The mission of the Harvard-MIT Division of Health Sciences and Technology (HST), established in 1970, is to develop and conduct research and educational programs across disciplinary lines within MIT and Harvard University, and the teaching hospitals in order to combine the sciences and engineering in the solution of problems in biology and medicine. By uniting the great strengths of the two universities, HST trains students for research and leadership roles in medicine, biomedical sciences and biomedical engineering. The program seeks to improve human health through its multidisciplinary, multi-institutional research and educational activities.
Recognizing that the future requires leaders who can effectively bridge the cultures represented by medicine, science, and engineering, the Division accomplishes its mission by providing truly multidisciplinary training in these three areas to both MD and PhD candidates. Accordingly, the HST student body and faculty have backgrounds and interests spanning the continuum represented by these areas, and have career and research objectives that depend on a substantial integration of these areas. The HST MD curriculum trains physicians who have a deep understanding of the underlying quantitative and molecular 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.
The research programs for students and faculty similarly reflect the mixing of cultures in applying the appropriate tools of medicine, engineering and science to address problems in human health and clinical medicine. They are focused on five main thematic areas:
Through these programs, HST seeks to explore the fundamental principles underlying diseases, discover new pharmaceuticals and devices to ameliorate human suffering, and train the next generation of physicians, scientists, and engineers to do the same.
Because of its inter-disciplinary 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 S. James Adelstein, Professor of Medical Biophysics and Executive Dean for Academic Programs at Harvard Medical School (HMS). Professor Martha L. Gray, Kieckhefer Associate Professor of Electrical Engineering is the M.I.T. Co-director, while Dr. Michael Rosenblatt, Robert Ebert Professor of Molecular Medicine, is the Harvard Co-director. Dr. Joseph Bonventre, Associate Professor of Medicine at HMS, serves as Associate Director of HST and Director of Student Affairs for HST-MD students.
During the 1996-1997 academic year, the directors and faculty considered a proposal from the Dean of Engineering, wherein HST would be administratively centered in the School of Engineering. After many meetings and long discussions, the HST Joint Faculty Committee approved a resolution stating that 1) It should be understood that the mission of HST will continue to be to develop and conduct research and educational programs across disciplinary lines among the schools of MIT, Harvard, and the teaching hospitals so as to bring to bear the physical sciences and engineering in the solution of problems in biology and medicine -in other words, to join together the great strengths of the two universities in the solution of problems in biology and medicine. and 2) that HST should continue to report directly to the office of the Provost at MIT and the Dean of Harvard Medical School.
HIGHLIGHTS OF THE YEAR
Mr. John Taplin, an MIT `35 alumnus, and his wife Virginia, have established a $2 million fund to advance research, study, and training in HST. The fund will recognize and support the work of HST faculty and students in building HST's infrastructure in the areas of biomedical engineering, physics, and chemistry.
The first four recipients of John F. and Virginia B. Taplin Awards were announced June 4th at commencement ceremonies for the Harvard-MIT Division of Health Sciences and Technology. The four inaugural recipients of the $50,000 awards are Elazer R. Edelman, M.D., Ph.D., class of `83 and the Thomas D. and Virginia W. Cabot Associate Professor of HST; Dennis M. Freeman, Ph.D., assistant professor of Electrical Engineering and Computer Sciences; W. Eric L. Grimson, Professor of Electrical Engineering and Computer Science; and Mehmet Toner, Ph.D., Class of `89 and associate professor of surgery and bioengineering, Harvard Medical School.
The keynote speaker for HST Commencement was David Ho, M.D., who was named Man of the Year in 1996 by TIME magazine for his widely acclaimed work in the battle against AIDS. The 1978 HST graduate stated that he would forever be indebted to the institution "where my clinical skills were honed, where my scientific research interests were solidified, and where I truly learned to tackle research with a multidisciplinary approach not limited by arbitrary boundaries that separate medicine from the physical sciences, engineering, and mathematics".
HST faculty will play an important role in the new National Space Biomedical Research Institute as part of an agreement signed with NASA on June 1. The 20-year agreement (five years with three 5-year extensions) is worth approximately $145 million. The director of the Institute is Laurence R. Young, Ph.D., Apollo Program Professor of Aeronautics at MIT and a member of the HST faculty. Richard Cohen `76, an HST core faculty member, will be one of the project team leaders.
The second Follow-up Study of MD graduates of HST was published in June 1997 (W. H. Abelman, B. D. Nave and L. Wilkerson. "Generation of Physician-Scientist Manpower: A follow-up Study of the First 294 Graduates of the Harvard-MIT Program of Health Sciences and Technology," Journal of Investigative Medicine 1997; 45:1-4). Faculty appointments in 64 medical schools were held by 212 (75%). Overall, 73.5% were engaged in research: 68% of Mds and 86% of MD-PhDs. One hundred and four (38%) spent more than 50% of their time on research: 29% of Mds and 60% of MD-PhDs. Seventy-five per cent of respondents were actively teaching. Thus, the goal of the program to produce physician-scientists and leaders in academic medicine was reached.
Dr. Richard Cohen, Professor of HST, holds a patent on a technique used to identify persons at risk for sudden cardiac death. Proceeds from this technology will support a new Distinguished Professorship in Health Sciences and Technology.
HONORS AND AWARDS
Robert S. Langer, Sc. D., the Germeshausen Professor of Chemical and Biomedical Engineering at MIT and member of the HST faculty, was awarded the 26th Killian Faculty Achievement Award. The Killian Committee commented that "Bob is a world leader in the development of polymeric drug delivery systems that allow humans to receive drugs in a physiologically normal manner". George Benedek, Ph.D., Alfred H. Caspary Professor of Physics and Biophysics and a long-standing member of the HST faculty, received the Proctor Medal from the Association for Research in Vision and Ophthalmology. David Ho (HST MD `78) was named "Man of the Year" by TIME magazine.
PROGRAM HIGHLIGHTS
HST offers approximately 70 courses in the biomedical sciences and biomedical engineering, a number of which have been developed jointly with other MIT departments. More than 150 faculty members at MIT and at Harvard Medical School contribute significantly to the academic programs of HST. The Division has a "core" faculty numbering ten individuals (including the directors).
A total of 299 graduate students were registered in HST degree programs during the academic year. There were 186 MD candidates of whom 91 were simultaneously pursuing PhD degrees. HST doctoral programs registered 113 students: 78 in the Medical Engineering and Medical Physics (MEMP) track, 37 in the Speech and Hearing Sciences (SHS) track, and 4 in the Radiological Sciences Joint Program which is sponsored jointly by HST and the Nuclear Engineering Department.
Admission to programs continues to be extremely competitive, with about 400 applicants for 40 MD slots, 175 applicants for 10 MEMP slots, and 30 applicants for 7 SHS slots.
The MD degree was awarded by Harvard Medical School to 29 HST students this year, of whom five received honors in a special field and eighteen received the combined MD-Ph.D. degree. Thirteen students received MEMP doctoral degrees from MIT. One student received a doctoral degree from the Radiological Sciences Joint Program. One student received a Master of Science degree in Health Sciences and Technology.
RESEARCH ACHIEVEMENTS
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 Harvard Medical School teaching hospitals (MGH, BWH, BIH, NEDH) and the Harvard Medical School quadrangle.
HEALTH HAZARDS FROM EMF
James C. Weaver, Senior Research Scientist, and colleagues at MIT, Yale and Chicago are carrying fundamental theoretical studies of the conditions under which weak electric and magnetic field (EMF) can alter biochemical processes, with the aim of clarifying the controversy regarding human disease and exposure to weak fields associated with the use of electrical power.
BIOMEDICAL ENGINEERING
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.
BIOMEDICAL PHYSICS
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.
BIOTECHNOLOGY AND TISSUE ENGINEERING
Lisa Freed, Research Scientist in HST and Gordana Vunjak-Novakovic, Research Scientist at Whitaker College are studying tissue formation using isolated cells, 3-dimensional polymer scaffolds, and bioreactor vessels. Ongoing research includes in vitro cultivation of cartilaginous and cardiac-like tissues, a recently competed 4 month microgravity experiment aboard the Mir Space Station, and the development and scientific testing of the cell culture facility for the International Space Station. These studies have significance for designing tissue engineering bioreactors and the production of functional tissue equivalents for clinical use.
Robert S. Lees, Professor of Health Sciences and Technology, and his colleagues, have recently been awarded a key patent for imaging the arterial tree with radiolabelled oligopeptides (short polymers of amino acids which resemble a small portion of a protein). This work was the first to show that short peptides could have the defined structure required to function in a way similar to the proteins after which they were fashioned to serve as diagnostic agents. The techniques developed in Dr. Lees's laboratory have been successfully incorporated into multiple diagnostic pharmaceuticals which are in clinical trial for imaging not only cardiovascular disease but also cancer and infection.
CENTER FOR EXPERIMENTAL PHARMACOLOGY AND THERAPEUTICS
This year, for the first time, graduates of the Clinical Investigator Training Program, a two year joint fellowship of HST and the Beth Israel-Deaconess Medical Center, received a Master of Science degree from Harvard Medical School. This unique program for clinicians, will, in the coming year, be joined by a parallel program for PhD's interested in applying their engineering, chemical, physical, or molecular science to problems of human disease. Funding has been secured for this program, and the first Fellows will enter the program in the coming year.
Research efforts have been centered on the application of quantitative measurements with such forms of technology as positron emission tomography, magnetic resonance imaging, and ultrasound to the process of drug development. In the fall of 1997, for the first time a course in drug development will be offered. This will be co-directed by Dr. Robert Rubin (HST), Dr. Stan Finkelstein (Sloan School), Dr. Tony Sinskey (Biology), and Dr. Charles Cooney (Chemical Engineering).
CLINICAL RESEARCH CENTER
Richard Wurtman, the Cecil H. Green Distinguished Professor, and Director of MIT's Clinical Research Center, now has a joint appointment in HST. Dr. Wurtman directs a basic-science laboratory that examines brain chemicals, - particularly neuro-transmitters and the molecular processes they control; he also carries out related human research within the Clinical Research Project. His current human studies involve: 1) the discovery that melatonin, a pineal gland hormone which his laboratory previously showed is secreted at night-time, normally controls sleep, and can be used to promote sleep (e.g., in older people, who often are melatonin-deficient); 2) the behavioral effects of exogenous Citicoline, a compound previously shown in this laboratory to promote the synthesis of membrane constituents (phosphatidylcholine) and of acetylcholine; and, 3) the use of nutrients which modify brain chemicals (like serotonin) to treat medically-undesirable weight gain and certain mood disorders.
MEDICAL INFORMATICS
Robert Greenes is the principal investigator for the Harvard-MIT-NEMC training program in medical informatics. This was competitively renewed this year for another 5 years. The review of the proposal by the National Library of Medicine received a stellar priority score. Participating groups in the renewed training program now include the Beth Israel Deaconess Medical Center and Children's Hospital, as well as prior participants at MIT, Harvard School of Public Health, New England Medical Center, Brigham and Women's Hospital, and Massachusetts General Hospital. The HST-based Masters program in Medical Informatics continues to grow, with 5 students now enrolled.
MEDICAL INSTRUMENTATION IN THE DEVELOPING WORLD
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.
MICROBIOLOGY AND MOLECULAR GENETICS
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.
MOLECULAR BIOLOGY OF HEMOGLOBIN SYNTHESIS AND HUMAN GENE THERAPY
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.
MRI IMAGING FOR ASSESSING CARTILAGE PHYSIOLOGY
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.
REGULATION OF GENE EXPRESSION
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 HRI is a hemoprotein with two distinct types of heme binding sites. These data have significance for further understanding of the role of HRI in the production of hemoglobin, a vital oxygen carrying protein.
VASCULAR BIOLOGY, TISSUE ENGINEERING
Elazer R. Edelman 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.
PERSONNEL
Elazer Edelman, M.D., Ph.D. was appointed Associate Professor of Health Sciences and Technology at M.I.T., with tenure. Dr. Edelman is an expert in the area of cardiovascular biology. Professor Nelson Kiang retired in September 1996.
FUTURE PLANS
The main focus for the upcoming year is to aggressively reach out to the Harvard and MIT communities for involvement as we continue to build the infrastructure associated with HST's five main programmatic areas:
These coupled, ongoing activities involve many of our students and faculty, and each offers the opportunity for participation by individuals from many departments in the MIT and Harvard communities.
The overall effort is aided significantly by the generous Taplin award program. Brief remarks concerning the focus areas follow:
Integrative molecular, cell, and tissue biology (quantitative physiology): This are encompasses the research of a great majority of our students, and it evolves naturally from their scientific interests and coursework. Our efforts have matured to the point that there is an opportunity for integrative educational and research initiatives. The Speech and Hearing Sciences Program is tangible evidence of our early accomplishments. Building in this area will be a major goal of the graduate committee.
Biomedical engineering/biological physics: Two initiatives launched during the 96-97 year will continue to strengthen biomedical engineering in the coming year. The multi-institutional consortium entitled CIMIT (Center for innovative minimally invasive therapies) seeks to bring investigators from MIT, MGH, and BWH to develop technologies for medical applications. The MIT home for this activity is the HST Biomedical Engineering Center for Instrumentation, headed by Prof. Elazer Edelman. The NASA Institute, NSBRI (National Space Biomedical Research Institute) is a multi-institutional consortium whose mission is to understand the physiological consequences of space flight and to develop adequate countermeasures to allow human travel to Mars. Biomedical Engineering is a major element of the educational and research opportunities offered therein.
Imaging sciences and technology: About 30 faculty from Harvard and MIT have been actively involved in developing a coherent program for graduate and medical students and postdoctoral fellows. We plan to formally launch this program during the 97-98 year. We are in the process of recruiting a faculty member to provide a geographic locus for biomedical imaging at MIT.
Medical informatics: 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).
Clinical therapeutic discovery, delivery and assessment: For several years the Clinical Research Center has been administratively linked to HST. With Prof. Robert Rubin's appointment to our faculty and the implementation of the Clinical Investigator Training Program, the interactions between HST and the CRC have become more substantial. The objective in the coming year is to work together to increase the number of faculty conducting research in the CRC, to involve CRC faculty in HST teaching, and to evaluate the opportunities for human research that could be promoted and facilitated by the CRC/HST.
Martha L. Gray
MIT Reports to the President 1996-97