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Black death: how we solved the centuries-old mystery of its origins

The Black Death evolved around Kyrgyzstan, according to new research.

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Tombstones investigated in new research, most from 1338. P.-G. Borbone/Nature, Author provided

It is not an exaggeration to say that the question of where and when the Black Death, the deadliest pandemic ever, originated is one of the biggest mysteries in human history. After all, the Black Death was the first wave of the second plague pandemic of the 14th to early 19th centuries. It killed some 50-60% of the population in Europe, the Middle East and North Africa and an unaccountable number of people in Central Asia.

Different proposals, based on competing theories, have been put forward. But in 2017, I came across some records describing an intriguing medieval cemetery in Kara-Djigach, Chüy Valley, northern Kyrgyzstan, which I suspected may hold the key. As part of a multidisciplinary team co-led by Maria Spyrou at University of Tubingen, we have now investigated several specimens from individuals buried at that site – and come up with an answer.

The idea that the Black Death originated in the east – territories overlapping, roughly speaking, Central Asia, Mongolia and China – dates back to the contemporaries of the pandemic in Europe and the Islamic world. The modern, academic Chinese origin theory dates back to at least to in 1756-8 and a publication about the history of Central Asia by French scholar Joseph de Guignes.

Other plague historians see Central Asia in general, and the Tian-Shan region, a mountain area on the border between China and Kyrgyzstan, as the Black Death’s cradle. But some scholars have argued for alternative regions as diverse as northern Iraq, the Caucasus, Russia’s Volga, western Urals or western Siberia, the Gobi desert and India. One historian even suggested that the Black Death beginnings was associated with some unknown cosmic event.

Similarly, the chronological origins of the pandemic have been disputed too. In a 2013 study, a team of microbiologists identified a major evolutionary event in which the main plague lineage (Branch 0) mutated and split into four new plague lineages: Branches 1-4. Dubbed the “Great Polytomy” or “Big Bang”, the researchers found that this event created the strain (on Branch 1), associated with the Black Death. The research, which was based on probability computations, dated this event to a period between 1142 and 1339. They also inferred that Y. pestis – plague bacterium - may have originated in the Tibetan-Qinghai Plateau in Asia.

Drawing on this work, it has been suggested that that the pandemic may have spread widely in the 13th century, thanks to the expansion of the emerging Mongol Empire.

Genetics to the rescue

Without securely dated ancient DNA from Central Asia, however, the question would ultimately remain unsolved.

This changed when I came across records of the Kara-Djigach cemetary – excavated by the Russian archaeologist Nikolai Pantusov in 1885 and 1886 and analysed by the Russian scholar Daniel Chwolson (1819-1911). Of the total 467 stones, covering the period 1248-1345, 118 are dated to 1338 – a suspiciously large proportions of deaths. Most most of the stones have little detail about the person they commemorate, just bearing the names and death dates, but there are ten longer inscriptions from those years, stating “pestilence” (mawtānā in Syriac, the language of ancient Syria) as a cause of death.

It was intriguing. Not only that “pestilence” was mentioned, but that the associated tombstones were all dated to 1338-9 - just seven to eight years before the arrival of the Black Death in Crimea, and its subsequent spread all over west Eurasia and north Africa. I had a strong gut feeling about the likely connection.

We therefore decided to genetically sequence the remains from several specimens from these plague year burials, and managed to get results from the teeth of seven different individuals. Our analysis detected the presence of Y. pestis in three specimens, thus confirming that pestilence was indeed caused by this bacterium. We also noted that the strain (on Branch 0) seemed to have just preceded the Great Polytomy, out of which the Black Death strain emerged shortly after. The study therefore indicates that the Black Death commenced shortly after (or possibly even during) this 1338-9 outbreak.

Image of the Tian Shan region.
Tian Shan region. Lyazzat Musralina,, Author provided

Of course, there is nothing to suggest that that Kara-Djigach was the specific source of the pandemic. Rather, we believe that the disaster started somewhere in the wider Tian Shan area, perhaps not too far from that site. It is important to bear in mind that Y. pestis is a bacterium that lives among wild rodent populations. We often associate plague with rats. But in Tian Shan, the prevalent rodent carriers of plague are marmots. It is therefore likely that it was their colonies that were the ultimate source of the 1338-9 outbreak.

Importantly, ancient plague strains found today in marmot colonies in Tian Shan plague reservoirs are evolutionarily even older than the Kara-Djigach strain. Therefore, we conclude that the Kara-Djigach strain must have evolved locally in marmot colonies within the extended Tian Shan region, rather than being introduced into the Kara-Djigach community from some faraway origin. At some point, the bacteria simply crossed over to human inhabitants of the region.

The publication in question has ended the centuries-old debate regarding the spatio-temporal origins of the Black Death. But what else do we take from it? To understand the phenomenon of emerging epidemic diseases, it is essential to have a big evolutionary picture. It is important to see how these diseases develop evolutionary and historically, and avoid treating different strains as isolated phenomena. To understand how the diseases develop and get transmitted, it is also crucial to consider the environmental and socioeconomic contexts.

We also hope that our study will set an example to other historians and scientists that hope to answer such big questions – showing that a collaborative approach involving colleagues from different fields and bringing together different skills, methods, experiences and talents, is the future of historical and paleaogenetic research.

Philip Slavin does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Sex work is real work: Global COVID-19 recovery needs to include sex workers

Societally, we need to recognize that sex workers have agency and deserve the same respect, dignity and aid as any other person selling their labour.

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Globally, sex workers have been left to fend for themselves during the pandemic with little to no support from the government. (AP Photo/Bikas Das)

During the pandemic, business shifted from in person to work-from-home, which quickly became the new normal. However, it left many workers high and dry, especially those with less “socially acceptable” occupations.

The pandemic has adversely impacted sex workers globally and substantially increased the precariousness of their profession. And public health measures put in place made it almost impossible for sex workers to provide any in-person service.

Although many people depend on sex work for survival, its criminalization and policing stigmatizes sex workers.

Research shows that globally, sex workers have been left behind and in most cases excluded from government economic support initiatives and social policies. There needs to be an intersectional approach to global COVID-19 recovery that considers everyone’s lived realities. We propose policy recommendations that treat sex work as decent work and that centre around the lived experiences and rights of those in the profession.

Sex work and the pandemic

The United Nations Population Fund (UNFPA) recently reported that apart from income-loss, the pandemic has increased pre-existing inequalities for sex workers.

In a survey conducted in Eastern and Southern Africa, the UNFPA found that during the pandemic, 49 per cent of sex workers experienced police violence (including sexual violence) while 36 per cent reported arbitrary arrests. The same survey reported that more than 50 per cent of respondents experienced food and housing crises.

Lockdowns and border closures adversely impacted Thailand’s tourism industry which relies partially on the labour of sex workers.


Read more: Sex workers are criminalized and left without government support during the coronavirus pandemic


In the Asia Pacific, sex workers reported having limited access to contraceptives and lubricants along with reduced access to harm reduction resources. Lockdowns also disrupted STI or HIV testing services, limiting sex workers’ access to necessary healthcare.

In North America, sex workers have been excluded from the government’s recovery response. And many began offering online services to sustain themselves.

A woman stands backlit next to a dimly lit bus that reads 'Thailand' with green lighting.
Sex workers stand in a largely shut-down red light area in Bangkok, Thailand on March 26, 2020. (AP Photo/Gemunu Amarasinghe)

Government vs. community response

Globally, sex workers have been left to fend for themselves during the pandemic with little to no support from the government. But communities themselves have been rallying.

Elene Lam, founder of Butterfly, an Asian migrant sex organization in Canada, talks about the resilience of sex wokers during the pandemic.

She says organizations like the Canadian Alliance for Sex Work Law Reform are working in collaboration with Amnesty International to mobilize income support and resources to help sex workers in Canada.

Organizations in the United Kingdom, Germany, India and Spain have also set up emergency support funds. And some sex worker organizations have developed community-specific resources for providing services both in person and online during the pandemic.

Global recovery needs to include sex workers

The International Labour Organization’s “Decent Work Agenda” emphasizes productive employment and decent working conditions as being the driving force behind poverty reduction.

Sociologist Cecilia Benoit explains that sex work often becomes a “livelihood strategy” in the face of income and employment instability. She says that like other personal service workers, sex workers also should be able to practice without any interference or violence.

In order to have an inclusive COVID-19 recovery for all, governments need to work to extend social guarantees to sex workers — so far they haven’t.

As pandemic restrictions disappear, it is crucial to ensure that everyone involved in sex work is protected under the law and has access to accountability measures.

A woman stands wearing a mask with a safety vest on in front of a collage of scantily clad women and a sign that reads 'nude women non stop'
A volunteer helps out at Zanzibar strip club during a low-barrier vaccination clinic for sex workers in Toronto in June 2021. THE CANADIAN PRESS/Frank Gunn

Recommendations

As feminist researchers, we propose that sex work be brought under the broader agenda of decent work so that the people offering services are protected.

  1. Governments need to have a legal mandate for preventing sexual exploitation.

  2. Law enforcement staff need to be trained in better responding to the needs of sex workers. To intervene in and address situations of abuse or violence is critical to ensure workplace safety and harm reduction.

  3. Awareness and educational campaigns need to focus on destigmatizing sex work.

  4. Policy-makers need to incorporate intersectionality as a working principle in identifying and responding to the different axes of oppression and marginalization impacting LGBTQ+ and racialized sex workers.

  5. Engagement with sex workers and human rights organizations need to happen when designing aid support to ensure that an inclusive pathway for recovery is created.

  6. Globally, there needs to be a steady commitment towards destigmatizing sex workers and their services.

Despite the gradual waning of pandemic restrictions, sex workers continue to face the dual insecurity of social discrimination and loss of income support. Many are still finding it difficult to stay afloat and sustain themselves.

Societally, we need to recognize that sex workers have agency and deserve the same respect, dignity and aid as any other person selling their labour.

The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.

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OU researchers award two NSF pandemic prediction and prevention projects

Two groups of researchers at the University of Oklahoma have each received nearly $1 million grants from the National Science Foundation as part of its…

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Two groups of researchers at the University of Oklahoma have each received nearly $1 million grants from the National Science Foundation as part of its Predictive Intelligence for Pandemic Prevention initiative, which focuses on fundamental research and capabilities needed to tackle grand challenges in infectious disease pandemics through prediction and prevention.

Credit: Photo provided by the University of Oklahoma.

Two groups of researchers at the University of Oklahoma have each received nearly $1 million grants from the National Science Foundation as part of its Predictive Intelligence for Pandemic Prevention initiative, which focuses on fundamental research and capabilities needed to tackle grand challenges in infectious disease pandemics through prediction and prevention.

To date, researchers from 20 institutions nationwide were selected to receive an NSF PIPP Award. OU is the only university to receive two grants to the same institution.

“The next pandemic isn’t a question of ‘if,’ but ‘when,’” said OU Vice President for Research and Partnerships Tomás Díaz de la Rubia. “Research at the University of Oklahoma is going to help society be better prepared and responsive to future health challenges.”

Next-Generation Surveillance

David Ebert, Ph.D., professor of computer science and electrical and computer engineering in the Gallogly College of Engineering, is the principal investigator on one of the projects, which explores new ways of sharing, integrating and analyzing data using new and traditional data sources. Ebert is also the director of the Data Institute for Societal Challenges at OU, which applies OU expertise in data science, artificial intelligence, machine learning and data-enabled research to solving societal challenges.

While emerging pathogens can circulate among wild or domestic animals before crossing over to humans, the delayed response to the COVID-19 pandemic has highlighted the need for new early detection methods, more effective data management, and integration and information sharing between officials in both public and animal health.

Ebert’s team, composed of experts in data science, computer engineering, public health, veterinary sciences, microbiology and other areas, will look to examine data from multiple sources, such as veterinarians, agriculture, wastewater, health departments, and outpatient and inpatient clinics, to potentially build algorithms to detect the spread of signals from one source to another. The team will develop a comprehensive animal and public health surveillance, planning and response roadmap that can be tailored to the unique needs of communities.

“Integrating and developing new sources of data with existing data sources combined with new tools for detection, localization and response planning using a One Health approach could enable local and state public health partners to respond more quickly and effectively to reduce illness and death,” Ebert said. “This planning grant will develop proof-of-concept techniques and systems in partnership with local, state and regional public health officials and create a multistate partner network and design for a center to prevent the next pandemic.”

The Centers for Disease Control and Prevention describes One Health as an approach that bridges the interconnections between people, animals, plants and their shared environment to achieve optimal health outcomes.

Co-principal investigators on the project include Michael Wimberly, Ph.D., professor in the College of Atmospheric and Geographic Sciences; Jason Vogel, Ph.D., director of the Oklahoma Water Survey and professor in the Gallogly College of Engineering School of Civil Engineering and Environmental Science; Thirumalai Venkatesan, director of the Center for Quantum Research and Technology in the Dodge Family College of Arts and Sciences; and Aaron Wendelboe, Ph.D., professor in the Hudson College of Public Health at the OU Health Sciences Center.

Predicting and Preventing the Next Avian Influenza Pandemic

Several countries have experienced deadly outbreaks of avian influenza, commonly known as bird flu, that have resulted in the loss of billions of poultry, thousands of wild waterfowl and hundreds of humans. Researchers at the University of Oklahoma are taking a unique approach to predicting and preventing the next avian influenza pandemic.

Xiangming Xiao, Ph.D., professor in the Department of Microbiology and Plant Biology and director of the Center for Earth Observation and Modeling in the Dodge Family College of Arts and Sciences, is leading a project to assemble a multi-institutional team that will explore pathways for establishing an International Center for Avian Influenza Pandemic Prediction and Prevention.

The goal of the project is to incorporate and understand the status and major challenges of data, models and decision support tools for preventing pandemics. Researchers hope to identify future possible research and pathways that will help to strengthen and improve the capability and capacity to predict and prevent avian influenza pandemics.

“This grant is a milestone in our long-term effort for interdisciplinary and convergent research in the areas of One Health (human-animal-environment health) and big data science,” Xiao said. “This is an international project with geographical coverage from North America, Europe and Asia; thus, it will enable OU faculty and students to develop greater ability, capability, capacity and leaderships in prediction and prevention of global avian influenza pandemic.”

Other researchers on Xiao’s project include co-principal investigators A. Townsend Peterson, Ph.D., professor at the University of Kansas; Diann Prosser, Ph.D., research wildlife ecologist for the U.S. Geological Survey; and Richard Webby, Ph.D., director of the World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds with St. Jude Children’s Research Hospital. Wayne Marcus Getz, professor at the University of California, Berkeley, is also assisting on the project.

The National Science Foundation grant for Ebert’s research is set to end Jan. 31, 2024, while Xiao’s grant will end Dec. 31, 2023.


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Pfizer vaults into sickle cell market as GBT deal confirmed

Pfizer’s reported interest in acquiring sickle cell disease specialist Global Blood Therapeutics (GBT)  has been confirmed, with the
The post Pfizer…

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Pfizer’s reported interest in acquiring sickle cell disease specialist Global Blood Therapeutics (GBT)  has been confirmed, with the $68.50-per-share deal valuing GBT at $5.4 billion.

As we reported this morning, the deal gives Pfizer already-approved SCD therapy Oxbryta (voxelator) – which industry watchers reckon could see a dramatic uptick in sales with Pfizer’s marketing muscle – plus a phase 3 antibody candidate, a phase 1 follow-up to Oxbryta that could offer improved dosing.

Oxbryta is the main asset in the deal, with Evaluate predicting sales could reach $1.5 billion in 2028 – a leap forward from the $195 million it made last year and $127 million in the first half of 2022.

Pfizer is expecting big things from the takeover , predicting that the company’s SCD franchise will bring in combined peak sales of more than $3 billion.

The boards of both companies have recommended the deal to shareholders, and the two companies suggested it should close before the end of the year – assuming of course it doesn’t fall foul of any antitrust issues raised by financial regulators.

The GBT deal comes at a time when the market for SCD therapies is undergoing significant change, with multiple new drugs reaching the market after years of stagnation and progress also being made with genetic therapies from the likes of bluebird bio, Vertex Pharma/CRISPR Therapeutics and Precision Bio/Novartis.

Oxbryta came to market in 2019, a few days after Novartis’ injectable anti-P-selectin antibody Adakveo (crizanlizumab), which is also tipped for blockbuster sales but like Oxbryta has suffered from a slow rollout.

CRISPR Therapeutics and Vertex are also in the running with their gene-editing candidate CTX001, in phase 1/2 trials which are due to generate final results later this year. If those results are positive the partners have said they could file for approval in the US before year-end.

Meanwhile, bluebird bio’s one-time gene therapy  lovotibeglogene autotemcel is supposed to be heading for regulatory filing in the US next year, although it has been delayed by an FDA partial clinical hold implemented after a persistent case of anaemia was seen in one adolescent patient in a clinical trial.

GBT’s inclacumab – another P-selectin antibody that could encroach on Adakveo – is in a pair of phase 3 trials due to generate results next year.

Meanwhile, there are a couple of orally-active pyruvate kinase R activators from Forma Therapeutics and Agios – etavopivat and mitapivat, respectively – in mid-stage development, and Pfizer has its own SCD candidate in PF-07209326, an E-selectin anatomist in phase 1.

It’s worth noting that this isn’t Pfizer’s first deal in SCD. In 2011 it paid $340 million for rights to rivipansel, a pan-selectin antagonist developed by GlycoMimetics, which failed a phase 3 test in 2019 and was jettisoned by Pfizer the following year.

The deal is another example of Pfizer splashing out on business development thanks to windfall cash generated by its COVID-19 vaccine Comirnaty and oral antiviral therapy Paxlovid. It comes shortly after the group closed a $6.7 billion acquisition of Arena Pharma, bringing on board etrasimod in late-stage testing for ulcerative colitis, and made an $11.6 billion takeover bid for Biohaven and its migraine therapy Nurtec ODT (rimegepant).

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