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We humans have been tinkering with the genes of plants and animals since we first started the process of domestication over 12,000 years ago. Admittedly, we didn’t know that genes existed for the vast majority of that time, but we figured out that selective breeding could ensure that desirable traits would end up being prevalent in our crops and livestock.

Today, we know that selective breeding is the progressive gathering of genes underlying those traits into a single genome. Over the past few decades we have incrementally improved our ability to do this in a more deliberate fashion. This has been facilitated by the calculated application of different technologies. Some of these involve removing harmful genes, while others necessitate the addition of genes underpinning the desired traits. Initially we relied on quite crude physical or chemical methods to introduce new genes; recently we’ve turned to more biological methods, such as viruses, to deliver chosen genes into the targeted genomes.

Now we have a new approach, one that represents a huge advance: genome editing. The most famous example of a genome editing tool is called CRISPR-Cas9, or CRISPR for short. It allows us to cut a genome at a specific point and to introduce, interrupt or remove genes at that point. In this two-part system, the CRISPR is a user-defined molecule that directs the DNA-cutting function of Cas9 protein to its matching site in the genome. Although genome editing systems have existed since the 1970s, CRISPR is by far the most user-friendly and accurate to date, incomparable to previous generations in terms of its accuracy and precision.

You might well have heard of CRISPR by now, unfortunately for the worst of reasons: the fuss over its use to make “designer babies” in China earlier this year. To recap: an academic took (legitimate) research into the potential use of CRISPR to edit human genes and decided to (illegitimately) put it into practice, implanting modified embryos into an expectant mother.

Nine months later, twins with edited copies of the CCR5 gene – theoretically making them HIV resistant – were born. Since the editing occurred when they were just a single cell, all of the cells in their bodies now carry the edited gene, not just the cells of their immune system. The normal CCR5 gene has been implicated in some aspects of brain development; so there is significant speculation that their brain function may have been altered and perhaps even enhanced.

Their birth catapulted the discussion of genome editing humans to the front of public consciousness. While that debate is a necessary and important one – clearly we need better regulation of genome editing in humans – it should not overshadow another, arguably more pressing one: How should we use this new technology, CRISPR, to ethically improve life? Rogue scientists notwithstanding, the next decade is likely to see us amending the animals and plants we created by gene tinkering for millennia - rather than editing humans.

Although genome editing systems have existed since the 1970s, CRISPR is by far the most user-friendly and accurate to date.

The Tipping Point - Green Editing

Beyond selective breeding

A genome is the entire collection of genes in an organism’s metaphorical book of life; an instruction manual to keep all the cells in an organism’s body working in unison. Any given characteristic of an organism is encoded by multiple genes, typically acting in concert. For example, even a trait as seemingly simple as eye colour has two major and eight minor genes implicated.

The basic principle of selective breeding is that if only individuals with desirable characteristics are allowed to reproduce with each other, these desirable characteristics will become concentrated in their offspring. Done carefully, and with repetition, each generation will be an incremental “improvement” on the last: the rules of genetic inheritance mean their offspring will, in general, accumulate the intended characteristics. However, not all offspring carry the desired characteristics – we all know someone who just doesn’t look anything like their parents!

Getting the right combination of genes to appear consistently takes time: traditional breeding involves a great deal of wasted effort, time, money, and ultimately, the lives of unwanted animals. Animals bred for a purpose they cannot not fulfil are disposed of. Technology can help: “Tudder” allows farmers to find good matches using a Tinder-style app. But we ought to use more sophisticated technologies to improve the entire process, not just to reduce the speed of selection to the time it takes to swipe right.

The greatest impact of this technology over the next decade is likely to be in making our agricultural practices more effective and ethical.

CRISPR could, and should, revolutionise the speed and efficacy of the traditionally arduous selective breeding process, and allow the application of hard-earned human knowledge without exposure to the element of chance.

Because CRISPR targets user-defined sequences, it works like a ‘find-and-replace’ function for genomes. Unlike previous techniques, CRISPR-based genome editing allows insertion or removal of genes involved in these desirable characteristics in a single generation. Furthermore, it is now relatively easy and cheap to confirm by DNA sequencing that only the intended edits have occurred. This means fewer unintended off-target effects compared to other genome editing techniques, and higher likelihood of picking up mistakes.

Farmers will be most interested in the obvious commercial advantages of improving crop and meat yields – but the rest of us should also be interested, because genome editing allows us to gain environmental benefits, too. The greatest impact of this technology over the next decade is likely to be in making our agricultural practices more effective and ethical.

A new green revolution

The total environmental impact of crops alone stretches from the clearing and maintenance of land for cultivation, water and nutrient consumption by the crops, harvesting of the crops and finally their transportation to a processing plant and onwards to the consumers. Not to mention the measures necessary to ensure crop survival and yield – meaning pesticides and herbicides – some known to affect both humans and non-target species in the surrounding environment.

A recent review of genome editing in crops found that most studies focus on improving yield over resistance to abiotic and biotic challenges. Higher crop yields mean less ground needed, both for crops but also for animal feed. For example, calving cows can require up to 30kg per day of dry matter intake (grass plus nutrients); thus increasing yields by even a small percentage has huge cumulative implications for many crop-reliant industries.

Crop yields aside, we can also reap environmental benefits by tackling crop resilience to environmental challenges. Crops including rice, potato, tomato, maize, barley and wheat are of agricultural significance in terms of their consumption both by humans and livestock. Their respective sensitivities to cold, salt, drought, nitrogen levels and damage by fungal, bacterial and viral infection are significant challenges to farmers. Aside from the obvious effects on their growth, these parameters also limit the places they can be grown, and thus the carbon costs of transporting them to market.

CRISPR is already being applied to tweak these characteristics in crops. World-wide, research findings are being applied to efficiently bring about the changes that crop farmers spend decades crossing plants to achieve using traditional breeding methods. For example, a gene called SDN-1 has been targeted by genome editing to make wheat resistant to a devastating mildew fungus. The management of this powdery mildew fungus is estimated to have cost the state of California alone $239 million in 2015.

Genome editing can also be used to improve outcomes and environmental impact in animal husbandry. Clever applications of CRISPR could have an immediate impact on certain livestock practices that create significant ethical issues. For example, CRISPR-Cas9 genome editing is being used to make pigs resistant to incurable virus infections, which otherwise have severe health consequences for the pigs, and cost an estimated $660 million to farmers in North America alone. Another example is bovine tuberculosis, a bacterial disease that cost the UK an estimated £44 million in 2017/18. Although the pasteurisation of milk in the UK has curbed transmission to humans, in other parts of the world it still occurs. In this context, the recent use of genome editing technologies to make cows resistant to bovine tuberculosis is to be welcomed.

Rewriting wrongs

We can also use genome editing to address issues that are more purely ethical in nature. For example, around seven billion male chicks are disposed of each year, often in ways that seem grotesque. This is because they can’t lay eggs – and thousands of years of selective breeding aimed at improving egg production means their meat isn’t appealing either. It’s been reported recently that a company has created a mechanical system to check the sex of a chick before it hatches. But that still means destroying billions of fertilised eggs – an unsavoury and wasteful approach.

The beef and dairy industries are similarly single-sex in their requirements; male calves grow faster and produce more meat than female calves, and only female calves produce milk. CRISPR can be used to tweak the genes that control offspring sex ratios, meaning no unwanted animals, destined only for disposal, are created in the first place. That’s not confined to chickens: for example, researchers in the USA are creating a bull that only sires male offspring, with promising results to date.

A less obvious application of CRISPR might be to address harmful traits created by traditional selective breeding. One major challenge of selective breeding of livestock is compromised immunity: the use of antibiotics and other interventions to increase the yields of increasingly inbred herds has made them vulnerable to attack by disease. Using CRISPR to address this could improve the health of these animals – with knock-on consequences for the overuse of antibiotics in agriculture, which is threatening the effectiveness of these essential drugs in human medicine.

At a more domestic scale, it is common knowledge that many breeds of cats and dogs are troubled by diseases specific to their breeds: for example, Dalmatians have severe issues with their kidneys due to a gene mutation that affects their ability to clear metabolites from their system. There are already reports of attempts to rectify this using CRISPR-based genome editing. In some cases, medical issues have resulted from breeding for aesthetic qualities: bulldogs have been bred to have “pushed-in” faces, but these cause the animals significant breathing problems; again, there is interest in using CRISPR to remove the gene variants responsible.

More positively, service dogs are used in roles from aiding the blind and disabled, to the police force and other public services. These animals are painstakingly selectively bred to meet their role requirements. Genome editing offers a faster way to obtaining good quality service animals, and reports of genome editing in this lesser-appreciated arena of life have been circulating for some time.

From animals to humans

Of note, the negative perceptions surrounding genetically modified organisms of old seem to particularly revolve around insertion of foreign genes into an organism’s genome. Headlines about “Frankenfoods” led to fear that this might lead to unforeseen (and undesirable) outcomes; though examples like the now FDA-approved AquaBounty Salmon, genetically modified to improve its growth rate and thus commercial value, demonstrate the safety and acceptability of even such organisms. Encouragingly, CRISPR can sidestep this particular concern by simply modifying what is already there. No added genes are necessary. It thus seems a smaller step away from “normal” genetic tinkering through breeding.

While the next decade in genome editing is likely to focus on plants and animals, we can also start cautiously probing its use in humans. Interestingly, work in animals is already having implications for future human medical interventions. For example, Duchenne muscular dystrophy is an incurable human disease, which also occurs in many pedigree dog breeds. A recent study used CRISPR-Cas9 genome editing to partially restore the function of the responsible gene in dogs, giving new hope for the development of a future cure for humans.

Genome editing offers the vision of being able to remove the cause of a disease, rather than merely treating its symptoms. Many human genetic diseases are caused by mutations in the human genome – errors which, if correctable by genome editing, have potential to yield huge advances in medical science. In fact, the first European CRISPR therapy for humans, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, is being trialled to treat beta-thalassemia, a disorder affecting the ability of blood cells to transport oxygen. This trial aims to make blood stem cells in patients revert to a foetal form of haemoglobin, which is known to bind oxygen better than the adult form.

So genome editing is a powerful technology with many potential applications. But it is important to note that unless you understand the problem, you can’t edit it out.

So genome editing is a powerful technology with many potential applications. But it is important to note that unless you understand the problem, you can’t edit it out.

We have already begun to focus on specific concerns in a range of fields including agriculture, livestock and human disease; the coming decade will see a plethora of new applications of genome editing. From near-future applications like the ones discussed above, to the treatment of colour-blindness and plants edited to remove greenhouse gases from the environment, and on to futures that only exist in the imaginations of enthusiastic research scientists. This technology has few theoretical bounds.

Importantly, for these to be properly developed, we will have to sharpen our understanding of genetics both generally and in specific organisms of interest. Only when the relationship between a gene and an outcome is understood can we begin tweaking it. Beta-thalassemia is a well understood, well studied, disorder, but many other genetic diseases are not.

As the “designer babies” incident in China demonstrated, attempting to use genome editing when we do not have a good understanding of the basics is likely to sow confusion and discord at a time when we still do not know what will come of this technology. However, CRISPR-based genome editing opens up unprecedented new capacities for research and previously unimaginable solutions to many problems, and with them new ethical challenges. We will have to learn from the failures of public engagement in the past and ensure the public are properly informed and engaged this time around.

Increasing the understanding of this technology, and science in general, will curb the likelihood of this technology being abused and misapplied.

Success in the scientific, social, cultural and economic domains is critical. The important thing to keep in mind about this is: genome editing is just a tool. Scientifically speaking, it is a very powerful tool, but how we use it, who owns it and who makes profit from it comes down to our choices in the arenas of politics and economics.

We have a global responsibility to use the power and precision of genome editing to make our practices and industries more ethically and environmentally sound. Most importantly, increasing the understanding of this technology, and science in general, will curb the likelihood of this technology being abused and misapplied.

The true power of any technology is only appreciated in its appropriate application. In many cases, it will allow us to resolve the complex issues and inadvertent harms created by thousands of years of well-meaning, but old-fashioned, genetic meddling. We must not miss this opportunity.

Dr Güneş Taylor is a postdoctoral training fellow at the Francis Crick Institute. Güneş has debated genome editing and related topics in forums including the Battle of Ideas, Fertility Fest, the Festival of Genomics, FutureFest and Virtual Futures, as well as in the Guardian newspaper’s Science Weekly podcast and in the pages of New Scientist magazine.