Author: Ben

  • The California home insurance conundrum

    As a California homeowner, I’ve watched with dismay as homeowner insurance provider after homeowner insurance provider have fled the state in the face of wildfire risk.

    It was quite the shock when I discovered recently (HT: Axios Markets newsletter) that, according to NerdWallet, California actually has some of the cheapest homeowners insurance rates in the country!

    It begs the Econ 101 question — is it really that the cost of wildfires are too high? Or that the price insurance companies can charge (something heavily regulated by state insurance commissions) is kept too low / not allowed to vary enough based on actual fire risk?

  • Why Intel has to make its foundry business work

    Historically, Intel has (1) designed and (2) manufactured its chips that it sells (primarily into computer and server systems). It prided itself on having the most advanced (1) designs and (2) manufacturing technology, keeping both close to its chest.

    In the late 90s/00s, semiconductor companies increasingly embraced the “fabless model”, whereby they would only do the (1) design while outsourcing the manufacturing to foundries like TSMC. This made it much easier and less expensive to build up a burgeoning chip business and is the secret to the success of semiconductor giants like NVIDIA and Qualcomm.

    Companies like Intel scoffed at this, arguing that the combination of (1) design and (2) manufacturing gave their products an advantage, one that they used to achieve a dominant position in the computing chip segment. And, it’s an argument which underpins why they have never made a significant effort in becoming a contract manufacturer — after all, if part of your technological magic is the (2) manufacturing, why give it to anyone else?

    The success of TSMC has brought a lot of questions about Intel’s advantage in manufacturing and, given recent announcements by Intel and the US’s CHIPS Act, a renewed focus on actually becoming a contract manufacturer to the world’s leading chip designers.

    While much of the attention has been paid to the manufacturing prowess rivalry and the geopolitical reasons behind this, I think the real reason Intel has to make the foundry business work is simple: their biggest customers are all becoming chip designers.

    While a lot of laptops and desktops and servers are still sold in the traditional fashion, the reality is more and more of the server market is being dominated by a handful of hyperscale data center operators like Amazon, Google, Meta/Facebook, and Microsoft, companies that have historically been able to obtain the best prices from Intel because of their volume. But, in recent years, in the chase for better and better performance and cost and power consumption, they have begun designing their own chips adapted to their own systems (as this latest Google announcement for Google’s own ARM-based server chips shows).

    Are these chips as good as Intel’s across every dimension? Almost certainly not. It’s hard to overtake a company like Intel’s decades of design prowess and market insight. But, they don’t have to be. They only have to be better at the specific use case Google / Microsoft / Amazon / etc need it to be for.

    And, in that regard, that leaves Intel with really only one option: it has to make the foundry business work, or it risks losing not just the revenue from (1) designing a data center chip, but from the (2) manufacturing as well.

    Axion processors combine Google’s silicon expertise with Arm’s highest performing CPU cores to deliver instances with up to 30% better performance than the fastest general-purpose Arm-based instances available in the cloud today, up to 50% better performance and up to 60% better energy-efficiency than comparable current-generation x86-based instances1. That’s why we’ve already started deploying Google services like BigTable, Spanner, BigQuery, Blobstore, Pub/Sub, Google Earth Engine, and the YouTube Ads platform on current generation Arm-based servers and plan to deploy and scale these services and more on Axion soon.

    Introducing Google Axion Processors, our new Arm-based CPUs
    Amin Vahdat | Google Blog

  • Starlink in the wrong hands

    On one level, this shouldn’t be a surprise. Globally always available satellite constellation = everyone and anyone will try to access this. This was, like many technologies, always going to have positive impacts — i.e. people accessing the internet where they otherwise couldn’t due to lack of telecommunications infrastructure or repression — and negative — i.e. terrorists and criminal groups evading communications blackouts.

    The question is whether or not SpaceX had the foresight to realize this was a likely outcome and to institute security processes and checks to reduce the likelihood of the negative.

    That remains to be seen…

    In Yemen, which is in the throes of a decade-long civil war, a government official conceded that Starlink is in widespread use. Many people are prepared to defy competing warring factions, including Houthi rebels, to secure terminals for business and personal communications, and evade the slow, often censored internet service that’s currently available.

    Or take Sudan, where a year-long civil war has led to accusations of genocide, crimes against humanity and millions of people fleeing their homes. With the regular internet down for months, soldiers of the paramilitary Rapid Support Forces are among those using the system for their logistics, according to Western diplomats.

    Elon Musk’s Starlink Terminals Are Falling Into the Wrong Hands
    Bruce Einhorn, Loni Prinsloo, Marissa Newman, Simon Marks | Bloomberg

  • Why don’t we (still) have rapid viral diagnostics?

    One of the most disappointing outcomes in the US from the COVID pandemic was the rise of the antivaxxer / public health skeptic and the dramatic politicization of public health measures.

    But, not everything disappointing has stemmed from that. Our lack of cheap rapid tests for diseases like Flu and RSV is a sad reminder of our regulatory system failing to learn from the COVID crisis of the value of cheap, rapid in-home testing or adopting to the new reality that many Americans now know how to do such testing.

    Dr. Michael Mina, the chief science officer for the at-home testing company eMed, said the FDA tends to have strict requirements for over-the-counter tests. The agency often asks manufacturers to conduct studies that demonstrate that people can administer at-home tests properly — a process that may cost millions of dollars and delay the test’s authorization by months or years, Mina said.

    “It’s taken a very long time in the past to get new self-tests authorized, like HIV tests or even pregnancy tests,” he said. “They’ve taken years and years and years and years. We have a pretty conservative regulatory approach.”

    Rapid tests for Covid, RSV and the flu are available in Europe. Why not in the U.S.?
    Aria Bendix | NBC News

  • Huggingface: security vulnerability?

    Anyone who’s done any AI work is familiar with Huggingface. They are a repository of trained AI models and maintainer of AI libraries and services that have helped push forward AI research. It is now considered standard practice for research teams with something to boast to publish their models to Huggingface for all to embrace. This culture of open sharing has helped the field make its impressive strides in recent years and helped make Huggingface a “center” in that community.

    However, this ease of use and availability of almost every publicly accessible model under the sun comes with a price. Because many AI models require additional assets as well as the execution of code to properly initialize, Huggingface’s own tooling could become a vulnerability. Aware of this, Huggingface has instituted their own security scanning procedures on models they host.

    But security researchers at JFrog have found that even with such measures, have identified a number of models that exploit gaps in Huggingface’s scanning which allow for remote code execution. One example model they identified baked into a Pytorch model a “phone home” functionality which would initiate a secure connection between the server running the AI model and another (potentially malicious) computer (seemingly based in Korea).

    The JFrog researchers were also able to demonstrate that they could upload models which would allow them to execute other arbitrary Python code which would not be flagged by Huggingface’s security scans.

    While I think it’s a long way from suggesting that Huggingface is some kind of security cesspool, the research reminds us that so long as a connected system is both popular and versatile, there will always be the chance for security risk, and it’s important to keep that in mind.

    As with other open-source repositories, we’ve been regularly monitoring and scanning AI models uploaded by users, and have discovered a model whose loading leads to code execution, after loading a pickle file. The model’s payload grants the attacker a shell on the compromised machine, enabling them to gain full control over victims’ machines through what is commonly referred to as a “backdoor”. This silent infiltration could potentially grant access to critical internal systems and pave the way for large-scale data breaches or even corporate espionage, impacting not just individual users but potentially entire organizations across the globe, all while leaving victims utterly unaware of their compromised state. 

    Data Scientists Targeted by Malicious Hugging Face ML Models with Silent Backdoor
    David Cohen | JFrog blog

  • Nope, the Dunning-Kruger Effect is just bad statistics

    The Dunning-Kruger effect encapsulates something many of us feel familiar with: that the least intelligent oftentimes assume they know more than they actually do. Wrap that sentiment in an academic paper written by two professors at an Ivy League institution and throw in some charts and statistics and you’ve got a easily citable piece of trivia to make yourself feel smarter than the person who you just caught commenting on something they know nothing about.

    Well, according to this fascinating blog post (HT: Eric), we have it all wrong. The way that Dunning-Kruger constructed their statistical test was designed to always construct a positive relationship between skill and perceived ability.

    The whole thing is worth a read, but they showed that using completely randomly generated numbers (where there is no relationship between perceived ability and skill), you will always find a relationship between the “skill gap” (perceived ability – skill) and skill, or to put it more plainly,

    (y-x) \sim x

    With y being perceived ability and x being actual measured ability.

    What you should be looking for is a relationship between perceived ability and measured ability (or directly between y and x) and when you do this with data, you find that the evidence for such a claim generally isn’t there!

    In other words:

    The Dunning-Kruger effect also emerges from data in which it shouldn’t. For instance, if you carefully craft random data so that it does not contain a Dunning-Kruger effect, you will still find the effect. The reason turns out to be embarrassingly simple: the Dunning-Kruger effect has nothing to do with human psychology. It is a statistical artifact — a stunning example of autocorrelation.

    The Dunning-Kruger Effect is Autocorrelation
    Blair Fix | Economics from the Top Down

  • A Heart Atlas

    The human heart is an incredibly sophisticated organ that, in addition to being one of the first organs developed while embryos develop, is quite difficult to understand at a cellular level (where are the cells, how do they first develop, etc.).

    Neil Chi’s group at UCSD (link to Nature paper) were able to use multiplex imaging of fluorescent-tagged RNA molecules to profile the gene expression profiles of different types of heart cells and see where they are located and how they develop!

    The result is an amazing visualization, check it out at the video:

  • Cat Bond Fortunes

    Until recently, I only knew of the existence of cat(astrophe) bonds — financial instruments used to raise money for insurance against catastrophic events where investors profit when no disaster happens.

    I had no idea, until reading this Bloomberg article about the success of Fermat Capital Management, how large the space had gotten ($45 billion!!) or how it was one of the most profitable hedge fund strategies of 2023!

    This is becoming an increasingly important intersection between climate change and finance as insurance companies and property owners struggle with the rising risk of rising damage from extreme climate events. Given how young much of the science of evaluating these types of risks is, it’s no surprise that quantitative minds and modelers are able to profit here.

    The entire piece reminded me of Richard Zeckhauser’s famous 2006 article Investing in the Unknown and Unknowable which covers how massive investment returns can be realized by tackling problems that seem too difficult for other investors to understand.

    Investing in cat bonds was the most profitable hedge fund strategy of 2023. Fermat delivered a 20% return, beating the average 8% achieved by hedge funds as a whole. While other cat bond funds did well too, Fermat’s $10 billion portfolio — capturing a quarter of the market — made it by far the most prolific investor to take advantage of a bumper year.

    Cat bonds investors are gambling on nature. If a disaster they’ve bet on occurs, their money is used to settle insurance claims. If it doesn’t, they get handsome returns. For decades, the instruments were a last resort reserved for super-rare events, such as a cataclysmic storm on the scale of Hurricane Katrina. But multibillion-dollar calamities have become alarmingly frequent on a warmer planet.

    “The insurance market is on edge,” says Seo. “It’s freaked out about risk and wants as little as possible.”

    How a Physics Whiz Made a Fortune Betting on Nature’s Catastrophes
    Gautam Naik | Bloomberg

  • Shein and Temu now drive global cargo

    Maybe you have shopped on Shein or Temu. Maybe you only know someone (younger?) who has. Maybe you only know Temu because of their repeat Superbowl ads.

    But these Chinese eCommerce companies are now the main driver behind air and ship cargo rates with Temu and Shein combined accounting for 9,000 tons per day of shipments!

    This is scale.

    Shein and Temu together send almost 600,000 packages to the United States every day, according to a June 2023 report by the U.S. Congress – is boosting air-freight costs from Asian hubs like Guangzhou and Hong Kong, making off-peak seasons almost disappear and causing capacity shortages, the sources said.

    “The biggest trend impacting air freight right now is not the Red Sea, it’s Chinese e-commerce companies like Shein or Temu,” said Basile Ricard, director of Greater China operations at freight forwarder Bollore Logistics

    Rise of fast-fashion Shein, Temu roils global air cargo industry
    Arriana McLymore, Casey Hall, and Lisa Barrington | Reuters

  • Geothermal data centers

    The data centers that power AI and cloud services are limited by 3 things:

    • the server hardware (oftentimes limited by access to advanced semiconductors)
    • available space (their footprint is massive which makes it hard to put them close to where people live)
    • availability of cheap & reliable (and, generally, clean) power

    If you, as a data center operator, can tap a new source of cheap & reliable power, you will go very far as you alleviate one of the main constraints on the ability to add to your footprint.

    It’s no small wonder, then, that Google is willing to explore partnerships with next-gen geothermal startups like Fervo in a meaningful long-term fashion.

    But Google is hoping the road to commercialization for next-generation geothermal will mimic the early days of the tech industry’s solar procurement efforts, Maud Texier, global director of clean energy and decarbonization development, told Latitude Media.

    “While there are some important differences between solar and geothermal technologies, we would like to see geothermal power follow a similar trajectory as solar has over the last few decades in terms of rapid cost declines and performance improvements,” Texier said.

    A geothermal plant

    Google: Geothermal could follow ‘similar trajectory’ to solar
    Maeve Allsup | Latitude Media

  • Dexcom non-prescription glucose monitor approved

    Cheap and accurate continuous glucose monitoring is a bit of a holy grail for consumer metabolic health as it allows people to understand how their diet and exercise impact their blood sugar levels, which can vary from person to person.

    It’s also a holy grail for diabetes care as making sure blood sugar levels are neither too high nor too low is critical for health (too low and you can pass out or risk seizure or coma; too high and you risk diabetic neuropathy, kidney disease, and cardiovascular problems). For Type I diabetics and severe Type II diabetics, it’s also vital for dosing insulin.

    Because insulin dosing needs to be done just right, I was always under the impression that one of two things would happen along the way to producing a cheap continuous glucose monitor, either:

    1. The FDA would be hesitant to approve a device that wasn’t highly accurate to avoid the risk of a consumer using the reading to mis-dose insulin OR
    2. The device makers (like Dexcom) would be hesitant to create an accurate enough glucose monitor that it might cannibalize their highly profitable prescription glucose monitoring business

    As a result, I was pleasantly surprised that Dexcom’s over-the-counter Stelo continuous glucose monitor was approved by the FDA. It remains to be seen what the price will be and what level of information the Stelo will share with the customer, but I view this as a positive development and (at least for now) tip my hat to both the FDA and Dexcom here.

    (Thanks to Erin Brodwin from Axios for sharing the news on X)

    Dexcom shared Stelo’s name, and that the device had been submitted to the FDA for review in February. The sensor will be worn on the upper arm and lasts for up to 15 days before it needs to be replaced, according Dexcom.

    Jake Leach, chief operating officer at Dexcom, told CNBC in February that Stelo will have a unique platform and branding. The platform will be tailored to the needs of these Type 2 patients, he said, which means it will not include many of the alerts and notifications meant for diabetes patients at risk of experiencing more serious emergencies.

    “It’s designed to be a simpler experience,” Leach said in an interview. “There’s a lot of people who could benefit.”

    Dexcom’s first-ever over-the-counter glucose monitor patch gets FDA clearance
    Ashley Capoot | CNBC

  • “Corporate” Design

    Read an introspective piece by famed ex-Frog Design leader Robert Fabricant about the state of the design industry and the unease that he says many of his peers are feeling. While I disagree with some of the concerns he lays out around AI / diversity being the drivers of this unease, he makes a strong case for how this is a natural pendulum swing after years of seeing “Chief Design Officers” and design innovation groups added to many corporate giants.

    I’ve had the privilege of working with very strong designers. This has helped me appreciate the value of design thinking as something that goes far beyond “making things pretty” and believe, wholeheartedly, that it’s something that should be more broadly adopted.

    At the same time, it’s also not a surprise to me that during a time of layoffs and cost cutting, a design function which has become a little “spoiled” in the past years and of which calculating financial returns is experiencing some painful transition especially for creative-minded designers who struggle with that ROI evolution.

    If Phase 1 was getting companies to recognize that design thinking is needed, Phase 2 will be the space learning how to measure, communicate, and optimize what the value of a team of seasoned designers brings to the bottom line.

    In recent years, there has also been a shift in the very nature of design leadership inside companies. Where the early corporate pioneers were in “building mode” to establish and integrate design capabilities, these functions are now focused on optimization. That is where the professionals at IBM and Accenture/Song come in, with creativity giving way to utilization as the primary metric of success, particularly in an economic downturn. 

    Magowan of Design Leaders is hearing this sentiment from his clients on the hiring side. “Companies are still adjusting,” he says. “Trying to understand how to embed design properly and not make the mistakes they made by hiring folks into design leadership roles who were not equipped.”

    This transition is not well-suited to most creative leaders, even proven ones like Powell. “Scaling takes attention,” he says. “But once you get there, then you need to keep turning the dial so that this [design] machine runs more and more efficiently. For me that is where it got to be not as fun.” Perhaps 2024, then, is the right moment for the big handoff to the folks at McKinsey Design to lead the charge armed with their corporate reports and CDO roundtables on business value and design effectiveness?

    The big design freak-out: A generation of design leaders grapple with their future
    Robert Fabricant | Fast Company

  • Costco Love

    Nice piece in the Economist about how Costco’s model of operational simplicity leads to a unique position in modern retail: beloved by customers, investors, AND workers:

    • sell fewer things ➡️
    • get better prices from suppliers & less inventory needed ➡️
    • lower costs for customers ➡️
    • more customers & more willing to pay recurring membership fee ➡️
    • strong, recurring profits ➡️
    • ability to pay well and promote from within 📈💪🏻

    Customers are not the only fans of Costco, as the outpouring of affection from Wall Street analysts after Mr Galanti announced his retirement on February 6th made clear. The firm’s share price is 430 times what it was when he took the job nearly four decades ago, compared with 25 times for the s&p 500 index of large companies. It has continued to outperform the market in recent years.

    Why Costco is so loved
    The Economist

  • How packaging tech is changing how we build & design chips

    Once upon a time, the hottest thing in chip design was “system-on-a-chip” (SOC). The idea is that you’d get the best cost and performance out of a chip by combining more parts into one piece of silicon. This would result in smaller area (less silicon = less cost) and faster performance (closer parts = faster communication) and resulted in more and more chips integrating more and more things.

    While the laws of physics haven’t reversed any of the above, the cost of designing chips that integrate more and more components has gone up sharply. Worse, different types of parts (like on-chip memory and physical/analog componentry) don’t scale down as well as pure logic transistors, making it very difficult to design chips that combine all these pieces.

    The rise of new types of packaging technologies, like Intel’s Foveros, Intel’s EMIB, TSMC’s InFO, new ways of separating power delivery from data delivery (backside power delivery), and more, has also made it so that you can more tightly integrate different pieces of silicon and improve their performance and size/cost.

    The result is now that many of the most advanced silicon today is built as packages of chiplets rather than as massive SOC projects: a change that has happened over a fairly short period of time.

    This interview with IMEC (a semiconductor industry research center)’s head of logic technologies breaks this out…

    What we’re doing in CMOS 2.0 is pushing that idea further, with much finer-grained disintegration of functions and stacking of many more dies. A first sign of CMOS 2.0 is the imminent arrival of backside-power-delivery networks. On chips today, all interconnects—both those carrying data and those delivering power—are on the front side of the silicon [above the transistors]. Those two types of interconnect have different functions and different requirements, but they have had to exist in a compromise until now. Backside power moves the power-delivery interconnects to beneath the silicon, essentially turning the die into an active transistor layer which is sandwiched between two interconnect stacks, each stack having a different functionality.

    What is CMOS 2.0?
    Samuel K. Moore | IEEE Spectrum

  • Store all the things: clean electricity means thermal energy storage boom

    Thermal energy storage has been a difficult place for climatetech in years past. The low cost of fossil fuels (the source for vast majority of high temperature industrial heat to date) and the failure of large scale solar thermal power plants to compete with the rapidly scaling solar photovoltaic industry made thermal storage feel like, at best, a market reserved for niche applications with unique fossil fuel price dynamics. This is despite some incredibly cool (dad-joke intended 🔥🥵🤓) technological ingenuity in the space.

    But, in a classic case of how cheap universal inputs change market dynamics, the plummeting cost and soaring availability of renewable electricity and the growing desire for industrial companies to get “clean” sources of industrial heat has resulted in almost a renaissance for the space as this Canary Media article (with a very nice table of thermal energy startups) points out.

    With cheap renewables (especially if the price varies), companies can buy electricity at low (sometimes near-zero if in the middle of a sunny and windy day) prices, convert that to high-temperature heat with an electric furnace, and store it for use later.

    While the devil’s in the details, in particular the round trip energy efficiency (how much energy you can get out versus what you put in), the delivered heat temperature range and rate (how hot and how much power), and, of course, the cost of the system, technologies like this could represent a key technology to green sectors of the economy that would otherwise be extremely difficult to lower carbon output for.

    Rocks and hotness have existed for billions of years, but it’s only now that the two can be used to help the world decarbonize — and it’s all because the insanely low cost of solar and wind power has made thermal storage economically possible.

    Cheap clean energy could unleash the power of thermal storage
    Eric Wesoff | Canary Media

  • The IE6 YouTube conspiracy

    An oldie but a goodie — the story of how the YouTube team, post-Google acquisition, put up a “we won’t support Internet Explorer 6 in the future” message without any permission from anyone. (HT: Eric S)

    IE6 had been the bane of our web development team’s existence. At least one to two weeks every major sprint cycle had to be dedicated to fixing new UI that was breaking in IE6. Despite this pain, we were told we had to continue supporting IE6 because our users might be unable to upgrade or might be working at companies that were locked in. IE6 users represented around 18% of our user base at that point. We understood that we could not just drop support for it. However, sitting in that cafeteria, having only slept about a few hours each in the previous days, our compassion for these users had completely eroded away. We began collectively fantasizing about how we could exact our revenge on IE6. One idea rose to the surface that quickly captured everyone’s attention. Instead of outright dropping IE6 support, what if we just threatened to? How would users react? Would they revolt against YouTube? Would they mail death threats to our team like had happened in the past? Or would they suddenly become loud advocates of modern browsers?

    A Conspiracy to Kill IE6
    Chris Zacharias

  • Using your ear to control devices

    Very cool that we’re still finding new things we can control that can be applied to making the lives of people better.

    I found that a small, middle-ear muscle called the tensor tympani can be tensed voluntarily, otherwise known as “ear rumbling.”

    In studies funded by the National Institute for Health and Care Research (NIHR), we found that about 55% of people could tense the muscle in isolation, and about 80% could do so when yawning.

    We believe that some people with neurological disabilities retain control over the tensor tympani, even when they’ve lost almost all other functionality. The muscle also moves physiologically as the eyes move, a fact that presents a further opportunity to track people’s intent or augment how we communicate non-verbally.

    The ear isn’t just an auditory input device; it also has the potential to be a complex input and output tool.

    Meet the Ear Muscle That Could Hold a Key to Assistive Tech
    Nick Gompertz | EETimes

  • Intel’s focus on chip packaging technology

    Intel has been interested in entering the foundry (semiconductor contract manufacturing) space for a long time. For years, Intel proudly boasted of being at the forefront of semiconductor technology — being first to market with the FinFET and smaller and smaller process geometries.

    So it’s interesting how, with the exception of the RibbonFET (the successor to the FinFET), almost all of Intel’s manufacturing technology announcements (see whitepaper) in it’s whitepaper to appeal to prospective foundry customers, all of it’s announcements pertain to packaging / “back end” technologies.

    I think it’s both a recognition that they are no longer the furthest ahead in that race, as well as recognition that Moore’s Law scaling has diminishing returns for many applications. Now, a major cost and performance driver is technology that was once considered easily outsourced to low cost assemblers in Asia is now front and center.

    IN AN EXCLUSIVE INTERVIEW ahead of an invite-only event today in San Jose, Intel outlined new chip technologies it will offer its foundry customers by sharing a glimpse into its future data-center processors. The advances include more dense logic and a 16-fold increase in the connectivity within 3D-stacked chips, and they will be among the first top-end technologies the company has ever shared with chip architects from other companies.

    A Peek at Intel’s Future Foundry Tech
    Samuel K. Moore | IEEE Spectrum

  • Iovance brings cell therapy to solid tumors

    Immune cell therapy — the use of modified immune cells directly to control cancer and autoimmune disease — has shown incredible results in liquid tumors (cancers of the blood and bone marrow like lymphoma, leukemia, etc), but has stumbled in addressing solid tumors.

    Iovance, which recently had its drug lifileucel approved by the FDA to treat advanced melanoma, has demonstrated an interesting spin on the cellular path which may prove to be effective in solid tumors. They extract Tumor-Infiltrating Lymphocytes (TILs), immune cells that are already “trying” to attack a solid tumor directly. Iovance then treats those TILs with their own proprietary process to expand the number of those cells and “further activate” them (to resist a tumor’s efforts to inactivate immune cells that may come after them) before reintroducing them to the patient.

    This is logistically very challenging (not dissimilar to what patients awaiting other cell therapies or Vertex’s new sickle cell treatment need to go through) as it also requires chemotherapy for lymphocyte depletion in the patient prior to reintroduction of the activated TILs. But, the upshot is that you now have an expanded population of cells known to be predisposed to attacking a solid tumor that can now resist the tumor’s immune suppression efforts.

    And, they’ve presented some impressive 4-year followup data on a study of advanced melanoma in patients who have already failed immune checkpoint inhibitor therapy, enough to convince the FDA of their effectiveness!

    To me, the beauty of this method is that it can work across tumor types. Iovance’s process (from what I’ve gleamed from their posters & presentations) works by getting more and more activated immune cells. Because they’re derived from the patient, these cells are already predisposed to attack the particular molecular targets of their tumor.

    This is contrast to most other immune cell therapy approaches (like CAR-T) where the process is inherently target-specific (i.e. get cells that go after this particular marker on this particular tumor) and each new target / tumor requires R&D work to validate. Couple this with the fact that TILs are already the body’s first line of defense against solid tumors and you may have an interesting platform for immune cell therapy in solid tumors.

    The devil’s in the details and requires more clinical study on more cancer types, but suffice to say, I think this is incredibly exciting!

    TIL therapy originated from research at the National Institutes of Health in the 1980s. It took decades to fine-tune, and Iovance had to overcome multiple regulatory delays bringing the therapy, formerly known as lifileucel, to market.

    Its clearance is the “culmination of scientific and clinical research efforts,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

    Iovance, with approval of ‘TIL’ cell therapy, readies for complex launch
    Ben Fidler | BiopharmaDive

  • Another Italian merchant invention: the decimal point!

    I’ve always been astonished by how many things we use now came from Renaissance Italian merchants: the @ sign, double-entry bookkeeping, banking, maritime insurance, and now the decimal point

    Van Brummelen suggests that Bianchini’s schooling in economics might have been key to his invention, because he wasn’t embedded in sexagesimal numbers from early in his career, as other astronomers were. But his approach was perhaps too revolutionary to catch on at first. “In order to understand what Bianchini was doing, you had to learn a completely new system of arithmetic,” he says.

    A century and a half later, however, “decimal notation was in the air”. Astronomers working with smaller and smaller subdivisions were inventing different systems, desperate for ways to simplify complex calculations. Clavius’s work influenced later popularizers of decimal fractions, such as Flemish mathematician Simon Stevin, as well as Scottish astronomer and inventor of logarithms John Napier, who adopted the decimal point. Chabás argues that historians should reassess Bianchini’s importance. Although he has been “eclipsed” by other figures, there’s clearly “a path of ideas”, he says, leading back to Bianchini.

    The decimal point is 150 years older than historians thought
    Jo Marchant | Nature