A new colleague with a common interest
In October 2007, Jatinder Ahluwalia was appointed to a senior lectureship at the University of East London (UEL) and so he became a colleague of mine. His appointment came some time after I had first come across a paper in Nature which he had co-authored (Ahluwalia et al, 2004 ). In fact it was several months after his appointment before I realised that my new colleague was the first author of this paper. He had been a graduate of the University of East London and had a PhD from Imperial College, London. He had been a postdoctoral fellow at University College, London. At the time of his appointment, one of my older colleagues remarked that he thought that Ahluwalia had gone to Cambridge University to do a PhD.
I first read this Nature paper soon after its publication and it attracted my attention because it seemed to indirectly add weight to my scepticism about the likely benefits of large intakes of antioxidants. Ahluwalia was the first author amongst a very distinguished list of seven other co-authors from one of Britain’s top research universities and the paper was published in one of the most respected and influential science journals in the world. I thus confidently cited this paper in several of my books and papers as part of my critique and questioning of the benefits of antioxidant supplements.
This Nature paper as well as a PhD from one of Britain’s top research universities would no doubt have been important factors in the decision to offer him the position at UEL.
The essence of the Nature paper
Certain types of white blood cells called neutrophils ingest bacteria and fungi as part of our defence against disease-causing organisms. The traditional story is that neutrophils then kill these ingested organisms by generating a pulse of potentially very destructive reactive oxygen species or free radicals; this is sometimes called the oxidative burst or respiratory burst. It is these same free radicals that, according to the oxidant theory of disease/aging, produce the cumulative damage that can ultimately lead to aging and chronic age-related diseases like cancer and heart disease unless they are rapidly quenched by antioxidants. Free radicals are normally regarded as potentially harmful substances generated as by-products of metabolism or exposure to noxious stimuli like radiation or cigarette smoke. However, in this instance they are performing a useful function in helping to kill pathogenic bacteria and prevent infection.
This paper cast considerable doubt about the central role of free radicals in the killing of ingested bacteria and fungi. This was interpreted as suggesting that perhaps the destructive capability of these species had been exaggerated and this was picked up and relayed at the time by popular journalists including on the BBC news web-site . It seemed to cast doubt about the whole idea of great potential benefits from high antioxidant intakes and even about the value of drugs designed as antioxidants. The headline used on the BBC web-site for the report on this paper was:
“Doubt cast on free radical theory”
The senior author for the paper, Professor Tony Segal, makes clear in some comments to the BBC that this was how the UCL team interpreted these results:
“However, our work shows that the basic theory underlying the toxicity of oxygen radicals is flawed”
“Many patients might be using expensive antioxidant drugs based upon completely invalid theories”.
An enzyme known as NADPH oxidase is known to play a central role in this killing of ingested pathogens; killing which is referred to as the innate immune response. Genetic defects in the NADPH oxidase enzyme results in a condition known as chronic granulomatous disease (CGD) in which sufferers have repeated bouts of infection and even normally harmless bacteria can sometimes produce illness. Many people who inherit variants of this condition die in early childhood. The traditional view is that this enzyme leads to production of reactive oxygen species including something called the superoxide ion and this kills the ingested bacteria. What Ahluwalia et al suggested was that the NADPH oxidase activity leads to an influx of potassium ions into neutrophils via something known as the BK channel and the resulting potassium rich environment leads to activation of proteases (protein digesting enzymes) which kill the bacteria.
The key tenet of this paper was thus that the BK channel plays a key role in the killing of ingested bacteria and thus as the title of the paper claims “is essential for innate immunity”. They reported that blocking this channel with specific inhibitors prevented bacterial killing within the neutrophils. This work seemed to confirm findings about the key role of potassium ions in activating proteases previously demonstrated by Segal’s group and to identify the channel through which potassium ions were entering.
Serious doubts about the paper’s findings emerge
Other groups around the world tried to repeat these findings without success. It later transpired that even staff members within UCL, tasked with repeating this work, were also having extreme difficulty in replicating those findings that had been largely generated by Ahluwalia.
In an editorial published in 2007 in the American Journal of Physiology, Thomas DeCoursey effectively demolishes the key tenets of this paper:
- Seven laboratories around the world had failed to show any effect on bacterial killing of the specific BK channel blockers used by Ahluwalia et al i.e. blocking the “essential” channel did not prevent the innate immune response.
- Two groups had shown very clear evidence that this BK channel which was claimed to be essential for in the killing of bacteria and fungi within neutrophils was not present in neutrophils.
De Coursey bemoans the fact that:
“A great deal of time, energy, and expense has been consumed by the efforts of many laboratories to evaluate what can only be described as an erroneous hypothesis”
He makes no accusation of deliberate misconduct and makes only minor criticism of the peer review process that allowed the paper to be published.
UCL investigates and acts
In November 2010 an article appeared in The Times Higher Education Supplement (THES) which reported that this paper had been retracted from Nature by the seven other authors and that a formal investigation report published by University College, London had found that Ahluwalia had almost certainly committed multiple acts of research fraud in generating the data upon which this paper was based. When I first read this THES article, I had just sent back corrected proofs for a new edition of a book on Dietary Supplements and Functional Foods in which this paper was once again cited. I had to contact my commissioning editor to get all reference to this paper deleted from the manuscript before the book was printed.
It was in September 2008 that Professor Segal at UCL first made formal allegations that Ahluwalia had committed multiple acts of research misconduct. After a preliminary screening process, a research misconduct panel was established and held a hearing in February 2010. Ahluwalia did not attend this hearing or submit written evidence even though he was invited to do so. The committee considered the following three allegations against Ahluwalia.
- That he deliberately altered the labelling of computer files containing results so as to misrepresent his results. The committee unanimously concluded that this charge was proven beyond a reasonable doubt and it is said that Ahluwalia admitted that he had done this in an interview with Professor Segal and another co-author Professor Andrew Tinker.
- That he deliberately contaminated preparations of the specific BK channel blockers iberiotoxin and paxilline with another chemical diphenyleneidonium (DPI) which blocks the production and the effects of free radicals produced by NADPH oxidase. This DPI would block bacterial killing by neutrophils and thus create the false impression that the specific BK channel blockers had produced this effect. Analysis of some of the stored samples of iberiotoxin and paxilline were shown by sophisticated chemical analysis to contain DPI which was not present in fresh supplies of these materials. It was considered highly unlikely that this contamination had occurred accidentally. The panel unanimously concluded that “on the balance of probabilities it was highly confident that this second charge was proven”.
- That he supplied white blood cells to another member of the research team in a separate laboratory which were not of the type that he claimed them to be; they were not neutrophils but monocytes which would be expected to give results like those he had claimed for neutrophils. Again the panel concluded unanimously that “on the balance of probabilities it was confident that the third charge was proven”.
The report also concludes that no other research staff at UCL were in any way implicated in these acts of research misconduct and that they were solely due the actions of Ahluwalia. Other members of the team had acted in good faith upon the results and materials supplied to them by Ahluwalia. The committee even commended three professors on the author list for:
“Their rigorous forensic investigations to explain the aberrant results of Dr Ahluwalia that had led to the uncovering of this serious fraud”.
This is an important point because if there had not been this “rigorous forensic investigation” then the unrepeatability of Ahluwalia’s result would probably have been assumed to be due to indeterminable errors or flaws in the design, execution or analysis of the experiments. The end result may still have been retraction of the paper but Ahluwalia’s misconduct would not have been uncovered and publicly exposed. Another probable scenario is that the paper would become discredited but remain in the literature and gradually fade into obscurity. It also seems that there were misrepresentations in what Ahluwalia said in2002 to obtain his position in Professor Segal’s lab. He made no reference to his dismissal from the graduate programme at Cambridge and he said that his first degree was awarded by Imperial College.
Other allegations surface
In February 2011, some three months after the allegations from UCL were made public, it became clear that this was not the first time that Ahluwalia had been accused of research misconduct. As had been suggested by one of my colleagues, Ahluwalia had indeed gone off to Cambridge in August 1996 after graduating from UEL and he was supervised there by Dr Martin Brand who was a Reader in Cellular Biology in the Department of Biochemistry. In a letter dated November 1997 to the Secretary of the Board of Graduate Studies at Cambridge, Dr Brand gives a detailed explanation of why he considered some of the chart recorder traces produced by Ahluwalia had been falsified. In this letter Dr Brand makes it clear that he was no longer prepared to supervise him and recommended that he be removed from his position as a Graduate student and shortly afterwards he was dismissed by Cambridge for suspected research misconduct.
Ahluwalia joined Dr Brand’s research group and was registered for a Certificate of Postgraduate Studies (CPGS), a precursor to registration for a PhD at Cambridge. In September of 1997, Dr Brand met with Ahluwalia to try to sort out some discrepancies in the data that had been included in his thesis for the CPGS. Ahluwalia was initially unable to produce traces to support the graphical data that had been included in his CPGS thesis. Ahluwalia also included data in his thesis that involved the use of experimental rats and of radioactive substances but no record of the use of rats or disposal of radioactive material was recorded in the official logs for the dates on which Ahluwalia claimed to have conducted the experiments. It is a legal requirement to log accurate details of animal use and radioactive disposals.
Dr Brand then asked Ahluwalia to prepare a summary daily log of all the experiments he had conducted and the results that had been obtained. This log did initially seem to identify which experiments had been conducted on particular dates and this was cross referenced to apparatus traces and to data recorded in his lab book. However when Dr Brand examined the traces closely he came to the very firm conclusion that these traces had been falsified; a conclusion supported by a senior research colleague. The implication was that in order to allay Dr Brand’s suspicions, Ahluwalia had fabricated traces to match the summary data submitted in his CPGS thesis. Ahluwalia was unable to produce any alternative satisfactory explanation for the anomalies in the traces. Ahluwalia’s funding was withdrawn at the end of 1997. He was formally dismissed from the graduate studies program at Cambridge on February 18th 1998.
After his dismissal from Cambridge, Ahluwalia started a PhD in 1999 at Imperial College, London under the supervision of Dr Istvan Nagy. This was in collaboration with the pharmaceutical company Novartis where his industrial supervisor was Dr Marco Compagna. He was awarded a PhD by the University of London in March 2003.
A paper published in the Journal of Neurochemistry (Ahluwalia et al, 2003) summarised data that was an important contribution to his PhD thesis. This paper reported that application of capsaicin (a compound found in chilli peppers) to cultured nerve cells led to the release of a compound called anandamide. Professor Segal from UCL conveyed some concerns about this paper to the authorities at Imperial. This paper was eventually corrected in 2010 (i.e. 7 years after publication). The amount of anandamide claimed to be released by capsaicin was reduced by 1000fold. This error was attributed to the use of incorrect units in the original paper (a simple typo?). Clearly there must be serious doubts about whether the original referees of the paper would still have recommended acceptance of the paper if the corrected units had been used in the first submission; the original amount said to have been released would have been a physiologically significant effect whereas the new amount could be regarded as just trace amounts. In 2011, the paper was retracted at the request of all of the co-authors except Ahluwalia. This retraction was prompted by Professor Segal’s suggestion that the anandamide concentration reported in the correction was below the limits of accurate detection by the analytical methods used.
In August 2011, Imperial College announced that it was reviewing the award of Ahluwalia’s PhD because this paper was a cornerstone of the thesis. The report of this investigation was eventually released almost two years later in July 2013 The conclusions of this investigation were that there was no evidence that Ahluwalia had committed fraud or misconduct in his work at Imperial and thus that the award of his PhD should stand. They concluded that the problems in the results of the anandamide experiments were due to basic arithmetical errors and defects in the experimental methods and protocols used i.e. he was guilty of incompetence rather than dishonesty.
The report stated that Ahluwalia’s laboratory notebooks were meticulously kept, chronologically referenced and easy to follow. The machine printout (from the mass spectrometer) appeared to be genuine. The long delay between announcing the investigation and the publication of the report was partly due to difficulties the investigating panel had in gaining access to the notebooks of Ahluwalia which were in the possession of the industrial partner in his PhD project, Novartis. Eventually on 17th December 2012 a nominated representative of the investigating panel was given supervised access to these notebooks on company premises.
Dr Nagy, Ahluwalia’s supervisor at Imperial, told the panel that he believed the finding with respect to anandamide were real effects although a number of deficiencies in the conduct of the experiments may have led to inaccuracies in the measurements of the amounts of anandamide released. He said that his team had confirmed using different methods that capsaicin did cause anandamide release but the amounts were different to those reported in the retracted paper. When I used the search terms “Nagy” “capsaicin” “anandamide” I got one hit after 2010, a paper published in 2016 .
The impact at UEL
Ahluwalia continued with his administrative, teaching and research activities at the University of East London after the publication and publicising of the UCL report in November 2010. He continued to supervise and assess undergraduate and postgraduate research projects. Negotiations for him to act as supervisor for new PhD students were continued with other members of staff being asked to join his supervisory team. The provost of UCL had informed the vice-chancellor of UEL about the results of their investigation into Ahluwalia’s conduct but other UEL staff were never formally made aware of these accusations. They were also given no indication of what steps UEL was taking in the light of what had by February 2011 become multiple allegations of research misconduct against him. His academic colleagues had to rely for information upon reports in the Times Higher Education Supplement (THES) and web-sites like RETRACTION WATCH which publicise and discuss cases of alleged research misconduct. There was a considerable amount of comment and discussion of this case being submitted to web-sites like RETRACTION WATCH. Some of this internet comment was highly critical of UEL for continuing to employ him and for allowing him to continue with his full range of academic duties. The perception of several of the contributors was that UEL was sitting on its hands and hoping that interest in the scandal would fade away; this perception was shared by several of his colleagues at UEL. It was rather ironic that UEL seemed to attract considerable critical comment and bad publicity even though his alleged offences had all taken place in other institutions. It was reported in the THES and Retraction Watch that UEL was conducting an investigation but no information about the scope and terms of reference of this enquiry were given and it was not made formally known to his colleagues that this investigation was taking place, who was conducting it, or its terms of reference.
Many of Ahluwalia’s colleagues at UEL, including myself, were very unhappy about him continuing to perform all of his academic duties with these very public and apparently substantiated accusations hanging over him. Many students were certainly aware of the allegations. In the middle of February 2011, just after the Cambridge allegations were made public and the paper in the Journal of Neuroscience had had its first correction, I became concerned that some colleagues were completely unaware of the allegations against Ahluwalia despite their having been in the public domain for more than three months. This demonstrates just how complete the lack of information and guidance to his colleagues was. At the other extreme, some UEL staff were fully aware of the scandal and several expressed the view that Ahluwalia should be suspended from his duties at the university whilst any investigation was ongoing. I was so dismayed by the apparent lack of action and guidance that I sent an internal e-mail to staff in my subject area copying in the dean of the faculty which covered the following main areas.
- I gave a concise account of the allegations against Ahluwalia at Cambridge and UCL and also detailed the problems with the anandamide paper from Imperial which at that time had undergone correction but had not yet been retracted. I referenced this account using URL links to the key sources of information that I had used. I thought it was important that all of the academic staff working closely with him should know exactly what he was being accused of and the provenance of these various allegations.
- I asked for information about how the university authorities viewed these external accusations and their relevance to UEL. Were they seen as broadly accurate and reliable? Were they considered relevant to UEL and not just to the institutions where the alleged offences occurred? I requested that staff be made aware of what investigations were being conducted and what the terms of reference of any investigations were.
- I tried to emphasise that this request for information was not just morbid curiosity and that several of us had had to deal with issues related to the affair and some guidance about how to deal with these issues was needed:
- I had to make changes to an in press book to delete reference to Ahluwalia’s work
- Some staff had been asked for guidance by students who were considering becoming self-funded PhD students under his supervision whilst others were being pressurised to act as co-supervisors with him
- Material from the Nature paper was being used in taught courses and project students had been referred to it
- Other staff had acted as co-authors with him including one who had collaborated with him on article about plagiarism; the irony of a person found guilty of research fraud writing about an integrity issue was not lost on the bloggers with one on the K2 Blog headlined “Set a thief to catch a thief?”.
- I also suggested that until all of the investigations and decisions about his future were resolved certain minimum steps should be taken to protect the reputation of the university and to protect its students. Both I and many of my UEL colleagues felt that some form of temporary suspension was the most appropriate action in view of the seriousness and high provenance of these multiple allegations. However, I suggested in my e-mail that certain minimum interim measures should be taken to protect, the university and its students, particularly any graduate students for whom Ahluwalia might play an advisory or supervisory role. I suggested, for example that he be asked to withdraw from supervising existing research students and he should not be part of the supervisory team of any new research students.
When I circulated this e-mail, I anticipated that it would be met with some hostility from the faculty management and I was quite prepared for that hostility to be directed towards me. I hoped that it would elicit some answers and produce guidance about how to handle some of the consequences of the affair. I also hoped that it would help break down the wall of silence that had surrounded this issue for over three months. Several of my colleagues sent me e-mails of support.
What I (naively?) did not expect was that within a few hours of my sending it to colleagues, it would be leaked on RETRACTION WATCH and be reported in that week’s THES with the phrase “UEL staff in uproar” mentioned in both sources. I immediately made clear that I was not responsible for this external leaking and this was accepted by the dean of the faculty. In the aftermath of this leaking, it was made clear that this was a matter for management to discuss and decide upon and that other staff should not discuss it. I had originally intended my e-mail to be the first stage of an ongoing, escalating process intended to elicit clear guidance and to make the ongoing actions of the university more apparent and transparent. Its leaking effectively ended my active involvement in this process.
One argument used to argue against Ahuwalia’s immediate suspension was that this would be tantamount to an assumption of guilt before the internal inquiry had been completed. It is, however, normal practice to temporarily remove a person accused of some offence from sensitive positions during the conduct of an inquiry if there is prima facie evidence of misconduct. Temporary suspension does not imply acceptance of guilt especially if the accused continues to be paid during the suspension.
It was also suggested to me that the university could not take action in relation to even very serious offences committed elsewhere even if his actions had tarnished the university’s reputation.
Even a cursory look at some of his activities at UEL would have supported the case for an immediate suspension until the internal investigation was completed. According to his staff profile, he began working at UEL in October 2007 and within a year of his arrival he had published 3 single author papers. All of these papers gave only his UEL address implying that the work was conducted at UEL and with no collaborators. The first of these papers, (Ahluwalia, 2008 ) was received by the journal on 26th October 2007 and published online on 5th November. This paper reported the use of blood cells from healthy consenting adults that had been obtained “according to appropriate ethical guidelines”. There is no indication of how ethical approval was obtained or from whom it was obtained; it seems hard to believe that this was approved by an ethics committee at UEL. A key part of the paper involved the use of a sophisticated piece of apparatus known as a patch clamp and it describes the make and model of this apparatus. There was no functioning patch clamp apparatus available at UEL in October 2007 and so these experiments could not have been conducted at UEL. To perform experiments without ethical approval and without acknowledging where they were performed would be a breach of ethical research standards. If one takes this paper at face value, one is led to believe that Ahluwalia started work at UEL in October 2007 and before the end of that month had obtained ethical approval for the work, set up all the necessary laboratory apparatus (including a patch clamp), obtained all of the requisite chemicals, performed the procedures, analysed the data and written the work up and edited it to publication standard! Surely in the light of all the other allegations against him this would have been enough to justify his suspension?
There were clearly some deficiencies in the CV submitted to UCL. Were there inaccuracies or omissions in his application to UEL? Was his period at Cambridge mentioned and his departure from the Graduate Studies programme explained? Were UEL aware of the investigation being conducted at UCL by Professor Segal?
In mid-July 2011, 8 months after the initial allegations from UCL were made public, staff within my faculty at UEL received a short e-mail stating that Ahluwalia no longer worked at the university. As far as I am aware, this is the only information most of his colleagues ever officially received about the affair. His departure from UEL was announced in the THES and elsewhere and was said to be following “a formal investigation involving external peer review” which had first been announced in December 2010. The university declined to give any further information about the nature or findings of this review and it is not clear to me whether he resigned, was dismissed or financially encouraged to leave.
My personal assessment of the how well this case was handled by the institutions involved
Ahluwalia started on his graduate studies in Cambridge in August 1996. He was accused of research fraud after about a year and dismissed in February 1998. His supervisors were quick to spot his suspected misconduct and acted rapidly to remove him and protect the university’s reputation. Presumably he left Cambridge without a reference and a gap in his employment history that would have to be explained to any future employer. To have taken any further action to publicise his alleged misconduct could have been perceived as harsh for a young and inexperienced scientist and a first offender.
At UCL he was employed as a postdoctoral fellow, following an apparently successful period as a doctoral student at Imperial College. Once it became clear that even colleagues within UCL were having problems reproducing his findings, a very thorough forensic investigation was undertaken and the report of these findings made public. From reading the report, this seems like a fairly sophisticated and multi-layered effort by Ahluwalia to deceive his collaborators. I believe that Ahluwalia’s colleagues at UCL made great efforts to unmask his misconduct and UCL’s handling of the affair seems to have been transparent and open. Professor Segal even gave an interview about the affair to the THES published in August 2012 and I have heard Sir Malcolm Grant who was president and provost of UCL speak about this case at a closed meeting.
Imperial College eventually investigated Ahluwalia’s conduct during the period that he had been registered for his PhD. Their report was completed in June 2013, almost 3 years after the accusations from UCL became public and this report is accessible on the internet. The initial response of Ahluwalia’s co-authors was to amend a key paper before eventually retracting it. The report into his conduct there was delayed because the panel could not get immediate access to his laboratory notebooks or interview him. His notebooks were held by the commercial partner for his PhD work. Eventually, one member of the investigating panel was given a day’s access to his notebooks on company premises. This seems like a less than satisfactory arrangement and the panel recommended in their report that in any future collaboration with a commercial organisation, the university should ensure that it is guaranteed access to data generated by its research degree candidates when legitimately required. My personal feeling is that the initial responses from Imperial were reluctant and that certain features of the investigation and report were less than ideal.
What about my own institution? I have less hard information about how UEL handled this matter than for any of the other three. A report into his activities was apparently commissioned but I have no information about its conduct, terms of reference or findings. When the scandal broke, all of the serious and evidenced allegations against Ahluwalia stemmed from the time before his appointment. I still believe that UEL should have temporarily relieved him of his academic duties (with or without full pay) whilst the internal investigation was in progress and I believe they had ample grounds to justify this. His actual or de facto suspension would probably have prevented all or most of the internal and external criticism of UEL at the time.
Cambridge, UCL and Imperial are all research intensive universities with a long history of managing top level research and researchers and they may well have dealt with previous cases of alleged research misconduct. As far as I am aware this is the first high profile accusation of this type that UEL has been faced with. UEL now has a very detailed research integrity policy, has staff in the graduate school with a specific integrity role, it is a subscriber organisation to the UK Research Integrity Office and adheres to the research concordat produced by UKRIO. There are courses and seminars for staff and research students dealing with aspects of research integrity. Everyone makes mistakes, my own sending of an electronic e-mail to many recipients, for example, now seems like a naive error of judgement. The important thing is to learn from our mistakes. I believe that UEL has made serious efforts to train researchers to make sure their research is ethical and has structures in place designed to help ensure high standards of research integrity. My strongest and abiding criticism of UEL’s actions would be the secrecy surrounding the whole affair even after the externally led investigation was completed. As John Gill wrote in his editorial relating to an article about this case:
“Sunlight is the best disinfectant, and the UK’s institutions and researchers must be fearless in shining a light on misconduct”.