Happy Monday Morning, Readers. Let’s be relentless this week!
In this week’s edition of BioWire, we’re reviewing a range of interesting and controversial topics at the boundaries of science and technology.
The discovery of Obelisks, viroid-like elements existing in our microbiome
Effects of myocarditis linked to COVID-19 mRNA vaccines
New DNA structures beyond the classic double-helix
J&J’s bid for FDA approval of a new autoimmune disease drug
Plus, we assess the latest player in the race for humanoid robots
Discovery of Obelisks: A New Class of Viroid-like RNA Elements in Human Microbiomes
Each of us hosts an entire community of microorganisms, primarily bacteria and fungi, living in and on our bodies—this is commonly known as the microbiome. It plays an essential role in processes like food metabolism in the gut and maintaining overall health. Interestingly, the bacteria of our microbiomes also harbor their own self-replicating molecules, which have captured the attention of researchers, particularly in the search for new antibiotics.
Recently, scientists discovered a new class of genetic elements called “Obelisks” lurking in our microbiomes (Zheludev et al, 2024). Unlike anything seen before, Obelisks are tiny, circular RNA molecules that don’t resemble any known viruses or viroids (small infectious agents). Surprisingly, they were found in about 7% of stool samples and an astonishing 50% of oral samples, indicating they are far more common than previously imagined.
Obelisks are especially interesting because of their unique folding patterns. Although they are circular in sequence, they fold into rod-like shapes and can produce novel proteins called “Oblins,” which have never been observed in other organisms. These proteins undoubtedly play some role in Obelisk’s replication efficiency, and it’s unclear how this impacts their environment. This raises big questions about their role in our bodies—are they harmless passengers, or could they influence our health in ways we don’t yet understand?
Long-Term Outlook of Myocarditis Linked to COVID-19 Vaccination and Other Causes
A recent study published in JAMA explored the long-term prognosis of myocarditis—a heart inflammation—following COVID-19 mRNA vaccination compared to myocarditis from COVID-19 infection or conventional causes (Semenzato et al., 2024). The study followed over 4,600 patients in France, including those with myocarditis after vaccination, for 18 months to understand how their conditions evolved and required management.
Myocarditis has been reported as a rare side effect of mRNA vaccines, particularly in young men after the second dose. Previous studies have shown that the risk of myocarditis is about 30 times higher after the second dose of the mRNA-1273 vaccine (Moderna) and 8 times higher after the second dose of the BNT162b2 vaccine (Pfizer) compared to unvaccinated individuals. Despite this elevated risk, the study found that patients with postvaccine myocarditis had better outcomes over time than those with myocarditis from conventional causes. The incidence of severe cardiovascular events, such as heart failure and hospital readmissions, was significantly lower among these patients compared to those with myocarditis from other sources.
This is good news for those suffering from this vaccine-related injury but probably not much consolation for those same individuals who were at an extremely low risk for COVID-19 in the first place. Furthermore, I can’t help but wonder if the results were inverse, i.e., myocarditis linked to COVID-19 vaccines were worse than other causes, if the paper still would have been published.
Why do I bring this up?
Research in many fields, particularly relating to COVID, has increasingly become an exercise in a different type of science—political science. For example, Cochrane Review, known for its rigorous, evidence-based approach, published an article in 2023 that failed to find a protective effect of masking against respiratory viruses like COVID-19 (Jefferson et al., 2023). This publication faced significant backlash and resulted in follow-up clarification and rephrasing of the conclusion, which didn’t necessarily reflect new evidence but rather the response to public and institutional pressure.
I’m not going to turn this into an essay on masking. But let’s end with this: Science should not be a balancing act between maintaining credibility and navigating politically charged topics. This fundamentally harms the accumulated trust earned over decades by our scientific institutions.
Hidden DNA Structures: Uncovering i-Motifs in the Human Genome
Whenever we think of DNA - the first thing that comes to mind is the iconic structure of the double helix. But what if that were an oversimplification? Well, scientists have recently discovered that our DNA contains an additional structure called i-motifs, which could play important roles in how our genes are regulated (Martinez et al, 2024). Unlike the classic double helix shape of DNA, i-motifs are formed by cytosine bases folding in unique ways, creating a "knot-like" structure. This new study found that i-motifs are not just rare occurrences; they are scattered widely across the human genome, appearing in regions that control gene activity.
The research team used advanced sequencing methods to map these i-motif structures in different human cell types. They found i-motifs in key areas of the genome, such as gene promoters (which help turn genes on), intergenic regions (between genes), and even within genes themselves. Interestingly, these structures were most common in genes that are active during specific phases of the cell cycle, hinting at a role in controlling how our cells function.
I love these types of discoveries because they challenge the way we look at things we previously took for granted and highlight how much we still have to learn about our DNA and its complex architecture. For the most part, DNA is a highly folded set of instructions for protein production. Sequences that are not being coded are highly folded away, while sequences that are coded are typically unraveled and accessible. So from this additional structure, we can likely infer that these i-motifs have some type of importance for the coding of the associated regions.
Will understanding these structures open new doors for medical research, offering potential targets for diagnostics and treatments for diseases where gene regulation goes awry, such as cancer? By mapping where i-motifs are found and exploring their functions, we may stumble upon new strategies for manipulating gene expression.
J&J Files for FDA Approval of $6.5 Billion Autoimmune Drug
Johnson & Johnson has filed for FDA approval of nipocalimab, a novel therapeutic that could revolutionize how autoimmune diseases are treated. Originally developed by Momenta Pharmaceuticals and acquired by J&J for $6.5 billion, nipocalimab targets a key pathway that extends the lifespan of antibodies in the body. Autoimmune disorders are characterized by the production of autoantibodies that mistakenly target the body’s own tissues. By blocking this pathway, nipocalimab reduces the levels of these harmful autoantibodies, directly addressing the root cause of diseases like generalized myasthenia gravis (gMG), lupus, and many others.
In the recent Phase 3 VIVACITY study, nipocalimab was used to treat gMG, a chronic autoimmune disorder that disrupts nerve-to-muscle communication. In this study, nipocalimab demonstrated dose-dependent reductions in autoantibodies and significant clinical improvements in patients with gMG. But the potential of this drug extends far beyond gMG. Nipocalimab’s ability to selectively reduce pathogenic antibodies without broadly suppressing the immune system positions it as a promising therapy for many autoimmune diseases! This should come as exciting news to the millions of people impacted by autoimmune disorders.
Although this drug class was pioneered by argenx’s Vyvgart, approved in late 2021, J&J’s nipocalimab stands out as the only FcRn blocker shown to provide sustained disease control when combined with standard care. This innovative approach targets the underlying mechanisms of autoimmune diseases rather than merely managing symptoms. If approved, nipocalimab could pave the way for safer, more effective treatments across a wide spectrum of autoantibody-driven conditions, marking a significant milestone in the battle against autoimmune disorders.
New humanoid robot - are we arriving or is this deceptive marketing?
NEO Beta, from 1X Technology, is the latest in the series of companies racing to develop humanoid robots. While our coverage of this has focused on Tesla’s Optimus, the NEO Beta is designed to mimic human anatomy with a “muscle-like” structure and a soft outer layer, giving it a lifelike appearance that blurs the line between human and machine (video 1). At first glance, it’s hard to argue with that description—NEO Beta’s movements are so realistic that they verge on uncanny, appearing almost too perfect, or even unsettlingly human.
However, a closer look at the promotional material raises questions. The most recent video of NEO Beta seems heavily curated, leaving it unclear whether we’re watching pure robotics, CGI enhancements, or just highly choreographed scenes. This marketing approach, showcasing the robot seamlessly performing real-world tasks, feels more like a performance than a demonstration of genuine capability. It raises the question: is this really a breakthrough in robotics, or are we being shown an illusion?
It feels odd for a company to sneak up in this space in such a profound way. Tesla is a company known for its execution in solving hard problems and delivering, even if the result is imperfect. Could NEO have really overcome this team so stealthily?
This reminds me of the hype surrounding electric vehicles, particularly the infamous example of Nikola, which positioned itself as a rival to Tesla with a now-iconic commercial of its electric truck. It was later revealed that the truck wasn’t driving at all; it was simply being pushed downhill. The parallels with NEO Beta are hard to ignore—either this robot has quietly surpassed Tesla’s Optimus, or something fishy is going on.
Only time will tell if I owe 1X Technology a sincere apology or not.
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References:
https://clinicaltrials.gov/study/NCT04951622
https://www.1x.tech/androids/neo
Antozzi, C., Guptill, J., Bril, V., Gamez, J., Meuth, S.G., Nowak, R.J., Quan, D., Sevilla, T., Jouvin, M.H., Jin, J. and Karcher, K., 2024. Safety and efficacy of nipocalimab in patients with generalized myasthenia gravis: results from the randomized phase 2 vivacity-MG study. Neurology, 102(2), p.e207937.
Jefferson, T., Dooley, L., Ferroni, E., Al-Ansary, L.A., van Driel, M.L., Bawazeer, G.A., Jones, M.A., Hoffmann, T.C., Clark, J., Beller, E.M. and Glasziou, P.P., 2023. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane database of systematic reviews, (1).
Peña Martinez, C.D., Davis, J.E., Challis, B.C., Chen, Z., Keniry, A., and Iyer, K.S. (2024). Human genomic DNA is widely interspersed with i-motif structures. Nature Communications, 15(1), 342.
Semenzato, L., Le Vu, S., Botton, J., Bertrand, M., Jabagi, M.J., Drouin, J., Cuenot, F., Zores, F., Dray-Spira, R., Weill, A. and Zureik, M., Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies. JAMA.
Zheludev, I.N., Edgar, R.C., Lopez-Galiano, M.J., De la Peña, M., Babaian, A., Bhatt, A.S. and Fire, A.Z., 2024. Viroid-like colonists of human microbiomes. BioRxiv.
Now that I'm three years into retirement the breakouts I used to get on my hands aren't a problem any more; the issue is thought to be an autoimmune disorder activated or worsened by stress, which explains why it was work-related. I'd have killed for something more effective than topical medications.
The other day I read a Substack that described "Friend" (or something), an AI device one can carry or wear. You're supposed to talk to it like you talk to a person. I guess. It replies in more or less appropriate ways and allows one to pretend to have an actual human relationship. With a disk. Except for Facebook, I can't remember the last time I saw anything so stupid, which means it will probably be a huge hit and I should buy stock.
Definitely looks like a human in a suit to me, haha. I would have liked it if it had unzippered its jacket to reveal a mechanical skeleton underneath. 😅
Very cool and interesting about the obelisks and i-motifs. Thanks for highlighting that.
I'm sure the anti-vax community is in a frenzy over that report and will entirely overlook the "and other causes" part, and especially this: "Despite this elevated risk, the study found that patients with postvaccine myocarditis had better outcomes over time than those with myocarditis from conventional causes."