Despite its limitations, the OR technique benefited from its close association with the development of the polymerase chain reaction. Kary Mullis, who also worked at Cetus, had synthesized the oligonucleotide probes being tested by Saiki and Erlich. Aware of the problems they were encountering, he envisioned an alternative method for analyzing the SCA mutation that would use components of the Sanger DNA sequencing technique. Realizing the difficulty of hybridizing an oligonucleotide primer to a single location in the genome, he considered using a second primer on the opposite strand. He then generalized that process and realized that repeated extensions of the two primers would lead to an exponential increase in the segment of DNA between the primers - a chain reaction of replication catalyzed by DNA polymerase.
As Mullis encountered his own difficulties in demonstrating PCR, he joined an existing group of researchers that were addressing the problems with OR. Together, they developed the combined PCR-OR assay. Thus, OR became the first method used to analyze PCR-amplified genomic DNA.
Mullis also encountered difficulties in publishing the basic idea of PCR (scientific journals rarely publish concepts without accompanying results). When his manuscript for the journal Nature was rejected, the basic description of PCR was hurriedly added to the paper originally intended to report the OR method (Mullis was also a co-author there). This OR paper thus became the first publication of PCR, and for several years would become the report most cited by other researchers.