Blog COVID-19

Alysson Muotri, a minibrain

Autistic Neanderthal minibrains operating crab robots via brain waves of newborn babies are to be launched into outer space for the purpose of interstellar colonization. No, I am not insane. Science Has Spoken.

Alysson Muotri. Probably the most popular neuroscientist in the media. Why???

For one, the “research” by this neuroscience professor at University of California San Diego uses all the buzzwords: minibrains, Neanderthals, autism, CRISPR and AI. For another, it is so insane, demented and unhinged and yet funded even by NASA while published in the highest journals that the logic implies it must be true then.

I am not the one for conspiracy theories, and suspect human stupidity behind most things. But in the case of Muotri I rather prefer a conspiracy of all neuroscientists and stem cell researchers fooling us all with a crazy circus clown show to provide distraction from some sinister grander scheme of world domination they are hatching unbeknownst to us.

Because the alternative explanation is that science is run by incompetent morons, gullible nincompoops and pathetic chickenshits. Welp.

Autistic Neanderthals

This is Muotri’s most recent paper. It appeared just now in Science, the top elite journal where YOUR research gets desk-rejected in the matter of minutes.

Cleber A. Trujillo, Edward S. Rice, Nathan K. Schaefer, Isaac A. Chaim, Emily C. Wheeler, Assael A. Madrigal, Justin Buchanan, Sebastian Preissl, Allen Wang, Priscilla D. Negraes, Ryan A. Szeto, Roberto H. Herai, Alik Huseynov, Mariana S. A. Ferraz, Fernando S. Borges, Alexandre H. Kihara, Ashley Byrne, Maximillian Marin, Christopher Vollmers, Angela N. Brooks, Jonathan D. Lautz, Katerina Semendeferi, Beth Shapiro, Gene W. Yeo, Stephen E. P. Smith, Richard E. Green, Alysson R. Muotri Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment Science (2021) doi: 10.1126/science.aax2537

For that masterpiece of brainless coucou-balderdash Muotri built on his own personal assumption that Neanderthals were autistic schizophrenics, who communicated in grunts and were unable to hold a stick the right way (to be fair, he is not alone with such theories). Muotri then extended his clever assumption to Denisovans, another extinct human subspecies. Then Muotri used his own minibrain to design a list of 61 genes which he decreed made modern humans like himself smart, and selected a random one as the most important for intellectual maturity: NOVA1. Muotri then CRISPRed an “archaic” NOVA1 gene version into what he and others call “minibrains”, clumps of neuron-like cells which differentiate in cell culture from induced pluripotent stem (iPS) cells. The Brazilian genius then compared those autistic (his own comparison!) NOVA1-mutant “Neanderthal” minibrains with “normal” minibrains from human cells, and discovered that the former were shrivelled and not as smart anymore.

How does one diagnose autism in minibrains in cell culture, you ask? A Spectrum article celebrating the professor’s genius explains:

“Muotri created his first brain organoids in 2014 with stem cells from the father of an autistic boy. Two years later, he found that organoids made using stem cells from autistic children have different network dynamics than those from neurotypical controls. […] The ultimate goal, he says, is to create organoids that can learn.

This pathetic sci-fi essay passed peer review in Science, because Muotri commandeers huge sums of donor support and government money which buys respect, manpower and very expensive fancy technology unavailable to losers. It’s a pity his research doesn’t involve western blots, if you know what I mean. In any case, by the virtue of Science‘s reputation, that cartoonish Fred Flintstone silliness became an indisputable science fact and everyone who laughs at it must be an ignorant flat-earth science denialist.

Journalists did as expected and celebrated the science breakthrough. Especially since anything about Neanderthals always makes great news, even and in particular during the COVID-19 pandemic. Muotri was quoted by STAT News:

“Perhaps a good experiment would be to go to the chimpanzee and add the human version of that gene,” Muotri said. “Would that make the brain develop slower and would that chimp become more human-like in terms of cognition?”

Why not trying with yourself first, especially if there is a lack of any kind of cognition? Science magazine also brought a news article, citing the big names in the field in support (hyperlinks and comments mine):

“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, […] 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 [who himself blamed Neanderthal genes for the alleged ethnic variations in COVID-19 susceptibility, in Nature]. 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,” [Arnold] Kriegstein says.

In such cases, it is very likely that the esteemed scholars cited by the journal press release were actually the peer reviewers of that same research paper. With titans like Pääbo and Kriegstein supporting Muotri, everyone who dares to pooh-pooh his work will become the proverbial toast and won’t publish a paper or get a grant ever again. This is how academia always works, but with Muotri this sketch is getting too silly now.

More minibrain expert praise arrived in Nature news reporting (hyperlink and comments mine):

““It’s an extraordinary paper with some extraordinary claims,” says Gray Camp [Pääbo’s coauthor, previously in his Leipzig institute], a developmental biologist at the University of Basel in Switzerland, whose lab last year reported2 growing brain organoids that contained a gene common to Neanderthals and humans.

The STAT News article has also this bit (highlight mine):

The study was performed on two cell lines from distinct neurotypical humans, and experts hope that more can be done on multiple cell lines from different ancestral, racial, and neurodiverse backgrounds to understand how the ancient gene variants impact different populations.

Racial backgrounds, do you see the potential? I would love to have the list of those “experts”, to warn prospective students about them. If Neanderthals can be denounced willy-nilly as mentally deficient autistic schizophrenics simply because Muotri says so, why not for example, Black people? A lot of scientists of a certain kind would embrace such minibrain research.

Crab robots

I wrote about Muotri’s Neanderthal bunk before. That was because the genius discovery of Muotri’s autistic Neanderthals as demonstrated by their shrivelled minibrains was touted by Science already in June 2018. The reason for such advanced breaking wind? Muotri published a conference abstract. Already back then, NOVA1 as The Gene was named, those were obviously the same experiments now published in Science. The Neanderthal minibrains were diagnosed with autism, because he California genius says NOVA1 is linked to autism and schizophrenia:

Several of these differences mirror what Muotri has found studying neuronal development in the brains of children with autism. “I don’t want families to conclude that I’m comparing autistic kids to Neanderthals, but it’s an important observation,” says Muotri, who has a stepson with autism.

Pääbo, the (likely) future peer reviewer of Muotri’s paper, sounded slightly sceptical, but others were excited (hyperlink mine):

“”We’re trying to recreate Neanderthal minds,” Muotri says. “I’m a little envious,” says Todd Preuss, a neuroanatomist at Emory University’s Yerkes National Primate Research Center in Atlanta

Top: perfect, round and highly intelligent human neurospheres (or mini-brains), bottom: small shrivelled and retarded “Neanderthal” mini-brains. Source: Muotri and Science magazine

The Science news piece from 2018 ended with (hyperlink mine):

Muotri has developed the modern human brain organoids to the stage where his team can detect oscillating electrical signals within the balls of tissue. They are now wiring the organoids to robots that resemble crabs, hoping the organoids will learn to control the robots’ movements. Ultimately, Muotri wants to pit them against robots run by brain Neanderoids.

It’s kind of wild,” says Simon Fisher, a geneticist who heads the Max Planck Institute for Psycholinguistics in Nijmegen, the Netherlands, who famously engineered mice to have a mutated human gene linked to speech disorders. “It’s creative science.

Neanderthal minibrains inside crab robots. Or maybe crap robots. The recent news coverage celebrating the new Science paper never mentions those, such a pity. The only evidence of the crab robots’ existence are videos on his phone which Muotri shows to journalists:

A video stored on his phone features a 1-foot-wide spidery robot cloaked in neon wires scuttling back and forth across a room. Unseen, the robot’s biological puppeteer directs its every move: The robot’s limbs move in response to a computer which, in turn, receives signals from an organoid in an incubator.

The robot steps at random, often bumping into walls, suggesting that the signals are not coordinated. Someday, Muotri says, he will create organoids that produce meaningful signals. With sensory feedback from the robot (say, from hitting an obstacle), the organoid might alter its firing patterns — ‘learn,’ that is — to direct the robot around the obstacle.

A minibrain cannot operate any robot, crab, crap or otherwise. Whatever Muotri has been showing to gullible journos there, cannot be what he claims it is. And yet nobody was laughing, quite the opposite, it’s “creative science”, Muotri is a genius exactly because nobody else but him produces such “results”. What is it with the scientific community? Are they afraid, stupid or just greedy devotees of academic bandwaggoning and trickle-down economy, hoping to receive funding crumbs off Muotri’s comic relief “research”?

Preterm infants

In between that press release from 2018 and the final Science paper in 2021, Muotri published in another fancy journal. The man who previously authoritatively said that “mature organoids (6 to 8 months old) resemble a first-trimester fetal brain“, now claimed his minibrains inside a dish display neuronal activity of preterm babies. Seriously.

Cleber A. Trujillo, Richard Gao, Priscilla D. Negraes, Jing Gu, Justin Buchanan, Sebastian Preissl, Allen Wang, Wei Wu, Gabriel G. Haddad, Isaac A. Chaim, Alain Domissy, Matthieu Vandenberghe, Anna Devor, Gene W. Yeo, Bradley Voytek, Alysson R. Muotri Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development Cell stem cell (2019) doi: 10.1016/j.stem.2019.08.002

What Muotri did there, was to declare two things: that his minibrains generate actual brain waves from inside the Petri dish, and that he developed a fancy high-tech AI thingy with which he can compare those “brain waves” from tiny cell clumps with the real brain waves of newborn babies. Lo and behold, the brain patterns were undistinguishable, or so the peer reviewers at Cell Stem Cell agreed. The story made huge news all over the world, when it appeared in the summer 2019. Muotri himself was quoted:

“After these organoids are in that six-to-nine-months range, that’s when [the electrical patterns] start to look a lot like what you’d see with a preterm infant”.

Instead of pointing fingers, laughing and pelting Muotri with rotten tomatoes and manure, the academic community scrambled to anxiously discuss the possibility of a human consciousness inside the minibrains. The bioethicists were in the state of highest agitation:

If we’re starting to see spontaneous brain activity that grows and develops as the organoid grows and develops, then we need to have some concerns about how ought we regard these things,” says Nita Farahany, professor of law and philosophy at Duke University. “Do they have some moral status?

Farahany, together with her other law and bioethics experts like Hank Greely, published already in 2018 a letter in Nature, just the year before Muotri’s preterm babies bullshit arrived. Having been asked about Muotri’s research in 2019, Greely considered minibrains’ “potential to perceive or to react to things” to be “likely.”

The reason for the confusion was that other minibrain researchers have been stoking the hype fires themselves. The scientific reality, that the minibrains, or neurospheres as they used to be known, are merely interesting 3D structures of various neurally differentiated cells (and definitely not an organ, never mind a brain-like one) was apparently not enough to raise the desired amount of research and business funding. Hence their fairytale invention of the minibrain which is almost but not entirely unlike the real brain. The concept became science fact in 2013, when Madeline Lancaster and Jürgen Knoblich published a paper in Nature. An expert was quoted (hyperlink mine):

““It’s a seminal study to making a brain in a dish,” says Clive Svendsen, a neurobiologist at the University of California, Los Angeles, who was not involved in the study. “That’s phenomenal.” A fully formed artificial brain might still be years away, he notes, but the pea-sized neural clumps developed in this work could prove useful for researching human neurological diseases.”

Well, 8 years have passed since, and now we have Neanderthal brains in a dish, isn’t science great. The “fully formed artificial brain” may be already maturing inside Svendsen’s or even Muotri’s head even as we speak. Look, the minibrains have since even evolved brain waves like preterm infants (although Knoblich himself cautiously warns in this regard: “The comparisons to real human fetal brains are viewed skeptically by some scientists.“). This is why not just the legal or ethics experts, even the insiders, the actual minibrain researchers are excited about the possibility to do actual brainstorming with their minibrains in a dish:

And if you make minibrains from your own iPS cells, you can finally have an intelligent thought exchange with your intellectually equal-level peers. Once bored or disagreeing, you can flush them down the toilet.

In October 2019, The Guardian called out an emergency, with red lines and all (that was before the real emergency of a COVID-19 pandemic). Experts were quoted:

“If there’s even a possibility of the organoid being sentient, we could be crossing that line,” said Elan Ohayon, the director of the Green Neuroscience Laboratory in San Diego, California. “We don’t want people doing research where there is potential for something to suffer.

Even Muotri’s own former mentor, the bigwig of neuroscience and stem cell research Fred “Rusty” Gage at Salk Insitute, warned:

I think it is never too soon to raise issues about ethics in science, so that a thoughtful dialogue can guide scientific research and decisions.

By the way, Muotri once claimed in a paper Muotri et al PNAS 2005 from Gage’s lab that embryonic stem cells create functional neurons when injected into a mouse brain, an impressive finding many labs struggled to reproduce ever since. In any case, the research was done unethically, as Muotri himself admitted to journalists, the failure to seek ethics approval earned him a “warning” from Salk Institute’s institutional review board. The paper was never corrected and continues declaring: “All experiments were performed in compliance with institutional and U.S. National Academies guidelines and with the protocol approved by The Salk Institute Animal Care and Use Committee“. That’s one example how powerful Gage is.

In reality, there is nothing for the bioethicists to be concerned for, except maybe for which kind of actual quality science we miss out on because we are so obsessed with the magic promises of the minibrains. It’s not like Muotri himself is worried about those alarm calls and concerns regarding his “research”. He actively incites them. He wants to be seen as an almighty science god who creates human consciousness out of nothing while holding it in his power to cure all diseases. The way his “research” simultaneously amazes, humbles and scares other scientists, ethicists and the public translates into power, money and fame for Muotri himself. Hence his statements like this, in a 2019 Cell Press release:

As a scientist, I want to get closer and closer to the human brain […] I want to do that because I see the good in it. I can help people with neurological conditions by giving them better treatments and better quality of life. But it’s up to us to decide where the limit is. It might be that the technology is not ready yet, or we don’t know how to control the technology. This is the same kind of discussion around CRISPR in babies, and that’s why we have ethics committees to represent all parts of the society.

Actually, what happened to the CRISPRed babies in China? Are they healthy or even alive? Did they ever exist? Nobody cares anymore, the attention span in science is very short. We have a pandemic going on, where we receive new kinds of all possible bullshit every day.

COVID-19 cured by minibrains

Still, one must stay in the limelight, and Muotri is great in this. He even gets quoted in newspapers on topics he has little to nothing to do with, like COVID-19. Nature titled in October 2020 about his research:

Can lab-grown brains become conscious?

[…] “The team’s finding led ethicists and scientists to raise a host of moral and philosophical questions about whether organoids should be allowed to reach this level of advanced development, whether ‘conscious’ organoids might be entitled to special treatment and rights not afforded to other clumps of cells and the possibility that consciousness could be created from scratch.

Now, in that Nature article, Muotri was described:

He has connected organoids to walking robots, modified their genomes with Neanderthal genes, launched them into orbit aboard the International Space Station, and used them as models to develop more human-like artificial-intelligence systems. Like many scientists, Muotri has temporarily pivoted to studying COVID-19, using brain organoids to test how drugs perform against the SARS-CoV-2 coronavirus.

Thank god, Muotri will save humanity from COVID-19 now.

Which kind of makes sense. The Californian genius already cured the Aicardi-Goutieres Syndrome (which is an autoimmune condition!) by repurposing HIV drugs stavudine and lamivudine onto iPS-derived minibrains. The proof that the cure works lies in the big impact factor of the journal Thomas et al Cell Stem Cell 2017 was published in. Muotri also deployed his minibrain model to both mechanistically solve and pharmacologically cure the Rett syndrome, a rare form of autism, in the recent paper Trujillo et al EMBO Mol Medicine 2020, the two new investigative neurological drugs dearly in need of a market being Nefiracetam and PHA 543613. On top of that, Muotri was busy finding a cure for Zika virus (which he tested on minibrains and published in Nature, Gugola et al 2016) when the pandemic arrived.

Oh look, the Minibrain Man already discovered the gamechanging covid-crushing medicine for the coronavirus infection, at least for the brain: the hepatitis B drug Sofosbuvir, by Gilead. The discovery was published as preprint Mesci et al 2020 in May (here a critical review), I expect it to appear in a major journal soon and make international news once again because we are talking about Muotri after all.

And in between of all that, Muotri also is about to send his minibrains into space.

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.””

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

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).


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2 comments on “Alysson Muotri, a minibrain

  1. Pingback: Dirty diseased Neanderthals – For Better Science

  2. Pingback: Neanderthals abused to support bully Alan Cooper – For Better Science

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