Welcome to DOPING.nl, the Anti-Doping Knowledge Center

This site has been established to host information about doping in the broadest sense of the word, and about doping prevention.

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The Anti-Doping Authority Netherlands (the Dutch Doping Authority for short) established this site and maintains it. The Doping Authority was founded in 1989 and it is one of the oldest NADOs in the world. Doping.nl was developed with financial support from the Dutch Ministry for Health, Welfare and Sport.

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This website was established because of the importance that the Doping Authority and the Ministry attach to the dissemination of information relevant to doping prevention. Disclosing and supplying relevant information is one of the cornerstones in the fight against doping in sport. However, in practice, a significant amount of information is still not available, or only available to a limited group of users. We therefore decided to bring together all the relevant information in a single site: Doping.nl.

Activities

The Doping Authority aims to supply as much information through this website as possible on an ongoing basis. The information will be varied but will focus primarily on: WADA documents like the World Anti-Doping Code, the International Standards like the Prohibited List, Doping Regulations, scientific articles and abstracts, decisions by disciplinary bodies (mainly CAS decisions).As well as making documents available, the Doping Authority aims to supply searchable documents when possible, and to add relevant keywords to ensure easy access.
In the future, Doping.nl will also become a digital archive containing older information that is no longer available elsewhere.

Target readers

This site has been designed for use by anti-doping professionals such as National Anti-Doping Organisations and International Federations but also for students, journalists and other people interested in the subject.

More information explaining how to use this website can be found under "help".

CAS 2020_O_6689 WADA vs RUSADA

17 Dec 2020

CAS 2020/O/6689 World Anti-Doping Agency v. Russian Anti-Doping Agency

  • World Anti-Doping Agency (WADA)
  • Russian Anti-Doping Agency (RUSADA)

Intervening Parties:

  • International Olympic Committee
  • International Paralympic Committee
  • Russia Olympic Committee
  • Russia Paralympic Committee
  • European Olympic Committees
  • International Ice Hockey Federation
  • Russian Ice Hockey Federation
  • Lilya Akhaimova, Regina Isachkina, Elena Osipova, Arina Averina, Olga Ivanova, Yana Pavlova, Dina Averina, Yulia Kaplina, Alexey Rubtsov, Ilya Borodin, Evgeniya Kosetskaya, Ekatarina Selezneva, Artur Dalaloyan, Elena Krasovskaia, Nikita Shleikher, Alina Davletova, Evgeny Kuznetsov, Vladimir Sidorenko, Evgenija Davydova, Sayana Lee, Inna Stepanova, Inna Deriglazova, Vladimir Malkov, Maria Tolkacheva, Yana Egorian, Polina Mikhailova, Dmitry Ushakov, Vladislav Grinev, Andrei Minakov, Sofiya Velikaya, Kristina Ilinykh, Nikita Nagornyy, and Andrey Yudin
  • Sasha Gusev, Daniil Sotnikov, Ilya Borisov, Igor Ovsyannikov, Nachyn Coular, Valeria Koblova, Elizaveta Sorokina, Ivan Golubkov, Elena Krutova, and Viktoria Potapova


This case deals with RUSADA’s alleged non-compliance of a critical requirement under the International Standard for Code Compliance by Signatories (ISCCS) to procure the delivery to WADA of authentic data from the Moscow Anti-Doping Laboratory.

In January 2020 WADA requested CAS for arbitration against RUSADA. Hereafter also the IOC, IPC, ROC, EOC, IIHF, FHR and two Athletes Groups filed their requests to intervene in the proceedings.

WADA contended that the Moscow Data had been materially and improperly altered prior to a copy being provided to WADA in January 2019. The alleged alterations included:

  • back-dating;
  • disk formatting;
  • deletions of database back-ups;
  • secure erasing of files;
  • selective removal of user action commands from command logs;
  • replacement of databases;
  • deletion of records;
  • removal of tables; and
  • missing command logs.

On that account WADA sought a finding of such non-compliance and the imposition of a number of consequences deriving therefrom. RUSADA opposed WADA’s claims. It denied that the data retrieved by WADA from the Moscow Laboratory was manipulated and, in the alternative, denied any responsibility for manipulations and challenged the validity of the Signatory Consequences sought by WADA.

The Intervening Parties’ submissions, in a number of areas, bore substantial similarity to those made by RUSADA or overlapped with submissions made by other Intervening Parties.

As a result of the Parties’ submissions the CAS Panel examined the following issues:

  • the validity of the ISCCS and WADA’s requirement that RUSADA procure the delivery to WADA of authentic data from the Moscow Laboratory;
  • whether RUSADA complied with that requirement; and
  • if not, what Signatory Consequences can and should be imposed.

At first the CAS Panel in this case dismissed the objections to its jurisdiction and settled a number of other procedural matters raised by the Parties.

The Panel established that RUSADA consented to the 2018 WADC, the ISCCS and the Post Reinstatement Conditions. This consent was not compromised or invalidated by the safegards in its defence.

Also the Panel established that the Post-Reinstatements Data Requirement was valid and binding on RUSADA, and non-compliance could lead to consequences under the ISCCS. The Panel does not accept RUSADA’s submission that there were no changes, losses or deletions of data pertaining to results of doping sample analysis.

Based on the evidence the Panel concludes that RUSADA failed to procure an authentic copy of the Moscow Data and therefore failed to comply with the Post-Reinstatement Data Requirement. The steps taken to manipulate the Moscow Data and deceive WADA could hardly be more serious. For that reason the Panel deems that WADA has established that RUSADA in non-compliance with the 2018 WADC.

The Panel regards that, despite having an opportunity to come clean and draw a line under this scandal by providing access to the Moscow Data, Russian authorities engaged in an extensive manipulation of that data. This conduct is likely to thwart or at least substantially hinder the ability to identify those athletes who participated in the doping scheme.

Having further found that RUSADA failed to comply with the Post-Reinstatement Data Requirement, the Panel has accordingly imposed consequences to reflect the nature and seriousness of the non-compliance and to ensure that the integrity of sport against the scourge of doping is maintained.

Nevertheless the consequences which the Panel has decided to impose are not as extensive as those sought by WADA. This should not, however, be read as any validation of the conduct of RUSADA or the Russian authorities.

Therefore the Court of Arbitrtion for Sport decides on 17 December 2020 that:

  1. The Request for Arbitration filed by the World Anti-Doping Agency (“WADA”) dated 9 January 2020 is partially upheld.
  2. The Panel has jurisdiction to determine this matter.
  3. The Russian Anti-Doping Agency (“RUSADA”) is found to be non-compliant with the World Anti-Doping Code (“WADC”) in connection with its failure to procure that the authentic LIMS data and underlying analytical data of the former Moscow Laboratory was received by WADA.
  4. The orders below come into effect on the date of this Award and remain in effect until the second anniversary of that date (the “Two-Year Period”).       [...]
  5. RUSADA is required to satisfy the following reinstatement conditions during the Two-Year Period (or any shorter period as agreed between WADA and RUSADA) in order to be reinstated as a compliant Signatory.      [...]
  6. RUSADA is to pay a fine to WADA of 10% of its 2019 income or USD 100,000 (one hundred thousand United States dollars) (whichever is lower) within 90 (ninety) days from the notification of the present arbitral award. Such amount shall accrue interest at a rate of 5% per annum in case of non-timely payment.
  7. The costs of the arbitration, to be determined and served to the parties by the CAS Court Office, shall be borne 80% by RUSADA and 20% by WADA.
  8. RUSADA is ordered to pay WADA a total amount of CHF 400,000 (four hundred thousand Swiss francs) as contribution towards its legal and other expenses incurred in connection with these arbitration proceedings within 90 (ninety) days from the date the present award. Such amount shall accrue interest at a rate of 5% per annum in case of non-timely payment.
  9. RUSADA and each Intervening Party shall bear its own legal costs and other expenses incurred in connection with this arbitration.
  10. All other motions or prayers for relief are dismissed.

Finding the golden genes: Advances in gene therapy could tempt some athletes to enhance their genetic makeup, leading some researchers to work on detection methods just in case

30 Sep 2009

Finding the golden genes : Advances in gene therapy could tempt some athletes to enhance their genetic makeup, leading some researchers to work on detection methods just in case / Patrick Barry. - (Science News 174 (2008) 3 (2 August); p. 16-21)

  • Doi: 10.1002/scin.2008.5591740321

New application of the CRISPR-Cas9 system for site-specific exogenous gene doping analysis

17 Nov 2020

New application of the CRISPR-Cas9 system for site-specific exogenous gene doping analysis / Joon-Yeop Yi, Minyoung Kim, Hophil Min, Byung-Gee Kim, Junghyun Son, Oh-Seung Kwon, Changmin Sung. - (Drug Testing and Analysis (2020) 17 November)

  • PMID: 33201595
  • DOI: 10.1002/dta.2980

Abstract

The increased potential for gene doping since the introduction of gene therapy presents the need to develop anti-doping assays. We therefore aimed to develop a quick and simple method for the detection of specifically targeted exogenous doping genes utilizing an in vitro clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) system. A human erythropoietin (hEPO) is a drug frequently used for doping in athletes, and gene doping using gene transfer techniques may be attempted. Therefore, we selected hEPO gene as a model of exogenous doping gene, and complemental single guide RNA (sgRNA) was designed to specifically bind to the four exon-exon junctions in the hEPO cDNA. For the rapid reaction of CRISPR-Cas9, further optimization was performed using an open-source program (CRISPOR) that avoids TT and GCC motifs before the protospacer adjacent motif (PAM) domain and predicts the efficiency of the sgRNA. We optimized the in vitro Cas9 assay and dual use of sgRNA for double cleavage and identified the limit of detection (LOD) of the 1.25 nM of the double cleavage method. We expect that the improved CRISPR-Cas9 method can be used for anti-doping analyses of gene doping.

Detection of non-targeted transgenes by whole-genome resequencing for gene-doping control

7 Aug 2020

Detection of non-targeted transgenes by whole-genome resequencing for gene-doping control / Teruaki Tozaki, Aoi Ohnuma, Masaki Takasu, Kotono Nakamura, Mio Kikuchi, Taichiro Ishige, Hironaga Kakoi, Kei-Ichi Hirora, Norihisa Tamura, Kanichi Kusano, Shun-Ichi Nagata. - (Gene Therapy (2020) 7 August)

  • PMID: 32770095
  • DOI: 10.1038/s41434-020-00185-y

Abstract

Gene doping has raised concerns in human and equestrian sports and the horseracing industry. There are two possible types of gene doping in the sports and racing industry: (1) administration of a gene-doping substance to postnatal animals and (2) generation of genetically engineered animals by modifying eggs. In this study, we aimed to identify genetically engineered animals by whole-genome resequencing (WGR) for gene-doping control. Transgenic cell lines, in which the erythropoietin gene (EPO) cDNA form was inserted into the genome of horse fibroblasts, were constructed as a model of genetically modified horse. Genome-wide screening of non-targeted transgenes was performed to find structural variation using DELLY based on split-read and paired-end algorithms and Control-FREEC based on read-depth algorithm. We detected the EPO transgene as an intron deletion in the WGR data by the split-read algorithm of DELLY. In addition, single-nucleotide polymorphisms and insertions/deletions artificially introduced in the EPO transgene were identified by WGR. Therefore, genome-wide screening using WGR can contribute to gene-doping control even if the targets are unknown. This is the first study to detect transgenes as intron deletions for gene-doping detection.

Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection

10 Oct 2018

Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig : a model case study for gene doping detection / Teruaki Tozaki, Shiori Gamo, Masaki Takasu, Mio Kikuchi, Hironaga Kakoi, Kei-Ichi Hirota, Kanichi Kusano, Shun-Ichi Nagata. - (BMC Res Notes 11 (2018) 10 October)

  • PMID: 30309394
  • PMCID: PMC6180624
  • DOI: 10.1186/s13104-018-3815-6


Abstract

Objective: Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 μg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction.

Results: The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the bloodstream within 1-2 days after administration. In contrast, low amounts of p.hEPO were detected at 2-3 weeks after administration. These results suggest that the proposed method to detect gene doping can help obtain information for experiments using horses.

 

Gene and Cell Doping: The New Frontier - Beyond Myth or Reality

2 Jun 2017

Gene and Cell Doping : The New Frontier - Beyond Myth or Reality / Elmo W.I. Neuberger, Perikles Simon. - (Medicine and sport science 62 (2017) 2 June; p. 91-106) 

  • PMID: 28578328
  • DOI: 10.1159/000465456

Abstract

The advent of gene transfer technologies in clinical studies aroused concerns that these technologies will be misused for performance-enhancing purposes in sports. However, during the last 2 decades, the field of gene therapy has taken a long and winding road with just a few gene therapeutic drugs demonstrating clinical benefits in humans. The current state of gene therapy is that viral vector-mediated gene transfer shows the now long-awaited initial success for safe, and in some cases efficient, gene transfer in clinical trials. Additionally, the use of small interfering RNA promises an efficient therapy through gene silencing, even though a number of safety concerns remain. More recently, the development of the molecular biological CRISPR/Cas9 system opened new possibilities for efficient and highly targeted genome editing. This chapter aims to define and consequently demystify the term "gene doping" and discuss the current reality concerning gene- and cell-based physical enhancement strategies. The technological progress in the field of gene therapy will be illustrated, and the recent clinical progress as well as technological difficulties will be highlighted. Comparing the attractiveness of these technologies with conventional doping practices reveals that current gene therapy technologies remain unattractive for doping purposes and unlikely to outperform conventional doping. However, future technological advances may raise the attractiveness of gene doping, thus making it easier to develop detection strategies. Currently available detection strategies are introduced in this chapter showing that many forms of genetic manipulation can already be detected in principle.

Synthetic certified DNA reference material for analysis of human erythropoietin transgene and transcript in gene doping and gene therapy

7 Jun 2016

Synthetic certified DNA reference material for analysis of human erythropoietin transgene and transcript in gene doping and gene therapy / A. Baoutina, S. Bhat, M. Zheng, L. Partis, M. Dobeson, I.E. Alexander, K.R. Emslie. - (Gene Therapy 23 (2016) 10 (October; p. 708-717)

  • PMID: 27439362
  • DOI: 10.1038/gt.2016.47


Abstract

There is a recognised need for standardisation of protocols for vector genome analysis used in vector manufacturing, to establish dosage, in biodistribution studies and to detect gene doping in sport. Analysis of vector genomes and transgene expression is typically performed by qPCR using plasmid-based calibrants incorporating transgenic sequences. These often undergo limited characterisation and differ between manufacturers, potentially leading to inaccurate quantification, inconsistent inter-laboratory results and affecting clinical outcomes. Contamination of negative samples with such calibrants could cause false positive results. We developed a design strategy for synthetic reference materials (RMs) with modified transgenic sequences to prevent false positives due to cross-contamination. When such RM is amplified in transgene-specific assays, the amplicons are distinguishable from transgene's amplicons based on size and sequence. Using human erythropoietin as a model, we produced certified RM according to this strategy and following ISO Guide 35. Using non-viral and viral vectors, we validated the effectiveness of this RM in vector genome analysis in blood in vitro. The developed design strategy could be applied to production of RMs for other transgenes, genes or transcripts. Together with validated PCR assays, such RMs form a measurement tool that facilitates standardised, accurate and reliable genetic analysis in various applications.

Establishment of two quantitative nested qPCR assays targeting the human EPO transgene

11 Jan 2016

Establishment of two quantitative nested qPCR assays targeting the human EPO transgene / E.W.I. Neuberger,  I. Perez, C. Le Guiner, D. Moser, T. Ehlert, M. Allais, P. Moullier, P. Simon, R.O. Snyder. - (Gene Therapy 23 (2016) 4 (April); p. 330-339)

  • PMID: 26752352
  • DOI: 10.1038/gt.2016.2


Abstract

For ethical and safety reasons it is critical to develop easily implemented assays with high sensitivity and specificity for gene doping surveillance. Two nested quantitative real-time PCR (qPCR) assays were developed that target the human EPO (hEPO) cDNA sequence in a circular form, representative of recombinant adeno-associated viral (rAAV) vector genomes found in vivo. Through an interlaboratory evaluation, the assays were validated and utilized in an in vitro blinded study. These assays are specific and extremely sensitive with a limit of detection (LOD) of 1 copy of circular plasmid DNA and a limit of quantification (LOQ) of 10 to 20 copies in the presence of 500 ng of human genomic DNA (hgDNA) extracted from WBCs. Additionally, using the two nested qPCR assays in a non-human primate study, where macaques were injected intramuscularly with a rAAV8 vector harboring a promoterless hEPO cDNA sequence, the viral vector was detected 8 to 14 weeks post-injection in macaque WBCs. The high sensitivity of the nested qPCR approach along with the capability of quantifying target DNA, make this approach a reliable tool for gene doping surveillance and the monitoring of exogenous DNA sequences.

Selective androgen receptor modulators for the treatment of late onset male hypogonadism

19 Dec 2013

Selective androgen receptor modulators for the treatment of late onset male hypogonadism / Christopher C. Coss, Amanda Jones, Michael L. Hancock, Mitchell S. Steiner, James T. Dalton. - (Asian Journal of Andrology 16 (2014) 2 (March-April); p. 256-261)

  • PMID: 24407183
  • PMCID: PMC3955335
  • DOI: 10.4103/1008-682X.122339


Abstract

Several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. Selective androgen receptor modulators (SARMs) have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for SARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. Similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of SARMs can be employed in the treatment of late onset male hypogonadism.

Excretion of 19-norandrosterone after consumption of boar meat

30 Oct 2020

Excretion of 19-norandrosterone after consumption of boar meat / Frank Hülsemann, Gregor Fußhöller, Christine Lehn, Mario Thevis. - (Drug Testing and Analysis (2020) Special Issue (30 October); p. 1-7)

  • PMID: 33125835
  • DOI: 10.1002/dta.2958


Abstract

The consumption of the offal of noncastrated pigs can lead to the excretion of 19-norandrosterone (NorA) in urine of humans. In doping control, GC/C/IRMS is the method of choice to differentiate between an endogenous or exogenous origin of urinary NorA. In some cases, after the consumption of wild boar offal, the δ13 C values of urinary NorA fulfill the criteria of an adverse analytical finding due to differing food sources of boar and consumer. However, consumption of wild boar's offal is not very common in Germany, and thus, the occurrence of such an analytical finding is unlikely. In contrast, the commerce with wild boar meat has increased in Germany within the last years. Up to 20,000 tons of wild boar meat are annually consumed. In order to probe for the probability of the occurrence of urinary NorA after consumption of wild boar meat, human urine samples were tested following the ingestion of commercially available game. In approximately half of the urine samples, traces of NorA were detected postadministration of 200 to 400 g boar meat. The highest urinary concentration was 2.9 ng/ml, and significant amounts were detected up to 9 h after the meal. δ13 C values ranged from -18.5‰ to -23.5‰, which would have led to at least two adverse analytical findings if the samples were collected in an antidoping context. IRMS analysis on German boar tissue samples showed that δ13 C values for wild boar's steroids are unpredictable and may vary seasonally.

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