“She Wanted It”

Epistemic Status: Things I Will Regret Writing

One of the most persistent arguments, often left implicit, that antifeminists have on their side is “Women want to be raped and abused.”

On one hand, this is an obvious logical contradiction if taken literally.  Rape is unwanted sex — how can you want something unwanted?

On the other hand, I can see why people might think this.

Don Giovanni, one of the classic archetypes of a man who’s attractive to women, is also a rapist.  It’s not ambiguous — in the opera, he breaks into a woman’s house to rape her while she fights him off.  No distinction is made by the librettist between his “seductive” charms and his violent attack; he goes to Hell for being a “libertine”, a sin that includes both.  We have a lot of art, often but not always created by men, that portrays male cruelty and male attractiveness as one and the same.

Men are more violent than women. This is a human universal, and true in many of our mammalian relatives as well. And success in violent conflict is, of course, an advantage for inclusive fitness, so there’s an evolutionary rationale for an attraction to men who are strong and good at winning fights.

From there, anti-feminists often jump to believing that women are more attracted to men who are violent to them.  This doesn’t directly follow, of course, but then you point to certain cultural trends — the high incidence of rape fantasies, the fact that many violent criminals have no difficulty finding female partners, the phenomenon of women who have been serially abused by multiple partners, the popularity of Fifty Shades of Gray — and you might start to wonder whether at least some women might have a thing for men who use force on them.

I think you have to talk about this thing frankly before you can put it to rest.

So let’s talk about Fifty Shades of Grey.

It’s a popular book, selling over 125 million copies worldwide. It was also written by a self-published author and gained popularity through word of mouth; almost all critics reviewed it poorly; so its popularity is an unusually strong signal that people genuinely like it.  Nobody is buying this book to impress people.

And it’s a description of a woman in an abusive relationship with a rapist.  I recommend Pervocracy’s very funny liveblog of the book for reference.

The question Pervocracy asks is — why are people into this?  Sure, there’s sex and BDSM with a handsome billionaire, and sure, some people find rape scenes or danger exciting, but Christian Grey is also just kind of pettily mean.  He’s controlling and peevish and consistently makes Ana miserable.  He keeps her isolated from her friends and family.   This book is intended to be erotica. What’s erotic about a guy treating you really badly?

Pervocracy doesn’t get it (or says he doesn’t for rhetorical effect) but I think I do.  The abuse isn’t being read as wish-fulfillment, but as verisimilitude.  I wouldn’t be surprised if the author and many of the fans have been in abusive relationships or grew up in abusive households.  It feels realistic and relatable that the main character has the experiences and feelings that they did.  The emotional punch of her suffering is cathartic. She’s sobbing herself to sleep? Yeah, I know that feel.

It’s a human desire to have your experiences validated — in the sense of getting confirmation that you really did experience what you did. Sometimes you get validation by seeing people like yourself represented in fiction. Sometimes you get it by expressing your thoughts and feelings and experiences to other people, and seeing that they understand, and maybe had the same thoughts, feelings, and experiences.

This is one explanation for why people like to read about tragic or horrifying events.  Real life contains tragedy and horror. We seek out representations (or symbols) of these things in order to process them and make sense of our own stories.  It was like this. I didn’t just imagine it.  I am real; people like me exist.  Or, I misunderstood; I thought it was like this, but there was this whole other side of it that I didn’t see at the time.

The satisfaction that can come from tragic fiction doesn’t feel like “this makes me happy” but rather “this is true.”  We want the world to make sense.

Fiction is not reality.  But, just as we often want to read about dark things because they help us cognitively manage the dark aspects of reality, it’s possible for people to seek out painful experiences in real life because they’re more familiar or make more “sense”.

A classic and maybe even defining feature of abuse is that the abused person is made to feel that it is normal or even right for them to be harmed. They’re told “You deserve it.” Or “this is just what relationships or families are like.”  Or “you aren’t being harmed, you’re fine.”  Over time, abused people may come to believe this.

And people who deeply believe that it is normal or right for them to be harmed may expose themselves to harm again, in order to confirm or validate their model of the world.  This is what “self-harm” or “self-destructive behavior” is.  It’s not that the harm makes them happy.  It’s that it makes them right.

If you take the predictive processing model seriously, the primary thing the brain does is try to be proven right — to adjust mental models and behavior until the brain can confirm “yep, I think it’s this way, and it is.”  In other words, validation is the thing we seek to maximize.  This is both the source of our ability to accurately model the world (we’re incentivized to create correct models) and to deceive ourselves (we’re incentivized to distort our perceptions to conform to our existing models.)

On this model, people may engage in self-destruction even if it doesn’t make them happy because it makes them right about how the world works, and that’s more important to a mind that runs on predictive processing.

(Incidentally, it’s illuminating that there’s an ambiguity in language between “valid” meaning “genuinely exists, is in fact a real thing” and “valid” meaning “good or worth seeking out.”  For instance, that ambiguity shows up in Song of Myself where the narrator seems to equivocate between saying “everything in reality, even the horrible parts, really exists” and “everything in reality is good and I bless it all.”  It’s possible that the mind implements aversion using the same predictive-processing mechanism it uses for truth, such that what we’re actually doing when we hate or oppose something is, on some level, attempting to execute the “this does not exist” operation. We keep trying to delete it from the top-down predictive model, but it persists, and the resulting mismatch attracts attention and is perceived as aversion.)

So, going back to abuse.

Maybe abused people really do have a higher risk of seeking out a repetition of the harm they experienced and were taught to believe was normal.  (I’m not making a statistical claim that most do, just that it could happen and seems like a phenomenon people talk about.)  This would show up in their choices of partners, their media consumption, their imaginations, etc.  It would comport with the common-sense observation that abused people sometimes end up fucked up.  It would fit with the common therapy goal of teaching these people to tell a new story about their experiences — that they don’t deserve to be treated with cruelty, that the reason they suffered was that they encountered a cruel person (or several), that even though life can be harsh, they can still make the best of it.

So I think the antifeminist account is confusing cause and effect.  It’s not that women want men to hurt them. It’s that men hurt women a lot.

***

“How could I have wronged her? She had five boyfriends before me who did the same thing I did!”

Well, no. You’re implicitly working on revealed preference theory here, when it isn’t warranted.  “She must have wanted it, because it happened to her repeatedly” is just untrue.  It could be bad luck, with no agency on her part at all.  And this isn’t probabilistically implausible, because bad luck tends to compound — when one person harms you, you can easily be put at practical disadvantages (like poverty) that put you in a vulnerable position that makes it easier for other people to further harm you.

But even if there were agency on her part in seeking out abusers, people do not only optimize for their own well-being.  People also, and in fact primarily, optimize for validation.

In other words, “Congratulations, asshole! Even if you’re right, you found someone who was hurting herself and decided you’d help her along.”

Revealed preference theory is an attempt to avoid paternalism by assuming that people know what’s good for themselves better than they know what’s good for others. People are different from each other, what’s good for some people is not good for others, and so it can be a practical simplifying assumption to behave as though what people choose is what’s best for them.

But it’s obviously true that what a person chooses, and what’s best for them, are not identical.

What’s actually good for a person is a complex, hard-to-specify thing which we can handwave with a word like “flourishing” or “eudaimonia.”  It’s hard to specify, but we don’t know zero things about it. In modern, colloquial language, I think the best word we have for the thing is healthy, as in, “make healthy choices,” and in close analogy with the concept of physical health. Someone who is in pain, or physically damaged, is less healthy.  So is someone who’s chronically miserable, or helpless, or keeps getting themselves into situations that cause them or others distress, or is stuck pursuing a very obsessive and limited and simplistic sort of satisfaction that’s more like “pain relief” than “joy”.

You shouldn’t be (intentionally, avoidably) making people less healthy.  You shouldn’t fuck people up.  You can’t always know what will fuck people up, so it’s a good idea to listen to what they say and honor their autonomy.  But if they say “this is fine” and then it harms them, that’s a bad outcome. And the more you could have predicted the harm, the more liable you are.

Legal frameworks, including concepts of rights, are constructions that indicate which moral boundaries will be enforced within a society; they’re not the whole of morality itself. There are immoral actions that it would be highly impractical and undesirable to make illegal.

So I believe that you shouldn’t have sex or get in a relationship with someone if you have strong, justified reason to believe it will be bad for them.  You should also, of course, respect consent.  That’s the part that can (imperfectly) be enforced by law.  But you also have to use a reasonable amount of your own judgment.  And, yes, this means that learning accurate models of what is good and bad for people’s wellbeing is a part of behaving ethically.

“But what looks like an unhealthy coping mechanism may actually be the best thing for a person!”  Yeah, well, I didn’t say “make snap judgments about what things look like,” but “try your best to understand how things are.”

***

I used to think that people had something like a Thanatos drive, a death wish or will-to-harm self and others.  I now think this is more parsimoniously explained as a special case of the universal drive for validation.  If you were attacked and gaslit into believing it was okay, you may be driven to attack others or to subject yourself to attack again, just to make your world make sense again and resolve the cognitive dissonance.

When that’s what’s going on, it’s like a snarl in the fabric of incentives.  Things naturally go down and farther down, to more death and destruction.  I suppose you could say that the people involved “want” that, in the very narrow sense that their brains are driving them to do it, but it clearly isn’t good for them.

You can’t always fix one of those tangles from the outside, but it’s a good idea to stop it from spreading, interrupt it, get people out of it when they have a decent chance of recovery, and so on.

From inside one of those tangles, it may be self-consistent, but it’s terrible, like Thamiel’s position in Unsong.

If you’re not Thamiel or one of his minions, you have no reason to cooperate with him, and every reason to oppose him.  You can’t talk him out of his internally-consistent opposite-day morality — but you sure as hell (pun intended) shouldn’t try to talk yourself into it.

And, likewise, if you see someone who appears to be optimizing for the opposite of health and happiness, you shouldn’t help them with that goal on the grounds of “revealed preference.”  It’s probably not going to make you healthy and happy either.

 

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Things I Learned From Working With A Marketing Advisor

Epistemic Status: Opinions stated without justification

I’ve been getting a bunch of advice and help at LRI from a marketing/strategy expert, and it’s been an education. She’s been great to work with — she kicks my ass, in a good way.  Basically, she takes my writing, rips it apart, and helps me put it back together again, optimized to make the organization look better.  Every kind of writing, from professional emails to website copy to grant proposals, gets a makeover.  I’m thinking of the experience as something of an introduction to the conventions of business/promotional communication, which are very different from the kinds of writing norms I’m used to.

Here are some of the general patterns I’ve been learning about, stated in my own words (and maybe mangled a little in translation).

Discretization

“People hate reading,” she tells me.

Seriously? You’re going to rip up my nice, fluent, carefully-written essay explaining my rationale and replace it with a table?

Yes. Yes we are.

She’s not wrong, though. I’ve had the experience of meeting with executives after sending them a two-page document, worrying that I should have written something more comprehensive, and finding they didn’t even read the two-pager.  I learn best through text, but clearly not everyone does. So promotional content needs to make allowances for the skimmers, the glancers, the reading-avoidant.

Hence: tables. Headers. Bolding key phrases.  Bullet points. Pictures and graphs. Logos. And, of course, slide decks.

Layout matters. If you cross your eyes until the page turns blurry and don’t read anything, how does it look? Is it a wall of text? If so, you need to break it up.

The principle of discretization is things should be broken up into separate, distinctive, consistently labeled parts.

What things? Everything.

Your website has parts. Your five-year plan has parts. Your value proposition has parts.

LRI doesn’t have a “product”, but in companies that sell a product, your product has parts called “features.”  Even when the “product” is sort of an abstract, general thing like “we produce written reports”, in order to make them legible as products, you have to have a list of distinct parts that each report contains.

Once you have parts, you need to get obsessive about matching and parallelism. Each part needs to have one, and only one, name, and you have to use the same name everywhere.  If your organization has Five Core Values, you don’t use near-synonyms to talk about them — you wouldn’t interchangeably talk about “single focus” or “narrow mission”, you’d pick one phrase, and use that phrase everywhere. Matchy-matchy.

You match your website navigation links to your page headers. You match your website to your grant proposals, your slide decks, your email phrasing, everything.  You put your logo on every-fucking-thing. It feels repetitious to you, but it just looks appropriately consistent to an outside observer.

When I was a child, I was into American Girl dolls. My favorite thing was the parallelism. Each doll had five books, with matching titles and themes — “Changes for Felicity”, “Changes for Samantha”, etc.  Each book came with its own outfit and accessories. The accessories were even parallel-but-unique  — each doll had her own historically-accurate school lunch, her own toys, and so on. Even more than I liked actually playing with my doll, I liked reading through the catalog and noticing all the parallels.  Ok, maybe I was a weird kid.

Anyhow, marketing is full of that stuff. Separating things into parallel-but-unique, hyper-matchy parts.  Same principle as tables of correspondences.

I suspect that what you’re doing is reifying your ideas into “existence.”  (In something like Heidegger’s sense).  You translate a general sort of concept (“I think we should test drugs to see which ones make animals live longer”) into something with a bunch of proper nouns and internal structure, and I think the result is the overall impression that now your organization exists, as a…thing, or a place, or a personage.  Like, the difference between an idea (e.g. the general concept of lifespan studies) and an agent (LRI).  It activates the “animist” part of your brain, the same part that believes that Facebook is a place or Russia is an agent, the part that feels differently about proper nouns from improper nouns.

(Proper nouns, btw, are another big thing in themselves, because of social proof. Just naming people or institutions in connection with your work — whether they be advisors or partners or employees or customers or collaborators or whatever — is legitimizing.  And proper nouns are, themselves, “discrete parts.” )

All this discretization imparts a sense of legitimacy. After discretizing my writing, it feels much more like “LRI exists as a thing” rather than “Sarah is proposing an idea” or “Sarah is doing some projects.”  Yeah, that’s a spooky and subjective distinction, but I think it’s probably a very basic marketing phenomenon that permeates the world around us. (Maybe it has a name I don’t know.)  I feel slightly weird about it, but it’s a thing.

Confidence + Pleasantries = Business Etiquette

One thing that came as a big surprise to me is how confident language you can get away with in a professional, non-academic context.

For example, not phrasing requests as questions.  “I look forward to hearing back.”  My instinct would be to worry that this was overly forward or rude; you’re essentially assuming the ask; but people don’t seem to mind.

Or removing all uncertain language. All the may’s, mights, and coulds.  How can you do that without making overstated or misleading claims? Well, it’s tricky, but you can generally finagle it with clever rephrasing.

I’m used to assuming that the way you show respect is through reticence and reluctance to ask for too much.  Especially when communicating with someone higher status than you.  To my surprise, really assertive wording seems to get better results with business types than my previous, more “humble” email style (which works great for professors.)

So, how do you keep from sounding like a jerk when you’re essentially bragging and making big requests?  A lot of pleasantries. A lot of framing phrases (“as we talked about in our last conversation”, “circling back”, “moving forward”, etc).  Wishing them a good weekend/holiday/etc, hoping they’re doing well, etc.

I’d previously noticed in office contexts how vital it is to just keep your mouth making words smoothly even when there’s not a lot of information density to what you’re saying.

Business “jargon” and “buzzwords” are unfairly maligned by people who aren’t used to corporate culture. First of all, a lot of them originally referred to specific important concepts, and then got overused as generic applause lights — e.g. “disruptive innovation” is actually a really useful idea in its original meaning.  But, second of all, it’s honestly just handy to have stock phrases if you need to keep talking fluently without awkward pauses.  People respond really well to fluency.  Palantir’s first exercise for all new employees is to give a software demo, which taught me that it is really hard to speak in public for five minutes without pausing to think of what to say next.  Stock phrases help you reach for something to say without appearing hesitant or afraid.

I was trained on writing style guides from literary or journalistic contexts, like Strunk & White, which teach you to be relentless in removing cliches and using simple short Anglo-Saxon words wherever possible.  Business language constantly violates those rules: it’s full of cliches and unnecessary Latinate locutions.  But I suspect there may actually be a function to that, in making you sound smoother, or setting the scene with comfortable and familiar wording before introducing new ideas.  “Good writing” is original and vivid; a good (i.e. effective) business email may not be.

 

Fasting Mimicking Diet Looks Pretty Good

Epistemic status: pretty much factual.

CW: diets, calories

One of the odd things about working on longevity is that now people ask me for lifestyle advice.

Or they ask me what I, personally do to live longer.

Mostly my response has been a lame “um, nothing?”

There are, as of now, no interventions shown to make humans live longer or slow or reverse the human aging process. And, of the interventions reported to make animals live longer, many are doubtful, and many are too risky or unpleasant to make the cost-benefit tradeoff look good for healthy people.

Also, as a personal matter, I’m just not very interested in my own “lifestyle optimization” for the most part. My motivation is about helping people, not especially staving off death for myself; I think I’m more mentally prepared for death than most people my age. Certainly I’ve thought about it more concretely. (BTW, if you too like to know all the gory and technical details about how people die, this blog by an ICU nurse is gold.)

And “lifestyle optimization” turns out to be heavily about diet and exercise, and…I confess, diet culture really creeps me out.  Not at all my thing.

That said, there is a lifestyle intervention that seems pretty evidence-based and also pretty low on risk and inconvenience: the Fasting Mimicking Diet, developed by Valter Longo of USC.

It’s actually been tested in a clinical trial on 100 healthy participants, where it improved a bunch of biomarkers related to aging and disease (reduced IGF and blood pressure, though no change in glucose, triglycerides, cholesterol, or CRP.)

The really good results are in mice, where it rescues both Type I and Type II diabetes as well as a mouse model of MS, reduces tumors by 45% and dermatitis by 50%, increases mesenchymal stem cells by 45x, improves motor and cognitive performance, and results in an 11% lifespan extension.

So, what is the FMD?

It’s a 5-day low-calorie, low-carb, low-protein diet, followed by a period of eating however you would by default.

Caloric restriction (reducing calorie intake about 1/3 from baseline or ad-lib) is probably the most replicated lifespan- and healthspan-extending intervention in animals. It’s about 30-40% life extension in mice and rats.  In monkeys, it extends lifespan little if at all, but delays age-related disease and hair loss.  However, the side effects are nontrivial — humans on CR experience weakness, lethargy, depression, muscle wasting, and neurological deficits. (Undereating also stunts growth in children and adolescents, and underweight in women causes infertility, miscarriage, and preterm birth.)

Mice seem to get most of the benefits of CR, including an equally extended lifespan, from an isocaloric but low-protein or low-methionine diet. Low-protein diets are safe for humans and might not be as damaging to quality of life, but they do definitely inhibit physical fitness/performance.

Alternate-day fasting in mice has a bunch of benefits,  including lifespan extension of 10-30% depending on mouse strain, as well as reduction in cancer incidence, and lower levels of neural damage in mouse models of Alzheimer’s, Huntington’s, Parkinson’s, and acute brain injury.  In a randomized controlled trial in humans, alternate-day fasting caused weight loss but no improvement in metabolic/cardiovascular parameters.

The FMD seems like the least amount of dietary restriction that is still known to cause life extension. 5 days/month of low calorie intake isn’t that big a commitment.

Valter Longo sells patented packaged foods for the FMD, but they’re pricey ($300 for five days).

What I find more aesthetic, and cheaper, is an adapted version, which I’m trying now:

For the first five weekdays of every month, eat nothing but (non-potato) vegetables, cooked in fat if desired.  The rest of the time, eat whatever you want.

It’s low-calorie and low-protein while containing vitamins, but it skips the calorie-counting and allows you to actually cook tasty food.

Since I’m breastfeeding, which is about a 500-calorie daily expenditure, it’s a little harder on me than it would be by default, so I’m adding the modification of if you feel weak or lightheaded, eat a fat source until you stop feeling that way.  I expect this is probably a good conservative measure for people in general.

This ought to be generally safe for healthy adults under 65.  The clinical trial reported no adverse effects more serious than fatigue.

It’s definitely not a good idea for children, diabetics, pregnant people, or people with disordered eating.

If you basically believe the science that periods of little or no food promote good metabolic processes (autophagy, reduced inflammation, increased neurogenesis & stem cell production) but you don’t want the nasty side effects of prolonged caloric restriction, some kind of intermittent or periodic fasting seems like a sensible thing to try.

I don’t think there’s any direct evidence that the FMD is better than intermittent fasting for health, but it seems easier to do, and maybe a bit better in terms of results from randomized human trials.

If you (like me) really don’t like the aesthetics of dieting — “special” pre-packaged foods, appearance insecurity, calorie counting, having to make excuses to the people around you for eating “weirdly” — a homebrew FMD is pretty ideal because you are spending very little time “on a diet”, and you are eating normal things (vegetables).  Also, it’s not necessarily a weight-loss diet, and you can conceptualize it as primarily about health, not looks.

don’t expect it to have nontrivial lifespan effects on humans, but it might be good for healthspan or disease risk, and that seems worthwhile to me.

Reflections on Being 30

Epistemic Status: Personal

I haven’t written a lot of personal stuff here recently, because I’ve been doing a lot more private contemplation, and been busy with life things. (Nonprofit and baby, among other things.)  But I thought I might want to put out some thoughts about what growing in maturity means to me and what I’ve come to believe — since I still believe firmly in the blogging medium and the practice of transparency.

Prudence

There’s a transition that a lot of people go through as they get older, that has to do with “practicality” or “prudence.”  They no longer want to do things that will predictably fail.  They are no longer as willing to deal with people who will predictably fail at life. They are no longer as interested in ideas that can’t stand up to practical tests.

I’ve noticed more of this spirit in myself as I get older, but I’ve always been somewhat ambivalent about it.  I like interestingness.  I want to avoid the natural tendency to stop exploring as I age.  Meeting new people, learning new things, having new experiences, expanding my boundaries, are still important to me.

On the other hand, I’ve really enjoyed becoming more adept at the “practical” or “operational” side of things — schedules, housework, childcare, managing a small organization, etc.  My identity up until now has been “talented mess” — so much so that I got an ADHD diagnosis quite by accident, and am now exploring the very different world of practicality and detail-orientation and organization.  It’s strange. It’s very calm, and it’s a satisfying challenge to keep up with things and bring more order to different parts of my life, and it’s completely non-narrative.  Life becomes a series of tasks, rather than a story.  I’m continually marveling that this is how some people have been living all along.

Of course, the real reason for being more prudent in your thirties or as a parent is hard necessity. You have less energy, and more responsibilities, and so you have to be more cautious with resources and time.  This isn’t something I really want to spin as a good thing — it’s scarcity, plain and simple.

You have to give up something, and the cheapest thing to give up is being a dumbass.

want to have an “abundance mentality”, to be generous and spendthrift with my time and energy; but sometimes I come up against irreducible scarcity.

A friend advised me last year to “have an ego.”  He meant it in Freud’s sense of the “rational self-interest” part of the psyche.  An ego is an institution you build around yourself, like the Republic of Sarah, or Sarah Incorporated.  Your household, your career, your reputation, your health, all these structures around yourself that you build and maintain and use to interface with the world.

So I did that.

I do a lot of adjusting and updating on these structures; in a sense that’s most of what I do all day long.  Taking care of my work, my family and household, my physical body, etc. Like a hermit crab, the little soft emotional creature that is me is hidden within all this prudence and structure.  I notice it works better. I notice people like it better.  But I’m a little melancholy about it.

Humanism

One value I still hold very firmly is something I call “humanism”, or being “pro-human” or believing in the worth of the human spirit.  I don’t think that has to go away with age.

The whole human mind, which is a general intelligence, which can learn anything and create anything, is a beautiful thing and not to be destroyed.

This is in contrast to some people who become traditionalists or authoritarians when they hit the age where they realize they need prudence. The temptation is to believe “people just need to be kept under tight enough control that they can’t do dumb shit, because the consequences of doing dumb shit are tragic.”

The thing is, I don’t think that controlling people actually is a feasible way to prevent tragedy.

A child prevented from making mistakes isn’t a perfect child, but an underdeveloped child.

If you manage to control someone’s behavior well enough to “keep them out of trouble”, there’s a good chance you’ve damaged their ability to problem-solve, and — I don’t know how to say this any other way — injured the sacred thing that makes them human.

People who say “autonomy is a figment, some people need to be controlled for their own good” are sometimes the same people who do actually really bad things to human beings, by dehumanizing them.

As I get less easily susceptible to opinions I hear, and more interested in the boring-but-true over the hot take, I become more humanist, not less so.  It’s not naive. It’s actually looking at what people are, and noticing that they are a lot more complex and able than cynics give them credit for, that “people aren’t all that special” or “some people aren’t really people” is a brute’s excuse.

You can totally be a mature person, or a parent, and still believe in humanism and autonomy.  People have been doing it for hundreds of years.

 

Direct Primary Care

Epistemic Status: PSA and raising questions

Medical care in the US is expensive. There aren’t that many demonstrated ways to make it drastically cheaper.

Direct primary care seems to be an exception.  It makes routine medical expenses 95% cheaper.

Yes, really.

If you have a cash-only, or “direct”, primary care practice — i.e. you don’t accept insurance — you can negotiate much lower wholesale rates from providers of tests (like EKGs, MRIs, blood tests) or prescription drugs. Why? Because you can guarantee the providers immediate payment, rather than the uncertainty and inconvenience of insurance reimbursement.  They’re willing to give you a discount for that.

Direct primary care also cuts down on paperwork for doctors, because they don’t have to document everything with the ICD codes that insurance companies require.

Atlas MD is an EMR designed for direct primary care practices that use a subscription model, founded by Dr. Josh Umbehr, who also uses it in his own direct primary care practice in Wichita.  I’ve spoken to him via phone and tried to poke holes in his model, and came away even more impressed.

My question is, could this model scale up nationwide — and would it still be as effective at cutting costs if it did?

Right now, as I understand, direct primary care practices negotiate individually with suppliers to get discounts. I imagine that it would be much more efficient if done by a nationwide chain of direct primary care practices.  Bulk wholesale purchases, after all, could be even cheaper than what a single practice might hope to get.

With Amazon moving into healthcare, direct primary care might get a chance to shine. Amazon has a lot of experience cutting prices through economies of scale & supply chain optimization. Jeff Bezos even funded direct primary care startup Qliance, which went bankrupt last year.

Direct primary care only works as a complement to insurance that pays for more catastrophic care like emergency room visits and specialists.  And if you can get a “minimalist” insurance plan that’s not redundant with the direct primary care membership, your total healthcare costs (membership + premiums) can be much lower.  The potential problem arises if it’s difficult (or illegal) to sell sufficiently “bare-bones” insurance plans — in that case patients wouldn’t be willing to pay out of pocket for a direct-care membership in addition to their already pricey insurance.

Umbehr has managed to negotiate deals with insurers to offer lower premiums when patients bought insurance along with direct care subscriptions, but maybe Qliance, which apparently struggled to keep customers, didn’t successfully pull it off.

At any rate, if I’m not missing something, this seems like an ideal opportunity for Amazon to make healthcare a lot more affordable. Are there barriers I haven’t thought of?

Oops on Commodity Prices

Epistemic status: Casual

Some patient and thoughtful folks on LessWrong, and, apparently, some rather less patient folks on r/SneerClub, have pointed out that GDP-to-gold, or GDP-to-oil, are bad proxy measures for economic growth.

Ok, this is a counterargument I want to make sure I understand.

Is the following a good representation of what you believe?

When you divide GDP by a commodity price, when the commodity has a nearly-fixed supply (like gold or land) we’d expect the price of the commodity to go up over time in a society that’s getting richer — in other words, if you have better tech and better and more abundant goods, but not more gold or land, you’d expect that other goods would become cheaper relative to gold or land. Thus, a GDP/gold or GDP/land value that doesn’t increase over time is totally consistent with a society with increasing “true” wealth, and thus doesn’t indicate stagnation.

paulfchristiano:
Yes. The detailed dynamics depend a lot on the particular commodity, and how elastic we expect demand to be; for example, over the long run I expect GDP/oil to go way up as we move to better substitutes, but over a short period where there aren’t good substitutes it could stay flat.

Commenters on this blog have also pointed out that the Dow is a poor measure of the value of the stock market, since it’s small and unnormalized.

These criticisms weaken my previous claim about economic growth being stagnant.

Now, a little personal story time:

Nearly ten years ago (yikes!) in college, I had an econ blog. My big brush with fame was having a joke of mine hat-tipped by Megan McArdle once. I did most of the required courses for an econ major, before eventually settling on math. My blog, I realized with dismay when I pulled it up many years later, consisted almost entirely of me agreeing with other econ bloggers I encountered, and imitating buzzwords. I certainly sounded a lot more mainstream in those days, but I understood — if possible — less economics than I do now.  I couldn’t use what I’d learned in school to reason about real-world questions.

I think I learn a heck of a lot more by throwing an idea out there and being corrected than I did back when I was not even asking questions.  A shy person cannot learn, an impatient person cannot teach” and all that.

Admittedly, my last post may have sounded more know-it-all-ish than it actually deserved, and that’s a problem to the extent that I accidentally misled people (despite my disclaimers.)  I actually tried, for several years, to be less outspoken and convey less confidence in my written voice.  My impression is that the attempt didn’t work for me, and caused me some emotional and intellectual damage in the meanwhile.  I think verbally; if I try to verbalize less, I think less.

I think the M.O. that works better for me is strong opinions, weakly held.  I do try to learn from knowledgeable people and quickly walk back my errors.  But realistically, I’m going to make errors, and dumber ones when I’m newer to learning about a topic.

To those who correct me and explain why — thank you.

Monopoly: A Manifesto and Fact Post

Epistemic Status: exploratory. I am REALLY not an economist, I don’t even play one on TV.

You can call it by a lot of names.  You can call it crony capitalism, the mixed economy,  or corporatism.  Cost disease is an aspect of the problem, as are rent-seeking, regulatory capture, and oligopoly.

If Scrooge McDuck’s downtown Duckburg apartment rises in price, and Scrooge’s net worth rises equally, but nothing else changes, the distribution of purchasing power is now more unequal — fewer people can afford that apartment.  But nobody is richer in terms of actual material wealth, not even Scrooge.  Scrooge is only “richer” on paper.  The total material wealth of Duckburg hasn’t gone up at all.

I’m concerned that something very like this is happening to developed countries in real life.  When many goods become more expensive without materially improving, the result is increased wealth inequality without increased material abundance.

The original robber barons  (Raubritter) were medieval German landowners who charged illegal private tolls to anyone who crossed their stretch of the Rhine.  Essentially, they profited by restricting access to goods, holding trade hostage, rather than producing anything.  The claim is that people in developed countries today are getting sucked dry by this kind of artificial access-restriction behavior.  A clear-cut example is closed-access academic journals, which many scientists have begun to boycott; the value in a journal is produced by the scholars who author, edit, and referee papers, while the online journal’s only contribution is its ability to restrict access to those papers.

Scott Alexander said it right:

LOOK, REALLY OUR MAIN PROBLEM IS THAT ALL THE MOST IMPORTANT THINGS COST TEN TIMES AS MUCH AS THEY USED TO FOR NO REASON, PLUS THEY SEEM TO BE GOING DOWN IN QUALITY, AND NOBODY KNOWS WHY, AND WE’RE MOSTLY JUST DESPERATELY FLAILING AROUND LOOKING FOR SOLUTIONS HERE.

 

Except that it’s pretty easy to see why. We have a lot of trolls sitting under bridges charging tolls to people who want to cross. Modern Raubritter can easily maintain a hard-to-refute image that they’re providing value, and so make it hard for anyone to coordinate to avoid them.  It’s genuinely risky to unilaterally skip college, refuse to publish in closed-access journals, or leave an expensive city with a booming economy.  You know you’re being charged a ton for some stuff you don’t want or need, but it’s hard to tell where exactly the waste is; it’s dissipated and concealed and difficult to disentangle.  As 19th century businessman John Wanamaker said, “Half the money I spend on advertising is wasted; the problem is, I don’t know which half.”

But, for now, let’s try to get a factual picture of what’s actually going on.

Stagnant Commodity-Denominated Growth

GDP is supposed to be adjusted for inflation, but the calculation of the inflation rate is pretty political and might be misleading. What happens if you instead denominate in commodities?

dow-to-gold-ratio-100-year-historical-chart-2018-05-30-macrotrends

This is the Dow-to-gold ratio for the past 100 years; as you can see, there are three major contractions in the places you’d expect: one in the Great Depression, an even deeper one that began around 1972, and the most recent in the Great Recession that began in 2008.

You get a similar picture looking at the US GDP-to-gold ratio:

and the global GDP-to-gold ratio:

In 100 years we’re looking at something like an average of 1.4% growth in gold-denominated stocks or GDP; and gold-denominated GDP is comparable to where it was in the 1980’s.

But maybe that’s just gold. What about GDP denominated in other commodity prices? Here’s US GDP in terms of crude oil prices:

fredgraph

Once again, this shows US GDP never really recovering from the 2001 tech bust, and not being much higher than where it was in the 80’s.

fredgraph (3).png

Compared to the global price of corn, again, US GDP barely seems to have an upward trend since 1980; something like 1.5% growth.

fredgraph (1).png

Compared to a global commodities index, once again, GDP seems no higher than it was in the 90’s.

This should make us somewhat suspicious that “real” GDP growth is overestimating growth in material wealth.

Of course, since median income has grown slower than GDP, this means that median income relative to commodities has actually dropped in recent decades.

fredgraph (4).png

Stagnant Productivity

Labor productivity, in dollars per hour, has risen pretty steadily in advanced economies over the past half-century.

laborproductivity.gif

On the other hand, total factor productivity, the return on dollars of labor and capital, seems to have stagnated:

Image result for total factor productivity

Total factor productivity is thought to include phenomena such as technological improvement, good institutions and governance, and culture. It’s been stagnating in other developed countries, not just the US:
Image result for total factor productivity

A Brookings Institute report broke down US total factor productivity by sector, and concluded that the declining growth from 1987 to today was in services and construction, while manufacturing and other sectors continued to improve:

Screen Shot 2018-05-30 at 6.37.51 PM

Services and construction, please note, pretty much match the “cost disease” sectors whose prices are rising faster than the rest of the economy can grow: education, housing, transportation, and especially healthcare.  As services become more expensive, they’re also becoming less efficient.

Declining productivity means that we’re doing less with more.  This is particularly true for innovation, where, for instance, we’re not getting much increase in crop yields despite huge increases in the number of agricultural researchers, and not getting much increase in lives saved despite increasing volume of medical research.

agyield

lifeexpectancy

Monopoly and Declining Dynamism

The Herfindahl Index is a measure of market concentration, defined by the sum of the squares of the market shares of firms in an industry. (If a single firm held a monopoly it would be 1; if N firms each had equal shares, it would be 1/N.)

US industries have become more concentrated since the mid-1990s, with the number of firms dropping and the Herfindahl index rising:

Screen Shot 2018-05-30 at 7.55.33 PM

Firms have also gotten larger:

Screen Shot 2018-05-30 at 7.57.30 PM.png

You can also look at concentration in terms of employment.  Education and healthcare are the most concentrated industries by occupation, while computers are the least:

Occupational groups by industry concentration, May 2012

There has been a steady increase in market power since 1980, with markups rising from 18% above cost in 1980 to 67% above cost in 2014.

 

Screen Shot 2018-05-30 at 8.40.26 PM.png

More concentrated industries can charge higher prices relative to costs.

As industries are becoming more concentrated, they’re also becoming more static. Fewer new firms are being created:

Fig. 2: Firm Entry and Exit Rates (1978-2011)

Americans are moving less between states:

Image result for falling labor mobility

And self-employment is dropping:

Image result for declining entrepreneurship

As market power increases (i.e. as industries become more monopolistic), you can get a scenario where the financial value of firms outpaces their investment in capital or their spending on labor.

With an increase in market power, the share of income consisting of pure rents increases, while the labor and capital shares both decrease. Finally, the greater monopoly power of firms leads them to restrict output. In restricting their output, firms decrease their investment in productive capital, even in spite of low interest rates.

If you divide the economy into “capital” and “labor”, you find a long-term decline in the share of labor and increase in the share of capital. But if you decompose the capital share, you find that the returns on structures, land, and equipment are static or declining, while pure profits are on an upward trajectory:

Screen Shot 2018-05-31 at 8.13.58 AM.png

This story is consistent with other long-term trends, like the increasing share of the value of firms that consists of intangibles — that is, “the value of things you couldn’t easily copy, like patents, customer goodwill, employee goodwill, regulator favoritism, and hard to see features of company methods and culture.

Screen Shot 2015-03-24 at 6.19.07 PM.png

Those intangibles constitute barriers to entry, precisely because they can’t be easily copied by new firms.  The rise of intangibles is also a sign of a more monopolistic economy.

It’s Not (Just) Regulation

Alex Tabarrok, a libertarian economist, argues that the decline in dynamism is not due to regulation.

Since the 1970’s, the most stringently regulated industry by far has been manufacturing:

Regulatory stringency by major sector

(“FIRE” here refers to finance, insurance, and real estate.)

However, more stringently regulated industries are not less dynamic:

Startup rates vs. regulatory stringency

Some of these results are weird, since #622, marked as a lightly regulated industry, is “Hospitals”, which I don’t really think of as freewheeling.  Maybe these numbers don’t include indirect effects like occupational licensing for medical professionals restricting the supply of people to work in hospitals.

But at any rate, regulations are not the only way to enforce monopoly power, and it seems that they’re not the decisive factor.  Governments have means other than regulation to promote monopoly (for instance, grants, contracts, or subsidies to insider firms, or increases in the scope of what can be patented and for how long).  And there are purely private mechanisms (like prestige/signaling in the scientific publishing industry) that can preserve monopolies as well.

Problems for the Middle and Lower Classes

US income inequality is rising; in real dollar terms, this looks like the rich getting richer while everyone else stays the same:

inequality

On the other hand, it’s worth moderating this picture by awareness of cost disease. High-income people as well as lower-income people are spending a larger fraction of their budget on housing and healthcare, which aren’t really improving much in quality.

Image result for household consumption in high income

Income mobility is also dropping:

Image result for declining income mobility

 

Some Slogans

Why is monopoly bad?

Monopoly drives up prices while depressing production.  That means we have fewer nice things. Yes, even for the “winners” of this negative-sum game, though of course the problem is worse for everyone else.

Monopoly and lack of innovation go together, since monopolists have less incentive to produce or compete.

Monopoly and intangibles go together.  Branding is a form of market power. As are patents.

Monopoly causes inequality; it also causes absolute economic insecurity (if necessities cost more, the poor are most harmed).

Monopoly is anti-meritocratic. It’s a troll guarding a bridge, not a hardworking genius inventor.

 

None of this tells us what to do about monopoly. I’m not at all confident that antitrust law works or is a fair solution to the problem.  There’s also reason to doubt that deregulation would fix everything, though fixing zoning and occupational licensing laws seems like it would at least help.

Introducing the Longevity Research Institute

I’ve just founded a nonprofit, the Longevity Research Institute — you can check it out here.

The basic premise is: we know there are more than 50 compounds that have been reported to extend healthy lifespan in mammals, but most of these have never been tested independently, and in many cases the experimental methodology is poor.
In other words, there seems to be a lot of low-hanging fruit in aging.  There are many long-lived mutant strains of mice (and invertebrates), there are many candidate anti-aging drugs, but very few of these drugs have actually been tested rigorously.
Why?  It’s an incentives problem.  Lifespan studies for mice take 2-4 years, which don’t play well with the fast pace of publication that academics want; and the FDA doesn’t consider aging a disease, so testing lifespan isn’t on biotech companies’ critical path to getting a drug approved.  Mammalian lifespan studies are an underfunded area — which is where we come in.
We write grants to academic researchers and commission studies from contract research organizations.  Our first planned studies are on epitalon (a peptide derived from the pineal gland, which has been reported to extend life in mice, rats, and humans, but only in Russian studies) and C3 carboxyfullerene (yes, a modified buckyball, which prevents Parkinsonism in primate models and has been reported to extend life in mice).  I’m also working on a paper with Vium about some of their long-lived mice, and a quantitative network analysis of aging regulatory pathways that might turn up some drug targets.
We’re currently fundraising, so if this sounds interesting, please consider donating. The more studies that can be launched in parallel, the sooner we can get results.

Wrongology 101

Epistemic Status: Speculative.

Jean-Paul Sartre’s Anti-Semite and Jew, available online here, is a really interesting study of the psychology of anti-Semitism, written in a time (1940’s France) when it was common for people to talk overtly about how much they hated Jews.  Sartre, being Gentile and from a culture where anti-Semitism was much more common than it is in 21st century America, had an opportunity to observe these people that I do not.  So while he paints an extremely unflattering picture of anti-Semites, one that’s almost hard to believe, I take it seriously.

What are anti-Semites like, according to Sartre?

They are lazy. Sartre gives the example of a man who believes Jews are given unfair advantages in passing an exam he failed, but readily admits that he didn’t study for it.

They are people-oriented rather than thing-oriented.  “They behave toward social  facts like primitives who endow the wind and the sun with little  souls.  Intrigues, cabals, the  perfidy of one man, the courage and virtue of another —  that is what determines  the  course of their business, that is what determines the course of the world.”

They are impulsive.  “the anti‐Semite understands nothing about modern society.  He  would be incapable of conceiving of a constructive plan; his action cannot reach the level of the methodical; it remains on the ground of passion.  To a long‐term enterprise he prefers an explosion of rage analogous to the running amuck of the Malays.”

They are bullies.  “He has chosen also to be terrifying.   People are afraid of irritating  him.   No one knows to what lengths the aberrations of his passion will carry him  —  but he knows, for this passion is not provoked by something external.  He has it well in hand; it is obedient to his will: now he lets go of  the reins and now he pulls back on them.”

They are conformists.  “This man fears every kind of solitariness, that of the genius as  much as that of the murderer; he is the man of the crowd.   However small his stature,  he takes every precaution to make it smaller, lest he stand out from the herd and find  himself face to face with himself.  He has made himself an anti-Semite because that is something one cannot be alone.  The phrase, “I hate the  Jews,” is one that  is  uttered  in  chorus;  in  pronouncing  it,  one  attaches himself to a tradition and to a community  —  the tradition and community of the mediocre.”

They are irrational.  “The anti-Semite has chosen to live on the plane of passion.” They like being angry (at the Jews), and seek out opportunities to work themselves up into a rage.  They deliberately say trollish things that make no sense: “Never believe that anti‐ Semites are completely unaware of the absurdity of their replies.  They know  that  their remarks are  frivolous, open to challenge.   But they are amusing themselves, for it is their adversary who is obliged to use words responsibly, since he believes in words. The anti‐Semites have the right  to play.”

They are mystical and anti-intellectual.  “The anti‐Semite has a fundamental  incomprehension of the various forms of modern property:  money,  securities,  etc.   These are abstractions, entities of reason related to the abstract intelligence of the Semite…What his subtle sense seizes upon is precisely that which the intelligence cannot perceive.” In other words: he cannot understand complicated abstract ideas which in principle anybody could grasp, with enough time and effort and ordinary thinking; but he believes he has magical powers of intuition that reach beyond the intellect and which the Jews innately will forever lack.

They are a mob. “He  wants  his  personality  to  melt  suddenly  into  the  group  and  be  carried  away  by  the  collective  torrent.   He  has  this  atmosphere  of  the  pogrom  in  mind  when  he  asserts  “the  union of all Frenchmen.”

Why would a person want to be wrong on purpose?

Sartre explains:

How  can  one  choose  to  reason  falsely?  It  is  because  of  a longing for impenetrability. The rational man groans as he  gropes for the truth;  he  knows  that his  reasoning is no more than tentative, that other considerations may supervene  to  cast doubt on it.  He never sees very clearly  where he is going; he is “open”; he may even appear to be hesitant.   But there are people who are attracted  by the durability of a stone.   They wish to be massive and impenetrable;  they wish  not to change.   Where, indeed, would change take them?   We have here a basic fear of oneself and of truth.  What frightens them is not the content of truth, of which they have no conception, but the form itself of truth, that thing of indefinite approximation. It is as if their own existence were in continual suspension.

In other words: the person who is wrong on purpose is afraid of the vulnerability of trying at a task that may fail.  In particular, he is afraid of the process of learning.  The “indefinite approximation” Sartre mentions is the process of double-checking, doubting, asking questions, second-guessing, saying “oops”, moderating or complicating one’s views, all the millions of mental motions involved in trying to understand things accurately. The person who is wrong on purpose wants to just stop all of that motion, forever.

Only  a  strong  emotional  bias  can give a lightning‐like  certainty; it alone  can hold reason in leash; it alone can remain impervious to  experience and last for a whole lifetime.

People choose to be wrong so that they can play a game that is by definition impossible to lose.  They don’t like trying or working hard. They don’t like expectations being placed on them.

The  anti‐Semite  is  not  too  anxious  to  possess  individual  merit.   Merit  has  to be sought, just like truth; it is discovered with difficulty; one must deserve it.  Once acquired, it is perpetually in question: a false step, an error, and it flies away.  Without respite, from the beginning of our lives to the end, we are responsible for what merit we enjoy.

But the anti-Semite wants a respite from responsibility, very badly.  He wants to be done.  He wants an end to trying altogether.

 Anti‐Semitism, in short, is fear of the human condition.  The anti‐Semite is a  man  who wishes to be pitiless stone, a furious torrent, a devastating thunderbolt‐anything except a man.

Sartre’s “Anti-Semitism” Isn’t Just About Jews

Sartre says explicitly that the character that made a Frenchman of his time into an anti-Semite could in other contexts apply to other races: “The Jew only serves him as a pretext; elsewhere his  counterpart  will  make  use  of  the  Negro  or  the  man  of  yellow skin.”

Sartre’s version of anti-Semitism is a lot like the American institution of herrenvolk democracy, established around the time of Andrew Jackson, in which white people, no matter how poor, formed a coalition that allowed them to be socially superior to black people, given arbitrary privileges over them and free to enact unpunished mob violence against them.

Anti-Asian prejudice (“sure, they’re smart, but they’re not really a good culture fit“) is also structurally very similar to the defiant mediocrity that Sartre describes in anti-Semites.

More controversially, there is something about the concept of Asperger’s Syndrome, which is no longer officially a medical designation and was arguably never a natural category, that matches this pattern.  Smart, logical people who just aren’t one of us, who may technically fulfill the requirements of a job but don’t have the right intangibles, who aren’t good at politicking, who naively believe in the literal rules, and who inevitably get bullied.

Structurally, we’re talking about a cartel, or a mob.  Mob in both the “mafia” and the “riot” sense.  Collusion to keep unmerited privilege, enforced by acts of random violence.

If you are trying to enforce an eternal privilege, something that cannot be lost no matter what you do, then being wrong, or being bad at things, or treating others badly, is the fundamental test of the security of your status.  Being wrong is both a badge and one of the perks of class membership.

Fascism and Mysticism

This article on Jordan Petersen is infuriating in some ways — there are gratuitous digs at masculinity and self-help that I don’t endorse — but it’s worth reading because it outlines his historical influences.

A range of intellectual entrepreneurs, from Theosophists and vendors of Asian spirituality like Vivekananda and D.T. Suzuki to scholars of Asia like Arthur Waley and fascist ideologues like Julius Evola (Steve Bannon’s guru) set up stalls in the new marketplace of ideas. W.B. Yeats, adjusting Indian philosophy to the needs of the Celtic Revival, pontificated on the “Ancient Self”; Jung spun his own variations on this evidently ancestral unconscious. Such conceptually foggy categories as “spirit” and “intuition” acquired broad currency; Peterson’s favorite words, being and chaos, started to appear in capital letters. Peterson’s own lineage among these healers of modern man’s soul can be traced through his repeatedly invoked influences: not only Carl Jung, but also Mircea Eliade, the Romanian scholar of religion, and Joseph Campbell, a professor at Sarah Lawrence College, who, like Peterson, combined a conventional academic career with mass-market musings on heroic individuals.

There is, historically, a connection between occultism and the study of mythology, on the one hand, and fascism, on the other. (I would add D.H. Lawrence to the list of fascist-sympathizing mystics.)  The literal Nazis were very fond of myth and magic — see the Thule Society.  Start exploring contemporary neopaganism and occultism and you’ll quickly run into people with some very disturbing politics.

There’s a historical explanation — both the Theosophists and the fascists drew intellectually from German Idealism — but Sartre gives a more psychological explanation.  Both the desire to enjoy unearned (racial) privilege and the desire to believe in occult forces essentially boil down to the desire not to be tested.  One can fail tests.

If you have an invisible, magical essence that makes you special, however — that can’t be taken away by any inconvenient facts.

Cartel Thinking

The Western Elite from a Chinese Perspective “, an account of a Chinese immigrant’s experiences at Cambridge, Goldman Sacks, and Stanford Business School, talks a fair bit about the mentality of seeking to live insulated from fair tests.

“In Communist China, I was taught that hard work would bring success. In the land of the American dream, I learned that success comes through good luck, the right slogans, and monitoring your own—and others’—emotions.”

When Puzhong makes a successful trade by accident at Goldman Sacks, he expects to be reprimanded for his mistake, but is instead rewarded. But “it was not enough to just be a good trader. It was also essential to be able to manage one’s boss, other colleagues, and those who report to them.”

In business school, he learns (amusingly enough) that the way one is supposed to express feelings in American elite culture seems a lot like falsifying them:

We talked about microaggressions and feelings and empathy and listening. Sometimes in class the professor would say things to me like “Puzhong, when Mary said that, I could see you were really feeling something,” or “Puzhong, I could see in your eyes that Peter’s story affected you.” And I would tell them I didn’t feel anything. I was quite confused.

One of the papers we studied mentioned that subjects are often not conscious of their own feelings when fully immersed in a situation. But body indicators such as heart rate would show whether the person is experiencing strong emotions. I thought that I generally didn’t have a lot of emotions and decided that this might be a good way for me to discover my hidden emotions that the professor kept asking about.

So I bought a heart rate monitor and checked my resting heart rate. Right around 78. And when the professor said to me in class “Puzhong, I can see that story brought up some emotions in you,” I rolled up my sleeve and checked my heart rate. It was about 77.  And so I said, “nope, no emotion.” The experiment seemed to confirm my prior belief: my heart rate hardly moved, even when I was criticized, though it did jump when I became excited or laughed.

This didn’t land well on some of my classmates. They felt I was not treating these matters with the seriousness that they deserved. The professor was very angry. My takeaway was that my interpersonal skills were so bad that I could easily offend people unintentionally, so I concluded that after graduation I should do something that involved as little human interaction as possible.

Puzhong is noticing that American elite businesspeople appear to be colluding rather than competing.  They’re not racing each other for profits, they’re signaling that they’re cozy insiders who will play nice and share the spoils with others who know the right buzzwords.  Cartel behavior, in other words.

I had always thought that things happen for reasons. My parents taught me that good people get rewarded while evil gets punished. My teachers at school taught me that if you work hard, you will succeed, and if you never try, you will surely fail.

If people are rewarded for reasons, then anyone who meets these publicly known criteria can gain rewards.  If rewards are given opaquely, then they can be safely restricted to existing insiders. Therefore, people who want to preserve cartel privilege have an interest in being mysterious and not making sense.

Applied Wrongology

I have never been an anti-Semite, for obvious reasons; I have never been a banker or MBA, either, and I like to think that racism is not particularly my vice.  But I do understand the longing for security.

It gets tiring to be tested all the time, to be subject to skepticism, to be second-guessed, to have expectations placed upon you.  It’s nerve-wracking to have to perform and worry that you’ll fail.  Merit is intimidating. Objectivity is daunting.

And, on the other hand, to float completely free, to have a space where you can just be, to feel the world is faintly gold-dusted and magical, to build castles in the air without any annoying people coming around to check on whether you’re being “productive” or whether the castles are, in fact, real…that would be lovely, wouldn’t it?  Doesn’t that seem more like the way life should naturally be?

And wouldn’t it be nice to be sure that nobody will ever come round to weigh and measure and count and judge?  Forever, no matter what?

I can’t, in sincerity, say people shouldn’t want that. It’s a very understandable thing to want, to be cut slack, to not be judged. At times I want it myself.

But Sartre’s anti-Semite only wants to be secure — he isn’t said to succeed.  Just because he wants to stop being human doesn’t mean he can get what he wants. Total security, and total absence of thought, is probably unattainable.

 

Good News for Immunostimulants

Epistemic Status: Moderate

Way back in 2015 I was writing about the connection between cancer remissions and the immune response to infection.  To recap the facts:

  • A plurality of recorded spontaneous cancer remissions happened when the patient had a strong immune response (often with fever) to a bacterial infection at the tumor site.
  • William Coley’s bacterial therapies for cancer at the turn of the 20th century, while not tested to the standards of modern experimental methods, did seem to produce recovery rates comparable or superior to chemotherapy.
  • Endotoxin, a poisonous substance found in the outer membrane of Gram-negative bacteria, can cause tumor regressions.
  • TNF-alpha, an inflammatory cytokine involved in the body’s response to endotoxin, is equally effective at causing tumor regressions; it is too dangerous to give to patients systemically, but is an effective cancer treatment for advanced melanoma when used in isolated limb perfusion.
  • There are quite a few cases, both in animals and humans, of inflammatory cytokines causing complete tumor regressions in metastatic cancers, particularly when injected directly into the tumor.

At the time, I predicted that if only there were a delivery mechanism that could more effectively isolate inflammatory cytokines to the tumor site, it might work safely for more than just special cases like isolated limb perfusion; and that there might be some delivery mechanism that made a bacterial therapy like Coley’s toxins work.

The heuristic here was that when I went looking for the biggest responses (remissions, complete tumor regressions) in the toughest cases (metastatic cancers, sarcomas which don’t respond to chemotherapy), many of them seemed to involve this picture of acute, intense activation of the innate immune response.

It turns out that two new therapies with very good results pretty much support this perspective.

CpG oligodeoxynucleotides,  a motif found in bacterial DNA, are the active ingredient in Coley’s toxins; they are the part of bacterial lysate that triggers the immunostimulatory effects.

Today, SD-101, a CpG oligodeoxynucleotide drug produced by the biotech company Dynavax, is about to present its results from two trials.

This January, Stanford scientists reported that SD-101 combined with another immunotherapy — but no traditional chemotherapy — eradicated both implanted and spontaneous tumors when injected into mice, both at the injection site and elsewhere.

We’ll have to see the results of the human trials, but this looks promising.

Another drug, NKTR-214, is an engineered version of the inflammatory cytokine IL-2, designed to localize more effectively to tumors.  The IL-2 core is attached to a chain of polyethylene glycols, which release slowly in the body, preferentially activating the tumor-killing receptors for IL-2 and resulting in 500x higher concentrations in tumors than a similar quantity of IL-2 alone.  This is the tumor-localizing property that could make inflammatory cytokines safe.

In patients with advanced or metastatic solid tumors, previously treated with PD-1 inhibitors, NKTR-214 resulted in 23% of patients experiencing partial tumor regression.

While this still doesn’t mean much chance of recovery, it’s still notable — any treatment for advanced cancers with more than a 20% response rate is remarkable. (Chemotherapy usually produces partial response rates in the 2-20% range for metastatic cancers, depending on cancer type and drug regimen.)

It’s early days yet, but I continue to think that immunostimulants have a lot of potential in cancer treatment.

Moreover, I think this is a little bit of evidence against the frequently heard claim that it’s impossible to “pick winners” in biotech.

The conventional wisdom is that you can’t know ahead of time which drugs that seem to work in preclinical studies (in vitro or in mice) will succeed in humans.

Most preclinical drug candidates do fail, it’s true. And there are a lot of reasons to expect this: mouse models are not perfect proxies for human diseases, experimental error and outright fraud often make early results unreplicable, and we don’t understand all the complexities of biochemistry that might make a proposed mechanism fail.

But the probability distribution over drug candidates can’t be uniform, or it would have been impossible to ever develop effective drugs!  The search space of possibly bioactive molecules is too large, and the cost of experiments too high, to get successes if drugs were tested truly at random.  We would never have gotten chemotherapy that way.

I think it’s likely that using the simple heuristic of “big effects in tough cases point to a real mechanism somewhere nearby” gets you better-than-chance predictions of what will work in human trials.