Gene-editing – a GMO by any other name…

February 26, 2016 by Dr. Janet Cotter

There is a considerable amount of hype regarding the ability of gene-edited crops and animals to transform agriculture. But what are those promises and do we really need gene-edited crops and animals?

The promises of gene-editing include crops “that better withstand pests, that have enhanced nutritional value, and that are able to grow on marginal lands” and “extending the shelf life of fruits, vegetables, and cut flowers; altering the plant architecture of fruit trees, ornamental flowers, and trees; improving yield potential; and enhancing plant pest and disease resistance”.

Animals too can be improved; proof-of-concept scientific papers have appeared on gene-edited goats, sheep, pigs, monkeys and dogs, as well as hornless cattle. Companies such as Du Pont are ready to develop (and patent) gene-edited crops, predicting they will be on our dinner plates in 5 years’ time.

If that’s the case then we owe it to ourselves to understand something about them.

What is gene-editing?

Gene-editing is a family of new genetic engineering techniques that form part of the new breeding technologies that the EU is currently considering how to regulate – considering whether to exempt GMO plants and animals produced by gene-editing from the GMO regulations.

Although gene-editing has been the subject of media coverage recently with regard to gene-editing of human embryos, very little attention has, so far, been paid to how gene-editing might affect agriculture and the food we eat in the future.

If it’s decided that gene-edited plants and animals are exempt from the EU GMO regulations, they could be in our environment and on our dinner plates unlabelled and untested. A scary thought.

A little background

A little background may be useful.

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.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 such as DNA, proteins and RNA that occur in cells to make them function, all of which are controlled by complex regulatory networks.

It turns out that the ways in which genomes function is a whole lot more complex than was thought back in the 1970s when genetic engineering was invented. This is important as it means that tweaking one part of a genome can unintentionally lead to alterations elsewhere, through pathways that may not be obvious, because a full understanding of how genomes work is still lacking.

Gene-editing – a glossary

There are several families of techniques that make up what is collectively known as gene-editing. 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).

Most of these use nucleases or ‘molecular scissors’ are enzymes (small proteins) that cut DNA. The molecular scissors are joined to an artificial protein or short stretch of artificial RNA that allows the molecular scissors to be guided to the desired “cutting point” of an organism’s DNA. The joined scissors guide are inserted into a cell nucleus in the laboratory. The DNA is cut and the organism’s own repair mechanisms then re-join the cut DNA but, usually, an artificial DNA template is also inserted into the cell that makes a crucial changes to the gene during the repair. The changes to DNA may be small, but enough to introduce a new trait.

ODM uses a slightly differ procedure. It introduces small, artificial stretches of DNA that nearly (but not completely) match a stretch of the organism’s DNA. This causes the cell’s own repair mechanisms to change a small section of DNA to match the incoming DNA.

Different language, same result

Despite the change of language, gene-editing is still genetic engineering.

Genetic engineering modifies genetic material using laboratory (‘in vitro’) processes instead of through the normal breeding process. In older genetic engineering processes (that is, the type that produced today’s commercial GM crops such as Roundup Ready soya) a genetic construct, usually involving a gene (or genes), is inserted into the genome at random.

The inserted gene(s) operates outside the control of the organism’s gene regulatory networks. Instead, it is constantly switched ‘on’ and the gene produces a protein that performs a function, e.g. tolerance to the herbicide Roundup.

A fundamental concern of genetic engineering is that the insertion of the genetic contrast may interrupt normal genome function. It may inadvertently alter the proteins an organism produces, or the new protein may alter a plant chemical pathway.

That’s why GMOs are prone to unexpected and unpredictable effects. These effects can be hard to discover, prompting concern for the food and environmental safety of GMOs.

Unexpected effects have been recorded in GM plants. These include unexpected chemical compounds in the plant, or changed levels of chemical compounds. For example, the concentration of glycoalkaloids (the main toxic compound in potatoes) both increased and decreased unexpectedly in leaves during separate genetic engineering experiments with potatoes.

Gene-editing can also insert new genes into an organism’s genome. The difference is that gene editing can also operate in a different way, by introducing what is analogous to a genetic ‘typewriter’ into the genome. That is, it inserts artificial elements (usually genetic material) into an organism’s genome that re-write a gene (or several genes). The rewritten gene(s) is then inherited into offspring, but the introduced element (the typewriter) is not. In this way, the gene (or genes) are said to be ‘edited’.

And the same concerns

Gene-editing is described as superior and more precise in comparisons with the old techniques of genetic engineering. Indeed, the softening of language from ‘engineering’ to ‘gene-editing’ implies that gene editing is somehow easier or less complex then genetic engineering. ‘Editing’ DNA sounds less invasive than ‘modifying’ or ‘engineering’ DNA. It suggests that gene-editing has a certain, predictable outcome. But does it?

Actually, many of the concerns with gene-edited organisms are very similar or the same as current GMOs. For example, one of the concerns with CRISPR (and other gene-editing techniques) is that they can cause ‘off target’ effects. That is, the molecular scissors might cut the DNA, not only in the intended place, but in additional, unintended places.

The considerable investment in genetic science in the last few decades had shown that our understanding of how genomes, RNA and DNA operate is woefully incomplete. For example, the environment affects gene expression – and we are only just discovering how important this might be – for humans as well as animals and plants. Life is complex so it isn’t really possible to simplify it to simple building bricks.

Many of these gene-editing techniques are very new. CRISPR, for example was invented in 2012/3 – and scientists are fighting over who owns the patent to the technique. This means we may not yet know what all the potential difficulties with the technique are, e.g. how prevalent are these off target effects?

As with older genetic engineering techniques, there are concerns that changes to the function or expression a gene can cause effects to other genes elsewhere in the organisms’ genome. It’s likely that gene-edited plants and animals will be just as prone to unexpected and unpredictable effects as current GMOs.

If the definition fits…

Gene-editing techniques may differ in their details but the outcome is a product that is a GMO, and needs to be regulated as a GMO. This is because the genetic material of the organism has been directly modified in the laboratory by in vitro processes, just like the older genetic engineering techniques. The use of laboratory techniques (as opposed to breeding) to change the genetic make-up of an organism is one of the ways GMOs are defined in both the EU and the UN treaty which regulates trade on living GMOs, the Cartagena Protocol on Biosafety.

Despite this, some developers assert that, because only small changes to the DNA are involved or the final product doesn’t contain genes from another organism (so-called ‘foreign’ genes), gene-edited crops and animals should be exempt from the GMO regulations, and hence exempt from environmental or human and animal health risk assessment.

Risk assessment isn’t perfect. Many of us think GMOs should never be released to the environment of food chain, with or without a risk assessment, and many don’t want GMOs in our food. But if gene-edited crops and animals aren’t regulated as GMOs, there would be no requirement to assess the risks these GMOs might pose to the environment or human and animal health – nor any requirement to label any foods produced by gene-edited crops as derived from GMOs. Gene-edited crops and animals would be released to our environment and, unknowingly, in the food chain without any consideration of the risks they might pose.

Empty promises…again?

GM crops have failed to deliver on their promises – of increased yields, lower chemical inputs, higher profits and enhanced nutrition. After 20 years there are still only two commercialised traits: herbicide tolerance and insect resistance. At the same time, they have caused numerous problems weed resistance from increased use of herbicides the GM crops are tolerant to and concerns about effects on wildlife, e.g. butterflies.

Despite all the hype surrounding gene-editing techniques, one of the first applications is for herbicide tolerant oil seed rape (canola). This is a clear indication these new technologies are primed to continue the paradigm of industrial agriculture.

The question we need to ask is do we need GM crops – gene-edited or otherwise? The answer is no.

Most of the traits farmers want in crops, desirable traits such as such as drought and flood tolerance or disease resistance occur naturally with the vast range of varieties that exist, often in traditional varieties or landraces (locally adapted, traditional varieties of domesticated animals or plants). The problem is these, these traditional varieties tend to be lower yielding than modern ones.

Understanding genes rather than manipulating them

In the decades since GMOs were commercialised, there has been remarkable progress in conventional breeding. Many breeders now use ‘molecular markers’ to track genes of interest (e.g. those conferring drought tolerance) through the breeding process using marker assisted selection (MAS), often termed smart breeding.

This means producing a drought tolerant plant becomes much quicker as breeders know before field trials whether the offspring contains drought tolerant genes, because of the tracking process during breeding.

MAS results in a conventionally–bred plant, but uses our knowledge of genes and genomes to assisted selecting varieties with desirable traits. There are many examples of MAS-bred varieties, including flood tolerant rice and stripe rust fungus resistant wheat. MAS utilises the diverse traits within these traditional varieties to breed desired traits into modern varieties, maintaining their yield. This makes them much more attractive to farmers and underlines the importance of traditional varieties as a genetic resource.

MAS varieties are not immune from patents, but, importantly, can be used in participatory breeding programmes, where farmers work together with scientists to breed new varieties – a more bottom-up approach to plant breeding.

Farming is what needs to change

Globally, there is concern that we are focused on only a very few crops for our food security, mainly crops like rice, wheat, soy, potatoes. There are many other crops that are not being utilised enough, such as millets, rye, yams, sweet potatoes and cassava. Increasing the acreage of such crops could help increase food security.

But it’s not only the crop varieties we farm, it’s how we farm those crops.

As many reviews of agriculture have shown, agriculture needs a wholesale reform. For example, the UN/World Bank Ag Assessment concluded that “Business as usual was not an option” – a sentiment echoed recently by the UN Food and Agriculture Organisation in a statement that “Agriculture can’t remain the same”.

Agriculture needs new ways of producing food – ones that don’t cost the earth. Thankfully, various forms of ecological farming, especially organic farming, are increasing globally as governments and scientists realise that, although yields may be lower, the benefits of organic farming terms of the environment: less pollution of soils and waters, better soil quality (including soil carbon content), greater biodiversity and health: reduced or eliminated pesticides in food become realised.

A vision of food and farming beyond GM is being articulated. All we need now is the political and societal will to implement that vision.