DNA (2003) PBS

Episode 4: Curing Cancer

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Episode 4: Curing Cancer

Bud Romine was diagnosed with incurable cancer in 1994. He was given three years to live. In 1996, a newspaper article caught his eye. The article described the work of a local doctor, Brian Druker, who was testing a new kind of cancer drug. In 1997, months away from death, Bud Romine became the first patient ever to take Gleevec. Within 17 days, Bud had returned to perfect health. Indeed, the drug seems to cure everyone with Bud's disease -- Chronic Myeloid Leukemia -- by fixing the DNA that causes it. Today, the prospect of more drugs that work at the level of DNA is a real one. In 1990, Gleevec was the only one in development. There are currently hundreds of drugs in development that might work in the same revolutionary way on different kinds of cancer.

The final work for the DNA scientists is identifying all the damaged genes that cause cancer. But with the Human Genome Project finished, a single lab will be able to do this in just five years. Fifty years after Crick and Watson discovered the double helix, the secret of life may finally be living up to its name.

Directed by Carlo Massarella, produced by Thomas Alkin, and edited by Julian Rodd.

Fixing Our Genes, by Magdalena Eriksson

Sensational headlines have been streaming across presses for several years now: GENE FOR OBESITY FOUND, SCIENTISTS IDENTIFY GENE LINKED TO HEART DISEASE, or CANCER GENE GIVES HOPE FOR CURE. Each refuels the hope that powerful therapies against such major health threats will soon emerge from the pipeline of medical science. Diagnostics based on genetics are now commonly used, for example, when considering surgery against breast cancer, and in prenatal screening for inheritable diseases. But we're still waiting for a generation of genetic treatments that may provide miraculous cure-alls to our most persistent and pernicious illnesses.

Expectations of genetic medicine surged after a breakthrough in 1990, when four-year-old Ashanthi De Silva from Cleveland became the first gene therapy patient. The girl suffered from a problem called severe combined immunodeficiency (SCID), often dubbed "bubble-boy syndrome" since its sufferers must live in a sterile environment or risk acquiring a life-threatening infection. De Silva's form of SCID was caused by a mutation in the gene for the protein adenosine deaminase, or ADA, an enzyme that is necessary for the immune system. De Silva's body could not produce functioning ADA.

In a pioneering experiment, De Silva's doctors gave her healthy copies of the gene that produces ADA. They placed the healthy gene inside a modified virus and allowed the virus to infect blood cells they had drawn from De Silva. They then injected the blood cells back into her body. The girl's new gene started to generate functioning ADA, resuscitating her immune system, and she has since lived a healthy life.

Yet, after this initial success, subsequent gene therapy procedures haven't always been so trouble-free. In De Silva's case, the single healthy gene she received was sufficient to restore her immune system. People who suffer from other single-gene diseases, such as cystic fibrosis, sickle-cell anemia, or hemophilia, may also find help in gene therapy. But many genetic diseases involve the malfunction of multiple genes, and fixing one gene is often a formidable task.

In a Paris hospital in 2001, a group of young children who, like De Silva, suffered from SCID participated in a study. In these children, SCID was caused by a mutation in a gene called gamma-c. Through gene therapy, they received DNA with a flawless gamma-c gene, which was expected to stimulate the growth of immune cells in their bone marrow. For most of the children, the treatment was a success. The gamma-c gene became an established component of the children's bone marrow cells, and they were able to live normal lives.

Time passed and suddenly the good news turned dark. A year after the treatment, in October of 2002, one of the children developed leukemia. At first, doctors dismissed the incidence as bad luck, but when a second child, in January 2003, also developed leukemia, they began to look for the cause.

They learned that genes delivered through viruses prefer to integrate at active, loosely packed, portions of the genome, rather than at random sites. The new gene had inserted itself near a gene called LMO2, which plays a role in leukemia. This unexpected DNA insertion turned on the production of the LMO2 protein, which caused the development of leukemia.

The doctors had inadvertently discovered another factor to consider for making gene therapy safe. The two children have since recovered from their leukemia, but the experiment shows the risks required for scientists to make progress and steadily increase their knowledge.

The French trial also illustrates how complex our genetic systems are and how difficult it is to predict what will happen when we upset its fine-tuned balance. If you touch one gene, surprising connections with other genes may announce themselves in unexpected ways. The very principle behind gene therapy sets it apart from many other therapies. Once a new gene has become a permanent part of the genome in a cell, you may no longer have the option of discontinuing the treatment in case its effects prove detrimental. For some time to come, gene therapy may remain a double-edged sword.

Source: PBS

Documentary Description

A half-century ago, two unknown scientists heralded the dawning of a new era in biology and human life as they entered an English pub! Of course, Jim Watson and Francis Crick were hardly exaggerating. Their achievements almost single-handedly launched the new science of DNA. Interviews with renowned scientists and stunningly realized animations and reconstructions of key experiments offer an unprecedented glimpse of the molecular basis of life.


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