Brain Organoids Cultivate the Case for Human Exceptionalism

Mel Brooks’s horror comedy Young Frankenstein is one of my all-time favorite movies. 

Perhaps my favorite scene in the movie has Igor (pronounced EYE-gor)—played brilliantly by Marty Feldman—informing Dr. Frankenstein that he (Igor) gave the doctor a brain from someone named Abby Normal to transplant into the monster’s head. 

Here is the dialogue from that scene:

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 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?

All humor aside, a 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 NOVA1 gene and in the process created “Neanderthalized” minibrains.1

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. This pioneering work bears on the question of human exceptionalism and, consequently, carries important implications for the RTB human origins model.

Brain Organoids
Brain or cerebral organoids are three-dimensional cell cultures that could be loosely described as miniature “brains.” Brain organoids are grown from pluripotent stem cells that are coaxed into developing 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.

Figure: One Process for Growing Brain Organoids
Credit: Wikipedia

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 “minibrains” to compare the influence that the NOVA1 gene has on brain growth and development in modern humans and Neanderthals and Denisovans.

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

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

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 “Neanderthalized” brain organoids. 

A Comparison of Modern Human and Neanderthal Brain Organoids
To create the Neanderthalized brain organoids, the researchers used CRISPR gene-editing technology to convert the modern human NOVA1 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. 

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. 

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.

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.

Corroborating Studies
These results don’t 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.

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

These observed genetic differences help explain the brain shape differences displayed by modern humans and Neanderthals inferred from the skull and facial anatomy differences. As 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: 

  • Perception of stimuli 
  • Sensorimotor transformation (which plays a role in planning) 
  • Visuospatial integration (which provides hand-eye coordination needed for making art) 
  • Imagery
  • Working and long-term memory 

The brain organoid comparisons also explain the differences in the growth and development of the skull and face of Neanderthals and modern humans. For example, a team of paleoanthropologists from the Max Plank Institute for Evolutionary Anthropology in Germany determined that as Neanderthals develop from the time of birth to adulthood, their skull never enters the “globularization” phase.4 In contrast, at birth the skull of modern humans is elongated, like that of Neanderthal infants. However, by one year of age globularization of the modern human skull begins. This result indicates that brain growth and development follow a different trajectory in Neanderthals and modern humans.

A convergence of evidence indicates that significant cognitive differences exist between modern humans and Neanderthals and supports an emerging consensus among anthropologists that human beings are exceptional.

Human Exceptionalism
Though it has become unpopular in some circles to claim human exceptionalism, ample evidence shows that modern humans stand apart from all extant creatures (such as the great apes) and extinct creatures (such as Neanderthals). Those who argue for human exceptionalism believe that it arises from a unique combination of four qualities:

  • An ability to represent the world and abstract ideas with symbols
  • An ability for open-ended manipulation of symbols
  • Theory of mind
  • A capacity to form complex, hierarchical social structures

It is reasonable to think that this unique set of behavioral and cognitive capacities arises out of the unique features of modern human brain anatomy and development. These features are undergirded by unique versions of genes responsible for craniofacial features and unique patterns of expression for genes responsible for our neuroanatomy and physiology.

For someone who holds to a Christian worldview, the case for human exceptionalism aligns with the biblical view that human beings uniquely bear God’s image. Thus, human exceptionalism can be marshaled as scientific support for the biblical perspective on human nature and identity.

Modern Humans, Neanderthals, and the RTB Human Origins Model
RTB’s human origins model adopts the view that human beings bear God’s image and seeks to find support from the scientific evidence toward this end. But RTB’s model also seeks to account for the existence and natural history of hominins, including Neanderthals, from a biblical standpoint. Our model regards Neanderthals (and other hominins) as creatures made by God, and with no evolutionary connection to modern humans. These extraordinary creatures walked erect and possessed some intelligence, which allowed them to cobble together tools and even adopt a level of “culture.” However, our model maintains that the hominins were not spiritual beings made in God’s image. RTB’s model reserves this status exclusively for modern humans.

Based on our view, we predict that biological similarities will exist among the hominins and modern humans to varying degrees. In this regard, we consider the biological similarities to reflect shared designs, not a shared evolutionary ancestry. 

We also expect biological differences because, according to our model, the hominins would belong to different biological groups from modern humans. We also predict that significant cognitive differences would exist between modern humans and the other hominins. These differences would be reflected in brain anatomy and behavior (inferred from the archaeological record). According to our model, these differences reflect the unique presence of God’s image in modern humans and the absence of God’s image in the hominins.

The Muotri team’s cutting-edge work evinces the notion that humans are exceptional, consistent with the biblical claim that we bear God’s image but Neanderthals do not.

Our brains are, indeed, abnormal compared to the brains of Neanderthals and the other hominins. Yet, the abnormal features of our brains make us exceptional. And that is no laughing matter.


Brain Structure Differences between Modern Humans and Neanderthals

Genetic Differences between Modern Humans and Neanderthals


  1. Cleber A. Trujillo et al., “Reintroduction of the Archaic Variant of NOVA1 in Cortical Organoids Alters Neurodevelopment,” Science 371, no. 6530 (February 12, 2021): eaax2537, doi:10.1126/science.aax2537.
  2. Richard E. Green, “A Draft Sequence of the Neandertal Genome,” Science 328, no. 5979 (May 7, 2010): 710–722, doi:10.1126/science.1188021.
  3. Laura L. Colbran et al., “Inferred Divergent Gene Regulation in Archaic Hominins Reveals Potential Phenotypic Differences,” Nature Ecology and Evolution 3 (November 2019): 1598–1606, doi:10.1038/s41559-019-0996-x; David Gokhman et al., “Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan,” Science 344, no. 6183 (April 17, 2014): 523–527, doi:1126/science.1250368; David Gokhman et al., “Differential DNA Methylation of Vocal and Facial Anatomy Genes in Modern Humans,” Nature Communications 11 (March 4, 2020): 1189, doi:10.1038/s41467-020-15020-6.
  4. Philipp Gunz et al., “Brain Development after Birth Differs between Neanderthals and Modern Humans, Current Biology 20, no. 21 (November 9, 2010): PR921–R922, doi:10.1016/j.cub.2010.10.018