Hi there, it’s Mehdi Yacoubi, co-founder at Vital, and this is The Long Game Newsletter. To receive it in your inbox each week, subscribe here:

In this episode, we explore:

• Endemic pathogens

• Creating something from scratch every day

• The myth of the well-read person

• Extreme ownership

• Selfies as a second language

• How a High-End Classic Car Goes Electric

Let’s dive in!

🥑 Health

🦠 Endemic Pathogens

I enjoyed reading this piece by Riva on how endemic pathogens could be responsible for many diseases. More generally, I think outside the box thinking made by rigorous citizen scientists will have a growing role to play in scientific discoveries.

Thinking Outside The Box On Infectious Disease

One idea largely anarchic to the current paradigm is that endemic pathogens cause issues as broad as cancer and schizophrenia. Oddly enough, the hypothesis that viral pathogens are neurodenegerative is increasingly grounded in evidence, yet, as a society, we’re still stuck to our idea that lifestyle correlations are entirely to blame. And yes, sure, while smoking may correlate with cancer, several herpes viruses, which two-thirds of us carry, induce tumors in animal species. Wellness fanatics flinch at people smoking, but have little to no insight into the herpes virus permanently lodged in their brain cells.

Due in part to how narrow and myopic biomedical research has become, the last fifty years of research seems to have massively underestimated the harm caused by endemic infectious diseases. We think of infectious diseases in the same way we think of video game bosses: external agents that get thrown into our global gameplay for us to defeat. COVID-19 was a great example of this. How much money, time and global effort did we put into preventing the viral spread of a new pathogen? The irony is, the pathogens that potentially will hospitalize and kill us are already inside us. Personally, I am far more scared of Epstein-Barr Virus than COVID-19, and I found it annoying to be lectured on pathogens from a government that seemed to have no issue with the endemicity of HSV and Epstein-Barr in our society. That said, it’s possible that, decades down the line, COVID-19 is also associated with long-term effects stemming from endemicity, which has also been my greatest fear for it. Who knows?

The point is: As a society, we don’t consider the role infectious disease can play in other types of chronic diseases, despite mounting evidence.

Here is Riva’s plan for the future:

Plans

I am optimistic that, in the future years, people will begin to grasp the link between infectious disease and chronic conditions, especially psychiatric issues. The question remains: how can capitalize on this knowledge to drive new breakthroughs?

After thinking through these topics, the first obvious thought was that it would be useful to setup a new philanthropic foundation to focus on the intersection of neuroscience and immunology. The initial goal of the foundation would simply be education and outreach. How many people with psychiatric disorders have never been tested for (or treated for!) the potential pathogenic causes behind their symptoms? Educating people on these topics and getting more doctors to offer the necessary blood and stool tests to rule out pathogenic causes before commencing psychiatric treatment could potentially help millions of people.

The second goal of the foundation would be to fund and incentivize research. Working with researchers in the field, we are currently compiling a list of datasets and tools that would be valuable to help us understand different disease causal mechanisms and their effects on the brain. Not all of it needs to be clinical or lab based. We have made great strives simply by parsing and making correlations with already existing published research. Depending on how valuable and hard certain data is to collect, we are then pricing research questions with the goal to offer bounties or grants for those willing to take the projects on. The bounty model also offers a way for philanthropic donors to have transparency on where the foundation's investments are going. This is personally important to me after years of being pitched non-profits that seem to serve as hobby projects for the wives of rich men in order to organize charity galas.

After spending some time working on the bureaucratic overhead of setting up a foundation, a chance conversation with a friend resulted in the offer of doing the outreach and bounty initiative under an already existing neuroscience foundation. Another close friend is launching a Focused Research Organization to look directly at several key areas of immunology and it is also our imperative to ensure her and her team get all the necessary funding. If you are interested in funding these research areas, please reach out.

Patrick Kearns @kearnsneuro

Phenomenal paper just published in Science persuasively demonstrating that EBV causes most if not all multiple sclerosis. Phenomenal epidemiological design and technical achievement. 👏 science.org/doi/10.1126/sc…

January 13th 2022

4,801 Retweets14,349 Likes

🌱 Wellness

🏗 Creating Something From Scratch Every Day

Here’s an idea to balance the ever-increasing consumption of things: creating something from scratch every day.

Myles Snider @myles_cooks

The antidote to consumer culture is to create something from scratch every single day. For me this often means cooking a meal. But it can be literally anything - painting, writing, music, etc. You just gotta do it.

April 17th 2022

1 Retweet23 Likes

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🧠 Better Thinking

🔮 The Myth of the Well-Read Person

It seems like, for most fields, reading a dozen of the right books would give you a good understanding of the essential ideas of the field. So why are there so few well-read generalists?

This article gives a great response to this critical question:

Why are there so few of these well-read generalists? I’m making it sound like you could understand most of what humans know about science and society in less than a decade. Why have so few people taken up this offer?

Apart from pure apathy, here are some of the failure modes which prevent people from becoming well read.

1. The returns to reading scale with intelligence, and most people are just not smart enough to comprehend a vast stock of knowledge. If intelligence is the ability to understand complex ideas, to notice patterns and make inferences, and to build connections between new information and existing knowledge, then it’s no surprise that dull people don’t get that much out of reading a lot. I’m always shocked when I talk to someone who claims to have read the same book or blog post I read, and they didn’t seem to absorb the basic thesis of the text. Undoubtedly, I have embarrassed myself in a similar way to others with a higher capacity to extract meaning.

2. People choose the wrong books. Either they become bored of uninteresting details or entertained by unenlightening stories and metaphors. I suggest the following strategy for reading about science in my post on barbell strategies:

Instead of reading mid-wit pop-sci books which just offer vague metaphors or irrelevant anecdotes, read books that are either pure fun (fantasy, sci-fi, manga, etc), or actual hardcore science (textbooks and review papers).

Venkatesh Rao @vgr

This feels like some sort of Midwit Matrix.

Art of Life 🦋 @Art0fLife_

20 books to read in your 20s = thread = https://t.co/LzkP9Y76Hg

April 11th 2022

91 Retweets2,202 Likes

I have more thoughts on this tweet from @vgr, mainly that I think the obsession around elitist content can be misguided sometimes, but on the most part, reading too many of these pop-sci popular books can be a massive waste of time & money.

⚡️ Startup Stuff

🦾 Extreme Ownership

This week, I had in mind the concept of “extreme ownership.” I find it to be a helpful reminder once every few weeks.

Ryan Denehy @DenehyXXL

The best founders realize that no matter the situation everything truly is your fault and your responsibility.

April 14th 2022

9 Retweets93 Likes

On the same idea of how to be an effective founder, I re-read this essay inspired by Keith Rabois’ leadership principles. Here’s the summary:

• Running yourself

  • Lead, don’t manage: Be proactive rather than reactive. “Lead” your team as opposed to “manage” a situation.

  • Understand your output: Your output is how much your team gets done + how much neighboring teams get done divided by how many people are on your team. Only add someone if they bring up the ratio of output to people.

  • Focus on inputs: Spend time on judging your team’s inputs, i.e. the quality of ideas, not on whether you can move revenue 3x this quarter, i.e. outputs.

  • Spend time on high leverage activities: Do things that have the most impact. Preparing one thing that affects many, like all-hands and dashboards, or do one thing with a lot of impact on one person, like a performance review.

  • Optimize your most valuable resource, your time: Actively manage your calendar and audit it by categorizing how you spend your time. Is it on top priorities? Is it on high leverage activities? Show your team real examples of great calendars. Batch tasks. Focus on the limiting step.

• Running your team

  • Gather information: Your job as an exec is to make the 4 right calls a year. Can’t do that without all the information so spend time gathering info. Get around filtering mechanisms by wandering the office.

  • Simplify the metrics and objectives: Find indicators as close to the inputs as possible. Make those and your team’s objectives as simple as clear as possible. Make sure the team understands the logical jump from achieving that objective to having a large impact.

  • Meetings and Decisions: 4 types of meetings, 1:1s, staff meetings, decision meetings, operating reviews. Clarify what type of meeting you are having. Make decisions by knowledge rather than position as much as possible and at as low of a level as possible.

  • Peak Performance: Identify whether it is motivation or capability hindering performance. Extend rope to junior people when the downside is low. Always increase their scope.

📚 What I Read

📱 Steve Jobs by Walter Isaacson

I recently decided to spend a few months reading only biographies. I started with Steve Jobs. Please send me your best recommendations!

Mehdi Yacoubi @Mehdiyac

I think I’m going to start reading only biographies for a little while.

April 17th 2022

12 Likes

🤳 Selfies as a Second Language

When new technologies create new languages:

Of the people I follow on Snapchat, about half are old people (lots of middle-aged white male VC's, maybe trying to make sense of what it is), the other half are young and what I'd consider Snapchat natives. As a product person, it's fascinating to observe stark divides in consumer behavior. Often these are generational divides, less discussed than technological shifts like those fueling platform shifts or industrial revolutions, but no less fascinating. Often, these behavioral changes happen because of technology shifts, as humans evolve with their new tools and altered environment. In Snapchat is one of the cleanest, most universal of these behavioral fault lines.

When I send a Snap to any of the people in my address book, the oldies respond, inevitably, with some text message, maybe an emoji if they're somewhat hip. If I send a Snap to a young'un, inevitably I'll receive a selfie in response.

Pair with: What is Snapchat?

💣 Collapse Won’t Reset Society

Some people think collapse would reset society. This piece argues it won’t:

This morning, you opened your phone and started scrolling. Your screen presented you with the usual updates: the nth wave of plague, the growing supply chain crisis, and two nuclear powers exchanging confrontational threats. You yawned and went to start your day. Collapse gets old fast. Chances are the threat of imminent destruction didn’t stop you from hurrying to work.

But to some, collapse can be a thrilling possibility. Keep scrolling, and you’ll eventually come across its devotees: they include backwood fundamentalists, deep green radicals, apocalyptic cults, and pessimistic online doomers, to name just a few.

The collapse of society can seem to hold an opportunity. Imagine no longer having to clock into work or pay taxes. Imagine money losing its importance when beans and bullets hold all the value. Imagine scheming lawyers and bankers getting their due when their wealth belongs to those strong enough to take it. Imagine a blank slate for those who see no place for themselves in our corrupt civilization.

🌐 Understanding Urbit

Urbit is a clean-slate OS and network for the 21st century:

We think the internet can’t be saved. The way things are going, MEGACORP will always control our apps and services because we can no longer run them ourselves.

The only way out of this mess is with a completely new platform that’s owned and controlled by its users.

Urbit is a new OS and peer-to-peer network that’s simple by design, built to last forever, and 100% owned by its users. Under the hood, Urbit is a clean-slate software stack compact enough that an individual developer can understand and control it completely.

We built this new stack to give people a single integrated tool for communicating and building communities – a tool they can trust, control, and extend to their liking. We want to do away with the terrible user experience of the current ‘frankenstack’ of apps and services that we all use today.

Urbit is designed to become an effective, customizable productivity tool for collaborators, and a calm noninvasive communication tool for friends and families.

🎙 Podcast Episodes of the Week

This week in podcasts:

• Professor Donald Hoffman — The Case Against Reality, Beyond Spacetime, Rethinking Death, Panpsychism, QBism

  • I’ve been fascinated by Hoffman’s ideas around consciousness ever since I learned about his work last year.

  • “What is the probability that natural selection would shape sensory systems to report true properties of objective reality?”

• Elon Musk on Twitter, Tesla, and the Future | Ted 2022

  • A great update on what everyone is currently talking about.

  • Pair with: The Besties discussing the issue.

🍭 Brain Food

🍺 Bar Talk: Informal Social Interactions, Alcohol Prohibition, and Invention

This paper studies the importance of informal social interaction for innovation. It does so by measuring the decline in innovation when wet counties turned dry during the Prohibition and banned alcohol consumption. It turns out that the adverse effects of prohibiting alcohol on innovation lasted only three years, after which groups found new ways to socialize and generate new ideas.

To understand the importance of informal social interactions for invention, I examine a massive and involuntary disruption of informal social networks from U.S. history: alcohol prohibition.

The enactment of state-level prohibition laws differentially treated counties depending on whether those counties were wet or dry prior to prohibition. After the imposition of state-level prohibition, previously wet counties had 8-18% fewer patents per year relative to consistently dry counties. The effect was largest in the first three years after the imposition of prohibition and rebounds thereafter. The effect was smaller for groups that were less likely to frequent saloons, namely women and particular ethnic groups.

Next, I use the imposition of prohibition to show that the social network exhibited path dependence in the sense that as individuals rebuilt their networks following prohibition, they connected with new individuals and patented in new technology classes.

Thus, while prohibition had only a temporary effect on the rate of invention, it had a lasting effect on the direction of inventive activity. Additionally, I exploit the imposition of prohibition to show that networks increase invention by exposing individuals to others' ideas in addition to simply facilitating collaboration and that informal and formal interactions are complements in the invention production function.

Pavel Asparouhov @Pavel_Asparagus

I've basically stopped drinking (maybe 3 drinks in the last 2 months) and it really reduces the possible social activities u can do in NYC. Why is the culture here so oriented around a mind numbing drug? Seems a lil demonic if u think about it

March 5th 2022

149 Retweets3,504 Likes

🎥 What I’m Watching

🧘‍♀️ How the Way You Respond to Anxiety Changes Your Life — Søren Kierkegaard on Angst

This video explores the life and work of Danish philosopher Søren Kierkegaard. In particular, it focuses on his contemplations and revolutionary understanding of angst, or anxiety, looking into questions like what is anxiety, where does it come from, and how can we use it to become who we really are?

Pair with: Kierkegaard on the Present (Passionless) Age

🔌🚘 How a High-End Classic Car Goes Electric

You can now transform your old classic car into an electric vehicle! ⚡

🔧 The Tool of the Week

🌌 Stars

Explore the cosmos through this beautiful visualization.

Pair with: The most beautiful video on Youtube.

🪐 Quote I’m Pondering

Beyond a certain point, intellect is worth less than a sunny temperament.

If you enjoyed this newsletter, make sure to subscribe if you haven’t 👇

👋 EndNote

Thanks for reading!

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Until next week,

Mehdi Yacoubi

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