Does SD-WAN Have a Future in a SASE World?
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2023 was the year that GPUs stood still
Andrew Cunningham
In many ways, 2023 was a long-awaited return to normalcy for people who build their own gaming and/or workstation PCs. For the entire year, most mainstream components have been available at or a little under their official retail prices, making it possible to build all kinds of PCs at relatively reasonable prices without worrying about restocks or waiting for discounts. It was a welcome continuation of some GPU trends that started in 2022. Nvidia, AMD, and Intel could release a new GPU, and you could consistently buy that GPU for roughly what it was supposed to cost.
That’s where we get into how frustrating 2023 was for GPU buyers, though. Cards like the GeForce RTX 4090 and Radeon RX 7900 series launched in late 2022 and boosted performance beyond what any last-generation cards could achieve. But 2023’s midrange GPU launches were less ambitious. Not only did they offer the performance of a last-generation GPU, but most of them did it for around the same price as the last-gen GPUs whose performance they matched.
The midrange runs in place
Not every midrange GPU launch will get us a GTX 1060—a card roughly 50 percent faster than its immediate predecessor and beat the previous-generation GTX 980 despite costing just a bit over half as much money. But even if your expectations were low, this year’s midrange GPU launches have been underwhelming.
The worst was probably the GeForce RTX 4060 Ti, which sometimes struggled to beat the card it replaced at around the same price. The 16GB version of the card was particularly maligned since it was $100 more expensive but was only faster than the 8GB version in a handful of games.
The regular RTX 4060 was slightly better news, thanks partly to a $30 price drop from where the RTX 3060 started. The performance gains were small, and a drop from 12GB to 8GB of RAM isn’t the direction we prefer to see things move, but it was still a slightly faster and more efficient card at around the same price. AMD’s Radeon RX 7600, RX 7700 XT, and RX 7800 XT all belong in this same broad category—some improvements, but generally similar performance to previous-generation parts at similar or slightly lower prices. Not an exciting leap for people with aging GPUs who waited out the GPU shortage to get an upgrade.
The best midrange card of the generation—and at $600, we’re definitely stretching the definition of “midrange”—might be the GeForce RTX 4070, which can generally match or slightly beat the RTX 3080 while using much less power and costing $100 less than the RTX 3080’s suggested retail price. That seems like a solid deal once you consider that the RTX 3080 was essentially unavailable at its suggested retail price for most of its life span. But $600 is still a $100 increase from the 2070 and a $220 increase from the 1070, making it tougher to swallow.
In all, 2023 wasn’t the worst time to buy a $300 GPU; that dubious honor belongs to the depths of 2021, when you’d be lucky to snag a GTX 1650 for that price. But “consistently available, basically competent GPUs” are harder to be thankful for the further we get from the GPU shortage.
Marketing gets more misleading
Enlarge / 1.7 times faster than the last-gen GPU? Sure, under exactly the right conditions in specific games.
Nvidia
If you just looked at Nvidia’s early performance claims for each of these GPUs, you might think that the RTX 40-series was an exciting jump forward.
But these numbers were only possible in games that supported these GPUs’ newest software gimmick, DLSS Frame Generation (FG). The original DLSS and DLSS 2 improve performance by upsampling the images generated by your GPU, generating interpolated pixels that make lower-res image into higher-res ones without the blurriness and loss of image quality you’d get from simple upscaling. DLSS FG generates entire frames in between the ones being rendered by your GPU, theoretically providing big frame rate boosts without requiring a powerful GPU.
The technology is impressive when it works, and it’s been successful enough to spawn hardware-agnostic imitators like the AMD-backed FSR 3 and an alternate implementation from Intel that’s still in early stages. But it has notable limitations—mainly, it needs a reasonably high base frame rate to have enough data to generate convincing extra frames, something that these midrange cards may struggle to do. Even when performance is good, it can introduce weird visual artifacts or lose fine detail. The technology isn’t available in all games. And DLSS FG also adds a bit of latency, though this can be offset with latency-reducing technologies like Nvidia Reflex.
As another tool in the performance-enhancing toolbox, DLSS FG is nice to have. But to put it front-and-center in comparisons with previous-generation graphics cards is, at best, painting an overly rosy picture of what upgraders can actually expect.
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NY Times copyright suit wants OpenAI to delete all GPT instances
Not the sincerest form of flattery —
Shows evidence that GPT-based systems will reproduce Times articles if asked.
Enlarge / Microsoft is named in the suit for allegedly building the system that allowed GPT derivatives to be trained using infringing material.
In August, word leaked out that The New York Times was considering joining the growing legion of creators that are suing AI companies for misappropriating their content. The Times had reportedly been negotiating with OpenAI regarding the potential to license its material, but those talks had not gone smoothly. So, eight months after the company was reportedly considering suing, the suit has now been filed.
The Times is targeting various companies under the OpenAI umbrella, as well as Microsoft, an OpenAI partner that both uses it to power its Copilot service and helped provide the infrastructure for training the GPT Large Language Model. But the suit goes well beyond the use of copyrighted material in training, alleging that OpenAI-powered software will happily circumvent the Times’ paywall and ascribe hallucinated misinformation to the Times.
Journalism is expensive
The suit notes that The Times maintains a large staff that allows it to do things like dedicate reporters to a huge range of beats and engage in important investigative journalism, among other things. Because of those investments, the newspaper is often considered an authoritative source on many matters.
All of that costs money, and The Times earns that by limiting access to its reporting through a robust paywall. In addition, each print edition has a copyright notification, the Times’ terms of service limit the copying and use of any published material, and it can be selective about how it licenses its stories. In addition to driving revenue, these restrictions also help it to maintain its reputation as an authoritative voice by controlling how its works appear.
The suit alleges that OpenAI-developed tools undermine all of that. “By providing Times content without The Times’s permission or authorization, Defendants’ tools undermine and damage The Times’s relationship with its readers and deprive The Times of subscription, licensing, advertising, and affiliate revenue,” the suit alleges.
Part of the unauthorized use The Times alleges came during the training of various versions of GPT. Prior to GPT-3.5, information about the training dataset was made public. One of the sources used is a large collection of online material called “Common Crawl,” which the suit alleges contains information from 16 million unique records from sites published by The Times. That places the Times as the third most referenced source, behind Wikipedia and a database of US patents.
OpenAI no longer discloses as many details of the data used for training of recent GPT versions, but all indications are that full-text NY Times articles are still part of that process (Much more on that in a moment.) Expect access to training information to be a major issue during discovery if this case moves forward.
Not just training
A number of suits have been filed regarding the use of copyrighted material during training of AI systems. But the Times’ suit goes well beyond that to show how the material ingested during training can come back out during use. “Defendants’ GenAI tools can generate output that recites Times content verbatim, closely summarizes it, and mimics its expressive style, as demonstrated by scores of examples,” the suit alleges.
The suit alleges—and we were able to verify—that it’s comically easy to get GPT-powered systems to offer up content that is normally protected by the Times’ paywall. The suit shows a number of examples of GPT-4 reproducing large sections of articles nearly verbatim.
The suit includes screenshots of ChatGPT being given the title of a piece at The New York Times and asked for the first paragraph, which it delivers. Getting the ensuing text is apparently as simple as repeatedly asking for the next paragraph.
ChatGPT has apparently closed that loophole in between the preparation of that suit and the present. We entered some of the prompts shown in the suit, and were advised “I recommend checking The New York Times website or other reputable sources,” although we can’t rule out that context provided prior to that prompt could produce copyrighted material.
Ask for a paragraph, and Copilot will hand you a wall of normally paywalled text.
John Timmer
But not all loopholes have been closed. The suit also shows output from Bing Chat, since rebranded as Copilot. We were able to verify that asking for the first paragraph of a specific article at The Times caused Copilot to reproduce the first third of the article.
The suit is dismissive of attempts to justify this as a form of fair use. “Publicly, Defendants insist that their conduct is protected as ‘fair use’ because their unlicensed use of copyrighted content to train GenAI models serves a new ‘transformative’ purpose,” the suit notes. “But there is nothing ‘transformative’ about using The Times’s content without payment to create products that substitute for The Times and steal audiences away from it.”
Reputational and other damages
The hallucinations common to AI also came under fire in the suit for potentially damaging the value of the Times’ reputation, and possibly damaging human health as a side effect. “A GPT model completely fabricated that “The New York Times published an article on January 10, 2020, titled ‘Study Finds Possible Link between Orange Juice and Non-Hodgkin’s Lymphoma,’” the suit alleges. “The Times never published such an article.”
Similarly, asking about a Times article on heart-healthy foods allegedly resulted in Copilot saying it contained a list of examples (which it didn’t). When asked for the list, 80 percent of the foods on weren’t even mentioned by the original article. In another case, recommendations were ascribed to the Wirecutter when the products hadn’t even been reviewed by its staff.
As with the Times material, it’s alleged that it’s possible to get Copilot to offer up large chunks of Wirecutter articles (The Wirecutter is owned by The New York Times). But the suit notes that these article excerpts have the affiliate links stripped out of them, keeping the Wirecutter from its primary source of revenue.
The suit targets various OpenAI companies for developing the software, as well as Microsoft—the latter for both offering OpenAI-powered services, and for having developed the computing systems that enabled the copyrighted material to be ingested during training. Allegations include direct, contributory, and vicarious copyright infringement, as well as DMCA and trademark violations. Finally, it alleges “Common Law Unfair Competition By Misappropriation.”
The suit seeks nothing less than the erasure of both any GPT instances that the parties have trained using material from the Times, as well as the destruction of the datasets that were used for the training. It also asks for a permanent injunction to prevent similar conduct in the future. The Times also wants money, lots and lots of money: “statutory damages, compensatory damages, restitution, disgorgement, and any other relief that may be permitted by law or equity.”
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Appeals court pauses ban on patent-infringing Apple Watch imports
still on hold —
Apple pulled the Watch Series 9 and Watch Ultra 2 from sale on December 21.
Jonathan M. Gitlin – Updated
Enlarge / The Apple Watch Series 9 released in September 2023.
Apple
Just before Christmas, Apple pulled two of its latest smartwatches from stores. The cause was not an unwelcome visit from the ghost of mechanical timepieces past but the International Trade Commission, which found that the California-based computer maker had infringed on some patents, resulting in the ITC banning the import of said watches. Yesterday, Reuters reported that Apple filed an emergency request for the courts to lift the ban and will appeal the ITC ruling.
And today, the US Court of Appeals for the Federal Circuit granted Apple’s wish, pausing the ban while it considers the tech company’s argument.
Apple’s watch problems started back in January. That’s when a court found that the light-based pulse oximetry sensor (found on the back of the watches) infringed patents held by Masimo, a medical device manufacturer also based in California.
At the time, Apple said since Masimo was not a consumer-focused company, it chose not to collaborate or acquire the medical device maker. Masimo, for its part, said that Apple led it on in discussions then took its idea and hired away Masimo engineers.
In October, the ITC upheld the ruling of infringement and started the process to ban imports of the watches, giving US President Joe Biden’s administration 60 days to review the case and possibly veto the ruling.
But the Biden administration has chosen not to interfere, unlike in 2013 when the Obama administration vetoed a ban on iPhones and iPads during a patent dispute between Apple and Samsung. Although the ITC’s import ban on Apple Watch Series 9 and Ultra 2 models was supposed to go into effect on December 26, Apple pulled the watches from sale a few days early. The older Apple Watch SE, which doesn’t use the infringing blood oxygen sensor, remains on sale.
“We strongly disagree with the USITC decision and resulting exclusion order, and are taking all measures to return Apple Watch Series 9 and Apple Watch Ultra 2 to customers in the US as soon as possible,” Apple said in a statement.
Apple had asked the CAFC to pause the ban until US Customs and Border Protection decides whether redesigned Apple Watches no longer infringe on Masimo’s patents, a decision that should be reached by January 12. Now the court has given the ITC a deadline of January 10 to respond to Apple.
This article was updated shortly after publication to reflect the court pausing the import ban.
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4-year campaign backdoored iPhones using possibly the most advanced exploit ever
NO ORDINARY VULNERABILITY —
“Triangulation” infected dozens of iPhones belonging to employees of Moscow-based Kaspersky.
Researchers on Wednesday presented intriguing new findings surrounding an attack that over four years backdoored dozens if not thousands of iPhones, many of which belonged to employees of Moscow-based security firm Kaspersky. Chief among the discoveries: the unknown attackers were able to achieve an unprecedented level of access by exploiting a vulnerability in an undocumented hardware feature that few if anyone outside of Apple and chip suppliers such as ARM Holdings knew of.
“The exploit’s sophistication and the feature’s obscurity suggest the attackers had advanced technical capabilities,” Kaspersky researcher Boris Larin wrote in an email. “Our analysis hasn’t revealed how they became aware of this feature, but we’re exploring all possibilities, including accidental disclosure in past firmware or source code releases. They may also have stumbled upon it through hardware reverse engineering.”
Four zero-days exploited for years
Other questions remain unanswered, wrote Larin, even after about 12 months of intensive investigation. Besides how the attackers learned of the hardware feature, the researchers still don’t know what, precisely, its purpose is. Also unknown is if the feature is a native part of the iPhone or enabled by a third-party hardware component such as ARM’s CoreSight
The mass backdooring campaign, which according to Russian officials also infected the iPhones of thousands of people working inside diplomatic missions and embassies in Russia, according to Russian government officials, came to light in June. Over a span of at least four years, Kaspersky said, the infections were delivered in iMessage texts that installed malware through a complex exploit chain without requiring the receiver to take any action.
With that, the devices were infected with full-featured spyware that, among other things, transmitted microphone recordings, photos, geolocation, and other sensitive data to attacker-controlled servers. Although infections didn’t survive a reboot, the unknown attackers kept their campaign alive simply by sending devices a new malicious iMessage text shortly after devices were restarted.
A fresh infusion of details disclosed Wednesday said that “Triangulation”—the name Kaspersky gave to both the malware and the campaign that installed it—exploited four critical zero-day vulnerabilities, meaning serious programming flaws that were known to the attackers before they were known to Apple. The company has since patched all four of the vulnerabilities, which are tracked as:
Besides affecting iPhones, these critical zero-days and the secret hardware function resided in Macs, iPods, iPads, Apple TVs, and Apple Watches. What’s more, the exploits Kaspersky recovered were intentionally developed to work on those devices as well. Apple has patched those platforms as well. Apple declined to comment for this article.
Detecting infections is extremely challenging, even for people with advanced forensic expertise. For those who want to try, a list of Internet addresses, files, and other indicators of compromise is here.
Mystery iPhone function proves pivotal to Triangulation’s success
The most intriguing new detail is the targeting of the heretofore-unknown hardware feature, which proved to be pivotal to the Operation Triangulation campaign. A zero-day in the feature allowed the attackers to bypass advanced hardware-based memory protections designed to safeguard device system integrity even after an attacker gained the ability to tamper with memory of the underlying kernel. On most other platforms, once attackers successfully exploit a kernel vulnerability they have full control of the compromised system.
On Apple devices equipped with these protections, such attackers are still unable to perform key post-exploitation techniques such as injecting malicious code into other processes, or modifying kernel code or sensitive kernel data. This powerful protection was bypassed by exploiting a vulnerability in the secret function. The protection, which has rarely been defeated in exploits found to date, is also present in Apple’s M1 and M2 CPUs.
Kaspersky researchers learned of the secret hardware function only after months of extensive reverse engineering of devices that had been infected with Triangulation. In the course, the researchers’ attention was drawn to what are known as hardware registers, which provide memory addresses for CPUs to interact with peripheral components such as USBs, memory controllers, and GPUs. MMIOs, short for Memory-mapped Input/Outputs, allow the CPU to write to the specific hardware register of a specific peripheral device.
The researchers found that several of MMIO addresses the attackers used to bypass the memory protections weren’t identified in any so-called device tree, a machine-readable description of a particular set of hardware that can be helpful to reverse engineers. Even after the researchers further scoured source codes, kernel images, and firmware, they were still unable to find any mention of the MMIO addresses.
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You’ll be paying extra for ad-free Prime Video come January
might want to level up —
Subscribers will have to opt-in to a pricier ad-free plan.
Amazon Prime Video
Amazon confirmed today in an email to Prime members that it will begin showing ads alongside its streaming Prime Video content starting January 29, 2024. The price will remain the same, but subscribers who don’t wish to see any ads will have to pay an additional $2.99 per month on top of their monthly or yearly Amazon Prime subscription. The change was first reported back in September.
“Starting January 29, Prime Video movies and TV shows will include limited advertisements,” Amazon wrote in an email sent to Amazon Prime subscribers. “This will allow us to continue investing in compelling content and keep increasing that investment over a long period of time. We aim to have meaningfully fewer ads than linear TV and other streaming TV providers. No action is required from you, and there is no change to the current price of your Prime membership.”
Subscribers who want to avoid ads can sign up for the extra monthly fee at the Prime Video website.
Prime Video isn’t the only streaming platform looking to increase revenues via ad-supported tiers and price hikes in a challenging economic environment: both Disney+ and Netflix, among others, have hiked their prices in recent months. HBO Max, Peacock, and Paramount+ all introduced lower-priced ad-supported options, and Netflix launched an ad-supported tier last year for $6.99 per month.
Netflix did recently grant subscribers an ad-free episode for every three episodes watched, as well as downloadable content. However, this was apparently designed to help advertisers “[tap] into the viewing behavior of watching multiple episodes in a row,” per the November Netflix announcement.
Disney+ and the Disney-controlled Hulu increased prices starting in October. The ad-free tier of Disney+ rose from $11 to $14 a month, while ad-free Hulu increased from $14 to $18 a month. Both services are also offered together for $20 a month, and the ad-supported tiers maintained their current pricing; both strategies seem intended to drive viewers to either sign up for multiple services or drop down to an ad-supported tier. This is the second price hike for both services in the last calendar year.
Apple TV+ announced monthly price hikes for several online services in October, including its catchall Apple One subscription service in October. Apple TV+ jumped from $6.99 to $9.99 per month, while Apple Arcade went from $4.99 to $6.99 monthly. Apple News+ used to cost $9.99 per month, but now it’s $12.99. “Raising these prices helps Apple stay attractive to shareholders even amidst the tricky economic context—or at least it will if consumers agree to keep paying,” Ars Senior Editor Sam Axon wrote at the time. “Raising prices too much could drive customers away; Apple seems to be betting that that will not be the case this time.”
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Big Tech is spending more than VC firms on AI startups
money cannon —
Microsoft, Google, and Amazon haved crowded out traditional Silicon Valley investors.
Enlarge / A string of deals by Microsoft, Google and Amazon amounted to two-thirds of the $27 billion raised by fledgling AI companies in 2023,
FT montage/Dreamstime
Big tech companies have vastly outspent venture capital groups with investments in generative AI startups this year, as established giants use their financial muscle to dominate the much-hyped sector.
Microsoft, Google and Amazon last year struck a series of blockbuster deals, amounting to two-thirds of the $27 billion raised by fledgling AI companies in 2023, according to new data from private market researchers PitchBook.
The huge outlay, which exploded after the launch of OpenAI’s ChatGPT in November 2022, highlights how the biggest Silicon Valley groups are crowding out traditional tech investors for the biggest deals in the industry.
The rise of generative AI—systems capable of producing humanlike video, text, image and audio in seconds—have also attracted top Silicon Valley investors. But VCs have been outmatched, having been forced to slow down their spending as they adjust to higher interest rates and falling valuations for their portfolio companies.
“Over the past year, we’ve seen the market quickly consolidate around a handful of foundation models, with large tech players coming in and pouring billions of dollars into companies like OpenAI, Cohere, Anthropic and Mistral,” said Nina Achadjian, a partner at US venture firm Index Ventures referring to some of the top AI startups.
“For traditional VCs, you had to be in early and you had to have conviction—which meant being in the know on the latest AI research and knowing which teams were spinning out of Google DeepMind, Meta and others,” she added.
Financial Times
A string of deals, such as Microsoft’s $10 billion investment in OpenAI as well as billions of dollars raised by San Francisco-based Anthropic from both Google and Amazon, helped push overall spending on AI groups to nearly three times as much as the previous record of $11 billion set two years ago.
Venture investing in tech hit record levels in 2021, as investors took advantage of ultra-low interest rates to raise and deploy vast sums across a range of industries, particularly those most disrupted by Covid-19.
Microsoft has also committed $1.3 billion to Inflection, another generative AI start-up, as it looks to steal a march on rivals such as Google and Amazon.
Building and training generative AI tools is an intensive process, requiring immense computing power and cash. As a result, start-ups have preferred to partner with Big Tech companies which can provide cloud infrastructure and access to the most powerful chips as well as dollars.
That has rapidly pushed up the valuations of private start-ups in the space, making it harder for VCs to bet on the companies at the forefront of the technology. An employee stock sale at OpenAI is seeking to value the company at $86 billion, almost treble the valuation it received earlier this year.
“Even the world’s top venture investors, with tens of billions under management, can’t compete to keep these AI companies independent and create new challengers that unseat the Big Tech incumbents,” said Patrick Murphy, founding partner at Tapestry VC, an early-stage venture capital firm.
“In this AI platform shift, most of the potentially one-in-a-million companies to appear so far have been captured by the Big Tech incumbents already.”
VCs are not absent from the market, however. Thrive Capital, Josh Kushner’s New York-based firm, is the lead investor in OpenAI’s employee stock sale, having already backed the company earlier this year. Thrive has continued to invest throughout a downturn in venture spending in 2023.
Paris-based Mistral raised around $500 million from investors including venture firms Andreessen Horowitz and General Catalyst, and chipmaker Nvidia since it was founded in May this year.
Some VCs are seeking to invest in companies building applications that are being built over so-called “foundation models” developed by OpenAI and Anthropic, in much the same way apps began being developed on mobile devices in the years after smartphones were introduced.
“There is this myth that only the foundation model companies matter,” said Sarah Guo, founder of AI-focused venture firm Conviction. “There is a huge space of still-unexplored application domains for AI, and a lot of the most valuable AI companies will be fundamentally new.”
Additional reporting by Tim Bradshaw.
© 2023 The Financial Times Ltd. All rights reserved. Not to be redistributed, copied, or modified in any way.
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Injection of “smart insulin” regulates blood glucose levels for one week
Sugary treat treatment —
Tests in animals show the material works like the body’s own system.
Enlarge / Smart insulin has the potential to make injections far less frequent.
People with type I diabetes have to inject themselves multiple times a day with manufactured insulin to maintain healthy levels of the hormone, as their bodies do not naturally produce enough. The injections also have to be timed in response to eating and exercise, as any consumption or use of glucose has to be managed.
Research into glucose-responsive insulin, or “smart” insulin, hopes to improve the quality of life for people with type I diabetes by developing a form of insulin that needs to be injected less frequently, while providing control of blood-glucose levels over a longer period of time.
A team at Zhejiang University, China, has recently released a study documenting an improved smart insulin system in animal models—the current work doesn’t involve any human testing. Their insulin was able to regulate blood-glucose levels for a week in diabetic mice and minipigs after a single subcutaneous injection.
“Theoretically, [smart insulin is] incredibly important going forward,” said Steve Bain, clinical director of the Diabetes Research Unit in Swansea University, who was not involved in the study. “It would be a game changer.”
Polymer cage
The new smart insulin is based on a form of insulin modified with gluconic acid, which forms a complex with a polymer through chemical bonds and strong electrostatic attraction. When insulin is trapped in the polymer, its signaling function is blocked, allowing a week’s worth of insulin to be given via a single injection without a risk of overdose.
Crucial to the “glucose responsive” nature of this system is the fact that the chemical structures of glucose and gluconic acid are extremely similar, meaning the two molecules bind in very similar ways. When glucose meets the insulin-polymer complex, it can displace some of the bound insulin and form its own chemical bonds to the polymer. Glucose binding also disrupts the electrostatic attraction and further promotes insulin release.
By preferentially binding to the polymer, the glucose is able to trigger the release of insulin. And the extent of this insulin release depends on how much glucose is present: between meals, when the blood-glucose level is fairly low, only a small amount of insulin is released. This is known as basal insulin and is needed for baseline regulation of blood sugar.
But after a meal, when blood-glucose spikes, much more insulin is released. The body can now regulate the extra sugar properly, preventing abnormally high levels of glucose—known as hyperglycemia. Long-term effects of hyperglycemia in humans include nerve damage to the hands and feet and permanent damage to eyesight.
This system mimics the body’s natural process, in which insulin is also released in response to glucose.
Better regulation than standard insulin
The new smart insulin was tested in five mice and three minipigs—minipigs are often used as an animal model that’s more physiologically similar to humans. One of the three minipigs received a slightly lower dose of smart insulin, and the other two received a higher dose. The lower-dose pig showed the best response: its blood-glucose levels were tightly controlled and returned to a healthy value after meals.
During treatment, the other two pigs had glucose levels that were still above the range seen in healthy animals, although they were greatly reduced compared to pre-injection levels. The regulation of blood-glucose was also tighter compared to daily insulin injections.
It should be noted, though, that the minipig with the best response also had the lowest blood-glucose levels before treatment, which may explain why it seemed to work so well in this animal.
Crucially, these effects were all long lasting—better regulation could be seen a week after treatment. And injecting the animals with the smart insulin didn’t result in a significant immune response, which can be a common pitfall when introducing biomaterials to animals or humans.
Don’t sugarcoat it
The study is not without its limitations. Although long-term glucose regulation was seen in the mice and minipigs examined, only a few animals were involved in the study—five mice and three minipigs. And of course, there’s always the risk that the results of animal studies don’t completely track over to clinical trials in humans. “We have to accept that these are animal studies, and so going across to humans is always a bit of an issue,” said Bain.
Although more research is required before this smart insulin system can be tested in humans, this work is a promising step forward in the field.
Nature Biomedical Engineering, 2023. DOI: 10.1038/s41551-023-01138-7
Ivan Paul is a freelance writer based in the UK, finishing his PhD in cancer research. He is on X @ivan_paul_.
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Getting to the bottom of how red flour beetles absorb water through their butts
On the third day of Christmas —
A unique group of cells pumps water into the kidneys to help harvest moisture from the air.
Kenneth Veland Halberg
There’s rarely time to write about every cool science-y story that comes our way. So this year, we’re once again running a special Twelve Days of Christmas series of posts, highlighting one science story that fell through the cracks in 2023, each day from December 25 through January 5. Today: red flour beetles can use their butts to suck water from the air, helping them survive in extremely dry environments. Scientists are honing in on the molecular mechanisms behind this unique ability.
The humble red flour beetle (Tribolium castaneum) is a common pantry pest feeding on stored grains, flour, cereals, pasta, biscuits, beans, and nuts. It’s a remarkably hardy creature, capable of surviving in harsh arid environments due to its unique ability to extract fluid not just from grains and other food sources, but also from the air. It does this by opening its rectum when the humidity of the atmosphere is relatively high, absorbing moisture through that opening and converting it into fluid that is then used to hydrate the rest of the body.
Scientists have known about this ability for more than a century, but biologists are finally starting to get to the bottom (ahem) of the underlying molecular mechanisms, according to a March paper published in the Proceedings of the National Academies of Science. This will inform future research on how to interrupt this hydration process to better keep red flour beetle populations in check, since they are highly resistant to pesticides. They can also withstand even higher levels of radiation than the cockroach.
There are about 400,000 known species of beetle roaming the planet although scientists believe there could be well over a million. Each year, as much as 20 percent of the world’s grain stores are contaminated by red flour beetles, grain weevils, Colorado potato beetles, and confused flour beetles, particularly in developing countries. Red flour beetles in particular are a popular model organism for scientific research on development and functional genomics. The entire genome was sequenced in 2008, and the beetle shares between 10,000 and 15,000 genes with the fruit fly (Drosophila), another workhorse of genetics research. But the beetle’s development cycle more closely resembles that of other insects by comparison.
Enlarge / Food security in developing nations is particularly affected by animal species like the red flour beetle which has specialized in surviving in extremely dry environments, granaries included, for thousands of years.
Kenneth Halberg
The rectums of most mammals and insects absorb any remaining nutrients and water from the body’s waste products prior to defecation. But the red flour beetle’s rectum is a model of ultra-efficiency in that regard. The beetle can generate extremely high salt concentrations in its kidneys, enabling it to extract all the water from its own feces and recycle that moisture back into its body.
“A beetle can go through an entire life cycle without drinking liquid water,” said co-author Kenneth Veland Halberg, a biologist at the University of Copenhagen. “This is because of their modified rectum and closely applied kidneys, which together make a multi-organ system that is highly specialized in extracting water from the food that they eat and from the air around them. In fact, it happens so effectively that the stool samples we have examined were completely dry and without any trace of water.” The entire rectal structure is encased in a perinephric membrane.
Halberg et al. took took scanning electron microscopy images of the beetle’s rectal structure. They also took tissue samples and extracted RNA from lab-grown red flour beetles, then used a new resource called BeetleAtlas for their gene expression analysis, hunting for any relevant genes.
One particular gene was expressed sixty times more in the rectum than any other. Halberg and his team eventually honed in a group of secondary cells between the beetle’s kidneys and circulatory system called leptophragmata. This finding supports prior studies that suggested these cells might be relevant since they are the only cells that interrupt the perinephric membrane, thereby enabling critical transport of potassium chloride. Translation: the cells pump salts into the kidneys to better harvest moisture from its feces or from the air.
Enlarge / Model of the beetle’s inside and how it extracts water from the air.
Kenneth Halberg
The next step is to build on these new insights to figure out how to interrupt the beetle’s unique hydration process at the molecular level, perhaps by designing molecules that can do so. Those molecules could then be incorporated into more eco-friendly pesticides that target the red flour beetle and similar pests while not harming more beneficial insects like bees.
“Now we understand exactly which genes, cells and molecules are at play in the beetle when it absorbs water in its rectum. This means that we suddenly have a grip on how to disrupt these very efficient processes by, for example, developing insecticides that target this function and in doing so, kill the beetle,” said Halberg. “There is twenty times as much insect biomass on Earth than that of humans. They play key roles in most food webs and have a huge impact on virtually all ecosystems and on human health. So, we need to understand them better.”
DOI: PNAS, 2023. 10.1073/pnas.2217084120 (About DOIs).
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