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Not medical advice.
Nick talks with Dr. Christopher Walsh about what actually differs between a human brain and a chimpanzee or mouse brain, and why that is still hard to name as a phenotype. Walsh, a neurologist and geneticist at Boston Children’s, walks through scale and association cortex, then the genome-first path: human accelerated regions, genes such as ASPM that can shrink a human brain toward chimpanzee volume, and mosaic mutations that come with building a large cortex.
Forthcoming work he describes finds that about a quarter to a third of late-fetal cortical neurons carry genetic defects, most of them gone by birth, with smaller defects still edited out through adult life. The conversation also covers why the developing brain overproduces neurons, how that editing relates to autism and other highly heritable disorders, and why most human-specific change is in gene regulation rather than new proteins.
ABOUT THE GUEST: Christopher Walsh, MD, PhD is Chief of the Division of Genetics at Boston Children’s Hospital, a neurologist, and an investigator of the Howard Hughes Medical Institute. His lab studies how the human brain develops and how it evolved.
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PRACTICAL TAKEAWAYS:
“The brain is done at 25” is an MRI-scale claim. Neurons are mostly in place much earlier. Myelin still comes in through the teens and twenties. Synapses, and some genetically imperfect neurons, keep changing after that.
A mosaic chromosome finding on IVF or amniocentesis can be limited to the placenta. Walsh’s point is that early embryos are routinely mosaic, and several correction paths exist, including dumping abnormal cells into the placenta.
Most of the 80–100 new mutations a child carries relative to the parents are inconsequential. Trouble is concentrated in a smaller set of dosage-sensitive genes, which is why most kids still turn out fine.
SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.
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