December 28, 2020, by Brigitte Nerlich

Genetics and genomics – when metaphors begin to matter

I remember in the not so distant past standing in the Wellcome Sanger Institute in Cambridge admiring the huge sequencing machines and chatting about public engagement with colleagues before giving a talk about genomics and metaphors. I also remember writing some things about gene editing and metaphor. In my mind all this related to basic science not basic survival.

Now all is different. We don’t need public engagement activities to raise awareness of the importance of genomics and medicine. We see every day how important advances in genetics and genomics are, especially in two respects: mapping the strains and variants of the new virus (here genome sequencing plays an important role) and developing new vaccines against the new virus and new strains of the virus (here gene editing or engineering may play an important role). One of these uses of genetics and genomics is uncontroversial, the other not.

Mapping strains

All over the world, scientists, including geneticists, epidemiologists and more, have made enormous efforts to track and understand the new coronavirus SARS-CoV-2. The UK in particular has always played an important role in sequencing research (starting with, amongst others, Frederic Sanger), and was therefore well placed to go into action.

As Bill Hanage said in a tweet: “It is quite hard to grasp just how much SARS-CoV-2 genome sequencing has happened in the UK, or how important that effort is right now. Whatever you might think about the country’s pandemic response the scientists deserve our admiration.” So true.

A new virus strain “was picked up by the Covid-19 Genomics UK (COG-UK) consortium, which undertakes random genetic sequencing of positive covid-19 samples around the UK. The consortium is a partnership of the UK’s four public health agencies, as well as the Wellcome Sanger Institute and 12 academic institutions.”

As a BBC news item said: “Sequencing the virus’s genome allows scientists to see how it is changing as it subtly mutates over time, and to uncover how outbreaks spread, by looking at clusters of a particular variant of the virus. This kind of genetic detective work allowed scientists to work out that the UK’s early outbreak in the spring was coming mainly from Europe rather than China, based on the variants that were circulating.”

Tracking, tracing and detective work are the metaphors of choice here, metaphors that we are used to and proud to use when talking about epidemics and epidemiology. So far so good. But now things get a bit more complicated.

Developing vaccines

The best way to end the pandemic is to vaccinate as many people as possible. Scientists, pharmacologists, virologists, viral immunologists, vaccinologists and industrialists all over the world started to develop vaccines as soon as the pandemic began, and now various vaccines have been developed – it’s quite incredible.

Some are based on the well-established technique of using an inactivated virus (like the Oxford-AstraZeneca vaccine), others are based on the novel technique of using a tiny fragment of genetic code from the pandemic virus (like the Pfizer-BioNthec and Moderna vaccines) – these are novel genetic vaccines.

In this case, what gets inside us are bits (or bytes) of genetic information, not anything material like bits of an inactivated virus (but, of course, the instructions still have to be delivered in some material fashion). Like the inactivated virus, this small but important fragment of genetic code (all 4284 characters of it) teaches the body how to fight Covid-19 and build up immunity. It wakes up the immune system and puts it on high alert.

These instructions (‘look there is a spike protein, go on do something’) are encoded and delivered by something called messenger RNA or mRNA – in this case synthetic mRNA (pioneered amongst many others by Katalin Karikó). This does not change anybody’s DNA. In fact “the mRNA strand never enters the cell’s nucleus or affects genetic material”. If you want to know how it all works read this instructive thread.

What happens if the virus mutates substantially? With the older method of developing vaccines, one would have to start all over again, but with the new method it might be possible to ‘just’ change or tweak or indeed edit the genetic instructions that tell the body to be on the look-out for the new virus.

I have just used the word ‘editing’ and so I looked around a bit to see how the phrase ‘gene editing’ was being used during the pandemic. It seems that ‘gene editing’ is not used by those explaining what some of the new vaccines do, because it’s not really gene editing – rather it’s genetic engineering. By contrast, the phrase ‘gene editing’ is used a lot by those opposing the new vaccines, where ‘gene editing’ has become a big red flag (e.g. “Merging of man and machine. That’s the gene editing vaccine they want you to get.”). Gene editing has also been discussed by bioethicists in the context of Covid.

I think it might be good to do more research into how communication between vaccine advocates and vaccine opponents works with this phrase hanging over the communication efforts like a ghost.

When metaphors matter

What happens, for example when either ‘side’ reads a sentence like this: “Engineers can now design strands of mRNA on computers, guided by algorithms that predict which combination of genetic letters will yield a viral protein with just the right shape to prod the human body into producing protective antibodies.” Or: “Moderna’s chief medical officer has described the company’s products as ‘hacking the software of life’ and permanently altering a person’s genetic code.” Or “It is another wondrous miracle from a biotech revolution in which knowledge of genetic coding will become as important as digital coding and molecules will become the new microchips.” I could actually not believe that I was reading this.

We are back to metaphors, that is, where I started from. I’d love to do more research on this in the future. How does such talk influence current vaccination discourse and more generally public understanding of genetics and genomics, so vital now to our survival now and in the future?

As Peter Hotez, Professor of Pediatrics and Molecular Virology & Microbiology, recently said, using a different metaphor: The Pfizer/BioNtech vaccine “provides a glidepath for using mRNA technology for other vaccines, including cancer, autoimmune disorders, and other infectious diseases, as well as vehicles for genetic therapies. It really does help accelerate the whole biomedical field.”

Image: Me at Wellcome Genome Campus, Cambridge, April 2018

Posted in biotechnologygenomicsinfectious diseasesMetaphorsScience Communication