Gene Editing: God’s Will or God’s Won’t

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

By Leonard M. Fleck, PhD

Give God a rest; do your own gene editing (and thinking). On August 2, 2017 the New York Times headline read, “In Breakthrough, Scientists Edit a Dangerous Mutation from Genes in a Human Embryo.” The mutation was of a gene called MYBPC3, and the result of that mutation is a disease called hypertrophic cardiomyopathy. This disease affects 1 in 500 people. Its victims are typically young athletes. CRISPR-cas9 is the technology used to accomplish the gene editing. More precisely, a synthetic healthy DNA sequence was injected into an egg cell fertilized by a sperm cell with the mutated gene. This healthy DNA sequence was supposed to be copied into the newly created embryo. In fact, however, the maternal DNA was copied, thereby correcting the paternal mutation in 72% of the resulting embryos. A total of 54 embryos were created, later destroyed, after genetic analysis had been done. The remaining embryos were genetically mosaic. This research received worldwide attention.

Embryo,_8_cells,_transparent_image

Image description: a black and white image of an 8-cell human embryo, day 3. Image source: Wikimedia Commons.

I want to raise two questions. How should we assess this research and its future possible uses from an ethical perspective? How should we assess public policies designed to regulate this research now and in the future? I am going to give more attention to this latter question in the context of a liberal, pluralistic, democratic political culture because many people would demand that the research itself be outlawed, not just regulated. The relevant question to ask is this: What sort of justification must be given for regulating or banning gene-editing technologies used to create or modify human embryos? The short answer I will defend in response to that question is that regulations must satisfy public reason and public interest requirements (as explained below).

From an ethical perspective, gene-editing technology represents considerable potential benefit, as the example of hypertrophic cardiomyopathy above suggests. At least 200 single-gene disorders could be corrected at the embryonic or pre-embryonic level, thereby preventing premature death or substantial diminishment of quality of life in these future possible children (as well as potential descendants of those children). To be clear, no gene-editing technology is ready for clinical application. Off-target effects remain a problem. From an ethical perspective, the risk-benefit ratio of such interventions today weighs too heavily on the risk side. Researchers, however, are confident that these risks can be overcome.

Assuming that the safety issues can be effectively managed, another ethical objection is that these future possible children (maybe for several generations) would not have consented to such fundamental interventions. I do not see this as a compelling objection. Parents today must consent to very risky surgery or other medical interventions in a two-year old child that could result in the death of that child or substantial lifelong impairment. We have to trust the judgment of parents and physicians in such circumstances. We have to believe they are all acting in the best interests of that child (absent compelling evidence to the contrary). This seems perfectly analogous to what would be occurring with gene-editing of an embryo. (For a broad overview of relevant ethical principles, see Wolpe et al., 2017.)

I now want to switch to concerns in the context of public policy. What sort of political justification would be needed to legitimize the complete banning of gene-editing research on human embryos? Here are two answers that are entirely “out of bounds” in a liberal, pluralistic society: (1) doing gene-editing of embryos is “playing God,” and (2) destroying embryos should never be regarded as an acceptable part of medical research.

The phrase “playing God” invokes amorphous religious associations, deliberately and arrogantly engaging in some life-or-death activity that is the exclusive prerogative of God. However, if this is supposed to be a compelling argument for public policy purposes, then large areas of medical practice would have to be outlawed as well. It might well be the will of God that I die from my heart attack, but I still want my surgeon to be agnostic and do the bypass surgery needed to save my life. God is typically described as being omnipotent, though millions of embryos are created annually with thousands of serious genetic disorders. Allowing those future possible children to suffer the awful consequences of those disorders by forbidding the development of the technology that could correct those disorders looks like willful social negligence, not impiety.

14441587544_cd85b811d1_k

Image description: a bone cancer cell (nucleus in light blue) at the microscopic level. Image source: ZEISS Microscopy/Flickr Creative Commons.

Critics of gene-editing rail against the possible, speculative harms this technology could unleash on future generations of children, all the while ignoring the very real harms current actual children are having to suffer as a consequence of these genetic disorders. This is not just shortsighted; it is ethically and politically perverse. Virtually everyone agrees that it would be premature today to do embryonic gene-editing with the intent of bringing that future possible child to birth. However, nothing would justify laws that would forbid going forward with the research until such time as it would be safe to introduce into the clinic.

Some religious critics will object to the destruction of embryos that will be integral to the development of this technology. We noted above that 54 embryos were created and destroyed in connection with the hypertrophic cardiomyopathy research. Some religious critics will see those embryos as having the moral status of persons with the same rights as you and I. However, this is where public reason must be invoked as the appropriate basis for formulating policy in a liberal, pluralistic society.

Public reason (Rawls, 1996) must be neutral or agnostic with respect to all religious belief systems or other comprehensive worldviews. From an objective, scientific perspective embryos have no capacity to feel pain, no consciousness, no interests, and no personal identity. Embryos are not mini-persons. Some religious adherents may believe otherwise. They are free to affirm that belief in the private social space of their religious community. However, they may not seek to create laws that would effectively impose that belief on citizens who did not share that belief. This would be an illegitimate, illiberal use of the coercive powers of government unless they were able to justify such laws through an appeal to public reasons and related public interests.

Public reasons are reasons that all free and equal reasonable citizens as citizens can accept as reasonable, as consistent with the best science and fair terms of cooperation in a just society. Public reasons are the currency of rational democratic deliberation. Public interests are interests that all citizens have, and that could not be adequately protected or enhanced without the use of the coercive powers of government to control those who would threaten those interests. Protecting air and water quality would be a clear example of a public interest.

A liberal, pluralistic society recognizes and respects many reasonable ways of living a good life. Individuals are free to order their lives in accord with many different reasonable values that do not represent a threat to the rights of others or to various public interests. Consequently, such a society will accept that some people will refuse to use gene-editing technology in the future to alter the genetic endowment of their future possible children. This is political respect for procreative liberty.

It would be illiberal and illegitimate for some political group to use the coercive powers of the state to force religious individuals to use gene-editing technology, contrary to their religious beliefs. Likewise, these religious individuals must be mutually respectful of the procreative liberty rights of others to use gene-editing technology to alter the genetic endowments of their future possible children. This would include paying taxes to support the medical and scientific research needed to develop safe and effective versions of embryonic gene-editing, keeping in mind the taxes needed to pay for the health care needs of children born with cystic fibrosis or muscular dystrophy or any number of other medical problems that could have been avoided with judicious gene-editing.

In conclusion, there can be reasonable disagreement regarding various uses of embryonic gene-editing technology. However, that disagreement will have to invoke public reasons and public interests. God’s will and God’s won’t are not public interests.

Fleck smallLeonard M. Fleck, PhD, is a Professor in the Center for Ethics and Humanities in the Life Sciences and the Department of Philosophy 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, December 14, 2017. 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.

Click through to view references

Posted in Bioethics in the News, Uncategorized | Tagged , , , , , , , , , , , , , | 7 Comments

Bioethics for Breakfast: Autism Spectrum Disorder: Fair Sharing of the Therapeutic Pie?

Bioethics for Breakfast Seminars in Medicine, Law and SocietyJeanette M. Scheid, MD, PhD, and Connie Sung, PhD, presented at the Bioethics for Breakfast event on November 30, 2017, offering perspective and insight on the topic, “Autism Spectrum Disorder: Fair Sharing of the Therapeutic Pie?”

Autism Spectrum Disorder (ASD), as the name implies, occurs across a broad spectrum of cognitive, psychological, behavioral, and social interactive manifestations. There is a genetic component to the disorder, though the precise pathology remains something of a mystery. There is no cure for the disorder, though there are some behavioral therapies that address what might otherwise be lifelong manifestations. A number of ethical issues might be raised regarding ASD. First, given some genetic connection to the disorder, should parents be strongly advised to have genetic testing (maybe Whole Genome Sequencing) to inform future reproductive decisions. Second, there are resource allocation issues related to potential therapies. There are at least two evidence-based behavioral interventions that have demonstrated effectiveness in improving aspects of the disorder. There are also a number of “therapies” that have little formal evidence-based support but strong advocates who expect insurance coverage. Third, the two accepted therapies require strong parental involvement in providing/ maintaining these therapies at home (which reduces social costs for these therapies). How might we best ensure such involvement? Fourth, therapeutic resources for ASD are disproportionately available across the lifespan. Is that an injustice? These questions and more were discussed by speakers and attendees.

Jeanette M. Scheid, MD, PhD
Jeanette M. Scheid, MD, PhD, is an Associate Professor of Psychiatry at Michigan State University. She is board certified in general and child and adolescent psychiatry. In that role she teaches medical students and residents and provides clinical care to children, adolescents and adults. Her primary practice sites are in community mental health and child residential treatment facilities. Dr. Scheid sees patients with a broad range of mental health concerns. She has particular interest in the systems of care and issues facing children and adolescents exposed to maltreatment.

Connie Sung, PhD
Connie Sung, PhD, is an Assistant Professor of Rehabilitation Counseling and co-director of Spartan Project SEARCH at Michigan State University. She received her PhD in Rehabilitation Psychology from University of Wisconsin-Madison and completed a pre-doctoral psychology internship at Waisman Center, Madison, WI. Previously as an occupational therapist and now as a rehabilitation counseling educator and researcher, she has over 10 years of experience working with individuals with autism spectrum disorder throughout the lifespan and has a special interest in working with the transition youth population. Currently, she is a principal investigator of several community-based participatory research projects, including evaluation of intervention strategies to improve psychosocial and vocational outcomes of transition-age individuals who are on the autism spectrum.

About Bioethics for Breakfast:
In 2010, Hall, Render, Killian, Heath & Lyman invited the Center for Ethics to partner on a bioethics seminar series. The Center for Ethics and Hall Render invite guests from the health professions, religious and community organizations, political circles, and the academy to engage in lively discussions of topics spanning the worlds of bioethics, health law, business, and policy. For each event, the Center selects from a wide range of controversial issues and provides two presenters either from our own faculty or invited guests, who offer distinctive, and sometimes clashing, perspectives. Those brief presentations are followed by a moderated open discussion.
Posted in Bioethics Events, Friends of the Center, Outreach, Uncategorized | Tagged , , , , ,

Dr. Cabrera presents at International Neuroethics Society and Society for Neuroscience meetings

Laura Cabrera photoDr. Cabrera recently attended two events in Washington, D.C.: The International Neuroethics Society (INS) annual meeting, and the 47th annual meeting of the Society for Neuroscience (SfN).

International Neuroethics Society

Julia Porter SfN 2017 conference poster

Image description: Dr. Cabrera’s undergraduate research assistant Julia Porter poses for a photo with their poster “Is low data reporting prevalent in clinical trials of psychiatric deep brain stimulation?” Photo courtesy of Laura Cabrera.

This year the INS meeting theme was “Honoring our History, Forging our Future,” bringing together a diverse group of scholars, scientists, clinicians, and professionals dedicated to the responsible use of advances in brain science. The intellectually stimulating and dynamic conference payed homage to the first fifteen years of neuroethics. Dr. Cabrera presented two posters. The first, “Ethical issues and somatic psychiatric treatments: professionals vs. public concerns,” discussed results from her past S3 grant with colleague Dr. Robyn Bluhm. Her second poster, “Is low data reporting prevalent in clinical trials of psychiatric deep brain stimulation?” was co-authored with Julia Porter, an undergraduate research assistant in Dr. Cabrera’s lab.

Dr. Cabrera also participated in a panel lead by Karen Herrera-Ferrá on the “Inclusion of Latin America within the globalization of neuroethics,” as part of the Neuroethics Program Leaders Council meeting which took place on November 11th.

Society for Neuroscience

Dr. Cabrera was one of the faculty organizing a short course on “Neuroethics and Public Engagement: Why, How, and Best Practices” as part of the pre-conference events. This was a very well-attended course with great participant engagement.

Dr. Cabrera also chaired, together with Edith Brignoni-Perez, the Neuroethics Social on November 13th. The event used films to discuss ethical issues in the portrayals of learning disabilities and neurodevelopmental disorders.

Posted in Center News, Research, Uncategorized | Tagged , , , , , , , ,

Dr. Fleck presents at Great Lakes Biorepository Research Network annual scientific meeting

Leonard Fleck photoCenter Professor Len Fleck, PhD, was a keynote speaker at the Great Lakes Biorepository Research Network (GLBRN) Annual Scientific Meeting, held at Beaumont Hospital-Royal Oak Campus on November 3. The title of Dr. Fleck’s presentation was “Precision Medicine, Ethical Ambiguity,” summarized below.

What is precision medicine? A short answer would be getting beyond “one size fits all” drug therapy, with all the side effects and misfits that implies (e.g. traditional chemotherapy). Instead, medicine would stratify patients with a specific disease, such as some cancer, into subgroups so that therapy could be tailored to the specific genetic features of their cancer. The overall goal is to maximize the beneficial effects of an available therapy for a specific patient, minimize debilitating or dangerous side effects, and save money for the health care system. How could there be ethical problems with goals such as that?

The most significant problem relates to health care justice, the fair distribution of access to the fruits of precision medicine. The basic problem is that these targeted cancer therapies are extraordinarily expensive. More than 70 of these cancer drugs have been approved by the FDA since 2000.

  • Cost: $70,000–$200,000+ for a course of treatment.
    • One form of combination therapy is priced at $86,000 per month.
    • Kymriah for Acute Lymphocytic Leukemia (ALL) is priced at $475,000 for a one-time treatment.
  • None of these drugs is curative.
  • Median gains in life expectancy for patients is measurable in weeks or months for the most part.
  • Several hundred more such drugs are in the pipeline.
  • Fojo and Grady have pointed out that these drugs yield incremental cost-effectiveness ratios (ICERs) of several hundred thousand dollars to more than a million dollars per Quality-Adjusted Life Year (QALY).

Imatinib (Gleevec) was approved in 2001 for the treatment of Chronic Myelogenous Leukemia (CML). It is extraordinarily effective for the 70% of these patients who have survived at least ten years beyond diagnosis. It was priced at $36,000 per year in 2001, and must be taken indefinitely. In 2016 imatinib was priced at $146,000, even though nothing at all changed with regard to the drug itself. Another drug, Iclusig, was priced at $120,000 for a year in 2015. In 2016 the price was raised to $200,000. We will pass over in stunned silence at the obvious ethical issues here.

As a society that seeks to be just and caring in meeting health care needs we struggle to identify the ethical norms that should govern access to these targeted cancer therapies. Keep in mind that these drugs are for metastatic cancer, almost always a terminal diagnosis. Consequently, we often appeal to inchoate (and problematic) ethical intuitions. We appeal to the “rule of rescue,” “last chance therapies,” “the pricelessness of human life,” and the “visibility of desperate patients,” all of which seem to generate an ethical obligation to fund access to these targeted therapies. Unfortunately, that obligation runs out of ethical steam once insurance runs out. In health care, our sense of obligation has evolved to select for money.

Some sad conclusions: (1) No moral theories or “compelling” moral arguments are going to yield clearly satisfactory ethical resolution to these allocation/ priority-setting challenges. Not just cancer counts (ethically speaking). (2) Ultimately, given limited resources (money) for meeting unlimited health care needs we will have to rely upon fair and legitimate processes of rational democratic deliberation constrained by relevant clinical evidence and broadly endorsed considered judgments of health care justice. (3) For the foreseeable future, precision medicine will remain infected with clinical uncertainty, ethical ambiguity, disingenuous politicking, and byzantine economic accounting (not to mention pharmaceutical philandering).

Posted in Bioethics Events, Center News, Friends of the Center, Outreach, Uncategorized | Tagged , , , , , , , , , , , ,

Dr. Fleck presents on ‘Genetics, Ethics, and the Future of Human Reproduction’ at community event

Leonard Fleck photoOn November 2, Center Professor Len Fleck, PhD, spoke at the Grace A. Dow Memorial Library in Midland, MI as part of a community engagement project. Dr. Fleck’s presentation, “From Chance to Choice: Genetics, Ethics, and the Future of Human Reproduction,” is summarized below. The premise for this presentation was a comment by Philip Kitcher in his book Lives to Come: The Genetic Revolution and Human Possibilities. His comment was that we had exited the age of genetic innocence and were now in the age of genetic responsibility (from which we could not exit).

Kitcher wrote that comment more than twenty years ago, when that comment still had a futuristic tinge to it. Today we are solidly in the age of genetic responsibility. Thirty years ago, future possible parents had to conceive “in fear and trembling” (to quote Soren Kierkegaard). They had no idea what genetic risks they might impose upon their future possible children. If a child was born with a serious, life-threatening genetic disorder, this was unfortunate, but no one was ethically blameworthy for that outcome. Today, with the availability of whole genome sequencing for about $1000, a couple can find out whether or not they might pose some serious genetic risk to their future possible children, along with alternative reproductive options that might allow them to bypass that risk, such as pre-implantation genetic diagnosis of eight-cell embryos conceived in vitro. With that new knowledge (or possibility for knowledge) comes new responsibility.

What sort of responsibilities might these future possible parents have? They might chose to have their children in the usual way. A liberal, pluralistic democratic society would be politically obligated to respect such a choice because these parents have both privacy rights and procreative liberty rights. This might mean a child will be born with cystic fibrosis, and all the health costs associated with that. That same liberal, pluralistic society will have obligations of justice and beneficence to provide the care (at social expense) needed by that child to have as good a life as possible (even though some taxpayers might object to paying for avoidable health care expenses).

There will also be many in our society who will object to permitting other future possible parents availing themselves of pre-implantation genetic diagnosis (PGD), which will involve the creation and discarding of some number of excess embryos carrying a serious genetic defect. However, this too is a liberty right and privacy right of these parents, which advocates for a Right to Life position may not justly deny these parents. Further, the cost of having a child via PGD will be about $40,000. This is a cost that might also require public financial support, which would be a matter of social genetic responsibility. Right to Life advocates might object to paying taxes to support an intervention to which they deeply conscientiously object. Still, this is what they are ethically and politically obligated to do. This is a matter of reciprocity, what the political philosopher, John Rawls, refers to as fair terms of cooperation.

In the future we will see our capacity to do gene editing at the embryonic level successfully evolve, which will require yet more ethical analysis of what this means for parental and social responsibility. It will also politically require much more mutual respect for diverse understandings of responsible reproductive decision making, which is what the ideals of a liberal, pluralistic society justly expects.

Posted in Bioethics Events, Center News, Outreach, Uncategorized | Tagged , , , , , , ,

Mass Shootings, Mental Illness and Stigma

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

By Devan Stahl, PhD

Over the past two months, we have witnessed two more mass shootings in Las Vegas and Sutherland Springs, TX. Once again, these incidents bring up the debates surrounding gun legislation and access to mental health care. In reference to the Texas shooting, President Trump commented, “This is a mental health problem at the highest level. It’s a very, very sad event.” Soon after, it was revealed that Devin Kelley, the Texas shooter, had briefly escaped from a mental hospital in 2012 after he made death threats against his superiors in the Air Force. Both the president and the media emphasized the connection between mental illness and mass shootings. In fact, Johns Hopkins University found that over one-third of all news stories about mental illness were connected to violence. Psychiatric journals are also more likely to publish articles connecting mental illness with aggression than mental illness and victimhood, even though persons with mental illness are ten times more likely to be victims of violent crimes, including police shootings. It is no wonder that 63% of Americans blame mass shootings on the failure of the mental health system.

When confronted with a mass shooting, it is hard not to assume that mass shooters are mentally ill. After all, what sane person could commit such a horrible act? The media and even psychiatric professionals are quick to look for associations between mental illness and mass shootings. After Adam Lanza took the lives of twenty children and six adults at Sandy Hook Elementary School, new research on the brains of mass shooters began. More recently, the brain of Stephen Paddock, who killed 59 people in Las Vegas, was shipped to the Las Vegas coroner’s office for a neuropathological examination to look for any “mental aberrance” to explain his behavior, even though neuropathologists admit correlating brain structures with behavior is “cloudy business.”

4573522770_4f03003afc_o

Image description: a cardboard sign is tied to a tree, with lettering that reads “stop gun violence :(” in blue and red. Image source: Tony Webster/Flickr Creative Commons.

Research shows us, however, that the link between gun violence and mental illness is far more complicated than it would appear. In general, it is hard to generalize about mass shooters because they are relatively rare. Although there is some evidence to show persons with severe or untreated mental illness might be at increased risk for violence when experiencing psychotic episodes or between psychiatric hospitalizations, many of these studies have been heavily critiqued for overstating connections between serious mental illness and violence. On aggregate, there is not a strong connection between mental illness and gun violence.

Close to 18% (43.4 million) of adults in the U.S. have some form of mental illness, which is on par with other countries, yet Americans are ten times more likely to die from guns than other citizens in high-income countries. The American Psychiatric Association found that around 4% of violent crimes perpetrated in America are attributable to mental illness and only 1% of discharged psychiatric patients commit violence against strangers using a gun. Persons with mental illness are less likely than those without a mental illness to use a gun to commit a crime. The vast majority of people with severe mental illness, including schizophrenia, bipolar disorder, and severe depression are no more likely than any other person to be violent. There is simply no clear causal link between mental illness and gun violence.

On the other hand, research shows that there are much stronger predictors of individual gun violence than mental illness, including: alcohol and drug abuse, domestic violence, past or pending violent misdemeanor convictions or charges, and history of childhood abuse.

There are a number of problems with associating mass shootings with mental illness. First, it stigmatizes millions of people living with mental health conditions. Research shows that negative attitudes surrounding mental illness prevent people from seeking treatment. Linking mental illness with violence threatens to restrict the rights and freedoms we afford ordinary citizens. Second, the burden of identifying would-be shooters has now fallen on psychiatrists who are not necessarily equipped to identify violent gun criminals. A number of states now mandate psychiatrists assess their patients for their potential to commit a violent gun crime, but psychiatrists are not great predictors of gun violence, and some research shows they are no more able to predict gun violence than laypersons. Psychiatrists who fail to identify mass shooters may now be held liable for crimes they fail to predict. Third, linking gun violence to mental health therapies may not help to reduce gun violence. Few of the persons who are most at risk for committing a violent gun crime have been involuntarily hospitalized, and therefore would not be subject to existing legal restrictions on firearms. Finally, the focus on mental health obscures other reasons for our nation’s gun violence problem. By focusing almost exclusively on mental health, we fail to identify the myriad of other factors, including historical, cultural, legal, and economic conditions that contribute to gun violence in our country.

It is easy to blame mass shootings on the “abnormal brain”–it is far more difficult to uncover or come to terms with the systemic causes of gun violence that wreak havoc on our communities. There are good reasons to ensure all Americans have access to mental health services, but access to such care is unlikely to stem the tide of mass shootings in our country. Mental illness has become a convenient scapegoat for politicians on both sides of the aisle when it comes to mass shootings, but it is time we begin to look more closely at other culprits.

Devan Stahl photoDevan Stahl, PhD, is an Assistant Professor in the Center for Ethics and Humanities in the Life Sciences and the Department of Pediatrics and Human Development in the Michigan State University College of Human Medicine.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, November 30, 2017. 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.

More Bioethics in the News from Dr. Stahl: Disability and the Decisional Capacity to Vote

Click through to view references

Posted in Bioethics in the News, Uncategorized | Tagged , , , , , , , , , | 21 Comments

Dr. Stahl presents on hoping for “miracles” at annual MSMS bioethics conference

Devan Stahl photoOn November 11, Center Assistant Professor Dr. Devan Stahl presented at the Michigan State Medical Society 21st Annual Conference on Bioethics. Held in Ann Arbor, the conference’s theme was “First do no harm: Avoiding Overdiagnosis and Overtreatment in Medicine.” Dr. Stahl gave the talk “Responding to those who Hope for a Miracle.”

Dr. Stahl presented strategies for engaging patients and families who request aggressive care with the hope of obtaining a “miracle.” As discussed in her latest article*, Dr. Stahl laid out a taxonomy of how the term “miracle” is used in the context of health care, as well as tips for healthcare providers responding to those particular invocations. The audience was presented with case studies that highlighted the different ways in which a patient may use miracle language as well as communication strategies that can help further a dialogue about appropriate and inappropriate uses of medical treatments.

* Note: viewing this article may require MSU Library or other institutional access.

Posted in Bioethics Events, Center News, Uncategorized | Tagged , , , , , , ,