Discovery of PCR principle

[Olav Hungnes]

The DNA amplification experiments of Dr. Kjell Kleppe are described in:

Kjell Kleppe et al (1971): Studies on polynucleotides XCVL. Repair 
Replication of Short Sythetic DNA's as catalysed by DNA polymerases, 
J.Mol.Biol.56,341-361.

The final statement of the paper reads:

"The principle for extensive synthesis of the duplexed tRNA 
genes which emerge from the present work are the following. 

The duplex would be denatured to form single strands. This 
denaturation step would be carried out in the presence of a 
sufficiently large excess of the two appropriate primers.

Upon renaturation, one would hope to obtain two structures, 
each containing the full length of the template strand appropriately 
complexed with the primer: DNA poymerase will be added to 
complete the the process of repair replication. Two molecules 
of the original duplex should result. The whole cycle could 
be repeated, there being added every time a fresh dose of the enzyme."

Seems like a perfectly good description of the PCR principle to me.

The impact of the idea at the time was, of course, limited by the 
state of the surrounding technology. Oligonucleotide synthesis 
was very cumbersome, DNA sequencing was not sufficiently developed etc.
And of course, the potential for automation given by a thermostable
polymerase was not realised. This last obstacle could have been 
circumvented, though, if the other conditions had been met, for 
instance by moving the reaction between sites of denaturing temperature 
and enzyme anchored to solid phase.

It would be interesting to see how the case would stand in a non-US court.

--
_______________________________________________________
Olav Hungnes                     ohungnes at extern.uio.no
National Institute               Phone  (+47)22042200
of Public Health                 FAX    (+47)22353605
Oslo, NORWAY
_______________________________________________________