Key Difference in Developing Human and Neanderthal Brains

Good things take time. Or at least that is what the adage claims.

It’s true when it comes to whiskey. Good whiskey takes time. It has to age. I don’t drink, so I don’t have firsthand experience sipping fine whiskey. But, as a chemist, I can tell you that I am fascinated by the chemical processes that produce whiskey.

Making whiskey—cooking grains in water, allowing the cooked grain to ferment, and then distilling the mix—can take as little as a week. But making good whiskey takes years. After distillation, whiskey is transferred to an oak barrel to age—for a minimum of three years. The best whiskey is aged in barrels for up to 25 years. (After 25 years in a barrel, the quality of the whiskey doesn’t improve.) The walls of the charred oak barrel remove impurities from the whiskey and introduce compounds that give whiskey its characteristic flavors. Aging also darkens the whiskey and leads to the evaporation of some of the alcohol, making the whiskey smoother and more mellow.

Recently, a research team from Germany learned that, like fine whiskey, brain development takes time. The investigators generated evidence that the neural stem cell division process takes longer in modern humans than it would have in the developing Neanderthal (and Denisovan) brain.1 (These stem cells form neurons and macroglial cells in the developing neocortex.) The researchers believe that this time difference impacts brain development. The longer time spent in cell division reduces the number of chromosome segregation errors, presumably leading to healthier, more robust brains for modern humans compared to the brains of Neanderthals (and Denisovans).

This study adds to the growing list of differences in brain anatomy and brain development between modern humans and Neanderthals, supporting the idea that modern humans are cognitively superior compared to archaic humans such as Neanderthals and Denisovans. It also aligns with the notion of human exceptionalism, which is a key feature of the RTB biblical creation model for human origins.

What Makes Modern Humans “Human”?
One of the goals of physical anthropology is to understand our origins and discover what, if anything, makes us unique as modern humans. Along these lines, anthropologists compare the biology and behavior of modern humans with other hominins such as Neanderthals. The availability of high-quality genomes for Neanderthals and Denisovans makes it possible to identify genetic similarities and differences between us and these now extinct archaic humans.

These genetic comparisons are invaluable and have identified several genetic features unique to modern humans, including differences in the genes that code for the proteins: KIF18A, KNL1, and SPAG5. These three proteins play a role in cell division, specifically during chromosome segregation. 

Neanderthals, Denisovans, and chimpanzees all share identical versions of these three proteins. On the other hand, the modern human versions are unique.

The genes that code for these three proteins are expressed at high levels in the developing neocortex. (This brain region is unique to mammals and is the seat of sensory and motor function.) The neocortex is significantly larger in modern humans than in the great apes and many of the hominins found in the fossil record. The larger size can be explained (at least, in part) by an increased number of neocortical stem cells and progenitor cells. (In the developing brain, these cells are precursors to neurons and macroglial cells.) These two cell types also proliferate more rapidly in the developing human brain.

These finds prompt the question: Are these specific genetic differences meaningful? That’s what the German researchers sought to determine.

Before we discuss the details of their study, it may be helpful to some readers to review the cell cycle and the cell division process called mitosis. Readers familiar with these two biological processes can skip ahead to the section entitled The Study.

The Cell Cycle and Mitosis
Right after the cell division process is completed, the newly formed daughter cell enters the G1 (gap 1) phase of the cell cycle. During the first stage of the cell cycle, the cell experiences growth. After the G1 phase, the cell enters the S (synthesis) phase, at which time DNA replication takes place. Following the S phase, the cell continues the growth process (the G2 phase), readying itself for mitosis (cell division).

Credit: Shutterstock

During the prophase—the first phase of mitosis—the chromatin in the cell’s nucleus condenses into chromosomes. This phase is followed by the prometaphase, during which time the cell division proteins begin to assemble. During metaphase, the replicated chromosomes line up along the metaphase plane (an imaginary plane located near the center of the nucleus before it dissolves). During the anaphase the chromosomes break apart at the centromere, with sister chromosomes pulled by the mitotic apparatus toward the cell’s opposite poles. During telophase the nuclear envelope forms around each set of chromosomes. Finally, during cytokinesis, the cell cleaves into two daughter cells.

The Study
The German research team wanted to understand if the differences in the gene sequences for KIF18a, KNL1, and SPAG5 proteins had any biological consequences. To accomplish this objective, they carried out a series of experiments involving brain organoids. 

Brain or cerebral organoids are three-dimensional cell cultures. 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 these cultured cells lack a blood supply, their growth becomes limited to about 3 to 5 mm. Depending on the growth conditions, brain organoids can develop into structures that loosely resemble different brain regions. The architecture, number of cell layers, and cellular diversity of the brain organoids increase over time.

In the first experiment, the research team created modern human and chimpanzee brain organoids. They learned that the apical progenitor cells found in the modern human brain organoids spend more time in the metaphase than those found in chimpanzee organoids. (Apical progenitor cells generate the types of neural cells found in the developing cortex.)

This time difference has important consequences. During cell division, a longer metaphase gives the chromosomes more time to align at the metaphase plane, ensuring greater accuracy when the chromosomes are pulled apart during anaphase. For this reason, the researchers observed a greater frequency of chromosome segregation errors in the cells found in the chimpanzee brain organoids than those found in modern human brain organoids.

The next experiment involved mice. The researchers used CRISPR gene editing to “humanize” the gene sequences of the mice KIF18a, KNL1, and SPAG5 proteins. (The gene sequences of these proteins in mice are the same as those for the corresponding chimpanzee, Neanderthal, and Denisovan genes.) They discovered that the apical progenitor cells of “humanized” mice spend more time in metaphase than the same cells found in the brains of wild-type mice.

Next, the researchers used CRISPR gene editing to “Neanderthalize” the gene sequences for the KIF18a, KNL1, and SPAG5 proteins in the stem cells used to grow modern human brain organoids. As expected, this change led to a shorter metaphase for the apical progenitor cells.

The next set of experiments was designed to assess the impact of changes in the duration of the metaphase for the CRISPR-gene-edited apical cells. The researchers observed fewer lagging chromosomes in the anaphase for (1) “humanized” mouse apical progenitor cells compared to wild-type mice, and (2) apical cells found in unaltered modern human brain organoids compared to apical cells in “Neanderthalized” brain organoids.

The researchers think that the results of their experiments indicate that the differences in the gene sequences of the KIF18a, KNL1, and SPAG5 proteins in modern and archaic humans are significant. The cells in the developing neocortex of Neanderthals and Denisovans would have been prone to a greater number of chromosome segregation errors than the developing neocortex of modern humans. These errors would have made modern human brains healthier than archaic human brains and would have rendered modern human populations more robust than archaic human populations. 

Also, it is not unreasonable to think that the increased number of chromosome segregation errors in the developing brains of archaic humans led to cognitive differences between modern humans and Neanderthals (and Denisovans). The results of this current study align with previous studies that: (1) have identified significant structural differences between the brains of modern humans and Neanderthals, and (2) have uncovered significant differences in gene sequences and gene expression patterns between modern humans and Neanderthals for genes that encode proteins that play a role in neural development and, in turn, cognitive capacities. (See Resources.)

In other words, there’s a growing body of evidence indicating that significant cognitive differences exist between modern humans and Neanderthals. This evidence helps fuel an emerging consensus among anthropologists that human beings are exceptional.

Modern Humans Are Exceptional
Though it makes many people uncomfortable to claim that modern humans are exceptional, mounting evidence shows that modern humans are unique compared to all extant creatures (such as the great apes) and extinct creatures (such as Neanderthals) with respect to our cognitive capacities. Those who argue for human exceptionalism believe that it arises from a unique combination of four qualities all modern humans possess:

  • an ability to represent the world and abstract ideas with symbols,
  • an ability for open-ended manipulation of symbols,
  • theory of mind, and
  • a capacity to form complex, hierarchical social structures.

It’s reasonable to think that this unique set of behavioral and cognitive capacities arises out of: (1) the unique features of modern human brain anatomy and development, (2) unique versions of genes responsible for our craniofacial features and neural development, and (3) unique patterns of expression for genes responsible for our neuroanatomy and physiology.

Modern Humans, Neanderthals, and the RTB Human Origins Model
The concept of human exceptionalism has an integral place in the RTB biblical creation model for human origins.

RTB’s model adopts the view that human beings bear God’s image and seeks to find support for that view from the scientific evidence. The scientific case for human exceptionalism can be marshaled to make the case that human beings do, indeed, bear God’s image. 

Our model goes one step further, seeking to account for the hominins, including Neanderthals, from a biblical standpoint. RTB’s model regards Neanderthals (and other hominins) as creatures made by God, without any evolutionary connection to modern humans. These extraordinary creatures walked erect and possessed some level of 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. Additionally, we 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 archeological 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.

Toward this end, the latest work by the team of German researchers aligns with these key predictions of the RTB model.

I’ll drink to that. Cheers!


Who Was Adam? by Fazale Rana with Hugh Ross (book)

Thinking about Evolution by Anjeanette Roberts, Fazale Rana, Sue Dykes, and Mark Perez (book)

Brain Structure Differences between Modern Humans and Neanderthals

Neanderthal Brains Make Them Unlikely Social Networkers,” by Fazale Rana (article)

Blood Flow to Brain Contributes to Human Exceptionalism,” by Fazale Rana (article)

Differences in Human and Neanderthal Brains Explain Human Exceptionalism” by Fazale Rana (article)

Did Neanderthal Have Brains to Make Art?” by Fazale Rana (article)

When Did Modern Human Brains—and the Image of God—Appear?” by Fazale Rana (article)

Brain Organoid Studies

Brain Organoids Cultivate the Case for Human Exceptionalism” by Fazale Rana (article)

Genetic Differences between Modern Humans and Neanderthals

Ancient DNA Indicates Modern Humans are One-of-a-Kind,” by Fazale Rana (article)

New Genetic Evidence Affirms Human Uniqueness,” by Fazale Rana (article)


  1. Felipe Mora-Bermúdez et al., “Longer Metaphase and Fewer Chromosome Segregation Errors in Modern Human than Neanderthal Brain Development,” Science Advances 8, no. 30 (July 29, 2022): eabn7702, doi:10.1126/sciadv.abn7702.