Embryonic stem cell (ESC) research has been a source of ethical, legal, and social controversy since the first successful culturing of human ESCs in the laboratory in 1998. The controversy has slowed the pace of stem cell science and shaped many aspects of its subsequent development. This paper assesses the main issues that have bedeviled stem cell progress and identifies the ethical fault lines that are likely to continue.

The time is appropriate for such an assessment because the field is poised for a period of rapid development. President Obama has removed the Bush administration’s restrictions on federal funding. A huge influx of federal research funds is in the offing and presumably a more rapid maturing of the science will take place. Stem cell science is also moving into the clinical realm. In March 2009, the Food and Drug Administration (FDA) approved the first clinical trial with an ESC-derived therapy for spinal cord injuries, an important first step — though by no means a final or a sure one — in moving ESC research out of the laboratory into clinical medicine. Finally, recent work with induced pluripotent stem (IPS) cells suggests that non-embryonic sources of pluripotent stem cells may one day be routinely available. Such a development will lessen the temperature of the ethical debate while raising other issues.

Lost at times in the heat of debate about stem cell research, or any controversial advanced technology, is the need for precision in debate and discussion. The details matter a great deal, ranging from the need to use words that have precise definitions, to accurately quote colleagues and adversaries, and to cite scientific and medical results in a way that reflects the quality, rigor, and reliability of the work at issue. Regrettably, considerable inaccuracy has found its way into the debates about stem cells, on all sides, with consequent fogging of the issues.

A key detail that is often overlooked in the debates about the uses of human embryonic stem cells in research comes from the nature of in vitro fertilization (IVF) treatment for infertility. Specifically, there are many frozen human embryos (more precisely called blastocysts) that are in excess of reproductive needs of the couple who generated them, and that must be either frozen indefinitely, donated to another couple, or destroyed.

The ethical debate on embryo research, particularly on whether to destroy human embryos for stem cell research, is sometimes said to involve a confrontation between religion and science. The claim is misleading at best. Ironically, religious claims have not infrequently been invoked by those who support human embryonic stem cell research, who have said that such research will enable us to “answer the prayers of America’s families” or present us with “the biblical power to cure.” And even religious organizations (as well as scientists and ethicists who share some of their concerns on this issue) have often made the case against the ethical acceptability of this research relying on science, and on general ethical considerations that transcend religious divisions. The Catholic Church, in particular, maintains that the ethical norm against directly taking the life of any innocent human being can be understood and embraced by people of good will, with or without religious faith, and that the application of this norm to the present controversy depends on an understanding of some basic facts about early human development.

Although the first human embryonic stem cells (hESCs) were produced in 1998, the direction of U.S. policy on stem cell research was set nearly 20 years earlier when the recommendations of a congressionally established Ethics Advisory Board were ignored by the Reagan administration. Thus began an unprecedented and unparalleled 30-year-long history of political intrusions in an area of scientific and biomedical research that has measurable impacts on the health of Americans. Driving these intrusions were religiously informed public policy positions that have usually escaped critical ethical analysis. Here I record my own encounters with this history of intrusions and the thinking behind them.

My most abrupt encounter with the politics of stem cell research occurred on September 6, 2006, at a hearing of the Senate Subcommittee on Labor, Health and Human Services and Related Agencies, chaired by Senator Arlen Specter. Just a week before, scientists at Advanced Cell Technology (ACT), a small Massachusetts biotech company, had published a paper in the journal Nature in which they described a method for extracting stem cells from early human embryos while leaving the embryos intact and viable. As head of ACT’s Ethics Advisory Board, I had supported this research.

The intense and extensive debate over human embryonic stem cell (hESC) research has focused primarily on the moral status of the human embryo. Some commentators assign full moral status of normal adult human beings to the embryo from the moment of its conception. At the other extreme are those who believe that a human embryo has no significant moral status at the time it is used and destroyed in stem cell research. And in between are many intermediate positions that assign an embryo some degree of moral status between none and full. This controversy and the respective positions, like the abortion controversy, is by now well understood, despite the lack of progress in resolving it. I have argued briefly elsewhere that early embryos do not have significant moral status, but I do not want to reenter that debate here. Instead, I want to focus on an issue that has had relatively little explicit and separate attention, but is likely to loom larger in light of the Obama administration’s partial lifting of the Bush administration’s restriction on the embryos that can be used in stem cell research that receives federal funding.

Moral status is the moral value that something has in its own right, independently of the interests or concerns of others. Research using human embryonic stem cells (hESCs) implicates issues about moral status because the current method of extracting hESCs involves the destruction of a human embryo, the moral status of which is contested. Moral status issues can also arise, however, when hESCs are transplanted into embryonic or fetal animals, thereby creating human/ nonhuman stem cell chimeras (“chimeras” for short). In particular, one concern about chimera research is that it could confer upon an animal the moral status of a normal human adult, but then impermissibly fail to accord the animal the protections it merits in virtue of its enhanced status. Understanding the public policy implications of this ethical conclusion is complicated by the fact that certain views about the moral status of the embryo cannot legitimately be used to justify public policy decisions. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras.

Acentral promise of human embryonic stem cell research is the potential to develop viable therapeutic approaches to a range of devastating diseases and conditions. Despite excitement over such advances, there are scientific and medical reasons to be cautious as stem cells and their products are introduced into patients. In response to such concerns, the International Society for Stem Cell Research (ISSCR) as well as ad hoc groups and individuals have offered approaches to governance of this research. While there are similarities among these governance models and they are in principle easily endorsable, in this paper I raise a set of concerns related to their implementation, suggesting areas where gathering data may facilitate more appropriate oversight. Next, I suggest areas that seem to have been neglected as these governance models have been developed so that they may be on the agendas of those seeking to revise these models in the future. Finally, I describe how some of the concerns that have arisen in considering the appropriate governance of stem cell research may be useful in science and translational research more broadly.

Stem cells derived from pluripotent cells offer the hope of new treatments for diseases for which current therapy is inadequate. Clinical trials are essential in developing effective and safe stem cell therapies and fulfilling this promise. However, such clinical trials raise ethical issues that are more complex than those raised in clinical trials using drugs, cord blood stem cells, or adult stem cells. Several clinical trials are now being carried out with stem cells derived from pluripotent cells, and many more can be expected in light of the rapid scientific progress in the field.

Degenerative neurological diseases are desirable targets for stem cell clinical trials. The FDA has approved Phase 1 clinical trials of neural stem cell transplantation for Batten Disease, Pelizaeus-Merzbacher Disease, and spinal cord injury. In Parkinson Disease (PD), stem cell transplantation could correct the primary pathophysiological defect — inadequate levels of the neurotransmitter dopamine. Current treatment is unsatisfactory in late-stage PD.

There are many kinds of clinical trials. The regulatory framework within which most drug development takes place appears to be the one that is to be applied to the development of novel stem cell-based clinical trials. In the standard drug development model, appropriate pre-clinical research is conducted (largely based upon non-human animal models), and investigators or research sponsors (typically a company) submit an investigational new drug (IND) application to the Food and Drug Administration (FDA).

If approved, typical clinical trials start with Phase I, which is usually a trial (with a small number of participants) to determine the maximum tolerable dose of a drug. Phase I trials are often referred to as “safety studies” because the primary goal of Phase I research is to determine if an intervention is safe (not whether it works).

Armed with expanded federal funding for human embryonic stem cell research and new methods for deriving pluripotent stem cells, stem cell researchers in the U.S. are poised to proceed with unprecedented speed toward the development of new clinical therapies. Staring into the new dawn of regenerative medicine, many observers may assume that the only responsible route to the clinic, both scientifically and ethically, is through FDA-approved clinical trials processes. Conventional wisdom dictates that, like pharmaceutical drugs and the use of biological therapeutics, stem cell-based therapies will have to pass through a series of controlled studies — initially to assess safety and toxicity, then efficacy and comparative efficacy — before they can be justifiably administered to patients outside a clinical trials context.

Innovative therapy is the name we give to novel medical interventions, radically different from the standard of care, provided in order to benefit a patient, rather than to acquire new knowledge. They are paradigmshifting, not incremental, responses to serious patient problems that standard medical care inadequately addresses. Innovative therapies are often devised by clinicians, not basic science researchers; they do not follow the linear model of basic research, to translation, to clinical research, to application. Instead, they come from thinking backwards from the patient’s circumstances, and forward from deep knowledge of how the body functions, to challenge the limits of current mechanisms for effecting cures.

Policy arguments in support of stem cell research often use economic benefit as a key rationale for permissive policies and increased government funding. Economic growth, job creation, improved productivity, and a reduction in the burden of disease are all worthy goals and, as such, can be used as powerful rhetorical tools in efforts to sway voters, politicians, and funding agencies. However, declarations of economic and commercial benefit — which can be found in policy reports, the scientific literature, public funding policies, and the popular press — have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the researchers who must work under its shadow?

While society debates whether and how to use public funds to support work on human embryonic stem cells (hESCs), many scientific groups and businesses debate a different question — the extent to which patents that cover such stem cells should be permitted to limit or to tax their research. The Wisconsin Alumni Research Foundation (WARF), a non-profit foundation that manages intellectual property generated by researchers at the University of Wisconsin at Madison, owns three patents that have been at the heart of the latter controversy. The story of WARF’s patents and the controversy they have fostered highlights not only continuing tensions between proprietary and nonproprietary approaches to developing science and technology, but also an at least partly reassuring capacity of public and private sectors to deal with those tensions in a way that can render them substantially manageable, and frequently more manageable as a technology matures.

In 1998, researchers established the first human embryonic stem cell line. Their scientific triumph triggered an ethics and policy argument that persists today. Bioethicists, religious leaders, government officials, patient advocates, and scientists continue to debate whether this research poses a promise, a threat, or a mixed ethical picture for society.

Scientists are understandably excited about the knowledge that could come from studying human embryonic stem cells. Most of them believe these cells offer a precious opportunity to learn more about why diseases develop and how they might be prevented or attacked. In their quest to gain support for stem cell research, scientists and others have claimed that the research could generate cures and treatment for everything from heart disease to cancer.

Essays on stem cell policy seem to fall into three categories. Some essays in this collection are about logic and principles. Others are about practices and beliefs. The former group draws lines and defends them, a normative project. The latter group attempts to explain the lines that already exist, a descriptive project that may have important normative goals. Still other essays, by scientists, are about growing stem cell lines instead of drawing them.

The purpose of this essay is to situate the lines being drawn around stem cell science in the larger landscape of health policy. I am interested in the things that cause health policy to take particular directions and the consequences of those directions for cost, access, and quality — all of which are determined in part by biomedical innovations such as those potentially derived from stem cells.

Many writers suggest that managed care had a brief life and that we are now in a post-managed care era. Yet managed care has had a long history and continues to thrive. Writers also often assume that managed care is a fixed entity, or focus on its tools, rather than the context in which it operates and the functions it performs. They overlook that managed care has evolved and neglect to examine the role that it plays in the health system.

This article argues that private actors and the state have used managed care tools to promote diverse goals. These include the following: increasing access to medical care; restricting physician entrepreneurialism; challenging professional control over the medical economy; curbing medical spending; managing medical practice and markets; furthering the growth of medical markets and private insurance; promoting for-profit medical facilities and insurers; earning bounties for reducing medical expenditures; and reducing governmental responsibility for, and oversight of, medical care. Struggles over these competing goals spurred the metamorphosis of managed care internationally.

Clinical research with children generates special ethical concern, raising the need for additional protections beyond those for research with competent adults. Most guidelines permit research with children when it offers a prospect of direct benefit, or poses minimal risk. Unlike many other guidelines, the U.S. federal regulations also allow institutional review boards (IRBs) to approve pediatric research that does not offer a prospect of direct benefit when the risks are no greater than a minor increase over minimal risk. To approve research in this category, IRBs must find that two additional conditions obtain:

Recent studies indicate that patients who are diagnosed with vegetative states may retain more awareness than their clinical assessments suggest. Disorders of consciousness traditionally have been diagnosed on the basis of outwardly observable behaviors alone, but new functional imaging studies have shown surprising levels of brain activity in some patients, indicating that even higher-level cognitive functions like language processing and visual imagery may be preserved. For example, one recently developed method purports to detect voluntary mental imagery solely on the basis of neural response patterns observed with functional magnetic resonance imaging (fMRI). This line of research has already led to some widely reported cases of patients who were discovered to have more brain activity than expected. In November 2009, Rom Houben, a Belgian man who was thought to be in a coma for 23 years, was diagnosed with locked-in syndrome through the use of neuroimaging; however, that assessment was later overturned by further testing.

Military reproductive health policies affect large numbers of women. In 2006 servicewomen numbered nearly 350,000 and comprised 14.5% of active-duty forces and 17.4% of the reserve force. In addition, approximately 165,000 female dependents of active duty military personnel and 157,000 female dependents of reserve duty personnel are between the ages of 12 and 22 and are eligible for military health care services. Dependents of military personnel are eligible for military health care coverage until age 21, or up to the age of 23 if considered a full-time student.

About 10% of active duty female servicemembers become pregnant each year. Pregnant servicewomen are considered non-deployable and are usually not assigned to overseas commands. Pregnant women in the Army, the service branch with the greatest number of women on active duty, can choose to remain on active duty, request temporary leave from service, or request separation from service. Separation options include either discharge, honorable or uncharacterized depending on rank, or transfer to individual ready reserve.