The Pakistan Genome Resource (PGR), one of the largest genomic studies ever conducted in South Asia, has revealed novel insights into gene function, disease susceptibility, and the translatability of preclinical findings to humans.Published in a Nature article, a collaboration between Novartis, Columbia University Irving Medical Center, and the Center for Non-Communicable Diseases, Karachi, Pakistan, examined 173,303 PGR participants, constituting 0.07% of the population of Pakistan, the fifth most populous country in the world.
The numbers alone are impressive, as the scientists identified more than 6.6 million coding genetic variants, with nearly half of them absent from existing global databases. But the PGR is particularly powerful not just because of its size but also because of the unique genetic structure of the population being studied with high levels of familial relatedness.
The study identified naturally occurring homozygous loss-of-function (LoF) variants in 6,476 genes, about one-third of all human protein-coding genes. The researchers confirmed several well-known genetic associations. For example, individuals carrying LoF variants in the APOC3 gene had significantly lower triglyceride levels, while variants in PCSK9 were linked to lower LDL cholesterol. While both genes are already important targets in cardiovascular medicine, the findings shore up the dataset’s credibility.
New links between genes and biological traits provide clues about conditions ranging from obesity and diabetes to liver disease and neurodegeneration. In one striking example, individuals lacking a functional version of the gene CIDEB, which has become a major target in metabolic research because rare mutations that inactivate the gene provide significant protection against liver diseases, appeared to have a lower risk of liver disease, strengthening the case for therapies that target this pathway.
Some findings provided new context to genes already being widely studied, such as LRRK2—a gene currently targeted by experimental Parkinson’s disease treatments. LoF mutations in LRRK2 showed signs of kidney dysfunction. It’s an observation that raises important safety questions and highlights why human genetic studies matter so much. Sometimes biology sends a warning before a drug reaches the market.
The research also challenged assumptions based on animal studies. A gene called PRDM9 is considered essential for fertility in mice. Yet several people in the PGR with completely inactive copies of the gene had healthy children.
Ultimately, the Pakistan Genome Resource is much more than a national database. It’s a reminder that human genetic diversity remains vastly underexplored. By studying populations that have historically been overlooked, researchers are uncovering entirely new biology that could lead to better treatments, safer drugs, and a more profound understanding of what makes us human.
F2G and Shionogi have reported positive Phase III results for the antifungal drug olorofim in patients with invasive aspergillosis who are not eligible for standard azole therapy. If approved based on this data, olorofim would become the first antifungal agent with a novel mechanism of action for invasive aspergillosis in over two decades.
“Invasive fungal infections remain difficult to treat and can be life-threatening especially in immunocompromised patients,” said Johan Maertens, MD, PhD, professor of hematology at University Hospitals Leuven in Belgium and principal investigator of the study. “The OASIS topline results add to the growing body of evidence supporting olorofim’s therapeutic potential in a hard-to-treat population with limited antifungal options. We’re hopeful this could offer a meaningful alternative for clinicians to treat challenging infections caused by Aspergillus.”
Invasive aspergillosis is a fungal infection with high mortality rates that mainly affects immunocompromised patients. Due to rising drug resistance and toxicity profiles of currently available therapies, a growing number of patients cannot be treated with azole antifungals, leaving them with limited options.
Olorofim belongs to a new class of antifungal agents called orotomides that was discovered by F2G. These drugs can selectively target an enzyme essential for the synthesis of pyrimidine that is shared across mold fungi including Aspergillus, making olorofim effective against a broad range of species including rare and drug-resistant strains.
The Phase III OASIS study recruited 225 adults with invasive aspergillosis who either had a refractory infection or were unsuitable for azole therapy. Participants received either oral olorofim or amphotericin B—an antifungal used to treat serious infections known for causing kidney toxicity.
After 42 days, the mortality rate among patients who took olorofim was 23.8%, compared to 24.3% for the control group. The rate of adverse events caused by the treatment was 35.8% for olorofim versus 63.9% for amphotericin B, with the difference being mostly driven by a higher rate of kidney toxicity in the control group.
“This is a promising new development in antifungal medicine—an area where patients have been underserved for more than 20 years,” said John Keller, PhD, director of the board and senior vice president of R&D at Shionogi. “In current clinical practice, safety and tolerability considerations, particularly effects on renal function, can pose significant challenges for treatment selection and continuation. Against this background, the results of the OASIS study suggest that olorofim has the potential to offer a new treatment option for patients with invasive aspergillosis.”
Based on these results, Shionogi and F2G plan to submit approval applications with regulatory authorities across the world. Under their commercial agreement, Shionogi will be responsible for commercialization in Europe and Asia, while F2G will oversee North America and other remaining territories.
Over the past 20 years, most newly approved antifungal drugs have belonged to existing drug classes, limiting progress against the growing threat of antimicrobial resistance. During that period, only a single antifungal with a novel mechanism of action reached the market: ibrexafungerp, which is approved for the treatment of vulvovaginal candidiasis infections. If approved, olorofim would offer a much-needed option in an indication where both existing treatment choices and therapeutic innovation have historically remained limited.
After more than 20 years working on viral and nonviral delivery modalities, Kenneth Greenberg, PhD, thought he had seen it all in genetic medicine delivery—until he met Steve Feinstein, MD, and Michael Davidson, MD, in 2021. Feinstein, a clinical cardiologist, had been working with ultrasound and contrast ultrasound for decades.
“Steve was scratching his head in the 90s trying to better diagnose heart disease patients, wondering why there’s a contrast agent for every other imaging modality except ultrasound,” Greenberg told Inside Precision Medicine.
Feinstein’s solution was microbubbles. These tiny gas-filled spheres (1-10 μm) with lipid, protein, or polymer shells can safely circulate through capillaries and resonate in response to ultrasound waves when injected intravenously, improving blood flow and tissue perfusion visualization before being cleared by the lungs and liver.
It was Feinstein that got the FDA to approve the first two ultrasound contrast imaging agents. Beyond diagnostics, he found new uses for microbubbles. Certain acoustic conditions could allow them to deliver therapeutic payloads directly into tissues.
Together with Davidson, a lipidologist and preventive cardiology specialist, Feinstein formed a long-term research partnership in Chicago’s academic medical community that resulted in the founding of SonoGene in 2000 to translate and commercialize ultrasound-mediated gene delivery.
Kenneth Greenberg, PhD, co-founder and CEO of SonoThera [SonoThera]
Though SonoGene never made a splash, Feinstein and Davidson were able to generate preclinical data, which Greenberg found “mindblowing.”
“It showed me that you could use ultrasound and nonviral DNA payloads to achieve delivery and gene expression,” said Greenberg. “This is in rodents, but it was enough to persuade me that if it worked in humans anywhere near as well as it does in rodents, it could completely change the landscape of gene delivery. I thought it was just such an elegant idea. These components have been available for years, and we can repurpose them in a creative way to accomplish things that you could never do with existing modalities.”
In 2022, Greenberg, Feinstein, and Davidson joined forces to launch SonoThera, backed by a $60.75 million Series A financing with the goal of developing a nonviral, ultrasound-mediated gene delivery platform capable of producing safe, targeted, redosable, and cost-effective genetic medicines.
Four years later, investors are reaffirming that vision. SonoThera closed an oversubscribed $125 million Series B financing to advance its lead programs to the clinic and develop its ultrasound-enabled delivery platform. The funding comes at a crucial time for genetic medicine, where delivery challenges continue to temper therapeutic innovation.
RIPPLE effect
The genetic medicine revolution has produced transformative therapies across rare diseases, oncology, and metabolic disorders. Yet despite the success of viral vectors such as adeno-associated virus (AAV) and nonviral systems such as lipid nanoparticles (LNPs), researchers continue to grapple with payload-size constraints, limited tissue targeting, inability to redose, manufacturing complexity, and immune-related toxicities.
For Kenneth Greenberg, PhD, those challenges create an opening for a fundamentally different delivery strategy. “The field and investors recognize that this is a big problem, and no one has yet been able to solve it,” he said. “Coming up from a very different angle, I think it is getting people excited that this could ever come.”
Rather than engineering new viral capsids or nanoparticle chemistries, SonoThera has built its platform around two technologies already widely used in medicine: ultrasound systems and microbubble contrast agents. The company’s innovation lies in combining them with naked DNA payloads and proprietary ultrasound waveforms, called RIPPLE, to drive gene transfer into tissues.
“Our strategy has been to use the existing infrastructure as much as possible and not to develop bespoke hardware or novel microbubbles,” Greenberg said. “We want this to be widely utilized and have great patient access and clinicians to be familiar with the systems and the components.”
Unlike AAVs or LNPs, SonoThera does not package DNA inside a carrier. Instead, naked DNA and microbubbles circulate independently in the bloodstream until ultrasound is applied to a target organ. “There are some common misconceptions about the mechanism,” Greenberg said. “The mechanism basically involves taking the genetic payload, which is naked DNA. It’s not encapsulated in anything.”
The ultrasound activates circulating microbubbles in a multi-step process. First, acoustic energy creates temporary gaps in the endothelial lining of blood vessels, allowing DNA to access target tissues. The microbubbles are then collapsed, creating transient pores in cell membranes that permit intracellular entry of the payload. Finally, ultrasound-driven modulation of the nuclear pore complex facilitates transport of DNA into the nucleus for transcription and protein production. “The ultrasound can basically do everything in one single profile,” Greenberg said. “We can modulate the waveform in ways to drive this mechanism of delivery. We don’t need receptors, endosomes, or anything like that, which gives the platform a huge advantage in versatility to target different organs.”
That receptor-independent mechanism may offer one of the platform’s biggest advantages. Existing delivery systems typically depend on receptor-mediated cellular uptake, which can activate innate immune pathways and restrict tissue tropism. According to Greenberg, microbubbles largely avoid those limitations. “It’s also key to how we avoid the immune system, the innate immune system’s response that typically gets triggered by viruses and LNPs,” Greenberg said.
Because microbubbles are micron-sized rather than nanosized, they never enter the cell and are destroyed extracellularly after ultrasound activation. The DNA itself enters cells independently. While naked DNA degrades relatively quickly in circulation, Greenberg said its half-life of roughly 30 to 60 minutes is sufficient because infusion and ultrasound delivery occur simultaneously.
In contrast, LNPs enter cells through endocytosis, carrying lipids and genetic cargo that can activate innate immune sensors such as cGAS-STING and TLR9. AAVs similarly rely on receptor-mediated uptake pathways that can provoke immune responses and limit redosing.
From sonoporation to clinical translation
The platform’s flexibility has become increasingly apparent as SonoThera expanded beyond its initial liver studies. The company subsequently evaluated delivery to kidney, skeletal muscle, heart, brain, and adipose tissue. “What we’ve found is that the delivery technology works in all organs in the body, as far as we can tell,” Greenberg said. The notable exception is the lung, where air attenuates ultrasound energy.
Perhaps most striking is the company’s work in the brain. The SonoThera platform can temporarily open the blood-brain barrier and deliver payloads using the same mechanism as other tissues. “A common misconception is that the bone can attenuate the ultrasound energy. But that’s not the case,” Greenberg said. “The frequencies are such that they can penetrate easily through the skull and get into the brain.”
If that capability translates clinically, it could represent a significant advantage over delivery technologies that remain largely confined to the liver or a limited set of tissues.
SonoThera’s initial pipeline targets diseases where current delivery systems struggle. In Duchenne muscular dystrophy (DMD), the full-length dystrophin gene is too large for AAV vectors. The company’s ADPKD program has a larger payload.
“The overarching strategy when we’ve approached indications is that it’s challenging to get access to large payloads that are prohibitively large for AAVs,” Greenberg said. “With our ADPKD program, the payloads are even larger. That’s about a 22 KB payload, while the DMD payload is about 13 kb.”
Redosing is also important. Many genetic diseases require long-term treatment, especially in children whose tissues grow. AAV therapies are rarely administered again due to immune responses, making therapeutic expression difficult. “There are indications where the disease really requires redosing over time,” Greenberg said. “DMD is a good example because we’re treating really young boys as their bodies grow.”
SonoThera delivers mutation-agnostic full-length dystrophin with redoseability. The company also targets skeletal muscle, heart, and diaphragm simultaneously to address cardiopulmonary complications that kill many DMD patients.
The platform uses episomal DNA rather than genome editing. Greenberg believes the DNA behaves like AAV-delivered episomes, becoming chromatinized in the nucleus and maintaining expression. “We’ve got durability data out to a year so far with a single treatment,” he said.
Target tissue will determine redosing frequency: rapidly dividing cells may dilute episomal DNA, but quiescent tissues may maintain expression longer. Despite its focus on gene replacement, SonoThera has shown compatibility with gene editing and targeted integration methods. “For us, it’s really about using the right tool for the right job,” Greenberg said. “We don’t want to do gene editing just because it’s sexy.”
The scientific foundation for SonoThera’s platform is rooted in sonoporation, a concept that has been explored academically for decades but has never successfully reached the clinic. Greenberg believes the field historically struggled with two major hurdles: achieving sufficient transfection efficiency and broad biodistribution. “In the first two years of the company, we basically focused on solving those problems and really innovating to achieve extremely high delivery efficiency and broad organ biodistribution,” he said.
Those advances have now positioned the company to enter clinical development. SonoThera is conducting IND-enabling studies, manufacturing activities, and GLP toxicology work while refining clinical trial designs with physician and disease-area experts. The initial studies will focus primarily on safety while also evaluating biomarkers and early signs of efficacy. In DMD, the company has already generated preclinical biopsies showing expression of full-length dystrophin protein in muscle tissue.
Although SonoThera’s internal pipeline currently focuses on rare diseases, Greenberg sees broader opportunities ahead. Pharmaceutical companies have increasingly shifted attention toward common diseases with larger commercial potential, and many are searching for delivery platforms that can overcome the limitations of AAV-based therapies.
Investor confidence—but can it scale?
Greenberg says industry interest in nonviral, redosable systems may be better for common diseases, especially when manufacturing costs and reimbursement issues make one-time treatments unsustainable. SonoThera will advance its pipeline and partner with larger companies seeking platform access to capitalize on those opportunities. “Our strategy as a small biotech company has been to have our internal pipeline but, in parallel, be able to have licensing deals and partnerships that allow us to expand the reach of the technology and the much larger patient populations.”
The oversubscribed $125 million Series B financing suggests investors increasingly view delivery as the next major frontier in genetic medicine. As SonoThera approaches the clinic, it faces many of the same questions every new gene-delivery platform has faced for creating a paradigm-shifting delivery modality: safety, durability, and scale.
Because SonoThera’s platform relies on ultrasound-driven physical mechanisms rather than biological targeting, factors such as organ size, anatomy, blood flow, and patient variability could provide challenges to translatability.
Delivering DNA to a mouse liver or muscle is very different from delivering therapeutic amounts of genetic cargo throughout the muscles, heart, and diaphragm of a growing child with Duchenne muscular dystrophy. While microbubbles have a decades-long track record as imaging agents, repeated therapeutic delivery tools are a different proposition.
While the company argues that naked DNA and ultrasound avoid many of AAV’s payload limitations, questions remain about the doses required for large organs and whether manufacturing and administration can scale efficiently. Relatedly, SonoThera has reported preclinical expression lasting up to a year after a single treatment, but long-term persistence remains unknown. If repeat dosing is required, the company will need to demonstrate that repeated ultrasound exposure and cycles of vascular permeabilization can be performed safely over time.
SonoThera’s appeal reflects a broader reality: despite decades of innovation, delivery remains genetic medicine’s biggest unsolved problem. The company’s platform is scientifically elegant and potentially transformative, but only clinical data will determine whether ultrasound-mediated gene transfer represents a true breakthrough—or simply the latest attempt to solve one of biotechnology’s most stubborn challenges.
With its biomedicine at an inflection point, India can seize the opportunity to scale up research and development at home and offer a distinct model of biomedical innovation for the global south.
Cervical non-invasive vagus nerve stimulation (nVNS) has emerged as a practical neuromodulation approach with FDA-cleared indications in primary headache disorders, yet skepticism persists over whether transcutaneous stimulation can reliably engage vagal fibers or whether observed benefits reflect nonspecific cervical activation. Here, we synthesize converging anatomical, biophysical, physiological, and clinical evidence demonstrating that nVNS does, in fact, activate vagal pathways without surgical implantation. We first review cervical vagus anatomy and the biophysical basis for target engagement, including ultrasound-measured nerve depth and multi-scale computational models showing that clinically relevant stimulation can recruit predominantly large myelinated vagal fibers. We then integrate mechanistic evidence across complementary modalities: functional imaging consistently modulates canonical vagal projection sites (including brainstem nuclei), electrophysiology demonstrates peripheral vagal recruitment and centrally transmitted evoked responses, immune studies reveal reproducible suppression of pro-inflammatory cytokines consistent with cholinergic anti-inflammatory reflex engagement, and autonomic biomarkers show shifts toward increased parasympathetic tone. Finally, we contextualize these mechanistic findings with sham-controlled randomized trials in cluster headache and migraine, where nVNS repeatedly outperforms sham for acute and preventive outcomes with a favorable safety profile. Together, these independent lines of evidence form a coherent mechanistic fingerprint that is difficult to reconcile with placebo or superficial muscle stimulation accounts. We conclude that nVNS provides a credible, scalable means of accessing vagal neurophysiology and represents a clinically validated, paradigm-shifting advance in bioelectronic medicine.
Testosterone. Methenolone. Nandrolone. Human growth hormone and EPO. Meldonium, modafinil, and mixed amphetamine salts. Clomiphene, anastrozole, levothyroxine, and liothyronine. Patches and capsules, creams and pills. A whole galaxy of steroids, metabolic modulators, and synthetic hormones coursing through the blood of a few dozen swimmers, sprinters, and weightlifters. And millions of dollars up for grabs for athletes who could break world records and usher in the age of superhumanity.
On Sunday, May 24, at a $50 million arena built in a casino parking lot in Las Vegas, I witnessed a libertarian thought experiment come to life. The inaugural Enhanced Games were the first sporting competition where participants were encouraged to take performance-enhancing drugs. The founders say they’re challenging dated sporting norms and helping to build a world where we can all live better, longer lives. Critics say the event is an embarrassment, that it glamorizes the use of dangerous substances and puts lives at risk.
The open-air venue was compact and decked out in bright blue, with a six-lane, 100-meter track down one side, a four-lane Olympic-length swimming pool down the other, and a weightlifting platform and stage at the front. You could see the golden façade of the Trump Hotel looming in the background. The scene had all the trappings of an NFL game, with the too-loud music and crowd work on the big screen—a “flex cam” gave the well-muscled an excuse to unveil their biceps. Between events, adverts flashed up for the line of performance products sold by Enhanced, the company behind the event: injectable peptides that supposedly support cellular energy and skin elasticity, daily supplement powders with names like “Stronger” and “Longer.”
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Australian swimmer James Magnussen was the first athlete to sign up with Enhanced but hasn’t broken any world records. He finished last in his two events in Las Vegas.
The day started with the weightlifters, under the blazing sun. But by 4 p.m., only one of them had even attempted a world-record lift. Two had pulled out injured. Some athletes were competing without taking drugs because of the money on offer, and as the competition went on, they had the better of their enhanced peers: Hunter Amstrong, a 25-year-old American swimmer and triple Olympic medalist, won the backstroke by more than a second. In the men’s 100-meter sprint, the non-enhanced US athlete Fred Kerley romped to an easy victory. “Man, they gotta do better than that,” he said of his doped opponents in his post-race interview. “They need to train a little harder, get on that shit a little bit more.”
At the bar, bodybuilders swapped before-and-after pictures and talked about their stacks, and VCs and finance bros traded LinkedIn details. Lukas Lakutsin, a 6-foot-10, 354-pound Russian bodybuilder who was milling around the entrance to the VIP suites, initially told me he didn’t use any performance-enhancing drugs. Except testosterone replacement therapy, of course. But he didn’t think that really counted. “I’m almost 34 years old,” he said. “I need to do this to stay strong.”
The “protocol” for Enhanced athletes only includes FDA-approved drugs. While Enhanced’s team might make recommendations, individuals have the final say on what they want to take, if anything.
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Jeremy Sigal, an influencer and author, wore a USA tank top that showed off hugely muscled arms adorned with prison tattoos. He told me he was proudly natural, in both his health and his personal life. “I’ve got an exceptional credit score,” he said. He has written 12 books on marketing and leadership. Later, I looked up his most recent book online. It’s called Simp to Pimp: 10 Steps to Fix Why She’s Not Banging You and lists AI as a coauthor.
What I saw in Las Vegas probably wasn’t the future of sport. But it was a perfect encapsulation of our present moment, as Silicon Valley biohackers, alt-right looksmaxxers, Make America Healthy Again boosters, and longevity-obsessed scientists all vie to remake reality in their own image. For them, the Enhanced Games offered a glimpse of a future where medical advances push the human race to new heights, and where they never have to get old.
I’ve tracked Enhanced’s journey from a crazy idea scribbled on a napkin to a public company valued at $1.2 billion. Behind the scenes, there have been power struggles, life-changing victories, and moments of total farce. As I recently, finally, watched the games unfold, two questions bounced around my head: Were they right? And what does that mean for the rest of us?
In December 2022, the Australian entrepreneur Aron D’Souza flew to Miami to spend New Year’s Eve with his friend and mentor Peter Thiel. A decade earlier, D’Souza had helped Thiel orchestrate the lawsuit that bankrupted Gawker—a stunning revenge against the gossipy New York media blog that had outed him as gay. Now he was armed with a disruptive idea that he thought Thiel, the billionaire cofounder of PayPal and Palantir, would love. It was inspired by the buff bodies he’d been seeing at the gym, highlighting a disconnect between a workout culture where the use of steroids was an open secret and a sporting establishment where it was, at least on paper, an inviolable taboo.
His initial pitch was provocative and confrontational: a grand sporting event to rival the Olympic Games, where competitors could take any substance they wanted—their body, their choice. The first time I met D’Souza, in the spring of 2024, he had founded the company and attracted some initial investment but seemed obsessed with taking on the fat cats at the International Olympic Committee and reinventing sports (even though he didn’t seem to be a huge sports fan himself). On Enhanced’s Discord server, I found a folder full of memes with names like IOC Clowns.jpg. The whole thing felt very unserious.
That would change.
D’Souza told me that Thiel had previously introduced him to Christian Angermayer, a German biotech billionaire, who would come onboard at Enhanced. He’s funded clinical trials of psychedelics through his company Atai Life Sciences and is helping bring them into the medical mainstream as a treatment for depression and anxiety. Angermayer says he spotted an opportunity to do the same thing for steroids. What he really wants is to redefine medicine, he told me. Its focus has already changed from treating disease to trying to prevent it; actively enhancing people’s health, he says, is just the next logical step.
By early 2024, Angermayer had brought his own people into key roles. The team included Michael Sagner, an anti-aging expert and private doctor who works with many of Hollywood’s leading men, and Max Martin, who has the jawline and cheekbones of an Instagram looksmaxxing influencer and the boundless enthusiasm of a puppy. (He started his own enhancement program a few years ago, when he was just 27.) Sagner would head up Enhanced’s medical commission, making sure the games were safe for the athletes. It was Martin’s job to make sure they actually happened.
In early May, Enhanced began trading on the New York Stock Exchange with an initial value of $1.2 billion. Christian Angermayer stands far right with Max Martin to his left (front row), and Aron D’Souza next to him.
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Tensions sparked as D’Souza’s freewheeling style clashed with the more sensible image that Sagner and others were now keen to present. “It was not just his personality and his abrasive way of talking,” Sagner told me recently. “Even when he was briefed on a scientific fact, he would just completely ignore it and say something outrageous.”
But the more outrageous D’Souza got, the more attention his idea received. In February 2024, James Magnussen, a retired Australian swimmer, became the organization’s first official athlete, and Enhanced promised to pay a million dollars to him, or anyone else, who could break the world record in the 50-meter freestyle.
The notion of a “steroid olympics,” as many have dubbed the Enhanced Games, had been kicking around for decades—for instance, in a Wiredarticle from the early 2000s and an SNLsketch from the 1980s. Two things helped finally make the Enhanced Games a reality. First, in November 2024, Donald Trump was again elected president of the United States. The Biden administration had been actively hostile to the games, but the founders saw a more receptive political environment in Trump world. Not long after the election, Enhanced announced a new tranche of funding led by 1789 Capital, a venture capital firm whose partners include Donald Trump Jr.
And second, in February 2025, an enhanced swimmer finished the 50-meter freestyle faster than anyone in human history. It wasn’t Magnussen, though. He had been injecting himself with testosterone to grow muscle, plus a cocktail of peptides that aimed to speed up recovery—but his journey hadn’t quite worked the way he’d planned.
A combination of reputational issues (no pools wanted to host his training) and physical complications (the regimen did help him get stronger, but he packed on so much muscle that it slowed him down in the water) meant he watched from the sidelines as the Bulgarian-Greek swimmer Kristian Gkolomeev—who had finished fifth at the Paris Olympics in 2024—came in two-hundredths of a second under the record and won a million-dollar payout from Enhanced. The idea has always been that breaking records would effectively prove the legitimacy of this enhancement project: Look what we can do now.
Enhanced swimmers like Magnussen (right) wore supersuits to compete, though they’ve been banned by World Aquatics since 2010.
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Gkolomeev, though, had a different motivation for participating: “One successful year in the Enhanced Games and I could make as much as I would in almost 10 careers,” he told me not long after setting the new record (notably, wearing a kind of “supersuit” that’s been banned by World Aquatics since 2010). Enhanced was paying its athletes a regular salary, on top of any potential bonus. And he had a young family to support and feared that the four-year stretch to the next Olympics would be long and precarious.
In May 2025, with a world record in the bag and a friendly administration in the White House, Enhanced was ready to announce its first games: They’d take place in May 2026 at Resorts World in Las Vegas.
At the same time, D’Souza made another big reveal: Enhanced Performance Products, a line of supplements available for a monthly subscription. The Enhanced Games now seemed less like a sporting event and more like a loss leader for selling testosterone injections, GLP-1s, or a range of peptides that are claimed, with little scientific evidence, to improve sleep or skin elasticity. Perhaps it was all a brilliantly executed marketing stunt.
“The games themselves now seem almost secondary to what appears to be an online marketplace for hormones, peptides, and other performance-enhancing compounds,” says Astrid Kristine Bjørnebekk, a steroids expert at Oslo University Hospital. “From my perspective, this significantly changes the nature of the project. It is one thing to organize a closed sporting event built around controversial principles, but openly marketing and commercializing substances such as testosterone, hGH, GLP-1 drugs, peptides, and other pharmacological compounds is something else entirely.”
As the games approached, more athletes joined. Some were genuinely elite. The US sprinter Kerley—who is serving a two-year ban for missing three drug tests—had won silver in the 100 meters in the Tokyo Olympics and a bronze in Paris. Ben Proud, a British swimmer, had won silver at the Paris Olympics and dozens of medals at world and European championships and the Commonwealth Games. He had been mulling over joining the Enhanced Games ever since the idea first emerged, but the tipping point seemed to come when Gkolomeev’s record was announced.
Some participants, like Magnussen and another swimmer, Megan Romano, had been tempted out of retirement. Romano hadn’t swum competitively for almost a decade. Others were at the start of their careers but ready to cash in their chips and bid goodbye to Olympic dreams for a potential six-figure payday. The $1 million payouts were reserved for records in the two flagship events—the 50-meter freestyle and the 100-meter sprint—but winning any other event would mean a prize of $250,000, with an additional $250,000 bonus for setting a world record.
Athletes would get paid even if they just showed up and finished last—as much as $50,000. This is all on top of the salaries that stretched into six figures in some cases, making the payout from the games more than many athletes make in a year.
Sport’s governing bodies reacted to each new athlete announcement with fury. World Aquatics threatened to ban for life any athlete who participated in the games, even if they didn’t take any drugs. Enhanced responded with an $800 million antitrust lawsuit against the global swimming organization, the World Anti-Doping Agency, and USA Swimming, alleging misuse of monopoly power.
American Fred Kerley (right) won the 100-meter sprint without performance enhancing drugs.
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In November 2025, a court in New York dismissed the case. Three days later, D’Souza, the mind behind the entire project, was out. A notice on Enhanced’s website said he had “transitioned out of the company’s day-to-day operations.” Martin would take over as CEO. “The investors basically said we need someone a bit more serious,” Sagner told me. In conversations, execs at Enhanced played down any suggestion of a feud—D’Souza was simply the ideas man, with little interest in the day-to-day dreariness of actually running a company. (Enhanced spokesperson Chris Jones wrote in a statement that “there is no tension between Aron and Enhanced that I’m aware of.” D’Souza did not respond to a request for comment.)
I got the sense that Enhanced, in its new iteration as a pharmaceutical subscription company, was almost embarrassed by the games. When I visited enhanced.com a couple of months before the event, they had been relegated to a sub-heading on the home page. D’Souza’s showmanship had helped get attention for what was becoming a run-of-the-mill telehealth business like Hims & Hers—albeit one well timed to take advantage of a shifting regulatory landscape around peptides, which Robert F. Kennedy Jr., the US secretary of health and human services, has been pushing the FDA to approve despite a lack of evidence that they’re actually effective.
Sagner is still loosely involved with Enhanced, but he says the medical commission was not consulted before it launched its line of performance products. (Jones did not respond to a question regarding this claim.) Sagner is scathing about what he sees as the “hype” around peptides. “I can tell you already, peptides do nothing,” he says—with the exception of human growth hormone and GLP-1. “The peptides that people use, black-market peptides that they buy online—they do nothing. We have tested them; 80% of them contain nothing. It’s saline solution, salt water, and some of them are contaminated.”
At the end of January 2026, a group of around 40 swimmers, weightlifters, and sprinters arrived in Abu Dhabi to start their individualized enhancement “protocol,” as Enhanced calls it. Officially, they would be taking part in a clinical trial, pending approval by the Abu Dhabi government and overseen by Guido Pieles, a Qatar-based cardiologist who has taken over the reins of Enhanced’s medical commission from Sagner.
The day started with the weightlifters, but by late afternoon, only one of them had even attempted a world-record lift.
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They would be allowed to choose only from a menu of specific FDA-approved drugs. Pieles broke them down into five categories: testosterone variants and growth hormones, which can both boost muscle mass; metabolic modulators that can tweak how the body burns fat; stimulants like Adderall to improve focus; and EPO, which can increase the amount of oxygen the blood is able to carry. While Enhanced’s team might recommend particular things, the athletes would have the final say on what they wanted to take, if anything. (As Oslo University’s Bjørnebekk points out, FDA approval “does not mean the substances are inherently safe, particularly not when used for enhancement purposes.”)
There would be regular blood tests, heart scans, and brain scans and access to the best training facilities money could buy. Pieles and others say the clinical trial will help inform the line of supplements Enhanced is offering consumers, but there’s actually very little overlap between the drugs the athletes were taking and the substances the company is currently selling.
Not long after they arrived in the Middle East, the athletes were awakened by the sound of explosions at a military base near their hotel. The US and Israel had struck Iran, and the Iranian regime was responding by peppering the region with missiles. “It wasn’t a pleasant situation,” says Andrii Govorov, the world record holder in the 50-meter butterfly, who a year earlier had become one of the first swimmers to join Enhanced. Govorov had some experience in these matters—back in Ukraine, he’d had a business selling cars that helped fund his swimming career, but he’d lost it after the Russian invasion.
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Swimming, sprinting, and weightlifting were the focus of the first Enhanced Games but in many ways the sports were the sideshow.
The conflict exacerbated delays in getting approval for the clinical trial and sourcing the drugs, and as a result, what was supposed to be a 12-week enhancement protocol got cut down to eight weeks. The athletes didn’t actually start taking the drugs until toward the end of March. For those who had always been clean, that represented the irreversible crossing of a line. “The first injection was very emotional, very tricky to navigate,” says Proud. “For me, that was the day I went from the Ben Proud that I always knew to a new person.”
Proud was joined in the enhancement program by his girlfriend, Emily Barclay, who had swum at college level without ever appearing at a major international event; she was working as a swimming teacher at a school in England. After that first injection, they left Abu Dhabi and spent a few days in Dubai as they reckoned with what they had done. “I just couldn’t be around the team,” Proud says. “I wanted to be by myself and feel those feelings, because it is a big deal to make that step, and I felt it.”
Those feelings were soon forgotten, though, as the drugs kicked in. Proud says he had incredible energy, and a drive to train that he hadn’t experienced before. Shania Collins, an American sprinter, says she had “increased strength, increased recovery, and increased mental clarity at practice.” Sagner and several athletes admitted there were some side effects: acne and some swelling around the joints; unwanted hair growth for the women, unwanted hair loss for the men.
Like Kerley, sprinter Tristan Evelyn from Barbados competed without taking any drugs. She too won big in Vegas, besting her Enhanced peers in two events.
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One thing the athletes wouldn’t talk about, though, is what drugs they were actually taking. They all had the same reason: not wanting to encourage copycats who might take enhancements without a doctor on hand to tailor programs to their needs.
The one exception was Thor Björnsson (testosterone, deca-durabolin, anastrozole, halotestin), a hulking Icelandic deadlifter and former World’s Strongest Man who played The Mountain on Game of Thrones. Björnsson first heard about the games on Joe Rogan’s podcast and was immediately interested. The rules for strongman competitions are somewhat less stringent than those for Olympic sports, though, and he actually had to reduce the number of substances he was taking to meet Enhanced’s FDA requirements.
Icelandic strongman Thor Björnsson actually had to reduce the number of substances he was taking to meet Enhanced’s FDA requirements.
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There is some debate over how much doping some of the athletes were actually doing. In a conversation last year, Gkolomeev told me he’d only really been “microdosing,” and he confirmed that his 2026 enhancement program was largely the same. Sagner says the doses the athletes were taking were a fraction of the amounts some Olympic athletes had been caught using in the past. I heard that a few athletes had decided not to take steroids or growth hormones and were only using modafinil, a narcolepsy medication that’s thought to improve focus.
The day before the games, I asked Angermayer what it would mean if clean athletes like Kerley and Armstrong won their events—what impact it would have on Enhanced’s business model of using sports as a showcase for its line of performance products if the people using those products didn’t actually win anything. “I know what you mean, but mostly our business model is headlines to drive attention,” he said. “Any debate is good for us.”
In early May, Enhanced began trading on the New York Stock Exchange with an initial value of $1.2 billion.
That same week, it was finally go time. The athletes and coaches left Abu Dhabi and flew to Las Vegas, where they were put up in five-star luxury at the Conrad hotel inside Resorts World while they made their final preparations.
When I got there a few weeks later, toward the end of May, I found it jarring to see these hulking presences walking around the casino in their Enhanced sportswear, weaving their way through packs of half-drunk tourists, with slot machines flashing in the background and cigarette smoke hanging in the air. I had expected the games to be a bigger deal within the city itself, but they were just one of a thousand things happening in Vegas that weekend—drowned out by a series of BTS shows at the football stadium, by the Golden Knights in the NHL playoffs, by No Doubt’s residency at the Sphere.
If this was a sporting earthquake, it was one whose tremors were mainly being felt online, where bodybuilding influencers livestreamed to their followers on Kick and Twitch, and where thousands watched on YouTube and Rumble. (D’Souza once told me he’d had “every major sports broadcaster” vying for the rights; in the end, Enhanced struck an exclusive streaming deal with Roku in the US.)
No tickets were sold, so the crowd was a mix of invited guests, investors, and influencers, some of whom had reportedly been flown in on a chartered jet.
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On the morning of the games, Enhanced held a medical symposium that was supposed to provide a taste of the company’s long-term objectives. The first speaker was Bryan Johnson, the longevity-obsessed entrepreneur famous for plowing his personal fortune into wild attempts to reverse his aging: receiving transfusions of his teenage son’s plasma, measuring his nighttime erections, taking more than 100 supplement pills a day. He spends $2 million per year on all this, but he looked pale and vampiric as he delivered the slightly off-brand message that, really, the most important thing was getting a good night’s sleep: “You don’t need to chase IV infusions; you don’t need to chase crystals. You don’t really need to do much of anything.”
At 2 p.m., I took two escalators from the conference room down to the arena, where spectators were filtering in. Though it had cost $50 million, it had been constructed in just three and a half weeks, and it showed; on the media tour the previous day, there were still loose screws on the floor of the bleachers.
There were a few thousand seats in an open grandstand down one side, and two rows of VIP suites on the other. No tickets were sold, so it was a strange mix of invited guests, investors, and influencers, some of whom had reportedly been flown in from Los Angeles on a chartered jet. The rapper Tyga was the biggest name to grace the “blue carpet,” although I did also spot Fabio James, a Michael Jackson look-alike who has had surgery to make the resemblance even stronger. Rumors swirled that Peter Thiel might show up; they proved unfounded.
In attendance was Fabio James, a Michael Jackson look-alike who has had surgery to make the resemblance even stronger.
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A few hours before the doors opened, journalists got a stern message from the organizers trying to bar us from interviewing guests. Still, I talked to a Cambridge professor who wanted to use Enhanced as a case study in innovation for his MBA students, a retired Brazilian swimmer with the Olympic rings tattooed on his forearm, and a biotech investor wearing an Enron hat. Proud’s family and friends were sheltered from the blazing sun in the shadow of the big screen.
D’Souza was nowhere to be seen. Nor was he really mentioned at all—not during the introductory press conference, where Martin was introduced as the “founder of the Enhanced Games,” nor during the event itself, where the athletes showered praise on Angermayer and Martin. But the tens of millions D’Souza had banked from the stock listing likely softened any blow. Plus, he’s already moved on to his next provocative venture: an AI-powered arbitration platform designed to scrutinize the work of journalists on behalf of the rich and powerful.
As the sun set behind the hills, casting the arena in soft gold light, there were still no world records. That and the wins for clean athletes seemed to put the whole Enhanced project in jeopardy—the knives were already being sharpened online. I asked the organizers whether this threatened the legitimacy of the project.
German swimmer Marius Kusch was among the dozen or so athletes who hit personal bests in Vegas.
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“Our response is that enhancements help athletes improve and, in some cases, break records. And yes, some non-enhanced athletes also won—because talent and ability also matter,” Enhanced’s Jones emailed last week. “Breaking world records is incredibly hard as the margin is infinitesimal, as we witnessed. Ignoring that 13 athletes some of whom 10 years later broke personal bests is disingenuous and selective reporting.”
Megan Romano was one of them, swimming faster in the 50-meter freestyle at 35 than she had at 22. And Emily Barclay knocked two seconds off her fastest time in the 100-meter freestyle, coming in second in that event and winning the 50-meter freestyle; she went home with a check for $375,000. “No one’s ever heard of this girl,” said Enhanced swim coach Brett Hawke afterwards. “She’s retired; she’s a nobody. She comes out tonight and swims a time that would have got a bronze medal in Paris.” For all the talk of “superhumanity” and pushing the boundaries of performance, making a 35-year-old feel 22 again is probably the perfect marketing message for the products Enhanced wants to sell.
Angermayer cheers on swimmer Megan Romano, who swam faster in the 50-meter freestyle at 35 than she did at 22.
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Enhanced’s executives say people should take enhancements only with medical supervision, but price could be a barrier to heeding that advice. The battery of health tests the company was giving its athletes in the run-up to the games cost $25,000 per athlete per month. The drugs themselves start at $75 a month and go up toward $200. While Jones says the products “are in line with industry price points,” there were almost certainly people watching who saw the drug-altered physiques of athletes like Gkolomeev or Magnussen and decided to find cheaper, less safe alternatives on unlicensed websites.
“Many of these substances require medical supervision and prescriptions, and several are associated with potentially serious long-term health consequences,” says Bjørnebekk. “Presenting them in this lifestyle-oriented and commercial format risks normalizing use while downplaying the medical risks and uncertainties.”
Although his world record-breaking time won’t stand as the official record, swimmer Kristian Gkolomeev will walk away from the Enhanced Games with a million dollar prize in the 50-meter freestyle.
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Before the night was over, Gkolomeev again had the chance to right the Enhanced ship. The final event of the night was the men’s 50-meter freestyle swim. His 2025 time had been surpassed by the Australian swimmer Cam McEvoy (without a supersuit) at the China Swimming Open a couple of months before, so he needed to lose another two-hundredths of a second to beat the new record of 20.88 seconds.
Gkolomeev was wearing the same supersuit he’d used the previous year, and he’d shaved off his mustache for a little extra streamlining. But he messed up his start—doing four kicks instead of five—and was trailing Proud at the halfway mark. His long arms levered him forward, though, and he reached the wall in 20.81. The spectators were on their feet as “WORLD RECORD” flashed red on the big screen. Martin vaulted over the glass partition from the VIP suites, beaming, to embrace Gkolomeev. They had their record.
Or did they? Online, people shared screenshots from the video feed, purporting to show that the clock had stopped before Gkolomeev’s hand touched the pressure sensor at the end of the pool. An Enhanced spokesperson gave a statement to the Guardian dismissing this as “completely unfounded internet drivel.” But hey—live by the sword, die by the sword. It’s quite possible Gkolomeev didn’t care. He had another million in the bank.
It remains to be seen if it’ll work out so well for the other athletes. Enhanced organizers recently announced a prize of $10 million for anyone who can break Usain Bolt’s 100-meter world record in 2027. They are adamant that the games will happen again next year. If they don’t, dozens of sporting careers will be over, and the athletes will join the long list of victims of VC-backed disruption.
My personal prediction is that Enhanced will pivot away from the risk and uncertainty of a flagship event—the company’s valuation plunged by almost $800 million when markets opened after what was perceived as an underwhelming set of results in Vegas. I expect you’ll see individual stunts and challenges, tightly controlled and filmed for virality and probably featuring your favorite YouTubers—think Björnsson bench-pressing Jake Paul.
D’Souza’s initial idea has served its purpose by capturing the world’s attention. But that won’t necessarily translate into success either. Though the company has had plenty of hype over the last 12 months, SEC filings published as part of its stock exchange listing reveal that it generated only $2,755 in revenue from its enhancements business in the first three months of 2026. Would what happened in Vegas be enough to juice sales?
Martin, Enhanced’s CEO, cheers on athletes from the stands. Company leadership insists the competition will take place again next year.
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As the athletes gathered on the stage to receive their prizes, Martin took the microphone and addressed the crowd. “Enhanced is culture,” he said. “We are at the pulse of where the world is going.” On this, at least, he’s probably right. Testosterone replacement therapy is rapidly moving into the mainstream, and while the science may still not be there on peptides, they have certainly exploded in popularity in the two years since Enhanced launched. And there are undoubtedly more substances yet to be discovered that will promise to improve people’s lives, or at least hold their appearance in stasis. The enhanced age is upon us, whether we want it or not.
As the fireworks went off and the Killersclosed out the event with “When You Were Young” (“Congratulations to … whoever deserves it,” said frontman Brandon Flowers), I wondered what that might mean for us mere mortals. Invoking Hunter S. Thompson’s Fear and Loathing in Las Vegas in a story about drugs and Las Vegas may be a cliché, but it struck me that fear played a big part in all of this. Fear of missing out. Fear of getting old. Fear of never making a dime on your life’s pursuit. Fear of waking up one morning and seeing your flabby, sunken face in the mirror while everyone around you shines and grins and thrives with white-toothed, alien smiles.
Before joining Enhanced, Romano had not swum competitively in almost a decade.
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But the big problem with Enhanced’s vision of superhumanity is the question of who gets to join in. “People will be able to enhance themselves if they have enough money,” Sagner had told me the night before the games. The rest of us, I fear, will just have to function as normal human beings.
Amit Katwala is a journalist and author covering science, culture, and where they collide. His latest book is Tremors in the Blood: Murder, Obsession and the Birth of the Lie Detector. He is based in London.
Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.
Announced in this Comment and in collaboration with Nature Medicine is the convening of the Brain Health for Economic Resilience Commission, a global, transdisciplinary effort to define, measure and operationalize brain health and cognitive capacity as foundational drivers of economic resilience.
The number of prescription drug shortages in the U.S. fell by 23% last year, marking the second consecutive year of declines and the lowest level since 2017, according to a new analysis that otherwise found troubling signs about medicines that are in short supply.
For instance, the average drug shortage lasted 5.3 years, exceeding the 4.3 years seen in 2024 and greatly outpacing the average two-year shortage experienced in 2019. Moreover, nearly two-thirds of out-of-stock medicines were in short supply for more than three years, and 39% were unavailable for more than five years.
Meanwhile, the 75 drugs that were in short supply last year spanned 130 therapeutic categories, indicating that shortages affected a wide range of diseases and patient populations, according to the analysis by U.S. Pharmacopeia, an independent organization that develops standards for medicines.
Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) reported encouraging interim results from an early clinical trial that tested a new dual vaccine against Lassa fever and rabies. The study found the vaccine to be safe and induced immune responses against both the Lassa fever and rabies viruses (RB). There are currently no vaccines against Lassa fever on the market.
“This vaccine is designed to protect against two viruses of global health importance,” said study principal investigator Justin Ortiz, MD, MS, professor of medicine at UMSOM and vaccine researcher at CVD. “By combining targets into a single product, it could reduce the need for separate vaccination efforts and streamline delivery in settings where access is limited.”
Ortiz is first and corresponding author of the researchers’ published paper in Nature Medicine, titled “Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial,” in which they said, “If efficacy is confirmed, this combination vaccine could help protect populations from two priority pathogens and have a meaningful public health impact in regions where both diseases remain major threats.”
The World Health Organization has identified Lassa virus (LASV) as a public health threat in western Africa and made Lassa fever a priority disease for research. “Transmission occurs primarily through contact with food or household items contaminated by urine or feces from Mastomys rodents, although person-to-person spread can occur via exposure to bodily fluids or contaminated surfaces,” the investigators noted in their paper. Like Ebola, Lassa virus can trigger severe illness and periodic outbreaks in African nations.
Lassa virus infections occur in 300,000 people every year resulting in 5,000 deaths, according to figures cited by the authors, but these numbers are likely an underestimate due to limited surveillance. The disease is particularly dangerous in pregnancy with over 80% of late-term infections resulting in deaths to the mother or fetus. Additionally, regions where Lassa fever is common, such parts of Western and Sub-Saharan Africa, also have a high burden of rabies, with thousands of deaths annually, a disease that is almost always fatal once symptoms develop. The newly reported first-in-human trial was designed to evaluate the safety and immunogenicity of an adjuvanted inactivated rabies virus expressing the Lassa virus glycoprotein complex (GPC) on the surface of the virus. “Scientists at Thomas Jefferson University developed an inactivated rabies-vectored combination vaccine derived from an attenuated rabies strain, LASSARAB, expressing both the rabies glycoprotein and the LASV (Josiah strain) GPC,” the authors explained. “The RABV platform provides a well-established foundation for a dual-target vaccine.”
For the randomized, controlled trial 54 healthy adult volunteers from the Baltimore area were randomly assigned to receive different doses of LASSARAB, with an adjuvant or a licensed rabies vaccine control. Participants received two vaccine doses 28 days apart. Immune responses were studied through 61 days post-vaccination for an interim analysis. The results indicate that LASSARAB was safe with no serious adverse events (AEs) reported after vaccination. Additionally, the candidate vaccine induced rapid and robust antibody responses against both Lassa and rabies viruses when compared with the control, which only induced an immune response against rabies virus.
The study is ongoing, and vaccine safety and immune responses will be further studied through 394 days post-vaccination. “The final study report will be prepared after study completion and will include serious AEs and AEs of special interest through day 394, protocol-defined exploratory LASV and RABV antibody responses assessed at days 121 and 394, and any additional post hoc analyses, as applicable,” the team stated.
If the results indicate continued elevated immune responses from vaccination, researchers will proceed with more advanced clinical trials. Importantly, this investigational vaccine can be freeze-dried for storage, enabling distribution to areas of the world where it may be difficult to maintain cold chains. Importantly, this investigational vaccine can be freeze-dried for storage, enabling distribution to areas of the world where it may be difficult to maintain cold chains.
“These data support the feasibility of a bivalent rabies-vectored vaccine integrated into routine immunization for regions where cold-chain capacity is limited,” the team added.
“This study highlights CVD’s commitment to tackling diseases of global significance,” commented Stefan Kappe, PhD, director of the Center for Vaccine Development and Global Health and the Myron M. Levine Endowed Professor of Pediatrics. “LASSARAB not only targets diseases of concern but utilizes a platform that could make distribution attainable in the areas of the world that are most affected by these diseases.”
Added UMSOM dean Mark T. Gladwin, MD, “Climate change is causing Lassa fever to extend its reach far beyond its Nigerian and West African origins, putting an estimated 700 million people at risk worldwide. By 2070, the number of countries across Africa that will develop ecological conditions suitable for Lassa virus spread could drastically increase, so a vaccine to prevent this deadly infection is desperately needed.”
Last year, before results were available, the trial was highlighted by Nature Medicine in its 2025 feature, “Eleven clinical trials that will shape medicine in 2026,” which identified studies to watch based on their potential to address major unmet health needs.
