You’ve probably noticed that the number of pages in newspapers and science journals does not expand and contract much while the importance of underlying news stories varies wildly. So is the hoopla surrounding the recent report of a demonstration of gene drive in mosquitoes about something hot or just a bunch of hot air? I’ll tell you what I think.
Arguably, I’m not an unbiased observer. I am tangentially related to testing the technology coming from the labs developing mosquito gene-drive technology. However, my children will attest to the fact that I’m an unflinching critic regardless of relationships. (Just ask my son whose novella I edited!) I simply have little capacity to change my opinion based on relational attachment.
With that disclaimer, I’ll weigh in on whether I think the recent report (“A synthetic homing endonuclease-based gene drive system in the human malaria mosquito”) of a gene drive system demonstration in Anopheles gambiae is hot, or does the wide reporting of this publication simply reflect the fact that there are hundreds of media outlets hungry for content, no matter how humble.
Background: Those developing genetic modification technology for mosquitoes have faced a daunting reality: In spite of the fact that many of these scientists have spent little time in the field, they still recognize that there are lots and lots and lots of mosquitoes out there! Raising the frequency of genes among such large numbers of mosquitoes so that malaria transmission is affected enough to make any difference is impossible. Impossible, that is, unless there were some way to cause the gene introduced into populations to increase in frequency by using a natural process such as genetic invasion (as observed with transposable elements), selection or something analogous to cytoplasmic incompatibility (as is being used against dengue in Aedes aegypti.
Enter the polyglot mosquito research group at Imperial College London and their whiz-bang protein-engineering colleagues at the Univ. of Washington in Seattle, USA. For the first time, they have demonstrated that a mobile genetic element called a homing endonuclease gene (HEG) can invade the genome of cage populations in a site-specific way and increase in frequency at rates consistent with models. (Yep: they got the controls right in spite of my certainty that they wouldn’t.)
If you can wade through the molecular biology you’ll realize that the targets of the HEGs were easily assayed fluorescent markers. Fluorescent markers. Big deal. How useful is that? Another academic exercise. But wait. It has already been demonstrated that the site specificity of HEGs can be artificially altered, and numerous genes have been identified as containing HEG targets. These facts mean their demonstration is not merely an academic proof-of-principle. As they claim: “…these genetic elements could overcome a major roadblock…genetic manipulation of entire field populations starting from a few laboratory individuals.”
Of course, the phrase “could overcome” is loaded with uncertainty about what changes that qualifier to “would.” What’s solid about the HEG scheme that has been demonstrated is that it not only brings site-specific spread into the equation (which reduces uncertainty about off-target effects) but it also reduces concerns about another bugaboo: loss of linkage between an effector and the drive mechanisms. Because the target will almost certainly be a genomic target whose disabling IS the effect, drive IS the effect and loss of linkage is irrelevant. (Still relevant is target site or HEG mutation, but that’s another issue.)
So kudos to the team that has made this advance. It’s a long road to turn pipe-dreams into toasts. But even given the difference between “could” and “would,” I’ll hoist a pint to this effort, even if it’s a British “hot” one.