A freezer malfunction at Harvard-affiliated McLean Hospital has severely damaged one-third of the world’s largest collection of autism brain samples, potentially setting back research on the disorder by years, scientists say.
An official at the renowned brain bank in Belmont discovered that the freezer had shut down in late May, without triggering two alarms. Inside, they found 150 thawed brains that had turned dark from decay; about a third of them were part of a collection of autism brains.
“This was a priceless collection,’’ said Dr. Francine Benes, director of the Harvard Brain Tissue Resource Center, where the brains were housed. “You can’t express its value in dollar amounts,’’ said Benes, who is leading one of two internal investigations into the freezer failure.
The damage to these brains could slow autism research by a decade as the collection is restored, said Carlos Pardo, a neuropathologist and associate professor of neurology at Johns Hopkins University.
The collection, owned by the advocacy and research organization Autism Speaks, “yields very, very important information that allows us to have a better understanding of what autism is, as well as the contribution of environmental and immune factors,’’ said Pardo, whose 2004 study of brains stored in the bank was the first to find that autism involves the immune system. “The benefit has been great.’’
With that understanding, more effective treatment or prevention becomes possible.
The McLean freezer, one of 24 in the Harvard Brain Tissue Resource Center, was protected by two separate alarm systems, and staff checked an external thermostat twice a day to ensure that the tissue samples were maintained at about minus-80 degrees Celsius. But on May 31, center Assistant Director George Tejada opened so-called Freezer U and wasn’t greeted by the expected blast of cold air. Though the alarms had not been triggered and the external thermostat read minus-79, the actual temperature was 7 degrees, roughly equivalent to a refrigerator. Based on the condition of the brains, Benes estimates the freezer had turned off three days earlier.
Benes said the situation is so unusual - the perfect storm of alarm and thermostat failure and the concentration of samples - that she cannot rule out foul play. She said she has not spoken to law enforcement officials, pending the completion of the internal investigation.
In the interim, she said, McLean will upgrade security in the freezer room, which is under lock and key and watched by a surveillance camera.
The freezer contained about 150 brain samples from people who had died with a neurological condition such as autism, Parkinson’s disease, or Alzheimer’s disease, or a psychiatric one like bipolar disorder or schizophrenia.
More than 50 of those brains made up one-third of Autism Speaks’ Autism Tissue Program, a repository of postmortem brain tissue from children and young adults with the condition. The next largest autism brain bank, at the University of Maryland, has about 60 autism brains, according to its website.
For at least 32 of the more than 50 damaged brains, the tissue had been divided, with half placed in the freezers and the other half placed in formalin, a preservative similar to one used in grade school dissection classes. The preserved halves of the brains remain, Benes said, but they yield different information than the frozen ones.
The defrosted tissue may still be useful for genetics research, said Benes, who is leading an investigation into the quality of the remaining tissue. The DNA, the strands of chemicals that make up the genes, should be OK, she said. But other molecules, including proteins, are probably heavily damaged.
Environmental and other factors can change the proteins produced by the genes, and it is these changes that autism researchers are eager to study, Pardo said.
Autism Speaks is conducting an assessment of the viability of the specimens for continued research. The Autism Tissue Program’s website lists 100 research papers published in peer-reviewed scientific journals based on these donated brains.
Although it is estimated that 1 in 88 children in America have autism, little is known about its cause and what occurs in the brain to produce its characteristic communication difficulties, social challenges, and repetitive behaviors.
The Harvard brain bank has been accepting donated brains of people with autism for about two decades, so it probably will take years to rebuild the collection.
Normally, the brains in the Autism Tissue Program’s collection are equally distributed among the freezers, but had been concentrated in Freezer U in late April to allow program researchers easy access to the samples, Benes said.
After that research was done, staff members were busy with other work and hadn’t had time to return the samples to other freezers, she said. “It was earmarked to be redistributed to sites in various other freezers [soon].’’
Tissue bank staff members do not routinely open the freezers to check internal temperatures, because doing so stresses the $12,000 units and exposes the samples to warmer air.
The Harvard Brain Tissue Resource Center is the nation’s largest and oldest federally funded brain bank and has been storing brains for research for more than 35 years. In addition to neurological and psychiatric conditions, the bank also includes brains from people without any known brain problems to use for comparison. The bank has set up a toll-free number for people who are concerned about samples: 1-877-733-4634. To donate a brain, call 1-800-272-4622.
Pardo said he does not blame McLean. Most researchers have their own freezer horror stories, he said, citing his own five years ago.
“I don’t believe this is human error. I think this is just one of those glitches that sometimes happen,’’ he said.
This incident should be a call to action for other storage facilities and the federal government to pay more attention to freezer safety for the sake of science and donor families, said Stephen W. Scherer, director of the McLaughlin Centre for Molecular Medicine at the University of Toronto and a senior scientist at The Hospital for Sick Children in Toronto.
“The donors, they should be upset, they should realize that this shouldn’t happen, but this shouldn’t dissuade people from continuing to donate, because it is the most important resource that autism science has right now,’’ said Scherer, who has done genetic analyses of brains in the bank.
“If this was to push people from donating going forward, that’s the only thing that would [make this] a worse disaster.’’
Christopher LePoer of Westborough said the damage made him even more grateful to have donated his son Alexei’s brain to the collection, after the 4-year-old snuck out of the house last month and was discovered in a nearby swimming pool. Alexei’s brain was not damaged by the freezer failure, said Benes, who notified the family about the failure on Friday. Because it came in so recently, it had been stored in another freezer.
Christopher LePoer, who has six other children, none of whom has autism, said he was shocked and touched that his son’s brain was now one of those remaining in the brain bank, and therefore even more important to research.
Alexei didn’t speak other than to parrot what others had already said, LePoer said, but he always had a smile on his face. “I just keep thinking about the research and hopefully the information that they can get from him.’’