First Thoughts on Germline Engineering

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For the first time in history, scientists have genetically modified human embryos. Researchers in China published a paper a few days ago in which they announced that they had used the genome-editing tool known as CRISPR to introduce changes to the genomes of human embryos. The target for the modifications was the gene associated with one of the world’s most prevalent genetic diseases, beta thalassemia, although the embryos that the researchers modified were not themselves affected by the mutations that cause the disease.

In an attempt to sidestep the ethical problems associated with experimenting on human embryos, the scientists used abnormally fertilized “tripronuclear” embryos, that is, single-celled embryos that had been fertilized by two sperm and that therefore contain three sets of chromosomes rather than the normal two. Such embryos have been used by scientists because they can develop to the blastocyst stage, though they are thought to be incapable of normal development much beyond that point. Whether the inability of these embryos to survive past this early stage of development should be taken as a sign that they are not and were never living embryos is a complicated philosophical and ethical question. Any answer to this question, however, should be supported by better evidence than the scientists offer in their paper: the facts that such embryos “invariably fail to develop normally in vivo” and that they are “discarded in clinics.”

This paper is groundbreaking more for crossing ethical boundaries than for the results it describes. The scientists achieved very poor accuracy in the genetic modifications they attempted to introduce, certainly far too low for the technique to seem remotely promising for any kind of clinical purpose. Many of the embryos were found to have off-target genetic modifications at various sites in their genomes. And since many of the embryos developed as genetic mosaics, with genetic differences between different cells, it would not even be possible for scientists or doctors to use preimplantation genetic diagnosis (PGD) to determine whether or not these genetic-modification attempts were successful.

Of course the most notorious ethical boundary that these scientists crossed is not their callous experimentation with human embryos — that, unfortunately, has become an all-too-acceptable part of medical research. What has shocked the scientific community is how this experiment crosses one of the last and oldest taboos of mainstream bioethics: it modifies the human germline. Genetic changes made to human embryos, unlike gene therapy conducted on adults, will not only affect the genetically modified child but also the genetically modified child’s descendants. Technologies like CRISPR are just what might make possible that dream and nightmare of genetically designed children — if we allow the technologies to be used to modify human embryos.

This announcement has not come as a surprise; germline modification has been expected and feared for decades, and just last year scientists used CRISPR to genetically modify the embryos of mice and primates, and the technique has been used in experiments to genetically modify human cells (not embryos) in vitro since 2012. Some of the results of this research have been promising, and hold out the hope for gene therapies that could be used to treat diseases ranging from HIV to cancer.

Concerned that this research could be used to modify the human germline, a group of scientists and ethicists met in Napa, California this past January to discuss the implications of the work. Following the meeting, they published an article in March in the journal Science recommending that steps be taken to

strongly discourage, even in those countries with lax jurisdiction where it might be permitted, any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications are discussed among scientific and governmental organizations.

Also in March, Nature published an essay calling for a voluntary moratorium on human germline modification, emphasizing the importance of “making a clear distinction between genome editing in somatic cells and in germ cells.”

The strong stance that the scientific community has taken against germline modification is an encouraging sign, to be sure. While some so-called ethicists, like Julian Savulescu at the University of Oxford, recklessly endorse the genetic modification of humans, the scientific community has displayed considerable prudence in its approach to this controversial issue. It would appear that the world’s two leading scientific journals, Nature and Science, both turned down the opportunity to publish this radical paper, and though the editors of neither journal have yet made any public statements on the matter, it would seem that they may have declined to publish on ethical grounds.

However, the prudence and moral seriousness with which the scientific community has treated germline modification throws into relief the way that most scientists, bioethicists, and doctors have already participated in even more unethical forms of research and reproductive medicine for decades. While taking a strong stand against genetically modifying embryos affected by genetic diseases, scientists and fertility doctors have participated in the development of techniques for selectively discarding embryos and fetuses with these same diseases. Genetic modification would further transform human procreation into a manufacturing process. On the other hand, in contrast to PGD, genetic modification technologies would allow doctors to act more like healers, preventing disease not by discarding the sick, but by treating them.

The existence and widespread acceptance of PGD, which is “safer” (at least for those embryos not found defective and discarded) makes it seem unlikely that there will be much demand for germline modification in the near future. Under some rare circumstances, as when both would-be parents carry two copies of a recessive disease-causing allele, or when one carries two copies of a dominant disease-causing allele, germline therapy may be the only way for them to have a child genetically related to both of them. But in most other cases, for germline modification to seem like a preferable alternative to PGD, would-be parents would have to hold a curious combination of pro-life scruples and indifference to the perversion of the meaning of human procreation represented by genetic modification.

New methods for modifying the human germline raise important questions for the future of human procreation. But in thinking about the ethical implications of genetic modification, we should also take the opportunity to look back at the reproductive technologies we have already come to accept. Not because our acceptance of these practices should subdue our disquiet at what is troubling in these new techniques, but because what is shocking about the genetic modification of human embryos can clarify and make new to us again what is troubling about the control we already exercise over future generations.

As we consider the mixed blessings of the biotechnology project that society has already grown to accept, we should reflect on how our reactions to what seems shocking and new can bring renewed clarity to the moral meaning of what has become familiar.

Brendan P. Foht, “First Thoughts on Germline Engineering,”, April 23, 2015.

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