Brain Preservation Foundation Prize Update

The Brain Preservation Foundation aims at advancing and validating the state of the art for preserving the fine structure of the human brain, containing the data of the mind. This is a goal of great value for the cryonics industry, and for the possible plastination industry that might arise to be its competitor. All too many people, billions, will die before the advent and widespread availability of working rejuvenation therapies, and it is madness that so little is done to preserve these individuals for a chance at a future life, given the present existence of technologies that can achieve this goal. But that is the world we live in, and one of many things it is worth trying to change.

The Brain Preservation Foundation runs a technology prize to help accelerate and publicize progress in preservation technologies. Here is a recent update on the current batch of competitors:

Brain Preservation Prize competitor Shawn Mikula has just published the first ever paper demonstrating how an entire mouse brain can be preserved at the ultrastructure level for electron microscopic (EM) imaging of its entire connectome. As is well known to all electron microscopists, the traditional protocol for preparing brain tissue for EM imaging only works for small pieces of tissue. The key problem has been that the mix of chemicals used to preserve (and stain) the lipid membrane of cells, is prone to precipitation and barrier formation within the tissue. This has limited high-quality ultrastructure preservation and staining to depths of just a few hundred microns thick. Dr. Mikula's paper shows that this can be overcome by adding a high concentration of formamide to the mix. According to his paper this is sufficient to completely eliminate barrier formation allowing for uniform preservation and staining of an entire mouse brain.

Are these results sufficient for Mikula to win the mouse phase of our Brain Preservation Prize? The short answer is yes - if the claims made in the paper can be verified by our imaging then Mikula will be awarded the mouse phase of our prize. Another key question is whether his 'formamide' technique will be able to be scaled up to a large mammal - like the pig brain required for the final phase of our prize, or a human brain? Dr. Mikula is already working to procure high-quality glutaraldehyde perfused pig brains on which to test his technique. I suspect that to scale up to these large brains his protocol will need to be modified to include vascular perfusion.

I want to also touch on the significant progress that has been made by our other competitor team, 21st Century Medicine (21CM). 21CM's core mission is to develop a cryopreservation protocol sufficiently benign that whole, donated human organs could be vitrified (stored below -130 degrees Celsius without ice formation) and rewarmed when needed for transplantation. They have had great success showing that viability can be restored in vitrified slices of tissue. Unfortunately it is much easier to get cryoprotectant solutions into and out of half millimeter slices than whole brains. The whole rabbit brains that 21CM has perfused with cryoprotectant agents (CPA) for our prize have shown significant amounts of shrinkage due to dehydration from the high concentration and fast ramping of CPA used. Electron micrographs of this tissue are thus difficult to interpret and we have been unable to accurately assess the degree of ultrastructure preservation by this technique. 21CM has ideas on how to overcome this hurdle (which they believe to be one of evaluation rather than preservation) but progress has stalled on those experiments due to the expense involved.

Recently however, 21CM has begun a set of experiments which overcomes this dehydration and shrinkage issue in a very simple and inexpensive, but unorthodox, way. They perfuse the rabbit brain with glutaraldehyde fixative prior to perfusion with CPA and low temperature vitrification! This pre-fixation is of course completely incompatible with recovery of function by simple rewarming, but it has the effect of stabilizing the vascular system and tissue sufficiently to allow long duration room temperature perfusion of CPA. Initial results show that these brains (stored intact briefly at -135 degrees C) are not shrunken by this procedure and electron micrographs of brain ultrastructure appear "textbook-normal".



I didn't know this prize. It's a very important prize and probably I will donate in the future.

Posted by: Antonio at May 26th, 2015 6:28 PM

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