R. Alexander Bentley, University of Tennessee

In my research focused on early farmers of Europe, I have often wondered about a curious pattern through time: Farmers lived in large dense villages, then dispersed for centuries, then later formed cities again, only to abandon those as well. Why?

Archaeologists often explain what we call urban collapse in terms of climate change, overpopulation, social pressures or some combination of these. Each likely has been true at different points in time.

But scientists have added a new hypothesis to the mix: disease. Living closely with animals led to zoonotic diseases that came to also infect humans. Outbreaks could have led dense settlements to be abandoned, at least until later generations found a way to organize their settlement layout to be more resilient to disease. In a new study, my colleagues and I analyzed the intriguing layouts of later settlements to see how they might have interacted with disease transmission.

Earliest cities: Dense with people and animals

Çatalhöyük, in present-day Turkey, is the world’s oldest farming village, from over 9,000 years ago. Many thousands of people lived in mud-brick houses jammed so tightly together that residents entered via a ladder through a trapdoor on the roof. They even buried selected ancestors underneath the house floor. Despite plenty of space out there on the Anatolian Plateau, people packed in closely.

For centuries, people at Çatalhöyük herded sheep and cattle, cultivated barley and made cheese. Evocative paintings of bulls, dancing figures and a volcanic eruption suggest their folk traditions. They kept their well-organized houses tidy, sweeping floors and maintaining storage bins near the kitchen, located under the trapdoor to allow oven smoke to escape. Keeping clean meant they even replastered their interior house walls several times a year.

These rich traditions ended by 6000 BCE, when Çatalhöyük was mysteriously abandoned. The population dispersed into smaller settlements out in the surrounding flood plain and beyond. Other large farming populations of the region had also dispersed, and nomadic livestock herding became more widespread. For those populations that persisted, the mud-brick houses were now separate, in contrast with the agglomerated houses of Çatalhöyük.

Was disease a factor in the abandonment of dense settlements by 6000 BCE?

At Çatalhöyük, archaeologists have found human bones intermingled with cattle bones in burials and refuse heaps. Crowding of people and animals likely bred zoonotic diseases at Çatalhöyük. Ancient DNA identifies tuberculosis from cattle in the region as far back as 8500 BCE and TB in human infant bones not long after. DNA in ancient human remains dates salmonella to as early as 4500 BCE. Assuming the contagiousness and virulence of Neolithic diseases increased through time, dense settlements such as Çatalhöyük may have reached a tipping point where the effects of disease outweighed the benefits of living closely together.

A new layout 2,000 years later

By about 4000 BCE, large urban populations had reappeared, at the mega-settlements of the ancient Trypillia culture, west of the Black Sea. Thousands of people lived at Trypillia mega-settlements such as Nebelivka and Maidanetske in what’s now Ukraine.

If disease was a factor in dispersal millennia before, how were these mega-settlements possible?

This time, the layout was different than at jam-packed Çatalhöyük: The hundreds of wooden, two-story houses were regularly spaced in concentric ovals. They were also clustered in pie-shaped neighborhoods, each with its own large assembly house. The pottery excavated in the neighborhood assembly houses has many different compositions, suggesting these pots were brought there by different families coming together to share food.

This layout suggests a theory. Whether the people of Nebelivka knew it or not, this lower-density, clustered layout could have helped prevent any disease outbreaks from consuming the entire settlement.

Archaeologist Simon Carrignon and I set out to test this possibility by adapting computer models from a previous epidemiology project that modeled how social-distancing behaviors affect the spread of pandemics. To study how a Trypillian settlement layout would disrupt disease spread, we teamed up with cultural evolution scholar Mike O’Brien and with the archaeologists of Nebelivka: John Chapman, Bisserka Gaydarska and Brian Buchanan.

Simulating socially distanced neighborhoods

To simulate disease spread at Nebelivka, we had to make a few assumptions. First, we assumed that early diseases were spread through foods, such as milk or meat. Second, we assumed people visited other houses within their neighborhood more often than those outside of it.

Would this neighborhood clustering be enough to suppress disease outbreaks? To test the effects of different possible rates of interaction, we ran millions of simulations, first on a network to represent clustered neighborhoods. We then ran the simulations again, this time on a virtual layout modeled after actual site plans, where houses in each neighborhood were given a higher chance of making contact with each other.

Based on our simulations, we found that if people visited other neighborhoods infrequently – like a fifth to a tenth as often as visiting other houses within their own neighborhood – then the clustering layout of houses at Nebelivka would have significantly reduced outbreaks of early foodborne diseases. This is reasonable given that each neighborhood had its own assembly house. Overall, the results show how the Trypillian layout could help early farmers live together in low-density urban populations, at a time when zoonotic diseases were increasing.

The residents of Nebilevka didn’t need to have consciously planned for their neighborhood layout to help their population survive. But they may well have, as human instinct is to avoid signs of contagious disease. Like at Çatalhöyük, residents kept their houses clean. And about two-thirds of the houses at Nebelivka were deliberately burned at different times. These intentional periodic burns may have been a pest extermination tactic.

New cities and innovations

Some of the early diseases eventually evolved to spread by means other than bad foods. Tuberculosis, for instance, became airborne at some point. When the bacterium that causes plague, Yersinia pestis, became adapted to fleas, it could be spread by rats, which would not care about neighborhood boundaries.

Were new disease vectors too much for these ancient cities? The mega-settlements of Trypillia were abandoned by 3000 BCE. As at Çatalhöyük thousands of years before, people dispersed into smaller settlements. Some geneticists speculate that Trypillia settlements were abandoned due to the origins of plague in the region, about 5,000 years ago.

The first cities in Mesopotamia developed around 3500 BCE, with others soon developing in Egypt, the Indus Valley and China. These cities of tens of thousands were filled with specialized craftspeople in distinct neighborhoods.

This time around, people in the city centers weren’t living cheek by jowl with cattle or sheep. Cities were the centers of regional trade. Food was imported into the city and stored in large grain silos like the one at the Hittite capital of Hattusa, which could hold enough cereal grain to feed 20,000 people for a year. Sanitation was helped by public water works, such as canals in Uruk or water wells and a large public bath at the Indus city of Mohenjo Daro.

These early cities, along with those in China, Africa and the Americas, were the foundations of civilization. Arguably, their form and function were shaped by millennia of diseases and human responses to them, all the way back to the world’s earliest farming villages.

R. Alexander Bentley, Professor of Anthropology, University of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Aman Agrawal, University of Chicago Pritzker School of Molecular Engineering

Billions of years of evolution have made modern cells incredibly complex. Inside cells are small compartments called organelles that perform specific functions essential for the cell’s survival and operation. For instance, the nucleus stores genetic material, and mitochondria produce energy.

Another essential part of a cell is the membrane that encloses it. Proteins embedded on the surface of the membrane control the movement of substances in and out of the cell. This sophisticated membrane structure allowed for the complexity of life as we know it. But how did the earliest, simplest cells hold it all together before elaborate membrane structures evolved?

In our recently published research in the journal Science Advances, my colleagues from the University of Chicago and the University of Houston and I explored a fascinating possibility that rainwater played a crucial role in stabilizing early cells, paving the way for life’s complexity.

The origin of life

One of the most intriguing questions in science is how life began on Earth. Scientists have long wondered how nonliving matter like water, gases and mineral deposits transformed into living cells capable of replication, metabolism and evolution.

Chemists Stanley Miller and Harold Urey at the University of Chicago conducted an experiment in 1953 demonstrating that complex organic compounds – meaning carbon-based molecules – could be synthesized from simpler organic and inorganic ones. Using water, methane, ammonia, hydrogen gases and electric sparks, these chemists formed amino acids.

Scientists believe the earliest forms of life, called protocells, spontaneously emerged from organic molecules present on the early Earth. These primitive, cell-like structures were likely made of two fundamental components: a matrix material that provided a structural framework and a genetic material that carried instructions for protocells to function.

Over time, these protocells would have gradually evolved the ability to replicate and execute metabolic processes. Certain conditions are necessary for essential chemical reactions to occur, such as a steady energy source, organic compounds and water. The compartments formed by a matrix and a membrane crucially provide a stable environment that can concentrate reactants and protect them from the external environment, allowing the necessary chemical reactions to take place.

Thus, two crucial questions arise: What materials were the matrix and membrane of protocells made of? And how did they enable early cells to maintain the stability and function they needed to transform into the sophisticated cells that constitute all living organisms today?

Bubbles vs droplets

Scientists propose that two distinct models of protocells – vesicles and coacervates – may have played a pivotal role in the early stages of life.

Vesicles are tiny bubbles, like soap in water. They are made of fatty molecules called lipids that naturally form thin sheets. Vesicles form when these sheets curl into a sphere that can encapsulate chemicals and safeguard crucial reactions from harsh surroundings and potential degradation.

Like miniature pockets of life, vesicles resemble the structure and function of modern cells. However, unlike the membranes of modern cells, vesicle protocells would have lacked specialized proteins that selectively allow molecules in and out of a cell and enable communication between cells. Without these proteins, vesicle protocells would have limited ability to interact effectively with their surroundings, constraining their potential for life.

Coacervates, on the other hand, are droplets formed from an accumulation of organic molecules like peptides and nucleic acids. They form when organic molecules stick together due to chemical properties that attract them to each other, such as electrostatic forces between oppositely charged molecules. These are the same forces that cause balloons to stick to hair.

One can picture coacervates as droplets of cooking oil suspended in water. Similar to oil droplets, coacervate protocells lack a membrane. Without a membrane, surrounding water can easily exchange materials with protocells. This structural feature helps coacervates concentrate chemicals and speed up chemical reactions, creating a bustling environment for the building blocks of life.

Thus, the absence of a membrane appears to make coacervates a better protocell candidate than vesicles. However, lacking a membrane also presents a significant drawback: the potential for genetic material to leak out.

Unstable and leaky protocells

A few years after Dutch chemists discovered coacervate droplets in 1929, Russian biochemist Alexander Oparin proposed that coacervates were the earliest model of protocells. He argued that coacervate droplets provided a primitive form of compartmentalization crucial for early metabolic processes and self-replication.

Subsequently, scientists discovered that coacervates can sometimes be composed of oppositely charged polymers: long, chainlike molecules that resemble spaghetti at the molecular scale, carrying opposite electrical charges. When polymers of opposite electrical charges are mixed, they tend to attract each other and stick together to form droplets without a membrane.

The absence of a membrane presented a challenge: The droplets rapidly fuse with each other, akin to individual oil droplets in water joining into a large blob. Furthermore, the lack of a membrane allowed RNA – a type of genetic material thought to be the earliest form of self-replicating molecule, crucial for the early stages of life – to rapidly exchange between protocells.

My colleague Jack Szostak showed in 2017 that rapid fusion and exchange of materials can lead to uncontrolled mixing of RNA, making it difficult for stable and distinct genetic sequences to evolve. This limitation suggested that coacervates might not be able to maintain the compartmentalization necessary for early life.

Compartmentalization is a strict requirement for natural selection and evolution. If coacervate protocells fused incessantly, and their genes continuously mixed and exchanged with each other, all of them would resemble each other without any genetic variation. Without genetic variation, no single protocell would have a higher probability of survival, reproduction and passing on its genes to future generations.

But life today thrives with a variety of genetic material, suggesting that nature somehow solved this problem. Thus, a solution to this problem had to exist, possibly hiding in plain sight.

Rainwater and RNA

A study I conducted in 2022 demonstrated that coacervate droplets can be stabilized and avoid fusion if immersed in deionized water – water that is free of dissolved ions and minerals. The droplets eject small ions into the water, likely allowing oppositely charged polymers on the periphery to come closer to each other and form a meshy skin layer. This meshy “wall” effectively hinders the fusion of droplets.

Next, with my colleagues and collaborators, including Matthew Tirrell and Jack Szostak, I studied the exchange of genetic material between protocells. We placed two separate protocell populations, treated with deionized water, in test tubes. One of these populations contained RNA. When the two populations were mixed, RNA remained confined in their respective protocells for days. The meshy “walls” of the protocells impeded RNA from leaking.

In contrast, when we mixed protocells that weren’t treated with deionized water, RNA diffused from one protocell to the other within seconds.

Inspired by these results, my colleague Alamgir Karim wondered if rainwater, which is a natural source of ion-free water, could have done the same thing in the prebiotic world. With another colleague, Anusha Vonteddu, I found that rainwater indeed stabilizes protocells against fusion.

Rain, we believe, may have paved the way for the first cells.

Working across disciplines

Studying the origins of life addresses both scientific curiosity about the mechanisms that led to life on Earth and philosophical questions about our place in the universe and the nature of existence.

Currently, my research delves into the very beginning of gene replication in protocells. In the absence of the modern proteins that make copies of genes inside cells, the prebiotic world would have relied on simple chemical reactions between nucleotides – the building blocks of genetic material – to make copies of RNA. Understanding how nucleotides came together to form a long chain of RNA is a crucial step in deciphering prebiotic evolution.

To address the profound question of life’s origin, it is crucial to understand the geological, chemical and environmental conditions on early Earth approximately 3.8 billion years ago. Thus, uncovering the beginnings of life isn’t limited to biologists. Chemical engineers like me, and researchers from various scientific fields, are exploring this captivating existential question.

Aman Agrawal, Postdoctoral Scholar in Chemical Engineering, University of Chicago Pritzker School of Molecular Engineering

This article is republished from The Conversation under a Creative Commons license. Read the original article.

David P. Baker, Penn State and Justin J.W. Powell, University of Luxembourg

Millions of scientific papers are published globally every year. These papers in science, technology, engineering, mathematics and medicine present discoveries that range from the mundane to the profound.

Since 1900, the number of published scientific articles has doubled about every 10 to 15 years; since 1980, about 8% to 9% annually. This acceleration reflects the immense and ever-growing scope of research across countless topics, from the farthest reaches of the cosmos to the intricacies of life on Earth and human nature.

Yet, this extraordinary expansion was once thought to be unsustainable. In his influential 1963 book, “Little Science, Big Science… And Beyond,” the founder of scientometrics – or data informetrics related to scientific publications – Derek de Solla Price famously predicted limits to scientific growth.

He warned that the world would soon deplete its resources and talent pool for research. He imagined this would lead to a decline in new discoveries and potential crises in medicine, technology and the economy. At the time, scholars widely accepted his prediction of an impending slowdown in scientific progress.

Faulty predictions

In fact, science has spectacularly defied Price’s dire forecast. Instead of stagnation, the world now experiences “global mega-science” – a vast, ever-growing network of scientific discovery. This explosion of scientific production made Price’s prediction of collapse perhaps the most stunningly incorrect forecast in the study of science.

Unfortunately, Price died in 1983, too early to realize his mistake.

So, what explains the world’s sustained and dramatically increasing capacity for scientific research?

We are sociologists who study higher education and science. Our new book, “Global Mega-Science: Universities, Research Collaborations, and Knowledge Production,” published on the 60th anniversary of Price’s fateful prediction, offers explanations for this rapid and sustained scientific growth. It traces the history of scientific discovery globally.

Factors such as economic growth, warfare, space races and geopolitical competition have undoubtedly spurred research capacity. But these factors alone cannot account for the immense scale of today‘s scientific enterprise.

The education revolution: Science’s secret engine

In many ways, the world’s scientific capacity has been built upon the educational aspirations of young adults pursuing higher education.

Over the past 125 years, increasing demand for and access to higher education has sparked a global education revolution. Now, more than two-fifths of the world’s young people ages 19-23, although with huge regional differences, are enrolled in higher education. This revolution is the engine driving scientific research capacity.

Today, more than 38,000 universities and other higher-education institutions worldwide play a crucial role in scientific discovery. The educational mission, both publicly and privately funded, subsidizes the research mission, with a big part of students’ tuition money going toward supporting faculty.

These faculty scientists balance their teaching with conducting extensive research. University-based scientists contribute 80% to 90% of the discoveries published each year in millions of papers.

External research funding is still essential for specialized equipment, supplies and additional support for research time. But the day-to-day research capacity of universities, especially academics working in teams, forms the foundation of global scientific progress.

Even the most generous national science and commercial research and development budgets cannot fully sustain the basic infrastructure and staffing needed for ongoing scientific discovery.

Likewise, government labs and independent research institutes, such as the U.S. National Institutes of Health or Germany’s Max Planck Institutes, could not replace the production capacity that universities provide.

Collaboration benefits science and society

The past few decades have also seen a surge in global scientific collaborations. These arrangements leverage diverse talent from around the world to enhance the quality of research.

International collaborations have led to millions of co-authored papers. International research partnerships were relatively rare before 1980, accounting for just over 7,000 papers, or about 2% of the global output that year. But by 2010 that number had surged to 440,000 papers, meaning 22% of the world’s scientific publications resulted from international collaborations.

This growth, building on the “collaboration dividend,” continues today and has been shown to produce the highest-impact research.

Universities tend to share academic goals with other universities and have wide networks and a culture of openness, which makes these collaborations relatively easy.

Today, universities also play a key role in international supercollaborations involving teams of hundreds or even thousands of scientists. In these huge collaborations, researchers can tackle major questions they wouldn’t be able to in smaller groups with fewer resources.

Supercollaborations have facilitated breakthroughs in understanding the intricate physics of the universe and the synthesis of evolution and genetics that scientists in a single country could never achieve alone.

The role of global hubs

Hubs made up of universities from around the world have made scientific research thoroughly global. The first of these global hubs, consisting of dozens of North American research universities, began in the 1970s. They expanded to Europe in the 1980s and most recently to Southeast Asia.

These regional hubs and alliances of universities link scientists from hundreds of universities to pursue collaborative research projects.

Scientists at these universities have often transcended geopolitical boundaries, with Iranian researchers publishing papers with Americans, Germans collaborating with Russians and Ukrainians, and Chinese scientists working with their Japanese and Korean counterparts.

The COVID-19 pandemic clearly demonstrated the immense scale of international collaboration in global megascience. Within just six months of the start of the pandemic, the world’s scientists had already published 23,000 scientific studies on the virus. These studies contributed to the rapid development of effective vaccines.

With universities’ expanding global networks, the collaborations can spread through key research hubs to every part of the world.

Is global megascience sustainable?

But despite the impressive growth of scientific output, this brand of highly collaborative and transnational megascience does face challenges.

On the one hand, birthrates in many countries that produce a lot of science are declining. On the other, many youth around the world, particularly those in low-income countries, have less access to higher education, although there is some recent progress in the Global South.

Sustaining these global collaborations and this high rate of scientific output will mean expanding access to higher education. That’s because the funds from higher education subsidize research costs, and higher education trains the next generation of scientists.

De Solla Price couldn’t have predicted how integral universities would be in driving global science. For better or worse, the future of scientific production is linked to the future of these institutions.

David P. Baker, Professor of Sociology, Education and Demography, Penn State and Justin J.W. Powell, Professor of Sociology of Education, University of Luxembourg

This article is republished from The Conversation under a Creative Commons license. Read the original article.