Designer Babies “R” Us

Asilomar and Napa, separated by 150 miles, are now linked as meeting sites for scientists to discuss the self-regulation of biotechnology. In Asilomar in 1975, the topic was recombinant DNA technology, or the joining of DNAs from different organisms. After discussions on the safety and risks, scientists and physicians voluntarily produced governing principles for their work, including a list of prohibited high-risk experiments. In January 2015, scientists again gathered in California, this time to discuss CRISPR-Cas9 technology, concluding that there is an urgent need for continued open discussion on its use for human genome modification.

The CRISPR-Cas9 system is utilized by bacteria to protect themselves from infection by viruses. Upon detection of invading DNA, the bacterium produces two types of short RNA, one of which matches the viral sequence. This guide RNA forms a complex with Cas9, a nuclease that can cut DNA upon binding. The complex can then bind to the complementary virus DNA target site, leading to its excision and degradation, thereby disabling the virus. This bacterial system has been co-opted by scientists for use in genomic engineering to change exogenous DNA in a variety of cells and animals. Mutations can be introduced by targeting genes-of-interest for excision by the complex, simplifying the creation of gene-knockout models to examine gene function. However, the technique can also be used to repair mutations by adding DNA segments carrying the correct genetic sequence along with the CRISPR-Cas9 complex. After excision, the cell will use this DNA as a template for its repair machinery, thereby introducing the ‘healthy’ sequence into the genome. If this is done in reproductive cells, the CRISPR-Cas9 system has the ability to modify human embryos, an application that has enormous ethical implications.

By editing the DNA of the egg and sperm cells, called “germline engineering”, it could be possible to correct mutations that cause diseases. For example, a researcher described the potential to harvest the eggs from women carrying the BRCA1 mutation, a dominant mutation that predisposes women to breast and ovarian cancer. CRISPR-Cas9 would be used in these eggs to correct the mutated DNA and create a viable embryo with the ‘healthy’ BRCA1 gene. This genetic change would then be passed on through future generations. However, the technology is still in its infancy – scientists do not yet know the potential for off-target effects, or even on-target editing with possible side effects. Furthermore, the width of its potential application is troubling to bioethicists. With recent advances that further streamline the system, the possibility of designer babies that could alter the scope of human evolution is more reality than science fiction. In fact, rumors abound that scientists outside of the United States have already submitted papers for publication that detail their use of CRISPR in human embryos.

Given the lack of regulations on germline engineering in the United States, Jennifer Doudna, the molecular biologist who helped develop CRISPR, convened scientists, ethicists, and law experts to discuss the concerns. The group detailed a number of steps to be taken, including: discouraging attempts at genome modification, creating forums for continued discussion, encouraging transparency of research to evaluate the safety of the technology, and finally the convening of a global group to openly discuss the merits and risks and recommend policies.

The meeting at Napa was essential to begin the conversation on CRISPR-Cas9 technology and attract public attention to these issues. However, there are many additional measures that need to be addressed in further discussions. Notably, and in contrast to the original Asilomar, the researchers did not call for a moratorium on the controversial germline engineering, instead only “strongly discouraging” the work. Until the safety and efficacy of CRISPR in germline editing is determined, a self-imposed pause on altering human eggs, sperm, or embryos, should be in place. It is possible the recent government-imposed ban on funding for the gain-of-function (GOF) studies on influenza and SARS viruses led to the scientist’s reticence to impart additional restrictions on their community. In contrast though, GOF studies have broad biosecurity implications - the escape of a virulent strain has the potential to affect the general public, while germline engineering affects only the individual and his or her progeny. Therefore, it remains to be seen what regulatory approach the U.S. government will elect to take regarding genome editing using the CRISPR-Cas9 system.

However, this raises an additional point that was not defined in the Napa meeting: Who is responsible for leading the discussions on the technology moving forward? Should it be left exclusively to the research community, or done in conjunction with national and international regulatory bodies? An overhaul of the current laws and legal system may be necessary in light of the uncertainty of the role that the U.S. government should play in regulating biotechnology. A potential model is the United Kingdom and their response to the issue of mitochondrial DNA replacement therapy, which is another form of germline modification. The procedure was banned while the government sponsored numerous scientific and ethical studies. After these demonstrated the safety of the technique, the House of Commons and Lords voted to approve the technique, albeit under strict regulation. A similar protocol may be useful for the U.S. and abroad to evaluate CRISPR-Cas9, in order to ensure the technology is used safely for germline editing.