Thread: 40th Annniversary of PCR Coming Up!

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....

Originally Posted by Puma Cat

Those were the days....

Waaay out of my field but that seems like a huge deal. Wow! Good one.

Originally Posted by XRS

Waaay out of my field but that seems like a huge deal. Wow! Good one.

It really was a big deal; it completely transformed the fields of molecular biology, molecular genetics, medicine, forensics, and other areas of biological science and ultimately, Society as a whole. It quite literally was as important for those fields as the invention of the Transistor was for Electronics (for the same foundational reasons).

The conception of PCR won the Nobel Prize in Chemistry for my co-worker and friend, Kary Mullis in 1993. The reason I specify "conception", rather than "invention" is that to receive a patent for an invention, you have to demonstrate "reduction to practice"; i.e. you have make it work in the real world. Kary was not able to demonstrate experimentally his conception worked, but after it was assigned to me to, I was able to show experimentally that it worked with accuracy, precision, reproducibly and repeatably; quality attributes that are key to demonstrate scientific rigor.

This is a key point about Science: it truly is a collaborative process.

Originally Posted by astrotoy

Thanks for the post. That was great that you were in on the very beginning of such an important conception. I served on a non-profit board with Ed Penhoet, who was CEO of Chiron. I remember in the early 90's of him talking about the process of buying Cetus and how much the legal fees were to do the deal. Did you move to Chiron after the merger? One side note, the non-profit Board was the Chabot Space and Science Center in Oakland, and I chaired the architecture committee. As part of the process we selected the architect of the project. During the selection, we interviewed several firms and they had to show us a large scale project they had designed. One of the firms had designed Don Glaser's home and we toured it. Glaser was one of the founders of Cetus and IIRC was the CEO.
Larry

Hi Larry,
Yes, I know who Ed Penhoet was. Chiron was literally right across the street from the "Shell Building" in Emeryville that was main site for Cetus for all of it's molecular biology work because, believe it or not, doing molecular cloning was "outlawed" in the city of Berkeley at the time. Cetus corporate headquarters were in Berkeley, but we had to do our all our cloning/sequencing work in Emeryville, which had no problem at all with companies doing cloning and sequencing.

The irony is that cloning was being done at Cal Berkeley, because the campus was part of UC's "federal land grant" land program, and therefore, the land it is located on is "state land", but is not part of the City of Berkeley. This is a great example of how "silly and stupid" politics can be at times.

And no, I didn't move to Chiron after the sale of the rights of PCR to Roche. I did have a job offer from a friend who worked at Chiron to work in his sequencing lab doing Sanger sequencing, but I decided to stay at Cetus at the time, and then to Roche.

I took the offer to work at Roche Molecular Systems site in Alameda after the Cetus deal with Hoffman-La Roche was done, but I left after 4 years because my manager was holding me back doing stupid research projects for his "publication record" in HLA Class II molecular biology that were of marginal academic interest at best, and of virtually no commercial value whatsover for the company, or more importantly, Society as a whole. I viewed it as complete waste of my time as I wanted to develop real applications in MoBio that would become actual PCR-based diagnostics for genetic testing that mattered in the REAL WORLD, and leaving Roche for Applied Biosystems was one of the best things I ever did during my career.