Pittendrigh C S, Caldarola P C, Cosbey E S
Proc Natl Acad Sci U S A. 1973 Jul;70(7):2037-41. doi: 10.1073/pnas.70.7.2037.
D(2)O is the only "chemical" agent that consistently affects the frequency of circadian oscillations: its effect is now known to be so widespread and predictable that its action merits closer study as a potential clue to the currently obscure concrete nature of circadian oscillators. The great diversity of D(2)O effects on biological systems in general is briefly reviewed and the need for rejectable hypotheses concerning the action of D(2)O on circadian clocks is stressed because current speculation on its action yields "predictions" expected from almost any hypothesis. We consider the hypothesis that it "diminishes the apparent temperature" of the cell and proceed to test this by examining the effect of D(2)O on temperature-dependent and temperature-compensated aspects of the circadian system in Drosophila. We find these components respond as differentially to D(2)O as they do to temperature; we conclude, however, with a warning that this result may be equivocal if, as we now suspect, the frequency of circadian oscillations is generally homeostatically conserved-not only in the face of temperature change, but change in any variable to which it is sensitive. More crucial tests of the temperature-equivalence hypothesis for D(2)O action are defined.
重水（D₂O）是唯一一种始终会影响昼夜节律振荡频率的“化学”物质：如今已知其影响广泛且可预测，因此，作为揭示当前仍不明晰的昼夜节律振荡器具体本质的潜在线索，其作用值得深入研究。本文简要回顾了重水对一般生物系统影响的巨大多样性，并强调需要提出关于重水对生物钟作用的可证伪假设，因为目前对其作用的推测几乎从任何假设都能得出“预测”。我们考虑了重水“降低细胞表观温度”这一假设，并通过研究重水对果蝇昼夜节律系统中温度依赖性和温度补偿性方面的影响来进行验证。我们发现这些成分对重水的反应与对温度的反应一样存在差异；然而，我们得出结论并警告，如果正如我们目前所怀疑的那样，昼夜节律振荡频率通常通过稳态得以维持——不仅面对温度变化如此，面对其敏感的任何变量变化亦是如此，那么这个结果可能并不明确。文中还定义了对重水作用的温度等效性假设更关键的测试。
