bglazer

What do you think they're meeting to talk about and managing?

Yes we can do targeted (de)methylation at cells via a system called CRISPRon/off. It’s a CRISPR with the DNA cutting part deactivated but retaining the DNA binding part. They then attach a protein that adds methylation (DNMT3A) or removes it (TET1). So it’s a huge protein machine and it has only been tested in a petri dish (maybe mice, not sure).

There’s a lot left to figure out. Delivery is hard. It would be hard to get it inside the right set of cells in a real person, you usually would only want to demethylate in a subset of cell types. There’s pretty steady progress being made in that area, but I think it will be several years before we fully solve that. Existing methods for doing this include hijacking a virus to deliver the DNA of the CRISPR system but those are one time only treatments because your immune system recognizes the virus and destroys it after one treatment. We use these viral delivery systems for some gene therapy treatments in real patients now. It presents a pretty terrible conundrum for patients who have to choose taking their one shot on an experimental treatment which may not work. Brave people!

Anyways, yes it is possible but it’s quite early in development.

Thanks, I was more asking from your perspective.

I’m a working research biologist, and I’m genuinely curious how he became so well known among the hackernews slice of the public. He seems to have hit on some very effective combination of research interests and public communication strategy.

I suspected it was the Lex Fridman podcast appearances, but I wasn’t sure if that was how most people became aware of him.

How do you keep up to date with his work?

I’m curious how you found Michael’s work? Like what led you to familiarize yourself with his research?

He seems to be essentially the only biologist that hackernews knows and he always (always!) comes up in biology discussion. I’m wondering how this particular situation arose.

I currently work in a chemical biology lab and I don’t think one disgruntled postdoc could wipe out humanity.

Also disgruntled is more or less unnecessary when combined with postdoc. Sort of goes without saying.

Has anyone in the rationalist, doomer community actually seriously engaged the real biology/virology of a “virus that wipes out humanity”? Playing Plague Inc doesn’t count.

I mean, we’re talking about real physical things, not first principles thought experiments here. Thus, they have limits imposed by physics and biology. Limits on transmission rate, lethality, particle size, evolutionary change rates, and so on. All of these interact and define a design space that nature has been searching for at unimaginable scale for as long as humans have existed. And yet here we are! Seems like “wiping humanity” might be really hard, perhaps impossible for a virus.

Perhaps I’m being uncharitable or insufficiently creative, but these people strike me as deeply unserious in their engagement with the actually real physical world of biology.

EDIT: Also, in this world, couldn’t an AI just “one shot” a vaccine and an effective treatment?

I'm not so sure. I haven't seen a true regional airline class VTOL yet, mostly just demonstrators that carry a few people, at that. The fact that it's larger is actually very important, the economics of a regional jet replacement make far more sense than that of an air taxi. I also doubt the similar range claim, lifting an airframe directly into the air without wings is far, far less efficient than just taking off with the benefit of lift. They're also way more complex and would require additional training for pilots.

Further, noise restrictions will probably limit VTOL's to airports, never underestimate the NIMBY's. Note that demo videos of eVTOL's almost always have background music rather than ambient sound.

Yeah I'm begging these authors to at least *read* the LLM generated README's. They're so, so incomprehensible because the LLM has a super limited theory of mind for readers. They always assume that external readers have access to the full context and history of decisions in the project development. These decisions and instructions from the user are extremely important for the model and almost completely irrelevant for an outside reader looking at a "finished" product. So, we get sentences like this:

"Where the levers were is not where they are. Overlapping the expert reads with the arithmetic was worth ~1.6x and shipped; the two that looked bigger — reading fewer bytes per token, and keeping more of them in RAM — were both measured and both refused, one because this family's router has no tail to demote and one because a cache the machine will not leave resident cannot be bought at any price."

What the fuck does that mean? Obviously some internal development decision, using the absolutely inscrutable internal terminology that Claude loves. If people would just read what they publish, I'm sure this would stick out immediately.

I'm not an LLM hater, I use them a ton and they work very well for writing complex code, it's undeniable. But they generate absolute dogshit first draft writing.

Yes this is on the 777x, which is in pre-production and flight testing, seeking approvals from the FAA

> If we go in and just check the DNA for Downs or Parkinson's

You should consider reading the wikipedia page about Parkinson’s disease.

Yes exactly, there are good and bad things to spend money on. This is a bad way to spend money for the reasons I explained above.

He's hubristic and selfish. None of his "research" is going to benefit anyone (himself included), making this essentially a huge waste of time and resources. Bryan will die just like all the rest of us, despite being very rich and self-obsessed. He could spend his enormous wealth on supporting real research and proper studies on real diseases that hurt lots of people. Instead he's acting like just another huckster promising a fountain of youth. He does this using bombastic terms and taboo methods (e.g. using his son as a blood boy), in a way that's calculated to direct enormous public attention towards himself. The science he advocates for is sketchy at best and the results of all his "experiments" will tell us nothing because we can't reproduce his methods (his program allegedly costs >$1M per year), nothing is blinded or controlled, and N=1. He's a bad person who uses bad methods to glorify himself and now he probably gave himself an autoimmune disease. He deserves to be mocked.

You’re probably thinking about non-small cell lung cancers. Small cell lung cancer (SCLC) is still absolutely devastating. The most progress made on SCLC has just been getting people to stop smoking, as its almost exclusively a smoker’s disease.

Anyways, I studied SCLC in grad school and saw lots of scans of people with tumors from their heads to their feet, and saw the enormous resources dedicated to caring for SCLC patients and to searching for a cure. It’s hard to overstate how profoundly evil the cigarette companies were and still are. They got people (children) addicted knowing what was coming for them, knowing they were killing them in horrific ways. Now we all get to pay for that in funerals and tax dollars.