Special Editorial Feature: Learning from Our Failures

Human Gene TherapyAhead of Print EditorialFree AccessSpecial Editorial Feature: Learning from Our FailuresTerence R. FlotteTerence R. FlotteEditor-in-ChiefSearch for more papers by this authorPublished Online:12 Oct 2023https://doi.org/10.1089/hum.2023.29246.editorialAboutSectionsPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail In this issue of Human Gene Therapy, we provide a venue for a deeper discussion of the tragic case of Mr. Terry Horgan, a 27-year old man with Duchenne muscular dystrophy (DMD) caused by a mutation in exon 1 of the Dystrophin gene. Terry underwent treatment with a high-dose (1 × 1014 vg/kg) intravenous infusion of recombinant adeno-associated virus 9 (rAAV9) vector delivering a CRISPR-based transactivator, making him the first person to receive a CRISPR-based treatment for the disease. Unfortunately, Terry suffered severe cardiopulmonary decline 6 days after receiving treatment, which led to his death. The scientific and clinical details of the case are described elsewhere.1 We, the senior editorial team of Human Gene Therapy, have chosen to provide the venue of this special editorial feature, not as a forum to discuss the science, but rather as a channel for those involved in this case to share additional unique perspectives from families and providers involved in cutting-edge human trials that do NOT go well.Throughout the history of human subjects research, there have been numerous tragic failures that have paved the way for later successes. This includes decades of failures in trials of chemotherapy for pediatric leukemias, bone marrow and solid organ transplants, and cancer surgeries.2 In each of these cases, intrepid patients and their providers chose to study their failures and their partial successes and to learn from them, and gene therapy researchers must follow that example. We must resist the temptation to only trumpet “successful” trial results. Of course, we always strive for positive outcomes in each individual pateint, but any experimental result that increases our knowledge is a success for the field as a whole. That is why we MUST as a field embrace our failures as much or more than our successes. It is only by studying, learning, and sharing undesired outcomes that we can improve as a clinical discipline.References1. Lek A, Wong B, Keeler A, et al. Death after high-dose rAAV9 gene therapy in a patient with Duchenne's muscular dystrophy. N Engl J Med 2023;389(13):1203–1210; doi: 10.1056/NEJMoa2307798. Crossref, Medline, Google Scholar2. Mukherjee S. The Emperor of All Maladies: A Biography of Cancer. Simon & Schuster: London, United Kingdom; 2010. Google ScholarFiguresReferencesRelatedDetails Volume 0Issue 0 InformationCopyright 2023, by Mary Ann Liebert, Inc., publishersTo cite this article:Terence R. Flotte.Special Editorial Feature: Learning from Our Failures.Human Gene Therapy.ahead of printhttp://doi.org/10.1089/hum.2023.29246.editorialOnline Ahead of Print:October 12, 2023PDF download