I am a big fan of Small Science. In spite of the riches unearthed by Big Science in the fields of biology and physics during the last fifty years, historically speaking much of scientific progress has come from small groups or individuals working with relatively cheap equipment and resources. For instance consider discoveries like the structure of DNA, the structure of proteins, nuclear fission, the cosmic microwave background radiation and the transistor. All of these have been the beneficiaries of Small Science. Even in those cases where large organizations have supported these developments, the key findings themselves have come from small groups left alone to pursue their own interests. The work done by these groups benefited from a maximum of flexibility and a minimum of bureaucratic interference.
More at SciAm: In praise of Small (and Cheap) Science