Stem Cell Science Research Articles

The Road to Balanced Oversight

![Figure][1] Earlier this year, an international group of scientists and others convened at Hinxton, England (see the related Policy Forum in this issue, p. [921][2]), to address the moral challenges facing collaboration in human embryonic stem cell research that emerge from differences in national laws. Although a focus on embryo research is understandable, it is not the only area of science in which societies differ in values and laws. Scientists throughout the world work under different regulatory regimes governing human subjects, nonhuman animals, pathogens and biohazards, genetic modification of organisms and plants, and access to medical and public health records. In some cases, these differences reflect disagreements about ethically permissible conduct that approach the intensity of debates about the moral status of the embryo. Whether the issue is research on chimpanzees, the creation of novel organisms, or the destruction of human embryos, scientists need to consider whether it is ethical to travel to other countries to engage in research practices that would not be legally permissible in their home countries. Many scientists may see this as a personal decision that should turn largely on whether they accept or reject the moral premises that underlie their nation's laws. Scientists also need to consider, however, the potential impact of “research tourism” on the public's trust in the scientific community and on the ethics of science itself. ![Figure][1] CREDIT: GETTY IMAGES An English stem cell scientist who failed to follow standards set by the United Kingdom's Human Fertilization and Embryology Authority (HFEA) when working outside the United Kingdom would probably be viewed by colleagues as acting unethically. Moreover, such conduct might compromise public trust in the effectiveness of the HFEA to keep embryo research within socially acceptable ethical bounds, and thus might have negative effects on public support for the science itself. Similarly, a U.S. clinical scientist who elected to conduct research in a country whose regulations were more lax than those set by the U.S. Common Rule governing research on human subjects would probably also be viewed by colleagues as acting unethically. In many contexts, this scientist would also be subject to government and institutional penalties. By contrast, the Hinxton group concluded that scientists living in countries that restrict elements of human embryonic stem cell research should be free to engage in those practices in more permissive countries without legal repercussions. At the same time, however, many in the group recognized the tension that taking this position raises for the ethics of science overall. Scientists should welcome societal oversight of their research, much as all citizens should welcome the benefits of a well-ordered, lawful society more generally. The question is not whether science should be given a special pass when it comes to the reach of national laws. Rather, it is how best to strike a balance between ensuring that science conforms to a society's values and respecting the global context in which science increasingly operates. Of course, striking this balance is made more complicated when there is substantive moral disagreement not only between societies but also within societies about whether a particular research practice or line of investigation is ethical. The case is complicated still further when, as seems to be true with regard to human embryonic stem cell research, much if not most of the scientific community lines up on one side of the moral issue. These specific conditions of moral disagreement may warrant particular circumspection on the part of lawmakers with regard to extraterritorial jurisdiction. That said, even if there is complete consensus within the global scientific community about the ethics of a particular scientific practice, scientists should not expect societies to defer to their views when it comes to matters of morality. Rather, scientists must continuously make their case to society by appealing to public moral reasons that are accessible to all. This is hard work that requires scientists to leave their laboratories and make themselves available to lawmakers, the public, and the media. At the same time, however, most scientists operate in institutional and professional cultures that rarely reward, and certainly do not prepare, scientists for engaging with the public. Until these structural disincentives to effective interaction between scientists and societies are remedied, we can expect the road to balanced oversight of science to be more complicated than it need be. [1]: pending:yes [2]: /lookup/doi/10.1126/science.1127990

Research policy and the mobility of US stem cell scientists

State and national research policies governing human embryonic stem cell science are affecting the career plans of scientists in this exciting but controversial field.

From bench to bedside? Biomedical scientists’ expectations of stem cell science as a future therapy for diabetes

The movement of scientific research from the bench to the bedside is becoming an increasingly important aspect of modern ‘biomedical societies’. There is, however, currently a dearth of social science research on the interaction between the laboratory and the clinic. The recent upsurge in global funding for stem cell research is largely premised on the promise of translating scientific understanding of stem cells into regenerative medicine. In this paper, we report on the views of biomedical scientists based in the United Kingdom who are involved in human embryonic stem cell research in the field of diabetes. We explore their views on the prospects and problems of translational research in the field of stem cell science. We discuss two main themes: institutional influences on interactions between scientists and clinicians, and stem cell science itself as the major barrier to therapies. We frame our discussion within the emerging literature of the sociology of expectations.

The International Society for Stem Cell Research (ISSCR): History and Perspectives

The International Society for Stem Cell Research (ISSCR) is an independent, nonprofit organization founded in 2002 to foster professional and public communication and education regarding stem cell research. Under the leadership of prominent stem cell scientists from around the world, the ISSCR membership has grown exponentially, creating a diverse, international community of researchers who have expertise in many facets of stem cell biology. The ISSCR is dedicated to promoting the exchange of ideas and has developed two major forums for dissemination of stem cell research and related issues, an annual meeting and an information-rich website. With the field of stem cell research and technologies rapidly advancing, discourse is more critical than ever to maintain high standards across the full spectrum of research.

Mahendra Rao, vice-president, research, stem cells and regenerative medicine, Invitrogen, Carlsbad, California

Stem-cell scientist heads for industry.

The Development of Adaptive Expertise in Biomedical Engineering Ethics

This paper is an investigation of the How People Learn (HPL) Legacy Cycle's ability to expand adaptive expertise across the developmental span of high school and college. Participants included high school and college students. Pre-test data indicated younger students (high school and first-year college students) were less knowledgeable about the science of stem cells than older students (second-, third-, and fourth year college students), and all students were low in adaptiveness. Post-test data showed that younger students achieved parity with the more advanced students in basic scientific knowledge. The younger students also became highly adaptive by the post-test, but the older students did not advance beyond their pre-curriculum levels. We hypothesize that the older students began the intervention with more preconceived notions about stem cells, and thus were less able to think and analyze flexibly within that framework.

Realizing the Cardiac Stem Cell Promise: a Case for Trophism

Recent advances in stem cell biology have given rise the new field of cardiac regenerative medicine. Specifically, the development of cardiac stem cell science now offers the promise of novel cardiovascular therapies based on a dynamic body of basic and translational research. Importantly, the potential wide-spread clinical application of this technology will require that therapies be optimized for individuals with potential impairments in cardiac stem cell function. To this end, the previous experience of hematopoietic stem cell therapies can provide important guidance in the development and maturation of the young cardiac stem cell field. Parallel to the impact that exogenous growth factors have made in the field of hematopoietic therapies, the discovery and potential application of the factor(s) that govern cardiac regeneration may speed the progression of cardiac stem cell technology into an assessable and potent clinical therapy.

Profile: Hui Zhen Sheng

As a stem cell scientist in China, Hui Zhen Sheng has had more trouble in the past few years than most researchers have encountered. But you'll never hear her complain about it.

Innovation in Biomedicine: Can Stem Cell Research Lead the Way to Affordability?

In November 2004, California voters approved a ten-year, US$3 billion stem cell research program to pursue cures for diabetes, Parkinson disease, spinal cord injuries, and other chronic conditions. Campaign organizers also claimed the state would receive royalties from new therapies, economic development in the form of jobs and taxes, and access to cheaper medicines [1]. Once the initiative passed, its proponents sought to scale back unrealistic voter expectations about rapid advances in the field—recent revelations of scientific fraud involving a prominent stem cell scientist will undoubtedly have that effect. Yet the goal that stem cell therapies resulting from the initiative will be made affordable for state residents remains in place. Toward that end, some California legislators are focusing on how the newly created California Institute for Regenerative Medicine (CIRM) should handle intellectual property (IP) generated by its grants. In August 2005, at CIRM's request, the state-funded California Council on Science and Technology (CCST) recommended that CIRM adopt with minor variations the federal Bayh–Dole system [2]. The 1980 Bayh–Dole Act gives research institutions the primary responsibility for maximizing the health- and economic-development benefits from government research funding. It encourages researchers or their institutions to patent inventions generated under government grants and transfer the technology to private firms. While the act gives the federal government the power to influence the affordability of the resulting technologies, it has never used this authority. The CCST report, embracing that stance, discouraged efforts to recoup revenue through high licensing fees and postponed a discussion of preferential pricing for state residents [3]. The report suggested such approaches would inevitably hinder the development of the public–private collaborations needed to bring new therapies to market. While regional governments frequently fund biomedical research in Europe, California is the first state in the United States to embark on a large-scale program. The size of its commitment suggests that the state will be a major patron of stem cell research for years to come. This gives California a unique opportunity to create a climate that will not only be hospitable to innovation but also simultaneously deliver affordable medicine. The state government can do this by redefining how government, medical researchers, and the private sector interact. In doing so, it could serve as a model for reforming the US and global biomedical innovation systems. Change is necessary for two reasons. First, under the current system, new technologies, no matter how marginally effective, come to market at the highest prices. These advancing medical technologies are a major cause of rapidly rising health-care spending throughout the industrial world. Second, biomedical innovation in the US, long considered the global leader, has slowed markedly in the past half decade. Despite escalating research spending in the public and private sectors, the number of new drugs and biologics recently approved by the US Food and Drug Administration (FDA) has fallen below previous eras (Figures 1 and ​and2).2). And those new therapies that have been approved tend to have less significance than medical advances of the past. While the popular press excitedly reports that breakthroughs in nanomedicine, targeted therapeutics, and genomic medicine are just around the corner, applications to launch clinical trials have fallen well below the levels of the early 1990s (Figure 3). Something beyond the usual culprit—higher failure rates—is at work [4]. Figure 1 Applications for New Drug Approvals Figure 2 New Drug Approvals at the FDA Figure 3 Applications to Begin Human Clinical Trials

Industry Watch

Biosignal & US Surgical Collaborate to Test Anti-biofilm on Catheters. Stem Cell Sciences and the University of Edinburgh Announce New Technology Transfer Agreement. CyGenics Expands Cord Blood Banking into India. Japan's Bioventures Today—TMRC Co Ltd. MerLion Pharmaceuticals Announces Drug Discovery Collaboration with Novartis Institute for Tropical Diseases. Taiwan's Vectorite Biomedical Collaborates with AMDL.

BioBoard

Life Therapeutics Announces Influenza Program. Bharat Biotech to Launch New Vaccines and Set up Manufacturing Facility in Malaysia. National Institute of Advanced Industrial Science and Technology (AIST) Completes the Genome Sequencing of Rice Malt. Cuba and China Sign Biotech Accord. New Oral Vaccine Combats Common Strains of Rotavirus and Boosts the Immunity of Children. A Rising Fear—Resistance to Tamiflu. Sinovac Biotech Begins Pandemic Flu Vaccine Clinical Trials. Korean Stem Cell Scientist Apologizes for Fake Research Results. Two Ventures To Make Bio-fuels from Palm Oil. Beijing Approves Drug Using Virus To Treat Cancer. CyGenics' Subsidiary to Distribute Bird Flu Test Kits.

Good News--and Bad

![Figure][1] This year, for the first time in half a century, the first day of hanukah and christmas day converged—good news for my family mix. But just before that day, the Science family found itself absorbed in a different temporal convergence, one that brought both good news and bad to us and to our readers in the scientific community. The troubling story of Professor Woo Suk Hwang and his colleagues appeared everywhere, as questions about a paper they had published in this journal unfolded amid a welter of charges, countercharges, proposed retractions, and two investigations. At about the same time, on the front page above the fold in the New York Times , appeared Judge John Jones' opinion in the Dover, Pennsylvania, school board case. ![Figure][1] For most of the scientific community, this second story relieved a longstanding concern. Some school boards (famously in Kansas and Pennsylvania, but also in many other U.S. states) had voted either to limit the teaching of evolution in science classes or to introduce it along with alternative explanations that were essentially religious in character. The rising tide of evangelical Christianity and its alliance with a conservative political movement seemed to foreshadow a national suspicion of science or a deep confusion about what science is or isn't, or possibly both. The Dover decision was a decisive, elegantly crafted resolution of the question before the court. Was intelligent design (ID) a new proposal, generated by the school board for consideration by students and teachers as an alternative to evolution, based on scientific grounds? Or was it instead a Trojan Horse proxy for the older notion of creationism? Judge Jones said, in no uncertain terms, that ID was not science, but rather creationism redux, and that it did not belong in a science classroom. He added that its advocates, “who so staunchly and proudly touted their religious convictions in public, would time and again lie … to disguise the real purpose behind the ID Policy.” The decision, in which the losers were charged attorneys' fees, can be found at . It's worth reading. The other story is a deeply disappointing one: for the scientists who did the work; for the scientific community (and especially those who have been excited by the therapeutic prospects of stem cell science); and for this journal. At this writing, we don't have a final report from an investigation now underway at Seoul National University. But preliminary findings and admissions by Hwang point to considerable fraud, leaving open only the question of whether some of the findings published in Science and other journals by Hwang's research group may survive. ![Figure][1] A journal cannot go into authors' laboratories in search of fraud. But we can and do encourage appropriate authorities to conduct investigations, and we supply information freely as investigations proceed. More actively, we are committed to examining our processes and ourselves in an effort to extract lessons for the future. In examining the reports by reviewers of the Hwang papers, we saw no reason to lack confidence in the authenticity of the data. But there is more to do, and at the end of this process we will be able to report to our readers and others what we have learned about how we might modify our treatment of papers with unusual potential impact. One question we have been asked by mainstream journalists is whether this is an indictment of the peer review system. Not at all; we believe strongly in the peer review system, but we have never thought it infallible. Carefully reviewed studies sometimes turn out to be wrong because later attempts at repetition fail. But peer review requires authors to provide more data and more confirming material, making it likelier that careful efforts at confirmation will follow. Fraud is something quite different, and very hard to detect. Of course, reviewers or editors might be sent to the authors' labs to look at the notebooks, imposing costly and offensive oversight on the vast majority of scientists in order to catch the occasional cheater. That's a bad idea. The reporting of scientific results is based on trust. It's better to trust our colleagues, despite the fact that on rare occasions one of them might disappoint other scientists and those hoping for cures. [1]: pending:yes

Magic Eggs and the Frontier of Stem Cell Science

Two myths about eggs figure prominently in the story of Korea's national origin. First there is the tale of Pak Hyeokkeose, the first ruler of Shilla, the ancient Buddhist state that evolved into what is now North and South Korea. According to legend, the six leaders of the city-states that would eventually become Shilla decided that they needed a king to rule over them. They gathered in the wilderness and prayed for guidance. Suddenly there was a flash of lightning, and on the ground appeared an enormous egg. Out of this egg emerged a young boy. The leaders quickly took the child and led him to a secluded temple in the south where he was raised to be king. Then there is the story of Seok T'alhae, the son of the king and queen of the Wanha region. He, too, emerged from a giant egg. But the king's advisors warned that this supernatural event was a bad omen. So the king put his son on a boat and sent him away. The boat eventually reached Shilla. There the boy grew up and became Shilla's fourth ruler. These myths provide a fitting metaphor for the recent stem cell scandal involving Dr. Woo Suk Hwang and colleagues at Seoul National University. Like the story of Korea's national origin, this modern tale began with the purported emergence of another kind of magical Korean egg--this time human eggs transformed through the wonder of somatic cell nuclear transfer. It was declared that from these special eggs sprang forth entities with enormous potential power--patient-specific pluripotent human stem cells that could teach scientists how to treat uncured diseases and injuries. South Korean leaders eagerly embraced these magic eggs and their precious contents. They created a safe haven to foster this research by building and financing the World Stem Cell Hub in Seoul. Many other world leaders determined that these magic eggs were a bad omen and refused to have anything to do with them. Korean scientists were left with the task of developing these unique eggs and nurturing their contents alone. Like the ancient narrative, this modern stem cell story was supposed to mark the naissance of South Korea, this time as a world leader in biotechnology and stem cell science. Scientists with research ambitions shunned by their own political leaders were to find a refuge for their controversial work in Seoul and thus help seal South Korea's new national identity. Unfortunately, the parallels do not end there. Like the story of the country's origin, the modern stem cell story also seems to have been built on an elaborate fiction. At the time of this writing, Korean investigators have found no evidence that Hwang and colleagues ever derived pluripotent stem cell lines from cloned human blastocysts, and the journal Science has editorially retracted Hwang's two landmark papers. (1) The Race Ahead As could have been predicted, the Korean stem cell candal has provided commentators around the world ample opportunity to remark on the various lessons to be drawn from this case. Among researchers, however, the scandal has produced a more surprising response. After the initial shock of this shameful news had passed, scientists began to realize that the playing field for embryonic stem cell research was far more level than they had believed. Emboldened by this realization, and perhaps encouraged by the Korean investigators' report that the Hwang team had successfully created cloned human blastocysts, many scientists are now reentering the global race to forge ahead in NT-hESC research--that is, to derive human pluripotent stem cells (hESCs) from embryos created via somatic cell nuclear transfer (NT). (2) Among the illustrious teams planning to pursue NT-hESC research this spring are researchers from the Harvard Stem Cell Institute; Advanced Cell Technology; the University of California, San Francisco; the University of California, Los Angeles; the Karolinska Institute in Sweden; Newcastle University; the Queen's Medical Research Institute at the University of Edinburgh; and the Institute of Psychiatry, London. …

Unchecked by guidelines, Indian stem cell scientists rush ahead

Unchecked by guidelines, Indian stem cell scientists rush ahead

Korean University Will Investigate Cloning Paper

SEOUL AND TOKYO-- Embattled Korean stem cell scientist Woo Suk Hwang and his university have bowed to pressure for an investigation into a growing list of questions about a landmark paper he and colleagues published online in Science on 19 May 2005. (Read more.)

Stem-cell scientist asks for retraction

Stem-cell scientist asks for retraction

The Battlefield of Pluripotency

How embryonic stem cells maintain the potential to differentiate into multiple cell lineages is still unclear. In this issue of Cell, Niwa et al. (2005) show that a duel between the transcription factors Oct3/4 and Cdx2 can restrict embryonic stem cells to either embryonic or placental fate. The vulnerability of lineage potential to transcriptional perturbation may reflect an essential feature of pluripotency.

Changing ethics rules land Spanish stem cell scientist in hot water

Changing ethics rules land Spanish stem cell scientist in hot water

Stem Cell Politics: The NAS Prohibitions Pack More Bark Than Bite

Frustrated stem cell scientists in the United States have responded enthusiastically to the voluntary guidelines for human embryonic stem cell research published by the National Academy of Sciences in April 2005. One likely reason for their considerable enthusiasm: the guidelines include very few prohibitions on embryonic stem cell research. In fact, the NAS guidelines preclude only three research activities involving either human embryos or human embryonic stem cells: (1) the research use of human embryos beyond fourteen days (or the appearance of the primitive streak, if that comes first); (2) the creation of embryonic chimeras involving the transfer of human embryonic stem cells into nonhuman primate blastocysts or the transfer of any embryonic stem cells into human blastocysts; and (3) the breeding of any chimeras into which human embryonic stem cells have been transferred at any stage of development. None of these prohibitions is particularly prohibitive. Currently, publicly funded stem cell research in the United States is severely restricted by the Bush administration's on the derivation of human embryonic stem cells using federal funds. By contrast, in most U.S. states, privately funded research is virtually unregulated. In the absence of a change in federal policy, scientists working with private or state funds could hardly ask for a better deal than the NAS voluntary guidelines. Scientists achieve the appearance of responsible self-governance and in so doing put pressure on the federal government to review and amend its stem cell research policy, which by comparison with the NAS guidelines now appears unnecessarily restrictive. All the while, current research funded privately or by states is essentially unimpeded. As the authors of the NAS guidelines themselves acknowledge, the first prohibition--the fourteen-day limit on embryo research--merely reiterates a longstanding international consensus on the time frame for permissible research involving human embryos. The problem with this is twofold: from a practical perspective, it is irrelevant; from a political perspective, it is blatantly rhetorical. Practically, at present, it is not biologically possible to maintain the human embryo outside of the body beyond fourteen days, so the guidelines forbid research that is, for the foreseeable future, impossible. But politically--especially in the U.S. context, where embryo research is essentially contested--to call this a prohibition is to engage in sleight of hand, for a on impossible research is hardly restrictive. Consider next the NAS on building certain kinds of part-human chimeras, those resulting from the transfer of human embryonic stem cells into nonhuman primate blastocysts and those involving the transfer of any embryonic stem cells into human blastocysts. This controversial practice is explicitly addressed in very few jurisdictions. The earliest guidelines on this kind of research were issued in 2002 by the Canadian Institutes of Health Research (Canadian counterpart to the U.S. National Institutes of Health). These guidelines include a comprehensive ban on creating part-human embryonic chimeras: no human embryonic stem cells, germ cells, or other cells likely to be pluripotent (that is, capable of differentiating into most of the body's cell types) may be combined with either a human or nonhuman embryo or fetus. …

Stem cell culture engineering

Stem cells have the capacity for self renewal and undergo multilineage differentiation. Stem cells isolated from both blastocysts and adult tissues represent valuable sources of cells for applications in cell therapy, drug screening and tissue engineering. While expanding stem cells in culture, it is critical to maintain their self‐renewal and differentiation capacity. In generating particular cell types for specific applications, it is important to direct their differentiation to the desired lineage. In vitro differentiation of stem cells usually produces a mixed population of different cell lineages with the desired cell type present only at a small proportion. Use of growth factors that promote differentiation, and expansion or survival of specific cell types are key in controlling the differentiation towards specific cell lineages. Our limited knowledge of their growth conditions as well as lack of appropriate markers associated with different stages of differentiation hinders the widespread use of stem cells. However, a variety of bioreactors exist for cell cultivation that can be readily adapted to provide a well controlled environment for studying the process of stem cell propagation and differentiation. Here we review the advances made in the field of stem cell culture; and discuss the employment of different platforms for stem cell cultivation that will facilitate the advancement of stem cell science into the realm of application based technology in the foreseeable future.