Call for Papers on “Lung Diseases in Reverse Translation: Bedside to the Bench”

“We don’t have to look for model organisms anymore because we are the model organism.”

—Sydney Brenner (2008)

Respiratory diseases currently account for some of the most frequent causes of severe illness and death worldwide. Of the so-called “big five” respiratory diseases, chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide; and asthma is the most common chronic disease of children (6). Lung cancer ranks first in men and second in women as cause of cancer-related deaths (13). Of the infectious diseases, tuberculosis is the most fatal, while pneumonia is the leading cause of death in children under 5 years of age. Clearly, the global burden of respiratory disease is massive (5–7, 15). This point is further underscored today by the ongoing coronavirus disease 2019 (COVID-19) pandemic (2).

Therefore, there is tremendous pressure to translate bench studies on lung diseases into new therapies and clinical management strategies as fast as possible. A key goal of current investigative lung science is often to identify either “druggable” disease-causing processes and pathways that can be manipulated to prevent, halt, or reverse the course of lung disease (3); or trigger or support processes that promote or restore homeostasis (8). This objective, of course, is an important and noble aim. In such basic science studies, the characteristics of the disease, often described many years before, have been used to inform experimental models in laboratory animals or in ex vivo and in vitro systems, representing the beginning of the “translational pipeline.” These preclinical models are then employed to identify pathogenic processes operative during the onset and progression of disease. Once specific pathways are identified, high-throughput, low-throughput, or targeted approaches are employed to select interventions that influence the targeted pathogenic process. These interventions are then validated in ex vivo, in vitro, and in vivo disease models. After that, the study moves from the bench to the bedside, and the utility of the intervention of choice is validated (or not), first in human toxicity and dosing studies, followed ultimately by larger multicenter clinical trials in humans. This translational approach has been tremendously successful in bringing new and refined clinical management strategies for affected patients into routine use, and that remains the hope of the extraordinarily accelerated efforts in drug (12) and vaccine (9) discovery currently underway in response to the COVID-19 pandemic.

Data gleaned from clinical trials in patients with lung disease, and the correlations drawn from comparisons between data sets generated from patient samples and those from (at times, questionable) experimental animal and in vitro models, have produced a wealth of valuable information about pathophysiological processes at play in lung diseases. However, the intense focus on translational science has meant that the balance of studies on “bedside to bench” versus “bench to bedside” has swung in favor of the latter, at the cost of interest in—and exploration of—clinical observations made about lung diseases for which we currently have no physiological explanation. This Editorial opens with a quotation by the Nobel laureate, Dr. Sydney Brenner, who stated at the 99th Annual Meeting of the American Association for Cancer Research which took place on 12th-16th April 2008 in San Diego, California, that “We don’t have to look for model organisms anymore because we are the model organism” (10)! While most lung scientists would disagree that experimental animal and in vitro models of lung disease have become obsolete, the point is well taken that the clinical course of—and biological material harvested from patients with—lung diseases also represent valuable resources that may guide and drive bench research. In his talk, Dr. Brenner challenged the notion that translational research is unidirectional, working from the bench to the bedside, and lamented that the reverse direction is all too often overlooked. With reference to the bench to bedside polarity, he commented, “I’m advocating it go the other way” (10). This challenge has been embraced by the editorial leadership of our Journal. Earlier this year, our Journal issued a Call for Papers “Deconstructing Organs: Single-Cell Analyses, Decellularized Organs, Organoids, and Organ-on-a-Chip Models” (1) which highlighted the tremendous opportunities presented to bench investigators by emerging technologies for the interrogation of clinical samples. Indeed, this rapidly expanding toolbox of new approaches brings lung scientists unprecedented capacity for understanding lung diseases and their heterogeneity, at both the population and molecular and cellular levels (11, 14).

Building on this theme, and in recognition of World Lung Day on 25th September 2020 (4, 6, 11, 14), the American Journal of Physiology-Lung Cellular and Molecular Physiology is issuing a new Call for Papers “Lung Diseases in Reverse Translation: Bedside to the Bench.” The objective of this Call for Papers is to stimulate interest in taking unexplored clinical problems and observations to the laboratory bench, to understand the physiological basis at a molecular and cellular level. To this end, we encourage the submission of Editorial, Perspectives, Mini-Review, or Review manuscripts that highlight clinical aspects of lung disease for which no physiological explanation has yet been established. This is a broad Call for Papers, and suitable topics may include, but are not restricted to:

• The unexplained effect or side effect of a pharmacological or other medical intervention used to manage patients with pulmonary disease.

• Any clinical component of perinatal, neonatal, adolescent, or adult pulmonary disease for which a physiological basis has not been clarified.

• Any aspect of normal or pathologic pulmonary physiology for which different (or conflicting) physiological bases have been proposed.

• Aspects of clinical pathophysiology that are not modeled in existing in vivo and in vitro preclinical models of human lung disease, with suggestions for how to do so.

Submissions under this Call for Papers are by invitation only. If you have identified an unexplored and/or under-investigated area of pulmonary pathophysiology that you feel might be a suitable topic for an Editorial, Perspectives, Mini-Review, or Review published under this Call for Papers, please contact our editorial leadership: Dr. Larissa A. Shimoda (at lshimod1@jhmi.edu) or Dr. Rory E. Morty (at rory.morty@innere.med.uni-giessen.de) to discuss your idea. If your idea is considered suitable for the submission of a manuscript, an invitation for submission will be extended. Deadline for submissions is June 30, 2021.

GRANTS

L. A. Shimoda is supported by the National Institutes of Health through National Heart, Lung, and Blood Institute Grant HL073859. R. E. Morty is supported by the Max Planck Society (MPI-HLR); the German Center for Lung Research (Deutsches Zentrum für Lungenforschung; DZL) (DZL-UGMLC), and the German Research Foundation (Deutsche Forschungsgemeinschaft; DFG) through EXC2026 [390649896], SFB1213 [268555672], KFO309 [284237345], Mo1789/1-1 [160966624] and Mo1789/4-1 [160966624].

DISCLOSURES

L. A. Shimoda is the Deputy Editor of the American Journal of Physiology-Lung Cellular and Molecular Physiology. R. E. Morty is the Editor-in-Chief of the American Journal of Physiology-Lung Cellular and Molecular Physiology. Both Editors are compensated by the American Physiological Society for their services.

AUTHOR CONTRIBUTIONS

L.A.S. and R.E.M. drafted manuscript; edited and revised manuscript; and approved final version of manuscript.