Arnold, SF, DM Klotz, BM Collins, PM Vonier, LJ Guillette, Jr., and JA McLachlan. 1996. Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272:1489-1492

• What was extraordinary about the original study by Arnold et al. was not synergy, as many examples of synergistic interactions among chemicals have been discovered .  The extraordinary dimension of the withdrawn results was the magnitude of synergy, up to 1600-fold.  Synergy exists. It just may not be that strong.
  
  Even with the withdrawal of this paper, synergy remains a huge challenge to risk assessment because synergy makes it very difficult to anticipate the health consequences of pesticides as most people experience them, which is in mixtures.  Testing rarely looks at interactions among chemicals and almost never in the complex soup that characterizes most people's exposures.
  
  
• Endocrine disruption was an issue long before McLachlan's study was even begun and its importance does not rest on one study.  Indeed, we completed the original Our Stolen Future manuscript before McLachlan started this study, and the book reached print (March 1996) before the study was published (June 1996).  In the scientific epilogue of Our Stolen Future (sent to print in September 1996) we observe that McLachlan's results, "if they can be replicated," heighten further the concern about interactions among chemicals because they indicate that interactions are even less predictable than had been understood.  Synergy was an important issue before McLachlan's study was published and remains one since it has been withdrawn.
  
  
• Industry critics present the McLachlan case an example of bad science. They miss the point, indeed they distort it, attempting to use it to deflect attention from the seriousness of the underlying issue.
  
  This pattern--important results published, results challenged, non-replicability confirmed, results withdrawn, is not unique in science even if this specific case is unfortunate.  Science proceeds by people performing their experiments, publishing them, and having other scientists challenge them.  McLachlan, while highly criticized by some industry critics, in fact behaved in the withdrawal in the best traditions of science.  As signals came back from other laboratories that the results could not be obtained, he turned his own laboratory back to the question and applied serious resources over many months to attempt to understand why this was happening.  Ultimately, when the nonreplicability was clear, he  contacted Science and withdrew the results. Other independent scientists commended McLachlan for the way he conducted himself in this case, and Tulane University conducted an independent review which confirmed McLachlan's integrity.

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