The main downside of this proposal is just complexity: it requires
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By the time Sanger sequencing was commercialized, the groundwork for an entirely new sequencing chemistry was already well underway. In 1985, Swedish biochemists Pål Nyren and Arne Lundin published a paper illustrating a procedure that measured the concentration of a molecule, called pyrophosphate (PPi), using an enzymatic cascade that emits light. In early 1986, Nyren realized that the method he’d helped develop could be applied to DNA sequencing, because PPi is naturally produced as a byproduct of DNA synthesis.5