Epigenetic Patents: A Stressful Environment for an Emerging Science.

Abstract

Genetic science has been a cornerstone of medical research for more than half a century. Since the discovery of the structure of DNA by Watson and Crick in 1953, the central dogma of molecular biology has been that there is a “residue-by-residue transfer of sequential information” from DNA to proteins,1 and this sequential information was understood to code for the expression of proteins that affected most aspects of health. The detection of DNA mutations associated with disease was regularly reported throughout the last decades of the 20th Century. Genetic research reached a critical point in 2003, when the Human Genome Project was completed and the sequence of the 3 billion nucleotides in the complete human genome was published. It had been expected that this information would solve many of the mysteries of medical science and suggest therapies for previously untreatable diseases. However, before the Project was complete, it became evident that the genomic sequence information would provide only a partial explanation of the causes and cures of disease. A more extensive understanding of genetic medicine would require an inquiry into the “epigenome” and the effect of the history of the cellular environment on gene expression. The biologically deterministic paradigm of the central dogma has now yielded to a more subtle understanding that gene function can be affected by environmental factors. Such factors can modify genes in somatic cells and lead to disease, or potentially modify genes in germ cells to pass harmful modifications to subsequent generations.2 Epigenetic research has suggested that environmental conditions can cause chemical modifications (such as the addition or removal of methyl groups) to DNA or histones to alter the health of humans and their offspring—even in a transgenerational manner—apart from changing the nucleic acid sequences of their genes. An early published example of this phenomenon was a Swedish study that showed an abundant food supply for a grandfather before his pre-pubertal growth spurt increased the likelihood that his grandson would die of a diabetes-related disorder.3 A father's poor food supply and a mother's ample food supply were associated with a lower risk of cardiovascular death in their subsequently born children.4 Differences in early post-natal life have also been found to result in lasting, transgenerational changes in behavior, mediated in part by changes in epigenetic histone marks and DNA methylation states.5 For example, early parental care-giving in rodents causes epigenetic changes that can alter an offspring's life-long response to stress, an effect that can be passed from one generation to the next, perhaps by affecting the parental care behavior of subsequent generations.6 One of the best-documented examples in humans of a transmissible epigenetic effect was the use of the estrogenic agent diethylstilbestrol (DES) to prevent miscarriages in pregnant women, which led to the development of a rare form of vaginal cancer in their prenatally exposed daughters.7 The growing knowledge of epigenetic science and the relation between this science and human health has led to an increasing number of patents that could aid in the discovery and treatment of the root causes of many common diseases. As these patents proliferate, however, a shifting legal landscape could reduce intellectual property rights in various aspects of epigenetic science, thus reducing commercialization of this new technology. This article examines epigenetic science and resultant patents, how these patents are changing over time as basic scientific discoveries lead to new treatments, and how future epigenetic patents might fare in the light of recent court decisions limiting the patent eligibility of biomedical technologies. A stressful prenatal and perinatal environment can alter the lifetime health of a human, and a harsh legal environment can have similar effects on the commercial development of new technologies.