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Can you spot the fake receptor? The coronavirus can’t either.

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Can you spot the fake receptor? The coronavirus can’t either.


As covid-19 continues to evolve in the US, researchers are now developing the next generation of therapeutics, including a new approach that could help reduce the time it takes to recover from the disease.

While existing treatments include antivirals, antibodies, and steroids, scientists in the US and Europe are now focusing on creating decoys of the receptors the virus normally binds to, potentially neutralizing its harmful effects.

To develop the new therapy, scientists first had to engineer mice with a variant of the human protein known as angiotensin-converting enzyme 2, or ACE2. This resides on the surface of cells and helps regulate phenomena such as healing, inflammation, and blood pressure.

While ACE2 receptors can be found on cells all over the body, they are especially prevalent inside the lungs, heart, kidneys, and liver—organs the disease typically attacks.

To protect the real ACE2 receptors, here’s how the decoy does its job:

Usually, spike proteins on the virus’s surface act like keys to ACE2 receptors, opening up the doorway to infection. But the decoys, administered intravenously or through the nose depending on the stage of the disease, intercept the spike protein, leading it away from real receptors. After infection, the treatment could reduce the viral load inside the body, which might mean faster recovery times for patients.

In one study led by Daniel Batlle, a professor of medicine at Northwestern University, mice that were infected with the disease and got the treatment had only mild symptoms compared with animals that went untreated, which died.

As of today, only one clinical trial of the ACE2 product has been completed in patients with moderate to severe symptoms. Even so, more and more researchers are supporting the new therapeutic.

Batlle’s team began working on decoy proteins in January 2020 after learning about the first US case, building on knowledge gleaned from China’s 2003 SARS-CoV outbreak.  

“We knew that it would be very likely that the receptor for SARS-CoV-2 would be ACE2, since it had been previously shown to be the case for SARS-CoV,” Batlle says.

But applying that knowledge wasn’t so straightforward. Michael Jewett, a professor of chemical engineering at Northwestern University who was not involved in the study, compares the intricate process of making a decoy to an especially fiendish puzzle.

“Reengineering complex biological systems can be tricky,” Jewett says. “It’s kind of like solving a puzzle and every time you put one piece in, the rest of the puzzle changes.”

Jewett also says that compared with antibody treatments, decoys should be lower in cost and easier to use. And some experts are optimistic about the decoy’s ability to ward off both the original viral strain and mutations to come.

In another study, using a process called deep mutational scanning, Erik Procko, a professor of biochemistry at the University of Illinois Urbana-Champaign, was able to view thousands of different ACE2 mutations in a single experiment and see which ones could better attract and bind to the virus. Then his team built decoys mimicking the ones that performed best. The decoys don’t attach to cells but float in the fluid between them to catch the virus before it binds to the real ACE2 receptors.

By using a combination of three mutations, his team was able to considerably increase the decoy’s affinity for covid-19. They created decoy receptors that bound to the virus 50 times more strongly than ACE2.

To test the approach, Procko’s team used mouse tissue instead of live animals. “In in vitro tissue culture, we know that some of the decoy receptors are just as potent—sometimes a little better, sometimes a little less so, but overall just as potent—as monoclonal antibodies that have emergency-use authorization or are in clinical trials,” says Procko. 

One concern was that one of these mutations could allow for so-called viral escape and help shore up the virus’s resistance to treatment. But because the decoys closely resemble natural receptors, says Procko, the virus isn’t likely to evolve unnaturally as a result of their action.

Because of differences in infrastructure and education, access to synthetic-biology technologies is unequally distributed worldwide. More research—and more funding—is needed before such a therapy will be publicly available. But advances like these may eventually help create low-cost, portable, easy-to-use treatments for the disease.

 “There are promising signs that decoys that very closely resemble the human ACE2 receptor will be potent and efficacious against all of these new variants,” Procko says. “I wouldn’t be surprised if we had some of those next-generation decoys reaching the clinic within a couple of years.”

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The hunter-gatherer groups at the heart of a microbiome gold rush

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The hunter-gatherer groups at the heart of a microbiome gold rush


The first step to finding out is to catalogue what microbes we might have lost. To get as close to ancient microbiomes as possible, microbiologists have begun studying multiple Indigenous groups. Two have received the most attention: the Yanomami of the Amazon rainforest and the Hadza, in northern Tanzania. 

Researchers have made some startling discoveries already. A study by Sonnenburg and his colleagues, published in July, found that the gut microbiomes of the Hadza appear to include bugs that aren’t seen elsewhere—around 20% of the microbe genomes identified had not been recorded in a global catalogue of over 200,000 such genomes. The researchers found 8.4 million protein families in the guts of the 167 Hadza people they studied. Over half of them had not previously been identified in the human gut.

Plenty of other studies published in the last decade or so have helped build a picture of how the diets and lifestyles of hunter-gatherer societies influence the microbiome, and scientists have speculated on what this means for those living in more industrialized societies. But these revelations have come at a price.

A changing way of life

The Hadza people hunt wild animals and forage for fruit and honey. “We still live the ancient way of life, with arrows and old knives,” says Mangola, who works with the Olanakwe Community Fund to support education and economic projects for the Hadza. Hunters seek out food in the bush, which might include baboons, vervet monkeys, guinea fowl, kudu, porcupines, or dik-dik. Gatherers collect fruits, vegetables, and honey.

Mangola, who has met with multiple scientists over the years and participated in many research projects, has witnessed firsthand the impact of such research on his community. Much of it has been positive. But not all researchers act thoughtfully and ethically, he says, and some have exploited or harmed the community.

One enduring problem, says Mangola, is that scientists have tended to come and study the Hadza without properly explaining their research or their results. They arrive from Europe or the US, accompanied by guides, and collect feces, blood, hair, and other biological samples. Often, the people giving up these samples don’t know what they will be used for, says Mangola. Scientists get their results and publish them without returning to share them. “You tell the world [what you’ve discovered]—why can’t you come back to Tanzania to tell the Hadza?” asks Mangola. “It would bring meaning and excitement to the community,” he says.

Some scientists have talked about the Hadza as if they were living fossils, says Alyssa Crittenden, a nutritional anthropologist and biologist at the University of Nevada in Las Vegas, who has been studying and working with the Hadza for the last two decades.

The Hadza have been described as being “locked in time,” she adds, but characterizations like that don’t reflect reality. She has made many trips to Tanzania and seen for herself how life has changed. Tourists flock to the region. Roads have been built. Charities have helped the Hadza secure land rights. Mangola went abroad for his education: he has a law degree and a master’s from the Indigenous Peoples Law and Policy program at the University of Arizona.

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan

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The Download: a microbiome gold rush, and Eric Schmidt’s election misinformation plan


Over the last couple of decades, scientists have come to realize just how important the microbes that crawl all over us are to our health. But some believe our microbiomes are in crisis—casualties of an increasingly sanitized way of life. Disturbances in the collections of microbes we host have been associated with a whole host of diseases, ranging from arthritis to Alzheimer’s.

Some might not be completely gone, though. Scientists believe many might still be hiding inside the intestines of people who don’t live in the polluted, processed environment that most of the rest of us share. They’ve been studying the feces of people like the Yanomami, an Indigenous group in the Amazon, who appear to still have some of the microbes that other people have lost. 

But there is a major catch: we don’t know whether those in hunter-gatherer societies really do have “healthier” microbiomes—and if they do, whether the benefits could be shared with others. At the same time, members of the communities being studied are concerned about the risk of what’s called biopiracy—taking natural resources from poorer countries for the benefit of wealthier ones. Read the full story.

—Jessica Hamzelou

Eric Schmidt has a 6-point plan for fighting election misinformation

—by Eric Schmidt, formerly the CEO of Google, and current cofounder of philanthropic initiative Schmidt Futures

The coming year will be one of seismic political shifts. Over 4 billion people will head to the polls in countries including the United States, Taiwan, India, and Indonesia, making 2024 the biggest election year in history.

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Navigating a shifting customer-engagement landscape with generative AI

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Navigating a shifting customer-engagement landscape with generative AI


A strategic imperative

Generative AI’s ability to harness customer data in a highly sophisticated manner means enterprises are accelerating plans to invest in and leverage the technology’s capabilities. In a study titled “The Future of Enterprise Data & AI,” Corinium Intelligence and WNS Triange surveyed 100 global C-suite leaders and decision-makers specializing in AI, analytics, and data. Seventy-six percent of the respondents said that their organizations are already using or planning to use generative AI.

According to McKinsey, while generative AI will affect most business functions, “four of them will likely account for 75% of the total annual value it can deliver.” Among these are marketing and sales and customer operations. Yet, despite the technology’s benefits, many leaders are unsure about the right approach to take and mindful of the risks associated with large investments.

Mapping out a generative AI pathway

One of the first challenges organizations need to overcome is senior leadership alignment. “You need the necessary strategy; you need the ability to have the necessary buy-in of people,” says Ayer. “You need to make sure that you’ve got the right use case and business case for each one of them.” In other words, a clearly defined roadmap and precise business objectives are as crucial as understanding whether a process is amenable to the use of generative AI.

The implementation of a generative AI strategy can take time. According to Ayer, business leaders should maintain a realistic perspective on the duration required for formulating a strategy, conduct necessary training across various teams and functions, and identify the areas of value addition. And for any generative AI deployment to work seamlessly, the right data ecosystems must be in place.

Ayer cites WNS Triange’s collaboration with an insurer to create a claims process by leveraging generative AI. Thanks to the new technology, the insurer can immediately assess the severity of a vehicle’s damage from an accident and make a claims recommendation based on the unstructured data provided by the client. “Because this can be immediately assessed by a surveyor and they can reach a recommendation quickly, this instantly improves the insurer’s ability to satisfy their policyholders and reduce the claims processing time,” Ayer explains.

All that, however, would not be possible without data on past claims history, repair costs, transaction data, and other necessary data sets to extract clear value from generative AI analysis. “Be very clear about data sufficiency. Don’t jump into a program where eventually you realize you don’t have the necessary data,” Ayer says.

The benefits of third-party experience

Enterprises are increasingly aware that they must embrace generative AI, but knowing where to begin is another thing. “You start off wanting to make sure you don’t repeat mistakes other people have made,” says Ayer. An external provider can help organizations avoid those mistakes and leverage best practices and frameworks for testing and defining explainability and benchmarks for return on investment (ROI).

Using pre-built solutions by external partners can expedite time to market and increase a generative AI program’s value. These solutions can harness pre-built industry-specific generative AI platforms to accelerate deployment. “Generative AI programs can be extremely complicated,” Ayer points out. “There are a lot of infrastructure requirements, touch points with customers, and internal regulations. Organizations will also have to consider using pre-built solutions to accelerate speed to value. Third-party service providers bring the expertise of having an integrated approach to all these elements.”

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