{"id":310005,"date":"2022-01-19T05:00:00","date_gmt":"2022-01-19T13:00:00","guid":{"rendered":"https:\/\/reasons.org\/?p=310005"},"modified":"2022-01-19T05:00:00","modified_gmt":"2022-01-19T13:00:00","slug":"brain-organoids-cultivate-the-case-for-human-exceptionalism","status":"publish","type":"post","link":"https:\/\/reasons.org\/adam-eve\/early-humans\/brain-organoids-cultivate-the-case-for-human-exceptionalism","title":{"rendered":"Brain Organoids Cultivate the Case for Human Exceptionalism"},"content":{"rendered":"\n

Mel Brooks\u2019s horror comedy Young Frankenstein<\/a><\/em> is one of my all-time favorite movies. <\/p>\n\n\n\n

Perhaps my favorite scene in the movie has Igor (pronounced EYE-gor)\u2014played brilliantly by Marty Feldman\u2014informing Dr. Frankenstein that he (Igor) gave the doctor a brain from someone named Abby Normal to transplant into the monster\u2019s head.\u00a0<\/p>\n\n\n\n

Here is the dialogue from that scene:<\/p>\n\n\n\n

Dr. Frankenstein: Igor, would you mind telling me whose brain I did put in?
Igor: And you won’t be angry?
Dr. Frankenstein: I will not <\/em>be angry.
Igor: Abby . . . someone.
Dr. Frankenstein: Abby someone. Abby who?
Igor: Abby . . . Normal.
Dr. Frankenstein: Abby Normal?
Igor: I’m almost sure that was the name.
Dr. Frankenstein: Are you saying that I put an abnormal brain into a seven-and-a-half-foot-long, fifty-four-inch-wide gorilla! Is that what you are telling me?<\/p>\n\n\n\n

All humor aside,\u00a0a large team of collaborators led by neuroscientist Alysson Muotri from UC San Diego performed a cutting-edge study that could have come from the annals of tales of horror. They grew brain organoids (organ analogues) in the lab from cells that were genetically modified to have the Neanderthal version of the\u00a0NOVA1\u00a0<\/em>gene and in the process created “Neanderthalized” minibrains.1<\/sup><\/p>\n\n\n\n

It wasn’t maniacal purposes that motivated the researchers. Instead, the team performed these experiments to determine if there are differences in the brain structure and development (hence, cognition) between Neanderthals and modern humans, with the goal of trying to understand what separates us from other species.\u00a0This pioneering work bears on the question of human exceptionalism and, consequently, carries important implications for the RTB human origins model.<\/p>\n\n\n\n

Brain Organoids<\/strong>
Brain or cerebral organoids are three-dimensional cell cultures that could be loosely described as miniature \u201cbrains.\u201d Brain organoids are grown from pluripotent stem cells that are coaxed into\u00a0developing into the different cell types of the nervous system by exposing the cultured cells to a variety of different growth factors. Lab workers can get the cell cultures to grow into three dimensions by cultivating them in a rotating bioreactor. These cultures take several months to grow and develop. Because the cultured cells lack a blood supply their size is limited to about 3 to 5 mm. Depending upon the growth conditions, brain organoids can develop into structures that resemble the cortex, the choroid plexus, retina, meninges, and hippocampus, for example. As the brain organoids grow and develop, their architecture, number of cell layers, and cellular diversity increase over time.<\/p>\n\n\n\n

\"\"<\/figure><\/div>\n\n\n\n

Figure: One Process for Growing Brain Organoids<\/strong>
Credit: Wikipedia<\/em><\/p>\n\n\n\n

Brain organoids have already proven to be a helpful research tool for investigators studying brain growth and development and neurological disorders, and for pursuing drug development. The Muotri research team’s work can be added to this list. They used these \u201cminibrains\u201d to compare the influence that the\u00a0NOVA1<\/em>\u00a0gene has on brain growth and development in modern humans and Neanderthals and Denisovans.<\/p>\n\n\n\n

The NOVA1 <\/em>Gene<\/strong>
The research team chose to focus on the impact of the NOVA1 <\/em>gene because when they compared modern human genomes with those of Neanderthals and Denisovans, they learned that the NOVA1 <\/em>gene variant found in modern humans is distinct from the version of this gene found in Neanderthal and Denisovan genomes.\u00a0<\/p>\n\n\n\n

This difference is intriguing because NOVA1<\/em> is a master regulator that influences the expression of other genes that impact brain development through a mechanism known as alternate splicing. NOVA1<\/em> plays a role in synapse formation and mutations to this gene have been implicated in neurological disorders.<\/p>\n\n\n\n

The genetic distinction alone is enough to conclude that the brains and, possibly, the cognition of modern humans and Neanderthals and Denisovans differed. But the researchers went one step further by creating and comparing the anatomy and physiology of modern human and \u201cNeanderthalized\u201d brain organoids.\u00a0<\/p>\n\n\n\n

A Comparison of Modern Human and Neanderthal Brain Organoids<\/strong>
To create the Neanderthalized brain organoids, the researchers used CRISPR gene-editing technology to convert the modern human NOVA1<\/em> gene in human-induced pluripotent stem cells into the Neanderthal\/Denisovan version. In turn, they used these genetically engineered induced pluripotent stems cells to grow brain organoids.\u00a0<\/p>\n\n\n\n

The team noticed significant differences between the modern human and Neanderthalized brain organoids. The modern human brain organoids were larger, smoother, and more spherical than the Neanderthalized brain organoids. The Neanderthalized cell cultures displayed rougher, more complex surfaces. Cell proliferation was slower in the Neanderthalized brain organoids than in their modern human counterparts. The Neanderthalized brain organoids also possessed a greater number of apoptotic cells.\u00a0<\/p>\n\n\n\n

The gene expression profile of the two brain organoids was different when characterized at 1 month and 2 months. These differences involved genes that are known to play a role in neural development. The neurons of the two brain organoids also displayed differences in the profile of synaptic proteins.<\/p>\n\n\n\n

While caution is in order when interpreting these results, they strongly suggest that the brains of modern humans and Neanderthals developed differently and displayed significantly different structural features that likely impacted cognitive capacities.<\/p>\n\n\n\n

Corroborating Studies<\/strong>
These results don\u2019t stand in isolation. Other studies have identified genetic differences between modern humans and Neanderthals that would reasonably affect brain growth and development and, in turn, cognitive capacities. For example, genome-wide comparisons of the Neanderthal and modern human genomes have identified different versions of genes that play a role in skull morphology (shape, form) and cognitive development.2\u00a0<\/sup><\/p>\n\n\n\n

Molecular anthropologists have also inferred gene expression differences in Neanderthal and modern human genomes for (1) coding regions implicated in neurological and neuropsychiatric disorders in modern humans, and (2) genes that play a role in facial and vocal tract development.3<\/sup><\/p>\n\n\n\n

These observed genetic differences help explain the brain shape differences displayed by modern humans and Neanderthals inferred from the skull and facial anatomy differences.\u00a0As it turns out, the modern human skull shape is unusual and distinct compared to the skulls of hominins such as Neanderthals. Hominin skull shape was elongated along the anterior-posterior axis. But modern human skull shape is globular, with bulging and enlarged parietal and cerebral areas. The modern human skull also has another distinctive feature: the face is retracted and relatively small. The skull shape difference impacts the shape of the modern human brain and the relative sizes of different brain regions. Many anthropologists believe that these anatomical features help explain modern humans’ advanced cognitive abilities. For example, the parietal lobe of the brain is responsible for:\u00a0<\/p>\n\n\n\n