Germline Editing Objections — Vol. 3
My colleague Adam Thierer recently pointed out, “Technological innovation is the single most important determinant of long-term economic growth and improvements in living standards.” This phenomenon can be most clearly seen in the field of medicine where technological innovation translates directly into lives saved.
Breakthroughs on gene editing and related treatments likely mean especially vast improvements in the management of genetic diseases like cancer and hemophilia. Just recently, Bluebird Bio announced “unheard of” results for its CAR-T therapy designed to treat multiple myeloma, a cancer of the plasma cells in bone marrow. The therapy generated a 94% response rate and helped 54% of patients remain in remission months after receiving the treatment.
Progress like this makes it continually more likely that gene editing and genetic medicine, including germline editing, will be as safe and effective as current treatment options in the not so distant future. In fact, Dr. Jennifer Doudna, the co-discoverer of the CRISPR gene editing system, believes that this prediction is “almost certain.”
Thus, “The major, long term obstacle to using germline editing in the clinic is restrictive public policies driven by negative public opinion.” In this series I have explored what I believe are the most common and most compelling objections to germline editing. In my first post I argued that germline editing does offer benefits that pre-implantation genetic diagnosis alone cannot. In my second post I argued that germline editing for therapeutic uses should not be labeled a eugenic practice. In this entry, I will explore the objection that germline editing should not be used because future generations cannot exercise their right of informed consent.
Objection: Future Generations Cannot Consent
One of the guiding lights in medical ethics dating back to the Hippocratic Oath is that the physician will never do injury or injustice to a patient. In modern research and medicine, this commitment to justice has come to include the obtaining of informed consent, meaning that affected patients both understand and explicitly give permission to a professional to perform an experiment or treatment.
Modern critics of germline genome editing have challenged the ethicality of the procedure saying that obtaining informed consent is extremely difficult, perhaps impossible, and that this problem outweighs any possible benefits that may accrue from germline editing.
Joanna Smolenski, a Ph.D. candidate at the CUNY Graduate Center, argues that informed consent is especially problematic in the research and clinical trial phase of germline editing. Among the first problems is the question of from whom doctors need to obtain consent. Some critics, like Smolenski, do not believe that embryos possess the same moral status of personhood as an individual who has already been born. This may mean that a different threshold of informed consent is needed when treating embryos. For other critics, embryos do possess the status of person and should be treated as such; nevertheless, obtaining informed consent in the same way as other individuals is clearly impossible.
Both sets of critics do agree that somehow, some form of informed consent from the child is needed, especially in the research phase. Smolenski points out that to rigorously evaluate the safety and efficacy of germline editing, a long-term, multi-generational study is likely needed. “Thus, undertaking such research at the embryonic level seems to commit the future person in question to ongoing monitoring throughout their lives, and plausibly the lives of their children as well.” Surely such invasive monitoring demands consent from that individual. Unfortunately, when that individual is in a position to understand risks and benefits and give proper consent, the procedure has already “irreversibly … been made.”
Anticipating challenges to this argument, Smolenski acknowledges,
[P]arents make decisions on behalf of their children all the time, both prior to birth (e. g., through the use of techniques like preimplantation genetic diagnosis) and after (selecting certain extracurricular activities, schools, childhood playmates, and so on). As guardians of their children, we consider it permissible for parents to make such decisions, and one might argue that germline modifications are just another kind of parenting intervention in line with others that parents routinely make.
She responds by countering that these sorts of choices about schools and playmates are reversible if the child should grow up and decide to sever these relationships. Germline editing is entirely different and cannot be undone, at least not easily.
Smolenski also recognizes that we generally accept parents who intervene on the child’s behalf with the understanding that the parent has the child’s interest at heart and wants to confer some benefit on the child. However, she argues that because of the extreme nature of germline editing, the parent cannot know whether it is truly in line with the child’s interests or even whether the procedure will be to the child’s benefit at all.
The Scope of Parental Prerogative: Law
The law has long recognized that parents possess wide powers when it comes to children and child-rearing. In the 1979 case Parham v. JR, the U.S. Supreme Court traced this deference back several hundred years to English common law as explained by William Blackstone in his Commentaries. Modern jurisprudence severely restricts governmental power in issues traditionally associated with intimacy and family life: children, sex, and death.
This tradition of deference to parents by U.S. courts began in the early 20th Century with Meyer v. Nebraska, in which the Supreme Court invalidated a Nebraska state law making it illegal for schools to teach any language except English to school children who have not yet passed the eighth grade. In the majority opinion the Court famously found the Fourteenth Amendment’s definition of liberty contained in the Due Process Clause to at least include, among other things, the rights “to marry, establish a home and bring up children … The established doctrine is that this liberty may not be interfered with, under the guise of protecting the public interest, by legislative action which is arbitrary or without reasonable relation to some purpose within the competency of the State to effect.”
In the almost one hundred years since Meyer, the Court has returned to this doctrine of familial liberty laid down in this case to explain the rights within the family structure, specifically citing Meyer in 116 cases. In one of those cases, Wisconsin v. Yoder, the Court observed that, “The history and culture of Western civilization reflect a strong tradition of parental concern for the nurture and upbringing of their children. This primary role of the parents in the upbringing of their children is now established beyond debate as an enduring American tradition.” It then quoted a discussion of Meyer from Pierce v. Society of Sisters noting that the child “is not the mere creature of the State” and characterizing parents, “those who nurture him and direct his destiny,” as possessing the right to “prepare him for [the] … obligations” of life. To prepare the child for such obligations, “the parental role implies a substantial measure of authority over one’s children” without excessive interference by the state.
The Court clearly stated in Cleveland Board of Education v. LaFleur that “freedom of personal choice in matters of marriage and family life is one of the liberties protected by the Due Process Clause of the Fourteenth Amendment.” Law professor John Lawrence Hill more fully explained the details of what the Court has interpreted this right to mean in practice in an article for the New York University Law Review:
The zone of family privacy and parental authority has been afforded both substantive and procedural protection under the due process clause. This cluster of constitutional protections includes the right of the family to live together, the right of parents to raise their children as they deem fit, and the right of parents to educate their children without state interference. The procedural protections recognized pursuant to the due process clause require that parental rights may not be terminated without notice and a hearing, and without at least clear and convincing evidence of parental unfitness.
The Court has also ruled that the privacy protections found in the Fourteenth Amendment extend to the parents’ right to terminate a pregnancy. In Roe v. Wade the Court “conclude[d] that the right of personal privacy includes the abortion decision.” The Court did, however, restrict this right when the pregnancy entered the third trimester, reasoning that the state’s interest in “protecting the potentiality of life” had grown substantially enough to be “compelling.”
Twenty years later the Court reaffirmed Roe’s “essential holding … of the right of the woman to choose to have an abortion before viability and to obtain it without undue interference from the State” in Planned Parenthood of Southeastern Pennsylvania v. Casey. While maintaining that essential holding, Casey both imposed an “undue burden” standard of review on abortion regulations and changed Roe’s trimester-based standard to a viability standard. This allowed the state to regulate abortion at any time during the pregnancy, in contrast to Roe, provided that these regulations did not impose an undue burden on the parents’ ability to seek an abortion before the point of viability. After the point of viability, the Court quoted Roe stating that the legislature may choose to “regulate, and even proscribe, abortion except where it is necessary, in appropriate medical judgment, for the preservation of the life or health of the mother.”
In 2007 in Gonzales v. Carhart, the Court applied the undue burden standard of Casey to uphold a federal legislative ban on intact dilation and evacuation, a specific type of abortion procedure. The decision declared that the ban did not impose “an undue burden on a woman’s right to abortion based on its overbreadth or lack of a health exception” when judged against the state’s interest in “preserving and promoting fetal life,” “protecting the integrity and ethics of the medical profession,” and “promoting respect for human life” in general.
While this evolution of case law arguably expanded the role of the courts and the state in the abortion decision, each case unquestionably affirmed the “essential holding” of Roe: that in the early stages of pregnancy the parents’ have broad power over the life of the fetus subject to very minimal input from the state.
The Scope of Parental Prerogative: Medicine
As medicine has become less patriarchal and more of a partnership between patient and physician, the concept of informed consent has become a necessary piece of ethical medical care and research. Since very young patients are incapable of giving informed consent in the same way that adult patients are, the medical field recognizes the authority of parents to give informed permission on behalf of their child.
In 1985, Dr. William Bartholome presented a statement of “Informed Consent, Parental Permission, and Assent in Pediatric Practice” to the American Academy of Pediatrics Committee on Bioethics that was eventually accepted as Academy policy. Bartholome was extremely dedicated to children and designed the statement to promote the “experience, perspective, and power of children.” Nevertheless, he recognized the importance of the child’s parents, since, “Decision-making involving the health care of young patients should flow from responsibility shared by physicians and parents.”
Parents share decision-making responsibility since most agree that their judgements represent the “best interests of the child.” While Bartholome notes that on occasion parents do “breach their obligations toward their children,” he recommends that physicians “carefully justify the invasion of privacy and psychologic disruption” that accompanies a decision to contradict “parental prerogatives.”
The most recent, revised statement entitled “Informed Consent in Decision-Making in Pediatric Practice” published by the Academy in the journal Pediatrics agrees that the physician and parents act as “co-fiduciaries” on behalf of the child in health decisions. The statement similarly recommends that physicians “respect … both the privacy of the family unit, within limits, and parental authority and responsibility for medical decision-making.”
Research ethics detailed by an expert commission in the Belmont Report in 1979 also affirm the authority of parents to act as advocates on behalf of their children.
Partly in response to the horrible tragedy of the Tuskegee syphilis experiments, Congress passed a law establishing a committee to identify the foundational ethical principles that ought to govern all biomedical research involving human subjects going forward. The committee completed its work and published their recommendations in the Belmont Report in the Federal Register in 1979.
On the subject of informed consent, the report notes that “special provision” may need to be made for those participants who are too young to provide proper consent. Third parties (in the case of children this would be parents, if possible) ought to be used to “protect [participants] from harm.” The report recognizes that these third parties are “authorized to act on behalf of the subject,” and possess the ability to “act in that person’s best interest.” For this reason, the third party ought to be involved in the research so they can make decisions about continued participation.
Especially in the last fifty years, medicine has evolved to recognize the autonomy of patients and the importance of including them in treatment decisions as much as possible. For young patients prior to their ability to provide consent, physicians have recognized and respected the wide right and responsibility of the child’s parents to act on behalf of their children, alongside the physician, in order to provide their children with the best possible medical care.
The Germline Editing Decision
Clearly, children cannot consent to the germline editing procedure. It is impossible for children to consent to anything that happens during pregnancy and several years after birth. The crucial question is whether it is still permissible or ethical for parents to choose germline editing despite this impossibility of consent.
The legal and medical history explored above seem to establish wide authority of parents to make decisions affecting their children. Much of this deference stems from the assumption that parents generally act in the best interest of the child, meaning that the action will likely benefit the child in the long run.
Most, if not all, therapeutic uses of germline editing qualify as in the best interest of the child. Being spared a debilitating genetic disease is better than having to live with such a disease for any amount of time. It also seems reasonable to assume that the child would have chosen to therapeutically use germline editing if they could have made the decision for themselves.
Furthermore, therapeutic uses of germline editing can also be considered as in the child’s best interest even if the procedure does not work as intended, provided that the technology has reached a clinically acceptable level of efficacy. Patients regularly undergo procedures that could be both ineffective and dangerous, particularly when they are faced with serious, often terminal diseases. For example, CAR T cell therapies, several of which have been approved by the Food and Drug Administration, show promise in managing certain types of cancer. Yet, these therapies often include dangerous side effects including neurological problems and a condition called cytokine release syndrome that results from chemicals released during the death of cancer cells. The health benefits that can result from these treatments, combined with the growing probability that these treatments will work as intended, render CAR T therapies in the patient’s best interest. Similarly, germline editing, when it can achieve clinically acceptable efficacy standards, can also be considered in the patient’s best interest.
Once treatment crosses from therapeutic uses to enhancement uses, determining the child’s best interest is less straightforward. While greater stamina, more muscle mass, or improved immunity against diverse pathogens would arguably benefit the child in the long run, it is not immediately clear that these benefits would offset the risks of germline editing in the same way they would in use against a debilitating disease.
Even in this grey area the law has recognized a substantial amount of parental authority to decide what will best prepare children to meet the obligations of life, protecting the parent’s right to take actions that many would perceive as clearly against the child’s best interest (like removing a child from school for religious reasons after they complete the eighth grade).
Removing a child from school, a decision which may not be in the child’s interest, is nevertheless reversible should the child choose to return to school once they are capable of making decisions for themselves. The decision to utilize germline editing is, at least, very difficult to undo. Still, courts have permitted parental decisions, like abortion, that profoundly affect the child and are decidedly irreversible.
(Granted, this deference stems largely from abortion being a constitutionally protected right under the privacy protections of the Fourteenth Amendment, at least during the early stages of pregnancy. But it is not out of the realm of possibility that these same protections could extend to the germline editing decision, since it includes elements of already protected abortion decisions and certain parenting decisions.)
This standard of reversibility tends to obscure the fact that all children are confronted with a set of circumstances over which they have no control, even in births of the old fashioned kind. The child born with Huntington’s disease was denied the chance to exercise any form of autonomy and will likely not be able to reverse these circumstances without resorting to gene editing. Harvard professor Michael Sandel, writing in The Atlantic, said,
At first glance the autonomy argument seems to capture what is troubling about human cloning and other forms of genetic engineering. It is not persuasive … it wrongly implies that absent a designing parent, children are free to choose their characteristics for themselves. But none of us chooses his genetic inheritance. The alternative to a cloned or genetically enhanced child is not one whose future is unbound by particular talents but one at the mercy of the genetic lottery.
Thus the fact that germline editing is irreversible should cause parents to carefully consider such a decision, but it should not immediately doom the procedure in the minds of ethicists.
Conclusion
This series has explored several weighty objections to the use of germline editing in humans. I agree that these objections raise some valid points and that they should be thoroughly considered. Critics from all sides of the debate need to converse on these issues. Dr. Eric Lander of the Broad Institute stated this sentiment superbly in a recent article on an entirely different topic: “I might disagree with some of their answers. But that’s OK. It’s an argument worth having.”
The argument is worth having because vast improvements in human health and well-being are the reward to discovering an ethical path forward for germline editing. Several somatic cell gene therapy products already seem to be improving the lives of individuals who have suffered from genetic disease for several years. With germline editing, we could potentially prevent such suffering well before the first symptoms begin to show.
This article attempted to demonstrate that it seems reasonable to allow individual parents, motivated by the bonds of parental love and the desire to help their children succeed, and their physicians to make decisions about germline editing for therapeutic uses, as this is likely in the child’s best interest.
That does not imply that a parent’s authority should be limitless in this arena. Broad guidelines that seek to preempt the worst possible, future abuses of this technology could be enacted to protect children (such “corner cases” could include mixing certain non-human genes with the developing embryo’s genes). Additionally, physicians could demand a higher standard of informed permission from parents in light of germline editing’s permanence and risks, as Stanford University’s Niklaus Evitt and his colleagues have suggested.
Beyond that, while the answers are less clear, there is wisdom in trusting that no one would be more cautious or more concerned for the well-being of a child than a loving parent guided by the expert advice of a committed physician.
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Look for an upcoming post exploring more of the literature on the rights of parents and of the unborn, like the work of philosopher Judith Jarvis Thomson.
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Additional Reading
“Germline Editing Objections — Vol. 1”
“Germline Editing Objections — Vol. 2”
“Advanced Medical Technology: Four Burgeoning Issues From 2017”
