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Let's Know Things

Let's Know Things

著者： Colin Wright
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A calm, non-shouty, non-polemical, weekly news analysis podcast for folks of all stripes and leanings who want to know more about what's happening in the world around them. Hosted by analytic journalist Colin Wright since 2016.

letsknowthings.substack.comColin Wright 政治・政府
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  • Cholesterol Therapies

    Cholesterol Therapies
    2026/06/16
    This week we talk about LDL, HDL, and cardiovascular issues.We also discuss one-time therapies, statins, and pharmaceutical economics.Recommended Book: Blood by Dr. Jen GunterTranscriptCholesterol is the most common type of what’s called a sterol, which is a type of steroid, but also structurally technically an alcohol. But functionally, and classified by scientists, cholesterol is a lipid, which in this case is similar to a fat in all but how the body uses it. Cholesterol is the type of sterol most commonly found in animals—other types are found in plants and fungi—and its function, and this is where it varies from fats, which are used to store energy, is to basically help hold the cell membrane together, and it also serves as an intracellular messenger.Cholesterol is especially prevalent in the brain and spinal cord of animals, but it’s found throughout their bodily tissues, as well, and again, it’s vital for holding everything together and helping things communicate, in addition to being a precursor for vitamin D, steroid hormones, and bile.You want to have cholesterol, then, as without it you would be dead.Too much cholesterol in the blood, however, can also make you dead, especially when it’s bound to what’s called low-density lipoprotein, or LDL, as that contributes to cardiovascular disease like heart attacks and aneurysms, which can massively impact one’s overall wellness and quality of life, and at extremes lead to the whole system shutting down as a consequence of heart attack, stroke, and the like.A lot of things can contribute to the development of cardiovascular disease, including habits like smoking, genetic predisposition, and the enthusiastic consumption of alcohol and unhealthy foods. But high blood cholesterol, of the LDL variety, is one of the top contributors, as these low-density clusters of lipoprotein can clog the pathways that blood takes throughout our bodies. Other, denser types of lipoproteins, HDLs, can clear it, like a heavier, denser substance pushing through clogs of less-dense materials that are gumming up a pipe, but LDL is at times accumulated as a result of consuming delicious but unhealthy foods, which are hard to avoid, and for some people the only consistently available and affordable foods; and for other people LDL accumulates as a result of their genetic predispositions—two things that are devilishly difficult to change.What I’d like to talk about today is a new type of therapy that may be very good news for people who struggle with the accumulation of LDL, and why this is being seen as very good news more broadly, at the scale of entire nations, as well.—Pharmaceutical company Eli Lilly is testing a new, experimental drug called VERVE-102 which is a one-time infusion that is currently administered over the course of about four hours, and once completed, it turns off a gene called PCSK9, which is responsible for making a protein that regulates cholesterol levels in humans.As I said, this drug is still being tested, so these are early results. But in a study of 35 people with high cholesterol levels, high levels of LDL or LDL-C, which is short for lipoprotein cholesterol, they found that this infusion, which again, is a one-time treatment, so get it once and then theoretically at least you never have to get anything done ever again, it reduced those LDL and LDL-C levels by as much as 62%, and that reduction was maintained a year and a half after the infusion; that’s how far out they’re retested so far, and the hope is that each retest will continue to show the same.On the strength of those very promising results, a Phase 2 study has been planned by the end of 2026, and the US Food and Drug Administration, the FDA, previously fast-tracked this existing study, because of the promise and potential this drug already demonstrated in early studies; all of which is considered to be very significant progress and possibility.To understand that significance, though, it’s useful to know some health stats. And I’m going to focus on the US here, as that’s where this drug is being developed, but many wealthy countries have similar stats, at least in terms of cardiovascular disease struggles.As of 2024, which is the last year we had good, cohesive data on this in the US, it was estimated that about 11-12% of the US adult population has high cholesterol levels. This typically doesn’t come with any symptoms, but it can contribute a higher risk for all those cardiovascular diseases, including heart attack and stroke. A further 86 million US adults have borderline or elevated cholesterol levels, which can easily tip higher, but also, even in that existing, elevated state, contribute to negative cardiovascular outcomes.There are treatments for high cholesterol, the most common of category of which are called statins, which reduce the production of LDL by inhibiting an enzyme that produces cholesterol in the body.Unfortunately, these drugs do come ...
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    14 分
  • SpaceX IPO

    SpaceX IPO
    2026/06/09
    This week we talk about initial public offerings, Anthropic, and investment flywheels.We also discuss AI, financial entanglements, and backstops.Recommended Book: Superconvergence by Jamie MetzlTranscriptAn initial public offering, or IPO, is what happens when a private company goes public and starts selling shares of itself, occasionally to just institutional investors like banks and sovereign wealth funds, but usually also to retail investors, which means normal people who buy stocks as part of their investment strategy.Often private companies go this route, go public, because it’s one of the primary ways of gleaning new, oftentimes large inflows of money, and that money can then be used for investments in assets for the company, but it also allows employees who have shares in the company as part of their compensation to cash out, to get paid possibly a huge bonus for all their efforts, and it’s often a means by which executives garner huge paydays for themselves, because they can now sell their accumulated shares, or borrow against them, or because they have something in their contract that says they get x amount of bonus money or new shares if they take the company public, or achieve a certain valuation goal—and going public is a good way to do that.This is also one of the primary ways investors in a company, whether that’s a bunch of smaller seed investors or big-name venture capitalists, to get their money back; the 10 or 100x-ing of their investment, getting ten or 100-times the money they put into the company, generally happens through an IPO, because it can balloon the valuation of that company, and it gives them a more conventional and reliable way of getting money back for their shares: they can just sell those shares on the open market.So an IPO allows a private company to make shares of itself available to others, on scale. And the ‘initial’ part of initial public offering points at the early days of the process, during which the baseline price of a share of stock is established.A fairly arcane and complex process has emerged around this, and it’s an entire industry at this point, with some institutions specializing in taking companies public, helping them get as high an initial price on that stock as possible. They also help them leap all sorts of regulatory hurdles set by the Securities and Exchange Commission, if they’re going public on a US exchange, at least, other bodies handle such things in other countries, and these going-public entities, called underwriters, which are usually investment banks, also typically have their own stake in the matter, earning compensation through a fee called a ‘gross spread,’ which is the difference between a discounted rate on the stock and what the stock is sold for on the open market on that first day it’s available.What I’d like to talk about today is a wave of very closely watched unusual, impending IPOs that are coming later this year, and one of them in particular that looks to be even more unusual than the rest.—SpaceX, OpenAI, and Anthropic are three of the largest companies in human history; on paper, at least.And that’s an important caveat. Market valuation for private companies is generally determined by how much investors are willing to spend on a percentage ownership of the company. So if you start a lemonade stand and I offer to buy 1/10th of that lemonade stand from you for $100, that implies, using this logic, that your lemonade stand has a valuation of $1000; 10 times that $100 that I offered to pay you.Such valuations are also informed by independent analyses from outside experts and institutions. SpaceX, for instance, pre-IPO, is estimated to be worth somewhere between $780 billion and nearly $2 trillion, depending on who you listen to, based on their assets, their potential future earnings, and any advantages they might have in the markets in which they operate.AI company Anthropic is estimated to be worth something like $965 billion, based on a May 2026 series H funding round, through which it raised $65 billion; based on that funding round, the calculations were done, and just shy of a trillion dollars is what the math says the company is worth, though some outside analyses say it’s worth a bit less than that, while others suggest it’s maybe closer to $1.4 trillion.OpenAI, a direct competitor of Anthropic, is valued at about $100 billion less than Anthropic based on its most recent $122 billion funding round, but again, analyses put the company’s actual value, what people and investors would pay for it on the open market, all over the place.Each of these companies have different variables acting upon them heading into a period in which it’s expected that all three will IPO.OpenAI kicked off the current AI race, for instance, but it’s burning money at an incredible rate, and has yet to make a profit, losing billions per year, and will probably continue to lose billions each year for a while ...
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    19 分
  • Jones Act Waiver

    Jones Act Waiver
    2026/06/02
    This week we talk about the Merchant Marine Act, trade routes, and incentives.We also discuss Wesley Jones, foreign competition, and artificial monopolies.Recommended Book: The Quantum Thief by Hannu RajaniemiTranscriptIn 1920, the then-Senator for the state of Washington, Wesley Jones, who was also the chairman of the Senate Commerce Committee, introduced the Merchant Marine Act as a method by which the American merchant marine could be sustained and remain competitive in the face of external competition, and in the wake of the destruction of a bunch of ship during WWI.The US Merchant Marine is all the commercial water-going vessels that are US flagged, and the crews of these vessels. During peacetime, these boats and ships conduct trade and other services along the United States’ coasts and throughout its internal waterways, its rivers and lakes. During wartime, these vessels and their crews are tapped to help move troops and weapons and supplies for offensive or defensive military efforts.The theory of this proposed Act, then, was to ensure that the US Merchant Marine would remain well-funded and well-taken-care-of, because lacking some kind of government support, there was a good chance it would either slowly degrade, not having enough business to pay for itself, or—and this has been a persistent concern for similar pseudo-fleets of merchant vessels around the world for the past few hundred years—it would fall into disrepair because it would be outcompeted by vessels and crew coming in from elsewhere that would charge lower prices, creating unsustainable economics for the locals and thus slowly degrading this economic and military asset.When this Act was proposed, in 1920, the preservation of this asset was on the mind of many US politicians, as the world had just emerged from World War I, and in that and previous conflicts, the US Merchant Marine had been pretty vital to ensuring the US eventually came out on the right side of things. It was also fundamental to the rebuilding of the US economy following difficult conflicts, because the moving of cargo from city to city along coastlines, and throughout long expanses of rivers—getting food from place to place, getting building supplies where they need to go—has always been important, especially following periods in which there isn’t a lot of building going on, and when supplies chains are reoriented toward other purposes, like fighting.So in addition to all the language the helps regulate trade within US waters and between US ports, and which says how the crew of such vessels have to be treated, this Act was also meant to provide protected status to US Merchant Marine vessels and crew, giving them a pseudo-monopoly on certain types of trade activities in the US.It was also—and this is important context—meant to give Senator Jones’ state of Washington a de facto monopoly on trade with Alaska. But it was sold to the rest of Congress and the country as a means of bolstering the funds flowing into the US Merchant Marine. Section 27 of this act, often called the Jones Act, requires that all goods transported between US ports be carried by US vessels built in the US, flying the US flag, owned by US citizens and with majority US citizen and permanent US resident crews.What I’d like to talk about today are the other consequences of the Merchant Marine Act of 1920, and in particular the Jones Act component of it, and why there’s been renewed opposition to the Jones Act in recent months.—The logic of the Jones Act, at least on the surface, is pretty straightforward.If you’re worried about foreign competition coming in and taking all the shipping jobs, swooping in from areas where crews aren’t paid as much, and where ships can be built cheaper, so they can charge less than US-made and -manned ships, all you have to do is require all the ships and people on the ships are of US-origin, and you’re good to go. Those foreign competitors aren’t allowed to take the jobs, and that sets the standards in a different place, allowing US vessels and their crew and owners to charge whatever they need to charge to sustain themselves.This, in theory at least, should also stimulate the US ship-building industry, as that monopoly means anyone who builds new ships stands a pretty good chance of making their money back. After all, there’s no dramatically cheaper competition out there, so you’ve got relatively little downward price pressure and seemingly plenty of customers, because there’s a lot of US coast, and a lot of internal waterways that have traditionally be used for trading purposes.In practice, though—and this isn’t uncommon with protectionist measures; things that seem like they should work for the intended purpose actually leading to other, less ideal outcomes—the Jones Act is often blamed for increasing prices on pretty much everything, and for increasing prices dramatically in places like Hawaii, Alaska, Puerto Rico, and ...
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    20 分
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