David Lang

Experiment Foundation @exp_foundation · 4d

Field Builders make the fields that make the future. More people should consider the role.

We’re backing at least 50 Field Builders to launch grant programs in emerging scientific fields. Each Field Builder will award $70,000 to researchers they recruit and receive a $5,000 honorarium for leading the work.

Applications for the Field Building Accelerator are open now through December 15, 2026: fieldbuilding.org

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Niko McCarty. Verified account @NikoMcCarty · Nov 4

My podcasts are way too long and way too technical. Few people have time to sit through 90 minutes of hardcore immunology!

But if there's just one idea to take away from my interview with Jake Glanville at Centivax, a company developing universal flu vaccines and antivenoms, then I think it's this:

First, influenza (and many other viruses or pathogens) mutate so rapidly that we keep getting infected by slightly different versions of them. And so the challenge of making a universal flu vaccine is to elicit antibodies that recognize many different strains, including ones that don't yet exist.

The normal approach to this problem is just to mix together antigens from many different strains and inject them into humans all together. But your immune system then generates separate antibodies against each antigen, without necessarily producing antibodies that recognize ALL of them.

(Imagine a vaccine with 20 different versions of influenza's hemagglutinin protein. Your immune system might make antibodies against version A, others against B, and others against C. But what happens when influenza mutates again, producing version 21? Your body has no antibodies.)

What we really want are antibodies that recognize regions of the virus that rarely change! These so-called "conserved epitopes" are more likely to be shared across past, present, and future strains of ther pathogen.

So Jake, noticing this problem, invented a thing called conservation–concentration coupling. The gist is that, instead of injecting ALL of the antigens into a human at high doses, you deliberately lower the concentration of each one. There's only a tiny bit of each antigen in the vaccine, in other words; too little to elicit an immune response on its own. (If a B cell comes along and recognizes only antigen A, that B-cell won't become strongly activated!)

If, however, a B cell comes along that recognizes some converved region across MANY of the antigens, and it can bind to all of them, then it WILL become activated. Even though each individual antigen is present at a very low concentration, the B cell effectively encounters 20 times as much antigen, or 20x the normal dose. It is stimulated enough to proliferate, while the B cells recognizing only individual strains get "outcompeted."

In other words, you're using antigen concentration to bias the immune system toward making broadly reactive antibodies. This is the key idea behind Centivax, and they've gotten really compelling data that this actually works in mice and humans (~180 patients in their phase I, which is now finished.)

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Niko McCarty. Verified account @NikoMcCarty · Jun 16

Announcing the Hyperspectral Biology Fund:

It's possible to see engineered microbes from space; not with the naked eye, but by the distinctive way their molecules absorb light.

The secret is hyperspectral cameras. Whereas a normal camera captures just three colors (red, green, and blue), a hyperspectral camera captures the full spectrum of light at every pixel. When merged with synthetic biology, one can create engineered organisms that sense something (a pathogen, explosive, pollutant, etc) and then monitor them using satellites with hyperspectral cameras orbiting Earth. The end goal is to build a planetary-scale biosensing network.

I'm giving away $75,000 in microgrants to help grow this field. Applications are due by July 10.

Thanks to @davidtlang and the Experiment Foundation for making this possible.

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Niko McCarty. Verified account @NikoMcCarty · Jun 16

Announcing the Hyperspectral Biology Fund:

It's possible to see engineered microbes from space; not with the naked eye, but by the distinctive way their molecules absorb light.

The secret is hyperspectral cameras. Whereas a normal camera captures just three colors (red, green, and blue), a hyperspectral camera captures the full spectrum of light at every pixel. When merged with synthetic biology, one can create engineered organisms that sense something (a pathogen, explosive, pollutant, etc) and then monitor them using satellites with hyperspectral cameras orbiting Earth. The end goal is to build a planetary-scale biosensing network.

I'm giving away $75,000 in microgrants to help grow this field. Applications are due by July 10.

Thanks to @davidtlang and the Experiment Foundation for making this possible.

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Paul Graham Verified account @paulg · May 4

It could actually be a significant problem that Europe doesn't have enough garages. This sounds like a joke, but I'm serious. Garages let you work on stuff that doesn't matter yet, which is how big things often start. The outliers of ideas need the outliers of space.

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