November 19, 2018

Mapping and Repairing the Brain: Implications for Global Health

By Anders GundersenResearch Assistant, HGHI

When it comes to the understanding of major disease progressions, humans have a profound grasp of the subject matter, at least more so now than at any point in history. However, our understanding of the brain and health conditions that specifically affect it lags behind what we know about the rest of the body. When we think about diseases and health conditions, such as Parkinson’s, Alzheimer’s, and Huntington’s diseases, they are characterized as being either untreatable or having treatments with significant negative side effects – likely a direct result of our poor understanding.

So how do we begin to understand them, and what can be done to improve our current treatments of brain-specific disorders?

First, we need to understand what is impeding our understanding. One issue with studying the brain is its spatial scale. Brain cells are massive relative to the size of typical cells, but their wiring – the neuronal connections guiding brain function – is tiny. Another issue is the time scale. The electrical impulses between neurons last for only milliseconds, while the progression of a disease such as Parkinson’s can be decades long. These discrepancies create confusion, and they highlight just how crude our current understanding of the brain is. But they do provide us with an important goal, which is to understand brain function at a level that makes it possible to treat such problematic brain disorders.

Ed Boyden is a Researcher and Professor of Biological Engineering and Brain and Cognitive Sciences at MIT, and his goal is exactly that; to turn scientific insights into technologies that are practically available and easily implementable in contexts where they can make an impact. It may seem rather broad, but that’s because it is. Global health is just one subject area that products of Dr. Boyden’s lab have influenced.

“One example of such technology influencing global health is the method of injecting an absorbent polymer into a tissue sample, adding water, and expanding the polymer while maintaining the tissue’s structural organization.”

Even the best microscopes have limited resolutions, meaning there will always be structures that a microscope cannot accurately image, but why spend money making microscopes better when you can simply enlarge your sample? Expansion pathology, as Dr. Boyden calls it, can be used in a host of circumstances, and has been.

“Clinicians have used it to more accurately diagnose early breast cancer lesions and nephrotic kidney disease.”

On top of this, it can be used to view structures that powerful microscopes can already see, but can make them large enough to be viewed on a standard light microscope, thus eliminating the need for costly and timely use of more powerful imaging technology (for which samples must often be sent out for third party analysis) in clinical contexts.

At the heart of Dr. Boyden’s mission is to take an idea or invention and make it as universally useful as possible. In the realm of expansion pathology, there are a few other ways it can be used. Dyes can be injected to tag proteins and view the foundational structure of any tissue by creating a “Brainbow,” machine learning algorithms can be applied to examine the breast cancer lesions that expansion microscopy made viewable, allowing artificial intelligence to make the diagnosis, and it can be done in reverse.

“By adding salt to the polymer, the sample will actually shrink instead of enlarge, which is applicable for the fabrication of tiny structures that would otherwise be astronomically expensive by comparison; a process that Dr. Boyden calls implosion fabrication.”

There are numerous other areas in which Dr. Boyden’s research group is involved, including Optogenetics, or using beams of light to trigger electrical activity in the brain. This has been shown in mice to trigger a “brain cleaning” protocol essential to the prevention of Alzheimer’s Disease. While still in its early stages, there is hope for this technique to non-invasively treat a number of neurological conditions, such as depression.

It is worth noting that Dr. Boyden was not only able to tactfully convert complex bench science into pieces easily digestible for our public-health-ears, but he was also able to convey that he is someone who aims to make a positive impact wherever possible and is eager to collaborate with those within and outside of his field. With his particularly effective combination of passionate, intelligent, and charming, he had us all hooked for more.