Publisher Health

A new study led by researchers at the University of North Carolina at Chapel Hill Institute for the Environment, Boston University School of Public Health and the Environmental Defense Fund finds that pollution from oil and gas venting and flaring results in $7.4 billion in health damages, more than 700 premature deaths, and 73,000 asthma exacerbations among children annually. Researchers also conclude that emissions are underreported and controlling emissions is not only profitable for operators, but also can significantly improve public health in surrounding communities.
Oil and gas producers worldwide use venting and flaring to release or burn away excess natural gas in crude oil production. The practice contributes to air pollution in surrounding and downwind communities resulting in increased risk of hospitalizations, emergency room visits, worsening asthma and even premature death.
“Being able to combine information from what states are reporting with satellite retrievals helped us quantify the emissions from this sector better than just relying on one source,” said Sarav Arunachalam, deputy director of the UNC Institute for the Environment and senior author of the study. “Using a comprehensive multipollutant modeling framework as shown in our study is needed to assess the overall air quality impacts of this sector, instead of just focusing on one pollutant. ”
According to the study, published in GeoHealth, flaring and venting activities contribute an estimated $7.4 billion in health risks and 710 premature deaths annually in the U.S. Of those deaths, 360 are attributable to fine particulate matter (PM2.5), ozone (O3) and nitrogen dioxide (NO2). Fine particulate matter is widely known to cause adverse health effects, but researchers say impacts from O3 and NO2 should not be overlooked.
“Our research shows that oil and gas flaring can have substantial health impacts, and that a large portion of these impacts come from NO2 and O3, two air pollutants which are commonly not considered in health impact assessments,” said co-author Jonathan Buonocore, an assistant professor of environmental health at Boston University School of Public Health.
Quantifying emissions for flaring and venting in the oil and gas industry has been difficult historically due to the intermittent nature of the practice and how those emissions are reported. The research team used satellite images from the Visible Infrared Imaging Radiometer Suite (VIIRS) instrument on the Suomi National Polar-orbiting Partnership (NPP) satellite to observe flaring and venting activities in combination with state and local reported data and found emissions that were up to 15 times higher for fine particulate matter, two times higher for sulfur dioxides and 22% higher for nitrogen oxides than what was reported in the U.S. EPA’s National Emission Inventories (NEI). These emissions contribute to health-harming air pollution in oil and gas basins and surrounding areas and exceedances in ozone ambient air quality standards.
Texas, Pennsylvania and Colorado had the highest health burdens in this analysis, accounting for 45% of the total number of flaring and venting air pollution excess deaths.

Researchers also found the air quality health burdens of flaring and venting fall disproportionately on low-income, Hispanic and Native American communities. Of the total early deaths caused by flaring and venting, one in three occurred in low-income census tracts, 30% occurred in Hispanic/Latino census tracts, and 10% occurred in Native American census tracts. Of the 73,000 childhood asthma cases, 40% occurred in Hispanic/Latino census tracts.
Researchers are hopeful these new insights will have significant benefits on air quality and human health by reducing emissions from flaring and venting activities.
“This research provides more evidence of the problem of excessive venting and flaring in the oilfield,” said Hillary Hull a co-author of the study and director of research and analytics at the Environmental Defense Fund. “This practice wreaks havoc on our climate, worsens quality of life and creates more health risks for people who live near this activity. State and national policies designed to put an end to this dangerous practice are sorely needed to protect the health and well-being of these communities.”
“The recent MethaneSat mission launched to monitor oil and gas projects and specifically identify, in near real-time, large sources of methane that some satellite missions may miss will further assist to quantify emissions from this sector in an unprecedented manner, and to develop mitigation measures for addressing climate change in addition to solving air quality problems,” added Arunachalam.

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Study findings were published in the journal Immunity.
Approximately 95% of the world’s population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx. EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers. Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis. There is no vaccine to prevent EBV infection nor a specific treatment.
In this study, NIAID investigators examined a viral protein called gp42, which the virus must use to infect B cells. Theoretically, a vaccine or antibody-based treatment capable of blocking gp42’s ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus’s ability to persist in those cells. The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42. The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42. Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion.
Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas. The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma. In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma.
If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants. People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus. The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note.
Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.

Poor sleep habits are strongly associated with long-term chronic health conditions, according to decades of research. To better understand this relationship, a team led by researchers in Penn State’s College of Health and Human Development identified four distinct patterns that characterize how most people sleep. These patterns are also predictive of long-term health, the researchers said.
Soomi Lee, associate professor of human development and family studies at Penn State, led a team in identifying these sleep patterns and their correlation to overall health. Their results were published in Psychosomatic Medicine.
Using a national sample of adults from the Midlife in the United States study, the team gathered data on approximately 3,700 participants’ sleep habits and their chronic health conditions across two time points 10 years apart. The data included self-reported sleep habits, including sleep regularity and duration, perceived sleep satisfaction and daytime alertness, as well as the number and type of chronic conditions.
Researchers used the data to identify four different sleep patterns. Good sleepers, who are characterized by optimal sleep habits across all datapoints. Weekend catch-up sleepers, who are characterized by irregular sleep, specifically short average sleep duration, but longer sleep times on weekends or non-workdays. Insomnia sleepers, who are characterized by sleep problems related to clinical insomnia symptoms, including short sleep duration, high daytime tiredness and a long time to fall asleep.

Nappers, who are characterized by mostly good sleep but frequent daytime naps. Researchers found that more than half of participants were identified as insomnia sleepers or nappers, both of which are suboptimal sleep patterns. Additionally, being an insomnia sleeper over the 10-year period was associated with a significantly higher likelihood of chronic health conditions, including cardiovascular disease, diabetes and depression.
Results also showed that people were unlikely to change their sleep pattern over the course of the 10 years. This was especially true for insomnia sleepers and nappers. The MIDUS study may not represent the entire population, researchers said, as it primarily comprises healthy adults, but — despite this — most participants displayed suboptimal insomnia sleeper or napper sleep patterns.
“These results may suggest that it is very difficult to change our sleep habits because sleep health is embedded into our overall lifestyle. It may also suggest that people still don’t know about the importance of their sleep and about sleep health behaviors,” Lee said. “We need to make more efforts to educate the public about good sleep health. There are sleep hygiene behaviors that people could do to improve their sleep, such as not using cell phones in bed, exercising regularly and avoiding caffeine in the late afternoon.”
While the sleep patterns were seemingly not age-related, researchers found that older adults and retirees were more likely to be nappers. They also found that those with less education and those facing unemployment were more likely to be insomnia sleepers.
According to Lee, the fact that phase of life and economic conditions can influence longstanding sleep patterns suggests that societal and neighborhood influences — including economic stressors and access to health resources — may have significant effects on individual health and, in this case, sleep habits.

All these findings strongly suggest the need for programs and interventions to promote healthy sleep and sleep habits, the researchers said. The identification of distinct sleep patterns also suggests that these prevention programs should not be one-size-fits-all and can be targeted based on a variety of factors, including the risk of chronic conditions and socioeconomic vulnerability.
“Sleep is an everyday behavior,” Lee said. “Sleep is also modifiable, So, if we can improve sleep almost every day, what outcomes might we see after several months, or even several years? Better sleeping habits can make many significant differences, from improving social relationships and work performance to promoting long-term healthy behaviors and healthy aging.”
Other researchers from Penn State on the team included Orfeu Buxton, professor of biobehavioral health and associate director of Clinical and Translational Science Institute, and David Almeida, professor of human development and family studies. Additional collaborators included Claire E. Smith, assistant professor of psychology, University of South Florida; Meredith Wallace, associate professor of psychiatry and biostatistics, University of Pittsburgh; Sanjay R. Patel, professor of medicine and epidemiology, University of Pittsburgh; and Ross Andel, professor in the Edson College of Nursing and Health Innovation, Arizona State University.
The National Institutes of Health’s National Institute on Aging funded this study.

More than 20 million Americans undergo colonoscopy screenings every year, and in many of those cases, doctors end up removing polyps that are 2 cm or larger and require additional care. This procedure has greatly reduced the overall incidence of colon cancer, but not without complications, as patients may experience gastrointestinal bleeding both during and after the procedure.
In hopes of preventing those complications from occurring, researchers at MIT have developed a new gel, GastroShield, that can be sprayed onto the surgical sites through an endoscope. This gel forms a tough but flexible protective layer that serves as a shield for the damaged area. The material prevents delayed bleeding and reinforces the mechanical integrity of the tissue.
“Our tissue-responsive adhesive technology is engineered to interact with the tissue via complementary covalent and ionic interactions as well as physical interactions to provide prolonged lesion protection over days to prevent complications following polyp removal, and other wounds at risk of bleeding across the gastrointestinal tract,” says Natalie Artzi, a principal research scientist in MIT’s Institute for Medical Engineering and Science, an associate professor of medicine at Harvard Medical School, and the senior author of the paper.
In an animal study, the researchers showed that the GastroShield application integrates seamlessly with current endoscopic procedures, and provides wound protection for three to seven days where it helps tissue to heal following surgery. Artzi and other members of the research team have started a company called BioDevek that now plans to further develop the material for use in humans.
Gonzalo Muñoz Taboada, CEO of BioDevek, and Daniel Dahis, lead scientist at BioDevek, are the lead authors of the study, which appears in the journal Advanced Materials. Elazer Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT and the director of IMES, and Pere Dosta, a former postdoc in Artzi’s lab, are also authors of the paper.
Adhesive gels
Routine colon cancer screenings often reveal small precancerous polyps, which can be removed before they become cancerous. This is usually done using an endoscope. If any bleeding occurs during the polyp removal, doctors can cauterize the wound to seal it, but this method creates a scar that may delay the healing, and result in additional complications.

Additionally, in some patients, bleeding doesn’t occur until a few days after the procedure. This can be dangerous and may require patients to return to the hospital for additional treatment. Other patients may develop small tears that lead the intestinal contents to leak into the abdomen, which can lead to severe infection and requires emergency care.
When tissue reinforcement is required, doctors often insert metal clips to hold tissue together, but these can’t be used with larger polyps and aren’t always effective. Efforts to develop a gel that could seal the surgical wounds have not been successful, mainly because the materials could not adhere to the surgical site for more than 24 hours.
The MIT team tested dozens of combinations of materials that they thought could have the right properties for this use. They wanted to find formulations that would display a low enough viscosity to be easily delivered and sprayed through a nozzle at the end of a catheter that fits inside commercial endoscopes. Simultaneously, upon tissue contact, this formulation should instantly form a tough gel that adheres strongly to the tissue. They also wanted the gel to be flexible enough that it could withstand the forces generated by the peristaltic movements of the digestive tract and the food flowing by.
The researchers came up with a winning combination that includes a polymer called pluronic, which is a type of block copolymer that can self-assemble into spheres called micelles. The ends of these polymers contain multiple amine groups, which end up on the surface of the micelles. The second component of the gel is oxidized dextran, a polysaccharide that can form strong but reversible bonds with the amine groups of the pluronic micelles.
When sprayed, these materials instantly react with each other and with the lining of the gastrointestinal tract, forming a solid gel in less than five seconds. The micelles that make up the gel are “self-healing” and can absorb forces that they encounter from peristaltic movements and food moving along the digestive tract, by temporarily breaking apart and then re-assembling.
“To obtain a material that adheres to the design criteria and can be delivered through existing colonoscopes, we screened through libraries of materials to understand how different parameters affect gelation, adhesion, retention, and compatibility,” Artzi says.

A protective layer
The gel can also withstand the low pH and enzymatic activity in the digestive tract, and protect tissue from that harsh environment while it heals itself, underscoring its potential for use in other gastrointestinal wounds at high risk of bleeding, such as stomach ulcers, which affect more than 4 million Americans every year.
In tests in animals, the researchers found that every animal treated with the new gel showed rapid sealing, and there were no perforations, leakages, or bleeding in the week following the treatment. The material lasted for about five days, after which it was sloughed off along with the top layer of tissue as the surgical wounds healed.
The researchers also performed several biocompatibility studies and found that the gel did not cause any adverse effects.
“A key feature of this new technology is our aim to make it translational. GastroShield was designed to be stored in liquid form in a ready-to-use kit. Additionally, it doesn’t require any activation, light, or trigger solution to form the gel, aiming to make endoscopic use easy and fast,” says Muñoz, who is currently leading the translational effort for GastroShield.
BioDevek is now working on further developing the material for possible use in patients. In addition to its potential use in colonoscopies, this gel could also be useful for treating stomach ulcers and inflammatory conditions such as Crohn’s disease, or for delivering cancer drugs, Artzi says.
The research was funded, in part, by the National Science Foundation.

Scientists know relatively little about particles released into the air when a vehicle driver brakes, though evidence suggests those particles may be more harmful to health than particles exiting the tailpipe.
In a new study in Proceedings of the National Academy of Sciences, University of California, Irvine researchers show how most of these particles emitted during light braking carry an electric charge — something that could potentially be exploited to help reduce air pollution from vehicles.
“We found that up to 80% of aerosol particles emitted from braking are electrically charged, and that many of them are in fact highly charged,” saidAdam Thomas, a doctoral candidate in the lab of Jim Smith, professor of chemistry, who led the study alongside UCI postdoctoral researcher Paulus Bauer.
To do the work, the team used a large lathe to spin a detached brake rotor and caliper. They then measured the electric charge of the aerosols emitted into the air and discovered the 80 percent figure.
“I was very surprised,” said Smith. “We were also surprised that this has not really been studied given how common cars are in human societies.”
The research is part of a broader team effort at UCI to understand the public health impacts of non-tailpipe emissions in areas beset by car traffic, including many areas in Southern California.
“The toxicity and health effects of brake wear particles are largely unknown,” said Manabu Shiraiwa, professor of aerosol chemistry at UCI and one of the researchers behind the university-wide project. “Recent results from my lab indicate that they may induce oxidative stress, but more research is needed.”
The new study reveals a problem that may grow as electric cars become more and more common over the next several decades. Electric cars, Smith explained, are not truly zero-emission vehicles, so municipalities need to think about strategies to reduce emissions from brake use as well as tailpipes.

The team found that the percentage of charged particles emitted largely depended on the material makeup of brake pads. Because the particles carry an electric charge, this should make it relatively easy to remove from the air.
“If they are charged, they can be removed easily from the air before they have a chance to have an impact at all on health,” said Smith. “All you would need to do is to collect them with an electrostatic precipitator — a device that exposes the charged particles to an electric field and efficiently sweeps them away.”
The public health risk posed by brake emissions is not borne equally by a population — lower-income parts of cities tend to be more traffic-heavy than others, which creates an environmental justice issue wherein certain socioeconomic classes are more exposed to brake emissions than others.
According to Professor Barbara Finlayson-Pitts, Distinguished Emeritus Professor of chemistry and the principal investigator of the project at UCI, emissions from braking are not well-characterized but are potentially significant in high-traffic areas. “These areas are often in poorer communities and highlight an important aspect of environmental justice that has been largely overlooked,” Finlayson-Pitts said.
The UCI team is working with local community organizations like the Madison Park Neighborhood Association in Santa Ana, which is helping disseminate UCI’s scientific findings to the public. Funding for the study came from fees paid by Volkswagen as part of a 2016 settlement reached with the California Department of Justice, which found that the company used devices that contributed to increased air pollution.

Researchers at the Francis Crick Institute and the National Institute for Health and Care Research Biomedical Research Centre at UCLH have highlighted the importance of continued surveillance of emerging SARS-CoV-2 variants and vaccine performance as the virus continues to evolve.
Published today as a research letter in The Lancet, their study compared the newer monovalent COVID vaccine, which specifically targets the XBB variant of Omicron (as recommended by the World Health Organisation), with older bivalent vaccines containing a mix of an Omicron variant and the original strain of COVID-19, which the UK deployed in Autumn 2023 before turning to monovalent vaccines1.
The researchers found that both vaccines generated neutralising antibodies against the most recent strain of Omicron, BA.2.86. However, the new monovalent vaccine generated higher levels of antibodies against a range of other Omicron variants.
The team collected blood and nasal mucosal samples both before and after a fifth dose vaccination from 71 participants of the Legacy study, a research collaboration between the Crick and the NIHR University College London Hospitals Biomedical Research Centre. They compared the antibody levels before and after vaccination.
All 36 participants who received the bivalent vaccine and 17 who received the monovalent vaccine had boosted levels of antibodies against all variants tested, including the newest strain BA.2.86, which caused a wave of infection this winter. But those with the newer monovalent vaccine had 3.5x higher levels of antibodies against the XBB and BQ.1.1 strains after their booster vaccination.
Since the Omicron virus is highly transmissible and the virus replicates in the nose and throat, the researchers tested the levels of antibodies in the participants’ nasal cavity.
They found that the monovalent vaccine increased their ability to produce mucosal antibodies against most of the tested variants, whereas the bivalent vaccine didn’t provide a significant boost.

Neither vaccine increased neutralising antibody levels in the nasal cavity against the newest variant, BA.2.86, suggesting that current vaccines may be less likely to stop transmission or prevent asymptomatic or mild illness, while still protecting against severe disease.
This highlights the importance of careful vaccine updates and continuing to complement a vaccination programme with the development of antibody drugs that work against all variants, as some more vulnerable people don’t respond well to vaccines.
Emma Wall, Senior Clinical Research Fellow at the Crick and Consultant in Infectious Diseases at UCLH, said: “The UK’s strategy to deploy stocks of older vaccines paid off last year, as both vaccines provided equal protection against the newest strain. However, ongoing monitoring is needed, as the virus is continuing to evolve, so vaccine-induced antibodies might not work so well in the future. In the long run, vaccines that are effective against all new variants and can block COVID-19 being transmitted from person to person are needed.”
David LV Bauer, Group Leader of the RNA Virus Replication Laboratory at the Crick, said: “The situation this winter could have been different if the newly emerged BA.2.86 and JN.1 variants were substantially distinct from older Omicron variants, but fortunately this wasn’t the case.
“Most new variants arise quicker than most clinical trials can produce data. But laboratory analysis can provide a detailed picture very quickly. Continued surveillance will help us stay on top of viral evolution.”

Numerous anti-cancer drugs function by targeting the DNA within cancerous cells, halting their proliferation. Yet, cancer cells occasionally develop mechanisms to repair the damage inflicted by these drugs, diminishing their effectiveness. Consequently, physicians are increasingly embracing a novel approach to cancer treatment known as precision medicine. This method involves selecting medications that precisely align with the unique attributes of an individual’s cancer. Precision medicine proves particularly beneficial in addressing cancers that have evolved to evade conventional treatments.
Trabectedin, a promising drug derived from the sea squirt Ecteinascidia turbinata, has shown potential in combating cancers resistant to conventional treatments. However, its precise mechanism of action has remained elusive — until now. A collaborative effort led by Dr. SON Kook and Professor Orlando D. SCHÄRER from the Center for Genomic Integrity within the Institute for Basic Science in South Korea, along with Dr. Vakil TAKHAVEEV and Professor Shana STURLA from ETH Zurich, Switzerland, has illuminated the inner workings of this mysterious compound.
Using highly sensitive high throughput COMET Chip assays to detect breaks formed in the genomes of cells, IBS researchers revealed trabectedin induces persistent breaks in the DNA of cancer cells. The researchers showed that these DNA breaks are only formed in cells with high levels of DNA repair, specifically those that operate a pathway called transcription-coupled nucleotide excision repair (TC-NER).
TC-NER is a vital mechanism that identifies DNA damage during transcription, initiating repair processes involving two endonucleases ERCC1-XPF and XPG. Trabectedin’s DNA damage disrupts this process by allowing the initial incision by ERCC1-XPF but blocking the subsequent action by XPG, halting the TC-NER process. This disruption of the repair process leads to long-lasting DNA breaks that ultimately kill cancer cells.
Analysis of the DNA break patterns induced by trabectedin revealed that breaks are formed throughout the genome, but only at sites where active transcription and with it, TC-NER occurs. Using this new insight into the mechanism of how DNA breaks are accumulated, the researchers sought to determine where in the genome these breaks occur. This led to the development of a new method called TRABI-Seq (for TRABectedin-Induced break sequencing), which allows for the precise identification of trabectedin’s action sites within tumor cell DNA.
“This incision by ERCC1-XPF creates a markable free hydroxyl group in the DNA, enabling us to sequence DNA and locate these breaks,” explains Dr. Son.
TRABI-Seq is being tested on various cancer cells to determine trabectedin’s efficacy in targeting tumors with advanced DNA repair capabilities, often associated with elevated transcription levels due to oncogene activation. It is hoped that these findings will help position trabectedin as both a predictive marker to identify vulnerable cancers and a therapeutic option for precision treatment. With its ability to target tumors resistant to conventional therapies, trabectedin may provide further hope in the fight against drug-resistant cancer with highly active DNA repair capabilities.

Air filters and opening windows can reduce classroom pollution by up to 36% — Surrey study
To improve air quality in classrooms, schools should use air purifiers during the school day and open the windows after hours. That’s according to a new study from the University of Surrey.
In England, 7,800 schools are in locations where air pollution breaches WHO limits. Last month, the Mayor of London, Sadiq Khan, announced that air purifiers would be installed in 200 of them.
Nidhi Rawat, a researcher at Surrey’s Global Centre for Clean Air Research (GCARE), said:
“Alternating purifiers with scheduled window openings is an effective way to clean up classroom air.
“The most effective combination depends on the characteristics and location of the classroom, and when the teacher opens windows.
“We also understand that keeping the windows open is not always comfortable or practical — so a sensible, tailored approach is recommended.”
Scientists monitored pollution in two classrooms at an infant school in Guildford, UK. It is 10 metres from the A3 road, passed by 31,000 cars each day.

They studied two classrooms: one facing the road and occupied by 4 to 5-year-olds, and one on the other side of the building, occupied by 6 to 7-year-olds.
In both classrooms, the best improvements in air quality happened when air purifiers were alternated with scheduled window openings. Coarse particle pollution fell by 18% in the classroom nearest the road and 36% in the other classroom. Carbon dioxide fell 28% in the classroom nearest the road and 11% in the other classroom.
Smaller improvements were detected when windows were opened without air purifiers.
Professor Prashant Kumar, director of GCARE, said:
“Our timely study can help policymakers choose when and how to optimise the benefits of air purifiers and window openings in the classroom.
“Globally, millions of children are forced to breathe poor quality air while they learn. We hope our study can be used to design ways to make classrooms safer and pupils healthier.”
The study is published in the Journal of Building Engineering.
It contributes to the UN Sustainable Development Goals 3 (good health and well-being), 4 (quality education) and 11 (sustainable cities and communities).

Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA.
Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily.
The researchers demonstrated their technique by screening cells with more than 1,000 different mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This method, which is easier and faster than any existing approach, and edits the genome rather than introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful than previously thought.
This technique could also be applied to many other cancer genes, the researchers say, and could eventually be used for precision medicine, to determine how an individual patient’s tumor will respond to a particular treatment.
“In one experiment, you can generate thousands of genotypes that are seen in cancer patients, and immediately test whether one or more of those genotypes are sensitive or resistant to any type of therapy that you’re interested in using,” says Francisco Sanchez-Rivera, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.
MIT graduate student Samuel Gould is the lead author of the paper, which appears today in Nature Biotechnology.
Editing cells
The new technique builds on research that Sanchez-Rivera began 10 years ago as an MIT graduate student. At that time, working with Tyler Jacks, the David H. Koch Professor of Biology, and then-postdoc Thales Papagiannakopoulos, Sanchez-Rivera developed a way to use CRISPR genome-editing to introduce into mice genetic mutations linked to lung cancer.

In that study, the researchers showed that they could delete genes that are often lost in lung tumor cells, and the resulting tumors were similar to naturally arising tumors with those mutations. However, this technique did not allow for the creation of point mutations (substitutions of one nucleotide for another) or insertions.
“While some cancer patients have deletions in certain genes, the vast majority of mutations that cancer patients have in their tumors also include point mutations or small insertions,” Sanchez-Rivera says.
Since then, David Liu, a professor in the Harvard University Department of Chemistry and Chemical Biology and a core institute member of the Broad Institute, has developed new CRISPR-based genome editing technologies that can generate additional types of mutations more easily. With base editing, developed in 2016, researchers can engineer point mutations, but not all possible point mutations. In 2019, Liu, who is also an author of the Nature Biotechnology study, developed a technique called prime editing, which enables any kind of point mutation to be introduced, as well as insertions and deletions.
“Prime editing in theory solves one of the major challenges with earlier forms of CRISPR-based editing, which is that it allows you to engineer virtually any type of mutation,” Sanchez-Rivera says.
When they began working on this project, Sanchez-Rivera and Gould calculated that if performed successfully, prime editing could be used to generate more than 99 percent of all small mutations seen in cancer patients.
However, to achieve that, they needed to find a way to optimize the editing efficiency of the CRISPR-based system. The prime editing guide RNAs (pegRNAs) used to direct CRISPR enzymes to cut the genome in certain spots have varying levels of efficiency, which leads to “noise” in the data from pegRNAs that simply aren’t generating the correct target mutation. The MIT team devised a way to reduce that noise by using synthetic target sites to help them calculate how efficiently each guide RNA that they tested was working.

“We can design multiple prime-editing guide RNAs with different design properties, and then we get an empirical measurement of how efficient each of those pegRNAs is. It tells us what percentage of the time each pegRNA is actually introducing the correct edit,” Gould says.
Analyzing mutations
The researchers demonstrated their technique using p53, a gene that is mutated in more than half of all cancer patients. From a dataset that includes sequencing information from more than 40,000 patients, the researchers identified more than 1,000 different mutations that can occur in p53.
“We wanted to focus on p53 because it’s the most commonly mutated gene in human cancers, but only the most frequent variants in p53 have really been deeply studied. There are many variants in p53 that remain understudied,” Gould says.
Using their new method, the researchers introduced p53 mutations in human lung adenocarcinoma cells, then measured the survival rates of these cells, allowing them to determine each mutation’s effect on cell fitness.
Among their findings, they showed that some p53 mutations promoted cell growth more than had been previously thought. These mutations, which prevent the p53 protein from forming a tetramer — an assembly of four p53 proteins — had been studied before, using a technique that involves inserting artificial copies of a mutated p53 gene into a cell.
Those studies found that these mutations did not confer any survival advantage to cancer cells. However, when the MIT team introduced those same mutations using the new prime editing technique, they found that the mutation prevented the tetramer from forming, allowing the cells to survive. Based on the studies done using overexpression of artificial p53 DNA, those mutations would have been classified as benign, while the new work shows that under more natural circumstances, they are not.
“This is a case where you could only observe these variant-induced phenotypes if you’re engineering the variants in their natural context and not with these more artificial systems,” Gould says. “This is just one example, but it speaks to a broader principle that we’re going to be able to access novel biology using these new genome-editing technologies.”
Because it is difficult to reactivate tumor suppressor genes, there are few drugs that target p53, but the researchers now plan to investigate mutations found in other cancer-linked genes, in hopes of discovering potential cancer therapies that could target those mutations. They also hope that the technique could one day enable personalized approaches to treating tumors.
“With the advent of sequencing technologies in the clinic, we’ll be able to use this genetic information to tailor therapies for patients suffering from tumors that have a defined genetic makeup,” Sanchez-Rivera says. “This approach based on prime editing has the potential to change everything.”

Researchers at the University of Minnesota Twin Cities may have discovered a mechanical explanation for instability observed in the lungs in cases of acute respiratory distress syndrome (ARDS), particularly in the aftermath of respiratory illnesses such as COVID-19 or pneumonia.
The research was recently published in the Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences.
Currently, there is no known cure for ARDS, a life-threatening lung injury that allows fluid to leak into the lungs. The researchers in this study say that as many as two thirds of all patients that passed away from COVID-19 had ARDS. There is not a clear reason on why specific people with a severe respiratory illness may develop ARDS, while others may not, but researchers in this study were looking to find that answer.
They identified the concentration of a lysolipid — a byproduct of the immune response to viruses and bacteria — that can have a major impact in adults suffering from ARDS. Increased concentration of this chemical eliminates the surfactant, a complex composed of fats and proteins generated in the lungs. The result is uneven lung inflation and, ultimately, respiratory distress in adults.
“This study looked into the correlation of the concentration of the lysolipid in the lungs. Once that fluid reached a certain level, it started to cause severe impacts,” said University of Minnesota Department of Chemical Engineering and Materials Science Professor Joseph Zasadzinski and lead professor on the research.
“Your average everyday person usually won’t need to think about this, but if a virus or infection is bothering your lung surfactant system and you end up in the hospital, then it could become top of mind very quickly,” Zasadzinski added
There are a natural amount of these lysolipids that exist in the human body, and as long as those stay below a specific concentration, the average person can breathe normally. When someone has a bad infection, those lysolipids increase, which can lead to respiratory distress. Once a patient is headed in that direction, there are not many ways of reversing those symptoms.

“This research shows frequency dependence, or how quickly you open and close the lungs. This could help doctors try to tailor the treatment process for each specific patient,” said Clara Ciutara, a 2023 Ph.D. chemical engineering and materials science graduate and first author of the study.
Previous research of neonatal respiratory distress syndrome (NRDS) in premature infants found that it could be treated by introducing replacement lung surfactant, but that was not the case in adults. It is the amount of lysolipid that determines the outcome of the surfactant in the lungs, not the breakdown of the existing lung surfactant.
The next step in the research will be to translate these ideas into a clinical environment and test to see if they can manipulate specific molecules to make them less active or stick to a specific place. This could help drop the concentration of the lysolipids to a threshold that may be able to reverse symptoms of ARDS and put people on the road to recovery.
In addition to Zasadzinski and Ciutara, the research team included University of Minnesota Department of Chemical Engineering and Materials Science NIH postdoctoral fellow Steven V. Iasella, undergraduate student Boxun Huang, and former postdoctoral associate Sourav Barman.
This work is supported by a grant from National Institutes of Health (NIH) Heart, Lung, and Blood Institute. All microscopy images were obtained at the University Imaging Center at the University of Minnesota.