Sir

We at the World Anti-Doping Agency (WADA) find parts of Donald Berry's Commentary 'The science of doping' (Nature 454, 692–693; 2008) potentially damaging to the fight against doping in sports.

WADA's accredited laboratories, including the French national laboratory LNDD (which handled the Floyd Landis case), must meet standards set by the International Standard for Laboratories (ISL) in validation methods, staff competency and chain of custody, for example. Compliance is assessed independently by bodies of the International Laboratory Accreditation Cooperation.

Berry casts doubt on the laboratory component of the anti-doping procedure as a whole, but he fails to mention that the majority of the substances reported by the anti-doping laboratories are exogenous substances not naturally present in human beings. The development of testing procedures for endogenous substances includes samples from normal reference populations and from subjects administered with the substance under investigation, so that test-sample status and positivity criteria can be established. To determine cut-offs for the ratio of testosterone to epitestosterone (T/E), tens of thousands of athlete samples were analysed to establish reference values. To detect exogenous administration of endogenous substances (such as pharmaceutical testosterone) by isotope-ratio mass spectrometry (IRMS), validation is based on a combination of hundreds of known positive and negative samples analysed by many WADA anti-doping laboratories operating under the scrutiny of the ISL and of the International Organization for Standardization (such as ISO 17025).

Each sample test includes positive and negative quality-control samples to assess the possibility of a false result. If these samples fail, the test must be repeated. An adverse analytical finding is not reported unless the quality criteria are met.

Laboratories participate in at least four rounds of blind and one double-blind proficiency test per year; the results of each round determine the accreditation status of the laboratory. False positives mean immediate revocation of accreditation.

Berry's implication that the results of T/E ratio and IRMS analyses are interdependent is not altogether correct: according to the WADA list of prohibited substances, IRMS analysis stands alone as the basis of an exogenous testosterone finding. This is supported by legal precedents.

Contrary to Berry's suggestion that anti-doping tests may not be sufficiently specific, mass-spectrometry identification of exogenous substances relies on at least three diagnostic ions to avoid any interference or misidentification. For immunoassays, antibodies in the initial testing and confirmation procedures must have different antigen-epitope specificity. For analytes that are too small to have two independent antigenic epitopes, two different purification methods or two different analytical methods are used.

WADA encourages its accredited laboratories to publish in peer-reviewed journals. Although complete information cannot be released without compromising the efficacy of an anti-doping test, this is made available to legal panels on request.

WADA's mandate is not to foster “a sporting culture of suspicion, secrecy and fear”, as suggested by your Editorial (Nature 454, 667; 2008), but to promote fair play by protecting clean athletes.

See also Doping: using flexible criteria could reduce false positives