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"The great end in life is not knowledge but
action" -Thomas Henry Huxley
We read almost daily in the newspapers about discoveries of
genes that are the "causes" of almost every human ailment
imaginable, from drug addiction to obesity to heart disease. Potential
new therapies are reported so frequently that one might predict a complete elimination of human disease in the next few years. Yet, most
of these exciting discoveries never go beyond the laboratory bench.
Obviously, some basic biomedical research is valuable even if it is not
translated to therapy of human disease. However, too many
important discoveries lie dormant, with little research effort directed
toward their potential for understanding human physiology and
pathophysiology, resulting in unrealized dividends from our investments
in basic biomedical research.
What are the causes of this gap between the astonishing advances in
basic research and the implementation of this knowledge to
understanding and treating human disease? Two important components of
translational research, integrative physiology and clinical physiology,
have suffered declining activity in recent years, greatly weakening the
translational research chain.
The term "translational research" is often used without much
thought about what it means. The American Physiological Society (APS)
has defined translational research as "the transfer of knowledge gained from basic research to new and improved methods of preventing, diagnosing, or treating disease, as well as the transfer of clinical insights into hypotheses that can be tested and validated in the basic
research laboratory." This definition implies that the process is
bidirectional, from the bench to the bedside, as well as from the
bedside back to the bench. Observations made in basic sciences can
translate into improved patient care, and clinical and population studies can stimulate new ideas and new research approaches in basic
science laboratories.
Until the 1980s, basic research and clinical studies were done side by
side in most academic medical centers. However, this no longer appears
to be the case. Two-track systems, with a research track and a clinical
track, are now the rule rather than the exception in academic medical
centers. Part of this split can be attributed to the introduction of
managed care, which was intended to produce efficient, cost-effective
medical practitioners. However, one of the unfortunate
consequences of this approach has been the loss of the
clinical researcher. This, in turn, has resulted in an almost complete
absence of clinical physiology, an important link in the translational
research chain.
Also contributing to the widening gap between basic research and
clinical medicine has been the gradual demise of integrative physiologists working at the whole animal level who can effectively interact with molecular biologists and clinical researchers.
Traditionally, the discipline of physiology has served as the bridge
between the basic sciences, such as biochemistry, and clinical
research. However, the technological advances in molecular biology and
genomics, and the funding pressures that have pushed research in these
directions, have led many of us to become very reductionist in our
research, to the extent that physiologists are becoming
indistinguishable from other basic scientists. In some ways, this is
beneficial to the discipline of physiology. Some of the most
interesting physiology takes place at the boundaries of our
discipline and results from combining knowledge of various fields, such
as biochemistry, genetics, engineering, pharmacology, and
bioinformatics. At the same time, however, there are fewer
physiologists conducting studies at the whole animal level, an area of
research that is critical to the strength of the translational research chain.
Recognizing this growing gap between basic science and clinical
research, the American Physiological Society recently has taken several
steps to encourage translational research. One of these initiatives was
to highlight translational research in APS publications, including the
American Journal of Physiology (AJP). In the June
issues of the APS Journals, the APS issued a special call for
manuscripts in the field of translational physiology. APS has
encouraged a broad definition of translational physiology in order to
facilitate continuing dialog among basic scientists, clinical
scientists, and population scientists. Translational physiology papers
submitted to the journal may 1) transfer clinical insights
into hypotheses that can be tested and validated in the basic research
laboratory, 2) transfer knowledge gained from basic research
to human physiology, or 3) report improved methods for diagnosing, treating, or preventing disease. The first manuscripts were
accepted in July and are being published in the November 2001 issue of
the AJP (1, 3).
The gap between basic sciences and clinical medicine obviously cannot
be closed simply by offering a forum for publication of
translational research. However, the APS also has developed plans to
highlight translational research at its meetings, to encourage
physiologists to develop interdisciplinary research teams that bridge
molecular physiology and genomics with organ system physiology and
clinical research, and to promote translational research as an
important career opportunity for physiologists. In the 1950s through
the 1970s, physiologists often received training in medicine as well as
basic research. The current training paradigm, however, usually
separates clinical medicine and research. Physiology training programs
often do not even provide coursework in pathophysiology, and PhD
candidates usually do not engage in human research. However, translational research no longer requires that the principal
investigator be a clinician. The article by Carter et al.
(1) in the November 2001 issue of AJP-Cell
Physiology illustrates this point. This team of researchers,
including PhD scientists and clinicians, reports a new method for
identifying hypertensive patients who are responsive to diuretic
therapy with amiloride. Physiologists with either an MD or PhD degree
obviously can play a key role in translational research and serve as
leaders in this effort, if they have the appropriate training and are
willing to lead multidisciplinary research teams. In this postgenomic
era, integrative physiologists are especially well positioned to
interact with other basic scientists, engineers, bioinformatics
experts, and clinicians in translating the wealth of genetic and
molecular information into a better understanding of how the human body functions in health and disease.
The APS is not alone in its efforts to highlight translational
research. The importance of this effort has been recognized by many
organizations, including the National Institutes of Health, the
American Cancer Society, the Burroughs Wellcome Fund, the Howard Hughes
Medical Institute, and others (2, 4). It is clear that new
approaches are needed not only in the way we conduct our research but
also in how we train basic scientists for the postgenomic era.
Correcting these problems will require the concerted efforts of many
organizations, including the APS, working together with government and
industry. Without effective translational research, the exciting
molecular discoveries that are currently being made at the research
bench will not benefit the patient. Highlighting and encouraging
translational research in APS journals is an important step in the
right direction.