#2 - Auto-immune disorders, Buying the Constitution, and Hyper-Subjectivity

An experiment in sharing what's been on my mind

Welcome back! Here's week two of an experiment in sharing more areas of frontier tech that are top of mind.

The Mystery of Auto-Immune Diseases and their Increase

Auto-immune diseases are one of those issues that have long been misunderstood, and under-studied. At a high level, they're a category of diseases that happens when the body's immune system mistakenly attacks cells, tissues, and organs.

Nearly 50M Americans are living with an auto-immune disease and women specifically are at least 2 times more likely to be affected than men, likely because at a baseline level, women have stronger immune systems then men.1 Some researchers believe that this stronger immune systems is why men in the US has a 3x likelier chance of ending up in the ICU because of Covid-19.2 Although the stronger immune system helps in some ways, it seems that its hyper-vigilance is correlated with the high prevalence of these diseases in women.

I've been interested in this space relative to women's health for a while but in last week's newsletter I mentioned that the growing application of genetic testing wrapped into direct-to-consumer healthcare businesses for very specific problems, which prompted a few twitter DMs on the subject.

Interestingly, even Narcolepsy seems to be an auto-immune disorder! immune-related genetic factors seem highly correlated.

Pregnancy and Hormonal Treatments

It’s by no means a scalable solution but one other fascinating tidbit is that there’s a documented path of women’s auto-immune disorder symptoms being lessened or eradicated by dosing with estriol. Mimicking, effectively, an auto-immune “flush” of sorts that happens with estriol during pregnancy. For rheumatoid arthritis, and multiple sclerosis for example, it’s common that symptoms drastically decrease during pregnancy. 3

I’m excited to see where the research here continues to progress!

Therapeutics

Compound’s lovely (and brilliant) bio intern, Dennis Gong happened to have also dived into the space, specifically looking to answer the question of why regulatory T cells, or Tregs, have had so much recent interest as a cell therapy modality and as a therapeutic target:

“Inflammatory and autoimmune diseases and disorders are hard nuts to crack.
Graft versus host disease (GVHD), organ transplantation, type 1 diabetes (T1D), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and multiple schlerosis (MS) among other autoimmune and inflammatory disorders are underserved by existing therapies and will represent a considerable public health burden as our population ages.

Current options are non specific and/or require long term administration.

Additionally, nonimmune diseases such as cardiovascular diseases, obesity, type 2 diabetes, and degenerative diseases of muscle and brain are exacerbated by inflammation. Even aging itself has been thought to have a root cause in inflammatory dysfunction.”

He gives a great overview of companies working in this space and highlights that Tregs are hard to manufacture and and we’re still at the pathway modification rather than cell modification point in research but we’re excited to see how the field progresses. We’re definitely eager to talk to researchers or founders working on this area!

*Here’s a good podcast from Radiolab on the prevalence of these diseases within women from Jordan Montgomery!

Buying the Constitution

Also, as a side note, I spent the weekend helping Constitution DAO get ready to buy one of 11 original copies of the constitution. It's been owned by a private seller for years and is now going on sale at Sotheby's!

We're hoping to use pooled funds to demonstrate the power of DAOs and get the constitution put on public view at a museum. We launched a Juicebox link last night and 88ETH or around 600k was contributed in about 3 hours; as I write this we're at about 729 ETH or 3.3M dollars!

Not to get too cheesy, but as my husband said, there's something very special about a massive paradigm shift in governing systems, the DAO, potentially being able to purchase a document that represented a different type of massive paradigm shift in governance systems.

If you've been meaning to learn more about DAOs/Web3, or just want to watch and be part of the fun, hop in the Discord linked on the website! You can read a long-form analysis in Packy McCorcmick's Not Boring Newsletter

What I've been reading:

(and are we in the era of hyper-individuality?):

The German philosopher Jürgen Habermas coined a phrase that captures Fredericks to the core: “the cultivated personality.” It is introduced in Habermas’s 1962 book, “The Structural Transformation of the Public Sphere,” which describes the advent of the European bourgeois, and the invention of modern subjectivity, in eighteenth-century Europe. During this period, the journal and the personal letter exploded in popularity, as individuals increasingly decided that their intimate thoughts were worth memorializing. “The first-person narrative became a conversation with one’s self,” Habermas wrote.”

  • for the past year or so I’ve been intrigued by the public discourse on covid decision making - the critiqued lack of trust in “rational, scientific thinking” and a willful ignorance of the frequency so many humans make important but non rational decisions. A friend suggested I read “philosophy: truth in transit” which gives a view into the shifting norms around truth over time, contrasting now with the default of faith per-enlightenment, and cultural waves of objectivity versus subjectivity. For those reasons I find the peek into one mans dive into the extremes of personal documentation and introspection, and centeredness on subjectivity fascinating. Are my own behavior on twitter and this man’s 60,000+ page journal two small pieces in a wave of hyper subjectivity and introspection?

  • Another article I enjoyed a day later is a perfect follow up: “For many aspiring authors, self-presentation as an aesthetic project feels necessary, particularly in the case of marginalized people who must be their own boosters — but it also means that success seems increasingly synonymous with the cultivation of a personal brand.” …” Increasingly, consumers are offered the image of art-making as a subgenre of celebrity, and the works of art themselves are allowed to remain laudable but forgettable byproducts.” Increasingly I find this transience dizzying. The temporality of discussions centered around this type of creativity feels like it verges on consumption for the sake of itself. “Popular culture—television shows, pop songs, memes—is every American’s first language, the one we acquire whether we want to or not.” When art is based on the popular and transient, what common language do we have to ground ourselves as mutual participants in the grand scheme of humanity?

Other Links I Found Fascinating:

Reddit users' obsession with the Fed's Reverse Repo ~ The Future of Sodium Batteries ~ Deep Dive on why Starship is still not truly understood ~ Successful test by company that spins spacecraft to launch them into orbit ~ A very simple guide to making a CPU

DeepMind spun out Isomorphic Labs, a for-profit computational drug discovery company (some people are worried this could endanger other companies access to AlphaFold's opensource data - what do you think?


Let me know what you think of this new format! As always, if you’re thinking about similar things or you disagree with me - I would love to chat! DM me on twitter or email me at nicolewilliams @ compound.vc. You can find more of my long-form writing here.

1

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292717/

2

https://www.nature.com/articles/s41467-020-19741-6

3

https://www.cell.com/trends/genetics/pdf/S0168-9525%2819%2930079-4.pdf