Rory

Working on a better tools for people with kidney disease. Read a book. Ride a bike. Pet a dog.

[Rory @deeplyunsure]

The best jokes have a TAM of 2 and appreciate with time.

[Rory @deeplyunsure]

@HostileCharts Fun before it breaks? Bring sauce

[Rory @deeplyunsure]

@psswordprotectd Scanned it recently and came away with the exact same impression. Imagine not knowing how to find things *you* like. Bananas

[Rory @deeplyunsure]

As you find the aspects of AI output that are most sloppy and jarring to you, embrace them fully — that’s where your skills are likely top of distribution.

[Daniel Jeffries @Dan_Jeffries1]

Human written code was mostly drek unless you were a genius like John Carmack.

Most human writing is garbage unless you're a master like Hemingway or Amy Tan.

Human driving is a nightmare that kills 1.2M and injures 50M more a year.

AI is an improvement for 99% of the pop.

[Jesse Singal @jessesingal]

Incredible collection of Ed Zitron predictions from a very non-Zitronian subreddit

https://t.co/DtrCzuNXaf

[Build Canada @buildcanada]

Our home, our destiny.

[Samuel Hammond 🦉 @hamandcheese]

I'm sometimes asked by Canadian colleagues and outlets for my take on what Canada should do on AI. My primary and exhaustive recommendation is to put Tobias Lütke in charge and use whatever based and arcane monarchical powers the Canadian constitution permits for implementation.

[Kevin A. Bryan @Afinetheorem]

@tylercowen & @ATabarrok don't need more acclaim, but look at this *2019* grant list. Alice Evans (great new book coming). Jason pre-Progress foundation. Saloni/Sam pre-Works in Progress. *17 year old* Aschenbrenner. Tyler's "how to spot talent" book clearly "self-recommending"!

[Stewart Brand @stewartbrand]

I will buckle down to work as soon as I finish reading the Internet.

[Rory @deeplyunsure]

@InverseMarcus @buccocapital YES. This is THE vehicle to save your family from the volcano in 1999 and I’m totally here for it.

But otherwise, hell no. Def thumbs down 👎 to LR and Jeep generally

[Rory @deeplyunsure]

Love a good game theory analysis thread that confirms all of my strategic priors

[Kent Fellows @GK_Fellows]

I'm firmly on team @stephenfgordon , but I really appreciate some of the counterarguments from folks like @trevortombe and @jbsteinberg. There's a lot to think about here.

Because other folks have brought up game theory here, a modest contribution to that line of thought.
1/10

[Saloni @salonium]

Most people have never heard of siRNA, but it’s going to change the face of medicine.
https://t.co/RLP1pxuICA

Much drug development today involves developing chemicals to fit into proteins and block them. But this almost never turns out as planned: many drug candidates get broken down in the body, interfere with other proteins and cause toxic side effects, or fail to be absorbed at all.

The majority of proteins are considered undruggable, because they lack a pocket for drugs to bind, or they are ‘intrinsically disordered’, without coherent structure.

What if, instead of trying to block the protein, you could simply switch it off?

In a new article, Jacob Witten explains the magic button to silence genes.

siRNA, or ‘small interfering RNA’, is a short strand of RNA that blocks the production of proteins. As a brief refresher, proteins in the body are produced through the sequence: DNA --> mRNA --> protein. siRNA molecules bind to the intermediate mRNA and target it for destruction, meaning the protein isn’t produced.

It’s a precision medicine: siRNA targets matching mRNA sequences like a barcode, so you can pick a gene of your choice, synthesize siRNA to match, deliver it to the right cells, and silence the protein. And a single dose can last months.

Several siRNA drugs have already been developed: patisiran for hereditary transthyretin amyloidosis, inclisiran for high cholesterol, and fitusiran for hemophilia, are just a few examples.

So far, all of them target the liver, which is an easy organ to deliver drugs to. But the principle can be applied to other organs too, and scientists are developing ‘molecular address labels’ to do it.

And while some of these diseases are caused by a single gene, not all are. High cholesterol, for example, is a complex disease, but it can be targeted with siRNA drugs as well, because the disease’s pathway hinges on a critical protein, PCSK9.

siRNA is exciting because it makes it possible to circumvent the problem of otherwise ‘undruggable’ proteins. And, unlike current gene-editing therapies, it can be given to people off the shelf, without needing to extract cells from the body, edit and replace them. But it’s still going to depend on having the right hypotheses of which genes to target and delivering the drugs safely to the right organs.

We now have a kill switch for harmful genes.

Read the full article here:
https://t.co/RLP1pxuICA

[gabsmashh @gabsmashh]

babe wake up, new term just dropped

[Rory @deeplyunsure]

This rules. 10/10 cool

[Georgia Channing @cgeorgiaw]

There is a child with a rare disease who is currently suffering and struggling to manage his symptoms. Rare as this is, you can directly help him.

Today we are launching the "Rare Disease, Real Kid" Hackathon, and there are $50,000 in prizes from @AnthropicAI and @awscloud.

We (@huggingface & @Sagebio) are helping this child open his genome and clinical data to the community, so that we can find what's caused his disease and what currently-approved drugs could help him.

I doubt I need to motivate this much further or explain how rare it is for a family to share their child's genome and clinical data, but if you're not sure, consider this:

Until very recently, it wasn't feasible for patients like this to get treatment because their disease was so rare that the economics could never justify the investment. Now, as we've seen, people with rare diseases are starting to be able to find the answers themselves (with the help of AI tools, cheaper sequencing, etc). This kid is not able to do that for himself and neither are his parents, so we're asking you for help. Both for this kid and to prove that it's possible for everyone else suffering from a rare disease.

More details in 🧵.
https://t.co/hjjagALtMu

[Rory @deeplyunsure]

@thsottiaux ETA on pro equivalent for business accounts?

[Scott Lincicome @scottlincicome]

https://t.co/w5LjoJoMg9

[Rory @deeplyunsure]

@DenySully Would have been a really weird investment until like five minutes ago…

But seems sensible now

[signüll @signulll]

assuming the current u.s. life expectancy of 79 years as a baseline, in your life you get:

~4,120 weekends
~8,240 weekend days
79 summers
316 seasons
79 birthdays
~980 full moons
~28,850 nights
~86,500 meals

at common frequencies post childhood:

- one major trip/year: 61 trips
- three major trips/year: 183 trips
- one great dinner/month: 730 dinners
- one memorable night/month: 730 nights
- one book/month: 730 books
- seeing a friend annually: 61 meetings
- seeing them every five years: 12 meetings
- moving every five years: ~12 homes
- building one startup every six years: perhaps 7 serious attempts during a conventional working life
- owning each car for five years: ~12 cars
- getting a new dog every 12 years: ~5 dog eras
- taking one proper family vacation/year: 61 vacations, but only ~18 while each child lives at home
- spending two weeks/year with parents after leaving home: 40 weeks over 20 years, versus ~936 weeks spent together during childhood

life feels long cuz days repeat. measured in meaningful repetitions, it is shockingly small.

[Eliot Pence @EliotPence]

Canada's Defence Industrial Strategy calls for 125,000 new defence-industry jobs by 2035, which is strikingly close to the ~125,000 people currently directly employed in Canadian automotive manufacturing.

Solution: Rapidly pull forward the DIS. Dont wait until 2035.

Start with:

1. Aerospace + autonomous systems (probably the biggest advanced-manufacturing opportunity in the world right now). Canada could conceivably build a C$10–20B+/year ecosystem. We built the first passenger jet (C102), the first operational drones (CL-89/289) and the first nd gen fighter (Avro Arrow). We can lead again.

2. Shipbuilding + maritime systems. Between submarines, surface combatants, icebreakers, autonomous maritime systems and decades of sustainment, this could support many billions of dollars annually. DRDC built the first autonomous submarine (Theseus) and the fastest experimental warship (Bras d'Or). We can lead again.

3. Munitions / missiles / energetics. This is potentially enormous if Canada becomes an exporter to the NATO alliance. We have more cellulose than any country on earth (BC and NB forests), and wide open spaces for production and testing of next gen munitions. The world's leading research institution on energetics (Purdue Energetics Research Center (PERC)) is co-led by a Canadian, Davin Piercey. Lets bring him back.

Collectively, this is around $50-70bn annualized revenue (5X more than the current Canadian defence industry revenue today) and around 20bn shy of the current overall auto industry.

[Nassim Nicholas Taleb @nntaleb]

Bessent, with his brilliant treasury fix, looks like a doctor attempting to cure a patient's pancreatic cancer with a combination of potent tranquilizers and yoga-style meditation.

[carl feynman @carl_feynman]

Richard Feynman (my father) divided perpetual motion machines into Perpetual Motion Machines of the First Kind, which violate the first law of thermodynamics (AKA conservation of energy), Perpetual Motion Machines of the Second Kind, which violate the second law of thermodynamics (entropy must increase), and Those Other Perpetual Motion Machines, which purport to get their energy from other laws of physics. 

The Second Kind is rarer; the only example I'm familiar with is one that my dad showed me the plans for. Once in a while, someone would come to him with a perpetual motion machine prospectus and ask if it was a good investment. One of these was a machine that claimed to extract heat energy from the air and run a generator with it. They had built half the machine, which worked as far as they could test it, and were looking for gullible investors to pay for finishing it. By carefully going over the immensely complex plans, my father and I found a "heat exchanger" that was supposed to take warm freon and cool air, and produce hot freon and cold air. Naturally, this heat exchanger was in the as-yet unbuilt portion. 

Those Other Perpetual Motion Machines get their energy from heretofore unknown physics, like cold fusion, vacuum fluctuations, or secret new physical laws that will be disclosed only on the payment of $1,000,000. These are worthy of much more serious physical investigation, since it is entirely concievable that someone will discover a new easy way of making energy. 

Back around 1970, my father went to a public demonstration of one of Those Other Perpetual Motion Machines. He discovered an electric cord running out of the back of the machine, plugged into the wall. When he unplugged the machine and pointed out to the inventor that a perpetual motion machine that had to be plugged in wasn't really perpetual, the inventor pushed a button on the control panel and the machine exploded. Several spectators were severely injured; I believe one man lost an arm. The inventor sued my father on the grounds that he had caused the explosion; my father suspected that the explosion was deliberate. The trial ended up with my father not having to pay.

Epistemic status: Childhood recollections, untainted by fact-checking. Originally an email from 1997.