Clare True had autism and periodic seizures, but nothing prepared her family for Christmas Eve in 2006, when the 26-year-old went to bed after watching a movie and stopped breathing.
“I got home from a party, went to check on her just after midnight, and she was — she was gone,” said her mother, Jane True.
Paramedics tried to revive the young woman, then rushed her to the hospital, and somewhere in that firestorm of activity and grief, the Trues, Jane and her husband, Jim, considered donation. “I thought of it as a gift, her brain,” she said. “To my mind, the idea that scientists would be learning from her for years to come — how can you put a price on that?”
Clare True’s was one of 150 specimens stored in a Harvard brain bank that was ruined because of a freezer failure, doctors acknowledged this month. The loss, while a setback for scientists studying disorders like Huntington’s disease, Alzheimer’s and schizophrenia, especially mortified those working on autism, for it exposed what is emerging as the largest obstacle to progress: the shortage of high-quality autopsied brains from young people with a well-documented medical history.
The malfunction reduced by a third Harvard’s frozen autism collection, the world’s largest. A bank maintained by the University of Maryland has 52, and there are smaller collections elsewhere. Altogether there are precious few, given escalating research demands. The loss at the Harvard Brain Tissue Resource Center makes donations from parents like the Trues only more urgent.
“There’s just no question that human tissue is the gold standard for research, said Dr. Gerald D. Fischbach, a professor emeritus at Columbia and director of life sciences at the Simons Foundation, which promotes autism research. “You absolutely need it to answer some very basic questions.”
The Harvard fiasco, first reported by The Boston Globe, has accelerated efforts by advocacy groups to reach out to families who might donate, said Alison Singer, president of the Autism Science Foundation. “I made calls as soon as I heard what happened,” she said.
Geraldine Dawson, chief science officer at Autism Speaks — the group that administers the autism brain donations at the Harvard bank — and a professor of psychiatry at the University of North Carolina, said, “This is indeed a setback, but it has motivated us more than ever to rebuild this precious resource.”
Ms. True, who lives in Kansas City, Mo., learned about brain donation through her work at an advocacy organization now called DUP15q Alliance for parents of young people like Clare, who have a genetic glitch on chromosome 15 that causes a tiny percentage of autism cases (and is often associated with seizures).
Unlike Alzheimer’s or other age-related neurological problems, autism spectrum disorders develop early, and the brains of children and young adults with autism are of most use to researchers. But the young do not usually die in hospitals. Death often steals them in accidents: drownings, falls and car crashes.
“The greatest challenge is to get parents to imagine something that they just don’t want to think about,” said Kadi Luchsinger, of Syracuse, who coordinates tissue donation for the DUP15q Alliance. “It’s the kind of decision you never want to have to make.”
But the Trues did, and they had to act fast. The cause of their daughter’s crisis was unknown and probably not a result of the seizures or autism, her mother said. As Clare lay on life support in the hospital, and doctors tried to revive her, Ms. True, her husband, and Clare’s two brothers paced in the waiting room.
“I don’t know that we even had to talk about it; we’d lost another daughter years earlier and decided to donate organs,” Ms. True said. “It’s what Clare would have wanted. She was always eager to donate blood.”
Sometime past 2 a.m., Ms. True called a hot line for the autism tissue donation program, and its staff got to work. The body was quickly moved to the medical center at the University of Kansas.
Between 7 and 8 a.m., specialists there removed the young woman’s brain and immediately froze it. It was shipped overnight in a box on dry ice to Harvard’s bank, which is housed at McLean Hospital in Belmont, Mass.
At McLean, as at other brain banks, doctors often separate the brain’s two hemispheres and freeze only half. The other half is preserved in a chemical called formalin. This was the case for all but one of the 53 specimens that were ruined at McLean, Dr. Dawson said; each frozen hemisphere that thawed has a counterpart that is preserved in formalin and is still valuable for studies.
But formalin, while it preserves the tissue, also alters proteins, making the samples poor material for studies of so-called gene expression. Scientists now know that a handful of genes account for a small percentage of autism cases, but they need human tissue to piece together exactly where in the brain — and when in development — those genes are expressed, Dr. Fischbach said. “We have had to divert a couple of research projects already” that depended on the frozen specimens, he said.
The arrival of an organ at a tissue bank is only the beginning of a long process, said H. Ronald Zielke, a professor of pediatrics who directs the National Institutes of Health Brain and Tissue Bank for Developmental Disorders, at the University of Maryland.
“We need to do extensive interviews with the parents to gather information about the person’s psychological state,” he said. “It’s not always easy, and that process can take a year or more.”
Some brains are lost in the handling. Others make for poor research material if more than 24 hours pass before freezing; brain tissue deteriorates quickly at room temperature. For still others, it’s not clear whether the child had autism, based on records and interviews.
In an average year, the Maryland bank obtains four to eight viable donations, said Dr. Zielke. The Autism Speaks project has obtained an average of fewer than 10 new specimens a year, said Dr. Eric London, who founded the program and leads autism treatment research at the New York State Institute for Basic Research. “When we first stared doing this, we were very squeamish about it,” Dr. London said. “We didn’t want to scare parents away.”
They are less squeamish now. Dozens of parents have come forward, acting despite their sudden loss. In the last few years, 13 families have donated brains through the group Ms. Luchsinger runs.
Most parents want to hear from the scientists afterward, and they do. Autism Speaks and the DUP15q Alliance make a point of informing donors how the tissue is being used — and the researchers doing the work get on the phone to answer and ask questions.
In recent years, Ms. True said, her daughter’s brain has helped investigators, at New York University and elsewhere, looking into seizure disorders, among other things.
This month, she got another kind of update. She learned that Clare’s brain — which held so many one-liners from favorite movies, and song lyrics, which she always sang beautifully — had been compromised. Autism Speaks informed all of the families of donors soon after the freezer failure was discovered.
“They said they wanted to tell us first, before it came out in the media,” Ms. True said. “I guess I felt — well, she’d been helping with research for five years, and it just made me see how important this was, given how little they know about these disorders.”
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