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.

You might like process philosophy.

https://plato.stanford.edu/entries/process-philosophy/

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.

Gene names aren't really acronyms in the traditional sense. Often they were originally conceived as acronyms at the time of the gene's discovery and naming, but the original acronym frequently reflects an incomplete or factually wrong understanding of the gene. For example, TP53 is a very very important gene in cancer. TP53 originally meant Tumor Protein 53, where the 53 signified its molecular weight of 53 kilodaltons. The problem is that the experiment used to measure TP53's molecular weight was incorrect and TP53 actually weighs about 44 kilodaltons. Oops, now we're stuck with TP53 for eternity. There are a ton more examples of this.

So, in biology a gene's name is sometimes an acronym but it's meaning is generally forgotten

The whole article is just that someone got a spam political text about the Texas Senate GOP primary.

This is demonstrably untrue. IQ has increased consistently for decades, far faster than genetic factors can explain. Environmental factors like education, nutrition, and medical care are the obvious explanation.

Yeah I have been reading a lot of posts like this lately. Technical blog post clearly written by an LLM summarizing something vibe-coded. They always start using project-specific jargon right away and they never give you enough context or backstory to understand why this thing exists. It's seems very clearly to be a symptom of someone pointing an LLM at a repo and telling it "write a github page for this project".

It really shines through in pieces like this that LLM's have a severely constrained worldview and underdeveloped theory of mind. They can't imagine that a line like "A 200-line POC that goes from 0/5 to 5/5 in four proposer steps" means nothing to me as a subtitle for the page. After all "proposer steps" and "5/5" are *right there* in it's context. Surely everyone has "proposer steps" in their context, right?

Ah causal data! It’s a shame none of the scientists or statisticians thought of getting causal data. How would we get that? Well maybe we could just inject amyloid into a person’s brain. Or simply remove all the amyloid from a person’s brain. That should do it, right?

I mean an amyloid injection is wildly unethical and it’s also not the natural progression of Alzheimer’s. Removing amyloid is a simple matter of investing billions of dollars into drug development. Also how do you tell whether that was actually “causal” if the patients improve after plaque removal.

I mean come on, you have to work the evidence and the experimental tools that we actually have. This kind of epistemic puritanism doesn’t help anyone.

This is insane, I love it.

I work in this field. It’s more or less correct but kind of lacking in detail. Cancer is a property of all multicellular life. I think it’s best understood as the behavior of a dynamical system that loses the feedback control that keeps cell growth under control.

Check out this paper from the Lander lab: https://elifesciences.org/articles/61026

It’s a bit jargon heavy but it’s a nice case study in how tumor growth is controlled through all the same mechanisms that normal tissue growth uses. Even cells with an outright cancerous gene mutation are basically still just doing normal growth and development.

This is quite similar to how eLife does publishing. You still have to submit to them but they basically just add reviewer comments and an “eLife Assessment” that serves as the quality/curation signal rather than a binary publish/reject

> If you're an influential figure at a top-5 department in your field ... you all hate $journal.

That's the problem, they don't hate these journals, they love them. Generally speaking they're old people who became influential by publishing in these journals. Their reputation and influence was built on a pile of Science and Nature papers. Their presentations all include prominent text indicating which figures came from luxury journals. If Science and Nature lose their prestige so do they (or at least that's what they think)

This was very apparent when eLife changed their publishing model. Their was a big outpouring of rage from older scientists who had published in eLife when it was a more standard "high impact" journal. Lots of "you're ruining your reputation and therefore mine".

I think we could understand consciousness perfectly and still find it divine. In fact, I think however it arises is probably so beautiful that it would be wrong not to call it divine. Of course not in a literal, theological sense, but I think the true deep complexity of the human brain and consciousness is worth the title.

We absolutely do know about the molecular pathways that cause smoking induced lung cancer. It’s TP53 and RB1 mutations (among many others). There are probably more than a hundred thousand published papers about precisely this question

> a certain age range your eyes determine they've grown to the correct size based on how well they focus

A certain age -> which one? Why?

your eyes determine -> How? What molecular growth signaling pathways are involved? How do they integrate with your brain's visual processing centers and how does that relate to "how well [your eyes] focus". Is there a biomechanical signal from muscle stress or eye curvature?

How would you test this? You'd have to change this process somehow to show that the effect is real, but you obviously can't do that with humans, so you'd probably have to use mice, but their eyes are different, but how so?

Without any of this information, it's a nice "just-so" story about cavemen looking at the horizon, but not much more than that.

That's a lovely theory, if quite imprecise in terms of the actual biology of eye development. The actually important part of science (the part that requires a lot of expertise and judgement) is figuring out how to make that an actually testable hypothesis and then whether or not its true.

Why does focusing on nearer things cause myopia? See if you're curious at even a basic level, you'd realize that there are important *details* about stuff like this where it actually helps to have some actual subject matter expertise and knowledge.

I occasionally say please and thank you to ChatGPT for my own sake, not for the LLM's. They're sufficiently similar to humans that allowing myself to be a jerk subtly degrades myself and makes it more likely that I'm a jerk to real people.