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.