When my paper (Develop. Growth & Differ. (2011) 53, 1-8) was accepted for publication, I sent a preprint to Prof. Denis Duboule with the following covering letter.
Prof. D. Duboule
5 November 2010
Dear Dr. Duboule,
I enclose a preprint of my work that is going to be published in Development, Growth & Differentiation.
My work is mainly based on the experiments of your gr oup. However, the interpretation of your results that I propose in the biophysical model differs from your two-phases model.
Any comments are welcome.
Sincerely,
S. Papageorgiou
Email:spapage@bio.demokritos.gr
As expected, I received no answer from DD.
Last month, an article by P.Tschopp and D. Duboule appeared in Dev. Biol. (2011), 351, 288-296 and, as a result, I thought of two experiments that could test both models (see my blog Two experimental proposals…). Since DD does not bother answering my letters, I sent my proposals to Patrick Tschopp (a co-author and PhD student of Duboule):
28 March, 2011
Dear Patrick,
I know your supervisor has strong objections against my biophysical model for Hox gene collinearity. Probably this is understandable since he believes he has found the ‘true’ explanation of collinearity.
In the attached propositions however, two experiments are described which can distinguish which model is correct (if any at all). In your lab these experiments are easily done.
In the quest for scientific truth, it is worth performing the above experiments even if you are convinced that the results will only confirm your predictions.
Looking forward to hearing from you.
Best wishes,
Spyros
S. Papageorgiou
P.Tschopp answered next day politely explaining why he could not undertake this task:
Dear Spyros,
thank you for your message. I have read already your recent review, in fact Denis gave me the print-out you sent him. However, I also stand by the conclusions and the model we deduced from our series of experiments.
The Evx3-Hoxd13 region has been investigated in quite some details, with the recent inversion as well as deletions encompassing Hoxd13. If only this stretch of DNA was deleted, no premature expression was observed, only when fragments more centromeric to Evx2 were affected (see Kondo and Duboule 1999; Tschopp and Duboule 2011).
A clean deletion of this intergenic region would require the generation of two new loxP sites, thus tedious ES cell work and at least 2 -3 years of follow-up. As I will be leaving the lab in less than two months, I will not be able to consider either one of the experiments you suggested!
Thanks anyway for your continued interest in our work.
Sincerely,
Patrick
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The same day I received an e-mail from D. Duboule himself in relation to my message to P. Tschopp:
Spyros,
I find your mail insulting- Why dont' you mind your own business?
If you have good ideas, go for it and leave us alone-
You just lack a sense of education-
D
Prof. Denis Duboule
Dept of Genetics and Evolution
Faculty of Sciences, University of Geneva
Sciences III, 30, Quai Ernest-Ansermet
1211 Genève 4, Switzerland
Tel (41) 22 3796771; Fax (41) 22 3796795
http//zoologie.unige.ch
Administration: Corinne Matthey-Ebener
Tel. (41) 22 7026770 (6785)
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I think this is too much!
I answer publicly to DD since my arguments might be of some interest to other members of the scientific community.
1. The readers can judge for themselves whose writings are insulting and rude.
2. Performing gr ound breaking experiments is one thing, their proper explanation is
another. In other disciplines (e.g. Physics) Experiment and Theory (although in
coherent cooperation) have been separated a long time ago. Probably E. Fermi was
the last gr eat Physicist- experimentalist and theoretician at the same time. Many
excellent biologists should accept this natural metamorphosis of their field, since
the quantitative analysis of their complex data requires the involvement of other
branches of Science like Mathematics and Physics.
Hand waving qualitative ‘models’ give place to accurate estimates and elaborate
calculations. Experiment, however, remains the indispensable foundation of the
scientific edifice. This sine qua non prerequisite underlies all efforts along the path
from hypothesis to Theory. Any criticism of proposed ideas, as long as it is based
on scientific arguments alone, is welcome, constructive and free to all.
3. Coming to the problem of Hox gene collinearity, it is more than 10 years that I try
to understand this enigma. I have formulated a model, the biophysical model,
which explains satisfactorily - to my taste- the existing data. The last years genetic
engineering experiments were performed almost exclusively in Duboule’s lab.
Duboule and co-workers have proposed the ‘two-phases model’ which, I think,
does not convincingly explain the data. It is ironical that all their new results fit
better in the biophysical model whereas many of their findings remain unexplained
by their model. I still believe it is worth performing the experiments I propose
above or arrange other similar setups to explore the behaviour of the posterior region
of the Hoxd cluster and compare it to the fixed end role of an elastic spring.
Passing over D’s out of temper response, I personally feel thankful to the work
of his team for their experimental achievements since their findings helped me
substantially in the formulation of my model.
Spyros Papageorgiou
Just found your blog. Good job to air everything.
ReplyDeleteanna