April 20, 2015

The Prospect of CRISPR/Cas9 Human Reproductive Technologies Stirs Urgent Policy Discussions

In recent weeks, there has been growing attention to the possibility that recently developed technologies which allow precise editing of genomic DNA could be used for human reproductive purposes, possibly modifying the genomic DNA of a fertilized egg or embryo to create heritable genetic changes. The growing use of the genome editing technology known as CRISPR/Cas9 (CRISPR), first reported in 2012, is permeating much of current genetic research and is driving the policy discussions. A meeting on germline applications held in January of this year at Napa, California, and convened by some of the founders of the original Asilomar conference on recombinant DNA, took up the question of using CRISPR for germline genome engineering. This working group, which included Dr. Jennifer Doudna, an originator of this technology, has now published a call for caution as this technology could be employed to perform germ line editing that would manifest in human offspring. The CRISPR technology allows for more precise and efficient editing in genomic DNA than earlier editing techniques, and has a number of useful applications, both for research and clinical use. According to several reports, there might be attempts at CRISPR-mediated human germline modification that are already underway but unknown and that possibility has stirred the scientific community to action. The participants at the Napa meeting called for further research and more transparent discussions for all stakeholeders. Finally, they called for scientists to refrain from employing CRISPR in any attempts at human germline engineering. The scientists agreed to:
Strongly discourage, even in those countries with lax jurisdictions where it might be permitted, 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. (In countries with a highly developed bioscience capacity, germline genome modification in humans is currently illegal or tightly regulated.) This will enable pathways to responsible uses of this technology, if any, to be identified. 
In parallel with that statement, a second group of researchers in the field of gene editing called for a complete moratorium on the use of CRISPR for germline genetic engineering. They stated:
In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited. At this early stage, scientists should agree not to modify the DNA of human reproductive cells. Should a truly compelling case ever arise for the therapeutic benefit of germline modification, we encourage an open discussion around the appropriate course of action. 
Already, there are published reports of germline modification in monkeys. As for human gene modifications writ large, in 2015, there is the established field of gene therapy, overseen by the Recombinant DNA Advisory Committee (RAC), and slowly embraced by the FDA. These therapies provide genetic alteration to living persons through their somatic cells, so there is no heritability of the changes. RAC was asked to consider fetal gene therapy protocols in the late 1990's, but concluded that the risk/benefit ratio did not justify approval. Current reproductive medicine offers preimplantation genetic diagnosis to prospective parents seeking to avoid transmitting known genetic diseases, but that technique does not involve genome editing. The speed at which CRISPR-based technologies are entering genetic science guarantees that the debate over controversial applications will continue. Not surprisingly, any proposed CRISPR-based reproductive technologies are likely to encounter much more resistance that many other assisted reproductive technologies (ARTs) have encountered to date. Will CRISPR-based reproduction elicit the kind of furious legislative responses to the possibility of human cloning that followed the creation of the cloned sheep Dolly in 1997? Since there are no credible reports of use, the public is not confronted with the issue, but the scientific and bioethical communities can see ahead, and are trying a proactive rather than reactive approach to getting a public debate started.

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