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Neanderthal minibrains vs human minibrains

Neanderthal minibrains vs human minibrains


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Minibrains are lab-grown balls of neurons that have some (distant) semblance to a brain.

One study showed that cells with the genome replaced with Neanderthal genes produced mini-brains that were "smaller and bumpier" than the Sapien mini-brains, suggesting a difference between the two species.

The trouble is, Sapiens and Neanderthals are extremly similar species (much closer than humans and chimps). Interbreeding made most humans today 2% Neanderthal. It seems very unlikely the difference in neural cyto-architecture would be so fundamental that it shows up in such a simple system as a minibrain. And if it was, it seems unlikely that the hybrid's brains would even be functional.

Another hypothesis is that the neanderthal genome or epi-genome was damaged by thousands of years of exposure. I would expect a fresh Chimp genome to produce similar mini-brains to a human because the species are very close and similar cognitively up to toddler age.

Is genetic damage rather than species-difference the more likely explanation for these minibrain differences?


Lab-Grown Neanderthal Minibrains Reveal How They’re Different From Humans’

So, you might have heard: Scientists figured out how to grow miniature brains out of stem cells. Cool, right? Well, now they managed to grow Neanderthal brains, too. As a result, we have more of an idea of why our populations flourished, helping us become the dominant species on Earth, while theirs faltered.

The short version: it comes down to the way the brain structures itself as it develops. Though the research has not yet found its way into a peer-reviewed publication, a presentation on the work from earlier this month (and reported by Science Magazine) noted that some key differences suggest that Neanderthals couldn’t communicate quite as goodly as we can able to. Their brains simply weren’t wired to handle it.

Humans aren’t very fast or strong. Our kneecaps are a cruel evolutionary joke and our hair makes no sense. Let’s not even get into those weird, saggy punching bags that hang off the front of some of us.

And despite all that, we conquered the world. The common understanding of how we did it, strengthened by these new Neanderoids (that’s what the researchers call the lab-grown minibrains) is that we are able to communicate and socialize. We developed massive tribes and communities that made us more powerful than any other animal out there.

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When the Neanderthal minibrains self-assembled in the lab, they resembled a popcorn shape. The human minibrains, on the other hand, were much more spherical, according to Science Magazine. The scientists behind the project noted that the the way the neurons developed and connected with one another resembled the way some neurons develop in people with Autism Spectrum Disorder. They weren’t drawing parallels between Neanderthals and people with autism, they clarified — r ather, the similarities in brain structures may suggest that the ability to communicate with others works differently there than with humans with different neural structures.

Minibrains grown from pluripotent stem cells give scientists a chance to better understand the brain and how it develops. And they give researchers a chance to test new pharmaceuticals on a (simplified) human model, which yields better results than animal tests.

And while these minibrains are still considered laboratory tools, scientists are already working out ethical guidelines for how they should be treated, should we someday develop the ability to grow more advanced brains in a lab.

But we aren’t there yet. Scientists, to be clear, didn’t grow a living Neanderthal — they used stem cells to carry Neanderthal genes to grow a tiny, simplified version of a brain-like organ.


Geneticists Are Growing Neanderthal "Minibrains" in a Lab — Here’s How

They're sprouting new theories about the link between humans and Neanderthals.

In order to study the brains of Neanderthals, researchers have mostly relied on analyzing fossilized skulls to infer what they may have contained. But according to geneticist Alysson Muotri, Ph.D., a new technique is emerging among his team of researchers at University of California, San Diego: growing Neanderthal minibrains.

At June’s UCSD conference called “Imagination and Human Evolution,” Muotri revealed that his team had used stem cells containing Neanderthal DNA and the genome editor CRISPR to create pea-sized lumps that could mimic the cortex, or outer layer of the brain. The controversial technique was first reported in Science on Wednesday.

To grow these minibrains, Muotri focused on a protein-coding gene known as NOVA1. Because this gene controls splicing of RNA from other genes, NOVA1 likely helped produce more than 100 proteins in Neanderthal brains, a great starting-off point for recreating one today.

Using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a tool for editing genomes and altering DNA sequences, Muotri’s team was able to take human skin cells and manipulate their genomes to turn them into pluripotent stem cells, capable of giving rise to several different cell types.

Conveniently, NOVA1 in a Neanderthal has only one base pair that is different from the modern human’s NOVA1, so CRISPR could allow the scientists to target NOVA1 in the human stem cells and swap in the Neanderthal base pair. Thus, the newly “Neanderthalized” stem cells were formed to grow into minibrains, or organoids that can reveal details surrounding the structure and function of an actual Neanderthal brain.

It takes months to grow a minibrain from Neanderthalized stem cells, but the process has already given Muotri new insight. His team of scientists found that neuronal cells within a Neanderthal’s NOVA1 migrate more quickly within the minibrain as it forms.

While the findings of this controversial technique have not yet been published, Muotri thinks this experiment will not only elucidate the links between human and Neanderthal brains, but could help scientists better identify distinctions or defects in human neuronal development.


Neanderthal-inspired ‘minibrains’ hint

Robert Gorter: when one studies evolutionary biology, one may ask the (philosophical) question: “what was first: the chicken or the egg?” Or, in other words, was there a plan to develop a physical body as we have today (Homo Sapiens) or could/would our body develop of out of an ad random process and at some point, we came out of it as the most adapted creature. One could argue that there was a plan to ultimately, crate the Homo sapiens as we know it and which would bare self-consciousness? Then, we could consider the animal world around us as try-outs to come to a best-possible completion. Evolution has produced astonishing number and variety in insects. Approx. 6 million insects have come into existence. One can get the feeling that early on in evolution, insects were used to intensively “experiment.”

Evolution of insects

The most recent understanding of the evolution of insects is based on studies of the following branches of science: molecular biology, insect morphology, paleontology, insect taxonomy, evolution, embryology, bioinformatics and scientific computing. It is estimated that the class of insects originated on Earth about 480 million years ago, in the Ordovician, at about the same time terrestrial plants appeared. Insects may have evolved from a group of crustaceans. The first insects were land-bound, but about 400 million years ago in the Devonian period one lineage of insects evolved flight, the first animals to do so. The oldest insect fossil has been proposed to be Rhyniognatha hirsti, estimated to be 400 million years old, but the insect identity of the fossil has been contested. Global climate conditions changed several times during the history of Earth, and along with it the diversity of insects. The Pterygotes (winged insects) underwent a major radiation in the Carboniferous (356 to 299 million years ago) while the Endopterygota (insects that go through different life stages with metamorphosis) underwent another major radiation in the Permian (299 to 252 million years ago).

Most extant orders of insects developed during the Permian period. Many of the early groups became extinct during the mass extinction at the Permo-Triassic boundary, the largest extinction event in the history of the Earth, around 252 million years ago. The survivors of this event evolved in the Triassic (252 to 201 million years ago) to what are essentially the modern insect orders that persist to this day. Most modern insect families appeared in the Jurassic (201 to 145 million years ago).

In an important example of co-evolution, a number of highly successful insect groups — especially the Hymenoptera (wasps, bees and ants) and Lepidoptera (butterflies) as well as many types of Diptera (flies) and Coleoptera (beetles) — evolved in conjunction with flowering plants during the Cretaceous (145 to 66 million years ago).

Many modern insect genera developed during the Cenozoic that began about 66 million years ago insects from this period onwards frequently became preserved in amber, often in perfect condition. Such specimens are easily compared with modern species, and most of them are members of extant genera.

Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, and speciation) that produced the diversity of life on Earth. In the 1930s, the discipline of evolutionary biology emerged through what Julian Huxley called the modern synthesis of understanding, from previously unrelated fields of biological research, such as genetics and ecology, systematics and paleontology.

The investigational range of current research widened to encompass the genetic architecture of adaptation, molecular evolution, and the different forces that contribute to evolution, such as sexual selection, genetic drift, and biogeography. Moreover, the newer field of evolutionary developmental biology (“evo-devo”) investigates how embryogenesis, the development of the embryo, is controlled, thus yielding a wider synthesis that integrates developmental biology with the fields of study covered by the earlier evolutionary synthesis.

Evolution is the central unifying concept in biology. Biology can be divided in various ways. One way is by the level of biological organization, from molecular to cell, organism to population. An earlier way is by perceived taxonomic group, with fields such as zoology, botany, and microbiology, reflecting what were once seen as the major divisions of life. A third way is by approach, such as field biology, theoretical biology, experimental evolution, and paleontology. These alternative ways of dividing up the subject can be combined with evolutionary biology to create subfields like evolutionary ecology and evolutionary developmental biology.

More recently, the merge between the biological science and applied sciences gave birth to new fields that are extensions of evolutionary biology, including evolutionary robotics, engineering,[1] algorithms,[2] economics,[3] and architecture.[4] The basic mechanisms of evolution are applied directly or indirectly to come up with novel designs or solve problems that are difficult to solve otherwise. The research generated in these applied fields in turn contribute to progress, especially thanks to work on evolution in computer science and engineering fields such as mechanical engineering.[5]

What is it about DNA that makes the human brain “human?” Seeking to understand how our complex brains evolved, researchers have now switched a single human gene out for its Neanderthal counterpart in brain tissue grown in a lab dish. Changes to the resulting organoid reveal the role this gene may have played in ancient—and modern—brain development.

“This is amongst the first studies of its kind to investigate how specific changes in the DNA of modern humans influences brain development,” says Debra Silver, a developmental neurobiologist at Duke University who was not involved with the work. Although past work has used similar approaches to examine the differences between the brains of humans and other primates, the new work looks at an even closer relative, where differences are expected to be more subtle.

Reconstruction of a Neanderthal male

Neanderthals are archaic humans that lived from 500,000 years ago to about 11,700 years ago, interbreeding with our species, Homo sapiens, for much of that time. Their brains were about as big as ours, but anthropologists think they must have worked incredibly differently, because in those hundreds of thousands of years, Neanderthals never achieved the sophisticated technology and artistry humans have.

Reconstruction Neanderthal female (Museum on Neanderthal in Germany)

To explore what differences might exist, neuroscientist Alysson Muotri at the University of California, San Diego (UCSD), and his team first compared the genomes of modern humans with those of Neanderthals and Denisovans -another archaic human- reconstructed from excavated bones. They found 61 genes for which modern humans all had one version and the archaic humans had another.

Reconstruction to express the differences between a Neanderthal and a current human (Neanderthal Museum Germany)

His team then used the gene-editing tool CRISPR on stem cells derived from human skin cells to modify a gene, NOVA1, known to regulate the activity of other genes during early brain development. Switching out just one DNA base turned that gene into a Neanderthal NOVA1. Next, the researchers grew little clusters of brain cells called organoids, with and without the Neanderthal version, and compared them. Organoids are a far cry from real brains, and those with a single Neanderthal gene can by no means be considered fully “Neanderthal” organoids, cautions Madeline Lancaster, a developmental biologist at the Medical Research Council’s Laboratory of Molecular Biology.

These brain organoids carry a Neanderthal gene. (MUOTRI LAB/UNIVERSITY OF CALIFORNIA, SAN DIEGO)

Nonetheless, changing that one gene altered the organoid’s growth, appearance, and electrical activity, Muotri and his colleagues report today in Science (February 2021). The modified organoid matured faster, yielding an uneven, complex surface instead of a smooth one. Its electrical activity revved up more quickly than that of its counterpart, and the connections between nerves, the synapses, depended on slightly different versions and interactions of key proteins. What’s more, the electrical impulses were not as synchronized as in the fully modern human organoid. “It looks almost like anything they could [test] showed a difference,” says Arnold Kriegstein, a developmental neurobiologist at the UC San Francisco School of Medicine (UCSF).

The results, which held up in tests using human stem cells derived from a different donor’s skin cells, “tell us their brains probably worked in a different way than [ours] do,” Muotri says.

Researchers are excited but cautious about these results. “It is amazing that by changing a single amino acid in a single protein, one creates an effect that is visible even in how the organoids look in the microscope,” says Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology. But because organoids represent only the earliest stages of development, “it’s difficult to know how [the changes] would manifest in a more mature brain,” Kriegstein says.

Although they can be powerful, organoids “are a difficult tool,” adds Wolfgang Enard, an evolutionary geneticist at Ludwig Maximilian University of Munich. They can be tricky to grow and their characteristics are often hard to replicate across batches.

But Muotri is undaunted. Now that they have the protocol nailed down, he and other UC San Diego researchers have launched a center to expand their study of archaic human gene variants. Having teased out the effects of one Neanderthal gene, they’re ready to tackle the other 60.


The Stem Cellar

The evolution of modern day humans has always been a topic that has been shrouded in mystery. Some of what is known is that Neanderthals, an archaic human species that lived on this planet up until about 11,700 years ago, interbred with our species (Homo sapiens) at some point in time. Although their brains were about as big as ours, anthropologists think they must have worked differently due to the fact that they never achieved the sophisticated technology and artistry modern humans have.

Since brains do not fossilize, it has been challenging to see how these two early human species have changed over time. To help answer this question, Dr. Alysson Muotri and his team at UC San Diego created so-called “mini-brains” using stem cells and gene editing technology to better understand how the Neanderthal brain might have functioned.

For this study, Dr. Muotri and his team closely evaluated the differences in genes between modern day humans and Neanderthals. They found a total of 61 different genes, but for this study focused on one in particular that plays a role in influencing early brain development.

Brain organoids that carry a Neanderthal gene.
Image courtesy of the Muotri Lab and UCSD

Using gene editing technology, the team introduced the Neanderthal version of the gene into human stem cells. These stem cells, which have the ability to become various cell types, were then used to create brain cells. These cells eventually formed brain organoids or “mini-brains”, 3D models made of cells that can be used to analyze certain features of the human brain. Although they are far from perfect replicas, they can be used to study physical structure and other characteristics. In a previous CIRM funded study, Dr. Muotri had used “mini-brains” to model an autism spectrum disorder and help test treatments.

Dr. Muotri and his team found that the Neanderthal-like brain organoids looked very different than modern human brain organoids, having a distinctly different shape. Upon further analysis, the team found that modern and Neanderthal-like brain organoids also differed in the way their cells grow. Additionally, the way in which connections between neurons formed as well as the proteins involved in forming these connections differed between the two organoids. Finally, electrical impulses displayed higher activity at earlier stages, but didn’t synchronize in networks in Neanderthal-like brain organoids.

According to Muotri, the neural network changes in Neanderthal-like brain organoids mimic the way newborn primates acquire new abilities more rapidly than human newborns.

In a news release from UCSD, Dr. Muotri discusses the next steps in advancing this research.

“This study focused on only one gene that differed between modern humans and our extinct relatives. Next we want to take a look at the other 60 genes, and what happens when each, or a combination of two or more, are altered. We’re looking forward to this new combination of stem cell biology, neuroscience and paleogenomics.”


Neanderthal Phrenology, by Smut Clyde

Previous generations didn’t have the video games and social media and digital communication that they could conjure into dire warnings about mental deterioration and the reversion of the young peoples into Morlocks. Instead they made do with the unprecedented speed and easy availability of automotive transport, which would inevitably change the skulls of drivers into a more elongate shape, as a form of streamlining, with concomitant effects upon the mind, heralding a a future of brutish, degraded, degenerate mentalities when the asylums would overflow. ***

A natural train of thought – the local commuter train, not the fast express service – leads us to Kochiyama et al. (2018), who recently compared the Neanderthal and the Anatomically Modern Skull, to delineate the differences in shape and infer how this must have impacted on Neanderthal cognition. By “the Neandertal Skull” we mean four individual crania, each reassembled from fragments with state-of-the-art ‘guesswork’ methods to interpolate the missing bits and the same for the four representatives of Cro-Magnon. Later steps in the guesswork logic assume that the volumes of brain lobes are linked rigidly to the shape of the skull, and only radial deformations are possible: for instance, if someone’s forehead is compressed, the frontal lobe behind it must be smaller.

Proof that Neanderthals were unable of any intellectually stimulating social interactions, from Kochiyama at al, Sci Reports 2018

This explains the absence of frontal-lobe functioning among Mayans, other pre-Columbian cultures, East Germanic tribes, French peasants, and umpteen other groups known to modify their infants’ cranial profiles with head-binding for aesthetic purposes and status enhancement.

Anyway… Kochiyama et al. are described as pioneers in this burgeoning new field of Quantified Neanderthal Phrenology:

But as SR co-author Naomichi Ogihara told Scientific American, they are the first to actually digitally reconstruct Neanderthal brains.
“Our method allows estimation of the shape and volume of each brain region, which is quite impossible just by analyzing the endocranial surfaces.”

The claim to precedence is true as long as one ignores a slightly-earlier and less-well-publicised study (Neubauer, Hublin and Gunz, 2018). Isn’t it always the same? You wait for ages for a paper on Neandertal Phrenology and then two come along at once.

Neanderthal brains were not sufficiently globular. They likely believed in flat-earth theory and were unable to build a classic 3-spheres-and-a-carrot snowman. From Neugebauer et al Science Advances 2018

It is quite likely that the notion of extrapolating from skull shape to brain function had occurred to many people in the past, but had previously been rejected as patently daft.

In the Golden Age of craniometry in the early 1900s, skull-caliper hobbyists and gentlemen dilettante-anthropologists liked to divide populations into those with bradycephalic and dolichocephalic heads… long narrow heads (the latter kind) were more common in Europe, and therefore superior. But no-one argued that the owners of wider, brachycephalic skulls also possessed larger temporal lobes and would be more skilled in language, memory and facial recognition.*

Now both studies fall within a recognised literary genre in which novelists and evolutionary psychologists and other authors of fiction speculate about the mental differences between Neanderthals and their anatomically-modern contemporaries, and about the racial-memory Original-Sin scars inflicted on the latter by the trauma of having to exterminate the former. Authors follow a roughly 30-year cycle, explaining the current revival of this literary tradition: see Wells 1921 Harness 1953 Golding 1955 Kurtén 1978 Auel 1980.**

It goes without saying that Neanderthals must have differed in some respect, for they are no longer extant and there must be some reason for this. Also no-one wants to miss an opportunity to talk about ourselves and ‘human nature’ in the guise of talking about what we are not. If Neanderthals had not existed then it would be necessary to invent them.

Avid Riddled readers (is there any other kind?) will recall the beginning of this revival with the ‘visual brain‘ theory from 2013. In this, evolution assigned so much of the Neanderthal cortex to processing visual information (in compensation for the lower level of lighting in their Northern European habitat of icecaps and blizzards and cave-bears) that no brain-power was left for social-cognition skills and they could not cooperate in groups. Larger eye-sockets were adduced as evidence, and explained as an adaptation to capture more photons. This is SCIENCE so evidence is not merely ‘provided’ or ‘tabled’, it is adduced.

It is a very silly theory even by the relaxed standards of Riddled, and I can only suppose that it was accepted into Proc. Roy. Soc. Bbecause the third author was Dunbar (of the eponymous Number). Some people might think that if Neanderthals had enlarged light-trap tarsier eyes, this would do away with the need for special night-sight neural processing requiring half their cortex… but those people are the same nay-saying skeptics and cavilling pedants who also point out that Neanderthals lived all across the Levant and were not exclusively adapted to Northern Europe (that’s just where a lot of caves are where their bones turned up), so their opinions can safely be ignored.

Press-release-regurging science churnalists at the time dwelt on the elongation of the Neanderthal side of the comparison:

And in fact, Neanderthal skulls suggest that the extinct hominids had elongated regions in the back of their brains, called the “Neanderthal bun,” where the visual cortex lies.
“It looks like a Victorian lady’s head,” Dunbar told LiveScience.

Here at the Riddled Institute of Impure Science and Gratuitous Innuendo, we attribute this cerebral elongation to the extreme rapidity of the Paleolithic forms of transport favoured by Neanderthals (or perhaps they practiced head-binding), but other scholars are slow to accept this explanation.

Neubauer et al. (2018) went along with the elongation / globular narrative to account for Cro-Magnon ascendancy. In contrast, Kochiyama et al. (2018) (returning to them at last!) struck off in a new direction. Unable to find any convincing cerebral differences between their Neanderthal and Cro-Magnon reconstructions, they kept fishing, and eventually reported that modern brains have larger cerebellums. Or cerebella, as the case may be. This in turn led them to the startling conclusion that the cerebellum, previously regarded as responsible for ‘muscle sequencing / coordination’ computations for routine movements, must in fact be the centre of our highest cognitive qualities. I am not making this up:

“A new scientific analysis shows that human skulls are shaped in a way that suggests they encased brains with slightly larger cerebellums than Neanderthals. The cerebellum is a brain region associated with activities like planning, adapting to new environments, switching between tasks, and building social relationships”.

“And because cerebellar volume is linked to abilities like cognitive flexibility, language processing, and working memory capacity, the scientists argue larger cerebellar hemispheres may have helped humans survive and adapt to a dangerous world while Neanderthals could not.”

This is the point where the usual pedants and critics object that the volume and neural density of the cerebellum also tend to be greater in men than in women. Which probably means:

Neanderthals were as unorganized, antisocial, unimaginative, multi-task failures as modern-day womenfolk!

After all that, it is a relief to turn to a recent paper with a different approach to the question of Neanderthal craniometry: Gregory et al. (2017) introduced the useful concept of the “NeanderScore” and reconstructed that prototypal skull shape by measuring living people and ranking them by their proportion of Neanderthal ancestry. High NeanderScorers tended to have bigger brains, especially at the back in an “occipito-parieto-temporal patch”, and were especially endowed in the region of the intraparietal sulcus (perhaps best described as important for visual-motor skills).

Gregory et al Sci Reports 2017, Figure 2. NeanderScore related brain changes in the intraparietal sulcus. Structural variation of the intraparietal sulcus (IPS) related to percentage of Neanderthal-derived SNPs (NeanderScore). Left and middle show lateral and posterior views of the right IPS on the average brain surface, illustrating the anatomical convergence of the associations of NeanderScore with greater sulcal depth (orange p < 0.05 FWE-corrected), gray matter volume (blue p < 0.005), and white matter volume (yellow p < 0.005).

“It should be noted that we did not find associations of NeanderScore with smaller frontotemporal volumes 38 or shortened anterior extension of the temporal lobes 13 , as might have been hypothesized from previous cranial analyses of H. neanderthalensis…”

The most recent, best-founded reconstructions of Neandertal appearance have an uncanny resemblance to Paula Modersohn-Becker‘s portraits of herself and husband Otto. Not that there’s anything wrong with that.

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* There is also Vendramini’s provocative idea that Neanderthals were superior predators while their anatomically-normal contemporaries were merely prey to be stalked and consumed. This provides a possible explanation for the extinction of the Cro-Magnons. As for Kurup and Kurup’s audacious but not particularly coherent notions about the autistic Neanderthal civilisation of Dravidian Lemuria, the less said the better.

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About Leonid Schneider

Independent Science Journalist and Cartoonist. Formerly molecular cell biologist. My academic CV at: https://orcid.org/0000-0002-6204-9470


2021, A Space Odyssey

In July 2019, UC San Diego and NASA announced to shoot Muotri’s minibrains up to the International Space Station (ISS). Why? Apparently this somehow has to do with the space colonisation programme, Muotri himself spoke of his concerns for the astronauts procreating and having maxibrain babies on interstellar travels while in zero gravity. The university press release explained:

“The first-ever project of its type is dedicated to T. Denny Sanford, a longtime advocate of stem cell research whose partnership has supported Muotri’s work as well as several key research entities, including the Sanford Consortium for Regenerative Medicine and UC San Diego Sanford Stem Cell Clinical Center.

On July 21, UC San Diego will partner with Space Tango to launch a payload of living brain organoids into space,” said Erik Viirre, MD, PhD, professor of neurosciences and director of the Arthur C. Clarke Center for Human Imagination. “The study results will have enormous implications for space colonization and human health. We hope to determine if humanity can reach into the broader cosmos.

So you see what impressive kind of donor support Muotri receives, next to the support from his academic bigwig peers like Gage, Kriegstein and Pääbo. Muotri himself described his space experiments as “groundbreaking” because false modesty is not his thing. A true expert on biomedical sciences and space technology as quoted:

““It’s been far too long that we’ve failed to grasp the importance of gravity in organ and embryonic development,” said David Brin, PhD, science fiction author, UC San Diego scholar-in-residence and advisor to NASA’s Innovative and Advanced Concepts program. “Our future path, in becoming an interplanetary species, could depend on discoveries that we’ll begin making with this mission.””

So proud of Alysson Muotri, scientist and professor @UCSDMedSchool!
This is awesome… very exciting work – brain organoids in a rocket – can't get better than that! @UCSDHealth @UCSanDiego @ResearchUCSD #neuroscience https://t.co/fnYFs4frPo

&mdash Dr.JoAnn Trejo-Unity, Decency, Science &Yes, Truth (@joann_trejo) July 18, 2019

The minibrains were not yet sent into space as promised, not on 21 July 2019 or later on. Maybe it all was a publicity stunt. However, in April 2020, UC San Diego announced that Muotri and other UCSD science entrepreneurs received a $5 million grant from NASA to establish a stem cell lab in space. Muotri’s grant partner Catriona Jamieson was quoted:

We envision that the next thriving ecosystem of commercial stem cell companies, the next nexus for biotechnology, could be created 250 miles overhead by the establishment of these capabilities on the ISS

On July 21, more than 100 “mini-brain” organoids grown @UCSanDiego will be launched to the @Space_Station to study microgravity’s effect on neural development—and investigate prospects for nurturing life beyond Earth. @ucsdhealth @NASA https://t.co/qhpTL6GjGp pic.twitter.com/u0Yga6nUan

&mdash UC San Diego (@UCSanDiego) July 8, 2019

Reagan’s Star Wars, but with capitalist stem cells. The same press release says about the launch date, originally announced for 21 July 2019:

The project’s first flight to the ISS is planned for mid-2021“.

Here my idea: why not sending some Neanderthal minibrains inside crab robots, not just into the Earth orbit, but to colonise the Moon? The Earth is dangerous anyway, what with the viruses raging, maybe Muotri would like to go to the Moon too, and commandeer his Lunar Neanderthal crab robot army via AI generated brain waves?

Either Muotri will end up the biggest embarrassment for his research field and maybe even NASA, or he will be awarded Nobel Prizes in everything: in medicine (for Neanderthal minibrains), in chemistry (for COVID-19 cures from minibrains), physics (for minibrains in space), for peace (for minibrains crab robots delivering democracy everywhere) and in economy (for getting all the funding money there is).

If you are interested to support my work, you can leave here a small tip of $5. Or several of small tips, just increase the amount as you like (2x=€10 5x=€25). I use my own minibrain to write all that.


Sasquatch Chronicles Blog

“Geneticists hope comparing prehistoric and modern biology will help them understand what makes humans unique. Scientists are preparing to create “miniature brains” that have been genetically engineered to contain Neanderthal DNA, in an unprecedented attempt to understand how humans differ from our closest relatives.

In the next few months the small blobs of tissue, known as brain organoids, will be grown from human stem cells that have been edited to contain “Neanderthalised” versions of several genes.

The lentil-sized organoids, which are incapable of thoughts or feelings, replicate some of the basic structures of an adult brain. They could demonstrate for the first time if there were meaningful differences between human and Neanderthal brain biology.

“Neanderthals are the closest relatives to everyday humans, so if we should define ourselves as a group or a species it is really them that we should compare ourselves to,” said Prof Svante Pääbo, director of the genetics department at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, where the experiments are being performed.”

14 Responses to “News of the strange: Scientists grow ‘mini-brains’ using Neanderthal DNA”

Oh yeah, this can’t be good. A brain with no feelings, thoughts- hey wasn’t that already done? (insert political party of your choice)


What Miniature Lab-Grown Brains Reveal About the Effects of Covid-19

Organoids are helping scientists study the coronavirus

While there’s growing evidence that animals may suffer from anxiety and depression and that some monkeys exhibit autism-like symptoms, schizophrenia seems uniquely human. Muotri’s lab is interested in finding out the biological underpinnings behind why humans are so susceptible to schizophrenia and other psychiatric and neurodevelopmental disorders.

A 2016 study suggested that schizophrenia is a modern development, one that emerged after humans diverged from Neanderthals. Other studies have found links between Neanderthal genes — many of us harbor between 1% to 2% of Neanderthal DNA — and the risk of depression and addiction. (My colleague Dana Smith at Elemental recently wrote about the various theories that explain why our brains evolved to be depressed.)

“I think reconstructing the evolutionary path that increases the complexity of the human brain will allow us to understand how those diseases became so frequent for us,” Muotri says.

To create the organoids, Muotri and his team first compared the genomes of modern humans to those of Neanderthals and Denisovans, another group of early hominids that split off from Neanderthals 400,000 years ago. The researchers were looking for genetic differences that could explain how modern humans evolved. They found 61 protein-coding genes that differ between us and our ancestral relatives. From there, they looked at genes involved in early brain development and narrowed in on one in particular: NOVA1, known to be a master regulator that affects the expression of other genes.

Muotri and his team then took skin cells from a “neurotypical” person — someone who doesn’t have neurodevelopmental disorders — and transformed them into stem cells, which have the ability to specialize into any cell type. They then used CRISPR gene editing to bestow the stem cells with the archaic variant of NOVA1 found in Neanderthals. Using substances known as growth factors, they coaxed the stem cells into neurons, which after months formed into tiny three-dimensional balls of brain tissue.

Compared to organoids with the modern-day version of NOVA1, the ones with the Neanderthal variant looked noticeably different. While the modern-day brain organoids were smooth and spherical, the Neanderthal organoids were smaller and bumpier, with a popcorn shape. The findings suggest the gene played a major role in the development of the modern human brain.

There were also differences in the way their cells multiplied and how their synapses formed. In the archaic version of the organoids, neuronal activity occurred at an earlier stage, suggesting that the Neanderthal neural network may have matured faster than that of modern humans. But the neurons in the Neanderthal organoids didn’t synchronize in the same way that those in the modern human organoids did.

The brain organoids are still far from actual brains. They lack blood vessels, which provide the brain with oxygen, as well as many cell types that exist in a real brain. And a study published last year in Nature found that brain organoids don’t replicate the intricate circuitry of the brain. In other words, they’re simplified models of the most complex organ. Since many human brain diseases are specific to particular cell types and circuits in the brain, this presents a challenge for using organoids to accurately model these disorders.

Muotri knows his brain organoids have limitations. “You cannot compare an organ or adult brain,” he says. “The organoid is just an indication of things that might change during development. It’s an extrapolation.”

H. Isaac Chen, MD, a neurosurgeon at the University of Pennsylvania who wasn’t involved in the new study, says there are probably more genes than just NOVA1 that make our brains distinct from those of ancient humans.

“Introducing specific gene variants into brain organoids is an interesting approach for understanding how they influence brain development,” Chen tells Future Human. “But it is not likely that a single gene variant is completely responsible for the differences in brain development between humans and extinct hominin species.”

Many psychiatric conditions are polygenic — that is, they involve several, even hundreds, of mutations in different genes.

Muotri’s team wants to look at the other 60 genes and what happens when each, or a combination of two or more, are altered in brain organoids.

As brain organoids get more advanced, Chen and others have raised ethical concerns about their use in research. Muotri’s lab has previously made brain organoids that emit humanlike brain waves, raising the possibility that they could someday develop consciousness. He has called for ethical guidelines around experiments that involve implanting human brain organoids into lab animals. While other groups have been testing brain organoids in mice, Muotri says his team has no plans to do so with their Neanderthal mini brains.

Chen isn’t worried that the Neanderthal organoids will become conscious anytime soon though. He says the possibility of growing a thinking Neanderthal brain in the lab is still far off.


The human brain is one the most complex creations of evolution. Its intrinsically convoluted structure wasn’t always like this though. Or was it? These mini brains in petri dishes could tell us.

Scientists have been trying to understand the brain and its journey for the longest time. Seeking to bridge the gap between how our brain is and how our brain was, this research even addresses the in-betweens. The complex structure of the human brain has always been in the centre stage when it comes to scientific research. Serving as a model for complex but mysterious yet the best machine ever, the brain in its present forms must have evolved from a primitive form where it was not equipped to be this functional.

One way to figure out if the brain has always been what it is right now is to compare it with those of our ancestral cousins. Though fossils are easily found, brains are not. Trying to arrange for the brain of our ancestral cousin- a neanderthal, that died almost 37,000 years ago, has been one monumental task in itself. Yet, to bridge the gap between availability and advancement, a research team grew tiny ‘mini brains’ in Petri dishes. Some of the brains were grown using the gene-editing tool Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR, to have a brain development gene taken from Neanderthal remains.

Scientists are growing Neanderthal like brains in petri dishes.

Researchers started with skin cells of a ‘neurotypical person’- which is a term that is used to refer to individuals who don’t have any known genetic defects linked to neurological disorders– so as to manipulate their genomes to turn them into pluripotent stem cells. Post this, CRISPR comes into play. This is where using CRISPR, NOVA1 gets targeted and swapped in the Neanderthal base pair to replace the modern human one. To ensure precision and avoid any errors that can be caused by DNA changes by CRISPR, resulting cells are sequenced and if any of them have unintended mutations, they are discarded.

Pondering upon questions like what is it in the DNA that differentiates between humans and its probable primitive form? Equipped with similar questions, researchers have now zeroed down to a single gene out for its Neanderthal counterpart in brain tissue grown in a lab dish. When comparing to the brain in it’s present form, the resulting organoid revealed that DNA may have had a major role in the development.

This study is unique not because the topic hasn’t been delved into before, but it’s definitely the first time tiny brains of ancient human cousins have been cultivated so as to compare it with the hybrid of the human organ as it is in its present state.

CRISPR and NOVA1 gets targeted and swapped in the Neanderthal base pair to replace the modern human one.


Watch the video: Το Ταξίδι της Τροφής, 1ο επεισόδιο: ΤΟ ΠΡΩΤΟ ΓΕΥΜΑ (May 2022).