For the moment, despite the plethora of other possible applications, much of the most impassioned discussion about CRISPR-Cas9 has focused on its potential for editing the nuclear DNA of human gametes or embryos — so-called germline editing. The critiques largely break down into two large categories that are used in ethical analyses of many different kinds of technologies and human actions. The first — which is present in some religious analyses, but is also the hallmark of secular approaches — might be called consequentialist [33]. On the one hand, it focuses on the possibilities for improving the human condition, through the elimination of deleterious characteristics or mutations. It might allow people who carry such traits to have children to whom they are genetically related without the prospect of passing on problematic or dangerous conditions. To the extent these changes would persist across the generations, it could benefit not only the immediate offspring, but also all of the descendants of those who use the technology. On the other hand, it is this same phenomenon — of a change that reverberates down through the generations — that increases concern about unintended effects whose disadvantages might grossly outweigh any advantages that genome editing confers. And, because these risks would be borne by those who had no say in the decision, it eliminates the most common justification for such actions — that is, that the risk-taker has made an informed and voluntary decision to encounter the risk. While this is certainly true in every case of parental decision-making on behalf of a future or existing child, in those situations the rearing parents will share with the child both the risks and the possible benefits, thus adding some situational constraints on rash action. But when those risks and possible benefits are largely felt by future generations, this constraint, in the form of self-interest and self-protection, is removed.
Critics will also point to the intrinsic uncertainty about downstream effects, and will invoke some form of the precautionary principle [34], which demands a strong justification before permitting any risk-creating activity, with risk defined both in terms of known hazards and unknown possibilities. The latter, of course, is incapable of measurement, which is where the precautionary principle can be stretched into a generalized prohibition. In cases of devastating genetic diseases, some might argue forcefully that the risks of editing procedures are acceptable. At the same time, we must admit that we cannot confidently predict all the consequences, whether of introducing deleterious traits or by losing unanticipated benefits to retaining particular alleles. The heterozygote advantage of the sickle cell hemoglobin mutation in resisting malaria infection comes to mind.
As to the justification for taking risks, a variety of means already exist to avoid passing on problematic traits, including the choice to forego biological reproduction, the use of donated gametes and embryos, or the use of pre-implantation and prenatal diagnostic techniques to avoid the birth of an affected child. Even while acknowledging that the option of embryo selection or selective abortion will be unacceptable or emotionally difficult for many, the availability of these alternatives will be seen as a means to diminish the prospective benefits of gene editing, by measuring those benefits solely in terms of marginal increases in personal choices and good birth outcomes.
Another thread in consequentialist argumentation concerns the wisdom of any effort to alter the human condition through genetic manipulation. Even before the glimmerings of a theory of genetic inheritance, societies across the world had eras in which they viewed selective breeding as a means to ensure the superiority of any resulting children. With the publication of Darwin’s works, and their manipulation into social theory by Herbert Spencer, a new age of ‘scientific’ eugenics was born. Couched in terms of social hygiene, it attracted followers from all parts of the political spectrum and combined crude understandings of genetics with a host of cultural prejudices. Not surprisingly, it led to ugly decades of the worst form of eugenics, with mass involuntary sterilizations and mass murder [35]. Genome editing, like its less efficient predecessors (including choice of gamete donors, or pre-implantation selection of embryos), is touted by some for its potential to clear deleterious traits from the family line, and criticized by others for its echoes of simplistic and cruel notions of genetic superiority and inferiority [36].
Closely connected to these concerns, but with some independent factors, is a second standard form of ethics analysis, one that focuses less on specific consequences and more on some set of fundamental principles of right and wrong, or on spiritual and religious views about the appropriate scope of human control over the planet and the species. These categorical approaches are frequently found in theological analyses of new biotechnologies. For example, towards the end of Simon Mawer's 1998 novel, Mendel's Dwarf [37], the protagonist, a hereditary dwarf, faces a choice:
"Benedict Lambert is sitting in his laboratory playing God. He has eight embryos in eight little tubes. Four of the embryos are proto-Benedicts, proto-dwarfs; the other four are, for want of a better word, normal. How should he choose?"
For those approaching the question from a religious point of view, many see the act of choosing as a usurpation of God’s role in mankind’s existence. During a 1997 consideration of cloning policy, for example, the National Bioethics Advisory Commission (NBAC) [38] listened as theologian Dr Gilbert Meilaender testified that Protestants, although stout defenders of human freedom, nonetheless "have not located the dignity of human beings in a self-modifying freedom that knows no limit, [not] even…God." Rev. Albert Moraczewski, a Catholic, testified that cloning "exceed[s] the…delegated dominion given to the human race. There is no evidence that humans were given the power [by God] to alter their nature or the manner in which they come into existence" [38]. But in the novel [37], Benedict's instinct about God's role is somewhat different:
“Of course we all know that God has opted for the easy way out. He has decided on chance.... You may…select two of the four normal embryos and send them over to the clinic for implantation …or…select the four achondroplastics, the four stunted little beings…and send them over instead…or… refuse to usurp the powers of God and choose instead to become as helpless as He…by choosing one normal embryo and one achondroplastic and leaving the result to blind and careless chance.”
It is evident that Americans do not share a common view on the act of choice where creating and altering life is concerned. While some see choosing as ‘playing God’, others see it as ‘playing human’. Indeed, Rabbi Elliot Dorff testified at that same NBAC meeting that we are "the partner of God in the ongoing act of creation. We are God's agent.... ". Examining Biblical texts, Rabbi Moshe Tendler testified that being such a partner means taking an active role, and that ‘artificiality’, far from being wrong or evil, is rather a sign of humanity's constructive contribution, a sign that we are doing our duty. Furthermore, a professor of Islamic studies, Aziz Sachedina, described how the Koran suggests that "as participants in the act of creating with God, God being the best of creators, human beings can actively engage in furthering the overall state of humanity by intervening in the works of nature, including the early stages of embryonic development" when the goal is to achieve a natural good, such as health or fertility [38].
It is equally evident that people around the globe do not share a common view on the act of choice where creating and altering life is concerned. In places such as Singapore, China or Israel, attitudes about the moral and legal significance of embryos and fetuses, and about the appropriate degree of human control over its environment and its destiny, have been shaped by different histories and religious traditions [39]. In Germany, where the events of World War II still loom large in the collective memory, anything that relates to genetics will be met by skepticism, especially if there is any hint of eugenics [40]. In France, the internal politics of a country dedicated to secularism since the 18th century but with powerful church influences has led to a degree of conservatism with respect to all forms of embryo research, and will likely have the same effect on debates about whether to make changes in the human germline [41]. By contrast, the United Kingdom has spent decades building a regulatory apparatus that is integrated with public opinion and legislative oversight, and which is allowed by law to exercise tight control not only over technologies, but even over every particular use of a technology, down to the laboratory, clinic and patient, something not often possible under the US system [42]. It should be no surprise, then, that the use of gene editing will likely proceed at wildly different rates among countries, cultures and regulatory systems.
To address this reality, a small group of scientists, lawyers and ethicists came together in early 2015 in Napa, California. The discussion there led to a call for a temporary moratorium on human applications of germ-line editing [26]. This was quickly followed by an announcement by the National Academy of Sciences and National Academy of Medicine that a joint initiative would be undertaken, with two major activities [28]. The first, an international summit, would gather scientists and thought leaders from around the globe, to discuss the state of the research around the world, to compare regulatory and cultural approaches, and to begin thinking about the kind of global norms that might be most appropriate to this area. The second, a study committee, will dig more deeply into the science, with an eye to understanding probable applications, their risks and benefits, and the applicable oversight systems.
In advance of these deliberations, The Hinxton Group [43], a self-organized international group of scientists and ethicists, has recently issued a statement on genome editing technologies and human germline modifications. Like others who have entered this discussion, they believe that technical advances are necessary before human germline applications should be undertaken. At the same time, they appear to make a tacit assumption that such manipulations will ultimately go forward, and, in this context, recommend that research on genome editing in human embryos should proceed under strict guidelines. While acknowledging the ethical concerns, they caution against over-regulation, which could inhibit orderly progression towards legitimate uses of the technology.
Even further along this path is the UK’s Human Embryology and Fertilisation Authority, which is now considering a specific proposal for use of gene editing on human embryos, in order to investigate the causes for repeated miscarriages [44]. The British and American systems of governance are quite different. In the USA, this procedure would likely be under the jurisdiction of the FDA, which would evaluate preclinical and clinical research data for a particular indication. If approved, the procedure could be advertised and promoted for only that indication and patient population, but physicians would have discretion to use it for indications or types of patients other than those for which it was approved. By contrast, in the UK, control over use is tighter — physicians and clinics must be licensed for each application. This allows for more precise control over dissemination of the technique, but at the cost of losing a degree of professional independence and judgment.