But it is not unethical in the same way as fabrication or falsification of data is. Someone indulging in the latter is likely to get fired. Immediately. Ask Jan Hendrik Schön.
While not citing other people's work (particularly for interesting research ideas) may not get a person fired, it could still blow up -- particularly when this offence is repeated -- to create an international scale embarrassment to the culprit and his/her organization. Ask Armando Córdova.
Thanks to Janet Stemwedel for the link to the C&EN story by William G. Schulz.
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Stockholms universitets naturvetenskapliga fakultetsnämnd
Stockholms universitet
106 91 Stockholm
Investigation of the allegation against Professor Armando Cordova, Stockholm University, concerning possible unethical behaviour in science
We, Torbjörn Frejd and Olov Sterner, both professors in organic chemistry at Lund University, have been appointed by the Faculty of Science at Stockholm University to investigate the possible misconduct in science on the part of Professor Armando Cordova. The allegations against him from several scientists are basically that he does not acknowledge the work of others, by not including them on joint papers or by referring to published work in an incorrect way, and thereby making himself appear more important in his scientific field than he actually is.
We would in the beginning of this report declare that we believe that publishing is the very essence of academic research. The scientific community as we know it can not exist if new knowledge is not transferred to fellow scientists, either in the form of publications in scientific journals or as oral presentations in public or in private. The rapidly growing competition for research grants and positions makes it necessary for all research groups to improve their scientific output, and it may be tempting, especially to young researchers, to attempt short-cuts that rapidly bring them to the border between normal and unethical behaviour. If left unattended, the short-term success that could be achieved by such behaviour would, by the laws of evolution, eventually force others to do the same in order to survive in research. It is therefore critical that accusations about unethical behaviour in science are taken seriously and investigated. It must of course be remembered that finger-pointing by itself does not prove anybody wrong. The academic world is full of extremely ambitious individuals that are in personal conflicts with their competitors, and false accusations must be treated seriously as well.
Short description of Armando Cordova’s carrier.
Professor Cordova carried out his PhD work in the area of lipase catalysed reactions at the Royal Institute of Technology under the supervision of Professor Karl Hult, Department of Biochemistry, and presented his thesis in 1998. After his PhD, Cordova was first a post-doctoral student in Professor Janda’s group at the Scripps Research Institute (TSRI) and then joined Professor Barbas’ group at the same institute. In Professor Janda’s group he worked with lipase catalysis and catalytic antibodies, and there were no publications in the field of organocatalysis using small molecules during this period. This research area was on the other hand the central topic in Professor Barbas’ group, and several publications were made during the stay in his group. Our conclusion is that Professor Cordova’s interest for organocatalysis started during his work in the Barbas group, and from an objective standpoint Cordova’s first work in organocatalysis originated from the postdoc period in the Barbas group. After returning to Stockholm, now as assistant professor (forskarassistent), at the Department of Organic Chemistry at Stockholm University, Professor Cordova has intensively investigated the area and has published a large number of papers in a short time period. Compared to other young academic scientists he has an outstanding publication record. He has consequently been awarded several important research grants and in 2006 he received the Erlander prize from the Swedish Academy of Sciences.
Our ambition in this investigation has been to be completely fair, and in order to get the full picture we have interviewed a number of persons. Some have been part of Professor Cordova's PhD-period, e.g. Professor Karl Hult and Professor Torbjörn Norin, while others, e.g. Professor Christina Moberg and Professor Jan Erling Bäckvall, are part of his present scientific environment. We have talked to Professor Cordova and all 6 PhD and postdoc students now working in the Cordova group, as well as to a former co-worker (Dr. Jesus Casas). We have also discussed with scientists that have been critical to Professor Cordova, e.g. Professor Donna Blackmond, Professor Karl Anker Jörgensen, and Professor Carlos Barbas III. In addition, we have tried to extract information from various scientific journals in order to establish the role of several individuals during the processing of manuscripts submitted for publication. However, most journals do not wish to contribute to investigations of this kind, and this has hampered the investigation. The contacts have been either in person, via telephone conversations and via e-mail exchange. A number of documents have been sent to us and we have had access to Professor Cordova’s laboratory notebooks at Stockholm University. After a thorough study of the information that we have acquired we have identified four cases in which we have become aware of different degrees of questionable or unethical behaviour. The cases are described and discussed below.
Case 1 (The Barbas case)
Professor Cordova joined the research group of Professor Janda in 1999 at The Scripps Research Institute (TSRI) and worked there for two years without any problems known to us. While still at Scripps, Cordova joined Professor Barbas’ group in 2001 to continue his postdoctoral period. The exact reasons for Cordova’s interest in joining Barbas group are not know to us, but apparently the research group was becoming more engaged in organocatalysis, a field in which Cordova had no previous publications. During this time Cordova and Barbas made several joint publications but they ended up in having different opinions and their cooperation broke down.
A manuscript describing research conducted during this period was submitted first to JACS (December 2002), and later to Tetrahedron Letters (Febr. 17th, 2003), by Professor Cordova, without the consent of Professor Barbas. Professor Barbas actually stopped the processing of the manuscript (a copy of the manuscript submitted to JACS was sent to us by Professor Barbas and is attached as Enclosure 1 and the manuscript submitted by Cordova to Tetrahedron Letters but later retracted is attached as Enclosure 2). In an e-mail to the Head of the Department of Chemistry at Stockholm University in April 2003, Professor Barbas explained the reasons for Cordova’s dismissal from TSRI due to unprofessional and inappropriate behaviour (Enclosure 3). The e-mail was later sent to us as a signed letter by Professor Barbas (Enclosure 4). In this letter and a separate e-mail to Professor Bäckvall, Professor Barbas asked for information whether Dr. Cordova was appointed as Assistant Professor at SU and was informed via e-mail from Professor Bäckvall that this was the case (Enclosure 5). Professor Barbas was also concerned about the possibility that Cordova would submit the manuscript discussed above again. Indeed, Cordova submitted the manuscript to Synlett on May 21st 2003 and it was published in Cordova’s name (sole author) in 2003 (Enclosure 6). We regard this as a clear case of unethical behaviour. Work done in the Barbas laboratories must have his approval as supervisor and responsible for the research group before publication. There is no doubt about this in the scientific community as far as we are aware.
It should be noted that this Synlett paper was based on the manuscript sent to but rejected by JACS (vide supra) and that it in its earlier form had the three authors Cordova, Turner, and Barbas (Enclosure 1). The almost identical manuscript was sent to Tetrahedron Letters with only Cordova as the author (vide supra, Enclosure 2). Although it was accepted for publication it was retracted after intervention by Professor Barbas.
According to Professor Cordova, he contributed to a substantial degree to another study that eventually was published in JOC (Enclosure 7). However, he was not included as an author but instead acknowledged for technical assistance. Looking in the supporting information of that JOC paper it is apparent that Professor Cordova’s spectral data are included (by comparing with copies of the raw data provided by Professor Cordova made available to us and deposited at Lund University), and it is reasonable to assume that he had contributed with a number of syntheses of the compounds dealt with in the publication. Professor Cordova regarded this as an injustice and a serious matter for him. On this matter Professor Barbas made a comment that it is possible that the collection of spectra were made also by others in the group and not only by Cordova (see Enclosure 8).
It should also be noted that during his stay in Professor Barbas group at TSRI, Professor Cordova on September 29th, 2002, submitted a research application to NIH as the principal investigator (Enclosure 8a). The application did not include Professor Barbas name but was supported by TSRI officially by the signing of Kaye I. Wynne (V. P., Office of Sponsored Programs) and Jeffrey W. Kelly (V. P., Academic Affairs). It is our impression that TSRI supported Professor Cordova’s application and that he would be an independent researcher at TSRI if the application were granted, although as far as we know it was not. However, it should be noted that this application contains a substantial part of what Professor Cordova later has realised and published. Thus, already in 2002 Professor Cordova suggested a number of reactions, which were proposed to be catalysed by low molecular weight amines. In view of close similarities of Cordova’s publications with publications made by others they should also be seen in the light of Cordova’s NIH-application.
On this matter professor Barbas explained the background for the NIH-application and that he (Barbas) agreed that Cordova submitted this application despite doubts on its quality. The comment by Professor Barbas is shown in Enclosure 8, which also contains other complaints.
Case 2 (The Blackmond case)
The Blackmond case is especially complex, and is therefore discussed in greater detail than the other cases. We have been granted access to the exchange of letters and e-mails between the involved parties, and have consequently been able to follow the case in a chronological order.
On November 21st, 2005, Professor Donna G. Blackmond (Professor of Chemistry as well as of Chemical Engineering and Chemical Technology at Imperial College in London, and holder of the Chair in Catalysis) submits a paper to Nature. The title is "Thermodynamic control of asymmetric amplification in amino acid catalysis", it was accepted for publication on March 30th 2006, and it was published in the June 1st issue (Nature 441, 621-623 (2006), Enclosure 9). The paper describes a new model that explains asymmetric amplification (nonlinear effect) in a chemical reaction catalysed by amino acids, and the basis of the model is the equilibrium between solid phases and the solution of a given amino acid in a ternary system. The nature of nonlinear effects in amino acid catalysis had up until then been debated, but the Blackmond Nature paper showed that they do exist and explained why. For the proline-catalysed aldol reaction they found that the relationship between the ee of the proline catalyst and the ee of the aldol product is linear at lower proline concentration, when proline is fully dissolved, but becomes nonlinear when the concentration is so high that dissolved proline is in equilibrium with solid proline. In the latter case the product ee is largely independent of the proline ee, and the same goes for the ee of the dissolved proline. When in equilibrium with solid proline, the ee of the dissolved proline remains at approximately 50 % even if the ee of the total proline varies between 10 and 90 %. This finding prompted the group to investigate the phase behaviour of proline, and they found that unequal proportions of the two enantiomers in amounts exceeding their solubility in DMSO gave two separate solid phases. One is the racemic compound (D:L 1:1), and the other contains only the excess enantiomer (D or L). Based on their extensive data they could construct a ternary phase diagram for the system D-proline, L-proline and DMSO, and this allowed them to identify the eutectic composition which for proline corresponds to a solution with an ee of approximately 50 % (as long as the total proline ee is not very low or very high). The group went on to study the ee in the solution at the eutectic point of several ternary systems of various amino acids in water. For serine it was found to be >99 %, meaning that close to racemic serine in water and in a concentration that exceeds its solubility will give a chiral amplification that equals that of enantiopure serine in solution. The findings indicate that amino acids may have been important for the start of biomolecular homochirality, and are therefore of a general interest. The paper and its conclusions is based on solid experimental data, published as supplementary information (Enclosure 10), and it is obvious that the Blackmond group had spent a lot of time and energy on this investigation. In particular, this work required careful measurement of the solubility limits of amino acids in water and other solvents, as well as accurate measurement of solution phase enantiomeric excess of the amino acids themselves at various overall ee values (not simply measurement of the ee values for the products of reactions catalyzed by amino acids). This work requires sophisticated reverse phase chiral HPLC and extensive analytical development to ascertain conditions for accurate separation of the enantiomers. It is also important to note that eutectic points (both concentrations and enantiomeric excess values) had not been published in the open literature prior to the Blackmond Nature paper.
Approximately one week later, on November 29th, Professor Blackmond delivers the Holger Erdtman Lecture at KTH (the Royal Institute of Technology) in Stockholm, and presents her findings concerning nonlinear effects in amino acid catalysis. Professor Armando Cordova is present in the audience.
During the week after the lecture, the Cordova group studies nonlinear effects in acyclic amino acid catalysis of an aldol reaction as a function of the catalyst concentration. The results are included in a manuscript that Professor Cordova submits to Chemistry - A European Journal (CEJ) on December 30th, 2005. The manuscript was accepted and published online on April 25th, 2006 (Chem. Eur. J. 12, 5383-5397 (2006), Enclosure 11). The title is "Direct asymmetric intermolecular aldol reactions catalyzed by amino acids and small peptides". It essentially describes how various amino acids, chiral amines and small peptides can catalyse direct asymmetric intermolecular aldol reactions with high stereoselectivity, and it does it by discussing four things: a) Structure-activity relationships; b) Synthetic scope; c) Catalysis in aqueous media and water; and d) Reaction mechanism. Towards the end of the manuscript, the authors introduce the concept "nonlinear effects". For alanine and valine, the results of an investigation of how the ee of the product of an aldol reaction in DMSO containing 10 equivalents of water at room temperature is affected by the ee of the amino acid catalyst (0.075 M, 30 mol%) is presented in Figure 1, page 5391. It is stated that the authors did not observe significant nonlinear effects in the alanine- and valine-catalysed reactions, but that a slightly positive effect can be observed at lower catalyst ee and a slightly negative effect can be observed at higher catalyst ee. Without any data, it is claimed that the effect is stronger if the concentration of the amino acid is increased to 100 mol%. With serine, a significant positive nonlinear effect is reported, and this is stated to be caused by" the different solubility of the two-enantiomer crystals of the scalemic serine catalyst mixture in wet DMSO". The authors also investigated the effect of a dipeptide, (S)-ala-(S)-ala, on the asymmetric aldol reaction, and found that the correlation between dipeptide ee and aldol product ee was perfectly linear. This is taken as an evidence for that only one molecule of the catalyst is involved in the transition state and the reaction mechanism. However, in the next sentence it is suggested that the absence of nonlinear effects in this reaction may be explained by the higher solubility of the dipeptide compared to alanine and valine.
The references/notes given in this part of the paper are the following:
1. When it is stated that no significant nonlinear effects were observed in the alanine- and valine-catalysed reactions, the reader is referred to (reference 28) two papers that support the existence of nonlinear effects in proline-catalysed intramolecular aldol reactions (Puchot et al, JACS 108, 2353 (1986), Enclosure 12) and Guillaneux et al, JACS 116, 9430 (1994), Enclosure 13), and one more recent paper that demonstrates linear relationships for proline-catalysed intramolecular and intermolecular aldol reactions but that primarily addresses the question if the reaction mechanism involves one or two prolines (Hoang et al, JACS 125, 16 (2003), Enclosure 14). The reader is directed to Cordova et al (Chem. Eur. J. 11, 4772 (2005), Enclosure 15) for the first observation of a positive nonlinear effect in a proline-catalysed intermolecular asymmetric aldol reaction. However, this paper does not discuss nonlinear effects.
2. The eutectic point appears in the text to be defined as the point of intersection of the plot of the ee of the amino acid catalyst against the ee of the aldol reaction product, of a nonlinear (reaction that displays a positive effect at lower ee:s and a negative effect at higher ee:s) and a linear (reaction with a linear relationship between catalyst and product ee:s) reaction. However, the wording is not clear, and the origin of this relationship is not discussed. In reference 29 the eutectic point is defined as "the point at which all three phases – (R)-amino acid, (S)-amino acid, and DMSO – can exist simultaneously."
3. When the remarkable nonlinear effect in the case of serine is explained, as being caused by the different solubility of the two-enantiomer crystals of the scalemic serine catalyst mixture in wet DMSO, the reader is directed to reference 30. This is P. Dziedzic, W. Zou, I. Ibrahem, and A. Cordova, unpublished results.
Several things in this manuscript are conspicuous:
1. The small section about nonlinear effects is out of the context of the main part of the manuscript. No experimental data are revealed, except in the figures, unlike the rest of the manuscript in which all the data are carefully presented in tables. There are several typographic errors and unclear wordings in this section.
2. There is no reference to the work of Professor Blackmond, although it is clear that Professor Cordova was present when she gave the Erdtman lecture and that he was impressed by her results. Instead, the references given in this section are to less relevant papers, and to work of his own that is unpublished (later shown to be carried out after the Blackmond lecture).
3. The same data presented describing the "slight" nonlinear effect with alanine in Figure 1 was published previously (Angew. Chemie Int. Ed., 44, 7028 (2005), Figure 1, Enclosure 16) by the Cordova group, lacking a few data points, but in that paper these data were clearly stated to represent linear behavior: "Plotting the enantiomeric excess of alanine versus that of β-hydroxy ketone 2 showed a linear correlation (Figure 1)."
4. The Cordova group appears to have a dim apprehension of the concept "eutectic point". The definition given in Footnote 29 is incorrect. No explanation of how or why the eutectic point should be related to a curve of product ee vs. amino acid ee is given. The cause of the nonlinear effect noted in the reaction catalysed by serine, perhaps the most significant result reported in the paper, is almost quashed by referring to "unpublished results". It is later shown that all experiments involving nonlinear effects with serine were carried out after Professor Blackmond's Erdtman lecture.
After reading the paper of Professor Cordova, Professor Blackmond on April 28th 2006 writes to Professor Bäckvall (Head, Department of Organic Chemistry at Stockhom University) and Dr. Compton (Editor, Chemistry – A European Journal) to raise the question of scientific misconduct on the behalf of Professor Cordova, as she recognised that concepts presented during her Erdtman lecture are used without referring to her work. Professor Blackmond points out several weaknesses with the paper; that the results reported on nonlinear effects lack backup of scientific data, are poorly interpreted and in some parts confusing or even wrong. She suggests that Professor Cordova is required to publish a Correction in the journal. The response from Professor Cordova comes one week later, on May 3rd, in which he chooses not to address the questions raised by Professor Blackmond but instead criticizes her Nature paper (provided by Professor Blackmond in her letter and by then accepted for publication) among other things for not citing the work of Cordova group, and others, appropriately. On May 6th Professor Blackmond delivers a point-by-point response to all items raised by Professor Cordova, and the conclusion can only be that Professor Cordova has no reason to complain. However, and more seriously, Professor Cordova accuses Professor Blackmond to have behaved incorrectly, as a referee, during the processing of a manuscript that Professor Cordova submitted to Nature in 2005. He writes "Notably, several of our speculations, scientific thoughts and writings [presented in the Cordova group Nature submission] can be seen in Blackmond’s paper." As this exchange of opinions was spread in the scientific community, this accusation eventually must be investigated and either supported by evidence or taken back. Although it has not been our task to examine the behaviour of Professor Blackmond, we would like to point out that nothing has appeared during this investigation that supports Professor Cordova's accusations. The key result reported in the Nature paper of Professor Blackmond is not the observation of nonlinear effects, but the presentation of a new model, based on meticulous scientific data, that explains that the asymmetric amplification is actually derived from the solid-solution behaviour of the amino acid in the solvent. Professor Blackmond meets the accusations in several letters, and is supported by the editor of Nature (Enclosure 17). She eventually asks for a written apology (on May 8th) to be sent to all those who were cc:ed on his original email, in which Professor Cordova should admit that her Nature paper does not in any way contain any of his "speculations, scientific thoughts and writings", that he declares categorically that his group has not "demonstrated and published several of the things that Blackmond writes in her paper and that she wants to do in the future", as well as that he states that the model for asymmetric amplification in amino acid catalysis that he proposed in his failed Nature submission is entirely unrelated to the model she proposed in her Nature paper and that the model he proposed in his Nature submission is entirely unrelated to the model he currently proposes in his CEJ paper.
Professor Blackmond now (May 3rd) demands answers to the following four specific questions:
1. Does Professor Cordova accept that the definition of a eutectic given in Ref. 29 [in Cordova's CEJ paper] is scientifically incorrect?
2. Does Professor Cordova accept that his statement that enantiomers can have different aqueous solubilities is scientifically incorrect?
3. Does Professor Cordova assert that the concepts and ideas that led to his statement "...the effect would become even higher and the curves would display a significant positive effect crossing the straight line of no linear effect* (eutectic point) to become negative again" are derived solely and independently from work in his laboratories?
*The phrase "no linear effect" appears to be a typographical error, and I understand this to mean "no nonlinear effect" or "linear effect".
4. Will Professor Cordova please clarify what independent work has been carried out in the Cordova laboratories, prior to the Erdtman lecture of Nov. 29th, 2006, to address amino acid phase behaviour and measure eutectic points?
The answers are delivered on May 5th.
1. Professor Cordova admits to have been using an incorrect definition and states that he will use the definition provided by Professor Blackmond in the future.
2. Professor Cordova admits to having made an incorrect statement. However, he still demonstrates a certain lack of understanding of the basic concepts of phase behaviour.
3. Professor Cordova asserts that "our intention was not to take away from Professor Blackmond the credit for introducing this concept. We fully agree that she was the first to introduce this concept."
4. Professor Cordova discusses his experience in the research field and the conclusions he has been able to make over the years. He ends with "We are now happy that Professor Donna Blackmond has demonstrated this and we will cite her paper and give her credit for this in all our future work." However, he does not clarify how he has measured eutectic points, stating only: "Based on what is known on the separation of enantiomers by recrystallisation we knew that eutectics are important for explaining the equilibrium of heterogeneous mixtures of diastereomers and enantiomers."
It then follows an exchange of opinions that includes demands for extracts from the Cordova group laboratory notebooks to show, among other things, if and when the data for the CEJ paper were produced and how the eutectic values were measured. Professor Cordova provides lab notebook excerpts and plots concerning experiments carried out during the week of Dec. 1-6, 2005, the week after the Erdtman lecture, as well as July 11th, 2005. The data obtained on July 11th, 2005, correspond to the plot in the Angew. Chemie paper cited above, in which Professor Cordova concluded that the system followed linear behaviour between amino acid ee and aldol product ee. This plot represents the only lab data presented by Professor Cordova in this case that were obtained prior to December 2005. These do not demonstrate that he could have independently developed the model relating eutectic composition and nonlinear effects. The laboratory notebook pages submitted by Professor Cordova showed no evidence that solution ee was actually measured, only that solution ee may be derived from his data; measurements of reaction product ee only were provided. The notebooks provide no data studying non-enantiopure amino acid catalysis as a function of amino acid concentrations, which is key to the eutectic model developed by Professor Blackmond. Professor Cordova could not present evidence that he made any observations of a link between nonlinear effects and amino acid concentrations and phase behaviour, or that he had any knowledge or understanding of such a link, prior to the Erdtman lecture of Professor Blackmond at KTH. Professor Cordova does not provide sufficient information about how he obtained the eutectic values, and there is no evidence that the Cordova group in fact constructed ternary phase diagrams. In addition, the written comments of Professor Cordova continue to demonstrate a lack of understanding of the principles of phase behaviour required for development of the eutectic model. For example, Professor Cordova states that the phase diagram for proline given in the Blackmond Nature paper is incorrect, and he proceeds to describe his view of how it should appear, including the following statements: "the phases identified as L-solid and D-solid are not really ‘solid enantiopure proline’. It is a phase region with a solid solution containing both L and D proline in the same solid phase…. In the same way the region identified as solid DL racemic compound is also a solid solution region with a solid solution containing different ratio of L and D proline depending on the specific position in the diagram." These statements indicate that Professor Cordova has a confused and incorrect concept of phase behaviour, including a misunderstanding of the nature of solids classified as racemic compounds, conglomerates, and solid solutions. To us, this supports us in our conclusion that the eutectic model could not have been developed independently by him.
After one month of discussions, including several letters to Professor Bäckvall, Professor Blackmond on May 29 raises the issue of scientific misconduct by – and the possibility of tacit internal support for – Professor Cordova to the Faculty Dean at Stockholm University, Stefan Nordlund. Within short, Professor Cordova agrees to the wording of the Corrigendum in CEJ (May 29th) and an official investigation of the conduct of Professor Cordova is launched (June 7th). The CEJ Corrigendum, which was published in the same issue on page 5175 (Enclosure 18), includes the following important points:
"We would like to point out an error of omission of a citation and present an accurate definition of eutectic in reference [29] in our paper (DOI : 10.1002/ chem.200501639 ; submitted : December 29, 2005, published online : April 25, 2005)."
"We were remiss not to state that the concept relating eutectics of amino acids to nonlinear effects in asymmetric catalysis had previously been presented at the Erdtman Lecture at KTH Stockholm by Professor D. G. Blackmond on November 29, 2005. This work is now published (see M. Klussmann, H. Iwamura, S. P. Matthew, D. H. Wells, U. Pandya, A. Armstrong, D. G. Blackmond, Nature 2006, 441, 621; submitted November 21, 2005). We fully agree that the Blackmond group was the first to introduce this concept."
"Our discussion implied that we measured the eutectics of valine and alanine in this work, which we did not. We would like to clarify the definition of a eutectic with respect to these scalemic amino acid systems. We stated that the eutectic point is the point at which all three phases, (R)-amino acid, (S)-amino acid and DMSO can exist simultaneously. We are grateful to Professor Donna Blackmond for providing us with the correct definition of a eutectic in the context of these amino acid systems: In an isothermal, three-component system at equilibrium consisting of (R)-amino acid, (S)-amino acid, and solvent, containing two distinct solid phases and one solution phase, the eutectic composition is dictated by the phase rule and is described as a point on the phase diagram where three separate phases intersect. The phase rule also dictates that the solution composition at the eutectic is fixed in this case and hence this composition is identical for any given (R)- and (S)-enantiomeric composition employed."
An Editorial Note in the Corrigendum states: "D. G. Blackmond and co-workers transmitted their experimental observations prior to A. Cordova et al. The data in the paper by Cordova and co-workers describing nonlinear effects at higher alanine and valine concentrations were obtained during the week December 1–6, 2005. In addition, the experimental data presented in Figure 2 in the paper by Cordova and co-workers (showing striking asymmetric amplification in an asymmetric aldol reaction using scalemic serine as catalyst) were acquired on December 5, 2005. The Nature paper by Blackmond and co-workers referenced above represents, to our knowledge, the first measurement of eutectic points of free amino acids that form racemic compounds and the first comprehensive interpretation of nonlinear effects in asymmetric catalysis using acyclic amino acids as catalysts."
With this, the matter could have come to an end. In a mail from Professor Blackmond to Professor Cordova on May 31st, cc:ed to the organic chemistry community at Stockholm University, she offers to normalise the relation, provided that the accusations from Professor Cordova are dealt with. Alas, this was not to happen. Professor Cordova continues to involve himself in the eutectic model developed by the Blackmond group. He has presented his data showing the nonlinear effect of serine due to phase behaviour at several international conferences. At the Organocatalysis Sympoisum in Glasgow, Professor Cordova on July 5th, 2006, gave a talk in which he presents data concerning nonlinear effects in acyclic amino acid catalysis from the CEJ paper and a Chem Commun. submission. He did cite the Nature paper of Professor Blackmond, but according to Professor Alan Armstrong (a coauthor on the Nature paper) he implies that his group came independently to this model of phase behaviour and nonlinear effects. This is clearly not the case. At the Organocatalysis Symposium in Tutzing, Germany, October 8-10, 2006, Professor Cordova again presented the serine result as an independent finding, noting only that the Blackmond work helps to explain his result (again witnessed by Professor Alan Armstrong).
In addition, Professor Cordova’s attempts to claim credit for the eutectic model in a further publication. A few days before the CEJ Corrigendum was agreed, Professor Cordova submitted a paper to Tetrahedron Letters that became available online on July 28th 2006 (Tetrahedron Lett. 47, 6657-6661 (2006), Enclosure 19). In contrast to the CEJ paper, this paper is devoted fully to the subject of the nonlinear effect caused by amino acid phase behavior. Professor Cordova publishes the same serine data that was published in the CEJ paper, stating: "In stark contrast to alanine and valine, we found a remarkably high amplification of the enantiomeric excess of aldol product 2 in the serine catalyzed asymmetric aldol reaction (Fig. 1)." This statement is made without citing the Blackmond Nature paper and without citing the CEJ Corrigendum. Professor Cordova does not give proper credit to the pioneering work in the field by Professor Blackmond. Her Nature paper is cited (as Ref. 17) but definitely not in an appropriate way. When he cites his own CEJ paper, he does not include a reference to the Corrigendum. In Footnote 18 of this Tetrahedron Lett. paper it is stated: "The ee’s of alanine and valine in the solution at the eutectic points were 60 % and 63 % ee, respectively." This is given without any supporting data, and again the question about how the Cordova group has measured the eutectics arises. In addition, his stated value of 63 % for valine differs from the value of 46 % published in the Blackmond Nature paper, but neither this discrepancy nor the Nature paper is mentioned in this context. Professor Cordova had stated on May 29th in the CEJ Corrigendum that he had not measured eutectic values for valine and alanine, which was confirmed by examination of his laboratory notebooks. As the Tetrahedron Lett. manuscript was submitted on May 25th, i. e. four days before, these eutectic values could not have been measured for that submission. A second Corrigendum, now linked to the Tetrahedron Lett. paper, is being drafted but has not yet been agreed upon and finalized.
The Tetrahedron Lett. paper is important in this case for several reasons: First, it demonstrates that even while he was agreeing the wording of the CEJ Corrigendum, Professor Cordova was in the process of submitting a further paper containing some of the same data and focusing specifically on the eutectic model uncovered by the Blackmond group, without giving proper credit to that work. Second, since the submission of the Tetrahedron Lett. paper covers the same time period and same scientific ground that was already agreed in the CEJ Corrigendum, his statement that he has measured eutectic point, made in a submission dated May 25th, when he has declared on May 29th that he has not, demonstrates that both statements cannot be true. Surprisingly Professor Cordova continues to attempt to claim some credit for this eutectic model, against all the evidence that has been revealed and that he himself has put forward. The fact that the same discussion that was settled in the CEJ Corrigendum is now back on the table, with no additional evidence to support Professor Cordova, and while he is under official investigation for scientific conduct related to this very issue, indicates that he has not altered the behaviour that led to the need for the first Corrigendum and the official investigation.
Case 3 (The Jörgensen case I)
The paper ”Asymmetric Organocatalytic Epoxidation of α,β-unsaturated Aldehydes with Hydrogen Peroxide” JACS, 2005, 127, 6964-6965 by the Jörgensen group was submitted on March 22nd, 2005, and available on the Web on April 22nd, 2005 (Enclosure 20). The publication concerns the epoxidation of α,β-unsaturated aldehydes by the use of hydrogen peroxide or other hydroperoxides catalysed by di(3,5-ditrifluoroomethylphenyl)prolinol TMS ether. The reactions were run in a mixed solvent consisting of dichloromethane and water at room temperature. High dia- and enantioselectivities were obtained. Best catalyst loading was 10 mol% for a rapid conversion. The reaction is tolerant towards a number of different solvents and several α,β-unsaturated aldehydes were tested with excellent results. The method is apparently general and thus very useful. One application was demonstrated for a natural product, a sex pheromone from an acaric mite. The publication does not include any results from experiments done with the simple non-trifluoromethylated derivative or sodium percarbonate.
The same year Professor Cordova published a paper (”Direct organocatalytic asymmetric epoxidation of α,β-unsaturated aldehydes” Tetrahedron Letters 2006, 47, 99-103, Enclosure 21) in which several similarities with the Jörgensen paper can be observed. This manuscript was submitted on August 3rd, 2005, and available online on November 16th, 2005. Professor Cordova’s manuscript was thus submitted more than 3 months after the JACS communication by Professor Jörgensen (Jörgensen’s paper I) was available to him. A control of the laboratory notebooks of Professor Cordova’s group showed that the work was done after Professor Jörgensen’s publication. It is clear that the Cordova paper presents the same synthesis protocol as published by Professor Jörgensen, although some details are different. One of the most important differences is the choice of catalyst. In Professor Cordova’s case he uses the simpler diphenyl prolinol TMS ether as the best catalyst while Jörgensen uses the tetrakis trifluoromethylated derivative. Professor Cordova uses hydrogen peroxide as does Professor Jörgensen but also another oxidant, sodium percarbonate, which Jörgensen does not use. Sodium percarbonate was shown to be an excellent oxidant in these reactions. There are a number of other differences but also a number of similarities between the two papers.
Professor Cordova makes references to Professor Jörgensen’s publications of relevance for the reactions at hand. However, Professor Cordova mentions in his reference 14 that Professor Jörgensen’s paper appeared during his own studies. This is highly questionable. Since there is a time gap of more than three months between the appearance of Professor Jörgensen’s paper and the submission of Professor Cordova’s manuscript it seems quite possible that Cordova got the idea to make the epoxidations of α,β-unsaturated aldehydes after he became aware of Professor Jörgensen’s work. Indeed, the Cordova notebooks also showed that the work was done after the appearance of the Jörgensen paper. It should be noted that there were no oxidation reactions included in the Cordova NIH application. In our view the Cordova paper is too close to Professor Jörgensen’s to be ethically acceptable, even if Professor Cordova took the opportunity to use a catalyst that Professor Jörgensen did not use. In any case, it would have been appropriate to acknowledge Professor Jörgensen’s work as an important background for his own work and explain in clear text why he chose the simpler TMS prolinol derivative.
Case 4 (The Jörgensen case II)
The Jörgensen paper II, JACS, 2005, 127, 18296-18304 ”A General Organocatalyst for Direct α-Functionalisation of Aldehydes: Stereoselective C-C, C-N, C-F, C-Br and C-S bond-Forming Reactions. Scope and Mechanistic Insight”, was submitted on September 12th, 2005, and published on December 3rd, 2005 (Enclosure 22). It concerns the action as organocatalyst of the silylether of α,α-bis(3,5-di-trifluoromethylphenyl)prolinol. The simpler α,α-diphenyl derivative is only shown in a scheme but not further investigated. A number of reactions were presented in which the catalyst gave high yields and stereoselectivities (α-aminations, Mannich rections, conjugate addition to MVK, α-fluorination, α-bromination and α-sulfenylation of aldehydes). Considerable attention was devoted to the mechanistic aspects.
Professor Cordova’s corresponding paper (Chem. Comm. 2006, 1760-1762 ”Direct catalytic asymmetric anti-selective Mannich-type reactions”) was submitted on February 14th, 2006 and was available on the web on March 15th, 2006 (Enclosure 23). The results are very similar to those presented in the Jörgensen paper II. However, Professor Cordova’s contribution fills a gap left by Professor Jörgensen in that Cordova uses the simpler diphenyl prolinol derivative.
How similar are these papers? The basic principle, i.e. the use of diarylprolinols as catalysts for the Mannich reaction, is essentially identical. However, Professor Cordova takes the chance to develop the Mannich reaction with the simpler derivative, which Professor Jörgensen did not. The derivative is a previously known substance. Professor Cordova makes a reference to the Jörgensen paper but does not put it in the proper context. Instead, he rather hides it in reference 14e and does not discuss it further despite its high relevance. Our critisism towards Professor Cordova concerns the obvious tactic of not fully acknowledging contributions by other groups especially when it concerns central parts of his own work. However, there is nothing unethical in making complementary investigations based on others work if due referencing is done. On this point Professor Cordova should have described the background of the Jörgensen paper much better to acknowledge the priority of that work. The similar tactics of Professor Cordova in the two of his papers mentioned here is striking and it seems to us to be a highly dubious way of presenting ones own results by essentially avoid commenting properly on others.
Conclusions
1. It is clear that Professor Cordova behaved unethically concerning the Synlett paper described in the Barbas case (Case 1). It is not acceptable to take full credit for work done under supervision without the consent of the supervisor. We here regard Professor Barbas as supervisor to Cordova even if Professor Cordova apparently had a position as Senior Research Associate at TSRI. According to Professor Barbas (Enclosure 8), the title Senior Research Associate is given to second year postdoctoral fellows. Professor Cordova had no lab of his own and no resources to run a research laboratory. At the time he appears to have been completely dependent on the laboratory infrastructure and other material and economical resources controlled by Professor Barbas. This is confirmed by the statement by Professor Barbas (Enclosure 8)
2. It is clear that Professor Cordova behaved unethically in the Blackmond case (Case 2), by publishing ideas that Professor Blackmond first made public (in the Erdtman lecture) as his own. He has, after a lot of discussions, admitted his mistakes in the CEJ Corrigendum, and with this the case could have been closed. However, it does not appear as if he learned the lesson, as he for instance refers to his CEJ paper without referring to the Corrigendum, and continues to give the impression that the model originally proposed by Professor Blackmond was developed in parallel in his group. He has not produced any supporting evidence in this direction and such a behaviour is absolutely not acceptable. In addition, there is the question about the accusations that Professor Cordova made, that Professor Blackmond used material from his rejected Nature manuscript and used them as her own. These are very serious allegations for any researcher in the academic system, that may affect Professor Blackmond's future career, and they have to be substantiated by an independent investigation or withdrawn together with a public apology by Professor Cordova.
3. Professor Cordova did not put Jörgensen’s work in the light in the way it should have been done (Cases 3 and 4). Professor Cordova’s contributions in case 3 and 4 are complementary to those of Professor Jörgensen but are, to a large extent, very similar. The contributions of the Jörgensen group concerning the epoxidation and the Mannich reaction should have been done more precise and accurate, admitting the priority of Professor Jörgensen’s work much clearer. Especially as the experimental work was carried out after the Jörgensen papers appeared on the web. We regard cases 3 and 4 as borderline unethical on behalf of Professor Cordova and he must put more efforts in proper describing and referencing work, which was published prior to his own.
One of us (TF) has inspected some of the laboratory notebooks of the Cordova group and could not find any evidence that the experiments related to the Jörgensen Case 3 and 4 that were published by Professor Cordova were not made. However, the way the experiments were described leaves a lot to be desired, which was emphatically put forward to Professor Cordova.
Our impression after conducting this investigation of Professor Cordova as a researcher is that he is unusually skilled and hardworking. Even if he only published half the amount of papers he would still be in a division of his own in Sweden. He obviously has a different view of the ethical rules that regulate how scientists share information. Although these rules are not printed, they are an important part of the formation of a researcher during the PhD and post-doctoral periods, and we feel confident that Professor Cordova was properly educated in these matters. However, in later years he has found it acceptable to hide or even omit references to relevant work of others, and we cannot see that this was done by accident. It happens too frequently, and we believe that it has been intentional. The journals do not have the capacity to reveal such behaviour in a systematic way. After some time the impression might easily be that this was real independent work as both papers were published during the same year. Thus, such behaviour is not acceptable, and it creates serious problems for Swedish chemistry in general and Stockholm University in particular. The problem needs to be solved in a way that is acceptable also for the international scientific community.
We are also concerned that the PhD and post-doctoral students in the Cordova group may get the impression that the publication policy by Professor Cordova is acceptable. This is disquieting, and it is evident that this new family of researchers need to be thoroughly informed about the generally accepted ethics in science. It should be added that one of Cordova's previous post-doctoral students decided to leave the group prematurely because he experienced unacceptable working conditions and publishing (Enclosure 24).
We strongly emphasize that if Professor Cordova is to continue in academic science he must adapt to normal ethics in publishing and presentations of results. Due credits to those who in fact published before him must definitely be made appropriately and not just left aside essentially uncommented in a reference. It is even more serious to intrude on others work by claiming priority or independent work without strong supportive evidence. In this respect it does not matter if he had the ideas long ago but never came about to actually perform the experiments and publish.
Torbjörn Frejd Olov Sterner
I am working on a project to investigate the ethics of this case. Does anyone have a link to the original source of the above comment? Thanks.
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