Peer Review: Value Added and Civility
Authors: Chi Van Dang
Journal: Cancer Research (2022)

Since many foundational observations have been made in physics and biology, science has become more complex as we delve into networks of factors that influence a physical system, such as climate change and weather, or tumor growth, such as metabolism and the tumor immune microenvironment. Therefore, peer review is essential for ensuring that studies on the complex nature of cancer biology are sound and advance our knowledge. Science progresses through scientific meetings and the literature, guided by the guard rails of peer review. I believe that the evolution of a manuscript through a proper peer review process almost always improve the quality of the work, particularly when reviewers suggest insightful and tractable experiments.On the other hand, scientists complain about the burdens imposed by reviewers, but the good, the bad, and the ugly sides of peer review rest upon us as a community—we are the reviewers that we are complaining about. Collectively, we can and should continue to improve this precious, yet imperfect, process by adding value as reviewers, being mindful of the importance of civility, and being aware of bias that could block the advancement of science. This imperfect system is the best process that has emerged to ensure that scientific findings are sound and provide a solid foundation for our understanding of the natural world. We, as reviewers and authors of the fabric of science, must help to form a more perfect system for generations to come.I remember having lunch on a sunny November day in 2009 at a CNIO meeting in Madrid with Dr. James Watson, who was surrounded by several journal editors and trainees. I am a bit of an amateur history buff, so I asked Dr. Watson what the peer review process was like when he and Francis Crick submitted their 1953 landmark paper to Nature. I must have jolted a litany of Dr. Watson's notions that burst forth upon this small lunch audience. Dr. Watson said that journal editors were smart scientists who could render decisions without peer review; in fact, he said the famed Nature paper was not peer reviewed. Then, he proceeded polemically to point out some of the drawbacks of a system that was institutionalized by the Royal Society in the 1600s. Although flawed, peer reviews are feedback loops to increase the quality of our empirical knowledge, but several major journals did not use outside reviewers until after the 1940s (1). Of historical importance, all three of Albert Einstein's 1905 paradigm-shifting “annus mirabilis” papers on special relativity, the photoelectric effect, and Brownian motion were not subjected to peer review, were accepted by editor-in-chief Max Planck, and were published in Annalen der Physik. Einstein, a 26-year-old examiner in the Patent Office of Bern, Switzerland, was arguably an “early career” investigator, whose unorthodox work on special relativity was met with resistance by peers who believed in the existence of “ether.”Many of us have experienced our peer review system, which is essential for ensuring the quality and validity of the body of evidence that supports specific hypotheses or conclusions. On the other hand, there is room for improvement. In the late 1980s, we learned that transcription factors could be parsed into DNA-binding domains and transcriptional activation domains (2). On the basis of this concept, my laboratory sought to test the hypothesis that MYC could function as a transcriptional regulator and found that the amino terminal end of MYC had strong transcriptional activity when fused to the yeast transcription factor GAL4 DNA-binding domain. As an early career investigator, I was thrilled by this foundational observation establishing MYC as a transcription factor and sent our manuscript out for publication. At the same time, another group took the identical hybrid GAL4 DNA–binding domain approach and identified the p53 transcriptional activation domain; their manuscript was sent to the same journal. I received a cover note from the editor and two reviews in regular mail, as e-mail did not exist. One review was supportive with constructive comments, and the other…not so much.The other review was typed on watermarked paper with a short paragraph that was quite negative and made an interesting tautological argument. The argument was that MYC function could not be gleaned from an artificial experimental system using the yeast GAL4 system, and hence, without knowing what MYC really does, this system could not uncover its function, QED. I was baffled because this critique could not possibly be addressed; a tautology cannot be empirically challenged. I contacted the editor, who was empathetic but did not support the publication of our work. The work on p53 using a parallel approach, however, was published. I was quite discouraged by this experience but turned it into a lesson learned. What I learned was to apply the golden rule when I am asked to review papers. We need to treat manuscripts under review as if they were ours, constructed after many years of toil, flawed as the work may be.The p53 transcriptional activation domain paper was authored by Sung Key Jang and Stanley Fields (3), who invented the yeast two-hybrid system published a year before. In retrospect, perhaps the “Matthew Effect” was at play here. This “rich get richer” effect was coined from the biblical Matthew 25:29 parable: “For whoever has will be given more, and they will have an abundance. Whoever does not have, even what they have will be taken from them.” This effect yields more favorable peer review outcomes for authors with name recognition and those affiliated with prestigious institutions (4). The Matthew Effect stacks against early career investigators, whom we should collectively celebrate as we do with the annual Cancer Research Early Career Award.It is critically important for us as reviewers to examine the submitted work agnostically and let the ideas and evidence speak for themselves. Furthermore, I believe that reviewers should add value to our peer review process by providing clear constructive criticisms and suggestions of pivotal experiments that could improve the work, or for that matter, refute its central thesis. Precise comments and recommendations are an essential part of responsible peer review. Vague critiques that cast doubt without recommending tractable experiments do not add value. This is the juncture where journal editors play key roles in the peer review process. Editors have the responsibility to deal with the feared uncharitable “third reviewer” and exercise editorial authority to override outlandish comments. While anonymity allows the peer review system leeway and diminishes retaliation, it also provides grounds for unrestrained rude behavior. As editors, we need to exercise fairness, and, as reviewers, we need to be civil and clear, welcoming and making room for the next generation of scientists and the next disruptive idea.The Committee on Publication Ethics (COPE; https://publicationethics.org), a nonprofit organization, provides a guideline for peer reviewing. The basic principles of this guideline pertain to the provision of proper expertise, confidentiality, protected information, conflict-of-interest, objectiveness, constructiveness, timeliness, and avoidance of biases against the origin of the manuscript based on the authors’ nationality, religion, gender, or political beliefs. The controversial classic 1968 study by Goldberg of “John” versus “Joan” suggested that women are more likely to rate male authorships favorably (5), underscoring implicit biases, which were later also documented for male reviewers. The COPE principles perhaps could be summarized by the golden rule and fairness. Despite these basic principles of civility, rude and unprofessional reviewers remain among us. In fact, a study revealed that unprofessional peer reviews span across papers from different gender and ethnic groups (6); half of the respondents to an anonymous survey reported that they had received unprofessional reviews. Importantly, the study uncovered that underrepresented groups in STEM perceive incivility of unfair reviews as negatively impacting their productivity and career advancement.The scientific publication industry has witnessed a paradigm shift with the emergence of servers storing preprints of manuscripts prior to formal peer review and publication in a scientific journal. Intriguingly, sharing of preprints meant to advance a field among colleagues occurred decades ago, most notably among physicists who launched arXiv.org around 1991 (7). The preprint culture was well-established in high-energy physics, which as a field treasures team science as illustrated by the creation of Large Hadron Collider (LHC) located outside of Geneva, Switzerland and into France.In 2013, bioRxiv was launched to host biological scientific preprints, which are now not considered by major journals to be a barrier for formal manuscript submission (8). In fact, direct citations of preprints in peer-reviewed papers are increasing as well as preprint downloads, and one study reports that published papers that were preceded by preprints trended toward a higher citation rate (9). The peer review system now faces preprints as a new source of information with which to judge manuscripts submitted for publication. For example, with the increasing citation of preprints, reviewers must now peruse preprints that could negate or support the thesis of a manuscript in question. However, while this additional information may be useful to assess the merit of a manuscript, preprints have not been formally peer reviewed and should be used with careful inspection and circumspection.With this shift in communication of scientific research, we are witnessing a shift in peer review. It is critically important, however, to emphasize that posting preprints is insufficient to ensure the robustness of the scientific literature without proper peer review. When done correctly, peer review makes science and scientists better. I hope that, by embracing the golden rule as a fundamental, immutable principle, we can strengthen our peer review system to better support the next generation of scientists, embrace diversity, and welcome unorthodox views.No disclosures were reported.