TOP SCEINCE
‘Bone biographies’ reveal lives of medieval England’s common people — and illuminate early benefits system
A series of ‘bone biographies’ created by a major research project tell the stories of medieval Cambridge residents as recorded on their skeletons, illuminating everyday lives during the era of Black Death and its aftermath.
University of Cambridge archaeologists analysed close to 500 skeletal remains excavated from burial grounds across the city, dating between the 11th and 15th centuries. Samples came from a range of digs dating back to the 1970s.
The latest techniques were used to investigate diets, DNA, activities, and bodily traumas of townsfolk, scholars, friars and merchants. Researchers focused on sixteen of the most revealing remains that are representative of various “social types.”
The full “osteobiographies” are available on a new website launched by the After the Plague project at Cambridge University.
“An osteobiography uses all available evidence to reconstruct an ancient person’s life,” said lead researcher Prof John Robb from Cambridge’s Department of Archaeology. “Our team used techniques familiar from studies such as Richard III’s skeleton, but this time to reveal details of unknown lives — people we would never learn about in any other way.”
“The importance of using osteobiography on ordinary folk rather than elites, who are documented in historical sources, is that they represent the majority of the population but are those that we know least about,” said After the Plague researcher Dr Sarah Inskip (now at University of Leicester).
The project used a statistical analysis of likely names drawn from written records of the period to give pseudonyms to the people studied.
“Journalists report anonymous sources using fictitious names. Death and time ensure anonymity for our sources, but we wanted to them to feel relatable,” said Robb.
Meet 92 (‘Wat’), who survived the plague, eventually dying as an older man with cancer in the city’s charitable hospital, and 335 (‘Anne’), whose life was beset by repeated injuries, leaving her to hobble on a shortened right leg.
Meet 730 (‘Edmund’), who suffered from leprosy but — contrary to stereotypes — lived among ordinary people, and was buried in a rare wooden coffin. And 522 (‘Eudes’), the poor boy who grew into a square-jawed friar with a hearty diet, living long despite painful gout.
Inside the medieval benefits system
The website coincides with a study from the team published in the journal Antiquity, which investigates the inhabitants of the hospital of St. John the Evangelist.
Founded around 1195, this institution helped the “poor and infirm,” housing a dozen or so inmates at any one time. It lasted for some 300 years before being replaced by St. John’s College in 1511. The site was excavated in 2010.
“Like all medieval towns, Cambridge was a sea of need,” said Robb. “A few of the luckier poor people got bed and board in the hospital for life. Selection criteria would have been a mix of material want, local politics, and spiritual merit.”
The study gives an inside look at how a “medieval benefits system” operated. “We know that lepers, pregnant women and the insane were prohibited, while piety was a must,” said Robb. Inmates were required to pray for the souls of hospital benefactors, to speed them through purgatory. “A hospital was a prayer factory.”
Molecular, bone and DNA data from over 400 remains in the hospital’s main cemetery shows inmates to be an inch shorter on average than townsfolk. They were more likely to die younger, and show signs of tuberculosis.
Inmates were more likely to bear traces on their bones of childhoods blighted by hunger and disease. However, they also had lower rates of bodily trauma, suggesting life in the hospital reduced physical hardship or risk.
Children buried in the hospital were small for their age by up to five years’ worth of growth. “Hospital children were probably orphans,” said Robb. Signs of anaemia and injury were common, and about a third had rib lesions denoting respiratory diseases such as TB.
As well as the long-term poor, up to eight hospital residents had isotope levels indicating a lower-quality diet in older age, and may be examples of the “shame-faced poor”: those fallen from comfort into destitution, perhaps after they became unable to work.
“Theological doctrines encouraged aid for the shame-faced poor, who threatened the moral order by showing that you could live virtuously and prosperously but still fall victim to twists of fortune,” said Robb.
The researchers suggest that the variety of people within the hospital — from orphans and pious scholars to the formerly prosperous — may have helped appeal to a range of donors.
Finding the university scholars
The researchers were also able to identify some skeletons as probably those of early university scholars. The clue was in the arm bones.
Almost all townsmen had asymmetric arm bones, with their right humerus (upper arm bone) built more strongly than their left one, reflecting tough working regimes, particularly in early adulthood.
However, about ten men from the hospital had symmetrical humeri, yet they had no signs of a poor upbringing, limited growth, or chronic illness. Most dated from the later 14th and 15th century.
“These men did not habitually do manual labour or craft, and they lived in good health with decent nutrition, normally to an older age. It seems likely they were early scholars of the University of Cambridge,” said Robb.
“University clerics did not have the novice-to-grave support of clergy in religious orders. Most scholars were supported by family money, earnings from teaching, or charitable patronage.
“Less well-off scholars risked poverty once illness or infirmity took hold. As the university grew, more scholars would have ended up in hospital cemeteries.”
Isotope work suggests the first Cambridge students came mainly from eastern England, with some from the dioceses of Lincoln and York.
Cambridge and the Black Death
Most remains for this study came from three sites. In addition to the Hospital, an overhaul of the University’s New Museums Site in 2015 yielded remains from a former Augustinian Friary, and the project also used skeletons excavated in the 1970s from the grounds of a medieval parish church: ‘All Saints by the Castle’.
The team laid out each skeleton to do an inventory, then took samples for radiocarbon dating and DNA analysis. “We had to keep track of hundreds of bone samples zooming all over the place,” said Robb
In 1348-9 the bubonic plague — Black Death — hit Cambridge, killing between 40-60% of the population. Most of the dead were buried in town cemeteries or plague pits such as one on Bene’t Street next to the former friary.
However, the team have used the World Health Organization’s methods of calculating “Disease Adjusted Life Years” — the years of human life and life quality a disease costs a population — to show that bubonic plague may have only come in tenth or twelfth on the risk rundown of serious health problems facing medieval Europeans.
“Everyday diseases, such as measles, whooping cough and gastrointestinal infections, ultimately took a far greater toll on medieval populations,” said Robb.
“Yes, the Black Death killed half the population in one year, but it wasn’t present in England before that, or in most years after that. The biggest threats to life in medieval England, and in Western Europe as a whole, were chronic infectious diseases such as tuberculosis.”
NOTES:
- Medieval Cambridge was home to just a few thousand people, with timber-framed houses clustered around a dozen churches, each with a small cemetery. A ten-minute walk in any direction ended in fields worked by many of the locals.
- Major Christian orders — such as Dominicans and Franciscans — had bases in the town, and the early University consisted of large hostels for religious students, with the first college, Peterhouse, established in 1284.
- Initially small and relatively poor, the colleges start to grow and multiply by the later 14th century thanks to endowments from aristocrats and royalty. By 1400 there were between 4-700 scholars.
- Remains from “All Saints by the Castle,” as well as from surrounding villages, had been in storage for decades, with some housed in the University’s Duckworth Laboratory, and others held in an old salt mine in Cheshire.
- Analyses of townsfolk from the “All Saints” cemetery suggest an adequate diet, mainly grains, vegetables and a little dairy. Around half of this group did not survive childhood, but of those that did, around half made it past the age of 45.
- Men from the Augustinian Friary were around an inch taller than those from town, with bone chemistry suggesting diets rich with meat and fish. The hospital inmates were the shortest group, likely as a result of poor and disease-ridden childhoods.
- Three people from the hospital, including 332 (‘Christina’), began life some distance away, maybe even as far as Norway. They may have been buried in the Hospital cemetery’s consecrated ground as an act of charity, after dying while visiting Cambridge — perhaps to trade at the town’s famous Stourbridge Fair.
In November 2021, Northwestern University researchers introduced an injectable new therapy, which harnessed fast-moving “dancing molecules,” to repair tissues and reverse paralysis after severe spinal cord injuries.
The researchers also found that, as the molecular motion increased, the treatment’s effectiveness also increased. In other words, the molecules’ “dancing” motions were crucial for triggering the cartilage growth process.
The study was published today (July 26) in the Journal of the American Chemical Society.
“When we first observed therapeutic effects of dancing molecules, we did not see any reason why it should only apply to the spinal cord,” said Northwestern’s Samuel I. Stupp, who led the study. “Now, we observe the effects in two cell types that are completely disconnected from one another — cartilage cells in our joints and neurons in our brain and spinal cord. This makes me more confident that we might have discovered a universal phenomenon. It could apply to many other tissues.”
An expert in regenerative nanomedicine, Stupp is Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. Stupp has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. Shelby Yuan, a graduate student in the Stupp laboratory, was primary author of the study.
Big problem, few solutions
As of 2019, nearly 530 million people around the globe were living with osteoarthritis, according to the World Health Organization. A degenerative disease in which tissues in joints break down over time, osteoarthritis is a common health problem and leading cause of disability.
In patients with severe osteoarthritis, cartilage can wear so thin that joints essentially transform into bone on bone — without a cushion between. Not only is this incredibly painful, patients’ joints also can no longer properly function. At that point, the only effective treatment is a joint replacement surgery, which is expensive and invasive.
“Current treatments aim to slow disease progression or postpone inevitable joint replacement,” Stupp said. “There are no regenerative options because humans do not have an inherent capacity to regenerate cartilage in adulthood.”
What are ‘dancing molecules’?
Stupp and his team posited that “dancing molecules” might encourage the stubborn tissue to regenerate. Previously invented in Stupp’s laboratory, dancing molecules are assemblies that form synthetic nanofibers comprising tens to hundreds of thousands of molecules with potent signals for cells. By tuning their collective motions through their chemical structure, Stupp discovered the moving molecules could rapidly find and properly engage with cellular receptors, which also are in constant motion and extremely crowded on cell membranes.
Once inside the body, the nanofibers mimic the extracellular matrix of the surrounding tissue. By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating bioactive signals for the receptors, the synthetic materials are able to communicate with cells.
“Cellular receptors constantly move around,” Stupp said. “By making our molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”
Motion matters
In the new study, Stupp and his team looked to the receptors for a specific protein critical for cartilage formation and maintenance. To target this receptor, the team developed a new circular peptide that mimics the bioactive signal of the protein, which is called transforming growth factor beta-1 (TGFb-1).
Then, the researchers incorporated this peptide into two different molecules that interact to form supramolecular polymers in water, each with the same ability to mimic TGFb-1. The researchers designed one supramolecular polymer with a special structure that enabled its molecules to move more freely within the large assemblies. The other supramolecular polymer, however, restricted molecular movement.
“We wanted to modify the structure in order to compare two systems that differ in the extent of their motion,” Stupp said. “The intensity of supramolecular motion in one is much greater than the motion in the other one.”
Although both polymers mimicked the signal to activate the TGFb-1 receptor, the polymer with rapidly moving molecules was much more effective. In some ways, they were even more effective than the protein that activates the TGFb-1 receptor in nature.
“After three days, the human cells exposed to the long assemblies of more mobile molecules produced greater amounts of the protein components necessary for cartilage regeneration,” Stupp said. “For the production of one of the components in cartilage matrix, known as collagen II, the dancing molecules containing the cyclic peptide that activates the TGF-beta1 receptor were even more effective than the natural protein that has this function in biological systems.”
What’s next?
Stupp’s team is currently testing these systems in animal studies and adding additional signals to create highly bioactive therapies.
“With the success of the study in human cartilage cells, we predict that cartilage regeneration will be greatly enhanced when used in highly translational pre-clinical models,” Stupp said. “It should develop into a novel bioactive material for regeneration of cartilage tissue in joints.”
Stupp’s lab is also testing the ability of dancing molecules to regenerate bone — and already has promising early results, which likely will be published later this year. Simultaneously, he is testing the molecules in human organoids to accelerate the process of discovering and optimizing therapeutic materials.
Stupp’s team also continues to build its case to the Food and Drug Administration, aiming to gain approval for clinical trials to test the therapy for spinal cord repair.
“We are beginning to see the tremendous breadth of conditions that this fundamental discovery on ‘dancing molecules’ could apply to,” Stupp said. “Controlling supramolecular motion through chemical design appears to be a powerful tool to increase efficacy for a range of regenerative therapies.”
Why do flies buzz around in circles when the air is still? And why does it matter?
“We don’t currently have robotic systems to track odor or chemical plumes,” van Breugel said. “We don’t know how to efficiently find the source of a wind-borne chemical. But insects are remarkably good at tracking chemical plumes, and if we really understood how they do it, maybe we could train inexpensive drones to use a similar process to find the source of chemicals and chemical leaks.”
A fundamental challenge in understanding how insects track chemical plumes — basically, how does the fly find the banana in your kitchen? — is that wind and odors can’t be independently manipulated.
To address this challenge, van Breugel and Stupski used a new approach that makes it possible to remotely control neurons — specifically the “smell” neurons — on the antennae of flying fruit flies by genetically introducing light-sensitive proteins, an approach called optogenetics. These experiments, part of a $450,000 project funded through the Air Force Office of Scientific Research, made it possible to give flies identical virtual smell experiences in different wind conditions.
What van Breugel and Stupski wanted to know: how do flies find an odor when there’s no wind to carry it? This is, after all, likely the wind experience of a fly looking for a banana in your kitchen. The answer is in the Current Biology article, “Wind Gates Olfaction Driven Search States in Free Flight.” The print version will appear in the Sept. 9 issue.
Flies use environmental cues to detect and respond to air currents and wind direction to find their food sources, according to van Breugel. In the presence of wind, those cues trigger an automatic “cast and surge” behavior, in which the fly surges into the wind after encountering a chemical plume (indicating food) and then casts — moves side to side — when it loses the scent. Cast-and-surge behavior long has been understood by scientists but, according to van Breugel, it was fundamentally unknown how insects searched for a scent in still air.
Through their work, van Breugel and Stupski uncovered another automatic behavior, sink and circle, which involves lowering altitude and repetitive, rapid turns in a consistent direction. Flies perform this innate movement consistently and repetitively, even more so than cast-and-surge behavior.
According to van Breugel, the most exciting aspect of this discovery is that it shows flying flies are clearly able to assess the conditions of the wind — its presence, and direction — before deploying a strategy that works well under these conditions. The fact that they can do this is actually quite surprising — can you tell if there is a gentle breeze if you stick your head out of the window of a moving car? Flies aren’t just reacting to an odor with the same preprogrammed response every time like a simple robot, they are responding in context-appropriate manner. This knowledge potentially could be applied to train more sophisticated algorithms for scent-detecting drones to find the source of chemical leaks.
So, the next time you try to swat a fly in your home, consider the fact that flies might actually be a little more aware of some of their natural surroundings than you are. And maybe just open a window to let it out.
One of just two vertebrates without a jaw, sea lampreys that are wreaking havoc in Midwestern fisheries are simultaneously helping scientists understand the origins of two important stem cells that drove the evolution of vertebrates.
The two cell types — pluripotent blastula cells (or embryonic stem cells) and neural crest cells — are both “pluripotent,” which means they can become all other cell types in the body.
In a new paper, researchers compared lamprey genes to those of the Xenopus, a jawed aquatic frog. Using comparative transcriptomics, the study revealed a strikingly similar pluripotency gene network across jawless and jawed vertebrates, even at the level of transcript abundance for key regulatory factors.
But the researchers also discovered a key difference. While both species’ blastula cells express the pou5 gene, a key stem cell regulator, the gene is not expressed in neural crest stem cells in lampreys. Losing this factor may have limited the ability of neural crest cells to form cell types found in jawed vertebrates (animals with spines) that make up the head and jaw skeleton.
The study will be published July 26 in the journal Nature Ecology & Evolution.
By comparing the biology of jawless and jawed vertebrates, researchers can gain insight into the evolutionary origins of features that define vertebrate animals including humans, how differences in gene expression contribute to key differences in the body plan, and what the common ancestor of all vertebrates looked like.
“Lampreys may hold the key to understanding where we came from,” said Northwestern’s Carole LaBonne, who led the study. “In evolutionary biology, if you want to understand where a feature came from, you can’t look forward to more complex vertebrates that have been evolving independently for 500 million years. You need to look backwards to whatever the most primitive version of the type of animal you’re studying is, which leads us back to hagfish and lampreys — the last living examples of jawless vertebrates.”
An expert in developmental biology, LaBonne is a professor of molecular biosciences in the Weinberg College of Arts and Sciences. She holds the Erastus Otis Haven Chair and is part of the leadership of the National Science Foundation’s (NSF) new Simons National Institute for Theory and Mathematics in Biology.
LaBonne and her colleagues previously demonstrated that the developmental origin of neural crest cells was linked to retaining the gene regulatory network that controls pluripotency in blastula stem cells. In the new study, they explored the evolutionary origin of the links between these two stem cell populations.
“Neural crest stem cells are like an evolutionary Lego set,” said LaBonne. “They become wildly different types of cells, including neurons and muscle, and what all those cell types have in common is a shared developmental origin within the neural crest.”
While blastula stage embryonic stem cells lose their pluripotency and become confined to distinct cell types fairly rapidly as an embryo develops, neural crest cells hold onto the molecular toolkit that controls pluripotency later into development.
LaBonne’s team found a completely intact pluripotency network within lamprey blastula cells, stem cells whose role within jawless vertebrates had been an open question. This implies that blastula and neural crest stem cell populations of jawed and jawless vertebrates co-evolved at the base of vertebrates.
Northwestern postdoctoral fellow and first author Joshua York observed “more similarities than differences” between the lamprey and Xenopus.
“While most of the genes controlling pluripotency are expressed in the lamprey neural crest, the expression of one of these key genes — pou5 — was lost from these cells,” York said. “Amazingly, even though pou5 isn’t expressed in a lamprey’s neural crest, it could promote neural crest formation when we expressed it in frogs, suggesting this gene is part of an ancient pluripotency network that was present in our earliest vertebrate ancestors.”
The experiment also helped them hypothesize that the gene was specifically lost in certain creatures, not something jawed vertebrates developed later on.
“Another remarkable finding of the study is that even though these animals are separated by 500 million years of evolution, there are stringent constraints on expression levels of genes needed to promote pluripotency.” LaBonne said. “The big unanswered question is, why?”
The paper was funded by the National Institutes of Health (grants R01GM116538 and F32DE029113), the NSF (grant 1764421), the Simons Foundation (grant SFARI 597491-RWC) and the Walder Foundation through the Life Sciences Research Foundation. The study is dedicated to the memory of Dr. Joseph Walder.
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