Foundations | The First Polymerase Chain Reaction
This page from my notebook lists the chemicals which I put together into a single, purple-capped tube on September 8th, 1983, in a reaction I labeled PCR01. No cycling, only one tube, no variations, no controls, and anyone familiar with PCR conditions used today will recognize very little here, except the idea.
I wasn't positive that the reaction would not cycle itself. I knew that any chemical equilibrium had some finite value, meaning that some portion of any nominally double-stranded DNA would be single-stranded. And to increase the initial population of single strands, I had to cut the template DNA with a restriction enzyme. And the primers were there in sumptuous abundance. I was certainly not a proponent of doing things the hard way if there were any other possibilities.
You might conclude that it was a long-shot experiment. I agreed, so [at midnight] I poured myself a cold Becks into a prechilled 500 ml beaker from the isotope freezer for luck, and went home.
I ran a gel the next afternoon [and] stained it with ethidium. It took several months to arrive at conditions [that] would produce a convincing result."
--Kary B. Mullis received the Nobel Prize in chemistry in 1993 for his discovery of the PCR method.