Dear Yves,

As I told you in my previous mail, I am sending you a file that should help you to have an objective appreciation of the situation. .../... I just want to inform you. I hope that you will read this file before you take any decision

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All the research programs that are presently developed in my team have been described in details in the grant applications that I have been submitted for many years (I do have copies) and in the text that I have written for the unit creation. All funds used by my team were obtained through contracts that I personally obtained. The only grant application that was written by Maryvonne last year has been rejected.

At mid august, I have asked Cecile and Maryvonne to provide me with a short report and their personal views on the scientific project that they wanted to develop in my group in the coming year.

In reply to my request, Maryvonne was unable to provide other ideas than the ones I had myself put in writing for the renewal of the Inserm unit.

Ii)The research program entitled « role of Nov in chongrogenesis and ossification » was initiated in 1994 with Gaëlle Chevalier (PhD student) through collaborations that I had established with the laboratories of F.Dieterlin in Nogent, P.Schofield in Cambridge and G.Dambrine at the INRA in Nouzilly. Other foreign laboratories have also been recently involved in this collaboration project.
ii) the search for « alterations of nov in bone pathologies » such as « Lander Giedon » has been initiated after the talk I gave at the Necker hospital in 1997, and my discussion with Pr A. Munich who introduced me to Dr Vekemans.

iii) The research project entitled : « role of Nov in development and pathologies of nervous system » has been initiated in 1993 by myself, during a trip to Hamburg where I met Dr Westphal who provided us glioblastoma cell lines. This project was the matter of grant applications and publications, long before Maryvonne Laurent joined my group in 1995. The expression and role of nov in neuroblastomas has also been undertaken in collaboration with Dr J.Bénard (since 1992) Dr H.Yeger (since 1995) and Dr A.Lombet (since 1996).

iv) the research program entitled « dosage of nov in normal and pathogical fluids » has been initiated in the lab since our discovery of nov in 1992. I can provide you with the copy of the grant application that I submitted to the Franco-chinese association on 26/04/092 in which we propose « to search for nov and related proteins in the serum of patients, in order to establish whether the production of increased amounts of nov and related proteins can be useful in early diagnosis of some cancer tumors. » The preparation of polyclonal and monoclonal antibodies has been started in 1996 and funded through grants that I obtained and collaborations that I have set up long before the arrival of Maryvonne Laurent in my team .

The development of an Elisa test has been initiated a long time ago in our laboratory and I have personally asked M.Laurent to work on this aspect. I must admit that this project was obvious. I have shown my interest in developing this approach when I hired R.Legeaye (a student from a technical school in Laval) and invited Pr S.Kyurkchiev in my laboratory. Both of them have participated very actively in the setting up of the Elisa test and immunological assay that were based on the use of purified antibodies that M.Laurent is presently using(the progress report of these two visitors that I can provide, clearly establish that I was in charge of this project and indeed directing it).

v) the research project « role and effects of nov in the control of normal and pathological cell proliferation » has been developed in my laboratory for so long that it is not even necessary to come back on that point. All the grant applications, progress reports and publications are there to testify for the implication of my team in this field.

Cécile’sanswer refers to her CNRS report for the year 98-99
i) the research program purification of nov from normal and pathological sources has been undertaken in my group for several years (see ann 2 and 3) long before we went away from the Curie Institute. This project appears as soon as 1995 in the grants applications that I personnally wrote and that were funded by several agencies.

ii) the program study of biological properties of nov has been our general theme for many years. Reading the research program that I have written for my team is enough.It talks by itself. I will only cite one project that I sent to the Pasteur Institute on 1991, may 29th(yes 1991 ! before our first paper on nov was published !) in which I quote our research projects regarding the tumorigenic potential of nov, the potential binding of nov to IGF, and the potential biological importance of the C terminal domain of nov. The partial identity of nov and IGFBP had led me to send Cécile visit M/Binoux at St Antoine. What a surprise to see that the study of the terminal portion of nov is among the original resaerch themes developed by Cécile.

Actually, some of the aspects of this research program should have been achieved for a long time ago if they had been run efficiently.

Of course the results that we have obtained and our increasing knowledge in the field lead us to perform new approaches, such as using production of nov by NCIH295R cells that Cécile wants to undertake. But this, as such, does not constitute a new research program.

For several years I am trying to convince Cécile and Maryvonne to examine whether other proteins of the CCN family, especially CTGF and Cyr 61.

This appears in a handful of fax, emails and laboratory meeting reports (see for example 2,3). Therefore, this aspect is not an original research program of Cécile or Maryvonne, but again it is a project that is a major one in my team.
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All the projects that Maryvonne is willing to "realistically" develop are, of course, all those that I asked her to work on, when she joined my laboratory.

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Cecile's projects are not, as she claims, the sole continuation of what was previously undertaken. I wish to remind you that in a meeting with M. Binoux on november 13, 1997, you and I had decided that we should examine whether the expression of nov was altered in adreno cortical tumors.

This project represented the continuation of experiments that my laboratory performed with Paul Schofield in 1992 and Herman Yeger in 1994,and which established that the adrenal was a major site of expression for nov.

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It is true that nov is public and I accept competition by groups outside of the unit, when it is taking in account the ethics rules. I have always tried to develop collaborative projects with potential competitors because I believe that sharing our knowledge and material is a unique source of scientific power.

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I think that the proposition I made in my previous mails and during the discussion that we have had on wednesday, would avoid any kind of conflict.

I hope that you have taken the time to read all this letter and that the informations I provide will help you to have an ojective view of the situation.

Cordially

Bernard Perbal