international member body for National Anti-Doping Organisations (NADOs). The minutes, reviewed by VICE Sports, included a "key item discussed by the List Expert Group" bulleted list. One of the bullets was for "Review of some substances or methods for their current status and/or their possible inclusion on the Prohibited List (e.g. nickel, higenamine, hyperbaric oxygen, nicomorphine, tramadol)." At the very least, this implies doubt as to whether Higenamine was a banned substance.

Meanwhile, WADA submitted its evidence to the UEFA panel, which included a short written statement which Morgan summarized as "we think it's banned and that's the end of it," along with seven studies.

Morgan described the studies WADA submitted as evidence as "strange." Morgan's team had already examined all seven studies and they were directly addressed in Kobilka's testimony. Five of the seven studies were conducted on rodents. One of the studies concluded Higenamine is primarily a beta1-agonist, which, again is not banned by WADA, and thus directly undermines WADA's own case. Two of the studies WADA included were co-authored by Professor Bloomer, one of the expert witnesses, which attested to Higenamine's negligible performance-enhancing effects and did not directly measure beta2-receptor responses.

According to both Jacobs and Morgan, WADA was originally going to send Dr. Kinahan, a member of the Prohibited List Expert Group and presenter of the PowerPoint slide submitted into evidence, to testify. But on July 5, two days before the hearing, UEFA informed Sakho's team that WADA would no longer be attending. Morgan said this has never happened in any other anti-doping case he has ever tried.

— Mamadou Sakho (@mamadousakho)March 29, 2016

Tweet from Sakho's official account from France vs Russia on March 29, which Sakho started. Although the sample in question had already been collected, neither UEFA nor Sakho had yet been informed of a positive test.

VICE Sports submitted a list of questions regarding the Sakho case to WADA. When asked if WADA had planned to send Dr. Kinahan to the hearing, WADA spokesman Ben Nichols did not directly answer the question. Instead, he wrote, "WADA regularly liaises with the members of its List Expert Group of which Audrey Kinahen is a member." When the question was repeated, WADA declined further comment.

In a separate question asking why WADA chose not to appear at the UEFA hearing at all, WADA once again did not answer the question, instead providing the exact same written statement it gave the Telegraph back in August about a completely separate matter: why it chose not to appeal UEFA's decision. When the question was repeated, WADA declined further comment.

Furthermore, WADA's spokesman reiterated their position that Higenamine is a beta2-agonist, stating "There have been publications describing higenamine as a beta-2-agonist since the late 1990s" and that Higenamine has been considered a banned substance since 2004, or as long as WADA has had a banned list. Yet, he also said nobody has tested positive for it until January 2016.

"Based on available literature," WADA's spokesman wrote over email, "the List Expert Group determined that the substance has a clear beta-2 agonist component and therefore should be considered prohibited."

However, VICE Sports could not locate any such literature dating back to the 1990s as WADA claimed. Neither could Morgan's team. Morgan said there were no studies even suggesting Higenamine's possible beta2-agonist properties until 2008 and called WADA's assertion "utter nonsense." VICE Sports also searched the National Institutes of Health's PubMed database and Google Scholar, but found no relevant results from the timeframe WADA specified. When VICE Sports asked WADA to provide citations for the studies to which they were referring, WADA sent VICE Sports a link to the NIH's Pubmed database home page and declined further comment.

The UEFA panel sided with Sakho. They ruled that there are "significant doubts" as to whether Higenamine is a beta2-agonist, a direct contradiction of WADA's position. The panel also ruled that even if Higenamine was covered by the prohibited list, WADA did not effectively communicate that to their labs as evidenced by the fact that a "majority" of WADA-accredited labs didn't test for it at all.

The fact that most labs weren't testing for Higenamine explains why there were no positive tests until last year despite having been "banned" by WADA for 13 years. And if the labs didn't know Higenamine was banned, then athletes couldn't be expected to, either. As such, the case against Sakho was dismissed, and WADA opted not to appeal the ruling to the Court of Arbitration of Sport.

But the damage to Sakho's career had been done. UEFA's decision came down on July 7, the same day France beat Germany 2-0 to advance to the Euro Finals. Starting at centerback alongside longtime France international Laurent Koscielny was Samuel Umtiti, making his first caps for the team in that tournament. Sakho, who has 28 career appearances for France, started three times for Deschamps in the 2014 World Cup and helped keep two clean sheets. It's impossible to say whether Sakho would have played in the Euros if not for the positive doping test given that Umtiti is a rising star and had just transferred to Barcelona. But Sakho almost certainly would have been called up.

Petite visite pour encourager toute l'équipe avant la finale !July 10, 2016

In 2017, WADA added Higenamine by name as a beta2-agonist to the updated banned substance list, despite the scientific debate over its status. This means that Sakho's case will never be repeated, at least not with Higenamine specifically. Anyone who tests positive for it in the future will have no excuses.

They will also have a difficult time challenging the science behind Higenamine being on the banned list. According to Jacobs, the Court of Arbitration for Sport has been unwilling to consider the scientific merit of banned substances during appeals once they're specifically named.

This is, in part, because the bar for banning a substance is incredible low. Any banned substance must meet two of three criteria according to WADA: 1) It has the potential to enhance or enhances sport performance 2) It represents an actual or potential health risk to the athlete 3) It violates the spirit of sport. Because the "spirit of sport" clause is basically a freebie, a substance need only to potentially pose a health risk or potentially enhance performance, either of which is an easy hurdle to clear.

Considering Sakho's case, UEFA's stern ruling, and the effects it had on his career, it's certainly fair to wonder if Sakho would consider a lawsuit. Jacobs didn't want to speculate on Sakho's intentions, especially since it would not be filed in the United States where Jacobs practices and he would likely not be involved. But he did say that a lawsuit is certainly "worth exploring."

However, there are some potential complications. One is as exactly who to sue. Jacobs said UEFA would probably argue that they were informed of a positive drug test and had to pursue it according to their bylaws. So too might the Cologne lab argue they were simply following WADA's instructions.

Then Jacobs paused and thought for a second. "I don't know what WADA would say."