The Case of Jesse Gelsinger

1. Objectives

  • Present an overview of gene therapy.
  • Describe one case and three ethical issues in gene therapy research.
  • Introduce the fundamental concepts of informed consent and conflict of interest.

Curriculum Integration Ideas

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

  • 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.

2. What's Gene Therapy? Back in the 1970's, 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 and as a way to prevent and cure genetic disease. 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 may seem to be theoretically straightforward, it has proven to be very difficult to do since the first gene therapy experiments began in the early 1990's.

Gene therapy is done by using a vector to insert tiny fragments of DNA into a diseased cell's nucleus. A vector is simply a shuttle that is used to carry DNA into a cell and then leave it there for the cell to use. 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. The vector is injected into a person's body directly, or it can be 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 the cells will absorb the new functional gene, and integrate it into the cells' own genetic makeup. Once this occurs, the inserted gene should function normally, creating the necessary proteins that were deficient before the therapy. The patient should become healthy as their new genes begin to work normally.

3. 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, read the following real life case:

17-year-old Jesse Gelsinger suffered from a genetic disease called ornithine transcarbamylase (OTC) deficiency. OTC deficiency is a genetic disease that prevents the body from breaking down ammonia, which is a metabolic waste product. In OTC patients, the excessive build-up of ammonia often causes death soon after birth, unless the patient's diet is immediately adjusted and monitored throughout their entire life. Jesse lived on a strict non-protein diet and he controlled his OTC fairly well. Jesse volunteered for a gene therapy experiment designed to test possible treatments for OTC. He thought he could help newborns afflicted with OTC by being a volunteer in the experiment. 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 called adenovirus- which is a modified version of the virus that causes you to get a cold. For the most part, Jesse was informed subjects had received adenovirus without serious complications. But for some reason Jesse was different. After injection of the vector, a fatal reaction was triggered. On September 17, 1999, four days after the injection, Jesse Gelsinger died.

4. What are 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:

Selection of Subjects: An ethical question that was raised in the Gelsinger case was whether relatively healthy, adult volunteers who had OTC (such as Jesse) 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, if adults were used, they could understand the risks, and weigh those risks against the potential benefits of the experiments. 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 or not they want medical treatment or decide if they want 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 had caused Jesse to die was relatively safe and that the deadly reaction was random and unforeseeable. However, as the investigation into Jesse's death continued, reports began to emerge that past research subjects as well as experimental animals had become sick from the vector. This revelation raised ethical concerns, since these previous problems were apparently not correctly communicated to Jesse and to the other volunteers. Jesse's family said that they were never adequately informed of these past cases. As a result, they claimed, when Jesse decided to volunteer he thought the risks were lower than they actually were.

A conflict of interest was identified that involved the lead scientist, Dr. Wilson. As it turned out, 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?