Most people salute the flag by respectfully placing their right hand over their heart, but not everyone does this. That's because some people (1 in 10,000) are born with their heart on the wrong side. Not only their heart, but all their internal organs are swapped left for right: liver, stomach, pancreas, gallbladder, spleen, colon, are all situated on the opposite side of the body from the familiar position depicted in anatomy books. There are no known medical disadvantages to having your organs on the "wrong" side, a condition called situs inversus, provided, of course, that your surgeon is advised of your situation prior to scrubbing up. This raises some interesting questions.

Why are people and most animals bilaterally symmetrical on the outside, but anatomically asymmetrical inside? It is not only anatomy. Behavior, brain function, and certain physiological processes show preferences for the left or right side of the body in both people and animals. Individuals within a population (both people and animals) have a dominant eye and ear (usually the right)-why? Language function, for example, is controlled by the left cerebral cortex in 97% of right-handed individuals and 66% of left-handed individuals. Certain diseases are more common on either the left or right side of the body-breast cancer is more common on the left, and so is immune hypersensitivity. (For an intriguing possible environmental contributor to left-sided cancer see:

There are also curious differences in body asymmetry associated with gender. The left foot tends to be larger in women but the right foot is usually larger in men. In people who are hermaphroditic, the ovaries are more than twice as often on the left side of the body and the testes are on the right. And if you were is perfectly normal for the left side of the scrotum to descend lower than the right, a pattern that is reversed if you are a left-handed male.

There are some deep mysteries here. Even if there is some advantage to having asymmetry in internal anatomy of brain and body structure, the more intriguing question is: Why aren't the chances of having your heart, language function, and handedness on the left or right side 50:50? Surely a random outcome is the most natural one to generate. There must be some very compelling reason for Nature taking sides to ensure that most of us are right-handed and only 1 in 10,000 of us has our hearts on the right. Are lefties different?

A connection between heart and brain?

A new study published in the current issue of The Journal of Neurological Sciences probes an interesting question: Will the left/right asymmetries in brain anatomy and function also be reversed in people with situs inversus, whose internal organs are the mirror image of normal? The answer goes to the heart of the question of whether dominance of a left/right brain function is genetically determined or environmental.

A skilled radiologist can see from a glance at your MRI whether you are left or right handed, because certain brain structures are either enlarged or reduced on either the left or right side of the brain. In the vast majority of people, the right frontal lobe juts forward ahead of the left frontal lobe. (Being right-handed myself, I had long ago noticed this asymmetry in my own brain scan, but like some of the other hidden asymmetries mentioned above, I had always assumed it was an idiosyncratic mild deformity. What a relief! No one knows why this is so or what difference it makes whether your left or right frontal lobe leads, but there are several other well-known anatomical asymmetries in different regions of the brain. Aya Ihara and a team of neurologists and radiologists working in Japan, report in the Journal of Neurological Sciences that in people with their hearts and other internal organs swapped left for right, the frontal lobe asymmetry in their brain was also reversed.

This finding means that whatever genetically controlled developmental mechanisms drive the asymmetrical arrangement of your guts, they also control this asymmetry in your brain. Using functional brain imaging the researchers also found that the language-dominant hemisphere was also swapped from the normal location in the left cerebral cortex to the right side in mirror image people. This reversal suggests a strong genetic component in controlling cerebral dominance of brain function-in this case language. One wonders about other functions predominating in either the left or right hemisphere-the Spock-like analytical logic of the left-brain vs. the creative, intuitive thinking of the right-brained artist. But in examining other brain regions with known anatomical asymmetries, the researchers found that many of them were not reversed in people with situs inversus. Thus, the plot thickens. There must be multiple region-specific mechanisms controlling left/right asymmetry in the brain in addition to the possibility of environmental influences. This returns us to the central question: does it matter which side of your brain does what?

A fishy finding
The dream experiment to answer this question would be to somehow reverse the normal asymmetry of the brain during embryonic development and then study the effects on the animal's brain function. That's exactly what Marnie Halpern and colleagues at the Carnegie Institution of Washington have accomplished. The researchers genetically modified zebrafish to reverse the normal asymmetry in part of the fish's brain (the parapineal region). Normally, the parapineal region is larger on the left side of the brain in 95% of zebrafish.

The researchers found that normal motor function was not altered in these mirror image zebrafish. An analysis of a wide variety of normal behaviors that favor the left or right side of the body were unaffected by reversing the normal asymmetry of this brain region. This included such things as normal swimming ability, escape responses and schooling behavior, and a strong preference for right-eyed dominance in examining novel scenes. But in a series of tests of social interaction between the mirror image fish and their normal kin, monitored by video camera and scored by computer, the researchers found that individuals with reversed brain asymmetry were extremely shy. The fish with their brain anatomy reversed hovered timidly at the sides of the fish tank like a fearful swimmer clinging to the edge of a public swimming pool, rarely venturing into the ruckus of other zebrafish darting all about the tank playfully. Their surprising finding suggests that neural circuitry connected to areas of the brain controlling fear, reward, and novelty seeking are altered when the asymmetry of their brain is reversed by genetic manipulation.

Although there is much to be explored concerning the left-right brain asymmetry in behavior, this research suggests that if we are to understand why handedness (and asymmetry of brains) is not 50:50 in a population, we must look beyond the simple mechanical operation of the brain and examine more subtle behavioral differences associated with handedness. These subtle differences in character traits could have advantages and disadvantages for individuals in a population. It must be important for the success of a species to have a minority of individuals with behavioral traits that are strengthened by mirror-image reversal from the "normal" arrangement of brain and body.

The lesson from Dr. Halpern's research (who happens to be left-handed) is not that left-handed people are shyer than right-handed people; clearly that is not the case. The findings show us that as a consequence of the simple fact that there are left/right asymmetries in brain structure and function, that if some of these circuits are swapped left for right, the reverse wiring will have consequences for the wide variety of complicated functions controlled by different brain circuits. This can include behavioral differences and character traits that affect social interaction, as well as other functions where a critical balance between novelty-seeking and fear are crucial.

The gene in zebrafish controlling development of asymmetry of the parapineal brain region was manipulated deliberately by scientists, but that does not mean the results are artificial. As suggested by the neuroimaging study of Dr. Ihara and colleagues, different genes control asymmetry of different regions of the brain. Normally Nature, through complex control mechanisms guided by eons of evolution, makes these genetic determinations individually every time a new life begins in every creature.

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