Dr. Cabrera a co-author of ‘Neuroethics’ article on deep brain stimulation and personal identity

Laura Cabrera photoCenter Assistant Professor Dr. Laura Cabrera and co-authors Dr. Robyn Bluhm and Rachel McKenzie have a new article available online in Neuroethics, “What we (Should) Talk about when we Talk about Deep Brain Stimulation and Personal Identity.” The article resulted from the team’s Science and Society at State funded project on “Psychiatric Interventions: Values and Public Attitudes.”

Abstract: A number of reports have suggested that patients who undergo deep brain stimulation (DBS) may experience changes to their personality or sense of self. These reports have attracted great philosophical interest. This paper surveys the philosophical literature on personal identity and DBS and draws on an emerging empirical literature on the experiences of patients who have undergone this therapy to argue that the existing philosophical discussion of DBS and personal identity frames the problem too narrowly. Much of the discussion by neuroethicists centers on the nature of the threat posed by DBS, asking whether it is best understood as a threat to personal identity, autonomy, agency, or authenticity, or as putting patients at risk of self-estrangement. Our aim in this paper is to use the empirical literature on patients’ experiences post-DBS to open up a broader range of questions – both philosophical and practical, and to suggest that attention to these questions will help to provide better support to patients, both before and after treatment.

The full text is available online via Springer Link (MSU Library or other institutional access may be required to view this article).

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We Should Tolerate and Regulate Clinical Use of Human Germline Editing

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Parker Crutchfield, PhD

In November of 2018, a Chinese scientist announced that he had edited the embryos of twin girls and that the twins had been born. The scientist, He Jiankui, used CRISPR, a revolutionary method of editing sequences of genes, to delete the gene CCR5 from the embryos’ sequences. The intention was to make the twins resistant to HIV. Editing human embryos and allowing those embryos to develop into living, breathing babies was widely condemned. However, now it appears possible, likely even, that the twins’ cognition was impacted, perhaps improved. This, however, was an off-target effect—it was unintended. On March 13, Nature published a comment from a group of scientists calling for a moratorium on clinical uses of human germline editing. This call is only for a moratorium on clinical uses, not on research on editing the human germline.

Despite the moratorium, I think a good argument can be made that tolerating the clinical use of human germline editing is morally permissible. Here is one such argument. The fact that He Jiankui edited the girls’ embryos suggests that it is inevitable that some scientists are going to engage in this behavior. Imposing a moratorium is unlikely to change this—the cat’s out of the bag. Given that the behavior is inevitable, we should ensure it is performed as safely as possible in order to reduce the risk of harm.

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Image description: an illustrated image of a strand of DNA with a piece being inserted, representing CRISPR-Cas9 technology. Image source: NIH Image Gallery/Flickr.

The Inevitability Argument

I’m claiming that because clinical use of human germline editing is now inevitable, we should tolerate and regulate it. Generally, arguments of this type don’t work. It isn’t generally true that just because something is going to happen anyway, we should not only tolerate that behavior, but also make sure that it is done safely. For example, it’s true that humans murdering other humans is inevitable (unless we can cognitively or morally enhance people through, for example, gene editing!). Despite prohibitions on murdering, it still happens and probably always will. But its inevitability doesn’t mean that we should tolerate it but ensure that it is done safely. We shouldn’t, obviously.

Sometimes the argument does work, though. Sometimes the inevitability of a behavior suggests that we should tolerate it under regulation. For example, people using IV drugs is, for the foreseeable future, inevitable. Given this inevitability, it is morally justifiable to tolerate the behavior and do what we can to ensure that it is done safely. One way we do this is through needle exchanges. More recently, similar arguments support the widespread availability of naloxone for overdoses. So, sometimes, but not generally, the inevitability of a behavior justifies the tolerance of the behavior in order to ensure it is performed safely.

Reducing Harm

Why does the Inevitability Argument work in the case of needle exchanges? Why does it fail in the case of murder? One difference is that we know murder is wrong. You can’t have the concept of murder without also having the concept of wrongness. To tolerate murder would be to tolerate something that is morally prohibited. But we should be more skeptical of the wrongness of IV drug use—it may not be wrong at all, to say nothing of policies that permit or prohibit it. Even if it is wrong, our confidence that it is so should be lower. Another difference is that in the case of needle exchanges with IV drug users, the tolerance and regulation is meant to reduce harm, not only to the users, but to society. On the face of it, it seems implausible that one could anticipate a parallel policy of tolerating and regulating murder to reduce harm. Rather, tolerating and regulating murder would increase harm.

Inevitability of Clinical Use of Human Germline Editing

Is the clinical use of human germline editing more like IV drug use, or more like murder? Supposing that whether the Inevitability Argument works depends on whether we know the behavior being tolerated is wrong, and whether tolerating it is intended to reduce harm, the clinical use of human germline editing seems much more similar to IV drug use than it does to murder. First, we don’t know whether the clinical use of human germline editing is wrong, unlike our knowledge that murder is wrong. Whether it is wrong or permissible or obligatory depends on a lot of factors, including on whether embryos have a moral status and whether we have a duty to future persons.

Second, what would tolerating the clinical use of human germline editing look like? It would require scientific and political oversight of methods, data, and follow-up clinical care. But more importantly, the tolerance and regulation of the clinical use of human germline editing would require that we know more about what the effects of it will be. The only way we can acquire this knowledge is by conducting research on the clinical consequences of editing the human germline. This is all to say that the intention of tolerating the clinical use of human germline editing is to reduce as much as possible any potential harms, both to the person whose embryo was edited as well as to society.

Tolerating and Regulating Clinical Use of Human Germline Editing

By these criteria, the clinical use of human germline editing looks much more like needle exchanges for IV drug use. If so, then the Inevitability Argument may work, suggesting that we should tolerate and regulate its practice. But this tolerance and regulation impose further requirements: we must closely monitor the behavior and support research on the effects of editing the human germline.

Scientists assert (without sufficient foundation, I think) that the behavior is wrong. Do we really know that the clinical use of editing the human germline is wrong? If so, what general principle grounds this knowledge? What are the consequences of this general principle for other lines of scientific research? Is the clinical use of human germline editing really inevitable?

parker-crutchfield-cropParker Crutchfield, PhD, is Associate Professor in the Program in Medical Ethics, Humanities, and Law at the Western Michigan University Homer Stryker M.D. School of Medicine, where he teaches medical ethics and provides ethics consultation. His research interests in bioethics include the epistemology of bioethics and the ethics of enhancement, gene editing, and research.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, April 18, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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What are the ethical implications of gene-editing human embryos?

No Easy Answers in Bioethics logoNo Easy Answers in Bioethics Episode 13

What are the ethical implications of gene-editing human embryos? Do we risk stifling scientific advancement by banning such medical research?

Guests Dr. Leonard Fleck, Acting Director and Professor in the Center for Ethics and Humanities in the Life Sciences, and Dr. Marleen Eijkholt of Leiden University Medical Center in the Netherlands discuss the pros and cons, stemming from the recent news out of China of gene-edited babies. They share thoughts on the ethical implications of using such technology to alter human embryos, both now and in the future.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full episode transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics—clinical ethics, evidence-based medicine, health policy, medical education, neuroethics, shared decision-making, and more. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

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Ketamine for Depression: Research versus Marketing

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Arthur Ward, PhD

Just weeks ago, the U.S. Food and Drug Administration approved Ketamine as the first new drug in decades for treatment of depression. Or rather, while the approval for psychiatric treatment was new, the drug itself has been around as an anesthetic since 1970. The story of why it took so long for this well-known and well-tested drug (millions of patients have received ketamine as anesthesia) reveals the complex interplay between medical practice, the economics of pharmaceuticals, and the challenges of research ethics. Ketamine and other psychoactive drugs hold a great deal of promise for the treatment of depression and suicidality, but we need to be measured in our approach. To that end, I recommend an accelerated pace of research, but a slower rate of FDA approval and therapeutic application until more is known about the long-term effects.

What is so special about ketamine? Traditional pharmaceutical treatments for depression such as SSRIs (selective serotonin reuptake inhibitors) work by increasing the levels of the neurotransmitter serotonin in the brain. Ketamine is totally different, acting instead on the neurotransmitter glutamate. While SSRI medications can take weeks or months to become effective, ketamine can sometimes be effective in hours. That is utterly remarkable and groundbreaking, especially given the urgent nature of a depressive crisis. Meta-analyses of recent clinical trials on short term use show clear promise, with as much as a 50% improvement over placebo after 72 hours.

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Image description: a photograph of the sky with rays of sunlight pouring out from behind a dark cloud.

Yet there are reasons to think that Janssen’s esketamine nasal spray needs further research before responsibly coming to market. Double-blind randomized controlled clinical trials (RCTs) on psychoactive substances are very difficult to administer when the experimental drug has known mind-altering properties; in short, those that don’t hallucinate will know they’re in the control group! In the four Janssen phase-three clinical trials, all participants were on SSRI medication (it would not be ethical to give a depressed patient no treatment at all), the experimental group received esketamine nasal spray, while a placebo nasal spray was used in the control group. Despite adding an “embittering agent” to the placebo spray, the control group would likely have known they did not receive the esketamine (which is a hallucinogen), and thus a great deal of scientific rigor of the experiment was lost. In ongoing and future clinical trials, Janssen is using an “active placebo,” combining the placebo nasal spray with midazolam (a benzodiazepine sedative) so that the control group might think they took esketamine. While this would be an improvement in the blinding process, ketamine and midazolam do not feel the same: Midazolam a depressant while ketamine has psychedelic properties.

A second concern with the limited research so far has to do with the unknown long-term effects of ketamine use. Millions have experienced the anesthetic in a single dose, but the effects of long-term use are largely untested. The four clinical trials of Janssen’s esketamine nasal spray lasted only four weeks, and of these, only one showed significant results. Could it cause neurological damage long-term to take many repeated doses of esketamine? We don’t know, because the research hasn’t been done yet.

There are also cautionary signals of over-exuberance in therapeutic application that warrant vigilance. We must be mindful of pharmaceutical economics: capitalism craves returning customers. The market tends to reward expensive treatments for chronic conditions, and stifles cheaper treatments that effect a cure. For use as an anesthetic, Ketamine currently is generic and can be acquired quite cheaply. However, the FDA has only approved Janssen pharmaceuticals to release a nasal spray version of the drug, with esketamine, a closely related chemical. In doing so, the FDA grants esketamine patent protection – guaranteeing that treatment will be upwards of $500 a dose (the recommended treatment is eight doses over a month, totaling $4,720 to $6,785). This price is just for the drug alone, and not the accompanying office visit, which requires several hours of observation by a professional, adding extra expense. Granted, if one is freed from the burden and danger of crushing depression, this is well worth the price! And there are many credible anecdotes of ketamine treatment providing rapid, permanent relief. However, looking at the data, this long-lasting effect does not seem to be the norm. Instead, most people require sustained, periodic maintenance sessions every few weeks or months. This then raises the troubling question of whether we might be cultivating a financially crippling chemical dependence for some patients – rather than a cure.

My words of caution should not be interpreted as scolding or alarmist. I am a cheerleader for ketamine research. So far, the best evidence is that ketamine and esketamine are able to help some people who found little relief from other antidepressant treatments, and this is a wonderful turn of events. Alternatively, I think we should perhaps slow the pace of how quickly we bring ketamine drugs to market, but accelerate the related research. We need more clinical trials, and not just on ketamine, but on a variety of other psychoactive drugs as well! The culture wars of the 1960s resulted in the shuttering of promising research into LSD, psilocybin, and MDMA, all psychedelics well-recognized to have efficacy for depression treatment. After decades of lost time, clinical trials of all three chemicals are now underway. As the writer Michael Pollan has recently asserted in interviews and in his book, How To Change Your Mind, we are in the midst of a new renaissance of research into psychoactive chemicals. I suggest that we embrace this experimentation momentum, but simultaneously keep watch over our shoulder, both for possible long-term side-effects and for drug marketing’s problematic economic pressures.

Arthur Ward photoArthur Ward, PhD, is a teaching professor of History, Philosophy, and Sociology of Science in Lyman Briggs College at Michigan State University.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, April 4, 2019. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

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Assistant Director Libby Bogdan-Lovis a co-investigator on breastfeeding project

Libby Bogdan-Lovis photoCenter for Ethics Assistant Director Libby Bogdan-Lovis is a co-investigator on the project “Buffers, Barriers, and Resiliency in Breastfeeding Behaviors of Asian American Mothers.” The project is funded by the Trifecta Initiative for Interdisciplinary Health Research, a collaboration between the Colleges of Communication Arts & Sciences, Engineering, and Nursing at Michigan State University.

The interdisciplinary research team includes principal investigator Joanne Goldbort of the College of Nursing, Mary Bresnahan of the College of Communication Arts & Sciences, and Jie Zhuang of the Bob Schieffer College of Communication at Texas Christian University.

Project Summary: While Asian American (AA) mothers are described as high initiators of breastfeeding, no previous studies have conducted a randomized trial of AA mothers’ breastfeeding and formula use behaviors and whether these mothers continue to breastfeed exclusively for the recommended six months. Using an online Qualtrics customized panel, we will conduct a systematic investigation of the breastfeeding behaviors and timing of the introduction of complementary foods, and use of formula of AA mothers over a one-year period. We will recruit 1200 women between the ages of 18 and 35, as follows: 400 AA mothers with children one-year or younger; 400 pregnant AA women; and 400 American mothers from all race/ethnic groups will serve as the control group. This longitudinal study will track pregnant AA women through the birth of their babies, and will assess breastfeeding support and behaviors after the initial data collection, at 3-months, 6-months, and at one-year.

Visit our website to learn more about current research projects in the Center for Ethics and Humanities in the Life Sciences.

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Dr. Kelly-Blake a co-author of new article in ‘Health Services Research and Managerial Epidemiology’

Karen Kelly-Blake photoCenter Assistant Professor Dr. Karen Kelly-Blake is co-author of an article published in Health Services Research and Managerial Epidemiology, “Sex Differences in Statin Prescribing in Diabetic and Heart Disease Patients in FQHCs: A Comparison of the ATPIII and 2013 ACC/AHA Cholesterol Guidelines.”

The team of Michigan State University College of Human Medicine researchers, Nazia Naz S. Khan, Karen Kelly-Blake, Zhehui Luo, and Adesuwa Olomu, found statin underprescribing for both men and women with atherosclerotic cardiovascular disease and diabetes mellitus in Federally Qualified Health Centers.

The full text is available online with open access via Sage Journals.

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Dr. Cabrera co-authors ‘AJOB Neuroscience’ commentary on deep brain stimulation for depression

Laura Cabrera photo“Interpreting Patients’ Beliefs About Deep Brain Stimulation for Treatment-Resistant Depression: The Need for Caution and for Context” is an open peer commentary available in the latest AJOB Neuroscience issue. Michigan State University co-authors Dr. Laura Cabrera, Assistant Professor in the Center for Ethics and Humanities in the Life Sciences and the Department of Translational Science & Molecular Medicine, and Dr. Robyn Bluhm, Associate Professor in the Department of Philosophy and Lyman Briggs College, are currently working on an NIH BRAIN Initiative funded project on a related topic.

Dr. Cabrera and Dr. Bluhm focus on two points raised by the Lawrence et al. paper. First, they discussed a couple methodological decisions made by the authors which may have had an important influence on the results presented in the article. The second point relates to the work of Dr. Cabrera and Dr. Bluhm, examining differences in the bioethics literature’s discussion of deep brain stimulation and public comments on newspaper and magazine studies covering the intervention; this part of the open peer commentary shows how their findings can help to deepen the analysis by Lawrence et al.

The full text is available online via Taylor & Francis Online (MSU Library or other institutional access may be required to view this article).

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