To close out the year, in this issue on page 14 we review major research developments in 2005, and on page 18 we discuss the issues that have had an impact on infrastructure and business in the life sciences. As ever, science marches on.

But it has not all been plain sailing. Here is a selection of quotes that illustrate my top five grumbles, controversies, and setbacks of the year.

1. Let's start with a scalding comment on a hot area of research, systems biology from straight-talking Dutchman Ronald Plasterk: "The fundamental misconception of systems biology advocates is that one could create a 'virtual cell,' and use big computers to model life and make discoveries. ... a role. One makes discoveries by watching, working, checking. They want to be Darwin, but do not want to waste years on the Beagle. They want sex but no love, icing but no...

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