In 2017, the great London university UCL invited an external expert commission to investigate its role into the deadly trachea transplants performed by the former UCL honorary professor and scandal surgeon Paolo Macchiarini. An already sacked UCL nanotechnology professor, Alexander Seifalian, whose lab made the two UCL plastic POSS-PCU tracheas in 2011, was announced as the main culprit on UCL side for all the suffering of these two patients Andemariam Beyene and Keziah Shorten, as well as some recipients of vascular grafts. All this despite Seifalian’s having had no clinical role, training or ambitions, as he professed in his interview to the investigative committee, which I now obtained.

The interview also makes perfectly clear that the investigative committee’s surprise finding, namely that the nanotechnology specialist fabricated non-GMP certified plastic grafts for clinical use behind everyone’s back, was actually slanderous. Not only did UCL know very well that the product, which their own business branch UCLB approved for clinical use in Iran, Switzerland and India, was not GMP-certified, they even used it on their own patient at UCL hospital UCLH, in an attempt to grow a plastic nose. Even the UK regulatory authority MHRA was informed, and apparently did not mind or interfere. All this did not stop UCL investigators from publicly fingering cancer survivor Seifalian as the only culprit for that GMP-non-compliance.

Finally, the committee had information that Birchall allegedly proposed to make a plastic trachea for the child patient Ciaran Lynch in December 2009. Seifalian refused, for technical reasons, but this definitely and literally saved the boy’s life. Ciaran, presently one of just 3 known survivors of ~20 trachea transplants performed by Macchiarini and his former close associate, the UCL laryngologist Martin Birchall, was operated in London in March 2010 with a freshly decellurised cadaveric trachea graft supplied from Italy; Macchiarini was the surgeon. That clever Birchall-attributed idea, of being the first one to implant the utterly untested plastic trachea, and into a child no less, was somehow dropped from the final UCL report. Sod knows why.

I wrote about the outcomes of the investigation last year (here), right after the investigative report was published. This is now a follow-up, to help UCL explain their past and present activities to the UK Parliament’s Science and Technology Committee.

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Seifalian with UCL’s lost plastic nose. Photo: AP

These were the members of the 2017 external commission at UCL, indeed all recognised experts in the relevant field.

Stephen Wigmore, Professor of Transplantation Surgery, University of
Edinburgh, Chair.

Alicia El-Haj, Professor of Cell Engineering, Keele University.

David Tosh, Professor of Stem Cell & Regenerative Biology, University of Bath.

Marc Turner, Professor Cellular Therapy, University of Edinburgh and Medical
Director, Scottish National Blood Transfusion Service.

Pankaj Vadgama, Professor and Director of IRC in Biomedical Materials

Only one of them had a clear conflict of interest: Marc Turner, who is also “Non-Executive Director” at Cell and Gene Therapy Catapult UK, a commercial entity which is key partner on Birchall’s (currently suspended) trachea transplant clinical trials. Chair Wigmore saw Turner’s COI actually as a qualification (more here). No wonder the investigators concluded with enthusiastic calls for those same clinical trials to be commenced.

The lost nose and other plastic bits

This was the POSS-PCU trachea team at UCL, according to Alexander Seifalian in the transcript of his interview by investigative committee (who is labelled “A”):

“PROFESSOR EL HAJ: So who in the trachea would you have collaborated with that would know about cells?

A. The trachea team whole lot was in a combination of 20 a group of people, Martin Birchall was clinician, you know, Peter — Paolo De Coppi is a surgeon but he does a lot of stem cell work. James — Sam James and he worked a lot on trachea and stuff. Mark Lowdell, so these were all like a big group PCU presenting and these people come and say the cell grows here or we need rougher surface or we need that much when you made the whole 15 micro — you need 10, that was a group thing”.

There is no Sam James at UCL, but there is a Sam Janes. Apparently, the investigators didn’t bother to check. The paediatric thoracic surgeon and regenerative medicine enthusiast Paolo De Coppi is not even mentioned once in the investigative report (aside of literature references). This despite the fact that he helped transplant cadaveric tracheas for two of the patients it discusses (both described here). As the 2017 inquiry was specifically not defined as a misconduct investigation, this was conveniently used as a rationale to deny Seifalian his right to appeal, once he was blamed for basically everything. On the other hand, Macchiarini’s clinical colleagues at UCL, first and foremost UCL’s main trachea transplanter Birchall, were whitewashed to such a degree that the latter ended up being responsible for absolutely nothing bad or untoward that happened.

And one of the worst things UCL investigators discovered was: POSS-PCU plastic for human trachea and vascular grafts was not GMP-certified, and thus not suitable for use in patients. This was sold in October 2017 as a bombshell revelation of horrendous conspiracy by one man: Seifalian. The committee’s chair Wigmore declared in The Guardian:

“It’s very serious and it’s quite frightening to think that someone could be manufacturing this kind of device without knowing the regulations that govern it”.

However, Wigmore and his colleagues knew all that already when interviewing Seifalian about the plastic POSS-PCU trachea for patient Beyene:

“THE CHAIRMAN: The graft was manufactured in your lab, was it not? So that is not GLP, GMP?

A. No.

THE CHAIRMAN: Was he [Macchiarini, -LS] not concerned about that?

A. No.

THE CHAIRMAN: Did he have any plans to sterilise it.

A. He did sterilise it.

THE CHAIRMAN: How?

A. In Sweden — actually we sterilise it. but we send it autoclave but he is sterilising it again over there”.

Nobody sounds shocked or surprised about lack of GMP certificate, or raises this as a critique point, quite the opposite. It was merely established that Seifalian previously tested if autoclaving affected the quality of the material: it did not. The quality of plastic trachea was indeed a central topic of Seifalian interview, the committee member Vadgama even seemed to assume that Seifalian might have synthesised the POSS-PCU scaffold wrong, which prevented it from turning into a living working trachea.

Here is the evidence that the investigative committee even knew Seifalian informed the Medicines and Healthcare products Regulatory Agency (MHRA) about his work, and then postulated in their final report and newspaper interview that the Persian scapegoat did all in secret:

“PROFESSOR EL HAJ: So we have heard about the path of POSS-PCU in a cardiovascular context and it appears very rigorous. There has been a lot of tests done all the way through the process. Who decided what to do? Is that the clinician, Hamilton [George Hamilton, -LS], who defined those experiments and decided which ones to run?

A. No, we — I was in contact a lot with MHRA. We went to see MHRA, they said what tests you require to take to clinical application. I was, you know —

PROFESSOR EL HAJ: Were you leading that?

A. Yes, well initially”.

Funny how the committee went from “rigorous” to “frightening”, by simply pretending to have forgotten what they heard and saw. Like that plastic nose UCL implanted into their own patient at UCLH. The nose is nowhere to be found in the final investigative report, because one is not supposed to stick one’s nose into certain things. Here it is though, the non-GMP compliant UCL plastic nose:

“THE CHAIRMAN: Yes, okay. And the other applications that you were interested in for POSS-PCU, one was ear or cartilage replacement with POSS-PCU. Where has that developed?

A. Well, because POSS-PCU is a bit hydrophobic, it tends to extrude so that’s — you know, we did a patient with nose and I mean (inaudible) water became extruded because the way the surgery was not done very well but I thought maybe polymer is maybe not good enough so we stopped that.

THE CHAIRMAN: So there was actually a nose?

A. Yes —

THE CHAIRMAN: Scaffold made for plastic surgery?

A. Yes, we made it. They planted it.

THE CHAIRMAN: Where was that?

A. At UCLH.

THE CHAIRMAN: Did it have to be removed?

A. Yes.

THE CHAIRMAN: What was the problem? Was it infection?

A. Because nose was sticking out. Again, I never saw the patient, neither afterwards, say, but then they say the polymer was trying to extrude, yes.

THE CHAIRMAN: It came through the skin.

A. Yes, not here on the arm.

THE CHAIRMAN: It was being grown under the —

A. Just polymer cell, but this was when implanted they didn’t vacuum it and it was in the solution, you know, like inside, it was — wasn’t done properly”.

A trachea for Paolo

We also learn how Seifalian, whose UCL lab was making plastic vascular grafts, became involved with the trachea transplanters Birchall and Macchiarini:

“THE CHAIRMAN: So the original plan for POSS-PCU was always as a vascular graft?

A. As I say, my plan was cardiovascular devices.

THE CHAIRMAN: Tell us about how the trachea came about.

A. So Martin Birchall, he moved from Bristol to UCL and at the time they done — just before he moved to UCL they done a decellularized trachea, a lady in Spain (Claudia Castillo in 2008, -LS], put in the thing. So when he came he was interested and he 21 moved to contact me, I can’t remember if people introduce me, or how it happened, so. And he was interested, he came to our department and said, he was interested, I had lots of PhD students, I had a big team, so he was interested in being part of our team, so he became supervisor. At the time not clinically, I didn’t know there was a problem with trachea or anything, just like a … so I don’t know how it happened we got this PhD [ Claire Crowley , -LS] who suggested or something to work on trachea, work on trachea but she started working on trachea. I didn’t exactly —

THE CHAIRMAN: So it was Birchall who introduced you to that idea rather than Macchiarini?

A. Yes, I didn’t know Macchiarini at the time. Actually Birchall introduced me to Macchiarini as well. So Birchall when he came, then I knew him then he say can we get — could you help me to get a job for Macchiarini? I said well I’m not in a position to get a job for him. So that’s what he introduced me to Macchiarini and — at that time”.

The committee however postulated in its final report:

Seifalian and Birchall. Photo: UCL

“In May / June 2011 Professor Macchiarini approached Professor Seifalian directly and asked him if he could manufacture a POSS-PCU tracheal scaffold that could be used for a transplant procedure. Professor Birchall was not involved in this process”

 

Probably UCL investigators trusted Birchall’s version more than Seifalian’s. Why, is anyone’s guess.

Birchall’s and Seifalian’s photogenic PhD student Crowley then transported the plastic trachea to Sweden and delivered it into Macchiarini’s strong caring hands, as an online article reported. Another version goes: Macchiarini came to UCL and picked it up himself. Whatever happened: there was apparently no proper courier delivery as UCL investigators claimed:

“Two tracheas were made and sterilised by autoclaving and then transported to Professor Macchiarini at the Karolinska using a commercial courier”.

Nowhere in the interview did the UCL investigators bother to ask Seifalian how the plastic trachea was transported to Sweden. They apparently just assumed that Crowley did it right and proper. This scientist defended her PhD thesis (after leaving out a large part of her trachea transplant research) and now helps UCL professor and trachea transplanter Paolo De Coppi with artificial oesophagus (more here).

Lucky boy

Birchall was recruited to UCL in 2009, and soon after, in August 2009, Macchiarini became UCL honorary professor (details here). We know Macchiarini was pursuing the idea of using plastic trachea already in 2009, because he noticed that his decellurised cadaveric grafts were collapsing and killing his patients (read here). This excerpt from Seifalian interview suggests that Birchall had a similar idea also, and wanted to test it on 10 year old Ciaran Lynch, a paediatric patient of a UCL colleague of his, the Great Ormond Street Hospital director Martin Elliott. One does not test utterly unproven therapies and materials on child patients, but this is UCL, so it’s probably OK.

“THE CHAIRMAN: Can I ask you, at the end of December 2009 they were planning a transplant in a boy called Patient ABC [most likely Ciaran Lynch, -LS] and they ended up putting a decellularized and recellularized scaffold in. But Martin Birchall spoke to you before then saying could you make a synthetic collagen scaffold in case we need it as an emergency. Do you remember?

Birchall with Ciaran, Photo: UCL

A. Repeat.

THE CHAIRMAN: Synthetic collagen. Did you ever make anything like that?

A. No.

THE CHAIRMAN: Did he ask you to make a POSS-PCU scaffold?

A. Well, I can’t 100 per cent remember. All the time think, he could have asked it but I just like, you know.

THE CHAIRMAN: But you don’t remember making a scaffold for a boy?

A. No, no. I know I never did.

THE CHAIRMAN: You would remember that.

A. I know the boy but I never made a scaffold for it. Collagen or PCU or anything. But he may have asked me but I never made or anything like that. And at the time I wasn’t working on the trachea. I mean we didn’t even have this student so”.

None of this is even hinted in the final investigative report. Which is weird, don’t you think? Wasn’t it relevant to the topic of UCL trachea transpalnts, or was it putting Birchall into a rather bad light? The first plastic trachea patient in the world was hence Beyene, operated on 9 June 2011 at Karolinska university hospital in Sweden, and became an international success story, for all parties involved except the patient, whom that plastic trachea slowly and painfully killed (read here). 3 years after Beyene’s death, UCL investigators keep drilling Seifalian why he made theat POSS-PCU graft without proper testing or approvals:

“THE CHAIRMAN: And did you know if what you were doing was actually legal?

A. I thought it was legal, yes. Because I thought he got the permission — I mean —

THE CHAIRMAN: What did he [Macchiarini, -LS] did he actually tell you about the patient and what it was for?

A. Yes, he said got this patient, he had a cancer, radiotherapy, cancer come back and there’s no other option and if you don’t help him he’s going to die. So you know, and he needed a trachea and he said, you know, you cannot use the celluloid but too long and it doesn’t survive and if you make this POSS-PCU in the trachea for it. And then we were asking for longer time, he said no, there is no time. You have to make it. Thing. And virtually to me if you want to work inside the patient of course you have to have permission, working in a hospital over the years, I mean nobody could go in the operating theatre and just stick something into a patient because always you need — even when we were doing liver I had to put a probe on the liver, I had to get ethical approval so I assumed he got all the permission.

THE CHAIRMAN: You didn’t ask him for paper copies?

A. No, because I mean, it wasn’t my job to ask him you know that kind of stuff.

THE CHAIRMAN: Did you ask anyone within UCL if it was okay for you to manufacture something to —

A. Yes, UCL were happy — UCLB.

THE CHAIRMAN: But that is a business arm, isn’t it?

A. Because all the polymer work — was under them. They got the patent and they got the things.

THE CHAIRMAN: But they are not responsible for patient safety or any — they don’t have any regulatory powers. They are really just a business development organisation”.

Apparently, UCLB was not expected to confer with UCL experts or any UK authorities, or do anything responsible at all, while physicist Seifalian was expected to know about thoracic surgery and trachea biology, and face off extremely powerful UCL surgery professors Macchiarini and Birchall who demanded a plastic trachea from him:

“THE CHAIRMAN: You don’t have to say yes.

A. Well, you haven’t worked in the — sorry. What your expertise but just when you work in thing people demand you should do. If you say no, it is not very happy, 20 people come to say you have to work on it and if you are a scientific person, two times you say no, of course end your life.

THE CHAIRMAN: How much work had you done on the trachea before you made this trachea for —

A. So, you know, so actually it was yes, Martin Birchall”.

UCL’s unwelcome patient

Also, I myself was also invited to give evidence before the commission in April 2017 (here is my transcript, if interested). Now it is perfectly clear that the real purpose was to silence my reporting, by putting me under some kind of bizarre non-disclosure agreement. At that time, I was namely investigating the role of UCL in the trachea transplant Macchiarini performed on a British patient, the 19 year old Keziah Shorten. She died soon after Birchall and other UCL surgeons implanted a plastic trachea into her, after that first decellurised cadaveric graft disastrously failed. With help of witnesses, I was able to establish the role of UCL surgeons Paul O’Flynn and Birchall and publish this article.

That was the email I received on 27 May 2017 from the chair of investigative committee Wigmore, while preparing the relevant article:

“Dear Dr Schneider, can I remind you that you promised the inquiry not to publish any further comments on these matters before the conclusion of the Special Inquiry into Regenerative Medicine Research at UCL. You may not understand but your interference does risk undermining the inquiry and you also risk compromising your own integrity as a journalist  if you were to prematurely publish information which later turns out to be either different or erroneous from what you believe. As I told you at the time of your interview the inquiry will address the majority of the areas where you have an interest and also other areas but needs proper time and consideration to reach its conclusion”.

It turned out, UCL even organised an multidisciplinary team meeting on 11 June 2010 to approve the cadaveric trachea transplant on Keziah, which was then performed in Italy on 13 July 2010. It took me almost a whole year of Freedom of Information (FOI) badgering until the UK Information Commissioner’s Office forced UCLH to answer. Turned out, UCL hospital lost all records and documentation of that multidisciplinary team meeting, or pretended to (read here). My further FOI inquiries in this regard were simply ignored by UCLH.

The UCL investigators apparently knew everything. This is another excerpt from Seifailian’s interview:

“PROFESSOR TURNER:  We have spoken a lot about the first trachea which you made for Andermariam Bayenne but my understanding was there was also a second trachea, POSS-PCU in September 2011 which went to Keziah Shorten of UCL. Was that made in a similar way, can you tell us a little bit about that?

A.  Yes, so lots of good news about it and Martin Birchall wanted to do this second trachea for this girl.  She already had — I believe she already had a trachea before [the cell was trachea and what a class] and the girl was very bad shape and not doing very well and  stuff and they want and I said no.  The reason I said no is Paolo Macchiarini did the first patient, the first operation and he said please do not touch her.  And I said no.  Paolo’s patient is Paolo’s patient.  And he thinks it is not good enough.  And so they have    a meeting, quite a regular meeting at UCLH, all the group cardiothoracic. The guy was from Imperial College and a few people, I can’t remember their names.  So I didn’t go.  And once my PhD students jointly with Martin Birchall called Claire Crowley she went.  I said I’m not involved.  I’m not doing anything.  Then once I went there they asked me to come, so important, please come come come and Martin Birchall said the girl’s going to  die or this thing and can you go to see.  I said no, I’m not going to see.  So once I went there and I came out,  I wasn’t sure to do or what to do.  But if Claire does it that’s fine by me.  So they will apply a lot of pressure on me to do it.  Is this girl going to die even but she made a trachea.

PROFESSOR TURNER:  Did Claire make the trachea in your  laboratory?

A.  In my lab, I’m still boss.  I’m in charge of it but like she had a different supervision, different.  That I’m  just saying the clinician, you have — half of UCL clinical people saying you should make it —

THE CHAIRMAN:  She was a student still?

A.  Yes, a PhD student so she made that.

PROFESSOR TURNER:  Was it structured on CT scan findings as  you did with the — or were you not close enough to say?

A.  That was done very badly.  Well, not so much —  I suppose CT scan and there was going to be a trachea but I think they put in a stent and in the last minute without doing a — so I just never … never.

PROFESSOR TURNER:  Was that product recellularized?

A.  Yes, not by us, by Mark Lowdell.

PROFESSOR TURNER:  That went to Professor Lowdell’s lab.

A.  Again, he was charged — I didn’t get involved. I didn’t go there.  As a matter of fact that bypass I wasn’t happy from the beginning and I had made sure I had very little involvement”.

Crowley with a plastic trachea in bioreactor. Likely the graft used for Keziah Shorten. Photo: Seamus Murphy/ VII Photo Agency/ CNN, under fair use.

The interview mentions the second multidisciplinary team (MDT) meeting UCL had to discuss a trachea transplant for Keziah. It was organised by Birchall by an email from 26 June 2011:

“Re: my call over the weekend, this takes top priority.

Having spoken to a lot of people this week and over the weekend, we need to organise an urgent MDT meeting this week to discuss Kaziah, a Paul OFlynn patient at UCLH.

First check on the time and day.

At this stage, something like 6pm on wedensday in the MDT room at UCLH would be ideal and the person to liaise with over booking and running the session would be ciaran mariner (this would be an exceptional airway MDT meeting: he organises these normally).

Jeremy George is scoping her on tuesday morning, so sometime after that. We would need Jeremy’s images and all radiology at the meeting ideally.

People who need to be there are:

me

jeremy

paul oflynn

martin hayward

guri [Guri Sandhu, -LS]

george hanna from Mary’s

a radiologist: ideally Tim [Timothy Beale, -LS], but he could suggest one of the UCLH guys if they can make it.

Alex if he can make it plus Claire, otherwise Claire [Seifalian and Crawley, resp. -LS]

Anil Patel also if he can come

emails are all copied in above, but any gaps, let me know asap.

Thanks

Martin”

Maybe it is time for UK authorities to interfere with the travesty, as UCL proved themselves unable to investigate their own past patient abuse. The results of that 2017 whitewashing, obfuscating and scapegoating exercise which UCL calls an investigation, are now being used to justify more cadaveric trachea transplants, like the one done on a child at Great Ormond Street Hospital in May 2017. Luckily, the 3 clinical trials are now busted, but of course the trachea transplanters still look for new opportunities.


 

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5 thoughts on “UCL trachea transplant inquiry: scapegoating, obfuscation and a lost nose

  1. On Thu, 31 May 2018 at 08:01, For Better Science wrote:

    Leonid Schneider posted: “In 2017, the great London university UCL invited > an external expert commission to investigate its role into the deadly > trachea transplants performed by the former UCL honorary professor and > scandal surgeon Paolo Macchiarini. An already sacked UCL nanotech” >

    Like

  2. I have issues with Seifalian for his involvement in predatory publishing, but he was clearly given the sticky end of the lollipop in this debacle.

    Like

  3. Perhaps UCL and Great Ormond Street Hospital can explain to us how Macchiarini was appointed as an honorary consultant at GOSH and assisted with Ciaran’s trachea transplant on 15 Mar. 2010?

    Date of transplant, see Update 10.05.2017: https://forbetterscience.com/2017/04/20/ciarans-success-story/

    UCL press release: http://www.ucl.ac.uk/news/news-articles/1003/10031903

    GOSH press release: http://webarchive.nationalarchives.gov.uk/20110927095549/http://www.gosh.nhs.uk/pressoffice/pressrelease_00851

    Could Macchiarini have been an honorary consultant at GOSH on 15 Mar. 2010 when his GMC registration began on 19 Mar. 2010? GMC Medical Register (touch wood the link works) https://bit.ly/2kEZrfW

    The operation was planned in Dec. 2009 and the donor trachea was decellularized 1 month before transplant at Careggi Hospital in Florence, where Macchiarini worked at the time, so there appears to have been time to register.

    I admit it’s better than Krasnodar where Macchiarini wasn’t licensed to practice medicine and never applied for a license.

    Like

  4. Now we know how factual the 2017 UCL investigative report is. Not really factual, that is. UCL now admitted to me they are utterly unable to verify this statement of the report:

    “Two tracheas were made and sterilised by autoclaving and then transported to Professor Macchiarini at the Karolinska using a commercial courier”

    How so? I placed a FOIA inquiry about this alleged courier transport, because other sources declare the trachea was either delivered by Claire Crowley herself, or picked up by Macchiarini at UCL. After one month, UCL replied:

    “We can confirm that we do hold some information of the description specified in your request.

    From our preliminary assessment, we estimate that compliance with your request would exceed the appropriate costs limit under section 12 of the Freedom of information Act 2000, which is currently set at £450 (equivalent to 18 hours work) by virtue of the Freedom of Information and Data Protection (Appropriate Limit and Fees) Regulations 2004.

    Section 12(1) states that:
    “Section 1(1) does not oblige a public authority to comply with a request for information if the authority estimates that the cost of complying with the request would exceed the appropriate limit.”

    The section 12(1) exemption applies because we estimate that to determine whether we hold the requested information and then to locate, retrieve and extract it, would take longer than 18 hours to complete. This is largely because of the way the information is held here at UCL, which means that it is only accessible through archived sources. This contributes towards making your request a complex one to meet.

    Specifically, the information you have requested relating to shipping records (courier company, package number, date of dispatch/delivery, other available details of the shipment) for POSS-PCU plastic trachea manufactured by UCL and delivered to Karolinska Institutet (KI) is difficult to locate. This is because we do not hold such records going back seven years. Furthermore, the time period requested predates the current system we have in place for such records. Therefore in order to determine whether we hold the requested information, we would have to locate and analyse our archived records. We have been advised that to retrieve the requested information from our archived records would take approximately five days. This would take us well over the appropriate limit at which point the University is no longer obliged to process the request. So in accordance with section 12(1) the Freedom of Information Act 2000 (the Act) this email acts as a Refusal Notice”.

    So, UCL themselves can’t verify their own transport claims. Meaning, they wilfully shared unfounded claims (or lies, if you prefer) with the public. How much of that report is actually based on facts and how much on claims and wishful thinking?

    Like

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