Fred Gilbert

Recent developments of three-dimensional printing of biomaterials in medicine have been portrayed as demonstrating the potential to transform some medical treatments, including providing new responses to organ damage or organ failure. However, beyond the hype and before 3D bioprinted organs are ready to be transplanted into humans, several important ethical concerns and regulatory questions need to be addressed. This article starts by raising general ethical concerns associated with the use of bioprinting in medicine, then it focuses on more particular ethical issues related to experimental testing on humans, and the lack of current international regulatory directives to guide these experiments. Accordingly, this article considers whether there is a limit as to what should be bioprinted in medicine; examines key risks of significant harm associated with testing 3D bioprinting for humans; investigates the clinical trial paradigm used to test 3D bioprinting; analyses ethical questions of irreversibility, loss of treatment opportunity and replicability; explores the current lack of a specific framework for the regulation and testing of 3D bioprinting treatments.

Clinical cases of frontal lobe lesions have been significantly associated with acquired aggressive behaviour. Restoring neuronal and cognitive faculties of aggressive individuals through invasive brain intervention raises ethical questions in general. However, more questions have to be addressed in cases where individuals refuse surgical treatment. The ethical desirability and permissibility of using intrusive surgical brain interventions for involuntary or voluntary treatment of acquired aggressiveness is highly questionable. This article engages with the description of acquired aggressiveness in general, and presents a rare clinical case to illustrate the difficulties of treating this population. To expand the debate further, this article explores the ethics related to invasive brain surgery in three parts: a) it examines coercive involuntary invasive brain surgery for the benefit of protecting others on individuals suffering from acquired aggressiveness who lack decision-making capacities to consent; b) it addresses voluntary psychosurgery on individuals suffering from acquired aggressiveness who are competent to consent; and, c) it questions whether acquired aggressive individuals, who are legally competent, have a duty to consent to invasive brain surgery, in order to maintain their autonomy by reducing or even eliminate their aggressive drives. Ensuring the safety and efficacy of surgical brain interventions could increase the ethical permissibility of voluntary treatment, but it would not necessarily entail ethical justification for proceeding with invasive brain surgery for treatment of intractable acquired aggressive behaviour

The phenomenological effects of deep brain stimulation (DBS) on the self of the patient remains poorly understood and under described in the literature, despite growing evidence that a significant number of patients experience postoperative neuropsychiatric changes. To address this lack of phenomenological evidence, we conducted in-depth, semistructured interviews with 17 patients with Parkinson's disease who had undergone DBS. Exploring the subjective character specific to patients' experience of being implanted gives empirical and conceptual understanding of the potential phenomenon of DBS-induced self-estrangement. Our study concluded that (1) the more patients preoperatively felt alienated by their illness, the more they experienced postoperative self-estrangement, and (2) the notion of self-estrangement seems to exist in association with certain common qualitative characters, namely, loss of control, which reflects a deteriorative estrangement, and distorted perception of capacities, which reveals a restorative estrangement. These findings indicate that subjective self-reports help us to understand some aspects of the potential phenomenon of DBS-induced self-estrangement.

There has been a surge in mass media reports extolling the potential for using three-dimensional printing of biomaterials to treat a wide range of clinical conditions. Given that mass media is recognized as one of the most important sources of health and medical information for the general public, especially prospective patients, we report and discuss the ethical consequences of coverage of 3D bioprinting in the media. First, we illustrate how positive mass media narratives of a similar biofabricated technology, namely the Macchiarini scaffold tracheas, which was involved in lethal experimental human trials, influenced potential patient perceptions. Second, we report and analyze the positively biased and enthusiastic portrayal of 3D bioprinting in mass media. Third, we examine the lack of regulation and absence of discussion about risks associated with bioprinting technology. Fourth, we explore how media misunderstanding is dangerously misleading the narrative about the technology.

The goal of this article is to shed light on Deep Brain Stimulation (DBS) postoperative suicidality risk factors within Treatment Resistant Depression (TRD) patients, in particular by focusing on the ethical concern of enrolling patient with history of self-estrangement, suicide attempts and impulsive–aggressive inclinations. In order to illustrate these ethical issues we report and review a clinical case associated with postoperative feelings of self-estrangement, self-harm behaviours and suicide attempt leading to the removal of DBS devices. Could prospectively identifying and excluding patients with suicidality risk factors from DBS experimental trials—such as history of self-estrangement, suicide attempts and impulsive–aggressive inclinations—lead to minimizing the risk of suicidality harm?

Optogenetics is being optimistically presented in contemporary media for its unprecedented capacity to control cell behavior through the application of light to genetically modified target cells. As such, optogenetics holds obvious potential for application in a new generation of invasive medical devices by which to potentially provide treatment for neurological and psychiatric conditions such as Parkinson's disease, addiction, schizophrenia, autism and depression. Design of a first-in-human optogenetics experimental trial has already begun for the treatment of blindness. Optogenetics trials involve a combination of highly invasive genetic and electronic interventions that results in irreversible and permanent modifications of an individual's nervous system. Given its novelty, its uncertain benefit to patients, and its unique risk profile of irreversible physiological alteration, optogenetics requires a reassessment of the ethical challenges for protecting human participants in clinical trials, particularly at formative stages of clinical evaluation. This study explores the evolving ethical issues surrounding optogenetics’ potential harm to participants within trial design, especially focusing on whether Phase 1 trials should incorporate efficacy as well as safety endpoints in ways that are fair and respectful to research trial participants.

Deep brain stimulation (DBS) has been regarded as an efficient and safe treatment for Parkinson’s disease (PD) since being approved by the Food and Drug Administration (FDA) in 1997. It is estimated that more than 150 000 patients have been implanted, with a forecasted rapid increase in uptake with population ageing. Recent longitudinal follow-up studies have reported a significant increase in postoperative survival rates of patients with PD implanted with DBS as compared with those not implanted with DBS. Although DBS tends to increase life expectancy for most patients with PD, this medical benefit does not come without attendant negative consequences. For example, emerging forms of iatrogenic harms are sometimes induced—harms which were not initially expected when clinicians proposed neurosurgery and patients or their guardians consented to the treatment. We report and discuss the clinical case of a patient who was implanted with DBS more than 20 years ago (at the time of writing) and is now experiencing unexpected stages of PD. This case illustrates how extending the life span without improving quality of life may introduce a burden of harms for patients and families. As well, this case shows why we should prepare for the expanding numbers of PD-implanted patients experiencing a gain of longevity but with severe stages of disease leading to diminution in quality of life. This newly observed effect of DBS treatment requires us to explore ethical questions related to iatrogenic harms, informed consent, end of life and caregivers’ burden.

To conclude that there is enough or not enough evidence demonstrating that deep brain stimulation causes unintended postoperative personality changes is an epistemic problem that should be answered on the basis of established, replicable, and valid data. If prospective DBS recipients delay or refuse to be implanted because they are afraid of suffering from personality changes following DBS, and their fears are based on unsubstantiated claims made in the neuroethics literature, then researchers making these claims bear great responsibility for prospective recipients' medical decisions and subsequent well-being. Our article “Deflating the ‘DBS causes personality’ bubble” reported an increase in theoretical neuroethics publications suggesting putative DBS-induced changes to personality, identity, agency, autonomy, authenticity and/or self and a critical lack of supporting primary empirical studies. This special issue of Neuroethics brings together responses to our initial publication, with our own counter-responses organized according to common themes. We provide a brief summary for each commentary and its main criticisms as well as a discussion of the way in which these responses can: 1) help clarify the meaning of PIAAAS, suggesting supplementary frameworks for understanding the impact of DBS on PIAAAS; 2) provide further empirical evidence of PIAAAS by presenting results from the researchers’ own work; and/or 3) offer a critique of our research approach and/or findings. Unintended postoperative putative changes to PIAAAS remain a critical ethical concern. It is beyond dispute that we need to develop reliable empirical and conceptual instruments able to measure complex cognitive, affective, and behavioural changes in order to investigate whether they are attributable to DBS alone.

One important concern regarding implantable Brain Computer Interfaces is the fear that the intervention will negatively change a patient’s sense of identity or agency. In particular, there is concern that the user will be psychologically worse-off following treatment despite postoperative functional improvements. Clinical observations from similar implantable brain technologies, such as deep brain stimulation, show a small but significant proportion of patients report feelings of strangeness or difficulty adjusting to a new concept of themselves characterized by a maladaptive je ne sais quoi despite clear motor improvement. Despite the growing number of cases in the DBS literature, there is currently no accepted or standardized tool in neuroethics specifically designed to capture the phenomenological postoperative experience of patients implanted with DBS or BCI devices. Given potential risks of postoperative maladaptation, it is important for the field of neuroethics to develop a qualitative instrument that can serve as a shared method for capturing postoperative variations in patient experience of identity and agency. The goal of this article is to introduce an instrument we have developed for this purpose and call for further neuroethical efforts to assess the phenomenology of implantable brain device use.

The idea that deep brain stimulation (DBS) induces changes to personality, identity, agency, authenticity, autonomy and self (PIAAAS) is so deeply entrenched within neuroethics discourses that it has become an unchallenged narrative. In this article, we critically assess evidence about putative effects of DBS on PIAAAS. We conducted a literature review of more than 1535 articles to investigate the prevalence of scientific evidence regarding these potential DBS-induced changes. While we observed an increase in the number of publications in theoretical neuroethics that mention putative DBS-induced changes to patients’ postoperative PIAAAS, we found a critical lack of primary empirical studies corroborating these claims. Our findings strongly suggest that the theoretical neuroethics debate on putative effects of DBS relies on very limited empirical evidence and is, instead, reliant on unsubstantiated speculative assumptions probablyin lieuof robust evidence. As such, this may reflect the likelihood of a speculative neuroethics bubble that may need to be deflated. Nevertheless, despite the low number of first-hand primary studies and large number of marginal and single case reports, potential postoperative DBS changes experienced by patients remain a critical ethical concern. We recommend further empirical research in order to enhance theoretical neuroethics work in the area. In particular, we call for the development of better instruments capable of capturing potential postoperative variations of PIAAAS.

Despite growing evidence that a significant number of patients living with Parkison’s disease experience neuropsychiatric changes following Deep Brain Stimulation treatment, the phenomenon remains poorly understood and largely unexplored in the literature. To shed new light on this phenomenon, we used qualitative methods grounded in phenomenology to conduct in-depth, semi-structured interviews with 17 patients living with Parkinson’s Disease who had undergone DBS. Our study found that patients appear to experience postoperative DBS-induced changes in the form of self-estrangement. Using the insights from patients’ subjective perceptions of postoperative self-change provides a potent explanation of potential DBS-induced self-estrangement.

Taiwan has a population of 23 million, of which some 500,000 are Aborigines. Recent conflicts over a national biobank as part of Taiwan's biotechnological industrial development, genetic research on Aboriginal origins, and commercialization of research findings involving Aborigines have raised a number of important ethical conflicts. These ethical conflicts involve on one hand, the importance of researchers' duties, and on the other hand, Aboriginal rights. This paper will go in three steps. First, this paper describes the three cases of ethical violations of Aboriginal rights committed by Taiwanese researchers in the course of their scientific duties. After having given an account of ethical conflicts between research duties and Aboriginal rights, the paper addresses larger ethical issues underlying this Taiwanese research context. Finally, the paper considers if stronger ethical regulation could reconcile Aboriginal rights and research duties.

The purpose of this commentary is to address an ethical issue introduced by Walter Glannon regarding whether responsibility can be affected by the use of performance enhancing drugs. Glannon uses the example of a surgeon taking drugs to enhance her capacities. I explore whether conducting surgeries while under the influence of performance enhancing drugs will affect the surgeon’s responsibility for performing more surgeries ‘and’ the surgeon’s responsibility for assuming the consequences of performing these surgeries. Here, the ‘and’ is cumulative: one is responsible for performing ‘and’ one is responsible for having taken performance enhancing drugs. Given that such accumulation could be interpreted as “more responsible”, this might challenge Glannon’s conclusion and impact the normative practices associated with enhancement drugs.

In her article, Pascale Hess raises the issue of whether her proposed model may be extrapolated and applied to clinical research fields other than stem cell-based interventions in the brain (SCBI-B) (Hess 2012). Broadly summarized, Hess’s model suggests prioritizing efficacy over safety in phase 1 trials involving irreversible interventions in the brain, when clinical criteria meet the appropriate population suffering from “degenerative brain diseases” (Hess 2012). Although there is a need to reconsider the traditional phase 1 model, especially with respect to first-in-human clinical trials involving novel technologies, the question arises as to whether it is appropriate to advocate for a new model that prioritizes efficacy over safety across all phase 1 clinical research trials involving irreversible interventions in the brain.

Taiwan has a population of 23 million, of which some 500,000 are Aborigines. Recent conflicts over a national biobank as part of Taiwan's biotechnological industrial development, genetic research on Aboriginal origins, and commercialization of research findings involving Aborigines have raised a number of important ethical conflicts. These ethical conflicts involve on one hand, the importance of researchers' duties, and on the other hand, Aboriginal rights. This paper will go in three steps. First, this paper describes the three cases of ethical violations of Aboriginal rights committed by Taiwanese researchers in the course of their scientific duties. After having given an account of ethical conflicts between research duties and Aboriginal rights, the paper addresses larger ethical issues underlying this Taiwanese research context. Finally, the paper considers if stronger ethical regulation could reconcile Aboriginal rights and research duties

Geron recently announced that it had begun enrolling patients in the world's first-in-human clinical trial involving cells derived from human embryonic stem cells (hESCs). This trial raises important questions regarding the future of hESC-based therapies, especially in spinal cord injury (SCI) patients. We address some safety and efficacy concerns with this research, as well as the ethics of fair subject selection. We consider other populations that might be better for this research: chronic complete SCI patients for a safety trial, subacute incomplete SCI patients for an efficacy trial, and perhaps primary progressive multiple sclerosis (MS) patients for a combined safety and efficacy trial.

Although being generally safe, the use of Deep Brain Stimulation has been associated with a significant number of patients experiencing postoperative psychological and neurological harm within experimental trials. A proportion of these postoperative severe adverse effects have lead to the decision to medically prescribe device deactivation or removal. However, there is little debate in the literature as to what is in the patient’s best interest when device removal has been prescribed; in particular, what should be the conceptual approach to ethically guide the decision to remove or maintain implants. The purpose of this article is to examine the ethical issues raised when patients refuse brain device explantation despite medical prescription. In order to illustrate these issues, we report and discuss a clinical case involving a patient suffering from treatment resistant depression who experienced forms of postoperative self-estrangement, as well as suicidal attempts, but who resists giving consent to device explantation

In early 2009, President Obama overturned the ban on federal funding for research involving the derivation of human embryonic stem cells (hESC). The Food and Drug Administration (FDA) also approved Geron’s first-in-human hESC trial for spinal cord injury (SCI) patients. We anticipate an increase in both research in the United States to derive hESC and applications to the FDA for approval of clinical trials involving transplantation of hESCs. An increase of such clinical trials will require a concomitant increase in the number of preceding preclinical assays. We examine important issues concerning the use of animals in SCI stem cell research that require a reevaluation of the moral permissibility of studies such as Geron’s.

Postmortem evidence of chronic traumatic encephalopathy (CTE) in the brains of American National Football League players who suffered concussions while playing have intensified concerns about the risks of concussion in sport.1 Concussions are frequently sustained by amateur and professional players of Australia’s three most popular football codes (Australian football, rugby league, and rugby union) and, to a lesser extent, other contact sports such as soccer. This raises major concerns about possible long-term neurological damage, cognitive impairment and mental health problems in players of these sports.