Physical cues in the womb, and not just genetics, influence the normal development of neural crest cells, the embryonic stem cells that form facial features, finds a new study led by UCL researchers.
The study published in Nature Cell Biologyfound that an increase in hydrostatic pressure sensed by the embryo can hinder the healthy development of facial features in mouse and frog embryos and in human embryoids (cell structures grown in the lab from human stem cells), suggesting that differences in pressure might affect the risk of facial malformations.
The researchers found that when neural crest cells are exposed to higher-than-usual levels of pressure, key cell signalling pathways are impeded, and the risk of craniofacial malformations significantly increases.
Lead author Professor Roberto Mayor (UCL Cell & Developmental Biology) said: “Our findings suggest that facial malformations could be influenced not only by genetics but by physical cues in the womb such as pressure.
“When an organism is experiencing a change in pressure, all the cells — including the embryo inside the mother — are able to sense it.
“Our work shows that embryos are sensitive to pressure, but we do not know how sensitive they are; for instance, will a change in the pressure inside the uterus be able to affect the embryo? This will require further research to understand how changes inside the body as well as in environmental pressure might influence human embryo development.”
The researchers say their findings could also have implications for stem cell research, as the study indicates that the development and differentiation (the process of stem cells becoming specialised cells) of stem cells are under the influence of pressure. Understanding this connection could transform how scientists manipulate stem cells for various therapeutic purposes.
The findings add to work by Professor Mayor and colleagues at UCL into how mechanical cues in the womb can influence the development of facial features, as they have previously found that cells in the developing embryo sense the stiffness of other cells around them, which is key to them moving together to form the face and skull.

Some pathogens hide inside human cells to enhance their survival. Researchers led by Prof. Marek Basler at the Biozentrum, University of Basel, have uncovered a unique tactic certain bacteria use to spread in the body without being detected by the immune system. In their study, they reveal the crucial role of a bacterial nanomachine in this infection process.
The inside of a cell provides as a hiding place for various pathogens. By residing in the cell, the bacteria can evade the immune response and spread within the body. Among these invaders are Burkholderia bacteria, including the species B. pseudomallei. This pathogenis known for causing melioidosis, a serious infectious disease prevalent in tropical regions. Due to the high mortality rate and the pathogen’s resistance to many antibiotics, B. pseudomallei is considered a potential biothreat agent.
In the less harmful relative B. thailandensis, the team led by Professor Marek Basler at the Biozentrum, University of Basel, has uncovered a cunning tactic the pathogen uses to spread within the tissue. “The bacteria are equipped with a nano-sized speargun, the so-called type VI secretion system, T6SS for short,” says Basler. “Burkholderia uses this T6SS to move from one cell to another without being recognized by the immune system.” The findings, recently published in the journal Cell Host & Microbe, change the current view of the T6SS’s role in Burkholderia infections.
Pathogen uses nanomachine to spread from cell to cell
From previous studies, it is already known that these intracellular pathogens rely on an unusual spread strategy: After entering the cell, they make use of cellular components, such as actin, to move to the cell membrane and form protrusions into the neighboring cell. Using their T6SS-speargun, the bacteria can also fuse the two cells allowing them to spread.
Unique strategy to spread undetected
By investigating the role of T6SS in more detail, the researchers have discovered a so far unknown and unique escape strategy of these bacteria. “We were surprised to see that Burkholderia can spread not only by inducing cell fusion but also by directly moving from cell to cell,” explains first author Dr. Miro Plum. The detachment of the protrusion from the cell membrane results in the formation of a vacuole within the neighboring cell. The pathogen inside this vacuole then breaks free by utilizing its T6SS to disrupt the surrounding cell membrane.
Surprisingly, spreading this way also enables the bacteria to infect new cells without alarming the immune system. “Normally, infected cells sense invaders by detecting damaged cell membranes, initiating immune responses to eliminate the pathogen,” emphasizes Plum. “However, cells fail to detect T6SS-disrupted membranes.” So, the pathogen remains undetected and can infect new cells.
Exploring the survival tactics of intracellular pathogens
Equipped with the T6SS nanomachine, Burkholderia bacteria can pursue a dual strategy: cell fusion and directly moving from one cell to another. “Our results advance the understanding of infections caused by Burkholderia, particularly its strategies for spreading and immune evasion,” concludes Basler. The researchers now want to explore the mechanisms that specifically trigger the T6SS assembly in bacteria inside the protrusions to gain deeper insights into the survival tactics of this intracellular pathogen.

Plant-derived nanoparticles have demonstrated significant anticancer effects. Researchers recently developed rice bran-derived nanoparticles (rbNPs) that efficiently suppressed cell proliferation and induced programmed cell death of only cancer cells. Furthermore, rbNPs successfully suppressed the growth of tumors in mice having aggressive adenocarcinoma in their peritoneal cavity, without any adverse effects. Given their low production costs and high efficacy, rbNPs hold great promise for developing affordable and safe anticancer agents.
Several types of conventional cancer therapies, such as radiotherapy or chemotherapy, destroy healthy cells along with cancer cells. In advanced stages of cancer, tissue loss from treatments can be substantial and even fatal. Cutting-edge cancer therapies that employ nanoparticles can specifically target cancer cells, sparing healthy tissue. Recent studies have demonstrated that plant-derived nanoparticles (pdNPs) that have therapeutic effects can be an effective alternative to traditional cancer treatments. However, no pdNPs have been approved as anticancer therapeutic agents till date.
Rice bran is a byproduct generated during rice refining process that has limited utility and low commercial value. However, it contains several compounds with anticancer properties, such as γ-oryzanol and γ-tocotrienol. To explore these therapeutic properties of rice bran, a team of researchers led by Professor Makiya Nishikawa from Tokyo University of Science (TUS) in Japan developed nanoparticles from rice bran and tested their effectiveness in mice models. Their study, published in Volume 22 of Journal of Nanobiotechnology on 16 March 2024, was co-authored by Dr. Daisuke Sasaki, Ms. Hinako Suzuki, Associate Professor Kosuke Kusamori, and Assistant Professor Shoko Itakura from TUS.
“In recent years, an increasing number of new drug modalities are being developed. At the same time, development costs associated with novel therapies have increased dramatically, contributing to the burden of medical expenses. To address this issue, we used rice bran, an industrial waste with anticancer properties, to develop nanoparticles,” explains Prof. Nishikawa.
The study evaluated the anticancer effects of rice bran-derived nanoparticles (rbNPs), which were obtained by processing and purifying a suspension of Koshihikari rice bran in water. When a cancer cell line named colon26 was treated with rbNPs, cell division was arrested and programmed cell death was induced, indicating strong anticancer effects of the nanoparticles. The observed anticancer activity of rbNPs can be attributed to γ-tocotrienol and γ-oryzanol, that are easily taken up by cancer cells resulting in cell cycle arrest and programmed cell death. Additionally, rbNPs reduced the expression of proteins, such as β-catenin (a protein associated with Wnt signaling pathway involved in cell proliferation) and cyclin D1, which are known to promote cancer recurrence and metastases. Moreover, the rbNPs reduced the expression of β-catenin only in colon26 cells without affecting the non-cancerous cells.
“A key concern in the context of pdNPs is their low pharmacological activity compared to pharmaceutical drugs. However, rbNPs exhibited higher anticancer activity than DOXIL®, a liposomal pharmaceutical formulation of doxorubicin. Additionally, doxorubicin is cytotoxic to both cancer cells and non-cancerous cells, whereas rbNPs are specifically cytotoxic to cancer cells, suggesting that rbNPs are safer than doxorubicin,” highlights Prof.Nishikawa.
To confirm the anticancer properties of rbNPs in the living body, the researchers injected rbNPs into mice having aggressive adenocarcinoma in their peritoneal cavity (enclosed by the diaphragm, abdominal muscles, and pelvis and houses organs like intestines, liver, and kidneys). They observed significant suppression of tumor growth with no adverse effects on the mice. Additionally, the rbNPs significantly inhibited metastatic growth of murine melanoma B16-BL6 cells in a lung metastasis mouse model.
Rice bran has several attributes that make it an excellent source of therapeutic pdNPs. Firstly, it is economic as compared to many other sources of pdNPs. Nearly 40% of the rice bran is discarded in Japan, providing a readily available source of raw material. Secondly, the preparation efficiency of rbNPs is higher than that of previously reported pdNPs. Besides being practical and safe as an anticancer therapeutic, the physicochemical properties of rbNPs are very stable. However, a few parameters, such as establishment of separation technologies at the pharmaceutical level, assessing production process control parameters, and evaluation of efficacy and safety in human cancer cell lines and xenograft animal models, must be investigated prior to clinical trials in humans.
In conclusion, rice bran, an agricultural waste product, is a source of therapeutic pdNPs that are affordable, effective, and safe, and has the potential to revolutionize cancer treatment in the future.
“By establishing a manufacturing method for rice bran nanoparticles with stable quality and confirming their safety and effectiveness, we can develop drugs for cancer treatment that are sustainable, eco-friendly, and affordable. Consequently, we may be able to help more cancer patients maintain good physical and mental health after treatment,” concludes Prof. Nishikawa.

Purdue University researchers are developing and validating a patent-pending treatment for incurable glioblastoma brain tumors. Glioblastomas are almost always lethal with a median survival time of 14 months. Traditional methods used against other cancers, like chemotherapy and immunotherapy, are often ineffective on glioblastoma.
Sandro Matosevic, associate professor in the Department of Industrial and Molecular Pharmaceutics in Purdue’s College of Pharmacy, leads a team of researchers that is developing a novel immunotherapy to be used against glioblastoma. Matosevic is also on the faculty of the Purdue Institute for Cancer Research and the Purdue Institute for Drug Discovery.
The Matosevic-led research has been published in the peer-reviewed journal Nature Communications.
The Purdue glioblastoma treatment
Matosevic said traditional cell therapies have almost exclusively been autologous, meaning taken from and returned to the same patient. Blood cells from a patient are engineered to better recognize and bind to proteins on cancer cells, then given back to the same patient to bind to and attack cancer cells. Unfortunately, these therapies have limited to no effect on glioblastoma.
“By contrast, we are developing immunotherapy based on novel, genetically engineered, fully off-the-shelf or allogeneic immune cells. Allogeneic cells are not sourced from the same patient, but rather another source,” Matosevic said. “In our study, we sourced — or rather engineered — cells from induced pluripotent stem cells. So we eliminated the need for blood and instead differentiated stem cells into immune cells, or natural killer cells, and then genetically engineered those.”
Matosevic said novel Purdue immunotherapy can be considered to have a true off-the-shelf source.

“We can envision having unlimited supplies of these stem cells ready to be engineered,” Matosevic said. “This does not require blood to be sourced. And because these are human cells, they are directly usable in human patients.”
Validation and next development steps
The research team tested its treatment by conducting animal studies with mice bearing human brain tumors, which were treated by direct injection of the newly engineered immune cells.
“Our preclinical studies showed these immune cells to be particularly remarkable in targeting and completely eliminating the growth of the tumors,” Matosevic said. “We found that we can engineer these cells at doses suitable for clinical use in humans. This is significant because one of the major hurdles to clinical translation of cell-based therapies to humans has been the poor expansion and lack of potency of cells that were sourced directly from patients. Using an off-the-shelf, fully synthetic approach breaks down significant barriers to the manufacturing of these cells.”
Matosevic said the next step to develop the glioblastoma treatment is to conduct clinical trials to treat patients with brain tumors, including those that were not successfully eliminated by surgery.
“Our ultimate goal is to bring this therapy to patients with brain tumors,” Matosevic said. “These patients urgently deserve better, and more effective, treatment options. We believe there is true potential for this therapy, and we have the motivation and capacity to bring it to the clinic.
“We are working with neurosurgical clinician collaborators to not only obtain funding, but also initiate clinical protocols,” he added. “We are also open to and always seeking new collaborations and partnerships with those who have interest in supporting our mission to translate this therapy to the clinic, where it is needed the most.”
Matosevic disclosed the innovative glioblastoma treatment to the Purdue Innovates Office of Technology Commercialization, which has applied for a patent from the U.S. Patent and Trademark Office to protect the intellectual property.
Matosevic and the research team received funding from the National Institutes of Health, the V Foundation for Cancer Research, the Purdue Institute for Cancer Research and industry partners.

Middle-aged and older adults believe that old age begins later in life than their peers did decades ago, according to a study published by the American Psychological Association.
“Life expectancy has increased, which might contribute to a later perceived onset of old age. Also, some aspects of health have improved over time, so that people of a certain age who were regarded as old in the past may no longer be considered old nowadays,” said study author Markus Wettstein, PhD, of Humboldt University in Berlin, Germany.
However, the study, which was published in the journal Psychology and Aging, also found evidence that the trend of later perceived old age has slowed in the past two decades.
Wettstein, along with colleagues at Stanford University, the University of Luxembourg and the University of Greifswald, Germany, examined data from 14,056 participants in the German Ageing Survey, a longitudinal study that includes people living in Germany born between 1911 and 1974. Participants responded to survey questions up to eight times over 25 years (1996-2021), when they were between 40 and 100 years old. Additional participants (40 to 85 years old) were recruited throughout the study period as later generations entered midlife and old age. Among the many questions survey participants answered was, “At what age would you describe someone as old?”
The researchers found that compared with the earliest-born participants, later-born participants reported a later perceived onset of old age. For example, when participants born in 1911 were 65 years old, they set the beginning of old age at age 71. In contrast, participants born in 1956 said old age begins at age 74, on average, when they were 65.
However, the researchers also found that the trend toward a later perceived onset of old age has slowed in recent years.
“The trend toward postponing old age is not linear and might not necessarily continue in the future,” Wettstein said.

The researchers also looked at how individual participants’ perceptions of old age changed as they got older. They found that as individuals aged, their perception of the onset of old age was pushed further out. At age 64, the average participant said old age started at 74.7. At age 74, they said old age started at 76.8. On average, the perceived onset of old age increased by about one year for every four to five years of actual aging.
Finally, the researchers examined how individual characteristics such as gender and health status contributed to differences in perceived onset of old age. They found that women, on average, said that old age started two years later than men — and that the difference between men and women had increased over time. They also found that people who reported being more lonely, in worse health, and feeling older said old age began earlier, on average, than those who were less lonely, in better health, and felt younger.
The results may have implications for when and how people prepare for their own aging, as well as how people think about older adults in general, Wettstein said.
“It is unclear to what extent the trend towards postponing old age reflects a trend towards more positive views on older people and aging, or rather the opposite — perhaps the onset of old age is postponed because people consider being old to be an undesirable state,” Wettstein said.
Future research should examine whether the trend toward a “postponement” of old age continues and investigate more diverse populations in other countries, including non-Western countries, to understand how perceptions of aging vary by country and culture, according to the researchers.

State-of-the-art artificial intelligence systems known as large language models (LLMs) are poor medical coders, according to researchers at the Icahn School of Medicine at Mount Sinai. Their study, published in the April 19 online issue of NEJM AI, emphasizes the necessity for refinement and validation of these technologies before considering clinical implementation.
The study extracted a list of more than 27,000 unique diagnosis and procedure codes from 12 months of routine care in the Mount Sinai Health System, while excluding identifiable patient data. Using the description for each code, the researchers prompted models from OpenAI, Google, and Meta to output the most accurate medical codes. The generated codes were compared with the original codes and errors were analyzed for any patterns.
The investigators reported that all of the studied large language models, including GPT-4, GPT-3.5, Gemini-pro, and Llama-2-70b, showed limited accuracy (below 50 percent) in reproducing the original medical codes, highlighting a significant gap in their usefulness for medical coding. GPT-4 demonstrated the best performance, with the highest exact match rates for ICD-9-CM (45.9 percent), ICD-10-CM (33.9 percent), and CPT codes (49.8 percent).
GPT-4 also produced the highest proportion of incorrectly generated codes that still conveyed the correct meaning. For example, when given the ICD-9-CM description “nodular prostate without urinary obstruction,” GPT-4 generated a code for “nodular prostate,” showcasing its comparatively nuanced understanding of medical terminology. However, even considering these technically correct codes, an unacceptably large number of errors remained.
The next best-performing model, GPT-3.5, had the greatest tendency toward being vague. It had the highest proportion of incorrectly generated codes that were accurate but more general in nature compared to the precise codes. In this case, when provided with the ICD-9-CM description “unspecified adverse effect of anesthesia,” GPT-3.5 generated a code for “other specified adverse effects, not elsewhere classified.”
“Our findings underscore the critical need for rigorous evaluation and refinement before deploying AI technologies in sensitive operational areas like medical coding,” says study corresponding author Ali Soroush, MD, MS, Assistant Professor of Data-Driven and Digital Medicine (D3M), and Medicine (Gastroenterology), at Icahn Mount Sinai. “While AI holds great potential, it must be approached with caution and ongoing development to ensure its reliability and efficacy in health care.”
One potential application for these models in the health care industry, say the investigators, is automating the assignment of medical codes for reimbursement and research purposes based on clinical text.

“Previous studies indicate that newer large language models struggle with numerical tasks. However, the extent of their accuracy in assigning medical codes from clinical text had not been thoroughly investigated across different models,” says co-senior author Eyal Klang, MD, Director of the D3M’s Generative AI Research Program. “Therefore, our aim was to assess whether these models could effectively perform the fundamental task of matching a medical code to its corresponding official text description.”
The study authors proposed that integrating LLMs with expert knowledge could automate medical code extraction, potentially enhancing billing accuracy and reducing administrative costs in health care.
“This study sheds light on the current capabilities and challenges of AI in health care, emphasizing the need for careful consideration and additional refinement prior to widespread adoption,” says co-senior author Girish Nadkarni, MD, MPH, Irene and Dr. Arthur M. Fishberg Professor of Medicine at Icahn Mount Sinai, Director of The Charles Bronfman Institute of Personalized Medicine, and System Chief of D3M.
The researchers caution that the study’s artificial task may not fully represent real-world scenarios where LLM performance could be worse.
Next, the research team plans to develop tailored LLM tools for accurate medical data extraction and billing code assignment, aiming to improve quality and efficiency in health care operations.
The study is titled “Generative Large Language Models are Poor Medical Coders: A Benchmarking Analysis of Medical Code Querying.”
The remaining authors on the paper, all with Icahn Mount Sinai except where indicated, are: Benjamin S. Glicksberg, PhD; Eyal Zimlichman, MD (Sheba Medical Center and Tel Aviv University, Israel); Yiftach Barash, (Tel Aviv University and Sheba Medical Center, Israel); Robert Freeman, RN, MSN, NE-BC; and Alexander W. Charney, MD, PhD.
This research was supported by the AGA Research Foundation’s 2023 AGA-Amgen Fellowship to-Faculty Transition Award AGA2023-32-06 and an NIH UL1TR004419 award.
The researchers affirm that the study was conducted without the use of any Protected Health Information (“PHI”).

Clarifying the cause of a skin disease led to the discovery of a new disease-causing gene, a new category of diseases, and new perspectives for both counseling and therapy. The Kobe University discovery is the first time that epigenetic silencing, the “switching off” of an otherwise intact gene, has been recognized as the cause for a skin disease.
Porokeratosis is a skin disease that leads to the development of annular or circular, red and itchy lesions. In some individuals, these develop all over the body, in some localized in lines, and in some only in one or very few spots. Kobe University dermatologist KUBO Akiharu previously discovered that patients need “two hits” to one of the four genes that, when damaged, were known to cause the disease. Kubo explains: “We get one set of genes from each of our parents, which means that, for all genes relevant to this disease, we have two copies. However, patients had one deficient copy in all of their cells, which means that they inherited that from one of their parents. But they also had later mutations in the other copy in those areas of the skin where the disease developed.” After that discovery, over fifty patients visited Keio University Hospital and Kobe University Hospital to get screened by Kubo, and among these they found eight patients who didn’t have deficiencies in any of the four genes known to cause the disease, and they also had slightly different symptoms. “I was convinced that there is a yet unknown cause of porokeratosis, and so my graduate student at Keio University, SAITO Sonoko, started to search for it.”
In The American Journal of Human Genetics, they now report that they identified a new gene, called FDFT1, that when damaged will cause porokeratosis. But while those patients who had lesions all over the body had one deficient copy inherited from one of the parents and one later mutation in the affected cells, which is similar to what is known for other causative genes, those with more localized lesions did not have such an inherited damaged copy. Kubo says, “These observations led to the hypothesis that not genetic, but epigenetic changes in FDFT1 are hidden as the first hits.” Epigenetic changes don’t affect the DNA sequence that constitutes the gene but refer to molecular tags a cell can add to DNA to indicate whether or not to produce proteins from the gene, depending on the tag. “And that is exactly what we found. Epigenetic silencing of FDFT1 during early embryonic development in a cell that will give rise to skin cells is the first hit in this type of porokeratosis.”
The whole picture therefore is that, in order to develop the disease, people need two damaged copies of the gene, “two hits.” One they acquire either from their parents or through epigenetic silencing early in their fetal development. This predisposes them to developing the disease but in itself is not symptomatic. In the case of epigenetic silencing, individuals are mosaics of predisposed cells, which derive from the one where the silencing occurred, and unaffected cells. A second defect in the other copy of the gene leads to the development of the disease: Similar to the previously known causative genes, the protein produced from FDFT1 is involved in the production of cholesterol and with both copies of the gene deficient, toxic by-products accumulate in the cells.
These results have many fascinating implications. First, the knowledge of the affected gene allows doctors to prescribe a treatment. “We conducted a therapeutic evaluation of atorvastatin (a blocker of cholesterol production) and cholesterol ointment in three individuals with FDFT1-deficient porokeratosis. All individuals exhibited reduced skin redness and thickening, pruritus (itchiness), and scaling within 4-12 weeks of treatment initiation, and no relapse was observed with continued use of the ointment,” the researchers write in the paper. Second, when counseling patients, for those who didn’t inherit a deficient gene from their parents it is reassuring news that they will also not pass the predisposition to the illness on to their children.
And third, “This is the first skin disease caused by early-development epigenetic silencing of a particular gene. Among all diseases, a fully comparable mechanism is only known in Lynch syndrome. We thus expect that epigenetic causes are hidden not only in these but also in other diseases, suggesting the existence of a category of diseases associated with the silencing of genes,” the researchers explain.

Primary health care, conditional cash transfers and social pensions have prevented 1.4 million deaths of all ages in Brazil over the past two decades, according to a study coordinated by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation. If expanded, these programmes could avert an additional 1.3 million deaths and 6.6 million hospitalisations by 2030.
The COVID-19 pandemic has exacerbated poverty and social inequalities worldwide, particularly in low- and middle-income countries (LMICs). In addition, the economic consequences of the ongoing war in Ukraine and soaring inflation are expected to push even more people into poverty in the coming years. This is what we call a polycrisis: multiple crises interacting in such a way that their combined impact is greater than the sum of the parts.
In terms of public health, worsening socioeconomic conditions mean higher rates of disease and death, especially among the most vulnerable people in LMICs. But social programmes can mitigate the health consequences of economic crises. Brazil has led one of the largest welfare state expansions over the past two decades, implementing a public universal healthcare system along with conditional cash transfer programmes (Programa Bolsa Familia) for the poorest families and social pensions (Beneficio de Prestacao Continuada) for the elderly and disabled.
Reductions in hospitalisations and deaths
In this study, ISGlobal researcher Davide Rasella and his team evaluated the combined effect of these three programmes (conditional cash transfers, social pensions and primary health care) on hospitalisations and deaths over almost two decades (from 2004 to 2019). “This is the first study to conduct a nationwide combined evaluation of cash transfers, social pensions, and primary health care for a such long period in a LMIC,” says Rasella, who coordinated the study.
Using data from 2,548 Brazilian municipalities, they show that high coverage of the three programmes led to reductions in overall hospitalisation and mortality rates, particularly among children under five years of age and adults over 70. A total of 1.46 million deaths were averted between 2004 and 2019. The research team then used forecasting methods to show that extending the programmes to the newly poor and vulnerable could avert up to 1.3 million additional deaths by 2030.
“We clearly show that expanding these three programmes is a viable strategy to mitigate the health impact of the current global polycrisis,” says Daniella Cavalcanti, co-first author of the study. “On the contrary, fiscal austerity measures would only result in a large number of preventable deaths.”

Published22 minutes agoShareclose panelShare pageCopy linkAbout sharingBy William McLennan, Colin Campbell and Abby NewberyBBC England InvestigationsDeadly drugs known as nitazenes are being smuggled into the UK inside dog food and catering supplies, a BBC investigation has found.Nitazenes – more deadly than heroin – have recently been linked to nearly three UK deaths a week on average.The BBC also found the drugs were being offered for sale on social media platforms including X and SoundCloud.SoundCloud said it had been “targeted by bad actors” while X did not respond to requests for comment. The posts on SoundCloud have now been removed. X, formerly Twitter, took down hundreds but many listings remain.Nitazenes, which are illegal in the UK, are synthetic drugs produced in laboratories. They are similar to heroin and morphine, but can be several hundred times more potent. It’s thought users often take them unknowingly – because they are hidden within other illegal substances by dealers looking to cut production costs. Nitazenes have been found by a publicly funded testing lab in a range of drugs, including street heroin and black market pills which dealers had wrongly claimed contained anti-anxiety drugs, such as Xanax and Valium. Our evidence suggests dozens of suppliers are advertising openly on the internet and sending nitazenes in the post from China, where they are manufactured in laboratories. There are many varieties of nitazene, with different chemical structures and potencies. The BBC found more than a dozen types of nitazenes being advertised under their various chemical names. The BBC investigation identified thousands of social media posts advertising the drugs, including:nearly 3,000 posts on SoundCloud, some dating back a year – posts on the music streaming service contained brief audio clips, often lasting just a few seconds, with the drug’s name and contact details appearing as the title of the trackmore than 700 posts on X – the oldest had been on the platform for more than 18 months, but the vast majority of posts had been published since the start of 2023one post from a supplier advertising on X in March 2024, who had been indicted and sanctioned in the US in September 2023 over the shipping of 15kg of nitazenes from ChinaPosing as a drug dealer, we contacted 35 suppliers – 14 of whom were advertising on SoundCloud, six advertising on X, and 15 whom we contacted via a website promoting wholesale chemical manufacturers. Thirty offered to post the drug to the UK. The BBC did not actually buy any nitazenes.The majority of suppliers claimed to work for companies that otherwise appeared legitimate, with professional websites and business addresses in Chinese cities. Most adverts followed a pattern, containing the names and pictures of the nitazenes, contact details for secure messaging platforms and promises of secure shipping or customs clearance.The New Drug ThreatAn investigation into the growing illicit trade in a new type of lethal drug called nitazenes.Watch now on BBC iPlayer (UK Only)The adverts appeared to target drug dealers, offering bulk purchases for the criminals to sell on in smaller batches. While we found evidence that dealers in the US and the UK are using social media to connect with the suppliers, we have no evidence of individual drug users doing this. The suppliers sent us videos and photos of the drugs, including kilogram bags on digital scales. Some explained they would evade customs by disguising the drugs in dog food and catering supplies. One supplier sent a video and pictures of a pristine laboratory where they claimed the drugs were made. More than £4.2m in Bitcoin had been transferred into the cryptocurrency accounts of 19 of the suppliers within the past two years, our analysis found. In secretly recorded video calls, our undercover reporter was repeatedly reassured by suppliers that the drugs were safe, despite them never having been cleared for medical use anywhere in the world. One supplier laughed as they explained how they used SoundCloud: “It’s a music platform but we can make an advertisement on it.” Another supplier felt that X was “good to use” and was better for advertising drugs as, in their experience, they were less likely to get blocked on X than on other platforms. Prof Vicki Nash, director of the Oxford Internet Institute, a department at the University of Oxford that researches online behaviour, says: “Finding adverts on this scale, hundreds, thousands of adverts, is horrifying with potentially a very significant risk to human life.” She adds that the BBC’s investigation has uncovered how criminals have been “blatantly misusing” SoundCloud – hiding adverts in what appeared to be music tracks – in a way that can be found on search engines. Adverts for nitazenes can also be found elsewhere online, but searching for the names of various nitazenes on other mainstream social media platforms returned only a handful of posts, or led to safety warnings. When nitazenes enter a local drug supply, it can quickly prove fatal. Four men died within a fortnight in Oxfordshire in 2021 after taking heroin laced with nitazenes.The drugs have been linked to at least 101 deaths in the UK between 1 June 2023 and 22 February 2024 – equivalent to nearly three deaths per week- according to the National Crime Agency (NCA). Claire Rocha – whose musician son Dylan, 21, was one of the first deaths linked to nitazene-contaminated drugs in the UK – describes the BBC’s findings as “shocking.” Dylan, whose band had been due to tour the UK before the Covid pandemic, was found dead at home in Southampton in 2021. Mrs Rocha described him as a “musical genius”. If you have been affected by the issues raised in this story, you can find sources of help and support from BBC Action lineIt has never been established how Dylan, who had received treatment for addiction, bought what he thought was heroin. A coroner ruled he would likely have been unaware the drug contained a nitazene. Dylan used SoundCloud to share his music, but there is no evidence he bought drugs via the site. A toxicologist found his death was caused by a combination of a nitazene, heroin and alcohol. Mrs Rocha says it was “absolutely crazy” that thousands of adverts were posted on SoundCloud and X. “How has that been allowed to happen?” she says. “How many people have died as a result of that being advertised there?” ‘Motivated by greed’Other opioids, including heroin and morphine, are made from poppy plants – and at one time, most heroin imported into the UK came from fields in Afghanistan. Some experts believe a recent crackdown on production by the Taliban could be pushing criminals towards nitazenes. But that is not the opinion of Charles Yates of the NCA – who says that the agency is monitoring and testing drug supplies. He believes there is “no direct link” between the Taliban’s actions and the rising prevalence of synthetic opioids.Instead, in most cases he believed criminals – whose “sole motivation is greed” – were using nitazenes because they are cheap.The agency is working with police, Border Force and international partners to ensure that “all lines of enquiry are prioritised and vigorously pursued to stem any supply of nitazenes to and within the UK”, he adds.In 2023, the US Drug Enforcement Agency (DEA) charged 11 Chinese companies over the sale of synthetic opioids, including nitazenes. Following a tip-off from the DEA, the Met Police shut down an illegal pill factory in west London that produced hundreds of thousands of counterfeit Xanax pills and other benzodiazepines, which also contained a powerful nitazene. It is thought to be the first time police disrupted an organised criminal group distributing nitazenes in the UK. The BBC has learned police found text messages on the gang’s phones after the raid in August 2022 which showed they had at first been reluctant to use nitazenes, but were pushed to use them by their China-based suppliers. ‘Unbelievably dangerous’In Whatsapp messages to our undercover buyer, many suppliers offered discounts on bulk purchases and some even advised how much to put into pills that would be sold illegally in the UK.But Caroline Copeland, a senior lecturer in pharmacology and toxicology at King’s College London, says the drugs are so strong, it is difficult to measure out a safe dose. “I don’t think there is even a safe dose,” she adds.Mike Trace, a former government drug tsar, says there is already an “overdose crisis” with nearly 5,000 drug deaths in England and Wales each year: “If nitazenes come into this market in a big way, that death rate could spiral and double or treble.”Since 2021, nitazenes have been found 54 times in samples of pills being sold by dealers as anti-anxiety drugs including Xanax and diazepam. The data was compiled by Wedinos, a Welsh government-funded programme which tests anonymous samples from across the UK. Experts say this increases the risk of overdose, with users unknowingly taking powerful opioids, potentially for the first time and with no tolerance for the drugs.’Worldwide epidemic’Last month, 14 varieties of nitazene were made Class-A under the Misuse of Drugs Act, outlawing possession and increasing sentences for supply. The sale and importation of all nitazenes had already been outlawed in the UK under the Psychoactive Substances Act. In China it is more complicated. Some have been outlawed by name, but new derivatives – which are being offered for sale online – do not appear to have been banned yet. Nitazenes have emerged as attempts are made to cut the supply of fentanyl, another synthetic opioid, which has driven an overdose crisis in the US. Authorities believe fentanyl – and chemicals that can be combined to make it – are also made in Chinese labs. In November 2023, the US and China announced a renewed collaboration to crack down on the trade. Previous co-operation between the two sides led to a number of breakthroughs including several convictions in China.SoundCloud has said it and other social media platforms were “being targeted by bad actors” and it has promised to do “everything we can to tackle this worldwide epidemic”. It says it uses both human moderation and software to identify and remove content that promotes drug sales, and “continues to evaluate and invest in best in class technology to aid in this effort”.It has removed nearly 3,000 posts. X has not responded to requests for comment. It removed hundreds of posts after being contacted by the BBC, but many still remained online four weeks later. We contacted all 30 suppliers who offered to sell us drugs, to ask why they were providing illegal and dangerous products. Only six responded – all claimed they had never sent the drug to the UK. The Home Office says there has been an “intensive operational effort to track down [nitazenes] and their suppliers – on the streets, at the borders and online”. It says that the Online Safety Act, which became law last year, makes it clear tech companies “must do more to swiftly remove this type of content… and prevent users from being exposed to it”.It adds that an enhanced “early warning system” which includes testing wastewater for the presence of synthetic opioids, would allow them to detect and respond to the drugs as quickly as possible.Additional research by Laura BunceHave you been affected by opioids? Do you have more information about this story? Email haveyoursay@bbc.co.uk.Please include a contact number if you are willing to speak to a BBC journalist. You can also get in touch in the following ways:WhatsApp: +44 7756 165803Tweet: @BBC_HaveYourSayUpload pictures or videoPlease read our terms & conditions and privacy policy

If you are reading this page and can’t see the form you will need to visit the mobile version of the BBC website to submit your question or comment or you can email us at HaveYourSay@bbc.co.uk. Please include your name, age and location with any submission. More on this storyUK too slow to act on lethal drug threat – doctorsPublished20 MarchWarning over potential risk of synthetic opioidsPublished31 July 2023Fourth wave of fentanyl crisis hits every corner of USPublished17 September 2023

In her three decades of working with elephant seals, Dr. Marcela Uhart had never seen anything like the scene on the beaches of Argentina’s Valdés Peninsula last October.It was peak breeding season; the beach should have been teeming with harems of fertile females and enormous males battling one another for dominance. Instead, it was “just carcass upon carcass upon carcass,” recalled Dr. Uhart, who directs the Latin American wildlife health program at the University of California, Davis.H5N1, one of the many viruses that cause bird flu, had already killed at least 24,000 South American sea lions along the continent’s coasts in less than a year. Now it had come for elephant seals.Pups of all ages, from newborns to the fully weaned, lay dead or dying at the high-tide line. Sick pups lay listless, foam oozing from their mouths and noses.Dr. Uhart called it “an image from hell.”In the weeks that followed, she and a colleague — protected head to toe with gloves, gowns and masks, and periodically dousing themselves with bleach — carefully documented the devastation. Team members stood atop the nearby cliffs, assessing the toll with drones.What they found was staggering: The virus had killed an estimated 17,400 seal pups, more than 95 percent of the colony’s young animals.