Germline Editing Objections — Vol. 1
New breakthroughs in gene editing therapies are demonstrating enormous potential to treat debilitating genetic diseases like cancer, sickle-cell anemia, and even brain disease. Yet, all of these therapies act on diseases that have already been detected. Significantly lowering or eliminating an individual’s propensity to develop the condition in the first place would be a truly revolutionary step toward eliminating a large amount of human suffering.
Removing the genetic mutations that contribute to these diseases using gene editing before a child is even born is certainly possible in theory. Currently, doctors can use in vitro fertilization (IVF) and pre-implantation genetic diagnosis (PGD) to predict the likelihood that a child will have a genetic disease. By adding gene editing technology to these techniques, doctors could, in theory, correct the child’s abnormal gene sequences pre-birth. Scientists from both China and the United States have already experimented with this idea in their labs.
Goldilocks: Regulation Edition
Clearly, technology powerful enough to affect the genome of generations to come should not be left completely unsupervised. The risk of adverse health events in both the patient and her progeny warrants some regulation.
However, the potential health benefits of stopping genetic disease in the germline that would accrue to both the patient and her progeny demand that this treatment be pursued.
Prominent Harvard psychologist Dr. Steven Pinker notes that biomedical research has steadily beaten back the suffering and early death that once was simply accepted as an inescapable part of the human condition. Gene editing promises especially “vast increases in life, health, and flourishing.” Given its potential life-saving power, gene editing ought not be “bog[ged] down … in red tape, moratoria, or threats of prosecution based on nebulous but sweeping principles …”
As I have discussed before, the key to effective regulation is focusing limited resources on those dangerous, unacceptable “corner cases” which pose irreversible, catastrophic harm to patients. As Harvard geneticist Dr. George Church points out, this weighing of costs and benefits already governs how we regulate many fields including “speed limits, blood alcohol levels, and age limits.” Focusing on these worst cases will go a long way toward striking the proper balance between safety and innovation.
The Possibility of “Soft Law” Regulation
Conceding that a technology with potentially deadly health risks like gene editing ought to be regulated is not necessarily a call for sweeping prohibitions or expansive legislation.
In response to the increasing gap between the development of powerful, new technologies and the implementation of governing frameworks to oversee them, combined with the growing rigidity of Congress and the traditional rule-making process, executive agencies (FDA chief among them) are making greater and greater use of “soft law” regulatory powers.
As Adam Thierer and I explained in our essay “‘Build & Freeze’ Regulation Versus Iterative Innovation,” these powers include guidance documents, best practices, multi-stakeholder co-regulation arrangements, public workshops, and certification programs. They generally include elements of industry input and cooperation.
Soft law powers give agencies the ability to be nimble and adaptive because they are not weighed down by the strictures of the rule-making process laid out in the Administrative Procedure Act. But these powers ostensibly do not have the force of law, leaving questions as to their enforceability if challenged. I pointed out in my last post that there is also the concern that the increased flexibility of agencies like FDA could be used to stymie gene editing just as easily as it could be used to foster it.
Despite these concerns that are embedded in the nature of soft law mechanisms, the FDA is using such regulatory mechanisms quite effectively to achieve a balance between safety and innovation. Instead of opting to halt scientific progress on gene editing with prohibitions, FDA has made use of innovative governance techniques to provide a framework in which genetic science can develop. Such is the proper use of regulation.
Objection: Just Use PGD
All of FDA’s focus has been on somatic cell editing, which has shown promise and enjoys the support of a majority of people. Over 85% of genetic professionals and about 64% of lay people support somatic cell editing for therapy. But germline editing, even for therapeutic purposes, tends to garner less support and bring up more safety- and ethics-related questions.
At the rate genetic science is moving, editing embryonic, germline cells to correct for disease-causing genetic mutations will likely be as safe and effective as many current treatments for these diseases in the not-too-distant future. In fact, Dr. Jennifer Doudna, the co-discoverer of the CRISPR gene editing system, believes this prediction is “almost certain.” In that case, restrictive regulation driven by negative public opinion looms as the largest obstacle to germline editing.
One of the common responses to proponents of germline editing from those who are wary of the long term consequences that accompany germline changes is that using current, better understood PGD techniques would provide the same health benefits without the potential danger of germline editing. As an example, Dr. Eric Lander, Director of the Broad Institute at MIT and Harvard, made this argument in a 2015 perspective published in the New England Journal of Medicine.
Lander rightly points out that “Genome editing would require making IVF embryos, using preimplantation genetic diagnosis … to identify those that would have the disease, repairing the gene, and implanting the embryo.” It would be easier and safer, he says, to cut out the last several steps and simply implant embryos that do not possess the genetic markers of debilitating diseases. This would ensure that the vast majority of children are born healthy, though Lander acknowledges that it would not be effective in the small number of cases in which all embryos will be affected by the genetic abnormality — as would be the case when both parents carry two recessive genes.
Germline Editing More Exponentially Curative
Germline editing not only reliably eradicates genetic disease in the patient to whom it is applied, but also ensures that abnormal genetics will not be passed on to succeeding generations. When using PGD alone, it is much more difficult to achieve such exponentially curative results. For two people who each carry an abnormal copy of a gene, most of the embryos they produce will also have at least one abnormal copy of that gene, meaning that the problem gene will remain in the gene pool and be passed down to the next generation.
Stopping abnormal genes from being passed on could require creating a large number of embryos in order to find one with two intact genes, which is not always possible. In a paper titled “The Ethics of Germline Gene Editing,” Cristopher Gyngell, Thomas Douglas, and Julian Savulescu note that almost 20% of couples are only able to produce a single viable embryo during IVF and most couples do not produce more than ten viable embryos.
PGD becomes even less effective, perhaps even impossible, when attempting to prevent diseases like diabetes and common cancers that are influenced by many different genes. Gyngell, et al., offer an example of such a condition.
Say 20 genes contribute to a particular trait. If a couple wish to use PGD to select for 20 different genes in an embryo, they would need to create around 10,000 embryos to make it sufficiently likely that one will have the right combination at all 20 loci.
Germline editing could offer a feasible way to reduce a person’s likelihood of suffering from these kinds of diseases, especially as our knowledge of gene editing and the genetic root of diseases grows.
Right-To-Life Concerns
For many, PGD is unacceptable since it involves discarding the abnormal and unused embryos. Church noted in his article “Compelling Reasons for Repairing the Human Germline” that the Vatican endorsed the idea of germline editing because it could allow couples to have healthy children without discarding any embryos, which the Catholic Church has long been against [1]. Pursuing germline editing, especially in sperm or egg cells before fertilization, could enable the millions of couples who choose not to utilize PGD for philosophical or religious reasons to still have biologically-related, healthy children.
These right-to-life concerns are largely absent from the germline editing debate thus far. Church has the most robust treatment of the argument that I have seen, even though he devotes barely half a paragraph to the topic. Many geneticists and ethicists skip over these concerns completely, despite the fact that argument alone could influence many people to undergo the procedure should it become available.
Conclusion
Most experts, including Lander, agree that laboratory research on germline editing ought to continue. They argue instead for a hold on any clinical applications of this technology until some point in the future if and when “we become technically proficient, scientifically knowledgeable, and morally wise enough and if we can make a compelling case.”
While the science is arguably not yet at a point at which it is safe and reliable enough to be used in the clinic, it is difficult to claim that a compelling case has yet to be made. I have written about the potential life-saving benefits of all forms of gene editing in numerous articles. Experts like Church and Pinker have also advocated for these technologies in speeches, interviews, and articles. The case is as simple as it is compelling: Gene editing allows us to save lives that otherwise would have been filled with suffering and death.
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[1] Here is the full passage to which Dr. Church references: “90. Germ line genetic engineering with a therapeutic goal in man would in itself be acceptable were it not for the fact that is it is hard to imagine how this could be achieved without disproportionate risks especially in the first experimental stage, such as the huge loss of embryos and the incidence of mishaps, and without the use of reproductive techniques. A possible alternative would be the use of gene therapy in the stem cells that produce a man’s sperm, whereby he can beget healthy offspring with his own seed by means of the conjugal act.”
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Watch for further installments in this Germline Editing Objections series
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Additional Reading
“Technology Could Enable Personal Medicine Whether We Like It Or Not”
