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School of Education at Johns Hopkins University-Why Einstein's Brain?

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Why Einstein's Brain?

by Marian C. Diamond, Ph.D.

The excitement of discovery is infectious. One new enticing finding leads continuously on and on and on. What discovery led me to study the ratio of glial cells to neurons in Einstein's brain back in the early 1980s? The answer is not found in a single, simple statement but is based on decades of work on how the environment affects the anatomy of the brain.

Reconstructing the series of events that led up to the final cell counts was a challenge, but roughly here is the sequence: (1) a comment by a friendly professor 25 years previously, (2) the results showing that brains from rats living in enriched conditions possessed more glial cells per neuron than brains from rats living in impoverished conditions, (3) a photograph from the journal Science showing a cardboard box sitting beside a desk with a caption stating that Einstein's brain was in that box, (4) a quiet afternoon during which everyone appeared to be busy but me so I had time to think, and (5) superb technical and statistical assistance.

In general, one could now say simply that 1 + 2 + 3 + 4 + 5 = the difference in the glial/neuron ratio in Einstein's brain compared with the average glial/neuron ratio in a sample of other human male brains. Let me now expand upon each part of the equation.

  1. One day in my teaching laboratory, a world renowned professor of neuroanatomy, Professor Gerhardt von Bonin, mentioned that he thought the inferior parietal cortex was more highly evolved than the prefrontal cortex. This idea was contrary to what is normally accepted. Since the number of glial cells per neuron increases as one ascends the phylogenetic tree, I reasoned that the more highly evolved area in the human brain should have more glial cells per neuron.
    From 11 human, male, preserved brains, I removed a sugar cube-size piece from right and left prefrontal and inferior parietal cortex, giving 44 samples. Thus, we had a data base of human cortical glial/neuron ratios. We learned the frontal cortex did have more glial cells/neuron than the parietal cortex.

    By now you must be wondering just what are nerve cells and glial cells. Only these two kinds of cells are responsible for all of the human behavior generated by the brain.

    What then is a nerve cell? A nerve cell is the major signally unit of the nervous system. A stimulus comes to the body, stimulates a nerve cells which sends the message to other nerve cells. There are 100 billion nerve cells in the brain, as many as stars in our galaxy.

    Each of these nerve cells can contact as many as 10,000 other nerve cells. Though a great variety of sizes and shapes exists, all share four common features: dendrites and a cell body, an axon hillock, an axon and axon terminal. The dendrites and the cell body are the receptive component; the axon hillock is the integrative component, the axon is the conductile component and the axon terminal is the output or secretory component. Through the wiring setup during development, and modified by learning, these nerve cells can generate complex behavior.

    What then are glial cells? Glial cells are the metabolic and structural support cells for the nerve cells. In general the nerve cells do not divide after birth, for example, in the outer layers of your brain you do not get new nerve cells after you are born.

    You must live your full one hundred years with the same nerve cells, but the glial cells do divide. Glial cells are more numerous than nerve cells. The glial/neuron ratio steadily increases with phylogeny with the preponderance of glia over neurons reaching its peak in humans.

    Don't ever sell glial cells short. What are some of their important functions ?

    a) They play an active role in establishing and maintaining the fundamental patterns of neuron circuits.
    b) They produce growth and trophic factors, playing a key role in regeneration and plasticity.
    c) Some play an active role in the formation of myelin which speeds impulse conduction. Myelinated fibers conduct more rapidly than unmyelinated fibers.
    d) Some glial cells respond to rapid repair of myelin in demyelinating diseases such as MS and ALS.
    e) Glial cells play a crucial role in immunological responses to various infections and toxic agents.
    f) Glial cells increase in number when nerve cells grow with enrichment.
    With these definitions you can now appreciate how important glial cells are to serve the nerve cells.
  2. Back to our story. In the early 1960s, the laboratories both of Joseph Altman at Purdue and ours had found that the cerebral cortex from rats living in enriched environments had more glial cells per neuron than the cortex from rats living in impoverished environments. Active cortical neurons needed more support cells.
  3. The graduate students had clipped a photo of the box with Einstein's brain from Science magazine and attached it to the laboratory wall. The caption mentioned that the brain was in Kansas. A daily exposure to its message was available for all who entered the laboratory.
  4. I was sitting by myself in my husband's office at UCLA one day with nothing to do but think. I wondered if I could obtain only four pieces of Einstein's brain comparable to the ones already studied. I picked up the phone and called the University of Kansas Department of Anatomy and learned that a Dr. Thomas Harvey, Missouri, had Einstein's brain. Why he took the brain to Missouri I do not know. Who was Thomas Harvey? He was the pathologist at Princeton at the time of Einstein's death. He had had the keen foresight so that when Einstein died, Harvey fixed his brain rapidly in formaldehyde to preserve the nerve cells before they disintegrated. Twenty-five years later I began negotiating by calling Thomas Harvey in Weston Missouri every six months for about three years before I received the four precious blocks of tissue in my mail box in the Life Sciences Building. When the package first arrived, the only person in the office was the office manager. I said rather breathlessly, " Guess what I have here in this box, Jerry? " He sort of gave me half of his attention and when I said "parts of Einstein's brain," he replied, "Oh, come on Marian." Believe me, after that when I asked him what I had received in the mail on another day, he certainly gave me his full attention.
  5. In a mayonnaise jar filled with fluid, here were my four sugarcube-size pieces of Einstein's brain. Evidently, Harvey had cut up the brain and embedded the pieces in a substance called celloidin which harden almost like plastic. Having the brain in this condition was ideal for my purposes because we wanted to count cells under the microscope. To do this it was necessary to make thin slices, 6 micra in thickness (a micron is one thousandth of a millimeter). In order to cut at this precise level of thickness the tissue had to be processed in celloidin. Preserving the brain in this manner does not allow for some other methods of examination such as refined chemical analysis. We were extremely fortunate to have the tissue preserved in a way that proved ideal for us. We had our 44 pieces of brain from the 11 normal males. We could now compare the glial neuron ratios in the 4 pieces from Einstein's brain with the 44 pieces from the normal males. With the help of an excellent technician and statistician (a scientist rarely works alone), we learned that in all four areas, Einstein had more glial cells per neuron than the average man, but in only the left inferior parietal area did he have statistically significantly more.

What is the function of this inferior parietal area? We studied both the inferior parietal and prefrontal association areas of Einstein's brain because such regions are known to be concerned with "higher" mental functions. These regions do not directly receive primary sensory information but rather, as their name implies, they "associate" or analyze inputs from other brain regions. The association cortices are the last domains of the cortex to myelinate, indicating their comparatively late development. Lesions in the inferior parietal regions result in gross impairment in writing, spelling and calculation. One mathematician with a lesion in the inferior parietal area found it difficult to draw or write formulae and could not use a slide rule. Another lost the versatility of imagery and the capability for complex thinking.

It is not possible at present to identify with a high degree of specificity the independent functions of these zones. Undoubtedly with higher resolution obtained from modern technology, such as more advanced MRI and PET scans than presently available, greater specificity will be localized in the future.

In our study, the differences in glial/neuron ratios were unusually large, but we only had one Einstein to compare with 11 males. The findings would be more valid if we had 11 Einsteins, but at least the study was a first step that no one had taken previously.

About the Author

Marian C. Diamond, Ph.D. is a neuroanatomist in the Department of Integrative Biology ay the University of California, Berkeley. She is co-author of Magic Trees of the Mind. She is also a member of New Horizons for Learning's International Advisory Board, advising us on the development of the News from the Neurosciences area of the website.

Why Einstein's Brain? is the text of a lecture delivered by Dr. Diamond at Doe Library on January 8, 1999.

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