How to resolve scientific controversy

by Alexey Bersenev on March 11, 2010 · 0 comments

in open science

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This is re-blog from Stem Cell Assays

I think scientific collaboration but not scientific competition can drive progress in the field promptly. Sometimes, collaboration is the only way to resolve a controversy, especially coming from “ping-pong studies“.

Imagine – 2 or more very respectful labs running experiments in order to answer the same scientific question, but using different models and techniques, finally getting different contradictory results. Whom should we trust and where is the truth? In this case investigators should talk, collaborate, set the same protocol to find the truth and give the answer to the community. Unfortunately we don’t see a lot of collaborations like this in stem cell research – the field is currently full of controversies.

I was happy to find a collaborative effort from leading scientists, resolving some controversy and providing us a showcase, in the most recent issue of Cell Stem Cell journal. Leonard Zon came up with a great idea of collaboration in order to answer a very controversial question about the role of N-cadherin (dispensable or indispensable) in hematopoietic stem cells (HSC). As result you can read consensus paper, coordinated by Len Zon and Cell Stem Cell editor – Deborah Sweet.

The discrepancies described above were generating confusion in the published literature and thus in the field. With the aim of resolving the controversy and providing clarification of the issues involved, we embarked on an interactive discussion approach. At our (L.I.Z.) request, the principal investigators from the two groups that have generated the majority of the conflicting published data, Linheng Li and Sean Morrison, participated in a telephone conference in which each investigator presented and discussed pertinent data slides. This meeting also included another investigator, Toshio Suda, who has published work suggesting a positive role for N-cadherin in the bone marrow, and the editor of Cell Stem Cell, Deborah Sweet.

Points of discussion under moderation of Len Zon:

This joint discussion was followed by a series of one-on-one phone meetings and two other telephone conferences with L.I.Z. During the discussion, it became clear that the disagreement centered on three major questions: (1) Do HSCs express N-cadherin? (2) Is the MNCD2 monoclonal antibody specific for N-cadherin? (3) Does N-cadherin play a role in HSC maintenance and regulation? Involving the groups who had previously come to differing conclusions in a joint discussion provided an efficient mechanism for critical analysis of key experimental data and honest expression of opinion about the relevant issues.

Collaboration set up was following:

With the available information, some conclusions about the first two issues became clear, and these will be outlined below. However, we were not able to reach an agreement on the third question on the basis of the available data. Upon the senior scientist’s suggestion, the Li and Morrison labs agreed to independently perform a limiting dilution competitive transplantation with the exact same experimental conditions and N-cadherin conditional knockout mice, with a view to comparing data and coming to a consensus conclusion. Several emails between the groups outlined in detail the methods, doses of cells, and mechanism of conditional inactivation of N-cadherin. Six months later, we set up a phone call to examine the data from the two laboratories.

The results of this collaboration effort you can get from the paper.

I think this example is remarkable. It shows how collaboration can lead and be done in order to solve important controversies in HSC research. The main lesson to learn from this first showcase – collaboration is possible and it is productive.

Who should initiate and lead such collaborations? My obvious answer – principal investigators, leading scientists and journal editors under independent expert’s moderation. I hope more PI’s and editors will read this post and get the message. All we (postdocs, PhD students) can do ourselves in this case – just spread the word.

What platforms and tools could be used for such collaboration? My obvious answer – any available to date. Letters and emails for editors of journals, phone- and video- conferences, teleconferences, internet with a variety of web tools. Unfortunately PI’s are too rigid in terms of using internet and collaborative web tools.

Quote from Deborah Sweet editorial:

From the perspective of a journal such as Cell Stem Cell, it seems to me that the only fair approach is to remain neutral in any conflict and to publish studies that meet editorial criteria and peer reviewer standards even if they seem to conflict with previous work. However, there comes a time in many scientific disagreements where additional experiments along similar lines to those published previously do not provide significant new insights.

I encourage all of you, as our readers, to use this feature and provide your perspective on articles that we have published. More informal online venues such as blogs, society-sponsored networks such as the ISSCR groups on LinkedIn and Facebook, and even Twitter, also provide mechanisms for scientific discussion about published work and its interpretation that can help highlight issues for the benefit of the field overall.

But controversy initially is a good thing which could be correlated with scientific progress and assays/ models development.

Controversies prompt everyone to rethink their assumptions and devise new experiments to address outstanding issues. Ultimately, therefore, disagreements help drive progress.

Until it become too much. In case of N-cadherin in HSC, for example. And when controversy persist too long, collaboration is the only way to solve it and drive scientific progress further. We should do it all the time and make results available immediately for community and public.

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