In this study, the researchers examined the effects of various health measures introduced during the pandemic, such as lockdowns and vaccinations. The study was conducted in a large cohort of people living with HIV, as well as in healthy individuals. The researchers found that inflammation biomarkers in the blood were low during the lockdown for people in both groups. However, when they exposed immune cells from the blood to microorganisms like viruses and bacteria in the lab, the immune system reacted much stronger than immune cells of individuals outside the lockdown.

Hygiene Hypothesis

As a possible explanation for this strong immune reaction, Professor Mihai Netea from Radboud university medical center points to the hygiene hypothesis. This hypothesis suggests that regular contact with microorganisms is beneficial because it keeps the immune system both active and tolerant at the same time. A lack of exposure to environmental factors might contribute to an immune system that overreacts, potentially leading to systemic reactions such as those encountered in inflammatory diseases and allergies.

Netea: ‘In our daily lives, we are constantly exposed to various micro-organisms. This helps train our immune system, teaching it to recognize which microorganisms are dangerous and which are harmless. During the lockdown, we missed that interaction because everyone stayed home and avoided each other. As a result, during and immediately after the lockdown periods, immune cells exposed to micro-organisms displayed a less well-regulated response, predisposing to hyperinflammation.’

Study Design

This research was made possible through a large study on people with HIV, initiated by Radboudumc and three other HIV treatment centers in the Netherlands. Recruitment for the study took place between October 2019, just before the COVID-19 pandemic, and October 2021. A total of 1,895 people with HIV are participating in this study, which is part of a broader research project on immune system function and the diversity of immune responses.

The study participants were divided into four groups:

• 368 individuals enrolled before the pandemic
• 851 individuals enrolled after the lockdown, but before vaccination or a COVID-19 infection
• 175 individuals who had contracted a COVID-19 infection
• 404 vaccinated individuals

In the lab, the researchers measured the level of inflammation in the participants’ blood. They also examined the interaction between isolated blood cells and viruses and bacteria.

Subsequently, the findings were validated in cohort of 30 healthy individuals tested during or after the lockdown period. Professor Andre van der Ven: ‘The results of this study primarily reflect people living with HIV, but we also examined a healthy control group. We saw similar results in this group, suggesting the effects may apply to the wider population. However, more research is needed for this group.’

Awareness of Impact

The study also revealed that vaccines and a COVID-19 infection influenced the immune system’s response, but these effects were relatively small and short-lived, Netea explained, and were negligible compared to the impact of the lockdowns on the immune system. Netea: ‘Lockdowns were necessary during the pandemic, especially at the beginning. However, it is important that we gain more insight into how social interactions affect and activate our immune system, so we can better manage the consequences. This way, we can apply such drastic social measures effectively and safely in a future pandemic.’

Surprisingly, the organoids were still healthy when they returned from orbit a month later, but the cells had matured faster compared to identical organoids grown on Earth — they were closer to becoming adult neurons and were beginning to show signs of specialization. The results, which could shed light on potential neurological effects of space travel, were published on October 23, 2024, in Stem Cells Translational Medicine.

“The fact that these cells survived in space was a big surprise,” says co-senior author Jeanne Loring, PhD, professor emeritus in the Department of Molecular Medicine and founding director of the Center for Regenerative Medicine at Scripps Research. “This lays the groundwork for future experiments in space, in which we can include other parts of the brain that are affected by neurodegenerative disease.”

On Earth, the team used stem cells to create organoids consisting of either cortical or dopaminergic neurons, which are the neuronal populations impacted in multiple sclerosis and Parkinson’s disease — diseases that Loring has studied for decades. Some organoids also included microglia, a type of immune cell that is resident within the brain, to examine the impact of microgravity on inflammation.

Organoids are usually grown in a nutrient-rich liquid medium that must be changed regularly to ensure that the cells have adequate nutrition, and to remove waste products. To avoid the need for lab work on the ISS, the team pioneered a method for growing smaller-than-usual organoids in cryovials — small, airtight vials that were originally designed for deep freezing.

The organoids were prepared in labs at the Kennedy Space Station and traveled to the ISS in a miniature incubator. After a month in orbit, they returned to Earth, where the team showed that they were healthy and intact.

To examine how the space environment impacts cellular functions, the team compared the cells’ RNA expression patterns — a measure of gene activity — to identical “ground control” organoids that had remained on Earth. Surprisingly, they found that the organoids grown in microgravity had higher levels of genes associated with maturity and lower levels of genes associated with proliferation compared to the ground controls, meaning that the cells exposed to microgravity developed faster and replicated less than those on Earth.

“We discovered that in both types of organoids, the gene expression profile was characteristic of an older stage of development than the ones that were on ground,” says Loring. “In microgravity, they developed faster, but it’s really important to know these were not adult neurons, so this doesn’t tell us anything about aging.”

The team also noted that, contrary to their hypothesis, there was less inflammation and lower expression of stress-related genes in organoids grown in microgravity, but more research is needed to determine why.

Loring speculates that microgravity conditions may more closely mirror the conditions experienced by cells within the brain compared to organoids grown under conventional lab conditions and in the presence of gravity.

“The characteristics of microgravity are probably also at work in people’s brains, because there’s no convection in microgravity — in other words, things don’t move,” says Loring. “I think that in space, these organoids are more like the brain because they’re not getting flushed with a whole bunch of culture medium or oxygen. They’re very independent; they form something like a brainlet, a microcosm of the brain.”

The paper describes the team’s first space mission, but since then, they have sent four more missions to the ISS. With each one, they’ve replicated the conditions from the first mission and added additional experiments.

“The next thing we plan to do is to study the part of the brain that’s most affected by Alzheimer’s disease,” says Loring. “We also want to know whether there are differences in the way neurons connect with each other in space. With these kinds of studies, you can’t rely on earlier work to predict what the result would be because there is no earlier work. We’re on the ground floor, so to speak; in the sky, but on the ground floor.”

This work was supported by funding from the National Stem Cell Foundation.

The study, published today in the journal Proceedings of the National Academy of Sciences (PNAS), shows that current estimates for the social cost of carbon, or SCC, fail to adequately represent important channels by which climate change could affect human welfare. When included, the SCC increases to just over $280 per ton of CO₂ emitted in 2020 — more than double the average published in the academic literature. The study’s estimate is also larger than the U.S. Environmental Protection Agency’s central estimate of $190 per ton of CO₂.

“When people worry about climate change, they worry about the risk and uncertainty it causes,” said lead author Frances Moore, an associate professor in the Department of Environmental Science and Policy at UC Davis. “They worry about long-term, persistent accumulating effects, such as climate change acting as a drag on economic growth. They worry about impacts to very unique natural systems or cultural heritage that are just irreplaceable. Those are what keep people up at night about climate change, and those are not fully included in SCC estimates currently used for policymaking.”

Climate change and the damage done

The social cost of carbon quantifies the damage a ton of carbon dioxide has on society and the economy, including food production, human health, property damage due to natural disasters, and impacts to natural systems. Estimates of the SCC are used widely in policy analysis, particularly to value the benefits of reducing greenhouse gas emissions. The United States, Germany, Canada and several states all have official SCC estimates used for policy making.

Most current government estimates, the study said, are incomplete and likely underestimate the benefits of reducing greenhouse gas emissions. This is because they omit some important ways climate change can affect human welfare, including via economic growth or effects on unique natural systems.

The study combines evidence from both the published literature and a survey of experts to fully integrate these elements into the SCC estimate, providing the most comprehensive assessment of SCC estimates to date.

Accounting for omissions

For the study, the authors synthesized 1,800 SCC estimates from the academic literature over the past 20 years and found a wide range of published values averaging $132 per ton of CO₂.

The scientists also conducted an expert survey with the authors of the literature, who said they thought the true value of the SCC was likely twice as large as the average of published values. Experts attribute this to a range of omissions in the academic literature, including limited representation of climate tipping points, effects on scarce ecosystems, or climate impacts with long-lived effects on the economy such as impacts on economic growth.

The authors then used machine learning to re-weight the literature, partially correcting some of the omissions identified by experts and using more recent evidence on discount rates. This produced a distribution of the 2020 SCC with a mean of $283 per ton of CO₂ and an interquartile range of $97 to $369.

The study states: “Incorporating climate costs into the prices of economic activities that emit greenhouse gases, either directly through carbon pricing or indirectly through emission regulation or subsidies of cleaner alternatives, is essential for averting the worst climate outcomes.”

The study’s coauthors are Moritz Drupp from the University of Hamburg, James Rising from the University of Delaware, Simon Dietz from the London School of Economics and Political Science, Ivan Rudik from Cornell University, and Gernot Wagner from Columbia Business School.

Researchers have long suspected that massive volcanic eruptions undersea caused carbon dioxide (CO₂) increases, global warming and depleted oxygen (called anoxia) in the ocean during the Mesozoic Period. Now, an international team of researchers, including Northwestern University Earth scientists, determined the precise timing of the volcanic eruption and OAE1a, which started 119.5 million years ago. The work adds to a growing volume of evidence that volcanic CO₂ emissions directly triggered the anoxic event.

The new study also determined that OAE 1a lasted for just over 1.1 million years. This new information helps scientists better understand how the Earth’s climate and ocean system operates and responds to stress — especially as it relates to current warming.

The study was published late last month in the journal Science Advances. It marks the most detailed and highly resolved dating of an ocean anoxic event ever achieved.

“Ocean anoxic events occur in part as a consequence of climatic warming in a greenhouse world,” said Northwestern’s Brad Sageman, a senior author of the study. “If we want to make accurate predictions about what we will see in the decades ahead with human-caused warming, this information is invaluable. The best way to understand the future is to look at data from the past.”

An expert on ancient climates, Sageman is a professor of Earth, Environmental and Planetary Sciences at Northwestern’s Weinberg College of Arts and Sciences and a co-director of the Paula M. Trienens Institute for Sustainability and Energy.

A Northwestern connection

The Cretaceous Period experienced two major and several minor ocean anoxic events, with OAE 1a as one of the two largest. The most likely cause: volcanic eruptions rapidly injected massive amounts of CO₂ into the ocean and atmosphere. These aren’t ordinary volcanoes but large igneous provinces that erupt up to a million cubic kilometers of basalt over several millions of years. When CO₂ reacts with seawater, it forms a weak carbonic acid, which literally dissolves sea creatures’ shells. The acid, combined with low oxygen levels, has significant consequences for sea life.

Researchers first began pondering ocean anoxic events in the mid-1970s, after a discovery by Northwestern geologist Seymour Schlanger and Oxford professor Hugh Jenkyns. When examining sediment samples from the Pacific Ocean floor, Schlanger and Jenkyns discovered black, organic carbon-rich shales that matched samples — in composition and age — from both the Atlantic Ocean and rock formations in Italy.

Widespread lack of oxygen was the most likely explanation for these deposits. Anoxia prevents the breakdown of organic matter from dead plants and animals, leading to a global pattern of organic enrichment. Instead of decomposing, the settling plankton and other fossils accumulated to form organic carbon-rich strata scattered around the globe.

“How were black shales forming at the same time in the deep oceans and up on land?” Sageman asked. “Schlanger and Jenkyns realized there must have been a massive global event that caused oxygen to decrease from the ocean surface all the way down to the seafloor.”

History solidified in stone

In the new study, researchers looked not to the depths of the oceans but to ancient strata along the northwest edge of a mountain on Japan’s Hokkaido Island. The rocks, or tuffs, formed from volcanic ash that settled and solidified over time. Tectonic activity lifted these layers above sea level during formation of the Japanese islands, leaving them exposed and accessible where streams carve through the temperate rainforest of Hokkaido. By collecting and analyzing the tuffs, Sageman, his Ph.D. student, Luca Podrecca, and their collaborators gained a glimpse into geologic history.

“Magma comes out of a volcano in liquid form and then begins to cool,” Sageman said. “During this process, crystals start to form. By the time the tuff solidifies, the crystals become a tiny closed system. They lock in atoms, and some of those atoms, like uranium, start to decay, meaning they convert from one isotope to another. That provides a tool to date the eruption, and, thus, date a specific layer within a stack of sedimentary rock. While the expertise of team members from Tohuku University in Japan, Durham University in the U.K. and Northwestern focuses on the characterization and global correlation of the strata, our collaborators at the University of Wisconsin-Madison and Boise State University are experts in the geochronological analyses.”

The researchers also used other types of isotopes, such as carbon, which tracks synchronous changes in the carbon cycle, and osmium, which tracks volcanic activity and changes in ocean chemistry.

“These isotope systems provide tools for correlating the OAE1a interval between sites in Hokkaido, southern France and other sites all around the globe,” Sageman said. “They give us markers for instants in geologic time.”

Pinpointing the exact timeline

According to this evidence, an abrupt shift in carbon isotope ratios — caused first by the spike in volcanic CO₂added to the carbon cycle (and later by the excess burial of organic matter) — occurred in the early Cretaceous at the beginning of OAE 1a. A concurrent shift in the isotopic ratios of osmium reflects a massive input of volcanic material into ocean waters. The timing of these events corresponds to eruption of the Ontong Java Nui complex, an enormous igneous province about the size of Alaska located in the southwestern Pacific Ocean.

Now that researchers know it took the oceans 1.1 million years to recover from the sharp increase in CO₂, they have more insight into how long the effects of CO₂-driven warming events might last and what the associated effects, such as ocean anoxia, may be.

“We’re already seeing zones with low oxygen levels in the Gulf of Mexico,” Sageman said. “The main difference is that past events unfolded over tens of thousands to millions of years. We’re driving roughly similar levels of warming (or more) but doing so in less than 200 years.”