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Director of the award-winning Clair Obscur: Expedition 33 has once again showered praise onto Hironobu Sakaguchi's Lost Odyssey, an overlooked classic made by the father of Final Fantasy.

Sandfall Interactive's Guillaume Broche recently appeared on an episode of Jeux Vidéo Club, which is kind of like the Criterion Closet for video games, where the director picked a few classic games from the archives and discussed how they influenced his own work.

The Clair Obscur: Expedition 33 director has many times cited old-school JRPGs as huge inspirations, but he dived deeper than ever into Lost Odyssey, a stone-cold Xbox 360 classic that came out after Sakaguchi's departure from Square Enix. It was essentially a Final Fantasy game in all but its name, and it didn't quite get the attention it deserved as a genre masterpiece at the time.

"It really was an exceptional game," Broche says. "It's a bit of an old-school game, very linear. There were random battles too, just like in the old Final Fantasy games. Everyone said, 'What is this game from another era?'... So it got torn apart even though the game is exceptional."

"The story is amazing. It's the last game that made me cry. The villain isn't that great. That's the only downside for me. But overall, I highly recommend it to anyone who loves Final Fantasy. It's one of those games that really left a mark on me - not just because it was fun, but emotionally. Every now and then, I think back on it, I listen to the music and immerse myself in it all over again. It's truly one of the most powerful, emotional experiences of my life as a gamer," he adds.

"Something that really stood out to me was that it was one of the last somewhat ambitious turn-based games with realistic graphics. Since then, we've had a lot of turn-based games - there are still plenty, like Octopath Traveler, Persona, even Yakuza - but turn-based games with dramatic, ambitious stories and realistic graphics haven't been around since Lost Odyssey. It was the last one."

It was the last one... until Clair Obscur: Expedition 33, that is. "It holds a special place in my heart because, for me, Clair Obscur is sort of the successor to that in a way - it was my favorite kind of game, and nobody was making them anymore," Broche continues. "So I said to myself, "Let's go." It's one of the best games in the world."

Lost Odyssey discs are still going for pretty cheap, though it's also available digitally on Xbox One and Xbox Series X|S.

"They're usually just really boring" - Clair Obscur: Expedition 33 lead says "perfect" games are like people with "no personality"

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Want to speed up your recovery after an injury or a workout? Some influencers are fans of shots of BPC-157 and TB-500 for that. Want scar-free, youthful skin and thick hair? Reddit posts rave about GHK-Cu and KPV. Want to build beautiful, bulky biceps? Some fitness influencers swear shots of ipamorelin will do wonders. This is the world of peptides — an assortment of chemicals that promise to boost your body and health — and people are self-injecting them in a growing wellness trend.

Promoted by bodybuilders and influencers, supporters of the "Make America Healthy Again" movement and Silicon Valley early adopters, peptides promise results that leave people better than well, fitter than fit. Yet despite getting glowing reviews on social media, most peptides have limited clinical evidence to support health benefits, whether it's helping to heal a rotator cuff injury, improving libido or building muscles. There's not much information out there on the drugs' effectiveness and even less on their safety.

In 2023 the Food and Drug Administration banned several peptides, including BPC-157, GHK-Cu, KPV and ipamorelin, from being produced in the U.S. by compounding pharmacies — facilities that legally make non-FDA-approved medications for individual use — because of " significant safety risks ." Many peptides are imported from outside of the country, and many made here are marketed for research use only. People who desperately want the promise contained in the tiny vials seek them out on online on legally dubious gray markets.

But accessing the shots might soon get easier. On the podcast The Joe Rogan Experience on February 27, Robert F. Kennedy, Jr., secretary of the Department of Health and Human Services, proposed legalizing the compounding of 14 peptides — and the FDA seems poised to grant his wish. Earlier this week the agency released plans to hold a meeting with independent advisers in July to review whether some U.S. pharmacies should be allowed to manufacture certain peptides , including BPC-157, TB-500 and KPV.

If the lift on peptides happens, a flood of people could start using the drugs , regardless of any safety concerns.

A Peptide by Many Names

A peptide is a chain of two or more amino acids — building blocks of proteins . The body's cells can produce numerous peptides, which perform various tasks or serve as signaling molecules.

Insulin is a peptide. So is human growth hormone — and semaglutide , the active ingredient in glucagonlike peptide 1 (GLP-1) receptor agonist drugs such as Ozempic and Wegovy . (GLP-1s are FDA-approved for managing type 2 diabetes and for weight loss). Buzzy new injections such as BPC-157 and GHK-Cu — touted for tissue repair — are derivations or synthetic versions of naturally occurring peptides. The public and online health retailers are starting to use "peptides" as a catchall term for any chemical taken for well-being, energy, exercise recovery, and more, says Luke Turnock, a criminologist who studies how people use enhancement drugs at the University of Lincoln in England.

And while people are using them as treatments, peptides aren't often described as drugs. "'Drug' has a certain stigma or negative connotation attached to it," Turnock says. The popularity of peptides has its roots in the bodybuilding and powerlifting communities, he explains, where "drug" has historically been tied to steroids — which are generally banned for professional athletes.

The term "peptides," meanwhile, stresses the natural origin of the molecules, says Flynn McGuire, who studies sports medicine at the University of Utah. "Because it's 'natural,' it is better or different, even though they're just drugs," McGuire says.

A Surge in Popularity

In the past few years, orthopedic surgeon Omar Rahman has seen a spike in interest in peptides. "I'm seeing more patients asking about peptides, often driven by the longevity and wellness space," says Rahman, who practices at Pacific Coast Sports Medicine in Los Angeles.

Because peptides encompass many products — some available by prescription, others on the gray market — the exact number of people trying them is hard to pin down. The subreddit r/peptides currently has more than 70,000 weekly visitors, and the related subreddit r/biohackers, which frequently hosts conversations on peptides, has more than 600,000. A scroll through TikTok offers pages of people sharing their "stacks" — combinations of injections people take to meet their personal goals, from muscle-building and exercise recovery to increased brainpower or a better tan.

"The real cultural tipping point in my mind seems to have been around 2022, when the GLP-1s really blew up," says Turnock, who is researching the peptide boom. He says injecting drugs became "normalized" when GLP-1 drugs approved to treat diabetes, such as Ozempic, were also shown to be effective for weight loss — and eventually became an approved treatment for obesity.

Some are turning to peptides because they feel doctors aren't giving them the help they need, says Dan Cushman, a sports medicine doctor at the University of Utah. Injuries to certain tissues, such as tendons, "are very slow to heal" with conventional treatments, he says. Mainstream treatment can also be expensive and painful. To someone desperate for relief, peptides might seem worth a try.

Peptide use is also linked to a growing interest in health autonomy, Turnock says. This is the idea "that doctors, if they're not prescribing what you ask for or they're not offering you these solutions, are acting as a barrier to your good health."

Stacking Up

McGuire, Cushman and colleagues published a review last year on one peptide they encountered frequently: BPC-157. The peptide is promoted as a way to stimulate multiple cellular pathways involved in blood vessel formation, cell growth, muscle repair and inflammation. Their review, however, found that most of the evidence of such health effects was from rodent studies , and only three small pilot studies had looked at BPC-157 use in humans.

In a regimen called the "Wolverine" stack, many people combine BPC-157 with injections of TB-500, another peptide that is supposed to promote healing but has even less research behind it. The "Wolverine" stack is named after the rapidly healing X-Men character. Add injections of GHK-Cu and KPV, and the stack is called "glow" or "KLOW." People claim that GHK-Cu increases wound healing, decreases scarring and helps regenerate collagen — and that KPV, derived from a hormone naturally found in the body, reduces inflammation. GHK-Cu is found in blood plasma and is an FDA-approved ingredient in topical antiaging cosmetics — but it is currently banned as an injectable because of safety concerns, such as the risk of immune reactions caused by impurities.

For muscle-building, the peptides ipamorelin and CJC-1295 are advertised as stimulating growth hormone release. Both have little clinical evidence behind them, however. Some people stack ipamorelin with GLP-1 drugs to try to lose fat while building muscle, though the effects of taking these injections together have not been studied.

Use at Your Own Risk

Clinical trial data for most of these peptides are thin. Not only are the effects anecdotal, but so are the doses. FDA-approved drugs, Cushman says, have been tested and reviewed not just for their efficacy but also for their safety. There is very little existing information on most of these peptides, he says, let alone on what happens if they are combined.

In many cases, the provenance of these peptides is even grayer than the gray market would suggest. "Patients are accessing peptides through online vendors, wellness clinics and compounding pharmacies," Rahman says. "That variability in sourcing is one of the biggest concerns, particularly when it comes to purity, dosing consistency and overall quality control."

The FDA does not allow production of BPC-157, GHK-Cu, KPV and ipamorelin in the U.S., for example, by compounding pharmacies because of safety concerns , so people are ordering them from overseas — usually from China. Some are buying peptides labeled as "for research only." Not all are stuck in the legal gray areas; other peptides are available from compounding pharmacies .

In Kennedy's February remarks about his aim to allow compounding of more than a dozen peptides in the U.S., he suggested that peptides made within the country would be safer than ones acquired abroad.

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"Americans deserve to know the quality of the products they are buying and deserve drugs that have been proven to be safe and effective," an HHS spokesperson told Scientific American in response to questions about Kennedy's comment and the timing of the lift. "The FDA's goal is to ensure that patients can obtain FDA-approved products, and when those aren't available or can't work because of a patient's unique situation, are made by licensed U.S. pharmacies."

But even if Kennedy's plan to make some peptides easier to compound in the U.S. is enacted, it does not necessarily mean the drugs are safe or effective. The FDA does not approve or review drugs from compounding pharmacies — it just monitors the active ingredients the facilities use.

If peptides become more readily available in the U.S. market, Cushman predicts, more "people are going to just start trying [them]" — whether there are data to back them up or not. The public may experience any benefits — and perils — of peptides before scientists quantify them in the clinic.

This article was first published at Scientific American . © ScientificAmerican.com . All rights reserved. Follow on TikTok and Instagram , X and Facebook .