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.

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.

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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  1. Belluck, P. In breakthrough, scientists edit a dangerous mutation from genes in human embryos. New York Times (Aug. 2, 2017).
  2. Church, G. 2017. Compelling reasons for repairing human germlines. New England Journal of Medicine 377: 1909-11.
  3. Cwik, B. 2017. Designing ethical trials of germline gene editing. New England Journal of Medicine 377: 1911-13.
  4. Jasanoff, S., Hurlbut, B., Saha, K. 2015. CRISPR democracy: gene editing and the need for inclusive deliberation. Issues in Science and Technology 32 (1): 11pp.
  5. Gyngell C., Douglas T., Savulescu J. 2016. The ethics of germline gene editing. Journal of Applied Philosophy 34: 498-513.
  6. Hyun, I., Osborn C. 2017. Query the merits of embryo editing for reproductive research now. Nature Biotechnology 35 (11): 1023-25.
  7. Joseph, Andrew. Gene-editing, religion and one scientist’s quest to reconcile the two.  PBS News Hour (Oct. 14, 2016).
  8. Ma H., Marti-Gutierrez N., Park S. W., et al. Correction of a pathogenic gene mutation in human embryos.  Nature 548: 413-19.
  9. Peters, T. 2017. Should CRISPR scientists play God? Religions 8: 61; doi: 10.3390/ rel8040061.
  10. Rawls, J. Political Liberalism. New York: Columbia University Press, 212-54.  This is the chapter titled “The idea of public reason.”
  11. Wolpe, P.R., Rommelfanger, K.S., and the drafting and reviewing delegates of the BEINGS working group.   Ethical principles for the use of human cellular biotechnologies.  Nature Biotechnology 35 (11): 1050-58.

7 thoughts on “Gene Editing: God’s Will or God’s Won’t

  1. Truly, the ‘advent’ of gene-editing technology has many humanitarian and scientific implications. Complicating the basis for its evolving conversation, there is no widely understood and accepted definition for HEALTH. Even the most current “A Merriam-Webster” dictionary uses succinct words such as “well-being” and “absence of disease.” Furthermore, the use of ‘healthy’ for describing inanimate objects begs a variety of anthropomorphic questions, especially in the absence of a widely accepted definition of HEALTH. Given its context as related to a human being, I offer the following:
    A PERSON may be defined as a fertilized ovum representative of the biologic species,
    .HOMO SAPIENS, with the clusters of Human Capabilities sufficient
    .for stable survival until after birth.
    HEALTH may be defined as a person’s daily expression of variably stable survival that is
    ….Endowed by the person’s individually unique clusters of Human Capabilities and
    .their transformation during maternal gestation to become a dependent person,
    .sufficient for survival after birth;
    ….Nurtured by the caring relationships originating before birth
    .from among the person’s family with a commitment to fulfill
    .the person’s caring, learning and creative cluster of Human Capabilities
    .for becoming an independent person and after birth
    .from among the person’s extended family and family neighborhood network
    .with a commitment to offer continuing support for the person’s family,
    .especially during the person’s early childhood;
    ….Matured by the iterative occurrence of disruptive events and
    .their interacting effects on the evolving resilience of the person’s
    .baseline homeostasis and innate temperament,
    .as ameliorated concurrently through the caring relationships
    .originating from within the person’s extended family; AND
    ….Sustained by the family traditions of the person’s extended family and
    .by the Common Good of the person’s community
    .until the person’s clusters of Human Capabilities are no longer sufficient
    .for survival from the cumulative effects of disruptive events and entropy.
    Of course, the word healthcare doesn’t occur. Ultimately, a person’s survival is dependent on how well their family pursues its responsibility to maintain a Personal Survival Plan (PSP) for each of its members. Each person’s PSP identifies a medical TRIAGE process for their health care as a strategy to achieve enduring Stable HEALTH. The equitably available, ecologically accessible, justly efficient, and reliably effective attributes of this health care is a whole different problem for the COMMON GOOD of each community. Obviously, our progress for solving the scientific mandate of our nation’s healthcare has not been matched by our progress for solving its humanitarian mandate. President Thomas Jefferson said it most precisely many years ago. This is what he said:
    .”I am certainly not an advocate for frequent and untried changes in laws and constitutions. I think moderate imperfections had better be borne with; because, when once known, we accommodate ourselves to them, and find practical means of correcting their ill effects. But, I know also, that laws and institutions must go hand in hand with progress of the human mind. As that becomes more developed, more enlightened, as new discoveries are made, new truths disclosed, and manners and opinions change with the changes of circumstances, institutions must advance also, and keep up with the times. We might as well require a man to wear still the coat which fitted him when a boy, as a civilized society to remain ever under the regimen of their barbarous ancestors.”

    1. I am not quite sure how to respond to your comment because your comment does not seem to have engaged directly the point of my essay. What I hoped to provoke thought about is this question: What should we (citizens of a liberal, pluralistic society seeking to be genetically responsible) judge to be the ethical responsibilities of parents for the genetic endowment of their future possible children? Further, when will it be ethically responsible for our society to permit the gene-editing of embryos, and for what purposes?

  2. As argued by Dr. Insoo Hyun on a recent visit to Michigan State University, performing gene-editing to remove a harmful mutation in an embryo means that IVF procedures must be performed. If so, why not use standard genetic screening to identify non-affected embryos? For most genetic diseases, one or both parents will likely be heterozygous, so the couple can produce oocytes and sperm that lack the deleterious mutation. It is hard to justify introducing the potential harm of a botched gene edit when a more straightforward approach is available.

    One might imagine a scenario where multiple editing reactions are applied to a single embryo to change several loci simultaneously (as has been done in experimental plants and animals). There, sorting through a few embryos won’t be enough to find a particular “optimal” combination of alleles. There, ethical considerations should weigh the likely unpredictable outcome of such approaches; genetic systems that have evolved and optimized over a long time are hard to “improve” on, unless we are talking agriculture, where we will willingly sacrifice overall fitness for specific market properties.

    Incidentally, the cited research from the Mitalipov laboratory has had considerable criticism; skeptics note that the proposed “repair” from the maternal allele may actually represent a large deletion that was not repaired at all.

  3. David, I am mindful of at least some of the scientific criticism of the research that was the starting point for this essay. However, given word limits, I had to settle for a more generic concern regarding off-target effects that had to be noted and carefully managed before this technology is available for clinical use. You are correct to emphasize that attempting multiple edits in the DNA of an embryo would be extremely risky, given the nature of genetic systems. There is simply too much at this point in time that we do not know about all those genetic connections to justify imposing those risks on some future possible child. And this is likely to remain true for a significant period of time into the future. However, to return to a major point of the essay, one way of doing that research and obtaining that knowledge is to create embryos that have been genetically edited in various ways and observe in vitro their development, at least for 14 days. Those embryos will be destroyed. This does raise a number of ethical and public policy challenges that need to be addressed by all of us as thoughtful citizens in a liberal, pluralistic society. Invoking God’s will tends to be a conversation stopper when we really need strategies for facilitating respectful public conversation regarding issues in which multiple reasonable social values are in conflict.

  4. Folks: Here is a P.S. to my essay. Work just published (using mice) suggests that it might be less problematic to edit the epigenome (which controls expression of genes) than to edit the DNA as such. Here is one brief report on that research:

    “The kindest cut may be no cut or, in the case of genome editing, no double-strand break (DSB). Although a DSB in DNA is the usual result when the CRISPR/Cas9 genome-editing system is used, modified versions of CRISPR/Cas9 avoid cutting into the genome and instead manipulate the epigenome. Rather than change genes—and risk introducing potentially harmful mutations—epigenome-targeting CRISPR/Cas9 systems change gene expression.

    Such epigenome-targeting CRISPR/Cas9 systems could have therapeutic applications, if only they could demonstrate sufficient safety, practicality, and efficiency. This last quality—efficiency—was emphasized in a recent study completed by Salk Institute researchers. These scientists developed a novel CRISPR/Cas9 system that preserves DNA integrity while activating target genes in mouse models of human disease. According to the scientists, their system ameliorated disease symptoms in mice afflicted with diabetes, muscular dystrophy, or acute kidney disease.” Those are the first couple paragraphs of that report.

    1. Hi Len, nice point. Such non-mutagenic approaches to changing gene expression are essentially the core of current drug therapy. Only, most drugs today are small molecules that are taken orally or by injection. And often they are relatively non-specific, affecting whole classes of genes. In the future, we may see more examples of regulation by biological machines that act within the nucleus to modulate gene expression in very targeted manners. In most cases, one can reverse their action by stopping the drug, so no issues about germline editing. This leads to another Bioethics topic; how are we to pay for such high-tech medicine?

  5. David, Your last question is the multi-billion dollar ethical and economic question. This is an issue I am addressing in a manuscript for Oxford University Press. As things are now, if the costs of these interventions had to be paid out of pocket by individuals, the proverbial 1% would be the only individuals who would be likely to afford these interventions. That raises the other question: Will insurance pay for it? of course, there is no thing as “insurance.” Instead, there are more than a thousand private insurers in the United States. Most of them have contracts with private employers who then decide whether or not these sorts of interventions would be a covered benefit. Of course, economists will tell you that employers do not really pay these costs. These costs are covered by reducing salaries/ wages of employees. Employers could ask their employees whether or not they want some form of germline or embryonic editing covered by their insurance plan. The predictable effect of asking that question would be deep divisions among employees, with a large majority believing they would likely have no need for such an intervention, and consequently, not wanting to see their income reduced to provide that benefit “for others.” We will also note the obvious: cost is related to quantity of need or desire. We have to ask the question: What do we imagine should be the boundaries on the use of this technology at social expense. There are thousands of potential genetic disorders with varying degrees of severity and likelihood of expression over the course of a life. Should all of them be available as options for gene editing for future possible parents, and paid for from some insurance funding mechanism? The ethical and economic challenges are mind-boggling, likely more so than the scientific challenges that will yield this future.

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