Remembering Kary Mullis and PCR
It’s been used to solve crimes, diagnose diseases, decode the human genome, trace our ancestry, and even find out who our parents are. It’s the technique called PCR - the polymerase chain reaction, that copies DNA and earned the Nobel Prize for its inventor, Kary Mullis. He died earlier this month, Chris Smith revisits their interview from years ago.
Chris - PCR, The Polymerase Chain Reaction, revolutionised the field of genetics. In a matter of hours, scientists could make millions of copies of a piece of DNA that they wanted to study. The technique was the 1983 brainchild of chemist Kary Mullis.
Kary - I was working in a company making these a little short pieces of DNA which we call oligonucleotides. They were very difficult to make. Then a really good friend of mine named Ron Cook brought a machine into my lab one day and he said “try this Kary, it'll replace your whole lab!”.
And in fact instead of needing about seven people to help me I figured I could probably get away with me and the machine and one other person and I probably wouldn't have to work too hard. So I was stuck with the problem of “do I fire five of my good friends here? Or is there any way I can think of increasing the market for oligonucleotides by a large factor?”
Chris - Widely regarded as a colourful character, Kary Mullis put his aptitude for science down to a childhood spent building rockets to fire frog astronauts since the high atmosphere above the family farm in North Carolina. En route to becoming a chemist, he dabbled in writing fiction, became a baker and took by his own admission plenty of LSD in the 1960s and 70s, remarking in one interview that “it was certainly much more important than any courses I ever took”. In fact he said an LSD trip helped him to dream up the PCR reaction process that led to his 1993 Nobel Prize.
Kary - I was driving up to my cabin up in Mendocino one Friday night. I just had in my mind this little picture which anybody familiar would say “hey, that's PCR”. One of the little oligonucleotides there was actually the business end and the other one was sort of a control. All I had to do was sort of say “you know what? If you did that and then did it again and did it again and then did it again you would start amplifying the piece of DNA that's between those two oligonucleotides”, and there would be no end of that process. You could do it forever if you wanted to.
Chris - What he'd envisaged was using two short pieces of DNA to flank the region he wanted to copy, and then using the enzyme DNA polymerase to shuttle back and forth between them to run off an exponential number of copies. But the idea could easily been killed off before it even got going.
Kary - The really critical next stage was getting me and my car and my new idea out of the highway because I had stopped right in the middle of a curvy two lane road up in Mendocino County. There were logging trucks using that road and I could have been slammed off the road and my idea and I would have suffered an ugly axe. I finally said “get out of the road for Christ's sake move over. Get onto this shoulder”. I got over on the shoulder I started making a few notes and as far as I was concerned by the time I got back to my cabin it was done. That was my job.
Chris - That discovery went on to change the world and the technique is now used everyday in thousands of laboratories and industries all over the world. Indeed in the early 90s Kary Mullis himself joined the bandwagon and used his own technique to found a jewelry business selling trinkets allegedly containing the copied DNA sequences of famous dead celebrities Elvis and Marilyn Monroe among them. But he also took pleasure in what others made of his contribution.
Kary - Nothing made me happier lately than - there's a song about it. It's like on YouTube if you look up PCR song you get this really well produced interesting song about my reaction.
Chris - His only regret he says was not capitalizing better on his discovery initially.
Kary - The one thing that I feel like would have been nice is if I’d have said “here it is but I'd like to keep one percent of it myself in terms of the profit from it”. I was young and foolish I guess. But I did get the Nobel Prize for it which is quite a fun thing to have happen to you.