Animal house

Abstract

While the JCI was originally conceived as a journal that would integrate various scientific approaches to the examination of human physiology and pathophysiology, we now find many of its pages filled with animal models of human disease. Is this a good thing?

Almost every day I consult the Editors’ internal manuscript tracking website to see what new manuscripts and reviews have come in and also to check our in-box for correspondence from authors. You won’t be surprised to hear that most of the letters we get are from authors of recently submitted papers. Generally these are complaints or appeals about manuscripts that we declined to publish. Here and there, we receive a letter from a more satisfied author whose paper we have provisionally accepted. These usually take the form of thanking us for our decision but wondering whether they really need to do the experiments asked for by Reviewer B.

Both of these types of letters are of course specific to the circumstances of a given manuscript. However we do get some generic correspondence, and by far the most common point raised is (to paraphrase) something along the following lines: “The JCI is no longer interested in clinical investigation”; “There is nothing clinical about the JCI”; or “The JCI these days is just another mouse models journal,” with this last comment causing particular anguish.

I was particularly struck by a very thoughtful note I received from a professor at a prestigious midwestern university, who wrote: “I have observed that the JCI, which was once my favorite journal, is no longer a journal of clinical investigation but rather a journal of mouse or molecular investigation. Well over two-thirds, and often over 90%, of the articles in a given issue are reports of work performed either in mice or in vitro, and clinical work involving human patients is very rare . . . I am very unlikely to submit our work to JCI in the future . . . Even though the work in mice is very important, I think this is a great shame and that you should consider renaming the journal as its content no longer reflects its title.”

Ouch!

I have thought about this letter at length because I believe that the JCI needs to be responsive to its constituency while also being responsible to our mission, which is to publish the best possible science pertaining to the genetic, molecular, cellular, or physiological basis of human biology and disease. I believe that this mission has probably changed little since the JCI’s inception over 80 years ago. What has changed, certainly, are the methods and tools used to investigate this area, and as techniques evolve, so have our expectations. It would be rare for many of the studies published at the beginning of the journal’s tenure to be acceptable now. Thus, studies in humans or using human tissue are not the only means to address human health, although the latter remains our main concern.

In the year since I have taken over as editor, about 35% of the papers that the Penn editorial board has either accepted or returned for revisions (with a positive note indicating interest) report on work done with either human subjects or human tissues. We believe that the remainder of the papers are relevant to human biology and disease, and indeed we hold nonhuman studies to different standards than we do human work, reflecting the obvious limitations of clinical investigation. We certainly recognize that human studies will almost always be more descriptive than animal studies, but this does not detract from our interest in clinical investigation that is well conducted, reports novel findings, and is likely to stimulate further studies in areas of potential impact and relevance to health and disease. I renew again my call for you to submit these papers to the JCI.

Our nonhuman papers are also not just about mice: the balance of the papers not using human subjects or tissues includes studies in mice, rats, nonhuman primates, dogs, sheep, pigs, ferrets, Drosophila, Xenopus, and C. elegans, among others. Not surprisingly, mice predominate, but this is not because we are interested in mice per se, but rather because in many instances they present the best system to examine and perform cause-and-effect experiments relevant to human diseases. We are not alone in this sentiment; the 2007 Nobel Prize in Physiology or Medicine was awarded to three scientists who developed and realized the techniques to create knockout mice. Regarding our name, while I can’t swear that we would choose the same name if we were starting the journal today, we are proud of our heritage and do not wish to lose it.

Last, I’d like to make one other comment. I responded via e-mail to the professor noted above, in response to which he expressed surprise that I had bothered to reply at all. Unlike Brad Pitt, my fan mail doesn’t exceed my capacity to answer it; at least not yet. Correspondents will find that I respond to everything but letters that rise (or stoop) to the level of hate mail. Letters about specific manuscripts may be answered by members of the Editorial Board on behalf of the journal. More general letters addressed to me will be answered by me directly, and I encourage them. As I have said before in this space, the JCI depends on authors and readers. We try to serve your needs as best we can, but to best do so, we need to know what you think.