If you undertake the journey into the sacred cave,

you will never grow old the way other people do (Part 1).

The summer after my sophomore year in high school I enrolled in a Guided Research Project and was paired with a neuroscientist at the Section on Neuropsychology at the National Institutes of Mental Health in Bethesda, Maryland, Dr. Mortimer Mishkin. When we first met, I wanted to research the phenomenon of “imprinting” as described by Konrad Lorenz, but Dr. Mishkin suggested I study the function of the corpus callosum instead.

The corpus callosum is the great cerebral commissure that bridges between the right and left hemispheres of the brain, connecting the cerebral cortex of the two halves of the brain and integrating the two. In humans, it consists of about 200 million neurons. This central anatomical structure puzzled pioneers of neuroscience such as Vernon Mountcastle and Warren McColluch; in the 1960s “split-brain studies”— by R.W. Sperry, Karl Pribam, and Michael Gazzaniga, of patients whose corpus callosum had been surgically severed to reduce grand mal epileptic seizures—dramatically illustrated the lateral specialization of hemispheric function.

Sectional drawing of the right hemisphere of a human brain, from an old German anatomy textbook. The corpus callosum is at center, inked in magenta.

During my summer of research, I met Dr. Mishkin one evening a week to show him my progress.  After some initial floundering, Dr. Mishkin admonished me that I had to do the work, and so I pulled myself together and dutifully took a bus downtown each day with my mother’s old leather briefcase, mounting the front steps to enter the great rotunda of the Library of Congress, where I could methodically call up specific articles from the scientific literature and make notes on five by eight index cards.  As the summer progressed, Dr. Mishkin taught me how to edit my work, and in the end I produced an illustrated 60-page report surveying all the scientific literature on this part of neuroanatomy.

The following summer, after my junior year, I worked in the lab and was introduced to a range of lab work.  The primary means of research at that time was the study of brain injuries. In our lab, we performed surgical ablations of brain tissue on Rhesus macaques, and then studied how these monkeys performed on specificly designed tests. After the period of testing, the monkeys were sacrificed, and their brains were removed, carefully sliced on a microtome, and mounted on slides so that the extent of surgical damage could be double-checked, a practice called histology. So this summer, I assisted in surgeries, animal testing, and histology, and learned about the experiments being conducted in the lab.  Numerous eminent scientists from all over America and the world would come to visit our lab, and I truly had a front-row seat to watch science in action.

Wisconsin General Test Apparatus. I rolled monkeys to a darkened test room muffled by a white noise generator. I would show the monkey in which of two wells I hid the peanut, then lower the opaque screen for a specific time delay, then raise the screen to see if the monkey could remember where the peanut was hidden—so-called “delayed response test.” Testing sessions might consist of 30 peanut events; right and left hidings followed a randomly generated printed schedule. Normal monkeys can readily learn to do this, but specific brain lesions impair this ability. [After Harlow, 1938.]

During this time Dr. Mishkin designed an experiment he nicknamed “Stefan’s study” and I was put in charge of testing several monkeys who I also got to name—Nietzsche, Kafka, Camus, Dostoyevski, all heroes of mine (though I was sorry to see what our surgeries would do to them). In addition to being an editor of several leading journals, Dr. Mishkin was noted for his localization studies of the frontal cortex, which seems responsible for higher associative thinking, and had devised a number of clever experiments differentiating sub-regions of this brain area, but of course it still remained a question what was actually going on in there.

During my senior year of high school, I left school early after my classes in English, Physics, and Biology, walked over to NIH, and spent the rest of the day in the lab. The summer after I graduated, Dr. Mishkin managed to rustle up an $800 grant from a drug company so that I was able to be paid for the first time.

Why do I bring all this up? Well, first of all, it’s fun to recall! And secondly, this was the time when I first began to think about balance. In this case, the balance between the left and right hemispheres of the brain, and more generally about the symmetries we find in Nature, especially in life-forms.  My central principle in the workings of things.

Making gargoyles today, for example, I find myself fashioning things two-by-two—two wings, two eyes, two ears—parts that are identical in the flat and take on handedness as they are bent into three dimensions. Nature, too, must find a duplicative approach like this efficient in some way.

One of the most striking features of neural organization is that it is organized contralaterally. That is, generally speaking, the left hemisphere of the brain controls the right side of the body, and the right hemisphere controls the left side of the body. Amazingly, this is true in all vertebrates throughout 500 million years of evolution, so there must be a profound reason for weaving neural pathways this way (not that anybody knows yet what that reason is). There are some exceptions: for instance, the olfactory nerves of each nostril project directly back to the olfactory bulbs on the same side; and the cerebellum, a small “sub-brain” beneath the back of the brain (the cerebellum is colored in bright cyan and grey in the sectional drawing above), projects neurons ipsilaterally, to the same sides of the cerebrum and body. But the auditory nerves of each ear project to the temporal lobe of the opposite hemisphere, the right visual field projects on the left occipital lobe and the left visual field, on the right, and the sensorimotor strips of each hemisphere control the limbs on the opposite side.

This mirror-world crossing-over is not a real asymmetry, of course, but since the large size of the corpus callosum allows the white matter of the two hemispheres to communicate extensively, this appears to “free up” cortical tissue to specialize unilaterally. For example, we know from brain-injured patients that highly localized areas on the frontal lobe of the left hemisphere —called Broca’s area and Wernicke's area—are essential for the production of speech and comprehension of language. In fact, the left hemisphere, which seems essential to the execution of language, is often referred to as the “dominant” hemisphere.

We are all familiar with handedness: some of us are right handed and others are left handed. You may be less aware that you have a “master eye”—the eye you use to sight a camera or a rifle, which also influences whether you bat right or left in baseball, surf or skateboard “goofy-footed,” kick with your left or right foot, or spin on skates to your right or left. Most people’s dominant eye is on the same side as their dominant hand, but not always, a case called “cross-dominance.”

So how do the two halves of our brains work together? In later years, when I would visit Dr. Mishkin, he bemoaned how few student scientists who went through our lab actually entered neuroscience. In my case, it was simply due to “a turn of events.” But those were the stone ages, and with today’s advances in imaging technology many of the old assumptions about brain function are being revisited and revised:

Dr. Mishkin, now 93 years old, eventually became the director of our laboratory, and for his lifetime of achievements was awarded a National Medal of Science by President Obama in 2009.