Autism: Banking on the future of our children

Everybody agrees that in order to find the cause(s) of autism, we have to focus our investigation on the brain. Only by looking directly at the brain can we achieve the high level of resolution required to visualize abnormalities of either cells or molecules depending on screening technique used. This is why scientists collect tissues, either frozen or fixed, in depositories called brain banks. When the number of samples is big enough for a research project, and the same can be matched to controls, tissues can be withdrawn and research done.

Given the importance of performing brain research in autism the National Alliance for Autism Research (NAAR) established an initiative in 1998 geared towards collecting postmortem tissue. The initiative was called the Autism Tissue Program (ATP) and I was one of its founding members. The Autism Tissue Program suffused into the research portfolio of Autism Speaks when these organizations merged together in 2006. The ATP does not work as a Brain Bank by itself but helps publicize the importance of tissue donation, collects informed consents, and helps establish appropriate diagnosis using research screening criteria.

Although the ATP is not a brain bank per se it works directly with the Harvard Tissue Resource Center in Boston, Massachusetts, to serve as its tissue repository. As of February 2012 the ATP listed 539 cases for all banks or private collections that have been noted as used in projects (Jane Pickett, personal communication, 2012). In all, since 2001 the ATP has supplied tissue for 122 projects in 15 countries yielding 100 published articles. A striking endeavor of the ATP has been the creation of a histological atlas comparing whole brain serial sections of 13 individuals with autism and an equal number of age-matched controls (Wegiel et al., 2010). A data access system provides information on existing tissues to allow investigators the sorting of cases (e.g., age, medication, hospitalization, seizure history). Information on individual cases, as well as on available tissue, can be found at http://www.atpportal.org (Pickett and London, 2005; Briacombe, Pickett, and Pickett, 2007).

In 2012 a freezer broke down at the Harvard Tissue Resource Center containing 54 of the 150 or so brain specimens that had been collected over the last 14 years. The two alarms on the freezer failed to warn nearby research personnel. It is unclear how the digital temperature readout also malfunctioned and for how long (days of weeks) were the samples left to thaw. By the time the malfunction was recognized, it was too late. Almost one third of the brains collected for researchers all over the world had been lost. Administrators of the brain bank did some hand waiving in an effort to save face. Their weak statement that some of the samples could still be salvaged for RNA work was pathetic at best and, as expected, never materialized. The fiasco is said to have set back research into autism by almost a decade.

An independent analysis commissioned by McLean Hospital (the academic facility housing the Harvard Tissue Resource Center) faulted the freezer’s digital controls for the loss of the brain samples. The backup system designed to detect freezer malfunctions also failed. Curiously enough, the company that manufactured the freezer (Thermo Fisher Scientific) was never able to reproduce the freezer malfunction and the circumstances surrounding this event.

It is a pity that nobody from the Harvard Tissue Resource Center took personal responsibility for the incident. Their public relations piece was aimed at minimizing damage, distancing themselves from the meltdown, and blaming the innanimate freezer. Pontius Pilates could not have done a better job at washing his hands from this whole affair.

As it so happens humans were responsible for the meltdown fiasco! Let’s forego the major coincidence that 2 alarms, a digital read out and back-up systems all failed simultaneously. Still, why were 54 brains of autistic individuals all stored in the same freezer when 24 freezer were available to distribute the samples?

Having managed 2 brain banks myself I always distributed samples having the same diagnosis among freezers just to prevent this eventuality. It seems that the samples were placed together for a demonstration to visitors from Autism Speaks. The visit occurred months before the meltdown after which the samples were never taken back to their original storage locations. Was this an oversight or was it more convenient to the staff of the brain bank? It is certainly easier sampling tissue for a series when all of them are found conveniently together in the same freezer. This and the lack of visual inspections makes me believe in the possibility of human error.

Brain donations are a sacred trust. Donors are giving away a piece of somebody they loved with the strict understanding that the tissue will be handled and used properly. Both the Harvard Tissue Resource Center and Autism Speaks broke the trust covenant with the donors. There was no attempt to take responsibility for the meltdown. Instead, both organizations exemplified a dismissive attitude. It was a foregone conclusion what would happen. The freezer was to blame.

References

Briacombe, M. B., Pickett, R., & Pickett, J. (2007). Autism postmortem neuroinformatic resource: The autism tissue program (ATP) informatics portal. Journal of Autism and Developmental Disorders, 37, 574–579.

Pickett, J., & London, E. (2005). The neuropathology of autism: A review. Journal of Neuropathology and Experimental Neurology, 64, 925–935.

Wegiel, J., Kuchna, I., Nowicki, K., Imaki, H., Wegiel, J., Marchi, E., Ma, S. Y., Chauhan, A., Chauhan, V., Bobrowicz, T. W., De Leon, M., Louis, L. A., Cohen, I. L., London, E., Brown, W. T., & Wisnieski, T. (2010). The neuropathology of autism: Defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathologica, 119, 755–770.

7 responses to “Autism: Banking on the future of our children

  1. I was depressed with the loss, the lack of transparency of the investigation, and the inane response from Autism Speaks. Writing the blog is part of my grieving process. Knowing that there are other people out there, like yourself, to share this concern makes me feel better.

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  2. Pingback: Autism Research: Distinguishing the good from the bad | Cortical Chauvinism·

  3. I totally agree!
    Personally I get very tired of appeals for my child’s brain when I see the lack of care regarding these specimens. If families make this sacrifice – and who among us would not prefer that our child (who has already suffered so much) to be buried intact- we need to see the same commitment to accountability on the part of these brain banks.

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  4. Thank you for your comments. I think that in my grieving process for the loss of the samples I got stuck in anger. If the process had been more transparent, if people had taken responsibility, if steps had been taken to avoid this in the future, I would have felt better.

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  5. I was so saddened by this, and shocked. I always wondered whether anything was salvaged. I am now collecting brains of animals with SIB and controls, and as my collection starts turning into a mini brain bank of it’s own, I realize that I may need to include a second freezer for my lab in my funding attempts, in order to split up this valuable resource.

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    • Unfortunately nothing at al was salvaged. What saddens me is that the people in charge never took responsibility for it. Furthermore, the government never took any steps–even right now the same brain bank is being included in an initiative to collect more brains. Sad indeed.

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