October 25, 2019, by Brigitte Nerlich
A road called ‘gene drive’ and the road to ‘gene drive’: Trials and tribulations of media analysis
As people might know, I enjoy doing media analysis of emerging biotechnologies, from cloning to gene editing and beyond.
I have lately become fascinated with something called ‘gene drive’, a new genetic engineering technology that was brought to public attention around 2014/2015 at the confluence of two ‘events’: the outbreak of Zika and advances in CRISPR-Cas9 as a new tool to ‘edit’ genomes more or less at will (declared breakthrough of the year in 2015).
Zika is an emerging infectious disease caused by the Zika virus. Like malaria or dengue fever, it is transmitted by mosquitoes. The Zika outbreak around 2015 made people think more intensively about how to deal with the spread of such diseases and about finding new ways of dealing with the spreaders, namely the mosquitoes.
CRISPR-Cas9 is a new genome editing tool that makes it easier for scientists to modify genomes, of, for example, mosquitoes, in such a way that the change spreads exceedingly quickly through a population bypassing normal laws of inheritance. With the help of this new technology called ‘gene drive’, whole populations of mosquitoes can thus, in theory, be changed, eliminated, replaced and so on. This has so far not been tried anywhere in the wild and is, as you can imagine, rather controversial. The use of gene drive using genome editing for insect/disease control was put on the map in 2014 by Kevin Esvelt and others and has attracted some media attention ever since.
How is this controversy reported in the media, we wondered? By ‘we’ I mean Sarah Hartley, PI on a Wellcome Trust funded ‘Talking about gene drive’ project, Aleksandra Stelmach, research fellow on the project, and I, co-applicant.
Easy-peasy I thought. Put the phrase “gene drive” into Nexis, my favourite news database, and see what happens, i.e. see how it spreads, possibly exponentially, through the main English speaking news outlets. So we did. What happened was chaos.
Dead ends, new pathways and resurfaced roads
There were two problems. There is somewhere in the United States a road called “gene drive”. That’s the first problem. The second problem was that despite using quotation marks in order to search for the exact phrase ‘gene drive’, the machine picked out instances of, for example, ‘the cart that Gene drives’ or ‘genes drive the development of x’ and so on. Yet another problem was that Nexis was, unbeknown to us, in a process of transformation and quite a few things, like downloading, didn’t work.
In the end, we used another search engine, one I am not so familiar with, namely Factiva. We found it quite useful, as it also provides access to graphs and keywords etc. We searched for ‘gene drive’ in four regions: US, UK, Australia and Uganda. There were still some problems, but we got some interesting corpora and data.
Just when we had started to analyse these, Nexis changed. It became usable again (but the exact phrase search thing still doesn’t really work). It even has little graphs now and key word analyses.
As I have access to Nexis but not Factiva (only Aleksandra has access to Factiva in Exeter), I did a bit of searching once Nexis worked again – I couldn’t resist. I got some interesting results, once I had discarded the still lurking roads called ‘gene drive’ and some other anomalies.
The road to ‘gene drive’
For this little post I just wanted to know how and when conversations about gene drive started to emerge (but as I said above they only really got going around 2015). What I found confirmed what I had already dug out in my first blog post on gene drive. The first English language news article using the phrase ‘gene drive’ was published in 2007. The second in 2009. The topic exploded after 2015 (but not as much other topics, such as epigenetics and the microbiome, for example). I still haven’t met anybody out in the real world who knew what I was talking about when I mention ‘gene drive’….
The 2007 article refers to research carried out into this issue about 20 years earlier, that is, around 1996/97. As the phrase ‘gene drive’ wasn’t used before 2007 in English news, I searched for the larger category of ‘genetically modified mosquitoes’ (or GMM) and found an article from 1996.
I’ll now say a little bit about these early articles. First the 1996 one (i.e. the first one on GMM), then the 2007 and then the 2009 ones (i.e. the first two on gene drive proper). In between there were of course many others relating to various forms of GMM, including gene drive before the name started to be used. And it should be stressed that research into what one might call population GM was carried out in the sixties by Chris Curtis and George Craig, for example.
The 1996 article, published on 15 June 1996 in The San Diego Union-Tribune, reports on research carried out at the University of California San Diego by Jane Burns and published in Proceedings of the National Academy of Sciences (PNAS). She talks about how one could in “a specific and controlled way… be genetically altering the mosquitoes so they can’t transmit diseases”. Her work dealt with Anopheles gambiae, which are mosquitoes that transmit malaria. They are also one the test organisms of choice used nowadays by gene drive researchers at Imperial College.
Burns compares what she does to ‘vaccinating’ the mosquitoes instead of vaccinating the people, a framing that is still being used today, for example by Austin Burt at Imperial College. In practice this means the GMM would have a trait conveyed by a “transferred gene” that “can be passed from generation to generation”.
How is this done? “Burns has succeeded in engineering the mosquito cells because she designed a virus that can penetrate the cells and deliver genes”. You have to read the whole article to understand exactly what’s going on! The title of the PNAS paper is: “Pantropic retroviral vectors integrate and express in cells of the malaria mosquito, Anopheles gambiae”. She basically succeeded in doing something that nowadays can be achieved more quickly by genome editing using CRISPR-Cas9 I think…
The 2007 article, also based on a paper published in PNAS – the first using the phrase ‘gene drive’ in our corpus – appeared on 25 July in US States News and is in fact a press release by Virginia Tech and the University of California Irvine. It starts by saying: “A decade ago, scientists announced the ability to introduce foreign genes into the mosquito genome. A year ago, scientists announced the successful use of an artificial gene that prevented a virus from replicating within mosquitoes” (that 2006 paper also appeared in PNAS – it focused on genetically modifying Aedes aegypti which transmit dengue fever).
The 2007 paper, also focusing on Aedes aegypti, “demonstrated the ability to express a foreign gene exclusively in the female mosquito germline”. The main player here was Zach Adelman. The gene drive system they developed used “the nanos (nos) gene, which is essential for germline formation”.
To explain how their ‘gene drive system’ works, Adelman used a metaphor, namely that of key. “’Think of the nanos instructions as a key to a room,’ Adelman said.” Unfortunately, we don’t hear much more about that key! The metaphor is not elaborated and the rest of the press release is pretty impenetrable to lay people!
The 2009 article, which appeared on 30 May 2009 in New Scientist, is quite long, well written, draws the reader in and focuses mainly on the use of Wolbachia in an Australian experiment. At the very end, the reporter Rachel Nowak also talks about various kinds of ‘gene drive’, but only briefly.
Back to a dead end – and the road ahead
Reading this New Scientist article, I remembered another one published in 2003 by Oliver Morton, entitled Splat!, and reporting on work relating to what one might call a proto-gene-drive carried out by Austin Burt and Andrea Crisanti at Imperial College. I searched Nexis high and low and I could not find the article. It should be there, but it wasn’t. This shows that one cannot rely on anything!
Anyway, the article describes the work of Burt and Crisanti very nicely and in much needed detail. It turns out that they developed a ‘gene drive’ before CRISPR-Cas9 was even on the horizon, which is interesting, as, confusingly, some people, even scientists and commentators in Nature, define gene drive by reference to CRISPR-Cas9. In the 2003 case, researchers used a different genetic trick to do what CRISPR-Cas9 now does, namely ‘homing endonuclease genes’.
Morton homes in on the most important aspect of gene drives, namely the copying of a genetic change from one chromosome to the other in a cell – which was also used in this case. “In organisms that have paired chromosomes, a gene present on only one chromosome normally gets passed on to exactly half the organism’s offspring. Unless, that is, the gene is an HEG [homing endonuclease genes]. An HEG on one chromosome in a cell can use that cell’s repair mechanisms to get itself copied onto the chromosome’s partner. If the cell in question is a cell that makes eggs or sperm, this copying means that all the eggs or sperm will contain a copy of the HEG – and so all the offspring get a copy. In this way HEGs can spread through a population very quickly indeed.” That’s ‘gene drive’.
Homing endonuclease genes or HEGs were, some say, “the first engineered ‘gene drive’”, but the news, at least as recorded by Nexis, didn’t pick that up. For gene drives to become newsworthy we had to wait for them to go CRISPR.
Finding a road through the semantic jungle
Gene drive research seems to have started about two decades ago (with roots that reach into the 1960s), but it will still be long time before gene drives will be deployed, if at all, according to most experts involved. GMM, by contrast, are being field-tested already.
For me, it will take an even longer time still to get my head around all the types of gene drives that I have now read about (natural and synthetic, global and local, crash drives, reversal drives and immunising drives…. there is even a lovely sounding daisy drive)! So I was quite relieved when reading through our Nexis samples and found Burt saying in 2018: “there isn’t even agreement on what a gene drive is”!
‘Gene drive’ seems to be an extremely polysemous phrase, that is to say, it has many meanings, some old, some new, some used by some people, some by others, sometimes denoting an object (a ‘cassette’), sometimes a process (‘mutagenic chain reaction’), and so on. This makes it very difficult for non-experts to talk about ‘gene drive’ in any, at least vaguely knowledgeable, way. That’s at least my personal impression!
I’d appreciate any help I can get to find a road through this semantic jungle! Something like this perhaps, metaphorically entitled ‘Sculpting Evolution, but catering more for the lay person.
Image: Road in California, Pixabay
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