A Deadly, Contagious Human Brain Protein Was Just Made in The Lab For The First Time

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According to ScienceAlert (This article and its images were originally posted on ScienceAlert June 6, 2018 at 09:29PM.)

This is how horror movies start.

Prions are terrifying proteins responsible for a number of devastating, infectious brain diseases – and for the first time, scientists have synthesised an artificial human prion in a lab.

But instead of starting some kind of zombie pandemic, the product of this research could actually help develop treatments for prion diseases.

“This accomplishment represents a watershed,” says neurologist Jiri G. Safar of Case Western Reserve School of Medicine.

“Until now our understanding of prions in the brain has been limited. Being able to generate synthetic human prions in a test tube as we have done will enable us to achieve a much richer understanding of prion structure and replication.”

And once researchers understand these aspects of prions, they are better equipped to develop the sorts of drugs that can slow these proteins down in the brain, potentially stopping their devastating spread.

Prions are proteins that have gone wrong, folding in abnormal ways. When they bind with normal proteins in the brain, they induce these to fold abnormally too; this cascading effect creates microscopic holes, turning the brain into a sponge.

This unstoppable brain damage causes dementia and loss of bodily control, eventually leading to death. And, as we have seen with mad cow disease, it can also move between other animals and humans.

Prion diseases are rare – only about 300 cases per year are reported in the US – but they often progress rapidly and are currently incurable, making it a particularly scary ailment.

In the past, researchers have managed to engineer rodent prions, but these were not infectious to humans, according to experiments with humanised mice.

And although there’s been some success in studying the details of mouse and hamster prion diseases, how these deadly proteins occur in humans is different in both structure and the mechanism of replication.

That’s why so far the mis-folding of human prions has remained a mystery – and the failure of recent therapeutic trials for treating prion disease indicates that what works in animal models doesn’t always work for humans.

In this latest study, scientists used a genetically engineered human prion protein expressed in E. coli bacteria, and managed to successfully synthesise a “highly destructive” human prion.

They tested it in transgenic mice expressing human prion proteins, and observed neurologic dysfunction, with a neuropathy suggesting a new, particularly toxic human prion strain.

In the process, they discovered that a cell molecule known as Ganglioside GM1 – which helps modulate cell-to-cell signaling – helps trigger infectious replication and the transmission of prion disease.

This discovery means they may be able to develop a medication that inhibits this molecule, blocking prion disease from spreading.

And they also found that the mere presence of mis-folded proteins isn’t what causes the severity of a prion disease. Instead, there are particular changes in the amino acid chains of the prion’s structure that determine how fast it replicates, how infectious it is, and which brain structures it targets.

“Our findings explain at the structural level the emergence of new human prions and provide a basis for understanding how seemingly subtle differences in mis-folded protein structure and modifications affect their transmissibility, cellular targeting, and thus manifestation in humans,” explains Safar.

A new strain of artificially created prion sounds terrifying, but this research could be a bold new step in helping treat prion disease by discovering auxiliary factors, and developing therapeutic approaches to blocking them.

Which, actually, is amazing.

The team’s research has been published in Nature Communications.

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This article and its images were originally posted on [ScienceAlert] June 6, 2018 at 09:29PM. All credit to both the author MICHELLE STARR and ScienceAlert | ESIST.T>G>S Recommended Articles Of The Day.

 

 

 

Human brain cells can make complex structures in a dish—is this a problem?

 

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According to Science – Ars Technica

The premiere of the second season of Westworld is a perfect time to ponder what makes us human. This is not new territory; such questions have long been dealt with in works of fiction, and they have appeared in science in the form of studies of creatures that have human-like characteristics—like consciousness—yet are not Homo sapiens.

These studies raise ethical questions whether the subject is an animal or an AI. Last May, a consortium of bioethicists, lawyers, neuroscientists, geneticists, philosophers, and psychiatrists convened at Duke to discuss how this question may apply to relatively new entities: brain “organoids” grown in a lab. These organoids can be either chimaera of human or animal cells or slices of human brain tissue. Will these lab-grown constructs achieve any sort of consciousness deserving of protection?

Why organoids?

If we ever want to understand, let alone cure, the very complex brain disorders that plague people—like schizophrenia, ASD, and depression—we need research models. And in order to be informative, these models must be accurate representations of the human brain. Yet as our models become more and more like the real thing (and for now, they are still quite a long way off), the problems with using them become so pronounced as to negate their utility—like Borges’ map.

With mental and psychiatric disorders being so debilitating, is it ethical to use active human neural tissues? If we advance our ability to create them to the point where they develop consciousness, is using them still ethical?

Brain organoids are generated much like other organoids—we’ve made them for the eye, gut, liver, and kidney. Pluripotent stem cells are cultured under conditions that promote formation of specific cell types. In this case, we can push cells to adopt the fate of particular brain regions. These different brain regions can even be combined in limited ways. These 3D organoids contain multiple cell types and are indisputably more physiologically relevant for research than a lawn of identical cells growing in a petri dish.

And they are becoming increasingly complex; last year, a lab at Harvard recorded neural activity from an organoid after shining light on a region where cells of the retina had formed together with cells of the brain, demonstrating that the organoid can respond to an external stimulus. This is clearly not the same as feeling distress (or anything else)—but it’s a significant advance.

Chimaera have also been created. In this context, they’re animals—usually mice—into which human brain cells have been implanted. (The implanted cells are derived from pluripotent stem cells, like those used to make the brain organoids above—they are NOT harvested from individual humans.) Again, this is done to provide a more physiologically relevant model of brain diseases, like Parkinson’s. When human glial cells were transplanted into mice, the mice performed better on some learning tasks.

The small size of the rodents used should restrict the ability of the human brain cells to grow, but they’re clearly impacting the mice. In terms of “human-animal blurring,” the consortium writes: “We believe that decisions about which kinds of chimaera are permitted or about whether certain human organs grown in animals make animals ‘too human-like’ should ultimately be made on a case-by-case basis—taking into account the risks, benefits, and people’s diverse sensitivities.”

Feelings

What if these entities were to develop sentience, whatever that means? Or the ability to feel pleasure or pain? Or the ability to form memories? Or some sort of self-awareness? How would we even determine if they had such capabilities? The EEGs usually used to measure consciousness don’t work on infants, who are clearly conscious and human, so they might not be applicable here either.

Researchers have studied human brain tissue for more than a century, but now we have the ability to manipulate that brain tissue, to induce certain neurons to fire, for example. If we develop the technology to retrieve someone’s memories from a slice of tissue, how would we deal with that, legally and ethically? Consent for donating this tissue would take on a whole other dimension. And since some aspects of this technology could presumably function even if the tissue donor was dead, would that change the definition of brain death?

Genetic engineers set their own regulations on the use of recombinant DNA at the Asilomar Conference of 1975. Elon Musk argues that it is time to start regulating AI right now. With the BRAIN initiative currently underway, it is encouraging to see neuroscientists trying to stay ahead of this game and develop ethical guidelines before these technologies develop. So once these technologies do arrive, at least there’s a chance that we can deploy them responsibly.

Nature, 2018. DOI: 10.1038/d41586-018-04813-x (About DOIs).

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This article and images were originally posted on [Science – Ars Technica] April 28, 2018 at 07:05AM. Credit to Author and Science – Ars Technica | ESIST.T>G>S Recommended Articles Of The Day