Hacker, artist, maker that works for the Museum of Science in Boston.
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Dwarf Fortress’ graphical upgrade provides a new way into a wildly wonky game

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Three dwarves heading into spooky, green-glowing caverns

Enlarge / Not pictured: the things that are far more dangerous to fortress-dwelling dwarves, like poor site planning, miasma, and a lack of drink.

After a long night of playing Dwarf Fortress, I had a concerned look on my face when I finally went to bed. My wife asked what was wrong. "I think I actually want to keep playing this," I said. I felt a nagging concern for many weeknights to come.

Available tomorrow on Steam and itch.io, the new version of Dwarf Fortress updates the legendary (and legendarily arcane) colony-building roguelike with new pixel-art graphics, music, some (default) keyboard shortcuts, and a beginners' tutorial. The commercial release aims to do two things: make the game somewhat more accessible and provide Tarn and Zach Adams, the brothers who maintained the game as a free download for 20 years, some financial security.

I know it has succeeded at its first job, and I suspect it will hit the second mark, too. I approached the game as a head-first review expedition into likely frustrating territory. Now I find myself distracted from writing about it because I keep thinking about my goblin defense and whether the fisherdwarf might be better assigned to gem crafting.

Getting hooked

Nearly 10 years ago, Ars' Casey Johnston spent 10 hours trying to burrow into Dwarf Fortress and came out more confused than before. The ASCII-based "graphics" played a significant role in her confusion, but so did the lack of any real onboarding, or even simple explanations or help menus about how things worked. Even after begrudgingly turning to a beginners' wiki, Johnston found nothing but frustration:

Where’s the command to build a table? Which workshop is the mason's? How do I figure that out? Should I just build another mason’s workshop because that may be faster than trying to find the right menu to identify the mason’s workshop?

In a few hours' time—and similarly avoiding the wiki guide until I'd tried going it alone for my first couple of runs—I got further into Dwarf Fortress' systems than Johnston did with her 10-hour ordeal, and I likely enjoyed it a good deal more. Using the new tutorial modes' initial placement suggestions and following its section-by-section cues, my first run taught me how to dig down, start a stockpile, assign some simple jobs, build a workshop, and—harkening back to Johnston's final frustrations—craft and place beds, bins, and tables, made with "non-economic stone."

That's about where the guidance ends, though. The new menus are certainly a lot easier to navigate than the traditional all-text, shortcut-heavy interface (though you can keep using multi-key combinations to craft and assign orders if you like). And the graphics certainly make it a lot easier to notice and address problems. Now, when an angry Giant Badger Boar kills your dogs and maims the one dwarf you have gathering plants outside, the threat actually looks like a badger, not a symbol you'd accidentally type if you held down the Alt key. If you build a barrel, you get something that resembles a barrel, which is no small thing when you're just getting started in this arcane world.

The newly added music also helps soften the experience for newcomers. It's intermittent, unobtrusive, and quite lovely and evocative. It seems designed to stave off the eeriness of too much silent strategizing without overstaying its welcome. I can appreciate a game that graphically evokes the 16-bit era without the audio-cue exhaustion common to the JRPGs and simulations of the time.

However gentler the aesthetics and guidance for a newcomer, all the game's brutally tough and interlocking systems are intact in this update. These systems crunch together in weird and wild ways, fed by the landscape, your recent and long-ago actions, and random numbers behind the scenes.

My first run ended in starvation and rock-bottom morale ("hissy fits" in common wiki language) because farming, butchering, and other procurements aren't covered in the tutorial. I shut down my second run early after picking a sandy area with an aquifer as a starting zone, thinking it would make glasswork and irrigation easier and being quickly disappointed with this strategy. I was proud on my third run to have started brewing and dispensing drinks (essential to dwarves' contentment), but I dug too close to a nearby river, and I abandoned that soggy fort as yet another lesson learned.

But I'll be back. For me, the commercial release of Dwarf Fortress succeeded at transforming the game from a grim, time-killing in-joke for diehards into a viable, if not graceful, challenge. I will start again, I will keep the badgers and floods at bay, and next time, I might have the privilege of failing to a magma monster, an outbreak of disease, or even a miscarriage of dwarf justice.

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jprodgers
53 days ago
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I've been looking forward to this, and I've been a DF player since 2007 or so. It's still going to be a very difficult game to get into, but at least some of the systems have been tidied up. DF is one of my favorite games, but it's not something I can recommend unless you are self motivated to both learn the game, and to pry the stories out of it.
Somerville, MA
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An escape pod was jettisoned during the fighting

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They say a week is a long time in politics, but it’s a lifetime on the internet. Like everyone else, we’ve been watching the goings on at Twitter with interest, and more than a dash of concern. Then the layoffs happened. It was time to get a lifeboat ready. After a lot of debate here at Pi Towers, we’ve now spun up our own Mastodon instance. The best thing about it? It’s running on a Raspberry Pi 4 hosted at Mythic Beasts.

It’s running on a Pi in the Sky ☁️.

Green links are good (verified) links, they’re how you can tell this is us on Mastodon.

Last week, Elon Musk walked into Twitter HQ carrying a kitchen sink, and within hours he had laid off half of Twitter’s staff. The lawsuits, then rehiring, started almost immediately afterwards. With the content moderation team cut to the bone, anecdotally at least, folks also started to see an uptick in abuse, spam, and other things. The changes in the way verification is going to work are worrying, and confusing. There are even discussions ongoing about putting the entire site behind a paywall.

That’s a lot of change in a short amount of time. So if you no longer feel like Twitter is a place to be, as some celebrities and academics have already, then you can now also follow us over on Mastodon.

If you haven’t yet joined you can sign up over at Mastodon.

What’s Mastodon? 🐘

Mastodon is yet another social media platform.

That doesn’t tell you a lot, does it? Let’s try that again.

Mastodon is an open-sourced Twitter alternative running as part of something called “the Fediverse.” Unlike platforms like Twitter or Facebook, Mastodon is federated. That means it’s decentralised. There isn’t just one central site where you can go and sign up, like you do for Twitter; instead there are lots of sites all of which talk to each other using a protocol called ActivityPub.

You can sign up to any Mastodon site — which are called instances — and you can follow folks who are on your own, or on any other, instance which is part of the fediverse. Instances all talk to each other, so which instance you’re on doesn’t generally make much of a difference to who you can follow, or who can follow you.

However, your instance is your “local community.” The instance you join could be for you and your friends, or it could be about what you do in your spare time, or for work. For instance, there are communities built around special interest groups like open-source software or cyber security, and geographical ones, like Scotland.

Why did you join Mastodon?

There are two main practical concerns. One is sociological, one is technical.

The changes coming to Twitter look to fundamentally change the way the site feels. The dramatic cuts that the moderation team seems to have taken will open up the platform to spam, scams, and other things that we don’t want to have to deal with on a day-to-day basis. But there are also issues around identity, and I’ve been thinking a lot about identity verification and trust since the announcements.

The announcements around Twitter Blue are concerning not because they give wider access to identity verification; we’d welcome that. Instead they don’t seem to do the opposite. It comes down to what identity itself means: a blue tick next to someone on Twitter no longer means that their identity has been verified by an employee of the company; it means that they can afford $8 a month. That’s not the same thing.

But putting all of that aside, Twitter is going to face technical problems. It probably won’t be a sudden and catastrophic collapse — in my head I have an image of a disk slowly filling up somewhere in Twitter’s data centre, and the site going down hard when it is full — it’s far more likely to be an accumulation of technical debt. Issues will pile up as the backlog of maintenance tasks and fixes that the reduced workforce just can’t get ahead of increases, and eventually, the site will end up as an unstable wreck. That isn’t good for any of us.

How do I join?

There are two ways you can join Mastodon. You can create an account on an existing instance, or you can create your own instance to host your own community and join the fediverse that way.

Because Mastodon is federated, joining an existing instance isn’t quite as simple joining a monolithic service like Twitter. You can sign up to any Mastodon instance to join the fediverse, and you should probably take a little bit of time to find a community that is right for you. On the other hand, you could start out by joining one of the “big” general servers, like mastodon.social, and then migrating to another instance later. Because moving between instances, and keeping your followers as you move, is something that’s entirely supported.

Alternatively, you can run your own server, and spin up your own Mastodon instance.

Why do you have your own instance?

We’ve opted to host our own instance. We’ve done this because, with multiple instances out there, we had to decide how to make sure people following us knew that our Raspberry Pi account was the “real” one.

Distributed systems are an interesting corner case when it comes to trust. Because when it comes to identity, you eventually have to trust someone. Whether that’s a corporation, like Twitter, or a government, or the person themselves. Trust is needed.

With Mastodon the root of trust for identity is the admin of the instance you’re on, and the admins on all the other instances, where you’re trusting them to remove “fake” accounts. Or, if you’re running your own instance, then it’s the domain name registrars. The details of our domain registration of the raspberrypi.social domain may be redacted for privacy, but our domain registrar knows who we are, and is the same registrar we use for all our other domains. They trust our government-issued identity to prove that we are Raspberry Pi Ltd. You can trust them, they trust the government, and ultimately the government trusts us because they can use Ultima Ratio Regum, the last argument of kings.

Although we are hosting our own instance, the development of the platform is all done by the folks at Mastodon. Mastodon itself, that’s the company behind the network, is a non-profit corporation based in Germany which is supported by both its sponsors and patreons, and because we’re committed to supporting platforms that support us, we’re putting our money where our mouth is and have become a platinum sponsor of Mastodon.

Are you leaving Twitter?

No. We’re not leaving Twitter: we like it there. It’s been our home these many years, but if the worst comes to the worst, we’re now part of the #TwitterMigration.

You’ll see us posting very similar stuff on both platforms, although Mastodon does offer us a bit more flexibility, including larger character counts and moderation that we own ourselves. So you’re going to see more content from us on Mastodon than you might on Twitter.

Because, right now, the way Mastodon presents posts is much more to our tastes: we have always preferred to see a feed made up of what the people we follow have to say when they say it. Twitter’s decision to curate the tweets in your feed never sat particularly well with us.

It is, however, vanishingly unlikely that you will ever hear any of us use the word “Toot” in conversation.

But I don’t know anyone?

You know us? But if you’re anything like us, you have probably spent a bunch of time trying to figure out who you want to follow on Twitter so that your timeline is full of kittens and puppies rather than Nazis and book burning. You’re not alone there, so people have gone off and built tools to help you migrate from Twitter into the fediverse. There are actually a bunch of tools, but the one we’ve used ourselves is called Debirdify. It uses some clever searches of people’s Twitter profiles to try and figure out if they’re also on Mastodon, and if so where.

Can I host my own instance?

Yes, but you’ll need your own server to do that. Our instance is running on a Raspberry Pi 4 hosted in a rack at Mythic Beasts in London, and it’s going to be rather interesting to see how it scales up.

That’s 96 Raspberry Pi 4 boards in a 3U rack unit.

You don’t have to host your instance on a Raspberry Pi, but if you can, why not? Right now both our instance, and Mythic Beasts‘ own instance, are hosted on Raspberry Pi 4.

Full details are coming later, probably sometime next week, when we’re going to do a full walk-through of how to host your own instance, including talking about how to do IPv6 natively with Mastodon. Because if your computer costs $35, your IP address shouldn’t have to cost $50.

If you want to host your own instance with Mythic Beasts, you can. Their host your own Raspberry Pi service is £7.65 per month, which comes awfully close to the new price point for Twitter Blue, and comes with 20GB of disk space. Alternatively, if you need to host a larger community, they’ve also committed to offering fully managed Mastodon instances. You can contact them for more information.

Either way, see you in the fediverse?

The post An escape pod was jettisoned during the fighting appeared first on Raspberry Pi.

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jprodgers
79 days ago
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Raspberry Pi foundation has probably the best writeup I've seen for getting off of twitter.
Somerville, MA
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Dwarf Fortress on Steam gets release date, trailer, and graphics beyond ASCII

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Two views of a <em>Dwarf Fortress</em> scene, in the original graphics and in the upcoming Steam/Itch.io release.

Enlarge / Two views of a Dwarf Fortress scene, in the original graphics and in the upcoming Steam/Itch.io release. (credit: Kitfox Games / Kevin Purdy)

The version of Dwarf Fortress that looks and sounds more like a game than a DOS-era driver glitch will be unearthed on December 6, the creators and its publisher announced Tuesday.

There's a trailer, a $30 price, and, should things go as planned, versions for Steam and Itch.io arriving that day. Buying these editions gets you a version with graphics, music, an improved UI and keyboard shortcuts, and—perhaps most importantly—a tutorial. It also supports the brothers who have worked on the game for more than 16 years, offering it for free and subsisting on donations. That free version of the game, ASCII graphics and all, will remain available.

You can see the difference in looks in the release trailer:

Dwarf Fortress Steam Edition trailer, featuring pixels that most humans can interpret as representations of real objects.

Or, for those not keen on moving-picture embeds, here are a couple of screenshots showing near-identical scenes from the trailer:

While the trailer is focused on the Steam release, Dwarf Fortress will also be sold through Itch.io, where creators typically receive a greater portion of proceeds. That's important for Zach and Tarn Adams, the two creators and coders who have seen the project through, and both dealt with family health concerns in recent years, including a cancer scare for Zach in the late 2010s.

What's the game actually like? Former Ars writer Casey Johnston spent 10 hours searching for that answer. Here's a snippet from her report:

I’m already in this thing, eight or so hours deep, so it's time to solve a problem. Googling the "non-economic stone" error takes me to the wiki. This error can happen “when a dwarf walls himself into a corner and is unable to leave to get more rocks. Be careful where you build your Mason's workshop, as some parts of it obstruct movement.” Otherwise, there may just be too many kinds of economic rock around (stone reserved for a special purpose) or a stockpile might block the loose stones that might be used for making things. I should be able to mine more and generate more loose stones, but I try mining around. Not a single thing changes.

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jprodgers
86 days ago
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I've been a DF player since 07, and I'm looking forward to the steam release, but it's certainly not a "game" for everyone.
Somerville, MA
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Open Circuits: Now available

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Earlier this year, I wrote about my then-forthcoming book, Open Circuits: The Inner Beauty of Electronic Components, co-written with our regular collaborator Eric Schlaepfer.

Open Circuits is a coffee table book full of close-up and cross-section photographs of everyday electronic components. And, it’s now shipping! As of today, it’s available in hardcover from your local bookstore, as well as to purchase online and in electronic versions.

Open Circuits, hardback

We also just launched a new website for the book, with links of where you can purchase it as well as lengthy galleries of images from the book and of outake photos.

We put up a list of sellers on the website, including direct from No Starch and our own store, where signed copies are available.

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jprodgers
86 days ago
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I've got this on my wish list.
Somerville, MA
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Dangerously wrong oxygen readings in dark-skinned patients spur FDA scrutiny

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A nurse uses a pulse oximeter on a patient in Plainfield, New Jersey, on October 26, 2016.

Enlarge / A nurse uses a pulse oximeter on a patient in Plainfield, New Jersey, on October 26, 2016. (credit: Getty | Bloomberg)

For years, studies have found racial bias in common oxygen-measuring devices called pulse oximeters, as well as alarming dangers from inaccurate blood oxygen measurements in dark-skinned patients. Now, the US Food and Drug Administration is summoning its expert advisers to review the problematic devices and consider new recommendations and regulatory actions.

The FDA announced Thursday that its advisory committee—the Anesthesiology and Respiratory Therapy Devices Panel (ARTDP)—would convene on November 1 to discuss pulse oximeters. Until then, the agency renewed emphasis on the safety warning it issued in February 2021, which noted that the ubiquitous devices "may be less accurate in people with dark skin pigmentation."

That warning closely followed a study from December 2020 that highlighted the racial bias of pulse oximeters amid the COVID-19 pandemic. The global spread of a respiratory disease with a hallmark symptom of breathing difficulty sent pulse oximeter usage soaring—elevating the problem of racial disparities. The 2020 study—led by researchers in Michigan and published in the New England Journal of Medicine—found that pulse oximeters were nearly three times more likely to miss dangerously low blood oxygen levels (hypoxemia) in Black patients compared with white patients.

From there, several other studies corroborated the racial bias and highlighted the danger it posed to dark-skinned patients during the pandemic and beyond. But, it certainly wasn't the first study to report the concerning bias. Researchers have long noted the racial disparity, with studies dating as early as 1991.

Dubious devices

Pulse oximeters were developed in the 1970s and have since become a mainstay in routine patient care, with current devices typically clipping onto a finger. They estimate blood oxygen saturation (SpO2) by assessing the relative absorbance of two wavelengths of light (red and infrared, generally) beamed into the finger, plus the pulse-based flow of blood through the arteries.

But, the devices were mainly tested and calibrated on light-skinned patients. Researchers suspect that the high levels of skin pigment, melanin, in dark-skinned patients can interfere with the absorbance measurements. Numerous studies have found that pulse oximeters tend to overestimate oxygen saturation in dark-skinned patients.

The dangers of those faulty readings were realized during the pandemic. A study published in May found that pulse oximeters' overestimation of SpO2 in Black and Hispanic patients with COVID-19 caused significant delays in care, including access to lifesaving treatments, such as dexamethasone. For some patients, the faulty readings meant their eligibility for treatment was never recognized by the devices. That study, led by researchers at Johns Hopkins University, appeared in JAMA Internal Medicine.

In July, another study in JAMA Internal Medicine by researchers in Boston found that darker-skinned patients in intensive care who had inaccurate pulse oximeter readings ended up receiving less supplemental oxygen. Meanwhile, a study published in the same month in BMJ by researchers in Michigan looked at records of more than 30,000 patients at the Veterans Health Administration between 2013 and 2019. It found that Black patients were more likely to have hypoxemia undetected by pulse oximetry. The study notes that hidden hypoxemia is linked to an increased risk of morbidity and mortality.

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jprodgers
130 days ago
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When I worked for the Museum of Science in Boston, one of the exhibits had a pulse oximeter in it, but it "took too long" to find a reading. So I went about trying to build one that would work more quickly at the expense of accuracy. I used both off the shelf and bought the sensors directly, and none of them would work with darker skin tones very well. They would take ages to give a reading, and when they did it didn't seem very accurate. Ultimately we dropped the pulse oximeter from the exhibit, because getting anyone to stand still for the time it took for a reading wasn't feasible.
Somerville, MA
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The mystery of why some people don’t catch COVID

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The mystery of why some people don’t catch COVID

Enlarge (credit: d3sign via Getty Images)

We all know a “COVID virgin,” or “Novid,” someone who has defied all logic in dodging the coronavirus. But beyond judicious caution, sheer luck, or a lack of friends, could the secret to these people’s immunity be found nestled in their genes? And could it hold the key to fighting the virus?

In the early days of the pandemic, a small, tight-knit community of scientists from around the world set up an international consortium, called the COVID Human Genetic Effort, whose goal was to search for a genetic explanation as to why some people were becoming severely sick with COVID while others got off with a mild case of the sniffles.

After a while, the group noticed that some people weren’t getting infected at all—despite repeated and intense exposures. The most intriguing cases were the partners of people who became really ill and ended up in intensive care. “We learned about a few spouses of those people that—despite taking care of their husband or wife, without having access to face masks—apparently did not contract infection,” says András Spaan, a clinical microbiologist at Rockefeller University in New York.

Spaan was tasked with setting up an arm of the project to investigate these seemingly immune individuals. But they had to find a good number of them first. So the team put out a paper in Nature Immunology in which they outlined their endeavor, with a discreet final line mentioning that “subjects from all over the world are welcome.”

The response, Spaan says, was overwhelming. “We literally received thousands of emails,” he says. The sheer volume rushing to sign up forced them to set up a multilingual online screening survey. So far, they’ve had about 15,000 applications from all over the world.

The theory that these people might have preexisting immunity is supported by historical examples. There are genetic mutations that confer natural immunity to HIV, norovirus, and a parasite that causes recurring malaria. Why would COVID be any different, the team rationalized? Yet, in the long history of immunology, the concept of inborn resistance against infection is a fairly new and esoteric one. Only a few scientists even take an interest. “It’s such a niche field, that even within the medical and research fields, it’s a bit pooh-poohed on,” says Donald Vinh, an associate professor in the Department of Medicine at McGill University in Canada. Geneticists don’t recognize it as proper genetics, nor immunologists as proper immunology, he says. This is despite there being a clear therapeutic goal. “If you can figure out why somebody cannot get infected, well, then you can figure out how to prevent people from getting infected,” says Vinh.

But finding immune people is an increasingly tricky task. While many have volunteered, only a small minority fit the narrow criteria of probably having encountered the virus yet having no antibodies against it (which would indicate an infection). The most promising candidates are those who have defied all logic in not catching COVID despite being at high risk: health care workers constantly exposed to COVID-positive patients, or those who lived with—or even better, shared a bed with—people confirmed to be infected.

By the time the team started looking for suitable people, they were working against mass vaccination programs, too. “On the one hand, a lot of people were getting vaccinated, which is great, don’t get me wrong,” says Vinh. “But those are not the people we want.” On the other hand, seeking out the unvaccinated “does invite a bit of a fringe population.” Of the thousands that flooded in after the call, about 800 to 1,000 recruits fit that tight bill.

Then the highly infectious omicron variant arrived. “Omicron has really ruined this project, I have to be honest with you,” says Vinh. It dramatically reduced their pool of candidates. But Spaan views omicron’s desecration in a more positive light: that some recruits survived the omicron waves really lends support to the existence of innate resistance.

Across the Atlantic, in Dublin, Ireland, another member of the group—Cliona O’Farrelly, ​​a professor of comparative immunology at Trinity College Dublin—set about recruiting health care workers at a hospital in Dublin. Of the cohort she managed to assemble, omicron did throw a wrench in the works—half of the people whose DNA they had sent off to be sequenced ended up getting infected with the variant, obviating their presumed resistance. To spread awareness of their research and find more suitable people, O’Farrelly went on the radio and expanded the call to the rest of the country. Again, enthusiasm abounded: More than 16,000 people came forward who claimed to have defied infection. “We’re now trying to deal with all of that,” she says. “I’m hoping that we’ll have one or two hundred from those, which will be unbelievably valuable.”

Now that they have a substantial cohort, the group will take a twofold approach to hunting for a genetic explanation for resistance. First, they’ll blindly run every person’s genome through a computer to see if any gene variation starts to come up frequently. At the same time, they’ll look specifically at an existing list of genes they suspect might be the culprits—genes that if different from usual would just make sense to infer resistance. An example is the gene that codes for the ACE2 receptor, a protein on the surface of cells that the virus uses to slip inside.

The consortium has about 50 sequencing hubs around the world, from Poland to Brazil to Italy, where the data will be crunched. While enrollment is still ongoing, at a certain point, they will have to decide they have enough data to move deeper into their research. “That’s going to be the moment we have people with clear-cut mutations in the genes that make sense biologically,” says Spaan.

Once they come up with a list of gene candidates, it’ll then be a case of narrowing and narrowing that list down. They’ll go through the list one by one, testing each gene’s impact on defenses against COVID in cell models. That process will take between four to six months, Vinh estimates.

Another complication could arise from the global nature of the project; the cohort will be massively heterogeneous. People in Slavic countries won’t necessarily have the same genetic variation that confers resistance as people of Southeast Asian ethnicity. Again, Spaan views this diversity as a plus: “This means that we can correct for ethnic origin in our analysis,” he says. But it also means, Vinh says, that they’re not just looking for one needle in one haystack—”you’re looking for the golden needle and the silver needle and the bronze needle, and you’re looking in the factory of haystacks.”

It’s unlikely to be one gene that confers immunity, but rather an array of genetic variations coming together. “I don’t think it’ll come down to a one-liner on the Excel sheet that says, ‘This is the gene,’” says Vinh. “If it happens to be a single gene, we will be floored.”

After all this work is done, natural genetic resistance will likely turn out to be extremely rare. Still, should they find protective genes, it could help to inform future treatments. There’s good reason to think this: In the 1990s, a group of sex workers in Nairobi, Kenya, defied all logic in failing to become infected with HIV during three years of follow-up testing. It was discovered that some were carrying a genetic mutation that produces a messed-up version of the protein called the CCR5 receptor, one of the proteins that HIV uses to gain entry to a cell and make copies of itself. Having the mutation means HIV can’t latch onto cells, giving natural resistance. This then inspired maraviroc, an antiretroviral used to treat infection, as well as the most promising “cure” for HIV, where two patients received stem cell transplants from a donor carrying the mutation and became HIV free.

It’s also possible that genetics doesn’t tell the full story of those who resist infection against all odds. For some, the reason for their protection might rest instead in their immune system. During the first wave of the pandemic, Mala Maini, a professor of viral immunology at University College London, and her colleagues intensively monitored a group of health care workers who theoretically probably should have been infected with COVID but for some reason hadn’t been. The team also looked at blood samples from a separate cohort of people, taken well before the pandemic. On closer inspection of the two groups’ samples, Maini’s team found a secret weapon lying in their blood: memory T cells—immune cells that form the second line of defense against a foreign invader. These cells, lying dormant from previous dalliances with other coronaviruses, such as the ones that cause the common cold, could be providing cross-protectivity against SARS-CoV-2, her team hypothesized in their paper in Nature in November 2021.

Other studies have supported the theory that these cross-reactive T cells exist and may explain why some people avoid infection. Maini compares the way these memory T cells might quickly attack SARS-CoV-2 to driving a car. If the car is unlike one you’ve ever driven before—a manual for a life-long automatic driver—it would take you a while to get to grips with the controls. But assume the pre-existing T cells are accustomed to automatics, and a SARS-CoV-2 encounter is like hopping into the driver’s seat of one, and you can see how they would launch a much quicker and stronger immune attack.

A previous seasonal coronavirus infection or an abortive COVID infection in the first wave—meaning an infection that failed to take hold—could create T cells that offer this preexisting immunity. But Maini points out a crucial caveat: This does not mean that you can skip the vaccine on the potential basis that you’re carrying these T cells.

More recently, Maini and her colleague Leo Swadling published another paper that looked at cells from the airways of volunteers, which were sampled and frozen before the pandemic. They figured, if the infection is getting shut down so quickly, then surely the cells responsible must be ready and waiting at the first sign of infection. The cohort in the study was small—just 10 people—but six out of the 10 had cross-reactive T cells sitting in their airways.

Off the back of her research, Maini is working on a vaccine with researchers at the University of Oxford that induces these T cells specifically in the mucus membranes of the airway, and which could offer broad protection against not only SARS-CoV-2 but a variety of coronaviruses. Such a vaccine could stop the COVID virus wriggling out of the existing vaccines’ reach, because while the spike protein—the focus of current vaccines—is liable to mutate and change, T cells target bits of viruses that are highly similar across all human and animal coronaviruses.

And a mucosal vaccine could prepare these T cells in the nose and throat, the ground zero of infection, giving COVID the worst shot possible at taking root. “We’re quite optimistic that that sort of approach could provide better protection against new emerging variants, and ideally also against a new transfer of a new animal zoonotic virus,” says Maini.

As for Spaan and his team, they also have to entertain the possibility that, after the slog, genetic resistance against SARS-CoV-2 turns out to be a pipedream. “That’s our fear—that we will do all this and we will find nothing,” says Vinh. “And that’s OK. Because that’s science, right?” O’Farrelly, on the other hand, has undeterred optimism they’ll find something. “You just can’t have people die and not have the equivalent at the other end of the spectrum.”

This story originally appeared on wired.com.

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jprodgers
136 days ago
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I know quite a few houses of people that haven't gotten it yet, mine included. We all are vaccinated, still wearing masks out in public, and generally avoiding large indoor gatherings.
Somerville, MA
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