December 24, 2015, by Brigitte Nerlich

On the metaphorical origins of gene drives

DSCN3907This morning I woke up to a bit of chat about ‘gene drive‘ – this year’s science breakthrough of the year –, first on twitter, then on the radio. This made me think about the use of terms like gene drive, gene driver, gene driving and where they come from. It also made me think about the metaphorical and visual images they conjure up, that is, about the issue of scientific and cultural imagination.

Gene drives on twitter and Radio 4

At about 06.55 this morning I saw a tweet from Jack Stilgoe saying that he was on his way to York to talk about gene drives on the Radio 4 Today programme. Roland Jackson then asked Jack whether he had listened to Huw Jones earlier on in the programme. I looked at the schedule. I had missed Huw’s item by a few minutes:

“0650: Science magazine’s breakthrough of the year is ‘gene editing’ but scientists are now excited about ‘gene driving’ because it offers the potential to eradicate some deadly viruses. Huw Jones is professor of molecular genetics at Rothamsted Research.”

I then tuned in to listen to the next item on the schedule which focused on ‘gene drives’, a genetic engineering technology which has recently received a boost and become much easier to develop with the advent of the gene editing tool CRISPR/Cas9. It potentially allows scientists to eradicate diseases like malaria by eradicating the insect population that spreads the disease.

“0810: Science magazine’s breakthrough of the year is ‘gene editing’ but scientists are now excited about ‘gene driving’ because it offers the potential to eradicate some deadly viruses. Tom Feilden reports and we hear live from Charles Godfray, Hope Professor of Zoology at the University of Oxford and Jack Stilgoe, senior lecturer at the UCL Department of Science and Technology Studies.”

Gene drives are attracting a lot of attention, most recently in a House of Lords report which argued for field trials in Britain, followed by an article for The Guardian by Jack and Sarah Hartley here at the Making Science Public programme arguing for more caution and an approach based on ‘Responsible Research and Innovation’. The 8.10 item on Radio 4 is worth listening to in this respect, as caution is advocated by both experts interviewed for the programme and as Tom Feilden sets out the pros and cons nicely in his introductory piece.

A few minutes into the programme, at 8.16 I saw a tweet from Oliver Morton, entitled ‘gene drive prehistory’ which showed the cover page of a 2003 issue of New Scientist illustrated with a wonderful pen and ink drawing of a mosquito with malaria written through it (probably by Belle Mellor, as Oliver Morton told me). The title page also carries the phrase ‘genetic annihilation’ which, like the word ‘extinction’ used in the Radio 4 programme, evokes some fears alongside the hope of eradicating fatal diseases like malaria, using GM insects/gene editing/gene drives.

As I am always interested in the origins of words, phrases and concepts, all this radio and twitter chat made me think about two things: (1) The etymology of the words ‘gene drive’ (and associated words used in announcing the Radio 4 Today item during which Jack Stilgoe was interviewed, namely ‘gene driver’ and ‘gene driving’, which were new to me), and (2) the images used to think and talk about this new technology. Basically, how are gene drives verbally and visually imagined? When trying to find out about these things, they nicely came together.

Gene drive’s locomotive metaphor

Gene editing and gene drive are not yet in the Oxford English Dictionary and I can’t yet find any useful information about their etymology. I therefore asked on twitter whether anybody knew who first used the term and got a totally truthful answer from Synthetic Future(s) (at 8.41): “I first used the term in 1983. After a luncheon of devilled pike and several glasses of port…” (I was just typing this, when my husband came in and asked me whether I wanted a glass of port to “stiffen the sinews”! I said it was a bit too early for that… but anyway… “Once more unto the breach, dear friends, once more”… with a cup of coffee).

As far as I can make out by looking at the news database Lexis Nexis, ‘gene drive’ was first used only quite recently in All English Language news, namely on 25 July 2007 in US State News in an article based on a press release. 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. But how does one apply what can be done with a small number of mosquitoes in a lab to the tens of millions of mosquitoes that spread disease worldwide?”

The article uses the phrase gene drive here: “Working with Aedes aegypti, the mosquito that carries yellow fever and dengue fever viruses, the researchers are working to create a ‘gene-drive system’ by using instructions copied from the nanos (nos) gene, which is essential for germline formation. ‘Think of the nanos instructions as a key to a room,’ Adelman said.”

I then tracked down Oliver Morton’s March 2003 article for New Scientist entitled “Splat!” and that proved very useful indeed (New Scientist177.2387 Mar 22, 2003: 32,34-35). In fact, it led me to the metaphorical source of ‘gene drive’ (I believe). Here is the abstract of the article: “Strange properties of DNA sequences called homing endonuclease genes (HEG) can be used to eradicate the whole species of mosquito. These genes have the capability to evade the normal rules of heredity, exploiting a loophole to get extra copies of themselves into the next generation. Morton discusses further the characteristics and behavior of HEG and its effects on mosquitoes.”

Oliver Morton reported on research carried out by Austin Burt at Imperial College London, especially on his 2003 article entitled “Site-specific selfish genes as tools for the control and genetic engineering of natural populations.” But he also points out that “Burt is not the first person to consider messing around with mosquito genes in order to tackle malaria. Chris Curtis of the London School of Hygiene and Tropical Medicine, has been publishing on the subject since the late 1960s, and recently the field has been positively swarming with ideas.”

I won’t summarise the whole article, which is well worth reading, if you can get access to it. What’s important is the following paragraph which seems to show that the phrase ‘gene drive’ has its metaphorical source in thinking about locomotives!

“To solve this problem [spreading genes that make mosquitoes less likely to transmit malaria through a population at large], the resistance genes need to be hitched to a ‘driver’ – a piece of DNA that spreads for some other reason. Various drivers have been discussed, including transposons and parasites that live within the mosquitoes’ cells, but they all share a significant drawback. ‘The crunch problem,’ says Curtis, ‘is how you make sure that the thing you want driven remains linked to the driving system.’ If you think of the driver as a locomotive and the things you want driven as the carriages, he says, then if the coupling between them breaks, the locomotive will drive off into the distance while the carriages start to roll backwards. There’s always a risk that a new mutation will uncouple the driver and its carriages, and even if the chances of this happening are very small, it’s still a fatal flaw. Work by some of Curtis’s colleagues suggests that if the engineered mosquitoes are just 20 per cent less fit than wild ones, and even if the chance of uncoupling is as low as one in a million, the locomotive always runs away and the resistance genes die out. To Curtis, that looks like the end of the line. ‘If we don’t have a reasonable prospect of driving those genes into wild populations, there’s no point.’”

However, only with the advent of the gene editing tool called CRISPR/Cas9 could gene drives ‘take off’, and edited genes can now potentially be ‘driven’ through a whole population of insects relatively easily.

Visual metaphors

So now that we have discovered the verbal metaphorical source for ‘gene drive’ (which however no longer seems to drive modern thinking/imagination about gene drives), what about visual metaphors? The only one I have found so far is an illustration that depicts a mosquito made up of cog wheels (unfortunately not quite locomotive parts) and which accompanies the imaginatively entitled article “Gene drives spread their wings” from December 2015.

I also put ‘gene drive’ into Google images to test the waters and only got boring diagrams, nothing imaginative, interspersed with now ubiquitous images of blood sucking mosquitoes, also used to illustrate the Radio4 Today programme featuring gene editing and gene drives. Does anybody know about more metaphors and images related to ‘gene drive’? I’d be interested to collect them! And of course, if anybody knows who really used ‘gene drive’ for first time….probably somewhere around 2005…

Image: Holiday snap – Swanage steam train

[This Making Science Public post also contributes to my social science work on the BBSRC/EPSRC funded Synthetic Biology Research Centre. You can find other posts on synthetic biology here]

Posted in genomicsimages and visualisationsLanguageMetaphorsresponsible innovationsynthetic biology