Singularity Hub https://singularityhub.com/ News and Insights on Technology, Science, and the Future from Singularity Group Sun, 22 Dec 2024 23:33:58 +0000 en-US hourly 1 https://wordpress.org/?v=6.5.2 https://singularityhub.com/uploads/2021/09/6138dcf7843f950e69f4c1b8_singularity-favicon02.png Singularity Hub https://singularityhub.com/ 32 32 4183809 Exosomes Are Being Hyped as a ‘Silver Bullet’ Therapy. Scientists Say No. https://singularityhub.com/2024/12/26/exosomes-are-being-hyped-as-a-silver-bullet-therapy-scientists-say-no/ Thu, 26 Dec 2024 15:00:46 +0000 https://singularityhub.com/?p=159957 When human stem cells were discovered at the turn of the century, it sparked a frenzy. Scientists immediately dreamed of repairing damaged tissues due to aging or disease.

A few decades later, their dreams are on the brink of coming true. The US Food and Drug Administration (FDA) has approved blood stem cell transplantation for cancer and other disorders that affect the blood and immune system. More clinical trials are underway, investigating the use of stem cells from the umbilical cord to treat knee osteoarthritis—where the cartilage slowly wears down—and nerve problems from diabetes.

But the promise of stem cells came with a dark side.

Illegal stem cell clinics popped up soon after the cells’ discovery, touting their ability to rejuvenate aged skin, joints, or even treat severe brain disorders such as Parkinson’s disease. Despite FDA regulation, as of 2021, there were nearly 2,800 unlicensed clinics across the country, each advertising stem cells therapies with little scientific evidence.

“What started as a trickle became a torrent as businesses poured into this space,” wrote an expert team in the journal Cell Stem Cell in 2021.

History is now repeating itself with an up-and-coming “cure-all:” exosomes.

Exosomes are tiny bubbles made by cells to carry proteins and genetic material to other cells. While still early, research into these mysterious bubbles suggests they may be involved in aging or be responsible for cancers spreading across the body.

Multiple clinical trials are underway, ranging from exosome therapies to slow hair loss to treatments for heart attacks, strokes, and bone and cartilage loss. They have potential.

But a growing number of clinics are also advertising exosomes as their next best seller. One forecast analyzing exosomes in the skin care industry predicts a market value of over $674 million by 2030.

The problem? We don’t really know what exosomes are, what they do to the body, or their side effects. In a way, these molecular packages are like Christmas “mystery boxes,” each containing a different mix of biological surprises that could alter cellular functions, like turning genes on or off in unexpected ways.

There have already been reports of serious complications. “There is an urgent need to develop regulations to protect patients from serious risks associated with interventions based on little or no scientific evidence,” a team recently wrote in Stem Cell Reports.

Cellular Space Shuttles

In 1996, Graça Raposo, a molecular scientist in the Netherlands, noticed something strange: The immune cells she was studying seemed to send messages to each other in tiny bubbles. Under the microscope, she saw that when treated with a “toxin” of sorts, the cells slurped up the molecules, planted them on the surfaces of tiny bubbles inside the cell, and released the bubbles into the vast wilderness of the cell’s surroundings.

She collected the bubbles and squirted them onto other immune cells. Surprisingly, they triggered a similar immune response in the cells—as if directly exposed to the toxin. In other words, the bubbles seemed to shuttle information between cells.

Dubbed exosomes, scientists previously thought they were the cell’s garbage collectors, gathering waste molecules into a bubble and spewing it outside the cell. But two years later, Raposo and colleagues found that exosomes harvested from cells that naturally fight off tumors could be used as a therapy to suppress tumors in mice.

Interest in these mysterious blobs exploded.

Scientists soon found that most cells pump out exosome “spaceships,” and they can contain both proteins and types of RNA that turn genes on or off. But despite decades of research, we’re only scratching the surface of what cargo they can carry and their biological function.

It’s still unclear what exosomes do. Some could be messengers of a dying cell, warning neighbors to shore up defenses. They could also be co-opted by tumor cells to bamboozle nearby cells into supporting cancer growth and spread. In Alzheimer’s disease, they could potentially shuttle twisted protein clumps to other cells, spreading the disease across the brain.

They’re tough to study, in part, because they’re so small and unpredictable. About one-hundredth the size of a red blood cell, exosomes are hard to capture even with modern microscopy. Each type of cell seems to have a different release schedule, with some spewing many in one shot and others taking the slow-and-steady route. Until recently, scientists didn’t even agree on how to define exosomes.

Over several years, the International Society for Extracellular Vesicles, or exosomes, has begun uniting the field with naming conventions and standardized methods for preparing exosomes.

The Wild West

While scientists are rapidly coming together to cautiously make exosome-based treatment a reality, uncertified clinics have popped up across the globe. Their first pitch to the public was tackling Covid. One analysis found 60 clinics in the US advertising exosome-based therapy as a way to prevent or treat the virus—with zero scientific support. Another trending use has been in skin care or hair growth, garnering attention in the US, UK, and Japan.

Exosomes are regulated by the FDA in the US and the European Medicines Agency (EMA) in the EU as biological medicinal products, meaning they require approval from the agencies. That did not stop clinics from marketing them, with tragic consequences. In 2019, patients in Nebraska treated with unapproved exosomes became septic—a life-threating condition caused by infection across the whole body—leading the FDA to issue a warning.

Clinics that offer unregulated exosomes “deceive patients with unsubstantiated claims about the potential for these products to prevent, treat, or cure various diseases or conditions,” the agency wrote.

Japan is struggling to catch up. Exosomes are not regulated under their laws. Nearly 670 clinics have already popped up, representing a far larger market than the US or EU. Most services have been marketed for skin care, anti-aging, hair growth, and battling fatigue, wrote the authors. More rarely, some touted their ability to battle cancers.

The rogue clinics have already led to tragedies. In one case, “a well-known private cosmetic surgery clinic administered exosomes…to at least four patients, including relatives of staff members with stage IV lung cancer, and found that the cancer rapidly worsened after administration,” wrote the authors.

Because the clinics operate on the down-low, it’s tough to gauge the extent of harm, including potential deaths.

The worry isn’t that exosomes are harmful by themselves. How they’re obtained plays a huge role in safety. In unregulated settings, there’s a large chance of the bubbles being contaminated by endotoxins—which trigger dangerous inflammatory responses—or bacteria that lingers and grows.

For now, “from a very basic point of view, we don’t really know what they’re doing, good or bad… I wouldn’t take them, let’s put it that way,” James Edgar, an exosome researcher from the University of Cambridge, told MIT Technology Review.

Unregulated clinics don’t just harm patients. They could also set a promising field back.

Scientific advances may seem to move at a snail’s pace, but it’s to ensure safety and efficacy despite the glitz and glamor of a potential new panacea. Scientists are still forging ahead using exosomes for multiple health problems—while bearing in mind there’s much we still need to understand about these cellular spaceships.

Image Credit: Steve Johnson on Unsplash

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ET May Look Nothing Like Life on Earth. Scientists Want a Universal Theory of Life to Describe It. https://singularityhub.com/2024/12/24/et-may-look-nothing-like-life-on-earth-scientists-want-a-universal-theory-of-life-to-describe-it/ Tue, 24 Dec 2024 15:00:28 +0000 https://singularityhub.com/?p=159910

We have only one example of biology forming in the universe—life on Earth. But what if life can form in other ways? How do you look for alien life when you don’t know what alien life might look like?

These questions are preoccupying astrobiologists—scientists who look for life beyond Earth. Astrobiologists have attempted to come up with universal rules that govern the emergence of complex physical and biological systems both on Earth and beyond.

I’m an astronomer who has written extensively about astrobiology. Through my research, I’ve learned that the most abundant form of extraterrestrial life is likely to be microbial, since single cells can form more readily than large organisms. But just in case there’s advanced alien life out there, I’m on the international advisory council for the group designing messages to send to those civilizations.

Detecting Life Beyond Earth

Since the first discovery of an exoplanet in 1995, over 5,000 exoplanets, or planets orbiting other stars, have been found.

Many of these exoplanets are small and rocky, like Earth, and in the habitable zones of their stars. The habitable zone is the range of distances between the surface of a planet and the star it orbits that would allow the planet to have liquid water and thus support life as we on Earth know it.

The sample of exoplanets detected so far projects 300 million potential biological experiments in our galaxy—or 300 million places, including exoplanets and other bodies such as moons, with suitable conditions for biology to arise.

The uncertainty for researchers starts with the definition of life. It feels like defining life should be easy, since we know life when we see it, whether it’s a flying bird or a microbe moving in a drop of water. But scientists don’t agree on a definition, and some think a comprehensive definition might not be possible.

NASA defines life as a “self-sustaining chemical reaction capable of Darwinian evolution.” That means organisms with a complex chemical system that evolve by adapting to their environment. Darwinian evolution says that the survival of an organism depends on its fitness in its environment.

The evolution of life on Earth has progressed over billions of years from single-celled organisms to large animals and other species, including humans.

Exoplanets are remote and hundreds of millions of times fainter than their parent stars, so studying them is challenging. Astronomers can inspect the atmospheres and surfaces of Earth-like exoplanets using a method called spectroscopy to look for chemical signatures of life.

Spectroscopy might detect signatures of oxygen in a planet’s atmosphere, which microbes called blue-green algae created by photosynthesis on Earth several billion years ago, or chlorophyll signatures, which indicate plant life.

NASA’s definition of life leads to some important but unanswered questions. Is Darwinian evolution universal? What chemical reactions can lead to biology off Earth?

Evolution and Complexity

All life on Earth, from a fungal spore to a blue whale, evolved from a microbial last common ancestor about four billion years ago.

The same chemical processes are seen in all living organisms on Earth, and those processes might be universal. They also may be radically different elsewhere.

In October 2024, a diverse group of scientists gathered to think outside the box on evolution. They wanted to step back and explore what sorts of processes created order in the universe—biological or not—to figure out how to study the emergence of life totally unlike life on Earth.

Two researchers present argued that complex systems of chemicals or minerals, when in environments that allow some configurations to persist better than others, evolve to store larger amounts of information. As time goes by, the system will grow more diverse and complex, gaining the functions needed for survival, through a kind of natural selection.

A rock made up of metal, with translucent olivine crystals suspended within.
Minerals are an example of a nonliving system that has increased in diversity and complexity over billions of years. Image Credit: Doug Bowman, CC BY

They speculated that there might be a law to describe the evolution of a wide variety of physical systems. Biological evolution through natural selection would be just one example of this broader law.

In biology, information refers to the instructions stored in the sequence of nucleotides on a DNA molecule, which collectively make up an organism’s genome and dictate what the organism looks like and how it functions.

If you define complexity in terms of information theory, natural selection will cause a genome to grow more complex as it stores more information about its environment.

Complexity might be useful in measuring the boundary between life and non-life.

However, it’s wrong to conclude that animals are more complex than microbes. Biological information increases with genome size, but evolutionary information density drops. Evolutionary information density is the fraction of functional genes within the genome, or the fraction of the total genetic material that expresses fitness for the environment.

Organisms that people think of as primitive, such as bacteria, have genomes with high information density and so appear better designed than the genomes of plants or animals.

A universal theory of life is still elusive. Such a theory would include the concepts of complexity and information storage, but it would not be tied to DNA or the particular kinds of cells we find in terrestrial biology.

Implications for the Search for Extraterrestial Life

Researchers have explored alternatives to terrestrial biochemistry. All known living organisms, from bacteria to humans, contain water, and it is a solvent that is essential for life on Earth. A solvent is a liquid medium that facilitates chemical reactions from which life could emerge. But life could potentially emerge from other solvents, too.

Astrobiologists Willam Bains and Sara Seager have explored thousands of molecules that might be associated with life. Plausible solvents include sulfuric acid, ammonia, liquid carbon dioxide, and even liquid sulfur.

Alien life might not be based on carbon, which forms the backbone of all life’s essential molecules—at least here on Earth. It might not even need a planet to survive.

Advanced forms of life on alien planets could be so strange that they’re unrecognizable. As astrobiologists try to detect life off Earth, they’ll need to be creative.

One strategy is to measure mineral signatures on the rocky surfaces of exoplanets, since mineral diversity tracks terrestrial biological evolution. As life evolved on Earth, it used and created minerals for exoskeletons and habitats. The hundred minerals present when life first formed have grown to about 5,000 today.

For example, zircons are simple silicate crystals that date back to the time before life started. A zircon found in Australia is the oldest known piece of Earth’s crust. But other minerals, such as apatite, a complex calcium phosphate mineral, are created by biology. Apatite is a primary ingredient in bones, teeth, and fish scales.

Another strategy for finding life unlike that on Earth is to detect evidence of a civilization, such as artificial lights, or the industrial pollutant nitrogen dioxide in the atmosphere. These are examples of tracers of intelligent life called technosignatures.

It’s unclear how and when a first detection of life beyond Earth will happen. It might be within the solar system, or by sniffing exoplanet atmospheres, or by detecting artificial radio signals from a distant civilization.

The search is a twisting road, not a straightforward path. And that’s for life as we know it—for life as we don’t know it, all bets are off.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: NASA’s Goddard Space Flight Center/Francis Reddy

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AI That Can Design Life’s Machinery From Scratch Had a Big Year. Here’s What Happens Next. https://singularityhub.com/2024/12/23/ai-that-can-design-lifes-machinery-from-scratch-had-a-big-year-heres-what-happens-next/ Mon, 23 Dec 2024 15:00:48 +0000 https://singularityhub.com/?p=159936 Proteins are biology’s molecular machines. They’re our bodies’ construction workers—making muscle, bone, and brain; regulators—keeping systems in check; and local internet—responsible for the transmission of information between cells and regions. In a word, proteins are crucial to our survival. When they work, we’re healthy. When they don’t, we aren’t.

Which is why recent leaps in our understanding of protein structure and the emerging ability to design entirely new proteins from scratch, mediated by AI, is such a huge development. It’s why three computer scientists won Nobel prizes in chemistry this year for their work in the field.

Things are by no means standing still. 2024 was another winning year for AI protein design.

Earlier this year, scientists expanded AI’s ability to model how proteins bind to other biomolecules, such as DNA, RNA, and the small molecules that regulate their shape and function. The study broadened the scope of RoseTTAFold, a popular AI tool for protein design, so that it could map out complex protein-based molecular machines at the atomic level—in turn, paving the way for more sophisticated therapies.

DeepMind soon followed with the release of AlphaFold3, an AI model that also predicts protein interactions with other molecules. Now available to researchers, the sophisticated AI tool will likely lead to a flood of innovations, therapeutics, and insights into biological processes.

Meanwhile, protein design went flexible this year. AI models generated “effector” proteins that could shape-shift in the presence of a molecular switch. This flip-flop structure altered their biological impact on cells. A subset of these morphed into a variety of arrangements, including cage-like structures that could encapsulate and deliver medicines like tiny spaceships.

They’re novel, but do any AI-designed proteins actually work? Yes, according to several studies.

One used AI to dream up a universe of potential CRISPR gene editors. Inspired by large language models—like those that gave birth to ChatGPT—the AI model in the study eventually designed a gene editing system as accurate as existing CRISPR-based tools when tested on cells. Another AI designed circle-shaped proteins that reliably turned stem cells into different blood vessel cell types. Other AI-generated proteins directed protein “junk” into the lysosome, a waste treatment blob filled with acid inside cells that keeps them neat and tidy.

Outside of medicine, AI designed mineral-forming proteins that, if integrated into aquatic microbes, could potentially soak up excess carbon and transform it into limestone. While still early, the technology could tackle climate change with a carbon sink that lasts millions of years.

It seems imagination is the only limit to AI-based protein design. But there are still a few cases that AI can’t yet fully handle. Nature has a comprehensive list, but these stand out.

Back to Basics: Binders

When proteins interact with each other, binder molecules can increase or break apart those interactions. These molecules initially caught the eyes of protein designers because they can serve as drugs that block damaging cellular responses or boost useful ones.

There have been successes. Generative AI models, such as RFdiffusion, can readily model binders, especially for free-floating proteins inside cells. These proteins coordinate much of the cell’s internal signaling, including signals that trigger senescence or cancer. Binders that break the chain of communication could potentially halt the processes. They can also be developed into diagnostic tools. In one example, scientists engineered a glow-in-the-dark tag to monitor a cell’s status, detecting the presence of a hormone when the binder grabbed onto it.

But binders remain hard to develop. They need to interact with key regions on proteins. But because proteins are dynamic 3D structures that twist and turn, it’s often tough to nail down which regions are crucial for binders to latch onto.

Then there’s the data problem. Thanks to hundreds of thousands of protein structures available in public databases, generative AI models can learn to predict protein-protein interactions. Binders, by contrast, are often kept secret by pharmaceutical companies—each organization has an in-house database cataloging how small molecules interact with proteins.

Several teams are now using AI to design simple binders for research. But experts stress these need to be tested in living organisms. AI can’t yet predict the biological consequences of a binder—it could either boost a process or shut it down. Then there’s the problem of hallucination, where an AI model dreams up binders that are completely unrealistic.

From here, the goal is to gather more and better data on how proteins grab onto molecules, and perhaps add a dose of their underlying biophysics.

Designing New Enzymes

Enzymes are proteins that catalyze life. They break down or construct new molecules, allowing us to digest food, build up our bodies, and maintain healthy brains. Synthetic enzymes can do even more, like sucking carbon dioxide from the atmosphere or breaking down plastic waste.

But designer enzymes are still tough to build. Most models are trained on natural enzymes, but biological function doesn’t always rely on the same structure to do the same thing. Enzymes that look vastly different can perform similar chemical reactions. AI evaluates structure, not function—meaning we’ll need to better understand how one leads to the other.

Like binders, enzymes also have “hotspots.” Scientists are racing to hunt these down with machine learning. There are early signs AI can design hotspots on new enzymes, but they still need to be heavily vetted. An active hotspot usually requires a good bit of scaffolding to work properly—without which it may not be able to grab its target or, if it does, let it go.

Enzymes are a tough nut to crack especially because they’re in motion. For now, AI struggles to model their transformations. This is, as it turns out, a challenge for the field at large.

Shape-Shifting Headaches

AI models are trained on static protein structures. These snapshots have been hard won with decades of work, in which scientists freeze a protein in time to image its structure. But these images only capture a protein’s most stable shape, rather than its shape in motion—like when a protein grabs onto a binder or when an enzyme twists to fit into a protein nook.

For AI to truly “understand” proteins, researchers will have to train models on the changing structures as proteins shapeshift. Biophysics can help model a protein’s twists and turns, but it’s extremely difficult. Scientists are now generating libraries of synthetic and natural proteins and gradually mutating each to see how simple changes alter their structures and flexibility.

Adding a bit of “randomness” to how an AI model generates new structures could also help. AF-Cluster, built on AlphaFold2, injected bits of uncertainty into its neural network processes when predicting a known shape-shifting protein and did well on multiple structures.

Protein prediction is a competitive race. But teams will likely need to work together too. Building a collaborative infrastructure for the rapid sharing of data could speed efforts. Adding so-called “negative data,” such as when AI-designed proteins or binders are toxic in cells, could also guide other protein designers. A harder problem is that verifying AI-designed proteins could take years—when the underlying algorithm has already been updated.

Regardless, there’s no doubt AI is speeding protein design. Let’s see what next year has to offer.

Image Credit: Baker Lab

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This Week’s Awesome Tech Stories From Around the Web (Through December 21) https://singularityhub.com/2024/12/21/this-weeks-awesome-tech-stories-from-around-the-web-through-december-21-2/ Sat, 21 Dec 2024 18:30:39 +0000 https://singularityhub.com/?p=159872 ARTIFICIAL INTELLIGENCE

OpenAI Upgrades Its Smartest AI Model With Improved Reasoning Skills
Will Knight | Wired
“The o3 model scores much higher on several measures than its predecessor, OpenAI says, including ones that measure complex coding-related skills and advanced math and science competency. It is three times better than o1 at answering questions posed by ARC-AGI, a benchmark designed to test an AI models’ ability to reason over extremely difficult mathematical and logic problems they’re encountering for the first time.”

ROBOTICS

New Physics Sim Trains Robots 430,000 Times Faster Than Reality
Benj Edwards | Ars Technica
“On Thursday, a large group of university and private industry researchers unveiled Genesis, a new open source computer simulation system that lets robots practice tasks in simulated reality 430,000 times faster than in the real world. …’One hour of compute time gives a robot 10 years of training experience. That’s how Neo was able to learn martial arts in a blink of an eye in the Matrix Dojo,’ wrote Genesis paper co-author Jim Fan on X, who says he played a ‘minor part’ in the research.”

AUTOMATION

Waymo Still Doing Better Than Humans at Preventing Injuries and Property Damage
Andrew J. Hawkins | The Verge
“They found that the performance of Waymo’s vehicles was safer than that of humans, with an 88 percent reduction in property damage claims and a 92 percent reduction in bodily injury claims. Across 25.3 million miles, Waymo was involved in nine property damage claims and two bodily injury claims. The average human driving a similar distance would be expected to have 78 property damage and 26 bodily injury claims, the company says.”

BIOTECH

A Third Person Has Received a Transplant of a Genetically Engineered Pig Kidney
Emily Mullin | Wired
“Towana Looney, 53, is off of kidney dialysis after undergoing the procedure at NYU Langone Health on November 25. She was discharged from the hospital on December 6, and her doctors say she is in good health. Her surgery is the latest in a series of similar procedures known as xenotransplantation, the practice of transplanting organs from one species to another.”

SPACE

We’re About to Fly a Spacecraft Into the Sun for the First Time
Eric Berger | Ars Technica
“On Christmas Eve, the Parker Solar Probe will make its closest approach yet to the Sun. It will come within just 3.8 million miles (6.1 million km) of the solar surface, flying into the solar atmosphere for the first time. Yeah, it’s going to get pretty hot. Scientists estimate that the probe’s heat shield will endure temperatures in excess of 2,500° Fahrenheit (1,371° C) on Christmas Eve, which is pretty much the polar opposite of the North Pole.”

TECH

Smart Glasses Won Me Over, and This Is the Pair That Did It
Joanna Stern | The Wall Street Journal
“Meta’s Ray-Bans and its prototype Orion hint at the future of smart glasses—sleek, stylish and truly wearable. This was the year smart glasses won me over. These lighter-weight face computers are the next step in how we interact with each other and our surroundings. This isn’t virtual-reality or a detour to the metaverse—you see the real world, just with digital stuff in it. And you look at your phone a lot less.”

ROBOTICS

‘Deep Research’ Shows How Google Can Win the AI Race
Mark Sullivan | Fast Company
“After I agreed to the plan, the agent got busy. …I watched as it raced over the internet and began compiling a list of sources. About three minutes later it had compiled a 60-item list of  source articles and publications, including research papers, journal articles, Medium posts, and Reddit discussions. From all these sources, the agent synthesized a 2,100-word, citation-filled essay that answered my question. Impressive.”

FUTURE

How to Disappear Completely
s.e. smith | The Verge
“We are watching the internet slip away as websites and apps rise and fall, swallowed by private equity, shuttered by burnout, or simply frozen in time—taking with it our memories, our cultural phenomena, our memes. …How comfortable are we with the disappearance of entire swaths of careers and artistic pursuits? And who is making these decisions—private equity or journalists, AI or archivists, billionaires or workers? The answers to these questions, and the way we define ourselves today, will shape our culture of the future.”

Image Credit: Resource Database on Unsplash

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Textbook Depictions of Neurons May Be Wrong, According to Controversial Study https://singularityhub.com/2024/12/20/textbook-depictions-of-neurons-may-be-wrong-according-to-controversial-study/ Fri, 20 Dec 2024 15:00:54 +0000 https://singularityhub.com/?p=159889 In the late 1800s, Spanish neuroscientist Santiago Ramón y Cajal drew hundreds of images of neurons. His exquisite work influenced our understanding of what they look like: Cells with a bulbous center, a forest of tree-like branches on one end, and a long, smooth tail on the other.

Centuries later, these images remain textbook. But a controversial study now suggests Ramón y Cajal, and neuroscientists since, might have missed a crucial detail.

A team from Johns Hopkins University found tiny “bubbles” dotted along the long tail—called the axon. Normally depicted as a mostly smooth, cylindrical cable, axons may instead look like “pearls on a string.”

Why care? Axons transmit electrical signals connecting the neural networks that give rise to our thoughts, memories, and emotions. Small changes in their shape could alter these signals and potentially the brain’s output—that is, our behavior.

“Understanding the structure of axons is important for understanding brain cell signaling,” Shigeki Watanabe at the Johns Hopkins University School of Medicine, who led the study, said in a press release.

The work took advantage of a type of microscopy that better preserves neuron structure. In three types of mouse neurons—some grown in petri dishes, others from adult mice and mouse embryos—the team consistently saw the nanopearls, suggesting they’re part of an axon’s normal shape.

“These findings challenge a century of understanding about axon structure,” said Watanabe.

The nanopearls weren’t static. Adding sugar to the neurons’ liquid environment or stripping neurons of cholesterol in their membranes—the fatty protective outer layer—altered the nanopearls’ size and distribution and the speed signals traveled down axons.

Reactions to the study were split. Some scientist welcomed the findings. Over the last 70 years, scientists have extensively studied axon shape and recognized its complex structure. With improving microscope technologies, discovering new structures isn’t surprising, but it is rather exciting.

Others are more skeptical. Speaking to Science, Christophe Leterrier of Aix-Marseille University, who was not involved in the study, said: “I think it’s true that [the axon is] not a perfect tube, but it’s not also just this kind of accordion that they show.”

Cable With a Chance of Stress Balls

Axons stretch inches in the brain with diameters 100 times thinner than a human hair. Although mostly tubular in shape, they’re dotted with occasional bubbles, called synaptic varicosities, that contain chemicals for the transmission of information with neighboring neurons. These long branches mainly come in two types: Some are wrapped in fatty sheaths and others are “bare,” without the cushioning.

Although often compared to tree branches, axons are shapeshifters. A brief burst of electrical signaling, for example, causes synaptic varicosities to temporarily expand by 20 percent. The axons also grow slightly wider for a longer period, before settling back to their normal size.

These tiny changes have large impacts on brain computation. Like an electrical cable that can change its properties, they fine-tune signal strength between networks, and in turn, the overall function of neurons.

Axons have another trick up their sleeves: They shrink up into “stress balls” with injury, such as an unsuspected blow to the head during sports, or in Alzheimer’s or Parkinson’s disease. Stress balls are relatively large compared to synaptic varicosities. But they’re transient. The structures eventually loosen and regain a tubular shape. Rather than harmful, they likely protect the brain by limiting damage to smaller regions and nurture axons during recovery.

But axons’ shape-shifting prowess is temporary and often only under duress. What do axons look like in a healthy brain?

Pearls on a String

Roughly a decade ago, Watanabe noticed tiny bubbles in the axons of roundworms while developing a new microscopy technique. Although the structures were much smaller and more tightly packed than stress balls, he banked the results as a curiosity but didn’t investigate further. Years later, the University of Bergen’s Pawel Burkhardt also noticed pearly axons in comb jellies, a tiny marine invertebrate.

In the new study, Watanabe and colleagues revisited the head-scratching findings, armed with a newer microscopy technique: High-pressure freezing. To image fine details in the brain, scientists usually dose it with multiple chemicals to set neurons in place. The treated brains are then sliced extremely thin, and the pieces are individually scanned with a microscope.

The procedure takes days. Without care, it can distort a neuron’s membrane and damage or even shred delicate axons. In contrast, high-pressure freezing better locks in the cell’s shape.

Using an electron microscope—which outlines a cell’s structure by shooting beams of electrons at it—the team studied “bare” axons from three sources: mouse neurons grown in a lab dish and those from thin slices of adult and embryonic mouse brains.

All axons had the peculiar pearl-like blobs along their entire length. Roughly 200 nanometers across, the nanopearls are far smaller than stress balls, and they’re spaced closer together. The beads likely form due to biophysics. Recent studies show that under tension, sections of a long tube crumple into beads—a phenomenon dubbed “membrane-driven instability.” Why this happens and its impact on brain function remains mostly mysterious, but the team has ideas.

Seeing Is Believing?

Using mathematical simulations, they modeled how changes in the surrounding environment impacts an axon’s pearling and its electrical transmission.

Axons are surrounded by a goopy, protective protein gel, like a bubble suit. But they still experience physical forces—like when we rapidly snap our heads. Simulations found that physical tension surrounding neurons is a key player in managing axon pearling.

In another test, the team stripped cholesterol from the neurons—a component in their membranes—to make them more flexible and fluid-like. The tweak lessened pearling in simulations and slowed electrical signals as they passed through the simulated axon.

Recording electrical signals from living mouse neurons led to similar results. Smaller and more compactly packed nanopearls slowed signals down, whereas axons with larger and widely spaced ones led to faster transmission.

The results suggest an “intriguing idea” that changing biophysical forces could directly alter the speed of the brain’s electrical signaling, wrote the authors.

Not everyone is convinced.

Some scientists think the nanopearls are an artifact stemming from the preparation process. “While quick freezing is an extremely rapid process, something may happen during the manipulation of the sample” to cause beading, Pietro De Camilli at the Yale School of Medicine, who was not involved in the study, told Science. Others question if—like a stress ball—the nanopearls form during stress and will eventually unfold. We don’t yet know: Microscopy is a snapshot in time, rather than a movie.

Despite pushback, the team is turning to human axons. Healthy human brain tissue is hard to come by. They plan to look for signs of nanopearls in brain tissue removed during epilepsy surgery and from those who passed away due to neurodegenerative diseases. Brain organoids, or “mini-brains” developed from healthy people could also help decipher axon shape.

Regardless, the study spurs the question: When it comes to brain anatomy, what else have we missed?

Image Credit: Bioscience Image Library by Fayette Reynolds on Unsplash

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Neuralink Rival’s Biohybrid Implant Connects to the Brain With Living Neurons https://singularityhub.com/2024/12/19/neuralink-rival-says-its-biohybrid-implant-connects-to-the-brain-with-living-neurons/ Thu, 19 Dec 2024 15:00:22 +0000 https://singularityhub.com/?p=159881 Brain implants have improved dramatically in recent years, but they’re still invasive and unreliable. A new kind of brain-machine interface using living neurons to form connections could be the future.

While companies like Neuralink have recently provided some flashy demos of what could be achieved by hooking brains up to computers, the technology still has serious limitations preventing wider use.

Non-invasive approaches like electroencephalograms (EEGs) provide only coarse readings of neural signals, limiting their functionality. Directly implanting electrodes in the brain can provide a much clearer connection, but such risky medical procedures are hard to justify for all but the most serious conditions.

California-based startup Science Corporation thinks that an implant using living neurons to connect to the brain could better balance safety and precision. In recent non-peer-reviewed research posted on bioarXiv, the group showed a prototype device could connect with the brains of mice and even let them detect simple light signals.

“The principal advantages of a biohybrid implant are that it can dramatically change the scaling laws of how many neurons you can interface with versus how much damage you do to the brain,” Alan Mardinly, director of biology at Science Corporation, told New Scientist.

The company’s CEO Max Hodak is a former president of Neuralink, and his company also produces a retinal implant using more conventional electronics that can restore vision in some patients. But the company has been experimenting with so-called “biohybrid” approaches, which Hodak thinks could provide a more viable long-term solution for brain-machine interfaces.

“Placing anything into the brain inevitably destroys some amount of brain tissue,” he wrote in a recent blog post. “Destroying 10,000 cells to record from 1,000 might be perfectly justified if you have a serious injury and those thousand neurons create a lot of value—but it really hurts as a scaling characteristic.”

Instead, the company has developed a honeycomb-like structure made of silicon featuring more than 100,000 “microwells”—cylindrical holes roughly 15 micrometers deep. Individual neurons are inserted into each of these microwells, and the array can then be surgically implanted onto the surface of the brain.

The idea is that while the neurons remain housed in the implant, their axons—long strands that carry nerve signals away from the cell body—and their dendrites—the branched structures that form synapses with other cells—will be free to integrate with the host’s brain cells.

To see if the idea works in practice they installed the device in mice, using neurons genetically modified to react to light. Three weeks after implantation, they carried out a series of experiments where they trained the mice to respond whenever a light was shone on the device. The mice were able to detect when this happened, suggesting the light-sensitive neurons had merged with their native brain cells.

While it’s early days, the approach has significant benefits. You can squeeze a lot more neurons into a millimeter-scale chip than electrodes and each of those neurons can form many connections. That means the potential bandwidth of a biohybrid device could be much more than a conventional neural implant. The approach is also much less damaging to the patient’s brain.

However, the lifetime of these kinds of devices could be a concern—after 21 days, only 50 percent of the neurons had survived. And the company needs to find a way to ensure the neurons don’t illicit a negative immune response in the patient.

If the approach works though, it could be an elegant and potentially safer way to merge man and machine.

Image Credit: Science Corporation

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How to Be Healthy at 100: Centenarian Stem Cells Could Hold the Key https://singularityhub.com/2024/12/18/how-to-be-healthy-at-100-centenarian-stem-cells-could-hold-the-key/ Wed, 18 Dec 2024 15:00:19 +0000 https://singularityhub.com/?p=159860 When Jeanne Calment died at the age of 122, her longevity had researchers scratching their heads. Although physically active for most of her life, she was also a regular smoker and enjoyed wine—lifestyle choices that are generally thought to decrease healthy lifespan.

Teasing apart the intricacies of human longevity is complicated. Diet, exercise, and other habits can change the trajectory of a person’s health as they grow older. Genetics also plays a role—especially during the twilight years. But experiments to test these ideas are difficult, in part because of our relatively long lifespan. Following a large population of people as they age is prohibitively expensive, and results could take decades. So, most studies have turned to animal aging models—including flies, rodents, and dogs—with far shorter lives.

But what if we could model human “aging in a dish” using cells derived from people with exceptionally long lives?

A new study, published in Aging Cell, did just that. Leveraging blood draws from the New England Centenarian Study—the largest and most comprehensive database of centenarians—they transformed blood cells into induced-pluripotent stem cells (iPSCs).

These cells contain their donor’s genetic blueprint. In essence, the team created a biobank of cells that could aid researchers in their search for longevity-related genes.

“Models of human aging, longevity, and resistance to and/or resilience against disease that allow for the functional testing of potential interventions are virtually non-existent,” wrote the team.

They’ve already shared these “super-aging” stem cells with the rest of the longevity community to advance understanding of the genes and other factors contributing to a healthier, longer life.

“This bank is really exciting,” Chiara Herzog, a longevity researcher at Kings College London, who was not involved in the study, told Nature.

Precious Resource

Centenarians are rare. According to the Pew Research Center, based on data from the US Census Bureau, they make up only 0.03 percent of the country’s population. Across the globe, roughly 722,000 people have celebrated their 100th birthday—a tiny fraction of the over eight billion people currently on Earth.

Centenarians don’t just live longer. They’re also healthier, even in extreme old age, and less likely to suffer age-related diseases, such as dementia, Type 2 diabetes, cancer, or stroke. Some evade these dangerous health problems altogether until the very end.

What makes them special? In the last decade, several studies have begun digging into their genes to see which are active (or not) and how this relates to healthy aging. Others have developed aging clocks, which use myriad biomarkers to determine a person’s biological age—that is, how well their bodies are working. Centenarians frequently stood out, with a genetic landscape and bodily functions resembling people far younger than expected for their chronological age.

Realizing the potential for studying human aging, the New England Centenarian Study launched in 1995. Now based at Boston University and led by Tom Perls and Stacy Andersen, both authors of the new study, the project has recruited centenarians through a variety of methods—voter registries, news articles, or mail to elderly care facilities.

Because longevity may have a genetic basis, their children were also invited to join, with spouses serving as controls. All participants reported on their socioeconomic status and medical history. Researchers assessed their cognition on video calls and screened for potential mental health problems. Finally, some participants had blood samples taken. Despite their age, many centenarians remained sharp and could take care of themselves.

Super-Ager Stem Cells

The team first tested participants with a variety of aging clocks. These measured methylation, which shuts genes down without changing their DNA sequences. Matching previous results, centenarians were, on average, six and a half years younger than their chronological age.

The anti-aging boost wasn’t as prominent in their children. Some had higher biological ages and others lower. This could be because of variation in who inherited a genetic “signature” associated with longevity, wrote the team.

They then transformed blood cells from 45 centenarians into iPSCs. The people they chose were “at the extremes of health and functionality,” the team wrote. Because of their age, they initially expected that turning back the clock might not work on old blood cells.

Luckily, they were wrong. Several proteins showed the iPSCs were healthy and capable of making other cells. They also mostly maintained their genomic integrity—although surprisingly, cells from three male centenarians showed a slight loss of the Y chromosome.

Previous studies have found a similar deletion pattern in blood cells from males over 70 years of age. It could be a marker for aging and a potential risk factor for age-related conditions such as cancer and heart disease. Women, on average, live longer than men. The findings “allow for interesting research opportunities” to better understand why Y chromosome loss happens.

Unraveling Aging

Turning blood cells into stem cells erases signs of aging, especially those related to the cells’ epigenetic state. This controls whether genes are turned on or off, and it changes with age. But the underlying genetic code remains the same.

If the secrets to longevity are, even only partially, hidden in the genes, these super-aging stem cells could help researchers figure out what’s protective or damaging, in turn prompting new ideas that slow the ticking of the clock.

In one example, the team nudged the stem cells to become cortical neurons. These neurons form the outermost part of the brain responsible for sensing and reasoning. They’re also the first to decay in dementia or Alzheimer’s disease. Those derived from centenarians better fought off damage, such as rapidly limiting the spread of toxic proteins that accumulate with age.

Researchers are also using the cells to test for resilience against Alzheimer’s. Another experiment observed cell cultures made of healthy neurons, immune cells, and astrocytes. The latter, supporting cells that help keep brains healthy, were created using centenarian stem cells. Astrocytes have increasingly been implicated in Alzheimer’s, but their role has been hard to study in humans. Those derived from centenarian stem cells offer a way forward.

Each line of centenarian stem cells is linked to its donor—their demographics, cognitive, and physical state. This additional information could guide researchers in choosing the best centenarian cell line for their investigations into different aspects of aging. And because the cells can be transformed into a wide variety of tissues that decline with age—muscles, heart, or immune cells—they offer a new way to explore how aging affects different organs, and at what pace.

“The result of this work is a one-of-a-kind resource for studies of human longevity and resilience that can fuel the discovery and validation of novel therapeutics for aging-related disease,” wrote the authors.

Image Credit: Danie Franco on Unsplash

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The Tech World Is ‘Disrupting’ Book Publishing. But Do We Want Effortless Art? https://singularityhub.com/2024/12/17/the-tech-world-is-disrupting-book-publishing-but-do-we-want-effortless-art/ Tue, 17 Dec 2024 15:00:43 +0000 https://singularityhub.com/?p=159845 Publishing is one of many fields poised for disruption by tech companies and artificial intelligence. New platforms and approaches, like a book imprint by Microsoft and a self-publishing tech startup that uses AI, promise to make publishing faster and more accessible than ever.

But they also may threaten jobs—and demand a reconsideration of the status and role of books as cultural objects. And what will be the impact of TikTok owner ByteDance’s move into traditional book publishing?

Microsoft’s 8080 Books

Last month, Microsoft announced a new book imprint, 8080 Books. It will focus on nonfiction titles relating to technology, science, and business.

8080 Books plans “to test and experiment with the latest tech to accelerate and democratize book publishing,” though as some skeptics have noted, it is not yet entirely clear what this will entail.

The first title, No Prize for Pessimism  by Sam Schillace (Microsoft’s deputy chief technology officer) arguably sets the tone for the imprint. These “letters from a messy tech optimist” urge readers to embrace the disruptive potential of new technologies (AI is name-checked in the blurb), arguing optimism is essential for innovation and creativity. You can even discuss the book with its bespoke chatbot here.

Elsewhere, in the self-publishing space, tech startup Spines aims to bring 8,000 new books to market each year. For a fee, authors can use the publishing platform’s AI to edit, proofread, design, format, and distribute their books.

The move has been condemned by some authors and publishers, but Spines (like Microsoft) states its aim is to make publishing more open and accessible. Above all, it aims to make it faster, reducing the time it takes to publish to just a fortnight—rather than the long months of editing, negotiating, and waiting required by traditional publishing.

TikTok Is Publishing Books Too

Technological innovations are not just being used to speed up the publishing process, but also to identify profitable audiences, emerging authors, and genres that will sell. Chinese tech giant and owner of TikTok, ByteDance, launched their publishing imprint 8th Note Press (initially digital only) last year.

They are now partnering with Zando (an independent publishing company whose other imprints include one by actor Sarah Jessica Parker and another by the Pod Save America team’s Crooked Media) to produce a fiction range targeted at Gen Z readers. It will produce print books, to be sold in bookshops, from February.

8th Note Press focuses on the fantasy and romance genres (and authors) generating substantial followings on BookTok, the TikTok community proving invaluable for marketing and promoting new fiction. In the United States, authors with a strong presence on BookTok have seen a 23 percent growth in print sales in 2024, compared to 6 percent growth overall.

Access to Tiktok’s data and the ability to engineer viral videos could give 8th Note Press a serious advantage over legacy publishers in this space.

Hundreds of AI Self-Publishing Startups

These initiatives reflect some broader industry trends. Since OpenAI first demoed ChatGPT in 2022, approximately 320 publishing startups have emerged. Almost all of them revolve around AI in some way. There is speculation that the top five global publishers all have their own proprietary internal AI systems in the works.

Spotify’s entry into the audiobook market in 2023 has been described as a game changer by its CEO and is now using AI to recommend books to listeners. Other companies, like Storytel and Nuanxed, are using AI to autogenerate audiobook narration and expedite translations.

The embrace of AI may produce some useful innovations and efficiencies in publishing processes. It will almost certainly help publishers promote their authors and connect books with invested audiences. But it will have an impact on people working in the sector.

Companies like Storytel are using AI to narrate audiobooks. Image Credit: Karolina Grabowska/Pexels

Publishing houses have been consistently reducing in-house staff since the 1990s and relying more heavily on freelancers for editorial and design tasks. It would be naïve to think AI and other emerging technologies won’t be used to further reduce costs.

We are moving rapidly towards a future where once-important roles in the publishing sector—editing, translation, narration and voice acting, book design—will be increasingly performed by machines.

Spines’ CEO and cofounder, Yehuda Niv, has said, when queried, “We are not here to replace human creativity.” He emphasized his belief this automation will allow more writers to access the book market.

Storytel and Nuanxed have both suggested the growth of audiobook circulation will compensate for the replacement of human actors and translators. Exactly who will benefit the most from this growth—authors or faceless shareholders—remains to be seen.

Side Hustles, Grifts, and ‘Easy’ Writing

I appreciate Schillace’s genuine, thoughtful optimism about AI and other new technologies. (I will admit to not having read his book yet, but did have a stimulating conversation with its bot.) But my mind is drawn back to the techno-utopianists of the 19th century, like Edward Bellamy.

In his 1888 novel, Looking Backward, Bellamy speculates on a future in which art and literature flourishes, once advanced automation has freed people from the drudgery of miserable labor, leaving them with more time for cultural pursuits.

The inverse seems to be occurring now. Previously important and meaningful forms of cultural work are being increasingly automated.

I could be shortsighted about this, of course. The publishing disruption is just getting underway, and we’ve already made some great strides towards dispensing with the admittedly often quite miserable labor of writing itself.

We’re moving closer to ‘dispensing with the admittedly often quite miserable labour of writing itself’. Image Credit: Polina Zimmerman/Pexels

Soon after the launch of ChatGPT, science fiction magazines in the US had to close submissions, due being inundated with AI-generated short stories, many of them almost identical. Today, there are so many AI-assisted books being published on Amazon, they have had to limit self-publishing authors to just three uploads per day.

AI-assisted publishing enterprises range from side hustles focusing on republishing editions of texts in the public domain to grifts targeting unsuspecting readers and writers. All these schemes are premised on the idea writing can be rendered easy and effortless.

The use of AI may have other, delayed, costs though.

Can AI Be a ‘Thinking Partner’?

When I was younger, writing and publishing a lousy short story just obliterated my time and personal relationships. Now, I can do so with a one-sentence prompt, if I have a mind to—but apparently, this will destroy a lake somewhere.

Of course, as the No Prize for Pessimism bookbot takes pains to remind me, using AI in the writing process needn’t be a matter of lazy auto generation. It can be used for generative drafting, which is then revised, again and again, and integrated into the text.

AI can operate as a “thinking partner,” helping the writer with ideation and brainstorming. The technology is in its infancy, after all: There is bound to be some initial mess. But whatever way it is used, AI will help writers get to publication faster.

8080 Books’ charter offers a lot of rhetorical praise for the form of the book. We are told that books “matter,” that they impart “knowledge and wisdom,” that they “build empathy.” 8080 Books also wants to “accelerate the publishing process” and see less “lag” between the manuscript submission and its arrival in the marketplace. It wants books that are immediate and timely.

Slow Can Be Good

But what is a book if it arrives easily and at speed? Regardless of whether it is AI-generated or AI-assisted, it won’t be quite the same medium.

For much of their history, books have been defined by slowness and effort, both in writing and the journey towards publication. A book doesn’t always need to be up to date or of the moment.

Indeed, the hope might be that the slowness and effort of its production can lead to the book outlasting its immediate context and remaining relevant in other times and places.

Greater speed and broader access may be laudable aims for these publishing innovations. But they will also likely lead to greater disposability—at least in the short term—for both publishing professionals and the books themselves.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: Muhammed ÖÇAL on Unsplash

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Study Suggests an mRNA Shot Could Reverse This Deadly Pregnancy Condition https://singularityhub.com/2024/12/16/study-suggests-an-mrna-shot-could-reverse-this-deadly-pregnancy-condition/ Mon, 16 Dec 2024 15:00:19 +0000 https://singularityhub.com/?p=159825 With a single shot, scientists protected pregnant mice from a deadly complication called pre-eclampsia. The shot, inspired by mRNA vaccines, contains mRNA instructions to make a protein that reverses damage to the placenta—which occurs in the condition—protecting both mother and growing fetus.

Pre-eclampsia causes 75,000 maternal deaths and 500,000 fetal and newborn deaths every year around the globe. Trademark signs of the condition are extreme high blood pressure, reduced blood flow to the placenta, and sometimes seizures. Existing drugs, such as those that lower blood pressure, manage the symptoms but not the underlying causes.

“There aren’t any therapeutics that address the underlying problem, which is in the placenta,” study author Kelsey Swingle at the University of Pennsylvania told Nature.

Thanks to previous studies in mice, scientists already have an idea of what triggers pre-eclampsia: The placenta struggles to produce a protein crucial to the maintenance of structure and growth. Called vascular endothelial growth factor (VEGF), the condition inhibits the protein’s activity, interfering with the maternal blood vessels supporting placental health.

Restoring the protein could treat the condition at its core. The challenge is delivering it.

The team developed a lipid-nanoparticle system that directly targets the placenta. Like in Covid vaccines, these fatty “bubbles” are loaded with mRNA molecules that instruct cells to make the missing protein. But compared to standard lipid nanoparticles used in mRNA vaccines, the new bubbles—dubbed LNP 55—were 150 times more likely to home in on their target.

In two mouse models of pre-eclampsia, a single shot of the treatment boosted VEGF levels in the placenta, spurred growth of healthy blood vessels, and prevented symptoms. The treatment didn’t harm the fetuses. Rather, it helped them grow, and the newborn mouse pups were closer to a healthy weight.

The new approach is “an innovative method,” wrote Ravi Thadhani at Emory University and Ananth Karumanchi at the Cedars-Sinai Medical Center, who were not involved in the study.

A Surprising Start

The team didn’t originally focus on treating pre-eclampsia.

“We’re a drug delivery lab,” study author Michael Mitchell told Nature. But his interest was piqued when he started receiving emails from pregnant mothers, asking whether Covid-19 mRNA vaccines were safe for fetuses.

A quick recap: Covid vaccines contain two parts.

One is a strand of mRNA encoding the spike protein attached to the surface of the virus. Once in the body, the cell’s machinery processes the mRNA, makes the protein, and this triggers an immune response—so the body recognizes the actual virus after infection.

The other part is a lipid nanoparticle to deliver the mRNA cargo. These fatty bubbles are bioengineering wonders with multiple components. Some of these grab onto the mRNA; others stabilize the overall structure. A bit of cholesterol and other modified lipids lower the chance of immune attack.

Previously, scientists found that most lipid nanoparticles zoom towards the liver and release their cargo. But “being able to deliver lipid nanoparticles to parts of the body other than the liver is desirable, because it would allow designer therapeutics to be targeted specifically to the organ or tissue of interest,” wrote Thadhani and Karumanchi.

Inspired by the emails, the team first engineered a custom lipid nanoparticle that targets the placenta. They designed nearly 100 delivery bubbles—each with a slightly different lipid recipe—injected them into the bloodstream of pregnant mice, and tracked where they went.

One candidate, called LNP 55, especially stood out. The particles collected in the placenta, without going into the fetus. This is “ideal because the fetus is an ‘innocent bystander’ in pre-eclampsia” and likely not involved in triggering the complication, wrote Thadhani and Karumanchi. It could also lower any potential side effects to the fetus.

Compared to standard lipid nanoparticles, LNP 55 was 150 times more likely to move into multiple placental cell types, rather than the liver. The results got the team wondering: Can we use LNP 55 to treat pregnancy conditions?

Load It Up

The next step was finding the right cargo to tackle pre-eclampsia. The team decided on VEGF mRNA, which can fortify blood vessels in the placenta.

In two mouse models of pre-eclampsia in the middle of their pregnancy, a single injection reduced their high blood pressure almost immediately, and their blood pressure was stable until delivery of their pups. The treatment also lowered “toxins” secreted by the damaged placenta.

“This is really exciting outcome, and it suggests that perhaps we’re remolding the vasculature [blood vessel structure] to kind of see a really sustained therapeutic effect,” said Swingle.

The treatment also benefited the developing pups. Moms with pre-eclampsia often give birth to babies that weigh less. This is partly because doctors induce early delivery as a mother’s health declines. But an unhealthy placenta also contributes. Standard care for the condition can manage the mother’s symptoms, but it doesn’t change birth weight. The fetuses look almost “shriveled up” because of poor nutrient and lack of oxygen, said Mitchell.

Pups from moms treated with VEGF mRNA were far larger and healthier, looking almost exactly the same as normal mice born without pre-eclampsia.

A Long Road Ahead

Though promising, there are a few roadblocks before the treatment can help pregnant humans.

Our placentas are vastly different compared to those of mice, especially in their cellular makeup. The team is considering guinea pigs, which surprisingly have placentas more like humans, for future testing. Higher doses of VEGF may also trigger side effects, such as making blood vessels leakier—although the problem wasn’t seen in this study.

Dosing schedule is another problem. Mice are pregnant for roughly 20 days, a sliver of time compared to a human’s 40 weeks. While a single dose worked in mice, the effects may not last for longer pregnancies.

Then there’s timing. In humans, pre-eclampsia begins early when the placenta is just taking shape. Starting the treatment earlier, rather than in the middle of a pregnancy, could have different results.

Regardless, the study is welcome. Research into pregnancy complications has lagged cancer, heart conditions, metabolic disorders, and even some rare diseases. Limited funding aside, developing drugs for pregnancy is far more difficult because of stringent regulations in place to protect mother and fetus from unexpected and potentially catastrophic side effects.

The new work “offers a promising opportunity to tackle pre-eclampsia, one of the most common and devastating medical complications in pregnancy, and one that is in dire need of intervention,” wrote Thadhani and Karumanchi.

Image Credit: Isaac Quesada on Unsplash

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This Week’s Awesome Tech Stories From Around the Web (Through December 14) https://singularityhub.com/2024/12/14/this-weeks-awesome-tech-stories-from-around-the-web-through-december-14-2/ Sat, 14 Dec 2024 15:00:45 +0000 https://singularityhub.com/?p=159818 ARTIFICIAL INTELLIGENCE

Google’s New Project Astra Could Be Generative AI’s Killer App
Will Douglas Heaven | MIT Technology Review
“Last week I was taken through an unmarked door on an upper floor of a building in London’s King’s Cross district into a room with strong secret-project vibes. The word ‘ASTRA’ was emblazoned in giant letters across one wall. …’The pitch to my mum is that we’re building an AI that has eyes, ears, and a voice. It can be anywhere with you, and it can help you with anything you’re doing,’ says Greg Wayne, co-lead of the Astra team. ‘It’s not there yet, but that’s the kind of vision.'”

COMPUTING

Graphene Interconnects Aim to Give Moore’s Law New Life 
Dina Genkina | IEEE Spectrum
“Destination 2D, a startup based in Milpitas, Calif., claims to have solved [two challenges associated with using graphene in chips]. Destination 2D’s team has demonstrated a technique to deposit graphene interconnects onto chips at 300 °C, which is still cool enough to be done by traditional CMOS techniques. They have also developed a method of doping graphene sheets that offers current densities 100 times as dense as copper, according to Kaustav Banerjee, co-founder and CTO of Destination 2D.”

AUTOMATION

Wayve’s AI Self-Driving System Is Here to Drive Like a Human and Take On Waymo and Tesla
Ben Oliver | Wired
“[In contrast to Waymo’s hybrid system] Wayve’s AI operates without high-definition maps or coded interventions, and learns unsupervised from vast quantities of unlabeled real-life or simulated driving videos. ‘I think the gap between that geofenced robotaxi model and what an embodied AI solution can do is stark and game-changing,’ Wayve founder Alex Kendall says. ‘The market’s now somewhat swinging in our direction, but there’s no prizes for having the right idea eight years ago. Now it’s all down to execution.'”

ARTIFICIAL INTELLIGENCE

Harvard Makes 1 Million Books Available to Train AI Models
Kate Knibbs | Wired
“Harvard University announced Thursday it’s releasing a high-quality dataset of nearly 1 million public-domain books that could be used by anyone to train large language models and other AI tools. …In addition to the trove of books, the Institutional Data Initiative is also working with the Boston Public Library to scan millions of articles from different newspapers now in the public domain, and it says it’s open to forming similar collaborations down the line.”

TRANSPORTATION

Electric Cars Could Last Much Longer Than You Think
James Morris | Wired
“Rather than having a shorter lifespan than internal combustion engines, EV batteries are lasting way longer than expected, surprising even the automakers themselves. …A 10-year-old EV could be almost as good as new, and a 20-year-old one still very usable. That could be yet another disruption to an automotive industry that relies on cars mostly heading to the junkyard after 15 years.”

ENVIRONMENT

AI’s Emissions Are About to Skyrocket Even Further
James O’Donnell | MIT Technology Review
“AI models are rapidly moving from fairly simple text generators like ChatGPT toward highly complex image, video, and music generators. Until now, many of these ‘multimodal’ models have been stuck in the research phase, but that’s changing. ‘As we scale up to images and video, the data sizes increase exponentially,’ says Gianluca Guidi, a PhD student in artificial intelligence at University of Pisa and IMT Lucca, who is the paper’s lead author. Combine that with wider adoption, he says, and emissions will soon jump.”

SPACE

NASA’s Boss-to-Be Proclaims We’re About to Enter an ‘Age of Experimentation’
Stephen Clark | Ars Technica
“‘If the launch doesn’t cost a half-billion dollars, we don’t need to spend many, many years and lots of billions to get it right with some super exquisite asset, when you can get into a rhythm of using all of these providers to get things up very quickly to see what works and what doesn’t, and then evolve into something else,’ Jared Isaacman said. ‘What happens when industry starts cranking out spaceships out of multiple factories? …You’re going to have lots and lots of people in space at one time, and that’s why I call it a light switch-like moment, where a lot of things are going to change.'”

AUTOMATION

The End of Cruise Is the Beginning of a Risky New Phase for Autonomous Vehicles
Andrew J. Hawkins | The Verge
“Eight years and $10 billion later, GM has decided to pull the plug on its grand robotaxi experiment. The automaker’s CEO, Mary Barra, made the surprise announcement late on Tuesday, arguing that a shared autonomous mobility service was never really in its ‘core business.’ It was too expensive and had too many regulatory hurdles to overcome to make it a viable revenue stream. Instead, GM would pivot to ‘privately owned’ driverless cars—because, after all, that’s what the people really wanted.”

FUTURE

Galactic Civilizations May Be Impossible. Here’s Why.
Adam Frank | Big Think
“For galactic-scale civilizations to exist in our Universe, they would have to overcome two major hurdles related to physics and biology. One is the sheer distance between each society. The other is biological life span. …Do the laws of physics and the dynamics of social arrangements (even alien ones) allow for galactic societies? As much as I love them (how else could I become a Space Pirate?), I fear the answer may be ‘no.'”

Image Credit: Thomas Chan on Unsplash

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