Food & Farming

Can we alter an organism’s DNA without selective breeding?

Rapid advances in our understanding of DNA have enabled scientists to transfer genes directly between different species, and even edit the genome itself<a href='https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1583-1' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/nature17946' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>!

Organisms produced in this way are often called genetically modified organisms, or GMOs<a href='https://www.britannica.com/science/genetically-modified-organism' target='_blank'><img src='/img/courses/ref.svg'/></a>. But this name is a bit misleading. As we learnt in the previous chapter, humans have been genetically modifying crops and livestock for thousands of years<a href='https://link.springer.com/article/10.1007/s11248-019-00118-5' target='_blank'><img src='/img/courses/ref.svg'/></a>. Therefore, we will be using a more precise term to describe the direct modification of an organism’s DNA: genetic engineering (GE)<a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Genetically engineered organisms (GEOs) get a lot of bad press, but they’re actually really useful, not just for sustainable agriculture but also for producing medicines and treating genetic diseases<a href='https://www.britannica.com/science/genetically-modified-organism/GMOs-in-medicine-and-research' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S1871678410005364' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062912/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41580-019-0131-5' target='_blank'><img src='/img/courses/ref.svg'/></a>.

In this chapter, we’ll look at how GEOs can be useful in agriculture and consider what the risks are.

The first GEOs were produced by transferring genes from one organism to another<a href='https://royalsociety.org/-/media/policy/projects/climate-change-science-solutions/climate-science-solutions-food.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a>. How does this work?

By copying and pasting genes from one plant to another, scientists have created crops which are higher yielding, more nutritious, and in many cases better for the environment than conventional crops<a href='https://www.tandfonline.com/doi/full/10.4161/gmcr.28098' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://oxfordre.com/environmentalscience/view/10.1093/acrefore/9780199389414.001.0001/acrefore-9780199389414-e-217' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S1871678410005364' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41586-019-1679-0' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Identifying the gene that controls a desired trait, copying that gene, and inserting it into the genome of another organism.

Crossbreeding two organisms to transfer desired traits.

Inducing mutations in an organism's DNA to achieve the desired traits.

Increasing yields in this way not only improves food security but can also improve farmers’ incomes<a href='https://www.sciencedirect.com/science/article/pii/S1871678410005364' target='_blank'><img src='/img/courses/ref.svg'/></a>. Clearly, there are many benefits to genetic modification. So why do many people still object to it?

What are the risks of genetic engineering?

While GEOs provide many environmental benefits, we must also consider their potential risks. Crops and livestock with resistance to insects and diseases could encourage pests to evolve around these defences, making them harder to control<a href='https://www.sciencedirect.com/science/article/pii/S2213453016300295#bib0265' target='_blank'><img src='/img/courses/ref.svg'/></a>.

And if the GEOs have been modified to be better adapted to their environment, they might outcompete wild populations for food and space, reducing biodiversity<a href='https://oxfordre.com/environmentalscience/view/10.1093/acrefore/9780199389414.001.0001/acrefore-9780199389414-e-217' target='_blank'><img src='/img/courses/ref.svg'/></a>. Alternatively, the GEO could breed with wild relatives, introducing the transferred gene into wild populations<a href='https://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-food/en/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Keep GEOs separate from their wild relatives

Insert another gene that allows modified DNA to be switched on and off

Producing GEOs that can’t reproduce (and so don’t pass on modified DNA) is useful for preventing gene escape<a href='https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.12242' target='_blank'><img src='/img/courses/ref.svg'/></a>. But this also prevents farmers from re-planting their seeds the following year. This forces farmers to rely on commercial seed suppliers, giving these companies a lot of control over the farmer’s access to GE technologies<a href='https://acsess.onlinelibrary.wiley.com/doi/abs/10.2135/cropsci2014.09.0669' target='_blank'><img src='/img/courses/ref.svg'/></a>. We will discuss this problem more in the Open Problems chapter.

Perhaps the biggest public concern over GEOs is the potential risk of GE food on human health<a href='https://www.pewresearch.org/science/2016/12/01/public-opinion-about-genetically-modified-foods-and-trust-in-scientists-connected-with-these-foods/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41538-018-0018-4' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.efsa.europa.eu/sites/default/files/corporate_publications/files/Eurobarometer2019_Food-safety-in-the-EU_Full-report.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a>. Is this justified?

When genes are transferred from one organism to another using conventional GE techniques, they can be inserted anywhere in the genome<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056666/' target='_blank'><img src='/img/courses/ref.svg'/></a>. It is possible that the location of this insertion could result in the production of toxins or the accidental disruption of other important genes<a href='https://www.sciencedirect.com/science/article/pii/S2213453016300295#bib0265' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a>. Transferred genes may also trigger reactions in people who are allergic to the organism from which the gene was copied<a href='https://www.sciencedirect.com/science/article/pii/S2213453016300295#bib0265' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Therefore, while scientists largely agree that GE food is just as safe as non-GE food<a href='https://www.nap.edu/read/23395/chapter/2#2' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.pewresearch.org/science/2015/07/23/an-elaboration-of-aaas-scientists-views/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.aaas.org/sites/default/files/AAAS_GM_statement.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://royalsociety.org/topics-policy/projects/gm-plants/is-it-safe-to-eat-gm-crops/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/292174/cst-14-634a-gm-science-update.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a>, it’s still important that GEOs are rigorously tested before they are sold<a href='https://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-food/en/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://academic.oup.com/toxsci/article/162/2/361/4675348' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://royalsociety.org/topics-policy/projects/gm-plants/how-are-gm-crops-regulated/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Many of these concerns relate to the transfer of genes between different organisms. So what if we could introduce desired traits by editing the DNA directly?

While traditional methods of genetic engineering involve the transfer of DNA from one organism to another, recent discoveries in molecular biology have made it possible to edit the genome of an organism directly<a href='https://www.sciencedirect.com/science/article/pii/S2213453016300295#bib0265' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S2211912418300877' target='_blank'><img src='/img/courses/ref.svg'/></a>.

The most efficient tool for genome editing we have today is the CRISPR-Cas system, often just called CRISPR<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

CRISPR is a natural system used by bacteria to defend themselves against viruses<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>. But how does it work?

The name CRISPR actually refers to a short sequence of DNA. In nature, the CRISPR sequence matches the DNA of viruses that have previously infected the bacterial cell<a href='https://www.cell.com/molecular-cell/fulltext/S1097-2765(14)00216-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276514002160%3Fshowall%3Dtrue' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>. If the virus tries to re-invade, these CRISPR sequences can be used by CRISPR-associated (Cas) proteins that act like sniffer dogs to find the matching DNA. When Cas proteins find the virus, they make a cut in the virus’s DNA and deactivate the intruder<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Using these principles, Cas proteins can be trained to locate and cut any gene in an organism’s genome, provided we know the gene’s DNA sequence<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>. With the help of the cell’s own repair systems (that fix any errors or breaks in the cell’s DNA), new genes can be inserted where the DNA has been cut<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795411/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

But CRISPR is not only used to transfer genes from one organism to another. It can also be used to edit the genome directly<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

If no new genes are introduced, the cell will still repair the snipped DNA. However, these repair mechanisms are not always accurate, and can disrupt the gene by adding or deleting letters in the DNA sequence<a href='https://academic.oup.com/nar/article/25/22/4650/2361155' target='_blank'><img src='/img/courses/ref.svg'/></a>. This might sound like a bad thing, but it can be really useful if the disrupted gene gives the organism a beneficial trait like disease resistance<a href='https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154027' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638350/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026172/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Furthermore, by introducing these new versions of genes into plant genomes, CRISPR can increase the genetic diversity of a species<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682324/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pubmed/27571968' target='_blank'><img src='/img/courses/ref.svg'/></a>. This in turn provides more genetic variation for traditional selective breeders to work with<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682324/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pubmed/27571968' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Since its discovery, there has been an explosion in research to develop new ways to use CRISPR technology<a href='https://www.nature.com/articles/nature17946' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682324/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S1097276517307074' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.cell.com/trends/plant-science/fulltext/S1360-1385(19)30243-2' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41467-018-04252-2' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41467-020-15053-x' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41580-019-0131-5' target='_blank'><img src='/img/courses/ref.svg'/></a>. For example, by modifying the Cas protein, scientists are now able to precisely edit each of the individual letters in a gene’s sequence<a href='https://www.nature.com/articles/nature17946' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/nbt.3811' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726555/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S1097276517307074' target='_blank'><img src='/img/courses/ref.svg'/></a>!

To defend against viruses by locating and cutting their DNA

CRISPR is much more precise and less expensive than traditional methods of genetic engineering<a href='https://link.springer.com/article/10.1007/s11248-019-00118-5' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1586-y' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1583-1' target='_blank'><img src='/img/courses/ref.svg'/></a>. In fact, CRISPR can be used to produce genome-edited organisms that have no ‘foreign’ DNA at all. This means that the edited genes are technically no different than those that crop up through the random changes (called mutations) that occur naturally in an organism’s DNA over time<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638350/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026172/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pubmed/29388938/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007326/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230560/' target='_blank'><img src='/img/courses/ref.svg'/></a>!

Farmers have been genetically modifying crops for thousands of years: genetic engineering just allows these changes to occur faster and more precisely<a href='https://link.springer.com/article/10.1007/s11248-019-00118-5' target='_blank'><img src='/img/courses/ref.svg'/></a>. GE crops have the potential to make agriculture more sustainable, while improving the income of farmers and the nutritional content of foods<a href='https://www.sciencedirect.com/science/article/pii/S1871678410005364' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062912/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

However, many people are still uncomfortable with the idea of GE food<a href='https://www.nature.com/articles/s41538-018-0018-4' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.gsb.stanford.edu/sites/gsb/files/jmp_sydney-scott.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a>. This is largely down to a lack of clear communication between scientists and the general public<a href='https://www.pewresearch.org/science/2016/12/01/public-opinion-about-genetically-modified-foods-and-trust-in-scientists-connected-with-these-foods/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.nature.com/articles/s41538-018-0018-4' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Advances in genome editing have made genetic engineering safer and more precise than ever before<a href='https://link.springer.com/article/10.1007/s11248-019-00118-5' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>, and it is now possible to genetically engineer products with no ‘foreign’ DNA at all<a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638350/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026172/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pubmed/29388938/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007326/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230560/' target='_blank'><img src='/img/courses/ref.svg'/></a>. For this reason, many argue that ‘food regulations’ - the rules dictating whether a product can be sold as food - should be based on the safety of the food itself, rather than the process by which it was produced<a href='https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/292174/cst-14-634a-gm-science-update.pdf' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.frontiersin.org/articles/10.3389/fbioe.2019.00026/full' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.europarl.europa.eu/RegData/etudes/IDAN/2022/690194/EPRS_IDA(2022)690194_EN.pdf ' target='_blank'><img src='/img/courses/ref.svg'/></a>. Indeed, this is already the case in the USA and Canada<a href='https://www.frontiersin.org/articles/10.3389/fpls.2020.00284/full' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.frontiersin.org/articles/10.3389/fbioe.2019.00026/full' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.sciencedirect.com/science/article/pii/S2452072119300371' target='_blank'><img src='/img/courses/ref.svg'/></a>.

Even so, assessment of the potential environment and health risks of all new products is still essential, as well as regulations to ensure these tools are only used for ethical purposes<a href='https://www.isaaa.org/resources/publications/pocketk/17/default.asp' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-food/en/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://royalsociety.org/topics-policy/projects/gm-plants/how-are-gm-crops-regulated/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733845/' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.frontiersin.org/articles/10.3389/fpls.2020.00284/full' target='_blank'><img src='/img/courses/ref.svg'/></a>.

By educating people about the benefits of GEO technologies and clearly addressing their concerns, GE food may become more widely accepted<a href='https://link.springer.com/article/10.1007%2Fs00299-016-1974-2' target='_blank'><img src='/img/courses/ref.svg'/></a><a href='https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031443/' target='_blank'><img src='/img/courses/ref.svg'/></a>.

So far we’ve looked at the problems of crop farming, and how genetic engineering, agroecology, and precision farming could be used to solve them. But what about farming animals? We’ll look at that in the next chapter.