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Exclusive: Nobel laureate embroiled in research scandal
A stem cell company co-founded by the leading geneticist Professor Sir Martin Evans conducted unlawful medical trials in Greece
A Nobel laureate has become embroiled in a major research scandal after it emerged that a stem cell company he co-founded conducted unlawful medical trials.
Professor Sir Martin Evans, one of the country’s leading geneticists and the former Chancellor of Cardiff University, was involved in trials in Greece which took place without authorisation, and were described by the country's regulators as a “violation” of national legislation.
He is accused of going on to mislead the British medical watchdog when seeking approval for a new round of trials at one of the UK’s leading hospitals.
Two years after winning the Nobel prize for his work on embryonic stem cells, Prof Evans went into business with Ajan Reginald, a struck-off dentist turned stem cell entrepreneur.
Mr Reginald was banned from practising as a dentist in 2005, after the Dental Practise Board found him guilty of mistreating dozens of patients and fleecing the board out of money by claiming payment for operations he had not done.
He is now the CEO and co-founder, along with Prof Evans, of a bio-medical firm called Celixir which is sponsoring a landmark heart disease trial at the Royal Brompton Hospital in London.
The trial, which involves injecting stem cells into patients’ hearts, promises to improve the quality of life for sufferers of heart disease which could offer hope to millions.
It was due to start in 2018 but it has been delayed for over a year after a whistleblower alerted regulators about Celixir’s previous trial in Greece which took place between 2012-15.
After receiving “allegations of improprieties” about the trials, the Greek regulator launched an investigation and found that they had taken place “without submission of application for approval by the National Competent Authority and favourable opinion by the Independent Ethics Committee”.
They said that Celixir committed a “serious GCP [Good Clinical Practise] and national legislation violation” as well as “further GCP violations”, adding that they had imposed sanctions on Celixir, the principal investigators of the study and the hospital where the trials took place.
Now Cardiff University is investigating an allegation that Prof Evans committed research misconduct by publishing a scientific paper based on an unauthorised trial.
Heart scarring on the 11 patients in the Greek trial had reduced 12 months after the treatment and their quality of life had improved significantly, according to the article which was published in the Journal of Cardiovascular Translational Research.
The journal article – which names Prof Evans as well as the leading heart surgeon Stephen Westaby among its authors – has also launched an investigation.
Mr Westaby said that all the patients in the Greek study “remain remarkably - and unusually - well”, adding: “I went to Greece to see that for myself.”
Celixir won approval from regulators for the UK trial after stating that the cells they intended to inject into British patients’ hearts had already been tested in Greek patients in an “authorised” trial.
However, it can now be revealed that Celixir misled both the regulators and prospective patients by citing the Greek trials.
An investigation by the Health Research Authority (HRA), the medical ethics watchdog, concluded that it is “unclear” which type of cells were injected into Greek patient’s hearts.
The HRA ordered Celixir to make “substantial” changes to their information brochures to ensure patients they recruit to the British trial were not misled. Celixir was told to remove all references to the Greek trial, and to make it clear that the Royal Brompton trial is a “First In Man” study.
Prof Patricia Murray, an expert in stem cell biology and regenerative medicine at Liverpool University, contacted the HRA last year to alert them about the inconsistencies in the Greek trial.
“I was concerned that British patients were being exploited,” she said. “This sort of thing brings the whole field of regenerative medicine into disrepute.”
A Cardiff University spokesperson said: “We can confirm that we have received an allegation in relation to this. It is currently subject to a preliminary review under the University’s Academic Research Misconduct Policy. It would be inappropriate to comment any further at this point.”
A spokesman for the HRA said: “Concerns within the remit of the HRA were investigated, and a summary of the outcome provided to the Research Ethics Committee (REC) that reviewed the original application to consider whether any of the information had implications for the committee’s opinion of the study.
“The REC considered whether potential participants would be provided with fair information about the study when making a decision to participate. The REC asked the sponsor to make a number of changes to the Participant Information Sheet which have since been submitted to and approved by the REC.”
A spokesman for the Medicines and Healthcare products Regulatory Agency said that they conducted an internal review after being made aware of “possible inaccurate information”, but added that the outcome of the review “did not alter" their approval for the trial to go ahead.
A spokesperson for Royal Brompton and Harefield Trust said: “This study has been reviewed and approved by the MHRA and the HRA. This includes review by an NHS Research Ethics Committee. Our participation as a trial site in any research study, is entirely contingent on receiving all necessary regulatory approvals.”
A spokesman for Celixir declined to comment. Prof Evans and Mr Reginald also declined to comment.
Professor Sir Martin Evans: The Nobel Laureate best known for creating 'knockout' mice
Best known for the creation of “knockout” mice, Professor Sir Martin Evans, 79, is one of the most respected geneticists in Britain.
He is widely credited with working out how to isolate embryonic stem cells, as well as helping to create mice genetically engineered to have human diseases.
The "knock-out" mice, as they were known, became a cornerstone of biomedicine, from basic research into devastating illnesses to the development of new treatments. The genetic techniques he pioneered revolutionised research into diseases from heart failure to cancer.
Prof Martin and his colleagues won the Nobel Prize in 2007. His chief contribution was to use special cells extracted from early-stage mouse embryos to deliver the modified genes.
After working as a lecturer at University College London and Cambridge University, he was appointed as Professor of Mammalian Genetics and Director of the School of Biosciences at Cardiff University, where he worked until his retirement in 2007.
In 2009 he was appointed president of Cardiff University, the same year that he went into business with Ajan Reginald. Their company, initially called Cell Therapy Limited has since rebranded as Celixir. He was also made Chancellor of Cardiff University, a ceremonial position which he held until 2017.