MIT Reports to the President 1995-96


The Harvard-MIT Division of Health Sciences and Technology (HST), established in 1970, is a collaborative program that facilitates and initiates educational and research opportunities that could not be exploited as effectively by either MIT or Harvard through independent efforts. The HST MD curriculum trains physicians who have a deep and quantitative understanding of the underlying science of medicine and biomedical research. The PhD programs combine rigorous scientific or engineering graduate training with an in-depth exposure to the biomedical sciences and clinical medicine. Both programs seek to prepare students for leadership roles in medicine and biomedical science. In addition to administering faculty research, the HST Division facilitates and administers multidisciplinary research at the interface of technology and medicine.

Because of its interdisciplinary and inter-institutional nature, HST's administrative home at MIT is the Whitaker College of Health Sciences and Technology. The Division is headed by two Co-directors who report to J. David Litster, Professor of Physics, Vice President for Research, and Dean For Graduate Education, along with and S. James Adelstein, Professor of Medical Biophysics and Executive Dean for Academic Programs at Harvard Medical School (HMS). On 1 February 1996, Professor Martha Gray, Kieckhefer Associate Professor of Electrical Engineering and Computer Science, was appointed interim Co-Director to succeed Dr. Roger Mark, Grover Hermann Professor of Health Sciences and Technology, who stepped down as Co-Director after ten years of service. Dr. Michael Rosenblatt, Robert Ebert Professor of Molecular Medicine, is the Harvard Co-director, and Dr. Joseph Bonventre, Associate Professor of Medicine at HMS, serves as Associate Director of HST and Director of Student Affairs for HST-MD students.



David E. Housman, Ph.D., co-director of Molecular Biology and Genetics in Modern Medicine, has been appointed the Ciba-Geigy Professor of Biology and MIT. An enthusiastic and highly esteemed teacher, Professor Housman is credited with the discovery of the genes responsible for Huntington's disease and myotonic dystrophy as well as for the isolation of the Wilm's tumor gene. Carl Rosow, M.D., Ph.D., Associate Professor of Anesthesia at Harvard Medical School, was chosen to receive the 1996 Irving M. London Teaching Award, recognizing the excellence of his teaching in Pharmacology. Laurence R. Young, Sc.D., Professor of Aeronautics and Astronautics at MIT and a member of the HST affiliated faculty, has been appointed the first Apollo Program Professor of Astronautics.



An objective of HST from its inception has been to foster development of interdisciplinary, inter-institutional collaborative research between the faculties of MIT and Harvard. The research of the HST core faculty and research staff covers a wide spectrum of biomedical areas including: auditory physiology (including therapeutics); pathophysiology, epidemiology, and therapy of atherosclerosis (including diagnostic instrumentation); biological response of tissue such as cartilage to mechanical, chemical and electrical factors; regulation of gene expression; gene therapy; virus replication and assembly; hyperthermia for cancer therapy; biomedical instrumentation; tissue engineering; systems physiology and modeling; physiological signal processing; vascular biology and pathophysiology; and fundamental pathophysiology of bone. Their research links include a number of HMS teaching hospitals (MGH, BWH, BIH, NEDH) and the HMS quadrangle.

HST also administers a number of research programs for affiliated faculty. The total projected fiscal year `96 research volume is $4.9M (including subcontracts). The research activities of the Clinical Research Center, organizationally part of HST, are reported separately.


H. Frederick Bowman, Senior Academic Administrator in HST and Director of the MIT Hyperthermia Program, reported the development of a needle embedded with microchips that can measure a variety of parameters, including temperature and oxygen levels, using a single device. The needle is 30% smaller in diameter than current probes and can be used for characterizing both normal and tumor tissues.


Richard J. Cohen, Professor of Health Sciences and Technology, is studying is studying the electrical and mechanical regulation and stability of the cardiovascular system. Dr. Cohen's laboratory has developed a noninvasive means of identifying individuals at risk for dying of sudden cardiac death. Sudden cardiac death in adults results from disturbances of electrical conduction processes in the heart and is the cause of 300,000 deaths per year in the United States alone. The technology developed in Dr. Cohen's laboratory has now been successfully commercialized for clinical use.


James Weaver, Senior Research Scientist, has discovered that "high voltage" (about 100 volt) pulses to human skin create new aqueous pathways that lead to large increases in molecular transport across the skin. This is interpreted as "skin electroporation", which is being investigated as a new approach to transdermal drug delivery and non-invasive sensing.


Lisa Freed, Research Scientist in HST, and Gordana Vunjak, Research Scientist at Whitaker College are studying in vitro tissue morphogenesis using isolated cells, three-dimensional polymer scaffolds and tissue culture bioreactors. Ongoing research involves cartilage and bone tissue engineering, physiological and pharmacological studies of contractile cardiac tissue constructs, and a long term microgravity bioreactor cultivation of cartilage constructs aboard the space station Mir. These studies have significance for designing tissue engineering bioreactors and the in vitro cultivation of functional tissue substitutes for clinical use.


Accomplishments in the laboratory of Robert S. Lees, Professor of Health Sciences and Technology, included advances in both basic science and clinical research. A new, more powerful and accurate method was developed for non-invasive assessment of human arterial vasoreactivity in normal and diseased tissue. The work was part of the Ph.D. thesis research of a Medical Engineering-Medical Physics (MEMP ) graduate student. In addition, a large angiographic arteriosclerosis regression trial was completed, part of which was the M.S. thesis of a MEMP student. An innovative device for treatment of refractory hypercholesterolemia, based on selective removal of low density lipoprotein, was undertaken in the laboratory and the data were critical in achieving FDA approval.


Dr. Chi-Sang Poon, Principal Research Scientist, investigates cybernetics, which, according to the definition of Norbert Wiener, is the study of communication and control in both living and man-made systems using principles and techniques drawn from the mathematical, physical, and engineering sciences as well as molecular, cellular and systems biology in physiology and medicine. One of the major contributions in the last year has been the development of a highly efficient and sensitive computational technique for the detection of chaotic dynamics in experimental time series (Nature 381:215-217, 1996; patent pending). Based upon a mathematical theory originally formulated by Wiener, this technique is now being used as a data analysis tool by investigators in various areas of biomedicine as well as other research fields such as earth sciences and economics. In our lab, we have successfully applied this technique to the diagnosis of patients with congestive heart failure based upon heart rate time series derived from their electrocardiograms.


Robert H. Rubin, M.D., Gordon & Marjorie Osborne Associate Professor, is involved with research primarily concerned with the development and application of quantitative imaging techniques to assess a patients physiology with the pharmacology of new drugs. In particular, his center has developed a technique for defining the distribution of CD4 lymphocytes noninvasively in individuals. The potential for this test is very great in defining therapy in AIDS patients and patients with immunologic disorders.


Dr. Stephen Burns has a long-term interest in the fate of medical instruments in the developing world. Specific issues include maintenance and repair and mechanisms for providing local technical expertise. In collaboration with the American Medical Resources Foundation, we have proposed a Center in the University of Hanoi to repair and up-grade medical instruments using modern computer technology. This involves understanding the instrumentation problem and replacing its original electronic control and display function with something ranging from a single-chip microcomputer to a locally procured personal computer. Mr. Neil Ghiso, HST-98, has upgraded a BEAR-3 respirator with a single-chip processor and traveled to Hanoi to design and initiate a study of current medical technology in Viet Nam. The respirator is an important technology, widely used, and dominated by air-handling hardware. The addition of a personal computer allows much more complex data-dependent control as well as providing quantitative measurement and data storage and retrieval; in summary--an upgraded instrument.


Lee Gehrke, Lawrence J. Henderson Associate Professor, is studying RNA-protein interactions in the context of virus replication and assembly. His laboratory identified a single amino acid that enables a viral coat protein to bind RNA specifically . These findings have significance for understanding mechanisms of virus replication and particle assembly.


Irving M. London, Professor of Health Sciences and Technology and Professor of Biology, Emeritus, is studying the regulation of hemoglobin synthesis at both transcriptional and translational levels. His laboratory has discovered and characterized the main enhancer elements that control the transcription of the human ß-globin. In collaboration with Dr. Philippe Leboulch of the Harvard Medical School faculty, he is also focusing on novel gene transfer strategies for the gene therapy of human diseases.


Professor Martha Gray's research activities this year have centered on the use of magnetic resonance for measuring composition and functional integrity of cartilage. The fixed charged density of cartilage is one of the most important factors in reflecting the mechanical integrity of cartilage. Our NMR methods have exploited the fact that there is a

quantitative relationship between the concentration of fixed charge and the concentration of ions in the tissue fluid. It is the concentration of these ions that we measure using MRI in order to infer functional integrity. With our new approach we have been able to identify focal lesions in intact joints and small explants of cartilage. The recent pilot studies suggests this method may be feasible clinically and in animal models. Thus, this approach has the potential to provide the unprecedented opportunity to nondestructively monitor disease progression and evaluate therapeutic efficacy.


Jane-Jane Chen, Principal Research Scientist, studies the regulation of hemoglobin synthesis by the heme-regulated eIF-2 alpha kinase (HRI) that is responsible for the translational regulation by heme of globin synthesis. Dr. Chen's group has demonstrated that expression of HRI is restricted to immature erythroid cells. They have also identified the N-terminal 103 amino acids of the HRI protein that are essential for heme-binding and heme regulation. These data have significance for further understanding of the role of HRI in the production of hemoglobin, a vital oxygen carrying protein.


Elazer R. Edelman, Hermann von Helmholtz Associate Professor, is studying how the physical contiguity of cells and adjacent tissues contributes to autocrine and paracrine modes of growth control. In particular he has used elements of pharmacology, cell and molecular biology and biochemistry, high resolution microscopy and computer-based image analysis, finite element analysis, and tissue engineering to examine the communication between the endothelial and smooth muscle cells of the blood vessel wall. He and his students have demonstrated that disruption of the normal regulation these two cells impose on each other is the hallmark of accelerated proliferative vascular

disease. These diseases now account for more morbidity and mortality than all other diseases combined.


Elazer Edelman, M.D., Ph.D. was appointed Associate Professor of Health Sciences and Technology at M.I.T. Dr. Edelman is an expert in the area of cardiovascular biology. Professor Nelson Kiang has announced plans to retire, and Professor Lou Braida, Henry Ellis Warren Professor of Electrical Engineering, has assumed the position of head for the Speech and Hearing Sciences Program.


The most pressing challenge for the Division is to identify and recruit a Co-Director to succeed Professor Mark.

Three main programmatic goals are envisioned for the upcoming year: imaging, graduate curriculum development, and medical informatics. A task force, headed by Professor Eric Grimson (Electrical Engineering and Computer Science), co-headed by Professors Deborah Burstein (Harvard Medical School and Beth Israel Hospital) and Ron Kikinis (Harvard Medical School and Brigham and Women's Hospital) and involving representatives from MIT and Harvard is working to establish milestones to direct initiatives taken by HST in imaging over the next 1-5 years. Subject areas for these initiatives could range from student advising to establishing a research center. Efforts in the area of graduate curriculum will center on a need to enhance focused interdisciplinary training. Although graduate students are expected to bring together the faculty expertise needed to do their multidisciplinary research, the HST Division has not aggressively organized faculty to teach graduate-level courses in these multidisciplinary areas. Promoting such courses has the dual benefit of providing role models for the students, and providing new insights and colleagues for faculty. Our goal is to initiate the development of one or two such courses in the coming year. Areas in which a need has been identified include: biomaterials, microscale engineering, sensory systems, biological thermodynamics, and imaging. Medical informatics is a discipline that reflects the explosion in computing power and in available information; it has evolved to satisfy the need for sophisticated and coherent approaches for addressing problems ranging from automated diagnosis to genotyping. For several years, HST has served as the academic home for a training grant in Medical Informatics. The goal for the coming year is to explore ways to leverage the current activities in medical informatics for the mutual benefit of the training grant participants and HST. Participating faculty from MIT and Harvard Medical School include Dr. Robert Greenes (Harvard Medical School, and PI of the training grant) and Peter Szolovitz (Electrical Engineering and Computer Science).

Martha L. Gray

MIT Reports to the President 1995-96