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.

 

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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.