With an ambitious mandate to cure cellular diseases, Harvard has launched an important new scientific enterprise, the Harvard Stem Cell Institute (HSCI). The public announcement was scheduled for April 23, although the news had been previously shared with alumni in a March 2 videoconference that linked sites in New York City, Cambridge, and Florida. Harvard already has outstanding faculty members and researchers working on stem cells, says Douglas Melton, Cabot professor in the natural sciences and chair of the Life Science Executive Committee for the Faculty of Arts and Sciences, who will codirect the new institute with Dr. David Scadden, professor and director of the Center for Regenerative Medicine at Massachusetts General Hospital (MGH).
HSCI will coordinate the teaching, training, and research of about 25 principal investigators and 64 affiliated member scientists, and will engage seven Harvard schools and six affiliated hospitals, focusing their research and clinical efforts on a singular goal: the use of stem cells to correct organ failure. (Stem-cell therapies have the potential to cure many diseases that involve cell loss.) Harvard is already well positioned to develop therapies in at least four areas: diabetes, blood diseases (including AIDS), neurodegenerative disease, and cardiovascular disease. "These four disease targets will be the initial priorities for the HSCI," says Melton. "Each has a set of [attainable] milestone achievements necessary to realize clinical therapies and a predictable, achievable route to clinical testing."
Melton and Scadden bring together clinical and research expertise in their joint leadership of the new institute. "David and I represent bookends on the problem," says Melton. "He's a clinician, a real doctor...and he works on the stem cell which has been studied the longest and about which the most is known"the hematopoietic, or adult blood, stem cell used in treating cancer patients through bone-marrow transplants. Notes Scadden, in a separate interview, "Doug is an expert in developmental biology." Melton's laboratory, working in concert with that of Baird professor of science Andrew McMahon and with Douglas Powers of Boston IVF (an in-vitro-fertilization clinic), recently developed and arranged to distribute free to qualified researchers 17 new human embryonic stem-cell linesmore than doubling the number currently available.
Such work is not without controversy. Although adult stem cells, such as the hematopoietic stem cells found in bone marrow, are uncontroversial and are used in treating tens of thousands of patients each year through transplants, they can create only the tissue from which they are derived (many claims to the contrary have been disproved in recent years). Blood stem cells can make only blood, for example. Because some tissues, such as the pancreas, do not appear to have an associated adult stem cell, it is impossible to use adult stem cells to treat diseases like Type 1 diabetes. Embryonic stem cells, on the other hand, can make any tissue in the body.
Most Harvard research on embryonic stem cells is done in animal models. Making new human embryonic stem-cell lines results in the destruction of a blastocyst, an undifferentiated mass of four to 50 identical cells that forms in the first few days after a sperm fertilizes an egg. Deriving a new stem-cell line is therefore controversial when performed on a human blastocyst, because some people and certain religious groups hold that this early stage of development represents a human life.
The 17 new Harvard stem-cell lines were therefore all developedaccording to earlier National Institutes of Health (NIH) guidelines and in the hope that they will one day help to save human livesfrom frozen blastocysts slated to be discarded by an IVF clinic. (Such clinics store tens of thousands of these early-stage fertilized eggs in a frozen state for implantation in female patients. When a patient's treatment ends, the blastocysts are either discarded, orwith the consent of the couple who owns themmay be used in medical research.) Because President Bush has banned the use of federal funds for research using stem-cell lines created after his national address of August 9, 2001, any work using these cells must be supported with private funds. At Harvard, all proposed research involving human embryonic stem cells is subject not only to the customary internal review, but also to scrutiny from a separate committee, headed by Cabot professor of biology Richard Losick, that has representation from throughout the University. Says Provost Steven E. Hyman, to whom the committee reports, "We really have to be thinking very deeply about the ethical implications of the new science and the new medicine."
Hyman has asked professor of government Michael Sandel, who also serves on the nation's President's Council on Bioethics, to lead a "free and active ethical [discussion], to create the intellectual background [for weighing] these [activities] both in terms of national policy and biomedical ethics." Given the highly politicized and emotional debate engendered by stem-cell research, a first-rate research institution like Harvard, with a tradition of rational, inclusive deliberation and responsible science, would seem well positioned to tackle both the ethical and scientific issues.
The center, one of several large, collaborative science projects announced in the last few years, was created as the result of a "grass-roots faculty effort," Hyman explains. "Science has changed and is changing. The current model, which is the individual laboratory investigator with her students and post docs," he says, "will remain a very important part of science. Having said that, it is really quite clear that much cutting-edge science will depend on large infrastructures....What we see are scientists who are at the cutting edge aggregating into new collaborative coalitions."
Even in that greater context, HSCI seems uniquely positioned to draw on resources from many parts of the University. Stem-cell science will be taught to undergraduates, graduate students, and medical students, and cuts across many areas, including biology, medicine, government and public policy, law, ethics, business, and religion. "We're a university that can cover this whole field," Melton says.
The institute will be "knit together in a very decided and focused way," in order to tackle specific scientific and clinical problems. Melton quickly sketches a matrix. On the horizontal axis he lists a series of disease targets: diabetes, blood disease, neurodegenerative disease, cardiovascular disease, and so on. Down the left axis, he jots some of the stages between isolating a stem cell and actually using it in a patient: self-renewal (keeping it dividing); targeted differentiation (signaling it to make the type of tissue that is desired); scaling up (making lots of the tissue for use in patients); transplantation (getting it into the patient); and clinical studies.
"The way the institute is organized," says Melton, "we might get all the people who are interested in diabetes together and ask how we are going to get a stem cell all the way into a patient." He continues, "Let's say we are stuck on the process of self-renewal. We can now bring together people from all different areas of disease expertise, people who never really talked to each other beforeneurologists, endocrinologists, hematologists"to try to solve the problem. A researcher working on Parkinson's disease might have come up with a novel way of ensuring self-renewal that could be applied to other disease targets.
"One of the key things is that people become multilingual," echoes Scadden. "Those who focus predominantly on clinical care will start to appreciate the necessary components of computational science and developmental biology that are all necessary to take advantage of emerging opportunities in stem-cell science and regenerative medicine." HSCI will have "a very big influence on developing new models of educating people. Having people from Harvard and MIT with training in mathematics and computational science as part of the creative process will be an important part of training the next generation of doctors and scientists so that they are comfortable with spanning these worlds." These new models of inquiry, Scadden hopes, will attract both students and faculty to work in regenerative medicine.
"Harvard [in] its history always has been striving to be a leader in critical areas of knowledge," says Hyman, "and areas like stems cells [are among] the most exciting intellectual challenges in the world today. We would really be abdicating our role as intellectual leaders if we didn't do everything in our power to make it possible for our faculty to engage in these new areas."
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