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Ideology Vs. Science: The Stem-Cell Battle By Kim Ribbink Across the globe, scientists are extolling the potential of stem- cell research to cure debilitating diseases, in spite of limits on federal funding as well as controversy surrounding the research. States and private investors have begun to step into the fray, and experts argue the importance of this research will become increasingly apparent as results emerge. n the race to find a cure for many of life’s most debilitating conditions, stem-cell research is both the promising golden child and, to its detractors, the black sheep of the family. Despite the controversy, high costs and risks, and potentially huge regulatory hurdles, research into the therapeutic potential of stem cells continues. And both public and private funding of stem-cell research is expected to increase. Total stem-cell public funding in the United States was about $210 million in 2004. Researchers from Navigant Consulting predict this will triple to $630 million by the end of 2005. As public funding increases, private spending for stem-cell research also will increase as more companies realize the vast therapeutic potential in this area. Navigant Consulting researchers estimate that $14.2 billion in total public and private resources will be dedicated to stem-cell research over the next 10 years with the United States, Australia, Israel, Singapore, South Korea, and the United Kingdom being the largest investors. Spending will be divided among labor costs, equipment and facilities, and cell culture and other supplies used to grow and maintain stem-cell cultures. Some experts say it could be 15 to 20 years before there are any clinical applications of this research, but its potential is huge. Navigant Consulting researchers predict that the first stem-cell therapeutics will be commercialized in the United States by 2009, with the U.S. market reaching more than $3.60 billion in revenue by 2015. (For more information, see page 43.) Scientists believe in the potential of stem-cell research to repair spinal cord injuries and to treat debilitating conditions, such as Parkinson’s disease, Alzheimer’s disease, cancer, and diabetes. The general public supports stem-cell research in overwhelming numbers, according to market research firm Harris Interactive. According to a 2004 Harris Poll, a 6-to-1 majority favors stem-cell research, an increase from a 2001 survey, when a 3-to-1 majority said stem-cell research should be allowed. But there also is resistance to the research, in particular to embryonic stem-cell research. In 2001, President George W. Bush issued an executive order limiting the use of federal funds to the 60 stem-cell lines that were in existence before August 2001. The executive order means the NIH’s research grants are restricted. Though President Bush permitted research on stem cells to continue if the stem cells were harvested from either placentas or cord blood or from adult sources, some experts say the restrictions on embryonic stem-cell research have cast a pall over this area of research in the United States. As this issue went to press, the Republican-controlled House of Representatives voted to lift the restrictions on embryonic stem-cell research. A similar bill has been presented in the Senate but not yet voted on. “According to NIH, about $230 million was spent on all of human stem-cell research in 2004, and this amount is paltry considering the importance of the problem of human stem-cell research and the benefits it could provide both in terms of science and treatment of people,” says Wise Young, M.D., Ph.D., chair of the Department of Cell Biology and Neuroscience at Rutgers University. Stem cells fall into three classes: multipotent, pluripotent, and totipotent. Stem cells that can give rise to a small number of different cell types are generally called multipotent. Pluripotent stem cells can give rise to any type of cell in the body except those needed to develop a fetus. A fertilized egg is considered totipotent, meaning that its potential is total; it gives rise to all the different types of cells in the body. Embryonic stem cells are derived from embryos that develop from eggs that have been fertilized in vitro and then donated for research purposes with informed consent of the donors. The embryos from which human embryonic stem cells (hESCs) are derived are typically four or five days old and are a hollow microscopic ball of cells called the blastocyst. “The distinction is in the potency,” says Sander M. Rabin, M.D., J.D., patent counsel with Whiteman Osterman & Hanna LLP. “Stem cells harvested from a blastocyst or embryo are totipotent, whereas those harvested from other sources are pluripotent and have less of a differentiation spectrum. So the preference is to work with those cells that have the capacity to develop into anything as opposed to a restricted set of organs and tissues.” A Wealth of Possibilities Researchers note that embryonic stem cells are capable of forming any of the almost 200 tissues and cells in the human body. “I don’t think that anyone would argue that this isn’t a major new platform for science and medicine,” says Andrew Cohn, government and public relations manager for the Wisconsin Alumni Research Foundation (WARF). According to experts in the field, much of the promise and excitement over hESCs lies in the fact that these cells are genetically programmed by nature to differentiate spontaneously into all the cells of the human body. “As such we are starting with the natural progression of human developmental biology,” says Thomas B. Okarma, M.D., Ph.D., president of Geron Corp. “In the manufacturing facility, we simply restrict the signaling these cells receive by selecting the compounds that we add to them to drive their differentiation down one particular pathway or another. So we’re not programming these cells to do something they’re not normally genetically predisposed to do. This is why the efficiency of production and differentiation is so high and why the molecular and cell biology of the differentiated cells is normal.” In addition, Dr. Okarma says because the degree of differentiation along each individual pathway can be controlled, scientists can choose the state of development of the therapeutic cells at the time they are harvested and placed in a recipient. “This is an important control element because it enables us to choose exactly the right moment to stop the differentiation production process to enable the transplanted cells to integrate with the diseased tissue into which we inject them,” Dr. Okarma says. Geron is developing three groups of products: therapeutic products for oncology that target telomerase, an enzyme that is expressed in nearly all cancer cells but not in most normal cells; pharmaceuticals that activate telomerase in tissues impacted by senescence, injury, or degenerative disease; and cell-based therapies derived from its human embryonic stem-cell platform for multiple chronic diseases. Research into hESCs continues to reveal other potential applications. “We have shown how to differentiate hESC into heart cells, into islet B cells, into all parts of blood, into motor neurons,” Mr. Cohn says. “This research gives us an opportunity to look at tissues that we have never been able to evaluate before in a petri dish so we can study them and figure out why they go bad and find ways to fix them. By being able to look at the very earliest cells, we will have the ability to study birth defects and infertility problems.” Dr. Okarma suggests that beyond the scientific merits, hESCs will impact medicine because of their scalable manufacturing characteristics. “The undifferentiated human embryonic stem cell expresses a high level of telomerase, and that telomerase expression not only enables the cells to continue to divide indefinitely but also to maintain genomic stability,” he says. “These cells are a self-renewing source for the scaleable manufacturing of replacement tissues.” This portends well for having a low cost of goods; a reliable, scaleable production process; and reasonable margins once products are commercialized, Dr. Okarma says. “The single biggest impediment to development, in the sense of commercializing and delivering cell therapies to patients worldwide, has been the cost of goods,” he says. “There is no other cell system that we’re aware of that has the scaleable potential of embryonic stem cells.” How long it will be before the science becomes a product remains unknown. A panel of eight academic experts in the field, brought together by MedPanel Inc., predicts that it will take a long time, a lot of work, and a great deal of money to turn scientific advancements into clinically relevant tools that may improve patient outcomes. The panelists believe the most likely applications include islet cell transplantation, spinal cord injuries, Parkinson’s disease, and dementia. But while much work needs to be done to ensure the basic science is thoroughly understood, the time from basic research to actual proliferation of the technology is shortening, Dr. Rabin says. “The time lag between breakthroughs in fundamental research in stem-cell biology and the actual deployment of a therapy based on that research can be expected to be shorter and shorter as we know more and more,” he says. a Technical Hitch New concerns over the Bush administration’s limitations on embryonic stem-cell research were raised when researchers at University of California, San Diego, identified an animal molecule — N-glycolyneuraminic acid — that contaminated one of the stem-cell lines in the National Institutes of Health stem-cell registry. The study was published online in Nature Medicine on Jan. 23, 2005. Scientists believe that, because all the stem-cell lines in the NIH registry have been grown using either mouse or fetal calf cells, others could be contaminated in the same way. The researchers involved advise that it would be safest to start over with newly derived hESCs. “The finding of contaminated stem cells would make these cells unusable in humans for several reasons,” Dr. Young says. “Firstly, the discovery that cells grown in animal serum will take on certain animal-related glycosylation patterns — carbohydrate, cylic acid residues — which will automatically trigger an immune response if these cells were transplanted into humans. So the exposure of cells to any animal serum reduces their use for transplantation. “The second fear is that many of the stem cells that have been grown for long periods of time with mouse feeder cells will have mouse genes inside them,” Dr. Young adds. “And this would rule out all the approved — not existing — embryonic stem-cells lines for transplantation purposes. There are a number of human embryonic stem-cell lines that have been created without contamination by mouse feeder cells. Unfortunately, these are not among those approved for funding by NIH.” A number of breakthroughs have been made in stem-cell lines. Scientists at WiCell, a nonprofit subsidiary of WARF, and the University of Wisconsin-Madison have shown that it is possible to grow hESCs in the absence of mouse-derived feeder cells. Until now, scientists have had to grow and sustain stem cells by generating mouse feeder cells from mouse embryos. Feeder cells, or fibroblasts, are connective tissue cells that form the matrix upon which stem cells grow. “Making the layers with mouse feeders was expensive, time consuming, and difficult,” Mr. Cohn says. “Doing away with this requirement means this whole area of science will be much more attractive to people because the entry costs will be less, and that’s a huge step forward.” Executives from Geron say the company has demonstrated that hESCs can be propagated in culture using defined growth factors without the need for feeder cells or media conditioned by feeder cells. “We have new lines that have been derived with our proprietary methods that have never seen an animal cell or an animal product,” Dr. Okarma says. Scientists at the Roslin Institute in Edinburgh, Scotland, famous for cloning Dolly the sheep, have produced what they claim are the first animal-free embryonic stem cells by placing the cells on a layer of a purified human protein called laminin and then adding “feeder” layers of human neonatal foreskin cells as a replacement for mouse feeder cells. While the breakthroughs by scientists worldwide are significant, the federal ban prohibits the NIH from funding such production. “Given the progress we have made, the restrictions from the President’s executive order are going to create a barrier, and we hope that can be changed,” Mr. Cohn says. Battling Controversy The restrictions have raised the ire of scientists nationwide. “We need to understand how it is that a cell can make so many different types of cells, and, even more important, we need to understand how the cell knows what kind of cell to make,” Dr. Young says. “This information is so important that I am astounded that our government has essentially held back research in this area.” Drawing on both his legal and medical background, Dr. Rabin proposes that to overcome some of the ideological opposition to stem-cell research one approach might be to distinguish between biological and moral life, or a blastocyst versus an embryo. A blastocyst is the cluster of cells that comes into existence within 10 to 14 days after the formation of a zygote, and, if allowed to develop in utero, will eventually form an embryo. “One legitimate place to draw a line between a blastocyst and an embryo is the development of that primitive streak, which is the earliest precursor of the human nervous system,” he says. “That primitive streak begins to form after about 14 days, and if one agrees that a human can’t experience being without sentient consciousness, then it’s impossible for consciousness to be present in the absence of a nervous system.” Nevertheless, Dr. Rabin adds that the gap cannot be bridged with those who believe full moral standing as a human begins at the moment of fertilization. An area that has generated even greater controversy is somatic cell nuclear transfer, or therapeutic cloning, in which the nucleus of an unfertilized egg cell is replaced with material from the nucleus of a somatic cell — skin, heart, or nerve cell, for example — and the cell is stimulated to begin dividing. Therapeutic cloning is distinct from reproductive cloning, which is intended for the creation of human beings. Some governments, including those in the United Kingdom, have made a distinction in the law. “England banned reproductive cloning through a piece of legislation, which, in one sentence, says, ‘nonfertilized eggs may not be transplanted into a human uterus,'” Dr. Young says. “This effectively bans reproductive cloning.” Nuclear transfer is being explored by researchers, such as scientists at the Roslin Institute, as a way to overcome rejection of hESCs. The potential for nuclear transfer is that it can generate stem-cell lines for therapy, as well as allow researchers to explore biologically how genetic disease is expressed tissue by tissue, Dr. Okarma says. But nuclear transfer is entirely different from embryonic stem cells. “Nuclear transfer has nothing to do with embryonic stem-cell based therapies; they are totally distinct,” Dr. Okarma says. “The detractors of this platform try to link them, thereby creating broad prohibition of both embryonic stem cells and cloning, and that’s a specious proposition. We do not need nuclear transfer to solve the potential immune rejection issues; we have other ways that are now validated to do that.” For example, in a research paper titled Human Embryonic Stem Cells Possess Immune-Privileged Properties, scientists from Geron and several research centers in Ontario, Canada, note that a 2004 study into the immune responses to hESCs illustrated that such cells have properties that enable them to be immunologically privileged. The hESCs were not recognized by human lymphocytes in vitro. The researchers propose that hESCs may represent an immune-privileged cell type that is capable of inhibiting local immune responses via direct cell-to-cell contact. “Pregnant women never reject immunologically the implanting blastocyst, and that’s remarkable because the implanting embryo is an allograft just like a kidney transplant: it is foreign to the mother because it expresses both mother and father tissue antigens,” Dr. Okarma says. “The blastomeres, the cells in the embryo from which embryonic stem cells are derived, secrete immunosuppressive substances to create an immune privilege site in the uterus at the site of implantation. The early differentiated descendants from the embryonic stem cells retain that property. We believe that the amount of immune suppression we will need to use in our first human clinical trials is much lower than what is traditionally used in bone marrow or organ transplantation.” State Initiatives Several experts in the field say the effect of the federal ban will cause the United States to fall behind other countries in its understanding and application of stem-cell research. The ban could even prove a brain drain. “There are American university researchers who have moved their operations to the United Kingdom, and their incentives involve not only issues of funding but issues of what sort of stem-cell research is permissible,” Dr. Rabin says. “For example, in the United Kingdom there is no proscription against therapeutic cloning.” Not everyone is in agreement, noting that various states have been stepping into the fray with financing of their own. The most notable example is California, which passed Proposition 71 in November 2004, supporting stem-cell research with a bond of $3 billion over 10 years. “California is spending probably more than the rest of the world combined,” Mr. Cohn says. “Other states — Illinois, New York, Massachusetts — are talking about doing funding of this research. And here in Wisconsin, the governor has made a proposal again to support stem-cell research.” On January 2004, then New Jersey Governor James E. McGreevey signed into law S1909, the “Stem Cell Research” bill, making New Jersey the second state in the nation to legalize stem-cell research. Under the act, physicians treating patients for infertility are required to provide information to allow them to make an informed and voluntary choice regarding the use of human embryos following infertility treatment. The act also prohibits the cloning of a human being. The act approved by the New Jersey legislature notes that publicly funded stem-cell research, conducted under established standards of open scientific exchange, peer review, and public oversight, offers the most efficient and responsible means of fulfilling the promise of stem cells to provide regenerative medical therapies. “Acting Governor Richard Codey has committed $150 million to build and equip the stem-cell institute of New Jersey, and there is a ballot asking for approval for a $230 million bond to provide $30 million a year for seven years to support stem-cell research in New Jersey,” Dr. Young says. Massachusetts also is moving ahead. On March 30, 2005, the state senate passed a bill that would allow somatic cell nuclear transfer, and the following day the Massachusetts House of Representatives voted 117 to 37 to pass legislation authorizing embryonic stem-cell research, a wide enough margin to override a veto from Governor Mitt Romney. “These states are offering or hoping to serve as economic magnets for stem-cell research and the spin-off industry in the same manner as nations in Asia and the European Union,” Dr. Rabin says. “Unfortunately, even if stem-cell research is funded by state dollars, one of the outcomes will be that the regulations that pertain to the types of stem-cell research that qualify for state funding will not be consistent.” In an effort to move the embryonic stem-cell issue forward, the National Academies, an independent organization engaged by Congress to provide advice on scientific matters, has proposed national ethical guidelines for human embryonic stem-cell research. The advisory group also has recommended that research institutions establish oversight committees to enforce the guidelines and that these committees be made up of legal and ethical experts as well as representatives of the public. Finding Other FUNDING SOURCES The federal ban also has created a trend toward private funding of stem-cell research, and various institutions have benefited from private contributions, Dr. Rabin says. “Andrew Grove, founder of Intel, gave $5 million to the University of California at San Francisco to make new stem-cell lines,” he says. “Stanford University started an institute to study cancer using stem cells with a $12 million anonymous grant. The Michael J. Fox Foundation for Parkinson’s Research has given more than $5 million to institutions and researchers.” Nevertheless, he adds that the political climate has driven many scientists away from the field entirely and has dampened investor enthusiasm, leaving some companies struggling. The limits on government spending mean stem-cell researchers have to look elsewhere for funding. Venture capitalists are unlikely to be major players, Dr. Young says. “Dennis Purcell, one of the leading venture capitalists, has pointed out two trends that make it very difficult for the venture capitalists to invest in stem cells,” Dr. Young says. “The first is the timeline; venture capitalists and their backers are looking for short-term returns. Also, venture capitalists like to wait until a technology is mature, and then they jump in at the very last moment to get that 20-fold return on their investment.” But Dr. Young believes that pharmaceutical companies will be looking for new approaches, and stem cells might be attractive to them. “Stem-cell research is going to be a source of a lot of intellectual capital,” Dr. Young says. Michael Hunt, chief operating officer and finance director of United Kingdom-based ReNeuron, says unless there is an overall ban on research, he does not believe the NIH restriction will have much relevance. “The NIH directive certainly hampers some of the early-stage research, but I think private money will fund the enterprises that will ultimately develop and commercialize this technology,” he says. Mr. Hunt says the United Kingdom has enjoyed an early lead in stem-cell research and the British government’s support of the research certainly helps. “The United States is very good at playing catch up; it’s done so in the past and no doubt will do so again in this field as, state by state, more and more money is put behind the research,” he says. “The United Kingdom is well positioned for the time being, and we’re very happy to be operating there.” Competition also is likely to come from centers in Singapore, China, and Korea, Mr. Hunt says, where governments are plowing resources into stem-cell research. A change in attitude in the United States will likely come when companies show results, Dr. Okarma believes. “What needs to happen is proof of concept in man,” Dr. Okarma says. “And if we are half right about the predictability of our animal work in spinal cord injury, it will change the landscape dramatically. And that’s what we’re waiting for. If we show safety and efficacy in spinal cord injury, then the debate changes dramatically.” PharmaVOICE welcomes comments about this article. E-mail us at email@example.com. Dr. Wise Young We need to understand how it is that a cell can make so many different kinds of cells, and, even more important, we need to understand how the cell knows what kind of cell to make. This information is so important that I am astounded that our government has essentially held back research on this area. June 2005 PharmaVOICE The Stem-Cell Market Navigant Consulting estimates that total stem-cell public funding in the United States was about $210 million in 2004 and will triple to $630 million by the end of 2005. As public funding increases, private spending for stem-cell research also will increase as more companies realize the vast therapeutic potential in this area. Two leading companies, Geron Corp. and ES Cells International, are both located in California and will benefit from the state’s favorable funding environment. Analysts predict that the first stem-cell therapeutics will be commercialized in the United States by 2009. Navigant Consulting’s analysts expect that ViaCell Inc.’s adult stem-cell-based cancer treatment, derived from umbilical cord blood, will be the first product to market in 2009. By 2015, U.S. stem-cell therapeutics will reach more than $3.60 billion in revenue, led by treatments for diabetes and cardiovascular disorders. The market growth will initially be driven by adult stem-cell therapeutics. But revenue from embryonic stem-cell therapeutics is expected to overtake this by 2012. Navigant Consulting estimates that $14.2 billion in total public and private resources will be dedicated to stem-cell research over the next 10 years, with the United States, Australia, Israel, Singapore, South Korea, and the United Kingdom being the largest investors. Spending will be divided among labor costs, equipment and facilities, and cell culture and other supplies used to grow and maintain stem-cell cultures. Investors are planning a number of centralized research facilities, associated with leading institutions, including the University of California San Francisco (UCSF), the University of California San Diego (UCSD), Harvard University, and the University of Wisconsin (Madison). “Because stem-cell biology is still in its infancy, much labor-intensive basic science research is necessary long before any safety testing, regulatory approval, or product commercialization can occur,” says Andrew Kim, senior consultant for Front Line Strategic Reports, Navigant Consulting. “Production and R&D scale-up is difficult, especially for the small academic research labs or biotech start ups, which are the majority of companies in this space.” Source: Navigant Consulting Inc., Chicago. For more information, visit navigantconsulting.com. Stem-Cell Market Share by Therapeutic Area (2015E) U.S. Stem-Cell Therapeutics Market (2005E to 2015E) Spinal cord regeneration 7% Reconstruction of blood system 5% HIV 4% Cardiovascular disorders 27% GVHD 3% Diabetes 48% Chrondrocyte <2% Bone regeneration 4% Others <1% 2009 2010 2011 2012 2013 2014 2015 Note: $ are in millions An Alternative Path Research institutes and companies worldwide are investigating ways to turn stem cells into therapies. A small handful have decided to focus on embryonic stem-cell research, including Geron Corp. and Advanced Cell Technology, while other companies are evaluating adult stem cells, cord blood, and the use of stem cells from umbilical cords and placenta. The approach U.K.-based ReNeuron has taken is through a proprietary somatic stem-cell technology derived from fetal material. “We’ve gone for the midway approach, in that we’re not focused on the pluripotent embryonic stem-cell research, where cells are extremely malleable or flexible and can turn into just about any other cell type, and nor are we adopting the fully adult stem-cell approach where scientists perhaps try to manipulate those cells in some way to generate cells to treat a disease condition pertinent to another region of the body,” says Michael Hunt, chief operating officer and finance director of ReNeuron. “We take our cells from the body region that’s appropriate to the disease state that we’re looking to treat.” The company believes that its approach offers the best chance of getting a stem-cell therapy that is widely applicable to significant disease states. ReNeuron has several programs under way. Its lead program is in chronic disability post-stroke, and the company believes it is the first to generate convincing preclinical efficacy data in stroke in rodent models. “We have moved forward in scaling up that program for chronic stroke indications, and we have those cells now banked to GMP,” Mr. Hunt says. “Recently, we had our first interaction with the FDA with a view to submitting a pre-IND, which we hope will allow us to commence clinical trials next year.” Mr. Hunt says much depends on getting regulatory clearance to commence clinical trials, but he predicts that the company will have a marketable treatment for stroke within the next five to 10 years. Another of ReNeuron’s programs is in diabetes. “We’re already at the stage where we have a cell line that secretes insulin, and we’re looking to move that onto the next stage now,” Mr. Hunt says. “We’re working with a European technology partner to move that through preclinical testing over the next few months. That program is about a year or so behind our stroke program, but so far it is showing great promise.” The company has secured its position with a worldwide exclusive license to the particular expansion technology that it uses, as well as patents that cover neural stem-cell transplantation generally and composition of matter patents specifically covering the individual stem-cell lines that ReNeuron has generated. ReNeuron is looking to license its technology for nontherapeutic use. “Certainly the cell lines we’ve generated have utility as drug screening or toxicology screening tools in the development of new conventional drugs, and that is an area where we’re actively looking at the moment; and we have some interest from commercial companies in that respect,” Mr. Hunt says. “But to us the real value is showing that we can generate an efficacious stem-cell therapy to treat patients, and in that respect we would look to keep the crown jewels in house until we have some type of clinical data that we believe will entice commercializing partners to the table.” Mr. Hunt believes another advantage to the company’s technology is that it avoids much of the controversy generated by the embryonic stem-cell approach and the use of early-stage embryos or the creation through cloning of embryos to be used to serve medical research. The company does have some controversy to contend with since it uses fetal material. But according to Mr. Hunt, the technology the company uses means it can grow many clonal cell lines from a single cell sample. “For instance with our lead stroke program, we had a selection process that determined the best cell lines to take forward into preclinical and then clinical testing,” he says. “To generate those cell lines, we selected the ones that were most viable and took only five tissue samples to generate more than 100 cell lines containing billions of cells. Similarly, we have a program addressing Parkinson’s disease, and in that case we’ve taken no more than two tissue samples that we believe will generate all the cells that we will ever need to use to produce a viable stem-cell product serving that particular disease. Although we can’t remove ourselves entirely from the ethical dimension, we believe our cell-expansion technology offers the best possible way of addressing the particular ethical concerns that this type of cell therapy may engender.” Michael Hunt The United States is very good at playing catch up; it’s done so in the past and no doubt will do so again in this field as state by state more and more money is put behind the research. Dr. Sander Rabin Legislation is being instituted in several states to assist the nascent stem-cell research that’s going on and to retain that research. One of the pillars of the research economy in the United States is biotechnology, and we ignore that, from the standpoint of economic well-being, at our peril. Andrew Cohn I don’t think that anyone would argue that stem-cell research isn’t a major new platform for science and medicine. Sound Bites from the Field Michael Haider is President and CEO of BioE Inc., St. Paul, Minn., which develops high-quality, antibody-based technologies used to create a variety of leading-edge diagnostic and therapeutic products designed to continually improve patient outcomes and quality of life. For more information, visit bioe.com. “Adult-source stem cells, primarily those obtained from umbilical cord blood and bone marrow, hold the greatest hope for near-term therapeutic application. In an environment of intense public and political debate over the use of embryonic stem cells for regenerative medicine purposes, adult-source stem cells present researchers and clinicians with a noncontroversial alternative. While there is much we still have to learn about adult-source stem cells, it appears from a therapeutic standpoint that they could be equally or more viable than their embryonic counterparts. For example, cord-blood stem cells pose no harm to mothers or babies during collection; have never differentiated into tumors after implantation; and greatly reduce the risk of potentially fatal graph versus host disease. Adult-source stem cells have a proven track record in treating diseases of the blood, such as a variety of leukemias and anemias. In addition, recent research has demonstrated that stem cells obtained from umbilical cord blood have the ability to differentiate into a variety of tissue types, including bone, fat, nerve, muscle, vascular, and liver. In the coming years, adult-source stem cells could very well be used to treat heart disease, as evidenced by preliminary results of some clinical studies occurring outside the United States. The use of adult-source stem cells to treat diseases of the central nervous system also shows great promise. For conditions such as Parkinson’s disease and multiple sclerosis, adult-source stem cells could provide the necessary therapy to alleviate specific neuron dysfunctions. Longer term, adult-source stem cells could be used in conjunction with other therapies to treat more complex central nervous system disorders, including Alzheimer’s disease.” Kirstin Matthews, Ph.D., is Research Associate, Science and Technology Policy, James A. Baker III Institute for Public Policy, Rice University, Houston. Rice University is an independent, coeducational, nonsectarian, private research university offering bachelors’, masters’, and doctoral degrees. For more information, visit rice.edu. “With the current situation of limited federal funding for human embryonic stem cells, the areas with the most innovative research have come from work being funded by private sources. The work in California at the Reeve-Irvine Research Center on healing spinal cord injury was a direct result of funding from The Christopher Reeve Paralysis Foundation and Geron. They have made amazing advances in treating acute spinal cord injuries in mice using cell-based therapies. There is also innovative research being produced at Harvard by Doug Melton, which is funded in part by the Juvenile Diabetes Research Foundation (JDRF). His group has started work to differentiate embryonic stem cell to insulin producing cells. Until funding for more basic research is established, the areas with the greatest potential are those with supportive private funding.” Patrick O’Shea is Senior VP and Managing Director, Palio Communications, Saratoga Springs, N.Y., a pharmaceutical marketing and advertising company. For more information, visit paliocommunications.com. “Because cord-blood stem cells are the building blocks of the blood and the immune system, their therapeutic possibilities are great. While stem cells are presently used to treat malignancies, immunodeficiency diseases, metabolic disorders, and hematologic diseases, such as sickle cell disease and aplastic or severely hypoplastic marrow states, expanding the use of cord-blood stem cells in the future is a possibility that will no doubt depend on successful basic science research. Much akin to the work being done with the more developmentally immature embryonic stem cells, the hope would be that researchers can ‘teach’ these hematopoietic cord-blood stem cells to differentiate into other cell types, i.e., cardiac muscle cells, neurons, and pancreatic islet cells. This would potentially offer new treatment paradigms for stroke, heart disease, diabetes, spinal cord injury, Alzheimer’s disease, and many other illnesses.” Charles A. Sims, M.D., is Cofounder and Medical Director of California Cryobank Inc., Los Angeles, the parent company of California Cryobank Stem Cell Services Inc., an umbilical cord-blood processing and storage company. For more information, visit familycordbloodservices.com. “I believe the hope and promise of stem-cell research is that it will unlock the door to understanding how a stem cell can become a heart or lung, skin or bone, or muscle. Why some cells become cancers that may kill and others can heal or repair a failing organ is still the question. Stem-cell research, I believe, is a voyage of discovery not unlike that taken by Columbus in 1492. He did not find the westward way to the Indies as he had hoped, but instead discovered a whole New World that was beyond anything he could have imagined as he set out in his little ship. It is my opinion that embryonic stem-cell research will result in therapies based upon non-embryonic stem cells. The embryonic stem-cell research will result in better understanding of cellular control and development of stem cells that are partially committed to adult organ development. These cells are found in cord blood, bone marrow, fat, and in most organs of the body. They are not prone to spontaneous tumor development, which is a problem with embryonic stem cells.” David E. R. Sutherland, M.D., Ph.D., is Professor and Head, Division of Transplantation, and Director, Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis. The Diabetes Institute is a pioneer and leader in aggressive and advanced treatment of diabetes through whole-organ pancreas transplantation and clinical islet cell transplantation. For more information, visit diabetesinstitute.org. “Stem-cell research has its greatest applicability right now in hematopoetic replacement or regeneration. But it definitely has great potential for pancreatic beta cell replacement or regeneration; a single cell line is all that is needed, not regeneration of an entire complex organ. I think it will come, but much more is needed to generate true beta cells rather than just insulin-producing cells. All the machinery for feedback inhibition or stimulation are needed, and thus more than an insulin gene needs to be activated in the stem cell derivative.” Dr. Thomas Okarma Unless the NIH changes its tune, it will have lost a role in developing what I think will be the biggest biomedical development of the 21st century. And that will be a very dark chapter for the NIH that will call into question its relevance to medical innovation. Experts on this topic Andrew Cohn. Government and Public Relations Manager, the Wisconsin Alumni Research Foundation (WARF), Madison, Wis.; WARF is an independent, nonprofit foundation chartered to support research at the University of Wisconsin-Madison and the designated technology transfer organization for the university. For more information, visit warf.org. Michael Hunt. Chief Operating Officer and Finance Director, ReNeuron, Surrey, United Kingdom; ReNeuron uses somatic stem cells to develop leading-edge therapies for neurodegenerative and other diseases. For more information, visit reneuron.com. Thomas B. Okarma, M.D., Ph.D. President, CEO, and Director, Geron Corp., Menlo Park, Calif.; Geron is a biopharmaceutical company developing and commercializing therapeutic products for oncology that target telomerase; pharmaceuticals that activate telomerase in tissues impacted by senescence, injury, or degenerative disease; and cell-based therapies derived from its human embryonic stem-cell platform for applications in multiple chronic diseases. For more information, visit geron.com. Sander M. Rabin, M.D., J.D. Patent Counsel, Convergent Technology Patent Law Group, Whiteman Osterman & Hanna LLP, Albany, N.Y.; Whiteman Osterman & Hanna has a diverse practice, with an emphasis on matters relating to the intersection of the public and private sectors. For more information, visit woh.com. Wise Young, M.D., Ph.D. Chair, Department of Neuroscience and Cell Biology, Rutgers, New Brunswick, N.J.; Rutgers, The State University of New Jersey, is one of the nation’s major state universities. For more information, visit rutgers.edu.