How world-first human trachea transplant that saved Sonia’s life was nearly torpedoed… by another surgeon’s research fraud: This gripping story highlights how falsified trials are threatening so many lives
- WARNING GRAPHIC CONTENT
- Sonia Sein, 56, can i take panadol and nurofen is a former social worker and grandmother of two from New York
- A life-threatening asthma attack led to such severe damage to her trachea
- Sonia became first person in the world to receive a human trachea transplant
Drinking in the sweet scent of the flowers her daughter had given her for Mother’s Day, Sonia Sein’s eyes brimmed with tears.
For nearly eight years, this simple pleasure had been only a dream. In fact, her health and quality of life was so poor that at just 56, Sonia, a former social worker and grandmother of two from New York, was preparing to go into a hospice, told by her doctors ‘there was nothing more they could do’.
A life-threatening asthma attack in 2014 had led to such severe damage to her trachea — the windpipe — that the only way Sonia could breathe was through a tube in her throat, depriving her not only of the ability to enjoy any scents as they passed through her nose, but also making it increasingly difficult to talk or even eat, let alone breathe.
Then in January last year, Sonia became the first person in the world to receive a human trachea transplant, using a healthy trachea from a deceased donor.
Sonia Sein, 56, is a former social worker and grandmother of two from New York
A life-threatening asthma attack led to such severe damage to her trachea
The operation was a significant milestone because the trachea has defied all previous attempts to use donor tissue. The main obstacle has been securing a blood supply to the transplanted trachea. So when surgeons found a way to circumvent this problem for Sonia, it made headlines around the world.
In the first UK interview since the experimental surgery, Sonia reveals how it has transformed her life: she’s now able to breathe freely again, eat normally and run around after her two grandchildren.
‘When my daughter LaTisha  gave me the flowers, they smelled so good I cried — I never thought I’d be able to do any of this again,’ says Sonia, 58.
‘When I go for walks I deliberately go past flower shops just to inhale the perfume.’
The ultimate test of the success of the surgery came two months ago when the hole in her throat, which had helped her breathe for so many years, was finally closed.
‘It was a big moment because I didn’t know if I would be able to breathe without it,’ says Sonia. ‘When I realised I could, I was so excited. Since he was a toddler, my 11-year-old grandson, Sebastian, had only seen me with the hole in my throat. When it was closed he started crying, saying he’d got his old nana back. That made me cry.’
But this lifesaving breakthrough nearly didn’t happen — the fact it did marks an important milestone not just for patients like Sonia, representing a victory against research fraud. In 2008, a charismatic Italian surgeon, Paolo Macchiarini, made headlines world wide after a study published in The Lancet revealed he’d transplanted a trachea from a dead donor — removing the cells from it to use it as a cartilage ‘skeleton’.
WARNING GRAPHIC CONTENT Sonia became first person in the world to receive a human trachea transplant
The operation was a significant milestone because the trachea has defied all previous attempts to use donor tissue
This was then seeded with the recipient’s stem cells (the body’s raw materials) — the implication was that the patient would ‘regrow’ their trachea, heralding a breakthrough in regenerative medicine.
Macchiarini then switched from donor tracheas to plastic ones, leading to more headlines as he took on a prestigious post at the world-renowned Karolinska Institute in Sweden.
Yet this breakthrough was anything but. For in 2014 it emerged that nearly all of the 17 patients worldwide who’d received these ’tissue engineered’ airways had died (the few still alive have survived in spite of the surgery).
Macchiarini had misrepresented data and exaggerated the effectiveness of his technique and was found guilty of research fraud.
He was given a 16-month prison sentence in Italy (where he’d operated on some patients) and last week, was found guilty in a Swedish court of causing bodily harm for performing the experimental procedure on a patient, and given a two-year suspended sentence.
Macchiarini’s case and others like it have far-reaching implications; not only can such fraud lead to potentially harmful treatments being given to patients, but pioneering research by other scientists can be halted, setting back progress.
Eric Genden, a head and neck surgeon at Mount Sinai Hospital in New York, who carried out the pioneering surgery on Sonia, had spent years working on his approach, but following Macchiarini’s announcements thought his work had ‘become obsolete, so basically shut down the lab’.
‘You can’t justify doing experimental surgery and immunosuppression [using drugs to stop the immune system rejecting the new organ] when you see something else that looks perfect, so you realise, wow, we’re out of business,’ he said last year.
Fortunately for Sonia, as Macchiarini’s work unravelled, Mr Genden went back to his idea.
Sonia had suffered from bad asthma all her life, regularly needing a nebuliser (a mask through which you inhale medication during severe asthma attacks), but says the asthma attack in October 2014 was ‘the worst’ she’d ever had.
‘I went to work and then out with friends, but when I came home, I couldn’t breathe,’ she says. ‘I couldn’t get any air in, even though I was using my inhalers and nebuliser to relieve it, I was suffocating. I couldn’t even call the emergency services — my neighbours had to, as I was gasping for air.
Yet this breakthrough was anything but. For in 2014 it emerged that nearly all of the 17 patients worldwide who’d received these ’tissue engineered’ airways had died (the few still alive have survived in spite of the surgery)
‘I was in hospital for two weeks, during which I was intubated, and then had a month in rehab.’
But the intubation that saved her life had also caused irreparable damage to her trachea, a pipe about 11 cm long that runs from the larynx (the voice box) to the lungs. One side of the trachea curves like a halfpipe and is composed of cartilage rings and ligaments; the other side is flat and mobile to move air to the lungs. Its job is to allow air in and out of the lungs and clean the lungs by trapping bacteria in mucus in the cilia, tiny hair-like cells that line it. The cilia sweep the mucus upwards and it’s coughed out.
The intubation and a subsequent tracheotomy — a hole in the throat through which a tube is passed to help with breathing — severely damaged 8 cm of Sonia’s trachea, causing scarring and a narrowing of the pipe.
In the seven years after the asthma attack, Sonia was in and out of hospital and had six major operations and more than ten procedures to try to improve her condition by cutting out the diseased area and reconstructing the trachea. These all failed.
‘I had a tube permanently inserted into my trachea through a hole in my throat to keep me alive,’ she says. ‘But every few days this would clog with mucus and I felt like I was suffocating.’
Daily life was fraught with fear. ‘I was constantly suctioning to clear the tube and used a humidifier to keep the air moist to help with breathing,’ she says. ‘I was careful when I went outside if it was too hot or cold, as this can also affect breathing. But most of the time I stayed at home and didn’t have much of a life because I couldn’t work or do too much.
‘I couldn’t really talk to people for more than five minutes because I couldn’t breathe. Even eating was problematic because the damage to my vocal cords meant that food would sometimes go down the wrong way.’
When the pandemic struck she ‘was very careful’ and while she didn’t catch Covid, she still ended up being in hospital most of the time with breathing problems. Despite ‘amazing support’ from her sister, Sandra, and her family, ‘it wasn’t a life and it was clear the condition was likely to kill me sooner or later — so I decided I’d have the tube removed and go into a hospice to be cared for until I died’.
Then one last Google search in 2017 changed everything. It revealed Mr Genden, who had been researching trachea transplants for 25 years.
After numerous consultations, he agreed to put Sonia forward as the first person in the world to have the operation. It took two years to get ethics approval for the procedure. Then, finally, a suitable deceased organ donor was found — a 37-year-old man. Choosing someone of the opposite sex means doctors can distinguish between the donor and recipient cells, to see how well the transplant had worked.
‘I was very keen to take it slowly as this is experimental surgery,’ says Mr Genden.
The risk for Sonia was that, in removing her own trachea, if the new one didn’t work, there was no artificial implant that could do the job instead. Sonia admits she was ‘scared and nervous’ before the procedure but felt she had ‘nothing to lose’. ‘I just thought even if I have five minutes of normal breathing, that would be great,’ she says. The 18-hour operation went ahead on January 13, 2021, with more than 20 surgeons and medical staff gathered in the operating theatre at Mount Sinai Hospital in New York. The team first extracted the donor’s trachea, and in the adjacent operating theatre removed Sonia’s diseased trachea.
Mr Genden stitched into place not just the donor trachea but — and this was the innovation that made the surgery possible — also part of the oesophagus, thyroid gland and thyroid arteries.
In the seven years after the asthma attack, Sonia was in and out of hospital and had six major operations and more than ten procedures to try to improve her condition by cutting out the diseased area and reconstructing the trachea
‘The key was including part of the donor oesophagus, as this meant the transplanted trachea already had its own blood supply which was then connected to Sonia’s blood vessels,’ says Mr Genden. Professor Guri Sandhu, a consultant ear, nose and throat surgeon at Charing Cross Hospital, in London, who is the UK’s leading damaged airway expert, described the surgery as ‘genius’.
Following the operation, Sonia was in hospital for a month but says she immediately felt better, despite being in pain. ‘As soon as I woke up I felt I was able to breathe,’ she says. A hole the width of a pencil was kept in her throat so doctors could easily examine her trachea in the months after surgery.
According to Professor Sandhu, this was the real test to see if the procedure had worked. ‘To know that the patient can finally breathe normally through the nose again is the glory moment,’ he says. ‘The patient has their life back.’
Around 150 people a year in the UK are diagnosed with serious tracheal damage — auto-immune conditions, radiotherapy for certain cancers and being placed on a ventilator can all cause it. ‘In the vast majority of cases, the damaged section of trachea — up to 6 cm long — can be cut out and the ends then stitched back together,’ says Professor Sandhu.
Deadly toll when doctors go rogue
Some of the more shocking examples of research fraud include the story of Don Poldermans, a former professor of cardiology in Holland. He claimed his research showed that beta-blockers (drugs used to treat high blood pressure and angina) should be used to reduce stress on the heart during non-cardiac surgery.
One of his studies showed that the drugs were associated with a tenfold reduction in heart attack or heart-related death in high-risk patients with existing heart disease within 30 days of surgery. He was later exposed for fabricating data and subsequent studies showed this approach actually increased the risk of death by 27 per cent.
It’s estimated that 800,000 people across Europe, including 80,000 Britons, died unnecessarily as a result.
More notoriously, Andrew Wakefield’s claim in 1998 that his research showed that the measles, mumps and rubella (MMR) vaccine was linked to autism was also discredited as fraudulent — but not before it had led to a huge drop in the number of children having the MMR jab. Wakefield’s study is being blamed for the re-emergence of measles in the UK and is also seen as the start of the anti-vax movement among parents rejecting the Covid vaccination for their children.
Just last year a review of 26 major trials of the drug ivermectin, an anti-parasite medicine that’s claimed can treat Covid, found that a third had serious errors or signs of potential fraud.
‘If the damage is more extensive, the only option is to keep a tracheotomy in permanently or insert a stent, a plastic or metal tube to keep the trachea open.
‘However, any artificial tubing will cause inflammation and further damage to the trachea, and because these tubes don’t contain cilia it leads to mucus plugging and the patient can feel like they are drowning.’
Mr Genden is understandably delighted by Sonia’s transformation, which was revealed in the American Journal of Transplantation in April 2021. ‘In 18 months, the trachea has never shown any signs of rejection and within 18 to 30 days her cells had grown into and repopulated the transplanted organ,’ he told Good Health.
The surgery is not without risks — transplant patients need to take immunosuppressant drugs potentially for the rest of their lives. But there is another side to this story that raises important issues for all patients.
Following his conviction, some of Paolo Macchiarini’s studies have been retracted by medical journals, and earlier this year UK cardiologist Dr Peter Wilmshurst, a campaigner for research integrity, called for the 2008 Lancet study to be withdrawn, too. The case, and others like it, have major implications for patients and scientists, says Dr Wilmshurst.
‘Research fraud causes harm to other researchers who spend time and often public money trying to take the next step, and then realise they can’t confirm the initial findings because they are based on a false premise,’ he told Good Health.
‘This delays new research, which has an impact on the health and lives of patients. In some cases, it actually causes harm to patients.’ (See box, previous page)
According to a study published in the journal PLoS One in 2009, as many as 2 per cent of scientists have ‘fabricated, falsified or modified data or results at least once’, and up to a third admit other questionable research practices.
‘The impact of research fraud is wide-ranging,’ says Dr Wilmshurst, who has given evidence to a House of Commons select committee on the issue. ‘It discredits science with the public and erodes the fundamental trust between doctors and patients which is essential for health research.’
‘As many trials are publicly funded, it is also a huge waste of taxpayers’ money.’
To address the problem, in 2020 the Cochrane Library (regarded as the gold standard of medical evidence review) launched procedures to crack down on fraud, such as checking whether a trial has been registered with a governing body before it started (so that the results can’t later be skewed to fit another thesis).
But more could be done to stamp out research fraud. Mr Genden is backing the call for The Lancet to retract the 2008 discredited study, telling Good Health that, after the furore it later caused, he ‘almost gave up on his research’.
In the end, his passion for finding a solution, which stemmed back to when he was a medical student and was involved in the care of a patient with a tracheal tumour who died, won through.
Sonia, understandably, is extremely thankful he persisted. ‘Having the trachea transplant has given me a new lease of life,’ she says. ‘It’s amazing.’
Source: Read Full Article