Cynthia B. Cohen

Memory for temporal order in Schizophrenia

Memory for temporal order information was examined in patients with chronic schizophrenia using the recency discrimination task. In this task, subjects were shown a pair of previously studied words and were asked to choose which one of the two words they had seen more recently. In addition, subjects performed the Wisconsin Card Sorting Test (WCST). The results showed that schizophrenic patients differed from normal control subjects in their performance on the recency discrimination task. In addition, for schizophrenic patients, performance on the recency discrimination task was inversely related to the number of perseverative errors on the WCST. These results provide further evidence of prefrontal-type cognitive deficits in schizophrenia.

Ethical and Policy Issues Surrounding the Donation of Cryopreserved and Fresh Embryos for Human Embryonic Stem Cell Research

The use of human embryos in human embryonic stem cell (hESC) research raises significant ethical and policy issues associated with their donation. Recent research conducted in several countries assesses the percent of persons with cryopreserved and fresh supernumerary embryos willing to donate them for research, their reasons for considering this option, and the concerns they raise about its personal import. Such research provides new insights into rising ethical and policy questions associated with embryo donation for hESC research that should be addressed. In response to such questions, it is argued here that consent to the donation of supernumerary embryos for hESC research should be sought in two or three stages, depending on whether fresh or frozen embryos are at issue, in order to provide patients and their partners with sufficient time and information before they make a final decision. In addition, steps should be taken to support the voluntariness of their decisions by having personnel other than the treating reproductive specialist or stem cell investigators solicit their consent. Prospective embryo donors should also be given a choice about the uses to which hESCs derived from their donated embryos will be put in order to honor their ethical convictions and ensure that there are sufficient embryos for this research. The well-being and rights of those who donate embryos for this research require the sort of support and protection that can be provided by an ethical and policy framework that allows hESC investigations to move forward according to standards that are transparent and that resound with public values.

Ethical Issues in Embryonic Stem Cell Research

To the Editor: In advocating the creation of embryos for stem cell research by means of somatic cell nuclear transfer, Dr Lanza and colleagues 1 fail to recognize at least 2 major issues. First, they overlook the fact that human embryos must be created from the eggs of women. Producing eggs engenders increased risks for women. Hyperstimulation can lead to liver damage, kidney failure, or stroke, and ovulation-stimulating drugs have been associated with ovarian cancer, according to some studies. 2 Although women might be willing to undergo such risks for the sake of having a child, it seems clear that either payment for eggs or coercion would have to be used to persuade women to produce eggs for stem cell research. 3 As with kidneys, hearts, and certain other body parts, society is reluctant to allow human eggs to enter into the stream of commerce, fearing that this would compromise extraeconomic values of deep importance. 4 Coercion as a means of promoting medical research has been strongly criticized. 3 Thus, before considering embryonic stem cell research, procedures need to be developed to protect women’s health and freedom from overbearing financial or other pressure. 5 Second, it is unlikely that a one-sided argument for embryo manufacture will change current US government research policies. Instead, it leaves stem cell research in the hands of private commercial enterprises, which are not bound by federal research regulations and tend to keep proprietary information secret. Lanza et al would continue this pattern of hidden research without accountable public oversight so that the creation of embryos through somatic cell nuclear transfer can move forward. Yet embryonic stem cell research enters a burgeoning field where inquiries into the uses of human procreative materials and procedures are being merged with those regarding genetic materials and procedures. Such research endeavors have major ethical and social implications for the value that is placed on procreation, the sorts of children that will be brought into the world tomorrow and in future generations, and, indeed, what it means to be human. Because of the public significance of such questions, there is, contrary to the opinion of Lanza et al, a pressing social need for a special oversight body to review and openly discuss all research—conducted in the public and private sectors—that involves both reproductive and genetic materials and procedures. 5

Use of “excess” human embryos for stem cell research: protecting women’s rights and health

Proposed National Institutes of Health guidelines for stem cell research are too narrowly drawn and do not adequately protect the freedom of choice and health of women who donate embryos. They need to be expanded to cover not only the point of embryo donation, but also that of embryo creation. Guidelines are provided to ensure that donors undergoing hyperstimulation and egg retrieval gave voluntary informed consent to the production of embryos that might later prove in excess. A standard for determining when embryos have been overproduced is presented to address the possibility that additional embryos will be created for stem cell research in violation of the guidelines and at risk to womens health.

Creating Human-Nonhuman Chimeras: Of Mice and Men

In recent years scientiac investigators have inserted human cells and material into animals in hopes of better understanding how they develop and whether the knowledge gained might have therapeutic value. Jason Scott Robert and Françoise Baylis (2003) focus on experiments in which investigators have added human (stem) cells to early animal embryos. These experiments are aimed at understanding the development of human tissue areas, such as the eye and brain, that are formed mainly during the prenatal period and then using the knowledge gained to repair the relevant cells in human beings. Such studies cannot be carried out in human embryonic animal models for safety and other ethical reasons. Some investigators have selected the mouse as the initial animal model; among them, some are considering the use of primates as the successor model. Robert and Baylis refer to experiments at Stanford in 1999 in which medical scientists injected human fetal neural stem cells into the brains of newborn mice (Uchida et al. 2000). Their goal was to learn about the development of these fetal cells; ultimately they hoped to create networks of neural cells that could be used therapeutically in human beings. Strictly speaking, these experiments did not involve the creation of the “human-to-animal embryonic chimeras” on which Robert and Baylis focus, because the fetal stem cell recipients were newborn mice. In the future, however, the Stanford investigators hope to carry out such studies in mouse embryos, using human embryonic stem cells (DeWitt 2002). At the University of Toronto scientists have proposed carrying out experiments in which they would insert adult retinal stem cells from cadaveric human eyes into early embryonic mice (Van der Kooy and Karpowicz, personal communication, 2003). They hope to specify retinal development from the embryonic stage to later retinal lineages, see whether human cells can adopt host cell cycle times, and replace damaged areas in the human eye. These retinal stem cell transplants would also involve the mouse, but at an early embryonic stage. Moreover, they would involve adult stem cells, not fetal or embryonic cells. In the future, the University of Toronto investigators hope to study transplants of adult human retinal stem cells into the eye and brain of fetal monkeys. These sorts of experiments raise provocative questions about the ethics of mingling human stem cells with those of animal embryos at the blastocyst stage. If human embryonic stem cells were transplanted into such mouse embryos, they might affect all the developing cells of those embryos, including brain and germ cells, possibly creating a human-mouse chimera. There is concern about whether the human fetal stem cells used at Stanford might also do this. A related concern arises about the proposed University of Toronto experiment. Would the fetal and adult stem cells retain their differentiated status and grow only in the selected area, or would they de-differentiate and enter all the cells of the animal embryos, including their brain and germ cells, thereby creating the risk that these changes could be transferred to future generations of these animals? Should we prohibit all such experiments? If we allow them, is there an ethical line beyond which they ought not go? How much and what sort of human stem cells would have to be injected into an embryonic mouse to render it a human being? Indeed, what characteristics would an animal have to display before we would assert that it was a human being? If a mouse with human brain and other cells looked like a mouse but thought and acted like a human being, would we consider it a mouse or a human being? Robert and Baylis, in their rich and perceptive article, ask three fundamental questions about these sorts of interventions:

Promises and Perils of Public Deliberation: Contrasting Two National Bioethics Commissions on Embryonic Stem Cell Research

National bioethics commissions have struggled to develop ethically warranted methods for conducting their deliberations. The National Bioethics Advisory Commission in its report on stem cell research adopted an approach to public deliberation indebted to Rawls in that it sought common ground consistent with shared values and beliefs at the foundation of a well-ordered democracy. In contrast, although the research cloning and stem cell research reports of the Presidents Council on Bioethics reveal that it broached two different methods of public deliberation—balancing goods and following an overarching moral principle—it adopted neither. Thereupon its prime mover, Leon Kass, influenced particularly by the approach of Leo Strauss, sought to develop a method of public deliberation guided by tradition and practical wisdom. When this failed, the Council fell back on a method that took account of shared fundamental values of a free democracy—a method remarkably akin to that employed by the National Bioethics Advisory Commission. Respect for diverse reasonable conceptions of the good in a democratic polity requires national bioethics commissions to seek and incorporate that which is valuable in opposing positions.

Future Directions for Oversight of Stem Cell Research in the United States

uman pluripotent stem cell research, meaning research into cells that can multiply indefinitely and differentiate into almost all the cells of the body, has become a minefield in which science, ethics, and politics have collided over the last decade in the United States. Presi- dent Barack Obama entered this highly charged territory when he indicated during his campaign that once in office he would issue an executive order expanding federally funded human embryonic stem cell (heSC) research and introduce rigorous oversight of it (Obama 2008a & b). Candidate Obama stated that he would require that the heSC lines involved were derived with donor consent from early embryos that otherwise would be discarded following in vitro fertilization (iVF) treatment. However, in contrast with the policy of President George W. Bush, he would do so without regard to the date of their derivation. He added that he would call upon the director of the National institutes of Health (NiH) to de- velop guidelines for federally funded heSC and other pluripotent stem cell research that would draw from the guidelines developed in 2005 by the National academies of Science (NaS) for privately funded research (National Research Council 2005). a similar policy was written into the 2008 version of the Stem Cell Re- search enhancement act, which reiterates the policy enunciated in earlier versions of this bill, passed twice by the Congress but vetoed by President Bush each time (House of Representatives, 110

The NIH Draft Guidelines on Human Stem Cell Research

New guidelines have positive aspects, but challenges remain in relation to previously approved stem cell lines, informed consent, oversight, and research embryos. With new draft guidelines to govern federal funding of human stem cell research, including human embryonic stem cell (hESC) research, the National Institutes of Health (NIH) have again taken on one of the most contentious endeavors of the day (1). There are positive aspects of the guidelines (2), but concern is growing that prior approvals of many widely used cell lines may not be in accord with specific wording requirements in the draft guidelines; such cell lines would need to be “grandfathered in” if research is to continue unimpeded (3). There are also several surprising omissions, surprising because they come in areas that are thoroughly addressed in the guidelines of the U.S. National Academies of Sciences (NAS) (4–6), which have become the gold standard for the conduct of stem cell research in the United States. Further, there has been little comment on the kind of initiative that would support future policy development.

The Interests of Egg Donors: Who Is Deceiving Whom?

ifornia Senate. Initially, the ambitious bill contained a wide array of provisions, including language mandating insurance coverage for infertility treatment, a limitation on the number of times a woman could donate eggs during her lifetime (four), the establishment of a registry for all egg donors in the state, and an assortment of disclosure requirements directed at ART patients and oocyte donors. After numerous amendments, a bare-bones bill was passed by the legislature and presented to Governor Davis. Even in its pared down form, the bill required ART physicians to provide oocyte donors with a standardized written summary of “health and consumer issues”, including disclosures about “the potential risks of oocyte donation, including the risk of decreased fertility and the risks associated with using the drugs, medications, and hormones prescribed for ovarian stimulation during the oocyte donation process” (sec. 1702[b][1][D]). Regrettably, Governor Davis vetoed the bill, citing an ongoing effort by the state Department of Health Services to develop guidelines for informing ART patients of the potential risks of treatment. Despite this setback, there is hope that lawmakers in California, home to 51 of the 360 fertility clinics located in the United States, will revisit the issue of ART disclosure and consent.1 If such a standardized disclosure pamphlet is developed, perhaps it can serve as a model for state lawmakers and ART program directors across the country. Of course, standardizing and mandating risk disclosure to oocyte donors does not resolve the myriad problems attendant to decision making in this area. Donors may continue to ignore or downplay known risks in the face of overwhelmingly attractive anancial incentives. But at the very least, egg donors can join the ranks of other medical patients whose irrational decisions are made in the face of full and fair risk disclosure.

Birth of a Network

Birth of a Network Ethics committees are developing at a remarkable pace. In 1982, only one percent of American hospitals had established these committees; today, over 60 percent of hospitals with 200 beds or more have them. Nursing homes and dialysis centers are organizing ethics committees as well. A movement that started in a small way is becoming large and significant. A striking feature of this spurt in growth of ethics committees is that we know little about the real phenomenon behind it. This sparsity of accumulated knowledge about how ethics committees function allows veteran committees to duplicate the work of their neighbors and leaves fledgling committees at a loss over howto constitute themselves and proceed. Moreover, ethics comittees are challenged to face distinctive issues today, even as they attempt to resolve many of the older, lingering ones. Can ethics be done by committee and, if so, what sort of ethics should they do? Do these comittees represent the patient or the community? Will they alter the traditional role of the family in medical decisionmaking? now that committees have gained experience, should their recommendations have mandatory force? While many are familiar with ethics committees and the issues they face, it is worth restating their purposes here. Ethics committees are interdisciplinary groups within health care institutions that advise about pressing ethical problems that arise in clinical care. A primary assumption on which they are founded is that cooperative, reasoned reflection is likely to assist decisionmakers to rech better conclusions. These comittees provide information and education to staff and surrounding communities about ethical questions, propose policies related to ethically difficult issues, and review patient care situations in which ethical questions are at stake. Burgeoning ethics committees keenly feel a need to share experiences and resources in order to fulfill these purposes. The Ethics Committee Network Project In response to this need, The College of Physicians of Philadelphia, with The Hastings Center and a network of ethics committees in the greater Philadelphia area, is mounting a project on institutional ethics committees. This effort, known as the Ethics Commitee Network Project, is funded by the William Penn Foundation of Philadelphia and is designed to provide a solid base of information and materials for ethics committees and to coordinate their activities at both regional and national levels. The project will assist in the development of a model network of ethics committees in the Philadelphia area and will apply the exprience of this group nationally. In turn, the regional network will benefit from knowledge gleaned from ethics committees around the country. The project will be directed by Bartholomew J. Collopy, Associate for Ethical Studies at The Hastings Center. …