NIGMS-Sponsored Integrative and Organ Systems Pharmacology: Synopsis of the 2005 Experience/Anticipation of the 2006 Short Courses

  1. David B. Bylund, Ph.D.,
  2. Laurence L. Brunton, Ph.D.2,
  3. Peter J. R. Cobbett, Ph.D.3,
  4. Adam M. Persky, Ph.D.4 and
  5. Peter C. Preusch, Ph.D.5
  1. 1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, 402/559-4788, Fax: 402/559-7495, dbylund{at}
  2. 2Department of Pharmacology, University of California San Diego, La Jolla, Ca
  3. 3Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI
  4. 4Division of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC
  5. 5Pharmacology, Physiology, and Biological Chemistry Division, National Institute of General Medical Sciences, Bethesda, Maryland

    Is training in systems and integrative pharmacology stillimportant? According to leaders in the pharmaceutical industry and academia, the demand for researchers with experience in the use of isolated organ systems and whole animal methods is high. Unfortunately, many graduate students in pharmacology receive only minimal exposure to these approaches, and students in other disciplines receive even less. Thus, there is concern about the ability of researchers to choose and use in vivo models that appropriately reflect human disease states and translate the results of basic cellular and molecular research discoveries into clinical advances. Future success will depend on the ability of researchers to integrate and communicate information across a range of studies, from the cellular and molecular level through suitable animal model studies and into the clinic (1).


    Systems and integrative pharmacology refers to research using substantially intact organ systems or in vivo animal models that demonstrate integrated responses characteristic of living organisms. These integrated responses result not only from complex interactions among molecules, cells, and tissues, but also from interactions among organs and organ systems (2). Such studies are important because the use of isolated cells and molecules in vitro does not always yield critical information relevant to tissues and organs in vivo.

    With the development of newer disciplines, such as bioinformatics and genomics, there is a need for broadly trained scientists conversant not only with computational and molecular biology, but also with the physiological and pharmacological characteristics of tissues and whole animals. Insights generated from molecular systems must be translated into testable hypotheses in intact systems. The development of genetically modified mice, however, has far outpaced their phenotypic characterization, and many behavioral and neurobiological investigations must thus await appropriate whole-animal models. The use of integrative techniques in drug development will no doubt lead to more drugs entering clinical trials and ultimately reaching the marketplace (3). Thus, there is a clear need for pharmacologists who can study integrative processes.

    A New Educational Opportunity

    The National Institute of General Medical Sciences (NIGMS; see has taken an important step to address the need for training in this area by funding Short Courses in Integrative and Organ Systems Pharmacology (4, 5)—four such Courses in 2005, as summarized in Table 1. The goal of these intensive, two- or three-week courses is to introduce students to important concepts and to provide a significant hands-on experience with experimental methods. In addition, these courses intend to enhance the ability of students to communicate across a range of science disciplines, reinforce training in the responsible conduct of animal research, and teach students to articulate the importance of animal research in developing new treatments for disease (3).

    Table 1.

    Four NIGMS-Sponsored Short Courses: Overview of 2005 and Anticipation of 2006

    The four programs that were funded this year were chosen from highly competitive applications, on the basis of pedagogical merits as determined by peer review. The fact that they provide regional coverage of the country (Table 1) was a fortuitous happenstance. These courses were selected to serve the scientific community broadly, not simply to support four institutional communities. The faculty, in fact, were drawn from a total of twenty academic, research, and pharmaceutical organizations, reflecting the intention to engage participation from the research community as a whole.

    The specific approaches offered by the four short courses that took place in 2005—and that will take place again in 2006—differ in their details, but they all cover basics of animal welfare, handling, and surgery, and they all provide an introduction to cardiovascular and behavioral/psychiatric approaches. The courses also include abundant hands-on laboratory experiences to reinforce basic principles of pharmacology. Additional topics such as the use of intact animals in drug development, safety pharmacology, and techniques for the quantitative analysis of data are presented.

    Four Summer Short Courses: Synopsis of the 2005 Experience

    The Michigan State course included demonstrations on cardiac assessment, radiotelemetry, and rodent exercise. The laboratory experiences included autonomic function, renal function, vascular contractility, gastrointestinal function, and intracerebroventricular cannulation. The course also provided an excellent mechanism for the MSU faculty to use their expertise—and the expertise of colleagues from off campus—to address the needs of graduate students from many disciplines in systems physiology in general and integrative pharmacology in particular. In fact, Michigan State plans to use their short course as the basis for developing a laboratory course for a Professional Masters Program in Pharmacology, currently under development.

    The University of California San Diego course focused on the central nervous system (e.g., nociception and neuropsychiatric disease), on the cardiovascular system (e.g., hypertrophic cardiac disease and heart failure) and its autonomic regulation, and on recent techniques for imaging organ function. For specific target phenotypes (e.g., hypertrophic heart, congestive heart failure, and limbic-motor dysfunction) or processes (e.g., nociception, acute inflammation, and nerve injury), the course reviewed basic molecular and cell biology, physiology, pathophysiology, and pharmacology. Overviews included preclinical models relative to current research, and hands-on training in the use of rodent (i.e., normal and knock-out) and large-animal models. The course also provided training in a variety of small-animal imaging techniques (i.e., PET, MRI, optical, and ultrasound), use of radiopharmaceuticals, and interpretation of imaging data. The course stressed basic principles of pharmacology, quantitative analysis of data, hands-on experience, and ethical use of animal subjects.

    “Large-animal cardiovascular biology is amazing!” — Student commentary

    The Nebraska course was the natural outgrowth of ongoing interactions between the pharmacology departments of The University of Nebraska Medical Center and Creighton University, both in Omaha. The two departments have jointly taught a molecular-based receptor and signal transduction course for many years, and there was a perceived need for a companion course that was tissue- and intact animal-based. With the collaboration of the UNMC Department of Physiology and their considerable expertise in systems physiology, the course developed around the paradigm of comparing drug responses in the intact cardiovascular system (dog) with those in isolated tissues (blood vessels and Langendorff heart). Additionally, behavioral paradigms were introduced for studying the central effects drugs in rats and mice, including pain, motor function, and learning and memory.

    The University of North Carolina at Chapel Hill course retained a strong emphasis on integrating mechanistic information into an understanding of drug disposition and action in the intact organ and, most importantly, in the intact organism. The course included labs on the perfused kidney, isolated perfused liver, and in situ intestine and brain perfusion, as well as behavioral and necropsy techniques. Taken as a whole, the topics comprising this short course provided technical aspects of animal experimentation (e.g., substrate administration and sample collection) and approaches to experimental design (e.g., animal models of disease, interanimal variability, and design optimization). The goal was to provide a strong foundation for selecting an appropriate in vivo or intact organ model to address specific hypotheses with judiciously generated experimental data.

    “The major strength of the course was the hands-on experience gained actually performing experiments with the animals.” — Student commentary

    Characteristics of Course Participants

    Before taking one of the short courses, many of the students had had little or no experience working with live animals. Student commentary subsequent to the 2005 courses, however, indicates the gaining of confidence in handling animals and in exploiting animal models appropriately. Based on student evaluations, in fact, the 2005 courses were a success in terms of meeting student expectations and needs and ins establishing student confidence in using and defending live animals and tissue preparations. Student responses to a summary questionnaire were overwhelmingly positive, with nearly all students agreeing or strongly agreeing with statements such as, “I feel confident in my ability to use live animals in my research,” and “I feel confident in my ability to defend the use of animals in research.” Other students appreciated “the broad spectrum of whole-animal and tissue techniques” and that “one of the highlights…was the interaction with people from industry.” Student feedback from the 2005 courses will be used to strengthen content for those students who enroll in the 2006 courses.

    “I received all the hands-on experience that I wanted for each individual experiment.” — Student commentary

    All four courses will be offered again in the summer of 2006. As reflected by this joint article, the program directors are working together to advertise the NIGMS-sponsored short courses to potential enrollees and to make each course a success; dates and contact information are given in Table 3. Students from any institution are eligible to apply to participate in the 2006 courses, at the venue of their choice. Interested graduate students, postdoctoral fellows, faculty, and researchers from industry should contact the short course programs directly. Although NIH is covering most of the cost of training, there is a modest course fee (including room and board) charged for most students. Support from the students’ home organizations will be encouraged to help cover these costs.

    “One of the highlights... was the interaction with people from industry....” — Student commentary

    It is expected that students trained by these courses will foster further development of integrative research programs at their home institutions. Industry and academic institutions are likely to provide opportunities for follow-up research experiences that will reinforce the applicability of training received through the short courses. It is anticipated that the short courses will develop and disseminate novel approaches to instruction that will strengthen training in this area at all institutions. As one of the instructors aptly taught: “In vivo veritas—it isn’t true until you have shown it in the intact animal!”


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