u/Lonely_Lemur

Between Spring of 1951 and the armistice of July 1953, an unnamed disease infected UN soldiers among the ridge lines and rice paddies of central Korea. They’d begin presenting with sudden headaches, high fever, a spreading flush in the face and neck, and then days later having blood seep from the skin. The doctors in the Mobile Army Surgical Hospital (MASH) units had never seen anything like it, resorting to attempts of treatment using the likes of quinine and penicillin but nothing worked. Thankfully the disease wasn’t spreading from patient to patient. But that made the central question more unsettling: where was it coming from? The answer seemed to be the ground itself.

Eventually, the condition became known as Korean hemorrhagic fever, one of the illnesses now grouped under hemorrhagic fever with renal syndrome, or HFRS. Some 3000 UN soldiers were infected during the war with an estimated 150-300 having died of it. Exactly what killed them would remain a mystery for over 25 years until the isolation of the Hantaan virus (named after the river in Korea) in 1978. The first hantavirus outbreak recorded by western doctors is a story of a disease that hid in plain sight. The mouse carrying it likely seen thousands of times by soldiers as they stepped by them or kicked them aside without a second thought.

A Pre-Korean War Timeline

Obviously, the disease had a history before western doctors first encountered it. Since hantaviruses can be found in both New- and Old-World mammal species like mice, shrews, and bats, it is thought the viral family itself traces back millions of years. It’s also thought that Chinese medical literature from the year 960 contains descriptions consistent with hantavirus disease. It’s also been suggested as a possible cause for trench nephritis, a type of renal disorder encountered by soldiers during the American Civil War and during World War I. HFRS was observed in hospital in the Vladivostok region in WWI. There was also epidemic disease consistent with HFRS seen in both Russian and Japanese troops along the Manchurian-Soviet border; the linked citation also lists the incredible amount of names hemorrhagic fevers had attained by publication in 1963. It’s a hell of a list to say the least. They describe hemorrhagic fevers in “the northern belt, extending from the Soviet Far East and Korea, across Manchuria and Mongolia to the Urals, the Upper Volga, and Murrnansk Oblast; and on to the Scandinavian countries, Czechoslovakia, Hungary, and Bulgaria”. It’s fair to say hanta-derived hemorrhagic fevers were uncommon but far from an extreme rarity in Europe and Asia. Japanese Army doctors in WWII Manchuria would describe an epidemic of hemorrhagic fever among their troops with 10,000 said to have been affected and with a death rate up to 30%. Before 1951, Korea hadn’t been a hotbed of cases, with only a few cases described in the extreme northeastern corner of Korea by the Siberian/Manchurian borders with no recognized presence in central Korea.

Hantavirus in the Korean War

The Korean war officially got its start on June 25^(th), 1950, when the North invaded the South. From the summer of 1950 to Spring of 1951, the war would be a highly mobile one, with front lines moving dramatically up and down the peninsula. Until then, there hadn’t been any reports of hemorrhagic fevers in the American forces. By June of 1951 the frontline had stabilized near the 38^(th) parallel, with UN forces constructing bunkers, trenches, and fortifying positions across the central front in what became known as the “Iron Triangle” region (Cheorwon-Kimhwa-Pyonggang). The Yunchon and Cheorwon area seems to have been the center of where the first cases of hemorrhagic fever start popping up, soon spreading to Gimhwa and Pyonggang. It’s been proposed that HFRS may have been accidentally introduced through the Chinese army during the Korean War. A Time magazine article from the time reports at least 25 deaths with hundreds sick since June. In November of the same year, the Associated Press would report on the outbreak:

“A strange illness for which no sure cure has been found has broken out among United Nations forces in Korea, Gen. Ridgway’s headquarters said today. Brig. Gen. William E. Shambora, surgeon of the Far East Command, said the mysterious malady strikes suddenly and is characterized by fever and a headache... Sulfa and antibiotics have failed to stem the disease... The malady is strikingly similar to that reported by the Japanese among their Manchurian troops in 1939.”

By April of 1952 there was an established Hemorrhagic Fever Center near the heavy concentration by the 38^(th) parallel with all suspected cases being evacuated by helicopter. The 8228^(th) MASH unit in Seoul is designated specifically as a medical center for hemorrhagic fever and cold-related injury, receiving over 2000 admissions that year alone, the vast majority of which were from the Army. There patients would undergo strict management of fluids, nursing care in critical phases, special positioning to prevent hypotension, electrolyte monitoring, and later dialysis. The virologist and civilian researcher for the army Dr. Joseph Smadel led a team to Korea to study the outbreak, finding 46 deaths among the 848 diagnosed cases (a case fatality rate of 5.6). The same year would mark the start of the 7^(th) Infantry Division’s formal control program involving the dipping of clothing in miticide, spraying the quarters with lindane, and rodent control. These would be crucial during the seasonal peak periods of May-July and October-December. This is also around the same time that the 11^(th) Evacuation Hospital in Wonju would become notable for their use of “artificial kidney” or dialysis machines, which was one of the earliest uses of dialysis in wartime for combat medicine.

The scientific investigation into its HFRS’s cause would continue through the war, with the Armed Forces Epidemiological Board’s Commission on Hemorrhagic Fever being tasked with investigating the disease. They saved 600 sera samples taken from 245 patients for future analysis. The 1954 medical report by Dr. Sidney Katz formally characterized the disease as “Hemorrhagic Fever of the Far Eastern Type” using what was known from the Russian and Japanese literature of the time to reconcile what he had seen in the Korean War data from UN troops. Katz’s report listed more than 25 diseases that could mimic early KHF, including malaria, scrub typhus, leptospirosis, and other hemorrhagic fevers. Scrub typhus is of particular note because it is actually present in Korea. The suspected vector of transmission changed over time, with early opinions leaning toward chigger mites which carried scrub typhus (thus the miticide dipping of clothes) or airborne transmission from rodent droppings, but they couldn’t isolate an agent of spread. Endemic cases among U.S. would continue to be documented through 1972 by South Korean physician, virologist, and epidemiologist Ho Wang Lee, with over 2800 total cases being observed from 1951 to 1972.

Lee’s team started capturing rodents during the ceasefire line in the 70s, even contracting the disease himself and being arrested by the South Korean military on suspicion of being a spy. In 1976, In 1976, they used sera from Korean hemorrhagic fever patients to show the same antigen is found in the lungs and kidneys of the striped field mouse (Apodemus agrarius). In 1978 the virus would be formally isolated from a sample mouse taken near the Hantan River, naming it the Hantaan virus with the genus subsequently being named after the first isolated sample.

The taxa would be greatly expanded across the next couple of decades, first with Seoul virus (carried by the Norway rat Rattus norvegicus) found to be distributed worldwide. A strain of the Hantaan virus was grown in a cell culture and found via electron microscopy to belong to the Bunyaviridae family, however with a lack of arthropod vector it is unique in that specific family of viruses. Sin Nombre virus would be identified in 1993 as a cause of a severe pulmonary syndrome in the Four Corners region of the American Southwest. The Andes virus, cause of the current outbreak aboard the MV Hondius vessel, was isolated in 1995 and was the first to be found to spread from person-to-person.

Ecology and Transmission: How Warfare Changed Both

As mentioned, the reservoir for the Hantaan virus in Korea and China is the striped field mouse. It also happens to be the most common small mammal in all of Korea, representing over 90% of the captured small mammals at training sites near the DMZ. They’re found throughout rural areas due to the agricultural fields and nearby forests/hilly regions (exactly that of the central Korean front during the war. The fatter, male mice hold significantly higher antibody prevalence than the smaller females. The transmission route is primarily via the inhalation of aerosolized rodent excrement like dried urine, feces, or nesting material which easily make their way into the air during types of cleaning like sweeping. Unlike the New World Andes virus, the variants found in Korea have no person-to-person transmission, a trait that complicated reasoning by early epidemiologists about why the disease wasn’t “catching.”

An aspect of the war itself that seems to have been crucial to an outbreak like was seen is the fact that in summer of 1951 the Korean War shifted from a mobile phase into static trench warfare. Digging into the hillsides to construct bunkers and trenches meant disturbing the soil, creating new rodent habitat, and would’ve produced the aerosolized dust that transmits the viral particles. Veterans recalled rats “nearly as big as cats” having been their “daily companions” through this period of the war. They were so prominent in the fortified positions because of the deforestation that was occurring as a result of bombing and deliberate land clearing which concentrated the mice in the remaining habitats near the bunkers and agricultural areas.

It’s hard to directly quantify the impact relative to other diseases, but in 1953 disease as a whole accounted for over 40% of the hospital admissions among Korean War combatants with hemorrhagic fever being but one component of that broader infectious disease burden that included malaria, dysentery, scrub typhus, and various respiratory illnesses. The course of illness was about five-to-six weeks due to the lengthy recovery which could involve gaining back as much as 50 pounds lost during the illness. Hemorrhagic fever during the Korean War was a nightmare no soldier was prepared for. Command was somewhat lucky it only took as many lives as it did, because a more virulent strain may not have been as kind on the numbers and even less kind on morale.

Biological Warfare?

Public health and germ warfare during the Korean War, author unknown, ca. 1952 https://www.nlm.nih.gov/hmd/topics/chinese-posters/poster-politics_101559945-sm.html

I’ll end with a bit on something that came out of the confusion that goes hand-in-hand with the fog of war. I’m admittedly going to rely heavily on the wiki here as I haven’t read the multiple books on the topic yet. The Chinese and North Korean governments both claimed that in 1951 and 1952 the United States was using biological weapons, citing the hemorrhagic fever and other diseases taking hold in their troops. The Soviet Union even took these claims to the UN. There was a bit of a history to this, as in 1949 the Soviets had put out propaganda claiming the US was testing biological weapons on the Alaskan Inuit populations, with the Chinese even claiming the US was working with Shiro Ishii, a Japanese WWII General who focused on biological warfare in China. North Korea claimed the US was spreading smallpox as a form of biological warfare in North Korea. Mass demonstrations would take place in the USSR and its Eastern Bloc countries

The central evidence during the Korean War was the confession of one Colonel Franke Schwable. The captured Marine pilot stated in February of 1953 that B-29s had flown biological warfare missions based out of Okinawa starting in November of 1951. He was one of a few POWs who made similar statements. The U.S. would declare the statements made as a result of torture and upon release they did take back those claims (although under threat of a treason charge). These claims had an air of credibility to them as the US had concealed some of the atrocities committed by the Japanese Unit 731 led by the aforementioned General Ishii, who was exempted from war crimes and placed on the American payroll in exchange for data (Operation Paperclip wasn’t the only time we used the worst of the worst to work on our behalf). While there wasn’t any confirmatory evidence about Ishii working on Korean War operations on behalf of the US, the years of lying about the Unit 731 arrangement made it hard to deny.

The strongest bit of counter-evidence comes from Soviet and Chinese documents that were released in 1998 by Kathryn Weathersby and Milton Leitenberg who work on the Cold War International History Project. They included hand copied records from the Russian Presidential Archive with a statement from their secret police (NKVD) chief stating “”False plague regions were created, burials … were organized, measures were taken to receive the plague and cholera bacillus. The advisor of the MVD DPRK proposed to infect with the cholera and plague bacilli persons sentenced to execution.” North Korea had literally gotten plague cultures from China and infected a couple of prisoners, then using those tissue samples to claim to the international investigators that the US was engaging in biological warfare. The same documents note the disinformation campaign started to wind down after the death of Stalin in March of 1953. I don’t know enough to judge the claims on their merits, and the U.S. record on Unit 731 makes blanket innocence hard to take on trust. But the available Soviet and Chinese archival evidence strongly suggests that at least part of the Korean War biological warfare campaign was deliberately fabricated. That said, the evidence for and against these specific claims are wrapped up in multiple books, so I don’t quite have the full grasp on the claims. If enough people want a piece on that or US bio-warfare in general, I’d be happy to research further!

I definitely didn’t have a hantavirus outbreak on a cruise ship on my 2026 infectious disease bingo board, but at least I get to turn a previous paper from grad school into something possibly useful for the public . The MV Hondius is a Dutch-flagged polar exploration vessel currently floating in Cabo Verde, an archipelago sitting off the coast of Senegal and Gambia. The ship had started in Ushuaia, Argentina on March 20^(th), but as of today we have lab-confirmation of hantavirus in at least one individual. Three passengers are dead with a 69-year-old British man in intensive care in Johannesburg. The thing is, hantavirus on a cruise ship is genuinely unusual, so let’s go over what the underlying epidemiology says might be going on aboard that ship.

The first fatality on the Hondius was a 70-year-old man who died of hemorrhagic fever aboard the ship (EDIT: this may not have been true hemorrhagic fever but a hemorrhagic pulmonary syndrome and the two often get conflated and then parroted by people like me trying to also report on the topic, more information is needed); his wife was evacuated to Johannesburg where she passed as well. The third death happened on the vessel itself, but details are still a bit murky. Two additional symptomatic individuals have been identified as crew (we’ll get to what that might mean). We’ve got at least 6 people affected, three of whom are dead. While we’re still in the “denominator problem” stage of this outbreak, not knowing how many people have been infected just not as severely or completely asymptomatically, that corresponds to a 50% fatality rate among those who have experienced symptoms so far. I assume that number will shift toward the lower end as things get investigated and milder cases are identified.

The main question the outbreak is how the rodent-borne virus got on the cruise ship. Rats on ships is not a new problem with regards to infectious disease outbreaks with countless examples from history (The Black Death and The Justinian Plague coming to mind).

Hantaviruses are a group of viruses with members across the world within the Hantaviridae family found in rodent hosts. The viruses co-exist with their rodent populations without causing major health problems in their hosts. It is when spillover occurs into humans that they can lead to severe and often fatal diseases. People typically catch it through the inhalation of aerosolized particles from rodent urine, feces, or saliva, something not uncommon when cleaning a shed, sweeping a barn, or working in fields. So while a cruise ship isn’t exactly the exposure pattern one would first think of, it’s not that abnormal either. The ship left Patagonia, well within the range of the ANDV hanta-variant carrying long-tailed pygmy rice rat and other possible carrier species in the area. It wouldn’t be weird for a couple of rodents to scurry their way into the bottom levels of a cruise ship while supplies for the planned journey are being loaded. Once aboard, the enclosed, climate controlled environment becomes a nice place for spreading aerosolized viral particles that would then be found in storage areas, supply closets, ventilation ducks, and the service compartments below deck where rodents could go unnoticed. The additional symptomatic individuals being crew makes me think this could be the case, but I’d need to see more skew toward crew being infected vs passengers, which I don’t think is the case yet. However it got on board, people have been infected and viral sequencing is underway in the labs which should help clarify which specific hantavirus strain we’re dealing with here.

Here’s the part that really worries infectious disease researchers and medical professionals working in the realm of ANDV. Most hantaviruses can’t spread from person-to-person. The major exception seems to be ANDV, which can go from person-to-person through contact with infected bodily fluids, with transmission being most likely during the prodromal phase or shortly after that has ended. Mortality rates are estimated at between 40-50% and there’s no specific anti-viral treatment or vaccine for it, care being supportive in nature with oxygen, fluids, and ventilation for severe cases that advance to Hanta Pulmonary Syndrome.

So, if sequencing confirms ANDV the containment methods needed change pretty drastically with the need for respiratory isolation of cases, rigorous contact tracing of all 170 passengers and 70 crew, monitoring for secondary transmission chains, and the hopeful removal of future sources of aerosolized rodent excreta. If we find out it’s a different variant like the Seoul virus that brown rats carry, the risk of person-to-person contact is much more negligible. We’ll see what happens in the coming weeks.

What to watch out for

Over the coming days and weeks I’ll update as new information comes out. Some things to look out for will be the sequencing results to determine ANDV vs a less problematic strain. I’ll be curious to see if we see more cases among the crew popping up as well, given they work in the areas where rodent excrement would be found more often. I’m also wondering what the temporal distribution of cases looks like. I haven’t been able to find anything on that yet, but were they clustered closely in time or spread out across days to weeks (the 1-5 week incubation period makes this question much more difficult to answer as well). We’ll also see if the ship’s own investigation finds any evidence of the rodents themselves, either bodies, nests, or droppings; I assume this has to be a major focus.

Starting in 2025, a new fungal infection started spreading through cities in the United States that most clinicians hadn’t heard of. It looked enough like eczema and other skin irritations to be routinely misdiagnosed, which also gets worse when treated with a doctor’s first thought of steroidal creams. The outbreak of Trichophyton mentagrophytes genotype VII (TMVII, pronounced “TM seven”) in Minnesota is currently the largest cluster to date and it started making headlines a few months ago. This is my attempt to see what we know about this newly emerging sexually transmitted infection roughly a year into the outbreak. It’s gotten less headlines than the mpox outbreak a couple of years ago, likely because a) it’s not a “pox” virus and b) because the spread has been a bit more limited comparatively. That said, TMVII isn’t showing signs that it’ll be slowing down anytime soon and I think more people should be aware that this is out there, even if it’s uncommon in their specific community or demographic.

So what is TMVII?
TMVII is a type of dermatophyte fungus which are the family of fungi that cause things like athlete’s foot, jock itch, and ringworm. Fungi of the sort are identified in an interesting way, whereby researchers sequence what’s called the ‘internal transcribed spacer’ region in the ribosomal DNA. These are highly variable and are an incredibly helpful way for identifying species of fungi; they’re seen as the universal DNA barcode maker akin to a QR-code that spits out the species name (science rules). Given its relationship to other fungal diseases, it’s not totally novel in some sci-fi sense of the word but we did only recently characterize the specific variant that is spreading along this new transmission route.
One distinction is pretty crucial and it’s one that we should all be thankful for. The TMVII strain that is circulating is thankfully not the same one (Trichophyton indotineae) causing anti-fungal resistant dermatophytosis epidemics in South Asia to which terbinafine is next to useless. The CDC’s page notes that the TMVII strain is not generally antimicrobial resistant. That said, there was a case report in March of this year that described a confirmed terbinafine-resistant TMVII case in a heterosexual woman following an unprotected sexual encounter abroad in Turkey. She was successfully treated with the broad-spectrum itraconazole anti-fungal but we should be alarmed about this case that was resistant to first-line treatment. The bigger issue is that anyone with TMVII and T. indotineae circulating at the same time could cause more TMVII cases to acquire resistance (just noting a worrisome possibility, not a trend that has been seen in the wild).

Clinically, it presents as a scaly, inflammatory plaque that is painful and can be pustular as well as itchy. Reported cases have reported these most heavily in the genitals, skin around the anus, the butt, and the folds where the thighs meet the hips with some facial involvement also being common in MSM.
The timeline
We still don’t have the full timeline laid out perfectly here, but a few things seem to fit together. The first hint that this kind of thing might’ve been spreading came from surveys of Nigerian sex workers in the early 2000s who had been reporting cases of possibly dermatophyte driven infections. Sex workers and travelers who had sexual contact in Southeast Asia were some of the earlier cases reported. It seems to next pop up in a straight couple from Denmark (click that link at your own discretion. NSFW image in the paper) although it’s not quite clear where the man got it from as it’s not discussed in the manuscript. Cases continued in Europe through the 20-teens. The spread seems to have accelerated from March 2021 onward with notable clusters in Paris including one where a tantric massage practitioner had infected 15 of their clients and a roommate. By 2023 TMVII was being reported among men who have sex with men (MSMs) in France, Italy, Spain, Switzerland, and Japan.
The first confirmed U.S. case came in June of 2024 in a man reporting genital lesions who’d traveled through Europe and California having had multiple male sexual partners. California’s Department of Public Health issued a warning that same month around the same time as four more cases were found in New York City, all of which were MSM in the age bucket of 30-39, two of which were linked via contact tracing and one with no travel history at all. That combo suggested stealth early domestic transmission was already well underway. Then came the Minnesota outbreak, sitting at more than 30 total cases as of February. Seattle and & King County reported a case in late March. As of May, we see that established transmission is likely in multiple states across the nation and cases are likely being under-detected by quite a bit.
Transmission and who is most at risk
Just to get a bit of the reasoning for specific language out of the way, under the World Health Organization’s definition of an STI, TMVII is a sexually transmitted infection, as it is predominantly spread through sexual contact. The documented U.S. case series that have came out have identified MSM sexual contact as the dominant transmission route as well, with all of the NYC cases having meen MSM, the Minnesota outbreak occurring among MSM networks, and King County noting the outbreaks occurring “among gay, bisexual, and other MSMs.” The French cluster was the largest documented transmission chain and was also anchored largely in sexual networks. Non-sexual transmission routes do exist, but according to the data we do have, they’re the less common route. Of course they should still be mentioned: the spores can likely survive on surfaces and in clothes, linens, or towels, and skin-to-skin contact of a non-sexual nature could also facilitate the spread. Asymptomatic spread is suspected but still unconfirmed from what I could tell. Pre-symptomatic transmission is considered well within the range of possibility though based on the French outbreaks wide incubation range of 2-52 days, but we need direct evidence to say for certain. Based on the available data, MSMs and sex workers are likely at the highest risk.
Diagnosis and Treatment
In an outbreak like this, diagnosis is a bit of a bottleneck, as diagnosing TMVII requires sequencing that very specific ITS region mentioned earlier. That can’t be done at every clinical lab, so state public health labs or reference centers at the city, county, state, or university level are sent most of the samples. It’s treated with oral terbinafine currently but the issue is the duration of the typical prescription may not be long enough. A typical prescription for terbinafine for ring work is two weeks, but the Barcelona report noted a 0% cure rate with two weeks or less of treatment vs an 80% cure rate in the three to eight week treatment courses. The CDC and MDH currently recommend treatment until at least two weeks past a full resolution of symptoms (which typically looks like a six-to-eight week course).

Public Health Implications

There’s a fundamental surveillance problem with TMVII, as these types of dermatophyte infections aren’t generally “notifiable” in any U.S. state, meaning they don’t have the requirement of notification to the national system like coccidioidomycosis or Candida auris do. That’s a legacy of our surveillance systems being largely built around bacterial and viral STIs, leaving us with a denominator problem, no baseline incidence rates, and little mechanism for detecting clusters unless someone happens to recognize the unusual patterns as happened in NY and MN. Let’s hope our STI surveillance systems can keep up with the ever-changing world that is the infectious disease ecology of STIs.

While reading the new 2026 Reich Lab paper, one question came to mind: Did the changing disease and metabolic environments drive a major share of recent human selection in West Eurasian populations? The paper is currently the biggest ancient-genomics research study on natural selection in humans ever done (though sure to be outdone relatively quickly, as is always the case in ancient DNA research). With almost 16,000 genomes , more than 10,000 of them ancient, spanning the past 18,000 years in West Eurasia and the Middle East, they used purpose-built computational models that were designed to detect consistent directional trends in the frequency of alleles in the genome. Their technique identified 479 genetic loci that showed a greater than 99% probability of genuine directional selection (either positive, driving the prevalence upward, or negative, doing the opposite and driving it downward) along with an additional 7,600 loci with better-than-chance odds of being a real signal that need further investigation.

But it’s the biological content of the signals they found that should interest any epidemiologist, especially those of us who like history. A substantial fraction of the signals are related to health, with immune function, blood types, gut health, inflammatory responses, and body composition all having changed substantially. The data seem to show that the transition from hunting and gathering to farming and on through the Bronze Age created somewhat of a biological pressure cooker, with people being selected for the ability to survive radically changing disease and nutritional environments.

This post is what the data tells me as a historical epidemiologist. Given the fact that I’m not a trained geneticist, any errors are my own and I’d love them to be pointed out by someone who knows the field or the paper very well. I’ll also be very clear when I’m moving from exactly what the evidence tells us and into some healthy speculation of my own. Reconstructing those past selective pressures is an absolutely fascinating task, but we don’t have all of the evidence needed to be exact so I’ll try to approach that with care.

Their Method and Why This Paper is Different

It helps a bit to know what prior ancient DNA selection studies were doing and why they struggled to detect the kinds of effect this new paper found. A common approach to detecting natural selection is to look for what are called “sweeps” in present-day genomes, which are essentially stretches of DNA where a variant rose so quickly that it dragged along the surrounding variants with it. This leaves a recognizable pattern that implies a reduction of genetic diversity. That method works well for very strong selection pressures that push an allele to near fixation in a population, but they missed the more subtle directional pressures that rise over millennia and never fully “sweeping”, so to speak.

Lead author Ali Akbari developed a method that sidesteps that problem by using ancient DNA as a time series. That let them ask the question “did this allele show consistent directional trends across multiple time points in the past?” They also claim to control for population structure, which can be a huge confounder in genetics work. The different ancestral groups would have mixed at different times and in different amounts which could theoretically make neutral alleles look like they were selected for because they rode into town on some expanding population. (I really hope I got all that right).

What Changed and When

The key finding is that natural selection in the West Eurasian populations measured was accelerating over the past 18,000 years, with a clear inflection point during the Neolithic transition from mobile, small hunter-gatherer groups to being settled, grain-dependent farming communities that began to spread into Europe from the Anatolia region something like 9,000 years ago. There also seems to have been a second acceleration event during the Bronze Age about 5,000 years ago. In the Nature news post that accompanied the new paper, Reich noted that it was “an economically and culturally transformative time.” I’d add that it was also a time of drastically changing infectious disease landscape. Either way, both temporal locations of those transitions make sense as having intensified selection pressures.

The Neolithic created the first conditions for more sustained infectious disease transmission that previous small-band hunter-gatherer groups would’ve largely been avoiding through that lifestyle. That’s because being sedentary comes with waste accumulation where people lived. Grain storage would attract rodents and animal domestication brought us into sustained, intimate contact with pathogens coming from cows, camels, pigs, and birds. As population density rose, respiratory and enteric diseases start making themselves known. The evidence is in their bones; Neolithic farmers were relatively unhealthy, and likely so from a young age. They were almost four centimeters shorter than their Upper Paleolithic and Mesolithic ancestors after adjusting for a predictive polygenic height score. That tells us they likely were enduring high disease burdens combined with high levels of nutritional deficits.

The Bronze Age brought massive migrations from the Pontic-Caspian Steppe into Europe about 5,000 years ago and brought very genetically distinct populations into contact for the first time. They also brought a new pathogen pool that included an ancient strain of Yersinia pestis (plague). Long-distance trade networks intensified and settlements grew alongside the disease environment that too was growing in complexity and interconnectedness. The genomic record reflects all of that. Taken together, we have a couple of transitions that strongly suggest some of the most intense periods of human selection in Western Eurasia happened to coincide with moments of rapidly changing disease ecology.

The Signals

Blood Type B Arrives

Apparently, the allele that gives one type B blood in the ABO blood grouping system was basically absent in West Eurasia before 6,000 years ago. Since then, it has risen to a roughly 8% frequency. The different blood types carry different susceptibilities to specific pathogens with cholera, norovirus, some respiratory viruses, and others showing ABO-dependent susceptibility patterns. Mesolithic hunter-gatherers in Europe were predominantly type O, which is also likely the newest to have arisen roughly a million years ago (as we share A and B with other primates). While we don’t know what pathogen the main driver was here, the B allele apparently offered the carriers enough of a reproductive advantage in the post-Neolithic environment to become much more prevalent than it had previously been.

My Best Guess: Blood type B likely arose to that high of a prevalence because it conferred some sort of resistance to either an enteric or respiratory pathogen that suddenly became common once farming and animal husbandry had been adopted. The timing is consistent with when those new zoonotic exposures would’ve arisen combined with the gut infections that came with crowded settlements.

The Celiac Paradox

This one took some thinking for me, as it is a rather counterintuitive finding. The major genetic risk factor for celiac disease (a variant at HLA-DQ) went from about 0% to roughly 20% in 4,000 years during and after the spread of wheat farming across West Eurasia. Today celiac impacts somewhere around 80 million people across the globe and a common narrative is that celiac is an “evolutionary mismatch” with our ancient guts having difficulties with modern wheat, but the new data makes the story much more complicated.

My Best Guess: That’s because HLA-DQ, and other celiac risk loci, is a core immune-recognition molecule that is meant to present foreign peptides to T cells and then set up the appropriate defense response. The specific allele that today is related to celiac presumably spread because it was advantageous in a gut ecosystem full of novel bacteria, parasites, and viruses that had been introduced by grain farming and animal domestication. On that reading, celiac is a side effect of the same immune response that had helped our ancestors survive a terrible gut infection in an early Neolithic village. The HLA-DQ variant rose because of some strong selection due to gut pathogens that were new to the sedentary Neolithic communities.

TYK2 and Tuberculosis

An allele on the TYK2 gene in its homozygous form is the strongest predictor of clinically severe tuberculosis infection, so it’s interesting to know that it rose from something like 2% to 9% from 5,500 to 3,000 years ago and then fell back to about 3%. That implies shifting selection pressures with something first favoring the allele and then penalizing it later. The negative selection over the last 2,000 years was one of the largest selection effects documented in a common variant, having been associated with a fitness reduction in homozygotes by roughly 20%. It’s not hard to understand why it would have dropped off, as TB was an incredibly powerful selective force not too long ago.

The rise in the allele is the more puzzling aspect of this. The variant in question is known to have some protective effects against certain autoimmune conditions, as it seems to put a damper on the inflammatory signals in ways that reduce autoimmune pathologies. That raises the possibility that it was selected for during a period when inflammatory overreaction was more of a liability than TB was.

My Best Guess: This one is very speculative, but TYK2 can be seen as part of our immune system’s control system, something like the volume knob, as it helps to control how strongly the body responds when it senses an infection or some tissue damage. The variant appears to turn part of that response down, which could have been useful when an early farming community was hit by a new mix of gut infections, parasites, new animal microbes, contaminated water sources, and the chronic inflammation that came with that. In that type of world, some of the danger was coming from the body’s damaging reactions to such a rough disease environment in early village life.

CCR5 and Immune Pressures

The CCR5 deletion is the one you may have heard of which confers nearly complete resistance to HIV-1 infection and is unusually common in Europeans while absent nearly everywhere else. HIV having arisen during the 20th century tells us that something much much older must’ve been selecting for the CCR5-delta32 variant. The new paper identifies that allele as one of the main signals with another paper from last year giving us some more context. With over 900 ancient genomes ranging from the Mesolithic to the Viking Age, they found the oldest carriers of this mutation dating back more than 6,700 years in the Western Eurasian Steppe. It then underwent a strong positive selection between 8,000 and 2,000 years ago with most of that occurring in Easter hunter-gatherer and Caucasus hunter-gatherer groups before moving westward with the Bronze Age steppe migrations. That timeline rules out a somewhat popular idea that this allele arose during the Black Death.

My Best Guess: The most plausible candidates for selection pressure on this variant would be other pathogens that use the CCR5 receptor like various bacterial infections including Yersinia pestis in its earlier, less virulent form. This area is contested heavily though, so take my guess with caution.

Inflammation and Barrier Tissues

A companion preprint that came out the day before the new Reich paper gives us some of the mechanistic context needed to interpret the Akbari paper’s findings. They note that positively selected alleles across the genome were most commonly found in the immune cells that live in what are called barrier tissues. Those include things like the gut mucosa and the respiratory tract that are often the front lines of fighting off pathogens.

My best guess: Some of the positively selected alleles are associated with increases in the risk of intestinal inflammation and autoimmune hypothyroidism, but protective for things like asthma and dermatitis. New farming communities created an environment with contaminated food and water and new respiratory infections that could travel more easily through their crowded cities. This one is likely just evolutionary trade-offs.

Body Fat (and being cautious in science communication)

The paper notes a type of coordinated selection across multiple genetic loci that are related to the modern-day polygenic risk score for body fat percentage that decreased by about one standard deviation over 10,000 years. They note this as consistent with what is called the “Thrifty Gene Hypothesis” that claims predispositions toward energy storage that were advantageous in hunter-gatherers became deleterious in more sedentary farming communities. That interpretation makes sense but should be taken a bit cautiously, as the modern UK Biobank sample the polygenic score is created from could be different in important ways that make the interpretation more gray than black and white. A modern polygenic score for bodyfat could inadvertently also be tagging other genes related to appetite, insulin, puberty timing, energy use, inflammation, and more. So, while the signal is definitely real and genetic predisposition to store body decreased over the past 10,000 years, comparing it to a modern label needs a bit more caution than the height example we had earlier. Today many people likely have a much higher body fat than their polygenic score would predict (I say as an American living in an obesogenic environment).

My best guess: This reflects the changing energy sources after the transition to farming. Mobile hunter-gatherers likely had an advantage when able to store energy efficiently during seasonal shortages, droughts, or failed hunts but farming shifted the balance with the new diets heavy in starch, comparatively sedentary lifestyle, and infectious diseases. A decrease in propensity to store body fat makes sense in that scenario.