Subhash Kulkarni is a faculty member at Beth Israel Deaconess Medical Center (an affiliate of Harvard Medical School), working on understanding the postnatal maturation, homeostasis, aging and dysfunction of the mammalian enteric nervous system.
Subhash recently published the Reviewed Preprint ‘Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease’ through eLife’s new model, and spoke to us about their experience.
As our study challenged established dogma, I knew it was important to provide multiple lines of evidence to ensure that our results were both robust and correct, and our inferences were nuanced. However, after three cycles of review at an earlier journal, the issues that ail the prevailing publication systems became apparent.
I found that the current system unfortunately does not provide for a mechanism where first reports of novel findings from small labs, that may be considered paradigm shifting in their own right, are reviewed on the merits of the data presented, and there is an inherent expectation from reviewers to “do more”.
These expectations of the reviewers, who often request more data without providing adequate justification for why these data (which often require costly experiments) are needed, often have no editorial checks. Without significant editorial oversight on reviewers’ expectations, each and every comment (regardless of the merit of the comment) from the reviewer has the ability to be a dealbreaker in the acceptance and eventual publication of the study. Thus, publishing a novel finding in journals presents a significant and often an impossible cost to small fledgling labs like ours.
I must add that while the consultative peer-review process of the older model at eLife was an improvement over the traditional system of peer review and publication, the consultative peer-review system did not catch or correct even inane mistakes of the reviewers, while seeking to impose significant costs to the authors of the study.
It was clear to me and our entire team, then, that what we needed is a fair review process, where the editorial insight at the end of peer review does not come in the form of traditional accept or reject decisions, but in the ability to provide a nuanced summary of the study and of the reviews.
This nuanced ‘editorial’ which would evenly represent the strengths and weaknesses of any study was exactly what our study needed, which by now had already been reviewed and rebutted four times. It was with this thought that the new eLife model (or eLife 2.0) was appealing to us and we decided to submit our study under the new model while ensuring that prior reviews and rebuttals were made publicly available at our preprint link on bioRxiv.
Like any new model, I expected some teething problems at eLife, but these were resolved by the excellent staff and editors at eLife.
The responsiveness and cordiality of the eLife editorial team ensured that I knew exactly what stage in the process we were at, and what the next steps would be. I am confident that with time, some of these early issues will be ironed out and that the process will be more seamless.
It would be remiss of us not to mention that in the new process, after the review was completed, our Senior Editor was responsive to our queries and comments, and always willing to provide additional clarification on assessments and review. The intent of the entire team to make peer review an easier process in eLife 2.0 for the authors is heartening, which allows the authors to focus on the science and not worry about the ‘gladiatorial up-or-down vote’ that we have unfortunately become accustomed to in the publishing process.
After going through a total of four cycles of review under the traditional model, and under the earlier model at eLife, I had no reservations of submitting through the new model.
This was principally driven by my confidence in our study, and in my view that the current models of publication are not suited for adjudicating studies from small labs that challenge established rules and dogmas.
As scientists, we teach our mentees that it is improper to repeat the exact same experiment every time and expect a different result. I often then wonder why it is so difficult for academics to embrace the truth that the current system of publishing has several flaws, and that the only way forward is to significantly innovate and improve on the existing system.
If we teach our mentees to improve on our current systems and meet unmet needs in science, then doing better in how we peer-review and publicly disseminate science should be at the top of our goals.
My only advice to our large and diverse community is to do everything we can to make science and peer review transparent. That starts with taking ownership of the review process by preprinting your study, publishing the reviews and rebuttals and thus making them public, and being open to the new eLife model or any other model that seeks to significantly improve upon the current systems where we lose countless working hours (and have sleepless nights) worrying about Reviewer 3.
Our study in eLife, which focuses on the developmental mechanisms driving the maturation and aging biology of the enteric nervous system (ENS) has several firsts – some of which reverse decades of dogma in developmental neuroscience.
Firstly, we showed that the adult ENS is in equal parts composed of two distinct neuronal lineages – the canonical lineage of neural crest-derived enteric neurons (NENs) and the non-canonical lineage of mesoderm-derived enteric neurons (MENs). Our study therefore reversed decades of dogma that stipulates that all vertebrate neurons are derived from the neuroectoderm.
Secondly, the study shows that the MENs, which have a different neurochemical profile than NENs, are born in the postnatal gut and their rapid expansion during the juvenile phase is correlated with maturation of this significant nervous system.
Thirdly, by showing that the expansion of MEN lineage continues in aging such that the aging ENS is almost completely composed of neurons of the MEN lineage, our report defines how the ENS ages to cause dysfunction, and shows that aging of the ENS is the culmination of its postnatal developmental process.
Finally, the report provides evidence that aging of the ENS is associated with dysfunction, and in mice, ENS aging can be reversed to normalize function by supplementation with a NEN lineage-promoting growth factor, GDNF. While these are just some of the highlights from our study, it significantly impacts the fields of developmental neuroscience, aging biology, and medicine.
The next goals for my lab are to expand our molecular understanding of mesodermal neurons in the adult gut, and study the diverse functions that they regulate. In addition, we are working on understanding the diverse factors that promote ENS aging, as well as the molecular factors that drive ENS rejuvenation, so that these discoveries can be rapidly translated into the clinic to help the millions of elderly patients suffering from age-associated gut dysfunctions such as chronic constipation.
To publish your work with eLife, or if you’d like to know more:
You can also read Subhash’s Reviewed Preprint ‘Age-associated changes in lineage composition of the enteric nervous system regulate gut health and disease’ or explore the latest Reviewed Preprints on our website.
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