skybrian's recent activity

  1. Comment on What’s new in biology: June 2026 in ~science

    skybrian
    Link
    From the article:

    From the article:

    The most effective weight-loss drug so far, cancer breakthroughs, gene editing for cholesterol, ancestral CRISPR systems, and more.

  3. Comment on After new drug’s ‘unprecedented’ results for pancreatic cancer, doctors look at other uses in ~health

    skybrian
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    From the article: [...] [...] [...]

    From the article:

    Enthusiasm around daraxonrasib is reaching a fever pitch. In the Phase 3 trial of 500 patients, the drug was shown to double the survival time of patients with advanced pancreatic cancer, a notoriously deadly cancer: 13.2 months, on average, compared to 6.7 months for people who got chemo. On Sunday, Wainberg and his colleagues presented those results at the American Society of Clinical Oncology’s annual meeting in Chicago. The full study was simultaneously published in the New England Journal of Medicine.

    [...]

    Now, the excitement is spilling over to other types of cancer. Daxaronrasib, which is taken as three pills once a day, works by targeting a mutation in the KRAS gene found across many cancers, including lung, colorectal, ovarian, endometrial and a type of bile duct cancer called cholangiocarcinoma.

    “Pancreas cancer may be the first for this drug, but there will be others,” said Dr. Brian Wolpin, who also led research on daraxonrasib and directs the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute. “Now the floodgates open.”

    The Food and Drug Administration has already put the drug on a fast track toward approval for pancreatic cancer, and earlier this month said it would permit Revolution Medicines to give it to patients outside of clinical trials in an expanded access program.

    [...]

    Studies for similar drugs in the pipeline are underway. Daraxonrasib is not a cure for cancer; tumors eventually figure out a way to grow again. Ideally, oncologists want an arsenal of drugs like it in line to give to patients when they develop resistance.

    Revolution Medicines’ Goldsmith said the company has three other such drugs, called RAS inhibitors, in clinical trials, with a fourth due to start later this year.

    Daraxonrasib’s effectiveness appears to expand beyond targeting the mutation. Overall survival was 13.2 months for all patients who got the drug, regardless of whether they had the KRAS mutation.

    [...]

    By all accounts, daraxonrasib is much less toxic compared to chemo. Some patients reported vomiting and diarrhea, as well as sores in the mouth and throat. Some developed a blistering rash that looked like a bad sunburn. Former Sen. Ben Sasse of Nebraska, who got the drug in a clinical trial, described the rash as “nuclear” on a New York Times podcast in April.

    1 vote

  5. Comment on Access to Fable and Mythos 5 cut off after US government order in ~tech

    skybrian
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    It's a chaotic way to do it, but if you think AI is moving too fast, it does slow them down a bit, so there's that. I find AI useful, but don't see a lot of upside in speedrunning it. What's the...

    It's a chaotic way to do it, but if you think AI is moving too fast, it does slow them down a bit, so there's that.

    I find AI useful, but don't see a lot of upside in speedrunning it. What's the hurry?

    2 votes

  6. Comment on Elon Musk net worth estimated at $1.1 trillion in ~finance

    skybrian
    (edited )
    Link Parent
    The tricky thing about opportunity costs is that they depend on counterfactuals: what would have happened otherwise? It's speculative, like imagining the future. When we buy food at a grocery...

    The tricky thing about opportunity costs is that they depend on counterfactuals: what would have happened otherwise? It's speculative, like imagining the future.

    When we buy food at a grocery store then we get to control who eats it, but when we don't, we don't normally worry that it will go to waste, because we imagine someone else might buy it. That might not be true! Maybe it's in the half-off bin and they'll throw it out tomorrow. We don't know enough to accurately predict how much waste will happen.

    Similarly, choosing not to buy muni bonds doesn't normally mean that government projects go unfunded, unless nobody else would do it.

    As I understand it, a liquidity trap is what happens when saving money doesn't do anything because businesses don't take out loans because they don't see profitable investment opportunities, because consumers aren't spending. It seems like this shows another way that the consequences of investment are situational. More bank deposits might sometimes result in more investment, but not in that situation. To understand the consequences, we need to know what the banks are doing and what consumers are doing.

    So I don't think modeling unspent money as corresponding to unused real-world resources works very well. I think it's more like not voting. A bank account or investing in an index fund is not quite like sitting out entirely, but it's still very passive, allowing the market or bankers to control the actual investment decisions.

    To make a stronger argument for not hoarding, how about if we compare with giving money to charity? There are charities that could scale up and poor people who have immediate spending needs.

    1 vote

  7. Comment on Elon Musk net worth estimated at $1.1 trillion in ~finance

    skybrian
    Link Parent
    A gold horde doesn't do anything harmful if it isn't spent. That seems neutral. The question is whether what billionaires (or anyone else) does by investing is better or worse than hoarding it....

    A gold horde doesn't do anything harmful if it isn't spent. That seems neutral. The question is whether what billionaires (or anyone else) does by investing is better or worse than hoarding it.

    Rather than saying investment is good on average and leaving it at that, I think we need to make distinctions. Some Investments are better than others.

    Unrealized gains are more limited than unrestricted personal funds, but they can still be a form of power. In the form of company stock, it's one way that company founders can control what those companies do and what projects they undertake.

    Musk is a pretty good example of that. Yes, some of the projects he decided to invest in seem well worth doing. Others were pretty clearly harmful.

    I shared an interview arguing that founder control is often good, or at least better than alternatives like private equity or leveraged buyouts.

    And Musk has been on both sides of that, with the Twitter takeover changing it from mediocre to considerably worse. Also, how did he finance it? Partially with bank loans.

    In the end, I think governance of huge budgets or huge investment funds is a tough problem no matter what. I find the rush to build data centers as quickly as possible somewhat mystifying. But it's not like Congress is doing a good job of spending money either.

    1 vote

  8. Comment on Elon Musk net worth estimated at $1.1 trillion in ~finance

    skybrian
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    Headline was wrong so I corrected it. SpaceX market cap is above 2 trillion. Musk owns 42% of that. On paper, for now, but we’ll see where it ends up. He certainly couldn’t sell all the shares....

    Headline was wrong so I corrected it. SpaceX market cap is above 2 trillion. Musk owns 42% of that.

    On paper, for now, but we’ll see where it ends up. He certainly couldn’t sell all the shares.

    Matt Levine wrote yesterday that a 20% pop would be just about ideal for an IPO:

    Here are four possibilities:

    1. Musk picked an arbitrary price that is way off-base, and the stock will fall 50% or go up 300% tomorrow.
    2. Musk picked a price that was precisely correct, because he is a genius, and the stock will go up 20% tomorrow. (Twenty percent is the perfect IPO pop, making money for investors without leaving too much on the table.)
    3. Musk picked an arbitrary price, but because of his reality-distortion powers, it became the precisely correct price. “If Elon Musk says the IPO price is $135 then that’s the perfect IPO price,” everyone will say, and there will be a perfect 20% IPO pop tomorrow. It doesn’t matter what anyone else thinks SpaceX is worth; it matters what Musk says.
    4. Actually there was some price discovery, and SpaceX is going public at roughly the market-clearing price. It just didn’t need an IPO roadshow process to figure out that price.
    11 votes

  9. Comment on "The therapeutic industry is platonic prostitution" in ~health.mental

    skybrian
    Link Parent
    It seems like you’re reading that the wrong way. I didn’t intend to imply that anyone didn’t have the capacity for happiness or that friendships didn’t happen. However, I do think being able to...

    It seems like you’re reading that the wrong way. I didn’t intend to imply that anyone didn’t have the capacity for happiness or that friendships didn’t happen. However, I do think being able to leave the community where you were raised often has positive benefits. Anyone who comes from a conservative or religious community that didn’t suit them should appreciate this.

    2 votes

  10. Comment on "The therapeutic industry is platonic prostitution" in ~health.mental

    skybrian
    Link Parent
    I assume people had friends, but you don’t choose your neighbors. I’m wary of speculating any further about their relationships. We do know that the material existence of peasants was absolutely...

    I assume people had friends, but you don’t choose your neighbors. I’m wary of speculating any further about their relationships.

    We do know that the material existence of peasants was absolutely awful. Half their children died.

    2 votes

  11. Comment on "The therapeutic industry is platonic prostitution" in ~health.mental

    skybrian
    Link Parent
    I assume so, but I don’t think historians know all that much about what they talked about.

    I assume so, but I don’t think historians know all that much about what they talked about.

  12. Comment on "The therapeutic industry is platonic prostitution" in ~health.mental

    skybrian
    Link Parent
    For most people and most of human history, peasants rarely had money and didn’t have banks or insurance. In hard times they relied on family and the charity of their neighbors. So yeah,...

    For most people and most of human history, peasants rarely had money and didn’t have banks or insurance. In hard times they relied on family and the charity of their neighbors.

    So yeah, relationships were vital because without them, if you got in trouble, you were dead. In good times, banqueting your neighbors was a way to build those relationships.

    This mode of existence was forced on them. Being able to travel by yourself, move to a new city, and make your own friends is only feasible due to the various innovations we take for granted in modern society. (Particularly for women.)

    4 votes

  13. Comment on How the Squamish struck gold in Vancouver in ~finance

    skybrian
    Link
    From the article: [...] [...] [...] [...] [...] [...] [...] [...] [...]

    From the article:

    Senakw has an unusual history. The land it is built on was home to the Squamish people until they were forced out in 1913. Almost a century later, a court case restored the land to the descendants of those who were expelled, along with almost 100 million Canadian dollars in compensation. Freed from the restrictive planning rules that hold back densification in the rest of Vancouver, the Squamish decided in 2019 to use the land to build apartment blocks that, as well as housing Squamish people, are expected to generate around C$10 billion in income, equivalent to more than two million per person.

    [...]

    This is a story of a dispossessed group that is making the most of a rare and remarkable set of circumstances to generate wealth through upzoning. But it is also a story with relevance all over the world. Senakw shows that when local residents stand to benefit from development, obstacles to housebuilding can be overcome, to the benefit of a much broader group of people.

    [...]

    By cross-referencing Miranda's extraordinary memory against Catholic church records, government surveys, and early anthropological notes, Kennedy and Bouchard could reconstruct not just genealogies but precise information on who lived where. ‘We transcribed all the Catholic records for the Squamish back to 1860’, Kennedy explains. Thanks to the connection between anglicized names in the church record and traditional Squamish names, ‘We could reconstruct where the houses were, who lived there, and their descendants... All of the success was thanks to Chief Miranda’.This painstaking work would prove invaluable in the court battles that began in late 1977, led by Chief Joe Mathias. It took several decades of legal dispute, but the case that turned the tide was decided in 2001: Mathias vs Canada. The case centered on the fiduciary duty of the federal government towards Indian Bands. Several other indigenous groups also made competing claims over the same land.

    [...]

    In a ceremony in 2002, the Squamish Nation sailed 28 canoes to the beach in Kitsilano, a symbolic homecoming for the Squamish people. The site did not seem especially valuable: a thin patch of land, approximately half of which lies directly beneath the Burrard Street Bridge in an unusual tri-point shape. With the neighborhood zoned largely for single-family housing, observers did not initially notice its development potential.

    [...]

    Vancouver is one of the most expensive housing markets in Canada. An average detached house there now costs over C$2 million (USD $1.5 million). Data scientist Jens von Bergmann and UBC associate professor Nathan Lauster estimate that the metro area has 130,000 to 200,000 suppressed households: people doubling up with family or roommates who would live independently if they could afford to. That backlog alone represents six to ten years of recent construction. In 1981, two thirds of 25- to 29-year-olds in Vancouver lived in their own households; by 2021, only a third did. Rental vacancy rates often hover below one percent; vacancy rates in more affordable housing markets, such as Austin, Texas, hover around ten.

    [...]

    Vancouver never managed to comprehensively reverse the downzoning of the early 1970s, despite the huge pressure on housing affordability since. But it did find a way to permit intensive development in narrow strips, typically along transport corridors, while leaving the suburban expanses largely untouched. The city is dependent on such developments: property taxes are low, so almost half of its C$3.5 billion capital budget comes from developer payments. Through a mixture of fixed development fees and Community Amenity Contributions, which are negotiated during spot rezoning on a case-by-case basis, planners extract funding for parks, childcare centers, and affordable housing units in exchange for permission to build. They aim to capture 75–80 percent of the land value uplift. Because each negotiation process can be lengthy, the city prefers to allocate a small number of highly valuable permits, creating an incentive structure that favors concentrated towers, rather than gentle density across the city.

    The downside is that the negotiation process is slow, expensive, and unpredictable. Von Bergmann notes that planners ‘typically get it wrong – they either charge too much or too little’. Getting it right requires predicting market conditions years in advance. Charge too much and the project is rendered unviable and dies, potentially taking the developer and many jobs down with it. Charge too little and the city misses out on valuable capital spending opportunities. Frances Bula, a journalist who has covered Vancouver planning for decades, describes the practical reality: ‘Big developers just cough up when planners demand.’ Smaller builders, including homeowners wishing to add small extensions to their own houses, lack the resources to play the game.

    This system is what is known as Vancouver’s grand bargain, and what leads to the largely untouched suburbs occasionally punctuated with tall, thin towers. The grand bargain generates some income for public spending, while minimizing property taxes and development across most of the city. But the price is paid through worsened housing affordability and the economic costs of suppressed construction.

    [...]

    While reserve land can be leased with federal permission, it cannot be alienated from the band, meaning freehold ownership cannot be transferred in any way. This means it cannot be parceled up and sold off. It also means that the land cannot be borrowed against, because securing a loan on land is only possible if the land’s ownership can be alienated in the case of default. Traditional development finance uses loans as residential mortgages. Apartments cannot be sold as condominiums (where each unit is privately owned, like a house, and each owner also has a share of the overall building), but must instead use leasehold, where residents purchase a right to live in a property for a set period of time rather than owning their home outright.

    These restrictions might have made the project impossible without support from the federal government, which agreed to a C$1.4 billion loan through the Canadian Mortgage and Housing Corporation, the largest in the corporation’s history. To work within leasehold constraints, the residential units were earmarked for 100 percent rental.

    [...]

    Yet reserve land also offered a crucial advantage: because it is reserve land, it is exempt from zoning rules which apply to the rest of Vancouver. The Squamish Nation made the decision to ‘maximize economic benefits for the Squamish community’, which, in Vancouver’s housing-starved market, meant maximizing density: 6,000 rental homes plus commercial space. It also meant opting not to impose many of the costly mandates that cities typically require. They maintained the same safety and building standards that other Vancouver developments adhere to, but stripped away height limits, inclusionary zoning, zero-emissions requirements, parking minimums, design panels, and the years of public consultation that other projects must stick to.

    [...]

    Mayor Stewart emphasized to me that Canada’s intensifying political discourse around ‘reconciliation’ was critical. Many dismissed this discourse as performative symbolism, but at Senakw it had practical consequences: ‘Promises about reconciliation forced governments’ hands when it came to enabling indigenous-led developments’. The Squamish Nation’s referendums gave the project a democratic legitimacy that Vancouver's usual stakeholder consultations rarely achieve. A city government that had spent years resisting modest density increases facilitated a far more ambitious project when backed by a clear community mandate and a compelling moral case.

    [...]

    On just one site, Senakw will provide a year’s worth of housing normally built in the city of Vancouver. It functions as a sort of policy laboratory, showing that cities like Vancouver can build many more homes if the decision-makers allow it.

    Senakw also offers two lessons for those of us in other cities who want to get more homes built. The first is about incentives. When the Squamish Nation’s members voted on development, they were voting on their own land, and for the economic development of their own community. They chose to maximize density and limit the costly requirements that cities like Vancouver typically impose on new developments because they would bear the costs of these requirements directly. Yet in terms of quality and safety, Senakw is just as good or better than other new developments built just across the river. But residents voting on their own projects make very different assessments of the value of some of these mandates and vote accordingly. Similar dynamics have appeared in other resident-led ballots such as estate regeneration programs in England, and Israel’s Pinui Binui program.

    6 votes

  15. Comment on What are you reading these days? in ~books

    skybrian
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    I recently finished Jo Walton’s Thessaly trilogy, which is a fantasy where the Greek gods are real and can travel through time. Athena decides to do an experiment to see if Plato’s Republic would...

    I recently finished Jo Walton’s Thessaly trilogy, which is a fantasy where the Greek gods are real and can travel through time. Athena decides to do an experiment to see if Plato’s Republic would actually work with the help of various philosophers from different times in history.

    If that seems like a terrible idea, well, you’re right, but it’s interesting how it falls apart and how they modify it. There are some unexpected twists. It’s quite fun.

    2 votes

  16. Comment on Claude Fable 5 and Claude Mythos 5 in ~tech

    skybrian
    Link Parent
    If you just mean “of some kind,” there are open-weights LLM’s already and some of them are fairly decent for writing code.

    If you just mean “of some kind,” there are open-weights LLM’s already and some of them are fairly decent for writing code.

    2 votes

  17. Comment on AI is bringing my friend out of retirement in ~comp

    skybrian
    Link Parent
    Companies do cost comparisons when deciding what to build or buy. A carbon tax would make solar look much cheaper than natural gas. (It already is often cheaper, but more so.)

    Companies do cost comparisons when deciding what to build or buy. A carbon tax would make solar look much cheaper than natural gas.

    (It already is often cheaper, but more so.)

    8 votes

  18. Comment on AI is bringing my friend out of retirement in ~comp

    skybrian
    Link Parent
    It’s common to say that that the environmental costs are “unsustainable” as if it were proven fact, just something everyone knows, but I’ve only seen weak evidence for it. There are prominent...

    It’s common to say that that the environmental costs are “unsustainable” as if it were proven fact, just something everyone knows, but I’ve only seen weak evidence for it. There are prominent examples such as xAI where they cut corners, but it doesn’t seem like it’s inherent. They run on electricity and there are good alternatives. And xAI is already installing solar. It’s only about 10% of their usage, but a carbon tax on data centers would be a quite doable and politically popular way to get them to install more. (Though, probably not politically doable nationally until after the Trump administration.)

    Also, we are going to need much more electricity generation anyway to convert to electric cars. There is a surplus of solar panels available from China and instead of tariffs we should be buying all we can and installing them everywhere.

    15 votes

  19. Comment on If Claude Fable stops helping you, you'll never know in ~tech

    skybrian
    Link
    Anthropic Walks Back Policy That Could Have ‘Sabotaged’ AI Researchers Using Claude (Wired) … …

    Anthropic Walks Back Policy That Could Have ‘Sabotaged’ AI Researchers Using Claude (Wired)

    “We’re changing Fable 5’s safeguards for frontier LLM development to make them visible,” Anthropic said in a statement to WIRED. “We made the wrong tradeoff and we apologize for not getting the balance right.”

    …

    Anthropic now says it’s changing course, and that Claude Fable 5’s safeguards for AI development will be visible to users. If the company suspects a user is trying to use Claude to build a highly capable AI it will alert them that it’s either refusing the request, or rerouting the user to a less capable model.

    Anthropic reversed the policy after it received fierce backlash from the AI research community. Anthropic has already taken steps to limit competitors from using Claude to build closed and open source AI models, but critics say that quietly degrading the model’s performance for certain users went a step too far. Claude’s coding agent has become a favored tool among developers, including those working on open-source AI research projects, and researchers tell WIRED that the company’s latest policy could have led to a troubling future in which only a handful of leading AI labs could perform advanced AI research.

    …

    “These safeguards prevent foreign adversaries from using our most capable models in ways that pose severe safety risks. The US and its allies hold an edge in frontier chips and the highly optimized software that runs them at full potential,” the company said in a statement to WIRED. “These safeguards ensure Claude isn't used to erode that advantage—by optimizing chips developed by those adversaries, for example […] In deciding whether to make them visible or invisible we faced a choice. A hidden safeguard is harder to probe and work around. This means the safeguards can be targeted much more narrowly.”

    Anthropic says that because this safeguard around AI development is now visible, it needs to cast a wider net, meaning more benign requests may trigger its safeguards. The company says it’s working to make its classifiers more precise as quickly as possible.

    9 votes

  20. Comment on Interview with Eric Ries discussing his book about corporate governance in ~finance

    skybrian
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    The author founded the Long Term Stock Exchange (see Wikipedia). I haven’t read the book yet, but I assume it will promote some of the ideas described there:

    The author founded the Long Term Stock Exchange (see Wikipedia). I haven’t read the book yet, but I assume it will promote some of the ideas described there:

    The exchange has promoted a system of tenure-based voting rights, in which shareholders gain increased voting power the longer they hold their shares, capped at ten times the ordinary voting power after ten years. This proposal has been controversial, with critics arguing it could entrench founder control, while proponents present it as an alternative to multiple-class share structure.

    LTSE rules restrict the use of executive bonuses tied to short-term performance and prohibit companies from issuing quarterly earnings guidance, although quarterly results remain required under U.S. securities law.

    In 2025, LTSE filed a petition with the SEC to allow all U.S. public companies, not only those listed on its exchange, the option to report earnings on a semiannual rather than quarterly basis. LTSE CEO Bill Harts argued that quarterly reporting is overly burdensome and detracts from long-term management. The exchange’s representatives met with SEC officials in advance of filing the petition.

    2 votes