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There seems to be no pattern to where humans pick up new viruses



Enlarge / A colorized transmission electron micrograph (TEM) of an Ebola virus virion.

A virus that normally infects animals makes the jump to humans, whose immune systems have never seen it before. It suddenly sweeps across the globe, leaving death and chaos in its wake. We’re living with that reality now and have gone through it previously with HIV, SARS, MERS, Ebola, Hanta, and various flu viruses that have threatened humanity in just the past few decades.

While there are many organizations that try to stay on top of threats of emerging diseases, it would be helpful if we could identify major sources of potential threats. If, for example, we knew that certain species were more prone to carrying viruses that could make the jump to humans, we could potentially survey the viruses found in those species, identify major threats, and potentially even develop therapies or vaccines in advance.

But a study published recently in PNAS suggests there’s no real pattern to where humans are picking up new viruses. Instead, groups with lots of species tend to have lots of viral species, and those make the jump to humans largely in proportion to the number of species.

Zoonotic risk

A disease that can be transmitted from animals to people is technically called “zoonotic.” While there are a variety of diseases that incorporate time in another species as part of their lifestyle—malaria is a classic example—the risk we’re concerned about is a virus that normally circulates within a non-human species but evolves the ability to spread within humans and leaves its original host behind.

These sorts of events are relatively common. Flu viruses seem to hop among us and our agricultural species with some regularity. Other viruses, like members of the hantavirus family, seem to frequently make the jump to humans without ever establishing the ability to spread from human to human.

It’s the latter feature that creates the risk for a global pandemic. Two earlier coronaviruses, SARS-CoV-1 and MERS, didn’t spread among humans as effectively as SARS-CoV-2, allowing containment methods to halt their spread before a pandemic could develop.

Are there any species that might be especially good launch pads for a pandemic? A couple of hypotheses suggests this could be the case. One hypothesis is that evolutionary distance matters. A virus that normally circulates in a species that’s related to humans is more likely to have components that can interact more effectively with the proteins that are present in human cells. If this were the case, we’d probably expect to see more zoonotic jumps taking place from viruses that infect our fellow primates.

An alternate idea has come out of the fact that this doesn’t seem to be consistently true. Bats, for example, have “gifted” humans with such distantly related viruses as SARS-CoV-1 and Ebola, and they’re not especially closely related to us. As a result, people have hypothesized that there might be what have been called “special reservoirs,” or species that, for ecological or lifestyle reasons, have ended up with viruses that can adapt more readily to human hosts. These special reservoirs could simply be more likely to live in close proximity to humans, raising the risks of transmission.

Two Glasgow researchers, Nardus Mollentze and Daniel Streicker, decided to conduct a test of these two hypotheses by figuring out whether there were any groups of species that were more likely to spread viruses to humans.

Building trees

To do so, Mollentze and Streicker built a comprehensive database of every virus that has been reported to make the jump to humans, as well as the host from which it jumped. In all, there were 415 different viruses that had a host assigned and could be used for the analysis (that’s out of 673 known virus species). These were spread across 30 families (the designation two levels above species) and had made their way out of 11 different orders of host species (an order is the level above family).

On their own, the results would seem to point to the special reservoir model, as hoofed ungulates (like our agricultural animals) and rodents collectively accounted for half the viruses that had transitioned to human hosts. But things got more complex when the authors tried to analyze the properties of a virus that made it more likely to make this transition. The best combination of properties, which could explain about half the probability of a zoonotic jump, was dominated by things like transmission through insects and a relatively simple replication cycle inside cells.

And, while the host’s order on the evolutionary tree appeared to matter at first, it mattered much less once the authors adjusted for a critical factor: how many individual species make up that order. For example, rodent and ungulate species may transmit more viruses to us, but there are a lot of species in these groups. If you adjust the rate by species number, the effect largely goes away. If you also control for the fact that we’ve identified far more virus species in mammals than in birds, then the effect becomes little more than statistical noise. The probability that a group of species will transmit a virus to humans becomes a function of how many species are in that group.

This is inconsistent with the special-reservoir hypothesis. But things don’t look great for the evolutionary explanation, either. While the zoonotic risk dropped as you got further from primates, this accounted for less than 1 percent of the overall risk.

In fact, if you simply estimated the number of zoonotic jumps based on the species number, groups that seemed threatening start to look fairly mundane. Rodents, for example, would be expected to have given 42 viruses to humans; we’re aware of 41 instances where that took place. Bats would be expected to have transferred 28 viruses to us but have only sent 22 of them. The one exception is, again, the ungulates, which seem to send viruses our way at rates above what we’d expect.

Now what?

The hope was that, by identifying the rules of zoonotic transfers, we could identify groups of species that have an elevated risk of causing problems and thus could be subjected to more careful monitoring. This analysis suggests that these groups might not exist. It doesn’t rule out the possibility that there are groups of species below the order level that are hotspots for zoonotic transfers. But at this point, the number of viruses transferred per group is likely to be small and might not stand out from statistical noise.

That said, some species/virus combinations are notable. For example, while bats are notable for having been the source of SARS-CoV-1 and Ebola, they’re actually most likely to transfer a new species of rabies virus to humans. Other primates are a major source of adenovirus and Dengue species, while rodents tend to transfer hantaviruses and arenaviruses.

While this isn’t especially good news for targeted surveillance efforts, that might not be bad news overall. Having obvious targets might mean we over-focus on those, leaving us vulnerable to risks we hadn’t anticipated.

PNAS, 2020. DOI: 10.1073/pnas.1919176117  (About DOIs).

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Prescription poop is here: FDA approves fecal slurry for unshakeable diarrhea



Enlarge / Laboratory technicians in France prepare stool to treat patients with serious colon infections by fecal microbiota transplantation (FMT), also known as gut flora transplant (GFT) in 2019.

For the first time, the US Food and Drug Administration has granted approval for a feces-based microbial treatment, which is used to prevent a recurring diarrheal infection that can become life-threatening.

The approval, announced Wednesday, is years in the making. Researchers have strained to harness the protective qualities of the complex, diverse, yet variable microbial communities found in healthy people’s intestines and stool. Early on, rich fecal matter proved useful for restoring balance and blocking infection in those whose microbiomes have been disturbed—a state called dysbiosis, which can occur from disease and/or use of antibiotic drugs. But, our understanding of what makes a microbiome healthy, functional, and protective remains incomplete.

Doctors, meanwhile, pushed ahead, informally trying an array of methods to transplant fecal microbiota from healthy donors to the guts of patients—via enemas, tubes through the nose, and oral poop-packed capsules. Fecal microbiota transplants (FMTs) have been used to treat various ailments, from obesity to irritable bowel syndrome, to mixed success. But it quickly became apparent that FMTs were most readily effective at preventing recurrent infection from Clostridioides difficile (C. difficile or just C. diff).

C. diff bacteria cause diarrhea and significant inflammation in the colon. Severe infections can be life-threatening. In people with dysbiosis, C. diff can proliferate in the intestines, producing toxins that can lead to organ failure. Older people, those who are hospitalized, and people with weakened immune systems are particularly susceptible to C. diff, which can recur over and over in some vulnerable patients. In the US, C. diff infections are associated with up to 30,000 deaths per year.

With the pressing need for effective treatments against C. diff, regulators were forced to wade through the mucky issue of regulating and standardizing something as unruly and myriad as fecal matter. It also led to years of microbial sleuthing, synthetic slurries, stool donations, and clinical trials.

Solid success

Now, a product has finally floated to the top: Rebyota, a blend of donor stool, saline, and laxative solution given in a single treatment as an enema. It’s teeming with heavily screened intestinal microbes at a concentration of 10,000,000 live organisms per milliliter. Its owner, Switzerland-based Ferring Pharmaceuticals, screens donors and their donated stool for a long list of infectious pathogens and other health factors.

In a Phase III clinical trial involving 262 participants—the results of which were published last month—Ferring’s scientists reported that treatment with Rebyota led to a higher prevention rate of recurrent C. diff infections than in a placebo group at a rate of 70.6 percent in the treatment group compared with 57.5 percent in the placebo group. Prevention of C. diff was defined as an absence of C. diff diarrhea for eight weeks following treatment or placebo. The treatment was well tolerated, with no serious side effects. The FDA noted that given the variability of fecal matter, there is a potential that it could contain an unforeseen infectious agent or food allergens.

The approval of Rebyota is “an advance in caring for patients who have recurrent C. difficile infection,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in an announcement. “Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening. As the first FDA-approved fecal microbiota product, today’s action represents an important milestone, as it provides an additional approved option to prevent recurrent CDI.”

Ferring—which acquired Rebyota in 2018 when it purchased its developer Minnestoa-based Rebiotix—also celebrated the approval.

“We believe this is a major breakthrough in harnessing the power of the human microbiome to address significant unmet medical needs. This is the first FDA approval of a live biotherapeutic and the culmination of decades of research and clinical development,” Ferring president Per Falk said. “Today’s announcement is not just a milestone for people living with recurrent C. difficile infection, but also represents a significant step which holds promise that many other diseases might be better understood, diagnosed, prevented, and treated using our rapidly evolving insights on the role of the microbiome in human health and disease.”

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Over a year later, Musk’s Neuralink still 6 months from human trials



Enlarge / The on-stage demo of the surgical robot practically extended into the audience.

On Wednesday night, Elon Musk hosted an update from his brain-computer interface company, Neuralink. Most of the update involved various researchers at the company providing overviews of the specific areas of technology development they were working on. But there wasn’t anything dramatically new in the tech compared to last year’s update, and it was difficult to piece the presentations together into a coherent picture of what the company plans to do with its hardware.

But probably the most striking thing is that last year’s update indicated that Neuralink was getting close to human testing. Over a year later, those tests remain about six months out, according to Musk.

Lots of tech

Neuralink involves a large series of overlapping technical efforts. The interface itself requires electrodes implanted into the brain. To connect those electrodes with the outside world, Neuralink is using a small bit of hardware implanted in the skull. This contains a battery that can be recharged wirelessly, and a low-power chip that gathers data from the electrodes, performs some simple processing on it, and then transmits that data wirelessly.

Getting all that in place requires delicate neurosurgery, and the company is developing a surgical robot to make that process safe and consistent.

On the other end of the process, neural signals have to be interpreted in near real time to understand what’s happening in a given brain region. This requires computer systems that can handle everything from patient-to-patient variability to hour-to-hour differences in brain activity. Finally, in some cases, the device will need to send information back to the brain in a way that the nerve cells there can interpret (either immediately or following a learning process).

That’s… a lot of things. And the event saw people talking about almost all of them. In many cases, the information was substantially similar to what was shown the year before. Various animals with implants were shown doing everything from playing Pong to manipulating cursors and typing using their implants—more examples than last year, but not radically different. Similarly, Musk talked a bit more about the implant’s processing capacity, now provided partly by an ARM processor. There are some indications of evolutionary progress, but there are no indications that it’s close to a finalized design that’s ready for a Food and Drug Administration submission.

Perhaps the most significant difference from years prior is the level of detail involved in the surgical robot. This time, there was both an on-stage demo of the hardware and a fair bit of time spent discussing the details of the surgical procedure it was being developed for. In the previous update, the development of the robot appeared to be lagging.

We’ve been here before

The event was said to be a general overview of the company’s activities, and the presentations seemed to cover all of the key areas Neuralink is working on. But there are issues with that approach.

One is that brain implants have been an active research area for decades. While the details are different, many things Neuralink was showing off have been done before. To an extent, that’s understandable. Neuralink is developing its own electrodes, implant, and processing system. As such, it needs to demonstrate that these systems can perform like previously tested electrodes in animal experiments. But, so far, at least, Neuralink hasn’t provided any indications that its systems are superior to those that have already been tested extensively or were on a trajectory to get there.

Meanwhile, some of its competitors progressed in the areas where Neuralink sought to differentiate itself. Blackrock Neurotech, for example, is now touting fully implantable electronics that offer wireless charging and data transfer. And the company has already sent hardware through a clinical trial and is applying for FDA approval. In fact, the company has several additional clinical trials in progress.

The custom surgical robot seems unique to Neuralink (though surgical robots are widely used for other purposes). But one of the Neuralink staff mentioned that the robot was a sticking point with the FDA, saying it’s difficult to demonstrate its safety to the satisfaction of regulators. And another one of its competitors, Synchron, hopes to avoid the need for major surgery by using blood vessels to get implants deep into the brain. And those devices have also managed to go through clinical trials already.

Another problem with Neuralink’s progress update is that it doesn’t clearly indicate that the company is ready to go to the FDA. Starting a clinical trial will mean that the company has finalized a hardware design (even if it’s working on next-generation hardware separately) and chosen a specific neural defect that it plans to treat. The update’s scattershot progress reports gave no indication that any of that has been done.

None of this is to say that there won’t ultimately be space for multiple technologies in the brain-computer implant space. Neuralink will likely eventually arrive where some of these other companies are now, or it might find a niche where its hardware is especially effective. But so far, the company isn’t sharing any information that indicates that it’s close to either result—much less accomplishing some of the more outlandish claims thrown around by Musk.

Neuralink’s presentation is available online. Oddly, for an organization run by a self-professed fan of free speech, the company has disabled comments on the video.

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A new satellite has become one of the 20 brightest stars in the sky



Enlarge / Observation of a BlueWalker 3 pass from Oukaimeden Observatory on Nov. 16 2022. The bright star lower left is Zeta Puppis.

CLEOsat/Oukaimeden Observatory/IAU CPS/A.E. Kaeouach

Last month, a Texas-based company announced that it had successfully deployed the largest-ever commercial communications satellite in low-Earth orbit.

This BlueWalker 3 demonstration satellite measures nearly 65 square meters, or about one-third the size of a tennis court. Designed and developed by AST SpaceMobile, the expansive BlueWalker 3 satellite is intended to demonstrate the ability of standard mobile phones to directly connect to the Internet via satellite. Large satellites are necessary to connect to mobile devices without a ground-based antenna.

In this emerging field of direct-to-mobile connectivity, which seeks to provide Internet service beyond the reach of terrestrial cellular towers, AST is competing with Lync, another company that also has launched demonstration satellites. In addition, larger players such as Apple and a team at SpaceX and T-Mobile have announced their intent to provide direct connectivity services.

So while there are many more such satellites coming, AST stands out at this time because it’s the first to launch an exceptionally large satellite, and it plans to start launching operational “BlueBird” satellites in late 2023.

IAU concerns

Since BlueWalker3’s launch in September, astronomers have been tracking the satellite, and their alarm was heightened following its antenna deployment last month. According to the International Astronomical Union, post-deployment measurements showed that BlueWalker 3 had an apparent visual magnitude of around 1 at its brightest, which is nearly as bright as Antares and Spica, the 15th and 16th brightest stars in the night sky.

For a few years, astronomers have been expressing concerns about megaconstellations, such as SpaceX’s Starlink satellites. While these are more numerous—there are more than 3,000 Starlink satellites in orbit—they are much smaller and far less bright than the kinds of satellites AST plans to launch. Eventually, AST plans to launch a constellation of 168 large satellites to provide “substantial” global coverage, a company spokesperson said.

Even one is enough for astronomers, however. “BlueWalker 3 is a big shift in the constellation satellite issue and should give us all reason to pause,” said Piero Benvenuti, a director at the International Astronomical Union.

The organization of astronomers is also concerned about the potential for radio interference from these “cell phone towers in space.” They will transmit strong radio waves at frequencies currently reserved for terrestrial cell phone communications but are not subject to the same radio quiet zone restrictions that ground-based cellular networks are. This could severely impact radio astronomy research—which was used to discover cosmic microwave background radiation, for example—as well as work in related fields.

Astronomers currently build their radio astronomy observatories in remote areas, far from cell tower interference. They are worried that these large, radio-wave transmitting satellites will interfere in unpopulated areas.

AST responds

An AST spokesperson provided a statement to Ars that said the impact of its satellites must be weighed against the “universal good” of cellular broadband for people on Earth. However, the company also said it is willing to work with astronomers to address their concerns.

“We are eager to use the newest technologies and strategies to mitigate possible impacts to astronomy,” the AST statement said. “We are actively working with industry experts on the latest innovations, including next-generation anti-reflective materials. We are also engaged with NASA and certain working groups within the astronomy community to participate in advanced industry solutions, including potential operational interventions.”

To that end, AST said it is committed to avoiding broadcasts inside or adjacent to the National Radio Quiet Zone in the United States, which is a large area of land that includes portions of West Virginia and Virginia, as well as additional radioastronomy locations.

A US-based astronomer who focuses on light pollution, John Barentine, told Ars he welcomed the company’s efforts to address radio interference. He also appreciates any efforts to mitigate effects on optical astronomy. However, Barentine warned, there is no recourse for astronomers but to take AST and other companies at face value due to a lack of regulatory oversight.

“Overtures by commercial space operators who commit that their activities in space will not adversely affect astronomy are made in the absence of any meaningful regulatory oversight that mandates mitigations,” he said. “AST SpaceMobile’s stated intentions are laudable, but for now, they’re just words. So I reserve judgment pending whatever actions the company takes.”

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