It all began with a simple question: How do bacteria defend themselves against viruses?

The answer was as strange as it was elegant: Bacteria develop clustered, repeated sequences in their DNA, that can remember dangerous viruses that attack them. To do this they take little mugshots, or small sections of DNA from the invaders, and stash them in their own genome, for future reference.

When biochemist Jennifer Doudna and her colleagues at the University of California, Berkeley, published the paper on their findings in 2012, it went largely unnoticed.

It all began with a simple question: How do bacteria defend themselves against viruses?

The answer was as strange as it was elegant: Bacteria develop clustered, repeated sequences in their DNA, that can remember dangerous viruses that attack them. To do this they take little mugshots, or small sections of DNA from the invaders, and stash them in their own genome, for future reference.

When biochemist Jennifer Doudna and her colleagues at the University of California, Berkeley, published the paper on their findings in 2012, it went largely unnoticed.

But it wouldn’t be long before it set off a revolution in genetics.

The clustered repeated sequences that the bacteria develop were named Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR).

What the bacteria do next would hold the key.

It turned out that the CRISPR sequences team up with certain proteins (Cas9) to form a pair of molecular scissors that cut away and destroy the virus DNA, once it is identified.

Once again, as so often in science, a seemingly random question (what’s this green mould in my petri dish?) had revealed new ways to change the world.

By 2020, the CRISPR-Cas9 genome-editing technique had been replicated and repurposed so it could tweak the genes of almost any living being. It earned Doudna and her fellow lead researcher Emmanuelle Charpentier the 2020 Nobel Prize in Chemistry.

“I remember thinking… when we publish this paper, it’s like firing the starting gun at a race,” she told The New York Times in 2022.

In just a few years, CRISPR has changed how researchers view food hybridisation, endangered-animal conservation, resilience-building in crops (even, potentially, in humans).

It is altering how we study and treat diseases.

In clinical trials, immune cells are being edited to better hunt down and attack cancers. CRISPR-edited bone marrow cells are being explored as a potential treatment for blood abnormalities such as sickle cell disease and thalassemia.

Could it also give us better tomatoes, a hybrid woolly mammoth-elephant that could help save Arctic forests, and perhaps even help us travel further in our search of habitable planets?

One of the biggest limitations of gene editing is the knowledge of the genome and its complexity. This is why the work that we see today is largely focused on recreating mutations and variations we have seen in nature by editing well-characterised genes, says Brad Ringeisen, executive director of the Innovative Genomics Institute (IGI) founded by Doudna in 2014.

There’s hope that all the tinkering won’t cause unintended consequences because we now know what we are looking for. “Gene editing creates precise changes with a specific aim, which makes it different from breeding technologies of past decades like mutation breeding which created random mutations in hope of finding an occasional beneficial one.”

Meanwhile, the carbon footprint of the gene editing process itself is negligible. It can be used to lower the enormous carbon footprint of agriculture or possibly to reinforce existing harmful practices.“I’d like to think everyone from farmers to CEOs is interested in being more productive with less impact,” Ringeisen adds.

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Plate expectations: Seedless fruits, healthier potato chips?

Could greens get crunchier, potatoes get healthier, and tomatoes calm rattled nerves?

In late 2021, Japanese company Sanatech Seed launched Sicilian Rouge tomatoes that were genome-edited to produce high levels of gamma-aminobutyric acid (GABA), a compound naturally found in the brain. The neurotransmitter has been linked to stress reduction and the lowering of blood pressure. While fruits such as strawberries, lychees and tomatoes naturally contain GABA, researchers gene-edited tomatoes to offer four to five times the amount compared to conventional varieties.

The tomatoes became the first food gene-edited using CRISPR-Cas9 technology to be commercially available in Japan. Also in 2021, Japanese stores began to sell puffer fish and sea bream genome-edited to grow bigger and meatier. These were developed by the Regional Fish Institute in collaboration with the Kyoto and Kindai universities.

In 2022, researchers in South Korea edited tomatoes using CRISPR technology, to make them richer in Vitamin D.

Agritech and seed companies are at the forefront of harnessing the potential of genetically edited food, driving development in the emerging field. A team of researchers at the US-based agritech company Pairwise, for instance, is working on a niche offering: less-pungent mustard greens. Seedless blackberries and pitless cherries are expected next, says Pairwise CEO Tom Adams.

Fruit waste, such as cherry pits or peach stones, can be a major inconvenience and a deterrent for consumers. “It’s not just about creating a new product; it’s about expanding access to healthy, fresh produce in a way that fits into modern lifestyles,” he adds.

While humans have always crossbred and hybridised produce, these changes are both more substantial, and are being effected much faster—a new more palatable variety of mustard greens took six months, as opposed to decades.

The key, of course, is CRISPR, which allows for more precise hybridisation, greater uniformity and the window of a few months to create truly new and exciting fresh produce.

“Gene editing will not replace traditional methods but will complement them. The beauty of gene editing is its precision. It allows us to build on the foundations of traditional agriculture while introducing innovations that weren’t feasible before,” Adams says.

Back to the promise of healthier potatoes, researchers at Murdoch University are working to eliminate acrylamide, a potentially cancer-causing compound that potatoes can form when put in cold storage and then fried. So far, a CRISPR-Cas9 system has managed to reduce acrylamide-producing abilities by about 80%, in a lab setting. It’ll be a while before the fries are ready.

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Monsters, Inc: Return of the mammoth, dodo, Tasmanian tiger?

The first three to be resurrected will be the woolly mammoth, Tasmanian tiger, and the dodo.

A team of more than 60 scientists spread across Boston and Dallas in the US and Melbourne in Australia have been working for three years on the Colossal Biosciences de-extinction project.

They are building comprehensive genomes and using CRISPR-Cas9 to splice DNA into the genes of these creatures’ closest living relatives. The result is unlikely to be a replica; it will be more akin to a hybrid organism.

“Historically, de-extinction has been defined as the process of generating an organism that either resembles or is an extinct species,” says Ben Lamm, CEO and co-founder of Colossal. “What we need to generate is an organism that is also improved through the resurrection of lost core genes, the engineering of natural resistances, and the addition of enhancements of adaptability which will allow it thrive in today’s environment of climate change, dwindling resources, disease and human interference.”

The woolly mammoth, which died out 4,000 years ago, is being resurrected via the Asian elephant. The resulting animal will likely have thick fur, subcutaneous fat, and Arctic-adapted haemoglobin. The hope is that a reintroduced hybrid species could help restore the Arctic grasslands, which they once helped nurture with their migratory pollination and their dung. These grasslands currently stand reduced to mossy forests and wetlands.

The dodo could, similarly, resume its vital role in seed dispersal in Mauritius. And the thylacine or Tasmanian tiger could reclaim its spot as an apex predator and keystone species in Australia.

Academic labs, biotech startups, and conservation-focused institutions are leading the charge, collaborating on projects that involve recreating extinct species or reserving ancient flora through cloning and genetic engineering.

The larger mission, of course, is to use these experiments to better understand how to help existing endangered species survive.

Already, for instance, Colossal Biosciences has used gene-editing to reintroduce lost genetic variation into the DNA of vulnerable pink pigeons in Mauritius as per the International Union for Conservation of Nature (IUCN).

Researchers at Macquarie University and the California Institute of Technology, meanwhile, in August, have developed a new gene-editing technique that could alter traits of wild populations in ways that de-fang invasive species. Australia’s highly poisonous cane toad, for instance, could be made less toxic, protecting the predators it is currently killing.

What will it mean to tinker in this way with a natural world already under threat from human activity?

“Ultimately, it’s not about whether we think the rights outweigh the wrongs,” is how Lamm sees it, “but whether we can evolve the technology and our approach in a way that ensures responsible, ethical progress.”

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Frontier forces: ‘New’ humans in space

Science fiction has long assumed that humans will be the aliens that land on other planets.

Could the species that eventually takes off for other planets be, well, a different kind of human?

Geneticists such as Christopher Mason at New York’s Weill Cornell Medicine (formerly, Cornell University Medical College) are already tinkering with how gene-editing could offer interplanetary travellers better protection. Soon, space agencies and private space companies may begin to explore the effects of space travel on the genetically-edited human body as well.

Space is, after all, an incredibly hostile environment.

Radiation levels on the moon reach more than 200 times the hourly rates experienced on Earth. Extended space travel poses the very real threats of cancers, organ damage, skin diseases, damage to eyesight — and that’s just from the radiation. Microgravity causes bone and muscle loss. A range of other conditions can be expected, given the altered nutrition, sleep cycles, and of course the lifestyle.

Equipping spacecraft with medical care is difficult. Resources can only be limited, small and light-weight. There is no way to reasonably predict the issues that might need tackling.

Overall, a more damage-resistant body would be ideal.

Paul Root Wolpe, a senior NASA bioethicist for 15 years, is now conducting research at Emory University in Atlanta to establish the Center for Conflict Transformation, Mediation, Civic Dialogue and Peacebuilding. He expects genetic screening to emerge as a major topic of discussion long before gene editing becomes a mainstream concern. Meanwhile, the questions gene editing raises are deep and complex. For one thing, there can be no single formula for all.

“A flight might carry space tourists, industry fliers who may be testing a new product in space, government employees, astronauts, and the flight staff,” says Wolpe. “There cannot be a single policy on the nature and extent of gene-editing, for such a diverse group.”

To even begin to formulate such an approach, our understanding of how human genes work would have to be far more extensive than it is today, he adds.

“At the moment, we are not close to being ready to use that technology adaptively on Earth, never mind in space.”

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Root to stem: Could plants get there first?

When it comes to building resilience, and turning genes on and off in order to counter threats and promote longevity, experiments have already begun in the world of plants.

Potatoes are being gene-edited to resist fungi in the warm, wet Peruvian Andes. Sorghum is being taught to resist parasitic plants such as witchweed in Africa. Grape vines in the US are being armed against a common powdery mildew.

There are even plans to edit the pearl millet to improve the shelf life of its flour after it is milled.

At the Innovative Genomics Institute (IGI) at the University of California (Berkeley and San Francisco), there has been excitement over small, early success in an effort to develop drought-tolerant rice.

This project seeks to alter the leaves of the rice plant, reducing the number of pores per leaf so that less moisture is lost from the plant.

“This could be a real game-changer for small farmers,” says Brad Ringeisen, executive director of IGI.

There is an added advantage. “Hybrid plants are often desirable because they are more productive, but they are also expensive because farmers can’t simply regrow them from seed,” Ringeisen adds. Here, because the gene itself has been edited, “this hybrid rice can be grown from seed and retain the beneficial qualities.”

Meanwhile, cattle are having their genes edited to make them more resistant to heat. In 2022, the US Food and Drug Administration approved heat-tolerant genome-edited beef cattle for human consumption. Similarly, the UK-based company Genus has genetically engineered piglets to protect them from porcine reproductive and respiratory syndrome, a deadly virus that affects pigs worldwide. US regulators are expected to approve the disease-proofed pig breed in the coming months.

How spooky could all this get?

In early 2023, scientists at the Israeli agritech company BetterSeeds used CRISPR-Cas9 editing tools to target genes responsible for plant architecture and flowering time in cowpeas.

When they were done, the plants grew stronger vertically and flowered in sync.

This will make for more efficient mechanised harvests, the company has said.

Much of the innovation has been coming from smaller startups and universities, which is a pleasant change from an industry dominated by a small number of multinational corporations. “I think the next five to ten years will answer many questions about which products are able to scale and what factors motivate adoption by farmers and consumers,” adds Ringeisen.