The work of Chinese scientist He Jiankui has dominated the science news for the past week and a half. He claims to have genetically modified two human embryos and implanted them in a woman, resulting in the successful birth of twin girls. You can read a summary of this work and an interview about it with NIH Director (and BioLogos founder) Francis Collins in this article from ScienceMag a week ago, or listen to an NPR story also featuring Collins from this morning. Despite the strong prohibitions against gene editing on human embryos in this country, everyone suspected it would be done somewhere else ever since the technology was developed. A little over a year ago we posted the article below by Darrel Falk, explaining how the technology works, and considering some of the ethical implications. At BioLogos, we are excited about the therapeutic potential for somatic gene editing technology, but we share the deep concern expressed by Dr. Collins and many other scientists about germline gene editing.
The rumors had been circulating for a week or so in scientific circles, but this past Wednesday’s announcement made it official: the potential to edit the genes of human embryos had made an enormous advance and is much closer to becoming feasible than almost anyone imagined. Here’s what was done and why its significance is of blockbuster importance.
Sperm from a male who carried an abnormal gene causing a heart defect were injected into a set of eggs (ova) from females who did not carry the defect. Along with the sperm the investigators also injected into the egg a tiny molecular machine called CRISPR/Cas—the equivalent of a pair of molecular scissors. CRISPR/Cas cuts DNA at highly specific sites. In this case, it was engineered to cut at the male’s defective heart-gene. This was repeated multiple times, the result being a set of fertilized eggs each carrying the male’s defective heart gene now cut in two.
Intriguingly, all human ova contain molecular equipment capable of finding and repairing any broken DNA. There are two ways in which this break-repair takes place. In process #1, the two broken ends are simply glued back together, but the gluing process generates a scar at the site of reattachment. Repair process #2 is much better. In this case, the ovum’s equipment seeks out and tries to find a spare non-defective copy of the gene. If successful at finding one, the equipment will copy from that spare as it seals the gap. With this second method of sealing the cut—using an uncut non-defective spare as a template—the abnormality in the father’s heart-gene is cured and a new perfectly good heart-gene sits in place of the old damaged one. In this particular experiment, the investigators injected spare copies of the non-defective version of the gene to encourage the second repair process and not the first. It turns out that “encouragement” was not necessary. The spare used by the fertilized eggs was a natural one—the non-defective gene put into the egg by the mother herself. (Females provide their ova (eggs) with one copy of each of their 20,000 genes.) What this means is that the defective gene brought into the egg by the father’s sperm was replaced by a brand new copy of the mother’s good gene.
Prior to these experiments scientists expected that there would be three very significant barriers to repairing defective genes in fertilized human eggs. First, preliminary work had shown that the engineered CRISPR/Cas sometimes missed its target—a colossal concern. In these experiments however, it appears to have been spot-on every time. The second potential problem was that the embryos would come to contain a mixture of cells (mosaics)—some repaired, some not. The investigators showed that by timing the CRISPR/Cas injection just right no mosaic embryos were produced. The third concern related to the two different “gluing” mechanisms mentioned above. Only Process #2 would result in a good gene. For an unknown reason Process #2 appears to be the only gluing-process the fertilized human egg uses—at least under these conditions.
Scientists expected these barriers to take a long time to surmount. There are many yet-to-do tests that will likely take years before proceeding to clinical trials with genetically repaired embryos implanted into the uteri of women. Indeed, such tests are currently illegal in the United States. This will not change without extensive discussion involving a broad swath of regulatory agencies, as well as the general public. However there is little doubt that, with these recent results, the age of genetic engineering of human embryos is about to begin—if not here in the United States, then at least elsewhere in the world.
As breath-taking as genetic engineering is becoming, there is another way of accomplishing a similar purpose that is fast becoming routine, and is carried out in many medical clinics. Through in vitro fertilization, it is frequently possible for parents who know that at least one of them carries a deleterious gene to undergo a technique known as pre-implantation diagnosis (PGD). This involves the in vitro fertilization of a set of ova, followed by genetic-typing and then implanting only those embryos which do not carry the deleterious version of the gene in question. Hundreds of children have already been born through this genetic selection technique and it can be used for detecting many genetic diseases. However, PGD involves eventually discarding unimplanted embryos—a major concern to many. So if gene editing is used instead, some argue, it will provide an alternative that does not involve discarding the embryos with a defective gene; instead the deleterious abnormality is repaired through genetic surgery.
Earlier this year, the National Academies of Science and Medicine released a 265 page report on the prospects and perils of gene editing. I highly recommend the clearly presented 90 minute video summary of its content. The future described in the Commission’s recommendations may, in light of the above findings, be even closer than expected. Direct testing of the technique to cure embryos of devastating genetic diseases such as Huntington’s, cystic fibrosis, early onset Alzheimer’s, and even some forms of breast cancer is drawing closer. The report also addresses genetic enhancement—altering genes to “enhance” human capabilities. Scientists do not know enough yet to embark upon such experiments, the report concludes. However, the report does not explicitly recommend against genetic enhancement in the future. Still, the potential for genetic enhancement is on the horizon—no matter how distant—and the report devoted a whole chapter to it.
Christians should be thoroughly aware of the technique’s ramifications. On the one hand, it has the potential to relieve much human suffering. There is a difference, however, between relieving suffering and “worshipping the creature rather than the Creator.” The line between the two is fuzzy, and it would be easy to cross it in little steps—each of which would seem so innocent at the time. Much Christ-centered wisdom will be needed in the coming days. It is important for Christians to become informed about what is on the horizon, so that they can prayerfully and humbly influence society in ways that, being centered in Christ, are wholesome and wise.