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The Blue Baby Syndromes

Did environment or infection cause a blood disorder in newborns?

Roger P. Smith

At a Standstill

Few pursuits are more frustrating to the biomedical scientist than attempts to investigate diseases of very low incidence. It is a mixed blessing that both episodes of infantile methemoglobinemia ended spontaneously, because at this juncture no further elucidation of either is in sight. Try as we might, we face formidable obstacles in studying diseases that no longer exist and for which there are no satisfactory animal models. Nor is there any incentive to carry out such studies.

The hypothesis that Avery has offered for the etiology of the endogenous disease is, of course, incompatible with the exogenous well-water nitrate hypothesis. If Comly was wrong, exogenous nitrates were a red herring, and the drinking water standard for nitrate has been set at an unnecessarily low level. Communities may have incurred needless expense in pursuing nitrate removal. However, the evidence for the involvement of well-water nitrate in the first miniepidemic is at least as strong, if not stronger, than the evidence for the involvement of gastrointestinal infections in the second. The clear dose-response relationship between the well-water nitrate content and the severity of the methemoglobinemia, and the logical explanation for the sensitivity of infants to nitrate, support the etiology proposed for the first episode, but their equivalents are lacking for the second.

Science is simply not always able to provide neat and clean answers, and in order to protect the public, expensive policy decisions must sometimes be made based on whatever facts are known. We seem to be forced to the conclusion that an exceedingly rare toxic condition, methemoglobinemia in infants, is linked to two episodes of exposure to endogenous nitrite, but generated by two entirely different mechanisms. More improbable still is that both episodes suddenly appeared and then spontaneously resolved over the space of a dozen years, each in the second half of the 20th century. As Sherlock Holmes famously remarked to Dr. Watson, “When you have eliminated the impossible, whatever remains, however improbable, must be the truth.” It also may be, in a way, a vindication of the now 50-year-old drinking water standard for nitrate.

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