Amanda J. Redig, a student at the Feinberg School of Medicine in Chicago, has written an article on the challenges in biomedical research and the increased need - and opportunity - for translational knowledge sharing between physicians and scientists.

An Indian fable tells the tale of several blind men asked to describe an elephant.  The man who reaches the tail declares the unknown animal to be like a rope; the man who brushes past the leg asserts that what is in front of him must be like a tree; while the final man bumps into the tusk and concludes that the unseen creature resembles a spear.  In the end, those of us who can see the elephant know that each individual assessment is both right and wrong: what is missing is the vision required to put all of the pieces together into a comprehensive whole.  What I want to know, as an MD/PhD trainee during arguably the most exciting time to be a student in the history of both medicine and biology, is whether the biomedical community is now confronting a similar challenge.  Recent advances offer a tantalizing glimpse of what our future could be, but has the quest to integrate an ever-widening information pool and spectrum of disciplines become an exercise in describing the elephant?

Without doubt the 20th century’s remarkable achievements in clinical therapies and scientific discovery provide a solid foundation for the enthusiasm with which we can move forward into the 21st.  Yet for every shining success story-the 85% survival rate for pediatric leukemias or the technical achievements behind transplant surgery-we must still confront the published survival curves for a disease like lung cancer.  And here, as with far too many other diseases, despite decades of effort and millions of dollars, not much has changed.  The complexity of understanding human health and disease means that we must continue what is often a painstaking process of piecing together insights that move from structural biology and model organisms to targeted therapies that do have efficacy in the clinic.  From Watson and Crick to chromosomal translocations and the development of imatinib, the connection between scientific advancement and new medical therapies is undeniable.  However, what I can’t help but wonder as I move through the process of dual training as a physician-scientist is if the current trajectory of our research efforts-the overlap between basic science and clinical medicine-is one that in the end will achieve the greatest results.  The progression from lab to clinic might be self-evident, but unless our framework for biomedical progress moves to truly integrate not only the expertise of multiple clinical specialties but also a full spectrum of scientific investigators, 21st century advancement in medicine cannot live up to its potential. 

The foundation of this challenge is clear: much of the time, physicians and scientists simply do not understand one another.  Both parties ask questions, but the good physician arrives at the same diagnosis as any other good physician while the good scientist sees what no one else has and arrives at a new conclusion.  Unfortunately, the stark differences in training and perspective that make laboratory investigators or clinicians successful within their respective fields can and do inhibit the success of potential collaborations that are not exclusively one discipline or the other.  Speaking to this challenge, much has been made in the literature of late about the directions of academic medicine, biomedical research, and the future of so-called translational research.  Editorials and analyses discuss the role of the physician-scientist or clinical investigator as a go-between (1,2) as well as concern about funding mechanisms and the increasing age at which investigators secure independent grants (3-5).  However, even as initiatives such as the National Institutes of Health roadmap or the recommendations of the Cooksey review are exploring ways to bridge science and medicine (6,7), there is also controversy over whether this is even a good idea let alone a feasible goal (8-10).  In the end, much of the discussion falls back to the fundamental differences between how basic scientists and clinicians ask questions-investigator-driven mechanistic grants on the one hand and large-scale correlative studies on the other.  Yet in order to build on the promise of the last century, our challenge is not merely to discuss the possibility of a new paradigm for biomedical research but rather to implement it.

First, we face the task of integrating physicians and scientists when the barriers between them are constructed with each year of the extensive training process.  In most cases, physicians must complete medical school, residency, and often some fellowship training before they have the time to become involved in meaningful laboratory research.  During this same training period, their early-career scientific colleagues have been just as immersed in the no-less rigorous and time-consuming program of focused graduate school and post-doctoral research.  By the time their paths overlap, the boundaries are set: physicians are physicians and bench scientists are bench scientists.  From the perspective of a post-doc who has spent the last ten years dissecting the most intricate of molecular details, the physician who waltzes into the lab not knowing how to pipet but expecting multiple first author publications in less than two years will never be a scientist.  On the other hand, for the senior resident who has thirty seconds to respond to a coding patient in the throes of cardiac arrest, the scientist planning to spend a career elaborating a pathway in fruit flies is out of touch with the real world.  Is it any wonder that each field can view the other with more than a healthy dose of skepticism and sometimes even outright resentment?

Unfortunately, the separation between these fields continues past the early stages of training. By the time a junior scientist is ready to start his own lab or a junior attending moves into her own niche as a professional, the responsibilities of career development at this crucial juncture take priority over exploring the complex challenges that will likely require input and ideas from both physicians and scientists to solve.  Molecular science is emphasized in the very beginning of medical school, but after that, the details take a back seat to the pathophysiology that is the territory of the physician.  This works for training clinicians, but what about clinician-investigators? In turn, Drs. Kaushansky and Shattil encourage aspiring physician-scientists everywhere as they editorialize about supporting the development of biomedical investigators in hematology-oncology, but this very same op-ed also highlights a hole in the cross-disciplinary mentoring of junior scientists (11).  If physicians who move into the scientific arena need support and mentoring to tackle multidisciplinary problems, then the same is true of their scientific peers seeking to apply scientific training to clinical problems.  Yet there seem to be few, if any, organized opportunities for scientists to be introduced to the clinical problems that their technical skills and hypothesis-driven training could help solve.  Even more problematic, although biomedical research buildings are often adjacent to academic hospitals in an attempt to promote translational research, it is much less common to see such collaboration with scientists several steps further away from medicine; engineering, applied math, and computer science have yet to become as closely integrated with biomedical research as molecular biology and genetics.  It is true that the more conventional partnership has led to some success stories-understanding the role of a single gene or pathway in disease has allowed the development of new therapeutic options.  However, as the aftermath of the Human Genome Project has made clear, the majority of chronic diseases-like cancer-that continue to cause great suffering around the world are too complex for the approach of inhibiting a single pathway or kinase to work.  Indeed, the molecular biology-based success of a targeted drug like imatinib remains to be replicated in the mathematically more complex signaling milieu of solid tumors.

While it is easy to take sides in the pull between medicine and science, morbidity and mortality statistics make it clear that we cannot afford to maintain the status quo: we need to fix the culture gap.  In order to translate our leaps and bounds of information acquisition into leaps and bounds that make a tangible difference in patients’ lives, we must broaden not only the scale of our vision but also the connections we are willing to forge to get there.  If communication-or lack thereof-amongst early-career trainees is a barrier to future success, then an added dimension to the training process might produce physicians and scientists with enough common vocabulary to minimize the height of the walls.  For example, Duke University’s medical training program-and now a joint medical school started in collaboration with the government of Singapore-includes a mandatory year of independent scholarship (12).  While the range of chosen research projects is broad, each graduating MD does so not only with firsthand experience of biomedical investigation but also with a new set of skills and language that can be a bridge to future collaborations outside of strictly clinical medicine.  Many academic institutions have recognized the need to better integrate medicine and the life sciences; key to these efforts will be not only involving medical appointees but also providing opportunities for scientists of all stripes to learn more about the clinical challenges-metastasis, antibiotic resistance, microimaging-that practitioners of medicine cannot solve on their own (13-15).  While excellence in a specific discipline should be the goal of graduate training, the gradual acquisition of blinders that prevent recognition of excellence in an outside specialty is not. 

What we are missing, it seems, is a greater focus on not only what our own skill set- whatever that might be-can bring to the table, but also what we stand to gain from the contributions of the others around us.  Although the initial steps of beginning an initiative that focuses on a problem, not a five-year grant project, can be daunting, the results of innovative collaboration are no less remarkable.  When the problem is that of infertility in young women who are cancer survivors, a reproductive biologist at Northwestern University chose to establish a partnership with an engineer to address the structural and biological challenge of ex vivo oocyte maturation.  The combined expertise of two divergent branches of science led to further expansion and a move towards the clinic.  Today, the Center for Families After Cancer encompasses the work of oncologists, surgeons, scientists, engineers, ethicists, and social scientists to move forward a new field that has been dubbed ‘oncofertility’ (16).  On their own, each member of this team held only part of the puzzle, but together their skills and uniquely valuable perspectives have combined to produce a vision that is both more extensive, more accurate, and ultimately more productive than anything they could have done on their own.  Within the time-span of a career, the members of this team will see a profound change-a giant step forward-in a clinical dilemma that until now had no solution.

And if this and similar advancements are slowly developing in some areas of medicine, then why not in one area after another?  As an aspiring oncologist, the challenges are clear-from lung cancer to pancreatic cancer, the list of malignancies for which there are very few options is still far too long.  Yet with the combined expertise of talented scientists and clinicians the world over, are we closer than we think to moving past the pieces of the elephant?  The mainstay of lung cancer therapy is some combination of surgical resection, radiation, and chemotherapy, which in the end most often delay, not prevent, the inexorable progression of the tumor.  But what if that picture changed?  Imagine a world that still started with thoracic surgery and the metastasis of lung cancer but then moved to a physical chemist and nanoscale visualization techniques implemented by an engineer and then data-mined by a mathematician using a program designed by a computer scientist who then together present a kinetic model of invasion to a molecular biologist who uses an animal model to uncover a mechanism and then collaborates with a pharmacologist to design an inhibitor cocktail which is prescribed by a medical oncologist working in tandem with a thoracic surgeon.  And in the end, the patient goes home to live, not to die. 

These changes have already begun and I know they will continue-but as baby steps or giant strides? The extent to which we can revolutionize both scientific inquiry and medical treatment is directly proportional to our ability to see beyond the walls that can-but only if we let them-separate us from our colleagues.  We owe it to ourselves, to each other, and most of all to the patients who are our family and friends and sometimes even ourselves, to work towards a future that is worthy of what we have already gained and what we stand to lose if we let our moment at this historic juncture slip away.  The men in the elephant fable are blindfolded, but we don’t have to be. 

Acknowledgements: I am grateful for the thought-provoking discussion and insightful commentary provided by Alan Hauser, MD, PhD and HG Munshi, MD during the preparation of this manuscript.

Amanda J. Redig

Feinberg School of Medicine, Northwestern University

a-redig@md.northwestern.edu

(1)  Varki A, Rosenberg LE. Emerging opportunities and career paths for the young physician-scientist. Nat Med 2002;8:437-9.

(2)  Dickson D. UK plans to encourage physician scientists. Nat Med 2000;6:490.

(3)  Weinberg RA. A lost generation. Cell 2006;126:9-10.

(4)  Vastag B. Increasing R01 competition concerns researchers. J Natl Cancer Inst 2006;98:1436-8.

(5)  McNally N, Kerrison S, Pollock AM. Reforming clinical research and development in England. BMJ 2003;327:550-3.

(6)  Zerhouni EA. Clinical research at a crossroads: the NIH roadmap. J Investig Med 2006;54:171-3.

(7)  Black N. The Cooksey review of UK health research funding. BMJ 2006;333:1231-2.

(8)  Marks AR. Rescuing the NIH before it is too late. J Clin Invest 2006;116:844.

(9)  Marks AR. Rescuing the NIH: the response. J Clin Invest 2006;116:1460-1.

(10)  Crowley W, Courtney J, Jameson L et al. The Clinical Research Forum and the Association of American Physicians disagree with criticism of the NIH Roadmap. J Clin Invest 2006;116:2058-9.

(11)  Kaushansky K, Shattil SJ. Bloodlines: the importance of mentoring for the future of hematology. Blood 2007;109:1353-4.

(12)  O’Connor Grochowski C, Halperin EC, Buckley EG. A curricular model for the training of physician scientists: the evolution of the Duke University School of Medicine curriculum. Acad Med. 2007;82:375-82.

(13)  Humphrey JD, Coté GL, Walton JR, Meininger GA, Laine GA. A new paradigm for graduate research and training in the biomedical sciences and engineering. Adv Physiol Educ. 2005;29:98-102.

(14)  Tadmor B, Tidor B. Interdisciplinary research and education at the biology-engineering-computer science interface: a perspective. Drug Discov Today. 2005;10:1183-9.

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