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Sculpting Nature's Masterpiece: The Big Brain

April 11, 2018

As Michelangelo lay on his back in the Sistine Chapel in Rome 500 years ago, moving his paint brush over the damp clay surface that would soon be transformed into his greatest masterpiece, he labored to see the shapes of his drawn figures, much as our ancestors labored in the dim light of the Chauvet caves in Southern France over 35,000 years ago. Those ancestors imagined scenes of wild animals and painted them with the newest tools of their age, creating their own spiritual and decorative environment for living. Their creation of art and tools soon led to other feats of the human imagination, including language, music, writing, the Renaissance, and the scientific method itself, which has eradicated polio on earth, built bridges and cell phones, and sent people to the moon and back.
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What was behind our ancestor's painting? More than their landscape or their culture, it was the "big brain" developing in humans that opened this path through history to Michelangelo's masterpiece. But the biological mystery remains - how did we get our big, folded brains that allowed us to zoom past other species in our creativity and mastery of our environment? Now we have a new dramatic clue.

A group at the Allen Discovery Center at Boston Children's Hospital and Harvard Medical School, led by Howard Hughes Medical Institute Investigator Christopher Walsh, along with Byoung-Il Bae's lab at Yale University, discovered evidence that a gene called "ASPM" (short for abnormal spindle-like microcephaly-associated) is behind the expansion of the cerebral cortex - the part of the brain responsible for cognition and other higher-order thinking in humans. The team used an ingenious method to remove, or knock-out, the gene in ferrets, and measure major reductions in brain volume. This suggests that the gene is responsible in part for the expanded brain size in humans, primates, and cetaceans (whales and dolphins).

The new finding suggests an evolutionary mechanism for brain expansion that works by controlling how strongly certain brain cells are attracted to a certain location in the developing brain, allowing the cerebral cortex to expand. This delicate dance of the brain cells had never been visible before, hidden away by the actions of the gene. As in great art that makes the unseen visible, this new study opens a new vista by making the unseen cell behaviors visible for the first time.

If this one gene can exert such a powerful effect on brain size, it offers new hope for unraveling the mystery of what makes us fully human.  One day, we may be able to construct the whole masterpiece of the human brain, with its control over our emotions, friends, and lives.

Learn more about the Allen Discovery Centers supported by The Paul G. Allen Frontiers Group.