Report of Advisory Council 2014 [ Aug, 2014 ]

The CDB Advisory Council (DBAC) held its eighth plenary meeting from February 24 to 27, 2014 to conduct an extensive review of the research programs and administrative organization of the Center. Dr Austin Smith, Chair of the DBAC, compiled the results of the Council’s evaluation and its recommendations for the future. The full text of that report is shown below.

※ The greater part of this report was written immediately after the Advisory Council convened at the end of February 2014.
There may be some parts of the report that are inconsistent with the current situation due to changing circumstances following the Advisory Council.
An Addendum was added to the report by the AC in August.

Advisory Council Report
RIKEN Center for Developmental Biology

Meeting Programme

The Advisory Council (AC) of the RIKEN Center for Developmental Biology (CDB) met in Kobe from 24-27 February 2014 to review the Center’s progress and activities. The meeting opened with a presentation from CDB Director Dr Takeichi who gave a scientific and budgetary overview of developments in CDB since the previous AC, including recruitments of several new team leaders and most recently a new Group Director. Further information was available to the AC through the 2014 white paper that had been prepared by CDB and circulated in advance of the meeting. Dr Takeichi also summarized the CDB response to AC recommendations from the previous meeting. He concluded by drawing attention to the request from President Noyori to Center Advisory Councils to assess international standing and to propose quantum leaps. RIKEN Executive Director Dr Kawai then gave an overview of the ongoing RIKEN investigation into the alleged misrepresentation of data and figures in the STAP publications in Nature by Obokata et al. Dr Sasai followed up with technical details for the information of AC members.

The main business of day 2 was review of the Group Directors and Project Leaders. Progress reports and future plans were provided in the advance documentation along with evaluations by external reviewers. Each Investigator gave a summary presentation and responded to questions from the AC. At the end of the afternoon AC members had the opportunity to meet and discuss with PhD students and post-doctoral researchers during a poster session followed by buffet.

The following day nine recently recruited Team Leaders and two support laboratory heads introduced their work and answered questions from the AC. In the afternoon the AC split into three groups to visit laboratories and hear research reports from remaining Team Leaders. The Team Leaders had been advised to speak about their most interesting progress rather than attempt to cover all their activities. The AC discussed future career options with several Team Leaders nearing the end of their 10 year term and preparing to leave CDB. The day ended with dinner with CDB Group Directors and Project Leaders.

On the final morning the AC retired for private discussion and to draft the report and recommendations. The AC had a further discussion with the Director Dr Takeichi about the STAP affair and a follow up meeting with Dr Sasai.

The Chair summarized the Advisory Council findings and recommendations to CDB principal investigators, with Dr Kawai in attendance by video. After the meeting the AC provided the Director with final evaluations of the Group Directors and Project Leaders and summary comments on Team Leaders. The AC provided RIKEN with the final written report in August 2014.

Overall Evaluation

RIKEN CDB is regarded worldwide as an exceptional research institute in the field of developmental biology. Many CDB investigators are at the international forefront in their subject. This is reflected in the fact that in 2012, CDB published 164 research papers, one third of which are in the leading international journals, including several in Nature, Science and Cell. Consistent with the high level of research output, CDB investigators have been very successful in external grant competitions, attracting over 1,100 million Yen per annum in both 2012 and 2013.

CDB covers the broad field of contemporary developmental biology, spanning from molecular evolution to regenerative medicine. Ambitious projects addressing major questions, often involving innovative cross-disciplinary approaches, have become the hallmark of CDB. CDB faculty comprises a good mix of senior, mid-career and junior investigators. Senior investigators are international authorities in their fields while many of the younger investigators are identified as leading talents. Indeed CDB is highly regarded for the opportunities it has provided to talented junior researchers through open recruitment and team leader turnover. CDB is deeply engaged with the international developmental biology community; hosting the highly successful annual CDB international symposia, developing partnerships with a range of institutions, holding joint meetings, and having a very full program of visiting seminar speakers. A particularly significant and valued function is the production of transgenic mice for researchers in Japan and many other countries by the CDB Animal Resources and Genetic Engineering Laboratory. Furthermore, CDB is very active in science communication to the wider community. Overall CDB makes an enormous contribution to the global visibility and reputation of RIKEN and of Japanese science.

The CDB is now established as a world-leading research institute. A quantum leap for CDB would be to become equally recognized as an international doctoral training center. The AC considers there is an excellent opportunity for CDB and RIKEN to establish, in partnership with the Universities, a truly competitive and international PhD program that would draw talented young scientists to Japan. Prestigious PhD programs are features of leading international research institutes such as EMBL. The AC also notes the energizing force of high caliber PhD students that would benefit CDB.

A key element in the success of CDB is that since its inception the Center has been led by a universally respected and admired scientist, Dr Takeichi. An equally outstanding scientist of broad vision must be appointed in the near future to build upon the foundations laid by Dr Takeichi and maintain CDB at the leading edge of developmental biology and stem cell research. However, the search to find a suitable successor to Dr Takeichi is proving a major challenge. Furthermore, Dr Nishikawa and Dr Aizawa, the two able and distinguished Deputy Directors, retired in 2013. In these circumstances it is now essential that interim support is provided for Dr Takeichi in management and organization of CDB.

Reviews of Group Directors and Project Leaders

The AC was pleased to see that resources had been re-deployed productively as previously recommended. All Group Directors were commended by external reviewers as leaders in their respective fields. All had original findings and major publications in the review period. The AC therefore supported renewal in all cases. The AC reached a similar positive opinion for renewal of Dr Niwa as Project Leader and was impressed by the translational drive and progress of Dr Takahashi (mid-term review). Finally, the AC supported the proposal to promote Dr Shibata to Project Leader, with appropriate mentoring.

Following are the recommendations and advice made by the AC in March 2014. However, certain comments have been revised by subsequent events and in order to complete the final report an addendum is provided recording the outcomes of correspondence and two internet conferences between AC members after June 2014.

STAP Issue
The AC considers that the CDB Director has handled the matter appropriately by instigating an investigation by RIKEN. The AC also appreciates that a corrigendum has been submitted to Nature and that a detailed protocol will be made available. These actions will go some way to mitigate the potential for reputational damage to CDB and to individual authors. The AC wishes to underscore that it is essential to avoid any impression that CDB does not take extremely seriously the proper presentation of scientific data. The AC has the following recommendations:

• The CDB Director to issue a public statement, coordinated with RIKEN, acknowledging the professional failure in elements of data representation and oversight in the original papers.
• The co-authors of the paper, in particular the senior CDB author, to be frank about these failures in all external and internal communications and to avoid expressions such as “innocent mistake”.
• Seminars on research integrity and data presentation to be conducted in CDB with compulsory attendance by all research staff and students. Expert speakers on research ethics should be available within RIKEN and the University system. In future, such seminars should be held at least once a year for all new staff and students.

At the end of the AC meeting, members learned of a proposal that CDB arranges an open symposium on reprogramming methodologies in the near future. This is an excellent suggestion.

Group Director Recruitment
As Drs Aizawa and Nishikawa have departed and a new Director has not been appointed, the AC considers that is now important to strengthen the broad scientific leadership and visibility of CDB by recruiting a further Group Director. Refreshing the senior leadership will also help to avert any impression that CDB may be becoming insular. The AC accordingly recommends that CDB undertakes a global search for a new Group Director in 2014 led by the Director, Masatoshi Takeichi.

Scientific quality must be the over-riding consideration and, as emphasized at previous AC meetings, it would bring many benefits if a non-Japanese of high international standing and with strong commitment to mentoring young scientists could be recruited. The AC considers that research area need not be defined too rigidly, although an individual working on mammalian development would seem most appropriate. In addition to placing an advertisement in Nature and other journals, the AC judges it would be productive to circulate the recruitment information to heads of leading research institutes. In addition, a CDB search committee should be convened to draw up a short-list of candidates and approach these individuals directly. AC members are willing to give this matter some consideration and suggest names.

The AC notes that Dr Niwa would be a strong candidate if he should choose to apply. He is a key investigator who is internationally prominent and plays an increasing responsible role in mentoring junior PIs within CDB. However, since he has another 5 years to his term as a Project Leader, it may be reasonable to recognise his excellent contribution in some other form, such as increased resources, than appointment to a GD position at this moment. Alternatively, in the special circumstances of this transition period an additional GD position could be created to accommodate the appointment of both Dr Niwa and an external individual.

Regenerative Medicine and Translational Research
The mission of CDB extends from fundamental discovery research through to pioneering clinical applications. The work of Dr Takahashi is exemplary in demonstrating a path from basic science to regenerative medicine. However, her team is currently a unique case in CDB. The AC recommends that it would be strategic for CDB to identify and establish additional project(s) in the Regenerative Medicine Development Program.

It is of paramount importance for CDB to sustain excellence in basic science, which is fundamental to innovation and discovery. Nonetheless, attention should also be paid to building genuine connectivity with translational researchers. Achieving this is not straightforward and institutions worldwide are struggling with the challenge. CDB is very well positioned, however, due to the combination of world-leading basic science, secure funding, and immediate proximity to clinical research facilities.

In the context of developing a broader translational programme, the AC recognises the merit of an appointment in Tissue Engineering. We look forward to learning about Dr Tsuji’s research and his integration into CDB at future AC meetings. In particular, we hope that he will grasp the opportunity to interact productively with developmental and stem cell biologists and thereby maximise the potential outcome of tissue engineering science.

The AC recommends that CDB should seek to motivate and promote translational science of the highest quality by bridging with excellent basic science. Groups in CDB should not all be expected to have a translational aim, but opportunities should be fostered for collaboration and engagement with pre-clinical and clinical research. Possible mechanisms might include: internal funding for pump-priming translational projects; research exchanges with leading international centres, for example the Langer laboratory at MIT and internships for clinically qualified researchers. The last mechanism may be facilitated by the RIKEN JRA scheme which highlights “making special efforts to foster the development of basic research in medical fields, and recent graduates of medical and dental universities who have acquired their medical or dental licenses are welcome to apply”.

PhD Programme
The AC was concerned that the number of PhD students has continued to decline although this can in part be explained by the departure of leading investigators Dr Aizawa and Dr Nishikawa. The AC also heard that there is a reduced interest in PhD studies among young Japanese at the present time. As highlighted in the previous AC report, training the next generation of researchers should be a key element in the mission of an international research institute such as CDB. Furthermore, graduate students are invaluable for the creativity and vitality of research groups. The opportunity exists to attract high quality students from outside Japan and the AC was interested to hear of the RIKEN International Program Associate scheme. It was also constructive to hear that the CDB Director is committed to increasing the number of the PhD students and that currently 20% of CDB graduate students are non-Japanese. The AC recommends that CDB takes full advantage of the RIKEN JRA and IPA schemes to attract high calibre PhD students and in addition increase use of internal funding to support PhD students. Preparedness to train PhD students should also be taken into account in future recruitment of Team Leaders and Group Directors.

The AC considers that CDB is ideally placed to organise a world-leading PhD programme in Developmental Biology and Tissue Regeneration that could attract students not only from Asia but worldwide. There are excellent models of International PhD Programmes available at EMBL, Wellcome Trust and several other organisations. Since a significant degree of planning and coordination is required, the AC recommends that CDB consider appointing a Graduate Studies Officer to take responsibility for administration, recruitment, course organisation, and pastoral provision for an international PhD Programme. This role might be combined with serving as liason officer with overseas institutions.

Team Leader Turnover
AC members are very pleased to see that CDB team leaders are succeeding in obtaining positions in Japanese Universities. The AC appreciates that establishing this new model has been challenging both for CDB leadership and for some individuals. However, a key benefit of turnover is that openings have been created to give opportunities to promising new investigators and refresh CDB. In the longer term, the Japanese Universities will appreciate the benefit to be gained from recruiting high quality research group leaders developed in CDB. Consequently it would become easier for CDB Team Leaders to make this transition, and the relationship between CDB and the Universities may be increasingly harmonious.

Post-doctoral Community
AC members were impressed with the quality of posters presented by students and post-docs. The AC would like to stress that a vibrant post-doc community is the engine room of a research institute. The AC recommends that CDB seeks to provide the best possible environment for post-docs. Measures should include offering mentorship from GDs and stimulating formation of an autonomous post-doc association that can arrange scientific and social events, and could also be given some responsibility for inviting seminar speakers and organising the annual retreat. The post-docs should also be encouraged to invite speakers to discuss career opportunities.

Sequencing Informatics
Dr Kuraku is to be congratulated for effectively streamlining provision of genomics support with associated bioinformatics processing. How, and at what level, to provide core informatics support for deep sequencing is a general challenge, but is critical to ensure quality control of data analysis in publications and provide standardisation of platforms for effective data exchange and collaboration. While some larger groups may employ dedicated bioinformaticians, this will not be reasonable for all groups. The AC recommends a review of sequencing informatics requirements and provision in CDB.

Presentation Skills
Oral presentations by GDs and Team Leaders and responses to questions varied in clarity and were in general below the standard expected in a North American or European institute. Almost all PIs have reasonable spoken English, but in some cases weaknesses are apparent in organisation of content, timing, style and response during discusssion. This is a significant issue because invitations to speak at meetings depend on the ability to deliver and defend a well-articulated presentation. The AC recommends that CDB arrange expert coaching in presentation skills for all PIs and post-docs.

Supporting Laboratories
The supporting laboratories are providing essential core facilities efficiently and to a high standard. They are a great asset to CDB. The AC appreciates that for some of the Unit Leaders the opportunity to spend some time on their own research can be incentivising. It is important, however, that such research proposals are reviewed robustly and do not conflict with core service provision.

GD Report Format
Several external reviewers commented on the difficulty of evaluating future research plans from the reports of some GDs. The AC agrees with this and furthermore did not find GD oral presentations generally illuminating about future plans. The AC recommends that future GD review reports follow a standard format. This could comprise: Background, 0.5 page; Progress during review period, 2.5 pages; Future plans, 3 pages; followed by publications, major invited talks, funding details, past and current lab members, and information on responsibilities in CDB.

ACAC membership turnover
All AC members feel closely connected to CDB and honoured to serve on the AC. Nonetheless, the AC recommends that membership should be refreshed for the next meeting.

Final Remark
The scientific content of the Group Director presentations was of very high quality but the AC sensed rather less excitement and enthusiasm than at previous meetings. Specific circumstances at the present time may be contributory, but the AC considers the apparent air of fatigue as an indication that the collegiate leadership team should be rebalanced and reinvigorated through new GD appointment(s).

Addendum to Advisory Council Report – August 2014

The drastic recommendations from the CDB Reform Committee caused alarm throughout the scientific community. Many scientists and scientific organisations from around the world approached AC members and offered to write letters of support for CDB and Dr Takeichi. In these circumstances, the AC discussed the issues in mid-June and summarized their viewpoints.

• RIKEN should explicitly express confidence in the integrity of past and present research by teams at the CDB not directly involved in the STAP affair. Scientists at the CDB who are blameless in this situation should not be treated harshly, or forced to move to other institutions. There is a serious risk of these internationally-known scientists leaving Japan for laboratories in other countries. This brain drain would be a major loss for Japanese science.
• The CDB should not be dismantled but be internally reorganised under a new leadership team. The process should be overseen by RIKEN but it would not be productive to impose a reorganisation plan from outside, nor to merge CDB with another institute.
• Research in developmental and stem cell biology is, and should remain, the core of the CDB scientific mission. As exemplified by the work of Dr Takahashi, pioneering work in CDB can underpin applications in regenerative medicine in harmony with CiRA and other research institutions.
• RIKEN should review research integrity training and monitoring, and reinforce formal guidelines for all its institutes.
• RIKEN should ensure that all its institutes have in place formal and enforceable processes for recruitment, mentoring and assessment of independent investigators.
• The AC also strongly recommended that the ongoing search for a new Director of international standing should be expedited.

Since the June discussion, the AC has continuously discussed various matters in two internet conferences and through correspondence. The unanimous AC opinions are as follows:

• The immediate circumstances are not conducive to attracting a new Director of the highest quality, vision and ambition. It is critical first to establish a consensus on the broad scientific mission of CDB with support from the Japanese scientific community as well as MEXT. The process of identifying and appointing the new Director must then be open and transparent.
• At the present time a Steering Committee for CDB Reconstitution would be most constructive. The functions of the Steering Committee should be:
  ・To formulate the future mission of CDB, taking into consideration the balance between fundamental and translational science and whether the research field should broaden beyond developmental biology, for example to encompass cell biology.
  ・o assess opportunities for alliances and collaboration, including with CiRA, Kobe prefecture, other RIKEN institutes, and Japanese Universities.
  ・To oversee the interim reorganisation of CDB
  ・To identify and nominate candidates for new Director
  ・To support the incoming Director as required
• A Japanese AC member should join the CDB Management Committee to bring fresh input and to ensure good communication and alignment with the Steering Committee. This individual would have particular responsibility for scientific reorganisation and for liaison with the Steering Committee and could be assigned the title co-Director.
• A new Director cannot be appointed under the cloud of the STAP affair. The investigations must be concluded and the findings and consequences communicated publicly.

The AC appreciates that some immediate measures must be taken to satisfy political and financial constraints. It is imperative, however, that a new Director will be fully empowered to lead the reorientation and rejuvenation of CDB. We therefore urge RIKEN to retain future flexibility in research programmes and organisation.

Conclusion
AC members are fully committed to supporting CDB through this difficult period. CDB is vitally important because developmental biology is central for regenerative medicine. The broadly based innovative research undertaken at CDB makes a unique and essential contribution. The Advisory Council is confident that CDB can and will rise again.

Austin Smith
Cambridge
26 August 2014

Membership of the Advisory Council

Professor Austin Smith, University of Cambridge (Chair)
Professor Margaret Buckingham, Institut Pasteur, Paris
Professor Toshio Suda, Keio University, Tokyo
Professor Chris Wylie, Cincinnati Children’s Hospital
Professor Stephen Cohen, Institute of Molecular Cell Biology, Singapore
Professor Hiroshi Hamada, Osaka University
Professor Haifan Lin, Yale University
Professor Patrick Tam, University of Sydney
Professor Ryoichiro Kageyama, Kyoto University