No Way Am I Doing That Experiment

There has been some interesting discussion over at Blue Lab Coats concerning how to respond to peer reviewer comments on a manuscript submitted to a journal. If a journal editor concludes that a submitted manuscript is potentially suitable for publication, then she will send an e-mail to the corresponding author saying something like this:

Based on the reviews, we will be happy to consider a revised version of your manuscript, in which you should modify the manuscript to address the concerns raised by the reviewers. It is important that you address the reviewers’ concerns in your revised manuscript and also in a point-by-point reply to the reviews that indicates how you have responded to each of the reviewers’ comments.

Suppose that the reviewers have asked for additional experiments that there is no fucking way you are going to perform before resubmission. What are the circumstances under which you can finesse this, and still get your paper accepted?

Here are some scenarios in which one can usually get away with not performing a suggested experiment. I will illustrate with mock verbiage from a putative point-by-point reply to the reviewer comments.
Scenario #1: Reviewer Asks For Another Control

As the reviewer points out, those experimental conditions were not used as controls for the experiments described. Rather, we used a whole bunch of other fucking controls. These are all better controls than the one suggested by the reviewer because they exclude the much more likely possibility that blah, blah, blah, rather than the highly unlikely possibility that bleh, bleh, bleh ruled out by the control suggested by the reviewer.

The important thing in finessing this scenario is to make a very convincing argument that the possible artifact ruled about the additional suggested control is much less likely to be occurring than the ones ruled out by the controls already performed. There are always an infinite number of possible controls for any experiment, and you obviously can’t do all of them. What’s important is to rule out the plausible artifacts. Authors need to band together and refuse to indulge reviewer requests for laborious additional controls that rule out exceedingly unlikely artifacts.
Scenario #2: The Experiments Actually Performed Are Interesting, But What Would Really Be Impressive Is Blah

While we appreciate that such a result might be “impressive”, it is not clear what it would add to the strength or nature of the conclusions concerning blabbity blabbity blab we have drawn from the experiments already performed. The suggested experiment has two possible outcomes, which would lead to two different conclusions.
However, distinguishing these possible conclusions does not tell us anything further about the strength or nature of the conclusions concerning blabbity blabbity blab we have drawn from the experiments already performed. The relevant point in terms of the conclusions of the maunscript is that–as our experiments already show–the effects we observe are not due to blah, blah, blah. Given the time-consuming nature of the suggested additional experiment–at least three months–we conclude that the cost in time and effort is not worth the potential benefit.

This is another situation where we authors have to band together and refuse to indulge reviewers’ attempts to transform our manuscripts from the ones we actually wrote to the ones they wish we had written. If the reviewer already considers the manuscript of sufficient interest and and convicingness to merit publication by the standards of the journal it has been submitted to, then fuck this “what would really be impressive” shit. It’s one thing if the reviewer thinks that the manuscript as submitted is not of sufficient interest. But if she thinks it is, then no fucking way am I gonna let her hold up publication for this kind of shit. Those experiments can go in the next fucking paper, thank you very much!
Scenario #3: What Would Really Strengthen The Main Conclusion Of The Manuscript (Which I Have Completely Misunderstood) Is Blah

Blaargh is the only known blingity encoded in the genome, thus making it nearly certain that the effects we see of kapow in our experiments are due to an effect on blaargh. Furthermore, the effect of kapow on blaargh is to inhibit wango, not to decrease the magnitude of wingo, as shown in the experiments of Figure 43. Since neither of the suggested experimental manipulations influence blaargh wango, such experiments would not be germane to the conclusions of the manuscript.

In this case, the reviewer has misunderstood the biological effect of the main experimental manipulation used in the manuscript, and has thus misunderstood the nature of the main conclusion of the manuscript. Based on these misunderstandings, the reviewer has suggested experiments that are irrelevant to the actual main conclusion of the manuscript and are only germane to what the reviewer erroneously thought was the main conclusion.
This is a tricky situation, since you wouldn’t have even gotten to this point of invited resubmission if this reviewer hadn’t already expressed substantial enthusiasm for the manuscript. So the last thing you want to do is lead the editor to conclude that this reviewer is such a clueless fuckwit that even her substantial enthusiasm for the manuscript must be discounted.
One final point: Regardless of the strength of your arguments against performing one or another suggested experiment, the most important consideration for the editor will always be the consensus of the reviewers. If you have three reviewers and a particular additional experiment was only suggested by one of them, you have a very good chance of finessing it away. If it’s made by two of them, you better have a very very strong argument. And if it’s made by all three, then forget finesse, and hit the motherfucking bench!