Reducing Respiratory Diseases

Major progress on reducing respiratory diseases is possible and is both technologically and economically feasible.

A century ago, waterborne diseases levied similar costs to those posed by respiratory viruses like colds and influenza today: endemic, periodically epidemic, and widely accepted as an inevitable feature of human life. Then, at the turn of the twentieth century, we decided they didn’t have to be. Pharmaceutical advances and clean water infrastructure made cholera, typhoid, and dysentery rare across much of the world within a matter of decades.

Why haven’t we already seen the same kind of transformation with respiratory viruses? Last August we hosted a symposium at Stripe with ~40 leading scientists, pharma R&D leaders, biotech venture capitalists, and regulatory experts to better understand if this is technically possible and, if so, why it hasn’t happened yet.

We heard two main reasons. First, it’s just technically very challenging: respiratory viruses represent hundreds of distinct, mutating strains across several families. Fortunately, new platform technologies, advances in our understanding of human immunology, biological data sets, and protein design tools mean we have our strongest ever suite of approaches for tackling it.

Second, the development of the broad-spectrum solutions needed to solve the first problem has historically been underfunded, neither a great fit for philanthropic nor commercial funding. While COVID generated a burst of activity around preventing and understanding respiratory infections through an influx of new funding, that hasn’t been sustained.

We believe that with enough focus and funding, these problems are tractable. Intercept is a $500 million philanthropic initiative that will take advantage of these new tools to catalyze the development of two types of products: broad-spectrum preventatives and air cleaning technologies. Together, these technologies can radically reduce the burden of respiratory infections, and can eventually help eliminate them altogether. 

Why this matters

Today, we treat respiratory infections like the cold and influenza as a minor nuisance. The evidence increasingly suggests otherwise.

* Healthy people spend roughly 15-25 days each year—about 5% of their lives—sick with respiratory infections like the common cold and influenza.1

* Common respiratory infections can lead to severe outcomes. In 2021 alone, there were 12.8 billion infections globally, mostly caused by viruses.2 Annually, over 65 million3 4 of these progress to serious lower respiratory disease and account for around 7% of deaths from major causes in the U.S.5 6 7

* Respiratory infections raise our risk of serious illness, often years later. While researchers are still early in establishing these connections, it seems plausible that society has meaningfully underestimated the significance of seemingly benign infections on short and long-term health, e.g.:

** 9.8x asthma risk by age 6 if infected with HRV between birth and age 3 in a high-risk cohort8

** 6.1x heart attack risk for 7 days after influenza infection9

** 4.5-5x dementia risk after severe influenza10

** 2.6-4.1x Alzheimer’s risk after severe influenza and pneumonia11

** 2.2-3x schizophrenia potential risk for infant if mother is infected by influenza during pregnancy12 13

** 1.3x risk of heart failure after RSV infection compared to influenza14

* Routine respiratory illness imposes a massive, persistent economic burden, driving 1–1.5% annual productivity losses—roughly $600B globally, or ~0.6% of global GDP—in non-pandemic years.15

* Emerging evidence suggests that severe prenatal16 17 and early postnatal18 respiratory infections might lead to reduced adult earnings and educational attainment later in life.

* Achieving broad protection against respiratory pathogens would meaningfully reduce pandemic risk, serving as a critical first line of defense—alongside air disinfection—against both natural outbreaks and increasingly accessible engineered biological threats. 

Two technologies, working together

No single technology can accomplish population-level infection reduction across all of these pathogens. A shot or pill that provided >90% protection against >90% of respiratory viruses (we’ll call these broad-spectrum preventatives or BSPs), but achieved ~60% uptake (a realistic ceiling based on existing vaccine uptake), would still fall short of of the population immunity required to dramatically reduce sustained transmissions.

This is because there are so many different kinds of respiratory viruses, many of which are highly contagious. It’s helpful to revisit the concept of R0 from the COVID pandemic: the number of people an infected person will infect in a fully unprotected population. While we can’t change the intrinsic R0 of a given virus, we can reduce any given virus’s effective reproduction number (Re): how infective a virus is in a given environment inclusive of interventions. To eliminate a virus, its Re needs to drop below 1. The vast majority of seasonal respiratory viruses have an R0 between 1 and 3. To eliminate an R3.0 virus, you need roughly 67% of the population to be protected.

So, to get closer to elimination, we also need a way to reduce the virions circulating in high density environments. During COVID the world experimented with various interventions like social distancing and personal protective equipment. But to reduce transmission durably for a large number of common respiratory viruses that are perennially circulating, we need solutions that are convenient and minimally disruptive.

We think the most promising category of products that accomplish these goals are those that remove pathogens from the air, particularly in high-density environments like offices, schools, and public transit. We’ll call these air cleaning technologies (ACTs) like air filtration and far-UVC antimicrobial light.

The uptake required for BSPs or for ACTs to be effective by themselves is extremely high. As a benchmark, commercial fire sprinkler penetration is about 40% in the US. Getting to 100% uptake would be extremely difficult. But when deployed together at realistic levels, BSPs and ACTs could achieve our goals.

From the Intercept blog which estimates that breakthroughs can be made with half a billion dollars. 

U.K. Navy Makes Smarter Decision Than U.S. Navy

The U.K.'s Navy, unlike the U.S. Navy, understands that building more 1980s era concept destroyers no longer makes sense. They've been paying attention to the Ukraine War in the Black Sea in which traditional surface combatants are being felled by drones. 

The U.S. hasn't been and instead is working on a "Trump-class Battleship" which is precisely the wrong direction, and more Arleigh Burke class destroyers.

Navy to build drone-equipped warships instead of replacing ageing destroyers

PA Media

Plans to replace ageing warships will be scrapped in favour of building at least six new modern "hybrid" vessels equipped to deploy drones as part of the UK's upcoming defence strategy.

The Ministry of Defence (MoD) said the new vessels would be more suited to the "pace and nature of modern warfare", and a better investment than a "small number of large expensive ships".

Defence Secretary Dan Jarvis said the new equipment would be "designed and built for the increasing threats we face".

Outgoing Prime Minister Sir Keir Starmer has committed to publishing the long-delayed defence investment plan (DIP) before the Nato summit in Turkey on 7 July after months of talks over how to fund it.

The MoD had been exploring options to replace the Type 45, the Navy's fleet of destroyers, with the Type 83, a concept vessel which was at an early design phase.

Instead, investment will now go towards six new Common Combat Vessels, which the department said would be capable of "coordinating uncrewed systems in the air, on the surface and under the sea to deliver more resilient air defence".

It said the change in approach would extend "the Navy's reach, resilience and firepower without a proportional increase in crew or cost".

From the BBC. 

Stocks

From here.

It is an open secret that the stock market in the U.S. is currently being driven by fewer than a dozen wildly overvalued tech stocks that account for the lion's share of it's growth (like the ones shown above, particularly Tesla and SpaceX).

The stock market is not particularly good at accurately estimating the true value of public held companies.

Inaccurate stock prices are an objectively bad thing at the level of the aggregate economy, because they cause investment capital to be misallocated. Too much money is allocated to investments that don't have as good of a likely return on investment, while too little money is allocated to investments that could produce better returns. And, since the stock market is huge, the economic consequences of these misallocations of investment capital on the economy are huge and negative.

Inaccurate asset prices also allocate personal wealth to people who hype their stocks to be worth more than they really are to stupid investors, basically, systemically creating immense returns to dishonesty.

Asset price bubbles aren't bad for everyone. There are two basic ways you can profit from them. One is to invest in the bubble asset despite knowing that it is overvalued, to ride its irrational surge in price, and to get out before the bubble pops. The other is to short the bubble asset and profit when the bubble pops, but this requires your short to be timed for when the bubble pops.

Why is the stock market so bad at pricing these stocks despite the fact that some of the smartest people in the country are employed to analyze and act on this data, and despite the fact that there is a lot of very good quality data about publicly held companies that can be used to value them accurately that is available?

One possibility is that a lot of investors in the stock market are on autopilot trading schemes, like index funds, that are free riding off the people who are actively trading individual stocks, that increasing numbers of ill-informed investors are actively trading individuals stocks as it has become easier to do so, and that the bad decisions of this dumb money is being amplified by autopilot trading.

Another explanation, not necessarily inconsistent with the first, is that this is a generational effect. Baby boomers are moving into their final years of employment and into retirement. They have immense stock market wealth. They are retired and bored, so they try actively trading individual stocks, and they are pouring money into the stock market that exceeds the extent to which stocks have reasonable values (as are individuals who save for retirement believing Social Security to be in peril and knowing that unlike Boomers, they have no defined benefit pensions). Due to the geriatric character of people with power who know what is going on, this is not a problem that they want to solve because they benefit from overvalued stocks in their retirement when they are living off of their investments. Political momentum for reform will come when the Boomers retire or when the bubble collapses, whichever comes first (and asset price bubbles inevitably collapse sooner or later even though the timing of when the bubble pops is notoriously difficult to estimate).

If the bubble sustains itself until the Boomers are mostly dead, the pain will be felt by Generation X and to a lesser extent Millennials (who will at least have more time to recover), in other words, by people like me.

My Picks In Colorado's 2026 Democratic Primary

A colleague of mine has worked as an attorney for both Hetal Doshi and Mike Dougherty, and tells me that while both have done a good job and are competent, that Hetal Doshi is the better leader of a larger organization like the AG's office and would do a better job. Jena Griswold has been a great SOS, but is not a seasoned lawyer with the expertise managing lawyers needed to be effective in the AG's office even though her heart is in the right place.

I prefer Amanda Gonzales, the clerk and recorder of Jefferson County, over Jessie Danielson, a former two term state senator and election law activist, because the SOS calls for administrative competence (which Amanda Gonzales has displayed) and not quality legislative innovation (which is where Danielson excels).

Congresswoman Diana DeGette has performed much better than John W. Hickenlooper and Michael Bennet in Congress (both of whom lead the U.S. Senate Democrats in supporting Trump, and have disappointed on some key issues before Trump 2.0, and have not been very active advocates) but is coasting, didn't advance very impressive bills when she had the chance, and in general, is not being as effective as she could be. DeGette's seniority also doesn't matter much when Trump is still President, limiting what that means in the next two years, and it is time to pass the baton to a new generation of leaders. Melat Kiros has a lot of passion, but isn't very accomplished and hasn't proven herself. Wanda James, whom I've spoken to personally and didn't immediately support when it didn't seem like she had a viable chance in the political climate at the time that I did, in contrast, has proven herself in both business and politics, and has more fire in her belly than DeGette does.

Phil Weiser is the obvious choice over Senator Bennet for Governor. Bennet did not distinguish himself as Denver Public Schools Superintendent, and has done a mediocre job as U.S. Senator, while Phil Weiser has risen to the challenge is resisting Trump vigorously and effectively as AG.

John W. Hickenlooper despite having done an excellent job as Mayor of Denver, and a decent enough job as Governor, has done a mediocre job as U.S. Senator and doesn't deserve another term. Julie Gonzales won't be one of the biggest Trump supporters in the Democratic Caucus in the Senate, and will be more pro-active in advancing federal legislation that moves the country in the right direction.

The highlighted candidates are my picks. There are four state legislative races in Denver where I currently don't know enough to make a pick (and probably won't, because I don't live in any of those districts).

Mad Kings

According to tradition, the Roman Republic was preceded by the Kingdom of Rome from 753 BCE to 509 BCE (244 years spanned by just seven kings).

The Roman Republic had lasted for about 482 years after it began with the establishment of the Roman consulate in 509 BCE. 

The first Roman emperor, Augustus, took office in 27 BCE. Tiberius, the second Roman emperor, who took office in 17 CE was reputedly mentally ill, although less flamboyantly that two of his three successors. Caligula, the third Roman emperor, took office in 37 CE. Nero, the fifth Roman emperor, took office in 54 CE.  Two later emperors before the split and then fall of the Roman empire were also considered mentally ill: Commodus who took office in 177 CE and Elagabalus who took office in 218 CE.

The Roman Empire split between the Western and Eastern (Byzantine) empires in 364 CE (391 years after the Roman Empire was established), and the Western Roman Empire fell in 476 CE (112 years after the split).

According to Google AI (I'm feeling lazy today):

The most notable and documented "mad kings" include:

• King Charles VI of France (1368–1422): Often called Charles le Fou (Charles the Mad), he suffered from manic episodes and the infamous "glass delusion," where he believed he was made of brittle glass and wore iron rods in his clothing to prevent himself from shattering. [1, 2]
• King George III of Great Britain (1738–1820): Known as the monarch who "lost America," George III suffered from prolonged bouts of mental instability—long thought to be porphyria—which caused him to experience severe logorrhea and depression, eventually necessitating a regency. [1, 2, 3, 4, 5]
• King Ludwig II of Bavaria (1845–1886): Famously dubbed "Mad King Ludwig," he was deeply eccentric, neglecting state affairs to focus entirely on building extravagantly expensive, fairytale-style palaces (such as Neuschwanstein Castle) before being declared insane. [1, 2, 3, 4]
• King Christian VII of Denmark (1749–1808): Suffering from severe mental illness and paranoia, his inability to govern left his kingdom in the hands of various regents and his royal physician. [1, 2, 3, 4, 5]
• Tsar Ivan IV of Russia (1530–1584): Better known as Ivan the Terrible, his early, capable rule slowly devolved into legendary paranoia and violent, sadistic outbursts later in his life, particularly following the death of his first wife. [1, 2, 3]
• King Nebuchadnezzar II of Babylon (634–562 BC): Often considered the original "mad king," the granddaddy of Babylonian rulers was struck down by a seven-year descent into animal-like insanity as recounted in the Book of Daniel.

In addition to some other European and Middle Eastern mad kings, there are at least two notable ones from Japan (a list that surely omits notable mad Chinese emperors):

• Emperor Yōzei (陽成天皇, Yōzei-tennō, 869–949, ruled 876–884) was described by the 14th-century historian Kitabatake Chikafusa as affected by madness, killing people and animals without reason. His unstable and violent behavior prompted his advisors to force his abdication in 884.^[29]
• Emperor Taishō (大正天皇, Taishō-tennō, 1879–1926, ruled 1912–1926) of Japan, had a variety of neurological disorders, which though at least partially physical in origin incorporated psychological elements as well. Discussion or criticism of an emperor, including that of health issues, remains a controversial subject in Japan for cultural, political, and religious reasons and is referred to as the Chrysanthemum taboo.^[30][31][32]

The United States of America will have persisted for 250 years from its self-declared birthday of July 4, 1776, in a few weeks. Mad kings were a problem that the Founders were familiar with at the time that they drafted the current U.S. Constitution (which took effect in 1789 and added the Bill of Rights in 1791). Indeed, this clear and present danger is the source of some of the emphatic anti-monarchy provisions of the U.S. Constitution.

Probably the most similar historical figures to Trump 2.0 are Nero and Caligula, although there are other somewhat similar examples from European and Asian monarchies.

There is great fear that President Trump signals the end of democracy in America, if not actually on his watch, but showing the way to, and heralding, its end. Then again, while some mad kings were followed by more sane monarchs, others were followed in fairly short order by the demise of the monarchy's power, or its abolition entirely.

The Credulous Masses

Twin New York Times articles identify the tendency of the public to fall for lies being made more brazenly by political candidates than ever before in the area of politics, and the ability of investors, collectively, to fall for stock valuations far out of line with economic reality due to dubious pitches about the future from billionaires, on the other hand, as a major source of our nation's woes.

Both ring true. We are a nation of suckers. People not in the habit of critical thinking and skeptical analysis of what they are told and promised have been targeted for misinformation and have fallen for it.

And, if that is the source of the problem with our mass institutions, than the solution needs to be to improve quality control by myriad means in our information distribution system. This is not self-correcting, because when suckers make bad collective decisions, either politically, or economically, we all pay a price for that.

40 Acres

An acre was traditionally meant to be the amount of land that a farmer could plow in a day with a farm animal's assistance.

40 acres was traditionally the amount of land necessary for a single family of unmechanized subsistence farms to support themselves. It is the most typical economic unit in which farmland and vacant land is sold, even today.

40 acres and a mule was what post-U.S. Civil War advocates for reparations to former slaves had advocated for (and obviously, did not achieve).

A square 40 acre plot is a quarter mile on each side (a.k.a. 1320 feet a.k.a. 440 yards), with a one mile circumference and a 16th of a square mile area.

The population density of subsistence farmers at this traditional pre-modern scale is about 100 people per square mile.

A survey township has 36 square miles (6 miles a side) and was traditionally the presumptive size of the smallest unit of local government, which at subsistence farming population density would have had about 3,600 people, and perhaps a bit more for a hamlet of perhaps 400 people who would make up the 10% or so of non-farmers who would have been present in a predominantly subsistence farming pre-modern society at the technology level that would have prevailed around the time of the American Revolution (250 years ago), so it might have had a total population of about 4,000 people. Non-farmers in hamlets like this would often include clergy, craftsmen in the skilled trades, doctors, veterinarians, and merchants.

In the brief period where there was democratic government and a predominantly pre-modern subsistence farming economy, people under age twenty-one couldn't vote, and neither could women, so perhaps 400-500 of those people would have been eligible to vote and/or participate in town meetings (in areas without slavery, as slaves couldn't vote either and were usually used to farm cash crops in any case).

In townships that were not governed in the town meeting style of New England towns, a typical town council would have had three elected trustees and sometimes an elected town clerk as well, so about one voter per 100 to 167 people would have been elected officials. This rate is similar to the rate at which people serve as precinct organizers in modern political parties.

A community of this size might have a single church that doubled as a community center and while pre-mechanized subsistence farming largely predated universal public education, a township would typically have something on the order of 2,000 school age children.

In that era about a quarter of children would have died in their first year and about half would have died before reaching adulthood. In any given childbirth, about 1% of pregnant mothers would have died in childbirth, and a typical woman would give birth six to eight times in a lifetime, leading to an excess of widowers over widows. There would be post-menopause age grandmothers in the community, but far fewer, proportionately, than there are today. Most elderly people would have lived with extended family. Then, as now, about a third of pregnancies would have ended in a miscarriage or stillbirth.

It would be unusual for a subsistence farming community to have more than a handful of people with post-secondary education (perhaps a priest and a government official or lawyer), and the percentage of people with the equivalent of a full high school education today would have been comparable to the percentage of people with graduate degrees today, although in some regions, a significant number of people without formal second education would nonetheless have been quite well-read autodidacts. Journalists and school teachers and merchants would typically not have a post-secondary education and would often not have the equivalent of a high school diploma today.