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This should not be done. I am not alone."1 This was bioethicist Ruth Macklin's reaction to an announcement made earlier this year by a team of Chinese scientists to the effect that they had "edited" the DNA of human embryos in an effort to correct a genetic mutation that can cause thalassemia, a serious blood disease.
To edit the DNA, the team used CRISPR/Cas9, an enzyme complex. When injected into a cell, CRISPR/Cas9 acts like micro-scissors. It targets the defective section of DNA, snips it out, and replaces it with healthy DNA provided by the researcher. The technique is well established for editing adult human cells—for instance, to modify a patient's bone marrow cells to increase resistance to HIV—and has also been used on animals. It is so common in genetics research, in fact, that it has become a verb, as in "I'm going to CRISPR that."2
When it is functioning correctly, CRISPR/Cas9 identifies all mutated segments and repairs each one with a corrected DNA segment. Every cell in the research specimen should be changed. That is not what happened in the Chinese study.
Problems with the Study
The research subjects in this case were 86 polyspermic zygotes, abnormal embryos acquired from fertility clinics. (The study authors justified the use of these embryos by claiming that they were nonviable because each had been fertilized with two sperm instead of one.) After injecting the single-cell embryos, the researchers waited two days while the cells divided. Only 71 embryos survived to this point, and gene segments of 54 of them were tested. Of this group, only 21 showed evidence of the targeted gene having been spliced out, and an even smaller number evidenced insertion of new genetic material. Some embryos exhibited mosaicism, a mixture of repaired and unhealthy cells. Moreover, the process apparently modified other, presumably normal gene segments. The high number of these "off target" mutations surprised the researchers. They admitted that if the entire genome had been tested, they would have found many more mutations.
In short, there were no embryos in the Chinese study that met the two basic criteria of success: precisely corrected genes in every cell, and no damage or alteration of other DNA. Junjui Huang, the team leader, was willing to sacrifice the abnormal embryos, but added that, "If you want to do it [CRISPR/Cas9 modification] in normal embryos, you need [the success rate] to be close to 100%."3
A Question of Compassion
Discussions concerning the ethics of genetic experiments on human embryos can easily devolve into rhetorical and emotional contests over the locus of compassion. On the one hand, genetic mutations can cause serious, progressive, and even fatal diseases. Success could mean that a child could live free of thalassemia and avoid a lifetime of blood transfusions or even an early death. Wouldn't it be heartless to oppose research that could accomplish that?
On the other hand, it must be remembered that the researchers' focus was not on curing a child already in existence but on genetic "prevention" for future children. And the price of paving the way for those potential future children is an as-yet-unknown number of human embryos, many of whom are already in existence at IVF clinics, who will be manipulated and then exterminated, all for the benefit of someone else. Shouldn't compassion be directed toward them?
Ethics & Concerns
Genetic engineering can be divided into two streams: (1) genetic modifications that are performed on adult human cells, called somatic cell therapy, affecting only the patient, and (2) germline modifications that are inheritable, that is, passed along to subsequent generations. In the case of somatic cell therapy, ethical concerns center on the customary issues of informed consent, safety, efficacy, and so forth. But with germline modifications, deeper questions are introduced: Should we limit the power of researchers to change future human beings? If so, where do we draw the line?
The response from Macklin and the majority of bioethicists was surprising in that it was not typical for most experiments involving human embryos. Usually, such announcements are greeted with at least tacit approval, but in the case of the Chinese study, concerns were widespread. The U.S.-based International Society for Stem Cell Research re-issued its call for a moratorium on germline alteration.4 The corporate sector followed suit, with the president of Sangamo BioSciences saying, "we need to pause this research."5 Francis Collins, director of the National Institutes of Health, stated that "NIH will not fund any use of gene-editing technologies in human embryos."6 Even one of the creators of CRISPR technology objected, and organized leading biologists to call for a moratorium.7
Many share Macklin's expressed concerns about the comprehensive, irreversible nature of what is being done. The embryo's every cell is changed—irrevocably. Collateral damage could be enormous, affecting a few or perhaps all of the other genes. Normal DNA could be edited for no good reason. Adverse effects might not be immediately evident, yet endure for generations.
Even if this kind of genetic engineering were perfected, it would do more than "cure" the embryo. It would also impose any unintended consequences on future generations. Modification of human DNA is not a neutral enterprise. There are incalculable risks of harm, such as the inadvertent modification of normal genes, or the triggering of other mutations that the original research subject might escape, but that his children or grandchildren would suffer from. To be sure, some of the unforeseen consequences might be beneficial. But the likelihood of unpredictable and horrifying effects underscores the need to hold the line against germline modification.
What's more, if the CRISPR "find and replace" technology succeeds in correcting lethal mutations, what will stop the drive to fix less worrisome genes, like the one that causes colorblindness? Or to "improve" upon normal genes, such as those that govern height? It's not hard to imagine two short parents desiring to adjust the growth genes in their children so they would be taller.
Genomic research, untethered by moral guidelines, is not likely to restrain itself. It is easy to say, "This line should not be crossed," as long as it is not technologically feasible to do so. But as unscrupulous research brings that possibility ever closer, resistance tends to wither. Nearly 70 years ago C. S. Lewis warned in The Abolition of Man that "if man chooses to treat himself as raw material, then raw material he will be." But not all, for as Lewis also wrote, "At the moment, then, of Man's victory over Nature, we find the whole human race subjected to some individual men."
The power of the few to decide what is best for the rest is an ancient temptation. Now is not the time merely for moral restraint, but also for active resistance to those "individual men." •
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