MIT Reports to the President 1995-96


The Clinical Research Center (CRC) was established in 1964, with grant support from the National Institutes of Health (NIH), to provide a facility in which Massachusetts Institute of Technology (MIT) investigators and their collaborators could apply the Institute's expertise in basic biochemical and biophysical mechanisms to the analysis of normal and pathologic processes in humans. MIT's CRC was the first federally supported clinical research center located in a university and not within a hospital. It was anticipated that in spite of its university venue, a large enough number of qualified physicians from MIT's faculty and staff would utilize the CRC to study normal volunteers, or patients with chronic diseases.

Scientists and physicians authorized to carry out research protocols using the CRC's facilities include: professors; research scientists who work exclusively at MIT; and those with primary appointments in local medical institutions whose research interests overlap extensively with those of MIT investigators. Research protocols must be approved by the MIT Committee on the Use of Humans as Experimental Subjects (COUHES) and the CRC Advisory Committee before they can be implemented. The CRC Advisory Committee, chaired by Dr. John Burke, Professor of Surgery at the Harvard Medical School, consists of 10 voting members plus six non-voting members of the CRC's program staff. The Committee reports to the Principal Investigator, Roger Mark, Professor and Co-Director of HST, and meets bi-monthly to evaluate protocols for their scientific quality, experimental design, statistical analysis and potential risk to human subjects. The Committee also sets general policies and reviews the operations of the CRC.


The CRC presently has a dual administrative locus within MIT. As a research unit, the CRC reports through Harvard-MIT Division of Health Sciences and Technology (HST) to the Vice President and Dean for Research, Professor David Litster. However, as a patient-care unit, the CRC is a part of the MIT Medical Department and reports to Dr. Arnold Weinberg, the Director of the Medical Department. Members of the CRC participate in the Medical Department activities; i.e., Quality Assurance, Pharmacy and Therapeutics, Medical Records, and Safety Committees.

On June 1, 1995, the CRC submitted a competing grant application to the NIH for renewal of funding for the next project period beginning in December, 1996. The CRC received its best priority score ever and anticipates funding of up to four years at a total of eight million dollars.


The CRC has continued to provide postdoctoral training for physicians who are participating in fellowship programs at MIT. These physicians have utilized the CRC's facilities to initiate research protocols and to participate in ongoing projects supervised by senior investigators and faculty. During 1995 - 96 six post-doctoral fellows and four graduate students participated in research projects at the CRC. At the undergraduate level, 13 Undergraduate Research Opportunities Program (UROP) students participated in clinical research projects with physician preceptors and faculty supervisors.


The hiring of women and minorities continues to be a high priority at the CRC; our primary problem in meeting affirmative action objectives has been attracting qualified minority candidates. The traditional means of advertising and posting positions in local colleges, universities, medical institutions, and minority organizations have not resulted in a significant response from qualified minorities.

This past year three research staff positions became available. Three women were hired, two minorities. Three Visiting Scientists were appointed, two women (one minority) and one male. The Center will continue its efforts to increase the pool of qualified minority applicants as positions become available.

Recently, Dr. Leticia Castillo, Visiting Scientist, was a recipient of a National Institutes of Health Research Supplement for Underrepresented Minorities award. This NIH program provides opportunities for minority scientists to gain further research experience and at the same time, allowing them to strengthen the pool of independent minority biomedical research investigators. Dr. Castillo is conducting studies on arginine metabolism.


During the past year, most of the research activities of the CRC have continued to be associated with three clinical areas, and to involve three groups of scientists, each led by a senior professor. These areas are: Nutrition/ Metabolism (Vernon R. Young, professor, MIT School of Science) - an area in which the CRC constitutes the major locus of MIT's activity, and one that is a traditional component of clinical research centers; Neurochemistry/Neuropsychopharmacology (Richard J. Wurtman, Cecil H. Green Distinguished Professor and Program Director, MIT CRC) - studies on the effects of drugs, foods and hormones on brain composition and behavior; studies on melatonin and sleep, and on biologic rhythms in sleep and hormone secretion; studies on a set of diseases characterized by affective and appetitive symptoms (i.e., depression, premenstrual syndrome, smoking withdrawal, carbohydrate craving, obesity), which seem to relate to brain serotonin; and Behavioral Neuroscience (Suzanne Corkin, Professor of Brain of Brain and Cognitive Sciences) - focusing on the effects of diseases on cognitive and related brain functions and on genetic and other mechanisms causing neurodegenerative disorders (i.e., Alzheimer's disease). Groups collaborate on multidisciplinary projects, e.g., obesity; depression; Alzheimer's disease. Moreover, numerous CRC research collaborators involve both an MIT professor and investigators at an outside hospital or research laboratory.

This year the CRC patient census totaled 352 inpatient days and 2,680 outpatient visits.


The Clinical Investigator Training Program (CITP), which is based in the GCRC, was recognized by the Faculty Council of the Harvard Medical School in the following fashion: all Fellows successfully completing the program will receive a Master of Medical Science in Clinical Investigation from Harvard -- recognition of their unique training and experience. In the coming year, the diadactic material developed for the CITP will form the basis of an elective program for medical students and graduate students, as well as a training program for scholars in Latin America and Asia.


This year the Center for Experimental Pharmacology and Therapeutics (CEPT) was established within HST under Professor Robert Rubin, and located within the CRC. Its mission is to facilitate application of MIT-generated quantitative science and technology to the study of human physiology and the discovery of treatments for disease. The focus of the CEPT is on pathophysiologically-oriented, patient-centered, quantitative, and measurement-based clinical research, as well as on the education of fellows and students in the performance of such research. Research programs relate to experimental therapies and to experimental measurement technologies. Both are viewed as probes for understanding normal physiology and for understanding and managing disease.


The computer facility is now independent of both the Vax and PDPN systems. It provides administrative report support and statistical assistance to all researchers. Design of the system fully integrates web services with the local database. Researchers continued to make use of the SAS statistical software available on the CRC computer system. They also began using the resources available on the Internet.


The Core Laboratory (CL) specializes in assays that directly support the research efforts of CRC investigators. The most important and complex assays are undertaken by the Mass Spectrometer Facility (MSF), where stable isotope tracer analyses are performed. The MSF is a shared instrument facility that allows CRC investigators to conduct human metabolic studies using stable nuclide tracers. Principal areas of investigation concern the regulation of energy substrate metabolism in health and disease, and the regulation of whole body amino acid metabolism, with particular reference to the nutritional requirements for indispensable and conditionally indispensable amino acids. Research at the MIT CRC has made important contributions to the further development of national and international dietary standards and the establishment of sound food and nutrition policies and programs. Studies continue to examine the role of dietary arginine as a precursor of signal transducer nitric oxide. The novel doubly labeled water (2H218O) method is being used to define the energy requirements for adolescent and elderly subjects, and the factors which affect these needs. These various investigations offer new basic knowledge about the physiology of human energy substrate and amino acid metabolism and, additionally, make practical contributions to problems in human nutrition.

High performance liquid chromatography (HPLC) techniques are also utilized by the CL. A Beckman System Gold Amino Acid Analyzer HPLC provides resolution of up to 42 physiologic amino acids. Other HPLC assays include tests for choline, tryptophan, the catecholamines and cytidine.


Richard J. Wurtman, M.D.

MIT Reports to the President 1995-96