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Acceptable practice?

Eivind Hovig ehovig at radium.uio.no
Wed Feb 4 09:37:17 EST 1998

This is to written to liven up the newsgroup, and to question the
editorial handling of submitted papers in a well known cancer journal.
Also, I suspect the issue applies to other fields as well.

The situtation is as follows: 
A paper was submitted to a well respected and known cancer journal on
detection of a novel pseudogene of a gene that has been relatively widely
used in detection of circulating cancer cells indicative of metastasis. In
fact the selected gene (called CK19) was chosen because the gene was the
most widely studied gene in the field. We demonstrate in our paper that
the novel pseudogene sequence in fact may well have interefered with
previously published reports, thus potentially invalidating them. We feel
that this is an important contribution that may help to clarify the
present confused state the field. As you may guess, the paper was turned
down. The correspondence on the paper is given below, for you to judge. Of
course, you do not have the actual paper at hand, but this is not critical
for most of the discussion below. In my opinion, this situation has
appeared because the paper reports a finding with a negative impact on the
research area.

We received only one single referee statement on this paper. This
statement is quoted in its entirety:

"1. The importance of this work should be seen in light of the future
applicability of CK19 transcript estimation for cancer detection and
monitoring. My own estimate is that this is only a moderately likely

2. The pseudogene reproted would not interfere with some of the most
commonly used primers and this therefore limits the applicablility of this

3. A major weakness in this manuscript is that the authors do not show
that the pseudogene would have given false positives in actual blood or
bone marrow samples. This needs to be demonstrated.

4. The real conclusion of the study is that primers P1 and P2 followed by
P5 and 6 in the sequence of primers described by Schoenfeld et al, and as
such, dows not really provide much new information."

This was our written complaint:
"Reviewers comment 1: Here it is stated that the reviewers personal
opinion is that there is only a moderate possibility that CK19 transcript
estimation will be used in cancer detection and monitoring. This
anticipation is self-fulfilling, as the nonprinting of present paper, with
its aim of clarification of a number of conflicting results on CK19
quantitation, published in several well-respected international journals,
will leave the field in the present state of confusion. Furthermore, no
arguments are presented to substantiate the opinion. We feel that a
rejection on this basis, without a scientific foundation, is an
unacceptable practice in science publishing, and fundamentally in conflict
with the advancement of science.

Reviewers comment 2 states that the reported pseudogene will not interfere
with some of the most commonly used primers and and that this limits the
applicability of the manuscript. As is discussed at length in the paper,
in fact only two of the many published primer sets evades the new
pseudogene, and then only with a couple of the actual primers. After the
submission of this paper, one new publication has also published a primer
set with a unique primer (Denis et al., Int J Cancer 74(5): 540-544, 1997
). Regardless, the reviewers statement is not in line with our perception
of reality, and the reviewer does not give any facts to demonstrate his
postulate, as opposed to our lengthy discussion of the topic in the paper.

Reviewers comment 3 claims that a major weakness of the manuscript is that
the authors do not show that the pseudogene would have given false
positives in actual blood or bone marrow samples and that this needs
demonstration. As is stated in the abstract, we used "... RNA and DNA
specimens extracted from peripheral blood nucleated cells of healthy
volunteers..." and "...found a novel pseudogene...". In fact, it is stated
that the paper is intiated by such findings. Furthermore, figure 1
displays PCR products from 5 healthy volunteers together with a positive
control, demonstrating what the reviewer claims is lacking. To us, it
appears as the reviewer at best has had a very superficial reading of the

Reviewers comment 4 about specific primers is unclear, as the sentence
lacks a verb, but is besides the main point of the paper. The main point
is that the novel pseudogene in fact may be a significant reason why CK19
transcript quantitation is not widely used in the clinic in a
micrometastasis setting. Of course, other primers than the ones suggested
by us may now be more rationally constructed on the basis of the sequence
information given in our paper.

On the basis of the above, we feel that neither Cancer Research or
paper-submitting authors in general are well served by accepting a review
of this quality, especially not as the sole review."
We received a reply from the editor-in-chief, confirming the rejection:
"Thank you for your letter regarding the manuscript.

We are sorry that you consider the review to be inadequate. Nonetheless,
the expert who evaluated the work judged it to be unacceptable for
publication, and the Editors concur with that assessment. Thus, the paper
cannot be reconsidered.

We regret that a more favorable decision could not be rendered on your
manuscript, and we hope that you will not be deterred from submitting
future work for our consideration."
You may note that this reply in fact does not even attempt to address ANY
of the points raised by our reply, also no alternate "expert" was

I think such handling by a well respected journal is a disgrace to both
the journal and the editorial staff.

Opinions on this are appreciated,


Eivind Hovig PhD, Senior scientist, The Norwegian Radium Hospital

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