Laurie Zoloth

New ISSCR Guidelines Underscore Major Principles for Responsible Translational Stem Cell Research

The International Society for Stem Cell Research (ISSCR) task force that developed new Guidelines for the Clinical Translation of Stem Cells discusses core principles that should guide the responsible transition of basic stem cell research into appropriate clinical applications.

Risk Stratification for Sudden Cardiac Death A Plan for the Future

Sudden cardiac death (SCD) remains a high priority public health problem necessitating a multi-pronged approach for treatment and prevention. Tachyarrhythmic sudden cardiac death (SCD-VT/VF; ie, death attributable to potentially reversible ventricular tachyarrhythmias [ventricular tachycardia (VT) or fibrillation (VF)]), is a major cause of SCD. Accurate assessment of risk for SCD-VT/VF is of critical importance to assist clinical decision-making regarding prescription of preventive therapies that reduce mortality. These therapeutic decisions include adherence to standard medical therapies, often in conjunction with tailored medications, implantable devices, catheter ablation, or heretofore untested treatments, such as spinal cord stimulation.1 In cases in which the therapy is invasive or carries its own risk, such as these latter interventions, each should be based on reliable demonstration of added benefit to the patient. Pre-emptive risk stratification for SCD-VT/VF has substantial implications to public health for the following reasons: (1) Heart disease remains the number 1 cause of death in the United States, with >600 000 deaths attributable to heart disease annually reported by the National Center for Health Statistics (http://www.cdc.gov/nchs/fastats/deaths.htm); (2) Approximately half of these deaths are estimated to be sudden; (3) Approximately 50% of all SCDs are the first recognized cardiac event; and (4) Only a minority of those who suffer out-of-hospital cardiac arrest will ultimately survive. Although the incidence of VF as a cause of out-of-hospital cardiac arrest is declining, it remains a leading cause.2 The introduction of the implantable cardioverter-defibrillator (ICD)—an effective, but costly therapy—has had meaningful, but limited, population impact on SCD2; thus, there are opportunities for new approaches (Figure) to address SCD. In particular, improved risk stratification techniques that identify individuals at high risk for SCD-VT/VF could have substantial impact,3 saving lives while stewarding medical resources for cases in which they are most effective. Since 2005, annual meetings …

Fertility Preservation and Adolescent Cancer Patients: Lessons from Adult Survivors of Childhood Cancer and Their Parents

Building on 40 years of progress in cancer detection and treatment, survival rates for childhood cancers have risen from 20 % to almost 80 % [1,2]. Approximately 270,000 Americans are childhood cancer survivors and, by 2010, an estimated 1 in every 250 adults will be living with a history of childhood cancer [2,3]. The early and late effects of treatment are beginning to take on greater importance for survivors, their families and providers [4]. Increasing numbers of childhood cancer survivors are beginning to face a new challenge in returning to normalcy after cancer. Infertility is one of the most common chronic medical problems reported by childhood cancer survivors [5] and can be a primary concern particularly among female survivors [6]. Female infertility has biological and psychosocial implications that cannot be easily addressed given the ethical and legal questions surrounding fertility preservation [7–9]. Recent advances in fertility preservation may soon offer potential methods for females of all ages to protect their reproductive capacity from damaging radiation and/or chemotherapy [10]. Current literature focuses on the further development of preservation techniques and the numerous ethical and legal questions, but little knowledge is available on the attitudes and opinions of childhood cancer patients and their parents regarding fertility preservation. Progress is being made in understanding the fertility issues that women may face after treatment. Infertility as an isolated health problem can be emotionally devastating for a woman [11] and is often viewed as a loss of one’s sense of femininity [12]. The risk of infertility touches on the most intimate aspects of a woman’s life after cancer, particularly her relationships, future plans for a family, and concerns about pregnancy and birth [4,12–16]. For cancer survivors who may be dealing with additional physical and emotional concerns, infertility may add yet another concern to an already lengthy list of fears and worries [17]. Some survivors describe that the loss of fertility can be as painful as facing cancer itself [15,18]. The situation is further complicated by the fact that female cancer survivors, particularly pediatric cancer patients, lack clear-cut options to address their fertility that are available to their male counterparts. Advancements in semen cryopreservation and intracytoplasmic sperm injection (ICSI) have revolutionized the reproductive outlook of male patients who have reached puberty [19]. Recent advances in reproductive science are beginning to change what is possible for female survivors as well. Traditionally, few options existed for female cancer patients who may want to have their own biological children in the future. The only two established techniques women have for fertility preservation are protecting the ovaries from radiation and emergency in vitro fertilization (IVF) [20,21]. While protecting a patient’s ovaries has become common practice, emergency IVF cannot be offered to patients diagnosed with cancer before puberty because mature oocytes cannot be collected [22]. The promise for female patients with childhood cancer lies in the strides made toward ovarian transplantation and in vitro follicle maturation. Ovarian transplantation involves the removal and cryopreservation of ovarian tissue before treatment and the reintroduction of tissue after treatment, either orthotopically or heterotopically, such as in muscle or subcutaneously [23]. Researchers have demonstrated that transplantation of cryopreserved ovarian tissue has led to human embryonic development when accomplished heterotopically [24] and to a live birth after orthotopic transplantation [25]. Another promising method of fertility preservation is in vitro maturation of immature oocytes. Similar to ovarian transplantation, ovarian tissue is removed and cryopreserved before fertility-threatening treatment. Once a woman is prepared to have a child, follicles can be isolated from the thawed tissue, matured in vitro in a three-dimensional culture system, and the mature oocyte can be fertilized through IVF. Murine oocytes have been collected from in vitro grown follicles, matured, and fertilized in vitro, which has resulted in live births [26]. Human trials, where one ovary is laparoscopically removed before treatment, are being conducted on adult patients in order to begin the experimental process of perhaps one day delivering this option to female cancer patients. As research begins to enter the clinical arena, a large number of unanswered questions remain regarding the application of the procedures, the legal and ethical considerations involved, and the receptiveness of patients and their families to fertility preservation. Thus far, very few studies have considered the viewpoints of childhood cancer patients and their parents [27]. Since decisions regarding fertility preservation must be made before treatment begins, parents, physicians, and patients are required to make a complex decision in a short amount of time during an extremely stressful situation, similar to the anxiety involved in the informed consent process of clinical cancer research trials [28]. In order for fertility preservation to become a realistic and valued addition to the treatment of childhood cancer patients, a better understanding of the decision-making process that parents and their children go through at the time of diagnosis and their interest in fertility preservation is needed. Further, a more thorough exploration of the patients’ and parents’ thoughts regarding the child’s fertility at the time of diagnosis as well as later in the patient’s life will be valuable in the continued advancement and eventual application of fertility preservation.

Review: a critical evaluation of arguments opposing male circumcision for HIV prevention in developed countries.

Abstract A potential impediment to evidence-based policy development on medical male circumcision (MC) for HIV prevention in all countries worldwide is the uncritical acceptance by some of arguments used by opponents of this procedure. Here we evaluate recent opinion-pieces of 13 individuals opposed to MC. We find that these statements misrepresent good studies, selectively cite references, some containing fallacious information, and draw erroneous conclusions. In marked contrast, the scientific evidence shows MC to be a simple, low-risk procedure with very little or no adverse long-term effect on sexual function, sensitivity, sensation during arousal or overall satisfaction. Unscientific arguments have been recently used to drive ballot measures aimed at banning MC of minors in the USA, eliminate insurance coverage for medical MC for low-income families, and threaten large fines and incarceration for health care providers. Medical MC is a preventative health measure akin to immunisation, given its protective effect against HIV infection, genital cancers and various other conditions. Protection afforded by neonatal MC against a diversity of common medical conditions starts in infancy with urinary tract infections and extends throughout life. Besides protection in adulthood against acquiring HIV, MC also reduces morbidity and mortality from multiple other sexually transmitted infections (STIs) and genital cancers in men and their female sexual partners. It is estimated that over their lifetime one-third of uncircumcised males will suffer at least one foreskin-related medical condition. The scientific evidence indicates that medical MC is safe and effective. Its favourable risk/benefit ratio and cost/benefit support the advantages of medical MC.

Waiting to be Born: The Ethical Implications of the Generation of “NUBorn” and “NUAge” Mice from Pre-Pubertal Ovarian Tissue

Oncofertility is one of the 9 NIH Roadmap Initiatives, federal grants intended to explore previously intractable questions, and it describes a new field that exists in the liminal space between cancer treatment and its sequelae, IVF clinics and their yearning, and basic research in cell growth, biomaterials, and reproductive science and its tempting promises. Cancer diagnoses, which were once thought universally fatal, now often entail management of a chronic disease. Yet the therapies are rigorous, must start immediately, and in many cases result in premature failure of the bodys reproductive ability. In women, this loss is especially poignant; unlike the routine storage of sperm, which is done in men and boys facing similar treatment decisions, freezing oocytes in anticipation of fertility loss is not possible in most cases, and creating an embryo within days of diagnosis raises significant moral, social and medical challenges. Oncofertility is the study of how to harvest ovarian tissue in women facing cancer to preserve their gametes for future use with IVF, thus allowing the decisions about childbearing to be deferred and reproductive choices to be preserved. The research endeavor uses the capacity of the ovarian follicle to produce eggs in vitro. Developing the human follicle to ovulate successfully outside the body is scientifically difficult and ethically challenging. Infertility is linked to long-standing religious and moral traditions, and is intertwined with deeply contentious social narratives about women, families, illness and birth. Is the research morally permissible? Perhaps imperative if understood as a repair from iatrogenic harms? How are considerations of justice central to the work? How will vulnerable subjects be protected? What are the moral implications of the work for women, children and families? What are the implications for society if women could store ovarian tissue as a way of stopping the biological clock? What are the moral possibilities and challenges if eggs can be produced in large quantities from a stored ovarian tissue?

Clinical ethics and the road less taken: mapping the future by tracking the past.

Although various aspects of clinical ethics consultation have been discussed in the literature, there has yet to be sustained systematic debate about the fundamental philosophical and methodological issues at stake in doing clinical ethics. Arguing that the field of clinical ethics is at ta critical crossroads, the author of this article outline the core issues that need to be addressed, debated, and resolved in order for the field to secure a meaningful future.

Stem Cell Research: A Target Article Collection Part I - Jordan's Banks, A View from the First Years of Human Embryonic Stem Cell Research

This essay will address the ethical issues that have emerged in the first considerations of the newly emerging stem cell technology. Many of us in the field of bioethics were deliberating related issues as we first learned of the new science and confronted the ethical issues it raised. In this essay, I will draw on the work of colleagues who were asked to reflect on early stages of the research (members of the IRBs, the Geron Ethicist Advisory Board, and the National Bioethics Advisory Commission) as the field debated the issues of consent, moral status, use of animal tissues, abortion, use of fetal tissue, and the nature and goals of entrepreneurial research. In this new capacity, ethicists weighed the problem of privacy, the role of justice considerations, and the issues of the marketplace in science. At this point, it is clear that far more issues remain unresolved than are settled, that there is largely unexplored territory ahead, and that the single most important task that faces us as a field is a steady call for ongoing conversation and public debate.

Today's Research, Tomorrows Cures: The Ethical Implications of Oncofertility

In contemporary society, translational medical research is the name of hope itself. For many, advances in modern medicine can be seen as a steady progression of science over dreadful and intractable illnesses, especially illness of children and young adults. Advances in the creation of families and protection of children have most clearly marked medicine’s success. Yet every scientific discovery and medical advance carries with it the inevitable dilemmas of choice and power. This chapter will look carefully at the effect on treatment when two trajectories of translational research converge to form a new field of inquiry—the field of oncofertility—and explore the ethical and social implications of the power that such research will create. Over the last 30 years, advances in reproductive technology have changed the event of infertility from a crisis of faith and generativity to a treatable medical condition. A breakthrough development in reproductive technology occurred with the historic birth of Louise Brown in 1978 through in vitro fertilization (IVF). Although infertility remains prevalent and is emotionally difficult for those it affects, it is now often curable, with nearly 85% of persons seeking treatment able to produce a child [1]. The advancements of assisted reproductive technology (ART), and particularly IVF, have increased the number of women who able to become pregnant using gametes from her and her partner, or by using donor sperm or eggs. It is, by many accounts, one of the measurable, tangible narratives of medical success, becoming so normative that in 2003, 112,872 ART cycles were carried out in the U.S. alone, resulting in 35,785 live births and 48,756 infants born using the techniques developed for the treatment of infertility [2]. This story of breakthrough advances in treating infertility parallels another—the successful treatment of previously fatal cancers, particularly cancers in children. Most people today who are diagnosed with cancer survive, with 5-year survival rates being well over 80% for many forms of cancer [3]. The idea of cancer has shifted from that of a death sentence to that of a chronic disease that will need to be monitored over the long term. With the increase in successful treatment of cancer patients, medical teams must now focus not only on the short-term treatments, but also anticipate long-term quality-of-life issues for their patients in the world beyond the “cure.” As survivors of cancer treatment are returned to the trajectory of their lives, they develop similar goals for education, career, and family life that their

Ethics Report on Interspecies Somatic Cell Nuclear Transfer Research

This report considers whether research involving the creation of human-animal interspecies somatic cell nuclear transfer (iSCNT) embryos raises new ethical issues, and if so, whether it requires additional or special criteria and oversight distinct from research on human-animal chimeras.

Gene Therapy: Charting a Future Course—Summary of a National Institutes of Health Workshop, April 12, 2013

Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances.