MIT Reports to the President 1997-98
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 multi-disciplinary, 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 multi-disciplinary training in these three areas to both M.D. and Ph.D. 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 M.D. curriculum trains physicians who have a deep understanding of the underlying quantitative and molecular science of medicine and biomedical research. The Ph.D. 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 Dennis Kasper, William Ellery Channing Professor of Medicine and Executive Dean for Academic Programs at Harvard Medical School (HMS). Professor Martha L. Gray, Kieckhefer Professor of Electrical Engineering is the M.I.T. Co-director, while Dr. Joseph Bonventre Professor of Medicine, is the Harvard Co-director. Dr. Richard Mitchell, Assistant Professor of Pathology at Harvard Medical School, serves as Associate Director of HST and Director of Student Affairs for HST-M.D. students.
HIGHLIGHTS OF THE YEAR
The second group of recipients of the John F. and Virginia B. Taplin Awards was announced June 5th at commencement ceremonies for the Harvard-MIT Division of Health Sciences and Technology. The four recipients of the $50,000 awards are George Daley, M.D., Ph.D., HST `91, Frederick Schoen, M.D., Ph.D., Professor of Pathology, Deborah Burstein, Ph.D., HST `86 and Associate Professor of Radiology, and Steve Massaquoi, HST `83, incoming assistant professor of Electrical Engineering and Health Sciences/Technology. The Taplin Awards were established by Mr. John Taplin, an MIT `35 alumnus, and his wife Virginia to advance research, study, and training in HST. The fund recognizes and supports the work of HST faculty and students in building HST's infrastructure in the areas of biomedical engineering, physics, and chemistry.
M.I.T.'s Commencement speakers were President Bill Clinton and Dr. David Ho, a 1978 HST graduate who was also the 1996 TIME magazine Man of the Year. Joseph Martin, M.D. Ph.D., Dean of the Harvard Medical School, was the keynote speaker at the HST commencement ceremonies on June 3rd.
The eleventh annual HST research day, The HST Forum, was held on March 12, 1998. The topic of the 1998 forum was "Neuroengineering", and Dr. Dennis Choi, M.D. Ph.D. (HST '78) the Andrew and Gretchen P. Lones Professor and Head of Neurology at Washington University School of Medicine in St. Louis, was the featured speaker. Fifty-three HST students presented their research at the Forum.
On June 3rd, HST and the MIT international Science and Technology Initiative jointly sponsored a special seminar, "Healthcare, East and West" by Dr. Wu Jie Ping, China's best-known physician and Dr. Huang Jie Fu, Vice President of the Chinese Medical Association.
Mr. Thanassis Martinos and his family have established the $1 million dollar Athina Martinos Research Scholarship fund to enable HST students to perform research under the mentorship of faculty at Harvard, M.I.T., and the Harvard-affiliated teaching hospitals.
Funding from the Whitaker Foundation allowed HST to launch an industrial internship program in biomedical engineering.
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 $500,000 Lemelson-MIT Prize, the world's largest cash prize for American invention and innovation. Professor Langer is a world leader in developing polymeric drug delivery systems.
Jeffrey Drazen, M.D., was honored at the HST commencement as the recipient of the 1998 Irving M. London Teaching award.
Joseph Bonventre, M.D., Ph.D., HST `76, HST co-director, has been elected President of the National Kidney Foundation of Massachusetts and Rhode Island.
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 302 graduate students was registered in HST degree programs during the academic year. There were 189 M.D. candidates of whom 88 were simultaneously pursuing Ph.D. degrees. HST doctoral programs registered 112 students: 67 in the Medical Engineering and Medical Physics (MEMP) track, 40 in the Speech and Hearing Sciences (SHS) track, 4 in the Medical Informatics M.S. program, and 4 in the Radiological Sciences Joint Program which is sponsored jointly by HST and the Nuclear Engineering Department.
The M.D. degree was awarded by Harvard Medical School to 29 HST students this year, of whom 6 received honors in a special field and 17 received the combined M.D.-Ph.D. degree. Nine students received MEMP doctoral degrees from MIT, and 1 student received a doctoral degree from the Radiological Sciences Joint Program. The inaugural degrees for several new graduate programs in HST were awarded this year: One student received a Master of Science degree in Medical Informatics; 3 students received the Ph.D. degree in the Speech and Hearing Sciences program, and 1 student received a Ph.D. from the Biological Physics/Biological Engineering program.
Eric Liao `99 and Maureen Su `00 presented platform lectures at the 58th annual Soma Weiss Research Day at Harvard Medical School. An additional 26 HST students presented research posters.
A new educational track in the Medical Engineering and Medical Physics program was launched. This new Ph.D. track in Cellular and Molecular Medicine enhances the training of engineers and physicists by emphasizing recent advances in molecular biology.
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.
BIOMEDICAL ENGINEERING/BIOLOGICAL PHYSICS
Elazer R. Edelman, M.D., Ph.D., HST '83, uses elements of continuum mechanics, digital signal processing, and polymeric controlled release technology to examine the cellular and molecular mechanisms that transform stable coronary-artery disease to unstable coronary syndromes. Tissue-engineered cells, for example, deliver growth factors and growth inhibitors for the study and potential treatment of accelerated arterial disease following angioplasty and bypass surgery. Edelman is motivated by a tough clinical problem: more than half of blocked blood vessels that are cleared by a procedure called balloon angioplasty become blocked again. His discoveries have lead to patents for endovascular stents, drug-delivery devices, tissue-engineered implants and new drug formulations.
Frederick J. Schoen, M.D., Ph.D., has made major investigative contributions in identifying, elucidating the mechanisms of, and solving the critical problems associated with the biomaterials and devices used clinically to replace diseased heart valves. His approaches have used basic biology, evaluations of clinical implants that have failed, and industrial developmental studies.
Richard J. Cohen, M.D., Ph.D., HST '76, 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 - which accounts for 400,000 deaths in adults each year in the US. For those at risk, there is an effective preventive therapy - an implantable cardioverter/defibrillator. Cohen's group at MIT analyzes tiny, microvolt level fluctuations in the electrocardiogram to identify individuals at risk. However, the pattern is so subtle that it can be detected only with sophisticated computer-based analysis. The technology developed in Dr. Cohen's laboratory has been licensed by Cambridge Heart, a company founded by Dr. Cohen, that is commercializing this technology for routine clinical use.
Robert S. Lees, M.D., 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.
Roger G. Mark, M.D., Ph.D., is devising intelligent patient monitoring systems. He also analyzes cardiac arrhythmias, or the rhythmic disturbances in the heartbeat often associated with heart ailments such as coronary heart disease. Other studies include physiological signal processing, cardiovascular system modeling, geographically distributed health-care systems, and elder care.
Michael S. Feld, Ph.D. heads the MIT Laser Biomedical Research Center, an NIH Biotechnology Resource Center housed in the MIT Spectroscopy Laboratory, which develops basic scientific understanding, new techniques and technology for advanced biomedical applications of lasers. In one area of interest, he and his colleagues have developed spectroscopic techniques for biochemical analysis of tissues and blood, and early diagnosis of cancer, atherosclerosis and other diseases. The techniques are implemented clinically by introducing a fiber-optic probe or catheter into the body, delivering excitation light, collecting spectroscopic signals remotely, and analyzing the data outside the body as the test is being done. One new and exciting result is HST Ph.D. student Vadim Backman's development of a light-scattering technique for measuring the size distribution of enlarged epithelial cell nuclei, an indication of pre-cancer (dysplasia) which is not visible to the eye. The first application studied a condition known as Barrett's esophagus, which is very difficult to diagnose.
George B. Benedek, Ph.D., and colleagues have found the molecular factors that produce lens opacification in cataracts. They have developed instrumentation for the early detection of cataract formation and are developing agents designed to inhibit cataract formation. Also, he and colleagues at MIT and Harvard Medical School have developed methods to assay and control the growth of fibrils of the protein beta amyloid. Plaques made up of these fibrils are believed responsible for neuronal damage in the brains of patients suffering from Alzheimers's disease.
Kenneth N. Stevens, Sc.D., has made several contributions in the area of speech and speech perception, integrating the thinking from linguistics, acoustics, and signal processing. The research in the laboratory of Dr. Stevens includes the development of models of the segmental and prosodic aspects of human speech production and models for the accessing of words from continuous speech. Dr. Stevens and his students have also been examining the acoustic and articulatory manifestations of certain neuromotor and laryngeal speech disorders, with the goal of developing quantitative approaches to the assessment and understanding of these disorders.
Dennis M. Freeman, Ph.D., focuses on hearing - the process of receiving and translating the sounds of speech, etc.
Via a bundle of microscopic hairs, sensory cells in the inner ear sense sound-induced motions of inner-ear structures and trigger neural messages that relay information about sound to the brain. Dr. Freeman and colleagues have devised video methods to measure the submicrometer motion of these sensory cells, which show for the first time how the microscopic hairs move in relation to other inner-ear structures. The studies should lead to a better understanding of our incredibly sensitive sense of hearing.
James C. Weaver, Ph.D., and colleagues at MIT are investigating electrochemical methods for creating enlarged pathways across skin, with the goal of providing rapid, controlled transdermal drug delivery of large molecules such as peptides, proteins and DNA.
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.
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.
Lisa Freed, Principal Research Scientist in HST and Gordana Vunjak-Novakovic, Principal Research Scientist in HST and Adjunct Professor of Chemical Engineering at Tufts University are studying tissue formation using isolated cells, 3-dimensional polymer scaffolds, and bioreactor vessels. Ongoing research includes in vitro cultivation of skeletal and cardiovascular 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.
Chi-Sang Poon, Ph.D., has developed a patented one of the world's smallest mechanical respirator for use with newborn mice that are genetically engineered for various research purposes. He has also developed and patented a novel computational technique that allowed investigators to discern the presence of significant chaotic dynamics in the normal heart beat and a decrease of such cardiac chaos in patients with congestive heart failure. Another major invention is a new artificial neural network architecture that can be trained must faster than ordinary neural networks and is amenable to implementation with analog very-large-scale-integrated circuits. In basic research, he found the first evidence of synaptic plasticity (the kernel of certain cognitive functions such as learning and memory) in the region of the mammalian brainstem which is important for the control of respiration and circulation - vital physiological functions that are generally thought to be non-cognitive.
IMAGING SCIENCES AND TECHNOLOGY
Medical and biological imaging have grown explosively during the century since Roentgen's discovery of x-rays. The contribution of imaging technology to medical science promises to be even greater in the next century as imaging expands to demonstrate function as well as anatomy. The advance of structural and functional imaging includes imaging technology for disease, brain function, auditory and speech process, gene expression, and cardiac imaging. Revolutionary research has propelled imaging technology for active treatment planning and monitoring.
HST is launching the Harvard/MIT Imaging Center to house new faculty and their imaging and image processing teaching and research facilities, and to create a critical link devoted to developing imaging technology.
Martha L. Gray, Ph.D. HST '86, co-director of HST, and collaborator Deborah Burstein, Ph.D., HST '86 use magnetic resonance for measuring composition and functional integrity of cartilage. Over the last century, clinicians and researchers have had to struggle to understand and treat diseases they couldn't "see" until significant cartilage destruction had occurred. This situation has the potential to improve dramatically with the method that Gray and Burstein have pioneered.
W. Eric L. Grimson, Ph.D., has conducted research in computer vision for more than 20 years. He is internationally known for his seminal work in stereo vision, object recognition, formal models of visual processes, image indexing and visual surveillance. His current research interests include applications of computer vision to medical image analysis, especially the topics of image guided surgery, construction of anatomical and functional models of tissue from medical imagery, and surgical simulators. Grimson and colleagues are developing three-dimensional visualization and navigation tools that allow a surgeon to see hidden internal structures (such as vessels, tumors, eloquent cortex), thus minimizing damage to surrounding structures during surgery. A system based on these tools is currently being used at Brigham and Women's Hospital in Boston.
Bruce Rosen, Ph.D., HST '84, Director of the NMR Imaging Center at Mass. General Hospital. He is well known for his contributions in the area of "functional" imaging - that is, magnetic resonance images of the brain in which areas having some functional activity (e.g., visual cortex) are highlighted by receiving increased blood flow.
The techniques Rosen and colleagues have developed are now being used by hospitals throughout the world in evaluating patients with acute stroke, and by neurosurgeons to non-invasively provide a "road map" of the functioning brain prior to surgery. Functional imaging tools are also being used by cognitive scientists and psychiatrists to study normal brain functions such as language and memory, and a host of mental illnesses including Alzheimer's disease, schizophrenia, and drug abuse.
Robert S. Lees, M.D., focuses on atherosclerosis, its causes, prevention, diagnosis and treatment. His broad range of contributions include the design and implementation of an ultrasound system for accurate noninvasive assessment of progression and regression of atherosclerosis, and the discovery of key oligopeptides (short polymers of amino acids which resemble a small portion of a protein) that functioned in a manner analogous to the full length protein and so, when radiolabeled, served as a diagnostic probe visualized by a special imaging procedure. These patented techniques developed in Dr. Lees's laboratory have been successfully incorporated into multiple diagnostic drugs which are in clinical trial for imaging not only cardiovascular disease but also cancer and infection.
James G. Fujimoto Ph.D., research group investigate laser diagnostic and therapeutic applications in medicine. A central theme of their research is the development and application of optical coherence tomography (OCT). OCT is a new medical imaging technology which can perform high-resolution, cross-sectional imaging of tissue microstructure in situ. This technology can function as a type of optical biopsy and has widespread applications ranging from the diagnosis of early neoplasia to guiding surgical intervention. The group performs vertically integrated research spanning physics, lasers and optics, biomedical studies in vitro and in vivo, and clinical studies. The group maintains collaborations with investigators at the Massachusetts General Hospital, the Harvard Medical School, the New England Eye Center, several Boston Area teaching hospitals as well as international collaborations.
EXPERIMENTAL DIAGNOSTICS/THERAPEUTICS
One of the most visible and obvious arenas in which the bench-to-bedside transfer is a two-way bridge is with regard to therapeutics. Drugs and therapies not only may treat disease by serving as probes, they can provide important insights into disease mechanisms and offer diagnostic opportunities. Most faculty in HST are involved at some point in clinical human studies. The support of a clinical research center at MIT and the teaching hospitals, and the recently launched Clinical Investigator Training program have significantly enhanced the infrastructure, further enabling translational efforts.
It's well recognized now that melatonin, the hormone secreted by the pineal gland, has the important role of telling us when to fall asleep, and helping us to remain asleep. This recognition, as well as the knowledge that giving people low doses of melatonin can be used to treat insomnia, have their origins in research done during the past two decades by Richard Wurtman, M.D. and his associates. Wurtman showed that melatonin is a true hormone, that it is normally produced at night, and that the reason for this daily rhythm is that environmental light, acting via the eyes, inhibits melatonin synthesis. Wurtman's studies in HST's MIT Clinical Research Center showed humans, like animal subjects, also produce the hormone at night, but not during the day. Moreover, in humans, night-time melatonin production was found to decrease markedly with age.
John A. Parrish, M.D., developed a novel treatment of psoriasis (oral psoralen photochemotherapy, or PUVA) which is now used worldwide. His research group at MGH introduced laser lithotripsy of kidney stones, selective laser therapy of vascular birthmarks and lesions, and novel laser-based diagnosis and treatments of selective cardiovascular disorders and malignancies. Dr. Parrish organized the first, and now the world's largest, multi-disciplinary research group to systematically study the basic nature of laser effects on tissue, the Wellman Laboratories of Photomedicine at MGH of which he is Director. Dr. Parrish is also Director of the MGH-Harvard Cutaneous Biology Research Center (CBRC), a research center committed to fundamental research in cutaneous biology as broadly defined. Dr. Parrish is also Director of Partners-MIT-Draper Center for Innovative Minimally Invasive Therapy (CIMIT), a multidisciplinary research and clinical effort to introduce new therapeutic and diagnostic procedures to improve health care.
Robert H. Rubin, M.D., has spent much of his clinical career studying and caring for transplant patients. Among his accomplishments are the development of new strategies for preventing the most important infections, particularly those due to viruses and fungi; the establishment of the link between certain viral infections and allograft injury and the development of certain malignancies; and the development of novel antimicrobial approaches that are effective not only in transplant patients, but also in such other immunocompromised patient populations as those with AIDS and cancer. As director of the HST Center for Experimental Pharmacology and Therapeutics, Dr. Rubin has pioneered in the application of positron emission tomography, magnetic resonance imaging and spectroscopy and other measurement technologies to the development of new drugs, including those designed for the transplant patient. With Alan C. Moses, M.D., Dr. Rubin heads a two-year Clinical Investigator Training Program, a joint effort of the Beth Israel Deaconess Hospital, HST, and Pfizer, Inc. Trainees gain direct experience in clinical investigation and a strong foundation in the statistical and computational sciences, biomedical ethics, principles of clinical pharmacology, in vitro and in vivo measurement techniques, and aspects of the drug development process.
Daniel Shannon, M.D., is a founder of the field of pediatric intensive care and pulmonology. For more than two decades, Dr. Shannon has been furthering his breakthrough studies into the rare condition of congenital central hypoventilation syndrome (CCHS). Shannon and his colleagues have added incrementally to their framework of knowledge about the problem, using whatever new tool they could find to test specific hypotheses. Still, the clinical problems - like a child's failure to breathe adequately when asleep - continue to stump clinicians and researchers alike. Shannon's latest research reflects his concern to use technology in the service of patients.
Robert S. Langer, Jr. Sc.D., a pioneer in biomedical and chemical engineering, is studying new ways to deliver drugs, including a skin patch/ultrasound treatment that allows large-molecule biotechnology drugs such as gamma-interferon (an immune system booster for cancer patients) and (erythropoetin (for severe anemia) to be absorbed easily into the body through the skin. Langer is also researching tissue engineering. He has developed biomaterials for medicine, including plastic that slowly dissolves and releases therapeutic drugs directly to tumors.
In 1996, this led to the first new treatment for brain cancer approved by the FDA in more than 20 years.
Robert Kit Lee, Ph.D., conducts research aimed at finding treatments for neurologic diseases, particularly for Alzheimer disease. Specifically, he is investigating the use of neurotransmitter-type drugs (e.g, beta-blockers, Prozac-type drugs) to prevent neurodegeration and the formation of amyloid plaques in Alzheimer's disease. Recently, he briefed the Prime Minister and cabinet ministers of Malaysia on the development of a biotechnology/pharmaceutical center to discover new drugs from indigenous plants found in the Malaysian tropical forests.
MEDICAL SCIENCES AND MOLECULAR MEDICINE
Lee Gehrke, Ph.D., studies the replication and assembly of viruses that use RNA as their genetic material. Key biochemical processes that allow viruses to replicate depend on docking interactions between RNA and protein molecules. Gehrke's laboratory is focused on identifying these docking signals, an effort that will facilitate therapeutic approaches for blocking virus replication and assembly. The research has led to the molecular identification of amino acids and nucleotide sequences that are crucial for forming the RNA-protein interactions; moreover, the work also suggests the shape or conformation of the molecules changes upon binding. Another aspect of Gehrke's work is understanding how viruses are able to gain an advantage over the infected host cell in expressing their own genetic information. Nucleotide signals in a viral messenger RNA have been identified that give the virus a competitive advantage, and the lab is now working to elucidate the detailed mechanism.
Irving M. London, M.D., Founding Director 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, he is also focusing on novel gene transfer strategies for the gene therapy of human diseases.
George Daley, M.D., Ph.D., HST '91, a Whitehead Fellow, is looking into how the bcr/abl gene product stimulates blood cell growth, and has begun work toward a possible new therapy for leukemia. He has made great progress in the search for genes involved in other blood cell disorders.
Richard Mitchell, M.D., Ph.D., researches the mechanisms underlying acute and chronic rejection in solid organ allografts, and more specifically in heart transplants. The work spans from mouse heart transplant models up to human hearts, and is focused on understanding the specific immunologic mediators that drive the rejection and failure of these allografts. His lab is particularly interested in the mechanisms that induce the process of "chronic vascular rejection" whereby the vessels in transplanted hearts become progressively more occluded until the grafts get starved for blood and die. The research may have much broader applicability, since the inflammatory mediators that drive the occlusive process in transplanted hearts may also be involved in mediating the vascular wall thickening that characterizes more "typical" atherosclerosis. Mitchell's lab uses a number of genetically-engineered mice ( so-called "knock-out" mice) that are either deficient in particular mediators (called "cytokines") or deficient in the receptors for those cytokines. In collaboration with other members of the HST community (such as Dr. Elazer Edelman), Mitchell has been trying new interventions to prevent the chronic vascular pathology. They have also developed collaborations with a number of pharmaceutical firms (Schering-Plough and Bristol Myers-Squibb) to evaluate new drugs that may reduce the vascular narrowing.
Jane-Jane Chen, Ph.D., 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.
BIOINFORMATICS AND MEDICAL INFORMATICS
Knowledge discovery and its dissemination in health care have been deeply influenced by recent advances in computer science and engineering. Medical and Biological Informatics (MBI) is the use of computer technology to extract, transport, and manage information from medical and biological data, and to model and support human decision-making in clinical and biological domains. The field is a scientific and engineering activity which is inherently multidisciplinary. Research challenges include: deducing and mapping genomic structure, predicting structure and function of proteins, representing medical knowledge for modeling diagnostic and prognostic decision-making processes, extracting new information from large clinical and biological datasets, building comprehensive electronic medical records (EMR) and clinical information systems, interfacing monitoring devices and the EMR, assuring privacy and confidentiality in medical transactions, analyzing and manipulating images, recognizing patterns of disease progression, analyzing costs and benefits related to medical use of information technology, computer-aided instruction, and utilizing the Internet for providing education and health care services.
Robert Greenes, M.D., Ph.D., Director of the Medical Informatics Training Program, established the Decision Systems Group (DSG) in 1978, to pursue methodologies for physician education and decision support. Dr. Greenes has had a 34-year history of work in the area of medical informatics. The DSG lab includes physicians, computer scientists, database experts, graphics and multimedia specialists, with primary focus on development of means for enhancing decision support and education in medicine, and for integrating these capabilities into clinical practice. For the past ten years, emphasis has been on the development of component-based approaches to implementing applications that provide a framework for integration of diverse information resources in a cohesive manner.
Peter Szolovits, Ph.D., and colleagues study the intellectual processes in medical decision making and build systems that help improve them. One example is Guardian Angel, a lifelong personal health-information system which, among other things, collects all health-relevant information about its subject, communicates with health-care providers, payers, etc., and helps the patient manage ongoing medical problems. He is also developing a World Wide Web-based electronic medical-record system that permits sharing of clinical information among health-care providers while assuring confidentiality of patient data. Another tool in development, Geninfer, computes the risk of genetic disorders based on analysis of an individual's pedigree and results of genetic tests. Geninfer is to be used by genetic counselors. Szolovits is also developing and testing a program that diagnoses and evaluates possible therapeutic interventions in heart disease.
Lucila Ohno-Machado, M.D., Ph.D., investigates machine learning techniques to extract information from clinical databases, especially in the form of predictive models for prognosis. She has used special methods to predict survival for patients with AIDS, to assess the probability of myocardial infarction in certain populations, to predict ambulation for patients with specific kinds of spinal cord injuries, and to predict outcomes in other clinical domains. Her research is focused on the development and evaluation of models involving binary outcomes. She is also interested in deploying practical models for direct use by patients, physicians, and health care managers, so that they can make more informed decisions. An example in this area is a project that uses artificial intelligence techniques for dealing with uncertainty to select suitable clinical trials for patients with certain types of breast cancer.
PERSONNEL
Elazer Edelman, M.D., Ph.D. was appointed Thomas D. and Virginia W. Cabot Associate Professor of Health Sciences and Technology at M.I.T., with tenure. Dr. Edelman is an expert in the area of cardiovascular biology. Martha Gray, Ph.D. HST co-director, was appointed J.W. Kieckhefer Professor of Electrical and Medical Engineering. Dr. Gray is an expert in cartilage physiology and imaging. Joseph Bonventre, M.D., Ph.D., was appointed HST co-director and Professor of Medicine. Dr. Bonventre's expertise is in renal physiology.
FUTURE PLANS
The Division is poised to move ahead with a strategic plan that was reviewed recently with the Whitaker College/HST Visiting Committee. The plan calls for future growth in our educational and research programs through emphasis on our five focus areas: biomedical engineering/biological physics; medical sciences and molecular medicine; imaging sciences and technology; bioinformatics and medical informatics; and experimental therapeutics, clinical therapeutic discovery, delivery and assessment. Guided by student interests, new and enhanced course offerings are under development in every focus area. Two examples of these initiatives include novel programs that emphasize biomaterials and neuroengineering. These activities complement the new MEMP Ph.D. track in Cellular and Molecular Medicine that was launched in the Spring of 1998. HST's medical imaging initiative, stimulated by funding from John and Virginia Taplin, is recruiting a new faculty member and is moving ahead with plans for a new Biomedical Imaging facility. 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. Career development of existing faculty and hiring new faculty are critical areas that will continue to receive priority as we move ahead. New faculty appointments are essential for meeting our objectives in each focus area, as well as in creating a critical mass of faculty, meeting adequate student-faculty ratios in instruction, and emphasizing strong and stable links with other departments at MIT and HMS.
Martha L. Gray