This biohacking company is using a crypto city to test controversial gene therapies
Follistatin is a glycoprotein encoded by the FST gene. To Minicircle, its most interesting property is that it suppresses myostatin, a protein that inhibits muscle growth. Missing myostatin means muscle cells can replicate and expand without the usual biological checks. As a result, animals with mutations in this gene—like the physically imposing “bully whippet”—are loaded with cartoonishly bulging muscles. Follistatin gene therapy, in theory, offers a fast track to this muscle-boosting effect.
Researchers have tried to harness this pathway to treat neuromuscular disorders that involve weak or underdeveloped muscles, like ALS and muscular dystrophy. Success has been limited: “So far, nothing has proven to work in human clinical trials like it does in animal models,” says Scott Harper, a principal investigator at the Center for Gene Therapy at the Nationwide Children’s Hospital in Ohio. Even so, Minicircle’s work to continue these efforts isn’t too unorthodox.
Where plans veer from the established literature and into territory closer to wellness quackery is that the startup aims to use follistatin gene therapy to enhance the muscles, and general well-being, of healthy participants too. Minicircle’s Mirror advertisement for the trial pitches the therapy as a kind of age-reversing and muscle-pumping elixir—something far less well supported by existing evidence.
“The follistatin gene therapy increases muscle mass in animals. It doubles bone density and halves body fat, the cardiovascular system is rapidly improved, the animals live longer, and they’re healthier,” claimed Davis. In fact, his and his associates’ ad hoc human experiments with follistatin are what served as the impetus to start Minicircle: “We’ve seen some very interesting effects,” he said.
But Harper says he hasn’t heard anything related to Minicircle’s more outlandish claims that follistatin gene therapy decreases chronic inflammation and body fat, boosts DNA repair, and promotes age reversal. Robert Kotin, a gene therapy expert and professor of microbiology and physiological systems at the University of Massachusetts Medical School, echoes Harper’s skepticism: “If I wanted to make a fountain-of-youth drug, I don’t think it would be follistatin.”
Experts also criticize the company’s namesake minicircle technology. This approach comprises a non-viral delivery method using a circular genetic construct—a “minicircle”—to traffic genetic material into target cells.
But human studies using the minicircle technique have so far failed to deliver DNA to the nucleus of the cell in a way that is clinically relevant, safe, and therapeutic, says one of its creators, Mark Kay, a Stanford University professor of genetics (although he notes that the method has found some success in vaccines). From what he could find out on Minicircle’s website, Kay doesn’t understand why the startup would succeed where others have failed. “Where’s the novelty in any of their technology?” he asks. “How is it different?”
Minicircle’s approach diverges from the main focus of the wider gene therapy field: the use of viral vector technology, where a neutralized virus delivers the new genetic material to the target cells. However, Kotin notes that the non-viral vector approach, like the one used by Minicircle, is far simpler and cheaper to produce—and less likely to induce certain adverse events, like fatal shocks to the immune system. The company’s claim of reversibility seems to rely on the idea that minicircles, unlike viruses, can be administered more than once, he says. (Of course, whether Minicircle’s treatments will work at all—reversibly or otherwise—is yet to be determined.)
The Download: AI films, and the threat of microplastics
The Frost nails its uncanny, disconcerting vibe in its first few shots. Vast icy mountains, a makeshift camp of military-style tents, a group of people huddled around a fire, barking dogs. It’s familiar stuff, yet weird enough to plant a growing seed of dread. There’s something wrong here.
Welcome to the unsettling world of AI moviemaking. The Frost is a 12-minute movie from Detroit-based video creation company Waymark in which every shot is generated by an image-making AI. It’s one of the most impressive—and bizarre—examples yet of this strange new genre. Read the full story, and take an exclusive look at the movie.
—Will Douglas Heaven
Microplastics are everywhere. What does that mean for our immune systems?
Microplastics are pretty much everywhere you look. These tiny pieces of plastic pollution, less than five millimeters across, have been found in human blood, breast milk, and placentas. They’re even in our drinking water and the air we breathe.
Given their ubiquity, it’s worth considering what we know about microplastics. What are they doing to us?
The short answer is: we don’t really know. But scientists have begun to build a picture of their potential effects from early studies in animals and clumps of cells, and new research suggests that they could affect not only the health of our body tissues, but our immune systems more generally. Read the full story.
Microplastics are everywhere. What does that mean for our immune systems?
Here, bits of plastic can end up collecting various types of bacteria, which cling to their surfaces. Seabirds that ingest them not only end up with a stomach full of plastic—which can end up starving them—but also get introduced to types of bacteria that they wouldn’t encounter otherwise. It seems to disturb their gut microbiomes.
There are similar concerns for humans. These tiny bits of plastic, floating and flying all over the world, could act as a “Trojan horse,” introducing harmful drug-resistant bacteria and their genes, as some researchers put it.
It’s a deeply unsettling thought. As research plows on, hopefully we’ll learn not only what microplastics are doing to us, but how we might tackle the problem.
Read more from Tech Review’s archive
It is too simplistic to say we should ban all plastic. But we could do with revolutionizing the way we recycle it, as my colleague Casey Crownhart pointed out in an article published last year.
We can use sewage to track the rise of antimicrobial-resistant bacteria, as I wrote in a previous edition of the Checkup. At this point, we need all the help we can get …
… which is partly why scientists are also exploring the possibility of using tiny viruses to treat drug-resistant bacterial infections. Phages were discovered around 100 years ago and are due a comeback!
Our immune systems are incredibly complicated. And sex matters: there are important differences between the immune systems of men and women, as Sandeep Ravindran wrote in this feature, which ran in our magazine issue on gender.
Welcome to the new surreal. How AI-generated video is changing film.
Fast and cheap
Artists are often the first to experiment with new technology. But the immediate future of generative video is being shaped by the advertising industry. Waymark made The Frost to explore how generative AI could be built into its products. The company makes video creation tools for businesses looking for a fast and cheap way to make commercials. Waymark is one of several startups, alongside firms such as Softcube and Vedia AI, that offer bespoke video ads for clients with just a few clicks.
Waymark’s current tech, launched at the start of the year, pulls together several different AI techniques, including large language models, image recognition, and speech synthesis, to generate a video ad on the fly. Waymark also drew on its large data set of non-AI-generated commercials created for previous customers. “We have hundreds of thousands of videos,” says CEO Alex Persky-Stern. “We’ve pulled the best of those and trained it on what a good video looks like.”
To use Waymark’s tool, which it offers as part of a tiered subscription service starting at $25 a month, users supply the web address or social media accounts for their business, and it goes off and gathers all the text and images it can find. It then uses that data to generate a commercial, using OpenAI’s GPT-3 to write a script that is read aloud by a synthesized voice over selected images that highlight the business. A slick minute-long commercial can be generated in seconds. Users can edit the result if they wish, tweaking the script, editing images, choosing a different voice, and so on. Waymark says that more than 100,000 people have used its tool so far.
The trouble is that not every business has a website or images to draw from, says Parker. “An accountant or a therapist might have no assets at all,” he says.
Waymark’s next idea is to use generative AI to create images and video for businesses that don’t yet have any—or don’t want to use the ones they have. “That’s the thrust behind making The Frost,” says Parker. “Create a world, a vibe.”
The Frost has a vibe, for sure. But it is also janky. “It’s not a perfect medium yet by any means,” says Rubin. “It was a bit of a struggle to get certain things from DALL-E, like emotional responses in faces. But at other times, it delighted us. We’d be like, ‘Oh my God, this is magic happening before our eyes.’”
This hit-and-miss process will improve as the technology gets better. DALL-E 2, which Waymark used to make The Frost, was released just a year ago. Video generation tools that generate short clips have only been around for a few months.
The most revolutionary aspect of the technology is being able to generate new shots whenever you want them, says Rubin: “With 15 minutes of trial and error, you get that shot you wanted that fits perfectly into a sequence.” He remembers cutting the film together and needing particular shots, like a close-up of a boot on a mountainside. With DALL-E, he could just call it up. “It’s mind-blowing,” he says. “That’s when it started to be a real eye-opening experience as a filmmaker.”