Publisher Health

People who carry three gene variants that have bene inherited from Neanderthals are more sensitive to some types of pain, according to a new study co-led by UCL researchers.
The findings, published in Communications Biology, are the latest findings to show how past interbreeding with Neanderthals has influenced the genetics of modern humans.
The researchers found that people carrying three so-called Neanderthal variants in the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.
Previous research has identified three variations in the SCN9A gene — known as M932L, V991L, and D1908G — in sequenced Neanderthal genomes and reports of greater pain sensitivity among humans carrying all three variants. However, prior to this study the specific sensory responses affected by these variants was unclear.
An international team led by researchers at UCL, Aix-Marseille University, University of Toulouse, Open University, Fudan University, and Oxford University, and part-funded by Wellcome, measured the pain thresholds of 1,963 people from Colombia in response to a range of stimuli.
The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.
The authors found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure. Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.

Fat tissue, for as much as it’s been vilified, is an incredibly complex and essential bodily organ involved in energy storage and hormone production, among other functions. Yet, modern lifestyles have led to a worldwide epidemic of obesity, and a corresponding increase in related conditions like type 2 diabetes and cardiovascular disease.
Researchers are attempting to uncover the basics of how fat tissue is structured and, specifically, inflammation associated with obesity, in the hopes of unlocking the connection between the accumulation of fat and poor health outcomes.
A new study from Lindsey Muir, Ph.D., Ph.D.-candidate Cooper Stansbury, and their colleagues uses single cell analysis of gene expression combined with spatial transcriptomics to reveal previous unrecognized immune cell types and interactions within adipose tissue. Spatial transcriptomics is a newer technology that captures all gene expression in small spots across an entire thin section of tissue.
Studying fat is easier said than done. In tissues that are organized into defined layers for example the spinal cord or the brain “it’s easier to do sanity checks with your data and identify this or that layer as a particular cell type and know that it should be expressing genes X, Y, and Z,” said Muir, a research assistant professor in the Department of Computational Medicine and Bioinformatics.
“With adipose, it’s a lot more challenging because the cell types are distributed evenly throughout the tissue, without defined cell layers.” In obesity, fat cells, or adipocytes, expand and can reach a limit that ultimately causes cell death and leads to inflammation.
To better understand the types of immune cells within adipose tissue and where they are in relation to each other in obesity, the team fed mice a high fat diet over the course of 14 weeks, collected fat tissue, and then used single cell and spatial analyses to produce a read out of all the mRNAs present in the sample.
Using a computational process known as clustering in the single cell data, they were able to group cells whose genetic makeup more closely resembled each other than other groups or the overall sample.

Prebiotics are used to foster the colonisation of beneficial bacteria in the gut. These indigestible dietary fibres are found in plant-derived foods such as onions, leeks, artichokes, wheat, bananas, and in high concentrations in chicory root. They support gut health by promoting the growth and activity of beneficial gut bacteria. Researchers have now investigated whether certain prebiotics can also influence brain function by improving communication between the gut microbiome and the brain.
The interventional study led by the University of Leipzig Medical Center indicates that consumption of high-dose dietary prebiotics leads to a reduction in reward-related brain activation in response to high-calorie food stimuli. “The results suggest a potential link between gut health and brain function, in this case food decision-making,” says PD Dr Veronica Witte, co-author of the study and a scientist at the University of Leipzig Medical Center.
Young to middle-aged adults with overweight were selected for the study who followed an omnivorous, Western diet. The 59 volunteers consumed 30 grams of inulin, a prebiotic from chicory root, daily for 14 days. During functional MRI imaging, participants were shown pictures of food and asked how much they desired to eat the meals depicted. Following the MRI experiment, they were provided with their highest rated dish and asked to consume it.
The MRI examination was repeated at four timepoints, before and after the prebiotic administration and before and after a placebo phase in which the participants were given a preparation with identical energy density but without prebiotics. When the participants evaluated high-calorie foods, there was comparatively less activation of reward-related brain areas after they had consumed the prebiotic fibre. This effect was accompanied by a shift in the composition of the gut bacteria.
The findings, derived from advanced neuroimaging, next-generation sequencing of gut bacteria, and combined analyses of potential metabolic pathways, suggest that functional microbial changes may underlie the altered brain response towards high-caloric food cues. Fasting blood samples from the participants underwent analysis for gastrointestinal hormones, glucose, lipids, and inflammatory markers. In addition, gut microbiota and their metabolites, namely short-chain fatty acids, were measured in stool samples. The research was conducted within the Collaborative Research Centre 1052, “Obesity Mechanisms.”
“Further studies are needed to investigate whether treatments that alter the microbiome could open up new avenues for less invasive approaches to the prevention and treatment of obesity. A better understanding of the underlying mechanisms between the microbiome, gut, and brain could help to develop new strategies that promote healthier eating habits in people at risk” says Dr Witte. A follow-up study is currently underway, examining the effects of long-term, high-dose prebiotic administration over six months on eating behaviour, brain function and body weight in people living with overweight and obesity.

Ciara Burns spent 42 days rowing across the Atlantic in 2021 as part of a team of twelve. Clearly, whoever ventures on such an adventure has to go to the extreme limits both physically and mentally. Therefore, a situation like this is very interesting not only from a sporting point of view, but also for science.
Throughout the journey, Ciara Burns, a student of TU Wien (Vienna), collected data, registered her heart rate with special sensors and kept records of her subjective well-being. Now the analysis of the data has been completed and the results have been published. Some lessons can be learned from this for similar extreme undertakings — especially about a close interplay between body and psyche.
How variable is the heartbeat?
“You can derive a lot of interesting findings from the heart rate recordings,” says Prof. Eugenijus Kaniusas, who heads the “Biomedical Sensing and Therapy” research group at TU Wien and provided scientific support for the project. “The variability of the heart rate is particularly important for us. From it, you can infer the general state of fitness, sleep quality and how well someone can regenerate during sleep.”
Normally, the heart rate is more regular during waking hours, and it varies more during periods of sleep. A large difference in heart rate variability between sleep phases and awake phases indicates that the body regenerates well during sleep. If the variability in sleep and wake phases is very similar, it is a sign that the body’s own regulatory and regenerative mechanisms are no longer functioning optimally.
Three hours of rowing, three hours of rest
The rowing team established a very unusual sleep rhythm for the duration of the Atlantic crossing: Around the clock, half the team was busy rowing, while the other half slept. They took turns every three hours. This strategy had already proven successful in similar projects before — but how does the body cope with this unnatural rhythm?

Traditional medical imaging works great for people with light skin but has trouble getting clear pictures from patients with darker skin. A Johns Hopkins University-led team found a way to deliver clear pictures of anyone’s internal anatomy, no matter their skin tone.
In experiments the new imaging technique produced significantly sharper images for all people — and excelled with darker skin tones. It produced much clearer images of arteries running through the forearms of all participants, compared to standard imaging methods where it was nearly impossible to distinguish the arteries in darker-skinned individuals.
“When you’re imaging through skin with light, it’s kind of like the elephant in the room that there are important biases and challenges for people with darker skin compared to those with lighter skin tones,” said co-senior author Muyinatu “Bisi” Bell, the John C. Malone Associate Professor of Electrical and Computer Engineering, Biomedical Engineering, and Computer Science at Johns Hopkins. “Our work demonstrates that equitable imaging technology is possible.”
The findings are newly published in the journal Photoacoustics.
“We show not only there is a problem with current methods but, more importantly, what we can do to reduce this bias,” Bell said.
The findings advance a 2020 report that showed pulse oximeters, which measure oxygen rates in the blood, have higher error rates in Black patients.
“There were patients with darker skin tones who were basically being sent home to die because the sensor wasn’t calibrated toward their skin tone,” Bell said.

A University at Buffalo-led research team has developed molecules that could help unclog thick, sticky mucus from the lungs of people suffering from cystic fibrosis.
The chronic disease is caused by a defective protein channel that prevents chloride ions from leaving cells and creating the watery conditions necessary to clear mucus. Researchers’ synthetic molecules offer something of a detour by binding to ions and carrying them through the cell membrane.
This binding increased a liquid layer vital for mucus clearance in cystic fibrosis cells by 50%, according to a study published Oct. 9 in Nature Chemistry.
“We found that these molecules can serve as an effective ferry to transport chloride across the cell and therefore restore the level of airway surface liquid, or ASL, to essentially that of a normal cell,” says the study’s lead author, Bing Gong, PhD, UB Distinguished Professor in the Department of Chemistry, within the College of Arts and Sciences. “One day, they could be leveraged into a drug that treats cystic fibrosis, a very painful and unpleasant disease.”
The inability to clear mucus makes breathing difficult and risk of infection high for the nearly 40,000 Americans living with cystic fibrous. It is one of the most common fatal genetic diseases in the United States.
“It is exciting when scientific discoveries can be applied in ways that will potentially improve the health and well-being of people with complex conditions like cystic fibrosis that have limited treatment options,” says co-author Daniel Miller, a UB PhD graduate who is now assistant professor of chemistry at Hofstra University.
Other co-authors from the Department of Chemistry include Thomas Szyperski, PhD, UB Distinguished Professor; Eva Zurek, PhD, professor; Yulong Zhong, PhD, research assistant professor; as well as PhD graduates Ruikai Cao, Robert Rossdeutcher and Thomas Sobiech. Additional co-authors represent Shanghai Jiao Tong University and the University of North Carolina at Chapel Hill.

Generating specific cell lineages from induced pluripotent stem cells and embryonic stem cells is the holy grail of regenerative medicine. Guiding iPSCs toward a target cell line has garnered much attention, but the process remains challenging. Now, researchers from Japan have discovered that an anti-nucleolin DNA aptamer, iSN04, can determine a cell’s lineage during differentiation. By demonstrating the generation of cardiomyocytes from murine pluripotent stem cells, their concept shows promise as a regenerative therapy.
Self-renewal and pluripotency-the capacity to form any cell lineage-are inherent characteristics of induced pluripotent stem cells (iPSCs). Furthermore, they are highly prized in regenerative therapies targeting cardiovascular, neurological, and metabolic diseases as they are immunologically suitable for transplantation back into a donor. Unfortunately, regenerative medicine is not yet feasible outside a laboratory setting as available protocols to generate target cells are complicated and expensive. This raises a pertinent question: Can regulating the fate of stem cells in clinical settings and at scale be made more economical?
A team of researchers from Shinshu University, the National Institute of Advanced Industrial Science and Technology, and the University of Shizuoka in Japan set out to address this question by leveraging nucleic acid aptamers. Aptamers are single-stranded pieces of DNA that bind to target proteins and are able to modulate signaling cascades during cell differentiation when a stem cell commits to a specific functional role or phenotype. They hold promise in regenerative medicine as they are easily modified, can be synthesized economically, and are suitable for long-term storage.
The team, led by Associate Professor Tomohide Takaya from the Department of Agricultural and Life Sciences at Shinshu University, recently discovered that an anti-nucleolin aptamer, myogenetic oligodeoxynucleotide iSN04, induced myocardial differentiation in embryonic stem cells (ESCs). The study was led by Mina Ishioka, a graduate student in Dr. Takaya’s laboratory, and published in The International Journal of Molecular Sciences on 21 September 2023.
“We had previously found that iSN04 promoted myogenic precursor cells (myoblasts) to differentiate into skeletal muscle cells and had hypothesized that the aptamer also enhanced differentiation of pluripotent stem cells. We were intrigued by the prospect of using iSN04 to promote iPSC differentiation into cardiomyocytes as this could lead to regenerating heart tissue,” says Dr. Takaya, elaborating on the team’s motivation to pursue the research.
Using various assays like RNA sequencing, cell staining and imaging, and molecular interaction and pathway analysis, the researchers investigated iSN04’s effect on murine ESCs and iPSCs. iSN04 treatment under differentiating conditions inhibited stem cell commitment to the cardiac lineage. However, when these pluripotent stem cells were treated after experiencing differentiating conditions for five days, specific marker genes were upregulated, and the cells committed to forming beating cardiomyocytes.
“Ours is the first report to confirm a DNA aptamer that allows cardiomyocytes to develop from iPSCs,” explains Dr. Takaya when asked about the significance of the work. “We uncovered two mechanisms of nucleolin interference with iSN04 at play whereby early treatment inhibits cardiomyogenesis, while treatment at a later stage enhances the generation of cardiac progenitors. First, iSN04 governs the translocation of nucleolin protein between the cytoplasm, plasma membrane, and nucleus. Second, it results in the modulation of the Wnt signaling pathway that governs cell differentiation.”
The immunostaining experiments revealed that nucleolin was retained in the nucleoli following iSN04 treatment. Nucleolar nucleolin has a role in chromatin remodeling and gene transcription, and interestingly enough, Wnt pathway genes were differentially expressed in the RNA-seq data following iSN04 suppression. The team postulates that the iSN04-anchored nucleolin alters gene expression and Wnt signaling. Ultimately, terminal cell differentiation commits to the cardiomyocyte lineage.
And how could these findings impact regenerative medicine and patients’ lives in the long term? Dr. Takaya provides insights into the broader implications of their work. “We believe there is a strong case to be made for further studies evaluating DNA aptamers in regenerative medicine. Aptamers are cost-effective and open up the possibility of producing specific cells from the patient’s stem cells. But it doesn’t end there! Since the aptamers can regulate stem cell fate, they can serve as therapeutic agents for many conditions linked to stem cell dysfunction,” he concludes.

A University of Massachusetts Amherst team has demonstrated in theory that a protein antigen from a childhood vaccine can be delivered into the cells of a malignant tumor to refocus the body’s immune system against the cancer, effectively halting it and preventing its recurrence.
The bacteria-based intracellular delivering (ID) system uses a non-toxic form of Salmonella that releases a drug, in this case a vaccine antigen, after it’s inside a solid-tumor cancer cell.
“As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients,” writes senior author Neil Forbes, professor of chemical engineering, in a paper published Thursday, Oct. 5, in Frontiers in Immunology.
The research, carried out in the Forbes Lab at the Institute for Applied Life Sciences (IALS), offers promise toward tackling difficult-to-treat cancers, including liver, metastatic breast and pancreatic tumors. UMass Amherst has filed for a patent that will be licensed to Ernest Pharmaceuticals, an IALS startup co-founded by Forbes, first author Vishnu Raman and bioengineer Nele Van Dessel, who developed the delivery system as a post-doctoral researcher in the Forbes Lab. They plan to seek FDA approval in an effort to start clinical trials within a few years.
“The idea is that everybody is vaccinated with a whole bunch of things, and if you could take that immunization and target it towards a cancer, you could use it to eliminate the cancer,” Forbes explains. “But cancers obviously aren’t going to display viral molecules on their surface. So the question was, could we take a molecule inside the cancer cell using Salmonella and then have the immune system attack that cancer cell as if it was an invading virus?”
To test their theory that this immune treatment could work, Forbes and team genetically engineered ID Salmonella to deliver ovalbumin (chicken egg protein) into the pancreatic tumor cells of mice that had been immunized with the ovalbumin “vaccine.” The researchers showed that the ovalbumin disperses throughout the cytoplasm of cells in both culture and tumors.
The ovalbumin then triggered an antigen-specific T-cell response in the cytoplasm that attacked the cancer cells. The therapy cleared 43% of established pancreatic tumors, increased survival and prevented tumor re-implantation, the paper states.

Some vapes are appearing with increasing nicotine levels that approach those in a carton of cigarettes. U.S. regulators did not authorize them, but have failed to keep them off shelves.Juul was once the cool vape, blamed for hooking teenagers on e-cigarettes, and it is set to pay billions of dollars in legal settlements.Then came Puff Bar, which was hot in high schools until federal officials began impounding those vapes. Elf Bar stepped in, and its products have been seized at the border. A parade of facsimiles is moving in right behind them: Virtue Bar, Juicy Bar, Lost Mary, Lost Vape and many more.The latest flood of illicit e-cigarettes is arriving from China in Barbiecore colors and fruit, ice cream and slushy flavors, and accounts for a major share of the estimated $5.5 billion e-cigarette market in the United States.The never-ending influx of vapes, some offering 5,000 or more puffs per device or escalating nicotine levels, has exposed a gaping lapse in enforcement by the Food and Drug Administration, which has authorized only a handful of the hundreds of options that line convenience store walls nationwide. Members of Congress, two dozen state attorneys general and even the Big Tobacco companies have stepped up their calls for the agency to get the situation under control.Granted, the latest pleas by the tobacco industry are viewed by antismoking groups as a cringe-worthy effort to lock down market share, but some others interpret the addition of these odd bedfellows as a sign of a market run amok.The F.D.A. “has been dealt a very difficult hand, and a lot of which includes putting the genie back — or stuffing the genie back — in the bottle,” said Erika Sward, assistant vice president of advocacy for the American Lung Association. “And I don’t envy them for that.”Agency officials said they had used every tool within their authority to crack down on e-cigarette outlaws. Yet recent fines issued by the agency topped out at about $19,000 per violation and largely targeted a few products sold at each store. The agency’s orders telling six manufacturers to stop selling certain products were directed at U.S. stores, some of which were in small cities.And though the F.D.A. has fired off hundreds of warning letters, the effect is barely felt: Flavored vape sales have surged 60 percent over the past three years, to 18 million vaping products a month in June from 11 million a month in early 2020, according to the C.D.C. Foundation.“The F.D.A. should not be having any of these flavored e-cigarettes on the market,” said Yolonda Richardson, president of the Campaign for Tobacco-Free Kids. “And so it just needs to do its job.”When the F.D.A. received expanded authority to regulate e-cigarettes in 2016, the objective was to draw a new line in public health: Smokers would have an alternative to traditional cigarettes, and tobacco use among minors would remain at historic lows.Seven years on, nearly 40 percent of e-cigarette users are 25 or younger, according to the Centers for Disease Control and Prevention. And of the 2,000 or so vaping and e-cigarette products on the market, the agency has only given the green light to about two dozen of them, and it still has to deal with a backlog of applications, according to research on the industry.There are few places where the problem feels more pressing than in high school bathrooms, where students crowd the stalls between classes to get a nicotine fix.Kyle Wimmer, an art teacher at Mountain Range High School in Westminster, Colo., helps students quit vaping through creating artwork out of relinquished vape pens.Kevin Mohatt for The New York TimesTeenage vaping rates have fallen roughly by half since their height during the Juul craze of 2019, to about 14 percent of high school students last year from nearly 28 percent at their peak, federal surveys show. Those rates were based on survey responses in which students said whether they had vaped within the past 30 days.Kyle Wimmer, an art teacher at Mountain Range High School, north of Denver, frequently hears from students dealing with nicotine addiction from e-cigarette use.He accepts discarded vapes and helps young people turn them into art. And as a teacher who has been open about his past struggles with alcohol, he’s also there to listen.“It’s hard to tell kids not to do this when they’re hooked because they can’t just stop,” Mr. Wimmer said, adding: “They’re having troubles. They’re struggling.”A vape-inspired piece at Mountain Range High School. “It’s hard to tell kids not to do this when they’re hooked because they can’t just stop,” Mr. Wimmer said.Kevin Mohatt for The New York TimesA growing body of research shows that while vapes may not be as toxic as cigarettes, they are far from healthy, particularly for adolescents who become addicted to nicotine while their brains are still developing.The American Heart Association has raised the alarm about possible cardiovascular effects from e-cigarettes and called for more research. One recent meta-analysis reported higher heart attack risks in e-cigarette users than in those who did not vape or smoke anything. (Cigarette smokers had the highest risk.)In recent years, the market has begun to move toward high-volume vapes advertising 5,000 to 6,000 puffs — with about as much addictive nicotine as is in a carton of cigarettes. The devices come in flavors that could appeal to younger adolescents such as birthday shake, gummy bear and watermelon ice, and they have higher concentrations of nicotine than were found before. The prices have also dropped, said Barbara Schillo, chief research officer for the Truth Initiative, who documented the trend in a recent study.“In other words, these disposable devices are getting bigger, stronger and cheaper,” Dr. Schillo said.Calls for change have only grown louder. In a letter sent in late August, 30 state attorneys general urged the F.D.A. to do more to deter youth vaping and to ban all but tobacco flavored e-cigarettes.Lawmakers, including Senator Richard J. Durbin, Democrat of Illinois and a leading opponent of e-cigarettes, have pushed for action. His office discovered nearly two dozen types of vapes being sold online even after the F.D.A. had denied their marketing applications and sent them warning letters.“I just don’t understand it,” Senator Durbin said in a floor speech last month, adding that the F.D.A. “is cowardly, refusing to use its full arsenal of enforcement tools — fines, injunctions — for even these most flagrant cases.”Even R.J. Reynolds, the maker of Newport and Camel cigarettes and the best-selling Vuse vapes, has invoked public health in a petition lodged with the F.D.A. seeking official action. It asked the agency to prioritize enforcement of flavored, disposable vapes.Luis Pinto, a spokesman for the company, said that devices aimed at young people and minors threatened the efforts of Reynolds and others to convert adult smokers to e-cigarette users. “The whole category is in peril,” he said.Reynolds’s Vuse e-cigarettes led vaping sales for a year ending in August, Goldman Sachs data shows, with $2.2 billion in sales. The “other” category, which included flavored imports, trailed with $1.6 billion in sales, with Juul close behind.Brian King, the F.D.A.’s tobacco center chief, said that the agency had ramped up warnings, fines and injunctions on illicit vape makers, sellers and distributors. He rebutted some of the criticism from “the cheap seats” and said enforcement efforts needed to be strategic and methodical.“It’s a very complex chess match, not a game of tic-tac-toe,” Dr. King said. “And we need to ensure that the actions we take are both scientifically and legally defensible.”The F.D.A. has been working with border authorities to seize imports of Elf Bar and Esco Bar products from China.Andrew Harnik/Associated PressF.D.A. officials meet regularly with Justice Department prosecutors, Dr. King said, describing them as critical partners. The agency has also worked with border authorities to seize imports of Elf Bar and Esco Bar products, he added. In addition, the agency has received funding to begin an effort to closely track the rapidly morphing vape marketplace.“Nothing’s off the table when it comes to enforcement,” he said.In late September, the F.D.A. announced 22 fines of $19,192 each against gas stations that received warning letters but did not stop selling Elf Bar products.The F.D.A. has required e-cigarette makers to file applications to sell their products and to submit proof that the products would be likely to compel cigarette smokers to switch — but not to attract new users. The agency has denied millions of applications and let some top-selling products remain on market pending decisions.Two years have passed since a court-imposed deadline required the F.D.A. to respond to all applications. Dr. King said it would finalize decisions, including on some Vuse and Juul vapes, by the year’s end.The lengthy, opaque approval process, marked with legal challenges and defiance of the F.D.A.’s decrees, has opened the door to the shape-shifting influx of unauthorized vapes that come by air, land and sea from factories in China (where flavored vapes are outlawed).The confusing mix of product statuses has prompted the Energy Marketers of America, an organization representing retailers, including convenience stores linked to gas stations, to file a petition with the F.D.A. seeking clarity about which e-cigarettes the stores can legally sell.Stores are “well positioned to aid in the fight against illegal and dangerous products by keeping them off their shelves,” according to the petition.

A new study highlights both the promise and the limitations of gene editing, as a highly lethal form of avian influenza continues to spread around the world.Scientists have used the gene-editing technology known as CRISPR to create chickens that have some resistance to avian influenza, according to a new study that was published in the journal Nature Communications on Tuesday.The study suggests that genetic engineering could potentially be one tool for reducing the toll of bird flu, a group of viruses that pose grave dangers to both animals and humans. But the study also highlights the limitations and potential risks of the approach, scientists said.Some breakthrough infections still occurred, especially when gene-edited chickens were exposed to very high doses of the virus, the researchers found. And when the scientists edited just one chicken gene, the virus quickly adapted. The findings suggest that creating flu-resistant chickens will require editing multiple genes and that scientists will need to proceed carefully to avoid driving further evolution of the virus, the study’s authors said.The research is “proof of concept that we can move toward making chickens resistant to the virus,” Wendy Barclay, a virologist at Imperial College London and an author of the study, said at a news briefing. “But we’re not there yet.”Some scientists who were not involved in the research had a different takeaway.“It’s an excellent study,” said Dr. Carol Cardona, an expert on bird flu and avian health at the University of Minnesota. But to Dr. Cardona, the results illustrate how difficult it will be to engineer a chicken that can stay a step ahead of the flu, a virus known for its ability to evolve swiftly.“There’s no such thing as an easy button for influenza,” Dr. Cardona said. “It replicates quickly, and it adapts quickly.”Avian influenza refers to a group of flu viruses that are adapted to spread in birds. Over the last several years, a highly lethal version of a bird flu virus known as H5N1 has spread rapidly around the globe, killing countless farmed and wild birds. It has also repeatedly infected wild mammals and been detected in a small number of people. Although the virus remains adapted to birds, scientists worry that it could acquire mutations that help it spread more easily among humans, potentially setting off a pandemic.Many nations have tried to stamp out the virus by increasing biosecurity on farms, quarantining infected premises and culling infected flocks. But the virus has become so widespread in wild birds that it has proved impossible to contain, and some nations have begun vaccinating poultry, although that endeavor presents some logistic and economic challenges.Culling chicken eggs at a quarantined farm in northern Israel.Atef Safadi/EPA, via ShutterstockIf scientists could engineer resistance into chickens, farmers would not need to routinely vaccinate new batches of birds. Gene editing “promises a new way to make permanent changes in the disease resistance of an animal,” Mike McGrew, an embryologist at the University of Edinburgh’s Roslin Institute and an author of the new study, said at the briefing. “This can be passed down through all the gene-edited animals, to all the offspring.”CRISPR, the gene-editing technology used in the study, is a molecular tool that allows scientists to make targeted edits in DNA, changing the genetic code at a precise point in the genome. In the new study, the researchers used this approach to tweak a chicken gene that codes for a protein known as ANP32A, which the flu virus hijacks to copy itself. The tweaks were designed to prevent the virus from binding to the protein — and therefore keep it from replicating inside chickens.The edits did not appear to have negative health consequences for the chickens, the researchers said. “We observed that they were healthy, and that the gene-edited hens also laid eggs normally,” said Dr. Alewo Idoko-Akoh, who conducted the research as a postdoctoral researcher at the University of Edinburgh.The researchers then sprayed a dose of flu virus into the nasal cavities of 10 chickens that had not been genetically edited, to serve as the control. (The researchers used a mild version of the virus different from the one that has been causing major outbreaks in recent years.) All of the control chickens were infected with the virus, which they then transmitted to other control chickens they were housed with.When the researchers administered flu virus directly into the nasal cavities of 10 gene-edited chickens, just one of the birds became infected. It had low levels of the virus and did not pass the virus on to other gene-edited birds.“But having seen that, we felt that it would be the responsible thing to be more rigorous, to stress test this and ask, ‘Are these chickens truly resistant?’” Dr. Barclay said. “‘What if they were to somehow encounter a much, much higher dose?’”When the scientists gave the gene-edited chickens a flu dose that was 1,000 times higher, half of the birds became infected. The researchers found, however, that they generally shed lower levels of the virus than control chickens exposed to the same high dose.The researchers then studied samples of the virus from the gene-edited birds that had been infected. These samples had several notable mutations, which appeared to allow the virus to use the edited ANP32A protein to replicate, they found.Some of these mutations also helped the virus replicate better in human cells, although the researchers noted that those mutations in isolation would not be enough to create a virus that was well adapted to humans.Seeing those mutations is “not ideal,” said Richard Webby, who is a bird flu expert at St. Jude Children’s Research Hospital and was not involved in the research. “But when you get to the weeds of these particular changes, then it doesn’t concern me quite so much.”The mutated flu virus was also able to replicate even in the complete absence of the ANP32A protein by using two other proteins in the same family, the researchers found. When they created chicken cells that lacked all three of these proteins, the virus was not able to replicate. Those chicken cells were also resistant to the highly lethal version of H5N1 that has been spreading around the world the last several years.The researchers are now working to create chickens with edits in all three of the genes for the protein family.The big question, Dr. Webby said, was whether chickens with edits in all three genes would still develop normally and grow as fast as poultry producers needed. But the idea of gene editing chickens had enormous promise, he said. “Absolutely, we’re going to get to a point where we can manipulate the host genome to make them less susceptible to flu,” he said. “That’ll be a win for public health.”