CRISPR in the Germline
By Bio-IT World Staff
March 20, 2015 | There is a renewed urgency to public conversations about the ethics of genome editing, thanks to the emergence of CRISPR, a gene engineering technology so effective and easy to use that scientists are racing to keep up with its potential applications. This is a profound change from past techniques for making precise edits to the genome, such as zinc finger nucleases or TALENs, which were so finicky and complex that only a few expert labs were following up on genome editing as a practical tool in the life sciences and medicine.
Yesterday, two significant publications on this issue appeared in the journal Science. The first, a policy statement, advocates for a global, voluntary moratorium on using CRISPR in human germline experiments. Unlike edits to somatic cells, which could be used to cure genetic diseases in single individuals, edits to germline cells could be passed from parent to child, making any changes induced by CRISPR permanent additions to a species' genetic variation. The authors of the policy article note that there is not yet a consensus on how specific CRISPR edits are — the technology is known to make "off-target" cuts to the genome, cutting DNA at sites similar, but not identical, to those deliberately targeted, raising the possibility of unintended effects. Notably, the lead author of this article is Jennifer Doudna, who along with Emanuelle Charpentier made the original discovery that CRISPR could provide a programmable method for editing genomes. The New York Times has additional coverage.
Meanwhile, the second publication offers a dramatic illustration of CRISPR's power in germline experiments. Two biologists from UC San Diego, Valentino Gantz and Ethan Bier, successfully used CRISPR to insert a mutation in a population of mosquitoes that caused them to produce less pigment, making the mosquitoes a pale yellow. This in itself is not remarkable: CRISPR has been used to modify traits in numerous species, including mice and cynomolgus monkeys. The twist in Gantz and Bier's experiment is that they caused their edited mosquitoes' genomes to actually produce the Cas9 protein, which makes cuts in the CRISPR system, as well as the guide RNAs that direct that protein to cut sites in the genome. As a result, an edit made to one copy of a chromosome in a cell naturally spreads to the other copy.
When an edit like this is made to the germline, the result is a "gene drive," where a mutation is more likely to be passed from parent to child than chance alone would predict. In this case, when the edited mosquitoes bred with one another, 97% of their children were yellow — compared to the 25% that would be expected without the gene drive.
A Science news piece on this paper quotes George Church, a renowned genome biologist, as calling the study "a step too far." Church has himself published on the possibility of using CRISPR in gene drives, as covered in Bio-IT World, but has also demanded safeguards to make the process controlled and reversible. Practical uses of gene drives could include disease control, by making insects that carry common infections like malaria resistant to the disease-causing parasites. More drastically, gene drives have also been suggested as a way to deliberately drive a species to extinction, for example by only allowing the male sex chromosome to be passed on from father to child, gradually eliminating females from the species.
Research on CRISPR will continue to expand in scope and ambition, as labs that have never previously attempted genome editing latch onto the technique as a simple tool to explore the field. If this research is to be constrained, voluntary moratoriums among scientists are likely the fastest route to implementing certain controls while the ethics of genome editing are publicly discussed.