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In CureVac’s failure, a possible verdict on the past (and future) of mRNA vaccines

When three companies emerged in the winter of 2020 promising that a fancy new technology called mRNA could pull the world out of a deadly pandemic, it was easy to overlook the fact that not all mRNA is created equal.
In fact, by the time Covid-19 broke…

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3 years ago

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When three companies emerged in the winter of 2020 promising that a fancy new technology called mRNA could pull the world out of a deadly pandemic, it was easy to overlook the fact that not all mRNA is created equal.

In fact, by the time Covid-19 broke out, the once insular world of mRNA research had split into two rival camps. CureVac, the world’s oldest mRNA company, used the RNA from textbook biology. Four bases or “letters,” spelling out the instructions to make every possible protein. A, U, G, C. But Moderna and BioNTech tinkered with their RNA. If you zoomed into an atomic level, it looked like someone took out one of the letters, flipped half of it on its head and put it back next to the other three, like a famous painting hung upside down on a museum wall.

That arcane bit of biochemistry had been the subject of intense debate for a decade. It was the focus of dozens of papers, the center of a $150 million patent and, ultimately, the reason Moderna existed at all. But the dueling approaches had never been put to a large-scale test in humans.

Then last month, CureVac announced Phase III results for its Covid-19 shot. They were disastrous. While BioNTech and Moderna built two of the most potent vaccines in history, CureVac’s was 47% effective, below the 50% threshold regulators around the world set as the minimum and far below the 90-plus percent flashed by Moderna and BioNTech. For some researchers trying to make sense of the wreckage, it was impossible not to think back to that single, flipped base.

“I think it was the lack of modification” that doomed CureVac, said Niek Sanders, who conducted one of the first studies examining the mRNA modification BioNTech and Moderna use.

“It is the glaring difference,” said Justin Richner, who studies mRNA vaccines at University of Illinois-Chicago.

Franz-Werner Haas

Despite the low efficacy, CureVac CEO Franz-Werner Haas has vowed to push for approval, relying on data showing stronger protection against severe disease and hospitalization. The company says variants drove down their efficacy, along with looser criteria they set for determining whether volunteers in their trial had symptomatic Covid-19.

“If you look from the outside you see okay, the difference is your modification, and maybe if [we] will modify it, then we will have similar results,” CureVac CTO Mariola Fotin-Mleczek said in an interview. “I think it’s actually more complex.”

CureVac indeed used a wider definition for Covid-19 cases than rivals, although none of the experts interviewed for this story named it as a reason for their shortfall. And the former argument has won little traction among vaccinologists, who point out that the Moderna and BioNTech vaccines have appeared highly effective against the variants CureVac faced.

If the modification proves to be the reason for that disparity — and other researchers stress it’s too early to tell — it could finally offer a tenuous verdict on a decade-old debate at the heart of a technology that has changed the world. Perhaps more importantly, it would be a sign for who may win the coming mRNA wars, as BioNTech and Moderna scale up their ambitions and Big Pharma and venture capitalists, inspired by or jealous of the Covid-19 success, pour billions into the field, pledging to develop mRNA-based treatments for rare diseases and vaccines for cancers and at least a half-dozen other viruses.

The data are “certainly not definitive,” says Jeffrey Ulmer, who’s worked on genetic vaccines across Big Pharma since 1990, including the last decade on mRNA. “Though it does raise an interesting, testable hypothesis.”

Drew Weissman and Katy Karikó at the University of Pennsylvania

Click on the image to see the full-sized version

Researchers have been pondering mRNA vaccines and therapies since the 1980s, but the idea initially gained little traction. Although the principal was elegant — hijacking cells’ internal machinery to produce whatever protein you wanted — what actually happened when you injected RNA into animals was less glamorous. The immune system saw mysterious strands of genetic material, thought virus and went into attack mode, triggering dangerous inflammation.

In 2005, though, Katalin Karikó, a University of Pennsylvania researcher who had been told for years that mRNA drugs couldn’t work, and her collaborator Drew Weissman devised a solution: nucleoside modification.

As they explained in a series of papers, the duo tapped into biology’s oldest evolutionary mechanism for identifying invaders. All life and many viruses use DNA. So to determine whether a strand of DNA came from itself or from a virus, bacteria developed a system of chemical tags that only their DNA have — a kind of molecular passcode. If DNA without that molecular passcode enters, the bacteria attack, like shooting a foreign plane out of regulated airspace.

Karikó and Weissman figured out that organisms, including humans, do the same for RNA, the other genetic code viruses can carry. So the pair designed RNA that mimicked that passcode, replacing one of the bases, uridine, with the upside down version that is commonly found in the human body: the aptly named pseudouridine.

In animal experiments, they showed that their modified RNA didn’t awaken the body’s defenses. To their surprise, it also vastly increased the amount of RNA the cells translated into protein. Suddenly, RNA therapies seemed possible.

Derrick Rossi

“The whole modified nuclease concept is what enabled high levels of protein being produced,” said Derrick Rossi, a stem cell biologist at Harvard, who has suggested Karikó and Weissman deserve the Nobel Prize. “And for the cells to be alive to do it.”

Karikó and Weissman tried to start a company but gained little traction. Rossi, though, was enthralled. After a series of experiments, in 2009 he brought it to the attention of his colleague Tim Springer. They pitched the idea to Flagship, who launched Moderna. The company eventually paid $76 million to license Karikó’s patent. BioNTech, launched in 2008, would do the same and hire Karikó and Weissman to boot. (Both companies technically use a slightly modified form of the modification, called N(1)-methylpseudouridine.)

Not everyone saw the same promise, though. Moderna, for all its fanfare, was the second big RNA company. A decade earlier, a German PhD student named Ingmar Hoerr accidentally discovered that he could get cells in a dish to produce protein by just giving them naked RNA. He founded CureVac in 2000 and, for years, pushed back against Moderna and BioNTech’s approach, claiming he could get better results with old fashioned RNA.

That held true when designing the Covid-19 vaccine. Fotin-Mleczek said they tested vaccine constructs with modified RNA but didn’t see a benefit.

“We never saw the need to use them,” she said.

Mariola Fotin-Mleczek

Click on the image to see the full-sized version

Hoerr believed he could actually harness that ancient immune response to his benefit. For most vaccines to work, they need an adjuvant, an ingredient — often aluminum or some kind of lipid — that can stimulate the innate immune system and set the body’s protective machinery in motion. To Hoerr, unmodified RNA was perfect. It could provide the adjuvant and the vaccine in one. And because it was so immunogenic, he claimed CureVac could inoculate at much lower doses than BioNTech or Moderna, allowing them to scale cheaply and rapidly.

That approach, though, meant playing with fire. For reasons researchers are still deciphering, the innate immunity unmodified RNA sets off can actually shut down cells’ ability to translate that RNA into protein. It’s likely a defense mechanism evolved to prevent virus-infected cells from churning out new viruses.

CureVac would have to design RNA in a sweet spot: potent enough to help the immune response but not so potent that cells just shut down. “You have to be not too hot, not too cold,” said Sanders.

Nevertheless, both approaches had backers. In 2015, the Gates Foundation invested $52 million into CureVac, a then-record investment for the NGO. The foundation examined the three big mRNA companies at the time and determined CureVac had a slight edge on inoculations, a former Gates employee told Endpoints News. They also reckoned Moderna was overvalued.

“We thought Moderna would be better for HIV [monoclonal antibodies],” they said. “We thought the CureVac technology was going to be better for making vaccines.”

CureVac put the first mRNA prophylactic vaccine, a rabies candidate, into the clinic in 2013. But the results were a disappointment. Only one of the volunteers who received the vaccine by injection even had a measurable immune response against rabies.

But CureVac slowly adopted improvements, including the lipid nanoparticles now used across all mRNA vaccines. They worked on ways to make their particular approach viable, most notably with a process called sequence optimization. Any protein can be “spelled” with numerous different RNA sequences. So CureVac came up with algorithms that allowed them to take whatever protein they wanted to code and write it with as few copies of U, the base that sets off the body’s alarms, as possible.

In 2020, CureVac emerged as an early frontrunner in the race for a vaccine and then quickly fell behind. They struggled to raise the pharma or government funds their rivals obtained, fell into a geopolitical standoff and lost Hoerr to repeated medical issues. Still, they emerged by the start of 2021 as a closely watched and sorely needed “second-wave” candidate. Executives said their tech would let them produce hundreds of millions of vaccines. The EU signed a deal for over 400 million doses.

“I would just be really surprised if it didn’t work well,” John Moore, an immunolgist at Cornell, told The New York Times in May.

Their failure in June was a stunning blow — although not, multiple experts said, a final verdict on mRNA vaccines.

Daniel Anderson

“There is no data that allow me to point to the lack of modifications in the CureVac vaccine to answer why they got a suboptimal response,” said Daniel Anderson, a chemical engineer at MIT and a scientific advisor to Translate Bio, a biotech that uses unmodified mRNA. “There are so many other differences: differences in doses, differences in the nanoparticle itself… differences in storage conditions.”

There are several other key places to look for differences between CureVac and the BioNTech and Moderna vaccines. mRNA vaccines aren’t discrete entities like some drugs; they’re complex recipes, requiring numerous decisions and optimizations that can go wrong.

Anderson and others pointed to possible differences in the lipid nanoparticle used to shuttle mRNA into cells, although Sanders notes that both CureVac and BioNTech rely on LNP technology from the same company. There are differences in how well each biotech manufactures and purifies their mRNA. And each of the biotechs also code for the coronavirus spike protein differently, using different sequences for the protein itself and different sequences for sections of RNA that change how that protein is expressed.

Jeffrey Ulmer

“There are optimizations up and down the molecule,” Ulmer said.

Peter Kremsner, the lead investigator on CureVac’s pivotal trial, argued CureVac used too small a dose: just 12 micrograms, or barely 1/10th what Moderna used. But Fotin-Mleczek acknowledged that their unmodified RNA prevented them from using any more vaccine. The company tested 16 and 20 microgram doses in Phase I, but rejected them as too intolerable.

Similarly, their RNA sequence was impacted by their decision to use unmodified RNA: It’s possible, Sanders said, that their sequence optimization software worked well in mice but not in humans.

The difference could also have come down to a failure to execute across all these different facets, particularly during a public health crisis, changes in leadership and tenuous resources. CureVac’s management had never inspired the same confidence as Stéphane Bancel or Ugur Sahin at Moderna and BioNTech did.

“It was not a surprise to anyone that Moderna executed better than CureVac did,” the former Gates employee said.

Where does CureVac — and the rest of the mRNA world — go from here? It’s a key question as Moderna and BioNTech, flush with cash, drastically scale their efforts while Pfizer, Sanofi, Novartis and GlaxoSmithKline either unveil plans to spend hundreds of millions of dollars on the tech or signal that they might.

“I don’t know how they can support their business after that failed trial,” said Rossi, the Moderna co-founder. “I don’t know who puts money into CureVac now.”

Yet CureVac retains a valuation near $10 billion and is working on a second-generation vaccine that will still rely on its unmodified RNA. Fotin-Mleczek said that company still believes it can get a better T cell response that way, inducing better and longer protection against infection.

Few, it seems, are retreating fully from Hoerr’s approach. Translate Bio, the mRNA company Sanofi paid $425 million cash and $1.9 billion in milestones to team on vaccines for Covid-19 and other infectious diseases, claims that they haven’t seen any differences between unmodified and modified mRNA in their animal work. They took an unmodified coronavirus candidate into Phase I in March.

Ron Renaud

“I wouldn’t say that we’ve seen advantages or disadvantages,” said Translate Bio CEO Ron Renaud. “We just don’t see differences.”

Other experts say that as companies have gotten better at purifying RNA over the last decade, filtering out detritus that can stoke the immune system, modified RNA’s advantages have dwindled.

And unmodified bases may still hold benefits for other applications of mRNA. Renaud noted that BioNTech uses classic RNA for some of its cancer vaccines, betting that its immune-stimulating properties will prove beneficial in the tumor. CureVac is doing the same, with two similar programs in the clinic. And so-called self-amplifying mRNA, a technology with a turbulent history but possible benefits for both infectious diseases and cancers, can only use unmodified mRNA.

Still, there are no human data to show unmodified vaccines can work and, after losing the Covid-19 race, CureVac, after two decades, may finally begin developing vaccines with modified RNA. In February, GSK gave CureVac more than $300 million to co-develop new vaccines. After the Phase III failure, analysts questioned whether they had picked the wrong horse.

“Can you reiterate and give us reasons for why you think the naked mRNA technology from CureVac may not be a problem here?” Goldman Sach’s Keyur Parekh asked GSK R&D chief Hal Barron at their investor day event.

Barron responded that they liked aspects of CureVac’s technology. But they would be applying it to vaccines with modified bases.

Fotin-Mleczek, though, made clear the company was not backing away from their flagship technology.

“The plan is to test other variants, including modification,” she said. “That doesn’t mean there’s any decision to switch — the decision is just to be open.”

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Government

Rand Paul Teases Senate GOP Leader Run – Musk Says “I Would Support”

Rand Paul Teases Senate GOP Leader Run – Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump…

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9 hours ago

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March 10, 2024

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Rand Paul Teases Senate GOP Leader Run - Musk Says "I Would Support"

Republican Kentucky Senator Rand Paul on Friday hinted that he may jump into the race to become the next Senate GOP leader, and Elon Musk was quick to support the idea. Republicans must find a successor for periodically malfunctioning Mitch McConnell, who recently announced he'll step down in November, though intending to keep his Senate seat until his term ends in January 2027, when he'd be within weeks of turning 86. 

So far, the announced field consists of two quintessential establishment types: John Cornyn of Texas and John Thune of South Dakota. While John Barrasso's name had been thrown around as one of "The Three Johns" considered top contenders, the Wyoming senator on Tuesday said he'll instead seek the number two slot as party whip. 

Paul used X to tease his potential bid for the position which -- if the GOP takes back the upper chamber in November -- could graduate from Minority Leader to Majority Leader. He started by telling his 5.1 million followers he'd had lots of people asking him about his interest in running...

...then followed up with a poll in which he predictably annihilated Cornyn and Thune, taking a 96% share as of Friday night, with the other two below 2% each. 

Elon Musk was quick to back the idea of Paul as GOP leader, while daring Cornyn and Thune to follow Paul's lead by throwing their names out for consideration by the Twitter-verse X-verse. 

Paul has been a stalwart opponent of security-state mass surveillance, foreign interventionism -- to include shoveling billions of dollars into the proxy war in Ukraine -- and out-of-control spending in general. He demonstrated the latter passion on the Senate floor this week as he ridiculed the latest kick-the-can spending package:   

In February, Paul used Senate rules to force his colleagues into a grueling Super Bowl weekend of votes, as he worked to derail a $95 billion foreign aid bill. "I think we should stay here as long as it takes,” said Paul. “If it takes a week or a month, I’ll force them to stay here to discuss why they think the border of Ukraine is more important than the US border.”

Don't expect a Majority Leader Paul to ditch the filibuster -- he's been a hardy user of the legislative delay tactic. In 2013, he spoke for 13 hours to fight the nomination of John Brennan as CIA director. In 2015, he orated for 10-and-a-half-hours to oppose extension of the Patriot Act. 

Rand Paul amid his 10 1/2 hour filibuster in 2015

Among the general public, Paul is probably best known as Capitol Hill's chief tormentor of Dr. Anthony Fauci, who was director of the National Institute of Allergy and Infectious Disease during the Covid-19 pandemic. Paul says the evidence indicates the virus emerged from China's Wuhan Institute of Virology. He's accused Fauci and other members of the US government public health apparatus of evading questions about their funding of the Chinese lab's "gain of function" research, which takes natural viruses and morphs them into something more dangerous. Paul has pointedly said that Fauci committed perjury in congressional hearings and that he belongs in jail "without question."   

Musk is neither the only nor the first noteworthy figure to back Paul for party leader. Just hours after McConnell announced his upcoming step-down from leadership, independent 2024 presidential candidate Robert F. Kennedy, Jr voiced his support: 

In a testament to the extent to which the establishment recoils at the libertarian-minded Paul, mainstream media outlets -- which have been quick to report on other developments in the majority leader race -- pretended not to notice that Paul had signaled his interest in the job. More than 24 hours after Paul's test-the-waters tweet-fest began, not a single major outlet had brought it to the attention of their audience. 

That may be his strongest endorsement yet. 

Tyler Durden Sun, 03/10/2024 - 20:25

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International

‘I couldn’t stand the pain’: the Turkish holiday resort that’s become an emergency dental centre for Britons who can’t get treated at home

The crisis in NHS dentistry is driving increasing numbers abroad for treatment. Here are some of their stories.

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12 hours ago

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March 10, 2024

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This clinic in the Turkish resort of Antalya is the official 'dental sponsor' of the Miss England competition. Diana Ibanez-Tirado, Author provided

It’s a hot summer day in the Turkish city of Antalya, a Mediterranean resort with golden beaches, deep blue sea and vibrant nightlife. The pool area of the all-inclusive resort is crammed with British people on sun loungers – but they aren’t here for a holiday. This hotel is linked to a dental clinic that organises treatment packages, and most of these guests are here to see a dentist.

From Norwich, two women talk about gums and injections. A man from Wales holds a tissue close to his mouth and spits blood – he has just had two molars extracted.

The dental clinic organises everything for these dental “tourists” throughout their treatment, which typically lasts from three to 15 days. The stories I hear of what has caused them to travel to Turkey are strikingly similar: all have struggled to secure dental treatment at home on the NHS.

“The hotel is nice and some days I go to the beach,” says Susan*, a hairdresser in her mid-30s from Norwich. “But really, we aren’t tourists like in a proper holiday. We come here because we have no choice. I couldn’t stand the pain.”

Seaside beach resort with mountains in the distance
The Turkish Mediterranean resort of Antalya. Akimov Konstantin/Shutterstock

This is Susan’s second visit to Antalya. She explains that her ordeal started two years earlier:

I went to an NHS dentist who told me I had gum disease … She did some cleaning to my teeth and gums but it got worse. When I ate, my teeth were moving … the gums were bleeding and it was very painful. I called to say I was in pain but the clinic was not accepting NHS patients any more.

The only option the dentist offered Susan was to register as a private patient:

I asked how much. They said £50 for x-rays and then if the gum disease got worse, £300 or so for extraction. Four of them were moving – imagine: £1,200 for losing your teeth! Without teeth I’d lose my clients, but I didn’t have the money. I’m a single mum. I called my mum and cried.

Susan’s mother told her about a friend of hers who had been to Turkey for treatment, then together they found a suitable clinic:

The prices are so much cheaper! Tooth extraction, x-rays, consultations – it all comes included. The flight and hotel for seven days cost the same as losing four teeth in Norwich … I had my lower teeth removed here six months ago, now I’ve got implants … £2,800 for everything – hotel, transfer, treatments. I only paid the flights separately.

In the UK, roughly half the adult population suffers from periodontitis – inflammation of the gums caused by plaque bacteria that can lead to irreversible loss of gums, teeth, and bone. Regular reviews by a dentist or hygienist are required to manage this condition. But nine out of ten dental practices cannot offer NHS appointments to new adult patients, while eight in ten are not accepting new child patients.

Some UK dentists argue that Britons who travel abroad for treatment do so mainly for cosmetic procedures. They warn that dental tourism is dangerous, and that if their treatment goes wrong, dentists in the UK will be unable to help because they don’t want to be responsible for further damage. Susan shrugs this off:

Dentists in England say: ‘If you go to Turkey, we won’t touch you [afterwards].’ But I don’t worry because there are no appointments at home anyway. They couldn’t help in the first place, and this is why we are in Turkey.

‘How can we pay all this money?’

As a social anthropologist, I travelled to Turkey a number of times in 2023 to investigate the crisis of NHS dentistry, and the journeys abroad that UK patients are increasingly making as a result. I have relatives in Istanbul and have been researching migration and trading patterns in Turkey’s largest city since 2016.

In August 2023, I visited the resort in Antalya, nearly 400 miles south of Istanbul. As well as Susan, I met a group from a village in Wales who said there was no provision of NHS dentistry back home. They had organised a two-week trip to Turkey: the 12-strong group included a middle-aged couple with two sons in their early 20s, and two couples who were pensioners. By going together, Anya tells me, they could support each other through their different treatments:

I’ve had many cavities since I was little … Before, you could see a dentist regularly – you didn’t even think about it. If you had pain or wanted a regular visit, you phoned and you went … That was in the 1990s, when I went to the dentist maybe every year.

Anya says that once she had children, her family and work commitments meant she had no time to go to the dentist. Then, years later, she started having serious toothache:

Every time I chewed something, it hurt. I ate soups and soft food, and I also lost weight … Even drinking was painful – tea: pain, cold water: pain. I was taking paracetamol all the time! I went to the dentist to fix all this, but there were no appointments.

Anya was told she would have to wait months, or find a dentist elsewhere:

A private clinic gave me a list of things I needed done. Oh my God, almost £6,000. My husband went too – same story. How can we pay all this money? So we decided to come to Turkey. Some people we know had been here, and others in the village wanted to come too. We’ve brought our sons too – they also need to be checked and fixed. Our whole family could be fixed for less than £6,000.

By the time they travelled, Anya’s dental problems had turned into a dental emergency. She says she could not live with the pain anymore, and was relying on paracetamol.

In 2023, about 6 million adults in the UK experienced protracted pain (lasting more than two weeks) caused by toothache. Unintentional paracetamol overdose due to dental pain is a significant cause of admissions to acute medical units. If left untreated, tooth infections can spread to other parts of the body and cause life-threatening complications – and on rare occasions, death.

In February 2024, police were called to manage hundreds of people queuing outside a newly opened dental clinic in Bristol, all hoping to be registered or seen by an NHS dentist. One in ten Britons have admitted to performing “DIY dentistry”, of which 20% did so because they could not find a timely appointment. This includes people pulling out their teeth with pliers and using superglue to repair their teeth.

In the 1990s, dentistry was almost entirely provided through NHS services, with only around 500 solely private dentists registered. Today, NHS dentist numbers in England are at their lowest level in a decade, with 23,577 dentists registered to perform NHS work in 2022-23, down 695 on the previous year. Furthermore, the precise division of NHS and private work that each dentist provides is not measured.

The COVID pandemic created longer waiting lists for NHS treatment in an already stretched public service. In Bridlington, Yorkshire, people are now reportedly having to wait eight-to-nine years to get an NHS dental appointment with the only remaining NHS dentist in the town.

In his book Patients of the State (2012), Argentine sociologist Javier Auyero describes the “indignities of waiting”. It is the poor who are mostly forced to wait, he writes. Queues for state benefits and public services constitute a tangible form of power over the marginalised. There is an ethnic dimension to this story, too. Data suggests that in the UK, patients less likely to be effective in booking an NHS dental appointment are non-white ethnic groups and Gypsy or Irish travellers, and that it is particularly challenging for refugees and asylum-seekers to access dental care.

This article is part of Conversation Insights
The Insights team generates long-form journalism derived from interdisciplinary research. The team is working with academics from different backgrounds who have been engaged in projects aimed at tackling societal and scientific challenges.

In 2022, I experienced my own dental emergency. An infected tooth was causing me debilitating pain, and needed root canal treatment. I was advised this would cost £71 on the NHS, plus £307 for a follow-up crown – but that I would have to wait months for an appointment. The pain became excruciating – I could not sleep, let alone wait for months. In the same clinic, privately, I was quoted £1,300 for the treatment (more than half my monthly income at the time), or £295 for a tooth extraction.

I did not want to lose my tooth because of lack of money. So I bought a flight to Istanbul immediately for the price of the extraction in the UK, and my tooth was treated with root canal therapy by a private dentist there for £80. Including the costs of travelling, the total was a third of what I was quoted to be treated privately in the UK. Two years on, my treated tooth hasn’t given me any more problems.

A better quality of life

Not everyone is in Antalya for emergency procedures. The pensioners from Wales had contacted numerous clinics they found on the internet, comparing prices, treatments and hotel packages at least a year in advance, in a carefully planned trip to get dental implants – artificial replacements for tooth roots that help support dentures, crowns and bridges.

Street view of a dental clinic in Antalya, Turkey
Dental clinic in Antalya, Turkey. Diana Ibanez-Tirado, CC BY-NC-ND

In Turkey, all the dentists I speak to (most of whom cater mainly for foreigners, including UK nationals) consider implants not a cosmetic or luxurious treatment, but a development in dentistry that gives patients who are able to have the procedure a much better quality of life. This procedure is not available on the NHS for most of the UK population, and the patients I meet in Turkey could not afford implants in private clinics back home.

Paul is in Antalya to replace his dentures, which have become uncomfortable and irritating to his gums, with implants. He says he couldn’t find an appointment to see an NHS dentist. His wife Sonia went through a similar procedure the year before and is very satisfied with the results, telling me: “Why have dentures that you need to put in a glass overnight, in the old style? If you can have implants, I say, you’re better off having them.”

Most of the dental tourists I meet in Antalya are white British: this city, known as the Turkish Riviera, has developed an entire economy catering to English-speaking tourists. In 2023, more than 1.3 million people visited the city from the UK, up almost 15% on the previous year.

Read more: NHS dentistry is in crisis – are overseas dentists the answer?

In contrast, the Britons I meet in Istanbul are predominantly from a non-white ethnic background. Omar, a pensioner of Pakistani origin in his early 70s, has come here after waiting “half a year” for an NHS appointment to fix the dental bridge that is causing him pain. Omar’s son had been previously for a hair transplant, and was offered a free dental checkup by the same clinic, so he suggested it to his father. Having worked as a driver for a manufacturing company for two decades in Birmingham, Omar says he feels disappointed to have contributed to the British economy for so long, only to be “let down” by the NHS:

At home, I must wait and wait and wait to get a bridge – and then I had many problems with it. I couldn’t eat because the bridge was uncomfortable and I was in pain, but there were no appointments on the NHS. I asked a private dentist and they recommended implants, but they are far too expensive [in the UK]. I started losing weight, which is not a bad thing at the beginning, but then I was worrying because I couldn’t chew and eat well and was losing more weight … Here in Istanbul, I got dental implants – US$500 each, problem solved! In England, each implant is maybe £2,000 or £3,000.

In the waiting area of another clinic in Istanbul, I meet Mariam, a British woman of Iraqi background in her late 40s, who is making her second visit to the dentist here. Initially, she needed root canal therapy after experiencing severe pain for weeks. Having been quoted £1,200 in a private clinic in outer London, Mariam decided to fly to Istanbul instead, where she was quoted £150 by a dentist she knew through her large family. Even considering the cost of the flight, Mariam says the decision was obvious:

Dentists in England are so expensive and NHS appointments so difficult to find. It’s awful there, isn’t it? Dentists there blamed me for my rotten teeth. They say it’s my fault: I don’t clean or I ate sugar, or this or that. I grew up in a village in Iraq and didn’t go to the dentist – we were very poor. Then we left because of war, so we didn’t go to a dentist … When I arrived in London more than 20 years ago, I didn’t speak English, so I still didn’t go to the dentist … I think when you move from one place to another, you don’t go to the dentist unless you are in real, real pain.

In Istanbul, Mariam has opted not only for the urgent root canal treatment but also a longer and more complex treatment suggested by her consultant, who she says is a renowned doctor from Syria. This will include several extractions and implants of back and front teeth, and when I ask what she thinks of achieving a “Hollywood smile”, Mariam says:

Who doesn’t want a nice smile? I didn’t come here to be a model. I came because I was in pain, but I know this doctor is the best for implants, and my front teeth were rotten anyway.

Dentists in the UK warn about the risks of “overtreatment” abroad, but Mariam appears confident that this is her opportunity to solve all her oral health problems. Two of her sisters have already been through a similar treatment, so they all trust this doctor.

Alt text
An Istanbul clinic founded by Afghan dentists has a message for its UK customers. Diana Ibanez-Tirado, CC BY-NC-ND

The UK’s ‘dental deserts’

To get a fuller understanding of the NHS dental crisis, I’ve also conducted 20 interviews in the UK with people who have travelled or were considering travelling abroad for dental treatment.

Joan, a 50-year-old woman from Exeter, tells me she considered going to Turkey and could have afforded it, but that her back and knee problems meant she could not brave the trip. She has lost all her lower front teeth due to gum disease and, when I meet her, has been waiting 13 months for an NHS dental appointment. Joan tells me she is living in “shame”, unable to smile.

In the UK, areas with extremely limited provision of NHS dental services – known as as “dental deserts” – include densely populated urban areas such as Portsmouth and Greater Manchester, as well as many rural and coastal areas.

In Felixstowe, the last dentist taking NHS patients went private in 2023, despite the efforts of the activist group Toothless in Suffolk to secure better access to NHS dentists in the area. It’s a similar story in Ripon, Yorkshire, and in Dumfries & Galloway, Scotland, where nearly 25,000 patients have been de-registered from NHS dentists since 2021.

Data shows that 2 million adults must travel at least 40 miles within the UK to access dental care. Branding travel for dental care as “tourism” carries the risk of disguising the elements of duress under which patients move to restore their oral health – nationally and internationally. It also hides the immobility of those who cannot undertake such journeys.

The 90-year-old woman in Dumfries & Galloway who now faces travelling for hours by bus to see an NHS dentist can hardly be considered “tourism” – nor the Ukrainian war refugees who travelled back from West Sussex and Norwich to Ukraine, rather than face the long wait to see an NHS dentist.

Many people I have spoken to cannot afford the cost of transport to attend dental appointments two hours away – or they have care responsibilities that make it impossible. Instead, they are forced to wait in pain, in the hope of one day securing an appointment closer to home.

Billboard advertising a dental clinic in Turkey
Dental clinics have mushroomed in recent years in Turkey, thanks to the influx of foreign patients seeking a wide range of treatments. Diana Ibanez-Tirado, CC BY-NC-ND

‘Your crisis is our business’

The indignities of waiting in the UK are having a big impact on the lives of some local and foreign dentists in Turkey. Some neighbourhoods are rapidly changing as dental and other health clinics, usually in luxurious multi-storey glass buildings, mushroom. In the office of one large Istanbul medical complex with sections for hair transplants and dentistry (plus one linked to a hospital for more extensive cosmetic surgery), its Turkish owner and main investor tells me:

Your crisis is our business, but this is a bazaar. There are good clinics and bad clinics, and unfortunately sometimes foreign patients do not know which one to choose. But for us, the business is very good.

This clinic only caters to foreign patients. The owner, an architect by profession who also developed medical clinics in Brazil, describes how COVID had a major impact on his business:

When in Europe you had COVID lockdowns, Turkey allowed foreigners to come. Many people came for ‘medical tourism’ – we had many patients for cosmetic surgery and hair transplants. And that was when the dental business started, because our patients couldn’t see a dentist in Germany or England. Then more and more patients started to come for dental treatments, especially from the UK and Ireland. For them, it’s very, very cheap here.

The reasons include the value of the Turkish lira relative to the British pound, the low cost of labour, the increasing competition among Turkish clinics, and the sheer motivation of dentists here. While most dentists catering to foreign patients are from Turkey, others have arrived seeking refuge from war and violence in Syria, Iraq, Afghanistan, Iran and beyond. They work diligently to rebuild their lives, careers and lost wealth.

Regardless of their origin, all dentists in Turkey must be registered and certified. Hamed, a Syrian dentist and co-owner of a new clinic in Istanbul catering to European and North American patients, tells me:

I know that you say ‘Syrian’ and people think ‘migrant’, ‘refugee’, and maybe think ‘how can this dentist be good?’ – but Syria, before the war, had very good doctors and dentists. Many of us came to Turkey and now I have a Turkish passport. I had to pass the exams to practise dentistry here – I study hard. The exams are in Turkish and they are difficult, so you cannot say that Syrian doctors are stupid.

Hamed talks excitedly about the latest technology that is coming to his profession: “There are always new materials and techniques, and we cannot stop learning.” He is about to travel to Paris to an international conference:

I can say my techniques are very advanced … I bet I put more implants and do more bone grafting and surgeries every week than any dentist you know in England. A good dentist is about practice and hand skills and experience. I work hard, very hard, because more and more patients are arriving to my clinic, because in England they don’t find dentists.

Dental equipment in a Turkish treatment room
Dentists in Turkey boast of using the latest technology. Diana Ibanez-Tirado, CC BY-NC-ND

While there is no official data about the number of people travelling from the UK to Turkey for dental treatment, investors and dentists I speak to consider that numbers are rocketing. From all over the world, Turkey received 1.2 million visitors for “medical tourism” in 2022, an increase of 308% on the previous year. Of these, about 250,000 patients went for dentistry. One of the most renowned dental clinics in Istanbul had only 15 British patients in 2019, but that number increased to 2,200 in 2023 and is expected to reach 5,500 in 2024.

Like all forms of medical care, dental treatments carry risks. Most clinics in Turkey offer a ten-year guarantee for treatments and a printed clinical history of procedures carried out, so patients can show this to their local dentists and continue their regular annual care in the UK. Dental treatments, checkups and maintaining a good oral health is a life-time process, not a one-off event.

Many UK patients, however, are caught between a rock and a hard place – criticised for going abroad, yet unable to get affordable dental care in the UK before and after their return. The British Dental Association has called for more action to inform these patients about the risks of getting treated overseas – and has warned UK dentists about the legal implications of treating these patients on their return. But this does not address the difficulties faced by British patients who are being forced to go abroad in search of affordable, often urgent dental care.

A global emergency

The World Health Organization states that the explosion of oral disease around the world is a result of the “negligent attitude” that governments, policymakers and insurance companies have towards including oral healthcare under the umbrella of universal healthcare. It as if the health of our teeth and mouth is optional; somehow less important than treatment to the rest of our body. Yet complications from untreated tooth decay can lead to hospitalisation.

The main causes of oral health diseases are untreated tooth decay, severe gum disease, toothlessness, and cancers of the lip and oral cavity. Cases grew during the pandemic, when little or no attention was paid to oral health. Meanwhile, the global cosmetic dentistry market is predicted to continue growing at an annual rate of 13% for the rest of this decade, confirming the strong relationship between socioeconomic status and access to oral healthcare.

In the UK since 2018, there have been more than 218,000 admissions to hospital for rotting teeth, of which more than 100,000 were children. Some 40% of children in the UK have not seen a dentist in the past 12 months. The role of dentists in prevention of tooth decay and its complications, and in the early detection of mouth cancer, is vital. While there is a 90% survival rate for mouth cancer if spotted early, the lack of access to dental appointments is causing cases to go undetected.

The reasons for the crisis in NHS dentistry are complex, but include: the real-term cuts in funding to NHS dentistry; the challenges of recruitment and retention of dentists in rural and coastal areas; pay inequalities facing dental nurses, most of them women, who are being badly hit by the cost of living crisis; and, in England, the 2006 Dental Contract that does not remunerate dentists in a way that encourages them to continue seeing NHS patients.

The UK is suffering a mass exodus of the public dentistry workforce, with workers leaving the profession entirely or shifting to the private sector, where payments and life-work balance are better, bureaucracy is reduced, and prospects for career development look much better. A survey of general dental practitioners found that around half have reduced their NHS work since the pandemic – with 43% saying they were likely to go fully private, and 42% considering a career change or taking early retirement.

Reversing the UK’s dental crisis requires more commitment to substantial reform and funding than the “recovery plan” announced by Victoria Atkins, the secretary of state for health and social care, on February 7.

The stories I have gathered show that people travelling abroad for dental treatment don’t see themselves as “tourists” or vanity-driven consumers of the “Hollywood smile”. Rather, they have been forced by the crisis in NHS dentistry to seek out a service 1,500 miles away in Turkey that should be a basic, affordable right for all, on their own doorstep.

*Names in this article have been changed to protect the anonymity of the interviewees.

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Diana Ibanez Tirado receives funding from the School of Global Studies, University of Sussex.

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International

Beloved mall retailer files Chapter 7 bankruptcy, will liquidate

The struggling chain has given up the fight and will close hundreds of stores around the world.

Published

16 hours ago

on

March 10, 2024

By

It has been a brutal period for several popular retailers. The fallout from the covid pandemic and a challenging economic environment have pushed numerous chains into bankruptcy with Tuesday Morning, Christmas Tree Shops, and Bed Bath & Beyond all moving from Chapter 11 to Chapter 7 bankruptcy liquidation.

In all three of those cases, the companies faced clear financial pressures that led to inventory problems and vendors demanding faster, or even upfront payment. That creates a sort of inevitability.

Related: Beloved retailer finds life after bankruptcy, new famous owner

When a retailer faces financial pressure it sets off a cycle where vendors become wary of selling them items. That leads to barren shelves and no ability for the chain to sell its way out of its financial problems. 

Once that happens bankruptcy generally becomes the only option. Sometimes that means a Chapter 11 filing which gives the company a chance to negotiate with its creditors. In some cases, deals can be worked out where vendors extend longer terms or even forgive some debts, and banks offer an extension of loan terms.

In other cases, new funding can be secured which assuages vendor concerns or the company might be taken over by its vendors. Sometimes, as was the case with David's Bridal, a new owner steps in, adds new money, and makes deals with creditors in order to give the company a new lease on life.

It's rare that a retailer moves directly into Chapter 7 bankruptcy and decides to liquidate without trying to find a new source of funding.

Mall traffic has varied depending upon the type of mall.

Image source: Getty Images

The Body Shop has bad news for customers  

The Body Shop has been in a very public fight for survival. Fears began when the company closed half of its locations in the United Kingdom. That was followed by a bankruptcy-style filing in Canada and an abrupt closure of its U.S. stores on March 4.

"The Canadian subsidiary of the global beauty and cosmetics brand announced it has started restructuring proceedings by filing a Notice of Intention (NOI) to Make a Proposal pursuant to the Bankruptcy and Insolvency Act (Canada). In the same release, the company said that, as of March 1, 2024, The Body Shop US Limited has ceased operations," Chain Store Age reported.

A message on the company's U.S. website shared a simple message that does not appear to be the entire story.

"We're currently undergoing planned maintenance, but don't worry we're due to be back online soon."

That same message is still on the company's website, but a new filing makes it clear that the site is not down for maintenance, it's down for good.

The Body Shop files for Chapter 7 bankruptcy

While the future appeared bleak for The Body Shop, fans of the brand held out hope that a savior would step in. That's not going to be the case. 

The Body Shop filed for Chapter 7 bankruptcy in the United States.

"The US arm of the ethical cosmetics group has ceased trading at its 50 outlets. On Saturday (March 9), it filed for Chapter 7 insolvency, under which assets are sold off to clear debts, putting about 400 jobs at risk including those in a distribution center that still holds millions of dollars worth of stock," The Guardian reported.

After its closure in the United States, the survival of the brand remains very much in doubt. About half of the chain's stores in the United Kingdom remain open along with its Australian stores. 

The future of those stores remains very much in doubt and the chain has shared that it needs new funding in order for them to continue operating.

The Body Shop did not respond to a request for comment from TheStreet.   

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