Some amazing things are going on, not all of which involve mRNA, although please please those of you with the ability to do so, do your part to ensure that stays funded, either via investment or grants.
Cremieux: It’s hard to oversell how big a discovery this is.
Heart disease is America’s #1 cause of death. With a combination of two drugs administered once every six months, it might be mostly defeated.
Just think about that how big this is! You will know your great-grandkids!
It is insanely optimistic that we have drugs that can reduce Lp(a) levels by [65%-]98% in trials right now.
If they succeed, they could help to crush heart disease and stroke.
Unlike LDL in general, Lp(a) levels are basically entirely genetic in origin and not open to lifestyle intervention. It is also widely accepted that the race differences are down to genes.
These drugs are examples of genetic discovery leading to a group difference fix via tech.
I wouldn’t go that far. Even if these trials are successful, it seems unlikely we’re talking about ‘mostly defeat,’ although we could plausibly be at ‘greatly reduce.’ Which could still be worth several years of life expectancy across the board. If we could also similarly help with other major causes of death and aging, you’d see compounding gains, but without that aging still catches up with everyone.
Unfortunately, America under the current administration is making deep cuts in basic research funding that leads to advances like this. Hopefully AI can make up for that.
A new major study finds that alcohol causes cancer, so government worked to bury the study. Time and time again we get presented with the fact that small amounts of drinking correlate with improved health in various ways, fooling many into thinking a little alcohol is healthy.
As opposed to the reality, which is that alcohol is bad for you no matter what, but that inability to drink is highly correlated with alcoholism and other traits that go along with poor health, whereas ability to drink only in moderation is a good sign.
So drinking in moderation, which is only a small amount bad for your health, is still a good sign for your health if you are drinking in moderation. Whereas heavier drinking consistently looks bad, perhaps even worse than it is.
Trump himself is not fooled, and does not drink at all, as he has seen the dangers of alcoholism in his own family. A wise choice.
Dylan Scott: They broke out their findings by different drinking levels — from one drink per day to three — and focused on health outcomes that have been proven to be associated with alcohol use. Their big-picture conclusion:
Among the US population, the negative health effects of drinking alcohol start at low levels of consumption and begin to increase sharply the more a person drinks. A man drinking one drink per day has roughly a one in 1,000 chance of dying from any alcohol-related cause, whether an alcohol-associated cancer or liver disease or a drunk driving accident. Increase that to two drinks per day, and the odds increase to one in 25.
…
In that context, the report is a harrowing read: Alcohol use is associated with increased mortality for seven types of cancer — colorectal, breast cancer in women, liver, oral, pharynx, larynx, and esophagus. Risk for these cancers increases with any alcohol use and continues to grow with higher levels of use, the study’s authors concluded.
Women experience a higher risk of an alcohol-attributable cancer per drink consumed than men. Men and women who die from an alcohol-attributable cause die 15 years earlier on average.
A 4% chance of dying on average 15 years earlier is a big deal.
This is not the first time a Trump administration defied the data on this.
US officials always solicit expert opinion as they prepare a fresh set of dietary guidelines. The input is usually compiled into one massive report from a group of experts called the US Dietary Guidelines Advisory Committee and then submitted to the Department of Health and Human Services and the Department of Agriculture, the two agencies that produce the guidelines.
That was how the process went in 2020, and at that time, the subcommittee of researchers dedicated to alcohol (including Naimi) advised the government to reduce the recommended limit down to one drink per day for men, from two. The Trump administration ultimately decided not to follow the recommendation.
A call to make statins be sold over the counter (OTC). This seems obviously correct, even if you are highly skeptical that the correlations cited here imply causation, or that they imply that intervening via statin cause this causation without important side effects. That’s a decision people can make for themselves at this point. But then a whole host of things should be OTC at this point that aren’t.
Alex Young: I’ve been working with an IVF startup, @herasight, that has already screened hundreds of embryos. Today we come out of stealth with a paper showing that our predictors for 17 diseases — validated within-family — beat the competition, with improved performance in non-Europeans.
In our paper, we detail our polygenic scores (PGS) for 17 diseases using a custom meta-analysis. We used state-of-the-art methods to create PGSs based on 7.3M SNPs. Our most predictive PGSs explained ~20% of the variance in liability for prostate cancer and type-II diabetes.
In practice what happens is you get your 5, 10 or 20 embryos, they profile each one, and you are choosing based on a variety of traits. What do you actually care about most? You are about to find out.
Kitten: Within a few years they’re going to be able to show you a very accurate picture of what each baby will look like as an adult.
That will trump every other consideration by a large margin.
I agree that this technology is coming. I agree it will matter to people. And why shouldn’t it matter, at least from a selfish point of view? It also might be a better way to select for other good things than you might think, as in general health and other positive traits are correlated with beauty. I do not think it will be anything like ‘this overrides everything else.’
Even the graceful failure mode for things like this is a really big deal.
Mason: I think this just ignores the realities of IVF tbh
20 healthy embryos is, for most people, 3-5 IVF cycles
Success for a single embryo transfer is 40-60%.
“Well, your dad and I wanted a boy and you were the second highest IQ male after Embryo 6 failed to implant.”
Yeah, these numbers are for mothers <35. It's crazy how many people think IVF is a safety net for aging out of your fertility window when you actually need to start the process quite young in order for it to be likely to work.
I mean that sounds pretty great? You got your choice of gender and a couple of IQ points, while presumably also dodging a variety of potential genetic disorders. That’s a pretty good haul.
What you actually get is not maximizing on one to two traits, although you do have that option. What you get is to do a general maximization over many traits. That is a lot more valuable if you are making reasonable decisions.
Mason is however making the very important point that if you want to use IVF and have confidence it will work at all, let alone confidence it will give you selection, you need to do it early. The younger you are, the better all of this will on average go, until such time as we figure out how to generate new eggs (which is plausibly only a few years away).
Gene Smith: We’re in this insane world right now where rich parents are going through IVF just to do embryo selection, and middle class parents who are ALREADY doing IVF are being told by doctors that embryo selection doesn’t work or is unethical.
If you’ve been to conferences on embryo selection or ones where the topic is discussed, you will realize the truth is basically the opposite. Most academic discussion of this is dominated by ethicists talking about how problematic it is or academics talking about its limitations.
And make no mistake, these discussions matter. They’re the main reason why even doctors who understand embryo selection rarely recommend it to their patients, even when it could significantly reduce the odds of a patient passing along a disease to their child.
Among the academics that care about this, a large majority are opposed to embryo selection for ideological reasons. There hasn’t been all that much quantitative analysis done on it. And what has been done often fails to capture how embryo selection is actually done in industry.
A lot of work has focused on selection on a single trait, which is easier to model, but not how selection actually works in practice. And many of the conclusions about its efficacy rely on outdated predictors which have improved substantially since publication.
He also reminds us that we are spending all our gene editing resources on rare diseases where we can stick the government gigantic bills and the ‘ethicists’ stop trying to ban you from helping, whereas the places where most of the value lies are complete ignored, even by people who would directly benefit.
Gene Smith: The situation in the gene editing field right now is kind of unbelievable. We’ve spent over a decade throwing billions of dollars at the gene editing for rare diseases and we still can’t get the editors inside most of the cell types we need to modify.
Everything is either for the liver or the eye or the bone marrow. We can’t get to the brain. We can’t get to the lungs. We can’t get to the heart. And we can barely fit a single editor into the best delivery vector so no one is even thinking about polygenic disease.
There is an extremely simple way to fix this: edit in embryos. All the stuff we can’t target right now because of delivery issues becomes almost trivial in embryos. You can literally stick a needle into the egg and squirt the editors in.
Alzheimer’s? Tractable. Diabetes? You can pretty much get rid of it. Heart disease? You can mostly make it a thing of the past. Breast cancer? Same deal.
…
The blame for this delay lies at the feet of academics. There are literally professors who go to conferences on gene editing and brag about how they’ve gotten governments to ban embryo gene editing.
[thread continues]
Bex: surely this is being done black budget and for the uber wealthy already. but I guess all that learning is hidden:(
Gene Smith: As someone working on the cutting edge of this field, I can tell you it’s definitely NOT. You underestimate how maddeningly myopic wealthy people can be about new tech. Fred Koch literally didn’t ask the cancer research center he funded to look into ways to treat his cancer.
The most cutting edge thing wealthy people are actually doing right now is embryo selection a la Herasight and Orchid.
I mean, it’s not that simple, of course it is not that simple, but it is a little bit that simple?
If you have the option to use the technology we do have, it seems crazy not to use it. Noor Siddiqui is being too righteous and superior about it even for me here, but if it really does cost as little as $2,500 to get selection over potential embryos, that is a better deal than essentially any remotely optional interventions you have access to after birth. The replies to such proposals are full of people saying how horrible all this is and having instinctual disgust and purity reactions, and calling everyone involved and the proposal itself various names, all of it patently absurd without any actual justifications.
I do strongly agree with Vitalik Buterin that while we should be very much in favor of embryo selection and most of the attacks on it are deranged, it is counterproductive and wrong to strike back by saying that since it condemns your children to be worse off that not using selection is unethical.
Vitalik Buterin: If you publicly telegraph that if you win your fight for acceptance you will immediately follow it up with a fight for imposition, do not be surprised if people decide to oppose your fight for acceptance from day one with a vigor only reserved for resisting imposition.
We’ve been over this one many times. If that which is not forbidden is compulsory, then that which I do not want to be compulsory must be forbidden.
Eliezer does a survey, finds ~80% of those who tried GLP-1 drugs report it helped lots versus those that didn’t, roughly confirming industry claims. That’s a fantastic success rate.
These marginal improvements make a huge practical difference. GLP-1s are now a lot like AI, in that we keep getting better versions and people’s impressions don’t update.
Scott Alexander: Update on Ozempocalypse: some pharmacies have stopped selling compounded GLP-1 drugs, others continue, with various flimsy legal excuses. Cremieux has a guide (partly subscriber-only) on how to order and use cheap “research chemical” GLP-1 from from peptide companies. And the Trump administration cancelled a Biden initiative to make GLP-1 drugs available via insurance.
There were official shortages of GLP-1 drugs, which allowed compounders to make and sell those drugs cheaply, on the order of $300/month, in essentially unlimited quantities. Alas, there is now no longer an official shortage, so the price is shooting back up again (~$1k/month) and supply is harder to find. We really should find a way to buy out those patents and make these drugs available for low prices (ideally for free, with at most a minimal consultation) for whoever wants them.
Egan Peltan: Today, Lilly revealed the weight loss & composition at 48 weeks
Sema: -13.5% (72% Fat)
Bima: -8.6% (100% Fat)
Bima + Sema: -16.4% (>90% Fat)
Patients on bima+sema saw >40% decrease in body fat with no changein lean mass at 24W. Overall, bima and bima+sema were well tolerated No striking SAE imbalances.
Eric Topol: The GLP-1 microdosing wellness and longevity craze without any data for dose or evidence of effect.
As usual this as worded confuses lack of formalized data and evidence for a lack of data and evidence. These are not the same thing. It is an entirely sensible strategy to experiment with different doses and to choose, with a drug that has big benefits, but also downsides, and is clearly safe. Self-experimentation can provide highly useful data and evidence, and clearly different people respond differently in terms of benefits and side effects at different doses.
Babb (from the WSJ article): What feels healthiest is taking the lowest amount that’s providing what I’m perceiving to be these health benefits.
The marketing involving microdosing does sound not great, especially its claims of other vague and hard to measure benefits.
There are still some potential safety issues where it would be good to have more confidence, I agree that we are not treating checking for such possibilities as seriously as we should given how many people are on these drugs. But also given how many people are on these drugs (about 6% of Americans right now), and how much many people are inherently suspicious that there is a catch, and how long people have been taking them for (including previously for diabetes) I am confident that if there was a showstopper problem it would have been found by now.
Andrew Rettek: Ozempic type drugs have been on the market for over seven years. It’s been about five years since 1 million Americans have been taking them. We have a pretty good idea of their side effects at this point. It’s longer than you thought, because people have been taking them for diabetes for years before they became popular for weight loss.
People instinctively think there must be a catch to GLP-1s. But for people in most circumstances there mostly isn’t one, at least not one of magnitude similar to the benefits, other than that for some people it doesn’t work?
GSV Bemusement Park: Look if you are trying to lose weight there is no reason to not be padding your efforts with a GLP-1 drug unless everyone in your family gets thyroid cancer.
If you buy smartly the cost is literally negative after accounting for the food you don’t eat, and you can always go back on if you regain weight.
If you follow me then your mutuals almost certainly include several helpful, literate people who will be thrilled to advise you.
You have nothing to lose but waistline.
Peter Hague: Ozempic skepticism seems entirely based on the animist-like idea that there is a conservation law for good fortune – all good things must have some equal cost imposed elsewhere. It’s not scientific skepticism, it’s superstition.
I’m really concerned too how “big pharma is trying to kill you/sterilise you with fake medicine” has gone from the fringes of Facebook mummy groups to the mainstream. It used to be the main complaint was they were greedy and withholding good medicine from sick people.
Dystopina GF: Anti-Ozempic people don’t understand that the average person isn’t supposed to be an iron-willed Übermensch. Average people simply reflect the quality of their society; they’re obese bc modernity is sick, not bc of some moral failing. Being thin should be effortless, the default!
A well-designed society is a system that makes good things as frictionless as possible. A poorly-designed society is one where it takes a Herculean effort to achieve the most basic elements of human health and fulfillment
John Pressman: The replies on this inspire serious misanthropy. The QT is straightforwardly correct and the replies make it obvious that all good things come from brutally, ruthlessly destroying the perverse costly signaling equilibria people naturally cover up utility with.
Of course, here I am saying that and then not taking them, but I am a bizarro case where I was able to get to my target through sheer willpower, and I have decades of experience dealing with essentially permanent hunger. That almost never works.
Andrew Rettek reports from a week discussing diet, exercise and GLP-1s at LessOnline and Manifest. Lots of people wanted to exercise, but felt they needed ‘demystifying’ of the gym and the general procedures involved. I very much feel this. Our on ramps suck, and mostly amount to ‘find a source and trust it.’ Which is way better than not exercising but doesn’t fill one with confidence or motivation – I’m spending a substantial portion of my time and willpower and energy on this, and different implementations differ a lot. Whereas for diet, Andrew observed people mostly weren’t interested, my guess is because they’ve already heard so many contradictory things.
GLP-1s served as a large scale experiment in drug compounding, and in sidestepping the FDA’s various usual regulatory requirements. The results were amazingly great, everything went smoothly. This is even more evidence for FDA Delenda Est, while noting that ‘fire a bunch of people at the FDA’ makes things worse rather than better. Removing requirements is good, but if there are going to be requirements it is necessary to be able to handle the paperwork and meetings promptly.
Going forward, the bigger question is: What happens if this actually works?
Cremieux: Eli Lilly just showed that you can lose tons of fat while barely losing any muscle using their activin type-II receptor inhibitor, bimagrumab.
We are approaching a golden era of weight loss, where everyone can easily be muscular and skinny.
Prepare for hordes of hot Americans.
Devon Eriksen: And I am predicting, here and now, that there will be a massive social pushback from people who would rather see their fellow Americans live out their lives sick, fat, and miserable than give up their just-universe fallacy.
At what point do we start to think of weight loss as fully treatable?
Shako: Increasingly in public I see obese people as glp1 deficient. I mean this seriously. There is a 200 pound 15 year old girl at this playground. It’s heartbreaking and we can treat it now.
Lots of people commenting diet and exercise work better. And yet vast amounts of Americans, often stupid and poor, die every year from preventable metabolic diseases. Do you think they just don’t know about diets?
Eliezer Yudkowsky: Tirzepatide doesn’t work on 20% of people, including me.
Shako: 🙏🏻 hope something does soon.
Not every case can be treated, since we have a non-response problem, and some people will run into side effects or risk factors. But a large majority of people with a problem still haven’t attempted treatment. Most of them should try. If you were already going to lose the weight on your own, you could do it easier with help?
What about the equilibrium, signaling and status arguments? That if we allow people to lose weight without willpower or personal virtue then that will make the signals harder to read and be Just Awful? Yeah, I don’t care.
If you lose weight without resistance training you’ll lose some muscle mass.
If you gain weight without resistance training you won’t gain muscle mass.
Thus, if you do both, yes, you end up worse off.
But that’s a choice, and it’s fixable by attacking ‘without resistance training.’
There are also other exercise methods. The point is clear.
Weight loss helps resolve back problems and otherwise make things hurt less. Few appreciate how big a deal this is. This was a big game changer for me on its own.
Man Down Ted: I may have a bit less hair, but I have FAR fewer body aches and pains than I did 10 years ago.
A lot of that is due to lowering the weight my body has to carry, but at least some of it is due to the fact that I will just make myself do 10 mins of yoga to loosen up, any time.
Meanwhile, half my male friends near my age have thrown their back out this year. Possibly more than half wake up stiff and sore from sleep every day.
Dropping the weight is good for dating,, but it’s GREAT for your long-term health and self image. And not THAT hard.
That is, no one knows much about how to do it right.
We do know many ways in which one can do it wrong.
If there were two concrete specific things I would have said I was confident about, one of them would have been ‘vegetables mostly good’ and the other would be ‘sugar bad.’ I don’t think it’s bad enough to stop me all that much on either front, but I do buy that sugar is bad on the margin.
And yet when Americans cut sugar consumption (modestly by ~10%, note the y-axis) the obesity rate still mostly kept moving up.
He blames this mess on selection. Once sugar got blamed, choosing to consume more sugar became correlated with other health decisions, some of which matter. The associations between sugar and health only show up, he claims, after 2012. And he says this generalizes – certain people eat certain diets. He finishes with a survey of some of the other problems.
I am inclined to be kinder, and see the epistemic problems here as actually super hard. Nutrition is remarkably different for different people, doing proper studies on humans is extremely hard, there are distinct effects for short, medium and long terms, a lot of this is about how you psychologically respond, lots of details matter and are hard to measure and can be changed without you realizing, and so on.
As far as anyone can tell Aspartame, a zero calorie sweetener, seems benign. I agree that this is great news so long as no one forces anyone to use it. I think the people this most annoys are people who believe that it is not as good an experience as sugar, and don’t want their sugar taken away, either legally or by those ‘worried about their health.’ Also, since no one knows anything about nutrition, I wouldn’t assume that there isn’t a catch.
From what I’ve seen, they go wrong enough often enough that starting to mess with them probably doesn’t make sense if you aren’t already messing with them.
Christoffer Bausted Nilsen: “When the facts change, I change my mind. What do you do, sir?” (source)
The graphs show dramatically accelerated PAV (Percent Atheroma Volume) and NCPV (Non-Calcified Plaque Volume) in those on Keto diets.
As always, beware conclusions from intermediate endpoints, and also different people often have very different reactions and averages can be misleading. But I agree this does not look good.
Cremieux: I’m a little annoyed that I spent so many years thinking keto was obviously good.
Now that we have a lot of data, it turns out that the people who said “fat—especially saturated fat—clogs your arteries” were just totally correct.
I should not have believed the contrarians.
I don’t think we have enough evidence here to draw that conclusion either?
Here’s a counterargument from someone thoughtful and sympathetic to Keto:
William Eden (not endorsed): As someone who has recommended paleo/keto diets in the past, let me lay out my current thinking:
ApoB is directly related to atherosclerosis progression (experts are right)
*Somepeople who go on keto skyrocket ApoB, and yes I think keto is bad for those people. This is where ultimately empirical results overcame the same things he derides in this discussion (“mechanistic” reasoning to support the answer you’re hoping to see).
Human PCSK9 mutants with no CVD changed my mind – and are the basis for a class of very strong therapeutics! However… I still think mechanisms are real. Some are better established, others speculative. Good theories predict the (very complicated) data My favorite thinker on the subject is Peter over at Hyperlipid, though he’s almost impossible to understand.
Just because high sat fat keto increases heart disease doesn’t mean the answer is to eat huge amounts of polyunsaturated fats either. Yes, I am a seed oil disrespecter. Mechanistically I think it causes the liver to hang onto fat instead of circulating it, but we can do better.
This video from Peter Attia is just 10 minutes and lays out the good drug options available today, including ones with better risk/reward than statins (though a *low dosestatin I think is fine with CoQ10 supplementation).
(Btw I think it’s absolutely clear that LDL must play some role in the body or it wouldn’t exist. I don’t 100% know all of its functions, but when you look across countries, low LDL is seen in developing countries with lots of infectious disease and other cardiovascular issues)
In terms of my diet advice, I do think a higher-fat diet that dips occasionally in and out of ketosis is likely optimal for long term performance and health. If you get high ApoB, swap out sat fat for monounsaturated fat, and consider drugs. Keto for >>1 month I have concerns.
In terms of my epidemic advice, I do think contrarians should try harder to grapple with mainstream evidence instead of dismissing it. *Especiallythe really strong evidence, and being able to see it as such. That’s why short term diet studies didn’t get me, but PCSK9 did. Fin.
He gives us the standard ‘correlation is not causation’ warnings that are at their peak in nutrition and a reminder that no one knows anything beyond that you need a basic set of nutrients and that different people are different.
The key thing about Keto, as its fans envision it, is it is the ultimate case of never do anything by halves. The idea of Keto is that you force your body into ketosis. That means consistent hardcore restricting of carbs. Most people can’t do it.
So almost any observational study is going to include a bunch of people who don’t actually do the thing and stay in ketosis, and being kind-of-keto doesn’t work.
Remember, when evaluating diets, that people basically neve stick to one for very long. The majority of people who say they’re ‘vegetarian’ will then admit they’ve eaten meat in the past week.
Keto is not optimized for longevity. You do it to feel and look better now, not to live for longer. Even if it has longevity costs, it might still be worth it. If you do want primarily longevity he suggests caloric restriction and pescetarianism, which is kind of the opposite of keto.
Keto is the only diet that worked for him in terms of current health, but of course different things work for different people.
I find these defenses:
Reasonable arguments.
Clear indications that very few people should be trying to be on a keto diet.
For keto to make sense, even if you mostly buy the counterarguments, given the risks involved (over a range of possible worlds):
You need to have extraordinary willpower and discipline, keeping in mind that most people who think they have it, don’t have it.
You need to be willing to spend that, and give up carbs, and endure all the hedonic and social costs involved, to stick to keto for real.
You need to prioritize short term health over longevity.
You need to have a body where keto happens to be relatively beneficial for you.
You keep avery close eye on various markers and your experience as you try it, and abort on the spot if an issue emerges, either in terms of your health or experience, or simply exposing that the willpower price is too damn high.
And that’s if you buy the counterarguments.
In practice, even if you think this is right for you to try, I’m willing to go ahead and say that on average you are wrong about that.
Not everyone can do this. Not everyone should attempt this. And most people in the position to need to do it should probably take GLP-1s.
It was still very nice to see a clear example of someone pulling off the pure willpower route who wasn’t me. And it sounds like she didn’t even use GLP-1s.
exfatloss: If you can maintain a healthy body weight by restricting your total food intake, but never give in to eat ad libitum because you know you’d gain fat, your satiety & appetite are broken. Until very recently, nobody needed to count calories to remain thin.
I’m not saying that staying thin did not get harder on many fronts, and it is entirely possible that there are other things making things harder on top of that, but the idea that in the past eating as much as you wanted of what you wanted wouldn’t have made you fat is Obvious Nonsense. Rich people from the past who could eat as much as they wanted, and didn’t care, totally got fat. Sure, people mostly stayed thin, but largely out of lack of opportunity.
Needing to control yourself to stay thin does not mean that your satiety is broken. You’re asking way too much of satiety. You’re asking it to give you the right highly calibrated signal in a radically different world than the one it was trained for.
This doesn’t require toxins or any particular villain beyond widespread variety and caloric availability, including many calorically dense foods, and greatly increased food variety and quality, and various cultural expectations of eating frequently. It is enough, and regardless of the original cause life is not fair.
Cremieux: Attempts to explain the obesity epidemic through contamination, toxins, conspiracies, seed oils, sugar, high-fructose corn syrup, lithium, or whatever else always strike me as annoying.
What we must explain is an increase of ~200-350 calories a day in energy balance. That’s all.
My answer is simple, and similar to Cremieux’s in the thread, that there was never really any robust natural ‘balance.’
For full disclosure, I say this as someone whose satiety has always been utterly broken to the point of uselessness. If left to my own devices I would put on insane amounts of weight very quickly. I might double my caloric intake. That’s what actually broken looks like. But don’t ask an evolutionary mechanism to give the right answer in a radically changed world, and don’t call it ‘broken’ when you have to adapt.
Yes, until recently that meant you had to work for it. That’s one option. The other? Good news, now we have Ozempic and other GLP-1s.
Key Smash Bandit: I started taking a million supplements and I do feel meaningfully better but the new problem is I have no idea which one did it, and taking all of them is expensive and annoying
Ryan Moulton: This is a fun task to try to design an experiment to resolve.
I would randomize to taking 50% each day, (ideally blinded, but whatever) and then record how I felt each day. Then after you have ~a month of data, fit a regression model from what you took to how you felt, probably also with at least terms for 1 day lag. Lean on L1 in lasso a lot, because you’re probably looking for a single thing rather than a large set.
Unfortunately there are what the economists call ‘long and variable lags’ in vitamin impact, both positive and negative. Even if it originally helped or hurt in a day, it might take a while for a supplement to wear off. Others only work via accumulation over time, or work on things other than observable mood.
Experimental design here is very hard. I would not want to maximize purely on the basis of how I feel within 24 hours.
Also, for various reasons, you cannot by default confidently equate any given pill with other pills from another source that claim to deliver the same dose of the same vitamin.
If I was going to run such tests, as much I would like to randomize every day, I would at minimum want to wait three or so days between swaps, and I would limit the multiple hypothesis testing. The data is going to be super noisy at best.
Josh Whiton: Halfway through university I was diagnosed with clinical depression. After a battery of tests and interviews with psychologists I eventually met with the psychiatrist who was to dispense my medication.
Instead he asked me a question that no one had ever asked.
“Why are you depressed?”
So I told him about the meaninglessness of life in an accidental universe where all life was just the product of chance.
“You want me to put you on medication because you’re an intellectual?” he said.
Then he said the wildest thing: “My concern is that your depression is part of a process and the drugs will slow it down.”
He told me to go home and observe all the thoughts in my mind instead of trying to escape from them. If in three days I still wanted the drugs, to come back and he’d give them to me.
So I went home and spent three days journaling, had three epiphanies about the nature of reality, and the year-long depression immediately lifted.
I wonder about all the kids like me who got the drugs instead.
Zac Hill: One of the things I was most brazenly wrong about was just basically making fun of people who thought that Canada’s euthanasia program would achieve scale.
As in, MAID now is already 5% of all deaths in Canada and is about to be available for mental conditions and parliament wants to grant access to minors, and I see a bunch of claims about it being aggressively pushed onto people in various ways. One wonders where this stops, once it starts. If it stops.
Former Quebec officials suggest that best “solution” for intellectually disabled woman without adequate support might be death. Which might be true, but wowie. This highlights where things might be going. Do you trust the state to not push such solutions on people who are financial burdens? To not cut off aid to them as part of an attempt to force such choices upon them? I notice my answer is very much no.
Joao Pedro de Magalhães: “It is highly unethical to stop aging” – reviewer commenting on one of my grant applications.
The grant focused on cellular rejuvenation, no mention to curing aging, but it shows we still have a long way to go to convince even fellow scientists that curing aging is desirable.
As in, you are trying to solve people’s health problems, but this might also cure aging, And That’s Terrible.
Here’s a bioethicist giving a Ted talk advocating that humans be ‘engineered’ to be, no not more intelligent or healthy or happy but (checks notes) intolerant to meat, at the same time that other ‘ethicists’ are screaming about how awful it is we might do embryo selection on positive traits.
And 41% stand ready here to outright deny physical reality.
How exactly would we design society such that it is not a disadvantage to be blind?
If I was blind and I heard people were claiming this, I’d be pretty pissed off at them.
Do you think, by answering that way, you are helping anyone?
Learning about your HIV status, when treatment is not available, dramatically reduces long term survival rates. Some of this is people adjusting rationally to the news, and engaging in generally riskier (to themselves) behaviors and having higher discount rates. Some of it is despair or overreaction. However it isn’t really an option not to tell them or not run the tests, for obvious reasons.
Here in New York they take every opportunity to push you to get tested for HIV, even when there is no reason to do that, as I found out on a recent hospital visit (it was an infection, I am 100% fine now, don’t worry).
Clash Report: Hot-mic moment at the Beijing parade.
Xi: “People rarely lived past 70 before. Now at 70 you’re still a child.”
Putin: “With biotech, organs can be replaced endlessly… people could even reach immortality.”
Xi: “Some predict people might live to 150 this century.”
I do see hope that some people might live to 150 this century, or even that some people alive today might live far longer than that. It will not happen because ‘organs can be replaced endlessly’ because that does not reverse aging, so the rate of new problems will keep doubling roughly every seven years, but we have other options.
Also, yeah, thinking ‘at 70 you’re still a child’ is both obviously false and reflective of the geriatric ruling class that is doing so much damage. Until your anti-aging technology gets a lot better no one 70+ should be in high office.
In response to RFK’s War on Vaccinations and as Florida repeals all vaccine requirements, there are now two state coalitions trying to defend our health. California, Oregon, Washington and Hawaii are going to form one set of recommendations. New York, Massachusetts, Connecticut, Delaware, Pennsylvania and Rhode Island will form another, likely with New Jersey, Vermont and Maine.
Freezing sperm young, if you can spare a little cash to do it, is a pretty great deal. Even if everything keeps working fine you cut down on mutation load a lot, and if something does go wrong you’re going to be very happy about it. It’s a lot of optionality and insurance at a remarkably cheap price, even if you factor in the chance that in the long term we’ll have other tech that renders it unnecessary.
Scott Adams has prostate cancer, we wish him well, thread has illustrations of exactly how unhinged a certain type of thinking got and how wide a set of medical topics. Luckily he himself has realized the mistake and although the odds are against him he now appears to be setting aside the quacks and getting real treatment.
A potentially serious incentive problem: If CRISPR treatments can permanently cure conditions, insurance companies have no reason to value a permanent solution more than a temporary one, so the whole system will underinvest in such treatments. Ultimately it should be fine, since at most this is a limited cost factor and thus not enough distortion to stop this from happening, and AI should improve development costs enough to compensate.
China, on the other hand, frequently abandons upper stages in orbit. China launched 21 of the 26 hazardous new rocket bodies over the last 21 months, each averaging more than 4 metric tons (8,800 pounds). Two more came from US launchers, one from Russia, one from India, and one from Iran.
This trend is likely to continue as China steps up deployment of two megaconstellations—Guowang and Thousand Sails—with thousands of communications satellites in low-Earth orbit. Launches of these constellations began last year. The Guowang and Thousand Sails satellites are relatively small and likely capable of maneuvering out of the way of space debris, although China has not disclosed their exact capabilities.
However, most of the rockets used for Guowang and Thousand Sails launches have left their upper stages in orbit. McKnight said nine upper stages China has abandoned after launching Guowang and Thousand Sails satellites will stay in orbit for more than 25 years, violating the international guidelines.
It will take hundreds of rockets to fully populate China’s two major megaconstellations. The prospect of so much new space debris is worrisome, McKnight said.
“In the next few years, if they continue the same trend, they’re going to leave well over 100 rocket bodies over the 25-year rule if they continue to deploy these constellations,” he said. “So, the trend is not good.”
There are technical and practical reasons not to deorbit an upper stage at the end of its mission. Some older models of Chinese rockets simply don’t have the capability to reignite their engines in space, leaving them adrift after deploying their payloads. Even if a rocket flies with a restartable upper stage engine, a launch provider must reserve enough fuel for a deorbit burn. This eats into the rocket’s payload capacity, meaning it must carry fewer satellites.
“We know the Chinese have the capability to not leave rocket bodies,” McKnight said. One example is the Long March 5 rocket, which launched three times with batches of Guowang satellites. On those missions, the Long March 5 flew with an upper stage called the YZ-2, a high-endurance maneuvering vehicle that deorbits itself at the end of its mission. The story isn’t so good for launches using other types of rockets.
“With the other ones, they always leave a rocket body,” McKnight said. “So, they have the capability to do sustainable practices, but on average, they do not.”
A Japanese H-IIA upper stage imaged by Astroscale’s ADRAS-J spacecraft last year. Credit: Astroscale
Since 2000, China has accumulated more dead rocket mass in long-lived orbits than the rest of the world combined, according to McKnight. “But now we’re at a point where it’s actually kind of accelerating in the last two years as these constellations are getting deployed.”
As generative AI has taken off since ChatGPT’s debut, inspiring hundreds of billions of dollars in investments and infrastructure developments, the top question on many people’s minds has been: Is generative AI a bubble, and if so, when will it pop?
To help us potentially answer that question, I’ll be hosting a live conversation with prominent AI critic Ed Zitron on October 7 at 3: 30 pm ET as part of the Ars Live series. As Ars Technica’s senior AI reporter, I’ve been tracking both the explosive growth of this industry and the mounting skepticism about its sustainability.
Zitron is the host of the Better Offline podcast and CEO of EZPR, a media relations company. He writes the newsletter Where’s Your Ed At, where he frequently dissects OpenAI’s finances and questions the actual utility of current AI products. His recent posts have examined whether companies are losing money on AI investments, the economics of GPU rentals, OpenAI’s trillion-dollar funding needs, and what he calls “The Subprime AI Crisis.”
Credit: Ars Technica
During our conversation, we’ll dig into whether the current AI investment frenzy matches the actual business value being created, what happens when companies realize their AI spending isn’t generating returns, and whether we’re seeing signs of a peak in the current AI hype cycle. We’ll also discuss what it’s like to be a prominent and sometimes controversial AI critic amid the drumbeat of AI mania in the tech industry.
While Ed and I don’t see eye to eye on everything, his sharp criticism of the AI industry’s excesses should make for an engaging discussion about one of tech’s most consequential questions right now.
Please join us for what should be a lively conversation about the sustainability of the current AI boom.
Acting on a demand from the Trump administration, Apple has removed apps that let iPhone users report the locations of Immigration and Customs Enforcement (ICE) officers.
“We reached out to Apple today demanding they remove the ICEBlock app from their App Store—and Apple did so,” Attorney General Pam Bondi said in a statement to Fox News yesterday. “ICEBlock is designed to put ICE agents at risk just for doing their jobs, and violence against law enforcement is an intolerable red line that cannot be crossed.”
Apple confirmed it removed multiple apps after hearing from law enforcement. “We created the App Store to be a safe and trusted place to discover apps,” an Apple statement to news organizations said. “Based on information we’ve received from law enforcement about the safety risks associated with ICEBlock, we have removed it and similar apps from the App Store.”
The app removals follow a September 24 shooting at a Dallas ICE facility that resulted in the deaths of two immigrants in federal custody and the shooter. The shooter, identified as Joshua Jahn, “searched apps that tracked the presence of ICE agents,” according to FBI Director Kash Patel.
ICEBlock creator Joshua Aaron disputed claims that his app could have contributed to the shooting. He pointed out that an app isn’t needed to find the locations of ICE facilities.
“You don’t need to use an app to tell you where an ICE agent is when you’re aiming at an ICE detention facility,” Aaron told the BBC. “Everybody knows that’s where ICE agents are.”
Apple cited “objectionable content”
Aaron said he was disappointed by Apple’s decision to remove the app. “ICEBlock is no different from crowd-sourcing speed traps, which every notable mapping application including Apple’s own Maps app [does],” he was quoted as saying. “This is protected speech under the First Amendment of the United States Constitution.”
And that makes perfect sense, because when you reduce hunters’ choices to simple math using what’s called the prey choice model (more on that below), these long-lost species offered bigger returns for the effort of hunting. In other words, giant sloths are extinct because they were delicious and made of meat.
Yup, it’s humanity’s fault—again
As the last Ice Age drew to a close, the large animals that had once dominated the world’s chilly Pleistocene landscapes started to vanish. Mammoths, saber-toothed tigers, and giant armadillos died out altogether. Other species went locally extinct; rhinoceroses no longer stomped around southern Europe, and horses disappeared from the Americas until European colonists brought new species with them thousands of years later.
Scientists have been arguing about how much of that was humanity’s fault for quite a while.
Most of the blame goes to the world’s changing climate; habitats shifted as the world mostly got warmer and wetter. But, at least in some places, humans may have sped the process along, either by hunting the last of the Pleistocene megafauna to extinction or just by shaking up the rest of the ecosystem so much that it was all too ready to collapse, taking the biggest species down with it.
It looks, at first glance, like South America’s late Ice Age hunters are safely not guilty. For one thing, the megafauna didn’t start dying out until thousands of years after humans first set foot in the region. Archaeologists also haven’t found many sites that contain both traces of human activity and the bones of extinct horses, giant armadillos, or other megafauna. And at those few sites, megafauna bones made up only a small percentage of the contents of ancient scrap piles. Not enough evidence places us at the crime scene, in other words—or so it seems.
On the other hand, the Ice Age megafauna began dying out in South America around 13,000 years ago, roughly the same time that a type of projectile point called the fishtail appeared. That may not be a coincidence, argued one study. And late last year, another study showed that farther north, in what’s now the United States, Clovis people’s diets contained mammoth amounts of… well, mammoth.
The FCC votes were criticized by advocacy groups. “Students who rely on long bus rides to complete assignments and library patrons who depend on hotspots for work, education, or telehealth will suddenly lose access to essential tools. This decision is a step backward,” said Joseph Wender, executive director of the Schools, Health & Libraries Broadband Coalition.
“Chairman Carr’s cruel move to delete our kids’ Internet connections won’t make America smarter,” said Revati Prasad, executive director of the Benton Institute for Broadband & Society. The FCC “openly voted to snatch back the opportunity to offer more Americans, especially in rural areas, the high-speed Internet access to do the business of life online—pay bills, make telehealth appointments, fill out school applications—after the library closes,” American Library Association President Sam Helmick said.
The advocacy groups said that in New Mexico, “Farmington Municipal Schools equipped its 90 buses with Wi-Fi, serving over 6,500 students daily. Parents reported that children returned home with homework already completed.” In Ohio, “the Brown County Public Library’s hotspot program allowed homeschool families to join virtual classes, entrepreneurs to run mobile businesses, and veterans to participate in telehealth appointments and certification testing.”
Helmick said the library association is also “discouraged by the lack of due process, which left no opportunity for staff, patrons and library advocates to give input on the draft order.” Gomez similarly criticized the process, saying the FCC didn’t release the draft order until after the deadline for interested parties to meet with commissioners’ offices.
Gomez: Programs weren’t illegal
Gomez disputed Carr’s legal argument, saying that “Congress gave the FCC permission to expand the applications of E-Rate funding as the technologies used to educate children evolve.” She pointed out that the Universal Service law says the FCC may designate additional services for support. Gomez continued:
When the E-Rate program was implemented, dial-up Internet was the standard, and today, September 30th, 2025, AOL is discontinuing dial-up service. It is safe to say the landscape of communications technology has changed dramatically throughout the life of the E-Rate program. As underscored during my visit to the High School for Environmental Studies in New York a couple of weeks ago, students are now using Chromebooks in classrooms on a regular basis, and they are expected to submit homework assignments online using platforms like Google classroom. These changes are made possible with support from E-Rate funding.
Gomez said that in 2003, under President George W. Bush, the FCC “expanded E-Rate support to cover Internet access for bookmobiles. It also clarified that E-Rate funding could cover a school bus driver’s use of wireless services while transporting students, a librarian’s use of wireless services on a library’s mobile library unit van, and teachers’ use of wireless services while accompanying students on a field trip. Expanding E-Rate support to cover hotspots and Wi-Fi on school buses was consistent with that precedent.”
But on other tasks, the model showed much more variable results. When asked to generate a video highlighting a specific written character on a grid, for instance, the model failed in nine out of 12 trials. When asked to model a Bunsen burner turning on and burning a piece of paper, it similarly failed nine out of 12 times. When asked to solve a simple maze, it failed in 10 of 12 trials. When asked to sort numbers by popping labeled bubbles in order, it failed 11 out of 12 times.
For the researchers, though, all of the above examples aren’t evidence of failure but instead a sign of the model’s capabilities. To be listed under the paper’s “failure cases,” Veo 3 had to fail a tested task across all 12 trials, which happened in 16 of the 62 tasks tested. For the rest, the researchers write that “a success rate greater than 0 suggests that the model possesses the ability to solve the task.”
Thus, failing 11 out of 12 trails of a certain task is considered evidence for the model’s capabilities in the paper. That evidence of the model “possess[ing] the ability to solve the task” includes 18 tasks where the model failed in more than half of its 12 trial runs and another 14 where it failed in 25 to 50 percent of trials.
Past results, future performance
Yes, in all of these cases, the model technically demonstrates the capability being tested at some point. But the model’s inability to perform that task reliably means that, in practice, it won’t be performant enough for most use cases. Any future model that could become a “unified, generalist vision foundation models” will have to be able to succeed much more consistently on these kinds of tests.
Oscar-winning director Guillermo del Toro adapts Mary Shelley’s classic tale of Victor Frankenstein, a brilliant but egotistical scientist who brings a creature to life in a monstrous experiment that ultimately leads to the undoing of both the creator and his tragic creation.
In addition to Isaac, the cast includes Jacob Elordi as the Creature; Mia Goth as Elizabeth Lavenza, who is engaged to Victor’s young brother William, played by William Kammerer; Lars Mikkelsen as Captain Anderson; Christoph Waltz as Heinrich Harlander, uncle to Elizabeth and wealthy financer of Victor’s experiments; Charles Dance as Victor’s father Leopold; Lauren Collins as Victor’s late mother Claire; David Bradley as the blind man; Sofia Galasso as the little girl; Ralph Ineson as Professor Krempe; and Burn Gorman as Fritz.
The trailer looks every bit as mythically epic and visually lavish as del Toro said he wanted for his version. “I remember pieces, the Creature says in a voiceover as footage plays out. “Memories of different men. Then I saw it. Your name. Victor Frankenstein. My creator. I demand a single grace from you. If you are not to award me love, then I will indulge in rage.”
We see lavish balls, Victor’s Gothic laboratory, a ship trapped in Arctic ice, and lots and lots of consuming fire—everything one could want in a Frankenstein movie from a master of macabre mythologies.
Frankenstein hits theaters on October 17, 2025. It will start streaming on Netflix on November 7.
In August, Trump claimed that chip tariffs could be as high as 100 percent while promising to exempt any tech companies that have committed to moving significantly more manufacturing into the US.
Since then, sources familiar with the investigation told Reuters that “the Trump administration is considering imposing tariffs on foreign electronic devices based on the number of chips in each one.” Under that potential plan, the tariff charged would be “equal to a percentage of the estimated value of the product’s chip content,” sources suggested.
Some expect that companies like the Taiwan Semiconductor Manufacturing Company (TSMC) may be exempted from these tariffs, based on a pledge to invest $100 billion into US chip manufacturing.
However, sources told Reuters that the Commerce Department has weighed offering “a dollar-for-dollar exemption based on investment in US-based manufacturing only if a company moves half its production to the US.” TSMC’s total market value is more than $1 trillion, so the US may seek more investments if the campaign to move half of Taiwan’s chip production into the US fails.
Brzytwa told Ars that tech companies are already struggling to do the math from Trump’s tariff stacking. And those headaches will likely continue. At a meeting last week with chip industry executives, Lutnick confirmed that Trump plans to use tariffs to push tech companies to buy US-made chips, The New York Times reported.
If those plans go through, companies would be expected to buy half their chips in the US, earning credits “for each dollar spent on American semiconductors, which they can use against what they spend on foreign semiconductors,” the Times reported.
Any company not maintaining “a 1:1 ratio over time would have to pay a tariff,” sources told The Wall Street Journal. For companies like Apple, the policy would require tracking every chip used in every device to ensure a perfect match. But there would likely be an initial grace period, allowing companies to adjust to the new policy as the US increases its domestic chip supply chain, the WSJ reported. And chipmakers like TSMC could potentially benefit, the WSJ reported, possibly gaining leverage in the market if it increases its US manufacturing ahead of rivals.
This particular booster, numbered Booster 15, launched in March and was caught by the launch tower at Starbase after returning from the edge of space. SpaceX said 24 of the 33 methane-fueled Raptor engines launching on the booster next month are “flight-proven.”
The Super Heavy booster flying next month previously launched and was recovered on Flight 8 in March. Credit: SpaceX
Similar to the last Starship flight, the Super Heavy booster will guide itself to a splashdown off the coast of South Texas instead of returning to Starbase.
“Its primary test objective will be demonstrating a unique landing burn engine configuration planned to be used on the next-generation Super Heavy,” SpaceX said.
The new booster landing sequence will initially use 13 of the rocket’s 33 engines, then downshift to five engines before running just the three center engines for the final portion of the burn. The booster previously went directly from 13 engines to three engines. Using five engines for part of the landing sequence provides “additional redundancy for spontaneous engine shutdowns,” according to SpaceX.
“The primary goal on the flight test is to measure the real-world vehicle dynamics as engines shut down while transitioning between the different phases,” SpaceX said.
Stepping stone to Version 3
After Flight 11, SpaceX will focus on the next-generation Starship design: Starship V3. This upgraded configuration will be the version that will actually fly to orbit, allowing SpaceX to begin deploying its new fleet of larger, more powerful Starlink Internet satellites.
Starship V3 will also be used to test orbital refueling, something never before attempted between two spacecraft with cryogenic propellants. Refueling in space is required to give Starship enough energy to propel itself out of Earth’s orbit to the Moon and Mars, destinations it must reach to fulfill the hopes of NASA and SpaceX founder Elon Musk.
The first flight of Starship V3 is likely to occur in early 2026, using a new launch pad undergoing final outfitting and testing a short distance away from SpaceX’s original launch pad at Starbase. Gerstenmaier, SpaceX’s vice president of build and flight reliability, told a crowd at a space industry conference earlier this month that the company will likely attempt one more suborbital flight with Starship V3. If that goes well, Flight 13 could launch all the way to low-Earth orbit sometime later next year.
Now that we know what Denisovans looked like, they’re turning up everywhere.
This digital reconstruction makes Yunxian 2 look liess like a Homo erectus and more like a Denisovan (or Homo longi, according to the authors). Credit: Feng et al. 2025
A fossil skull from China that made headlines last week may or may not be a million years old, but it’s probably closely related to Denisovans.
The fossil skull, dubbed Yunxian 2, is one of three unearthed from a terrace alongside the Han River, in central China, in a layer of river sediment somewhere between 600,000 and 1 million years old. Archaeologists originally identified them as Homo erectus, but Hanjiang Normal University paleoanthropologist Xiaobo Feng and his colleagues’ recent digital reconstruction of Yunxian 2 suggests the skulls may actually have belonged to someone a lot more similar to us: a hominin group defined as a species called Homo longi or a Denisovan, depending on who’s doing the naming.
The recent paper adds fuel—and a new twist—to that debate. And the whole thing may hinge on a third skull from the same site, still waiting to be published.
This digital reconstruction makes Yunxian 2 look less like a Homo erectus and more like a Denisovan (or Homo longi, according to the authors). Credit: Feng et al. 2025
Denisovan or Homo longi?
The Yunxian skull was cracked and broken after hundreds of thousands of years under the crushing weight of all that river mud, but the authors used CT scans to digitally put the pieces back together. (They got some clues from a few intact bits of Yunxian 1, which lay buried in the same layer of mud just 3 meters away.) In the end, Feng and his colleagues found themselves looking at a familiar face; Yunxian 2 bears a striking resemblance to a 146,000-year-old Denisovan skull.
That skull, from Harbin in northeast China, made headlines in 2021 when a team of paleoanthropologists claimed it was part of an entirely new species, which they dubbed Homo longi. According to that first study, Homo longi was a distinct hominin species, separate from us, Neanderthals, and even Denisovans. That immediately became a point of contention because of features the skull shared with some other suspected Denisovan fossils.
Earlier this year, a team of researchers, which included one of the 2021 study’s authors, took samples of ancient proteins preserved in the Harbin skull; of the 95 proteins they found, three of them matched proteins only encoded in Denisovan DNA. While the June 2025 study suggested that Homo longi was a Denisovan all along, the new paper draws a different conclusion: Homo longi is a species that happens to include the population we’ve been calling Denisovans. As study coauthor Xijun Ni, of the Chinese Academy of Sciences, puts it in an email to Ars Technica, “Given their similar age range, distribution areas, and available morphological data, it is likely that Denisovans belong to the Homo longi species. However, little is known about Denisovan morphology.”
Of course, that statement—that we know little about Denisovan morphology (the shapes and features of their bones)—only applies if you don’t accept the results of the June 2025 study mentioned above, which clocked the Harbin skull as a Denisovan and therefore told us what one looks like.
And Feng and his colleagues, in fact, don’t accept those results. Instead, they consider Harbin part of some other group of Homo longi, and they question the earlier study’s methods and results. “The peptide sequences from Harbin, Penghu, and other fossils are too short and provide conflicting information,” Ni tells Ars Technica. Feng and his colleagues also question the results of another study, which used mitochondrial DNA to identify Harbin as a Denisovan.
In other words, Feng and his colleagues are pretty invested in defining Homo longi as a species and Denisovans as just one sub-group of that species. But that’s hard to square with DNA data.
Alas, poor Yunxian 2, I knew him well
Yunxian 2 has a wide face with high, flat cheekbones, a wide nasal opening, and heavy brows. Its cranium is higher and rounder than Homo erectus (and the original reconstruction, done in the 1990s), but it’s still longer and lower than is normal for our species. Overall, it could have held about 1,143 cubic centimeters of brain, which is in the ballpark of modern people. But its shape may have left less room for the frontal lobe (the area where a lot of social skills, logic, motor skills, and executive function happen) than you’d expect in a Neanderthal or a Homo sapiens skull.
Feng and his colleagues measured the distances between 533 specific points on the skull: anatomical landmarks like muscle attachment points or the joints between certain bones. They compared those measurements to ones from 26 fossil hominin skulls and several-dozen modern human skulls, using a computer program to calculate how similar each skull was to all of the others.
Yunxian 2 fits neatly into a lookalike group with the Harbin skull, along with two other skulls that paleoanthropologists have flagged as belonging to either Denisovans or Homo longi. Those two skulls are a 200,000- to 260,000-year-old skull found in Dali County in northwestern China and a 260,000-year-old skull from Jinniushi (sometimes spelled Jinniushan) Cave in China.
Those morphological differences suggest some things about how the individuals who once inhabited these skulls might have been related to each other, but that’s also where things get dicey.
An older reconstruction of the Yunxian 2 skull gives it a flatter look. Credit: government of Wuhan
Digging into the details
Most of what we know about how we’re related to our closest extinct hominin relatives (Neanderthals and Denisovans) comes from comparing our DNA to theirs and tracking how small changes in the genetic code build up over time. Based on DNA, our species last shared a common ancestor with Neanderthals and Denisovans sometime around 750,000 years ago in Africa. One branch of the family tree led to us; the other branch split again around 600,000 years ago, leading to Neanderthals and Denisovans (or Homo longi, if you prefer).
In other words, DNA tells us that Neanderthals and Denisovans are more closely related to each other than either is to us. (Unless you’re looking at mitochondrial DNA, which suggests that we’re more closely related to Neanderthals than to Denisovans; it’s complicated, and there’s a lot we still don’t understand.)
“Ancient mtDNA and genomic data show different phylogenetic relationships among Denisovans, Neanderthals and Homo sapiens,” says Ni. So depending on which set of data you use and where your hominin tree starts, it can be possible to get different answers about who is most closely related to whom. The fact that all of these groups interbred with each other can explain this complexity, but makes building family trees challenging.
It is very clear, however, that Feng and his colleagues’ picture of the relationships between us and our late hominin cousins, based on similarities among fossil skulls in their study, looks very different from what the genomes tell us. In their model, we’re more closely related to Denisovans, and the Neanderthals are off on their own branch of the family tree. Feng and his colleagues also say those splits happened much earlier, with Neanderthals branching off on their own around 1.38 million years ago; we last shared a common ancestor with Homo longi around 1 million years ago.
That’s a big difference from DNA results, especially when it comes to timing. And the timing is likely to be the biggest controversy here. In a recent commentary on Feng and his colleagues’ study, University of Wisconsin paleoanthropologist John Hawks argues that you can’t just leave genetic evidence out of the picture.
“What this research should have done is to put the anatomical comparisons into context with the previous results from DNA, especially the genomes that enable us to understand the relationships of Denisovan, Neanderthal, and modern human groups,” Hawks writes.
(It’s worth a side note that most news stories describe Yunxian 2 as being a million years old, and so do Feng and his colleagues. But electron spin resonance dating of fossil animal bones from the same sediment layer suggests the skull could be as young as 600,000 years old or as old as 1.1 million. That still needs to be narrowed down to everyone’s satisfaction.)
What’s in a name?
Of course, DNA also tells us that even after all this branching and migrating, the three species were still similar enough to reproduce, which they did several times. Many groups of modern people still carry traces of Neanderthal and Denisovan DNA in their genomes, courtesy of those exchanges. And some ancient Neanderthal populations were carrying around even older chunks of human DNA in the same way. That arguably makes species definitions a little fuzzy at best—and maybe even irrelevant.
“I think all these groups, including Neanderthals, should be recognized within our own species, Homo sapiens,” writes Hawks. Hawks contends that the differences among these hominin groups “were the kind that evolve among the populations of a single species over time, not starkly different groups that tread the landscape in mutually unrecognizeable ways.”
But humans love to classify things (a trait we may have shared with Neanderthals and Denisovans), so those species distinctions are likely to persist even if the lines between them aren’t so solid. As long as that’s the case, names and classifications will be fodder for often heated debate. And Feng’s team is staking out a position that’s very different from Hawks’. “‘Denisovan’ is a label for genetic samples taken from the Denisova Cave. It should not be used everywhere. Homo longi is a formally named species,” says Ni.
Technically, Denisovans don’t have a formal species name, a Latinized moniker like Homo erectus that comes with a clear(ish) spot on the family tree. Homo longi would be a more formal species name, but only if scientists can agree on whether they’re actually a species.
An archaeologist comes face to face with the Yunxian 3 skull Credit: government of Wuhan
The third Yunxian skull
Paleoanthropologists unearthed a third skull from the Yunxian site in 2022. It bears a strong resemblance to the other two from the area (and is apparently in better shape than either of them), and it dates to about the same timeframe. A 2022 press release describes it as “the most complete Homo erectus skull found in Eurasia so far,” but if Feng and his colleagues are right, it may actually be a remarkably complete Homo longi (and/or Denisovan) skull. And it could hold the answers to many of the questions anthropologists like Feng and Hawks are currently debating.
“It remains pretty obvious that Yunxian 3 is going to be central to testing the relationships of this sample [of fossil hominins in Feng and colleagues’ paper],” writes Hawks.
The problem is that Yunxian 3 is still being cleaned and prepared. Preparing a fossil is a painstaking, time-consuming process that involves very carefully excavating it from the rocky matrix it’s embedded in, using everything from air-chisels to paintbrushes. And until that’s done and a scientific report on the skull is published, other paleoanthropologists don’t have access to any information about its features—which would be super useful for figuring out how to define whatever group we eventually decide it belongs to.
For the foreseeable future, the relationships between us and our extinct cousins (or at least our ideas about those relationships) will keep changing as we get more data. Eventually, we may have enough data from enough fossils and ancient DNA samples to form a clearer picture of our past. But in the meantime, if you’re drawing a hominin family tree, use a pencil.
If you watch this for a full hour, leave a comment to receive absolutely no prize.
Epic Games has disabled a Fortnite emote based on the HBO show Peacemaker after the latest episode cast the dancing animation in a potentially different light.
The remainder of this post contains spoilers for Season 2 of Peacemaker.
The “Peaceful Hips” emote, which was first introduced to the game on September 15, mirrors the dance motions that John Cena’s character Christopher Smith makes during the opening credits sequence for the show’s second season. In the dance and the emote (which can be applied to any character in-game), the dancer briefly flails their arms at opposing right angles before shaking their hips seductively.
Some are seeing the dance in a different light after the sixth episode of the show’s second season, “Ignorance is Chris,” which revealed that the alternate universe featured throughout the season has been controlled by swastika-brandishing Nazis. With that knowledge front of mind, the arm movements in the dance emote could be seen as a winking reference to the arms of a swastika.
“[In] season 2 there’s a lot more of the story of the season in the intro, [in] the first season there wasn’t as much of a reference to the story,” choreographer Charissa Barton said in a video interview posted by Warner Bros. last month.
The opening dance sequence to Season 2 of Peacemaker.
The arm motions mean what?
Fans have been picking up on hints of the show’s eventual Nazi-related reveal (including from that opening dance) as the second season has aired over recent weeks. But the confirmation of the link in Sunday’s episode had Epic quickly re-evaluating the emote by Sunday night.
