A Literal Look into H.M.'s Mind

Discoveries take time, and scientists must be meticulous in the steps leading to these discoveries. I like to think of science as building a house. First you lay the foundation, the most important part of the process. Then you add to the foundation piece by piece, following a carefully laid out plan.

As you put the plan to action, and the house begins to take shape, you might need to make a few adjustments to make sure that the kitchen or family room is just right. Over time, the result is the house of your dreams, and while it might have taken a bit longer than you expected, all of the waiting suddenly becomes worthwhile.

Today, I'm going to follow up on a story I began to tell you last week, that truly embodies the discovery process. As you may remember, we were discussing the contribution that H.M. made to science during his lifetime. On December 2, 2008, H.M. died, and in his death he continues to contribute to science. He donated his brain so that researchers could continue to learn from his life.

By donating his brain, researchers can now examine the structures of his brain and relate it to observational data that they have collected over the past 50 years. They can look at the distribution of different components of these regions, and relate these structural observations to their behavioral notes. The possibility for advancing our understanding of the brain, damage to the brain, and the formation of memories is immeasurable.

The process of obtaining and preparing his brain for research has been a long, hard task. Researchers only get one shot at processing the tissue correctly. It began a year ago, where upon his death, H.M.'s brain was scanned with magnetic resonance imaging (MRI) to provide one final set of brain images while it was still in the skull. The brain was then removed and the tissue preserved for two months in formalin. Once the body dies, the tissue does as well. By preserving it, we insure that the tissue won't break down over time, but remains intact in a state akin to suspended animation.

Once completed, the preserved brain was moved to the University of California at San Diego as the newest addition to the Brain Observatory. The Brain Observatory is a fairly young research institute that acts as a library of human brain tissue. It is collecting donated brains from both healthy and diseased individuals, and hopes to create an online digital library of these specimens. This library will be available to anyone interested in the brain. Thus, this library will allow researchers to ask countless questions about the brain while allowing access to the public as well, providing a resource to provide further education about the brain and the scientific discovery driving our knowledge of this complex organ.

On December 3, 2009, after a year of preparation, the Brain Observatory was able to finally slice H.M.’s brain into smaller sections, a 30-hour procedure. This event was video-streamed online. Each slice measured 70 microns in thickness, resulting in anywhere from 26,000 - 36,000 slices for a human brain.

Some of these slices have been selected for digitizing. This entails mounting each slice on a slide and then staining each tissue with a particular dye. Each dye labels a specific component of the brain, such as brain cells (neurons) or support cells for the neurons. The slides will then be digitized and made available online to all who are interested. (To see the slicing process, click here).

By selecting a sampling of slices, rather than using them all, researchers create a series of images akin to a child's flip book. Just like these books, which tell a sequential story as you flip through, these sequential slide images provide researchers with a complete series of H.M.'s brain. An added advantage to using only a sampling of the brain slices for imaging is that the remaining tissue can be preserved and used for other experiments. This is a common technique that researchers use to "get more bang for their buck," since tissue like H.M.'s can be difficult to obtain.

It took a year - almost to the day - to even begin slicing H.M.'s brain for analysis. Digitizing the images will take months, or maybe longer. That may seem like a long time, but the discovery process is just beginning. This is the foundation for a house of research that is yet to come.