Chrisprattalpharaptr
Ave Imperaptor
No bio...
User ID: 1864
tl'dr at the bottom.
It was the early 20th century. These were heady times for biology; Thomas Hunt Morgan was doing groundbreaking work in Drosophila which culminated in the concept of the gene. Griffith reported some experiments that launched a series of investigations over the following decades by Hershey & Chase/Avery and McLeod showing that DNA, not protein, is the hereditary material in the cell. And in a lab in the Rockefeller Institute, NYC, a French surgeon was using proto-tissue culture techniques to create an immortal chicken heart.
A full century ago, some smart scientists were already asking how cellular theory intersected with aging and senescence, and whether there where limits on cell division. To great acclaim, Dr. Carrel claimed to have found the answer: he grew embryonic chicken heart cells in a stoppered flask. For 20 years the cells thrived as he fed them a steady diet of embryonic chicken fluid and claimed to the media that:
In 1921, an article in The World by Alessandro Fabbri engaged his audience with an account of how large the volume of the cells cultured could have been, telling readers that it would have been like a “rooster … big enough today to cross the Atlantic in a stride,” and “so monstrous that when perched on this mundane sphere, the World, it would look like a weathercock.” Three years later, the New York Tribune published an article to celebrate the twelfth birthday of the culture.
You might be skeptical at this juncture - maybe you learned about a certain limit in high school named after a famous scientist waiting in the wings. While it was long accepted in the 20th century that cells could divide forever and the answer to aging lay elsewhere, the development of modern tissue culture techniques in the 50s set the stage for Leonard Hayflick (I linked a great radiolab interview above - in his mid 80s, he still stored a ton of cell lines in liquid nitrogen tanks in his garage. There's probably some fascinating cell lines in there that the rest of us have forgotten about). And indeed, Leonard Hayflick showed with much more rigorous technique that differentiated cells isolated from human adults had a definite lifespan, and would naturally senesce and die after a certain number of divisions in vitro, and presumably in vivo as well. A large amount of work went into defining the 'Hayflick limit' for various cell types in different contexts, and more importantly, it was discovered that certain cancerous cells could indeed be adapted to grow in cell culture indefinitely. It turns out Carrel's protocol of adding fresh embryonic fluid to his chicken heart culture was most likely adding fresh stem cells (although we also cannot rule out fraud as the experiment supposedly could not be replicated) on a regular basis.
You may wonder, dear reader, why I bothered to lay this out for you? Well, if you think about it, there's one obvious exception to the Hayflick limit - your germ line. Your gametes represent an unbroken cellular lineage stretching all the way back to the first spark of cellular life in the primordial soup. And this week, a heroic paper described another exception to the Hayflick limit and actually succeeded in creating the immunological equivalent of Carrel's chicken heart.
When T cells recognize their specific antigen, they enable a initiate a genetic program to both rapidly divide and also release effector proteins that unleash a range of defensive mechanisms against the invading pathogen. You've probably heard of the different COVID proteins used in the vaccines; each of those proteins consisting of hundreds of amino acids is chopped up into 8-20 amino acid long 'bytes' that can be recognized by T cells. While your immune response consists of a mishmash of dozens to hundreds of T cell lines specific for different antigens (polyclonal), scientists have developed ways to track a single clone specific for a single antigen. Here, the authors infect mice with a virus (VSV) and track T cells specific for a peptide (VSV-N52-59). Techniques have also been developed to take T cells out of one mouse and transfer it to a new mouse, and the last piece of the technological puzzle missing for Carrel - a method for differentiating transferred T cells from the endogenous T cells already present in the new mouse.
So the basic outline of the study is to infect a mouse with VSV, isolate those T cells, transfer to a new mouse, infect that mouse with VSV, isolate those T cells, transfer to a new mouse...ad infinitum. They kept it up for 10 years, or 5 times the lifetime of a mouse - roughly equivalent to stimulating some T cells around the time Columbus landed in America and having them still be growing today. Curiously, the telomere length is unaffected despite the cells acquiring a number of markers we normally associate with dysfunction (PD-1 of cancer checkpoint blockade fame, TIM3, TOX, KLRG1, etc) and a distinct transcriptional signature. And more importantly, they're still immunologically functional and capable of further division.
How do T cells do it? Hell if I know. But the standard models of ROS, telomeres, mitochondrial dysfunction, etc. just aren't able to explain it. Like the best studies, this hints at a deeper truth we're nowhere close to uncovering, and I despair of meaningfully understanding the system in my lifetime. It's still a beautiful fucking paper though, and I pity the post-doc who's been shuffling T cells around mice for the last 8 years of his life.
tl;dr - Mice live two years, scientists have shown that you can take differentiated T cells (not stem cells!), stimulate them with a virus, transfer them to a new mouse and so on and so forth for more than 10 years (!). They calculate this to be a 10^40 fold expansion of the original group of T cells.
Chrisprattalpharaptr
Ave Imperaptor
2yr ago
It's true, and it's also awash in other hypocrisies. I could use the John Stewart 'I'm just a comedian, bro defense because I mostly was just trying to entertain, but if you want:
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An expectation of more citations and sources for claims being made, or if the data doesn't exist/can't be collected, acknowledgement of that fact.
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Embracing brevity, concision and clear communication as terminal values rather than long manifestoposts (obviously some leeway for people writing personal stories or stream of consciousness rants).
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Some self-awareness when mocking others for status-signaling.
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Embracing intellectual humility (something akin to the old 'epistemic status: xyz...')
To some extent, this is just me imposing my values on others which is why I tried not to be explicitly prescriptive. The community should be what the community wants to be. Hopefully someone out there laughed.
Chrisprattalpharaptr
Ave Imperaptor
6mo ago
And the flip side of this is that as soon as a worker is negative EV or whatever the appropriate metric is, they're liable to be laid off. This is just the equilibrium where neither party can trust the other and there is at will employment. I imagine economists like it and would say that the employee who moves and gets a raise or a company laying off unproductive workers is more efficient, and what do I know, maybe they're right.
I was chatting with a Japanese employee of a large company with offices in both Japan and the US. He says that rather than layoffs, they get put on 'career improvement plans.' In his case, it involved completely retraining his specialty and moving his family to the US, but he kept his job and stayed at the same company. We could probably have this situation if we wanted, but I'm unsure it's actually superior.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I do lament that the vast majority of what gets published is totally worthless, but I'm wishy-washy on whether the fundamental driver is that less capable people are getting into these positions or if it's almost purely a result of incentive structure. In the end, I think it's probably both, but let me sketch it out. This is basically an attempt to steelman the possibility that, say, the 85th percentile of folks who could have even plausibly thought about pursuing a career in academia actually has gotten to be a lot better than they were in the past. Then, since total faculty numbers are stagnant, it wasn't as easy to just look at traditional measures and pick out the highest quality folks (akin to how you can't necessarily just look at OTB chess rating nowadays), but since you couldn't just wait and let the rating system self-correct over time, because, uh, you don't have a self-correcting rating system like ELO for academics, they had to go hard in on shit like just making some number or other go up.
I had a longer post written, but I just don't have the heart to argue about wokeness anymore. So here's an abridged version: I've been through two biotech companies at this point, so I've had exposure to maybe 60-70 young scientists who should be at the peak of their idealist phases. PhD and postdoc at some premier institutions in the USA. I've asked around, and a grand total of zero people at either company have read any serious amount of science fiction. A couple fellow PhD students did, the CSO at the second company mentioned having read Dune and a Game of Thrones in high school, I doubt any of the faculty I interacted with did. Most people don't read at all. All of this makes me sad, and lonely.
There are plenty of highly profitable activities given the existing incentive structure that do virtually nothing to move the needle scientifically or in terms of actual benefit to society - go make another monoclonal antibody to some target people haven't tried yet, or shuffle around different combinations of checkpoint blockade, or make another oncology small molecule that extends mean progression-free survival by three months. You'll probably make a boatload of money if you get a lucky pull of the slot machine lever.
So, yes. Definitely agree that we've lost the ability to dream big and be ambitious in the right ways. Don't know how to fix it when I need 7-8 figure investments to do even basic projects.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I'll preface this by saying I agree with the concerns around GoF research and that it is a real problem.
Now, to add some context: This is the preprint in question.
Don't trust '100% mortality' hyped up by a news org, it's the equivalent of hack tech writers claiming '100% cancer cure rate' in some mouse model. You can get '100% mortality' with a high enough dose of relatively benign rhinoviruses that just cause colds in humans. In this preprint, the authors infected with 500,000 PFUs (plaque forming units, supposedly one PFU = 1 virus). This may not bring much comfort to people, but the LD50 of a mouse-adapted stain of COVID is 1000 TCID50 (similar to PFUs), or two orders of magnitude lower. It's hard to get a direct comparison, but here's another paper reporting an LD50 of 1000 PFUs in ferrets.
You're probably not going to die next year of GX_P2V infection. Beware articles in the New York Post throwing red meat to the base.
I don't have time to do this topic justice, but as for 'banning GoF research' - this would not have been classified as GoF research under most paradigms. Wild virus isolates were passaged in cell culture; this is simply how you propagate virus for study. Generally, propagation in vitro attenuates viruses and makes them less pathogenic, modulo some cases (admittedly similar to this one) where you may pass viruses adapted to one species in cells from another.
We produce a lot of vaccines and gene therapy vectors this way, although even those examples contain multitudes. Maybe you want a carveout for very well understood processes that we've been doing for years, but you'd have to think very carefully about crafting it.
Chrisprattalpharaptr
Ave Imperaptor
2yr ago
Not to keep ragging on you, but does it give you any pause that your proposal massively advantages your own community in terms of political power while disenfranchising those you dislike? Are you impartially proposing something that would better society or do you have a fairly significant conflict of interest?
It would be like me proposing that only people with advanced degrees could vote and rationalizing it in technocratic terms about how we're the most capable, intelligent, whatever parts of society. A master's degree gets you one vote, a PhD gets you 5, people with dual degrees (MD/PhD, etc) get 10, whatever. Sounds plausible, but do you trust me?
I am broaching a large anti-mRNA topic, and throwing down. I have placed plenty claims that I expect to be rebutted.
It'd be a bit easier if you could summarize with some bullet points of the claims you're actually throwing down to be rebutted - it's a fairly long and meandering post.
I am having a lot of trouble with this. The pfizer vaccine is associated with an increase in Pulmonary Embolism, which is a blood clot in the lungs. There is severe disinterest in classifying these types of blood clots. I noticed that the scientific establishment went very far to profile "microclots" of the COVID-19 disease
Note that COVID has an RR of 2.2 for pulmonary embolism, the patient population for which is likely heterogeneous (vaccinated, unvaccinated, vaccinated + infection, etc). Does vaccination significantly reduce that number in such a way as to be net beneficial along this single axis? I'm not sure we could power that study, particularly now that everyone is some mess of vaccinated/infected/vaccinated + infected and we can't reliably differentiate them anymore. On the one hand, rates of PE are fairly high in hospitalized patients, who are the ones who would have most benefited from vaccines - on the other hand, the same study doesn't note much of a change in PE risk in hospitalized patients after vaccines became widely available. Moreover, the slow pace of updating the vaccines combined with decreases in COVID virulence make the calculus very difficult in whether the vaccines even provide significant benefit at this point - a point being reported on in the MSM.
Note also that the major caveat of the paper you link is that they're forced to compare to historical data, so we're effectively comparing PE rates in two historical periods - one of which saw the emergence of a major new respiratory virus causing PE! From the paper you linked:
Further, the AMI, DIC, and ITP signals were not robust when additional baseline rates were evaluated, while the PE signal might be explained by differences in rates between the pre-COVID-19 and peri-COVID-19 periods.
Also:
The statistical signals of four serious outcomes are not necessarily causal and may be due to factors potentially unrelated to vaccination. Additional analyses indicated that the potential association was less than twice the historical rates and may be associated with factors not accounted for in the near real-time surveillance methods. For example, the elderly Medicare population that received the BNT162b2 vaccine differed from other elderly COVID-19 vaccinated populations, including a preponderance of nursing home residents and populations with a higher comorbidity burden. These demographic and medical differences were not fully accounted for, since expected rates were only standardized to a subset of characteristics – age, sex, race, and nursing home residency status.
Be careful drawing facile conclusions from large correlational studies like this. And not to be a paternalistic douchebag (feel free to ignore if you know better) but you might find it helpful to skim the discussion of a paper if you aren't familiar with the field to at least get a feel for the limitations or alternative explanations of the study.
That's all I found. Can you help me with information on clotting from the Flu?
There's plenty of papers: Here's a review that will have a summary and a couple dozen primary references if you're interested. Many primary papers investigating the mechanisms as well.
except we saw autopsy results in Germany that prove there can be sudden death after vaccination from the myocarditis related arryhthmia/dysrhythmia.
What study are you referencing? The last time I looked into myocarditis it was vanishingly rare, a tiny number of deaths were attributable to it and those individuals seemed to have many other medical conditions. Usually sudden death after vaccination would be related to anaphylaxis due to an allergy to some vaccine component, whereas the myocarditis takes a few days to develop.
I understand that for your first encounter with the virus, your odds profile is completely different. If you already had Covid-19, you have natural immunity. Any further mRNA vaccination is offering a risk without a benefit, now that your immune naivety is broken.
As well say this for tetanus, flu, rabies or any of the other viruses we need boosters for. Immunity wanes particularly quickly for respiratory viruses. Note also that the Moderna booster is a half dose, so modulo some weird memory effects likely has lower rates of adverse events.
I don't think we know the risk of myocarditis after reinfection; it's almost certainly lower, but I could only find two case reports so it's difficult to draw any conclusions or calculate the relative benefit of vaccination. Moreover, tens of thousands of elderly patients die of flu every year, and I can guarantee you that they aren't immunologically naive. Natural immunity isn't a silver bullet.
We keep getting dragged down by considering every SARS-2 infection as potentially lethal, when this was really never true. I believe this has created a pervasive "magical model" of viruses where the virus touches one of your cells, and suddenly has a key to every organ in your body (please rebut me).
I'm not sure I understand your point here.
Immunity, the virus is being kept very mild, and I am highly suspicious of anyone who presents a sequalae based on unique characteristics of SARS-2, when it infects your upper respiratory tract, like the hundreds and thousands of respiratory virus strains that were ostensibly new, and passed through us dozens of times. The true nature of the human ecology and it's interaction with reparatory viruses, since the group Mammalia existed, suddenly seems like a especially dangerous aberration in our times (edit note - typo and word change for group).
It's true. It does seem like COVID is progressing towards being 'just another virus' that people get repeatedly during flu season and we've watched in real time the emergence of a new 'cold' virus. I'd argue it's the first time we've watched this happen with modern technology (HIV and seasonal flu strains being related, but distinct in my opinion). None of this precludes a hyper-pathological variant cropping up next year, but I suppose I'd bet against it.
That being said, we've been infected by influenza for at least 1,500 years and it's still a major public health concern. A truly protective vaccine would be a major coup, and investing resources in these problems is worthwhile even if lockdowns and mask mandates are not.
Am I outing myself as a desperate Mottian by being so befuddled by the seeming lack of interest in a new type of vaccine that can cause heart damage at comparable rates to a novel coronavirus infection. Imagine updated IFRs if you include the recirculating infections going around now.
The calculus for the vaccines was just much better early in the pandemic. Who cares about PE; it's vanishingly rare. Even in your study of nursing home patients only 10,000 out of 25,000,000 had a PE, an with a fatality rate of 5% (probably needs to be adjusted upwards for the elderly population) that's 500 deaths, with maybe 100-200 of those attributable to vaccination (see caveats above). Now do the math for deaths in that population if they had all been unvaccinated and exposed to COVID.
mRNA seems to be the problem. Check the wikipedia article for "solid lipid nanoparticle." Kind of short. A few years of science (okay, I know the line was "decades," which is not impressive compared to centuries of other vaccines). mRNA spreads throughout your body via your blood stream, and this is a technology flaw in the mRNA platform.
How do you think conventional vaccines make it to your lymph nodes? Both mRNA and conventional vaccines transit from the site of vaccination to your lymphoid organs via blood/lymph.
The centuries of science around conventional vaccines in the ages before we knew what B/T cells were probably don't count for much, and I doubt the live cowpox vaccines that you'd prefer had fantastic safety profiles. The fact that you need tens of millions of doses of vaccine to maybe tease out a signal of a potential side effect is, by and large, a very good safety profile.
J&J, while still newer, did not show any concerning safety signals, and was eventually pulled because it cannot be updated efficiently, and humans become tolerant to the vectors. Or, J&J caused blood clots, killed people, and was pulled/discouraged to direct people to 'safer' mRNA vaccines. I would get more viral vectors, but probably only if I was going somewhere exotic and expected an encounter with a pathogen of special interest to me. J&J platform was also a human virus and will be treated by your immune system as a virus. You, and your mammalian ancestors have naturalistically encountered viruses since the beginning. This is not a fallacy!
It was pulled because both the safety profile and efficacy were worse. And of course it's a fallacy, on par with people have always dumped raw sewage in the Thames and cholera is just a fact of life. There's strong data that the mRNA-vaccines are safer and better than J&J or other non-mRNA vaccines developed abroad, unless you put a huge premium on living 'naturally.'
I'm out of characters, but note that antigens are also 'conjured' at the ribosome with your viral vectors.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I'm unaware of any other demographic whose existence is only made possible by pharmaceutical companies stepping in to stop 16-50% of the population and its subgroups from dying in the streets due to self-inflicted pathogens.
The infant mortality rate was 46% a scant 200 years ago. Presumably it would reach that again in the absence of modern medicine and sanitation. Literally every demographic is heavily dependent on government and corporate spending.
Chrisprattalpharaptr
Ave Imperaptor
3mo ago
When will the AI penny drop?
Amara's law seems to apply here: everyone overestimates the short-term effects and underestimates the long-term effects of a new technology. On the one hand, many clearly intelligent people with enormously more domain specific knowledge than me. On the other hand, I have a naturally skeptical nature (particularly when VCs and startups have an obvious conflict of interest in feeding said hype) and find arguments from Freddie deBoer and Tyler Cowen convincing:
That, I am convinced, lies at the heart of the AI debate – the tacit but intense desire to escape now. What both those predicting utopia and those predicting apocalypse are absolutely certain of is that the arrival of these systems, what they take to be the dawn of the AI era, means now is over. They are, above and beyond all things, millenarians. In common with all millenarians they yearn for a future in which some vast force sweeps away the ordinary and frees them from the dreadful accumulation of minutes that constitutes human life. The particular valence of whether AI will bring paradise or extermination is ultimately irrelevant; each is a species of escapism, a grasping around for a parachute. Thus the most interesting questions in the study of AI in the 21st century are not matters of technology or cognitive science or economics, but of eschatology.
The null hypothesis when someone claims the imminence of the eschaton carries a lot of weight. I dream of a utopian transhumanist future (or fear paperclipping) as much as you do, I'm just skeptical of your claims that you can build God in any meaningful way. In my domain, AI is so far away from meaningfully impacting any of the questions I care about that I despair you'll be able to do what you claim even assuming we solve alignment and manage some kind of semi-hard takeoff scenario. And, no offense, but the Gell-Mann amnesia hits pretty hard when I read shit like this:
It emails out some instructions to one of those labs that'll synthesize DNA and synthesize proteins from the DNA and get some proteins mailed to a hapless human somewhere who gets paid a bunch of money to mix together some stuff they got in the mail in a file. Like, smart people will not do this for any sum of money. Many people are not smart. Builds the ribosome, but the ribosome that builds things out of covalently bonded diamondoid instead of proteins folding up and held together by Van der Waals forces, builds tiny diamondoid bacteria. The diamondoid bacteria replicate using atmospheric carbon, hydrogen, oxygen, nitrogen, and sunlight. And a couple of days later, everybody on earth falls over dead in the same second.
I've lost the exact podcast link, but Tyler Cowen has a schtick where he digs into what exactly 10% YOY GDP growth would mean given the breakdown by sector of US GDP. Will it boost manufacturing? Frankly, I'm not interested in consooming more stuff. I don't want more healthcare or services, and I enjoy working. Most of what I do want is effectively zero-sum; real estate (large, more land, closer to the city, good school district) and a membership at the local country club might be nice, but how can AI growing GDP move the needle on goods that are valuable because of their exclusivity?
Are there measures of progress beyond GDP that are qualitative rather than quantifying dollars flowing around? I can imagine meaningful advances in healthcare (but see above) and self-driving cars (already on the way, seems unrelated to the eschaton) would be great. Don't see how you can replicate competitive school districts - I guess the AI hype man will say AI tutors will make school obsolete? Or choice property - I'd guess the AI hype man would say that self-driving officecars will enable people to live tens of miles outside the city center and/or make commuting obsolete?
I can believe that AI will wreak changes on the order of the industrial revolution in the medium-long term. I'm skeptical that you're building God, and that either paperclipping or immortality are in the cards in our lifetimes. I'd be willing to bet you that 5 and even 10 years from now I'll still be running and/or managing people who run experiments, with the largest threat to that future coming from 996 Chinese working for slave wages at government-subsidized companies wrecking the American biotech sector rather than oracular AI.
In either case, I don't know about AI x-risk. I am much more worried about 2cimerafa's economic collapse risk. But in both scenarios I am increasingly of a perspective that I'll cheekily describe as "You shouldn't get to have a decision on AI development unless you have young children". You don't have enough stake.
I'll call your 'don't get a say on AI development unless you have young children' and raise you 'you don't get to have a say on abortion unless you have a uterus' or 'you don't get a say in gun control unless you own an AR-15' or 'you don't get a say in our adventures overseas unless you serve(d) in the military.'
What's the general principle you want to employ here, and if you want to restrict it to certain use-cases, what's your rationale? In theory we should all have a say in all aspects of how our society is run. Maybe in practice we don't want the specifics of highly technical questions like the storage of nuclear waste to be decided by referenda, but self-determination and broad involvement of the populace in moral questions seems to be a fundamental value of the western political tradition.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Absolutely disgusting. The people peddling the more extremist rhetoric about Trump should be ashamed. On the bright side, perhaps those people will shut up for a while and we can regain some level of sanity for at least a little while.
As (nearly) always happens, I expect the actual outcome here to be the complete opposite of the shooter's goals and Trump just won the election by a landslide.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Humanity is also locked into a demographic decline that will eventually disrupt the stable global order and world economy. No solutions tried so far have worked or even shown promise. It may be too late for such solutions to prevent the decline.
150 years ago we were thought to be locked into a Malthusian explosion whereby widespread famine and war were inevitable as we bred like moties and exhausted our resources. Things that seemed inevitable can reverse themselves fairly easily, and I'd agree with /u/2rafa that we haven't seriously tried to reverse the trend. People respond to incentives, and if the current regime incentivizes DINKs, there's no reason we can't create a new one that punishes them. If nothing else, childfree people are greatly outnumbered by people with children.
for longevity/anti-aging science which seems poised for some large leaps
Don't hold your breath my man. The longevity/anti-aging field (if I can be permitted to throw a bit of shade for a moment) suffers from a profound lack of talent and attention from the wider scientific community. First, consider that any new discovery takes 10-15 years to be translated into the clinic (see: CRISPR 'discovered' for realsies in 2012, first clinical trials in people started in the early 2020s). So, even if I'm putting my foot in my mouth and the definitive breakthrough in aging research will be published tomorrow, anyone telling you that a drug is less than 10 years out is almost certainly wrong. If you show me the first immortal mouse, I'll get excited and think that maybe we could translate a human drug in 5-10 years, although even then we often fail! (see: Alzheimer's, MS, most oncology drugs)
Second, consider that whatever neo-Rasputin tells you, we genuinely have no clue how aging works, let alone how to manipulate it productively. All the conjecture about seven forms of cell damage will remain conjecture until someone actually manipulates any of those things, and makes an otherwise healthy, wild-type mouse live significantly longer. Rapamycin/caloric restriction probably doesn't clear that bar (see section on CR) and doesn't work in higher mammals for that or some other reason, and putting telomerase back into a mouse with progeria certainly does not.
Thirdly, consider that the academics in the space suffer from a profound lack of ambition/vision, while those who have either are, unfortunately, grifters. See: Calico, which launched with 3.5 billion (massive for a biotech):
We are not a traditional biotechnology company, nor are we an academic institution. We have combined the best parts of both without the constraints of either.
Their ALS drug is interesting, but in the last 11 years most of what they've produced is more academic naked mole rat sequencing papers, plus what looks like a pivot into oncology and 'age-related diseases' rather than aging. I'd elaborate on the grifter side, but that would probably ruffle too many feathers to be worth it.
I recently read the Situational Awareness report by Leopold Aschenbrenner, which is a matter-of-fact update on where things absolutely seem to be heading if straight lines continue to be straight for the next few years.
I recently read it too, and listened to the >4 hour podcast. It's certainly interesting, and I won't pretend to be in a position to judge any of the content regarding AI/ML which is far outside my wheelhouse.
That being said...people don't genuinely expect ASI to be omnipotent, right? Like, I assume Hari Seldon psychohistory-level AI just isn't possible, or is far enough away to be irrelevant. I also expect that the abilities of ASI to manipulate nature will mirror our own. That is to say, I expect them to be god-tier engineers and coders, but while I expect them to be capable of running circles around people in the stock markets, generating a flawless model of the economy that can predict any event seems virtually impossible. Put a different way, I expect that the hard/soft science divide will continue to exist the same way that I can still beat AlphaZero at chess if you put me up a queen in the endgame.
All that to say, when I try to use AI today for biology research it's strictly limited by what we already know. If I ask it for novel theories about aging, it spits out word salad that I can read in any old review on Pubmed rather than modeling the world from the ground up and generating a new hypothesis. Perhaps this is one of the 'unhobblings' Mr. Aschenbrenner references, or perhaps the models I have access to have been RLHF'd away from hallucinating anything interesting, but it's not clear to me how throwing more Pubmed articles into the training data set is going to address this problem. And even then, if some emergent quality enables it to piece together a broad worldview, it's not clear to me how the eschatological diamondoid-bacteria scenario is possible (setting aside how dumb an idea diamondoid bacteria are compared to much easier options for eradicating humans). Molecular dynamics simulations just seem too computationally intensive to do in silico experiments deterministically (although I'm not super knowledgeable about this field and would be curious if anyone else here has any input) at the cellular level, which requires some black boxing, which requires empirical experiments in the lab...
To be clear, I'm bullish on AI and even bullish on AI in biology. Nothing would make me happier than some godlike AI oracle that could satisfy my curiosity, I'm just skeptical that even the ASIs pitched by proponents like Aschenbrenner will be as omnipotent as advertised.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
The dysgenics is trivial to solve with embryo selection
IVF costs 10-30k per cycle, with a success rate of around 20-30%. There are around 3.5 million births per year in the US. Even discounting sequencing costs (you want whole genome? Just a SNP chip?), assuming I'm understanding you correctly, won't your program have a roughly hundred billion/year budget? Not to mention that many women don't want to do ivf.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
Hilary had all of those as well and lost just the same.
Define democrats winning in a 'walkover' and conditional on Trump being the republican nominee I'll take the other side of that bet.
Chrisprattalpharaptr
Ave Imperaptor
2yr ago
This isn't to say they aren't tasty in their own way, they just clearly aren't meat. The best ones I've had barely rise to the level of "gas station sausage patty" in terms of flavor and texture.
There's at least some niche segments of the market where this won't matter. Some people like meat but want to reduce how frequently they eat it for environmental and ethical concerns. Although given the manufacturing process, I wonder how the emissions for lab grown meat would actually stack up...
Economically though, the whole process is a nightmare because cell culture has been developed for the medical field where costs don't matter, not the consumer market where there's actual competition. I was looking into this awhile back because I had some startup ideas that ran into similar problems as lab grown meat. The generic stuff (amino acids, sugars, lipids, etc) isn't bad, but the big problem is 'growth factors,' or recombinant proteins. In your body, the division of most cell types (and particularly muscle) are strictly controlled to avoid cancerous growths. They're typically quiescent unless certain soluble proteins stimulate receptors on their surface. Growing and purifying a cocktail of these proteins has been horrendously expensive, so people typically use fetal bovine serum (FBS) instead which costs 1500-2000$ per liter, and you use it at a final concentration of 5-10% so...a 10L bioreactor would cost you 2k in FBS alone, and produce about 250g/L or 5lbs of meat.
Obviously things have gotten cheaper (one of those articles mentions a plant-based substitute for FBS which I hadn't heard about previously), and economies of scale, but that paper mentions a floor of ~20$ per pound of meat which is a big ask even for the most motivated millenial-pseudo-vegetarian. Essentially, these people are going to have to develop an entirely new array of techniques tailored towards economic food production rather than medical research. Or just grow yeast instead.
Chrisprattalpharaptr
Ave Imperaptor
2yr ago
Hilarious that foxnews.com is currently headlining an article about Desantis receiving a standing ovation, with the Trump announcement buried below Bankman-Fried, the LA mayoral race and the UVA football shooting.
Chrisprattalpharaptr
Ave Imperaptor
3mo ago
I've attached a reply from Gemini 2.5
Consider this a warning; keep posting AI slop and I'll have to put on my mod hat and punish you.
It uses patsies or useful idiots to assemble a novel pathogen with high virulence, high lethality, and minimal predromal symptoms with a lengthy incubation time. Maybe it find an existing pathogen in a Wuhan Immunology Lab closet, who knows. It arranges for this to be spread simultaneously from multiple sites...This doesn't require superhuman intelligence that's godlike. It just has to be very smart, very determined, patient, and willing to take risks. At no point does any technology that doesn't exist or plausibly can exist in the near future come into play.
Do you really think you can do that with existing technology? I'm not confident we've seriously tried to make a pathogen that can eradicate a species (mosquito gene drives? COVID expressing human prions, engineered so that they can't just drop the useless genes?) so it's difficult to estimate your odds of success. I can tell you the technology to make something 'with a lengthy incubation time and minimal predromal symptoms' does not exist today. You can't just take the 'lengthy incubation time gene' out of HIV and Frankenstein it together with the 'high virulence gene' from ebola and the 'high infectivity' gene from COVID. Ebola fatality rate is only 50%, and it's not like you can make it airborne, so...
Without spreading speculation about the best way to destroy humanity, I would guess that your odds of success with such an approach are fairly low. Your best bet is probably just releasing existing pathogens, maybe with some minimal modifications. I'm skeptical of your ability to make more than a blip in the world population. And now we're talking about something on par with what a really motivated and misanthropic terrorist could conceivably do if they were well-resourced.
I'm still voting against bombing the GPU clusters, and I'm still having children. We'll see in 20 years whether my paltry gentile IQ was a match for the big Yud, or whether he'll get to say I told you so for all eternity as the AI tortures us. I hope I at least get to be the well-endowed chimpanzee-man.
Chrisprattalpharaptr
Ave Imperaptor
4mo ago
I am but a humble biologist, and know little of warfare, politics and economics. But I'm surprised to see nobody has mentioned that the majority of US aid to Ukraine was spent with US arms manufacturers. Many Trump supporters (or at least democrat-haters) bemoaned the atrophied state of US/European arms production when Russia was producing more shells than NATO per month. China can kick our ass in drone production. Setting aside all questions of morality (which I obviously find more compelling than your median Trump supporter), why not use the conflict in Ukraine as an opportunity to re-arm? So to answer your question...pretty much anything and everything that we can make that wouldn't enable Ukraine to steamroll the Russian army and march on Moscow. No NATO troops, no air support (just intel), no nuclear umbrella (for now).
As an aside, isn't domestic spending to onshore manufacturing a key goal of the Trump administration? Why the monomaniacal focus on tariffs and not industrial policy more broadly? And particularly tariffs on our allies...but I suppose that's a different discussion.
while the conversation about the current state has certainly been productive, it seems to me that rationalization on either side is always a failure mode, and the cure is predictions:
Indeed. I've seen you post half a dozen times here something along the lines of (and feel free to correct my paraphrasing): 'My model of the world is that the ingroup will consistently choose to harm the outgroup as much as possible. In 2020, protesters burned down billions of dollars worth of homes/businesses to harm the outgroup. When Red-tribe Kyle Rittenhouse tried to defend innocents he was attacked and then tried by the Blue-tribe Justice system that refused to prosecute the crimes of the rioters.
When the pandemic happened, Blue tribe health officials instituted draconian lockdowns that minimally impacted the white-collar laptop-class but wrecked Red tribe laborers and Red tribe parents.
My model of the world predicts these events perfectly! Do you have a better model, and if so, does it accurately predict the world?'
To which I would say, would your model predict:
- Trump wouldn't prosecute Hilary in 2016?
- The lack of major civil unrest, stochastic terrorism, or any major backlash to the repeal of Roe v. Wade aside from some Democratic electoral wins in 2022?
- The end of vaccine mandates in public and private spheres and the end of lockdowns?
- The utter lack of any major protests, civil unrest, or loss of faith in the electoral system after Trump beat Harris? (you want comments that aged like milk - look at the people who were claiming election fraud the morning of November 5th and even through that evening)
- The utter defeat of abolish the police and any of the George Floyd era movements?
- The lack of significant stochastic terrorism (remember the breathless doomposting about how easy it would be for disaffected lone wolf Red Tribers to blow power substations and other critical infrastructure?) through a year of electoral campaigning and the actual election?
To be clear, I doubt I could have predicted these events with any accuracy. But my observation is that you couldn't have done that either. If you want to prove me wrong, make some concrete predictions about the next four years. Will Trump incarcerate Biden or some other major democrat? Trump assassinated by an activist? Significant uptick in lone wolf attacks? World War III?
The only thing your model has going for it is that nobody pays attention to things that don't happen, even when that's the critical evidence against your argument. But whenever something controversial happens, you pop up and point towards the big flashing sign saying 'EVERYTHING SUCKS.' It's the same sensationalism that governs journalists, wrapped in a Bayesian/rationalist worldview.
Biden family's alleged corruption has evolved over time, here and in the broader public, and the specific events and disclosures that have shaped that conversation. My perception is that many of the arguments made to defend Biden, his family, and the conduct of the investigations into their activities have aged exceedingly poorly.
I admit to being disappointed in Biden, the pardon is deplorable and shouldn't have happened. I remain unconvinced that Joe Biden is particularly corrupt (...pardon notwithstanding), and I'm skeptical that Hunter is particularly corrupt by the standards of DC.
In particular, it seems to me that this saga has been an excellent example of a common pattern of group behavior wherein the facts, as they emerge, consistently break against the tribal narrative. This pattern seems to me to be a good indicator of entrenched tribalism attempting to deny reality, and likewise a good demonstration of the limits and shortcomings of that tribalism, which should guide us to a better understanding of how the Culture War is likely to play out.
One tribal narrative was that Biden was corrupt and abused his office to get rich. The other tribal narrative is...well, that the Bidens aren't particularly corrupt. Setting aside which direction the facts are consistently breaking, one tribal narrative has to be false in order for the other to be true. In your model, since you clearly believe Red Tribers are correct, are entrenched Red Tribalists denying reality?
edit: well, OP changed substantially after I hit post.
Chrisprattalpharaptr
Ave Imperaptor
10mo ago
Dropping a literal biblical plague of retards on your political opponents should be classified as a war crime. We need a new Hague.
I've been saying the same thing for years, but Anime Con keeps happening and nobody puts the organizers on trial for crimes against humanity.
Chrisprattalpharaptr
Ave Imperaptor
1yr ago
I agree overall, although I'd argue that the progress enjoyed by the current generation of Chinese adults is highly unlikely to be replicated by their children. I expect they'll go down the same path we did unless 'Capitalism with Chinese Characteristics' and endless readings of 'Xi Jinping Thought' can save them.
My money is on pessimism setting in 20-30 years from now, and foreign capital moves to Vietnam or Africa or whatever the next manufacturing base will be.
Chrisprattalpharaptr
Ave Imperaptor
2yr ago
You yourself commented a few months back about doing a 'double-take' when reading some of my recent writing, suggesting (in different language) that I was becoming 'radicalized' on a few topics. One area you've counter-radicalized me is the conversation around falling birthrates in the west, and frankly, I'm coming to align more with the TwoXChromosome worldview that it's just a trojan horse for social control.
Don't get me wrong, I'm more concerned about the birthrate than I was. I'll even grant that surrogacy makes me uncomfortable, though more because I dislike the idea of disempowered people (surrogates in the third world are even more gross) being exploited in yet another way.
However, in the last 24 hours, we've had two comments explicitly shaming people who want to have children, specifically because the way they're trying to have children is aesthetically displeasing to you.
Wait what? Yes I do! I'm all for tolerance, and living and letting live, but you're not going to make me see this as a lovely family moment, and anyway I don't remember signing on to turning a fundamental human experience into an industry when I supported the gay rights movement. Accept the limits of your biology, and move on.
The limits of our biology are changing by the year. Will you make your children accept the limits of their biology and watch them be crippled by polio, or something? As Doglatine put it when seeing the reflexive support amongst locals for Russia's invasion of Ukraine, your position is boiling down to a reactionary rejection of anything the left and/or mainstream like, rather than a prospective, constructive worldview. So with that in mind, I have to ask: If, tomorrow, I invented a way to boost the birthrate comfortably above replacement (or to whatever arbitrary value you want), it's eugenic, it's whatever you want it to be - but it doesn't involve traditional, cis-het men repeatedly sticking their penises inside conventionally attractive cis-het stay-at-home tradwives followed by 9 months of pregnancy discomfort and childbirth - are you going to be joyful that we solved our demographic problem and charted a course towards our brave new future of eugenic John Von Neumanns? Or are you going to be upset that we didn't do it the way you wanted and those nasty degenerates are still having buttsex and dying xir hair blue?
If your answer is the latter (and I suspect for many of the Katja Grace haters it is), then yeah, I have to say TwoX are probably right about you.
Given the utter dominance of the trans ideology, the vindication of the slippery slope argument, and the extrapolated trajectory of these ideas, I believe we have no other choice - Transhumanism must be destroyed!
Still reactionary. Have you ever laid out a positive vision for what you want the future to be, since you don't like mine? I'm curious to hear what you actually want as opposed to talking about those awful people doing things that you don't like.
More songs about buildings and food discussion of trans matters, this time courtesy of Freddie deBoer.
Care to explain the reference? Is the album name a spoof on buildings and food being a common topic in the 70s musical zeitgeist?
Having seen how the progressive agenda around education is a steaming pile of what makes the roses grow
It's not clear to me how the conservative agenda (at least in America) is much better, but we can let that potshot slide for the moment.
Well then eff me, Freddie, if it's not genetics and it's not physiology and biology not real, what is gender identity tied to?
Maybe... feelings? I feel like a woman?
To perhaps offer a steelman, there are certain cultural practices and norms tied to gender that are essentially arbitrary in the modern environment. There's no inherent reason that women should be forced to shave their legs/armpits to be considered attractive, for instance, or that men shouldn't do the same. There's no biological imperative that men shouldn't be allowed to wear dresses, or makeup, or be considered submissive or cute. Ditto for being the majority caregivers after your child is more than a few years old, and earlier if you aren't breastfeeding. We long ago left the Hobbesian jungle of burly men hunting megafauna with stone tools, and physical strength is largely irrelevant in a world of Zoom meetings, work-from-home and knowledge economies. I'd argue that many of these gender norms have fluctuated throughout history. So what if someone identifies with a set of traits or characteristics that our society would typically associate with the opposite gender, regardless of whether this is caused by genetics/early childhood experiences or environmental exposures/'feelings' (themselves a product of all of the above, even if you try to use vocabulary suggesting that they are transient or unimportant)?
This in and of itself causes problems for people arguing that we should eradicate the gender binary entirely, and I haven't seen anyone square that circle convincingly. I'm personally more particular to those worldviews where most gender norms should be abolished and trans identity is more of a kludge in response to society enforcing a binary, but I'm not representative of everyone on the left.
Frequent rebuttals to this argument are often rooted in evolutionary psychology or Chestertonian fences. Or, as you frequently argue in other posts, it's 'just a fetish' and/or sexual predators trying to sneak under the radar to rape people, none of which I find particularly convincing. You can point to trans rapists; but then again, so can I for most of your favored groups, and these niche cases don't invalidate the cause as a whole.
It does seem that society is undergoing some kind of upheaval in response to generations of Women's lib, and where the new equilibrium will fall, I can't say. Perhaps the optimum would be one where everyone could freely choose for themselves, and while most people would naturally occupy the gender roles the correspond to their birth, there wouldn't be any stigma or disgust associated with people who (for whatever reason) do not. But...that just sounds a lot to me like trans acceptance, no? There used to be a futurist transhumanism strain here that was more optimistic and trans-positive that has either been driven off or converted to conservative trad thinking, which is a shame.
Then why isn't it possible to feel like a black woman? To have that same yearning about identity and conviction that what you are "assigned at birth" is not the truth of what you really are?
It's not a bad question. My personal response would be that black women are typically viewed as less attractive, as loud, stupid, etc. externally by society, regardless of whether they personally identify with any of those traits as well as a shared cultural history/tradition that is frequently tightly intertwined with the history of racism, segregation, slavery, etc. in the west. Thus the many examples highlighted here like Rachel Dolezal and the fake native American women which are most often rooted in self-advancement or Munchhausen-like addiction to sympathy, no? A white man who likes basketball and rap is viewed by society as...just a normal man as opposed to transracial, whereas a black man doing the same is viewed significantly differently. Meanwhile, a white man who likes wearing dresses and makeup is certainly not viewed by society as just a normal man, thus the 'trans' identity and pushback against social norms.
There's also the everpresent (although perhaps less frequently explicitly expressed of late) undercurrent of a post-racial/gender GLSC future. Such a world could still have 'trans' people who are born one sex and express traits that current times would code as of the opposite sex, whereas black women would just be women with more or less pigment. Assuming we reached some kind of equality without racialized underclasses, and maintained it for at least several generations.
But I can recognize that the logic isn't perfectly airtight.
He sings along to the chorus like a good right-thinking person on the right side of history. But maybe those who don't hold the conventional progressive position aren't all dishonest or activated by unthinking bigotry and prejudice? Something to think about.
This reads like 'mainstream view bad!' boo-outgroup. Ironically (considering the second half of your statement), you act as if the only way one could hold mainstream views on LGBTQ issues is to be a self-righteous, intellectually dishonest NPC. Just as I don't believe that you are dishonest or bigoted, maybe consider that Freddie and I actually do spend some time thinking about issues and arrive at our own conclusions.
Biden seems, on a deeply personal level, to hate the US military and its treatment of its men, due to his son Beau's death-by-burn-pit-carcinogens. In fact, I rather suspect the withdrawal from Afghanistan was so insanely rapid (foolishly, of course, but still) because Biden personally said "get our fucking troops out of there LITERALLY RIGHT NOW BECAUSE YOU FUCKING PIGS KILLED MY SON." So I am heartened by his realization -- unlike so many of my country's insane leaders -- of the true cost of American military mobilization.
I've seen this come up a couple of times over my years here, and always meant to go dig up a quote I remembered from Obama's memoirs. Finally bothered to do it. For what it's worth, Obama's version of events regarding military leaders pushing for a troop surge in Afghanistan:
Among the principals, only Joe Biden voiced his misgivings. He had traveled to Kabul on my behalf during the transition, and what he saw and heard on the trip—particularly during a contentious meeting with Karzai—had convinced him that we needed to rethink our entire approach to Afghanistan. I knew Joe also still felt burned by having supported the Iraq invasion years earlier. Whatever the mix of reasons, he saw Afghanistan as a dangerous quagmire and urged me to delay a deployment, suggesting it would be easier to put troops in once we had a clear strategy as opposed to trying to pull troops out after we’d made a mess with a bad one.
Rather than deciding on the spot, I assigned Tom Donilon to convene the NSC deputies over the course of the following week to determine more precisely how additional troops would be used and whether deploying them by summer was even possible logistically. We’d revisit the issue, I said, once we had the answer. With the meeting adjourned, I headed out the door and was on my way up the stairs to the Oval when Joe caught up to me and gripped my arm. “Listen to me, boss,” he said. “Maybe I’ve been around this town for too long, but one thing I know is when these generals are trying to box in a new president.” He brought his face a few inches from mine and stage-whispered, “Don’t let them jam you.”
...
IN LATER ACCOUNTS of our Afghanistan deliberations, Gates and others would peg Biden as one of the ringleaders who poisoned relations between the White House and the Pentagon. The truth was that I considered Joe to be doing me a service by asking tough questions about the military’s plans. Having at least one contrarian in the room made us all think harder about the issues—and I noticed that everyone was a bit freer with their opinions when that contrarian wasn’t me.
...
In mid-February, Donilon reported that the deputies had scrubbed General McKiernan’s request and concluded that no more than seventeen thousand troops, along with four thousand military trainers, could be deployed in time to have a meaningful impact on the summer fighting season or Afghan election security. Although we were still a month away from completing our formal review, all the principals except Biden recommended that we deploy that number of troops immediately. I gave the order on February 17, the same day I signed the
Recovery Act, having determined that even the most conservative strategy we might come up with would need the additional manpower, and knowing that we still had ten thousand troops in reserve if circumstances required their deployment as well.
It was published mid-November 2020, so while events may have been spun one way or the other to make Biden look good, at least it wasn't done to boost him in the election.
Virtually nobody is satisfied with the moderation here, but for a plethora of different reasons. Which probably means it's as close to optimal as we can get.
For what it's worth, I have a lot of respect for all the new people who decided to be mods.
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