Integrity in science (by Piet Borst)

Integrity is nowadays intensively discussed in academic research. Individual scientists should take their own responsabilities and teach good pratices to their trainees and staffs. However pressure to publish and survive in the academic word have been shown to partly contribute to misbehavior. So it is not the sole responsability of the individuals, and academic institutions must accompany their staffs. Many institutions have made official statements about responsible practices but those statements are usually very vague. We found one exemple of a head of an institute who gave during his director mandate very precise, balance and practical advice to the staff of his institute. With the authorization from the author (Piet Borst), we have decided to publish this statement and hope that it can help others.

 

Integrity in science (by Piet Borst)

19-3-2010 12:00

In the years 1993-1996 the staff of the NKI-AVL has discussed a few times the subject of scientific integrity. This discussion is reflected in our present procedure for the investigation of allegations of fraud. This procedure meets the high administrative and legal requirements of the NIH.

Integrity is more, however, than the lack of fraud. This was also explicitly stated in the Preamble and General Considerations of the NKI-AVL Statement on Scientific Practice of July 19, 1995, on which there was a consensus in house. Integrity was also a major topic in the article on “Scientists and the integrity of research” of Alberts and Shine (ref 1), discussed in the Research Raad of May 1995.

Given this discussion, I think that there should now be agreement in house on what should be done and not done in research. However, in view of a few recent minor differences of opinion, it seems useful to discuss a few practical examples to indicate how I interpret our code of scientific integrity. Most of the examples concern what the late Howard Temin called “sharp practices” rather than lack of integrity.

1. New materials

Investigator A in house isolates a new antibody (or cDNA, or new diagnostic procedure, etc.), that is also useful to other people. As long as results with this monoclonal have not been published (and therefore is not in the public domain) A can restrict the use of this monoclonal to his, or her own group. It is also reasonable to prevent access to the monoclonal until its specificity has been carefully determined. If A decides to hand over the monoclonal to investigator B before publication, A can demand that this will become part of a collaborative project. Co-authorship can be part of this deal. It may turn out in practice that B has done nice experiments with the unpublished monoclonal without any contribution of A, either in the design or in the interpretation of the experiments. It would then be elegant if A removes his name from the final publication. It is also sensible to do so, because if A is not closely involved in the investigation, he runs a risk by associating his name with research that is unsound. Co-authorship is not improper, however. Whether investigator A will provide the monoclonal to investigator B in our institute is up to A. I like to see this happen and such an early exchange of useful reagents contributes to the synergy between investigators that we aim for in the institute. However, if A chooses not to do so, this is his right. It is not elegant, but also not improper.

The story changes when data on the monoclonal have been published and it has thus entered the public domain. At that moment A should ensure that the monoclonal is available to other investigators. If the monoclonal is for sale, it is obvious that there are no strings attached to the sale. It is improper, however, to attach strings to monoclonals that are not for sale. Obviously A can ask B to pay reasonable costs; obviously A does not need to provide B with unlimited amounts of the monoclonal (allowing B to sell the reagent). A can not demand, however, that the monoclonal will be part of a collaborative project or that A will be co-author on articles that are based on research produced with the help of the monoclonal. This would be improper and a number of scientific journals actually require that materials described in articles will be provided to other investigators without any conditions. Some monoclonals have commercial value and in that case it is reasonable that the recipient is requested to sign a Materials Transfer Agreement. We also do this sometimes ourselves if we send materials to others. The Institute has a standard agreement for this purpose.

Internationally there is some discussion about transgenics and knock-out mice. The investment in generating such mice is considerable and also some respectable investigators maintain that this investment gives investigator A the right to keep the mice for himself for a period of one to three years. There is also a practical problem. Knock-out mice are usually generated in the 129/Ola strain and this is poor breeder. Back-crossing into FVB takes a year and most investigators in this research area find it reasonable to wait until this back cross is completed before they hand out their mice. I can see some merit in this reasoning, but formally there is not a real difference between knock-out mice and monoclonals. If another investigator insists on getting the published 129/Ola mice, then investigator A is obliged to deliver a breeding pair against cost price.

2. Ideas

Ideas are free and good investigators are generous with this commodity. Often the best investigators are more frequently found in acknowledgments than in the list of authors. Nevertheless ideas regularly result in differences of opinion. Investigator B is sure to have made a crucial contribution to the research of A (the suggestion to use Chinese T-cells, the suggestion to use TLC, the suggestion to talk to C), but A considers this the standard type of little help that you get from your friends and sees no reason to include B as co-author. These are difficult matters for which no precise rules exist. My advice is to be generous towards your colleagues and tough towards yourself. Nearly everybody has the tendency to overestimate his own contribution to the research of others and underestimate the contribution of other people to his own work. This is why B has contributed more than you think, and this is also why your own contribution might have been more trivial than you thought. Generosity is also important to profit optimally of the know-how of others. By involving people with good ideas in your research and by forcing them in the final phase to look again very carefully at the results (because they are included as co-author) your research can only gain in quality. Toughness towards yourself is useful to avoid being seen as a sharp operator or, even worse, being made responsible for research that you understand insufficiently and that may eventually turn out to be not so good or even incorrect.

If differences of opinion arise about such matters it is wise to consult at a very early stage the Laboratory Research Coordinator or the Director of Research, or another experienced investigator who is not part of the conflict. Such differences of opinion are most easily solved if they do not escalate and if both parties are still talking to each other.

3. Facilities

In principle, equipment is run and supervised by the person for whom the equipment has been bought. The institute pays, however, and therefore an investigator can never tell a colleague that you cannot use “my” centrifuge. In principle, all equipment in the institute is at the disposal of competent investigators who know how to handle the equipment. Obviously, we have to remain practical: an investigator who suddenly decides to use another piece of equipment has to start at the end of the line. The fact that the pipette tips on floor H8 are being bought with money of the institute, does not mean that all other floors can send people to H8 to get pipette tips.

A variation on this theme concerns equipment bought by investigators with their own grant money. This equipment is also property of the institute, since the grant application could never have been submitted without the permission of the scientific directorate. When the applicant leaves the institute the equipment stays, unless another deal is made between institute and investigator. The situation becomes more complicated when investigator A gets a monoclonal from investigator Z in the United States and B wants to use this monoclonal as well. If A has received the monoclonal for his own experiments and under the conditions that he will not hand out the monoclonal to other investigators, then A cannot do so. However, if Z has sent B to A, because A already received the monoclonal from Z, then it is obvious that A shares with B. Not sharing is then improper. This holds a fortiori for materials not in limited supply, such as cell lines or cDNAs.

4. Territoria

Primates have a strong territorial instinct and investigators are no exception. If investigator A has done elegant experiments on the domestic chicken for years, and investigator B, on another floor of the institute, decides to start working on the chicken as well, two types of negative reactions may ensue:

a. nice that you want to collaborate with me (but B does not want to collaborate at all);
b. stay away from my chicken.

Emotionally these reactions are understandable, but rationally they can not be defended and they have to be considered improper. The chicken is in the public domain, and if B wants to work on the chicken this is her decision. It is obviously desirable that NKI-AVL investigators working on the same topic or with the same object try to profit from each others know-how, experience and scientific contacts. Hence, collaboration is to be preferred and the scientific directorate will strongly stimulate such collaboration. It also looks strange to outsiders if investigators from the same institute work on the same topic without collaboration or cross references and if they submit independent grants without consulting each other. In the final analysis, however, this is B’s decision. Rather than remonstrate, A should ask himself why B avoids collaboration. Is A too dominant, ungenerous?

There should be no difference of opinion, however, about the ethical aspect of this conflict: It is not elegant to refuse collaboration, but not improper. It would be improper, however, if A would make it difficult for B to start up her research.

5. Confidential information

It is self-evident that confidential information should remain confidential, but in practice this does not always happen. It is nice to be able to tell other people that a colleague in the NKI-AVL has made an important discovery, but this breach of confidentiality may not be so nice for your colleague. Even if this colleague has the habit to talk freely about her unpublished results, she usually prefers to do this herself.

A mistake often made is that investigators evaluate articles or grant applications of the direct competitors. Even if the investigator does this in good faith (and this will usually be the case), this does not exclude an unfavourable outcome for the competitor. The problem is not only that you could apply sharper criteria or absorb confidential data without realizing, you can also evaluate the articles of your competitors better than other referees. Hence, you will evaluate the articles unintentionally in a more critical fashion than the average referee. It is therefore wise to avoid such conflicts of interests and return articles or projects from your direct competitors directly without reading them.

6. Patients

Good clinical (epidemiological) studies are usually based on large numbers of patients. Usually these patients are contributed by different hospitals and this can lead to problems about co-authorship, especially in retrospective clinical (epidemiological) research or in prospective epidemiological or psychosocial studies. Such studies require either the medical records of patients seen years ago (retrospective studies) or the help of the responsible doctor to interview the patients. Doctors who contribute patients or patients’ records for such a study usually expect in The Netherlands to be included as co-author if the study leads to publishable results. Often this co-authorship is already agreed on before the grant application for the research is even submitted (selling the hide before shooting the bear).

Clinical and epidemiological studies are as good as the quality of the data contributed and many clinicians find it reasonable that the expertise and effort required to carefully collect these data should be honored by co-authorship, even if the co-authors make no important contribution to the design of the study, the interpretation of the data or to the writing of the article. Given the prevalent practice in The Netherlands and elsewhere I would not like to call this unethical. I would like to emphasize, however, that this type of co-authorship entails risks. It does not comply with the requirements spelt out by the leading medical journals, such as the NEJM (see ref 2). Moreover, this practice can make a respectable clinician co-responsible for serious mistakes that have been made behind her back by the co-authors. I therefore recommend modesty in studies coordinated by others and in which our institutional contribution is modest. For the NKI-AVL project leader who wants to start a national or regional study, it can be useful to form a collaborative group if a lot of co-authors stand in line. Clinton and Blair can then publish on behalf of the Netherlands group for evaluation of the risk of secondary fraud. The responsibilities are then clearly defined.

7. Co-authorships

The main points have been discussed in previous sections and in both annexes. However, conflicts still arise from insufficient consultation of co-authors. Unfortunately, it still happens that articles are sent to a journal without the O.K. of all co-authors. It happens even more frequently that articles are drastically revised without the co-authors knowing this. Sometimes it is necessary to include new experiments in a revised version. In that case it is unacceptable and improper to return the article to the journal without all co-authors having studied the supplemental information and its interpretation and without all co-authors having agreed to the revisions.

References:

1. “Scientists and integrity of research” by Albert & Shine [Science 1994, vol 266, p.1660]
2. “Rules for co-authorship of the New England Journal of Medicine” February 1991, relevant parts (vol. 324, p. 425-426

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