Categories
Finance Startups

Day 1286 and Halfway There, Living 2024 On A Prayer

An estimated 50% of the global population is participating in elections across 60 countries. That includes as supra-national entities like the European Union holding major elections. Naturally this made anyone who has to do any type of planning anxious.  

Concerns about access to compute and adequate energy, overbearing and inconsistent regulatory regimes impacting exits, growth and liquidity events, and the post-ZIRP monetary policy driving up cost of capital have been in the foreground of startup communities.

I see this reflected in my H1 investments. Access to energy, access to compute, and decentralization of both compute & energy are directionally the major trends that I believe will matter over the next decade. 

CapEx concerns and hyperscaling may grip the Magnificent 7 and worry analysts at Goldman Sachs but I’d encourage students of economic history to look to Carlotta Perez and her theory of deployment in previous economic innovation cycles for a more nuanced take. I think simple reads of over-investment are for suckers. 

From where we stand, capital serves the founders who make things of real value. That takes time. Regular builders have simpler needs while they do it: the freedom to make what they want with readily accessible tools without interference. 

We originated #FreedomToCompute as a tagline that shows our values. Not only has it driven me deal flow, but the coalition of e/acc, crypto, and El Segundo hardware/deep tech autists even changed a political party’s platform.

I’ll admit that I was surprised by the Republican Party’s adoption of innovation in crypto, artificial intelligence, and space as a core policy plank. They must really be courting startups as a constituency but I’m happy to have as many as possible aligned with us.

Science and progress are values traditionally associated with liberalism’s left leaning parties, but it seems the axis of “the best is yet to come”  is a wide coalition. My heuristics have thusly been updated so we can remain up and to the right. 

Anna Gat’s Axis of Hope

Categories
Culture Politics

Day 1285 and Platform Changes

I don’t want to make this into a whole thing but the Republicans have posted the GOP party platform. The Silicon Diaspora is now such an important constituency we’ve got enough sway to move policy.

A network state of e/acc, crypto builders, Bitcoiners, El Segundo hardware startups, deep tech autists and white pilled Space dorks changed a political party’s platform.

And it wasn’t the one I expected. Scientific progress was something I’d come to associate with liberals. It would seem Democrats are not as certain about being technically progressive anymore. But the middle that builds is a constituency.

It’s such a small thing and I know politicians don’t have a track record of doing what they say. But the idea that a ragtag group of internet friends could get our issues given place of pride in a platform feels nice. A multimodal pro-social game yielded a positive sum.

We want more technology being built quickly by those with the agency to do so. We’ve got diseases to cure, climate change to adapt to, software to be coded, nuclear reactors to be spun up and a long path to space from there.

I hope the value of better medicine, better tools, and more ambition makes its way to everyone.

For now I think it’s cool that I can see where every line in this policy document came from. A very hodge podge group of internet weirdos in Discords, policy shops, Twitter communities, and group chats got politicians to agree with us. It feels kind of nice. I believe FreedomToCompute is a constitutional American right and we are proving our case

Categories
Biohacking

Day 1284 and The Average Person

I am in the middle of a “don’t try this at home” biohacking experiment in which I am using a low dose nicotine patch to treat my week seven Covid malingering. A quick overview of the method of action.

Nicotinic acetylcholine receptors (nAChRs) have been proposed as potential therapeutic targets for COVID-19. Research suggests that the SARS-CoV-2 spike protein may interact with nAChRs, potentially influencing the disease’s pathophysiology.

nAChRs

I am doing alright with it. I was wary of keeping the patch on all night long (I am very sensitive to stimulants such that I won’t drink caffeine past 10am) so I removed it at about 5pm. That may have been a mistake.

Yesterday my Whoop recorded physiological stress. I wasn’t coughing, I had more capacity for exertion, and I felt generally less exhausted.

But I didn’t come down easily for sleep. I ended up taking a number of anti-inflammatory medications as well as an Ambien. My heart rate was stable but I felt “up” which I don’t care for at night.

And I did not wake up to good news. My HRV absolutely tanked. There are lots of confounding variables here in that I got good restorative sleep (medicine induced surely) but some strain has clearly been too much. 40% down isn’t a rousing endorsement.

I am also noticing a lot of chatter around addiction and whether or not it’s responsible to discuss these things. The fear that the average person is in fact prone so addiction and will have adverse affects. Which I’m sure is true. I don’t think normal people should take unnecessary risks and it’s good to have the minimum viable dose be none at all.

It’s wise to remember that I am not at all living in average circumstances nor do I have average medical conditions so I am not necessarily who you should be looking to for health advice. You should do the basics like eat more protein, lift heavy things, sleep an adequate amount, be in the sun and move around, and manage your baseline health metrics first.

Categories
Biohacking Chronic Disease

Day 1283 and nAChRs

Never one to take things laying down, I started a crazy “n of 1” experiment today. My family doctor prioritizes keeping up on literature. We’d chat about anti-inflammatory research in reputable journals.

But I am on week seven of Covid symptoms simply not clearing. I’ve been coughing when under stress or exertion, my seasonal allergies exacerbated the issue, my reconditioning of my cardiovascular system wasn’t going great and I was exhausted.

At a visit with my osteopath who helps with my chronic autoimmune issues in my spine (I’ve been diagnosed with ankylosing spondylitis) I mentioned my ribs felt tender and constricted from Covid coughing.

She asked me if I was familiar with the research coming out about Nicotinic acetylcholine receptors and Covid-19 treatments. She’s casual like that.

Now I am a child of the internet so I’m passingly familiar with Gwen’s work documenting scientific literature on nicotine but I had not ever thought I’d try it myself.

In a joking “don’t try this at home” way my osteopath said she’d seen folks use nicotine patches for a week to shorten their Covid symptoms to some success.

Now for some caveats. In any type of crazy self treatment it’s important to consider your risks and consult a professional. Don’t do anything without your doctor’s input. Every medicinal treatment has risk and side effects.

I am using going to use a 7mg slow release nicotine patch (of the type made for smoking cessation) for the next 3-5 days to see if it impacts my over-stayed their welcome Covid symptoms. I started my experiment at 9am Saturday July 6th.

I am treating this as a “kitchen table” science experiment in which I am clearly an N of 1 from which you can only take anecdotal evidence. But maybe one data point becomes many and with the network effects of social media maybe we push forward other experiments.

Here is what I know so far thanks to searches from perplexity AI but I encountered some of the papers through mutuals on Twitter, some on forums, others I’d discussed with physicians, some were just raw dogging Google Scholar.

The AI synopsis I’m sharing isn’t meant to be conclusive just to give interested parties a starting place to see why I believe this is an experiment I’m comfortable running on myself.

Nicotinic acetylcholine receptors (nAChRs) have been proposed as potential therapeutic targets for COVID-19. Research suggests that the SARS-CoV-2 spike protein may interact with nAChRs, potentially influencing the disease’s pathophysiology[1].

Nicotine and other nAChR agonists could modulate inflammation and the immune response, offering therapeutic benefits[2][3].

Sources
[1] Simulations support the interaction of the SARS-CoV-2 spike protein
[2] Disorders of the Cholinergic System in COVID-19 Era—A Review of
[3] SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine

Given that I’m working with inflammation as my primary issue which is not modulated even without Covid, I was obviously quite curious to learn about this cholinergic system and potential for up regulation. I’d seen discussions as early as 2020 about the curious fact that smokers had experienced some protection from Covid infections.

This all clicked in my head as being testable on my own without significant risk. Gwern had significantly reduced my concern about nicotine usage where previously as a child of the drug wars I’d put smoking nicotine in basically the same category of dangers as injecting heroin. It is not.

It seems it is possible we’ve got an explanation for why smokers didn’t catch covid at the rates you’d expect and they did better with the infections. We may even have things to learn from it to improve treatments.

Nicotine agonists could potentially be used to prevent inflammation in COVID-19 patients by modulating the immune response. Nicotine, a cholinergic agonist, has been shown to inhibit the release of pro-inflammatory cytokines, which could help mitigate the cytokine storm associated with severe COVID-19[1][2][3].

The cholinergic anti-inflammatory pathway, activated by nicotine, suppresses maladaptive inflammatory responses, suggesting that nicotine or similar agonists might offer therapeutic benefits in managing COVID-19-induced inflammation[3][4][5].

Sources via PerplexityAI.
[1] Nicotine and Covid
[2] Can nicotine alleviate the dysregulated inflammation in COVID-19? L
[3] Medicinal nicotine in COVID-19 acute respiratory distress syndrome
[4] Nicotine and the nicotinic cholinergic system in COVID‐19 – PMC
[5] Cytokine Release Syndrome (CRS) and Nicotine in COVID-19

Stopping a maladaptive inflammatory response is one of my top goals. If I can test it out with a cheap over the counter substance well I’m interested.

Andre Watson the CEO of Ligandal (not an investor just a fan) an AI discovery platform for precision targeting of therapies suggested a method of action for nicotine’s effect.

Nicotine and quercetin were some of the earliest predicted compounds to reduce the binding affinity of the spike protein to ACE2 — which in turn, we described the MOA of here: biorxiv.org/
TL;DR is that reducing the affinity may increase neutralizing immune response.

I do want to reinforce that I am aware nicotine is addictive. I’ve had to take drugs that form chemical dependencies in the past. I’ve used Prednisone in the less controlled phases of my spinal condition and tittering off that steroid is a nightmare. But it can be done. It is doable with a plan, careful monitoring, and supervision.

All evidence suggests this experiment isn’t long enough for me to develop a dependency let alone an addiction. I am thankfully free from any genetic predisposition to addiction in my family.

I plan to do a B3 Niacin flush at the end which is meant to help tittering. I will also be monitoring my heart rate as Nicotine has a tendency to raise your BPM so if I don’t like what I see I’ll lower dosage or stop usage.

With all that said, let’s see if it helps me out. I’ll post because it is in my nature.

Categories
Community Media

Day 1281 and Independence Day

On day 915, which was last year’s 4th of July I wrote about the aspirational America as an idea. It involved blowing shit up. It seems like each Independence Day I find a way to praise Roland Emmerich’s fine science fiction film.

I haven’t watched it yet today but hopefully I’ll at least put on a few clips to enjoy fighter pilots, aliens, inspirational Presidential speeches and fireworks.

The backdrop of drama in the media about Joe Biden is in some ways an ideal way to recall the fractious American community. A continent held together not by ethnicity or religion but by entirely abstract ideals is going to constantly tested.

The theory of print capitalism posits that capital sprung from the solidarity of nationalism presented for the first time in mass media. The common cause of one’s countryman makes it easier to levy for taxes for conflict.

We are far beyond print in our media now. It’s almost cheap to call out media climate “totalizing” an it undersells the experience. Social media makes the experience of Americanness so fluid it ranges from aesthetic choice to the anarcho-tyranny of ailing power.

And yet we try to do better as the general temperament of the nations. America is a place where the founding mythos is that anyone from anywhere can become one of us.

The nationalism of belonging in America has nothing to do with meeting a check box of criteria. Though we are trying to make it more so with bureaucracy. The ideal is that free country sets the condition so anyone succeed. Liberty is a hard fought thing. You can celebrate it in a manner that’s pleasing here. Namely fireworks.

Happy 4th of July everyone. I’m as committed to the American project. The frontier is in our souls and we search it out together in freedom.

Categories
Chronic Disease

Day 1282 and Summertime Sadness

Montana has blessedly been free of excess heat and fire season doesn’t seem to have arrived. But it was a wet spring and I fear we have a long summer ahead of me. I live in one of the best possible places to spend a summer and I still find it challenging m.

I was looking back at pictures from this time last year and I was not in the best health. I’ve never been a summer person and I have to accept some aspect of its misery is likely to forever plague me.

Other people have season affect disorder in the winter. I guess my people are a winter people. I can’t wait for snow to return.

Maybe I’m not alone in finding summertime unbearable. Lana Del Ray croons through summer’s emotional ghosts. Crime gets worse when it’s hotter.

I’m sure my mood is affected by the lingering Covid (does it count as long when you feel shitty 7 weeks later?) as well as the general unease in American politics. I’ll do what I can to shake it. But I’ll never understand anyone’s affection the season.

Categories
Media Politics

Day 1280 and Campaign Season

I am very much beginning to wish I had not watched the presidential debates. I want to say it’s been amusing to watch the different flavors of panic, but it makes me feel a bit gross.

Schadenfreude feels like a cousin to envy. It’s a dirty vice you shouldn’t be swift to cultivate in yourself even if it’s a very human response. I’d prefer to cultivate what virtues I can embody even if imperfectly.

I don’t want to lose my head just because everyone else seems to be doing so but it’s hard not pay attention to the politics when it’s the 4th of July week. I know I can’t do anything about national politics so I continue locally and on issues where we can have clear impact like housing and regulatory reform.

It’s possible that having more hands on experience with on community boards and with local permitting made the more tangible aspects of “Yes In My Neighborhood” campaigns clear to me.

I would prefer to be active in my contributions and focus on solutions. Am I angry and afraid when I see national politics and grand geopolitical news? Of course. If I thought about it too much I’d remember that everyone involved is human just like me. Then I’d worry even more. So I’ll try to focus on moving what I can.

Categories
Emotional Work Media

Day 1279 and Not The Whole Story

I have recently been prioritizing correcting mistaken impressions of the world. As the rationalist set say, I like to update my heuristics.

It’s just not all that uncommon to believe wrong things and for the wrong reasons. We find out with alarming about retracted studies, updates to long held beliefs about culture or politics, or simply something galling about reality. And so sometimes we have to adjust our priors. We never have the whole story.

I recently found myself comparing myself to another person only to get quickly reminded of a set of circumstances that made our situations basically incomparable. I simply didn’t have the whole picture.

My mother loved a hippie bumper sticker about the folly of sincere youthful knowledge.

Quick ask your teenage for advice while they still know everything

The best part of middle age is discovering just how little you know. It can feel paralyzing at times. I’m sure you can imagine how “I don’t know the whole story” can be interpreted in many ways. I hope to be on the sunny side of learning.

Two men sit on a bus. On the dark side facing a dark mountain we see scared sad man with a “I don’t know the whole story” thought bubble. On the bright side of the bus with a wide vista a man thinks “I don’t know the whole story!”
Categories
Culture Startups

Day 1278 and Follow On

I’d like to think I’ve got a talent for understanding how hype and momentum are built.

I learned this skill set by doing. I picked it up simply by being a cool kid working in the trenches of the business of style.

How does hype turn into capital? Well it’s complicated. Consider two significant trends from my youth. Was Indie Sleeze a real cultural moment or manufactured? Did we get taken in by the HypeBeast? Ask Glenn Youngkin in his Caryle Group era about his Supreme investment. Get Gavin McInnes and James Jebbia to go a couple rounds about their relative wealth. and come back to me. Still unsure? Ask Barbara Kruger about the clusterfuck of uncool jokers.

The original culture and the commodification of the culture is a spectrum and the Tommy Hilfiger Event Horizon is infinite. Who makes culture, who money and who only brings money can be challenging to calculate.

The thing about cool, it’s sine qua non, is that it grapples at every stage of its existence with its own validity. Cool thrives as a grounding process to what’s actually happening in reality.

Cool is a relational experience between someone or something authentically popular amongst a group that relates well with each other.

And that relational power is validated by some wider need in the world for their belief, innovation, art, product or philosophy. Sometimes this can be quite irrational surely but consensus is hard to come by. One of the classic essays in validation of cool is geeks, mops and sociopaths in subculture evolution.

The validation of something “cool” eventually reaches a point of opportunistic acceptance by those merely into a thing for the capital. Sometimes it’s social and sometimes literal currency.

These so called “sociopaths” who follow the momentum often do not realize that they are just in it to capitalize on cool. I don’t want to suggest anyone in a thing for money or cachet is a sociopath just that incentives for status are significant drivers for people.

Often we need the people in it for the money. It’s wonderful that angel investing exists and momentum investors have perfectly rational incentives. Sometimes you will even see significant self awareness about this. If you put resources into a community and don’t cause trouble you are often welcome.

Now you can refer to this type in startup investing as dumb money. The follow-on capital that is riding on the work of others who authentically believed before a thing was cool is a necessary part of the ecosystem.

I don’t at all mind when someone is a follower. You can be “a cringe follower late adopter” or whatever terminology we are now using to describe laggards in the adoption curve.


 Everett Rogers in his book Diffusion of Innovations

Unless you are a pain in the ass, actively predatory, or making your contribution more trouble than it’s worth, you should go ahead and lend your support if you can take the risk.

Don’t take it personally when hipsters sneer. They may have been earlier than you but it’s fine to back winners. Just don’t expect the founders to give you special dispensation for getting on board when it was safe to do so. It’s right that the alpha premium applies. I personally love it when not only am I right but I got paid more for the privilege.

Categories
Community Politics

Day 1277 and Don’t Lose Your Head

Everyone has their entertainment and mine is makes me a little bit of a stereotype. I hate podcasts but do most of my chores while listening to Bloomberg’s Odd Lots podcast.

I was catching up today with an interview with equities analyst Tom Lee. My attention got caught and stuck on his description of Bitcoin.

“Yes, Bitcoin is unlike other asset classes because there is a cooperative value. You know, the people who contribute to the network benefit from it. And that’s different than any other asset class.”

From Odd Lots: Why Tom Lee Thinks We Could See S&P 15,000 by 2030, Jun 24, 2024

Now I don’t think this is unique to Bitcoin. Cooperative value can be found in everything from nationalist politics to luxury handbag resale pricing. But I do this it’s important to have cooperative values be baked into a network for it accrue value.

We’ve traditionally mitigated concerns about market cooperation through clear property rights and legal protections. We’d backed up those claims with things as abstract as a monarch. We’ve evolved to it to the slightly more concrete full faith of the United States and Byzantine bodies of securities law. Fiduciary duty and all that.

But as we become less inclined to trust that the buck does in fact stop “anywhere” we are looking for ways to mitigate that risk. How to operate in a world without trust? You develop trustless protocols. Humans have plenty of intuitions about trust and many these intuitions struggle without a clear person with authority to act.

So I ask if we are heading into a “headless” age?

As distrust in institutional power struggles we are seeking out new ways to continue the business of life and civilization even if a high trust society is in question.

We’ve got networks like Bitcoin that work without a head. We have new corporate structures like decentralized autonomous organization (DAOs) that can operate strictly based on cooperative rules, and indeed now entire memetic cultures (like e/-cc) which hold power while being headless.

Lest you think this is some frontier tech idea that doesn’t apply to you we’ve headless content moderation systems & headless retail platforms. Huge swathes of financial tech is living above the API.

You could even argue that we’ve got headless political parties as the Democrats and Republicans both struggle with defacto heads nobody particular trusts. I don’t know if we can live in a headless democracy. Deciding who is a citizen is a very different matter than deciding who is a shareholder.