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Genome editing (hopefully) simplified

WHAg Window – giving a view from our perspective…..

In a recent article we outlined concerns about genome editing. Since then we have been asked to give a simple guide to what it actually is. Well…deep breath and fingers crossed, and referring to far more knowledgeable people than I am, here is a shot it.

First of all, should it be called genome editing or gene editing? Are they the same thing?

Yes, to most intents and purposes, they refer to the same things. The term “genome editing” is scientifically more correct but “gene editing” is more popularly used. Colleagues at Beyond GM use “genome editing” to describe the method or technology and “gene edited” (as in plants, animals etc) to describe the product or outcome but let’s not get too pedantic.

Ok, so what is it?

Whichever of these terms you use is a catch-all, umbrella name for is a suite of new genetic engineering techniques that can be, or might be or can potentially be, used in plant and animal breeding, in human medical and animal veterinary treatments. It can be used to create heritable traits or non-heritable changes.

Catch-all? What’s included?

The term covers an array of geeky sounding names which hide behind funny sounding acronyms and initials. These include ODM (oligonucleotide directed mutagenesis), ZFN (zinc finger nucleases), TALEN (transcription activator-like effector nucleases and, the one becoming the most widely used, CRISPR (clustered regularly-interspaced short palindromic repeats).

Other technological developments are being included in the “catch-all” – or possibly hidden under the umbrella – the whole time but for the sake of brevity, simplicity and sanity, the one I’ll focus on now, and the one you will have come across most often, is known as CRISPR-Cas.

Is it a GMO?

No and yes. No, because it is a technological process and a GMO (a genetically modified organism) is the end product of a technological process known as genetic engineering. But, yes, because genome editing (whichever method used) is a genetic engineering process and any resulting product is a GMO.

You’ve heard that it’s not genetic engineering

“Gene editing is not genetic engineering” has become a favoured line of its protagonists. I nearly wrote “lie” there because that line is tantamount to one, or is the result of misinformation and/or ignorance. All honest and transparent genetic engineers and researchers in the field, will own up to the fact that genome editing is a process of genetic engineering. In 2016, in a major ruling, the European Court of Justice concluded that it is and that it is within the scope of EU laws on genetic engineering and GMOs.

The technical stuff - can’t avoid the technical stuff any longer

Here’s bit of background which may be useful, thanks to colleague, Janet Cotter, for this. If you feel you are losing the will to live, scroll down and see if things are more digestible later.

  • Genetic material is a fundamental part of every organism and is made up of DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).

  • In plants, animals and humans, genetic material is stored mainly in the genome, which occurs in the nucleus of almost all cells.

  • The genome is made up of DNA. Part of this DNA makes up our genes, which produce proteins.

  • It’s these proteins that perform many of the functions of a cell. Other DNA in the genome regulates the genes, telling them when and where to switch on and off.

  • RNA is a different type of genetic material. It used to be thought of as just an intermediary between DNA and proteins, but recent discoveries have found it can perform a large number of functions, such as (alongside DNA) regulating genes, silencing genes and repairing DNA.

  • It’s largely these recent discoveries about the roles of RNA that have demonstrated the many reactions and interactions between elements that occur in cells to make them function, all of which are controlled by complex regulatory networks.

So, where is genome editing in all of this?

Genome editing is where a small cut is made in the DNA.

You may have heard the metaphor likening it to the “cut and paste” function on a computer/word processor. Well, it’s not really like that. That’s part of the pro-narrative that bedevils this issue.

You may have also heard the term “molecular scissors”, which is supposed to elicit images of home dress making, a sort of 21st century cut and sew pattern book. It’s not really like that either.

“Cut and paste”, “cut and edit” – what does it all mean?

Right, to quit the imagery; first of all, the “molecular scissors” are enzymes (which are small proteins also called nucleases). These enzymes create a cut in the DNA after they have been guided to the targeted point by an artificial protein or artificial stretch of RNA.

The mythical “paste” part of the edit then occurs either by organism’s own system repairing the cut or by inserting a template of artificial DNA or RNA which directs the repair.  

At this point transgenic i.e. “foreign” DNA, bacteria or virus’ can also be inserted.

In all three instances, changes occur to the gene during the repair process.

It is important to note, that this is entirely an “in vitro” (“within glass”) procedure – taking place in a test tube, culture dish, or elsewhere outside a living organism.

An important bit more about the edit repair

There is more information about this process and a nice diagram here.

Unfortunately, I have to introduce a new term here in order to explain what is becoming a policy and political issue in the debate to deregulate genome editing.

The term is site directed nucleases or SDN, and there are three of them called (relatively considerately) SDN 1,2 and 3. This term refers, firstly, to the process of directing the process (the enzyme cut) to a targeting point in the DNA and then to the type of repair mechanism mentioned above.

SDN1, is where the organism repairs itself; SDN2 is where an artificial DNA or RNA template is inserted; and SDN3 is where significant foreign genetic material is inserted with the template to create a transgenic organism.

Unintended and “off-target effects”

All genetic engineering causes disruption to the genome of the targeted organism, that’s the point of it after all. The claim for genome editing is that it is more precise and therefore less disruptive and damaging than earlier genetic engineering, and even than some types of traditional breeding.

However, the evidence is mounting of far more significant unintended and off-target effects than initially thought. Much of this evidence has come to light in medical research but has implications for food safety.

It is notable that genetic engineers and researchers working in the medical field are much less gung-ho, more cautious and more open to regulation of the technology than those in agriculture where the significance of these unintended and off-target effects is regarded as less important.

The GMO or like nature controversy

As I mentioned earlier the European Court of Justice ruled the genome editing is genetic engineering and falls within the scope of the GMO laws.

The essential points about the legal definition of GMOs and the process of producing them is that they and it would not occur (or normally occur) in nature. As we have seen, genome editing takes place entirely outside of natural, living organisms “in glass”. So how can anyone argue that genome editing is anything other than genetic engineering and outside of nature?

It is widely accepted that SDN3’s are GMOs and fall under the GMO regulation. But it is argued, that SDN1 does not involve any insertion of foreign genetic material, relies on the organism’s (plant or animal) own living repair process and results in something that might be found in natural or traditional breeding processes – or it is claimed, is “akin to nature” or “like nature”.

It is further argued, that some applications of SDN2 might also considered in the same way.

You might have a simple response to that claim.

Simplified but not simple

I have tried and I hope made a passable job of explaining this. The links in the article give far more information, as do the websites of Beyond GM and GMWatch. They are on the sceptical side of the debate but there are plenty of information sources on the pro-side. Regrettably, many of them are organisations and bodies who ought to be giving impartial information are amongst them.

We are clear that we believe this is a technology incompatible with a wholistic approach to health. But it might have a role in what some might perceive as “sustainable” farming and food. In which case, a more open, honest, transparent discussion of the technology would be helpful. I hope this attempt at explaining terminology has helped a bit.

Lawrence Woodward

Lawrence Woodward OBE

About the Author:  I’m the chairman of WHAg, founder and director of the Organic Research Centre (ORC), and regularly advise & speak about the principles and methods of organic agriculture. 

Genome editing: invasive and hollowing out the whole

Credit: natural products global

Genome editing is the new “sustainability” buzzword. In the recent House of Lords consideration of amendments to the Agriculture Bill there were frequent references to “precision breeding”, “new plant breeding techniques” and “modern breeding methods” for plants and livestock – all of them euphemisms for genome editing.

This latest incarnation of genetic engineering technology is not one particular method. It is a whole suite of them with differing characteristics. But you wouldn’t know that from the sweeping generalisations made about this “game-changing” technology which, it is claimed, is “akin to natural processes” but “more precise” and has such benefits and negligible risk that it should immediately be freed of regulatory oversight where it will lead the way in a transformative “bioeconomy”.

In the past, such claims for GMOs have been met with incredulity, a healthy dose of scepticism and more than a little bit of ridicule from NGOs and civil society. Not now. There is an increasing willingness to accept that genome editing has – at least the potential – to advance the cause of “sustainable” food and farming, have animal welfare benefits and more speedily tackle some of the difficult issues caused by climate change.

Some have begun accept the claims that genome editing impacts in a way that is similar to natural processes and could be accepted in regenerative, agroecological and even organic farming. One of our partners, Beyond GM, has been running a programme called “A Bigger Conversation” exploring the claims, perspectives and attitudes surrounding genome editing. Some of the findings have been surprising – from all sides.

Surprising support for genome editing

The latest event in this programme was a webinar which started out to explore the broader issues of “sustainability” – whatever that means nowadays, which all the panelists, including WHAg’s Lawrence Woodward, agreed isn’t very much.

But when the conversation got down to the potential benefits of genome editing some really controversial things emerged.

Compassion in World Farming CEO Philip Lymbery was concerned that adoption of genome editing could entrench industrial farming systems but he nevertheless, supported it’s use in some circumstances. He asked:

“What if, chickens were successfully gene edited so the only eggs with female embryos are viable…If successful, this technology could be a revolution, ending at a stroke, the killing of birth of 5 billion sentient creatures a year.”

In an earlier BGM meeting, support had been expressed for the use of genome editing to deal with dehorning cattle.

Lymbery also voiced support for cell-based meat analogues. While not all of these involve genome editing some of them do.

Organic farmer Guy Singh-Watson also offered some support for gene editing, noting: “I’m not adamantly against the technology” and that “If you could give us a blight resistant potato, I would find it very hard to argue against.” He, nevertheless expressed real concerns around the system, which seems to go hand in hand with GM technology.

As the “Bigger Conversation” programme has revealed these perspectives are becoming more widely held.

The antithesis of whole health

It might be there is a role for genome editing in something that is called “sustainability” but Lawrence Woodward is adamant that it is the antithesis of a whole system approach to health, which is built on the integrity of the whole living organism, be it soil life, plants, animals and man within a living, functioning ecosystem.

Woodward and Hugh Jones, Professor of Translational Genomics for Plant Breeding at Aberystwyth University recently had an online exchange about these concepts and practices. The discussion can be viewed here and from it lots of background references to genome editing, plant breeding approaches, the wholistic philosophy behind the organic approach to health and perspectives on gene function can be accessed.

In the exchange Woodward notes that, “The development of the concepts of organic plant breeding and seed has been primarily driven by ideas rooted in, anthroposophical, holistic, socially focussed agroecological perspectives. From these emerge the precept to “respect the genome and the cell as an indivisible functional entity” and to “follow the concept of respecting integrity of life.”

The consequence of this precept for organic plant (and animal) breeding is that: “any technical or physical invasion into the isolated cell is refrained from and plant specific crossing barriers are respected, irrespective of potential benefit risk assessments.”

Genome editing is clearly invasive and is not wholistic. There have not been enough studies to determine how much of a risk it is to the process of health and well-being. There are no studies to indicate any benefit to the function of the process of health but as the rationale behind genome editing is to “cut and paste”, “cut and delete”, it is surely reasonable to call it “hollowing out the whole”.

Watch the full-length video recording of the webinar here.

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