Genetic Medicine: Prescription for Conflict

PRODUCERS: Kathy McAnally

Although the ability to predict, prevent and treat disease with genetic technologies such as gene therapy, stem cell research, and xenotransplantation seems like a real possibility, it is not without controversies and roadblocks.

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New & Noteworthy, 2007
by Jennifer Jongsma

In Genetic Medicine: Prescription for Conflict, The DNA Files looked at technologies such as gene therapy and stem cell research that have raised public debate. Although the ability to predict, cure, and prevent disease with genetic technology seems like a real possibility, it is not without controversies and roadblocks.

The basic concept of gene therapy remains as seemingly simple as it did in 2001: introduce into a target cell a piece of genetic material that will either cure the disease or slow down its progression. Unfortunately, researchers still struggle with safely delivering genes into the right place. Although disarmed viruses are the most efficient for delivery, they also have the potential to cause dangerous unwanted effects, including changes in organ function, plummeting blood cell counts, and death. Nonviral vectors (such as aerosol sprays, lipid-coated capsules, and synthetic vectors) rarely have toxic or immunological effects, but they are inefficient. Successful approaches may require combining the best features of both.

Researchers also are discovering that getting a gene into a patient's cells doesn't always mean successful treatment. In July 2007, a patient who received investigational gene therapy in a clinical trial for active inflammatory arthritis died. In this study, a recombinant adeno-associated virus (AAV)-derived vector delivered a DNA sequence that encodes a soluble form of the tumor necrosis factor-alpha receptor. The gene was delivered into the affected joint with the goal of reducing inflammation and disease; however, the patient experienced an extreme adverse event and died four days later. Although the company conducting the clinical trial, Targeted Genetics, issued a statement saying that the clinical course that this individual experienced has never been seen as a consequence of exposure to AAV vectors or naturally occurring AAV, the U.S. Federal Drug Administration immediately put the trial on hold pending further investigation into what exactly caused the patient's death.

In early 2005, the state of California took a huge step in promoting stem cell research. Voters established the California Institute for Regenerative Medicine with the passage of Proposition 71, which provided $3 billion in funding for studies at California universities and research institutions. Stem cell research is a complicated and interdisciplinary field with a lot of promise, and there are still major problems to be worked out in figuring out how to grow cells, prompt their specialization, and then deliver them. So far, most studies are directed toward using these cells to understand disease progression rather than finding a "cure" for diseases such as Parkinson's, Alzheimer's, or diabetes type 1.

Genetic technologies applied to medicine have experienced a great deal of scrutiny in recent years. Although results have been encouraging, untimely gene therapy--related deaths reinforce the need for careful and informed progress.

Original Program Description, 2001

We may be on the verge of a medical revolution, with treatments for diseases like Parkinson's and cancer right around the corner.

But amidst the hope and hype surrounding genetic technology, there is also a difficult set of unanswered questions. How safe is the research on genetic medicine? Is it ethical and aimed at the public good?

In this program, we explore three technologies that have raised public debate: gene therapy, stem cell research and xenotransplanation.

Gene therapy is a set of approaches intended to replace damaged genes with healthy ones, often using a disarmed virus to deliver a package of "good" DNA into the patient's cells.

Although there were no major breakthroughs early on, the treatment seemed fairly safe until 18-year-old Jesse Gelsinger died during a gene therapy clinical trial in 1999. This tragedy caused a reexamination of the safety of such studies and federal regulators ordered some of them stopped. Among these were studies that used an inserted gene to promote the growth of blood vessels in heart disease patients.

Critics say promising research was stymied. FDA regulators counter that safety must come first.

Stem cell research is another promising therapy that has touched a social and political nerve in recent years.

Embryonic stem cells are cells in an embryo that have yet to form specific cell types like blood, bone, muscle or nerve cells. The discovery that they can be nudged to become almost any tissue has caused a boom in research into their potential to heal everything from nerve damage to brain injury.

There has also been a more quiet revolution in the study of adult stem cells, which can also be made to grow certain types of tissue.

Embryonic stem cell research became the big science story of 2001 as the public debated whether it is right to destroy embryos in the quest to save lives. Amid the furor, private companies like California-based Geron continued to pursue their research.

Genetic Medicine: Prescription for Conflict also looks at the field of xenotransplantation, a fancy word for using animal tissues and organs in human patients.

There are thousands of people on waiting lists for organ donations who will never get them in time. If animal parts could be made compatible to the human body, they could help ease the supply problem and save lives.

The main issue here is how to weigh the potential benefit of a promising therapy against the potential of releasing a new disease into the population. We meet Jeff Getty, a man with AIDS who pressed his doctors to try a baboon bone marrow transplant. His story raises issues about community consent versus an individual's willingness to take on risk.

Finally, we touch on the debates around germ-line gene therapy and cloning, two equally controversial areas of medical research. Each raises fundamental questions about who we are and how much tinkering with our genome we are willing to accept.