The effects of business practices, licensing, and intellectual property on development and dissemination of the polymerase chain reaction: case study

Abstract

Introduction: Polymerase chain reaction (PCR) was a seminal genomic technology discovered, developed, and patented in an industry setting. Since the first of its core patents expired in March, 2005, we are in a position to view the entire lifespan of the patent, examining how the intellectual property rights have impacted its use in the biomedical community. Given its essential role in the world of molecular biology and its commercial success, the technology can serve as a case study for evaluating the effects of patenting biological research tools on biomedical research.

Case description: Following its discovery, the technique was subjected to two years of in-house development, during which issues of inventorship and publishing/patenting strategies caused friction between members of the development team. Some have feared that this delay impeded subsequent research and may have been due to trade secrecy or the desire for obtaining lucrative intellectual property rights. However, our analysis of the history indicates that the main reasons for the delay were benign and were primarily due to difficulties in perfecting the PCR technique. Following this initial development period, the technology was made widely available, but was subject to strict licensing terms and patent protection, leading to an extensive litigation history.

Discussion and evaluation: PCR has earned approximately $2 billion in royalties for the various rights-holders while also becoming an essential research tool. However, using citation trend analysis, we are able to see that PCR's patented status did not preclude it from being adopted in a similar manner as other non-patented genomic research tools (specifically, pBR322 cloning vector and Maxam-Gilbert sequencing).

Conclusion: Despite the heavy patent protection and rigid licensing schemes, PCR seems to have disseminated so widely because of the practices of the corporate entities which have controlled these patents, namely through the use of business partnerships and broad corporate licensing, adaptive licensing strategies, and a "rational forbearance" from suing researchers for patent infringement. While far from definitive, our analysis seems to suggest that, at least in the case of PCR, patenting of genomic research tools need not impede their dissemination, if the technology is made available through appropriate business practices.

Figure 1

Timeline of key events in the early development of PCR.

Figure 2

Cetus Corporation income, 1984–1990. All figures in U.S. dollars. Source: Cetus SEC filings 1985–1990.

Figure 3

Citation trends. (a)-(c) Scientific papers citing PCR, pBR322 cloning vector, and Maxam-Gilbert sequencing by year after initial publication. Citation counts were obtained by searching Web of Science citation databases by year for articles referencing the seminal publication for each technology. Counts begin with the first full year after publication. For PCR, the citation count includes references to both the 1985 Saiki paper and the 1987 Mullis paper. (d) Normalized citation data. Y-axis represents percent of total citations in a given year for each technology. X-axis in all graphs (a-d) represents years after initial publication.

Figure 4

Linear correlations. (a) Parametric plot of PCR citations versus Maxam-Gilbert citations, with calculated Pearson correlation coefficient and p value. (b) Parametric plot of PCR citations versus pBR322 citations, with calculated Pearson correlation coefficient and p value.