We thank McManus and colleagues for their comments and for opening a public debate on the implications of our study. Like them, we celebrate the extraordinary successes of biological research and the promises of exciting current initiatives such as Illuminating the Druggable Genome (IDG) program, the International Mouse Phenotype Consortium, or the Structural Genomics Consortium. These past and current successes, however, do not obviate the need to broaden our understanding of biology and to provide the best possible conditions for future investigations and discoveries.