Although the quest to sequence a human genome began in 1990, the techniques it used had already been in development for more than twenty years. And those DNA sequencing methods, in turn, were directly inspired by protein and RNA sequencing research stretching all the way back to the 1940s.
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Detecting fluorescence from a single DNA molecule proved difficult in practice, however. And so, in 2004, Solexa acquired the IP rights to a method called colony sequencing, developed by French scientists Pascal Mayer and Laurent Farinelli, to solve the detection problem. Colony sequencing affixed DNA fragments to a surface and amplified them over and over, generating “colonies” containing massive numbers of identical DNA strands. By reading the fluorescence from each strand in a colony simultaneously, it became possible to determine the base added at each step with much better accuracy, since random errors in individual strands would be averaged out by the consensus signal.