In a previous blog, I highlighted the ease with which CRISPR/Cas9 technology could be used to edit DNA sequences in almost any cell (1). At my institution the gene targeting and transgenic mouse facility is exclusively using CRISPR/Cas9 to engineer its mouse models and I suspect the same is true at any number of centers around the world. The advantage of this technology is that genetically manipulated mice can be created in half the time and at almost half the cost of the previous technology, which employed homologous recombination in embryonic stem cells. CRISPR/Cas9 also eliminates the need to breed chimeric mice for multiple generations into inbred strains before experiments can be performed on them.
However, in my previous blog I also mentioned the “eugenic potential of the technology to engineer almost any polymorphism into the embryo of an organism”. My concern was that “The era of “bespoke” genes is now at least within the realm of possibility and it will be a challenge of both science and society in general to apply this technology in an ethical way.” Recently, papers in both Science and Nature have laid out position papers on just this topic. Edward Lanphier and colleagues argue in Nature (2) that “There are grave concerns regarding the ethical and safety implications of this research. There is also fear of the negative impact it could have on important work involving the use of genome-editing techniques in somatic (non-reproductive) cells.” Because of these fears his paper called for a moratorium on experiments that manipulate human embryos and other reproductive cells. These authors were concerned with quality control of the genetic manipulation and the fear that we don’t know enough about the long term implications of the technology to justify its use to create human embryos that would produce live births. In an accompanying article in Nature (3), David Cyranoski mentions that there are suspicions that some researchers have already created human embryos with edited genomes and that papers describing such work have been submitted for publication. Lanphier et al urge that a dialogue be started, “both to establish how to proceed in the immediate term, and to assess whether, and under what circumstances — if any — future research involving genetic modification of human germ cells should take place. Such discussions must include the public as well as experts and academics.”
In the Science article David Baltimore and others report on a meeting that was held in Napa, California in January 2015 to discuss the ethical and moral implications of the use of CRISPR/Cas9 technology in human genetic engineering (4). Similar to the Lanphier article, these individuals also strongly discouraged “any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations.” They emphasized that there need to be, “forums in which experts from the scientific and bioethics communities can provide information and education about this new era of human biology”. In addition, they want to “encourage and support transparent research to evaluate the efficacy and specificity of CRISPR-Cas9 genome engineering technology in human and nonhuman model systems”.
Clearly, we are at a crossroads. The technology to rapidly manipulate genetic material in cells is readily available, relatively inexpensive and not particularly difficult to implement. However, the general public has only just become aware of its implications. As with many scientific revolutions there is a tremendous potential to benefit mankind as well as grave concerns about its appropriate use. Consequently, there exists a pressing need to establish ethical guidelines for employing these tools in ways that facilitate their potential to benefit us while, simultaneously, protecting us from their unethical use.
Joe Lorenzo, M.D.
Farmington, CT, USA
Should We Ban Manipulating the Genome of Human Germ Cells?
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