Is there a baby in the bathwater? Maybe: some methodological issues for the de novo protein synthesis hypothesis.

The de novo protein synthesis hypothesis has a long history and will no doubt continue to influence research. Yet, the primary behavioral evidence for this claim continues to come from studies in which amnesia is produced by broad scale protein synthesis inhibitors such as anisomycin. What is remarkable is the uncritical acceptance of the idea that because anisomycin is a protein synthesis inhibitor then it must have produced amnesia because it prevented translation. Several viable alternative interpretations of such experiments are discussed here and it is concluded that there is nothing to be gained by the continued use of broad-scaled antibiotics to address this hypothesis. Moreover, this approach cannot answer two critical and related questions - why must new proteins be synthesized and what are they? A focus on specific proteins such as those synthesized locally and upregulate the translation of other proteins may be a promising approach to answering these questions.