Showing posts sorted by date for query SMOKING. Sort by relevance Show all posts
Showing posts sorted by date for query SMOKING. Sort by relevance Show all posts

Wednesday, September 04, 2024

 

Can you identify the new threat attracting Gen Z to nicotine use?



Survey finds just 1 in 4 adults could identify nicotine pouches if they saw them, but they are skyrocketing in popularity



Ohio State University Wexner Medical Center

Nicotine Pouches 

image: 

A new national survey by The Ohio State University Comprehensive Cancer Center —Arthur G. James Cancer Hospital and Richard J. Solove Research Institute finds just one in four Americans could identify a nicotine pouch outside of its packaging. As these products skyrocket in popularity, experts worry they’re a gateway to nicotine addiction for teens and young adults.

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Credit: The Ohio State University Comprehensive Cancer Center.




COLUMBUS, Ohio – About half of adults can identify cigarettes and e-cigarettes, but just one in four would recognize oral nicotine pouches, and these easily available products are growing increasingly popular among teens and young adults, according to a recent study commissioned by The Ohio State University Comprehensive Cancer Center – Arthur G. James Hospital and Richard J. Solove Research Institute (OSUCCC – James).

Oral nicotine pouches are small packets filled with a flavored powder containing nicotine and other chemicals that are tucked between the lip and gums. Researchers at the OSUCCC – James Center for Tobacco Research are concerned that these oral nicotine pouches are so appealing and easy to use that they could be a gateway to future tobacco product addiction for Gen Z.

Epidemiologist Brittney Keller-Hamilton, PhD, says these products are available in low- and high-nicotine concentrations, making them appealing to both new users and people who are already addicted to nicotine. 

“We're starting to hear from college students that they find it easier to use nicotine pouches at work or in class because they are easier to conceal. They also do not require you to spit excess saliva like older tobacco oral products (dip, snuff),” said Keller-Hamilton, who studies nicotine pouch use and regulation at the Center for Tobacco Research. “One of my biggest concerns with nicotine pouches is that as youth experiment with these products, they might not find them to be satisfying enough to continue to meet a growing nicotine craving and then might transition to more harmful products.” 

She notes that regulation of these products is minimal, and that removing flavorings, prohibiting online sales, and increasing the price could discourage youth experimentation and, therefore, reduce their risk of becoming addicted to nicotine. 

As students go back to school, Keller-Hamilton cautions parents to pay attention to what is in their teenagers’ backpacks.

“Many products are cleverly packaged to conceal the real content – vapes as highlighters or pens, oral nicotine pouches as mints. Unfortunately, due to loose industry regulation, they are very easy to obtain for underage youth, and they are far from harmless. We know that when people start using any nicotine product, including nicotine pouches, before their brain is finished developing, it primes their brain for a stronger nicotine addiction and also primes their brain for addiction to other substances,” said Keller-Hamilton. “It’s really important for parents to talk with their kids about the dangers of these products and seek help from their pediatrician if they’re concerned about nicotine addiction.”

Study results and methods
For this survey, 1,000 adults aged 18 or older were asked about their ability to recognize nicotine products with and without the visual aid of packaging, as well as their perceptions about the health effects of these products.

Ohio State’s recent survey showed that 70% of adults believe nicotine pouches are harmful to health and lead to addiction, but just 25% say they could identify a nicotine pouch out of its container or packaging. The survey also found that those between the ages of 18-29 are more likely to know someone who uses nicotine pouches, as opposed to older adults.

This study was conducted on behalf of the OSUCCC – James by SSRS on its Opinion Panel Omnibus platform. The SSRS Opinion Panel Omnibus is a national, twice-per-month, probability-based survey. Data collection was conducted from July 19-22, 2024, among a sample of 1,008 respondents. The survey was conducted via web (n=976) and telephone (n=32) and administered in English. The margin of error for total respondents is +/- 3.5 percentage points at the 95% confidence level. All SSRS Opinion Panel Omnibus data are weighted to represent the target population of U.S. adults ages 18 or older. 

To learn more about research at the Center for Tobacco Research, visit cancer.osu.edu/CTR. For resources on nicotine use and cessation in youth, visit tobaccofreekids.org. Adult smoking cessation support is available at The Ohio State University Wexner Medical Center. To schedule an appointment, call 614-293-QUIT (7848) or visit medcenter.osu.edu

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at the Center for Tobacco Research at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute are concerned that the fruity flavors and discreet design of nicotine pouches are a gateway to addiction for Gen Z.

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The Ohio State University Comprehensive Cancer Center



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Monday, September 02, 2024

Fermented lingonberry juice shown to reduce inflammation and support gut health in IBD

AVAILABLE AT IKEA

By targeting both the mouth and gut, fermented lingonberry juice harnesses potent bioactive compounds to curb microbial dysbiosis and protect against inflammation, offering a promising natural solution for managing IBD.



Image Credit: Mila_22 79 / Shutterstock


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Sep 2 2024


In a recent study published in the journal Nutrients, scientists in Finland and Sweden discussed the anti-inflammatory, anti-proteolytic, antimicrobial, and prebiotic properties of fermented lingonberry juice and its potential benefits in alleviating inflammatory bowel disease (IBD).

Background

The role of the gut microbiome in human health has been widely explored in recent years, and the link between the oral and gut microbiomes and their impact on gastrointestinal inflammation has been of significant interest. The study highlights that oral microbes can influence gut health, exacerbating conditions like IBD through the transmission of oral pathogens to the gut. The gut microbiome is involved in numerous metabolic processes in the host, including modulating the immune responses and influencing the permeability of the intestinal mucosa.

Dysbiosis in the gut microbiome can influence the integrity of the extracellular matrix in the mucosal epithelia and degrade proteins such as cadherin, collagen, laminin, claudin, and occludin in the basement and junctional membranes. A combination of loss of integrity in the mucosal barrier and the innate immune responses triggered by the microbiome can result in various metabolic and autoimmune disorders and increase the risk of cancer.

Gut microbiome dysbiosis has been linked to a wide range of diseases, including arthritis, asthma, diabetes, obesity, cardiovascular disease, IBD, and even mental health disorders. Studies have proposed the use of prebiotics and probiotics for the management of obesity and inflammatory bowel disease.

Inflammatory bowel disease

The excessive inflammation of the mucosal layer in the intestines characterizes inflammatory bowel disease. While the underlying causes are not known, alleles for specific genes, such as those coding for major histocompatibility complex (MHC), are known to increase the susceptibility to the disease.

Other factors such as smoking, drugs, diet, pathogens, and changes in the gut microbiome are believed to trigger IBD. Crohn’s disease and ulcerative colitis are the two major forms of IBD. Ulcerative colitis impacts only the lower intestines, while lesions in the entire gastrointestinal tract characterize Crohn’s disease. External symptoms of IBD include weight loss, diarrhea, and malnutrition.

Both classes of IBD also manifest in oral symptoms, with aphthous stomatitis or canker sores and pyostomatitis vegetans, or pustules in the oral mucosa appearing in cases of ulcerative colitis. The oral symptoms of Crohn’s disease include mucogingivitis, bumps at the back of the throat, and tag-like lesions. A wide range of non-specific symptoms common to both forms also include dry mouth, halitosis, gingivitis, submandibular lymphadenopathy, periodontitis, and decreased saliva production. The study emphasizes that oral manifestations may precede gastrointestinal symptoms, and oral health is crucial for managing overall IBD symptoms.

Probiotics are recommended for symptom alleviation in IBD based on their ability to lower oxidative stress, strengthen the intestinal barrier, lower pathogenic load, and increase the abundance and diversity of beneficial bacteria. Probiotics can also lower the levels of pro-inflammatory cytokines and increase the levels of anti-inflammatory immune responses.

Lingonberries

Vaccinium vitis-idaeaor lingonberries, grows wild in the northern hemisphere. Numerous in vivo and in vitro studies have reported that the fractions isolated from lingonberries have anti-inflammatory, antioxidant, antimicrobial, anti-proteolytic, and anti-cancer properties.

The study identifies specific bioactive compounds in lingonberries, including flavonoids, phenolic acids, and stilbenes, such as resveratrol, which are noted for their antimicrobial and anti-inflammatory effects.

Studies using murine models of obesity have shown that these phenolic compounds can alter metabolic and inflammatory states by impacting the gut microbiome. Lingonberry juice has also been found to lower the ratio of Firmicute to Bacteroidetes in mice, which has proven beneficial in preventing excess weight gain.

Fermented lingonberry juice is also known to inhibit the growth of opportunistic pathogens such as Streptococcus mutansFusobacterium nucleatusCandida, and Porphyromonas gingivalis in the oral cavity. A natural mouth rinse based on fermented lingonberry juice has been developed, and its clinical trials show multiple benefits for oral health, including reduced periodontal inflammation and increased growth of probiotic lactobacilli.

Fermentation also enzymatically breaks down large molecules into small ones, increasing the bioavailability of phenolic compounds and improving their absorption. Fermented lingonberry juice has been found to lower the levels of proteolytic inflammation in the oral cavity and selectively inhibit the growth of pathogens while promoting the growth of beneficial bacteria.

Furthermore, studies examining the efficacy of the fermented lingonberry juice oral rinse reported improvements in oral health, reduced periodontal inflammation, lower gum bleeding and oral plaque formation, and a decrease in the proteolytic and opportunistic microbial load in the oral cavity. The study suggests that these benefits may extend to the gut if the juice is swallowed, potentially aiding in the management of IBD.

Conclusions

To summarize, the researchers discussed the link between the oral microbiome and the risk of chronic inflammatory and metabolic disorders through gut microbiome dysbiosis. They propose that oral health interventions, including the use of fermented lingonberry juice, could indirectly benefit gut health by modulating the oral microbiome.

Additionally, the study examined the involvement of the oral microbiome in IBD and presented the potential benefits of lingonberry and fermented lingonberry juice in modulating the oral and gut microbiomes to promote the growth of beneficial bacteria and lower inflammation.

The researchers recommend further research and human clinical trials to examine the beneficial effects of lingonberry in lowering gastrointestinal inflammation and alleviating the symptoms of IBD.

Journal reference:
  • Pärnänen, P., Räisänen, Ismo T & Sorsa, T. (2024) Oral Anti-Inflammatory and Symbiotic Effects of Fermented Lingonberry Juice — Potential Benefits in IBD. Nutrients 16. DOI:10.3390/nu16172896, https://www.mdpi.com/2072-6643/16/17/2896


Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

 Research finds particulate pollution during pregnancy may impact newborn kidney function

In a recent cohort study published in the journal eBioMedicineresearchers investigated the potential effect of gestational exposure to particulate air pollution on cord blood cystatin C levels, a marker for kidney function.

They found that increased exposure to black carbon and fine particulate matter during pregnancy, particularly in the third trimester, was associated with higher cord blood cystatin C levels, suggesting potential negative effects on newborn kidney function.

Study: Newborn glomerular function and gestational particulate air pollution. Image Credit: Deemerwha studio/Shutterstock.com

Background

Researchers have previously hypothesized that a lower number of nephrons at birth increases the risk of hypertension, and early environmental exposures can have a long-term impact on health. Optimal kidney function is critical for maintaining body homeostasis.

However, assessing kidney function in neonates is challenging. Cystatin C, a protein produced by nucleated cells and filtered by the kidneys, has emerged as a valuable marker for glomerular filtration in newborns, as it is not influenced by muscle mass or inflammation.

Ambient air pollution, especially particulate matter of diameter <2.5 micrometers (PM2.5) and black carbon (BC), is a significant contributor to global disease, linked to cardiovascular, respiratory, and kidney issues. PM2.5 is known to cause cardiovascular problems, which are closely related to kidney health.

Maternal exposure to PM2.5 is shown to be associated with higher blood pressure and lower birth weight in newborns, potentially affecting kidney development.

While studies have shown that air pollution increases cystatin C levels and decreases glomerular filtration in adults, there is a lack of research on its effects on cystatin C levels in newborns, highlighting a gap in understanding the early-life impact of pollution on kidney function.

Therefore, researchers in the present study investigated whether cystatin C levels are altered in the cord blood plasma of neonates owing to exposure to ambient air pollution, specifically BC and PM2.5.

About the study

In the present study, medical and lifestyle data of 1,484 healthy mother-newborn pairs with singleton pregnancies between 2010 and 2020 were obtained from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort in Belgium.

Pairs lacking cord blood samples or missing data were excluded. Exposure to air pollution in the form of BC and PM2.5 was estimated using a model that integrated satellite land cover data and pollution data from monitoring stations.

Daily exposure values were averaged for the entire pregnancy and across trimesters. Cord blood samples were collected within 10 minutes of delivery, stored, and analyzed.

Cystatin C levels were measured in the samples using an accredited immune turbidimetry assay, where cystatin C binds to antibody-coated latex particles for quantification, providing insights into kidney function in newborns.

Statistical analysis involved the use of multiple linear regression analyses, distributed lag models, logistic regression analyses, and sensitivity analyses adjusting for various covariates, including age, education, smoking habits, alcohol consumption throughout pregnancy, and ethnicity.

Results and discussion

The average birth weight of newborns was 3,417.52 g, with 49.6% being girls, and the average gestational age was 39.2 weeks. Cord blood cystatin C levels averaged 2.16 mg/L. Mean exposure to BC and PM2.5 during pregnancy was found to be 1.18 μg/m³ and 12.65 μg/m³, respectively, remaining relatively constant across trimesters.

Significant associations were found between BC exposure during the entire pregnancy and elevated cord blood cystatin C levels, with a 0.5 μg/m³ increase correlating with a 0.04 mg/L rise (p<0.01). For PM2.5, a 5 μg/m³ increase was found to be associated with a 0.07 mg/L increase in cystatin C (p<0.01).

The first trimester showed associations with BC but not with PM2.5. Sensitivity analyses indicated that adjusting for additional covariates did not significantly alter effect estimates. Notably, the third trimester (beyond week 27) was identified as the most significant exposure window.

Higher exposures to PM2.5 and BC during the entire pregnancy and specifically in the third trimester increased the risk of higher cord blood cystatin C levels, with a 0.5 μg/m³ increase in BC linked to a 37% higher risk and a 5 μg/m³ increase in PM2.5 associated with an 80% higher risk.

The study is strengthened by its large, representative sample of well-characterized newborns and mothers with a prospective follow-up and high-resolution spatial air pollution model for fetal exposure estimation. However, the study lacks the use of additional markers to assess kidney function, such as creatinine.

Conclusion

In conclusion, the study shows that exposure to PM2.5 and BC during pregnancy, especially beyond week 27, is significantly linked to elevated cord blood cystatin C levels in newborns. This indicates the negative impact of particulate air pollution on kidney function since birth.

Therefore, monitoring early life exposure to particulate air pollution may be crucial for improving kidney health later in life. These findings warrant further research and aim to inform public health policy for improved outcomes in newborns.

Journal reference:


Dr. Sushama R. Chaphalkar

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.  

Science is rewriting the history of horse domestication

As they spread, horses reshaped ecology, social structures and economies at a never-before-seen scale.



Perspective by William Taylor
September 1, 2024 
THE CONVERSATION

Across human history, no animal has had a deeper impact on human societies than the horse. But when and how people domesticated horses have posed an ongoing scientific mystery.

Half a million years ago or more, early human ancestors hunted horses with wooden spears, the very first weapons, and used their bones for early tools. During the late Paleolithic era, as far back as 30,000 years ago or more, ancient artists chose wild horses as their muse: Horses are the most commonly depicted animal in Eurasian cave art.

Following their first domestication, horses became the foundation of herding life in the grasslands of Inner Asia, and key leaps forward in technology such as the chariot, saddle and stirrup helped make horses the primary means of locomotion for travel, communication, agriculture and warfare across much of the ancient world. With the aid of ocean voyages, these animals eventually reached the shores of every major landmass — even Antarctica, briefly.

Archaeologists William Taylor (left), and Aidan Marler (right) investigate an ancient horse jaw bone in western Mongolia. (Yancen Diemberger)

As they spread, horses reshaped ecology, social structures and economies at a never-before-seen scale. Ultimately, only industrial mechanization supplanted their near-universal role in society.

Because of their tremendous impact in shaping our collective human story, figuring out when, why and how horses became domesticated is a key step toward understanding the world we live in now.

Doing so has proved to be surprisingly challenging. In my new book, “Hoof Beats: How Horses Shaped Human History,” I draw together new archaeological evidence that is revising what scientists like me thought we knew about this story.

A domestication hypothesis

Over the years, almost every time and place on Earth has been suggested as a possible origin point for horse domestication, from Europe tens of thousands of years ago to places such as Saudi Arabia, Anatolia, China or even the Americas.

By far the most dominant model for horse domestication, though, has been the Indo-European hypothesis, also known as the “Kurgan hypothesis.” It argues that, sometime in the fourth millennium B.C. or before, residents of the steppes of western Asia and the Black Sea known as the Yamnaya, who built large burial mounds called kurgans, hopped astride horses. The newfound mobility of these early riders, the story goes, helped catalyze huge migrations across the continent, distributing ancestral Indo-European languages and cultures across Eurasia.

But what’s the actual evidence supporting the Kurgan hypothesis for the first horse domestication? Many of the most important clues come from the bones and teeth of ancient animals, via a discipline known as archaeozoology. Over the past 20 years, archaeozoological data seemed to converge on the idea that horses were first domesticated in sites of the Botai culture in Kazakhstan, where scientists found large quantities of horse bones at sites dating to the fourth millennium B.C.

Other kinds of circumstantial evidence had already started to pile up. Archaeologists discovered evidence of what looked like fence post holes that could have been part of ancient corrals. They also found ceramic fragments with fatty horse residues that, based on isotope measurements, seem to have been deposited in the summer months, a time when milk could be collected from domestic horses.

The scientific smoking gun for early horse domestication, though, was a set of changes found on some Botai horse teeth and jawbones. Like the teeth of many modern and ancient ridden horses, the Botai horse teeth appeared to have been worn down by a bridle mouthpiece, or bit.

Together, the data pointed strongly to the idea of horse domestication in northern Kazakhstan around 3500 B.C. — not quite the Yamnaya homeland, but close enough geographically to keep the basic Kurgan hypothesis intact.

There were some aspects of the Botai story, though, that never quite lined up.

From the outset, several studies showed that the mix of horse remains found at Botai was unlike that found in most later pastoral cultures: Botai is evenly split between male and female horses, mostly of a healthy reproductive age. Killing off healthy, breeding-age animals like this on a regular basis would devastate a breeding herd. But this demographic blend is common among animals that have been hunted. Some Botai horses even have projectile points embedded in their ribs, showing they died through hunting rather than a controlled slaughter.

These unresolved loose ends loomed over a basic consensus linking the Botai culture to horse domestication.

New tools, new questions

In recent years, as archaeological and scientific tools have rapidly improved, key assumptions about the cultures of Botai, Yamnaya and the early chapters of the human-horse story have been overturned.

In 2018, nuclear genomic sequencing revealed that Botai horses were not the ancestors of domestic horses but of Przewalski’s horse, a wild relative and denizen of the steppe that has never been domesticated, at least not in recorded history.

Next, when my colleagues and I reconsidered skeletal features linked to horse riding at Botai, we saw that similar issues are also visible in ice age wild horses from North America, which had certainly never been ridden. Even though horse riding can cause recognizable changes to the teeth and bones of the jaw, we argued that the small issues seen on Botai horses can reasonably be linked to natural variation or life history

This finding reopened the question: Was there horse transport at Botai at all?

Leaving the Kurgan hypothesis in the past

Over the past few years, trying to make sense of the archaeological record around horse domestication has become an ever more contradictory affair.

For example, in 2023, archaeologists noted that human hip and leg skeletal problems found in Yamnaya and early Eastern European burials looked like problems found in mounted riders, consistent with the Kurgan hypothesis. But such problems can also be caused by other kinds of animal transport, including the cattle carts found in Yamnaya-era sites.

So how should archaeologists make sense of these conflicting signals?


A clearer picture may be closer than we think. A detailed genomic study of early Eurasian horses, published in June in the journal Nature, shows that Yamnaya horses were not ancestors of the first clearly domestic horses, known as the DOM2 lineage. And Yamnaya horses showed no genetic evidence of close control over reproduction, such as changes linked with inbreeding.

Instead, the first DOM2 horses appear just before 2000 B.C., long after the Yamnaya migrations and just before the first burials of horses and chariots also show up in the archaeological record.

For now, all lines of evidence seem to converge on the idea that horse domestication probably took place in the Black Sea steppes, but much later than the Kurgan hypothesis requires. Instead, human control of horses took off just before the explosive spread of horses and chariots across Eurasia during the early second millennium B.C.

There’s still more to be settled, of course. In the latest study, the authors point to funny patterns in the Botai data, especially fluctuations in genetic estimates for generation time — essentially, how long it takes on average for a population of animals to produce offspring. Might these suggest that Botai people still raised those wild Przewalski’s horses in captivity, but only for meat, without a role in transportation? Perhaps. Future research will let us know for sure.

Either way, out of these conflicting signals, one consideration has become clear: The earliest chapters of the human-horse story are ready for a retelling.

The writer is an assistant professor and curator of archaeology at the University of Colorado at Boulder. This article was produced in collaboration with theconversation.com.


Sunday, September 01, 2024



‘He was in mystic delirium’: was this hermit mathematician a forgotten genius whose ideas could transform AI – or a lonely madman?

Phil Hoad
Sat 31 August 2024 

Alexander Grothendieck photographed at his home in Lassarre, France, in 2013.
Photograph: Peter Badge


LONG READ


One day in September 2014, in a hamlet in the French Pyrenean foothills, Jean-Claude, a landscape gardener in his late 50s, was surprised to see his neighbour at the gate. He hadn’t spoken to the 86-year-old in nearly 15 years after a dispute over a climbing rose that Jean-Claude had wanted to prune. The old man lived in total seclusion, tending to his garden in the djellaba he always wore, writing by night, heeding no one. Now, the long-bearded seeker looked troubled.

“Would you do me a favour?” he asked Jean-Claude.

“If I can.”

“Could you buy me a revolver?”

Jean-Claude refused. Then, after watching the hermit – who was deaf and nearly blind – totter erratically about his garden, he telephoned the man’s children. Even they hadn’t spoken to their father in close to 25 years. When they arrived in the village of Lasserre, the recluse repeated his request for a revolver, so he could shoot himself. There was barely room to move in his dilapidated house. The corridors were lined with shelves heaving with flasks of mouldering liquids. Overgrown plants spilled out of pots everywhere. Thousands of pages of arcane scrawling were lined up in canvas boxes in his library. But his infirmity had put paid to his studies, and he no longer saw any purpose in life. On 13 November, he died exhausted and alone in hospital in the neighbouring town of St-Lizier.

The hermit’s name was Alexander Grothendieck. Born in 1928, he arrived in France from Germany as a refugee in 1939, and went on to revolutionise postwar mathematics as Einstein had physics a generation earlier. Moving beyond distinct disciplines such as geometry, algebra and topology, he worked in pursuit of a deeper, universal language to unify them all. At the heart of his work was a new conception of space, liberating it from the Euclidean tyranny of fixed points and bringing it into the 20th-century universe of relativity and probability. The flood of concepts and tools he introduced in the 1950s and 60s awed his peers.

Then, in 1970, in what he later called his “great turning point”, Grothendieck quit. Resigning from France’s elite Institut des Hautes Études Scientifiques (IHES) – in protest at funding it received from the ministry of defence – put an end to his high-level mathematics career. He occupied a few minor teaching posts until 1991, when he left his home underneath Provence’s Mont Ventoux and disappeared. No one – friends, family, colleagues, the intimates who knew him as “Shurik” (his childhood nickname, the Russian diminutive for Alexander) – knew where he was.

Grothendieck’s capacity for abstract thought is legendary: he rarely made use of specific equations to grasp at mathematical truths, instead intuiting the broader conceptual structure around them to make them surrender their solutions all at once. He compared the two approaches to using a hammer to crack a walnut, versus soaking it patiently in water until it opens naturally. “He was above all a thinker and a writer, who decided to apply his genius mostly to mathematics,” says Olivia Caramello, a 39-year-old Italian mathematician who is the leading proponent of his work today. “His approach to mathematics was that of a philosopher, in the sense that the way in which one would prove results was more important to him than the results themselves.”

In Lasserre, he lived in near-complete solitude, with no television, radio, phone or internet. A handful of acolytes trekked up to the village once his whereabouts filtered out; he politely refused to receive most of them. When he did exchange words, he sometimes mentioned his true friends: the plants. Wood, he believed, was conscious. He told Michel Camilleri, a local bookbinder who helped compile his writings, that his kitchen table “knows more about you, your past, your present and your future than you will ever know”. But these wild preoccupations took him to dark places: he told one visitor that there were entities inside his house that might harm him.

Grothendieck’s genius defied his attempts at erasing his own renown. He lurks in the background of one of Cormac McCarthy’s final novels, Stella Maris, as an eminence grise who leads on its psychically disturbed mathematician protagonist. The long-awaited publication in 2022 of Grothendieck’s exhaustive memoir, Harvests and Sowings, renewed interest in his work. And there is growing academic and corporate attention to how Grothendieckian concepts could be practically applied for technological ends. Chinese telecoms giant Huawei believes his esoteric concept of the topos could be key to building the next generation of AI, and has hired Fields medal-winner Laurent Lafforgue to explore this subject. But Grothendieck’s motivations were not worldly ones, as his former colleague Pierre Cartier understood. “Even in his mathematical milieu, he wasn’t quite a member of the family,” writes Cartier. “He pursued a kind of monologue, or rather a dialogue with mathematics and God, which to him were one and the same.”

Beyond his mathematics was the unknown. Were his final writings, an avalanche of 70,000 pages in an often near-illegible hand, the aimless scribblings of a madman? Or had the anchorite of Lasserre made one last thrust into the secret architecture of the universe? And what would this outsider – who had spurned the scientific establishment and modern society – make of the idea of tech titans sizing up his intellectual property for exploitation?

* * *

In a famous passage from Harvests and Sowings, Grothendieck writes that most mathematicians work within a preconceived framework: “They are like the inheritors of a large and beautiful house all ready-built, with its living rooms and kitchens and workshops, and its kitchen utensils and tools for all and sundry, with which there is indeed everything to cook and tinker.” But he is part of a rarer breed: the builders, “whose instinctive vocation and joy is to construct new houses”.

Now his son, Matthieu Grothendieck, is working out what to do with his father’s home. Lasserre lies on the top of a hill 22 miles (35km) north of the Spanish border, in the remote Ariège département, a haven for marginals, drifters and utopians. I first walk up there one piercingly cold January morning in 2023, mists cloaking forests of oak and beech, red kites surveying the fields in between. Grothendieck’s home – the only two-storey house in Lasserre – is at the village’s southern extremity. Hanging above the road beyond are the snow-covered Pyrenees: a promise of a higher reality.

Matthieu answers the door wearing a dressing gown, with the sheepish air of a man emerging from hibernation. The 57-year-old has deeply creased features and a strong prow of a nose. Inheriting the house where his father experienced such mental ordeals weighs on him. “This place has a history that’s bigger than me,” he says, his voice softened by smoking. “And as I haven’t got the means to knock it into shape, I feel bad about that. I feel as if I’m still living in my father’s house.”

A former ceramicist, he is now a part-time musician. In the kitchen, a long, framed scroll of Chinese script stands on a sideboard, next to one photograph of a Buddha sculpture and two of his mother, Mireille Dufour, whom Grothendieck left in 1970. (Matthieu is her youngest child; he has a sister, Johanna, and brother, Alexandre. Grothendieck also had two other sons, Serge and John, with two other women.) Above Matthieu’s bed is a garish portrait of his paternal grandfather, Alexander Schapiro, a Ukrainian Jewish anarchist who lost an arm escaping a tsarist prison, and later fought in the Spanish civil war.

Even with all his wisdom and the depth of his insight, there was always a sense of excessiveness about my father. He always had to put himself in danger

Schapiro and his partner, the German writer Johanna Grothendieck, left the five-year-old Grothendieck in foster care in Hamburg when they fled Nazi Germany in 1933 to fight for the socialist cause in Europe. He was reunited with his mother in 1939, and lived the remainder of the war in a French internment camp or in hiding. But his Jewish father, interned separately, was sent to Auschwitz and murdered on arrival in 1942. It was this legacy of abandonment, poverty and violence that drove the mathematician and finally overwhelmed him, Matthieu suggests: “Artists and geniuses are making up for flaws and traumas. The wound that made Shurik a genius caught up with him at the end of his life.”

Matthieu leads me into the huge, broken-down barn behind the house. Heaped on the bare-earth floor is a mound of glass flasks encased in wicker baskets: inside them are what remains of the mathematician’s plant infusions, requiring thousands of litres of alcohol. Far removed from conventional mathematics, Grothendieck’s final studies were fixated on the problem of why evil exists in the world. His last recorded writing was a notebook logging the names of the deportees in his father’s convoy in August 1942. Matthieu believes his father’s plant distillations were linked with this attempt to explain the workings of evil: a form of alchemy through which he was attempting to isolate different species’ properties of resilience to adversity and aggression. “It’s hard to understand,” says Matthieu. “All I know is that they weren’t for drinking.”

Later, Matthieu agrees to let me look at his father’s Lasserre writings – a cache of esoterica scanned on to hard disk by his daughter. At the start of 2023, the family were still negotiating their entry into the French national library; the writings have now been accepted and at some point will be publicly available for research. Serious scholarship is needed to decide their worth on mathematical, philosophical and literary levels. I’m definitely not qualified on the first count.

I open a first page at random. The writing is spidery; there are occasional multicoloured topological diagrams, namechecks of past thinkers, often physicists – Maxwell, Planck, Einstein – and recurrent references to Satan and “this cursed world”. His children are struggling to fathom this prodigious output, too. “It’s mystic but also down to earth. He talks about life with a form of moralism. It’s completely out of fashion,” says Matthieu. “But in my opinion there are pearls in there. He was the king of formulating things.”

After a couple of hours’ reading, head spinning, I feel the abyss staring into me. So imagine what it was like for Grothendieck. According to Matthieu, a friend once asked his father what his greatest desire was. The mathematician replied: “That this infernal circle of thought finally ceases.”

* * *

The colossal folds of Mont Ventoux’s southern flank are mottled with April cloud shadow as cyclists skirt the mountain. In the Vaucluse département of Provence, this is the terrain where Alexander Grothendieck took his first steps into mysticism. Now, another of his sons, Alexandre, lives in the area. I wander up a bumpy track to see the 62-year-old ambling out of oak woods, smiling, to meet me. Wearing a moth-eaten jumper, dark slacks and slippers, Alexandre is slighter than his brother, with wind-chafed cheeks.

He leads me into the giant hangar where he lives. It is piled with amps and instruments; at the back is a workshop where he makes kalimbas, a kind of African thumb piano. In 1980, his father moved a few kilometres to the west, to a house outside the village of Mormoiron. In the subsequent years, Grothendieck’s thoughts turned inwards towards bewildering spiritual vistas. “Even with all his wisdom and the depth of his insight, there was always a sense of excessiveness about my father,” says Alexandre. “He always had to put himself in danger. He searched for it.”

Grothendieck had abandoned the commune he had been part of since 1973 in a village north of Montpellier, where he still taught at the university. From 1970 onwards, he had been one of France’s first radical ecologists and became increasingly preoccupied with meditation. In 1979, he spent a year dwelling intensely on his parents’ letters, a reflection that stripped away any lingering romanticism about them. “The myth of their great love fell flat for Shurik – it was a pure illusion,” says Johanna Grothendieck, who bears her grandmother’s name. “And he was able to decrypt all the traumatic elements of his childhood. He realised he had been quite simply abandoned by his own mother.”

This preoccupation with the past intensified into the mid-1980s, as Grothendieck worked on the manuscript for Harvests and Sowings. A reflection on his mathematical career, it was filled with stunning aphoristic insights, like the house metaphor. But, choked with David Foster Wallace-like footnotes, it was relentless and overwhelming, too – and steeped in a sense of betrayal by his former colleagues. In the wake of his revelations about his parents, this feeling became a kind of governing principle. “It was a systematic thing with our papa – to put someone on a pedestal, in order to see their flaws. Then – bam! – they went down in flames,” says Alexandre.

Although he still produced some mathematical work during this period, Grothendieck delved further into mysticism. He looked to his dreams as a conduit to the divine; he believed they were not products of his own psyche, but messages sent to him by an entity he called the Dreamer. This being was synonymous with God; as he conceived it, a kind of cosmic mother. “Like a maternal breast, the ‘grand dream’ offers us a thick and savorous milk, good to nourish and invigorate the soul,” he later wrote in The Key of Dreams, a treatise on the subject. Pierre Deligne, the brilliant pupil he accused in Harvests and Sowings of betraying him, felt his old master had lost his way. “This was not the Grothendieck I admired,” he says, on the phone from Princeton’s Institute for Advanced Study.

He became totally isolated. He was no longer in contact with nature. He had cut ties with everyone

By summer 1989, the prophetic dreams had intensified into daily audiences, “absorbing almost all of my time and energy”, with an angel Grothendieck called either Flora or Lucifera, depending on whether she manifested as benevolent or tormenting. She tutored him in a new cosmology, central to which was the question of suffering and evil in God’s greater scheme. He believed, for example, that the speed of light being close to, but not precisely, 300,000km a second, was evidence of Satan’s interference. “He was in a form of mystic delirium,” says another former pupil, Jean Malgoire, now a professor at Montpellier University. “Which is also a form of mental illness. It would have been good if he could have been seen by a psychiatrist at that point.”

In real life, he had become forbidding and remote. Matthieu spent two months in Mormoiron working on the house; during that time, his father invited him in only once. His son blew his top: “He’d lost interest in others. I could no longer feel any authentic or sincere empathy.” But Grothendieck was still interested in people’s souls. On 26 January 1990, he sent 250 of his acquaintances – including his children – a messianic, seven-page typed epistle, entitled Letter of the Good News. He announced a date – 14 October 1996 – for the “Day of Liberation” when evil on Earth would cease, and said they had been chosen to help usher in the new era. It was “a kind of remake of the most limited aspects of Christianity”, says Johanna.

Then in June 1990, as if to firm up his spiritual commitment, Grothendieck fasted for 45 days (he wanted to beat Christ’s 40), cooling himself in the heat of summer in a wine barrel filled with water. As he watched his father shrivel to an emaciated frame reminiscent of the Nazi concentration camp prisoners, Alexandre realised he may have been emulating someone else: “In some way, he was rejoining his father.”

Grothendieck almost died. He only relented when persuaded to resume eating by Johanna’s partner. She believes the fast damaged her father’s brain on a cellular level in a way impossible for a 62-year-old to recover from, further loosening his grip on rationality. Shortly afterwards, he summoned Malgoire to Mormoiron to collect 28,000 pages of mathematical writings (now available online). He showed his student an oil drum full of ashes: the remains of a huge raft of personal papers, including his parents’ letters, he had burned. The past was immaterial, and now Grothendieck could only look ahead. One year later, without warning, he moved away from his house on a trajectory known only to him.

* * *

A circular slab of black pitted sandstone, fashioned by Johanna and now smothered in wild roses, marks Grothendieck’s resting place in Lasserre churchyard. It’s almost hidden behind a telegraph post. The mathematician was alone when he died in hospital; after several weeks in their company, he had spurned his children again, only accepting care from intermediaries.

The presence of his family seemed to stir up unbearable feelings. In his writings, he evaluates the people in his life for how much they are under the sway of Satan. But, as Alexandre points out, this was also a projection of his own seething unconscious: “He didn’t like what he saw in the mirror we held out to him.”

They only discovered his whereabouts in Lasserre by accident: one day in the late 90s Alexandre signed up for car insurance, and the company said they already had an address for an Alexander Grothendieck on file. Deciding to make contact, Alexandre spotted his father across the marketplace in the town of St-Girons, south of Lasserre. “Suddenly, he sees me,” says Alexandre. “He’s got a big smile, he’s super-happy. So I said to him: ‘Let me take your basket.’ And all of a sudden, he has a thought that he shouldn’t have anything to do with me, and his smile turns the other way. It lasted a minute and a half. A total cold shower.” He didn’t see his father again until the year he died.

At least until the early 00s, Grothendieck worked at a ferocious pace, often writing up the day’s “meditation” at the kitchen table in the dead of night. “He became totally isolated. He was no longer in contact with nature. He had cut ties with everyone,” says Johanna.

He vacillated about the date of the Day of Liberation, when evil on Earth would cease. Recalculating it as late August or early September 1996 instead of the original October date, he was crestfallen at the lack of celestial trumpets. Mathematicians Leila Schneps and Pierre Lochak, who had tracked him down a year earlier, visited him the day afterwards. “We delicately said: ‘Perhaps it’s started and people’s hearts are opening.’ But obviously he believed what we believed, which was that nothing had happened,” Schneps says.

Experiencing an “uncontrollable antipathy” to his work, that he attributed to malign forces but sounds a lot like depression, he wrote in early 1997: “The most abominable thing in the fate of victims is that Satan is master of their thoughts and feelings.” He contemplated suicide for several days, but resolved to continue living as a self-declared victim.

The house was weighing on him. In 2000, he offered it to his bookbinder, Michel Camilleri, for free, deeming him the perfect candidate because he was “good with materials”. The sole condition was that Camilleri look after his plant friends. When Camilleri refused, he was outraged – seeing the hand of Satan once more. A year later, the building was nearly destroyed when his unswept stove chimney caught fire. Some witnesses say Grothendieck tried to prevent the firefighters from accessing his property (Matthieu doesn’t believe this).

The curate at Lasserre church, David Naït Saadi, wrote Grothendieck a letter in around 2005, attempting to bring the hermit into the community. But Grothendieck fired back a missive full of biblical references, saying Saadi had a “viper’s tongue” and that he should nail his reply to the church noticeboard.

By the mid-00s, his writing was petering out. The endpoint of his late meditations, according to Matthieu, is a chronicle in which his father painstakingly records everything he is doing, as if the minutiae of his own life are imbued with immanence. Matthieu finds these writings so painful to read that he kept them back from the national library donation. Grothendieck was lost in the rooms and corridors of his own mind.

* * *

In mid-April, dapper Parisians are filing out of the polished foyer of a redeveloped hotel in the seventh arrondissement, heading for lunch. The first French TV programmes were broadcast from the building; now, Huawei is pushing for a similar leap in AI here. It has set up the Centre-Lagrange, an advanced mathematics research institute, on the site and hired elite French mathematicians, including Laurent Lafforgue, to work there. An aura of secrecy surrounds their work in this ultra-competitive field, compounded by growing suspicion in the west of Chinese tech. Huawei initially refuse to answer any questions, before permitting some answers to be emailed.

Grothendieck’s notion of the toposdeveloped by him in the 1960s, is of particular interest to Huawei. Of his fully realised concepts, toposes were his furthest step in his quest to identify the deeper algebraic values at the heart of mathematical space, and in doing so generate a geometry without fixed points. He described toposes as a “vast and calm river” from which fundamental mathematical truths could be sifted. Olivia Caramello views them rather as “bridges” capable of facilitating the transfer of information between different domains. Now, Lafforgue confirms via email, Huawei is exploring the application of toposes in a number of domains, including telecoms and AI.

Caramello describes toposes as a mathematical incarnation of the idea of vision; an integration of all the possible points of view on a given mathematical situation that reveals its most essential features. Applied to AI, toposes could allow computers to move beyond the data associated with, say, an apple; the geometric coordinates of how it appears in images, for example, or tagging metadata. Then AI could begin to identify objects more like we do – through a deeper “semantic” understanding of what an apple is. But practical application to create the next generation of “thinking” AI is, according to Lafforgue, some way off.

A larger question is whether this is what Grothendieck would have wanted. In 1972, during his ecologist phase, concerned that capitalist society was driving humanity towards ruin, he gave a talk at Cern, near Geneva, entitled Can We Continue Scientific Research? He didn’t know about AI – but he was already opposed to this collusion between science and corporate industry. Considering his pacifist values, he would probably also have been opposed to Huawei’s championing of his work; its chief executive, Ren Zhengfei, is a former member of the People’s Liberation Army engineering corps. The US department of defense, as well as some independent researchers, believes Huawei is controlled by the Chinese military.

Huawei insists it is a private company, owned by its employees and its founding chairman, Ren Zhengfei, and that it is “not owned, controlled or affiliated to any government or third-party company”.

We are at the very beginning of a huge exploration of these manuscripts. And certainly there will be marvels in them

Lafforgue points out that France’s IHES, where Grothendieck and later he worked, was funded by industrial companies – and thinks Huawei’s interest is legitimate. Caramello, who is the founder and president of the Grothendieck Institute research organisation, believes that he would have wanted a systematic exploration of his concepts to bring them to fruition. “Topos theory is itself a kind of machine that can extend our imagination,” she says. “So you see Grothendieck was not against the use of machines. He was against blind machines, or brute force.” What is unsettling is a degree of opaqueness about Huawei’s aims regarding AI and its collaborations, including its relationship with the Grothendieck Institute, where Lafforgue sits on the scientific council. But Caramello stresses that it is an entirely independent body that engages in theoretical, not applied research, and that makes its findings available to all. She says it does not research AI and that Lafforgue’s involvement pertains solely to his expertise in Grothendieckian maths.

Matthieu Grothendieck is clear about whether his father would have consented to Huawei, or any other corporation, exploiting his work: “No. I don’t even ask. I know.” There is little doubt that the mathematician believed modern science had become morally stunted, and the Lasserre papers attempted to reconcile it with metaphysics and moral philosophy. Compared with Grothendieck’s delirious 1980s mysticism, there is structure and intent here. They begin with just under 5,000 pages devoted to the Schematic Elemental Geometry and Structure of the Psyche. According to the mathematician Georges Maltsiniotis, who has examined this portion, these sections contain maths in “due and proper form”. Then Grothendieck gets going on the Problem of Evil, which sprawls over 14,000 pages undertaken during much of the 1990s.

Judging by the 200 or so pages I attempt to decipher, Grothendieck put herculean effort into his new cosmology. He seems to be trying to fathom the workings of evil at the level of matter and energy. He squabbles with Einstein, James Clerk Maxwell and Darwin, especially about the role of chance in what he viewed as a divinely created universe. There are numerological musings about the significance of the lunar and solar cycles, the nine-month term of a pregnancy. He renames the months in a new calendar: January becomes Roma, August becomes Songha.

How much of this work is meaningful and how much empty mania? For Pierre Deligne, Grothendieck became fatally unmoored in his solitude. He says that he has little interest in reading the Lasserre writings “because he had little contact with other mathematicians. He was restricted to his own ideas, rather than using those of others too.” But it’s not so clear-cut for others, including Caramello. In her eyes, this fusion of mathematics and metaphysics is true to his boundary-spanning mind and could yield unexpected insights: she points out his use of the mathematics of vibration to explain psychological phenomena in Structure of the Psyche. “We are at the very beginning of a huge exploration of these manuscripts. And certainly there will be marvels in them,” she says.

Grothendieck remained hounded by evil until the end. Perhaps, shattered by his traumas, he couldn’t allow himself to forgive, and to conceive of the world in a kinder light. But his children, despite the long estrangement, aren’t the same. Matthieu rejects the idea that his father repeated the abandonment he suffered as a child on them: “We were adults, so it’s nothing compared to what he went through. He did a lot better than his parents.”

The shunning of his children wounded Johanna, but she understands that something was fundamentally broken in her father. “In his mind, I don’t think he left us. We existed in a parallel reality for him. The fact that he burned his parents’ letters was extremely revealing: he had no feeling of existing in the family chain of generations.” What’s striking is the trio’s lack of judgment about their father and their openness to discussing his ordeals. “We accept it,” says Alexandre. “It was the trial he wanted to inflict on himself – and he inflicted it on himself most of all.”