Usually those who write about genome editing or designer babies tend to start off by describing a dystopian world probably referencing Gattaca, where if you were conceived naturally you are a “God-child” labelled an invalid and deemed lower class.
The topic of designer babies has been explored before in a Science Brainwaves blog post: Designer babies- What’s It All About? but a recent technological breakthrough brings this topic back with a vengeance. In this blog post I explore the reality behind it.
1975 Asilomar, California
Recombinant DNA technology boosted biotechnology and its potential drastically, so in 1975 a meeting was held to discuss the relevant safety issues. The result was an agreement of principles and recommendations to be applied to the research. A similar meeting was held this year- 24 January in Napa, California and some of the same people that attended the 1975 meeting also attended this one. Their goal was similar to the one in 1975: to discuss principles, review safety and ethical guidelines on the new technology that had developed in the interim.
The technology that had developed in that time was the application of zinc finger nucleases (ZFN) (Urnov et al 2010 Nature Reviews Genetics 11, 636–646) and CRISPR-Cas9 (Jinek et al 2012 Science 337: 816-821) for genomic engineering. Both act like a pair of scissors, cutting DNA and allowing for an insert.
ZFN have zinc finger protein (ZFP) sites that bind to targeted DNA while the enzyme nuclease (in FoKI) cuts the DNA. The first time this was used as a tool for genetic engineering was to knockout a gene in a Chinese hamster ovary cell. However there were issues involved in its design, synthesis and validation that posed a barrier to its adoption. Sangamo BioSciences a biotech company in California took on this technology to further develop it. But CRISPR-Cas9 seems to have superseded ZFN.
CRISPR-Cas9 is a molecular system that gives bacteria adaptive immunity to viruses. It comprises of a protein that guides RNA to bind to DNA and then breaks the DNA. Even though CRISPR has been known to cut target DNA since 2010, it was not until 2011 when Cas9 was included and in 2012 it was adapted with the protein to break DNA. The Cas9 that was previously included was that of the bacteria Streptococcus pyogenes, however in a paper published just this month in Nature a smaller and more efficient Cas9 has been identified allowing for a broader range of genetic targeting.
Setting the scene
The technological developments are coming thick and fast. Big players are emerging (some at MIT and Harvard in Boston, USA and China) and fertility companies are starting to commercialise work conducted by stem-cell experts. The reason for this is that there is big difference in the type of cells that can be genetically engineered. Germline cells are sperm and ovaries which once edited can pass on changes to the next generation. Somatic cells are all other types which only affect the individual to whom they belong. The scientists have issue on both technical and ethical grounds with editing germline cells and its effect on future generations. The idea behind genome editing is to correct genetic diseases, such as cystic fibrosis, haemophilia, some cancers and sickle cell anaemia. While everyone agrees on the medical benefits, editing germline cells carries a different and significant impact affecting . . . take a breath, here is a long list by Nuffield Bioethics Council: justice, sustainability, crop breeding, livestock engineering, pharmaceutical development, individual liberty, autonomy and human reproduction.
From the meeting in January the scientists came to a unanimous agreement: All genetic germline modification must halt. They identified recommendations and outlined the next steps on ensuring safety and open discussion. Sending in their recommendations to Science, this was consequently picked up on by Nature and The Guardian. The dust had not even settled completely when just last week Junjiu Hang at University of Guangzhou in China published in Protein and Cell that he had genetically modified embryos, even though they would not give rise to live births. Despite this both Nature and Science rejected his paper on ethical grounds and this has caused a ripple effect of additional worry within the scientific community. On the other side, some scientists are worried that the media or others might demonise this work to such an extent that the full benefits might never be realised. Not everyone in the scientific community agrees with this moratorium.
So what now? Even the Chinese scientists agree that using CRISPR-Cas9 clinically is premature. With the red light bringing the studies to a (potential) halt, the debate is entering the political arena. For now you will not be seeing any re-designed humans, but this is not over so watch this controversial space!