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The Post-Genomic Red Journal

Charting the Path from Hope (Not Hype) to Cure

Brigham and Women's Hospital

Address correspondence to: Steven D. Shapiro, M.D., Parker B. Francis Professor of Medicine, Chief Pulmonary and Critical Care, Brigham and Women's Hospital, Harvard Medical School, 15 Francis St., Boston, MA 02115. E-mail: sshapiro{at}rics.bwh.harvard.edu

Approximately 15 years ago, as the disciplines of cell and molecular biology were rapidly advancing and lung biologists were applying these techniques to answer medically relevant questions, Jerry Brody, Bob Senior, and Mary Williams insightfully believed that a new journal was needed to communicate findings to this expanding scientific community. Hence, in concert with the American Thoracic Society and its partner the American Lung Association, the "Red Journal" was born. John McDonald, and then Mike Holtzman, applied their considerable scientific knowledge and vision of the lung to make the Red Journal what it is today: the leading forum for both the original, lung-based, basic research that forms the building blocks, and the perspectives and reviews that assemble the blocks, to provide an overall picture of the lung in health and disease.

During these years we have witnessed the most remarkable progress in the history of biological science. Initially, discoveries included the generation of antibodies, cloning of genes, and production of recombinant proteins. Though often taken for granted today (or simply purchased), these tools remain essential ingredients in understanding gene and protein expression, structure, and function. With the completion of the human genome project, every gene has now been cloned and sequenced. Whereas the functions of the proteins they encode had been largely unknown, genetic mutants in lower organisms, and, more recently, genetic engineering in mice, are allowing us not only to define protein function, but also to understand physiologic mechanisms and dissect disease pathways in mammals.

Chronic obstructive pulmonary disease (COPD) is a great example that highlights both the advances made and the challenges ahead. At the inception of the Red Journal, the elastase–antielastase hypothesis was well entrenched, and research focused on the characterization of neutrophil elastase, its inhibitor 1-antritrypsin, and elastin itself. Despite marked advances on these fronts, the study of COPD was relatively stagnant, with few new ideas regarding additional molecules or cells that could participate in the disease process. In part owing to genetically engineered mice, we now appreciate that other matrix components (e.g., collagen), proteinases (including cysteine and matrix metalloproteinases), and inflammatory cells (particularly macrophages and perhaps T cells) are also involved. New concepts suggest that death of structural cells can initiate the process of lung destruction. Moreover, we have also discovered that unsuspected mediators such as the Th1 cytokine interferon- as well as the Th2 cytokine interleukin-13 have the capacity to cause emphysema when overexpressed. Having identified many families suffering from COPD and a few causative genetic loci independent of 1-antitrypsin, investigators have also made inroads from a genetic standpoint. Nevertheless, problems persist. We still lack a coherent, unified understanding of pathogenetic pathways that lead to COPD. And, most importantly, as the disease becomes epidemic worldwide, our patients have yet to realize any benefit from our toils.

And there is the rub. It is undeniable that our expanding knowledge has not significantly influenced patient care. So, while basic scientists revel in the "scientific revolution," clinicians question whether this "movement" is pure hype, ATS members question the relevance of this journal, and the public awaits a payoff on their investment. Are these expectations unreasonable? Is it our mission to learn about the lung or to improve patient care? I would argue both, as most readers would. Indeed, as part of the ATS, the Red Journal has a broader mission. And as clinician-scientists or Ph.D. scientists funded by the National Institutes of Health (or foreign equivalents), improving patient care should be part of our long-term goal (and not just the first paragraph of a grant proposal). In addition, it is a noble endeavor that brings even greater meaning to our careers.

So how do we get from here to there? First, it should be noted that in many areas we are already progressing toward the clinic. Academic and pharmaceutical scientists' "proof of concept" studies have given companies the courage to develop rationale therapy. The way forward is to integrate traditional hypothesis-driven studies in the test tube, cell culture, and whole organism with new "big science," including genomic physiology and imaging, genetic engineering, functional genetics and genomics, proteomics, and bioinformatics, to define comprehensive (patho)physiologic pathways.

What role will the Red Journal play in this process? Foremost, the Journal will continue to publish novel, high quality original work in lung cell and molecular biology. To acquire the best manuscripts possible, we will strive toward increasing our impact factor, already number one in its class. And to prelude our having to turn away outstanding reports from our constituents, we will attempt to increase page limits by generating funds (strategies to be discussed in future issues), and managing space more efficiently (e.g., with use of online supplemental material). We will also continue Mike's effort to expand the perspectives/reviews in the "front end" of the journal. In addition to the popular "Perspectives" that put journal findings into a broader context, we will add perspectives on outside articles, realizing that seminal work in the field will also be published in other journals. We will also add reviews that address the important "big science" disciplines mentioned above, as well as other cutting-edge techniques, so that the repertoire of skills available to lung biologists is second to none. Finally, we will expand the newly established translational reviews. We hope that these manuscripts will be of interest both to the Ph.D. researchers who appreciate the clinical value in their work and to more clinically oriented pulmonologists. Although we do not anticipate that this journal will be a reading favorite of every ATS member, it is hoped that all will take great pride in the Red Journal as the vehicle where basic concepts are discovered, put into context, and handed off to our sister "Blue" journal for translation on the way to the clinic. The result should be a fundamental transformation and improvement in lung health care within the next decade. The ball is in our court—game on.

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