The Rockefeller University Center for Clinical and Translational Science is devoted to maximizing the bidirectional opportunities for clinical and translational research. Building on Rockefeller University Hospital's illustrious history as the birthplace of American biomedical science and translational research, and funded in part by an NIH Center for Clinical and Translational Science Award (CTSA), the Center is designed to provide an optimal infrastructure to conduct clinical and translational research and to educate the next generation of physician scientists committed to patient-oriented research.
 
 

In 1897, the Reverend Frederick Gates, Jr., the senior philanthropy advisor to John D. Rockefeller, read Osler's Principles and Practice of Medicine and concluded that despite the limited success in understanding and treating disease at that time, the recent advances in microbiology opened the way to much greater opportunities to improve health by scientific inquiry. This idea resulted in the founding of The Rockefeller Institute for Medical Research in 1901 and The Rockefeller Hospital, the first hospital in the United States devoted exclusively to medical research, in 1910. Subsequently, in 1953, the National Institutes of Health (NIH) established the Clinical Center as a medical facility devoted to medical research and in 1963 the NIH expanded its extramural program to support clinical facilities devoted to medical research through the General Clinical Research Centers (GCRC) program. From its inception, the Rockefeller model was driven by several organizing principles that remain vibrant today and are central to the newly established Rockefeller University Center for Clinical and Translational Science.

1. Medical research requires undivided focus and thus all investigators, including physician investigators, should be fully salaried by Rockefeller and physicians should not engage in fee-for-service medicine. This principle remains operative today, protecting virtually all of investigators' time for research.
2. Physician-scientists should be encouraged to investigate the basic mechanisms underlying their clinical observations and be provided with laboratory space and resources to conduct the studies. Thus, Avery, MacLeod, and McCarty pursued their observations on clinical pneuomococcal pneumonia to the bench, ultimately making their landmark discovery, and perhaps the landmark discovery of the twentieth century, that DNA confers genetic information from their observations on the transfer of virulence from one pneumococcal strain to another. More recently, Dr. Ralph Steinman's interest in immunologic disease led him to discover antigen-processing dendritic cells. The importance of these cells to the immune response has not only changed the paradigm of immunity, but also opened up new translational opportunities in cell therapy using dendritic cell-based vaccines, including the ones under study by Drs. Dhodapkar and Darnell at the Rockefeller University Hospital, as well as a major new vaccine center with support of the Gates Foundation focused on the development of HIV and malaria vaccines that harness dendritic cell biology directly in patients, a collaboration by faculty members from five different laboratories David Ho, Michel Nussenzweig, Jeffrey Ravetch, Charles Rice, and Ralph Steinman.
3. Basic science investigators should be encouraged to focus on projects of medical significance. Thus, studies conducted at Rockefeller by the Ph.D. chemist Van Slyke truly transformed clinical medicine by his developing assays to measure CO₂, oxygen, blood urea nitrogen (BUN), amino acids, and electrolytes in human blood.
4. Scientists should be free to pursue new directions for their research, unencumbered by the constraints often imposed by a traditional departmental structure. Thus, Dr. Vincent Dole radically changed the focus of his research from the biochemistry of metabolic disorders when he came to appreciate the enormity of the substance abuse problem in New York City, resulting in the development by him and his colleagues Marie Nyswander and Mary Jeanne Kreek of methadone, the first effective drug for managing substance abuse.
5. Although animal studies are valuable, there is no substitute for rigorous hypothesis-driven studies of disease pathophysiology in humans. Thus, Dr. David Ho and his colleagues profoundly altered the accepted concept of the pathogenesis of HIV infection when his studies conducted in patients at Rockefeller demonstrated that HIV rapidly replicates in infected individuals, and that very large numbers of lymphocytes are destroyed by HIV each day, leading the way to the development of the multi-drug regimens that have revolutionized the care of HIV patients. Similarly, Dr. James Krueger's cellular and molecular analyses of the skin of patients with psoriasis at Rockefeller not only changed the pathophysiologic paradigm of psoriasis from a disease of unchecked proliferation to a disease of autoimmune dysregulation, but also ushered in a new era of effective therapies that built rationally from this new paradigm.
6. Trainees should be given independence and maximum flexibility in designing their educational programs. From its beginnings, the Rockefeller Institute for Medical Research selected for self-confident and independent trainees who subsequently went on to leadership positions in their disciplines. Thus, it has been estimated that by the late 1930s, nearly one-half of the full-time Chairs of Medicine in the United States were occupied by individuals who had trained at Rockefeller.¹ That initial spirit of selecting independent and self-confident learners has remained a hallmark of the Rockefeller University PhD, MD-PhD, and Clinical Scholar Programs. Thus, all of these programs emphasize mentored research experiences, tutorial learning, and flexibility in curriculum design.
7. Rockefeller should focus on research on illnesses that affect all of humankind, even when studies of diseases primarily affecting the underdeveloped world are not supported by external agencies or not scientifically fashionable. This long-term commitment to global health challenges extends back to Dr. Max Theiler's pivotal studies identifying an attenuated strain of the yellow fever virus that remains the basis of the highly effective vaccine that is still used today. That commitment is equally palpable today in the work of Dr. John McKinney on tuberculosis, Dr. George Cross in parasitology, and most notably, Dr. David Ho and his colleagues who have undertaken the daunting tasks of both developing and testing an HIV vaccine specifically designed to protect recipients from an HIV strain that is endemic in a region of China but not in the U.S.
8. The decision to maintain focus on scientific productivity by retaining and refining the unique aspects of the Rockefeller structure. The noted University of Wisconsin sociologist, Dr. J. Rogers Hollingworth, has studied in detail the academic structures that have been most successful in fostering the achievement of breakthrough science. He singled out Rockefeller as the institution where, despite the small size of its faculty, "more major discoveries occurred…than at any other research organization during the twentieth century."² He attributed that success to Rockefeller's structure, emphasizing its relatively compact size, interdisciplinary nature, organization by laboratories, solid financial support, intimate social climate, and excellent leadership as among the most important elements. Thus, Rockefeller has chosen to focus on the challenging, and ever increasingly complex, interface between scientific discovery and clinical potential. This focus permits undivided attention and resource commitment to this goal.
9. The essential role of Clinical Research Nursing to the success of the research mission of the Rockefeller University Hospital has been recognized since the inception of the Hospital in 1910. As a result, throughout its history and extending to the modern day, Rockefeller University Hospital has placed and continues to place enormous emphasis on training a cadre of nurses with in depth knowledge of the scientific basis of the studies being conducted, unique skills to conduct the studies efficiently, and an absolute commitment to participant safety and the protection of human subjects.
10. The "home" for clinical investigation and clinical investigators at Rockefeller since 1910 has been, and remains, The Rockefeller Hospital, led by a Physician-in-Chief charged with mentoring junior investigators and developing a coherent, integrated research program. All members of the faculty, both basic and clinical, are encouraged to participate in the research opportunities and to share in governance and strategic planning. Since the inception of GCRC program support at Rockefeller in 1963, the Physician-in-Chief has had the benefit of sharing governance and mentoring with the GCRC Program Director and Associate Program Director, as well as benefiting from the advice and strategic planning conducted by the GCRC Advisory Committee (GAC).

The new Center for Clinical and Translational Science provides an ideal opportunity for the faculty at Rockefeller to creatively build on this rich tradition and not only meet the evolving regulatory requirements, but also spearhead novel initiatives to advance modern clinical investigation nationally. Thus, coupling new resources for functions that are of growing importance with the flexible administrative structure at Rockefeller allows us to tailor our new initiatives to meet both Rockefeller's and the nation's needs. Most importantly, it provides encouragement and resources to bring the scientific method to the study of the clinical research process itself, thus assuring that there will be future advances in the design, organization, and conduct of clinical investigation.

References

1. J Hirsch, Rufus Cole and the Clinical Approach, in Creating a Tradition of Biomedical Research; Contribution to the History of the Rockefeller University, Darwin H. Stapleton, editor. Rockefeller University Press, New York, 2004)
2. J. Rogers Hollingsworth, Institutionalizing Excellence in Biomedical Research: The Case of the Rockefeller University in Creating a Tradition of Biomedical Research; Contribution to the History of the Rockefeller University, Darwin H. Stapleton, editor. Rockefeller University Press, New York, 2004.

Rockefeller University (the name adopted in 1965 in recognition of the inauguration of the graduate degree programs) occupies 15 acres of enclosed grounds on the Upper East Side of New York, immediately adjacent to Memorial Sloan- Kettering Cancer Center (MSKCC) to the west and the Stanford I. Weill Medical College of Cornell University and New York-Presbyterian Hospital to the north. The Hospital Building is an eight story structure in the middle of the campus that houses the inpatient and outpatient facilities as well as the laboratories of five investigators conducting clinical studies (Breslow, Coller, Dhodapkar, Krueger, and Rice), all of which were modernized within the past several years. Additional patient-related space and a conference room are occupied in the adjacent Nurses Residence and Founder's Hall buildings, which are attached by enclosed walkways. The laboratories of all other investigators on the campus are in buildings that are attached by completely or partially enclosed walkways and they can all be reached on foot within approximately four minutes.

The Rockefeller University Hospital is a free-standing, independent research hospital licensed by New York State Department of health, and fully accredited by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). It differs from other hospitals in its dedication to medical research, and thus, for example it does not have an emergency room available to the public.

Virtually all patients admitted to the hospital or evaluated in the Robert and Harriet Heilbrunn Outpatient Research Center are in one or more research protocols. Patients are not charged for their hospital care or their physicians' services. The Hospital's costs are supported by the University and funds from the NIH NCRR Clinical and Translational Science Award, and salary support for the physician-scientists comes from the University and affiliated institutions as well as grant support.

The governing body of the Hospital is the Hospital Committee of the Board of Trustees, which also serves as an external scientific advisory committee, being composed in part of distinguished physician-scientists, including Drs. Edward Benz, President and CEO of the Dana-Farber Cancer Institute, Joseph Goldstein, Nobel Laureate and Chairman of the Department of Molecular Genetics at Dallas Southwestern Medical School, and David Nathan, President Emeritus of the Dana-Farber Cancer Institute. The Hospital Committee meets three times a year and hears reports on scientific progress and Hospital operations, as well as reports from Clinical Scholars on their projects to the Hospital Committee. The Hospital Committee advises the Physician-in-Chief and the President of the University on the operations of the Hospital, physician-scientist recruitment, scientific direction, and strategic planning for the clinical research program and the Center for Clinical and Translational Science.

The Hospital and its clinical programs are led by the Physician-in-Chief, Dr. Barry Coller, who also serves as the Principal Investigator of the Clinical and Translational Science Award and director of the Clinical Scholars program, the University's educational program for young physician-scientists, thus insuring that the Hospital's functions serve the scientific and educational goals of the University. Further integration of Hospital activities to support the clinical research mission is achieved by having Dr. James Krueger serve as both the Medical Director of the Hospital and the Co-Director of the Clinical and Translational Science Award. The Chief Executive Officer of the Hospital is Dr. Barbara O'Sullivan, who trained in Intensive Care medicine and has substantial experience in hospital administration. Dr. O'Sullivan also serves as our hospitalist, focusing on patient safety and setting standards for the nursing and medical staffs. Dr. O'Sullivan also leads her own clinical research studies related to individuals' perceptions of their participation in clinical research studies and assists other investigators with their studies. She is a member of the IRB, GCRC Advisory Committee (GAC), and other administrative committees, thus insuring communication between the Hospital leadership and the scientific enterprise.

The Medical Staff Executive Committee (MSEC), which sets medical policy for the Hospital, differs from comparable bodies at other institutions in focusing on the research mission. It is composed of investigators, Clinical Scholars, and key Hospital staff personnel, and chaired by Dr. Jan Breslow, Head of the Laboratory of Biochemical Genetics and Metabolism. It is charged with medical staff credentialing and insuring that the Hospital functions in compliance with applicable State and JCAHO standards. Since the Hospital's mission is to support medical research, the MSEC also is charged with insuring that the Hospital functions, and rules and regulations advance the research mission.

There are approximately 75 different laboratories on the campus, each led by a Head of Laboratory (HOL) who reports directly to the President. HOLs span the academic ladder from assistant to full professor, but only full Professor HOLs have tenure. There are no academic departments, allowing each laboratory freedom to switch directions in pursuit of new scientific information. Studies involving human subjects that are conducted in the Hospital inpatient or outpatient units are, however, under the jurisdiction of the Physician-in-Chief. The budget of the University is $252 million, of which $115 million is research grant support and support provided to faculty members who are part of the Howard Hughes Medical Institute.