UNDERSTANDING ICARUS: A Brief History of Steroid Doping

In December 2016, the World Anti-Doping Agency (WADA) published its second comprehensive report on the Russian government-funded doping program (McLaren, 2016). He concluded that between 2011 and 2015, “more than 1,000 Russian athletes competing in summer, winter and Paralympic sports could be identified as participating in or benefiting from manipulation in order to hide positive doping test results.” (McLaren, 2016). The McLaren report also describes the involvement of the Russian secret service (FSB) in achieving “unprecedented levels of corruption” at the 2014 Sochi Winter Olympics.

Before the start of the games, the FSB removed thousands of so-called “tamper-proof” bottles from the Anti-Doping Laboratory in Moscow and conducted experiments to open the bottles without breaking the seal. Through trial and error, they developed a special tool that allowed bottles to be opened without breaking the seal (Schwirtz & Ruiz, 2016).

Before the start of the games, the athletes donated their urine, free of PEDs, to the Russian authorities for freezing. The athletes then consumed PED and competed in games. So the urine samples collected from the games tested positive for the PED, but they were smuggled out of the Anti-Doping Laboratory at night through holes in the wall and taken away by FSB agents disguised as sewer engineers. The FSB removed the tamper-resistant caps and the PED-contaminated urine was replaced with a thawed clean sample. The bottle, which now contains a clean sample, was smuggled back into an anti-doping laboratory and then tested and proven to be “clean” (Schwirtz & Ruiz, 2016).

So what PEDs are these athletes taking?
For many years, anabolic steroids have been shown to be the most commonly detected doping agent in sports (Geyer et al, 2014). For example, of the 4,500 adverse analytical and atypical results reported by WADA accredited laboratories in 2012, 2,279 (~ 50%) were from anabolic agents (Geyer et al, 2014).

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Anabolic steroids are synthetic hormones that are structurally similar to testosterone and its derivatives. They are created by structurally modifying the structure of testosterone in the spine in an attempt to make the hormone more anabolic and less androgenic (i.e., less masculinizing) (Kicman, 2008). They are known to increase muscle size, muscle strength, accelerate recovery, and reduce the anti-catabolic effects of exercise (Weitzel et al, 2009). The most commonly found anabolic steroids from WADA are testosterone, nandrolone, stanozolol, and dianabol (Kicman, 2008).
Dr. Grigory Rodchenkov, the previous director of the Anti-Doping Laboratory in Moscow and the star of the new movie Icarus on Netflix, used his Ph.D. skills in analytical chemistry to create a cocktail of anabolic steroids that many Russian athletes brought to London. Olympic Games 2012 and throughout the Winter Olympics in Sochi. To speed up the absorption of steroids and shorten the detection window, he dissolved the drugs in alcohol – Chivas whiskey for men, Martini vermouth for women (Schwirtz & Ruiz, 2016). Dr. Rodchenkov’s formula was accurate: one milligram of steroid mixture for every milliliter of alcohol. Athletes have been instructed to add liquid in their mouths, under their tongues to absorb drugs (Schwirtz & Ruiz, 2016).

It became apparent that many Russian athletes took anabolic steroids between 2011 and 2015 and received a performance boost while still testing “pure”.

But what is the history of anabolic steroids? When did athletes first start using anabolic steroids and when did we first test them?

The story of testosterone dates back to 1849 with Charles Edward Brown-Sequard, considered by many to be the founding father of modern endocrinology (Hoffman et al, 2009). This is because he postulated the existence of substances that we now know as hormones secreted into the bloodstream that are capable of affecting distant organs.

Brown-Sequard conducted an experiment in which he injected himself with testicular extracts from guinea pigs and dogs and claimed that he had improved muscle strength, mental ability and appetite. Although these results were never confirmed, his research did make an impact, and some medical records show that 12,000 doctors used these testicular extracts and called them the Brown-Sequard Elixir, which they touted as the Elixir of Life (Hoffman et al, 2009).

From this work, two other scientists (Zoth and Pregl) began to investigate injections of testicular extracts on muscle strength and athletic performance. They injected themselves with bovine testicular extracts and measured the strength and fatigue of their middle fingers during a series of different exercises (Hoberman et al, 1995).

In 1896, Zoth published his findings and stated that these testicular extract injections improved muscle strength. Although it is now believed that these results were likely due to a placebo effect, Zot may have been the first to suggest hormone injection for athletes in an attempt to improve their performance (Hoffman et al, 2009).

In the early 1930s, there was a lot of interest in trying to synthesize artificial testosterone, and finally, in 1935, the first paper was published in which testosterone was synthesized from cholesterol (David et al, 1935).

“Shortly after testosterone was isolated in 1935, it was found to be virtually inactive when taken orally.”

After oral administration, testosterone is absorbed from the small intestine and travels to the liver, where it is rapidly metabolized, mainly to inactive compounds (Saudan et al, 2006). To get around this problem, pharmaceutical companies realized that they could inject testosterone intramuscularly after the addition of certain chemical side chains known as esters (Kicman, 2008).

Following this discovery of oral activity, pharmaceutical companies began to manufacture synthetic oral anabolic steroids, altering the chemical structure of testosterone to create a more anabolic steroid, less androgenic, with a slow rate of liver inactivation. and a completely different metabolism within the body (Saudan et al, 2006).

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The first clinical trials of testosterone injections began in 1937 (Hoberman et al. 1995), and by the early 1940s, it was clear that testosterone could enhance muscle growth (Hoffman et al. 2009).

In 1945, Paul De Cruif published a popular book called The Male Hormone, which argued that testosterone can increase muscle mass, rejuvenate people and improve their performance into old age. He even suggested that it would be interesting to see how athletes perform if they begin to use testosterone systematically (De Kruif, 1945). His guess would soon come true, and in the late 1940s, there were reports of West Coast bodybuilders using steroids and they began to infiltrate strength sports in the early 1950s (Hoffman et al, 2009).

At the 1954 World Weightlifting Championships, Dr. John Ziegler was on the US weightlifting medical team and informed his Russian counterpart that Soviet weightlifters were using testosterone. Ziegler returned home immediately after this World Cup and began experimenting with testosterone use (Hoffman et al, 2009).

During his early experiments with testosterone on athletes, he became interested in side effects such as an enlarged prostate and an effect on libido. He began looking for a cure to minimize these effects (Hoffman et al, 2009).

In 1958, the FDA in America approved the production of the oral steroid Dianabol, and it appeared to have fewer side effects than testosterone at the time (Todd, 1987).

Zeigler assigned Dianabol to three members of his weightlifting team and linked it to an intense training program. These athletes have experienced tremendous increases in performance (Hoffman et al., 2009).

News of the effectiveness of oral steroids spread to other sports throughout the 1960s. In 1965, the oral anabolic steroid Turinabol was synthesized by an East German pharmaceutical company and subsequently used by East Germany in a state-sponsored doping program designed to accelerate athletic performance (Ungerleider, 2001).

The atrocity in the doping program of the East German state was completely ignored after the medical reports of athletes were published in the early 1990s (Ungerleider, 2001). At the height of the program, more than 1,500 doctors and scientists were employed and up to 10,000 athletes were affected.
The vast majority of these athletes were unaware of the oral anabolic steroids they were taking because they were described as “vitamin pills that compensate for their deficiencies. food “(Costello, 2013).

“The vast majority of these athletes were unaware of the oral anabolic steroids they were taking because they were described as vitamin pills that compensate for their nutritional deficiencies.

Doping was performed on male and female athletes, some of whom were only 10 years old. For female athletes, doping mainly led to the permanent masculinization of body parts (Ungerleider, 2001). More than 1,000 athletes and women are believed to have suffered severe, long-term physiological and psychological harm from the doping program, and the German government has established a £ 2.5 million compensation fund to compensate these athletes for the horrors they unknowingly endured. (Costello, 2013).

For the 1968 Mexico City Olympics, it was reported that a third of American athletics athletes were using steroids in advance of the 1968 Olympics. In 1969, steroid use became so widespread that John Hendershott, the American Athletics editor at the time, called anabolic steroids the “breakfast of champions” (Hoffman et al, 2009).

However, what is notable about steroid use in the 1960s, although it was widespread and athletes claimed to have performance-enhancing effects, the International Olympic Committee (IOC) did not include anabolic steroids on the banned substance list at the time.

The conclusion of the scientific medical literature at the time was that anabolic steroids did not have performance enhancing effects, and therefore the IOC did not consider it necessary to prohibit these drugs, despite the fact that athletes claimed that they improved performance incredibly (Hoffman et al., 2009).

The main reason for this fundamentally flawed scientific conclusion was that most of the studies conducted during this time had flawed research designs, used low doses of steroids, and did not standardize training stimulus, calorie intake, or protein intake. Episode 2 of the Anti-Doping Science podcast describes these initial experiments, as well as experiments that ultimately proved conclusively that steroids increase performance (Bhasin et al, 1996).

In 1973, the first testing procedures for anabolic steroids were proposed. This test became known as a radioimmunoassay test and could detect oral steroid metabolites in an athlete’s urine. This test was tested during the 1974 Commonwealth Games in Auckland, New Zealand, and nine out of 55 samples tested positive for anabolic steroids (Hoffman et al, 2009).

The radioimmunoassay test was adopted by the IOC and was used during the 1976 Olympic Games in Montreal. Of the 275 tests conducted, only eight tested positive for anabolic steroids, suggesting that anabolic steroid use was low among athletes in these games. However, data from surveys conducted in games shows that 68% of competing athletes have used anabolic steroids at some point during training, and therefore the detectable compounds have left their bodies by the time they were tested in games (Hoffman et al, 2009).
In 1980, a new test for testosterone doping was developed that worked by comparing the ratio of testosterone to a similar hormone called epitestosterone in urine (Hoffman et al, 2009). The basic idea behind this ratio is that the vast majority of normal healthy men and women have a testosterone to epitestosterone ratio (T: E ratio) of 1: 1 (Kicman and Gower, 2003). Therefore, if someone injects testosterone, we will witness an increase in urine testosterone levels, but not a simultaneous increase in epitestosterone levels, and their T: E ratio will increase. Athletes with a 6: 1 T: E ratio were initially considered suspicious of doping, but recently this threshold was lowered and now 4: 1 is considered suspicious (Kicman and Gower, 2003).

A T: E ratio test was used at the 1980 Moscow Olympics and found that 20% of the athletes tested had a T: E ratio of 6: 1, and 7.1% of women had a 6: 1 T: E ratio (Hoffman et al., 2009).

“The T: E ratio test was used at the 1980 Moscow Olympics and found that 20% of the male athletes tested had a T: E ratio of 6: 1, while 7, 1% of women have a T: E ratio of 6: 1. “

These results show that doping is still widespread in Olympic sports, but the T: E ratio test has significantly increased the chances of an athlete being caught doping with testosterone.

The T: E ratio has proven to be a big problem for East Germany and their state-funded doping program. Records show that in 1981, after the collapse of the country, a meeting was held to develop scientific methods to circumvent the trials (Hoffman et al, 2009). By 1982, East Germany discovered that they could simultaneously administer testosterone and epitestosterone, increasing both ratios and consistently staying below the 1: 6 threshold that was suspicious for doping at the time (Hoffman et al, 2009).

Just two years after the complex and reliable testing at the Olympics, cheats have already developed doping protocols to bypass testing procedures.

The T: E ratio was also used at the 1983 Pan American Games in Caracas, Venezuela, where a total of 15 athletes tested positive for testosterone due to the increased ratio. This included 11 weightlifters, one cyclist, one fencer, one sprinter and one shot putter. In addition, 12 American athletes left the Games prior to the competition, due to the assumption of their absence, as they feared being caught as cheaters (Hoffman et al, 2009).

This news amazed the American media and shocked journalists. Subsequently, it became known that college sports in the United States (i.e., the NCAA) and professional sports organizations (such as the NFL, MLB, NBA, and NHL) are doing nothing to try to catch anabolic steroid users. Based on this, it has been speculated that 50% to 75% of the attacking and defensive lineman in the NFL used steroids in the 1980s (Hoffman et al, 2009). The exact usage levels will never be known.

Ben Johnson tested positive for the oral anabolic steroid Stanozolol after winning the 1988 100m Olympic Final in Seoul. Five more sprinters in the 100m final, now called the most corrupt race in history, have since been tarnished by various doping controversies, but Johnson remains the emblematic leader in the field of anabolic steroid doping in sports (Moore, 2013). >

The Olympic champion’s 100m test positive for steroids was highly controversial, and Ben Johnson was ostracized and humiliated by the media (Moore, 2013). Subsequent public outrage led the US government to pass the first Anabolic Steroid Control Act of 1990, which classified 27 steroids, along with their esters and isomers, as a Class 3 drug, which meant that possession could lead to prison conclusion (Hoffman et al. al, 2009).

In 1999, the IOC convened the World Conference on Doping in Sport in Lausanne, Switzerland, and this conference served as the basis for the International Anti-Doping Initiative that led to the formation of WADA in 2001 (Hoffman et al.). al, 2009). By 2002, the WADA Code was published, and this documentation contains international standards for laboratories, test procedures, substances on the prohibited list, provisions on the length of prohibitions and rules regarding prohibited substances required for medical reasons (therapeutic use exemptions or TUEs) (WADA, 2015).

“Before the WADA Code was published in 2002, there was no uniformity in doping protocols by sport and different governing bodies had different anti-doping rules.”

Most IFs had their own anti-doping rules, which, while based heavily on the IOC’s Anti-Doping Code, still resulted in large differences between sports. For example, a lack of consistency between International Federations, National Doping Organizations and Governments meant that two athletes in different sports could test positive for the same substance under the same circumstances, but both received different ban lengths, such as a ban on six months compared to a lifetime ban (Young, 2017).

The WADA Code has revolutionized anti-doping protocols and has made great strides in creating a global anti-doping initiative that fulfilled its mission to harmonize anti-doping rules around the world (Young, 2017).

In 2003, a syringe containing an unknown compound was sent to the United States Anti-Doping Agency (USADA). The compound in the syringe was isolated and determined to be tetrahydrogestrinone or THG, which was a new undetectable steroid at the time (Hoffman et al, 2009).

GTG is colloquially referred to as “Clear” due to its ability to induce increases in muscle mass and strength, but remains undetectable by anti-doping testing protocols (Kicman, 2008).

“THG was colloquially called” Clear “because of its ability to induce increases in muscle mass and strength, but it is not detected by anti-doping testing protocols.”

THG is an example of a designer steroid – a steroid clearly designed to bypass the doping test. To create a designer underground steroid, chemists will have access to information on steroids synthesized decades ago by pharmaceutical companies but never marketed for use. These steroids have never been studied in humans, and scientists have not identified their characteristic metabolites that you find in urine to trigger a positive test. While this practice of making designer steroids to bypass anti-doping tests appears to be limited, as current testing procedures rely on known metabolites in urine, unknown steroids can escape detection and represent a new way to avoid doping tests. (Kicman, 2008).

The designer steroid THG was linked to the BALCO laboratory in California, and a subsequent scandal ensued showing that steroid doping was a widespread problem in many sports in the United States (Hoffman et al, 2009).

Many athletes have been linked to the BALCO scandal, including three-time Olympic gold medalist Marion Jones, 100m world record holder Tim Montgomery and baseball legend Barry Bonds. This steroid doping scandal will trigger a change in legislation, and in 2004 the US Senate held hearings on the abuse of steroids and their precursors by athletes. By the end of 2004, a new anabolic steroid control law had been enacted, which contained 26 new steroid compounds, including many of the steroid precursors (“prohormones”) and designer steroids such as THG (Collins et al, 2008).
Many anti-doping scientists believe that designer steroids and a new class of tissue-specific steroids known as Selective Androgen Receptor Modulators (SARMS) represent the next generation of anabolic steroids (Kicman, 2008). Both of these categories of steroids have not yet been approved for sale by the relevant health authorities because they have not been proven to be safe for human consumption. Despite this fact, SARMS is often detected in routine drug tests and can be purchased online (Ayotte et al, 2017)

Strategies for detecting anabolic steroids will only improve over time, but history shows us that when testing improves, so does the ability to dodge tests.

About the author

Alex Colliari-Turner earned his degree in biological sciences from Oxford University and will be completing his PhD at the University of Brighton in September 2017 on the molecular mechanisms of muscle memory. His thesis will focus on comparing blood and muscle biopsies from pure versus steroid users to compare differences in gene expression in order to further expand research on steroid effects and improve muscle memory efficiency at the cellular level. He maintains a page and an anti-doping science podcast.