Hacking the Code of Life

by Nessa Carey

  We often can’t produce and distribute the food where it is most needed, and that’s essentially a logistics problem. This is compounded by the issue of food waste. In countries with less developed infrastructure, a huge proportion of food spoils before it can reach the people who need it. In industrialised nations, vast amounts of perfectly nutritious food are rejected from the commercial food chain on aesthetic grounds. Yet more is discarded by stores or thrown out by customers who have over-ordered. Globally about a third of all food produced for humans is wasted.12

  If we are to feed our extended global family, we therefore need to solve various major issues. We need to decrease meat consumption, stop over-eating, and use all the food we produce. These require changes in human behaviours; a rapid rolling-back of the obesogenic environments in which most inhabitants of the industrialised world live; and a resetting of our attitude to food as a cheap, throwaway commodity. Unfortunately, as individuals, governments and societies we are remarkably useless at taking long-term decisions that are in our own interests. Working out why we are so useless at this is too big a job for science, but maybe science can help with the production of better and more plentiful food? That’s where gene editing can come in.

  Speeding up breeding

  Plants have certain characteristics that can make them quite challenging for any form of genetic engineering. Plant cells are surrounded by a thick wall, which can cause difficulties when trying to force new genetic material into them. Many of the most commercially valuable plant species, such as wheat, potatoes and bananas, have also developed really complicated genomes. In almost all mammalian species the cell contains two copies of each gene (one inherited from the mother and one from the father). But at various points in their evolution, many plants have duplicated their entire genomic information. Bread wheat, for example, has six copies of every gene. So if you want to change a gene in bread wheat, you have to change all six copies, making the job much harder than in mammalian cells.

  But plants also have useful characteristics that can outweigh their problem areas for gene editing. If you edit a gene in a mouse’s leg, for example, you can’t create an entire edited mouse from that leg. But – as any gardener who has ever tried to get rid of a persistent weed like ground elder or bindweed can tell you – many plants can produce an entire organism just from a tiny bit of root that has been left in the soil of the flowerbed. So, once you have gene edited plant cells successfully, it can often be fairly straightforward to propagate lots of identical plants.

  Plant scientists recognised very quickly that the new techniques for gene editing could revolutionise the efficiency, speed and ease of creating new plant varieties. The first gene-edited plants were created just one year after Doudna and Charpentier’s seminal paper, by a number of research groups.13,14,15 Since then, researchers have improved the techniques and extended them to a whole range of plant species.

  It might be tempting to wonder why we need to bother with gene editing for plants, given that we have been creating new varieties for millennia, simply by cross-pollinating ones that have features we like. Well, one reason is speed. For slow-maturing plants like citrus fruits, which also have low fertility, it can take a lifetime to determine if the new offspring have the desired characteristics and will breed true. With modern gene editing techniques, this could be speeded up to less than the time it takes to complete a PhD project.

  In other cases, there may be very little natural variety to work with in a population. In the 1970s the appearance of the English countryside changed irrevocably as almost all elm trees were wiped out by a fungus carried by a beetle. In 2004, researchers used DNA sequencing technologies to show that almost all English elms were genetically incredibly similar. They were essentially clones of an original tree imported during the Roman invasions two thousand years earlier.16 The lack of genetic variation meant there were no English elms that were resistant to the fungus, and trying to create them via crossing individuals would be futile. Gene editing could in the future create a way to introduce variety into a very genetically restricted plant population.

  One of the other issues with traditional breeding techniques is exemplified by the Elsanta strawberry. Supermarkets love this variety. The berries grow very large, as long as they get plenty of water. They are red and luscious looking, and survive shipping well without going mushy. There is just one problem. They taste of absolutely nothing. That’s because during the creation of this variety, achieved by crossing various other strawberry plants, the versions of the genes that give that wonderful sweet strawberry taste of summer were lost along with the ones that cause mushiness or a pale colour. But gene editing holds the promise of being able to change just the precise genes you want to alter, while leaving all the others untouched.

  Creating better crops, one edit at a time

  Promise is one thing, delivery quite another. But with the extraordinary speed that has characterised the gene editing field, potential benefits are being realised remarkably quickly.

  Researchers are finding new ways to minimise waste. Although mushrooms are technically fungi, they are usually found in the vegetable section of supermarkets, so we’ll include them here. White button mushrooms have a tendency to go brown as they age, and are often needlessly thrown out when this happens. Researchers have been able to use gene editing to create mushrooms that don’t go brown.17 This could drive down food waste easily.

  There’s a very important interaction between food and human health. We all know the importance of a balanced and varied diet, but what if one of the components of a typical diet is the very thing that makes you ill? Coeliac disease affects about 1% of the population. In this condition, the body’s immune system mounts a harmful reaction to the gluten proteins found in wheat. This damages the lining of the gut, resulting in diarrhoea and vomiting, and in its most extreme forms it can lead to malnutrition and gut cancers. A research group at the Institute for Sustainable Agriculture in Cordoba, Spain, used gene editing to inactivate 35 of the 45 genes in wheat that produce the specific gluten proteins that trigger the immune over-reaction. Delightfully, they reported that the resulting flour was good enough to create baguettes, but not suitable for baking sliced white loaves.18 Coeliacs of France, rejoice.

  Gene editing can be used to drive down the cost of some flavours. Traditional beers get their characteristic taste from the use of hops in the brewing process. Hops are expensive and difficult to grow and harvest in a typical agricultural setting. They are also a thirsty crop, needing about 50 pints of water for every pint of beer produced. Researchers at the University of California, Berkeley adapted gene editing technologies so that brewer’s yeast would produce the flavours normally created by hops.19 The technology worked so well that employees of a local craft brewery actually thought the gene-edited product had a better taste than the traditional hop-infused ale.

  Increasing the yield from crops, ideally without having to use additional expensive inputs, is a key target for agricultural companies and farmers, both commercial and subsistence. Rice is the staple food for more than half the world’s population and is especially important in low- and middle-income countries.20 Maintaining and improving rice yields is vital for food security.

  Gene editing has been used in a collaboration between the Chinese Academy of Sciences in Shanghai and Purdue University, Indiana to achieve just this. There is a set of thirteen genes in rice which helps the plant to tolerate environmental stresses such as drought and salinity. Using traditional cross-fertilisation techniques, agronomists in the past have been able to create rice plants which are less susceptible to these stresses. Unfortunately, these hybrid plants had decreased yields, because the same genes are also involved in growth suppression. The scientists in the joint US–Chinese team speculated that if they could just introduce the right combination of mutations into these genes, they would be able to generate hardy rice which also cropped really well. It’s a task that would be nigh-on impossible using old-fashioned cr
osses – it would take too long and you would need to carry out too many generations of crosses to have even a hope of getting the exact combination of gene variants you wanted. But with the new gene editing techniques, the researchers were able to achieve the outcome they wanted in just a couple of years. They created a variety that was just as good at tolerating stress as any other type of rice, but which generated 25% to 31% increase in yields in field trials. This is a huge jump in productivity in a vitally important crop.21

  Creating new varieties of important food crops that can tolerate adverse environmental conditions could be vital for agriculture. Ironically this is because our ever-increasing human population is putting ever greater stresses on production. Salt levels are increasing in agricultural land and this decreases plant growth and yield. Geographers have calculated that 20% of total cultivated land and 33% of irrigated agricultural lands worldwide are affected by high salinity, and that this figure is increasing by 10% every year.22

  Agricultural land is also becoming more arid. The United Nations has calculated that the livelihoods of 1 billion people are threatened by desertification, and these are often some of the poorest people on the planet to begin with.23 Competition for water is already acting as a factor in national and international conflict situations.24

  Desertification is one of the reasons why the new gene editing techniques are so rapidly finding uses in creating crop varieties more resistant to these kinds of stresses. It’s very encouraging that the rice story has shown this approach is feasible, that scientists can increase resistance to environmental stresses with no negative – and indeed sometimes positive – effects on yield. A similar technique has been employed to create maize which can tolerate drought while still increasing yield by 4%.25

  All the technology is moving in the right direction, creating crops which are robust, better able to cope with environmental stresses and deliver increased yields with no increase in expensive inputs. It’s tempting to assume that there is a very happy outcome heading our way. But at least two issues may mitigate against this, and neither is a scientific one. It’s not about how the technology develops, it’s about how the technology will be used, by people and their governments.

  If the new varieties of gene-edited crops allow farmers to use existing farmland more efficiently, that will indeed be a great achievement. But we always have to beware of unintended consequences. What if instead the new varieties are used to bring more land under cultivation, converting previously marginal or agriculturally useless land into farmed fields? This will inevitably cause more biodiversity loss, as these marginal lands are often the only place where species are able to cling on to some habitat. If the new technologies are implemented without addressing the fundamental issues of food waste and over-consumption, they will at best be delaying a doomsday scenario, and at worst pushing us towards it faster. Science alone cannot solve the problem.

  Reaching the market

  The other issue with the creation of gene-edited crops is an equally problematic one. Will producers be allowed to plant and harvest them, and will they be allowed to sell them to consumers? There is no global consensus on this, and the long history of opposition to GM crops – genetically modified crops – suggests the path to adoption may be rather stony.

  It partly depends where you live. In 2014, over 70 million hectares of land in the USA were used to grow GM crops. In Europe, the equivalent acreage was about 0.1 million hectares.26 This is largely due to the different regulations in these territories, and these in turn have been heavily influenced by pressure groups and consumer campaigns. This has affected adoption in other regions of the world.

  Researchers have become intensely frustrated by the opposition to GM crops, and never more so than in the case of Golden Rice. As we have already seen, rice is a staple foodstuff for billions of people worldwide. It’s not a perfect source of nutrients, however, and one of the things it can’t supply is vitamin A. Vitamin A is vital for a healthy immune system and for the developing visual system. To quote the World Health Organization: ‘An estimated 250,000 to 500,000 vitamin A-deficient children become blind every year, half of them dying within 12 months of losing their sight.’27 These deaths are in addition to the 1 to 2 million deaths from infectious diseases that could be prevented if all pre-school children received adequate amounts of vitamin A.28

  Golden Rice was genetically engineered to express extra genes in the rice seeds, leading to the production of beta-carotene. Beta-carotene is easily converted into vitamin A in the human body. The original paper describing the production of Golden Rice was published in 2000.29 Subsequent additional research has improved Golden Rice yet further, increasing the amount of beta-carotene that it produces. Trials with volunteers have demonstrated that humans do indeed convert the beta-carotene in this crop to vitamin A, and at levels high enough to prevent blindness and infections.

  And yet – Golden Rice may finally reach consumers in Bangladesh and the Philippines in the next few years, but that’s not guaranteed. That’s over two decades since it was first grown under laboratory conditions. Of course, there was bound to be development time; no one expected this to reach its target groups in desperately poor countries overnight. But two decades?

  This isn’t a case where greedy corporations have prevented the poorest people in the world from accessing a desperately needed product. All the companies involved in the production of Golden Rice agreed quite rapidly to make it available at the same price as normal rice to subsistence and small-scale farmers, and with no restrictions on them harvesting and storing seeds to replant.

  The biggest opponents have been western pressure groups such as Greenpeace. In 2016, over 100 Nobel laureates – about one third of all living Nobel medal holders – wrote an open letter to Greenpeace criticising their position on genetically modified organisms and on Golden Rice in particular.30 Greenpeace’s response was essentially predicated on the argument that accepting the implementation of Golden Rice would mean a lack of opposition to all GM crops.

  There is a certain philosophical logic here – if you oppose GM on principle, then you must oppose all GM. Whether these opponents have ever sat down and explained that principle to a bereaved parent or a child who has avoidably and irreversibly lost their sight is something you might be interested to know about.

  When science and regulation meet

  The phrase ‘gene editing’ is used to refer to the technology that has developed since 2012, which permits scientists to alter genomes with exceptional precision and ease. It is essentially a sub-type of genetic modification, as it uses molecular techniques to alter the genome of organisms. However, in addition to its simplicity of use, gene editing has a number of differences and advantages over the earlier technologies. It can be used to create smaller modifications to the genome, and leaves fewer extraneous genetic elements. In its most technically exquisite form, gene editing leaves no molecular trace at all. It may just change, in a precisely controlled manner, one letter of the genetic alphabet. In this manifestation of gene editing, it is impossible to distinguish between an organism that was edited by scientists in the laboratory and a naturally occurring variant with the same change in the same letter.

  Objections to the early forms of GM were often based around the significant changes that had been introduced into the genome. These led to fears that ‘foreign’ genes – often inserted to ensure high-level expression of the desired trait – would spread throughout wild populations and distort plant ecosystems, or create new variants that had abnormal functions. There were also concerns that GM foods would be damaging to human health, usually through unspecified mechanisms.

  None of these dire predictions has come to pass, although that doesn’t mean that it was foolish to have concerns. Innovative technologies may have unexpected and unanticipated consequences, and it’s entirely appropriate that there should be periods of monitoring and staged implementation.

  Absolutely nothing in life is risk-free. The prob
lem is that we are all very bad at assessing risk. A train crash with multiple fatalities scares people into commuting by motorbike, a spectacularly less safe means of transportation. Small new risks frighten us much more than larger old ones, because we have integrated the old levels of risk into our lives, and we don’t think about them.

  It’s unreasonable to expect any new technology to be absolutely risk-free. What we should expect is that at the least it is no more risky than the existing technology. There are few if any convincing data that even the ‘old-fashioned’ GM plants pose a level of risk that exceeds that of traditional plant breeding methods. Given the greater degree of precision of gene editing, and the more limited disruption of the genome compared with earlier generations of GM, it’s interesting to see how regulators are treating edited plants.

  Between 2016 and early 2018, the US Department of Agriculture informed the creators of over a dozen gene-edited crops that it didn’t need to regulate them. On 28 March 2018 the US Secretary of Agriculture, Sonny Perdue, authorised a press release31 confirming that this would now be an ongoing strategy, rather than something that would need confirmation on a one-by-one basis. It’s an important precedent, as it means that such plants can be designed, cultivated and sold without regulation, accelerating their uptake and entry into the market.

  The rationale was quite simple. If the gene editing resulted in a genetic change that does or could occur in nature, then there’s no need for the regulators to get involved. The change could be altering a letter in the code, adding or deleting a few letters, or even adding in sequences from close relatives. All of these changes could occur through normal plant breeding. The regulators therefore adopted the position that it was irrational to accept a change if it arose through traditional horticultural techniques, but to reject the same, genetically indistinguishable change if created through editing.