Although the newest gene drives have been proven to spread efficiently as designed in laboratory settings, concerns have been raised regarding the safety of releasing such systems into wild populations. Questions have emerged about the predictability and controllability of gene drives and whether, once let loose, they can be recalled in the field if they spread beyond their intended application region.

Now, scientists at the University of California San Diego and their colleagues have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild. On Sept.18, 2020 in the journal Molecular Cell, research led by Xiang-Ru Xu, Emily Bulger and Valentino Gantz in the Division of Biological Sciences offers two new solutions based on elements developed in the common fruit fly.

“One way to mitigate the perceived risks of gene drives is to develop approaches to halt their spread or to delete them if necessary,” said Distinguished Professor Ethan Bier, the paper’s senior author and science director for the Tata Institute for Genetics and Society. “There’s been a lot of concern that there are so many unknowns associated with gene drives. Now we have saturated the possibilities, both at the genetic and molecular levels, and developed mitigating elements.”

The first neutralizing system, called e-CHACR (erasing Constructs Hitchhiking on the Autocatalytic Chain Reaction) is designed to halt the spread of a gene drive by “shooting it with its own gun.” e-CHACRs use the CRISPR enzyme Cas9 carried on a gene drive to copy itself, while simultaneously mutating and inactivating the Cas9 gene. Xu says an e-CHACR can be placed anywhere in the genome.

“Without a source of Cas9, it is inherited like any other normal gene,” said Xu. “However, once an e-CHACR confronts a gene drive, it inactivates the gene drive in its tracks and continues to spread across several generations ‘chasing down’ the drive element until its function is lost from the population.”

The second neutralizing system, called ERACR (Element Reversing the Autocatalytic Chain Reaction), is designed to eliminate the gene drive altogether. ERACRs are designed to be inserted at the site of the gene drive, where they use the Cas9 from the gene drive to attack either side of the Cas9, cutting it out. Once the gene drive is deleted, the ERACR copies itself and replaces the gene-drive.

“If the ERACR is also given an edge by carrying a functional copy of a gene that is disrupted by the gene drive, then it races across the finish line, completely eliminating the gene drive with unflinching resolve,” said Bier.

The researchers rigorously tested and analyzed e-CHACRs and ERACRs, as well as the resulting DNA sequences, in meticulous detail at the molecular level. Bier estimates that the research team, which includes mathematical modelers from UC Berkeley, spent an estimated combined 15 years of effort to comprehensively develop and analyze the new systems. Still, he cautions there are unforeseen scenarios that could emerge, and the neutralizing systems should not be used with a false sense of security for field-implemented gene drives.

“Such braking elements should just be developed and kept in reserve in case they are needed since it is not known whether some of the rare exceptional interactions between these elements and the gene drives they are designed to corral might have unintended activities,” he said.

According to Bulger, gene drives have enormous potential to alleviate suffering, but responsibly deploying them depends on having control mechanisms in place should unforeseen consequences arise. ERACRs and eCHACRs offer ways to stop the gene drive from spreading and, in the case of the ERACR, can potentially revert an engineered DNA sequence to a state much closer to the naturally-occurring sequence.

“Because ERACRs and e-CHACRs do not possess their own source of Cas9, they will only spread as far as the gene drive itself and will not edit the wild type population,” said Bulger. “These technologies are not perfect, but we now have a much more comprehensive understanding of why and how unintended outcomes influence their function and we believe they have the potential to be powerful gene drive control mechanisms should the need arise.”

The research was published September 10 in Nature and forms part of the latest Worldwide Fund for Nature (WWF) Living Planet Report. The work was led by the International Institute for Applied Systems Analysis (IIASA), a research institute based in Austria.

“This important paper adds further evidence that food and environmental security are not incompatible,” said Fabrice DeClerck, a co-author and senior scientist at the Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT), who co-authored 2019’s EAT-Lancet report that outlined food system transitions to feed 10 billion people sustainably by 2050.

In a novel approach to explore future terrestrial biodiversity trends as affected by habitat conversion, the researchers built an ensemble of models to better understand possible future scenarios, much in the same way the International Panel on Climate Change (IPCC) creates future climate projections. They explore different assumptions — conservation and restoration efforts, and the impact of more sustainable food production and consumption practices — to build a timeline for a reversal in biodiversity loss.

“We wanted to assess in a robust manner whether it might be feasible to bend the curve of declining terrestrial biodiversity due to current and future land use, while avoiding jeopardizing our chances to achieve other Sustainable Development Goals (SDGs),” said David Leclère, the lead author and IIASA researcher. “If this were indeed possible, we also wanted to explore how to get there and, more specifically, what type of actions would be required, and how combining various types of actions might reduce trade-offs among objectives.”

The study comes at a relevant time for international discussions related to climate, conservation and food systems, including the United Nations Convention on Biological Diversity, which is taking stock of its Strategic Plan for Biodiversity 2011-2020.

The research was also featured in the 5th Global Biodiversity Outlook, released this week.

“We found that apart from increased conservation efforts, the most important actions to revert the loss of biodiversity are all related to how we manage the food system,” said Mario Herrero, the chief research scientist for agriculture and food at CSIRO, Australia’s national research agency. “Key transitions towards healthy and sustainable diets, renewed waste reduction efforts and increases in productivity will help enormously restore ecosystems. These are central elements where we need investment and action and are an integral part of the forthcoming World Food Summit.”

How much loss is already locked in?

Even under a best-case scenario, ongoing land conversion will drive further biodiversity loss before the curve starts bending. At least a third of the projected losses in the coming years are unlikely to be avoided under any scenario. Potential biodiversity losses were found to be highest in the regions richest in biodiversity, including sub-Saharan Africa (SSA), South Asia, Southeast Asia, the Caribbean and Latin America.

The study’s baseline projections for biodiversity loss — which include global and local extinctions and reductions in viable population levels for plants and animals — will be driven by the loss of about 5.3 million km2 of unmanaged forest and natural vegetation by 2050. To have a chance at reversing biodiversity loss — or bending the biodiversity curve towards restoration — about 9.8 million km2 must be restored by 2050. This implies a significant increase to the Bonn Challenge, an international agreement to bring 3.5 million km2 into restoration by 2030.

While study does not factor in the impact of climate change, the authors discuss climate’s increasing role in biodiversity loss, writing:

“Land-use change is currently the largest single threat to biodiversity, but other threats will increase in importance in the future, in particular climate change.”

Additionally, the “Integrated Action Portfolio” proposed by the researchers to address biodiversity loss implies doubling crop yields in SSA, which will be no easy feat. “While significant yield gaps prevailing in this region might offer opportunities, closing the yield gap in a sustainable manner will require investments and innovative policies, and might be complicated by climate change,” they wrote.

“We need to adopt a zero land conversion approach,” said DeClerck. “We need to realize that doubling productivity in SSA amongst others is a core contribution to the biodiversity and food security challenge, combined with producing the foods that contribute to, rather than detract from public health.”

While a rapidly shifting climate is hurting biodiversity, Climate will also play a big role in the sustainable intensification of agriculture, especially in places like sub-Saharan Africa where agricultural production will need to increase considerably in order to meet land conservation goals.

Terrestrial habitats will need to be better protected, the researchers argue. Even if current global agreements to protect 17 percent of land by 2020 are more than doubled to 40 percent and include biodiversity hotspots, about half of biodiversity losses projected under the study’s baseline scenario will not be avoided.

But the effectiveness of protected areas is declining as pressures on those areas are growing.

The report is not all bad news. Complementing research published in the past couple of years, the team found that integrated efforts that target habitat conservation, improved production practices and significant shifts towards healthy and less wasteful diets enable reversing the loss of biodiversity. These efforts are similarly necessary to achieve climate security and are not incompatible with global food security targets. Urgent action is needed this decade, however, to have any chance of transitioning to a net-nature positive scenario.

Tesserae are tectonically deformed regions on the surface of Venus that are often more elevated than the surrounding landscape. They comprise about 7% of the planet’s surface, and are always the oldest feature in their immediate surroundings, dating to about 750 million years old. In a new study appearing in Geology, the researchers show that a significant portion of the tesserae have striations consistent with layering.

“There are generally two explanations for tesserae — either they are made of volcanic rocks, or they are counterparts of Earth’s continental crust,” says Paul Byrne, associate professor of planetary science at North Carolina State University and lead author of the study. “But the layering we find on some of the tessera isn’t consistent with the continental crust explanation.”

The team analyzed images of Venus’ surface from NASA’s 1989 Magellan mission, which used radar to image 98% of the planet through its dense atmosphere. While researchers have studied the tesserae for decades, prior to this work the layering of the tesserae hasn’t been recognized as widespread. And according to Byrne, that layering would not be possible if the tesserae were portions of continental crust.

“Continental crust is composed mainly of granite, an igneous rock formed when tectonic plates move and water is subducted from the surface,” Byrne says. “But granite doesn’t form layers. If there’s continental crust on Venus, then it’s below the layered rocks we see.

“Aside from volcanic activity, the other way to make layered rock is through sedimentary deposits, like sandstone or limestone. There isn’t a single place today on Venus where these kinds of rocks could form. The surface of Venus is as hot as a self-cleaning oven and the pressure is equivalent to being 900 meters (about 985 yards) underwater. So the evidence right now points to some portions of the tesserae being made up of layered volcanic rock, similar to that found on Earth.”

Byrne hopes that the work will help to shed light on more of Venus’ complicated geological history.

“While the data we have now point to volcanic origins for the tesserae, if we were one day able to sample them and find that they are sedimentary rocks, then they would have had to have formed when the climate was very different — perhaps even Earth-like,” Byrne says.

“Venus today is hellish, but we don’t know if it was always like this. Was it once like Earth but suffered catastrophic volcanic eruptions that ruined the planet? Right now we cannot say for certain, but the fact of the layering in the tesserae narrows down the potential origins of this rock.”

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Materials provided by North Carolina State University. Note: Content may be edited for style and length.