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Ancient “chewing gum” contains a 5,700-year-old genome

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Enlarge / This artist’s reconstruction shows “Lola” as a young girl, with items that likely would have been part of her daily life, but we have no way of knowing how old she was when she chewed and discarded the lump of birch-bark pitch.

Tom Björklund

5,700 years ago, a woman in what is now Denmark chewed a lump of birch-bark pitch for a while and then dropped it. Millennia later, the DNA she left behind reveals her entire genome, a census of the bacteria living in her mouth, and a few hints about a recent meal.

Meet “Lola”

If you’re a hunter-gatherer who needs to haft a stone tool, birch-bark pitch makes a handy adhesive, but you might have to chew it to make it pliable enough to work with. Pitch is watertight and contains an antiseptic compound called betulin, so it’s great at preserving DNA. In fact, archaeologists in Scandinavia have found more human DNA in bits of chewed pitch than they have in skeletons (which have been relatively rare at prehistoric Scandinavian sites we’ve studied thus far).

But this is the first time researchers have managed to sequence an ancient person’s whole genome from a lump of chewed pitch. Only about a third of the DNA bioarchaeologist Hannes Schroeder, of the University of Copenhagen, sampled was human; the other 68 percent came from the ancient woman’s microbiome and traces of a prehistoric meal. This single discarded piece of ancient chewing gum tells us that the ancient woman, who Schroeder and his colleagues have nicknamed Lola, was probably lactose intolerant, ate duck and hazelnuts, and may recently have had pneumonia. She also had blue eyes, dark brown hair, and dark skin.

“This combination of physical traits has been previously noted in other European hunter-gatherers, suggesting that this phenotype was widespread in Mesolithic Europe and that the adaptive spread of light skin pigmentation in European populations only occurred later in prehistory,” wrote Schroeder and his colleagues.

She lived through the Neolithic revolution

The detail we can extract with DNA turns a seriously unprepossessing artifact into a deeply personal link to life in the past. It also sheds light on the much larger cultural upheaval that was reshaping Lola’s world. While Lola was eating hazelnuts at the prehistoric settlement now called Syltholm, people from southwest Asia were spreading westward across Europe, bringing a new way of life with them: farming.

Around the time Lola lived in Denmark, the hunter-gatherer culture called Erlebolle gave way to the Funnel Beaker culture, a way of life built on farming and livestock. From archaeological data, we know that cultural change happened very quickly in Denmark, with people’s settlement patterns and ways of making a living changing almost overnight. But what we don’t know is whether that’s because new people moved in, displacing the old Erlebolle hunter-gatherers, or if it’s because the people already living in Denmark adopted new ideas.

Lola’s genome suggests that she’s not related to the Neolithic farmers who swept westward. And that implies that the newcomers didn’t immediately replace or absorb the hunter-gatherers who had been living in Denmark since the end of the Ice Age. In Lola’s day, it seems that at least a few of the old hunter-gatherer groups were still around, even if they’d adopted new ways of life. That lines up well with other genomic evidence from elsewhere in Europe, but it’s important not to draw firm conclusions based on a single genome.

It's definitely not much to look at, but this lump of ancient chewing gum contains a treasure trove of information.
Enlarge / It’s definitely not much to look at, but this lump of ancient chewing gum contains a treasure trove of information.

Theis Jensen

Duck and hazelnut were on the menu

But what was Lola’s life like during this time of cultural change? A small percentage of the DNA in the pitch came from other things she had recently chewed: hazelnut and a species of mallard, bits of which must still have been in her mouth when she picked up the pitch. That’s potentially a more detailed image than you wanted, but it suggests that even after Lola’s community took up farming, they still relied on wild foods, too. Duck bones and hazelnuts at the site back up the DNA evidence.

Lola’s genome also contained alleles that are usually associated with the inability to produce lactase—an enzyme that’s important in digesting milk—as an adult. If lactose intolerance was still common among people in Scandinavia just after the Neolithic revolution (the wave of migration and cultural change that introduced agriculture to most of Europe), then Europeans probably evolved the ability to drink milk as adults relatively recently, after dairy farming became a common way of life. DNA evidence from other sites supports that idea, too.

A Neolithic case of pneumonia?

Most of the DNA recovered from the lump of pitch belonged to bacteria and viruses. At other sites, archaeologists have gotten some information about ancient microbiomes from DNA and proteins preserved in calculus—hardened dental plaque still clinging to the teeth of ancient skeletal remains. But calculus is a long-term record of the tiny organisms that live in your mouth; the DNA Lola left behind in her chewing gum is more like a snapshot.

Overall, Lola’s oral microbiome looked a lot like modern ones (there are whole datasets of oral microbiomes for comparison). Other than a few bacteria associated with periodontal disease, the microbes in Lola’s mouth were harmless, and that’s still the case for modern people. Schroeder and his colleagues did find some genetic sequences from the Epstein-Barr virus, which is something Lola would have in common with about 90 percent of adults in the world today. It’s likely that the virus never made her sick; most people catch it as children and never experience symptoms (occasionally Epstein-Barr virus can cause a serious fever or increase a person’s risk of Hodgkin’s lymphoma and some autoimmune diseases later in life).

Lola may have been recovering from a case of pneumonia on the day she chewed the birch-bark pitch, because genetic sequences from the bacterium Streptococcus pneumoniae showed up in her microbiome. Schroeder and his colleagues found several sets of genes called virulence factors, traits associated with the pathogen’s ability to infect a host and thwart the immune system. S. pneumoniae has a knack for picking up virulence factors from other related bacteria, so ancient DNA may help researchers trace its evolutionary history.

Hints about an even more ancient past

Lola’s genome also tells archaeologists about the first people to move into Scandinavia after the ice sheets retreated between 12,000 and 11,000 years ago, generations before she lived at Syltholm.

Based on other archaeological and genetic evidence, we know that after the ice’s retreat, people from different areas of Eurasia moved into Scandinavia along two routes. Some hunter-gatherers from mainland Europe moved northward through Denmark, while others from farther northeast moved southward along the coast of Norway. Lola is much more closely related to the group from mainland Europe—in fact, her genome carries no traces of ancestry from the second group at all.

Schroeder and his colleagues say Lola’s DNA supports the current theory that the people moving in from the northeast (archaeologists creatively call them Eastern Hunter-Gatherers) hadn’t reached southern Denmark by 5,700 years ago. But that idea, Schroeder and his colleagues admit, must be taken with a grain of salt, because we only have one genome to work with.

As always, we need more data, but for now, researchers have something to chew on.

Nature Communications, 2020 DOI: 10.1038/s41467-019-13549-9 (About DOIs).

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FDA advisors green-light Pfizer boosters for people 65+ and at-risk groups

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Enlarge / Vials with COVID-19 Vaccine labels showing logos of pharmaceutical company Pfizer and German biotechnology company BioNTech.

A committee of independent advisors for the Food and Drug Administration has voted unanimously (18 to 0) in favor of authorizing a booster dose of the Pfizer/BioNTech COVID-19 vaccine for people aged 65 and older, as well as people at high risk based on an underlying medical condition and/or occupational exposure (e.g., healthcare workers). The booster doses are recommended to be given at least six months after completion of the primary two doses.

If the FDA moves forward with the advisory committee’s recommendation—which it likely will—boosters will be offered to those two groups based on an Emergency Use Authorization.

Prior to voting in favor of authorization for the two groups, the committee rejected the idea of approving boosters for all people ages 16 and up with a resounding vote of 16 to 2 against.

Generally, the committee—Vaccines and Related Biological Products Advisory Committee (VRBPAC)—felt there was simply too little safety data to make an assessment, particularly for young males at highest risk of developing a rare COVID-19 vaccine side effect of inflammation of or around the heart (myocarditis and pericarditis). In addition, the committee felt there was not convincing data that overall vaccine protection from severe disease, hospitalization, and death has waned to the extent that a booster shot is necessary.

“A third dose is likely beneficial,” Ofer Levy, a voting VRBPAC member and infectious disease expert at Harvard, said after voting against boosters for all. “That’s already true for the immunocompromised. It’s likely beneficial, in my opinion, for the elderly and may eventually be indicated for the general population. I just don’t think we’re there yet in terms of the data.”

The votes came after a tumultuous all-day meeting in which advisory committee members seemed to chafe at the expectation that they would green-light boosters for the general population. Last month, the Biden Administration announced ahead of the FDA’s review that it was prepared to roll out boosters for the vaccinated starting the week of September 20. The announcement reportedly prompted frustration and anger inside the regulatory agency, leading two high-ranking vaccine regulators to announce their resignations.

Vaccine effectiveness

One of those resignations was Marian Gruber, the now-outgoing director of the FDA’s Office of Vaccines Research and Review. At the opening of today’s proceedings, she thanked her staff, noting that it was likely her last VRBPAC meeting. In her opening remarks, she emphasized that the decision of whether to approve a booster dose hinges on determining if it’s “safe,” which “involves weighing whether its benefits outweigh its risks.” For younger males, that leaves the tricky question of whether the potentially increased risk of myocarditis/pericarditis would be outweighed by the potential benefits of a third dose, given that younger males are already at lower risk of severe disease than older groups and still appear to have high levels of protection from the two primary doses.

CDC epidemiologist Sara Oliver presented a synthesis of data suggesting that vaccine efficacy against infection has declined over time, but protection against hospitalizations has remained strong. Comparing pre-delta vaccine efficacy in adults aged 18+ to the latest post-delta data, the range of vaccine efficacy against infection fell from 72 to 92 percent pre-delta to a range of 39 to 84 percent post-delta in July. For hospitalization, vaccine efficacy prior to delta ranged from 84 to 97 percent, dropping to a range of 75 to 95 percent in July after delta.

Critically, when the agency’s analyses just looked at older populations rather than all adults together, vaccine effectiveness still appeared strong, with an efficacy of over 88 percent in people aged 75 and above. However, Dr. Oliver noted data from Qatar suggesting that protection from hospitalization declined in people aged 60 and over after 25 weeks from vaccination, though the confidence intervals were extremely wide.

Similarly, experts from Israel presented data suggesting that vaccine efficacy continues to wane over time, with elderly groups seeing less protection against severe disease. Israel is ahead of the US by about three months in getting a large chunk of its population vaccinated. Thus, the country is seen as a bellwether of vaccine effectiveness. In light of data suggesting widespread waning of protection, Israel rolled out a booster shot on July 30 to all those 16 and over, beginning with the elderly. In the time since, Israel data suggests the boosters stymied confirmed cases in people over 60 and provided a more than 10-fold reduction in relative risk of severe disease in that age group. Unfortunately, there hasn’t been enough time since boosters were rolled out to younger males to generate useful data on safety that could inform a decision in the US.

Data concerns

In another presentation at the meeting, statistician Jonathan Sterne of the University of Bristol warned against taking real-world vaccine efficacy estimates at face value due to a variety of confounding factors. Those include differing characteristics of people who get vaccinated compared with those that don’t, as well as past COVID infections providing some protection in the unvaccinated. Vaccine efficacy estimates can be influenced by the timing of people’s vaccinations, the risk factors each group may have, the waves of infection, and how waves are timed with vaccinations. Many of these factors could add up to make vaccine effectiveness appear lower than it actually is. For instance, people who were first in line to get a vaccine included those with compromised immune systems, thus increases in infection and severe disease could perhaps represent the problem of poor immune responses in those populations rather than a significant waning of protection overall.

In addition, it’s important to note that Israel defines severe disease differently than the US, counting people with high respiratory rates and blood-oxygen levels below 94 percent. In the US, studies often define severe disease as those requiring hospitalization or intensive care or those who die as a result of their infection.

Pfizer presented its own case for boosters, showing US data suggesting that protection against infection has waned but that protection against hospitalization has not. The company argued that Israel’s data foreshadows waning and suggests that boosters will prevent upticks in severe disease and death among vaccinated people.

As for safety, Pfizer and the FDA gave separate presentations that picked through Pfizer’s data on safety, which only involved 306 people between the ages of 18 and 55. The data suggests that a third dose boosted antibody levels to levels comparable if not greater than was seen following second doses. Likewise, side-effects from a third dose were similar to what was seen after a second dose, with the most common effects including pain at the injection site, fatigue, headache, chills, and muscle pain.

Overall, VRBPAC was swayed by the data from Israel suggesting that older people may soon become more vulnerable to severe disease, hospitalization, and death and that booster doses can safely increase protection. But with such little safety data on the younger groups and without a clear and growing risk of severe disease in those younger groups, the members were unconvinced that boosters should be offered to all people ages 16 and up at this time.

Final decisions

In their final deliberations, the members landed on those ages 65 and older as well as people at high risk. The cutoff and definitions are shaky. The committee did not have decisive data on what age group to draw the line at, with some committee members suggesting those above 50 or 60. In the end, the FDA reworded the final voting question, which included the cutoff of 65.

Additionally, the committee felt it was necessary to include people at high risk of severe disease from underlying conditions, given the possibility of further waning and the need to protect healthcare systems from being overwhelmed. Who might qualify under those terms is yet to be defined by an advisory committee for the Centers for Disease Control and Prevention—the Advisory Committee on Immunization Practices—which is set to meet September 22.

In a similar vein, the VRBPAC felt it was important to include those at high risk of infection due to occupational exposure, given that booster shots may reduce the risk of infection and transmission. With hospitals across the country strained and buckling under the weight of the delta coronavirus wave, the committee wanted to ensure that healthcare workers, frontline workers, and teachers could have maximum protection—again—to protect the overall healthcare systems.

Though the decision today may disappoint some hoping for a blanket green light for boosters, the committee was pleased that it followed the science and resisted any pressure from the Biden administration.

“I think this should demonstrate to the public that the members of this committee are independent of the FDA and that, in fact, we do bring our voices to the table,” Archana Chatterjee, a voting VRBPAC member and Dean of Chicago Medical School.

Moving forward, VRBPAC chair Arnold Monto noted that if the booster doses are authorized using an EUA, it will be easy to revisit data in the near future to determine if and when boosters for wider groups may be needed.

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Study: Hottest star in the Milky Way is likely remnant of ancient supernova

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Enlarge / Hubble Space Telescope mosaic image of the Crab Nebula, a six-light-year-wide expanding remnant of a star’s supernova explosion in 1054 CE

NASA/ESA/J. Hester & A. Loll (Arizona State University

In August 1181, astronomers in China and Japan witnessed a bright “guest star” in the night sky that we now know to have been a supernova—one of just a handful of recorded supernovae in our Milky Way that were visible to the naked eye. It shone brightly for a full six months before it disappeared. Astronomers haven’t been able to identify the remnant of the source for SN 1181 for centuries, and that detail is crucial to determine which class the supernova belongs to. Now, an international team of astronomers think they’ve pinpointed that source as one of the hottest stars in the galaxy within the Pa30 nebula, according to a new paper published in the Astrophysical Journal Letters.

As we’ve written previously, there are two types of known supernova, depending on the mass of the original star. An iron-core collapse supernova occurs with massive stars (greater than ten solar masses), which collapse so violently that it causes a huge, catastrophic explosion. The temperatures and pressures become so high that the carbon in the star’s core begins to fuse. This halts the core’s collapse, at least temporarily, and this process continues, over and over, with progressively heavier atomic nuclei. When the fuel finally runs out entirely, the (by then) iron core collapses into a black hole or a neutron star.

Then there is a thermonuclear supernova. Smaller stars (up to about eight solar masses) gradually cool to become dense cores of ash known as white dwarfs. If a white dwarf that has run out of nuclear fuel is part of a binary system, it can siphon off matter from its partner, adding to its mass until its core reaches high enough temperatures for carbon fusion to occur. 

There are also rarer types of supernovae. Among the earliest and most famous “guest stars” was recorded by Chinese astronomers around July 4, 1054. It was visible in broad daylight for 23 days. The remnants now form the Crab Nebula. Some have hypothesized that SN 1054 was a  so-called “electron-capture” supernova, first described some 40 years ago.

If that is indeed the case, SN 1054 has a 21st century cousin. Back in June, we reported that a team of astronomers had identified a second recent supernova—dubbed SN 2018zd—that meets all the criteria for an electron-capture supernova.  In this scenario, a star isn’t heavy enough to produce an iron core collapse supernova, and yet it’s not light enough to prevent its core from collapsing entirely. Instead, such stars stop the fusion process when their cores are composed of oxygen, neon, and magnesium. In this scenario, electrons get gobbled up by the neon and magnesium in the core, thereby causing the core to buckle under its own weight. The end result is a supernova.

According to this new analysis, SN 1181 appears to belong to another relatively rare category known as Type Iax. It’s related to the Type Ia category, in which the supernova is the result of a binary star system where one of the two stars is a white dwarf. Typically, the white dwarf siphons off hydrogen and helium from its companion star, eventually hitting a critical mass and exploding, destroying the white dwarf in the process. But there are cases, such as SN 2012Z, where the white dwarf only loses half its mass and leaves behind a zombie star as a remnant.

False-color images of Parker's star and the nebula Pa30, which scientists now believe are connected with reports of a supernova seen in 1181.
Enlarge / False-color images of Parker’s star and the nebula Pa30, which scientists now believe are connected with reports of a supernova seen in 1181.

Andreas Ritter et al., 2021

“SN 1181 was until now the only remaining historical supernova of the last millennium without a certain counterpart,” the authors wrote. For years, the most likely candidate remnant was a radio and x-ray pulsar known as 3C-58, which currently rotates about 15 times per second. That would mean the pulsar hasn’t lost much rotational energy over the last 900 years. SN 1054’s remnant, the Crab Nebula, in contrast, has lost roughly two-thirds of its rotational energy. And according to recent radio surveys of 3C-58, the pulsar is likely much older than SN 1181 and hence could not be the remnant.

Enter the disk-like nebula Pa30, first discovered by astronomers in 2013, which surrounds a rare, massive Wolf-Rayet star known as Parker’s Star. The authors determined that the dust and gas in Pa30 is expanding at more than 1100 km/sec, and the team used that velocity to derive its age: about 1000 years. This makes it an excellent candidate for the remnant of SN 1181.

“The historical reports place the guest star between two Chinese constellations, Chuanshe and Huagai. Parker’s Star fits the position well,” said co-author Albert Zijlstra of the University of Manchester. “That means both the age and location fit with the events of 1181.”

Astronomers had previously hypothesized that Pa30 and Parker’s Star resulted from the collision and ensuing merger of two white dwarf stars, producing a Type Iax supernova, and Zijllstra et al.‘s findings are in keeping with that hypothesis. “Only around 10 percent of supernovae are of this type and they are not well understood,” said Zijlstra. “The fact that SN1181 was faint but faded very slowly fits this type. It is the only such event where we can study both the remnant nebula and the merged star, and also have a description of the explosion itself. It is nice to be able to solve both a historical and an astronomical mystery.”

DOI: Astrophysical Journal Letters, 2021. 10.3847/2041-8213/ac2253  (About DOIs).

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The FAA releases initial report on Boca Chica launches, and it’s not terrible

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Enlarge / SpaceX’s Booster 4 is lifted on to its orbital launch mount in South Texas.

The Federal Aviation Administration released a draft environmental review of SpaceX’s plans for orbital launches from South Texas on Friday, kicking off a 30-day public comment period.

The long-awaited procedural step is the first of several regulatory hurdles that SpaceX must clear before obtaining final permission to launch its Super Heavy booster and Starship upper stage from a site near Boca Chica, Texas. Such a launch likely remains months away, but it now appears that the feds will ultimately greenlight South Texas for orbital launches. That seemed far from assured before today.

The document, formally called a Draft Programmatic Environmental Assessment, evaluates the potential environmental impacts of SpaceX’s Starship program, including launch and reentry. It also reviews debris recovery, the integration tower and other launch-related construction, and local road closures between Brownsville and Boca Chica beach.

For the large majority of these analyses, the FAA document finds “no significant impacts.” The impact of noise to surrounding communities, including South Padre Island located several miles away, was believed to be one of the biggest concerns. But an independent assessment found noise levels to be manageable.

One exception came under the “biological resources” category. “The FAA has determined the Proposed Action would adversely affect species listed under and critical habitat designated under the federal Endangered Species Act,” the report states. However, there may be a way to mitigate these impacts. Another potential area of concern is excessive road closures of Highway 4. This may be one reason why SpaceX is proposing an average of five Super Heavy launches a year during the operational phase of the program.

Following the release of this draft assessment, the FAA will hold virtual public hearings on Oct. 6 and 7 before the public comment period ends on Oct. 18, 2021. SpaceX founder Elon Musk asked for support on Twitter, shortly after the FAA released the draft document. “Please add your voice to the public comments,” Musk said. “Support is greatly appreciated! Humanity’s future on the moon, Mars & beyond depends upon it.”

After the public comment period closes, the FAA will finalize its environmental assessment. Following this, the FAA will issue one of three rulings: a Finding of No Significant Impact (FONSI), Mitigated FONSI, or issue a Notice of Intent to prepare an Environmental Impact Statement. A “FONSI” would allow the formal launch licensing process to proceed. If a full Environmental Impact Statement is needed, launches from South Texas would likely be delayed by months, if not years, as more paperwork is completed.

SpaceX has not revealed the full extent of its launch plans for Super Heavy and Starship, but the document suggests the company may eventually land its Super Heavy booster down range, on a platform in the Gulf of Mexico, and Starship may land in remote islands in the Pacific Ocean. SpaceX also will likely conduct launches from a platform in the Gulf of Mexico, as well as a pad at Kennedy Space Center.

The upside of Friday’s document release is that SpaceX can now move forward with some confidence that it ultimately will at least be able to conduct orbital test flights of Super Heavy and Starship from South Texas. This is critical as the site is just a couple of kilometers from the factory where the company assembles the giant rocket and spacecraft.

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