Researchers are exploring the possible benefits of pairing doses from two different Covid-19 vaccines.In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.As growing numbers of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.“It might be that actually this flexibility becomes essential in the future,” he said.Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

Researchers are exploring the possible benefits of combining doses from two different Covid-19 vaccines.In January, Britain made a change to its vaccine guidelines that shocked many health experts: If the second dose of one vaccine wasn’t available, patients could be given a different one.The new rule was based on sheer guesswork; there was no scientific data at the time demonstrating that mixing two coronavirus vaccines was safe and effective. But that may change soon.In February, researchers at the University of Oxford began a trial in which volunteers received a dose of the Pfizer-BioNTech vaccine followed by a dose of AstraZeneca’s formulation, or vice versa. This month, the researchers will start analyzing the blood of the subjects to see how well the mix-and-match approach works.As a growing number of vaccines are being authorized, researchers are testing other combinations. A few are in clinical trials, while others are being tested in animals for now.Mixing vaccines might do more than just help overcome supply bottlenecks. Some researchers suspect that a pair of different vaccines might work better than two doses of the same one.“I think we’re on the cusp of some interesting data,” said Adam Wheatley, an immunologist at the University of Melbourne in Australia.The concept of mixing vaccines — sometimes called a heterologous prime-boost — is not new to our pandemic era. For decades, researchers have investigated the approach, hoping to find potent combinations against a range of viruses, such as influenza, H.I.V. and Ebola.But scientists had little to show for all that research. It was easy enough to demonstrate that two vaccines may work well together in a mouse. But running full-blown clinical trials on a combination of vaccines is a tall order.“For a single company to develop two parallel arms of a vaccine is twice the work and twice the cost,” Dr. Wheatley said.Some of the early successes for heterologous prime-boosts came in the search for vaccines for Ebola. Many researchers focused their efforts on presenting the immune system with a protein found on the surface of the Ebola virus.The gene for that protein was inserted into a different, harmless virus. When people received an injection of the vaccine, the harmless virus entered their cells; the cells then read the instructions in the Ebola gene and mass-produced Ebola’s surface protein. The immune system encountered the Ebola protein and made antibodies against it. And those antibodies protected the vaccinated people if they became infected with a full-blown Ebola virus.This type of vaccine, called a viral vector vaccine, came with a big risk: The recipients might develop immunity to the viral vector after just the first dose. When the second dose arrived, their immune systems could swiftly wipe out the viral vector before it delivered its payload.A number of vaccine makers decided to sidestep this potential threat by using different viruses for each dose. That way, the viral vectors in the second dose would be as new to the immune system as the first was. In 2017, for example, researchers at the Gamaleya Research Institute in Russia created an Ebola vaccine whose first dose contained a virus called an adenovirus. The second shot used another virus, called vesicular stomatitis virus.When the Covid-19 pandemic began last year, the Gamaleya researchers used a similar strategy to create vaccines against the new coronavirus. The first dose used the same adenovirus as in their Ebola vaccine, called Ad5. The second dose contained a different human adenovirus, Ad26. The researches inserted a gene into both viruses for the protein on the surface of the coronavirus, called spike.Studies revealed that the vaccine, now known as Sputnik V, provided a strong defense against Covid-19. In clinical trials, the researchers found that it had an efficacy of 91.6 percent. Sputnik V is now in use in Russia and 56 other countries.Recently, the Gamaleya institute joined forces with AstraZeneca, which makes its own Covid-19 vaccine. AstraZeneca’s consists of two doses of a chimpanzee adenovirus called ChAdOx1. Last week, the company reported that its vaccine had an efficacy of 76 percent.The Gamaleya and AstraZeneca teams want to see how well their vaccines work together. They have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s ChAdOx1 and another of Sputnik V’s Ad26.A spokesman for AstraZeneca said that one trial in Azerbaijan is underway, and a second, in Russia, is still under review by the country’s ministry of health.Dr. Jakob Cramer, the head of clinical development at CEPI, a vaccine development organization, said that vaccines using viral vectors were not the only kind that might benefit from mixing. In fact, certain combinations might provoke a different, more effective immune response than a single type of vaccine. “Immunologically, there are several arguments in favor of exploring heterologous priming,” Dr. Kramer said.Another kind of Covid-19 vaccine being tested contains the actual spike protein, rather than genetic instructions for it. Some of the vaccines contain the entire protein; others contain just a fragment of it. Currently, there are 29 protein-based vaccines for Covid-19 in clinical trials, although none have been authorized yet.Dr. Wheatley and his colleagues have been testing protein-based vaccines in mice. They injected the full spike protein into the animals as a first dose. For the second dose, they injected only the tip of the spike, a region known as the receptor-binding domain, or R.B.D.Dr. Wheatley and his colleagues found that the mixture worked better than two doses of the spike or of the R.B.D.The researchers suspect that the first dose produces a broad range of antibodies that can stick to spots along the length of the spike protein, and that the second dose delivers a big supply of particularly potent antibodies to the tip of the spike. Together, the assortment of antibodies does a better job of stopping the coronavirus.“You’re able to basically take that initial immunity that was elicited to that spike vaccine, and then really focus it down onto that R.B.D.,” Dr. Wheatley said.Other combinations of vaccines may bring benefits of their own. Some vaccines, especially protein-based ones, do a good job of generating antibodies. Others, such as viral vectors, are better at training immune cells. A viral vector followed by a protein boost might offer the best of both worlds.John Moore, a virologist at Weill Cornell Medicine, cautioned that there was no guarantee that clinical trials would reveal a benefit to mixing vaccines. In the search for an H.I.V. vaccine, researchers tried combining viral vectors and protein boost without success, he noted. Still, Dr. Moore said, the story might turn out differently for coronavirus vaccines.“I’d like to see these studies done,” he said. “Doing it in the Covid space is completely rational, but may not be necessary.”Some researchers are investigating heterologous vaccines not to find a superior mixture, but simply to open up more options for countries desperate to vaccinate their populations. Last week, India held back exports of vaccines to other countries as it grappled with a surge of Covid-19. For countries that were counting on those vaccines, a safe alternative for second doses could save lives.After Britain was criticized in January for suggesting that vaccines could be mixed, researchers at the University of Oxford set out to put the idea to a formal test. In a trial called Com-Cov, they recruited 830 volunteers to test the two vaccines authorized by the British government: AstraZeneca’s adenovirus-based vaccine and the vaccine by Pfizer-BioNTech.Pfizer-BioNTech’s vaccine uses a fundamentally different technology to produce spike proteins in the body. It contains tiny bubbles with genetic molecules called RNA. Once the bubbles fuse to cells, the cells use the RNA to make spike proteins.One group of volunteers is receiving a Pfizer-BioNTech shot followed by AstraZeneca, while another will receive them in the reverse order. The other volunteers are receiving the standard two-dose version of the vaccines.Later this month, the Oxford team will draw blood from the volunteers, examining their antibodies and immune cells to see whether the heterologous prime-boost creates an immune response roughly as strong as two doses of each of the authorized vaccines.If more vaccines are authorized in Britain, the Com-Cov team may add them to the trial. Dr. Matthew Snape, who is leading the Com-COV trial, hopes it will be useful not just to his own country but to others that will be trying to vaccinate their citizens over the next few years.“It might be that actually this flexibility becomes essential in the future,” he said.Dr. Cramer said CEPI is planning to support additional heterologous prime-boost studies. There are plenty of possible studies to run. Worldwide, 13 vaccines are now in use against Covid-19, with 67 more in clinical trials.“In the current situation, we have a quite a luxurious position of having so many advanced, effective vaccines,” Dr. Wheatley said.As the number of authorized vaccines grows, the possible combinations in which they can be used will explode. Recently, researchers at China’s National Institutes for Food and Drug Control scaled up their research on heterologous prime-boosts by trying out four different vaccines that have either been authorized in China or are in late-stage clinical trials there — vaccines based on adenoviruses, proteins, RNA and coronaviruses that have been inactivated with chemicals.The researchers injected mice with a first dose of one vaccine, then a second dose of another. Some of the combinations caused the mice to produce stronger immune responses than mice that received the same vaccine for both doses.Whether scientists carry out more experiments on other vaccines will depend on the willingness of the vaccine manufacturers. “You’re requiring quite large pharmaceutical companies to play nice together,” Dr. Wheatley said.Dr. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases, suspects that a number of companies will be willing to let their vaccines be tested in combinations. “It’s always better to be a part of something that is going to be used,” he said, “than to wholly own something that isn’t.”

More than just a sign of illness, mucus is a critical part of our body’s defenses against disease. Every day, our bodies produce more than a liter of the slippery substance, covering a surface area of more than 400 square meters to trap and disarm microbial invaders.
Mucus is made from mucins — proteins that are decorated with sugar molecules. Many scientists are trying to create synthetic versions of mucins in hopes of replicating their beneficial traits. In a new study, researchers from MIT have now generated synthetic mucins with a polymer backbone that more accurately mimic the structure and function of naturally occurring mucins. The team also showed that these synthetic mucins could effectively neutralize the bacterial toxin that causes cholera.
The findings could help give researchers a better idea of which features of mucins contribute to different functions, especially their antimicrobial functions, says Laura Kiessling, the Novartis Professor of Chemistry at MIT. Replicating those functions in synthetic mucins could eventually lead to new ways to treat or prevent infectious disease, and such materials may be less likely to lead to the kind of resistance that occurs with antibiotics, she says.
“We would really like to understand what features of mucins are important for their activities, and mimic those features so that you could block virulence pathways in microbes,” says Kiessling, who is the senior author of the new study.
Kiessling’s lab worked on this project with Katharina Ribbeck, the Mark Hyman, Jr. Career Development Professor of Biological Engineering, and Richard Schrock, the F.G. Keyes Professor Emeritus of Chemistry, who are also authors of the paper. The lead authors of the paper, which appears today in ACS Central Science, are former MIT graduate student Austin Kruger and MIT postdoc Spencer Brucks.
Inspired by mucus
Kiessling and Ribbeck joined forces to try to create mucus-inspired materials in 2018, with funding from a Professor Amar G. Bose Research Grant. The primary building blocks of mucus are mucins — long, bottlebrush-like proteins with many sugar molecules called glycans attached. Ribbeck has discovered that these mucins disrupt many key functions of infectious bacteria, including their ability to secrete toxins, communicate with each other, and attach to cellular surfaces.

Mount Sinai researchers have found that a widely available and inexpensive drug targeting inflammatory genes has reduced morbidity and mortality in mice infected with SARS-CoV-2, the virus that causes COVID-19. In a study published today in the journal Cell, the team reported that the drug, Topotecan (TPT), inhibited the expression of inflammatory genes in the lungs of mice as late as four days after infection, a finding with potential implications for treatment of humans.
“So far, in pre-clinical models of SARS-CoV-2, there are no therapies — either antiviral, antibody, or plasma — shown to reduce the SARS-CoV-2 disease burden when administered after more than one day post-infection,” says senior author Ivan Marazzi, PhD, Associate Professor of Microbiology at the Icahn School of Medicine at Mount Sinai. “This is a huge problem because people who have severe COVID19 and get hospitalized, often do not present symptoms until many days after infection. We took a different approach, and sought to find a potential therapy that can be used during later stages of the disease. We found that the TOP1 inhibitors given days after the infection can still limit the expression of hyper-inflammatory genes in the lungs of infected animals and improve infection outcomes.” Moreover, says Dr. Marazzi, topotecan (TPT), an FDA-approved Topoisomerase I (TOP1) inhibitor, as well as its derivatives, are inexpensive clinical-grade inhibitors available in most countries around the world for use as antibiotic and anti-cancer agents.
Although the pathophysiology of SARS-CoV-2 is not yet fully understood, scientists have observed that the virus triggers excess production of cytokines and chemokines — chemicals which are secreted by cells of the immune system to help fight infection. An exaggerated immune system response, which characteristically occurs in the lungs of COVID-19 patients, can flood the infected area with white blood cells, resulting in inflammation, possible tissue damage, organ failure, and death. Reduction of the inflammatory state in such patients could therefore improve their clinical outcomes.
In a previous study published in Science in 2016, the same group at Mount Sinai found that inhibiting the activation of inflammatory genes could help prevent animal deaths from viral and bacterial infections and suggested this could be a potent strategy against future pandemics. The current study, led by Mount Sinai along with partners from Singapore, Hong Kong, the United Kingdom, the United States, and other global sites, expands on that earlier work to show how epigenetic therapy (which addresses the chemical modifications that influence gene expression) could be harnessed against severe cases of COVID-19.
The team’s research suggests that many other anti-inflammatory agents are less effective against COVID-19 because they target only a single inflammatory mediators, such as IL6 or IL1, or a specific gene expression program. “The fact is, a multitude of inflammatory genes and signaling pathways are dysregulated during a SARS-CoV-2 infection,” explained lead author Jessica Sook Yuin Ho, PhD, a postdoctoral researcher at Icahn Mount Sinai. “We demonstrated that TOP1 inhibitors were able to broadly or systemically dampen inflammatory gene expression in animal models, regardless of the gene or activation pathway.”
Co-author Mikhail Spivakov, PhD, head of the Functional Gene Control group at the MRC London Institute of Medical Sciences added, “We found that infection prompts extensive changes in the 3D connections between inflammatory genes and the ‘molecular switch’ regions that control their expression. This may partially explain why inhibiting topoisomerase, a protein that helps reshape DNA, helps dampen the cells’ hyper-inflammatory response.”
The safety and efficacy of this treatment strategy in humans will soon be evaluated at clinical sites around the world, including India, where a trial recently began and Singapore, where the National Medical Research Council of Singapore has also funded a phase 1 clinical trial of topoisomerase 1 inhibition in COVID-19. The World Health Organization (WHO) is also expected to play an important role in subsequent studies.
“Findings from our work suggest that repurposing the TOP1 inhibitor could be a valuable global strategy for treating severe cases of COVID-19,” emphasizes Dr. Marazzi. “Particularly attractive is the fact that TPT is already FDA-approved and that its derivatives are inexpensive, with generic formulations existing throughout the world. This makes these drugs readily accessible and available for immediate use in both developing and developed countries across the world.”

After more than three decades of research, scientists have proven that the cancer affecting up to one in four adult California sea lions necrospied at The Marine Mammal Center in Sausalito, CA, is caused by a sexually transmitted herpesvirus. The cancer, known as sea lion urogenital carcinoma, has clear parallels to cervical cancer in humans and provides a helpful model for human cancer study.
Scientists have long suspected this cancer was associated with a virus, but this is the first study to prove this theory. The study, which was published in Animals, an open-access, peer-reviewed journal, concluded that genital herpesvirus is a driving factor in the development of sea lion urogenital carcinoma. The research also suggests there is an underlying trigger or event that causes the virus to induce cancer in some infected sea lions and not others. Wild California sea lions have among the highest prevalence of a single type of cancer in any mammal, including humans.
A second recently published paper (Sea lions are dying from a mysterious cancer. — Los Angeles Times) led by the same team showed that pollutants such as PCBs and DDT play a significant role as co-factors in the development of this cancer. This is particularly relevant to Southern California where there is a large DDT dumpsite in the Southern California bight which is also where the majority of the sea lion population gather each year to give birth and raise their pups (How the waters off Catalina became a DDT dumping ground — Los Angeles Times).
“The confirmation that this is a virally induced cancer combined with the knowledge that contaminants play a significant role in the cancer’s development means that we can use these sea lions as a naturally occurring disease model to better understand how cancer develops and spreads in all species, including humans,” says Dr. Alissa Deming, the lead author of the study who completed this work during her Ph.D. studies at University of Florida in Gainesville, FL., while she was a Research Fellow at The Marine Mammal Center in Sausalito, CA. (Dr. Deming is now Director of Clinical Medicine at the Pacific Marine Mammal Center in Laguna Beach, CA.)
The Marine Mammal Center is the world’s largest marine mammal hospital and has been on the forefront of researching and understanding cancer in California sea lions and its connection to both ocean and human health. Since cancer in sea lions was first discovered in 1979, researchers have found that between 18-23 percent of adult sea lions admitted to the Center’s hospital have died of the fatal disease. In 2010, the Center brought together an array of international researchers to form the Sea Lion Cancer Consortium to further investigate this disease, many of whom helped co-author the paper.
“This research is critical as these sea lions may hold the key to understanding virally induced cancers as well as how cancer metastasizes, or spreads through the body,” says Dr. Pádraig Duignan, Director of Pathology at The Marine Mammal Center and a co-author on the study. “This knowledge is an important link that could help scientists better understand various cancers in people.” Most cancers are caused by an accumulation of several factors, making it challenging to study cancer in traditional laboratory models. However, wild sea lions experience multiple layers of stressors including infectious agents, exposure to pollutants, nutrition, and environmental influences, all of which are much more representative of how cancer develops in the “real world.”
According to Duignan, “the cancer begins in the sea lion’s genital tract and aggressively spreads throughout the sea lion’s body, resulting in death, often from kidney failure.” Because of the advanced state of cancer by the time these patients strand on beaches and are rescued by rehabilitation centers, euthanasia is the only humane option. “This cancer is devastating to see in California sea lions. They come to the hospital in end-stage disease,” says Dr. Deming.
The paper was the result of an international, cross-discipline effort, combining multiple techniques from a variety of specialists to unlock the mysteries of this disease. The research relied on novel techniques using RNAscope® Technology and Base Scope™, tools that allow researchers to pinpoint high viral gene expression within tumor tissue but not in surrounding healthy tissue.
“Our study was the first time that this revolutionary technique has been used on a marine mammal species,” says Dr. Kathleen Colegrove, Clinical Professor of the Zoological Pathology Program at the University of Illinois Urbana-Champaign, and a key researcher on the study. “This proved that the virus was integral to cancer development and was not just being detected in the reproductive tracts or tissue as a bystander.”
Story Source:
Materials provided by The Marine Mammal Center. Note: Content may be edited for style and length.

Insurers are stuck with the big bills from Lenox Hill, but the public ultimately pays through higher premiums.The Lenox Hill Greenwich Village emergency department, where patients have been charged extraordinarily high prices for coronavirus tests. This photo was taken in mid-March; the blue parts of the signs advertising Covid testing have since been removed.Steven Molina Contreras for The New York TimesLenox Hill Hospital in Manhattan advertised its “Covid-19 Testing” on a large blue and white banner outside its Greenwich Village division’s emergency room. The banner said nothing about cost.But cost turned out to be the testing’s most noteworthy feature. Lenox Hill, one of the city’s oldest and best-known hospitals, repeatedly billed patients more than $3,000 for the routine nasal swab test, about 30 times the test’s typical cost.“It was shocking to see a number like that, when I’ve gotten tested before for about $135,” said Ana Roa, who was billed $3,358 for a test at Lenox Hill last month.Ms. Roa’s coronavirus test bill is among 16 that The New York Times reviewed from the site. They show that Lenox Hill arrives at its unusually high prices by charging a large fee for the test itself — about six times the typical charge — and by billing the encounter as a “moderately complex” emergency room visit. In one case, a family accrued $39,314 in charges for 12 tests this winter, all taken to fulfill requirements for returning to work or school. In another, an asymptomatic patient walked in because she saw the banner outside and wanted a test after traveling. Her insurance was charged $2,963.Federal legislation last year mandated that coronavirus testing be free for patients, so individuals are typically protected. None of the patients tested at the Lenox Hill emergency room were billed directly for the service. But eventually, American patients bear the costs of these expensive tests in the form of higher insurance premiums.Patient bills show that at least one additional hospital owned by Lenox Hill’s parent group, Northwell Health, has charged emergency room fees to patients at a mass testing site.“It felt like deception, and an effort to try and get money that they are not entitled to,” said Ute Tabi. She was reviewing her family’s insurance claims and saw a $2,793 charge for a drive-through coronavirus test her husband got at a Northwell hospital in the New York suburbs, Huntington Hospital on Long Island. The hospital pursued the family for a share of the bill, which Ms. Tabi has so far refused to pay. The Times has been asking readers to submit bills so that we can understand the costs of coronavirus testing and treatment. So far, more than 600 patients have participated. Their bills have revealed high charges and illegal fees, as well as patients who face substantial medical debt for coronavirus treatment. If you have a bill for coronavirus testing or treatment, you can share it here.Northwell Health, a nonprofit, operates 23 hospitals in the region, and received about $1.2 billion in emergency health provider funding in the federal CARES Act last year.The chain recently came under scrutiny after The Times revealed it had sued more than 2,500 patients for medical debt during the pandemic. It has since dropped those cases.Northwell, which defended its coronavirus testing charges as appropriate, has since removed the blue signs at the Greenwich Village division advertising the service.Officials said patients tested at the emergency room received more advanced care than they would elsewhere. They declined to comment on specific patient cases but said their protocols involve notifying patients that their test will come with emergency room fees. A sign with the information is taped to a plexiglass shield at the registration desk.“I don’t think of the emergency room as a testing site,” said Barbara Osborn, Northwell’s vice president for communications.But the Lenox Hill in Greenwich Village has tested 15,000 patients for coronavirus over the course of the pandemic. Patients interviewed by The Times said they went there because of the banner outside, not to seek emergency care. They were asymptomatic and seeking tests as a precaution before traveling or socializing.Ms. Roa spotted the emergency room fee through an unusual circumstance. Her wallet had been stolen, and she was checking her bills. She feared her identity had been stolen because she had no memory of visiting an emergency room.“I called my insurance and was freaking out, asking who has my identity, what will this bring,” she said. “After maybe 45 minutes, I got transferred to someone who was able to tell me that this was all about a Covid test.”Congress inadvertently encourages expensive testsAmericans have taken about 370 million tests during the pandemic. The price of each — as with most services in the American health system — can vary widely from one hospital or doctor’s office to another.State-run testing sites in New York do not charge patients or collect health insurance information for the Covid nasal swab tests. A study published last year found that a swab test at a hospital can run from $20 to $850. Some independent laboratories have charged more, billing $2,315.The Lenox Hill Greenwich Village center bills $671 for its coronavirus test, six times what major labs such as LabCorp and Quest charge. The rest of the price discrepancy comes from the emergency room fees.Doctors and hospitals that bill higher prices for testing can rely on new federal protections to ensure they are paid. Congress passed a law last year that requires insurers to fully cover coronavirus testing costs and not apply any patient co-payments or other fees to the service.Insurers must also pay for services that are necessary to obtain the coronavirus test, such as a doctor’s visit or, in the case of Lenox Hill, an emergency room facility fee.“This is such a gold mine for hospitals because now they can charge emergency fees for completely healthy people that just want to be tested,” said Renee Hsia, a professor of emergency medicine at the University of California, San Francisco, who researches medical billing. “This is what you’d expect from a market-oriented approach to health care. It’s the behavior our laws have incentivized.”Emergency rooms in the United States typically charge patients something called a facility fee, the price of walking through the door and seeking care. The fees have risen sharply in recent years, and can cost about $200 for a simple visit or $1,800 for the most complex cases.Hospitals like Lenox Hill often defend these costs as necessary to fulfill federal laws that require them care for all patients regardless of their ability to pay.“If someone does not have insurance, we still provide the same level of care as we would to someone who has insurance,” said Rich Miller, Northwell’s chief business officer.Emergency room fees are common in the American system but rare in the world of coronavirus testing. At The Times’s request, the data firm Castlight Health analyzed insurance claims for 1.5 million coronavirus tests.It found that less than 4 percent of coronavirus tests are billed through emergency departments. The vast majority of those tests are associated with large claims that have many charges, suggesting the nasal swab was incidental to a more complex visit.Only about 5,000 bills out of the sample of 1.5 million — about 0.3 percent — were billed in a way that looked similar to Lenox Hill’s fees, the Castlight data shows.At the Lenox Hill site, Mr. Miller explained, there are actually two separate coronavirus testing processes. Patients who arrive with a doctor’s order for a coronavirus test are routed to a service center that does not charge emergency room fees.Patients who come in without that prescription are sent to the emergency room for an evaluation, where they will incur the facility fee charges. About 75 percent of coronavirus tests at Lenox Hill Greenwich Village are routed through the emergency room, a practice Mr. Miller defended.“Anyone who would have been billed for an emergency room visit would have been assessed accordingly to see if other things were wrong with them,” Mr. Miller said. “We believe we’re adequately disclosing that this is an emergency department visit, and will be billed as E.R.”Short visits, surprising billsFounded in 1857, Lenox Hill has long served a wealthy clientele at its main division on the Upper East Side of Manhattan. It is where Beyoncé gave birth in 2012, and is the subject of an eponymous Netflix documentary series that shows the hospital’s inner workings.In 2010, New York State awarded Lenox Hill the rights to take over the Greenwich Village building left empty by the closing of St. Vincent’s Hospital. It replaced it with a free-standing emergency room.It would stay open 24 hours and provide care to patients regardless of their ability to pay. But unlike traditional emergency rooms, it is not physically attached to a larger hospital.Free-standing emergency rooms have proliferated in recent years, across the country and across New York City. Montefiore, Northwell and N.Y.U.-Langone have all opened them within the last decade.Supporters have praised them for expanding critical care access without building an entire hospital, a potential boon to underserved urban and rural areas.But they have also faced criticism for how they price care, especially for simple visits. One analysis conducted by the health insurer UnitedHealthcare found that the average cost for a visit related to a common condition like a fever or cough was 19 times higher in free-standing emergency rooms than in urgent care centers.“Free-standing emergency departments simultaneously represent the best, innovative side of American health care and the pure profit motive,” said Dr. Jeremiah Schuur, chair of the emergency medicine department at Brown University’s Alpert Medical School.The prices at Lenox Hill’s free-standing emergency room caught the eye of local government officials shortly after it opened. New York City’s Community Board 2, which has jurisdiction over Greenwich Village, held a meeting in 2016 to discuss several cases. One patient was charged $1,000 to have a bee sting looked at, and another faced fees of $3,000 related to a sprained ankle.Sarah Nathan was not looking for emergency-level care when she was tested at Lenox Hill Greenwich Village. She just needed a test to return to her job as a nursery school teacher.The bill for her visit came to $3,194, which her insurance negotiated down to $2,084. She recalls asking a front desk representative whether she would be billed for an emergency room visit. She said she was told she would not be.Ms. Nathan worries about the impact these high fees could have on her premiums.“My insurance is so expensive already, and it infuriates me that they’re adding to the cost of that for New Yorkers,” she said.Coronavirus tests were scarce at the start of the pandemic, but have since become plentiful, raising questions about why Lenox Hill advertised testing at this site.Northwell owns an urgent care center that is a 15-minute walk from the Lenox Hill emergency room. The urgent care center’s charge for a Covid nasal swab test and doctor visit usually comes to $350 — nearly 90 percent less.

SharecloseShare pageCopy linkAbout sharingimage copyrightReutersThe head of the World Health Organization (WHO) says further investigation is needed to conclusively rule out a theory that Covid-19 emerged from a laboratory in China. Tedros Adhanom Ghebreyesus said on Tuesday that although a laboratory leak is the least likely cause, more extensive research is needed.The virus was first detected in Wuhan, in China’s Hubei province in late 2019.The Chinese government has dismissed the allegations of a virus leak.Since the novel coronavirus was first identified, more than 2.7 million people are known to have died from it, with more than 127 million cases worldwide.An international team of experts travelled to Wuhan in January to probe the origins of the virus. Their research relied on samples and evidence provided by Chinese officials. Dr Tedros said the team had difficulty accessing raw data and called for “more timely and comprehensive data sharing” in the future. image copyrightReutersThe team investigated all possibilities, including one theory that the virus had originated at the Wuhan Institute of Virology. The institute is the world’s leading authority on the collection, storage and study of bat coronaviruses. Former US President Donald Trump was among those who supported the theory that the virus might have escaped from a lab.But a report by WHO and Chinese experts released on Tuesday and seen by AFP news agency, said the lab leak explanation was highly unlikely and the virus had probably jumped from bats to humans via another intermediary animal. Wuhan- City of silenceWuhan marks its anniversary with triumph and denialHowever the theory “requires further investigation, potential with additional missions involving specialist experts,” Dr Tedros said. “Let me say clearly that as far as WHO is concerned, all hypothesis remain on the table,” he added. Also on Tuesday, WHO investigation team leader, Peter Ben Embarek, said his team had found no evidence that any laboratories in Wuhan were involved in the outbreak. He added that his team had felt under political pressure, including from outside China but said he was never pressed to remove anything from the team’s final report.Dr Embarak added that it was “perfectly possible” that cases were circulating in the Wuhan area in October or November 2019. China informed the WHO about cases on 3 January, a month after the first reported infection. Shortly after, the US and 13 allies including South Korea, Australia and the UK, voiced concern over the report and urged China to provide “full access” to experts. The statement said the mission to Wuhan was “significantly delayed and lacked access to complete, original data and samples”.The group pledged to work together with the WHO. China has refuted claims the virus originated in a lab and says that although Wuhan is where the first cluster of cases was detected, it is not necessarily where the virus originated. State media has claimed that the virus may have arrived in Wuhan on frozen food imports.The country has largely brought its own outbreak under control through quick mass testing, stringent lockdowns and tight travel restrictions.

It makes evolutionary sense for long-lived animals to have complex social relationships — such as friends and enemies — researchers say.
Some species and individuals focus their energy on reproduction (live fast, die young), while “slow-living” animals prioritise survival and tend to live longer lives.
In the new paper, University of Exeter scientists argue that natural selection favours complex social structures among slow-living animals — meaning that knowing their friends and enemies is easier for animals with longer lifespans, and helps them live even longer.
Meanwhile, fast-lived species should only bother with such social relationships if it increases their chances of reproduction.
“Slow-living species can afford to invest in social relationships, as they live long enough to enjoy the pay-offs,” said Professor Dave Hodgson, Director of the Centre for Ecology and Conservation on Exeter’s Penryn Campus in Cornwall.
“There is strong evidence that strong social bonds are beneficial for survival in slow-living species, including humans.

Drinking beetroot juice promotes a mix of mouth bacteria associated with healthier blood vessels and brain function, according to a new study of people aged 70-80.
Beetroot — and other foods including lettuce, spinach and celery — are rich in inorganic nitrate, and many oral bacteria play a role in turning nitrate to nitric oxide, which helps to regulate blood vessels and neurotransmission (chemical messages in the brain).
Older people tend to have lower nitric oxide production, and this is associated with poorer vascular (blood vessel) and cognitive (brain) health.
In the new study, by the University of Exeter, 26 healthy older people took part in two ten-day supplementation periods: one with nitrate-rich beetroot juice and another with nitrate-free placebo juice, which they drank twice a day.
The results showed higher levels of bacteria associated with good vascular and cognitive health, and lower levels of bacteria linked to disease and inflammation.
Systolic blood pressure dropped on average by five points (mmHg) after drinking the beetroot juice.

Remote monitoring using airborne devices such as drones or satellites could revolutionise the effectiveness of nature-based solutions (NBS) that protect communities from devastating natural hazards such as floods, storms and landslides, say climate change experts from the University of Surrey.
Grey structural measures (a collective term for engineering projects that use concrete and steel) like floodgates, dams, dikes and sea walls are still the most common methods to guard against natural hazards. However, these ‘grey measures’ are expensive and lack the long-term flexibility and sustainability needed to help communities manage their growing population and address the planet’s ongoing struggle against urbanisation and climate change. While NBS are cost-effective, their usability and reproducibility are often hindered by the lack of standard monitoring methods, tools and indicators.
In a comprehensive study published in the Earth-Science Reviews journal, researchers from Surrey’s Global Centre for Clean Air Research (GCARE) collaborated with experts from across Europe to analyse monitoring methods that measure the effectiveness of NBS — such as wetlands, forest restoration projects and installation of green walls.
In the paper, the team found that while there is a need for combining ground and remote monitoring methods for holistic assessment, the advances in remote monitoring techniques present a significant source of hope for routinely, continually and accurately measuring the effectiveness of NBS and quelling skepticism around choosing NBS over grey-engineered options. Remote monitoring offers the ability to cover large geographical areas, and high-resolution imagery could change the way farmers, scientists, hazard managers and other decision-makers view NBS usage and applicability.
However, the study also warns that the lack of globally accepted standards to gauge an NBS success hinders their progress and use and needs to be urgently addressed.
Professor Prashant Kumar, Associate Dean (International) and the Director of the GCARE at the University of Surrey, said: “Unfortunately we do expect a significant uptick in natural hazards, thanks to climate change. Therefore, our decisions on how we protect ourselves are crucial, and nature-based solutions have the advantages of being flexible and not adding to the damage caused to our environment.
“I hope that this review begins an urgent discussion on how we can move forward as a scientific community and start to develop an accepted framework for measuring the effectiveness of nature-based solutions.”
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