One of Nature Medicine's peer reviewers recently told the editors that it is unreasonable of the journal to seek advice from more than three reviewers for a paper, because it places an undue burden on authors.
Juan-Carlos Lopez, the journal's chief editor, explains on the blog 'Spoonful of medicine' (http://blogs.nature.com/nm/spoonful/2008/02/strength_in_numbers.html) that this practice, which is not undertaken lightly, is often necessary. One reason for this is that one of the referees may be someone who has not reviewed for the journal before, who may turn out to be either too tough or the opposite — what editors call “wet”.
Second, many submissions to Nature Medicine are multidisciplinary studies. In some cases, the editor will need one reviewer with expertise on animal experiments, another to advise on potential relevance to human disease, and others who are knowledgeable in the various disciplines and technologies involved.
Third, editors don't ask authors to address every point each referee raises. So, as Lopez says, “two referees times two does not necessarily equal four sets of comments”!
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From the blogosphere. Nature 451, xiii (2008). https://doi.org/10.1038/7182xiiic
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DOI: https://doi.org/10.1038/7182xiiic