40th Anniversary of PCR coming up in November

It just occurred to me today that the 40th Anniversary of the first experiments demonstrating that the polymerase chain reaction, aka "PCR" is next month, in November.

I was working as molecular biologist at Cetus Corp. in the SF Bay Area at the time, and my colleague and head of our DNA Synthesis lab, Kary Mullis, conceived of the idea of PCR, but given he was a terrible "bench scientist", could not get it to work.

Our VP of R&D, Tom White, assigned me with the responsibility of determing if PCR actually worked or not, and I did those experiments in the first part of November, 1983.

And...it did! I remember showing my manager the very first results, which were encouraging, and we were "off to the races", as it were.

For those who haven't wrapped their head around exactly what PCR does, it's fairly simple: it performs the same function in molecular biology that a transistor does in electronics: it specifically amplifies a "signal of interest" against "background" so that it can be easily, reproducibly, and repeatibly detected.

The rest, they say, is history.

Just for yucks, here's the title pages of some of my key papers published in PCR: the first being the first use of PCR for molecular nucleic acid cloning, and the second, using it to characterize the Retinoblastoma VNTR (variable number tandem repeat.). Using PCR was a veritable breakthrough for cloning because projects to clone a single single-copy gene from the human genome could take several months to the better part of a year at the time, and with PCR, we could clone the specific target directly, and drop it into M13 for DNA sequencing in less than a week!



I used the second paper on amplifying the Retinoblastoma VNTR as the basis for establishing a PCR-based method for bone marrow transplantation surgeons to be able to, for the first time, quantitatively monitor allogeneic bone marrow transplant engraftment. Which I must say, was pretty dang cool....



Those were the days....

 

Amazing, sbaf truely has amazing people. PCR is such a fundamental step in diagnostics and research now that we don't even wonder about its history.

 

Epic! You are the rockstar I never knew I had interacted with. I do real time qPCR all the time for gene expression, and can't even conceive how we could do any biomedical research without PCR.

 

Thank you for all your contributions!

 

As a geneticist, Thank You. Your work predated my bench time but I was fortunate to have bench top thermocyclers for pcr and sequencing with radiolabelled didexoxynucleic acids run on polyacrylamide gels. A far cry from using 10X today..dB

 

Thanks, gents, for your comments. I feel fortunate to have simply been a guy with the right skills in the right place at the right time to have made something of a contribution to Science and Society.

Very cool to see that there are some other molecular biologist/scientist-type guys here as well. You guys know firsthand how "foundational" PCR has become in molecular biology, diagnostics, and medical and veterinary science.

Cheers, gents.

 

Yep, I’m in vetmed and PCR can be particularly indispensable when trying to drill down on differential diagnoses. Thank you!

 

Yeah, PCR is amazing for that. With appropriately-designed oligo probes, e.g. ASOs (allele-speific oligonucleotide) probes, you can accurately and precisely differentiate genetic differences down to a single base-pair.

 

I showed this thread to my GF (marine biologist) and her jaw kinda dropped. "you guys talk about this? on there??"

I'm glad most of y'all are smarter than me, sometimes. cheers, @Puma Cat for being in the right place at the right time, and most importantly, for knowing the right things.

 

Told my wife as well and she was also very impressed. She oversees the COVID “RAT” rapid test distribution for our area, and she knows how inaccurate they are. She wondered out loud whether at-home PCR testing would ever become a thing.

 

There are already efforts to develop them.
I think they are more likely to be point of care rapid PCRs ( in a clinic or mobile set up) because of the sensitive nature of the test. The NIH also has the covid triggered RADx program which is supporting developments and research in diagnostics.

Table top pcr for selected viruses in 15 min - far cry from puma cat's times!!
cobas® Liat® Analyzer (roche.com)

 

This is very cool. Thank you Puma Cat for being the first to getting such a foundational tool of molecular biology to work. It truly changed the world.

 

Yes, I'm familiar with the Roche COBAS® system; I've used it in the past. The systems developed by Applied Biosystems, where I went to work after Roche bought out* the rights to PCR from Cetus Corp. in 1992 were more effective and flexible for working with a broader range of applications than the Roche COBAS® system

*– In 1985, after the first paper was published in Science, I received a one-time bonus of $3000 for my work on PCR, demonstrating with scientific rigor it actually worked. In 1992, the execs at Cetus "cashed out" by selling the patents on PCR to Hoffman-LaRoche for $300 million, making millions in compensation for each of them, but true to the best principles of American Capitalism, they gave nothing back to their scientific team who developed it. Zip, nada, niente...