Tag: genetics

If Whole Genome Sequencing is So Cheap and Quick, Why Shouldn’t Everyone Have It Done?

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

By Leonard M. Fleck, PhD

The headline in New York Times Magazine reads: “Scientists can now sequence an entire genome overnight.” This is amazing. It took ten years and $3 billion to do the first mapping of the human genome, all three billion base pairs. Today the entire genome of any individual can be mapped for less than $1000. Why is that important? There are preventative, diagnostic, therapeutic, reproductive, and public health reasons. The public health reasons are most evident with the speed with which all the variants of COVID-19 have been mapped.

Having one’s genome mapped can provide an individual with some foreknowledge of health risks to which they might be vulnerable (always keeping in mind environmental factors linked to inherent genetic risks, also keeping in mind the uncertainty and probabilities associated with the vast majority of health risks identified in this way). The risks of medical harm related to genetic ignorance can be reduced. A family of genes referred to as P450 determine whether we are normal, fast, or slow metabolizers of drugs. If we are fast metabolizers, a normal dose will be metabolized too quickly with diminished effectiveness. If we are slow metabolizers, a normal dose will accumulate to potentially life-threatening levels in some cases. Roughly 7% of 1200 FDA approved medications are affected by actionable germline inherited pharmacogenes. Even more importantly, 18% of outpatient U.S. prescriptions (more than four billion per year) are affected by actionable germline pharmacogenomics.

Whole Genome Sequencing (WGS) can assist future possible parents to determine the best reproductive option if they know they represent specific genetic risks to future possible children, e.g., if each were a carrier for a mutated cystic fibrosis gene. In addition, WGS can be used to make accurate diagnoses of very rare disorders that would otherwise require harmful, invasive, diagnostic odysseys. This will be very important in the context of infants in the NICU or children in the PICU.

A technician who has long dark hair and is wearing safety glasses, a white coat, and purple gloves, loads DNA samples into a desktop genomic sequencing machine
Image description:  A technician loads DNA samples into a desktop genomic sequencing machine at the Cancer Genomics Research Laboratory, part of the National Cancer Institute’s Division of Cancer Epidemiology and Genetics (DCEG). Image source: Daniel Sone/National Cancer Institute/Unsplash.

I remind students that unlike normal medical tests that only yield information about the person who has the test, genetic tests tell us about genetic features of a range of close relatives. Hence, if a genetic test identifies a serious health vulnerability in me, that information can be used to alert other family members of that same vulnerability of which they might otherwise have been ignorant (and which might well be medically manageable before clinical symptoms emerge that might then suggest an irreversible disease process). The therapeutic potential of WGS is most evident today in the case of metastatic cancer. WGS can provide base-pair resolution of an entire tumor genome in a single run, thereby revealing the unique mutations and genomic alterations in the cancer tissue. This will often allow the identification of a targeted cancer therapy, such as imatinib, that targets the distinctive genetic features of a cancer, such as chronic myelogenous leukemia.

In the reproductive context WGS can be used as a non-invasive prenatal screening tool to offer a comprehensive assessment of the fetus. Likewise, WGS could be used at birth as a screening tool to offer a more comprehensive assessment of the infant than the current gene panel, which is only looking for fifty-six rare genetic disorders. This increases the opportunities for timely therapeutic interventions, when available.

Given all these potential therapeutic benefits, what would be the potential ethical challenges? Cost is an issue that raises health care justice problems. Though the sequencing itself costs less than $1000, the analysis, interpretation and counseling bring the cost to $3000 (though in the case of cancer treatment the cost will be $10,000). Few health insurers cover these costs. Should access to WGS then be publicly funded, as a matter of health care justice, perhaps as part of a basic benefit package guaranteed to all? If all 330 million Americans wanted WGS, the cost would be $990 billion. Would that be either a wise or just use of limited health care resources, given all sorts of other unmet health care needs in our society?

One of the main rationales for doing WGS is preventive, i.e., to identify significant health vulnerabilities whose risk of actualization can be reduced by behavioral change. However, the critical question is whether we can be very confident that most patients would commit to the required behavioral changes. Available medical evidence suggests pessimism in this regard, which would imply that WGS with this expectation represented a poor use of social resources. No one believes McDonald’s business plans are threatened by WGS.

If WGS is used to replace current neonatal screening practices, are the privacy rights of newborns put at risk, given later in life genetic vulnerabilities that would be revealed? Would these concerns be mitigated if only medically actionable information were revealed to parents, all other information being set aside until that child reached adulthood? However, what exactly is the scope of “medical actionability?” That child might be vulnerable to some serious genetic disorders much later in life. This would not be a concern for the child as a child. But that child might have older relatives for whom this information would have considerable potential relevance. What are the ethical issues associated with either revealing or failing to reveal that information to potentially “at-risk” relatives?

A very important feature of genetic information gleaned from neonatal WGS (and all WGS for that matter) is that the vast majority of that information will be either of unknown or highly uncertain significance. This will be especially true because of the thousands of mutations that would be part of anyone’s DNA. For parents of a newborn, such uncertainty could be distressing for years and years. However, there is also the uncertainty associated with the responsibilities of primary care physicians in this regard. Who is supposed to have responsibility for tracking changes in genetic knowledge regarding those genetic variations in an individual as medical research advances? And who would be responsible for conveying this new information to parents or adult children, and judging what should be told and when? This is a very complex medical information management problem, relative to which current physician complaints regarding the electronic medical record would fade into insignificance.

Let us assume that WGS is going to be done more thoughtfully and more parsimoniously, such as a diagnostic or therapeutic context where such information would be most useful. What will still happen is the discovery of all sorts of incidental genetic information, sometimes with frightening potential consequences. Imagine this bit of medical dialogue: “Mr. Smith, we were looking for the genetic roots of your heart disease (which we found), but we also discovered your genetic vulnerability to an early-onset form of dementia.” Many patients would not want to know this. How is a physician supposed to know what a patient does or does not want to know in this regard?

Finally, WGS could generate new problems of health care justice. Imagine that the incidental finding in the prior paragraph was a 10% lifetime risk of some serious but treatable cancer. I personally would not be especially distressed by such a finding. However, other individuals might be especially anxious and demand all manner of expensive diagnostic tests on a semi-annual basis to rule out any indications of disease initiation. Would that individual have a just claim to such resources at social expense?

To return to the title of this essay, perhaps the fact that WGS is quick, easy to do, and relatively inexpensive is insufficient reason to justify the promiscuous promulgation at social expense of this technology. Perhaps more thoughtful social and professional deliberation regarding the issues identified in this essay would yield less ethically fraught uses of WGS. Then again there could be the 2030 version of the electronic medical record with room for terabytes of genetic information and thousands of new tabs and subtabs!

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Leonard M. Fleck, PhD, is Professor in the Center for Bioethics and Social Justice 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, May 6, 2021. 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. Fleck: Religious Coercion of Physicians: Whose Conscience Is It Anyway? Health Care and Social Justice: Just Take Two Aspirin for Your Tumor If You Cannot Afford Your Cancer Care; Medicare For All: This Is Going to Hurt; Greed Is God: The Divine Right to Avaricious Drug Pricing; Gene Editing: God’s Will or God’s Won’t

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Dr. Fleck presents on public funding for whole genome sequencing at International Bioethics Retreat

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Dr. Leonard Fleck, professor in the Center for Ethics, participated in a keynote debate this month as part of the 24th annual International Bioethics Retreat that was presented virtually from Paris. Each year, “experts in medicine, philosophy, law, and health policy are invited from around the world to present their current research projects.”

Within the debate format, Dr. Fleck addressed the question: “Whole Genome Sequencing: Should It Be Publicly Funded?” Dr. Fleck defended the affirmative in this debate, while Dr. Leslie Francis of the University of Utah defended the negative. Continue reading below for Dr. Fleck’s summary of the debate.

Whole Genome Sequencing: Should It Be Publicly Funded?

Below are the key elements in the affirmative side of that debate, as well as acknowledgment of legitimate points made by Dr. Francis.

We can start with the question of what Whole Genome Sequencing [WGS] is. It refers to creating a complete map of all three billion base pairs of DNA in an individual. Next, how might WGS be used? It can be used for preventive, diagnostic, therapeutic, reproductive, and public health purposes? It can be used by adults as part of a preventive strategy, i.e., identifying genetic vulnerabilities to disorders that might be managed or prevented through behavioral change. WGS can be used diagnostically to correctly identify very rare disorders that otherwise will require a costly and painful diagnostic odyssey. This is most often true in the case of infants.

WGS is used therapeutically in the case of metastatic cancer. Both the patient and cancer tumors would be mapped in order to find a genetic driver of the cancer that could then be attacked with a targeted cancer therapy, such as trastuzumab to attack a HER2+ breast cancer. WGS can be used in a reproductive context to do non-invasive prenatal assessment of a fetus. Likewise, some advocate using WGS to do neonatal genetic screening in place of the heel stick and blood draw that will test for 56 childhood genetic disorders. WGS could test for hundreds of very rare genetic disorders that can affect children. The public health context is very visible right now as we do WGS of the COVID variants now emerging.

Why public funding? The key argument is that it is a matter of health care justice. WGS costs about $1000 for the sequencing itself, and another $2000 for the analysis, interpretation, and counseling. Insurers will generally not pay for WGS. Roughly, only the top quintile in the U.S. economic spectrum can afford to pay for WGS out of pocket. This can yield significant health advantages for them, most especially avoiding various sorts of genetic harms. More precisely, the relatively wealthy might learn of one or more health risks through WGS that would suggest the need for additional testing and therapeutic interventions, all of which would be paid for by their insurance. The less financially well off may have good health insurance but be unaware of the need to use it in a timely way without the advantage of WGS. One possible result is that a curable disease becomes incurable when symptoms are clinically evident. This is an injustice that can be avoided if access to WGS is publicly funded.

My esteemed debate partner Dr. Francis emphasized that the ethics issues are much more complex than simply matters of health care justice. The distinctive feature of any form of genetic testing is that it yields considerable information about any number of first-degree relatives who may or may not want an individual to know that information. If we do WGS on a neonate, for example, we might discover that neonate has an APOE 4/4 variant for early dementia. That means at least one parent has that vulnerability, which they might not wish to know. In addition, do those parents have any obligation to notify any other relatives of their potential vulnerability? What if, instead, it was a BRCA1 mutation for breast or ovarian cancer? More problematic still, what if WGS is used at public expense in prenatal screening with the result that some parents choose to have an abortion. Would advocates for a Right to Life view have a right to object to their tax dollars being used to facilitate access to a procedure to which they conscientiously object? This is why we have debates.

CRISPR Dangers Highlight the Need for Continued Research on Human Gene Editing

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

By Jennifer Carter-Johnson, PhD, JD

The excitement and potential of CRISPR to treat severe genetic conditions by editing disease-causing DNA has taken an unexpected hit. A recent Wall Street Journal article highlighted the unexpected results from a CRISPR study in which attempts to edit a human gene responsible for blindness resulted in the loss of the entire chromosome from the cells in the embryos. These results echo another study conducted in human cell lines published earlier in 2019.

CRISPR is a targeted gene editing process that allows scientists to direct genetic modifications with far more precision than prior procedures. CRISPR has been touted as a gigantic leap in the ability to modify DNA by creating or repairing pinpoint DNA mutations without affecting other areas of the chromosome on which the gene resides. The recent study indicates that the technique might not be as straightforward in humans – and thus neither will be its use to fight disease.

Blue DNA double helix puzzle with missing pieces
Image description: A partially assembled puzzle that is an image of blue double helix DNA molecule structures. Image source: Arek Socha/Pixabay

CRISPR Technology – Promise and Problems

The value in CRISPR mediated genetic modification can be seen in a wide variety of biotechnology products, such as genetically modified crops and new biologics. But perhaps the most exciting and most controversial potential for CRISPR can be found in the desire to modify embryonic genomes to remove genetic abnormalities for which we currently have no cure.

This promise of embryonic gene editing is appealing not only because it would remove the condition from the child born from the gene-edited embryo, but also because the offspring of that child would also be free of the condition. CRISPR gene editing – because it is done at the embryonic stage – creates germline mutations that are passed to future generations. In a therapeutic use of CRISPR, those mutations would be cures for often untreatable diseases.

However, it is this very promise that raises many of the problems with CRISPR embryonic gene editing. Much debate has surrounded embryonic gene editing. Until this recent news, there were fears that CRISPR may make gene editing too easy. The technological development of CRISPR in embryonic gene editing is moving at a breakneck pace as scientists around the world are working on procedures. Biohackers work in their garages and livestream the use of CRISPR to edit their own genomes.

Many are debating which genes should be targeted and how fast the research into actual trials should proceed. Most agree that severe diseases would be the best place to start, but should the technology be deployed for cosmetic benefits such as eye color, or diseases for which a treatment exists? The dangers of CRISPR editing are unclear, and there has been an informal moratorium on the use of the technology to create children. Despite that, there has been at least one rogue scientist who has created genetically modified embryos and brought them to full term birth.

International Policy on Human Gene Editing

The scientific research is not occurring in a vacuum. Each country decides how CRISPR can be used in its medical system – both when the technique is safe enough and on which diseases it should be used.

An international commission recently pronounced that the technology is not ready for clinic implementation because scientists don’t understand the full safety issues surrounding its use in human embryos. The commission described some of the potential clinical uses in the future and outlined a basic safety protocol for approval.

One of the creators of CRISPR, Jennifer Doudna, has also spoken out against applying CRISPR too hastily to embryonic gene editing. 

Based on the recent studies showing loss of chromosomes, the international commission and other scientists are correct to call for a moratorium on clinical embryonic gene editing.

Blue and green DNA double helixes and binary code
Image description: An abstract image of blue and green double helix structures and binary code (zeros and ones) against a black background. Image source: Gerd Altmann/Pixabay

CRISPR – The Path Forward

The setback in CRISPR gene editing does not mean that the technology and research should be discarded. The potential to change lives is too great; however, the dangers of use with our current understanding are even greater. So how do we move forward with CRISPR in embryonic gene editing? The answer must include balance – in research strategies and in voices.

While the technology is not ready for clinical use, and we have not yet determined which uses would be appropriate if it were available, the science should not stand still. The research surrounding CRISPR gene editing will yield insights into human biology that we cannot predict. For example, the loss of chromosome length in human embryonic cells undergoing CRISPR treatment seems to be different than the response of other species of embryonic cells. And debates about the appropriate use of the technology will allow us to discover more about ourselves as humans. 

As we debate the best way to develop and deploy CRISPR technology, we should look to a variety of stakeholders. Scientists have a solid track record in understanding when recombinant DNA technology has potentially hazardous implications. In the 1970s, the Asilomar Conference allowed scientists to put together research guidelines that allowed the technology to be developed without harming public health. In fact, the international scientific consensus not to use the technology such as described above indicates that scientists are beginning that work. Such a moratorium on clinical uses gives us time to understand how to deploy the technology in the safest manner.

Additionally, there is a role for the voices of the patients whose lives could be changed by the technology. Patients may not be in the best place to judge when the technology should be deemed safe enough to deploy, but they certainly will have input about which mutations cause hardships that merit the risk of germline editing. Many of these patients already work with scientists on potential treatments for their diseases. CRISPR discussions may open another avenue for many.

Finally, there is a role for legal regulation of the use of CRISPR. Governments should listen to the voices of scientists and potential patients in drafting these regulations. But as shown by the example of at least one rogue scientist, there needs to be teeth to the moratorium on CRISPR clinical use at this time. CRISPR and its use in human gene editing raise complicated issues and hold great promise as a powerful tool to defeat genetic diseases. The development of those technologies will not be straightforward or without risk and will require more basic science research to achieve clinical efficacy. But with proper planning, we may learn more about ourselves as humans on the path to a cure.

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Jennifer Carter-Johnson, PhD, JD, is Associate Dean for Academic Affairs and Associate Professor of Law in the Michigan State University College of Law. Dr. Carter-Johnson is a member of the Michigan State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Tuesday, December 15, 2020. 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. Carter-Johnson: Biohacking: How a DIY Approach to Biology Can Shape Our Future; Web of Interests Surrounding Medicines Makes Patient Access Increasingly Difficult; Humanity in the Age of Genetic Modification; Defining The Spectrum of “Normal”: What is a Disease?; Dawn of False Hope: Spread of “Right To Try” Laws across the U.S.

Continue reading “CRISPR Dangers Highlight the Need for Continued Research on Human Gene Editing” →

Dr. Cabrera a co-author of human enhancement editorial in ‘Frontiers in Genetics’

Laura Cabrera photoCenter Assistant Professor Dr. Laura Cabrera and co-author Dov Greenbaum have written an editorial published in Frontiers in Genetics, titled “ELSI in Human Enhancement: What Distinguishes It From Therapy?”

The open access editorial, published June 23, is available in full from Frontiers in Genetics.

Listen: Genes, Behavior, and the Brain

No Easy Answers in Bioethics logoNo Easy Answers in Bioethics Episode 17

We can look at an individual’s DNA and know what their hair color is, but what about their behavioral traits? This episode features Center for Ethics Assistant Professor Dr. Laura Cabrera, and Dr. Mark Reimers, Associate Professor in the Neuroscience Program in MSU’s College of Natural Science. Drawing from their expertise as neuroscience researchers, they discuss what we know about how our DNA affects our behavior—from IQ scores to mental illness. They also explore possible ethical issues that may arise in the near future related to the study of behavioral genetics and gene expression.

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. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

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.

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

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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.

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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.

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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.

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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.

Humanity in the Age of Genetic Modification

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

By Jennifer Carter-Johnson, PhD, JD

Scientists have recently announced that they had used the new gene editing technique, CRISPR, to remove remnants of ancient viruses that had integrated into the pig genome. An amazing feat of genetic engineering to be sure—but the article is notable as a first step in “humanizing” pig organs for use in organ transplant by removing pig-specific viruses before they can infect human organ recipients. The idea of humanizing pigs should make us wonder—what does it mean to be human? How much genetic modification can pigs undergo and still be pigs? How do we define humanity for our neighbors and ourselves? How much genetic modification would it take to remove the label of humanity?

These questions are not asked in a vacuum nor is the research being conducted solely for philosophical inquiry. We need organs to save lives. There are over 116,000 people on the organ donor list and only 33,611 organ donations each year. About 20 people die every day in the U.S. waiting for a match so that they can receive a new heart, kidney or lung. Additionally, not everyone who actually receives a transplant has a successful outcome.

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Image description: a Lego figurine of a person dressed in a pig costume is shown in the foreground against a yellow and white background. Image source: clement127/Flickr Creative Commons.

Transplant rejection occurs because each person has a fairly unique set of signal markers on their cells that allow the immune system to identify “self.” Bacterial or viral infections trigger immune responses in part because they change the infected cell’s signal markers from “self” to “foreign.” A transplanted organ also looks “foreign” to the recipient’s immune system due to the difference in signal markers, and this immune response leads to transplant rejection. For instance, identical twins would have very little risk of transplant rejection, while two unrelated people of different backgrounds would likely be unable to donate to each other. Thus, doctors search for the greatest amount of match between recipient and donor, and then suppress the recipient’s immune system to further decrease the risk of transplant rejection.

Using animal organs introduces yet more foreign signals to the organ recipient, leading to the desire to humanize those organs with markers that signal “human” and “self” to the recipient. In fact, doctors have been using pig heart valves in transplants since the 1970s. These hearts valves are extracted and then stripped of live cells to decrease the risk of rejection. This preparation procedure limits types of transplants that can be performed, and even with preparation, rejection issues may eventually arise.

Therefore, today’s scientists are working to use genetic engineering to modify pig organs to express the same cell markers that signal “self” to a human recipient. The referenced article described the development of pigs without endogenous retroviruses that some fear could infect recipients. From that basis, scientists could use several different techniques to develop pigs with humanized organs. One technique would be to genetically modify an embryo such that the pig’s cells express more “human” markers and less “pig” markers. Another technique that has been pioneered recently would be to inject human cells into a pig embryo such that the resulting chimeric pig would grow a genetically human organ.

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Image description: three pigs are shown outside through metal fencing. The main pig appears to be smiling. Image source: Peppysis/Flickr Creative Commons.

Both of these techniques raise the question of what it means to be human. Merriam-Webster defines the noun human as “a bipedal primate mammal (Homo sapiens) : a person.” Furthermore, the adjective definition of the word human, “having human form or attributes,” broadens that definition in an ambiguous way that leaves us no closer to an answer than before. After all, the point of humanizing cells is to give them human attributes for organ transplantation. Surely, that isn’t enough to make the pig a human? Pigs with genomes edited to have organs that look more “human” will likely still act like pigs. But we don’t truly know how multiple genetic changes will present. Looking to the chimera technique, would a chimeric pig with the heart and kidneys of a human still be a pig? What if some of those human cells colonized the brain and some percentage of neurons were human? How do we answer the question of humanity? Do we ask what percentage of the body is human? Do we see if the animal still acts like a pig or test its skills on the SAT?

In contrast, does a person who receives a pig heart transplant cease to be human and become a pig? Humans do not have a great track record of recognizing humanity in others. Perhaps in recent times, we in the United States have not had to consider what qualifies as human. A baby born from a human mother is a human. But this concept has not always been so straightforward. Constitutional definition of a slave as 3/5 of a person and the idea of blood quantum to limit Native American rights go back to the beginning of our country. More broadly, Hitler wanted to develop a master race and viewed Jews as subhuman – leading to horrific abuses and mass murder. Today, some countries still view women as property rather than humans with rights.

Genetic technologies will challenge how we view ourselves, our neighbors, and the next generation. Genetic testing has revealed Neanderthal genetic code in many of us due to interbreeding thousands of years ago. CRISPR-based tools will eventually allow parents using artificial reproductive technologies to select genetic traits for their children. How many modifications would it take for a child to cease to be human? Perhaps super strength or gills to breathe under water sound like fantastic science fiction now, but so too did the tablets and communicators of Star Trek in the 1960s and the watch phone/TV from Dick Tracy in the 1940s. Returning to the idea of organ transplants, would a skin bag full of organs derived from a human’s cells but with no brain be considered a human? Would your answer differ if there was a brain but no higher order brain function? Such an option could reduce organ rejection to nil if a person’s cells could be used to create their own replacement organs.

The dangers of relegating a population to second tier status because they are genetically different from the norm have been explored across fiction from Animal Farm to the X-Men. Humanity’s history suggests that those stories are rooted in our inability to see humanity in those we deem as other. Advances in science mean that we need to define what it means to be human in order to avoid abuses equal to slavery or Nuremberg. Our world is changing and so too will humanity – whether or not we are prepared.

j-carter-johnsonJennifer Carter-Johnson, JD, PhD, is an Associate Professor of Law in the College of Law at Michigan State University. Dr. Carter-Johnson is a member of the Michigan State Bar and the Washington State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, November 9, 2017. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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How do we explain to patients what genetic test results might mean for their baby when they have only been validated in other populations?

Bioethics Brownbag & Webinar Series logoExpanded Carrier Screening for an Increasingly Diverse Population: Embracing the Promise of the Future or Ignoring the Sins of the Past?

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Race and ethnic groups have been tracking heritable conditions endemic within their communities for decades, but past public health screening programs—e.g., sickle cell testing for African Americans 1970s—were adopted with little thought to scientific accuracy or potential discrimination. Currently, carrier genetic testing is generally offered under professional guidelines aiming to balance potentially clinically actionable information with concerns about healthcare costs and patient anxiety: recommended testing on the basis of family history, self-reported race or ethnicity, or for a condition deemed worthy of universal screening. But some private companies have begun to offer expanded carrier screening, testing all conditions for all patients. Scientists at one such company reported in 2016 in JAMA that expanded carrier screening might increase detection of potentially serious genetic conditions. But what are the implications of returning ancestry information when patients seek medical advice? How do we explain to patients what results might mean for their baby when they have only been validated in other populations? This talk will explore policy options at the intersection of race, reproduction, and commercial use of data.

sept-13-bbagJoin us for Kayte Spector-Bagdady’s lecture on Wednesday, September 13, 2017 from noon till 1 pm in person or online.

Kayte Spector-Bagdady, JD, MBioethics, is a Research Investigator in the Department of Obstetrics and Gynecology at the University of Michigan Medical School and also leads the Research Ethics Service in the Center for Bioethics and Social Sciences in Medicine (CBSSM). Her current research explores informed consent to emerging technologies with a focus on reproduction and genetics. Kayte received her J.D. and M.Bioethics from the University of Pennsylvania Law School and School of Medicine respectively after graduating from Middlebury College. She is a former drug and device attorney and Associate Director of President Obama’s Bioethics Commission.

In person: This lecture will take place in C102 East Fee Hall on MSU’s East Lansing campus. Feel free to bring your lunch! Beverages and light snacks will be provided.

Online: Here are some instructions for your first time joining the webinar, or if you have attended or viewed them before, go to the meeting!

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