Russian Doping of a Different Sort: Russian and Eastern European Drugs Hiding in Plain Sight as Alternative Doping Agents

Russian doping has been at the forefront of people’s minds as the 2020 Tokyo Olympic Games fade in our memories and we prepare for the 2022 Beijing Olympics to begin in February. The state-sponsored doping that culminated at the 2014 Sochi Olympics continues to cast shade over Russian sport–excuse me, the Russian Olympic Committee (ROC)–and indeed global competition, as the ensuing discussion and veiled accusations mar the Olympic spirit. But perhaps people should also be concerned about Russian doping of a different sort, one that is not often considered but should be. History has shown that athletes use Russian and Eastern European drugs as doping agents and yet few are prohibited today.

The World Anti-Doping Agency (WADA) Prohibited List outlines the substances that are banned in international competition including the Olympics. The 2021 WADA Prohibited List consists of 333 compounds listed by name, but the inclusion of catch-all language also prohibits related substances in many product categories. To be found, however, drugs have to rise to a level of concern and be targeted first and the WADA list primarily focuses on drugs of Western origin. Only four drugs of Russian or Eastern European origin appear to be included. Certainly there are others out there that would be attractive as doping agents.

Let’s take a look at the four drugs on the WADA Prohibited List that are of Russian or Eastern European origin and explore alternatives that athletes may be using today.

The story starts with bromantan, which was developed in the 1980s at the Russian Academy of Medical Sciences in Moscow. It can be found under the brand name Ladasten and is technically an actoprotector. Research out of Korea in 2012 explored bromantan in The Pharmacology of Actoprotectors: Practical Application for Improvement of Mental and Physical Performance. The writers described actoprotectors as “synthetic adaptogens with a significant capacity to improve physical performance.” The literature noted, “Bromantan was first found in an athlete sample at the 1996 Atlanta Olympics and was officially banned in 1997 as a stimulant.” There have been 11 adverse findings for bromantan in the WADA system since 2006.

Perhaps this is not surprising as a perfect alternative, bemitil, also known as metaprot, is described in the literature above and remains widely available online today, often at sites that offer Russian medicines or nootropics. The paper above explains that “nowadays, bemitil is manufactured in Ukraine (commercial name: Antihot) and is widely used in preparing Ukrainian national sport teams for international competitions.” It also notes, “Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

“Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762282/

Bemitil was added to the WADA monitoring program list in 2018, 38 years after the Moscow Olympics you will note, but is not yet prohibited. If it does get prohibited, fear not there are alternatives for it, too. A site that sells Eastern European drugs like bemitil, MOSPharma.com, suggests four related products including noopept (see below) and trekrezan “from Russian pharmaceutical company Usolye-Siberian CPP,” with activity that “increases endurance during physical and mental stress.”

Next on the list of Russian doping agents is mescocarb, a central nervous system (CNS) stimulant and a dopamine reuptake inhibitor patented originally in Russia in 1970 by Vni Khim Farmatsevtichesky. Also known as Armesocarb, it is currently in clinical trials as an antiparkinsonian drug from Melior Pharmaceuticals. It has been sold under the brand name Sydnocarb with a nod to the technical chemical category in which it fits, mesoionic sydnone imine. Mesocarb does not appear to be widely available today online. It has been prohibited in sport since at least 1996 based on references to it at that time, but it has only been responsible for two adverse analytical findings since 2006.

There are also Russian alternatives to CNS stimulants with semax as one option. A poster on black market products with suspiciously doping relevant ingredients – annual report from the 2016 Manfred Donike Workshop discussed that semax “acts as a nootropic agent on the central nervous system and regulates dopamine and serotonine levels.” MOSPharma.com describes semax as “100% original from the Russian CJSC INPC Peptogen,” and notes it is used “to stimulate the central nervous system and enhance memory, focus, mental and physical performance, analytical skills.”

Carphedon, otherwise known as phenylpiracetam, is the next on our list and one of a family called racetams that are generally considered nootropic drugs. In 2019, researchers from the Czech Republic considered Carphedon at the Crossroads: A Dangerous  Drug or a Promising Psychopharmaceutical? They explain this substance was “developed in Russia as a stimulant to keep astronauts awake on long missions, and occasionally used in Russia as a nootropic prescription for various types of neurological disease.” Carphedon “was synthesized in 1990 by Russian chemists as a combination of two drugs, nootropic piracetam and amphetamine stimulant.” A 2012 review of Piracetam and Piracetam-Like Drugs describes them as “modulators of cerebral functions,” used for, “various therapeutic interventions relating to the CNS, including (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety.”

Handwritten notes from 1997 show carphedon was considered by my father, sports drug-testing guru Dr. Don H. Catlin, and colleagues at the IOC Medical Commission for addition to the prohibited list at the time. The notes describe carphedon as, “adaptogenic, registered in 1994 in Russian pharmacopeia that might help with space travel and improve workload.” The drug has caused 122 adverse analytical findings since 2006.

If you peruse the piracetam review highlighted above, you will find nine other racetam options that may be considered as doping agents. None is listed by WADA today. Neither is noopept, otherwise known as omberacetam, which has become one of the most popular nootropic agents on the market today. The National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) notes that “noopept was patented by Russian-based pharmaceutical company JSC LEKKO Pharmaceuticals in 1996.” The information cites that the “research shows Noopept has similar effects, but works differently than other nootropics in the racetam-family.” A number of sites compare the effects of phenylpiracetam to noopept with nootriment.com, suggesting that “both are purported to have benefits for memory, concentration, mood and alertness.”

From a banned substance standpoint, phenylpiracetam is on the WADA Prohibited List while noopept is not listed nor is it targeted. A synthetic drug, noopept, is widely available in supplement form despite it not qualifying as a dietary supplement ingredient according to the Dietary Supplement Health and Education Act of 1994 (DSHEA), which defines legal supplement ingredients in the U.S. It shows up in 32 dietary supplement products in the NIH Office of Dietary Supplements Dietary Supplement Label Database. In 2016 a BSCG blog post I wrote considered noopept could be the next big doping agent hiding in plain sight. That still remains the case today.

Last but not least of the four Russian doping agents is meldonium, otherwise known as mildronate. One will remember the maelstrom that ensued when meldonium was added to the WADA Prohibited List in 2016. There were 515 positive drug tests for meldonium in 2016, making it the most common substance found that year in Olympic sport. Tennis star Maria Sharapova was among them. There were 269 more positives from 2017 to 2019 for a total of 784. Meldonium is included on the WADA Prohibited List as a metabolic modulator in category S4.

Scientists from the University of Latvia and the Latvian Institute of Organic Synthesis that created meldonium, described it as “an anti-ischemic drug.” Its performance-enhancing potential has been the subject of much debate likely because it is a complex substance that has a variety of effects. An excerpt from a 2005 paper written by the aforementioned scientists, Mildronate: An Antiischemic Drug for Neurological Indications, describes it as follows.

“Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients’ mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced.”

The meldonium saga more than demonstrated athletes around the world had recognized an obscure anti-ischemia agent as a doping option and had started to use it. When it was prohibited, Russian scientists boasted they already had alternatives. As reported in USA Today from Moscow, “Federal Medical-Biological Agency head Vladimir Uiba says Russia has found ‘several drugs which are not banned and work significantly better than meldonium.’”

You don’t have to look far. Mexidol is broadly available on sites that cater to Russian medicine as well as on a site called DrDoping.com; very subtle. It is also available on Amazon from Pharmasoft at $21 for 50 tablets with a label that suggests it be used for “Anxiety Relief, Anti-Stress, and Ischemic Condition.” Mexidol, an anti-oxidant, was patented in 2002 in Russia with the patent describing the “invention relates to preparations used for prophylaxis and treatment of different forms of cardiac ischemia disease, atherosclerosis and acute circulation disturbances, cerebral insults.” With indications for ischemic conditions, it certainly appears similar to meldonium.

In a 2007 paper, Mexidol effects in extreme conditions, T.A. Varonina with the Institute of Pharmacology, Russian Academy of Medical Sciences notes, “Mexidol can be prescribed to humans to maintain efficiency in all kinds of extreme situations.” Could hundreds of Olympic athletes be using mexidol as an alternative to meldonium today?

A 2019 review from Russia of Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke compares mexidol to actovegin, which gained some notoriety as a potential doping agent around 2009 as explored in the Daily News. Actovegin, which DrDoping.com carries in pill form, is an extract from calf blood and is not on the WADA Prohibited List. In the article Olivier Rabin, WADA’s science director, suggests, “Actovegin could be used as a component of sophisticated blood doping methods, in which athletes withdraw, manipulate, and re-inject their blood to boost their endurance, or in conjunction with the use of erythropoietin, or EPO.”

When we ran independent drug-testing programs for several leading cycling teams in the peloton years ago, a key member of a team said to me after an event, “You know, Oliver, we aren’t doing anything that is over the line but we are doing everything we can up to the line.” That simple philosophy likely rings true across sport today.

People often ask if the Olympics or sport in general is clean today. To answer that simply, the system is very good at finding drugs that are currently defined as prohibited substances. None of the Russian or Eastern European drugs we note here–bemitil, trekrezan, semax, noopept and other racetams, actovegin, or mexidol–is on the WADA Prohibited List today. These Russian or Eastern European drugs certainly seem to be potential alternatives to prohibited drugs, but if they are not yet defined as such then using them is not yet considered doping. If sites like DrDoping.com has found them, who else might have them?

Oliver Catlin is the longtime president and co-founder of BSCG (Banned Substances Control Group), an international third-party certification and testing provider. With a background in sports anti-doping, he is widely regarded as a thought-leader in the field of sports nutrition and dietary supplements.

2018 PyeongChang Winter Olympic Games Review

Don Catlin, M.D., at Vancouver 2010 Opening Ceremony – Photo by Oliver Catlin

We watched with the rest of the world as the 2018 PyeongChang Winter Olympic Games unfolded. In the face of tense politics, doping scandals, and other controversy, the Olympic ideals still shined through, sometimes in unexpected ways. Having been fortunate to attend six amazing Winter Olympic Games (Don got to go to seven, I think), we figured why not provide some perspective on these. Here is our 2018 PyeongChang Winter Olympic Games Review.

Most Amazing Victory – Ester Ledecka. Who knew someone could win a gold medal in snowboarding and skiing! Some people don’t think that the two sports are compatible, some don’t even want both sports on the same mountain. This woman just went out and ripped it up, twice, however many planks were strapped to her feet. Well done, Ester.

Clean Athlete Awards – Jessica Diggins and Kikkan Randall. In an Olympics marred by the Russian doping scandal, we always appreciate it when you can literally see that athletes are clean. Not that we advocate that a visual determination replace anti-doping testing, but some people you can just tell are not doping. We thoroughly enjoyed watching these ladies win clean, and with amazing smiles! We also appreciate the other courageous cross-country skiers who signed the letter in 2016 demanding a stronger stance on doping, including notably the four Russian women who signed. Thanks to all of you for working to defend your sport from the scourge of doping.

Classiest Athlete – Yevgenia Medvedeva. OK, we admit we watched the ladies figure skating final and it was pretty amazing. The talent and class displayed by all the young ladies is unbelievable. However, one shined above the rest. Despite missing the gold medal by a heartbreaking 1.31 points that even experts could not decipher, this woman took disappointment with amazing class for an 18-year old. She genuinely embraced her younger upstart Alina Zagitova and accepted her silver medal with a smile. She could be overheard saying she “did everything she could.” That statement represents what Olympic athletes are all about. We don’t know much about this Russian athlete otherwise, but in PyeongChang this little Anna Karenina showed enormous class.

Most Notable Olympic Farewell – Lindsey Vonn. Although you leave the 2018 PyeongChang Olympic Games with a bronze medal, which most people could only hope for, you will always be the golden girl of American skiing. You took yourself to the pinnacle of your sport and beyond, and you brought your country with you. Along the way you’ve inspired generations of Olympians for years to come. We wouldn’t be surprised to see a woman like you one more time in Beijing four years from now, but if not thank you for all the amazing Olympic moments.

Strangest Doping Incident – Doping in Curling, really? We thought people drank beer during curling, but doping? Of course it would be an Olympic Athlete from Russia with meldonium as the offending substance, such perfect irony.

Ugliest Controversy – The ugliest controversy in these Olympics goes to the argument between Dick Pound and others in the IOC over whether or not to allow the Russian delegation to be permitted to fly the state colors during the closing ceremonies. It took long enough to finally get some kind of ban enacted and the corresponding statement made that state-sponsored doping is unacceptable, and it was going to be overturned during the Games? Way to go Dick Pound for sticking up for clean sport, as always! Or should we thank the second Olympic Athlete from Russia for doping and closing the door on that argument.

Most Inspiring Olympic Athlete – One athlete that epitomized the ideals of the Olympic movement and displayed them proudly in every fiber of his being by bringing athletes from all nations together sadly was not present in PyeongChang, but he was there is spirit. And his spirit we know will continue to inspire generations of Olympians for years to come. The Olympic Family lost Steven Holcomb, a beloved member of the bobsled community, in May 2017. But in the true spirit of the Olympic movement he went down the track many times in PyeongChang in the form of tribute bracelets on the wrists of many of his sliding colleagues, his parents cheering with tears in their eyes in the stands. Despite not being present, this man, and his spirit, made for the most inspiring Olympic athlete of this Games. We wish we could have known him and been inspired by his spirit.

Most Amazing Olympic Moment – It was hard to miss the unity demonstrated at the Opening Ceremonies with South Korea and North Korea marching together as one. This was a powerful symbol of the peaceful celebration of sport that the Olympics represent. We appreciate that this unity was achieved during the Games, and I think we all hope the peace was more than just for show and lasts.

The Olympics are truly an amazing gathering of athletes from all different countries, politics, races, sizes, sexes, orientations, faiths, and more. For all these moments and more, the Olympic Games remain one of the most amazing spectacles of human interaction and accomplishment in this world. They deserve to be truly appreciated, celebrated, and protected. We can’t wait for the years to pass to see what amazing feats and memorable moments Tokyo, Beijing, Paris, and Los Angeles will produce.

WADA EPO Testing Methodology Remains Sound and Strong Despite Colvert Case Discussion

My father, Dr. Don Catlin, has always been one of the most frank and open experts in the anti-doping industry. That is in part what attracts media to him still today. Yet, this style poses challenges as intents and comments can sometimes be misused. His comments have been used recently to suggest that there are flaws with the EPO drug-testing process in place today. To clarify, the WADA EPO testing methodology remains sound and strong despite the Colvert case discussion.

The case of Steven Colvert has been discussed as a potential example of a case that demonstrates the flaws in the WADA EPO testing methodology, but really it is an example of the complexity of the EPO test and why thorough analysis is needed to establish solid results—which the results in this case appear to be. Confusion can arise when visual analysis is considered alone, or when results are not considered in their entirety or without the benefit of scientific tools. To understand the realities of the Colvert case, one must first gain an understanding of the science involved.

Erythropoietin (EPO)

EPO testing today includes the use of three primary methods; IEF, SDS-PAGE and SAR-PAGE. All three methods have been carefully validated and peer reviewed across multiple laboratories and they have been in use for many years. There is an array of research showing the breadth and capability of the methods. We have published papers based on the seminal methods Dr. Francoise Lasne and other colleagues in the doping control industry have created in this complex realm of science. We certainly would not have based our own research on these techniques if we did not believe the methods to be valid and strong.

The EPO testing methodology is outlined in the WADA Technical Document – TD2014EPO. We recommend that those who wish to completely understand the methodology review the document. The harmonized methodology outlined is designed to create consistency in results between laboratories. There is an image on page 11 that is useful in evaluating Colvert’s results.

This complexity of EPO sport drug testing stems from the reality that EPO is a naturally present substance in the human body. This requires methods to be able to distinguish natural EPO from synthetic, or exogenous, forms. The three EPO testing methods evaluate band patterns with variable shading that migrate from a natural EPO pattern when a drug is used.

It is pretty easy to see a positive when therapeutic quantities of a drug are used as there are large migrations in the band patterns. The results are much more difficult to visually determine when an athlete has microdosed, or when an athlete has stopped using in an attempt to clear the drug from the system, as these situations present band migration patterns that can be very subtle and difficult to distinguish visually from negatives.

It is important to realize that EPO testing does not rely on subjective visual analysis of band migration patterns. There is underlying science applied in the data review process to take visual subjectivity out of the equation. Densitometry, defined as the quantitative measurement of optical density in light-sensitive materials, is performed to scientifically evaluate the shading of bands. GASepo—a software solution for quantitative analysis of digital images in EPO doping control, has been developed to present a “method of robust calculation of the cut-off line, band segmentation and classification algorithms.” So, there is sound quantitative science applied beyond visual review of results.

The recent documentary Troubling Science – Steven Colvert Doping Conviction, as well as the October 26, 2016 article that preceded it, did not adequately consider the underlying science in our view. The response from our esteemed colleague Dr. Christiane Ayotte, Laboratory Director at the WADA-accredited laboratory in Montreal, outlined the scientific conclusions made and included references to the densitometry and software applications used to produce the results such as this image.

The Norwegian authors of the 2016 article suggest that Colvert’s SAR-PAGE results are not indicative of EPO drug use based on his lane being “not much different from other lanes.” They discuss the diffuse staining above the blue line, which was used to determine a positive result for Colvert, as a standard staining anomaly that PAGE testing is subject to with different sample conditions. That conclusion discounts the fact that sample conditions are standardized prior to analysis and it also fails to consider that the staining that appeared in Colvert’s lane did not appear for other negatives in the sample group run at the same time under the same conditions.

Having performed the EPO testing methods in our own labs, we are certainly familiar with staining challenges. Indeed, the 2-3 day tests that are performed are highly sensitive and require extremely skilled analysts in order to create bands that are consistently free from what WADA describes as, “spots, smears, areas of excessive background or absent signal in a lane that significantly interfere with the application of the identification criteria.” In such circumstances, the WADA technical document calls for “invalidating the lane.” The SAR-PAGE results that include Colvert’s sample appear to be an excellent model of results that are free of any staining anomalies.

When the documentary was filmed, Don was asked to visually evaluate Colvert’s SAR-PAGE results, with the filmmaker pointing and asking if Colvert’s looked negative. Don ultimately agreed with that assertion, going on to say that he has seen 20 like it and that the lab must not know what it is doing. A rather astounding statement on its own.

When I was shown Colvert’s SAR-PAGE results, I was able to visually determine the positive sample. To me the slight diffuse staining above the blue line is visually different than the other negative samples. Perhaps my 40-year-old eyes are better than Don’s as he approaches the 80-year milestone later this year. This shows that two people with expertise in evaluating EPO testing results can come to different visual conclusions, which reinforces the importance of the underlying science used to properly determine a positive or negative result.

Colvert’s SAR-PAGE results are an example of the subtle migration patterns that make EPO testing complex and difficult to properly evaluate visually. The peaks laid over SAR-PAGE results by the software application help in the results review process and take subjectivity out of the equation as this image shows with Colvert’s sample on the left, a positive control in the middle, and a negative at right.

Furthermore, the IEF results in Colvert’s case are also indicative of the presence of exogenous EPO. This test requires the two densest bands to be above the line and in Colvert’s sample there are actually three above the line making the visual results easy to recognize. So, two separate validated testing methodologies were used to establish Colvert’s results.

It should also be noted that two different laboratories confirmed these results. This is in fact required under the WADA technical document in order to avoid the reporting of false positives that could be subject to intra-laboratory differences. Both laboratories came to the same positive conclusion.

Some paranoid theorists might point to laboratory malfeasance painting pictures of scandalous anti-doping scientists purposefully contaminating samples. That notion is absurd as our colleagues in anti-doping laboratories are among the most ethical scientists we know. The recent Russian doping debacle and the gross ethical transgressions of our old friend, former Russian laboratory director Grigory Rodchenkov, have called into question the ethics of the anti-doping industry as a whole, one of the most unfortunate ramifications of his actions. Yet we would point out that even Grigory considered it anathema to purposefully taint an innocent athlete’s urine and he refused to do so despite direct orders from above.

What does bother us about Mr. Colvert’s case is not the results, but rather the vehement and passionate defense Mr. Colvert has lodged on his own behalf. His words, and his strong statements in defense of clean sport, are certainly convincing. But we have seen such convincing statements before, from both innocent and guilty athletes. Even stars like Alex Rodriguez and Lance Armstrong told convincing tales once. These stories are one of the most difficult elements we confront in anti-doping.

The Colvert case discussion demonstrates the complexity of the EPO test and data review process. Even well-meaning, qualified scientists, including Don, can be critical of it in certain circumstances. Yet at its core, and through the complexity, the WADA EPO testing methodology remains sound and strong.

Don and I would like to extend our apologies for the remarks about the Cologne WADA accredited laboratory, which were not intended to be disparaging. The Cologne laboratory and staff are some of the most capable, ethical and committed partners in the global fight against doping, and we very much respect their undeniable work as leaders in the industry.

Catlin Perspective on Netflix Documentary ‘Icarus’ and Russian Doping

By Oliver Catlin

With the high-profile “Icarus” documentary now available on Netflix and in selected movie theaters, I wanted to take a moment to provide perspective on some points my father, anti-doping pioneer Dr. Don H. Catlin, and I have considered in regards to “Icarus” and Russian doping in general.

We offer a warning to those who have not yet seen the film that the following contains some spoilers.

Participation in ‘Icarus’ Documentary

When a documentary maker contacts my father looking for help for an anti-doping piece, he tries to lend his support and expertise whenever possible. He did so with Bryan Fogel, even though he was unfamiliar with Fogel’s previous work. In his request for participation, Fogel stated that the primary aim of his film would be a historical review of anti-doping scientific developments and a discussion of my father’s many achievements in the field and anything else my father wanted to discuss. Fogel also mentioned an interest in doping himself prior to riding in a top amateur cycling race to hopefully demonstrate he could beat the anti-doping system. “You are the expert on the subject—I am the filmmaker… let’s discuss and formulate a schedule and a plan and hopefully be aligned!” he wrote in his pitch.

As a key expert at the highest levels of sports drug testing for more than three decades, Don was excited to have an opportunity to share his historical insights about a myriad of professional experiences and developments in the field. Though he hesitated at the thought of helping someone to dope or attempt to game a system he had helped to build, he found himself curious how doping might impact someone in a real-world race environment. Fogel, however, was eager to discuss how difficult it was to evade detection and where the current holes in the system might be and how they could be exploited. Don shared some discussion with Fogel about the filmmaker’s ideas, but orchestrating the doping activity or trying to demonstrate that the current anti-doping system could be thwarted was not something my father was interested in doing.

About Grigory Rodchenkov

Over the years, my father has crossed paths with many other capable, dedicated scientists in the anti-doping field. He has enjoyed working with this committed group to help build the best anti-doping system possible for the protection of sport and the athletes. When Fogel asked if there was anyone he knew who might be able to help with his doping agenda, my father believed his dedicated colleagues, especially those in WADA-accredited labs, would decline as he did. Without question, most of them have high ethical standards and scrupulous laboratory practices, and take pride in their anti-doping work. He could think of only one person who might be willing to assist Fogel: Grigory Rodchenkov, then the director of Russia’s anti-doping laboratory in Moscow.

My father had known Rodchenkov for many years and respected his scientific work but over time was less certain of his ethics. While my father could never have imagined how extensive the Russian state-sponsored doping and its cover-up were at the 2014 Sochi Winter Olympics under the direction of Rodchenkov, he did believe Rodchenkov was operating in a different realm than the rest of his colleagues.

My father and others in the anti-doping community had been suspicious of Russia’s doping activity for many years. Prior to the airing of the earth-shattering ARD exposés in Germany in 2015 and 2016, allegations of widespread malfeasance in Russian track and field were publicly reported in 2014 with the help of courageous athletes by the ARD’s award-winning journalist Hajo Seppelt.

Some Context About Russian Doping

Russian state-sponsored doping of its top athletes has likely been going on for years. At one point in “Icarus,” Fogel raises the possibility that it goes all the way back to 1968. Thanks to the Russian magazine Smena, we know that in 1988, prior to the Summer Olympics in Seoul, South Korea, the Soviet team was pre-tested aboard a ship offshore. The Soviets purportedly wanted to ensure their doped athletes could pass the IOC tests. Victor Uralets, the director of the Moscow anti-doping laboratory from 1980 to 1992, essentially corroborated this story publicly in 2016 and indicated that he left the lab because he did not believe what he was being asked to do was ethical or safe. He now works at a testing lab in Northern California where he no longer has to deal with what he described as the embarrassment involved with cheating. We commend Victor for having the courage to leave a corrupt system.

In 2002, at the Winter Olympics at Salt Lake City, two Russian cross-country skiers, as well as a Spanish cross-country skier, were suspended after testing positive for darbepoetin alfa, a new form of the blood-booster EPO, or erythropoietin. It was the first time the test, developed by the French scientist Dr. Françoise Lasne, had been employed successfully. My father, who oversaw the drug testing at these Olympics, martialed the introduction of this new test that produced these historic positive results. Perhaps these early findings were merely the tip of the iceberg in the larger scheme of Russian doping that has been unveiled.

A Silver Lining

One small bit of silver lining loosely discussed in “Icarus” is the actual effects of doping on Fogel’s cycling performance, which decreased the year he rode dirty. By originally dedicating himself to training, proper nutrition, and riding clean, Fogel came in 14^th place in the Haute Route Alps in 2014, 4^th in his 40 – 49 age class. With a focus on doping, beating the system, and riding with a dirty mentality the following year, he came in 27^th place and 12^th in his age class. While a mechanical issue impaired a direct comparison of the two performances, we are left to wonder what the real effect of his doping might have been. Did it improve performance or did it hinder it, as Fogel’s results appear to show?

Fogel described it being easier to train and recover when he was doping, that the banned substances made it mentally easier to perform at a high level. When you are in a race situation and constantly challenging your maximum capability, however, is such an effect really beneficial? Or could the mental strength necessary to overcome suffering exhibited by clean riders sometimes actually enhance performance more than banned drugs? The mental capacity to deal with suffering and pain is vital in the grueling sport of cycling, and we wonder if that is actually diminished if one makes the sport easier by doping.

Many people will probably view “Icarus” and be dismayed as we were by its sordid tale of Russian doping, but we are also buoyed by the larger picture. We must remember it was not Rodchenkov or Fogel who were responsible for unveiling the ugly truth of state-sponsored Russian doping; it was the courageous athletes caught in its web, such as Yuliya Stepanova and her husband Vitaliy, who at great risk to themselves came forward to expose what was happening. The athletes themselves are driving change and endorsing clean sport more and more, and that is extremely powerful.

Oliver Catlin is President of BSCG (Banned Substances Control Group), a leading dietary supplement testing and certification provider since 2004. A graduate of UC Berkeley’s Haas School of Business, he has worked as an executive in the anti-doping and dietary supplement industries for nearly fifteen years.

Dr. Don H. Catlin and Performance-Enhancing Drug Tests

The Development of Key Performance-Enhancing Drug Tests

Since founding the UCLA Olympic Analytical Laboratory in 1982 and serving as its director for 25 years, Don H. Catlin, M.D., has been instrumental in discovering new performance-enhancing drugs and establishing methods to uncover athletes’ use of various substances. His research, while both conducting doping control and simply focusing on new and evolving drugs, has been vital in the creation of many of the tests currently used to detect performance-enhancing drugs. As the New York Times noted in 2007, “Some call Dr. Don Catlin… the father of drug testing in sports.”

He and his son, executive Oliver Catlin, founded the well-regarded supplement certification provider BSCG (Banned Substances Control Group) in 2004. The Catlins’ expertise is unparalleled and often sought on the more complicated issues facing both anti-doping research and supplement testing. Here, we’ll take a brief look at some of Dr. Catlin’s key performance-enhancing drug (PED) breakthroughs and where more information can be found about them.

Renowned anti-doping pioneer Dr. Don H. Catlin in his Los Angeles laboratory in 2008. (Photo from The Catlin Consortium.)

Developed the CIR Technique to Distinguish Natural from Artificial Testosterone

In the late 1990s, Dr. Don Catlin was the first to develop and offer the carbon isotope ratio, or CIR, test to determine whether testosterone or an anabolic steroid has been made naturally by the body or has come from a prohibited substance. This highly accurate test was the first technique capable of detecting synthetic testosterone, rather than simply gauging the body’s reaction to the substance. Dr. Catlin used for comparison a person’s endogenous reference compound (ERC) such as cholesterol to help determine the body’s natural carbon make-up. The testosterone CIR test was considered revolutionary and has proven useful and highly reliable; despite many challenges by athletes testing positive over the years, the Court of Arbitration for Sport has never found any fault with it.

More Info

See an info-graph about his test put together in 2006 for the New York Times: http://www.nytimes.com/imagepages/2006/08/01/sports/02landis-graphic.html

Academic Publication

Catlin DH, Hatton CK, Starcevic S. Issues in detecting xenobiotic anabolic steroids and testosterone by analysis of athletes’ urine. Clinical Chemistry 1997;43:1280-1288.

First Reported Use of a Form of EPO (Darbepoetin Alfa) in Sport

While overseeing the drug testing at the 2002 Winter Olympic Games in Salt Lake City, Dr. Catlin revealed the use of a form of EPO, or erythropoietin, (darbepoetin alfa), for the first time in sport. He used a new test developed by French scientist Dr. Françoise Lasne to detect this long-lasting form of EPO, a then newly approved drug for anemia patients that helps boost red blood cells and aids in endurance but can lead to serious health outcomes such as heart attack and stroke. Three Olympic cross-country skiers, including gold medalists Larissa Lazutina of Russia and Johann Muehlegg of Spain, were suspended and their medals stripped after they were found using the substance in Olympic competition.

More Info

For a thorough introductory account of this story, read the nonfiction book “The Night Olympic Team” (Boyds Mills Press, 2008), written for older kids by Caroline Hatton, Ph.D., one of the scientists working in the Olympic lab under Dr. Catlin.

Academic Publication

Catlin DH, Breidbach A, Elliott S, Glaspy J. Comparison of the isoelectric focusing patterns of darbepoetin alfa, recombinant human erythropoietin, and endogenous erythropoietin from human urine. Clinical Chemistry 2002. 48: 2057-9. Full Text PDF

First Reported Designer Steroid, Norbolethone

In 2002, Dr. Catlin was the first to report the use of a designer anabolic steroid in sport. He identified norbolethone (or norboletone) for the first time in an athlete’s urine sample. Norbolethone had been developed in the 1960s as a treatment for growth and weight gain but was deemed harmful and never brought to market. Patrick Arnold and Victor Conte introduced it to athletes through the Bay Area Laboratory Co-operative (BALCO). Dr. Catlin’s discovery of the substance was a wake-up call that some athletes were abusing designer steroids. The Chicago Tribune named Catlin Sportsman of the Year for 2002.

More Info

More about norbolethone and Dr. Catlin’s original test can be found on PubChem, a website of the U.S. National Library of Medicine: https://pubchem.ncbi.nlm.nih.gov/compound/norbolethone#section=Top

Academic Publication

Catlin DH, Ahrens BD, Kucherova Y. Detection of norbolethone, an anabolic steroid never marketed, in athletes’ urine. Rapid Communications in Mass Spectrometry 2002. 16:1273-5.

Second Reported Designer Steroid, THG

In 2003, Dr. Catlin identified and developed a test for THG, or tetrahydrogestrinone, the second reported designer anabolic steroid. This discovery famously came from a sample contained in a used syringe delivered anonymously to USADA (United States Anti-Doping Agency), who subsequently passed it along to Dr. Catlin for testing. THG was the active ingredient in “The Clear,” a previously “undetectable steroid” created and distributed by BALCO to some top American and British Olympic and professional athletes. Dr. Catlin credited his large team of capable researchers and chemists with finding the substance and developing a new test for it, saying the accomplishments “took all the skills that are represented in this lab.” In 2009, Newsweek magazine named coach Trevor Graham’s decision to send the syringe to USADA one of the decade’s “Top-10 History-Altering Decisions.”

More Info

For more about Dr. Catlin and the BALCO story, read this 2004 Washington Post article by Amy Shipley: “One Mastermind Behind Two Steroids,” July 29, 2004. http://www.washingtonpost.com/wp-dyn/articles/A22151-2004Jul28.html

Academic Publication

Catlin DH, Sekera MH, Ahrens BD, Starcevic B, Chang YC, Hatton CK. Tetrahydrogestrinone: discovery, synthesis, and detection in urine. Rapid Communications in Mass Spectrometry 2004. 18: 1245-9.

Third Reported Designer Steroid, Madol or DMT

In 2004, Dr. Catlin identified madol, the third reported designer anabolic steroid. Madol, short for methylandrostenol, and also known as DMT, or desoxymethyltestosterone, (not to be confused with dimethyltryptamine) was the active ingredient in the third generation of “The Clear,” found during a raid of the BALCO lab in 2003. The steroid, a potent testosterone derivative that can seriously damage the liver and heart, was designed in the early 1960s but never made it to market. After being discovered in dietary supplements, DMT was made a controlled substance in the United States in 2010.

More Info

For more about DMT, THG, and BALCO, see the news article “Athletics: New steroid designed to fool drug-testers,” from Reuters, The New Zealand Herald, Feb. 2, 2005. http://m.nzherald.co.nz/sport/news/article.cfm?c_id=4&objectid=10009252

Academic Publication

Sekera MH, Ahrens BD, Chang YC, Starcevic B, Georgakopoulos C, Catlin DH. Another designer steroid: discovery, synthesis, and detection of ‘madol’ in urine. Rapid Communications in Mass Spectrometry 2005. 19: 781-4.

Multiple Reports of New Anabolic Steroids

In 2005, Dr. Catlin discovered five new designer anabolic steroids in dietary supplements sent to him for testing by the Washington Post. One substance found in the supplement Halodrol-50 closely resembled oral turinabol, the principal anabolic steroid abused by East German Olympic athletes in the 1960s and ’70s. Some 800 athletes later reported serious ailments after taking that steroid, referred to as “the blue bean.” Halodrol-50 was discontinued but a version called Halodrol resurfaced online in 2016.

Dr. Catlin also found the new designer steroid methasterone in the supplement Superdrol. This discovery prompted anti-doping authorities to focus on curtailing the sale and use of pro-hormone supplements, often toxic to the liver. WADA (the World Anti-Doping Agency) soon added the compound to its list of banned substances in sport, and in 2009 the U.S. Food & Drug Administration (FDA) raided Bodybuilding.com in part over the sale of the compound, which represented the largest enforcement action up to that time in the supplement industry.

More Info

See early Washington Post story, “Steroids Detected In Dietary Tablets,” by Amy Shipley, Nov. 30, 2005: https://www.washingtonpost.com/archive/sports/2005/11/30/steroids-detected-in-dietary-tablets/938990b4-5956-48a5-8804-7f5ae6d561e3/?utm_term=.9d357da69081

“Designer Steroids: Hide and Seek” by Amy Shipley, Bonnie Berkowitz, and Christina Rivero, Washington Post, Oct. 18, 2005. http://www.washingtonpost.com/wp-dyn/content/graphic/2005/10/18/GR2005101800648.html

“Forgotten victims of East German doping take their battle to court,” by Luke Harding, The Guardian, Oct. 31, 2005: https://www.theguardian.com/sport/2005/nov/01/athletics.gdnsport3

“Bodybuilding.com, LLC and Jeremy DeLuca Plead Guilty in Federal Court to Violating FDCA,” FDA News Release, May 22, 2012. https://www.fda.gov/ICECI/CriminalInvestigations/ucm305494.htm

Academic Publication

Catlin DH. Anabolic steroids. In DeGroot LJ, Jameson JL, eds. Endocrinology Elsevier Saunders 2006; 5th Edition: 3265-82. (Book chapter.)

First Report of the Designer Stimulant Methylhexaneamine

In 2006, in another analysis of a dietary supplement at the behest of the Washington Post, Dr. Catlin was first to identify the designer stimulant methylhexaneamine, a potentially deadly amphetamine-like substance. This compound was found in Ergopharm’s Ergolean AMP, a product formulated by BALCO chemist Patrick Arnold, who was then awaiting sentencing for his role there. The product was pulled from the market, but in 2011 USADA issued an official warning to athletes to avoid the dangerous stimulant in a range of supplement products after a rash of positive test results. Unlike some problematic supplement ingredients, this compound often could be found in supplement ingredient lists—under the names methylhexaneamine, 1,3-dimethylamylamine (DMAA), dimethylpentylamine (DMP) 4-methylhexan-2-amine, Geranamine, and geranium oil, extract, or stems and leaves.

More Info

For more information, see the original Washington Post story “Chemist’s New Product Contains Hidden Substance,” by Amy Shipley, May 8, 2006. http://www.washingtonpost.com/wp-dyn/content/article/2006/05/07/AR2006050700913_2.html

USADA Advisory “Beware: Your Supplement Could Cause a Positive Test,” June 16, 2011. http://www.usada.org/athlete-advisory-methylhexaneamine-and-dietary-supplements/

A Multitude of Contributions

Dr. Catlin’s contributions to detecting PEDs have extended beyond these remarkable breakthroughs. Among other things, he determined the pharmacokinetics of steroids such as androstenedione (“andro,” formerly sold over the counter) and DHEA, provided analytical consulting as part of government action to identify and expose designer drugs like the aromatase inhibitor 6-OXO and the designer steroid Tren in supplement products, and succeeded at adapting a test for the potent blood-boosting drug CERA (sold under the brand name Mircera) for equines.

More Info

For more information about Dr. Don Catlin and his current work safeguarding supplements, visit the BSCG website at http://www.bscg.org/.

Note: The term “designer steroid” is defined as a synthetic steroid derived by simple chemical modification from another steroid, often an anabolic steroid. The word “designer,” however, can refer to compounds that are either novel or recycled and repurposed as performance-enhancers. Today these problematic substances sometimes find their way into legally sold supplement products.

— Joseph Taylor