Whose DNA Is It, Anyway?

As her mother slipped into the disoriented world of Alzheimer’s disease, Oleta Toliver poured herself into a project that offered hope. She began turning up at nursing homes, church groups and family reunions near her Texas home, trying to coax Alzheimer’s patients and their families to donate DNA to Texas Tech University.

Most families were eager to help. A Texas Tech scientist was using the DNA to search for Alzheimer’s genes, and the rogue genes, in turn, had the potential to point researchers toward a cure. More than 10,000 people from 2,400 families eventually gave DNA to the effort, many at blood-drawing events arranged by Toliver.

Then, after nine years, the gene hunt suddenly stopped. The university fell into a dispute with the lead researcher over who controlled the DNA collection and who could use the samples. Amid the fight, all work was suspended in January 2000.

“I feel like we’ve been cheated,” said Toliver, 74, who fears that Alzheimer’s disease will one day afflict others in her family. “The people who contributed samples, this was their prayer -- that we could in some way help with this disease. But it’s been years of wasted time.”

Each year, thousands of people donate DNA to medical research, often in the hope that finding a new gene will lead to a promising insight, a new diagnostic test or a better treatment for a disease or disorder that plagues their families.

These DNA collections are often the raw material for scientific breakthroughs, and many researchers and patient groups believe that they should be managed like lending libraries, open to any scientist. But too often, they say, researchers refuse to share DNA, even when taxpayers are covering the costs.

Sometimes, scientists hoard DNA in hopes of being first to publish career-boosting discoveries. At other times, scientists want to protect their ability to file patents on genes. Or, they may be simply unwilling to take the time to resolve the privacy and technical issues that cooperating with other scientists requires.

The lack of sharing has hindered research into Alzheimer’s disease, autism and several rare disorders, scientists and patient groups say. Some patient groups have become frustrated and are building their own DNA banks.

“It’s just surreal to me that people won’t share DNA, and it’s so obviously not in the patients’ interest,” said Jonathan Shestack, a Los Angeles film producer whose son has autism. Shestack said the hunt for autism genes was moving at “30 miles an hour instead of 70 miles an hour” because some scientists refused to pool DNA samples. “To think that one person or a few people can stymie this research is crazy.”

“What’s at stake here is: Whose DNA is this, anyway?” said Dr. Katrina Gwinn-Hardy, a researcher at the National Institute of Neurological Disorders and Stroke. “These samples are given to us with the trust that we use them to learn more about diseases so we can help people.”

She said scientists she knows have gone so far as to water down the DNA they send her to keep more for themselves.

“We were absolutely livid,” said Judith Tsipis, a biology professor at Brandeis University, outside Boston, about her experience with gene-hunters. In the late 1980s and early 1990s, a group Tsipis works with recruited DNA donors for a Miami Children’s Hospital researcher, considering it a gift to the public. The donors hoped that the researcher would find the gene for Canavan disease, a brain-wasting illness that was killing their children, and that doctors would use the new genetic knowledge to test parents and unborn children for Canavan at little or no cost.

That happened. But the Miami hospital also filed for a patent on the Canavan gene without telling the DNA donors, the parents say in a lawsuit.

After the patent was awarded in 1997, the suit says, the hospital set fees and other conditions that prompted some clinics to drop their testing programs.

“Our children were dying, but this was a way we could help others,” said Tsipis, whose son, Andreas, died of Canavan in 1998. “That’s why we provided samples and raised money for the research.” The hospital says that the parents agreed to the patent -- and that its fees will never cover the cost of creating the test.

No law requires scientists to share the DNA they collect in the course of research. However, many scientists say that sharing DNA from patients is in the public interest, because it allows more researchers to study a particular disease.

In April, the international Human Genome Organization, which tries to promote collaboration on gene research, declared that collections of DNA data are “global public goods” and a “public resource,” although scientists, private companies and research institutions also have a right to “fair return” on their contributions to DNA databases. Since 1999, the National Institutes of Health has said that researchers must share the DNA they gather as a condition of receiving federal grants.

But while scientists say sharing has become far more widespread in recent years, many also complain some researchers praise the rules on sharing in public while trying to subvert them in private. They say that the NIH sharing rules are unevenly enforced -- and that researchers sometimes shop around for the grant administrator who will let them keep DNA to themselves the longest.

Scientists say this goes on because sharing can damage, rather than help, their careers. “In academia, you are rewarded by your individual contribution and what papers you write,” said Dr. Daniel Geschwind, a neurology researcher at UCLA. “People want to be the first author on a paper. They don’t get credit in their career for being the 15th author.

“That fosters excellence and competition, which is good,” he said. “But on some level it inhibits sharing.”

Privacy rules can also make sharing difficult. Donors must give written approval before a scientist can pass their DNA to other researchers, but rules vary from one institution to another and consent forms have changed over time.

Before approving a sharing request, officials at research institutions sometimes require scientists to obtain new consent forms from everyone who gave DNA to a collection, which may be difficult for DNA banks that have been built over many years. That has led to cases where a collection is no longer being studied by a university -- yet is unavailable to interested researchers at other institutions.

Officials have become so aggressive in setting consent and privacy rules that some scientists “are throwing up their hands” and pursuing research with fewer complications, said Dr. John Opitz, a geneticist at the University of Utah.

Unless sharing becomes more the norm, many scientists believe that the biggest problems in gene-hunting will remain unsolved. That is because many diseases arise from the complex interactions of multiple genes, each of which may make only a small contribution to one particular illness.

Gene-hunting has become important because it can help answer the mystery of exactly what goes wrong in the body to cause illness: Many diseases occur because a person has a mutated, or altered, form of one or more genes. These genes then produce faulty proteins -- or sometimes incorrect amounts of protein -- causing the body’s cellular machinery to go awry.

Finding and studying these mutant genes can produce new insights about disease on its most basic, molecular level.

Frustrated by the various hurdles to sharing DNA, a number of patient groups say they have come to an important realization: Whoever controls the DNA controls the breadth and direction of research. These groups are building their own collections of DNA.

“We want to make sure that research will continue for years to come. We want it to be open to many researchers, as opposed to just one researcher who may change interests or jobs,” said Brenda Conger, whose 10-year-old son has CFC, or cardio-facio-cutaneous syndrome, which has left him with mental retardation and heart and vision defects.

The group she leads, the CFC Family Network, plans to draw blood from patients at a conference near Washington this weekend to start its own DNA bank.

Shestack, the father of an autistic son, found that it was not easy to claim a role in the elite world of gene-hunting.

As a producer of “Air Force One” and other movies, Shestack thought he had a knack for persuading talented people to work together on big projects. But that was before he tried to push scientists to cooperate on the hunt for autism genes.

“The politics of medical research,” he concluded, “are every bit as rough as in the movie business.”

Shestack and his wife, Portia Iversen, started a foundation called Cure Autism Now after their son, Dov, now 11, was diagnosed with the disorder. Because the cause was so poorly understood, scientific advisors recommended that the group focus on finding autism-related genes.

At least four teams were already searching. Many experts thought they would need DNA from at least 100 families with two or more autistic members.

When Shestack and Iversen began calling the scientists to offer help, they made a discovery: As a group, the scientists had collected DNA from the necessary 100 families. Individually, however, no single team had DNA from anywhere near that number. And because the teams were not sharing samples, none of them had enough DNA for a thorough study.

And so Shestack made a plea: Pool the DNA. “And they all, to a man, said no,” Shestack said. Even when he and Iversen offered money and access to more autism patients, the scientists refused to share their samples, Shestack said. “Everyone wanted to be first to find the genes -- their careers depended on being first -- and they didn’t want anyone else to get a competitive advantage,” he said.

Finally, Shestack and Iversen came to the conclusion that the families could only influence the research world by carrying the coin of their realm: DNA. So, starting in 1997, they raised money, hired a staff and collected DNA from autism patients and their families.

Within a year, the Autism Genetic Resource Exchange had DNA from 100 families -- more than any of the research teams. The collection has since grown to more than 400 families and cost more than $6 million in private donations to build.

Unlike the DNA held by most teams, the autism exchange’s DNA is available to any scientist who asks. More than 95 researchers have used the collection, publishing 18 papers in peer-reviewed scientific journals.

“It’s been enormously valuable to us,” said Dr. Arthur Beaudet, chairman of the department of molecular and human genetics at Baylor College of Medicine in Houston. “We wouldn’t have had the resources and team to collect and characterize samples on our own. It made it possible for us to try out some of our ideas.”

Toliver, who helped Texas Tech collect DNA from Alzheimer’s patients, is not interested in trying to manage a DNA collection on her own. She still has faith in Shirley Poduslo, the scientist who originally built the Alzheimer’s collection at Texas Tech.

Toliver was running a support group in her hometown of Brownfield, in the Texas Panhandle, as she coped with the challenge of caring for her mother, who died in 1993. “She went through all the stages of dementia,” Toliver recalled. “She would run out of the house into traffic. It was hard to see this dainty little woman, who had been so refined, get angry and yelling and hollering.”

Poduslo told the support group in 1991 that if she had more DNA samples to study, she would make more progress on finding Alzheimer’s genes. “She said 100 would be good,” Toliver said. “And when we got her the 100, she said another 100 would be good.”

The two women worked together for nearly a decade on the collection effort, which was funded with state money. Then, new management came to Poduslo’s department at the university, and she was relieved of some of her duties in January 2000.

Poduslo decided to leave Texas, but she wanted to continue work on the DNA samples she had collected for so long. Texas Tech said patients had not consented to their samples leaving campus. Litigation was filed. In the meantime, all work stopped.

Last month, the dispute ended when a refrigerated truck pulled into Texas Tech and took about 1,600 of the 10,000 DNA samples to Poduslo’s new laboratory at the Medical College of Georgia in Augusta.

Now, each side can continue its work, but at a price. Division of a DNA resource undercuts the statistical power that comes from studying a lot of samples.

“It’s ridiculous,” Bartha Maria Knoppers, a law professor at the University of Montreal, said of dividing the Alzheimer’s DNA bank. “How does that in any way help the families who contributed samples?”

Toliver is still bitter about how Texas Tech treated Poduslo and that the research was allowed to stop. She and her husband are Texas Tech graduates, but they have written the university out of their will.