Gene Therapy Research & the Case of Jesse Gelsinger | NYU Langone Health

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High School Bioethics Project Learning Scenarios Gene Therapy Research & the Case of Jesse Gelsinger

Gene Therapy Research & the Case of Jesse Gelsinger

This learning guide, created by NYU Langone’s High School Bioethics Project, presents an overview of gene therapy, describes one case and three ethical issues in gene therapy research, and introduces the fundamental concepts of informed consent and conflict of interest.

Curriculum Integration Ideas

This guide may be used in life or social science classes where there are units for topics including the following:

  • the scientific method and experimentation on human subjects
  • basic concepts in genetics and molecular biology such as transcription and translation
  • basic virology
  • research regulations and public policy

What Is Gene Therapy?

In the 1970s, scientists started dreaming up new ways to treat people who have genetic diseases. One idea was to directly alter a person’s genome to fix genetic mistakes. This is called gene therapy. The basic theory driving gene therapy is that by removing and replacing a particular gene or set of genes that are dysfunctional with normal functioning genes, you can cure a disease. While this approach is theoretically straightforward, it has proven to be very difficult to do since the first gene therapy experiments began in the early 1990s.

Gene therapy is done by using a vector to insert tiny fragments of DNA into a diseased cell’s nucleus. Generally, the vectors used in gene therapy are viruses. A virus can hold onto the DNA as it enters cells and then deliver the DNA to the cell. Vectors can be injected into a person’s body directly or mixed up with some of the person’s cells outside the body that are then replaced.

Once the vector is delivered to the target cells, scientists hope that they will absorb the new functional gene and integrate it into their own genetic makeup. Once this occurs, the repaired gene should function normally.

Ethics in Real Life: The Case of Jesse Gelsinger

To begin thinking about some of the ethical issues in gene therapy research, and human experimentation in general, we explore the following real-life case.

Seventeen-year-old Jesse Gelsinger had a genetic disease called ornithine transcarbamylase (OTC) deficiency. OTC deficiency prevents the body from breaking down ammonia, a metabolic waste product. In patients with this disease, the excessive buildup of ammonia often causes death soon after birth, unless the patient’s diet is immediately adjusted and monitored throughout their entire life. Gelsinger lived on a strict non-protein diet and controlled his OTC fairly well.

Gelsinger volunteered for a gene therapy experiment designed to test possible treatments; he thought volunteering could help newborns afflicted with OTC. He enrolled as a subject in a gene therapy experiment in which a vector carrying a normal OTC gene was injected into his liver. The vector being used to deliver the OTC gene was adenovirus, a modified version of the virus that causes the common cold.

Gelsinger was informed that previous subjects had received adenovirus without serious complications. But he had a negative reaction to the injection, and four days later, on September 17, 1999, he died.

What Are the Ethical Issues?

There are a number of ethical issues that have emerged from gene therapy research, and particularly from the Gelsinger case. Many of these issues are common to experiments involving human volunteers; some are unique to gene therapy. Here are three specific to this case.

Selection of Subjects

An ethical question that was raised in the Gelsinger case was whether relatively healthy adult volunteers with OTC (such as Gelsinger) should have been used as subjects. At first it was suggested that babies born with OTC be used in the experiment with their parents’ consent. So why not simply experiment on newborns that had OTC, since they were already very sick? If infants were to be used, their parents would have to give informed consent first. A concern was raised as to whether parents with very sick newborns could really understand that gene therapy experiments were very risky and probably would not help their baby. In contrast, adults with the condition could understand the risks and weigh them against the experiment’s potential benefits. Adults were chosen because they could better comprehend the risks of the experiment and provide informed consent. Would you make the same decision?

Informed Consent

Everyone has the right to determine whether they want medical treatment or decide to participate in an experiment. The notion that people should be fully informed and able to freely consent to participation in a research trial is accepted as a minimum requirement for the use of human subjects in an experiment.

At first, it was thought that the vector that caused Gelsinger’s death was relatively safe and that the deadly reaction was random and unforeseeable. However, as the investigation into Gelsinger’s death continued, reports began to emerge that past research subjects and experimental animals had become sick from the vector. This revelation raised ethical concerns, since these previous problems were apparently not correctly communicated to Gelsinger and to the other volunteers. Gelsinger’s family said that they were never adequately informed of these past cases. As a result, they claimed Gelsinger believed the risks were lower than they actually were.

Conflict of Interest

A conflict of interest was identified that involved the lead scientist, Dr. James Wilson. Dr. Wilson had a financial interest in the development of the adenovirus vector being used in the OTC gene therapy trial. If his gene therapy vector worked correctly and was successful, he could make a lot of money by using it to treat people or by selling it to other researchers. This conflict of interest may have influenced the decisions made by Dr. Wilson as he continued with his experiments. Do you think a researcher can make sound decisions about an experiment when they have a stake in the outcome of those experiments?