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.
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 human 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.”
The way forward: Merging IT and operations
“People in operations see a ton of opportunity,” says Irani-Famili, who has worked in the energy sector for the better part of a decade. For problems they encounter every day, OT dreams up potential fixes. For example, if there’s a power outage, relevant supervisors could automatically get notifications wherever they are. Or staff availability data could flow through company systems so supervisors and managers can more easily assign projects or shifts.
“And then they go and talk to IT, and IT’s response might be ‘Not possible. This could be breaking every security protocol,’” Irani-Famili says. Operations sees solutions to problems. IT sees cybersecurity, integration, and support risk. “But from the operations perspective, what they see is IT red tape, IT is not collaborating, or IT is not playing the game.”
It’s easy to describe IT and OT as different departments with different objectives and starkly different cultures. They are often managed independently in organizations and treated as isolated groups that cater to specific problems and employ their own protocols. But that results in inefficient, costly setups that fail to foster innovation and standardization.
As global economies gain steam after near collapse amid the 2020 coronavirus pandemic, the pressure is on to boost productivity, innovation, and agility. Companies need to increase the speed of business by digitizing processes and using the internet of things and artificial intelligence (AI) to extract actionable insight from large data sets.
To undergo such digital transformation in industries that rely heavily on physical assets—manufacturing, oil and gas, transportation, energy, and utilities—organizations must integrate IT and OT into one seamless organization that connects systems on both sides.
“IT/OT convergence is an inevitability,” says Fay Cranmer, senior managing director in Accenture’s natural resources practice and former chief information officer at mining company Rio Tinto. “It’s the only way to have a full digital transformation, especially in the heavy industry space.”
But there are significant challenges to overcome. Many industrial environments are characterized by legacy equipment, time-honored, manual processes, and resistance to change—from both sections of the business, OT and IT. Often the attitude is, OT alone knows how to generate the products and services that produce revenue for the company.
Conversely, IT folks often think only they know how to help modernize OT departments, by enabling the systems that allow the benefits of AI, the internet of things, and other digital technologies. True collaboration is a must, but the complexity of new technology and infrastructure merging with legacy machines prompts questions concerning investment, leadership, and governance.
Bala Arunachalam, an executive in oil and gas for more than 30 years, says specific industry characteristics are a big factor. “This industry is a legacy industry. For them to move onto the technology space, to capitalize on the opportunity that is in front of them, is a struggle.”
As physical assets, whether in the factory or out in the field, become digitized through internet-of-things technology; as applications, data storage, and data processing move to the cloud; and as employees stick to their home offices more than a year into the pandemic, any perceived boundaries between OT and rest of the business are crumbling. “The challenge is that we need to bring data together across all those boundaries,” says Cranmer. The biggest hurdles, she says, are organizational and cultural. “The technological side is much more easily overcome than the human side.”
The good news is there are guidelines that organizations can follow to achieve the IT/OT integration that’s so critical for successful digital transformation initiatives.
Download the full report.
Forget dating apps: Here’s how the net’s newest matchmakers help you find love
The thread took off. Morgan basked in the feel-good vibes of seeing people find each other—“I love love!”—and reveled in the real-life connections she was able to mastermind: multiple dates in her hometown of Portland, Oregon; someone who was thinking of flying to meet somebody in New York because of the thread; even a short relationship. Even today, people continue to add their pictures to the thread, seeking love all across the United States.
If this feels a bit like old-fashioned matchmaking, it is. But it’s a long way from gossipy neighborhood grandmas setting up dates. These operations are often ad hoc, based on platforms like Twitter and TikTok, and—unlike the dating apps, with their endless menu of eligible suitors—hyperfocused on one person at a time.
Play by mail
Randa Sakallah launched Hot Singles in December 2020 to solve her own dating blues. She’d just moved to New York to work in tech and was “sick of swiping.” So she created an email newsletter using the platform Substack that had a seemingly simple premise: apply via Google Form to be featured, and if you are, your profile—and yours only—is sent to an audience of thousands.
Yes, each profile features the requisite information: name, sexual orientation, interests, and some photos. But crucially, it has a wry editorial slant that comes from Sakallah’s questions and the email presentation. This week’s single, for example, is asked what animal she would be; the answer is somewhere between a peacock and a sea otter. (“My main goals in life are to snack, hold hands, and maybe splash around a bit,” she writes.)
Sakallah says part of the appeal of Hot Singles is that only one person’s profile is delivered via email on Friday. It’s not a stream of potential faces available on demand, she says, which makes it possible to really savor getting to know a single person as a human being and not an algorithmically offered statistic.
“I try to tell a story and give them a voice,” says Sakallah. “You really want to think about the whole person.”
Dating apps may be quick and easy to use, but critics say their design and their focus on images reduces people to caricatures. Morgan, who started the long-running Twitter thread, is a black woman who says that the dating-app experience can be exhausting because of her race.
“I’ve had friends just put their photo and an emoji up, and they would get someone asking them to coffee so fast,” she said. Meanwhile, “I’d have to put more work into my profile and write paragraphs.” The results of her effort either didn’t get read or attracted a slew of uncomfortable, racist comments. “It was frustrating,” she says.
Scratching a different itch
Dating-app fatigue has a number of sources. There’s the paradox of choice: you want to be able to select from a wide variety of people, but that variety can be debilitatingly overwhelming. Plus, the geographic parameters typically set on such apps often actually make the dating pool worse.
Alexis Germany, a professional matchmaker, decided to try TikTok videos during the pandemic to showcase people and has found them immensely popular—particularly among people who don’t live in the same place.
“What makes you think your person is in your city?” Germany says. “If they’re a car ride away or a short plane ride away, it could work.”
These weird virtual creatures evolve their bodies to solve problems
“It’s already known that certain bodies accelerate learning,” says Bongard. “This work shows that AI that can search for such bodies.” Bongard’s lab has developed robot bodies that are adapted to particular tasks, such as giving callus-like coatings to feet to reduce wear and tear. Gupta and his colleagues extend this idea, says Bongard. “They show that the right body can also speed up changes in the robot’s brain.”
Ultimately, this technique could reverse the way we think of building physical robots, says Gupta. Instead of starting with a fixed body configuration and then training the robot to do a particular task, you could use DERL to let the optimal body plan for that task evolve and then build that.
Gupta’s unimals are part of a broad shift in how researchers are thinking about AI. Instead of training AIs on specific tasks, such as playing Go or analyzing a medical scan, researchers are starting to drop bots into virtual sandboxes—such as POET, OpenAI’s virtual hide-and-seek arena, and DeepMind’s virtual playground XLand—and getting them to learn how to solve multiple tasks in ever-changing, open-ended training dojos. Instead of mastering a single challenge, AIs trained in this way learn general skills.
For Gupta, free-form exploration will be key for the next generation of AIs. “We need truly open-ended environments to create intelligent agents,” he says.