Bench to Bedside and Bedside to Bench: Where Are We?

The Academy of Optometry has, as its mission, change in optometric practice through education and research. Its entire annual meeting is based on this pursuit with both education and research as the key elements of the program. The Academy’s American Optometric Foundation (AOF) has the same commitment and supports young optometric researchers who focus their careers on education and discovery in eye and vision. Indeed in recent years this mission is reflected in the annual theme of every Academy meeting, “Today’s Research; Tomorrows Practice.” Vision and eye research “at the bench” truly opens the possibilities for new diagnostic and treatment regimes, and nowhere is that perhaps more apparent than in pharmaceutical research. However, it occurs through many other “bench” research areas of physiology, psychology, molecular and cell biology, optics, vision perception, and most recently molecular genetics. In recent times, the National Institutes of Health (NIH), particularly through NIH Director Elias Zerhouni, has emphasized the translation of basic research into medical advances in what might be called “bench to bedside” translational research. It also occurs in the clinic with rigorous clinical research studies involving patients, often as part of their patient care. The emphasis on the importance of the relationship between research and practice is understood as fundamental to Academy Fellows and expressed most clearly by Academy activities, including the publication of this Journal. However, significantly, the Academy of Optometry, more than most arms of the profession, implicitly accepts that this relationship is a double-sided coin, both “bench to bedside” and “bedside to bench,” and conducts itself accordingly. In “bedside to bench” actions, clinicians inform basic science researchers of the clinical issues that are either unresolved or incomplete for the care of their patients. They also bring critical observations and tentative testable hypotheses to the discussion. In short, this is critical to informing the biomedical research agendas intended to advance patient care. In turn, attentive bench and patient care researchers can relate their discovery initiatives to these observations and clinical hypotheses; in the best biomedical environments, this is an iterative process of both discovery and application, which can fairly be described as translational research. In “bench to bedside” research, the fundamental discovery of the way cells survive and communicate in the body, for example, provides new ideas for the application at the “bedside” in patient care. Certainly, the best of today’s pharmaceutical research is driven by an understanding of the multiple cellular mechanisms and pathways involved in both the normal and disease process. So-called “biologic” drugs are among those derived from such knowledge, and they target specific pathways or processes to enhance or inhibit them in the interest of better health or disease treatment. In short, the coin has two sides and I like to think that more and more we will be able to create environments where clinicians and researchers can keep the coin oscillating with the kind of motion that provides much more than either side of the coin can produce alone. In a recent editorial (“Translational Medicine: A Two-Way road”) announcing the new Journal of Translational Medicine, the author articulates the two sides of this coin and explains how “bedside to bench” was the motivation for a new open access BioMed Central journal that began in 2003.1 In particular, Francesco Marincola’s editorial points to the need for a forum explicitly for advancing the “bedside to bench” side of the coin, something he argues currently gets much less attention from the NIH than the “bench to bedside” aspect. He argues persuasively that far too often neither the clinician nor the bench scientist has the appropriate tools or mutual respect needed to capitalize on the other’s contributions. Indeed, there is a long history of these difficulties often noted by limited meaningful interactions between clinicians and those engaged in bench and clinical research within optometry and ophthalmology departments. Francesco Marincola notes1 that: “Translational research should be regarded as a two-way road: Bench to Bedside and Bedside to Bench. However, Bedside to Bench efforts have regrettably been relegated to a Cinderella role because the scientific aspects are poorly understood by full time clinicians and the difficulty of dealing with humans poorly appreciated by basic scientists. In practice, Bedside to Bench information, though conceptually valuable, is often frustrated by an unsympathetic review process.” He goes on to assert: “The review process for such work should be assigned to clinical scientists competent not only in the intricacies of molecular or cell biology but also intimate with the reality of Internal Review Boards, ethics committees, Governmental Regulatory Agencies and most importantly the humane aspects of dealing with sick individuals and their families. This approach may focus both basic and clinical scientists and those struggling to fill the gap between them on the effective treatment of diseases affecting women, men and children making translational research more than an interesting concept.” One approach to bridging this gap has been to train researchers both as clinicians and basic or clinical scientists. Certainly, we have seen impressive insightful discovery as a result of such combined training; optometry and medicine have long recognized this in faculty recruitment. In its 2001 report by the Committee on National Needs for Biomedical and Behavioral Scientists, the National Academy of Science (NAS) drew NIH’s attention to a growing problem in attracting clinicians to the research agenda.2 NIH commissioned the NAS report on NRSA trainee needs. Indeed, as they examined biomedical research, they highlighted the alarming reduction in clinicians engaged in research, whether at the bench or at the bedside or clinic (patient care research) from 1984 to 1997. The biggest workforce need for biomedical researchers was in the area of clinician trained basic and clinical researchers. MD/PhD and MD researchers dropped from close to 23,000 in 1985 to 14,434 in 1997; this represented a 40% drop in a little over a decade despite very significant increases in NIH research dollars available over the same period. (In the last 6 years, the NIH budget has doubled.) NAS deplored the reduction and pointed to the critical clinical perspective and sensitivity contributions clinicians bring to the biomedical research effort, whether they are engaged in bench research or more direct patient care research. NIH has, to its credit, been aggressive in recent years trying to stem that trend and to attract more clinicians to the research enterprise. Since 2001, changes in the guidelines of the National Eye Institute (NEI) of the NIH dramatically changed the likelihood of attracting young clinicians into a research career. Now training grants and programs are specifically designed to attract clinicians to research programs. In particular, four changes made this possible. Key among these was the introduction of an attractive NIH Loan Repayment Plan (LRP) to clinicians who engaged in research or research training; up to $35,000 of past education debt (e.g., in optometry school) is forgiven annually. Second was the targeting of research training opportunities with faculty-level stipends intended to entice some clinicians for full-time research training (e.g., K23, K12 grants). Third, existing training programs, like the T32, provide a 3-year training program in which a maximum of 1 year had previously been the requirement for all those holding doctoral degrees, including OD and MD. The T32 also set a new precedent for a separate category of clinician postdoctoral trainees (other than PhD). Finally, beginning in 2002, the traditional NIH postdoctoral training programs increased the stipends for trainees. In optometry, there is now NIH research training grant support from optometry student to established practitioner. During the summers, the T35 summer program enables optometry students to engage in mentored research activities. There is also support for advanced research training for the PhD or Master’s degrees (e.g., T32) as well as for established clinicians who want to add research training to their established clinical experience and skills (e.g., K12). There are now three schools of optometry with this latter program where clinicians can be fully engaged in research training while receiving stipends comparable to a faculty salary (University of California at Berkeley, Indiana University, and The Ohio State University). The research enterprise is facing both challenges and exciting opportunities. Vision and eye research, both bench research and that directly involving patients, has its full share of opportunities. The proliferation of new technologies, especially imaging technologies, and the fast-paced advances in the understanding of cellular and genetic processes underlying disease are among the more obvious advances that provide excitement and opportunity in our field. The Glenn A. Fry Award Lecture by Suzanne Fleiszig at the 2005 Academy meeting gave us a strong sense of optometry’s presence in this area. However, there are many other fields in which there is also reason to be excited. Among these are certainly the wonderful new possibilities for fundus examination, which will allow us to see tiny blood vessels three times smaller than we now see and directly observe individual photoreceptors in the living eye. These same technologies offer promise for advanced vision correction and are beginning to be incorporated in refractive surgery corrections and contact lens designs. Both are made possible by the ability to correct an eye’s individual optical aberrations beyond the sphere and cylindrical corrections. Neil Charman, as the Prentice Medal Award Lecturer at the 2005 Academy meeting, presented a superb presentation of the developments in this field that, arguably, he pioneered. [Both the Prentice and Fry Lectures will be published in future issues of Optometry and Vision Science.] Biomaterials research has made the possibility of corneal implants (“onlays”) a reasonable expectation in the near future (see the Max Schapero Memorial Lecture article by Deborah Sweeney in this issue), as it has already impacted intraocular lenses. Certainly new contact lens materials have provided significant advances in contact lens care in the last 5 to 7 years. On the clinical care horizon are instruments and signal processing strategies that now are actively used in research and large clinical centers for capturing the tiniest, most complex electrical signals of the retina and visual pathways. These instruments provide what might be thought of as an objective visual field measure for conditions like glaucoma, diabetes, and macular degeneration. Finally, the advances made in both technology and communication with the Internet hold great promise for a different, more team-oriented patient care, even with essential team members at remote sites—all through telemedicine.3 So onward with translational research, in both directions. Optometry and its patients will surely benefit from investing in the effort! Anthony J. Adams Berkeley, California