Germline gene therapy: We're ready.

Recently, Chinese researchers attempted to modify embryos using “germline gene therapy.” If successful, this technique would create a heritable change and affect future generations, were those embryos to be used ([ 1 ][1]). A firestorm in the scientific community followed, with some researchers calling for an absolute ban on attempts to treat even lethal diseases with germline gene therapy. D. Baltimore, P. Berg, and a group of “interested stakeholders” met to discuss the issue and concluded: “At present, the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any attempts at human engineering are sanctioned, if ever, for clinical testing” (“A prudent path forward for genomic engineering and germline gene modification,” D. Baltimore et al. , Perspectives, 3 April, p. [36][2]; published online 19 March). With apparent nostalgia, Baltimore et al. noted that the group “included some of the leaders in the original 1970s discussions about recombinant DNA research at Asilomar and elsewhere.” Many in the biomedical community do not regard the Asilomar experience as a success ([ 2 ][3], [ 3 ][4]). It exaggerated the potential risks of recombinant DNA technology, modern biotechnology's core technique; gave rise to a years-long research moratorium; and induced NIH to draft and promulgate “biosafety” guidelines. Those process-based guidelines, which were focused on the use of a single technique instead of on the risks of experiments, have plagued genetic engineering research ever since: Although NIH pared back the stringency of its guidelines, stultifying process-based approaches to regulation have remained at other federal agencies ([ 4 ][5]). ![Figure][6] Sickle cell anemia. IMAGE: © CAROL & MIKE WERNER/VISUALS UNLIMITED/CORBIS A moratorium would once again be misguided, as are the arguments of those who advocate it. In his Letter “Eugenics lurk in the shadow of CRISPR” (22 May, p. [871][7]), R. Pollack invokes abstract concerns about “eugenics,” showing remarkable insensitivity to the current suffering of patients with horrific genetic diseases. Rudolf Jaenisch, a biology professor at the Massachusetts Institute of Technology, has argued that gene editing is unethical for diseases such as Huntington's ([ 5 ][8]), which is genetically dominant, meaning that only one defective gene copy causes the disease and only half of the parents' embryos will inherit it. Jaenisch objects because the editing procedure must begin before we know whether the embryo has the Huntington's gene, posing the unacceptable risk of altering a normal embryo. However, Jaenisch has knocked down a straw man. Nobody is proposing to modify normal embryos in the foreseeable future. An appropriate—and, indeed, compelling—application would be to correct the debilitating and ultimately lethal sickle cell anemia. In genetics terms, sickle cell anemia is an autosomal recessive disease, which means that every one of a patient's chromosomes carries a defective gene (unlike Huntington's disease). The sickle cell gene bears a mutation in one nucleotide of DNA, which in turn gives rise to a single amino acid substitution in one discrete location of the protein chains of hemoglobin. Unlike Huntington's disease, 100% percent of the offspring of two parents with sickle cell disease will be afflicted with the disease. The repair of this sort of molecular lesion has been performed successfully in animals for decades. Shouldn't 21st-century medicine offer the possibility of repairing embryos that will become patients with sickle cell disease, and eliminate the disease from future generations? Technologies are seldom successful right out of the gate, but the concept of “perfecting” a technology seems to have eluded Harvard stem-cell researcher George Q. Daley, who recently said about germline gene therapy, “This is an unsafe procedure and should not be practiced at this time, and perhaps never” ([ 5 ][8]). Never? Maybe it has been a while since Dr. Daley has seen a patient like one I remember well—a 20-year-old with sickle cell anemia who had suffered three strokes, been crippled by hemorrhages into his major joints, and was in unrelenting pain from the arthritis that resulted. Germline gene therapy should be used sparingly and with scrutiny, to be sure, but we don't need a moratorium. We do need to push the frontiers of medicine to rid families of monstrous genetic diseases. 1. [↵][9]The Economist, “To the crack of doom” (2 May 2015); [www.economist.com/news/science-and-technology/21649607-scientists-china-havejust-crossed-one-biotechnologys-red-lines-crack][10]. 2. [↵][11]DNA Learning Center, “Initial feelings on Asilomar meeting, James Watson” ([www.dnalc.org/view/15423-Initialfeelings-on-Asilomar-meeting-James-Watson.html][12]). 3. [↵][13]“Trying to Bury Asilomar,” James Watson Papers (1978); . 4. [↵][14]1. D. L. Kershen, 2. H. I. Miller , Iss. Sci. Technol. XXXI, 2 (2015); . 5. [↵][15]1. G. Kolata , “Chinese scientists edit genes of human embryos, raising concerns,” The New York Times (23 April 2015); [www.nytimes.com/2015/04/24/health/chinese-scientists-editgenes-of-human-embryos-raising-concerns.html][16]. [1]: #ref-1 [2]: /lookup/doi/10.1126/science.aab1028 [3]: #ref-2 [4]: #ref-3 [5]: #ref-4 [6]: pending:yes [7]: http://www.sciencemag.org/content/348/6637/871.1.full [8]: #ref-5 [9]: #xref-ref-1-1 "View reference 1 in text" [10]: http://www.economist.com/news/science-and-technology/21649607-scientists-china-havejust-crossed-one-biotechnologys-red-lines-crack [11]: #xref-ref-2-1 "View reference 2 in text" [12]: http://www.dnalc.org/view/15423-Initialfeelings-on-Asilomar-meeting-James-Watson.html [13]: #xref-ref-3-1 "View reference 3 in text" [14]: #xref-ref-4-1 "View reference 4 in text" [15]: #xref-ref-5-1 "View reference 5 in text" [16]: http://www.nytimes.com/2015/04/24/health/chinese-scientists-editgenes-of-human-embryos-raising-concerns.html