The Fate of Human Genome Editing

In 2015, scientists worldwide met in Washington to discuss the future of editing the human genome. Sparked by the growing availability of CRISPR-Cas9, biologists met to discuss the possibilities surrounding the editing of the human genome, and whether this practice would be morally sound. The main point of contention: Should we be able to edit genes that are inheritable, therefore changing the gene pool of future generations? For better understanding of the moral matter, one must understand the abilities of the CRISPR-Cas9 technique.

CRISPR-Cas9 has the ability to edit the genetic code in the human germline (i.e eggs and sperm). CRISPR, or clustered regularly interspaced short palindromic repeats, in the genome are transcribed into crRNA segments. crRNA are guides for matching DNA sequences. When a specific gene is located by the system being guided, the Cas9 enzyme is binds and cuts the DNA, resulting in the targeted gene being "shut off".

When scientists from the National Academy of Sciences of the United States, the Institute of Medicine, the Chinese Academy of Sciences, and the Royal Society of London met in 2015, provided evidence that editing inheritable genes in the effort to cure diseases is not always applicable. Specifically, in the cases of cancer and diabetes, many different genes can affect the heredity of the disease. However, also presented at the conference was the case of Huntingtons in which genetic editing may be the only way to ensure that the child does not develop the disease. The meeting of the societies and academies was not to affect hard change, as they have no current ability to implement legislation, but to ensure that the practices are moral above all. The new technique and technology available today is like none other before it, and therefore we must proceed into scientific exploration with caution so as not to do more harm than good. The scientists opened up an important discussion in regards to the future of genetic editing and the future of our gene pool - a conversation that should remain open and be revisited often.

Gene Editing in Human Embryos

Just one day after the WSJ ethical debate article was published, Scientific American published an article reporting that a second, separate lab in China has published a study using the CISPR/Cas9 technique to introduce a HIV-resistant mutation into embryos. While this too, seems like a great trait to introduce to a human embryo, there are still questions of ethics within the study. I was happy to find some explanation of the ethics within this second experiment, as provided by one of the co-authors, Yong Fan. Fan explained that there were 213 fertilized human embryos collected from 87 patients that were "unsuitable for implantation" with in vitro therapy and donated with consent of the egg donor. The reasoning that these embryos were considered "unsuitable" for the in vitro fertilization but adequately "abnormal" for embryonic research was due to an extra set of chromosomes. In contrast, other researchers working with human embryos sometimes opt for "normal" embryos. Kathy Niakan from the Francis Crick Institute in London will utilize "normal" or "viable" human embryos in research on in effects of the inactivation of certain developmental genes and their connection to miscarriages. In London, Niakan will use the CISPR technology as well, however she will be restrained by strict ethically motivated licencing requiring her to end all experiments within 14 days.

By the end of Fan's experiment, only 26 embryos were chosen to receive this modification and of the 26 only 4 were successful. With a high demand for 100% success rates in human embryological genetic studies, this study will certainly be under fire as well. A neuroscientist from Emory University notes in the Scientific American article that the high rates of failure highlight the difficulty in human studies, and perhaps studies of primate embryos would be more suitable fat this time to perfect gene editing techniques. I think that this could be an excellent idea to jump start future research without jeopardizing human embryos. With such low success rates in current published human embryo gene editing studies, and high rates of ethical concern, it is very reasonable to consider research with primates. While this will not completely eliminate ethical concerns, I believe it will give scientists a very similar model organism that can help fine tune embryonic gene editing techniques in mammals.

Ethics and Embryos

In terms of ethics, studies involving human subjects are constantly questioned. Many people fear the consequences of "designer babies" or unpredictable outcomes of altering DNA in such a complex organism at crucial stages, while others argue the benefits of eliminating dangerous heritable diseases. While the debate of ethics continues in America continues today, April 2016, scientists in China have moved past talking, and into testing the possible benefits of gene editing in human embryos. Nearly a year ago, April 2015, Protein and Cell published a controversial article about a Chinese study led by Junjiu Huang on genetic modification of human embryos. In this study, embryos were injected with an enzyme complex known as CISPR/Cas9, a tool that binds and splices DNA at specific locations. With this technique Huang and his colleagues attempted to edit the HBB gene, which may mutate to cause beta thalassemia. Unfortunately, their experiments was considered unsuccessful for many reasons. Firstly, 71 out of the original 86 embryos survived the first 48 hours after injection. Of the 71 surviving embryos, most were tested and a mere 28 had been successfully spliced. The experiment was halted with such a low success rate, and unexpectedly numerous additional mutations.

 An article published in Nature's news section noted that Huang's study was rejected for publications by both Nature and Science magazines due to the great question of ethics. Throughout the articles I have found, I am definitely curious about the ethics of this study too. While the experiment is clear, I have many questions about the before and after details of the study, as I imagine that many people within this ethical debate do. In the Nature article, there were multiple times in which the use of "abnormal" embryos and avoidance of "normal" embryos in these types of studies were mentions. What makes the embryo normal or abnormal?  Where do the embryos come from and what happens to them after the study? While I think that genetic modifications of human embryos could be an important technique to eliminating genetically coded issues such as diseases, it is a very difficult and risky task due to the numerous issues of ethics brought to light within this research.