STI College Surigao

CASE OF JESSE GELSINGER AND TREATED SCID INFANTS

In partial fulfillment in the subject of

SCIENCE, TECHNOLOGY AND SOCIETY

Prepared by
Purol, Annalyn
Umbina, Ag Kezia Faith
Taganas, DarelDave
Saray, Mary Rose
Beto, Christian Gallegher Rule
Bilazon, May Atria
Cortes, John Bernard
Elan, Rochie Ann
Undang, Jenny
Tupal, Cindy
Ballesteros, Maevel
BSHM- 402

Submitted to
Ms. Shane Abeguel T. Eviota

June 12, 2023

 I. BACKGROUND OF THE CASE
In 1999, the tragic case of Jesse Gelsinger brought the ethical challenges and safety concerns of
gene therapy to the forefront of public attention. This landmark case involved the death of Jesse Gelsinger,
an 18-year-old patient suffering from a rare genetic disorder called ornithine transcarbamylase deficiency
(OTCD). The case also encompassed several infants with Severe Combined Immunodeficiency (SCID),
commonly known as "bubble boy" disease, who received gene therapy treatment at the same institution.

The main issue in this case was the safety and ethical oversight of gene therapy, a promising but
relatively new field of medical research aimed at correcting genetic disorders by introducing functional
genes into patients' cells. The therapy involved the use of genetically engineered viruses, called viral
vectors, to deliver the desired genes into the patients' cells.

Jesse Gelsinger was enrolled in a clinical trial at the University of Pennsylvania's Institute for
Human Gene Therapy (IHGT), which aimed to develop a gene therapy treatment for OTCD. On September
13, 1999, Gelsinger received the experimental gene therapy treatment, but within hours, he experienced a
severe immune response that led to multiple organ failure, resulting in his tragic death four days later.

In addition to Gelsinger's case, the clinical trial at IHGT had also treated several infants with SCID
using a similar gene therapy approach. These infants had a life-threatening immunodeficiency condition
that left them susceptible to severe infections. The treatment aimed to correct the genetic defect
responsible for SCID and restore their immune function. Unfortunately, some of the infants experienced
adverse effects from the gene therapy, including liver toxicity, prompting a halt to the trial.

The involved in this case are Jesse Gelsinger: Jesse Gelsinger was an 18-year-old young man with
OTC deficiency who volunteered to participate in the gene therapy trial; Researchers and Physicians: The
trial was conducted by a team of researchers and physicians at the University of Pennsylvania's Institute
for Human Gene Therapy, including James M. Wilson, the principal investigator of the trial; and
Regulatory Bodies: The trial was overseen by the U.S. Food and Drug Administration (FDA) and the
Recombinant DNA Advisory Committee (RAC), which are responsible for ensuring the safety and ethics
of clinical trials involving gene therapy.

The public opinion of gene therapy at that time was mixed. There was significant optimism
surrounding the potential of gene therapy to revolutionize medical treatment by providing targeted and
potentially curative approaches for genetic disorders. However, the Gelsinger case and the adverse events
in the treated SCID infants raised concerns about the safety and oversight of gene therapy research.

These incidents led to increased scrutiny and questioning of the ethical principles guiding gene
therapy trials, including issues related to informed consent, transparency, risk assessment, and the role of
institutional review boards (IRBs). There were calls for more rigorous oversight and regulatory measures
to ensure the safety and ethical conduct of gene therapy research.

The Gelsinger case highlighted the need for a critical evaluation of the risk-benefit ratio in gene
therapy trials, the informed consent process for research participants, and the importance of transparent
reporting of adverse events. It prompted a reevaluation of the ethical framework governing human
subjects research and the establishment of stricter regulations and guidelines to safeguard the well-being
of participants in gene therapy trials.

Over the years, the tragic events of the Gelsinger case have significantly influenced the field of gene
therapy. They have catalyzed improvements in the regulation, oversight, and safety monitoring of gene
therapy trials, contributing to the development of more robust ethical guidelines and research practices.
The case serves as a sobering reminder of the importance of ethical considerations, rigorous safety
assessments, and transparent reporting in the pursuit of scientific advancement and patient well-being in
the field of gene therapy.

II. THE POTENTIAL BENEFIT BEING PROMISED BY GENE THERAPY

The Jesse Gelsinger case was a tragic event that occurred in 1999 and raised significant ethical
concerns regarding gene therapy research and its potential risks. Jesse Gelsinger, an 18-year-old patient
suffering from a genetic disorder called ornithine transcarbamylase (OTC) deficiency, participated in a
clinical trial for gene therapy at the University of Pennsylvania. The primary benefit promised by gene
therapy in this case was the potential to treat and cure Jesse's OTC deficiency, a condition that can be life-
threatening and severely impact a patient's quality of life.

Gene therapy is a promising field of medicine that aims to treat or prevent diseases by modifying a
person's genetic material. It involves introducing functional genes into the patient's cells to replace or
repair faulty genes associated with the disease. Theoretically, gene therapy holds the potential to provide
long-lasting or permanent treatments for genetic disorders by addressing the root cause at the genetic
level.

The primary benefit being offered through gene therapy was the potential for a long-lasting or
permanent solution to the underlying genetic defect causing OTC deficiency. By introducing a corrected
version of the defective gene into Jesse's cells, gene therapy aimed to provide a functional copy of the gene
that would enable the production of the missing or malfunctioning enzyme responsible for metabolizing
ammonia.

The actual result of the gene therapy in Jesse Gelsinger's case, however, tragically led to his death.
Jesse enrolled in a clinical trial at the University of Pennsylvania in 1999, where he received an
experimental gene therapy treatment for his OTC deficiency. Shortly after receiving an experimental viral
vector-based gene therapy treatment, he experienced a severe immune response known as a cytokine
storm. This immune response triggered a systemic inflammatory reaction that caused multiple organ
failures, leading to his tragic death within days of the treatment. The investigation into the case revealed
that there were significant flaws in the experimental protocol, including inaccurate assessments of the
risks involved and inadequate informed consent processes.

The case of Jesse Gelsinger highlighted the risks and limitations of gene therapy at that time. It
revealed that the potential benefits of gene therapy were overshadowed by the potential risks associated
with the treatment. The adverse reaction experienced by Jesse raised concerns about the safety of gene
therapy and highlighted the need for more rigorous preclinical testing and close monitoring of patients
during clinical trials.

Since Jesse's case, significant advancements have been made in gene therapy research, with
improved safety measures and enhanced understanding of the technology. Gene therapy has shown
promise in treating various genetic disorders, including inherited retinal diseases, severe combined
immunodeficiency (SCID), and certain types of cancer. It has the potential to provide long-term or
permanent solutions to genetic disorders by targeting the underlying cause at the genetic level.

Today, gene therapy holds the promise of personalized medicine, where treatments can be tailored
to an individual's unique genetic makeup. It has the potential to revolutionize the field of medicine by
offering innovative therapeutic approaches for previously incurable genetic diseases. However, it is crucial
to continue rigorous research, thorough testing, and close monitoring to ensure the safety and efficacy of
gene therapy interventions before they are widely adopted for clinical use.

It is important to note that the case of Jesse Gelsinger played a significant role in shaping the field
of gene therapy, leading to improved safety standards and increased ethical considerations in clinical
trials. The tragic outcome of his treatment emphasized the need for transparency, informed consent, and
careful evaluation of the risks and benefits in gene therapy research and clinical practice.

III. ERRORS AND MISTAKES THAT OCURRED

The case of Jesse Gelsinger, which occurred in 1999, involved the administration of a gene therapy
treatment that resulted in Jesse's tragic death. Several errors and mistakes were identified in this case,
highlighting the need for improved oversight and ethical considerations in human research trials. The
following is a detailed analysis of the errors and mistakes that occurred:

a. Inadequate informed consent process: One significant error in the case was the failure to provide
adequate informed consent to Jesse Gelsinger and his family. Informed consent is a crucial ethical
requirement in research, especially when it involves experimental interventions. The consent
process should include clear and comprehensive information about the nature of the intervention,
 potential risks, and possible benefits. In this case, it was found that the consent form used did not
sufficiently disclose the potential risks involved, leading to a lack of understanding on the part of
Jesse and his family.
b. Inaccurate risk assessment and reporting: Another critical mistake was the inaccurate assessment
and reporting of risks associated with the gene therapy trial. The researchers involved failed to
disclose relevant information about previous adverse events in animal studies, which could have
influenced Jesse's decision to participate. The failure to accurately communicate the risks involved
compromised the transparency and integrity of the trial.
c. Inadequate oversight and regulation: The case also revealed shortcomings in the oversight and
regulation of the trial. The investigators received approval from the Institutional Review Board
(IRB), which is responsible for ensuring the protection of human subjects in research. However,
there were concerns regarding the adequacy of the review process and the IRB's understanding of
the risks involved. This lack of effective oversight contributed to the continuation of the trial despite
the presence of potential dangers.
d. Overlooking safety concerns: The researchers involved in the trial were aware of the potential risks
associated with the gene therapy, including the possibility of severe immune reactions. However,
they proceeded with the trial despite having concerns about the safety of the experimental
treatment. This disregard for safety concerns was a significant error that ultimately resulted in Jesse
Gelsinger's death.
e. Conflict of interest and financial pressures: The case also raised concerns about conflicts of interest
and financial pressures influencing decision-making. James Wilson, the principal investigator of
the trial, held a significant financial stake in the gene therapy technology being tested. This financial
interest may have influenced the objectivity of the research team and compromised their ability to
fully evaluate and disclose the risks associated with the treatment. One of the investigators had
financial ties to the company sponsoring the trial, which potentially compromised impartial
decision-making. The financial interests involved may have influenced the researchers to downplay
the risks and push ahead with the trial.
f. Poor communication and transparency: Throughout the trial and subsequent investigation, there
were instances of poor communication and lack of transparency. The full extent of risks and adverse
events was not adequately disclosed to the public, leading to a loss of trust in the scientific
community. The lack of transparency hindered the understanding of the case and the ability to learn
from the mistakes made.
g. Insufficient post-trial follow-up: After Jesse Gelsinger's death, there were criticisms regarding the
lack of comprehensive post-trial follow-up and support for the participants and their families.
Proper post-trial care and monitoring are crucial to address any potential long-term effects or
 complications arising from experimental interventions. The failure to provide adequate post-trial
care further highlighted the ethical lapses in the case.

It is essential to note that these errors and mistakes in the Jesse Gelsinger case have led to
significant advancements in research ethics and the regulation of clinical trials. The case has served as a
catalyst for reforms to ensure better protection of human subjects and the implementation of more
rigorous oversight and transparency in gene therapy research.

IV. ACTIONS TAKEN

The Jesse Gelsinger case is a significant event in the history of medical research ethics. It involved
the death of Jesse Gelsinger, a young man who participated in a clinical trial for gene therapy at the
University of Pennsylvania in 1999. The case prompted a thorough examination of the ethical issues
surrounding human research subjects and led to several actions taken by organizations and individuals
involved.

Organizations Involved:

1) University of Pennsylvania: The clinical trial took place at the Institute for Human Gene Therapy
at the University of Pennsylvania. The institution was responsible for conducting the trial and
overseeing its ethical aspects.
2) Food and Drug Administration (FDA): The FDA is the regulatory body responsible for ensuring the
safety and efficacy of drugs and medical interventions. It was involved in the oversight of the clinical
trial and subsequent investigation.
3) National Institutes of Health (NIH): As a major funding source for medical research, the NIH
played a role in overseeing the ethical conduct of the clinical trial and providing guidance on
research involving human subjects.

Actions Taken by Organizations:

1) University of Pennsylvania: Following Jesse Gelsinger's death, the university launched an internal
investigation into the incident. They suspended all gene therapy trials and implemented several
reforms to improve patient safety and informed consent processes. These reforms included
enhanced oversight, stricter participant eligibility criteria, and increased transparency in reporting
adverse events.
2) FDA Investigation: The FDA conducted a comprehensive investigation into the Jesse Gelsinger
case, examining the actions of the researchers and the institutional oversight. The investigation led
to increased scrutiny of gene therapy trials and resulted in stricter regulations for conducting such
trials in the future.
 3) NIH Guidelines: The NIH revised its guidelines for gene therapy research, placing greater emphasis
on safety, participant protection, and rigorous oversight. The new guidelines introduced a more
rigorous review process for gene therapy protocols and emphasized the importance of informed
consent and risk-benefit assessment.

Actions Taken by Authors of the Study:

1) Publishing Study Findings: The authors of the original clinical trial study published their findings
in the journal Human Gene Therapy. The publication of the study allowed for transparency and
dissemination of information about the experimental treatment, contributing to the scientific and
ethical discourse surrounding gene therapy.
2) Collaboration with Investigators: After the adverse events occurred, the authors of the study
cooperated with the investigators from the University of Pennsylvania, FDA, and NIH, providing
information and insights into the trial design, informed consent process, and potential contributing
factors to Jesse Gelsinger's death. Their collaboration aimed to improve the understanding of what
went wrong and prevent similar incidents in the future.

The Jesse Gelsinger case prompted significant actions by various organizations involved in medical
research ethics. These actions focused on improving participant safety, strengthening oversight and
regulations, enhancing informed consent processes, and fostering a better understanding of the ethical
considerations in gene therapy research. The case serves as a reminder of the importance of upholding
ethical standards and ensuring the welfare of research subjects in scientific investigations.

V. EFFECT ON GENE THERAPY AS A STUDY AND MEDICAL PROCEDURE

The case of Jesse Gelsinger had a significant impact on the field of gene therapy as both a study and
a medical procedure. Jesse Gelsinger was a participant in a clinical trial for gene therapy in 1999, which
aimed to treat his inherited metabolic disorder. Tragically, he suffered a severe immune reaction and died
as a result of the experimental treatment. This event raised several ethical and safety concerns, leading to
profound changes in the regulation and conduct of gene therapy research.

i. Ethical Considerations:
The Gelsinger case highlighted the importance of ethical considerations in gene therapy research.
It raised questions about informed consent, as Gelsinger's family claimed they were not adequately
informed of the potential risks involved. In response, researchers and regulatory bodies have since
implemented stricter protocols to ensure thorough informed consent processes in gene therapy
trials. This case also emphasized the need for transparency and ethical oversight throughout the
research and development of gene therapies.
ii. Safety Regulations:
 The adverse events and subsequent death of Jesse Gelsinger prompted a reevaluation of safety
regulations and monitoring procedures in gene therapy. The study identified potential risks
associated with the use of adenoviral vectors, which were used in Gelsinger's treatment. As a result,
regulatory agencies, such as the U.S. Food and Drug Administration (FDA), implemented more
stringent guidelines for gene therapy trials, emphasizing the assessment and mitigation of potential
risks to participants. This case underscored the importance of comprehensive preclinical testing
and monitoring strategies to ensure patient safety in gene therapy studies.
iii. Improved Vector Systems:
The Gelsinger case prompted researchers to explore safer and more efficient vector systems for gene
therapy. Adenoviral vectors were associated with an immune response in Gelsinger, leading to
severe complications. Subsequently, researchers shifted their focus towards alternative vector
systems, such as adeno-associated viruses (AAVs) and lentiviruses, which have demonstrated
improved safety profiles in subsequent trials. The case accelerated the development and
optimization of these vectors, enhancing the overall safety and efficacy of gene therapy approaches.
iv. Enhanced Regulatory Oversight:
The Gelsinger case resulted in increased regulatory scrutiny and oversight of gene therapy research.
Regulatory agencies introduced more rigorous guidelines and monitoring mechanisms to ensure
the safety of participants in clinical trials. These measures include more thorough preclinical
testing, stringent patient selection criteria, comprehensive reporting of adverse events, and
independent review boards to evaluate study protocols. The aim was to strike a balance between
promoting innovation and protecting patient welfare.
v. Public Perception and Trust:
The Gelsinger case had a profound impact on public perception and trust in gene therapy research.
The incident received significant media coverage, which raised awareness of the risks associated
with experimental treatments. This led to heightened public scrutiny and increased demand for
transparency, accountability, and long-term safety data in gene therapy trials. Researchers and
institutions have since prioritized open communication and engagement with the public to build
trust and address concerns related to gene therapy research.

The tragic outcome of the Jesse Gelsinger case had far-reaching effects on gene therapy as a study
and medical procedure. It prompted increased emphasis on ethical considerations, stricter safety
regulations, the development of safer vector systems, enhanced regulatory oversight, and a greater focus
on public trust and transparency. These changes have contributed to the advancement of gene therapy
research, with improved safety measures and increased confidence in the field.
VI. PERSONAL STAND REGARDING THE ISSUE
Our personal stand regarding the case of Jesse Gelsinger is that it revolves around a clinical trial
conducted at the University of Pennsylvania in 1999, in which Jesse Gelsinger, an 18-year-old with a
genetic disorder, died as a result of complications arising from the experimental treatment he received. In
evaluating the reasonableness and fit of the actions taken by the organization(s)/author(s), it is important
to consider the ethical principles and guidelines that should govern clinical trials and experimental
treatments.

One crucial aspect of conducting any experimental treatment or clinical trial is obtaining informed
consent from the participant or their legal guardian. In Jesse Gelsinger's case, there were concerns raised
about the adequacy of informed consent. Some argue that the risks associated with the experimental
treatment were not fully disclosed to Jesse and his family, potentially compromising their ability to make
an informed decision. Clinical trials must undergo rigorous risk-benefit analysis to ensure that the
potential benefits outweigh the potential risks for participants. In Jesse Gelsinger's case, it was later
revealed that the experimental treatment carried a higher risk than initially believed. This raised concerns
about the thoroughness of the risk assessment performed before the trial and the level of oversight
provided by the regulatory bodies involved.

Furthermore, it is essential that experimental treatments are based on sound scientific evidence
and preclinical studies. In the case of Jesse Gelsinger, there were concerns about the scientific validity of
the treatment approach used and the accuracy of the preclinical data. This raises questions about the level
of scrutiny and review the treatment received before it was tested in humans. The case highlighted the
importance of transparency and accountability in clinical trials. Following Jesse Gelsinger's death,
investigations were conducted to identify the failures and shortcomings in the trial. These investigations
led to the development of new guidelines and regulations to prevent similar incidents in the future.

Based on the information available, it is clear that the actions taken in the Jesse Gelsinger case were not
reasonable or fit. There were significant ethical lapses and failures in the trial, including issues related to
informed consent, risk assessment, scientific validity, and oversight. The case exposed flaws in the system
and highlighted the need for more robust ethical guidelines and regulatory oversight in clinical trials.

It is crucial to learn from the mistakes made in this case to ensure the protection and well-being of
future research participants. Efforts have been made to improve ethical standards, transparency, and
accountability in clinical trials, with the aim of preventing similar tragedies from occurring in the future.
References:
Gene therapy research & the case of Jesse Gelsinger. NYU Langone Health. (n.d.).
https://med.nyu.edu/departments-institutes/population-health/divisions-sections-centers/medical-
ethics/education/high-school-bioethics-project/learning-scenarios/jesse-gelsinger-case
The death of Jesse Gelsinger, 20 years later. Science History Institute. (2023, June 1).
https://sciencehistory.org/stories/magazine/the-death-of-jesse-gelsinger-20-years-later/
Sibbald, B. (2001, May 29). Death but one unintended consequence of gene-therapy trial. CMAJ :
Canadian Medical Association journal = journal de l’Association medicale canadienne.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/
As Gelsinger case ends, gene therapy suffers another blow | science - AAAS. (n.d.).
https://www.science.org/doi/10.1126/science.307.5712.1028b
Stanford Medicine. (n.d.-b).
https://med.stanford.edu/content/dam/sm/bioethics/documents/Gelsinger%20-
%20Oxford%20Textbook.pdf