Epistemic Spot Check: The Demon Under the Microscope (Thomas Hager)

Description

How much would it suck to be the guy who invented sulfa drugs? You dedicate your life to preventing a repeat of the horrors you saw in the war, succeed in that and so much more, and then 10 years later some idiot leaves a petri dish open and completely replaces you as the father of man’s triumph against bacteria.  Actually he left the lid off before you found your thing, but ignored the result until you hit it big because everyone knew you couldn’t fight disease with chemicals, until you proved you could.  It’s the ultimate silver medal.  The Demon Under the Microscope is the tale of that guy.

It’s by the same author (Thomas Hagen) as The Alchemy of Air.  It’s also set in the same corporation, and about field that was transforming from science to industry.  The writing style is similar.  I originally didn’t intend to fact check this book very hard because I already knew what to expect from the author (a little too invested in the subject but basically accurate), but the habit is too ingrained at this point and I couldn’t keep reading until I’d checked out the first few chapters.

 

Evaluation

Claim: “Domagk [the researcher] had the ability to see. He watched everything, noted slight variations, quietly filed it all away.”  (p. 18).

The wounds themselves he accepted as the results of war. But the infections that followed—surely science could do something to stop those. He focused on the bacteria, his personal demons, “these terrible enemies of man that murder him maliciously and treacherously without giving him a chance.” “I swore before God and myself,” he later wrote, “to counter this destructive madness.”  (p. 20).

Who knows but it’s pretty.  Someone in the same position as thousands of others (in this case a WW1 medic), caring more , and going to fix it (via sulfa drugs) is my moral aesthetic.  Of course there could be another surgeon in the same place with just as much care and potential who got blow up or gassed.  The Alchemy of Air prioritized poetry over provability, so I don’t entirely trust this, but I like it.

Claim: Cholera was a big problem for German soldiers.

This would be a weird thing to make up, but I’m a little confused.  There had been a cholera vaccine for over 20 years by that point.

Claim: Gas gangrene is bad.

True.

Claim: Sir Almroth Wright created a typhoid vaccine that was deployed during WW1, saving may lives.  During WW1 he established a laboratory researching wound infections.

True.  He was also prescient enough to foresee the risk of drug-resistant bacteria.  Of course he also thought that bacteria were associated with but not the cause of disease, and that scurvy was caused by poorly preserved meat.  Being right is hard.

Claim: Doctors at the time thought that a dry wound was more resistant to infection; however dryness inhibited white blood cells and thus ultimately increased infections. They also thought wounds needed to be completely covered to prevent reinfection, but this created the ideal environment for anaerobic bacteria like Clostridium perfringens (which causes gas gangrene).

True. I was surprised to find ideal wound moistness still isn’t entirely settled, but the book’s description seems essentially in good faith.  Demon goes on to say that by the 1920s, doctors believed they were basically powerless and their job was to get the body’s own healing systems a pillow and some tea.  They took this so far that:

“A physician doing drug research was a physician taken away from patient care. There was an unsavory aspect to a physician’s developing a drug for money. There were ethical questions about testing drugs on patients. Developing new drug therapies smacked of a return to the discredited age of bleedings and purgings.”

 

To repeat: researching new treatments was considered distasteful at best and morally outrageous at worst.  And brain differentiation was once considered phrenology redux.  I just don’t think we’re very good at seeing where medicine is going (p40).

Claim: Section on Leeuwenhoek. 

True but missing time data.  Given that everything discussed so far happened in the range of 1890-1920, I would have have explicitly mentioned I was going 250 years into the past.  As it was, the only reason I noticed was that I recognized some of the names on the list of Leeuwenhoek’s contemporaries. The kindle edition may have made this worse.   But everything Hager actually says on Leeuwenhoek’s work in inventing the microscope seems accurate.

Claim: [crickets] (no page)

There’s no false statements, but I found the absence of discussion of the 1918 Spanish Flu epidemic puzzling.  Demon’s narrative is that seeing the horror of infected wounds in World War 1 drove Domangk to dedicate his life to preventing them.  Spanish Flu killed 5% of the entire world over the course of three years, and had a massive effect on troop movements and training in WW1.  From a military perspective it might have been more important.  We know now that the flu is really hard to vaccinate against, but at the time they didn’t even know it was a virus.  If you were a motivated medic looking for something to care about, Spanish Flu was a really obvious choice.  Demon mentions Spanish Flu in passing but not as an influence on Domangk, and that feels incomplete to me. Why gangrene in particular, when there were so many horrors happening at the time?

Claim: Streptococcus is the cause of everything bad.

True.  I knew it was possible to die from a scratch, but reading about everything strep causes really made me appreciate how few technological innovations are between us humans and mass die offs.  Strep causes childbed fever, St. Anthony’s Fire, meningitis, scarlet fever, pink eye, necrotizing fasciitis… Strep is the cockroach of human-infecting bacteria.  And for a while, all we had to do was take a pill and it was completely harmless.

Of course now we have MRSA (Methicillin-resistant Staphylococcus aureus) (whose natural habitat is the hospital, just like strep).  And multiply resistant gonorrhea.  And tuberculosis resistant to most known antibiotics.  The bad old days are on our heels, is what I’m saying.

One weird thing is I finished this book with the vague impression that sulfa drugs had saved a lot of lives but not actually knowing how many.  This article estimates that sulfa drugs led to a 2-3% drop in overall mortality, which translated to a 0.4-0.7 year increase in life expectancy.  That only covers up until 1943: presumably it had a bigger impact as distribution increased, or at least would have if penicillin had not taken over.

Overall Verdict

Pretty good, with some oversights.  Like Alchemy of Air the beginning is the best part, and if you find your attention flagging I’d just let it go.  I found the subject matter more innately interesting than Alchemy of Air but the writing a little less so.  Demon spends less time on the personal lives of the scientists, which was a selling point for my roommate but a disappointment for me.

This post supported by Patreon.

Status Through Disbelief

Reading The Remedy, or really anything about the time after formalized western medicine but before the germ theory of disease, is an exercise in terror or frustration.  How could anyone think attending a childbirth with autopsy gunk on your hands was a good idea?  Or leaches.  Who looked at those and said “I’ll bet those will make people healthier”?

My first reaction reading The Colony, about a Hawaiian leper colony founded shortly after the germ theory became entrenched, was “oh no doctors, you overapplied the lesson.”  Leprosy has an epidemiology a lot like tuberuclosis: long periods between infection and symptoms, and an ease of spreading that means everyone is constantly exposed to it.  This makes it look like an inborn condition, not a contagion.  Leprosy and TB are actually pretty closely related too.  I assumed that doctors looked at their failure with TB and overcorrected.  It didn’t work because only a small fraction of people are suspectible, and (it’s implied although never stated outright) they will be exposed to it whether symptomatic patients are quarantined or not.

Then I remembered that shunning lepers* predates germ theory by a couple of thousand years.   Ancient and medieval people were completely capable of identifying disease as contagious and instituting a separation.  So why didn’t industrial-age doctors?

Then I remembered that while the peasantry considered it obvious that disease was contagious and should be shunned, they considered it equally obvious that leprosy was punishment from God for sin and the black plague could be avoided by killing Satan’s minions, the cats.  Nobody talks about all the things everyone knew that doctors correctly disbelieved in.

Without a lot of proof, I strongly suspect that doctors signaled intellectual rigor and membership in the medical class by disbelieving things the peasantry believed.  Believing things the peasantry does believe doesn’t signal either of those things even if the belief is correct.  No one gets credit for believing eating food is good and eating Belladonna is bad.  If you’re not very careful in that environment, it’s easy for peasants’ belief in something to become evidence against it.

This is similar to the process of the toxoplasma of rage, in which people signal membership in an ingroup by loudly believing its most dubious claims.  I also highly suspect it’s what’s going on with dietary constraint and toxins.  It is obviously true that what you eat matters, some things you put in your body will damage your cells, getting rid of them is good, and there are things you can take to get rid of them.  It’s called heavy metal poisoning and chelation.  Or if you’re Huey the dopamine dog, chocolate and activated charcoal.  But dietary constraints and belief that specific things were bad for you got associated with special snowflakenes, so you can signal intellectual rigor by dismissing them.  This despite the fact that nutrition obviously makes a difference in your health, that humans vary across many dimensions and there’s no reason to assume they wouldn’t vary across digestion and nutritional needs.  Likewise things we put in our mouth obvious have the capacity to hurt us and there’s no reason to assume we have an exhaustive list of those, or that they’re identical across all humans.

In D&D terms: people are advertising their will save bonus by how credible an idea they can disbelieve.  No one wants to be this guy:


[Thor rushes Loki, only to run through the illusion and trap himself in the cage]

Disbelieving everything is an easy way to be right most the vast majority of the time.  For every correct idea that’s an almost infinite number of wrong ones, and even those that are true are incomplete (see: physics, Newtonian).  But if everyone disbelieves everything, we will never discover anything new.

I’m not in a position to criticize anyone for being frustrated at people for being wrong.  I lived that life for a long time.   But I try to counter it now by remembering that humans aren’t really capable of distinguishing “laughably wrong” from “correct, and world changing” without investing a lot of energy.  If there aren’t negative externalities and they’re not asking anything from me, their investment  in their crackpot idea is something like an insurance policy for me, or a lottery ticket.  Most won’t pay off, but when they do I’ll be glad they were there.

“Minimal negative externalities” and “at no cost to me” are important caveats.  Children need vaccinations, and I don’t want the government paying for medicinal prayer.  But if a functional, taxpaying citizen wants to spend their own money to get their chakras realigned every six months?  Yelling at them seems like a waste of energy.  Hell, they may have a genetic variation that enhances the placebo effect to the point it is medically significant.  The human brain is weird and we don’t even know what all the pieces are, much less how they work.  If someone investigates something that’s a positive for me, even if all they do is conclusively prove it doesn’t work.

chakras

You can believe people are wrong, you don’t have to accept all ideas as equally valid.  But what I would suggest, and what I’m attempting to do myself, is to make the amount of energy you put into your disbelief proportional to the harm the idea causes, not its wrongness.  To have wrong ideas drop out of sight, resurfacing only if they cause problems or turn out to be a winning lottery ticket.   I think that on net this leads to a better world, and in the meantime I’m calmer and less annoyed.

*Which really means shunning anyone with skin discoloration, ancient people not being entirely up on their bacteriology.

Review: The Remedy: Robert Koch, Arthur Conan Doyle, and the Quest to Cure Tuberculosis (Thomas Goetz)

I love this book so much I gave it to my cats to cuddle, which would have made a more impressive visual if I hadn't gotten the kindle version.
I love this book so much I gave it to my cats to cuddle, which would have made a more impressive visual if I hadn’t gotten the kindle version.

I don’t even know where to start.  This book was fun to read and I felt like I learned a lot.  It covered both the specific facts of Robert Koch’s quest to prove germ theory and cure tuberculosis, and provided a good general sense of how science and medicine move forward and don’t.

A couple of specifically interesting points: doctors fought germ theory tooth and nail.  They also rejected stethoscopes as technological interlopers to be disposed of because they threatened the doctors importance, while using so many leaches prosperous countries had to import them.  The naive interpretation is “doctors are idiots, their reluctant to use quantified self data is proof they haven’t changed.”  This is the first time I’ve seen any hint as to why they found germ theory so implausible.  In the particular case of tuberculosis, everyone was exposed all the time, and it took the infection years to become symptomatic.  Preventing any one exposure wouldn’t have had noticeable results.  Another early-identified bacteria was Anthrax, which didn’t follow a typical exposure pattern either.  The doctors still come out looking pretty bad for refusing to wash their hands between autopsies and childbirth, but marginally less than they might have.

I knew this already, but it was good to have a reminder that the first person to suggest the germ theory of disease, Ignez Summelweis, died in an insane asylum.  This either means that people with truly visionary ideas can be broken when we reject them, or germ theory was so crazy it took a crazy person to see it.  Goetz doesn’t mention it but according to my dad Summelweis was also an asshole, which I try to remind myself every time someone mean says something I disagree with.

Remember last week when I suggested using microchips to force people to finish their antibiotics?  Several friends seriously questioned the effect of that, since they didn’t estimate the contribution of unfinished antibiotics to antibiotic resistance as very high.  The Remedy says that the current protocol for drug resistant TB is to have a medic visit a patient every day for 6 -24 months to observe them taking their pills, because drug resistant TB is that big a problem and the pills are that unpleasant.  So at least in that situation swallowable microchips would be an enormous improvement.

Apparently syphilis is always the [nationality] disease, where the nationality is not the speaker’s.  French is the most popular, but far from the only

I’ve always found the methods section the most boring of any paper or textbook.  I want to know what we learned, not how.  But The Remedy (and to a lesser extent Neanderthal Man, which I reviewed last week) made it seem interesting.  I’m still not terribly interested in microscopy, but it was deeply interesting to see how advances in technology enabled scientific advances.  Using or inventing new technology is how you move the world forward.  And when I thought about it, the modern field that most reminds me of the wide-open-ness of microbiology in the mid 1800s is programming.  That is where I get the most sense of possibility.  I still really care about translational health (in fact this book taught me that that is the word for what I am trying to do with this blog) and mental health, but I am feeling more and more like staying in programming would be the best way to accomplish that.

Being a cyborg proves more boring than anticipated.

Barack Obama recently announced doubling funding to fight antibiotic resistance, which would be more impressive if there wasn’t a significant step that cost the government nothing: ban use of antibiotics for livestock, which currently account for 80% of antibiotics produced.  Hell, taxing use of antibiotics in livestock would reduce the problem and generate revenue.  Representative Louise Slaughter has introduced a bill to (more or less) do this for five years running and it has gone absolutely no where.  So this feels a little like California introducing water restrictions on people while saying nothing about agricultural use, which coincidentally is 80% of their water use.

But maybe Obama’s new money will go to one of the lesser contributors towards antibiotic resistance: people who don’t finish their prescriptions.  Researchers are studying a new microchip that sends a signal when it is being digested.  They’re using it for severely mentally ill patients, who for various reasons sometimes have trouble staying on their meds (good luck to the first schizophrenic to explain to their new doctor that their old doctor tracked their medication by making them swallow computer chips), but what if we used them for antibiotics?

This isn’t a simple solution.  To have it do any good you have to either punish people for not finishing them (which is extremely hard on low income people) or pay them for finishing (hello terrible incentives).  People who split prescriptions are often trying to save themselves the doctor’s visit more than the cost of the medication itself, and this doesn’t address that.  But it seems like we ought to be able to do something with this.

Oral Probiotics for Dental Health

Bias disclosure: I started taking oral probiotics because my doctor told me to and I have vaguely positive feelings about probiotics.  I kept taking them because simple inspection with my tongue showed I was developing fewer dental plaques.  But the friend I recommended them to wanted actual data, so I did some digging.  The results were overwhelmingly positive.  They reduced not only cavities, but in the study that checked, total antibiotic usage.  In your face, friend who asked for data.

But only one of those tested a probiotic lozenge, the rest were milk products supplemented with Lactobacillus rhamnosus.  Not all Lactobacillus species scored so well, so I went to check what my supplement had.  Turns out it has no Lactobacillus at all.   So I went back to google scholar and checked the bacteria I was actually taking (Bacillus coagulans and Streptococcus salivarius).  Luckily the news was still good: in head to head trialsBacillus coagulans was found to be as effective as a mix of Lactobacillus rhamnosus and Bifidobacterium species, and Streptococcus salivarius also performed well.

Then I found the motherload: someone did a comparative survey.  This was less helpful to my cause.  Oral probiotics were almost universally found to be helpful to children, but results in adults were mixed.   My first argument is “well, yeah, adults develop fewer cavities per unit time than children, so you’d need a bigger sample over a longer time period to detect a difference.”  But the studies looked at intermediate results like “bad” bacteria presence, and even the 15 month trial in older and elderly people didn’t see a difference.

My conclusion is that oral probiotics are definitely good for children, and in light of the additional data for my personally, good for me, but possibly not for all adults.  I still feel confident recommending other people try them, but not that they stick with them if they don’t see results.

Antibiotics: is there anything they can’t do?

Until fairly recently, gastric ulcers were a disease of stress and spicy food.  Those things probably did make it worse, but it turned out ulcers were almost always caused by overuse of NSAIDS or an H. pylori infection.

Back pain is the prototypical malingerer’s disease.  The medical establishment isn’t saying you’re faking it, but given that back pain is positively correlated with low job satisfaction, to the point that job tenure and unemployment are considered when predicting someone’s recovery time.  The most charitable explanation is that the pain is real, but working through it is ultimately more beneficial than rest, so people who love their job or hobby enough push themselves through it, and people who hate their job don’t have the incentive.  The uncharitable explanation is that they’re faking it because they are lazy.

Or maybe they have a severe bacterial infection.  There’s new evidence that people who fail to recover after a herniated disk are suffering from a bacterial infection that can be treated with prolonged antibiotics.  Patients treated with antibiotics continued to improve after the antibiotics were discontinued, suggesting they got to the root of the problem.

And then there’s a bunch of non-specific symptoms that may or may not be associated with chronic Lyme disease, which may or may not be cured by antitbiotics.  And even though Toxoplasmosis is not a bacteria, the treatments are commonly used antibiotics.  Part of me wants to recommend everyone take a broad spectrum antibiotic holiday every few years, just to sweep up all the low level things that must exist but we don’t know to look for.

But you still can’t have them for the flu.  That’s just stupid.

Any straw that doesn’t break your back must be weightless.

Toxoplasma gondii is a single-cell parasite usually associated with cat feces, although undercooked meat is the more common form of infection.  For years, everyone knew that T. gondii was totally harmless unless a pregnant woman caught it at a very particular stage in the pregnancy, at which point it caused miscarriage or devastating birth defects.  I probably learned about this younger than most because this was my parents official reason for not letting me have a cat while they were trying to conceive.  But eventually I got my cat and never thought about it again*, because I was not a pregnant woman.  While the concept was gross, 20% of the US and 30-60% of the world has it, so clearly it’s harmless.

Then science began to poke around a bit more.  Toxoplasmosis causes pretty drastic behavior changes in rat, as demonstrated by this adorable video of rats attempting to cuddle a cat…

…which is actually a video of a paramecium attempting to get this cat to eat the rats so it can sexually reproduce in the stomach.  Enjoy that mental image.  If it can have such a strong effect in rats, might it have some measurable effect in humans as well?

Yup.

First, T. gondii was always considered dangerous in immunocompromised individuals (e.g. AIDS patients). But it gets worse. Research revealed associations between T. gondii and lower IQ in children (which may reverse with treatment), suicide attempts, decreased novelty seeking, car accidents,  lower IQ  in men, greater friendliness and sexuality in women , and perhaps 20% of all schizophrenia.**

Here is what I think is going on.  The human body is incredibly robust.  It can take a number of hits and show only a very minor decrease in function.  But if you already have enough hits against you (HIV, age, genetic predisposition to schizophrenia), it can have a big effect.  Or maybe it will do nothing, but it uses up one of your hits, so when the next blow comes, you don’t have the energy to fight it.    This is why the phrase “only dangerous in immunocompromised individuals” bugs me so much.  First, everyone who doesn’t die of trauma lives at the mercy of their immune system.  Second, immune function is not bimodal.  There’s lots of people that don’t have AIDS, but do have, I don’t know, multiple chronic complex infections in their jaw requiring extensive surgery to remove.  Or they’re poor and have substandard housing and nutrition.  Or they pick up a second parasite while camping.

Telling these people- who don’t have AIDS or leukemia, but aren’t functioning at optimal either- that T. gondii, or any other aggravator, can’t affect them is like telling a working-poor person that ATM fees can’t hurt her because she’s not homeless.  It’s great that the fees are a rounding error to you, but don’t discount the cost they impose on others

*Which turned out to be totally justified.  Owning a cat is not a risk factor for toxoplasmosis, and I happen to have been tested as part of a larger parasite screen last year and am certifiably toxoplasmosis free.

**A lot of these studies are associational, which I usually frown upon.  I find it more valid in this case because causational studies in animals show similar effects.