In the 12 years since I wrote this, I attended graduate school and have been working as academic researching metabolism- while I had little training in biology when I first wrote it. I do now think that the Gilbert Ling/Association-Induction theory is mostly incorrect, but that the rest of the essay mostly stands without it, and wish I had not mentioned it, as it doesn’t contribute anything important to the main points. The modern picture of cell biology is quite complex, and doesn’t really bare much resemblance to any of the competing simplistic theories of the 1960s.
CasioTheSane
Karma: 526
“The
OneidaRationalist Community was a19th21st-century utopian religious sect that practiced communal living, ‘complex marriage,’ and eugenics before transforming into a famoussilverwareAGI ruin manufacturing business.”I wrote the above as an alternate-history joke, before realizing that it was, unfortunately, already pretty close to the truth.
I don’t want immortality unless we can solve the problem of the most uniquely evil and cruel people in society amassing increasingly large amounts of money and power over their lifetimes, eventually installing themselves as autocrats, and then using this position to inflict as much harm as possible. Historically, the major check on this phenomenon has been that those people eventually die.
Our current world with immortality added on, is one where the values and goals I identify as humanity—and as making life worth living—die out much more rapidly than they would even under steadily decreasing populations. I’d rather pass on to my immediate children a finite lifespan with some possibility of freedom and joy.
As I mentioned, I do actually sometimes get negative feedback from people, but overall the effect is positive, because it causes people to interact with me spontaneously when I have trouble initiating social interactions, and I’ve made quite a few good friends just from that. Being polarizing is way better than being neutral for meeting people and making friends. I also suspect being avoided by a person that would negatively judge someone they don’t know just for wearing a hat is probably also a positive thing. It’s a functional thing I need because I’m bald with pale skin and spend a lot of time outdoors in a sunny climate, so people that think that is “cringe” are most likely not nice people. I didn’t choose to be bald, or sun sensitive, and haven’t found anything else that works as well- and trust me I tried because I felt very awkward about wearing a noticeable hat at first. I would liken that to thinking eyeglasses, a wheelchair, or a cane are cringe.
Once I was publically mocked by a group of guys in eastern Europe (Czech Republic) that thought it was hilarious that I was probably a local, trying to dress like an American cowboy or something. It made their day, and mine when I responded verbally with an American accent, and they started apologizing and laughing.
While I think finding ways to make future generations healthier and smarter is a worthy goal, I don’t think we understand enough yet to do this without potentially severe unintended consequences, and I wouldn’t consider doing it myself with our current technology. It’s a good bet that many of the seemingly deleterious mutations we’d like to eliminate also offer some benefit we don’t understand- given that we have already discovered many instances of mutations with apparent intelligence/health tradeoffs, and disease resistance/health tradeoffs. If you’re selecting embryo populations for mutations correlated with specific desirable traits, you should also expect that you are selecting for worse outcomes in all other potentially desirable dimensions including those that are potentially even more important than those optimized for, but we have no clear concept of, or labels for. If you do this at scale, you’re also systematically selecting for a less diverse, less robust population.
Also, I think a lot of neurodivergent people (including myself, and probably quite a lot lot of other LWers) have become irrationally obsessed with their own childrens raw intelligence above all else, due to emotional trauma. Growing up and being labeled as gifted, but also having (at the time undiagnosed) ADHD, I strongly felt that the only thing people liked about me was my intelligence, and that without it I would be unworthy of love or friendships. The idea of my child not being exceptionally intelligent, and therefore suffering immensely was terrifying to me, and made me irrationally obsessed with something mostly outside my control. Indeed, I am a parent now, and my son is both exceptionally bright and neurodivergent, but I now understand now that neither I or him need to be exceptionally bright to be loved or accepted.… we just need to have boundaries, and choose to only associate with the (numerous) people that will accept or even like that we are different, rather than those that dislike it but tolerate us for what we can practically provide them. Moreover, what those people begrudgingly tolerated me for wasn’t even my actual intelligence, but my ability to accomplish difficult things for them with my intense ADHD hyperfocus. Of course intelligence is extremely useful and important, but shouldn’t be valued above all else out of a trauma derived sense of terror.
Interesting, thanks for sharing. I am also on the west coast, and wear wide brimmed hats (usually cowboy hats), which is somewhat unusual and many of the people comment on it, complement it, or ask me about it.
The truth is, I’m not really trying to make a fashion statement, I’m just bald and don’t want to get cancer on my head… and this hat design is uniquely functional in that it blocks the sun, doesn’t blow off in the wind, and doesn’t look incredibly dorky and non-breathable like the nylon sun hats they sell at REI. Yet people make a big deal about it and the social dynamics of peoples reactions are confusing and surprising to me.
The social reactions are interesting… I am shy and introverted, so it ends up being a good ice breaker, as people approach me about the hat frequently, and they notice and remember me a lot more readily. I have (rarely) had some really negative reactions, usually also from very leftist people that say the hat made them assume I was a “conservative piece of ****” or something along those lines, and were very surprised I didn’t fit that stereotype after talking to me. I very often get asked the exact same thing word for word: “I love your hat, where did you get it?” Yet those people are almost always already choosing to not wear hats, and I assume don’t and won’t actually buy and wear a hat, so I am a little confused about this question. My best guess is that they are trying to complement my style while qualifying that they aren’t trying to ‘hit’ on me.
As someone that has been a strength athlete, and part of fitness communities for many years, I have never seen a real world instance of someone becoming generally less attractive to the opposite sex, or having trouble finding partners due to lifting weights.
Building noticeable amounts of muscle is much harder than most people who haven’t tried to do so assume. The “grotesquely muscular” men on, e.g. bodybuilding magazines are essentially fake, and not something that really happens to people that lift weights, except for a few minutes in a staged photo that requires months of preparation. To get like that you need a combination of massive doses of steroids, weight training and perfect dieting as a literal full time job, and one in a million genetics… plus a combination of crash dieting and severe dehydration aka “water cutting” to time a photo or contest for a specific day. Even those guys just look “fit” during a normal day with normal clothes on.
Your average person that does hard strength training seriously say 2-4 times per week, but still eats mostly normal foods, and avoids steroids will get much physically stronger, but will rarely look extremely different from how they did before. They might look slightly healthier and more attractive, but often won’t even be immediately noticeable as athletic, not alone “having huge grotesque muscles.”
For muscle mass to be very visible you also need really low body fat, at least in the 10-15% range, and maintaining that long term without losing the muscle is really difficult. A young ~6′ tall adult man with normal genetics won’t be able to be that lean and be over about 190-200lbs, which means they will appear more ‘skinny’ than muscular if wearing clothing.
Late reply I know, but I wanted to add that I was very surprised by your take on Brett Kavanaugh, and wanted to explain my more negative interpretation of those events, as I see it as very helpful to Trump directly, and not about principles. Some points:
-Backing down from anything almost always involves giving up political power, and encourages people to challenge you in the future. Trump is known for consistently almost never giving up without a fight, even in situations like losing an election. This strongly discourages people from challenging you in the future, because they know it will be a big fight, even if they win.
-His goal appears to have been to install essentially a sycophant supreme court, that would consistently rule in his favor rather than based on laws, principles, etc. and Kavanaugh seemed to be someone likely to do this (and arguably has done so), and even more so after Trump fought so hard for him. It would have been very hard to find a replacement candidate like this.
-Why don’t you find the sexual assault allegations credible? I think people should be assumed innocent until proven guilty, but they don’t much seem like a conspiracy to me. Trump himself in his own words, e.g. statements on the “Access Hollywood” tape, and quotes about Epstein, etc. seems to frequently brag about being a sexual predator himself, and generally would not consider that a disqualification for any job.
Growing crops for biofuel cannot produce more carbon than it consumes over long time scales, because the only source of carbon available to the system is the carbon in the atmosphere. If they are saying biofuels aren’t carbon neutral over long time scales, where is this extra unlimited supply of carbon coming from?
High intensity deliberate practice that you can only do for short amounts of time per session
How is that different from flow work?
I’m not sure if you’ve read Mihály Csíkszentmihályi or not, but he argued that flow states are more likely when a task is more complex/challenging, and the person has a high level of appropriate skill that makes it possible (with substantial effort) to complete the task.
For me this often occurs while programming, sailing, or doing math- especially if I need to solve a new problem with those skills that will be especially challenging.
Once I’m in ‘flow’ it is a distinct mental experience—I am totally into it and lose any sense of time passing, or of needing to motivate myself until I am interrupted either by my own body, or by something external.
Cal Newport in Deep Work (his own word for flow work) defines “Deep Work” as anything that requires skills that would take at least a year to develop if a person was already generally educated, smart, and motivated.
I stopped using pomodoros for flow-work, because it would break my flow state. I’ve found roughly 2 hour chunks work better for flow, without any particular warning to stop me if I feel like going longer. If I am in flow, I want it to keep going as long as possible, until I am fatigued, or the problem is solved.
But I would have thought that if there was widespread ‘central hypothyroidism’, someone would have twigged by now, since that form does show up if you do a full panel of hormone tests
Which tests? I am not aware of any simple blood test that measures the endpoint of thyroid activity on metabolic rate (except, arguably, cholesterol levels), rather than just the state of the T4->TRH->TSH->T4 feedback loop.
mostly T4 with a bit of extra T3′, but no-one has particularly clear ideas on what works and what doesn’t or why
The challenge with T3 is it has a very short half-life, one would need to take very small doses impracticably often to achieve stable levels. Taking mostly T4 with a bit of T3 helps compensate for the reduction in T3 production due to feedback without the problems caused by trying to obtain nearly all T3 directly from a supplement.
Thanks for the reference to Ray Peat, I hadn’t heard of him before. Can you link to the best expression of his thoughts?
His own essays at raypeat.com are the only accurate source, but can be challenging to read. Most of the summaries you will find online don’t do him justice.
he was basically making his patients hyperthyroid
Why is this a reason not to reject it? He is essentially arguing that the major cause of cardiovascular disease is population-wide high rates of hypothyroidism. It would be a circular argument to dismiss that because his treatment leads to a greater than average metabolic rate. One would also need evidence of a disadvantage that outweighs the advantages. His patients seemed to be doing well, or at least he doesn’t report them exhibiting any classic signs of hyperthyroidism. He was primarily adjusting dose based on body temperature to the upper end of the normal non-hyperthyroid range.
to help them lose weight
I have seen studies on thyroid supplementation as a weight loss strategy, and it causes loss of lean tissue (muscle, etc.) more than fat.
You wouldn’t need to invoke the idea of ‘hormone resistance’ because TSH and T4 tests normally used to diagnose hypothyroidism don’t measure the active hormone—T3. T4 is just a prohormone with very little direct activity on metabolic rate.
In primates, metabolism is regulated primarily in the liver by T4->T3 conversion, so if this is inhibited for any reason it will suppress metabolism without showing up on those tests. Low calorie intake, and poor nutrition are known to cause this (e.g. Euthyroid sick syndrome). In cases of poor liver conversion, supplementing T4 can actually make symptoms worse, as it will further suppress metabolism by lowering the small amount of T3 production from the thyroid (via the TSH feedback loop).
I assume you have heard of Ray Peat? I personally had good luck applying his ideas to increase my energy levels, and my pulse, body temperature, and cold tolerance raised as well—without supplementing thyroid. His general idea is pretty simple- just look at what conditions and nutrients maximize T4->T3 conversion, and provide them (low stress, high nutrient diet).
Broda Barnes work is very interesting. It blows my mind that he published a paper in The Lancet showing that desiccated thyroid lowered cholesterol levels and seemed to prevent cardiovascular disease in his patients, and that it remains virtually un-discussed and uncited (http://www.ncbi.nlm.nih.gov/pubmed/13796871).
You’re right, we do understand the pathophysiology of many diseases, and those are the ones that have been mostly eradicated. The major chronic diseases that remain are very poorly understood such as type II diabetes, cancer, cardiovascular disease, and alzheimer’s.
I spend a lot of time reading about ‘alternative’ ideas about these diseases, and many seem promising, but aren’t taken seriously by the mainstream. It’s definitely possible that they’re ignored for a good reason, but I haven’t been able to find the reasons yet. This is the biggest problem I’ve found with trying to be ‘critical of everything.’ In very few instances do I find myself quickly understanding and agreeing with the mainstream view. Instead, the more I read the more my opinion seems to diverge from the mainstream view. I have made an effort to discuss these issues personally with specialized experts, so they could help point out factors I may be missing, or not understanding correctly. I am a PhD candidate in the life sciences, so I have the opportunity to meet with research professors at my university in person to help clarify my understanding.
Here are two example theories, regarding cancer and cardiovascular disease in particular.
1) The idea that cancer isn’t initiated by genetic mutations, but that mutations are a downstream phenomena that results after damage to the mitochondria occurs.
This stems from the initial observation by Warburg, that lack of control over glycolysis is part of the cancer cell phenotype. This phenotype can be triggered by a large number of factors which inhibit mitochondrial respiration including hypoxia. Later it was found that the mitochondria in cancer cells undergo a phenotypic change, where the cristae structure is lost. Nuclear transfer experiments have shown that a ‘mutated’ cancer nucleus placed into a healthy cell cytoplasm does not exhibit a heritable cancer phenotype. Conversely, a healthy nucleus placed into a cancerous cell cytoplasm does exhibit a heritable cancer phenotype.
Here is a review article covering the evidence for this hypothesis:
Cancer as a metabolic disease: implications for novel therapeutics http://carcin.oxfordjournals.org/content/35/3/515
More evidence for this hypothesis includes the observation that active thyroid hormone levels (T3) are inversely correlated with cancer mortality rates in the general population. T3 is a key regulator of mitochondrial respiration:
Thyroid hormones and mortality risk in euthyroid individuals: The Kangbuk Samsung Health Study. http://www.ncbi.nlm.nih.gov/pubmed/24708095
2) The finding that treatment for hypothyroidism drops cholesterol levels significantly, and virtually abolishes cardiovascular disease without the side effects seen from statins. The late Broda O. Barnes was an experimental endocrinologist and a clinical doctor, and he extensively documented this phenomena in his books and publications.
The idea here is that the central mechanism of cardiovascular disese is a low metabolism which inhibits cholesterol clearance from the blood via reduced steroid hormone synthesis, and reduced bile synthesis. The pathophysiology of cardiovascular disease begins with a long residence time of cholesterol particles in the blood, resulting in their oxidation. This can be reversed by any strategy that restores a normal (higher) metabolic rate: a carefully designed diet and/or thyroid hormone supplementation.
Here is a good introduction to this idea:
The Central Role of Thyroid Hormone in Governing LDL Receptor Activity and the Risk of Heart Disease http://blog.cholesterol-and-health.com/2011/08/central-role-of-thyroid-hormone-in.html
I am not insisting that these ideas are correct, or are some sort of ‘well proven answer’ to these diseases. I’m just pointing out that they seem promising, but are relatively ignored. If they prove accurate, much of the mainstream research on these phenomena would seem to be barking up the wrong tree.
You might notice that both of these examples are essentially the same theory. This is an appealing concept to me: most age-related chronic diseases may be centered around a common process of age related impaired mitochondrial function and/or improper hormonal regulation of mitochondrial function. Insufficient chemical energy (ATP) to fuel normal biological function would have widespread consequences, and could present as a diverse array of seemingly disconnected symptoms. I’ll admit, this sounds somewhat like a modern molecular version of vitalism. However, unlike vitalism it makes specific testable predictions, and involves a very specific mechanism. It’s also consistent with the ‘free radical’ and ‘tissue peroxidizability index’ theories of aging, which involve (among other things) progressive oxidative damage of unsaturated fats (such as cardiolipin) in the mitochondrial inner membrane.
I have been attempting to do this with biology and medicine, seriously for about 5 years now. Not by actually repeating experiments, but in trying to understand the original evidence, and see if I agree that it was interpreted correctly. Of course this is nearly impossible as biology is too broad and complex for one person to understand all of the details.
It’s a confusing mess, but I think I am still learning a lot. Even if I come to agree with most of the mainstream ideas, I’d like to think I’d then understand them more deeply, in a way that is more functionally useful.
For much of medicine, there really isn’t any biological basis or evidence to review. Much of modern medicine involves covering up symptoms with drugs proven to do this, without understanding the underlying cause of the symptom.
Excellent post, thanks for putting so much work into a clear explanation. I will re-investigate Ling’s work more carefully, and also see if I can find the mistakes in his thermodynamics calculations you mention. I have been biased towards his work and not looking critically enough, because it seems to explain some surprising observations about drug activity I’ve found in my own research- but that’s no excuse.
I am interested in the possibility that Ling could be entirely wrong about membrane physiology, but this gel phase shift phenomena could still be important in the cell. If Ling and Pollack are wrong about long distance effects from protein surfaces, that might not destroy their arguments as the cytosol is very dense, and the distance between proteins is very short. Albert Szent-Györgyi also did some work on this idea that is very different from Ling’s.
One of my committee members works on physics simulations of protein hydration shells, and I am going to meet with him and see what he thinks about this. The simulations I have seen don’t show significant water structuring, as the water molecules have too much thermal energy.
That’s a good point about intelligence, the way I used that word without defining it in this article is sloppy.
I am interested in the ability to solve important problems. Maybe instead I should talk about something more easily definable such as mental endurance, or limiting the stress response from focused work? Personally, I think if I could work longer in one sitting on a hard problem without stress or fatigue, that alone would count as “increased intelligence” for practical purposes.
I think there are links between the stress response and nutrient availability. In lab mice anyway, sugar seems to reduce stress hormone production during stressful situations. However in practice this might be harmful to doing focused work, if stress improves focus.
Thanks for pointing out the issue of brain energy consumption vs mental activity. I think this entire article hinges on the (unfounded?) assumption that the two are strongly correlated. I am confused about this, and need to learn more about it. I see many articles and researchers claim massive increases in energy consumption with hard mental activity, and others that claim there is none which seems very strange. How are they measuring this? I wonder if people under general anesthesia have much lower, or about the same energy requirements as an awake person?
This seems like an attempt to mock the general trait of being willing to discuss or consider controversial ideas, rather than any kind of actual refutation of the essay.
When I wrote this, I was basically an excited kid that had little understanding of biology, but was excited about the general idea of a controversial iconoclastic theory. I now work in this field as an academic PI researching metabolism, and don’t find the Association-Induction hypothesis useful.
If I were to criticize this essay myself now, I’d start by pointing out that there is no solid logical connection between the rest of the essay and Association-Induction. Sure, it seems pretty likely or even self evident that brains work better if they at least have enough metabolic energy to function normally, but that hardly hinges on some fringe 1960s theory of cellular biology being correct, and it doesn’t mean they will work even better if they have even more energy. The modern picture of cell biology bears little resemblance to any of the competing theories of the 1960s, and has much better data- we have stuff like live video inside cells from lattice light-sheet microscopy (LLSM) that don’t require as much theorizing, in many cases we can now just literally watch what is happening. Some of the modern picture of cells aligns with Association-Induction: for example cells are quite packed full of stuff, and molecules are pretty well channeled directly to where they need to go, they are not very accurately modeled as a well mixed solution in a container as was the mainstream view in Ling’s time, but sodium-potassium pumps certainly exist and are important.
I find this attitude toxic, it considers anyone even willing to discuss or consider a controversial theory as some type of grifter or con artist, when it is the type of thinking that is often most important to encourage in young scientists for them to make real contributions. Gilbert Ling didn’t end up having the ultimate grand unifying theory of biology after all, and may have made some big mistakes, but he wasn’t trying to deliberately deceive anyone, and shouldn’t be grouped in with snake oil salesmen.