William L. Allen

An Overview of Stem Cell Research and Regulatory Issues

Stem cells are noted for their ability to self-renew and differentiate into a variety of cell types. Some stem cells, described as totipotent cells, have tremendous capacity to self-renew and differentiate. Embryonic stem cells have pluripotent capacity, able to form tissues of all 3 germ layers but unable to form an entire live being. Research with embryonic stem cells has enabled investigators to make substantial gains in developmental biology, therapeutic tissue engineering, and reproductive cloning. However, with these remarkable opportunities many ethical challenges arise, which are largely based on concerns for safety, efficacy, resource allocation, and methods of harvesting stem cells. Discussing the moral and legal status of the human embryo is critical to the debate on stem cell ethics. Religious perspectives and political events leading to regulation of stem cell research are presented and discussed, with special attention directed toward the use of embryonic stem cells for therapeutic and reproductive cloning. Adult stem cells were previously thought to have a restricted capacity to differentiate; however, several reports have described their plasticity potential. Furthermore, there have been close ties between the behavior of stem cells and cancer cells. True eradication of cancer will require a deeper understanding of stem cell biology. This article was written to inform medical scientists and practicing clinicians across the spectrum of medical education about the research and regulatory issues affecting the future of stem cell therapy.

Identification of Biomarkers in Breast Cancer by Gene Expression Profiling Using Human Tissues.

Breast cancer is the second leading cause of death by cancer in women. To identify biomarkers with potential diagnostic and therapeutic utilities in breast cancer, gene expression profiling from real patient tissues was used to discover significantly deregulated genes out of 50,739 genes of human transcriptome. Total RNAs were extracted, and the gene expression profiles of 32 cancerous and normal tissues were established using Agilent gene expression microarray technology. The results were analyzed with Agilent GeneSpring 12.6 software. Here we provide detailed experimental methods and analysis for the microarray data, which have been deposited into Gene Expression Omnibus (GEO) under GSE57297.

DTC genetic testing companies fail transparency prescriptions

In 2007, the American Society of Human Genetics issued recommendations for what the new and largely self-regulating industry offering genetic tests directly to consumers should disclose to potential customers. Websites for every DTC company offering health-related genetic tests as identified by a public policy group were evaluated for compliance with those transparency recommendations. The results showed that only six of the 25 companies studied met even 70% of the standards and that overall, the industry complied with the disclosure standards just 44% of the time. Further, the study revealed that even when companies met the letter of the law, they often failed to disclose to consumers the shortcomings associated with the tests and thus promoted genetic determinism. By failing to meet the spirit of the ASHG transparency recommendations, the DTC genetic testing industry demonstrates disdain toward the ethical principle of informed consent.

Proceedings of the second annual deep brain stimulation think tank: What's in the pipeline

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinsons disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Let's Do Not Resuscitate Placebo Cardiopulmonary Resuscitation

In a 1998 New England Journal of Medicine Sounding Board, Gail Gazelle posed the question, “The ‘Slow’ Code: Should Anyone Rush to Its Defense?”(Gazelle 1998). No great rush to defend it materialized, but at least one letter to the editor anticipated the essence of Lantos and Meadow’s proposal. Eran Segal and Talia Halamish-Shani characterized the slow code as “a ritualistic comforting hand on the shoulder of a grieving family member, rather than as an aggressive, deceitful show” (Segal and Halamish-Shani 1998). In their target article, Lantos and Meadow (2011) attempt a heroic resuscitation of the moribund “slow code” by reframing it as a symbolic gesture rather than a medical intervention. As my article title implies, I find their proposal unconvincing. Their account of the problem they want to solve, however, is right on target. Some patient families do not embrace decision making about cardiopulmonary resuscitation (CPR) or other life-sustaining interventions as an empowerment by which they avoid prolonged dying for their loved ones. In my own family’s experiences as well as in numerous clinical ethics consults, I have observed a cognitive dissonance in some family decision makers. They resist what they perceive as being conscripted as accomplices in the demise of their loved ones. Some ultimately manage to condone the inevitable reluctantly, and others simply never can bring themselves to endorse giving up, especially if they see it as abandonment of the patient’s will to survive or to “die trying.” In such cases, even when the decision maker acknowledges that death is inevitable, being asked to agree to the terms of surrender seems to some as if they are being asked—or worse, forced—to collaborate with the enemy. Lantos and Meadow are also right that when underlying values between family decision makers and physicians diverge, conflicts between them often cannot be resolved simply by more empathic dialogue. Understanding and dialogue should be thoroughly and authentically attempted before concluding that divergent views are irreconcilable, but there are times when authorized decision makers and professional care providers cannot resolve their differences by dialogue alone. Lantos and Meadows acknowledge that in such cases “it is not clear what actions by physicians would meet the needs or the demands of such family members.” Perhaps when it is not clear that physicians have any effective medical interventions to offer families, they should recognize the limits of medicine, rather than resorting to feigned resuscitation efforts. Resolving conflicts by

Accommodating Conscience Without Curtailing Women’s Rights, Health, and Lives

Nelson (2018) makes a plausible legal argument that homicide charges are warranted when individual and institutional medical providers, due to conscientious objection, refuse to disclose or to provide emergent pregnancy termination for a woman who dies as a result. In response, I want to expand the analysis to ascertain whether in similar cases civil claims are plausible, not only in cases in which women die, but also in cases when women don’t die but suffer harms. Nelson recognizes that district attorneys elected by voters may be reluctant to file homicide charges against physicians and hospitals that refused emergent terminations based on conscience. Private plaintiff’s attorneys, however, who might bring a wrongful death civil law claim, would not have that political risk. Moreover, the lower standard of proof in a civil claim, “mere preponderance” rather than “beyond reasonable doubt,” would make a claim substantially easier to prove than homicide. Recently, the ACLU sued on behalf of Tamesha Means. Ms. Means entered Mercy Health Partners, a Catholic hospital in Michigan, for emergent care from labor contractions at 18 weeks. Diagnosed with premature rupture of membrane and told her fetus was not viable, she was not told the risks of infection and sepsis if she continued the pregnancy, nor of the option to terminate it, much less that hospital policy prohibited termination. Sent home, she returned the next day with pain, bleeding, and fever. Her physician suspected chorioamnionitis (intra-amniotic bacterial infection). When her fever subsided, she was sent home and told to return if fever returned or contractions became unbearable, again without warnings about the risks of continued pregnancy or the option of termination. She returned hours later in pain and delivered an infant that lived 3 h. The pathology report confirmed acute chorioamnionitis and acute funistitis (inflammation of the connective tissue of the umbilical cord) (Means v. United States Conference of Catholic Bishops 2015). By the time a public health researcher disclosed that this had happened to five women at the same hospital (Redden 2016), Michigan’s statute of limitations on medical malpractice had passed. So the ACLU suit claimed ordinary negligence against the U.S. Conference of Catholic Bishops (USCCB) and officers of Catholic Health Ministries (CHM), a national Catholic sponsor of hospitals like Mercy Health Partners. The federal trial court dismissed the USCCB for lack of jurisdiction, which the Sixth Circuit Court of Appeal upheld (Means v. United States Conference of Catholic Bishops 2016). The trial court also dismissed CHM, reasoning that analysis of the negligence claim would require the court to interpret the Ethical and Religious Directives (ERDs), which would entail excessive entanglement in religion in violation of the Free Exercise Clause of the First Amendment. Recognizing its ruling would leave women in similar cases no recourse, the trial court noted such claims could be pursued under medical negligence law. The defendant, CHM, had raised Michigan’s liability protection for refusal of abortion as a defense, and the court declined to rule on whether the conscientious objection

Ethical Issues in the Neurointensive Care Unit

Patients present daily in neurosurgical intensive care units with illnesses that require physicians to consider not only diagnostic and therapeutic questions but ethical issues as well. While these ethical concerns are often asked and answered only at an intuitive level, physicians in the intensive care unit face an increasingly complex set of ethical and legal concerns, such as allocation of resources, medical futility, withholding and withdrawal of life-sustaining treatment (LST), and palliative sedation, among others. Adequate answers to such complex issues require critical analysis of issues rather than a merely intuitive approach.