More than just a matter of time

Abstract

A response to the editorial “On patenting time and other natural phenomenon” by Jacques Cohen.

I am pleased to accept the invitation from Dr. Jacques Cohen to respond to his editorial entitled “On patenting time and other natural phenomena” (in this issue). I am a professor and endowed chair at Stanford University. I teach students of developmental biology, genetics, stem cell biology and regenerative medicine. I have conducted basic science research on human germ cell and embryo development for more than 15 years in the hope of unveiling fundamental processes and potentially translating the findings into improvements in the clinic (if possible).

From this vantage, then, I was surprised to read that we were seeking to “patent time” and “natural phenomena”. To continue the pun, I find these suggestions to be “patently untrue”. In brief, my colleagues and I at Stanford University have been awarded patents on assays intended to distinguish optimal embryos for transfer in IVF from those most likely to meet demise. Moreover, the suggestion that the diagnosis of embryo viability in a dish is a natural phenomenon is not realistic. Simply put, our discoveries, assays and intellectual property in no way address a “naturally occurring phenomenon”. Clearly, there is no need to distinguish quality amongst as many as 5–10 embryos (or even more) in natural conception; and in nature women simply do not conceive outside of the body.

The story here is not about a broken patent system – the story here is one regarding how the patent system worked, in this case, to help patients, promote science, and secure funding in the notoriously under-funded area of reproductive health. Patenting of intellectual property in this case was intended to enable clinical translation of findings through carefully controlled clinical studies that are expensive to conduct. My colleagues and I openly encourage researchers, academics, scientists and clinicians to read our results, test our conclusions, and conduct further research; indeed we are collaborators on much research in the field. We further hope that the licensing of our intellectual property might assist those who seek assisted reproduction. For those who are interested, I explain some of the intricacies and necessities of the university and the research communities below. Suffice to say, we seek to conduct what we hope will always be the best research on a global scale even though the going is difficult, materials are in short supply and funding is scarce. A necessary component to clinical translation is industry engagement and industry competition.

More than a decade ago, my laboratory began the endeavour of constructing a map of human embryo development, encompassing molecular, genetic and epigenetic information. However, because of the 1996 Dickey-Wicker Amendment (Annas, 2010), no federal funds were available for human embryo research resulting in destruction of the embryo, even for supernumerary embryos donated to science by patients undergoing IVF. Human embryo research is one of the most resource-demanding areas of study, and it is critical to understanding the origins of life and disease. If we could not study human embryos at the molecular, genetic and epigenetic levels, we could not comprehensively probe the factors linking embryonic, fetal, perinatal and adult health and disease. So we sought non-federal funding. I have learned that fundraising through diverse constituencies of non-profit and for-profit organizations is critical to enabling meaningful research and training in this field. By combining the talents of diverse personnel, first when I was at the University of California at San Francisco (UCSF) and then at Stanford University, we have followed a path of invention that resulted in the first description of the human transcriptome (Dobson et al., 2004), the first non-invasive, image-based method to predict human embryo development by classifying normal versus abnormal measurements of cell division timings (Wong et al., 2010) and the first correlation of time-lapse parameters with ploidy (Chavez et al., 2012).

Our discoveries at each of these forks in the road – but especially with regard to the use of three specific cell cycle timing parameters to identify good developmental potential in embryos grown in vitro – were deemed to be novel and innovative by the scientific and clinical communities, and contrary to common practices at the time (Keissling, 2010). We were very pleased that our work was named one of the top ten medical discoveries of the year by TIME Magazine (Park, 2010). We are also pleased that our findings have spurred additional research, as evidenced by the dozens of papers citing Wong et al., 2010. This demonstrates that our research benefits other researchers, and also highlights the need for large-scale studies to broaden and standardize the technology for patients. Private funding, first to my laboratory, and then later via licensing of intellectual property from Stanford University, enabled the first prospective, multi-center study validating the predictive power and the clinical utility of Auxogyn’s Eeva assay for improving embryo selection (Conaghan et al., in press). Ongoing academic-industry collaboration further established the first algorithm that may assess risk of embryo aneuploidy by time-lapse imaging. In the end, it is the patients that I hope will benefit most from the patent system, as innovations may be able to be improved and brought to the clinic.

Another example of how patents have enabled inventors to accelerate the translation and iterative improvement of the original research is evident in the field of fetal DNA testing and research aimed at diagnosing genetic anomalies in a fetus by detecting and analyzing cell-free fetal DNA in maternal blood. Non-invasive assays will be of great importance to mothers who do not wish to take the risk of miscarriage associated with amniocentesis or chorionic villus sampling. Overall, investment of private capital is making innovations in non-invasive diagnosis possible, given that translating a novel idea to a clinical benefit requires significant resources covering: (i) basic research and invention, (ii) validation in human embryos, (iii) validation in prospective, multi-site clinical studies ensuring usefulness across patient segments, and (iv) consideration of patient adoption (e.g. cost) (Harper et al., 2012). In other words, without patents to protect the inventions made in this process, it would be nearly impossible to attract the investment finance needed to move a technology from the research and development phase, through clinical trials, through the regulatory process, and ultimately to commercialization. I note further that, in the best-case scenario, the patent system also requires inventors to teach others how to practice their technology, thus facilitating iterative improvements upon the work of predecessors.

In summary, I am privileged to serve as professor and director of several educational programs that reflect the enthusiasm that our students have for developmental biology research in the classroom, laboratory and beyond. As my group and others work together to understand early human development and other mysteries such as the complex origins of human disease, our efforts will continue to be focused on adding knowledge to basic science with the hope of translating findings to the clinic.