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Human Pain, Literally Served On A Plate

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A 39-year-old Spaniard — Santiago Ramón y Cajal — changed the history of science with a study hidden in the little-known Barcelona Journal of Medical Science, published on November 25, 1891. At a time when the brain was believed to be a continuous network, like a spider’s web, Cajal demonstrated that it was actually composed of individual cells — neurons. In that groundbreaking article, he even envisioned the transmission of nerve impulses, adding arrows to his sketches. For the first time, the movement of sensations and thoughts was depicted.

More than 130 years later, a team led by doctor Sergiu Pasca has used millions of human cells to create a true mini-nervous system in their laboratory, capable of detecting a pain signal and transmitting it right before our eyes. It is, quite literally, human pain served on a plate.

Cajal created modern neuroscience, and Pasca has revolutionized it. In 2015, he used a chemical cocktail to reprogram skin cells, rewinding their development back to an embryonic state and inducing them to become self-organizing neurons in a small cluster. Two years later, he joined a cluster of these cells from the cerebral cortex with another cluster of cells from the deep brain. To his amazement, the two clusters fused, forming functional connections between them. Pasca, a 43-year-old Romanian-American, named these astonishing structures “assembloids.” Three years later, he managed to connect three spheres, containing cells from the cerebral cortex, spinal cord, and muscle. He had recreated the circuitry of voluntary movement.

It took Pasca and his team five more years to take the next leap. They modified skin cells from volunteers to turn them into neurons representing the four key regions of the neural pathways that transmit stimuli, such as pain or the sensation of a caress, from the skin to the brain.

This time, four tiny clusters were joined together: spinal ganglion, spinal cord, thalamus, and somatosensory cortex. The result, in Pasca’s words, was “like a tiny sausage.” A two-centimeter-long sausage, composed of four million human cells transmitting a painful stimulus to one another, in his laboratory at Stanford University. His new study was published on Wednesday in Nature.

Chronic pain is a devastating disorder, affecting almost a quarter of the population. Understanding its biology and finding better treatments is a challenge,” Pasca explains via videoconference. “The scientific community has already studied pain pathways in many ways, but until now, they have been piecemeal: only sensory neurons, only the response of the cerebral cortex… Now we have the advantage of being able to observe all human cells noninvasively, without harming anyone,” he says. Researchers trigger the sensation of pain with substances like capsaicin, found in hot peppers.

An adult human brain is composed of approximately 86 billion neurons. Pasca’s mini-nervous system only has four million and lacks cells from key regions, such as the amygdala, which is linked to the emotion of pain. However, the Stanford doctor believes these assembloids will be very useful in illuminating neurodevelopmental disorders, such as autism spectrum disorders.

“Many people with autism have hypersensitivity to touch, sounds, or visual stimuli. It’s clear that there is something different about how their nervous system processes sensory information,” he argues.

Sergiu Pasca in his laboratory at Stanford University.

Pasca is hopeful. “Autism, ultimately, is a disorder of social behavior. It involves altered social communication, as well as repetitive movements. Why does it also have a dysfunction in sensory processing? Does that directly contribute to the disorder? Or is it a kind of side effect? We simply don’t know,” he explains. “We can introduce the various genetic mutations associated with autism into assembloids and observe how they disrupt circuits from the outset. It’s a very exciting opportunity to begin to address the biology of this disorder,” he says.

The doctor directs the Stanford Center for Brain Organogenesis, with figures such as U.S. neuroscientist Karl Deisseroth, the father of optogenetics — a revolutionary technique that enables neurons to be turned on or off using bursts of laser light, made possible by the introduction of light-sensitive genes from algae.

In 2022, Pasca, Deisseroth, and their colleagues grafted pellets of human cerebral cortex cells into the brains of rats, resulting in the implanted tissue integrating and influencing the animals’ behavior. A year ago, Pasca’s team used a kind of genetic band-aid to correct an autism-related syndrome in one of these human cerebroids inserted into a rat.

“The new assembloids are not simple structures. They are composed of four parts, measure more than a centimeter, and require about 200 days to make. Although they are challenging to produce, we can imagine that the process will be scalable and thousands upon thousands of assembloids could be created and used to test drugs,” reflects Pasca, whose university has patented the invention. “The best medications we have today for pain are opioids. They are very effective, but they are also highly addictive. To find alternatives, we need to understand the biology behind the circuits,” he explains.

Neurobiologist Félix Viana directs a pain research program at the Institute of Neurosciences in Sant Joan d’Alacant in Spain. “This new work is, technically, very interesting. It’s like four Lego blocks that you can connect, and there’s a signal that goes from the neurons that connect with the outside world to those in the cerebral cortex, but pain circuits are much more complex than that,” says Viana, who did not participate in the study.

For this expert, the mere six months of development of the neurons of the assembloids represents a very early phase, far removed from adult reality. “Furthermore, pain is a subjective sensation,” says Viana. “It’s the subject who has to tell you if they feel it and to what degree. The assembloids will never feel pain. They might be of some interest in preliminary drug analyses, but I’m skeptical that they will produce useful results in the short term.”

Pasca’s team has already taken another significant step, although for now, they have only released preliminary results. The researchers have recreated the cortico-striatal-thalamic-cortical circuit, one of the brain’s key pathways responsible for cognitive, emotional, and motor functions. Once again, the structure consists of four connected spheres, but this time with looped connections, resembling real circuits. The Stanford team has used these more sophisticated structures to study mutations in the ASH1L gene, which is linked to autism spectrum disorders and Tourette syndrome. In the mutated assembloids, the activity is abnormal.

“If you have a pellet of human muscle cells, it doesn’t do much, but if you attach it to a piece of spinal cord, you can control the contraction of that muscle. The brain is more than the sum of its parts,” says Pasca. “When you attach two pellets, new properties emerge. That’s the goal of assembloids: to capture those new properties that arise from the interaction of cells through the nervous system.”

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Eight Films And Series About Pope Francis

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John Paul II was a Pope who was a great fan of cinema, who even worked in a theater company in Nazi-occupied Poland and wrote three plays (later adapted into films). Francis was a Pope who loved film and television, and who understood how to spread his message through the screen. Whether in fiction or factual documentary, Jorge Mario Bergoglio starred in the following productions:

‘Francis: Pray for me’ (2015)

Darío Grandinetti, as the Pope in 'Francis: Father Jorge.'

Director Beda Docampo Feijóo (born in Spain, but Argentinian, as his family emigrated when he was just a few months old) cast Darío Grandinetti as the Pope shortly after the start of his papacy (he was elected on March 13, 2013). In reality, through the eyes of a Spanish journalist, played by Silvia Abascal, who is writing a report on Francis, the audience is taken through Bergoglio’s entire life (and thus he is played by three actors of different ages). Francis: Father Jorge offers a somewhat stiff portrait. Available on DVD, but not on streaming platforms.

‘Call Me Francis’ (2015)

Another work that attempts to get closer to the Pope before he was appointed Bishop of Rome. An Italian production, although with a mostly Argentinian cast, it was directed by a capable Daniele Luchetti (My Brother is an Only Child). The film version, at just over 90 minutes long, was screened in a Vatican theater in 2015. The other version, the four-hour miniseries (Chiamatemi Francesco), covers 52 years of Francis’ life, from 1961 to his election in 2013, and was released in 2016. As a young man, he is played by Rodrigo de la Serna (who takes up most of the film); as an adult, by Sergio Hernández. The film is available on Tivify, and in Latin America on Netflix.

‘Pope Francis: A Man of His Word’ (2018)

Wim Wenders premiered his film at the Cannes Film Festival, where the German director joked that the protagonist wouldn’t attend the event “because it’s Sunday and he’s working.” The documentary is essentially a hagiography in which the viewer accompanies the Pope on his travels, with images interspersed with interviews Wenders conducted with the Pontiff to elicit his opinions. For the most controversial topics, the filmmaker uses a conversation with Bergoglio on the papal plane during one of his trips. Francis is a good protagonist: he knows how to speak to the camera, is convincing and elegant in his speeches, quotes Dostoevsky, jokes with his audiences, and cries out against the mistreatment of nature and the prevailing economy, which pushes many human beings to the margins of society. Available on Apple TV and Prime Video.

‘The Two Popes’ (2019)

Jonathan Pryce, as Pope Francis in ‘The Two Popes’

In the history of the Catholic Church, there had never been cohabitation between a retired Pope and a sitting one, a fascinating process that Fernando Meirelles recounted in The Two Popes with Jonathan Pryce as Francis and Anthony Hopkins as Benedict XVI. The script is the work of Anthony McCarten, an expert in biographical film stories, and he succeeds when he launches into fictionalizing the conversations. The two actors and the script were nominated for an Oscar. Pryce was chosen for his undeniable resemblance; and the film was titled The Pope until Hopkins was cast and his agent imposed the change. Available on Netflix.

‘Francesco’ (2020)

Russian documentary filmmaker Evgeny Afineevsky (who has made two excellent films on the wars in Ukraine and Syria) explored the figure of Francis through his messages on controversial topics, using all kinds of archival materials. For those convinced of the cause. Available on Apple TV.

‘Stories of a Generation with Pope Francis’ (2021)

A four-part series filmed with people over 70 in front of the camera. It features a diverse cast of unknown faces, from a Nigerian artist, a South African photographer, and a Vietnamese shoemaker, to Martin Scorsese, Jane Goodall, and, of course, Pope Francis, who hovers over the entire film. Their reflections cover love, life’s struggles, work, and dreams both fulfilled and yet to be fulfilled. Available on Netflix.

‘The Letter: A Message for our Earth’ (2022)

Produced by YouTube Originals, and therefore accessible in its entirety on the platform, this documentary by Nick Brown (an expert in nature films) describes Francis’ encounters with various people directly affected by the climate crisis. The encyclical Laudato Si is set in the background. Available on YouTube.

‘In Viaggio, Traveling with Pope Francis’ (2022)

Star Italian documentary filmmaker Gianfranco Rosi accompanied the Pope on several of his trips to complete a portrait of a Pontiff who visited 53 countries in his first nine years in office. The film was nominated for a David di Donatello, the Academy of Italian Cinema’s annual awards. Available on Apple TV.

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Chile

Francis’ Fight Against Pedophilia: A Thorny Challenge

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In 2018, EL PAÍS launched an investigation into pedophilia in the Spanish Church and has an updated database of all known cases. If you are aware of any cases that have not been reported, please write to us at: abusos@elpais.es. If the case is in Latin America, the address is: abusosamerica@elpais.es.

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Clerical pedophilia was Pope Francis’ most difficult battle during his 12-year pontificate, and although he personally committed himself to it, often making radical decisions, the rest of the hierarchy — the bishops and the Vatican bureaucracy — did not always support him. He issued regulations, always delivered harsh speeches, and exuded humanity in his encounters with victims, but the thorough cleansing and acceptance of the truth, the effective implementation of his reforms, did not depend solely on him.

Francis moved in fits and starts, but there is still much to do; he was unable to handle everything alone. A common criticism from victims’ associations around the world is that this has been an era of fine words and many measures, but little progress. In the uneven balance of this battle, the case of Spain is significant: the Pope always looked the other way. Despite the investigation by EL PAÍS, which has already revealed hundreds of cases, Francis decided to delegate management of the problem to the Spanish Church and not confront it. The result has been years of denial, inaction, and opacity, with little or no progress.

When Jorge Mario Bergoglio took the Chair of St. Peter in March 2013, he continued the line of his predecessor, Benedict XVI; no obvious about-face was noticed. He assumed the Church had already reacted. Indeed, one of his first decisions was to reject the U.N.’s request that year to remove “from their posts and hand over to the police all those found guilty of sexual abuse of minors.” Francis resisted. “The responsibility lies with the judicial system,” the Holy See responded.

The Argentine pope had many open fronts, and among all the reforms he implemented, he decided in March 2014 to create an ad hoc body, the Pontifical Commission for the Protection of Minors. However, over the years, it has contributed little and has gone through moments of crisis itself, with open criticism from some members regarding its ineffectiveness and denunciations of internal difficulties. The commission took almost 10 years to produce its first report, presented in October 2024, without impact figures or critical assessments of already known problems.

It took five years for anything to change, due to a first personal experience with the scandal that altered the Pope’s position: the abuse cases in Chile. During his January 2018 trip to Chile and Peru, along with a heated welcome in Santiago, he also encountered protests from a group of victims attacking the bishop of the city of Osorno, accused of covering up pedophiles.

The victims of the sexual assaults by priest Fernando Karadima received a terse response from the Pope: “There is not a single piece of evidence against him.” But that episode stirred him inside, especially after meeting with some of the victims, an experience that deeply moved him. He also realized that the information he was receiving from the bishops was unreliable. He then ordered his own investigation into the case by two of his most trusted men, the Bishop of Malta, Charles Scicluna, and the Spanish priest Jordi Bertomeu. The outcome of their report was devastating, forcing the Pope to acknowledge in a letter to the Chilean community that he had “made serious errors of judgment.” He summoned all of Chile’s bishops to the Vatican and forced them to resign en masse in June 2018.

After the Chilean Church’s hecatomb, the scandal seemed to spill over, with new cases in other countries, from Germany to Australia, sometimes accusing prominent figures, such as Cardinal and Archbishop Emeritus of Washington Theodor McCarrick, who was eventually expelled. The French Episcopal Conference also announced the launch of a major independent investigation, which concluded in 2021 with a report citing more than 330,000 cases.

Similarly, the scandal began to emerge in Spain, thanks to a report by EL PAÍS. In October 2018, this newspaper launched an investigation that, in its first article, counted only 34 convictions for ecclesiastical pedophilia in the previous 30 years. Today, this newspaper’s database, the only one in Spain that tracks the phenomenon, lists 1,550 accused and 2,870 victims. These figures were obtained with little cooperation from the Spanish Church, which denied the problem and replied that there were “few cases.”

Faced with an avalanche of cases worldwide, in 2018 Francis thanked the press for their work, called the Church hierarchy, which looked the other way, “wolves” and convened bishops from around the world to a summit at the Vatican dedicated exclusively to pedophilia.

In February 2019, the Pontiff approved a major reform of canon law, a motu proprio called Vos estis lux mundi, which required investigations of pedophile clerics upon knowledge of any clue, even delivered anonymously, or reports in the press. Until then, for the Church, victims who appeared in the media did not exist, only if they went to a bishop or the superior of a religious order.

Francis also opened avenues for reparation for those affected and included cover-ups as a serious crime. In 2019, the Vatican published a vademecum with rules for handling cases, required each diocese to open victim assistance offices, and lifted the papal secrecy surrounding these crimes.

In Spain, however, the Church resisted investigating past cases and revealing what it knew. Even at the beginning of 2021, the Episcopal Conference (CEE) was still maintaining that there were “zero or very few cases” in Spain. By then, this newspaper had already counted 243 accused and at least 550 victims.

Francis did not comment on what was happening in Spain until the Vatican finally issued a brief statement in support of the Spanish victims, when in December 2021 EL PAÍS handed the Pope a report with 251 previously unpublished cases. The impact of this work led the Spanish parliament to commission an independent investigation by the Ombudsman, and the Episcopal Conference was finally forced to undertake its own investigation: although it always said it would never do so, it commissioned an audit from a law firm.

This newspaper submitted four more reports in the following years, with a total of 783 accounts in more than 1,600 pages. The Vatican has never responded to this, delegating everything to a Spanish Church that, today, has nearly 70 bishops and religious superiors accused of covering up or silencing cases.

The Pope did not even react in 2023 to the survey in the Ombudsman’s report, which estimated the percentage of abuse victims in the Spanish Church at 1.13% of the entire population, equivalent to about 440,000 people, according to media estimates. It was a strange silence, considering his criticism of the handling of the scandal following similar studies and reports in countries such as the United States, France, Portugal, and Italy.

What is known about the scandal is, in reality, the tip of the iceberg, according to experts, and the Church has continued to move with its usual reluctance and opacity. In each diocese, the bishops continue to do as they please, and when complaints reach Rome, they get bogged down in bureaucracy.

Francis achieved occasional changes, through sporadic impulses, and often nothing happened if victims or journalists managed to interview him and tell him their story. An example is the Gaztelueta case, an Opus Dei school in Biscay in the Basque Country, which was canonically closed despite the Supreme Court’s condemnation of the accused teacher. However, after speaking with the victim, Francis ordered it reopened, resulting in the expulsion of the pedophile.

The same thing happened with the case of the Sodalicio de Vida Cristiana, a powerful ultraconservative organization in Peru. The first complaints were filed in 2001, then more reached the Archbishopric of Lima in 2011. In 2015, the scandal erupted via a book written by two journalists, Paola Ugaz and Pedro Salinas, but still no action was taken until the two reporters went to Rome to see Francis in person in 2022, to tell him personally what was happening.

Then the Pope again commissioned Scicluna and Bertomeu to conduct their own investigation. In less than three years, the Sodalicio was dissolved, this very month. But if the journalists hadn’t gone to see the Pope, perhaps nothing would have happened. Thousands of victims around the world haven’t been that lucky, and are still waiting for an answer.

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The Pope Who Defied The Extreme Right Worldwide

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Francis, whose papacy began in 2013 and ended on Monday with his death, witnessed from the highest seat in the Church the rise of nationalist and xenophobic far-right movements across the West. In the face of this defining phenomenon of our time, his stance was clear and unequivocal: firmly against it. His opposition extended not only to discrimination against immigrants, but also to the excesses of neoliberalism — prompting many conservatives to label him a Pope aligned with the left.

While he remained a critic of abortion and opposed equal recognition for heterosexual and same-sex couples — who, according to Church doctrine, cannot form a “natural family”— the Argentine pontiff also resisted pressure to turn the Holy See into a spearhead in the so-called “culture wars” against the “LGBTQ+ lobby” and “gender ideology.” This position earned him open hostility from prominent figures on the far right, and even drew criticism from leaders of the so-called moderate right.

The Pope faced more than just criticism in his native Argentina — he was subjected to outright insults. Argentine President Javier Milei, during his early days as an ultra-liberal polemicist entering political life, frequently made Francis the target of his attacks.

On his X account (then Twitter), Milei lashed out in 2017, telling the Pope to “fuck off” and calling him a “disgusting leftist” for defending the concept of “social justice,” which he vehemently rejects. “It would be good if you started distributing the Vatican’s wealth to the poor. You piece of shit,” he wrote, addressing the pontiff directly. A year later, he escalated his rhetoric, branding Francis a “leftist son of a bitch” and calling him “the representative of evil” within the Church.

In Italy, Matteo Salvini, leader of the far-right Lega party, has been Francis’ most prominent political adversary. In 2019, during Salvini’s tenure as Interior Minister and peak political influence, tensions boiled over. That year, a Polish cardinal close to Francis clandestinely entered the utility room of an occupied building where 400 people were living without electricity — and restored the power. The act infuriated Salvini, who saw the cardinal become a hero of the left. “We’ll send the Vatican the €300,000 bill that the building owed,” Salvini said. Soon after, he found himself on the receiving end of one of the Pope’s pointed remarks: “A politician must not sow hatred and fear.”

Later that same year, when Francis posed for a photo wearing a badge that read “Let’s open the ports,” in support of migrants, Salvini fired back: “He takes care of souls; I take care of the five million poor Italians. I open the ports only to those with permission.”

Caesar and God

Far-right leaders have often cited the biblical phrase “Render unto Caesar what is Caesar’s and unto God what is God’s” to push back against Pope Francis when his messages challenged their politics.

In France, National Rally leader Marine Le Pen cited the phrased in what was her most high-profile clash with the pontiff. She did so in 2021 after Le Nouvel Observateur reported the Pope was “concerned” about the rise of the far right.

“I am convinced that many believers would be delighted if the Pope would focus on what happens in the churches and not at the ballot box,” added Le Pen, who often cloaks her Islamophobic rhetoric in appeals to France’s Christian heritage — a cause the pontiff has never supported.

Her far-right rival Éric Zemmour went further: “But what does the Pope want? Does he want Christian Europe, the cradle of Christianity, to become an Islamic land? I would like him to explain this?” he asked in 2023.

In Spain, Francis has been in the crosshairs of Vox. In 2020, in the midst of the debate over the minimum wage, the Pope voiced his support for a universal income. Vox leader Santiago Abascal responded by stripping him of papal authority: “The opinion of citizen Bergoglio,” he said, seemed “respectable, like that of any other citizen.” “But I don’t share it,” Abascal added, stating that he doesn’t comment on “whether Communion should be given or not,” and, in the same vein, the Bishop of Rome should not meddle in political matters. “Render unto God what is God’s, and unto Caesar what is Caesar’s,” he concluded.

Vox’s former spokesperson, Iván Espinosa de los Monteros, responded in 2019 to one of the Pope’s messages against the rejection of foreigners by saying: “I think it’s great that the Pope welcomes as many illegal immigrants without papers as he wants to the Vatican.” But, he added, the Pope should not tell other sovereign states what to do.

Two years later, in 2021, he criticized “a head of state of the Vatican, of Argentine nationality,” for apologizing for the “sins” committed during the conquest of the Americas. This request for forgiveness sparked irritation beyond Vox.

Madrid premier Isabel Díaz Ayuso, from the conservative People’s Party (PP), found it “surprising” that “a Spanish-speaking Catholic” would speak that way about “a legacy that brought Spanish” and “Catholicism” to the American continent.

Former Spanish prime minister, José María Aznar, also weighed in on the controversy: “I’m not going to join the ranks of those asking for forgiveness.”

From immigration to the Amazon

The Pope’s last public remarks were made on Sunday, when he spoke out against the “contempt for immigrants.” Given he made this comment after meeting U.S. Vice President J.D. Vance, many interpreted it almost unanimously as a rebuke of the Trump administration — one of many. Immigration was, after all, the issue that most frequently caused clashes between the Bishop of Rome and far-right leaders. But it wasn’t the only one.

The range of issues was wide. In 2020, he drew the ire of then-Brazilian president Jair Bolsonaro after posting on social media: “I dream of an Amazon region that fights for the rights of the poor, the original peoples and the least of our brothers and sisters, where their voices can be heard and their dignity advanced.”

“The Amazon is ours,” responded Bolsonaro, denying that the forest belongs, as the Pope maintains, to all of humanity.

One detail illustrates just how much of an obstacle Francis was to the far right. Steve Bannon, former strategist and ideologue of Trumpism, had already identified him as an enemy to confront during Trump’s first term. In 2017, The New York Times reported that Bannon, while serving as a Trump advisor, was forging alliances with some of the Pope’s internal critics in the Vatican, including American Cardinal Raymond Burke, in an effort to undermine the leader of the Church. Two years later, Bannon complained to NBC News about a Pope who he said is constantly “putting all faults in the world on this populist nationalist movement.”

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