[Note: Shared for #AutisticHistory archive purposes. This is NOT An Autistic Ally.]
Whose DNA Is It, Anyway?
Three NIH institutes are trying to open up collections of DNA to spur hunts for disease genes, but clinicians fear that molecular biologists will skim the cream off years of their painstaking work
“I thought the movie business was rough,” says Los Angeles filmmaker Jon Shestack, but in the past 2 years, “I’ve learned that this business is much rougher.” Shestack–who produced the blockbuster movie Air Force One–is talking about the rush to gather and analyze DNA from families who may carry disease-related genes. He acquired an insider’s view of the “brutal” academic struggle for priority when he tried to persuade researchers who have collected genetic data on autism, a disorder that’s been diagnosed in his own 5-year-old son, to share their collections. Shestack hoped that sharing might speed the pace of research. But when he approached some of the best and brightest researchers in the field, he says, they told him they’d rather keep control of their own materials.
Shestack and his wife, Portia Iversen, took matters into their own hands. They started an organization 2 years ago called Cure Autism Now (CAN), which, along with lobbying for more resources for autism research, will collect and share its own DNA samples. With help from Lee Ducat, founder of the Juvenile Diabetes Foundation, who used a similar strategy in the 1980s for diabetes research, Shestack and Iversen have created the Autism Genetic Resources Exchange (AGRE). In the past 6 months, Shestack claims, “we have enrolled 200 families.” AGRE is training 15 people to conduct diagnostic interviews, getting ready to collect DNA, and contracting with the Coriell Cell Repositories in Camden, New Jersey, to transfer the DNA to “immortalized” cell lines that will be made available to qualified researchers on a nonexclusive basis. Shestack says this should open the field to new researchers–perhaps even “a gunslinger with a big lab” who may be new to autism research but can get quick results. “A lot of people don’t like it,” Shestack observes, including researchers who have devoted years to the field. “That’s too bad,” he says, but “it would be irresponsible for us to do anything else” but share data.
That kind of claim, along with counterarguments from medical researchers, will be reverberating throughout the medical genetics community in the next few months as institutes at the National Institutes of Health (NIH) try to do on a larger scale what CAN is doing for autism. As investigators turn from the relatively straightforward task of finding single genes that cause rare disorders to the bigger challenge of finding genes that might interact to cause common diseases such as autism, many are running into the same problem: They need access to high-quality clinical data and DNA from huge numbers of affected families. But clinical researchers, who spend years painstakingly diagnosing patterns of illness in families and collecting blood samples, are wary of handing these materials over to molecular biologists–gunslingers with big labs–who might cream off the results and the glory. They say they deserve a chance to work with the data, and they worry that the quality may suffer as investigators, faced with a deadline for releasing their data, rush to collect and analyze it.
The tide seems to be turning against these arguments. Like CAN and the diabetes support groups, some NIH institute directors don’t want to wait for investigators to offer up their data and are drafting policies to make it easier for geneticists to get their hands on materials collected at NIH’s expense. “There’s been a lot of gritting of teeth” over this, says geneticist Aravinda Chakravarty of Case Western Reserve University in Cleveland, Ohio. “But I think we have to start with the principle that competition is good … and we should make these collections as widely available as possible.”
Opening the data banks
These tensions are coming to a head this fall at the National Heart, Lung, and Blood Institute (NHLBI). As Science went to press, NHLBI chief Claude L’Enfant was planning to meet with his advisory council on 23 October to consider a set of recommendations to open up the institute’s extensive collections of clinical data. L’Enfant notes that NHLBI has “enormous resources, close to 1.5 million blood samples,” including 50 years of clinical data collected from subjects in a heart study based in Framingham, Massachusetts. The samples, which are under the control of individual investigators and their universities, in some cases could be extended to cover three generations. L’Enfant worries that “these blood samples could remain on the shelf forever unless we address the issue [of collaboration] in a very positive way.”
L’Enfant and his advisory panel will be taking their cues from a report put together by a “Special Emphasis Panel” on genetics co-chaired by Eric Lander, director of the Whitehead Institute/MIT Center for Genome Research in Cambridge, Massachusetts, and Roger Williams, director of the University of Utah Cardiovascular Genetics Research Unit in Salt Lake City. The panel says investigators have regarded DNA they’ve collected as “a precious, finite resource” and do not readily share it. To solve this problem, it urges NHLBI to establish a central service for immortalizing DNA in cell lines and maintaining the cells in a repository. Overseers would select material for the repository, ensure privacy, and pass on requests for access. NHLBI-funded investigators would be expected to make their materials generally available through this system.
The panel also suggests that NHLBI put money into small grants covering the cost of shipping materials, particularly to anyone interested in testing out a new hypothesis. Moreover, to make sure that NHLBI’s resources are widely publicized, the panel says the institute should create a World Wide Web site to provide detailed information about clinical data collected by grantees, listing all studies of more than 150 people.
NHLBI will probably endorse all these recommendations, says L’Enfant. But it is likely to provoke a big debate when it tackles one key question: How long should an investigator be allowed to retain exclusive control of data he or she has collected before turning it over to the central repository? The panel doesn’t suggest a deadline; it merely proposes that new grants be offered as an incentive to encourage more rapid release of data from completed projects. “I would say about a year” is reasonable, says L’Enfant.
The issue has prompted a review at National Institute of Mental Health (NIMH) as well. On 19 September, NIMH director Steven Hyman’s advisory council adopted most of a special report recommending changes to clear the way for a new “genetics initiative.” The report, written by an eight-member panel chaired by Samuel Barondes, a University of California, San Francisco, psychiatrist, and including Chakravarty and the ever-present Lander, recommended some organizational changes that “we have already implemented,” says Hyman. But the council couldn’t agree on the panel’s recommendation that all genetic materials gathered at NIMH expense should be shared “after a 12- to 18-month proprietary period.”
“We had a very vigorous debate” on this at the council meeting, says Hyman. Members focused on the question of “how do you trade off the need to provide an incentive to investigators [by rewarding them with exclusive use of materials] versus the need to share DNA samples.” Although the council reached no conclusion, Hyman says NIMH will set a policy soon. He claims that “you won’t meet a serious geneticist who doesn’t agree that we need to share.” But Hyman also recognizes that the questions of what to share and from what point to measure the 18-month time limit “are not niggling issues” for investigators.
Problems in compulsory sharing
Hyman has good reason to be cautious. Efforts by NIMH and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to open data from prior collaborations have turned out to be highly controversial.
NIMH led the way 2 years ago, when it took control of the interview results, clinical data, and DNA gathered by researchers at nine sites who had collected material from hundreds of families affected by Alzheimer’s disease, schizophrenia, and manic depression. NIMH began making allof it available at cost to qualified scientists. Many companies interested in making products for mental disorders–including Merck, Pfizer, Millennium, Sandoz, and others–immediately bought the immortalized DNA samples. Many academic researchers have also acquired the materials to use as a means of testing a hypothesis in a second data set.
Some researchers think NIMH erred in forcing its researchers to yield up this raw material so rapidly. One East Coast psychiatrist, who asked not to be named, believes sharing is desirable, but says the choice should be the clinician’s: “This is our life’s work,” this researcher says. Michael Conneally, a longtime leader of genetics research at Indiana University School of Medicine in Indianapolis, says many of his colleagues “felt that NIMH jumped the gun and were a little hasty in letting [materials] out.” He thinks “these groups didn’t get a really good chance at trying to find genes before the materials were released.” Because it is hard to gather clinical data–particularly for behavioral disorders–Conneally thinks the clinical teams should have “a minimum of 5 years” of exclusive time to analyze the DNA they’ve collected, and “a maximum of 10 years.”
The NIAAA leadership is sympathetic to this view. Enoch Gordis, NIAAA’s director, says, “Of course, the molecular biologists would like to get their hands on all this stuff and win their Nobel Prizes, but the work was done by others.” He also argues that the biggest effort, deserving the lion’s share of credit, is not the molecular biology but “finding the families, chasing after them, interviewing them–this is very labor intensive.”
Gordis himself has had to weigh these interests in negotiating the release of data from the massive Collaborative Study on the Genetics of Alcoholism. COGA, which has been funded by NIAAA at a cost of $57 million since 1989, has collected material on 4100 individuals affected by alcohol dependence, and it is about to publish its first major findings. The principal investigator of the multicenter effort, Henri Begleiter of the State University of New York in Brooklyn, says one publication, to appear later this year, will debunk claims of linkage between alcoholism and the gene for the D2 receptor, and others will identify several “hot spots” on chromosomes that COGA researchers have linked to alcoholism. Now, NIAAA wants to make COGA’s materials more widely available.
After a year of negotiating, NIAAA and the COGA investigators agreed last year that all the materials supporting this work will be released to the world in September 1999, roughly a decade after COGA was launched. Meanwhile, Gordis says, COGA is entertaining and approving requests for material on a case-by-case basis. “It’s a situation where everybody is right,” says Gordis, and he thinks COGA has made a reasonable compromise.
That deliberate pace has advantages that go beyond fairness, clinical researchers add. Those working with families with autistic children, for example, worry that forcing data to be released may erode quality. Geneticist Gerard Schellenberger of the University of Washington, Seattle, points to a widespread concern that the rush to collect families could lead to duplication of data sets. If investigators conduct their gene hunts in groups of families that are not truly independent, this could undermine the value of the statistical results. In addition, Schellenberger worries about moving too fast and prematurely “freezing” the diagnostic criteria used to select individuals for analysis. It is important, he thinks, to permit flexibility so that different theories can be fully tested.
But advocates of pooling family data have answers for such concerns. “This isn’t a magic act,” says CAN’s Shestack: “All you have to do is keep good records” that place a unique identifier on each sample. He also thinks it should be possible for any investigator to sort the data according to any particular interest–once the raw materials have been characterized and made available.
In the end, the affected families seem likely to prevail in this discussion, and the NIH institutes and the researchers they fund will no doubt find a way to adjust. For as Shestack none too subtly points out, the subjects in autism research outnumber the investigators by 60,000 to one
More With Cure Autism Now
Autistic people have fought the inclusion of ABA in therapy for us since before Autism Speaks, and other non-Autistic-led autism organizations, started lobbying legislation to get it covered by insurances and Medicaid.
ABA is a myth originally sold to parents that it would keep their Autistic child out of an institution. Today, parents are told that with early intervention therapy their child will either be less Autistic or no longer Autistic by elementary school, and can be mainstreamed in typical education classes. ABA is very expensive to pay out of pocket. Essentially, Autism Speaks has justified the big price tag up front will offset the overall burden on resources for an Autistic’s lifetime. The recommendation for this therapy is 40 hours a week for children and toddlers.
The original study that showed the success rate of ABA to be at 50% has never been replicated. In fact, the study of ABA by United States Department of Defense was denounced as a failure. Not just once, but multiple times. Simply stated: ABA doesn’t work. In study after repeated study: ABA (conversion therapy) doesn’t work.
What more recent studies do show: Autistics who experienced ABA therapy are at high risk to develop PTSD and other lifelong trauma-related conditions. Historically, the autism organizations promoting ABA as a cure or solution have silenced Autistic advocates’ opposition. ABA is also known as gay conversion therapy.
The ‘cure’ for Autistics not born yet is the prevention of birth.
The ‘cure’ is a choice to terminate a pregnancy based on ‘autism risk.’ The cure is abortion. This is the same ‘cure’ society has for Down Syndrome.
This is eugenics 2021. Instead of killing Autistics and disabled children in gas chambers or ‘mercy killings’ like in Aktion T4, it’ll happen at the doctor’s office, quietly, one Autistic baby at a time. Different approaches yes, but still eugenics and the extinction of an entire minority group of people.
Fact: You can’t cure Autistics from being Autistic.
Fact: You can’t recover an Autistic from being Autistic.
Fact: You can groom an Autistic to mask and hide their traits. Somewhat. … however, this comes at the expense of the Autistic child, promotes Autistic Burnout (this should not be confused with typical burnout, Autistic Burnout can kill Autistics), and places the Autistic child at high risk for PTSD and other lifelong trauma-related conditions.
[Note: Autism is NOT a disease, but a neurodevelopmental difference and disability.]
Fact: Vaccines Do Not Cause Autism.