AI Medical Diagnosis

Google has just published a paper on a major trial of their new medical diagnosis AI, which they call AIME. As the graph above shows, AIME scored significantly better than primary care physicians on pretty much every metric. (This google blog post is the best summary)

This is not especially surprising; one of AI's most famous early achievements was getting very good at predicting the 5-year survival chances for heart disease patients. One analysis I read of that study said that maybe AI did better because it was focused only on quantifiable data, whereas the human physicians were distracted by other factors. Anyway, results like this have been around for twenty years.

In the current study, the investigators took a standard LLM and trained it using transcripts of recorded doctor-patient conversations. But just as chess programs learn by playing against themselves, AIME honed its skills via "a novel self-play based simulated diagnostic dialogue environment with automated feedback mechanisms to enrich and accelerate its learning process." That is, the AI simulated both the doctor and the patient, holding thousands of conversations with itself.

The investigators then had a bunch of physicians hold conversations with patients via texting, with no face-to-face interactions, while AIME had similar conversations with other patients. The physicians and AIME both then issued diagnoses. Both the conversations and the diagnoses were then evaluated by "specialist physicians" who scored them for quality and accuracy without knowing which were human doctors and which were AIs.

Two things to note about this are that 1) the physicians did not have face-to-face interactions with the patients, which at least some doctors think makes a big difference (which is why telemedicine is controversial), and 2) the scoring was still done by humans. Since we have other data (from the cardiology studies) showing that in some cases AI can be better than any human, that is a limitation on the accuracy of the whole study.

In another note, some people think the future will be doctors using AI assistants, but Google has data showing the AIME is more accurate than a doctors/AI combo.

Google tries to soften the blow by saying this is all about supplying medical expertise in parts of the world where doctors are in short supply, but I think this points to a vast array of professions in which AI already is or soon will be better than people.

I, for one, would be happy to see investment bankers be entirely replaced by machines.

Major Meta-Study on the Health Effects of Cannabis

Summary of findings, with a lot of the references and numbers removed:

Results: 101 meta-analyses were included. From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system, psychological effects, and vision in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others. (GRADE=moderate).

Cannabidiol improved 50% reduction of seizures and seizure events (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate).

For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress.

For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate).

In the general population, cannabis worsened positive psychotic symptoms and total psychiatric symptoms (GRADE=high), negative psychotic symptoms, and cognition (GRADE=moderate).

In healthy people, cannabinoids improved pain threshold, unpleasantness (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (GRADE=high).

For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate).

For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (GRADE=moderate).

Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate).

Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age, low birth weight; in drivers, car crash; and in the general population, psychosis. 

Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).

Conclusions Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.

Other than the rather remarkable effect on seizures and a modest effect on nausea (n.b., we have much better anti-nausea drugs), I think pretty much all the positive findings here can be explained by the simple fact that people like being high. This study also adds to the data showing that long-term cannabis use is dangerous for your mental health, although possibly not any more dangerous than whiskey.

Meanwhile, at the Memory Disorder Unit

The Memory Disorder Unit in Massachusetts is “the federal prison system’s first purpose-built facility for incarcerated people with dementia.” Katie Engelhart in the NY Times:

There is a prisoner who thinks he is a warden. “I’m the boss. I’m going to fire you,” Victor Orena, who is 89, will tell the prison staff.

On some days, Mr. Orena is studiously aloof — as if he is simply too busy or important to deal with anybody else. On other days, he orders everyone around in an overwrought mafioso tone: a version of the voice that, perhaps, he used when he was a working New York City mob boss decades ago, browbeating members of his notorious crime family. This makes the real prison warden laugh.

On a recent morning, Mr. Orena sat in his wheelchair beside a man with bloodshot eyes. I asked them if they knew where they were.

“This is a prison,” Mr. Orena said, brightly.

“Why are you here?” I asked.

“I don’t remember,” he frowned. “I don’t know.” . . .

Down the hall from where Mr. Orena was sitting — past the activity room with the fish tank, where a cluster of men were watching “King Kong” on TV — there is a cell belonging to another man who wakes every day to discover anew that he is in prison. Some mornings, the man packs up his belongings and waits at the door. He explains that his mother is coming to get him.

“She sure is,” a staff member might say, before slowly leading him back to his cell.

Because of the long sentences we hand out to violent criminals, America now has thousands of very old men in prison, only a few of them in facilities that provide them any special care or treatment. Every time I read about this I get a feeling of the surreal; surely the long-term imprisonment of doddering old men in diapers is one of the weirder things going on in American today. Obviously these men can't just be released but I wonder how much more it costs to keep them in prison than in some other kind of facility.

"Walking naturally after spinal cord injury using a brain–spine interface"

Here's some truly amazing medical science:

A spinal cord injury interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis. Here, we restored this communication with a digital bridge between the brain and spinal cord that enabled an individual with chronic tetraplegia to stand and walk naturally in community settings. This brain–spine interface (BSI) consists of fully implanted recording and stimulation systems that establish a direct link between cortical signals and the analogue modulation of epidural electrical stimulation targeting the spinal cord regions involved in the production of walking. . . . The participant reports that the BSI enables natural control over the movements of his legs to stand, walk, climb stairs and even traverse complex terrains. Moreover, neurorehabilitation supported by the BSI improved neurological recovery. The participant regained the ability to walk with crutches overground even when the BSI was switched off. This digital bridge establishes a framework to restore natural control of movement after paralysis.

To back up a bit: Scientists, including the ones responsible for this work, had previously built similar systems to pick up signals within the spinal chord and transmit them past the damaged section to a receiver on the other side. But this never worked very well, and the subjects never felt like they were walking naturally.

So this time they implanted their sensors in the brain. Scientists had previously identified the precise brain regions that formulate instructions to the legs, and the article makes it sound like implanting electrodes to pick up signals there was no big deal. The impulses were converted to a digital signal and transmitted directly to receivers below the spinal damage, which converted them back into analog electrical stimulation of the lower spinal chord. This, they find, works far better than the old method, restoring at least one person to something like natural walking.

NY Times:

In a study published on Wednesday in the journal Nature, researchers in Switzerland described implants that provided a “digital bridge” between Mr. Oskam’s brain and his spinal cord, bypassing injured sections. The discovery allowed Mr. Oskam, 40, to stand, walk and ascend a steep ramp with only the assistance of a walker. More than a year after the implant was inserted, he has retained these abilities and has actually showed signs of neurological recovery, walking with crutches even when the implant was switched off.

“We’ve captured the thoughts of Gert-Jan, and translated these thoughts into a stimulation of the spinal cord to re-establish voluntary movement,” Grégoire Courtine, a spinal cord specialist at the Swiss Federal Institute of Technology, Lausanne, who helped lead the research, said at the press briefing.

Amazing. Even more amazing would be if such a system could restore control of the arms to people who have lost the use of all their limbs, and I can't think of any reason why that wouldn't be possible using this technology.

Scott Siskind on Psychosomatic Illness

Scott Siskind reported, based on his reader survey, that Long Covid seemed to be partly psychosomatic. This led to quite a discussion in his comments. Part of his reponse was this:

Almost all organic conditions have a psychosomatic shadow. Consider heart attacks. These are as organic as they come. But about a third of cases where people come into the emergency room with sudden-onset sharp chest pain are having a psychosomatic issue, usually a panic attack.

You’ll find the same thing across almost any condition. Seizures? Probably about 25% of them are psychosomatic. Headaches? These can be caused by a host of organic issues (brain cancer, meningitis, dehydration, etc) but also by stress. Leg paralysis? Can be caused by leg injuries or conversion disorder. Blindness? Psychosomatic blindness has fallen out of style these days, but used to be quite popular - the British commander in the Revolutionary War had it. Having insects crawling all over your body? Can be caused by insects crawling all over your body, or by delusional parasitosis.

If there were no organic cases of Long COVID, it would make COVID one of the only coronaviruses in its family not to have a postviral syndrome. But if there were no psychosomatic cases of Long COVID, it would make Long COVID maybe the only condition in history with zero psychosomatic shadow. So when responsible people have this discussion, they’re not asking “are any cases real?” or “are any cases psychosomatic?”. They’re asking what percent are in which category. People really want to root for “Team It’s All Psychosomatic, If You Say It’s Organic You’re Gullible” or “Team It’s All Organic, If You Say It’s Psychosomatic You’re A Monster”, but that’s not how any of this works.

There are links for all the claims at the original post.

But right now I am mainly wondering how I managed to read half a dozen books about the Revolutionary War without ever learning that Henry Clinton had repeated attacks of hysterical blindness.

Societal Pain

Since I was so irritated by the recent NY Times piece on "medical gaslighting," it seems fair that I should call attention to Nicholas Kristoff's excellent Times essay on chronic pain. Yo, journalists, this is how to write about mysterious medical conditions: with an open mind, and with your eye on the whole world that surrounds the sufferers, not just their own gripes about doctors. As one doctor tells Kristoff,

I believe pain is the most complex experience a human body can have.

These days Kristoff mainly writes about the woes of the working class, among which chronic pain looms large. As he says, pain plays a big part in many stories of addiction and downward spiral. Some people will tell you that the opiate crisis took off when doctors began prescribing opiates for chronic pain rather than just specific injuries, and of course self-medicating with dangerous drugs is how many addictions begin. Every close examination of "deaths of despair" finds chronic pain among the major factors.

To Kristoff, chronic pain is largely a socio-economic problem:

chronic pain is not just a result of car accidents and workplace injuries but is also linked to troubled childhoods, loneliness, job insecurity and a hundred other pressures on working families.

Some of this is very much class based; 

One study found that poor Americans are more than three times as likely to report pain as wealthy Americans. Another found that just 2 percent of those with graduate degrees report severe pain, while almost 10 percent of high school dropouts do.

But another factor is clearly youthful trauma. People who were sexually abused as children suffer much more chronic pain than others, as do people who were ever in foster care. Certain doctors have argued that in fact all chronic pain derives from trauma, but that is too simple and neo-Freudian for me, and I think also for Kristoff. But the connections in the data are too strong for this not to be a factor.

In that awful "Medical Gaslighting" piece the villains are doctors who won't take conditions seriously or recommend radical measures, but Kristoff finds many people who have received multiple unhelpful surgeries, like this woman who suffers from lifelong abdominal pain:

For a while, doctors thought it was irritable bowel syndrome. Then they said it was endometriosis, leading to surgery at the age of 20 and a full hysterectomy a year later.

None of that helped, and doctors later diagnosed interstitial cystitis, part of a spectrum called painful bladder syndrome. All of these diagnoses — irritable bowel syndrome, endometriosis and painful bladder syndrome — are commonly applied to people with chronic pain that is difficult to explain.

So what should we do? The bad news is that nothing works for everybody. The good news is that we have identified a menu of approaches that can help a lot of people. One of the doctors Kristoff spoke to says he always starts out by recommending more sleep and more exercise. (Of course insomnia is another part of the pain, depression and addiction cycle, so that advice is cruel for some people, but, again, this is a menu.) Other things that help some people include physical therapy, psychological counseling, meditation, yoga, acupuncture, psychedelic drugs, and masssage.

To me the most serious side of this problem is its connection to the broader ills of our society. Loneliness is strongly connected to chronic pain. Probably in that case the causality goes both ways, with loneliness causing suffering and pain keeping people from going out with friends. But to live within a supportive community seems to be the best rememdy for many of our ills, and we don't know how to achieve that. Economic insecurity is another major factor, and what to do about ever increasing inequality and the difficulty less educated people have finding steady work seem to be problems that are very hard to solve.

My philosophy of life might boil down to believing that everything is complicated. Everything major in life is probably more complicated than we can even imagine. And that is absolutely how I feel about chronic pain, except that I think I know one thing, which is that your simple explanation that pins everything on sexism or racism or capitalism is useless and wrong.

Against "Medical Gaslighting"

First, I am sick of the word "gaslighting." In the play and movie of that name, a wicked husband launched a concerted plan to convince his wife that she was insane. One used to see the word occasionally, used in exactly that sense: a plan to undermine somebody's grasp of reality. Now it just means "lying" or "being intentionally confusing," and another once interesting word drowns in the mass of trivial speech.

Second, it has become an article of faith in some quarters that doctors ignore women. There are bunches of studies that show this, several of which are cited in the recent NY Times piece, "Woman are Calling Out Medical Gaslighting." This piece does not mention that there are also bunches of studies that show the opposite, but they do exist. Pain is a big topic in all of this, but neither this article nor any other I have seen on this theme mentions that1) it is really difficult to measure pain, since the response varies so much from person to person, and 2) it is medical folk wisdom that men understate their pain for reasons of machismo, which is why doctors take men's complaints more seriously. Every doctor has a story about a man who had a knife blade in his abdomen or a broken leg but put off going to the doctor for months because the pain "wasn't that bad."

The target of the anger involved has also shifted. When there weren't many female doctors, people blamed the sexism of doctors. Now that there are plenty of female doctors, and this has had no effect on the torrent of women complaining that they are ignored, we blame the medical system: the way trials are set up, the way doctors are trained, the categories of insurance companies. Activists used to complain that many medical trials involved only men, which was true, because researchers were terrified of damaging the fetus of a woman who didn't know she was pregnant, and because hormonal cycles were a complicating factor. This led the US Congress, back in 1993, to pass a law requiring that most government-funded studies include women. So now they do, and this has had no effect at all on the number of women who think they have been ignored and misdiagnosed.

And maybe there is something to all of this. Doctors ignore and misdiagnose people all the time, and in fact regularly kill people with their mistakes. Because doctors' time is so expensive, the length of visits and consults keeps shrinking, meaning that many subtle problems will not be caught. But if you are measuring the effectiveness of our health care system in terms of outcomes, which I would say is the best way, it works great for women. In the US, women live six years longer than men and have lower death rates from almost every disease that both sexes can get.

What bothers me is that you are not allowed to say, you, know, the world is full of hypochondriacs, many of whom are women. In fact all the doctors I know will say that they waste huge amounts of time dealing with hypochondriacs, and that most of the ones they see are women. Plus, and this is important, all the patients who appear in these stories are pushing for more: more drugs, more surgery, more interventions of every sort. It goes unmentioned that maybe doctors should have a role in resisting this pressure, both because of cost and because unneeded medical interventions kill hundreds of people every year. A typical story goes like this:

Jenneh Rishe could easily run six miles in under 45 minutes — until suddenly she couldn’t. In the spring of 2019, Mrs. Rishe, now 35, began finding her daily jogs a struggle.

Years earlier, she had been diagnosed with two congenital heart conditions that, she said, doctors told her would not affect her daily functioning. Yet she was getting worse: Intense chest pains woke her up at night, and she started using a wheelchair after passing out too many times.

Mrs. Rishe, who lives in Los Angeles, found a highly recommended cardiologist in the Midwest and flew there to see him. He immediately dismissed her symptoms, she said. “People who have these heart conditions aren’t this sick,” she remembers him saying. He prescribed a new heart medication, told her to exercise and sent her home.

Unsatisfied with her care, Mrs. Rishe saw yet another doctor, who ordered extensive tests that found her arteries were spasming from a lack of oxygen. “I was basically having mini-heart attacks, whenever I was having chest pain,” she said. Two months later, she had open-heart surgery to correct the problem, which she later learned may have saved her life.

Is that true? How would we know? Hundreds of thousands of Americans believed that heart bypass surgery saved their lives, until we got good studies showing that it has no effect. The truth is that heart bypass surgery probably killed several times as many people as it "saved." As one among tens of thousands of victims of overtreatment – I lost most of the hearing in my left ear because of unnecessary surgery I had as a child, besides the trauma involved in all those hospital visits and never being able to swim – I bristle whenever anyone suggests that our hospitals aren't cutting people open enough.

And just because Jenneh Rishe felt better after her surgery doesn't mean it helped her; the relationship between any medical intervention and improving health is complicated and uncertain, and this applies to surgery as well. Thousands of people think they were helped by surgical procedures that can be shown, statistically, to do the average patient no good.

There is also the problem, which I have written about several times, that people are insulted when a doctor suggests that their pain may be psychosomatic. But psychosomatic pain is very much a real thing, and there is no reason why anyone should be insulted by that diagnosis any more than one of "fibromyalgia." People feel dismissed, but that is the fault of their own prejudice, not anything to do with the medical system. All doctors understand this, and many studies have confirmed it; people who are depressed or upset about their lives or going through divorce or have lost their jobs often suffer from pain that has no obvious physical cause. Sometimes that pain is debiliating. What do people like Jenneh Rishe think doctors should do? Lie?

What happens in our medical system is this: tens of thousands of patients flow into clinics every day, complaining of their suffering. Some of them have problems that are easy to recognize and treat. But a very large number have problems that are complex and subtle. For a lucky few, a doctor recognizes this right away, most likely because he or she has recently seen another case just like it. But for most it means a dreary round of specialist visits and lab tests and people who sigh and scratch their heads, and frankly the people who do end up getting treated are mostly the ones who push hardest for somebody to do something. And even those, once they get treated, may never be cured; I know people who have been through this for years about their chronic pain, never finding a cause, never getting any help but steroids and painkillers that have side effects nearly as bad as their conditions.

We expect too much from medicine. If you think that our medical system should be able to cure everything that ails you and give you a life free of suffering, sorry, it doesn't work like that. If you think your doctor should have more time to listen to your complaints and think hard about all the strange conditions you might have, well, maybe. But how are you going to pay for that? And this is one thing about medicine that is not better in other parts of the world, at least the ones I know about; costs are kept down in Europe partly by limiting the interactions people have with doctors.

If you think that every woman whose complaints have been dismissed by a doctor as psychosomatic is a truth-telling victim of a sexist system, then you are in the grip of ideology. Somebody has been gaslighting you, and it isn't doctors.

CRISPR Therapy for Sickle-Cell Disease: Progress Report

The first patients with the dreaded sickle-cell gene were treated with gene editing therapy back in 2019. After three years, all 31 seem to be doing ok. (Articles on the therapy: here, here)

So what now? The treatment is very complex. It involves removing bone marrow from the patient, editing the DNA of the hemocytoblast cells that produce red blood cells, and putting billions of those cells back into the body. No information on the cost has yet been made public but it is surely in the millions of dollars. There are about 100,000 people in the US who have the condition, most of them black, many poor. That's a big burden for Medicaid and the rest of the insurance system.

And globally, most of the 20 million people with the condition live in Sub Saharan Africa. What happens when they start migrating to the US and Europe and applying for asylum on the basis that without this treatment they will die?

Other people question the treatment because nobody knows how long it will last. Hemocytoblasts don't live forever, and presumably the new ones the body makes will have the sickle cell gene. Can we afford to give people this treatment every decade?

CRISPR technology is advancing rapidly, so presumably the cost of the gene editing and cell cloning steps will come down. But bone marrow surgery is a mature technology and it is likely to remain very expensive. I suppose in the long run the solution will be to use gene editing to remove the faulty gene from the population, but then again I suppose that will have to wait on an effective vaccine for malaria. 

This is going to create a lot of ugly fights in years to come.

A thought comes to mind: the reason we don't have flying cars, as people like to ask, is that we are spending our resources helping people live longer, healthier lives.

Fllint's Water and Endless Outrage

Depressing:

This is very sad: Marc Edwards, the Virginia Tech professor who first exposed toxic levels of lead in the water supply of Flint, Michigan, was initially a hero to the Flint community. Thanks to him, Flint became the target of nationwide outrage, and steps were finally taken to reconnect Flint to the (safe) Detroit water supply. In less than a year, lead levels in Flint water had dropped to safe levels.

So what did Edwards do? Well, he’s a scientist, and just as he had honestly exposed Flint’s problems in the first place, he also continued to honestly report the results of the intervention. When the water was once again safe, he said so—and that turned him from a hero into a pariah.

We've been through this before with dangerous contaminants that you can't see, taste, or smell: once people become afraid of them, they find it very hard to let go of that fear. And in this strange political moment, anyone who finds a reason to be outraged absolutely refuses to let go of that. It's as if we horde our anger as our most valuable possession. By August 2016, Edwards was saying publicly that Flint's water was safe:

But that narrative contradicted the perspective of advocates and groups such as Water Defense, an environmental nonprofit started by actor Mark Ruffalo, which brought in its own expert to sample the water in Flint….Edwards’s tests continued to show that contaminant levels had dropped. In September 2017, his findings were in line with the state’s, showing lead levels within federal regulations….The state had been providing residents with bottled water for drinking, but Edwards maintained they could also drink out of the tap again if they used filters, and that unfiltered water was safe to bathe in.

….Some residents, however, heard something else in Edwards’s conclusions. Abel Delgado, a Flint resident and activist who signed the letter criticizing the professor, says that he and others felt betrayed when Edwards seemed to imply the crisis was over. The professor appeared to be “giving in to the narrative of the state, and not the narrative that Flint was facing,” he says….Lawrence Reynolds, a pediatrician in Flint and a member of Michigan Gov. Rick Snyder’s Flint Water Advisory Task Force, says Edwards was “irresponsible” to tell residents that they no longer had to worry about the water.

"Irresponsible" to report the findings of science. And let me tell you, they were testing the heck out of Flint's water by then.

But wait, it gets worse. While the amount of lead in Flint's water was in violation of US safety standards and at a level most experts consider unsafe, the amount of lead in the blood of Flint's children never got especially high. It was always lower than the average level in Detroit, for example, where the water is fine but there is all sort of lead in paint, soil, and other places. But now Flint is experiencing a rise in the number of students in special education, and the amount of disruptive behavior reported by special education teachers. Studies have not found any corrolation between the students being placed in special ed and their exposure to lead.

The scientists who studied this seem to be baffled, and they suggest that it was caused by a nocebo effect. (That's the opposition of placebo, that is, something you think will hurt you does hurt you.)

A nocebo effect is consistent with the trend of rising special education enrollment after the [Flint water crisis] was exposed. As a top news story of 2016, the crisis engendered negative psychological effects described by residents as “Flint fatigue,” and the surrounding international media coverage has continued for over five years with negative headlines. The news reports and their popularity on social media and negative perceptions of Flint community leaders and parents could have heightened negative expectations about the effects on children, who readily accept and act on information from those they trust.

So not only is all the alarm about water in Flint no longer necessary, it is actively harming children.

I suspect this is only one example of many harms done by our need to feel persecuted and angry about it.

Black Death News

Mass grave of plague victims in southern France, from 1720-1721

The bubonic plague is all over the history and archaeology web sites, because of some recent publications that claim to make major advances in our understanding. The new work is certainly interesting, so let's have a look at it.

First, as I already noted here, modern genetic research has confirmed that both the Black Death of 1346-1350 and Justinian's Plauge of 541-542 were infections of Yersinia pestis. Certain skeptics had expressed doubt about this ever since Yersinia pestis was first identified as the plague organism, but this is now close to 100% certain.

Also, there has been a lot of genetic work on the evolution of Yersinia pestis over time. The most recent thinking is that the organism has been around for at least 8,000 years. This fits with archaeological data suggesting plague infections in eastern Europe and Ukraine by 4,000 BC. One recent study found that the dangerous variant that caused Justinian's Plague and the Black Death emerged around 2600 BC in the Tian Shan Mountains of western China. There have also been further refinements in the study of the great plagues, as I will explain.

Plague lives most of the time in communal rodents, especially the kind that live in tunnels on open plains. It's oldest hosts seem to be marmots and ground squirrels of the Asian steppes. But after it crossed the Pacific to California during the Chinese plague outbreak of the 1890s it went native in North American prairie dogs, where it still lives, occasionally infecting Americans who spend too much time around wild prairie dogs, for whatever reason.

Citizens of Tournai bury plague victims, 1348

So why did the plague repeatedly break out of the marmot population and spread out of the steppes and into settled regions of China, Europe, and the Middle East? That is the big question. Plague can live for a while using rats or mice and humans as hosts, but this always seems to burn out after a time, with the disease eventually retreating back to the steppes. How does the disease jump, in a major way, from marmots to rats and people?

The two theories that have gotten the most play over the course of my lifetime have been the weather and geopolitics. 

Weather theories emphasize that the amount of land in central Asia wet enough for grain farming has changed over the centuries, expanding in wet eras and shrinking in dry eras. So if an area that had been too dry for farming, and was thus full of marmots, got wet enough to be plowed up, the disease-spreading fleas might jump from marmots to the mice and rats that live off grain, starting a cascading spread. This makes sense but not much has been done to refine the model, so far as I can tell because establishing the rainfall history of central Asia is extremely difficult.

The geopolitical theories focus on how likely it was that people, rats, and mice that had gotten the plague somewhere in central Asia would move into settled areas, bringing the plague with them. The big text here is Plagues and Peoples by William H. McNeill (1976) who argued that the two great plague episodes of western Europe happened because the whole steppes region was unified under great empires – the Huns in the 5th century, and the Mongols in the 13th – dramatically increasing the movement of people and their rodent friends across the region and into distant cities.

One problem with McNeill's theory is the timing; by 1346 when the Black Death got started, the Mongol Empire was already breaking up, so movement was more difficult than it had been back in the 1250s. But remember that most of the time, the plague is spread by flea bites, and maybe it just takes a while for it to become endemic in the rats and mice of a region and spread to the next region and so on. The theory fits quite well with the 19th-century Chinese plague, because in the second half of the 1800s the Chinese government was making a push to develop its desert areas in the west, for example by expanding irrigated farming, so there was probably a lot of movement between those areas and China's crowded cities.

One of the new articles getting attention is by British historian Peter Sarris; it was in Past & Present in 2021. Sarris showed that the genetic history of the several different strains of Yersinia pestis that had by then been identified in burials of the 6th century did not at all fit the narrative of Justinian's Plague that comes to us from Byzantine historians. The ancient narratives said that the plague appeared first in Egypt, spreading from there to Syria and thence to Constantinople. That would be very weird, since the plague has never been identified in wild African rodents, and McNeill dismissed that claim out of hand. The new evidence supports McNeill, since the most basal strain identified so far was found in burials in England. One plausible genetic tree has the plague beginning in central Europe in the mid 400s AD, that is, during the career of Attila the famous Hun. 

If confirmed, this is an important point: the disease seems to have entered the Roman world a full century before historians noted major outbreaks of plague. As to why it took so long to reach pandemic proportions, and why the pandemic then spread rapidly across areas that under this model may have recently been exposed to some level of plague, nobody knows. Anyway a model that has the plague starting in one city anywhere in the Mediterranean world and spreading from there appears to be dead.

The Mongol Siege of Baghdad

The other articles that have gotten a lot of attention are "The Four Black Deaths" by Miranda Green (2020) and "Plague and the Fall of Baghdad (1258)  by Green and Nahyan Fancy (2021). Fancy and Green argue that the Mongols brought the plague with them when they invaded Persia and the Middle East in the 1200s. They say they have Persian and Arab sources that describe the plague spreading with the Mongol armies, and that also describe shipments of grain brought into the Middle East from Central Asia. Persian historian al Shirazi wrote that after the Mongold captured Baghdad in 1258,

Emerging from their subterranean places of hiding, the few survivors saw Baghdad lying in complete ruin, its streets filled with the decaying and disfigured corpses of hundreds of thousands of the city’s former residents. . . all who survived the sword having died from the plague. 

Fancy and Green argue that the Mongol invasion led to Yersinia pestis getting established in the rats of Middle Eastern and Caucasian cities, and that

The fourteenth century plague outbreaks represent local spillover events out of the new plague reservoirs seeded by the military campaigns of the thirteenth century.

This is what the genetics of Yersinia pestis seem to be telling us: that both great plagues of western Europe somehow emerged from populations of the disease that had been established in the west a hundred years earlier. Thinking about the history of the Plague in Europe after 1350, this fits, since once the plague was established, Europe saw a bunch of local and regional plagues breaking out over and over for 350 years.

That still leaves me wondering what caused the two big plagues to break out in the first place, I mean, it takes a bit of gall to call the Black Death a "local spillover event." It must somehow be connected to the other unexplained thing about the plague, how it changes form. Most of the people who died in the Black Death were probably not bitten by fleas; apparently if enough people get the plague within a small area it begins to infect the lungs and becomes transmissable via airborn droplets, which we call Pneumonic Plague. If you get the plague this way, you get pneumonic plague, which is highly contagious, and the rapid spread gets going. This still happens around the world, often enough that the WHO is actively pursuing a vaccine. But how and why, we have no idea. And note that while pneumonic plague is far more contagious than bubonic, and epidemiologists think this is the only way to really have a plague pandemic, medieval writers on the plague all described lots of buboes (enormously swollen lymph nodes), which you only get with the flea-spread bubonic version.

One model of the big pandemics would be that the plague, long established as an endemic infection of rats and occasional infector of people, starts raging among the people and rats of a city and somehow makes the jump to the pneumonic form, which gets the real dying started, as well as the panicked flight that spreads the disease across the continent.

But that still leaves a whole lot to be explained.

One-Sentence Character Studies of Mass Shooters

The NY Times is running a long, sad feature that consists mostly of one-line statements made about mass shooters. A typical sample goes like this:

He was bankrupt and had liens on his property.
Eight killed and six injured in San Francisco on July 1, 1993

He was evicted and his wife and daughter left him.
Six killed and one injured in Paso Robles, Calif., on Nov. 8, 1992

His wages were being garnished for child support.
Four killed in Watkins Glen, N.Y., on Oct. 15, 1992

He began hearing voices and talked about committing violence.
Four killed and 10 injured in Olivehurst, Calif., on May 1, 1992

He lost his job and his water heater broke.
Five killed and one injured in Fort Lauderdale, Fla., on Feb. 9, 1996

He had schizophrenia and stopped taking his medication.
Five killed and three injured in Bronx, N.Y., on Dec. 19, 1995

He was upset about a performance evaluation at work.
Four killed in Los Angeles on July 19, 1995

He was fired and had sought help at a mental health clinic.
21 killed and 19 injured in San Ysidro, Calif., on July 18, 1984

He was upset that his wife had left him.
Six killed in College Station, Tex., on Oct. 11, 1983

He ranted in his classroom and was suspended from teaching.
Eight killed and three injured in Miami on Aug. 20, 1982

He was in a pay dispute with his employers.
Six killed and four injured in Grand Prairie, Tex., on Aug. 9, 1982

He became reclusive and avoided all social interactions.
Four killed and one injured in Coraopolis, Pa., on July 21, 1980

He began hoarding food and planning for the end of the world.
Five killed and 11 injured in Daingerfield, Tex., on June 22, 1980

He thought his family and co-workers were trying to poison him.
Four killed in Warwick, R.I., on June 17, 1978

The message of the authors is that most of these people were obviously risks to the community, but either nothing was done about them, or not enough, and they call for much more investment in community mental health care. Based on what I know, that seems to be true in some cases but not others. Hundreds of thousands of American men have their wages garnished for child support, and many are mad about it, but most never shoot anybody. Most people hoarding food for the coming collapse of civilization seem pretty harmless, too. Looking backward it is easy to say of many, "he was obviously headed for trouble and somebody should have stepped in," but without knowing the future that becomes very difficult, and in some cases you would have to look much more deeply than this to have any clue that a real crisis was coming.

The Opioid Conundrum

Pushing out opioids leads to abuse, but curtailing them has its own problems (NY Times):

Anne Fuqua keeps a list of suicide deaths. She’s chronicled hundreds of cases of chronic pain sufferers who have killed themselves after losing access to opioid medication since 2014. Recently, she almost became an entry.

Ms. Fuqua, a former nurse, has an incurable genetic disorder that causes ‌agonizing spasms and shaking. She can only function when she takes opioids. She’s one of the estimated five million to eight million Americans with chronic pain who regularly rely on them. But in November, her doctor’s license to prescribe controlled substances was suspended by the Drug Enforcement Administration — marking the second time she’s been left to fend for herself to avoid pain and withdrawal because of law enforcement action against a pain clinic.

Between the mid-1990s and the early 2010s, the number of opioid prescriptions written for Americans roughly doubled, driven by dishonest pharmaceutical marketing campaigns and unscrupulous entrepreneurs who opened so-called pill mills to sell drugs. Medical guidelines, legislation, law enforcement and other measures have since returned painkiller prescribing to pre-crisis levels. But because people who lose access to medical opioids are rarely provided with immediate treatment (whether they are experiencing pain or addiction or both), the result has been more overdose and suicide deaths, not fewer.

I wrote here a few years ago about a case in which a man sued a doctor for prescribing the opioid pills that got his wife addicted and helped lead to her death. He was furious at the doctor, but one of the witnesses for the defense was the dead woman's mother, who said that she had been so crippled by pain that to have been given a few years of better life was a blessing even if the drugs eventually killed her. Opioids are bad for you, but so is chronic pain.

The US government recently reduced the amount of opioids that pharmaceutical companies are allowed to produce by 5%, and there are reports of shortages and people not being able to get their prescriptions filled. It is of course possible that some of these people would be better off cutting back on pills and pursuing other approaches to pain management, but randomly cutting 5% off cold turkey seems like a cruel way to run the experiment.

I don't think anything about chronic pain or opioids is simple, and I get irritated with people who want to blame everything on evil pharmaceutical companies. As I have written before, I have a sense that our struggle with chronic pain has strong psychological and sociological components, but I don't see how "let's build a better, less lonely world" is much of a policy. People are suffering, and every effort we make to reduce addiction means some people are not treated for pain. Many of them turn to illegal suppliers, which is one reason for the spike in Fentanyl deaths. 

Finding the balance is hard.

Back Pain and the Mind-Body Problem

From the NY Times, here's another testimonial to the curative power of John Sarno's psychological approach to back pain:

For more than a decade, I had a near-constant throbbing in my left piriformis, a small muscle deep in the butt. I tried treating it with physical therapy, ultrasound and Botox injections. At one point, I even considered surgery to cut the muscle in half in order to decompress the sciatic nerve that runs underneath.

Then, in 2011, I picked up a library copy of the 1991 best seller “Healing Back Pain: The Mind-Body Connection.” It claimed that, in order to distract the sufferer from repressed anxiety, anger or feelings of inferiority, the brain creates pain in the neck, shoulders, back and butt by decreasing blood flow to the muscles and nerves.

The book’s author, Dr. John Sarno, was a rehabilitation physician at New York University and something of an evangelist, touting a methodology bolstered by anecdotes from his practice and passionate testimonials from patients like Howard Stern or Larry David, who described his recovery from back pain as “the closest thing that I’ve ever had in my life to a religious experience.”

According to Dr. Sarno, nearly all chronic pain is caused by repressed emotions. By undergoing psychotherapy or journaling about them, he said, you could drag them out of your unconscious — and cure yourself without drugs, surgery or special exercises. I chose journaling and began writing pages-long lists of everything I was angry, insecure or worried about.

I appreciated the tidy logic of Dr. Sarno’s theory: emotional pain causes physical pain. And I liked the reassurance it gave me that even though my pain didn’t stem from a wonky gait or my sleeping position, it was real. I didn’t like that no one in the medical community seemed to side with Dr. Sarno, or that he had no studies to back up his program.

But I couldn’t deny it worked for me. After exorcising a diary’s worth of negative feelings over four months, I was — in spite of my incredulousness — cured.

Of course this doesn't mean Sarno's method really cured our author; believing that if you get better, the last thing you tried must have cured you, is medieval medical thinking. Sometimes chronic conditions get better on their own.

But then this is equally true of surgery. As I have mentioned here before, I have two acquaintances who swear that disk repair surgery magically cured them from years of terrible back pain. But since large-scale studies show that, on average, disk repair surgery does little good, who knows?

Back pain is really complicated. It is much more common among people who have experienced a trauma in their lives like divorce or job loss. It is more common in economically depressed areas. And yet it strikes some happy people whose lives seem as good as anyone else's. It is, as some people say, a "bio-social-psychological" condition.

But to deny that pain has a psychological component, to believe that even mentioning psychological factors is some kind of insult, is unhelpful. Our brains are part of our bodies, exquisitely connected to every other part of us, bound together in ways that sometimes mystify us but are very much real.

Omicron and Anime

The Omicron variant was already spreading in the US before it even had a name; public health officials have confirmed multiple cases contracted in November. At least two of them may be associated with a big convention called Anime NYC, attended by 53,000 people November 19-21. This isn't confirmed, but New York is trying to call or email everyone who attended, urging them to get tested.

The urge to resume pre-pandemic life is overwhelming, but it looks like the virus is not through with us yet.

Scott Siskind on Ivermectin

Scott Siskind has a long post on Ivermectin that I find fascinating and important. The basic story is this:

Early in the Covid pandemic, doctors and hospitals around the world tried all sorts of treatments, and when one of them seemed promising, many tried running small experimental trials. This was, I think, a very impressive expression of the extent of scientific prowess in the world, as hospitals from Bangladesh to Colombia experimented with different treatment regimens and published their results. Of course most of those trials were not very good, because they were necessarily small and conducted in the midst of a pandemic that was stretching hospitals to their limits. But people tried.

One finding that emerged from those trials was that Ivermectin, a common treatment for roundworm and other parasites, seemed to have a positive effect against Covid-19. Siskind goes through all of these trials and finds that while a few were fraudulent and most were bad, some were pretty good, really as good as one could expect under the circumstances. The three best to show positive results were from Bangladesh, India, and Colombia.

So word started to circulate on the Internet that Ivermectin was an effective treatment for Covid-19. The WHO and the US CDC denounced this and said it was nonsense, but they did not offer any rebutting evidence beyond "that's a treatment for worms, why would it effect a virus?" Neither the WHO nor the CDC was exactly covering itself with glory back then, what with the reversals over masking and quarantines and so on. So around the world people started dosing themselves with Ivermectin against Covid.

Here's the first important question: what does it mean to "trust the science"? Does that mean "listen to the CDC", which had already reversed itself on every important Covid-related question? Or does it mean "believe these two dozen studies from around the world that show Ivermectin is effective"? Another factor that played into this, in the US, was suspicion of pharmaceutical companies, everybody suspecting that they wanted Ivermectin downplayed because it is off-patent and very cheap. If you pretended to own a horse you could even get it without a prescription. This was a case where if you "did your own research", early in the pandemic, you would genuinely have found that the large majority of the available studies flatly contradicted the advice that the CDC and the WHO were giving.

This stirred the western medical establishment to investigate, and this summer we got the results of two larger, more rigorous trials, one in Canada and one in Argentina, that found no effect. But by that point belief in the efficacy of Ivermectin was already entrenched in the folk culture and the debate over it had become a political mud-slinging match.

Science is hard, and when it become tangled with politics it gets even harder.  People believe in a vast number of questionable medical practices partly because the establishment is wrong all the time, and because, occasionally, offbeat remedies really do outperform what the establishment doctors are pushing. Slogans like "trust the science" just don't capture the complexity of the world. If you want a serious look at that complexity, read Siskind's post.

_________

Incidentally, if you are wondering why those studies about Ivermectin found positive effects, look at where they were carried out: Bangladesh, India, and Colombia, all countries where roundworms are a serious problem. If you get really sick with Covid-19 they give you steroids to depress parts of your immune system. If you happen to be infected with roundworms or some other parasite, that can cause them to explode, giving you a "hyperinfection" that can kill you. If you dig deep enough into obscure parts of the Covid-19 guidance provided by the WHO you find that they actually recommend giving Covid patients with roundworm infections Ivermectin to prevent this. So co-infection with worms might explain why Ivermectin seems to help in the tropics but not in Canada or Argentina.

Glial Cells, Chronic Pain, and the Weird Obsession with Physical Causes

According to the people who count up stuff like this, more than a billion people around the world suffer chronic pain. "Chronic pain" here means pain that is either unrelated to obvious physical injury or lasts long after the obvious damage has healed, and that lasts at least two months. Chronic pain is a slow-moving medical catastrophe and also big business, which explains why there have been a ton of studies about what causes it.

Today's NY Times has a story about the role of glial cells in pain. One the one hand it is interesting biomedically, as we figure out that the cells we used to think just served as scaffolding for neurons actually do a lot of other stuff. One the other it suffers from the weird obsession with proving that chronic pain has some identifiable physical cause and is not just "in your head." Like this:

For pain sufferers, this is a welcome validation of their reality. “Learning this,” said Cindy Steinberg, the national director of policy and advocacy at the U.S. Pain Foundation, and a chronic pain patient herself, “is enormously helpful to those of us who suffer chronic pain.” In a chronic-pain support group Ms. Steinberg runs, she said that people find it a huge affirmation to learn there’s a distinct biology underlying their pain. It confirms what they’ve long known but often see doubted by doctors and friends: That their pain is as real as any other.

To which I say, there is no such thing as "unreal" pain. Every thought you have, every feeling no matter how fleeting, is something physical happening in your brain. What else could it be? If your pain were caused by obsessing about how cruelly your mother treated you, that would still be a physical thing, and if glial cells are involved in processing pain, then they would be involved in that pain, too.

On the other hand, even pain with overtly physical causes like stab wounds is also a psychological phenomenon, and some people can control it by modulating their thoughts. Remember that some studies have found petting a dog or cat reduces the sensation of pain more than powerful opiates do. Just as there is no pain that is not physical, there is no pain that is not psychological, because you experience it in your mind.

Very good studies have shown that chronic pain is more likely to strike people who have other stressors in their lives, like a divorce or losing a job. This includes both pain that seems to have an overt physical cause like a ruptured spinal disc and pain that does not. The notion that chronic pain could be entirely caused by some problem with glial cells strikes me as absurd; it is easy to show that for many people it is a symptom of a life out of whack. Which, again, does mean that it is not physical, because everything in your mind is physical, or that it could simply be wished away.

At a theoretical level we have understood the complex connections between mind and body at least since Hippocrates. But people keep acting like they are completely separate things, and newspapers where people ought to know better keep publishing stories about entirely imaginary distinctions between things in your mind and things going on with your nerve cells.

US Covid-19 Case Rate vs. Population Density

Above, average daily number of Covid-19 cases diagnosed last month per 100,000 inhabitants; below, population density. The extent to which these are mirror images is quite remarkable. I suppose that's partly because places like New York and Los Angeles had many more cases in the first wave. But you have to think that given how spread out people are in most of Alaska, even a little bit of caution could easily have given them the lowest rate.

TMS, Autism, and Depression

In an interview at The Cut, John Elder Robinson claims that transcranial magnetic stimulation, or TMS, caused him to "wake up" from autism; among other things he was suddenly able to feel, viscerally, the power of angry insults, and the beauty of a pair of eyes. 

I left the hospital figuring nothing had happened: I was thinking to myself, What kind of crazy fool was I to think that I was gonna do this TMS and suddenly the world was gonna change? But then I got in the car to go home, and I turned on my iPod and it just hit me that the music was real and alive. It had a power and clarity I hadn’t experienced before, and I started thinking about who the song was written for and what it was about. . . . The next day at work I looked at one of my colleagues and I thought to myself: He has the most beautiful brown eyes. That’s the type of thought I simply do not have. I don’t usually have any comment on your eyes because I don’t look in anyone’s eyes. For me to look in your eyes and say that they are beautiful is totally out of character. When I got to work I walked into the waiting room, as I usually do, and I looked at everyone and there was this flood of emotion. I could see it all: They were scared and anxious and eager, and never in my life had I seen something like that. I had to step out of the room because I didn’t know how to cope. It felt like ESP.

The interview is impressive enough that I spent some time reading about TMS. Here's a quick description:

TMS is a noninvasive procedure that uses magnetic pulses to stimulate nerve cells in the brain. During treatment, a coil is placed against the patient’s scalp and the TMS energy passes through the skull into the outermost layer of the brain. While the idea of electrical brain stimulation has been around for centuries, early techniques involved inserting actual wires — a dangerous and risky procedure. Noninvasive stimulation via electromagnetic energy is much newer — the first successful experimental use took place in the ‘80s. Since then, it’s evolved into a powerful tool for neuroscientists. It’s also a therapeutic tool for stroke recovery, depression, and anxiety relief.

Various claims have been made over the past few years that it can "cure" autism. Better studies, alas, have not confirmed this. What is really driving interest in the therapy is not a desire to eliminate autism, but to treat depression in autistic patients. I did not know until yesterday that high-functioning autistic people suffer much more depression than others, with some studies finding rates as high as 50%. SSRIs don't seem to work very well, because they mainly to make autistic people irritable.

Here's a summary of a recent major study:

In a pilot study in adults with autism and depression, transcranial magnetic stimulation, or TMS, was effective in reducing depressive symptoms and had some effects on autistic symptoms, report researchers at the Medical University of South Carolina in Autism Research. This study suggests that TMS warrants further study as a potential treatment for adults with both depression and autism.

This has me wondering about how autism and depression might be connected; both seem to flatten the emotional world. Since the medical literature I can find isn't very encouraging about TMS as a "cure" for autism, could it be that what really happened to Robinson was a lifting of depression? On the other hand his description of being suddenly overwhelmed by other people's emotions doesn't fit that very well.

Fascinating, whatever is really going on.

Sensitives

This is from an review of The Sensitives by Oliver Broudy in the January 29 TLS:

Brian Welsh is the sort of American who, in his previous life, could have stood in for a great many people. Growing up in the American Midwest, he was a well-liked extrovert in high school. He worked in a lumber yard, and then as a medical technician. He married. He lived in a modest house. He was full of easy raillery. Later, he would say that he hadn't been a particularly empathetic sort of person – other people's suffering didn't touch him – but at the time it didn't much matter. His life worked – until it didn't. From one day to the next, or so it seemed in retrospect, he was blown out of that life by the onset of incomprehensible symptoms. It started with paint fumes fogging his brain and perfume setting his heart racing. Soon after, he could no longer tolerate certain foods and the list kept getting longer. He was perpetually fatigued, and he felt himself disappearing into a rabbit hole full of invisible toxic threats. He had, in a sense, become allergic to the flesh of the modern world – to its solvents, powders, solutions, fuels, and fumes. he became fearful, even eccentric. His wife divorced him.

In his new book, Oliver Broudy describes Brian's "merciless humbling." Sensitivity to synthetic chemicals "stripped away everything" . . . now Brian lives alone in a high-altitude forest in Arizona, which as the most unadulterated air he could find.  

According to surveys, millions of people suffer from similar complaints, although mostly not as extreme as Brian's.

What are we to make of this?

These people are suffering, some of them horribly; many have lost their jobs, their marriages, their friends. But of what are they suffering?

"Synthetic chemicals" is just two words, not a real category. There is no conceivable mechanism that could make our immune systems respond to all human-made organic molecules, or even all complex hydrocarbons. The actual molecules have too little in common with each other for our exquisitely sensitive immune systems to be fooled in that way. Whatever is going on, I don't see how it could be what some of these people think it is.

And yet here we have people whose lives have been overthrown. Some of them seem like flakey hypochondriacs, but many do not. Many seem like ordinary enough people, no crazier than the rest of us, except for the debilitating reactions that are ruining their lives.

It seems to me that this has to have a psychological component; I can't imagine any biochemistry that could explain such a wide range of allergic responses. But I wonder if there is some sort of physical reaction that underlies many cases. Maybe some people become allergic to one chemical, or one class of chemicals, and since they can't pin down the exact cause they become suspicious of all chemicals, and so on in a self-destructive spiral.

I fear this sort of problem is becoming one of the hard realities of the modern world. We suffer much less from bacteria and viruses than our ancestors, and we can keep our hearts healthy enough that most of us live into our 80s. But millions of people suffer from vague immune-related complaints that we can't explain or treat, and thousands of lives have been ruined in ways that leave us baffled.

Life Expectancy

Interesting article by Steven Johnson in the New York Times about human life expectancy. Up until around 1750, average human life expectancy seems never to have cracked about 35 years. It often fell below that figure, due to disease or famine, but never rose above it. This was true for all classes of society; so far as we can tell (obviously the data sets are small) aristocrats had about the same life expectancy as peasants or slaves. That's because disease did not care about your status:

During the outbreak of 1711 alone, smallpox killed the Holy Roman emperor Joseph I; three siblings of the future Holy Roman emperor Francis I; and the heir to the French throne, the grand dauphin Louis.

Modern statisticians have noticed that this began to change in the 1700s. It changed first with aristocrats; historian T.H. Hollingsworth showed that by 1770 the life expectancy of British aristocrats had risen to 45 years. This change pointed the way to the modern demographic regime, in which everyone lives much longer but the rich live significantly longer than the poor. One factor singled out by Johnson is variolation, a sort of primitive inoculation that was used in many parts of Asia and brought to Britain from the Ottoman Empire in the 1720s. But since life expectancies in the Ottoman Empire and India were not above 35 and probably much less I'm not convinced; maybe variolation worked much better when administered by skilled and therefore expensive physicians. Jenner's vaccination technique, introduced in the 1790s, worked much better.

Anyway life expectancies in rural Europe continued to rise through the nineteenth century; one British statistician found that by 1843 it had reached 50 in mostly rural Surrey. But the overall life expectancy of Europeans rose more slowly, because of the dire situation in industrial cities. In 1843, again, life expectancy in Liverpool had fallen to 25. This had many causes, including pollution, cholera, and gin, but one singled out by contemporaries was bad food. Before refrigeration it was just very hard to get massive quantities of fresh food into dense urban neighborhoods without spoilage, so poor urban people were regularly eating dubious meat, cheese, fish, and especially milk. That's why Louis Pasteur got so famous; not for disproving the spontaneous generation of microbes but for making milk safer at a time when spoiled milk was sickening millions. If the poor tried to avoid such dangerous foods they ended up living on fried potatoes and beer, which is unhealthy in other ways.

And here we get to the part of the story that really interests Johnson. What reversed this trend and got urban life expectancies rising was not so much scientific advances, although those were important, but the great reforming social movements of the day. The crusade to make life healthier had many prongs: Temperance, regulation of the food chain, dietary guidelines, exercise (spread through the "muscular Christianity" Teddy Roosevelt espoused), the City Beautiful movement with its parks and tree plantings,  the construction of sewers, chlorination of drinking water, the paving of streets, the draining of swamps, the banning of dubious patent medicines: in a word, Progressivism. Taken together it worked, and by 1900 life expectancy was up to 50 for all the rich western nations and has continued to rise. 

The same is true for more recent health advances; penicillin was a fantastic discovery, but antibiotics only had an impact on our health because the US and then other governments spent billions to develop them, and the spread of health insurance made them affordable. The safety movement with its "intrusive" regulations has made cars, trains, and factory work much, much safer.

Johnson's article seems to be arguing against the straw man view that "science" made things better by itself, but nobody who knows any history thinks that. Modernity was always as much about organization as it was about science and technology. Steam locomotives were technologically amazing but they weren't much good without railroads, which were built using primitive hand-labor methods but made possible by modern political and business changes. Nineteenth-century sewers were no better than Roman sewers – in fact they were often worse – but they were built by the thousands of miles in every city, by politicians who cared about the health of their working class voters.

I sometimes say that modern Republicans are trying to bring back the Gilded Age, but it is important to remember that even the Gilded Age benefitted from a century of crusades for public improvement. Real Libertarians, and many Anarchists, want to go much farther back and strip away the protections our societies built up across the 1800s. They, and all the other people who want to smash things, should think harder about the precious legacy of caring for each other that we have built up, and on the fact that taken together these measures have doubled the length of our lives.