Patient Jesse Gelsinger died on September 17, 1999 after being in ordinary medical condition less than four days prior, consequently halting many gene therapy trials and stigmatizing the promising field. At the age of two, Gelsinger was diagnosed with a milder version of ornithine transcarbamylase deficiency (OTC), a hereditary birth defect in which the body cannot produce an enzyme responsible for the removal of nitrogen. This less severe form allowed him to reach eighteen years of age, long past the typical month-long lifespan of OTC patients, bringing him to see the day in which he was informed of a new gene-therapy clinical trial aimed at treating the illness in babies.
Eager to save the lives of neonates with grim prognoses, he agreed to the gene therapy injection of adenovirus vectors, aimed at delivering functional OTC genes to his cells and therefore integrating the gene into his DNA. Unbeknownst to him, he was entering a trial riddled with conflicts of interest, non transparency, and hasty planning. He was enticed by the promise of curing those with his same disorder, unaware that previous participants experienced significant reactions to the treatment and that the injection caused three primates to experience fatal clotting disorders and liver inflammation (Sibbald, 2001). The field of gene therapy collapsed as scientists were left to question the myriad of ethical dilemmas surfaced by the tragedy. Should a healthy adult such as Gelsinger have been part of this clinical trial when it was aimed at newborns? What level of transparency is owed to the participants of such trials? Can scientists make safe and ethical decisions when they are poised to benefit from the success of their trials (NYU Langone Health)?
This last question became particularly relevant when it became clear that Dr. James Wilson, the researcher leading the trial, may have had motivation for forging on even after the therapy was proven to cause dangerous side effects. Before this clinical trial, regulations on disclosure were ineffective at preventing dangerous incidents, since the “FDA monitoring — which it now admits was sometimes ‘less than adequate’ — used to require sponsors to disclose financial undertakings that might constitute a conflict of interest when they applied for approval or licensure of their products'' (Sibbald, 2001). It was identified that Wilson had stock in Genovo, the company which financed his institute; by producing a successful gene therapy for OTC, Dr. Wilson would have gained prestige, a large amount of money from selling his treatment to other researchers, and, most notably, a large sum from his stocks. No matter how much society would like to place its trust in the ethics of scientists, this trial was deeply demonstrative of the ease by which morals are compromised.
This conflict of interest in conjunction with the lack of informed consent led to a new era of regulations on clinical trials including the creation of the Gene Therapy Clinical Trial Monitoring Plan and the Gene Transfer Safety Symposia, both of which aim to regulate disclosure and the monitoring of clinical trials. Although one may feel placated by these policies, it is vital to recognize that there will always be a new cutting-edge innovation like gene therapy – a new groundbreaking treatment to previously untreatable diseases. How many Jesse Gelsinger-esque tragedies will society have to experience before we proactively institute rules, regulations, and restrictions instead of hastily cleaning up after failed clinical trials?
One is reminded of this constant technological progression through tracing the history of biomedical advancements, noticing that vaccines led to anesthetics led to germ theory led to medical imaging led to antibiotics led to organ transplants led to antiviral drugs led to stem cell therapy led to immunotherapy, all of which ushered in the field of gene editing. Exemplifying the extent to which human control over evolution has advanced, gene editing is arguably both one of modern society’s most promising and dangerous new technologies, allowing one to play God with the building blocks of life around them. In order to reap the benefits of this technology and all future technologies without harming more people than are helped, both regulatory committees and material inspection facilities must be put in place to oversee who is given the privilege of receiving and administering novel treatments. The creation of such institutions before society experiences a repeat of the Gelsinger disaster is vital to the prevention of unregulated inquiry. These regulatory and monitoring boards must be established with the authority and power to decide the legal and moral limits of gene editing and its successive advancements. Most importantly, these committees must function by balancing the risks posed by drugs and technologies against the benefits they provide to individuals, the scientific community, and society as a whole.
Whether biomedical science becomes an abused or prosperous field depends on man, and we can only determine the future of new innovations if the world sets regulatory systems in place. When society continues to make era-defining advancements, the real question becomes how many abuses of science will we observe before we learn from our mistakes?
Works Referenced
“Gene Therapy Research and the Case of Jesse Gelsinger.” NYU Langone Health, https://med.nyu.edu/departments-institutes/population-health/divisions-sections-centers/medical-ethics/education/high-school-bioethics-project/learning-scenarios/jesse-gelsinger-case.
Sibbald, B. “Death but One Unintended Consequence of Gene-Therapy Trial.” CMAJ : Canadian Medical Association Journal, Journal De L'Association Médicale Canadienne, U.S. National Library of Medicine, 29 May 2001, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/.
Bender, Eric. “Regulating the Gene-Therapy Revolution.” Nature News, Nature Publishing Group, 12 Dec. 2018, https://www.nature.com/articles/d41586-018-07641-1.
Rinde, Meir. “The Death of Jesse Gelsinger, 20 Years Later.” Science History Institute, 16 July 2019, https://www.sciencehistory.org/distillations/the-death-of-jesse-gelsinger-20-years-later.
Comments