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Brains thaw at Harvard repository

It’s a scientist’s nightmare come true. Molecular information stored within 147 brains was lost when a freezer failed at Harvard’s brain bank at McLean Hospital in Belmont, Massachusetts. Two alarm systems monitored the freezer’s temperature, but clearly, that wasn’t enough.

Most devastating is the fact that one-third of the brains derived from deceased people with autism. Donors are in short supply, and therefore autism researchers who rely on brain tissue for insight into the neurological disease consider these brains precious. Although the DNA within the samples probably remains intact, RNA and proteins were destroyed as the temperature warmed from −80° Celsius to 7° Celsius over three to four days in late May, according to a spokesperson at the centre.

“It’s a tragedy for the families who donated the brains, and it must be heartbreaking for the researchers to have lost this tissue,” says Ron Zielke, director of the National Institute of Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders at the University of Maryland in Baltimore. This and the Harvard centre at McLean are the only repositories in the United States that distribute autism brain tissue to researchers around the world. “Only about five to six brains become available per year, so when you lose a significant number like this, that means years worth of donations,” Zielke says.

Human mistakes and technological errors caused the disaster. Normally, to mitigate any risk of freezer malfunction, the employees disperse the autism samples between 24 freezers, says Francine Benes, director of Harvard’s centre. However, in April, almost one-third of the autism collection was consolidated into a single freezer in preparation for a visit from the Autism Tissue Program, which distributes brain samples to investigators who request it. Staff from the programme completed their work on 1 May, but the staff kept the brains consolidated because they were busy. “We were barraged with requests for samples, and the tissues seemed to be safe in that freezer, so we kept them there,” explains Benes. “Twice a day, our staff look at the electronic panel outside of the freezer that tells you its temperature and status, and it read, OK.”

The freezer, a 2004 model from Fisher Scientific, comes with a built-in alarm that sounds when the temperature drops significantly, and a second independent monitor automatically calls five staff at the centre on their mobile phones in succession. “None of our devices were triggered,” says Benes. On 31 May, an investigator opened the freezer door to retrieve brains, and felt the shock of no frozen air. After staff at Autism Speaks, the non-profit organization based in New York that leads the Autism Tissue Program, alerted the families of donors, the Boston Globe covered the mishap.

In a few weeks, an investigation into the freezer breakdown will be made public. Although foul play will be considered, 30 days of security-camera tape suggests that’s not the issue, Benes says. Refrigeration systems commonly break down. So, the big question concerns the sensors that watch temperature.

Freezers at the NICHD Brain and Tissue Bank are equipped with monitors that sound an alarm when the sensors act up. For example, freezer temperatures usually fluctuate within a fraction of a degree and the monitor will notice when a sensor stabilizes on a single digit, explains James O’Malley, a national sales manager for Amega Scientific, which manufactures the AmegaView surveillance system at the NICHD. “I don’t know what happened [at McLean], but it sounds like the sensor system might have locked in at a reading, that can happen when a temperature probe goes bad,” O’Malley speculates. The Amega system also monitors its own power, and sends alerts and updates by e-mail and text messages, in case something goes wrong with phone lines. “It’s all about redundancy,” says O’Malley.

Our freezers don’t implement this higher level of monitoring, at least to the best of my knowledge, says Peter Paskevich, director of research administration at McLean Hospital. Still, he says, the centre values redundancy. “Every one of our freezers has emergency power in case the electricity fails, and we have CO2 tanks in each freezer to keep the space cool for about 24 hours if the refrigeration fails,” Paskevich says. But here, the refrigeration and two sensors went down at an odd time when many brains were stashed in a single, unlucky spot. “Would you think that everything would fail at once?” says Paskevich.

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    Ron Zielke said:

    Although the thawing of these autism brains means that they will not make their maximum contribution to research, it is important to note that these brains have already contributed extensively to research. Brains donated to the Autism Tissue Program and the NICHD Brain and Tissue Bank for Developmental Disorders have been the source of thousands of samples for autism research resulting in over 150 research publications on autism. It is not unusual that samples from any one brain may have already been shipped to 10 to 50 researchers. Although the brains could have supplied more samples in the future if they had not thawed, their donation has already made meaningful contributions to autism research. Post mortem research has provided information on the cellular structure, neurotransmitters and their receptors, oxidative stress and multiple other areas that may lead to pharmacological interventions in the future.
    Because of the significant findings from studies with post-mortem tissue, it is vital that families of autistic family members consider tissue donation. I estimate that less than 10% of the possible brain donations actually occur. Tissue donation is a personal decision which has to meet the emotional needs of the family, but if a family wants to donate tissue after a loved one dies, both the NICHD Brain and Tissue Bank (1-800-847-1539) and the Autism Tissue Program (1-877-333-0999) will work with the family to achieve this goal.

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