It's ok to be angry about capitalism
- Thread starter XsjadoBlaydette
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The California fires wouldn't have got so bad without overabundance of dry land. Part global warming, of course. But not talked about enough (or at all?!) is the largest private ownership of water and aquaduct network/infrastructure (on earth!) company poisoning and drying the local environment to farm unsuitable crop pistachios. Nor their decades of lobbying to sanction their only competitor Iran (as if lobbying was even needed for attacking Iran but hey no neocolonialist politician is gonna compromise an extra cheque by admitting so)
The wonderful company
The wonderful company
Does the sign read "beware of the leopard"? =p
Being more serious, I know of an example of someone who back in the pre-Musk had their Twitter account quietly restricted so that only mutual followers could see their tweets. You couldn't even find their stuff if you searched for it. You had to follow and be followed by them or use a direct link to the tweet in question to see their stuff. Reddit does something similar with shadowbanning - ostensibly meant to be used as a form of anti-spam, but, umm, not remotely always.
Not what I meant. Messages shouldn't get downgraded because of the message itself like what Twitter did as well. If I'm into a certain subject, I should be getting fed all types of posts about that. If I don't interact with certain types of posts, then the algorithm will stop sending those my way. But I shouldn't not see them because they may contain "misinformation". I should stop seeing them because I'm not interested.
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I think one of the issues there is the lack of transparency. The companies want to pretend there's some sort of thought, care and attention going into their actions and algorithms so they can't tell us in case people go round them, but my suspicion is that they mostly don't want us to realise how much of a shitshow their supposed regulation is, never mind that the shitshow is additionally compromised to improve their profits.
Ah wow they're actually doing it. They're doing a...do they know they doing it? Has no-one played? There's always a lighthouse? Always a boat? Brow sweat hoarding?? Family values??? Tonics?!?0
www.technologyreview.com
Regular visitor/customer is Brian Johnson the billionaire (ex?) mormon claiming he's doing science to live forever and uhh look, he hears your criticisms, but us humble ole humanity's totes gonna benefit from it if successful and won't be locked out through aggressively class-based gatekeeping, pinky promise! Though if his recent interviews are anything to go by: with claims like "there's just no science oh why hasn't they done the science??" responding to COVID vaccine question along with dodgy supplement product business, there's chance his grifting and intelligence stats conflict too much to stumble into success. If we're lucky.
This biohacking company is using a crypto city to test controversial gene therapies
Under bespoke “innovation-friendly” regulation in Próspera, Honduras, Minicircle is conducting trials to try to find the keys to longevity.
www.technologyreview.com
Regular visitor/customer is Brian Johnson the billionaire (ex?) mormon claiming he's doing science to live forever and uhh look, he hears your criticisms, but us humble ole humanity's totes gonna benefit from it if successful and won't be locked out through aggressively class-based gatekeeping, pinky promise! Though if his recent interviews are anything to go by: with claims like "there's just no science oh why hasn't they done the science??" responding to COVID vaccine question along with dodgy supplement product business, there's chance his grifting and intelligence stats conflict too much to stumble into success. If we're lucky.
its bioshock, ok there said now!This biohacking company is using a crypto city to test controversial gene therapies
Under bespoke “innovation-friendly” regulation in Próspera, Honduras, Minicircle is conducting trials to try to find the keys to longevity.
The advertisement—posted on Mirror, a Web3 publishing platform, in March last year—outlined an eye-catching if perhaps confusing proposal: “Access NFTs for a follistatin plasmid phase I clinical trial in Prospera ZEDE, Honduras.”
The ad had been posted by a biotech startup called Minicircle, which was recruiting participants for a clinical trial of gene therapy. But several details made it unusual. For one, it instructed would-be guinea pigs to purchase an NFT to take part. Upon completing the study, it promised, they would receive payment in cryptocurrency. And while it notes the geographical location of the trial, test subjects may not have immediately understood that it would get underway in what is essentially an experimental crypto city—Próspera, Honduras.
The unconventional recruitment effort marked a curious development in the space of gene therapy, a cutting-edge field that has endured decades of false starts and setbacks. FDA-approved gene therapy treatments remain rare, but those breaking through come with eye-watering price tags, in part because of the cost and complexity involved in their creation.
Over the past few years, a parade of newly released gene therapies have consecutively claimed the title of most expensive drug in the world; the current honor goes to the $3.5 million hemophilia B treatment Hemgenix, launched in November 2022. These therapies are produced by the likes of Novartis and CSL Behring, pharma giants that have amassed years’ worth of clinical trial data and followed rigorous testing procedures under the exacting gaze of the US Food and Drug Administration.
A new class of crypto investors have bold plans to rebuild society from scratch. But their pet projects risk repeating the region’s long history of corporate colonialism.
Minicircle is taking something of a different tack. The startup, which is registered in Delaware, aims to fuse elements of the traditional drug testing path with the ethos of “biohackers”—medical mavericks who proudly dabble in self-experimentation and have long hailed the promise of DIY gene therapies.
The eccentricities don’t end there. Minicircle’s trials are going ahead in Próspera, an aspiring libertarian paradise born from controversial legislation that has allowed international businesses to carve off bits of Honduras and establish their own micronations. It’s a radical experiment that is allowing a private company to take on the role of the state. While much attention has been paid to the charter city’s use of Bitcoin as legal tender, the partnership with Minicircle is an important milestone toward another goal—becoming a hotbed of medical innovation and a future hub of medical tourism.
It’s against this unusual backdrop that Minicircle is trying to lead biohacking’s charge into the mainstream, or at least somewhere near it—studying gene therapies that target familiar conditions like muscular disorders, HIV, low testosterone, and obesity, and doing so with the backing of tech moguls and under the purview of bespoke “innovation-friendly” regulation. It ultimately aims to democratize access to gene therapies, with an emphasis on discovering the right nucleic cocktail to promote longevity.
“The entire Big Pharma system right now is centered around making extremely expensive drugs for extremely rare diseases that very few people have,” said Minicircle’s founder and CEO, Mac (short for Machiavelli) Davis, on the Finding Founders podcast in June 2020. “I want to make affordable drugs for diseases that everybody has.”
“I think the potential of the minicircle technology is radically transformative and beneficial for everyone on Earth,” he continued, referring to the company’s key technique for delivering gene therapy into people’s cells. “The keys to immortality: we’ve already discovered some of them. Our choice is just whether … to try it out and not be hampered by fear and regulation.” (Minicircle didn’t respond to a request for comment or to a written list of specific queries; quotes from Davis that appear in this piece are all pulled from the podcast.)
In the event that Davis’s lofty aspirations aren’t realized, Minicircle’s endeavors may at least open up a new frontier for consumer-marketed gene therapies, in the mold of the thriving market for unlicensed (and potentially risky) stem-cell therapies.
Most scientists I spoke with are less than enthusiastic about Minicircle’s undertaking, expressing skepticism about its methods and aims, while experts in medical ethics are concerned about how the trials will move forward—and what they could mean for the burgeoning and sometimes unscrupulous medical tourism industry.
These experts also say the red-tape-trimming stance of special economic zones like Próspera can set off alarm bells (though the charter city staunchly defends its regulations).
“One concern with spaces like that is that there may not be … many resources put into making sure that medical research is adequately overseen,” says Leigh Turner, the executive director of the bioethics program at the University of California, Irvine. “There can be clinics and hospitals that no one's really paying much attention to, in terms of what kinds of marketing claims they're making, or what clinical practices they're engaged in.”
While such jurisdictions can be home to credible, evidence-based medical operations, they can also stimulate “a much more problematic side of medical practice,” Turner adds— “one that's taking advantage of deregulation and lack of oversight.”
“The problem with that,” he concludes, “is that it can end up posing significant risks to patients.”
“I’m going to do this thing that I bet you thought was totally impossible”
This isn’t the first time biohackers have tried to disrupt the field of gene therapy. One group attempted to create a knockoff version of Glybera, a $1 million gene treatment for an inherited disease—an endeavor MIT Technology Review covered back in 2019. While those efforts don’t appear to have borne fruit, Minicircle is running with the same grassroots spirit, combined with more serious financial backing.
Minicircle’s connections to the biohacking movement run deep. Before founding the company in 2019, Davis worked at Ascendance Biomedical, which was run by the late Aaron Traywick, a biohacker best known for injecting himself with an untested herpes treatment. (His death was unrelated to biohacking; he accidentally drowned in a sensory deprivation tank.) Another one of Ascendance Biomedical’s associates, Tristan Roberts, made headlines a few years ago for injecting himself with an untested HIV treatment that Davis reportedly helped create.
On the podcast, Davis enthused about “genetic modification at home,” hailing “the art of creatively questioning fundamental assumptions that people have about the limitations of biology using experiments … like, ‘I’m going to do this thing that I bet you thought was totally impossible.’”
It’s certainly no accident that Minicircle opened its first gene therapy clinic in Próspera, which is formally administered as a Zone for Employment and Economic Development (ZEDE) in Honduras. A bustling private enclave on the tropical island of Roatán, Próspera has pulled in investment from Peter Thiel and Marc Andreessen and is managed by an international group of libertarians (although they reject this label, claiming instead to champion a nonideological manifesto of freedom and prosperity).
The charter city has garnered outsize international media coverage over the past several years, including a story I reported for MIT Technology Review, because of the way it has pitched itself to investors—including a move-fast-and-break-things approach toward what are usually heavily regulated industries. This has meant implementing its own laws designed to stoke financial experimentation and, more recently, medical innovation.
It’s a philosophy that appears to resonate with biohackers as well as tech titans. Thiel, who has pumped millions into longevity research and has said the possibility of injecting himself with the blood of young people is “really interesting,” has also invested directly in Minicircle; the company appears to have raised at least $150,000 in 2021 from Thiel and Naval Ravikant, a cofounder of AngelList and a prominent tech and crypto investor. (Thiel and Ravikant did not respond to requests for comment.) OpenAI CEO Sam Altman has also confirmed to MIT Technology Review that he has plowed $250,000 into the startup.
At least one prominent scientist sees a potential upside to growth in the biohacking space: George Church, a professor of genetics at Harvard Medical School who has previously consulted on biohacking endeavors, tells me he welcomes the evolution of biohacking self-experimentation into full-blown clinical trials. He isn’t familiar with Minicircle’s work specifically, but he says of the general premise, “As long as nothing goes wrong, it could herald a revolution in cost reduction.”
That, of course, is a big caveat.
Could Minicircle succeed where others have repeatedly failed?
Although Minicircle’s website doesn’t share a lot of information about its clinical goals and how its trials are designed, some of its communications have certainly raised eyebrows—not least the startup’s snappy tagline, with its reference to “reversible” gene therapy.
From what experts in genetics and bioethics that I spoke with could glean from the company’s public materials, some of its intended trials appear to draw (at least partly) on a preexisting body of scientific evidence. But some aspects of the work are more out of left field and carry the hallmarks of the longevity-obsessed crypto milieu. (There’s the use, for instance, of NFTs; while some medical researchers have proposed that NFTs could be used to track patient consent for medical trials, Minicircle didn’t respond to questions about exactly what role they’ll play here.)
At least one trial for follistatin gene therapy, with an unknown number of participants, seems to already be underway, according to press materials from Próspera. In its various materials online, Minicircle makes reference to a wide range of clinical aims for the therapy; while some of its rationale appears grounded in the scientific literature, other elements are far more unconventional.
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.)
Clinicals trials notwithstanding, Minicircle’s ultimate aim seems to be consumer-marketed therapies. While many companies offer dubious stem-cell treatments directly to consumers, UC Irvine’s Turner notes that this is relatively virgin territory for gene therapies.
Overseeing the pilot trial of Minicircle’s follistatin gene therapy is Glenn Terry, founder of the Global Alliance for Regenerative Medicine (GARM), a clinic specializing in regenerative medicine and stem-cell therapies in Roatán. Although Terry initially agreed to a conversation about the clinical trials, I was later told he would be out of the office for the next four to six weeks. (When I followed up six weeks later, I still didn’t get an interview.)
“GARM is fairly typical of the businesses marketing unlicensed, unproven stem-cell interventions,” says Turner, who has come across the clinic in his work examining the ethical issues related to stem-cell and regenerative medicine. “When you look at what they’re advertising, and look at the claims that are being made about stem-cell therapies, these are just not evidence-based claims.”
(A GARM spokesperson wrote in an email that this was an “uninformed and seemingly unsupported opinion,” adding: “The suggestion that a physician of Dr. Terry’s caliber would be involved in any situation with questionable ethics is absurd and it is insulting.”)
“It’s ass-backwards the way they’re doing things”
Próspera believes its unique approach to regulation will help enable a flourishing ecosystem of medical innovation.
It has pitched itself as an up-and-coming medical tourism destination, with Minicircle leading the way. The city has cited as inspiration special economic zones like the Boao Lecheng International Medical Tourism Pilot Zone in China, where the Chinese state is encouraging the growth of international medical tourism partly through market-friendly regulation.
According to language on Minicircle’s website, the reason it’s carrying out the trials in Próspera is that it’s much cheaper than in the US. But once it has the preliminary data from Próspera, Minicircle says it plans to take its next round of trials stateside.
Patricia Zettler, an associate professor of law at Ohio State University and a specialist in food and drug policy, says it’s not uncommon for companies to carry out offshore clinical trials, although she notes that the practice has attracted controversy for the potential lack of transparency and oversight.
But Stanford’s Kay rejects Minicircle’s reasoning. “It’s ass-backwards the way they’re doing things,” he says. “If they really had a treatment that looked like it might work … there would be no trouble raising money.”
Zettler notes if the startup does in fact intend to pursue follow-up trials in the US, it will have to satisfy the FDA with regard to how the initial trials were conducted. This would include meeting expectations around data transparency and compliance with human subjects protection norms—covering informed consent, balance between the potential risks and benefits of the research, and assurances that no person was coerced into participating—as well as confirming that the clinical trials were designed to produce useful evidence about safety and effectiveness.
For its part, Próspera has defended its health regulations. A July 2022 Twitter thread outlining its partnership with Minicircle says that they “avoid onerous prescriptive regulation in favor of closely monitored self-regulation with clear lines of accountability and demonstrated financial capacity to make restitution.”
In the same thread, Próspera notes that under its legislation, medical providers can choose to either follow preexisting medical regulations from an OECD country, propose their own regulation “that is demonstrated to be as safe and effective as the regulations already reciprocally recognized,” or operate under common-law liability principles. The charter city has pitched this flexibility, including the possibility of suggesting one’s own bespoke regulation, as a unique selling point to potential investors.
Asked specifically about what regulation would cover the Minicircle trials, a spokesperson for Próspera offered something of a non-answer: “Próspera’s regulatory system for the health-care industry involves an innovation-friendly array of regulatory guardrails, including clear disclosure of risks and legal responsibility for delivering safe and effective medical services and products, all subject to periodic compliance certifications and audits, and with financial accountability backed by mandatory insurance coverage.”
“There is every reason to expect that health services and products will be as safe or safer in Próspera than in any OECD country,” it concluded.
https://www.technologyreview.com/20...eap-version-of-a-million-dollar-gene-therapy/
A group of independent biologists say they plan to copy a costly gene therapy. Are they medicine’s Robin Hood or a threat to safety?
When I asked Próspera if Minicircle’s trials could lead to a day when medical tourists receive gene therapy in the private city, a spokesperson only said: “Due to the privacy rights of (e)Residents, we are not free to address the specific questions you have posed.” (First pioneered by Estonia, e-residency allows businesses to digitally register in Próspera without a physical presence there, theoretically making the “business-friendly ecosystem” accessible from anywhere in the world.)
The ongoing fight over Próspera’s future
Before Minicircle realizes its long-term plans for a gene therapy revolution, it will have to overcome a more pressing threat: Próspera is currently engaged in a standoff with the Honduran government over its very existence.
Its status as a ZEDE was enabled by a law passed in 2013 that was championed by the former president, Juan Orlando Hernández (who is now facing drug trafficking charges in the US). The new administration of Xiomara Castro voted in April 2022 to repeal the ZEDE legislation, labeling it unconstitutional. The decision must be ratified in the current legislative period, which started in January, before becoming law.
In the meantime, Próspera has filed a claim against the government over alleged violations of legal agreements that it says guaranteed the jurisdiction’s long-term protection, estimating potential damages as high as $10.78 billion.
Próspera declined to respond to the question of whether the clinical trials could be affected by the ongoing legal wrangling, but at least one Honduran government official has expressed opposition. “It is one of the reasons why they wanted ZEDE(s) in this country: to experiment and do everything that cannot be done in developed countries,” José Carlos Cardona Erazo of the government’s Social Development Office tweeted in Spanish in July.
“They continue to move forward as if nothing happened,” says Matthew Harper, former British honorary consul and a long-term resident of Roatán. “It’s being perceived as very arrogant [by locals on Roatán] that they’re proceeding.”
Indeed, Venessa Cárdenas, a resident of the neighboring village Crawfish Rock, which has an acrimonious relationship with Próspera, tells me that although she was aware that Próspera was building a medical clinic, she hadn’t heard anything about the clinical trials. She’s not surprised by this, she says: “We as locals don’t have certain information because they say one thing here, and one thing internationally and on social media.” (A Próspera representative claims it is “more transparent than any other governing body in Honduras” and that “no unconsenting islanders will be affected by operations of Minicircle.”)
For their parts, Kotin and Kay both say they worry that desperate people suffering from the conditions being studied might sign up for the trials despite their shaky scientific grounding.
“I’ve had patients come to me because they hear about a treatment in some other country, and they’re spending all their life savings to get the treatment,” says Kay. “And it’s all bogus.”
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Walgreens CEO describes drawback of anti-shoplifting strategy: ‘When you lock things up…you don’t sell as many of them’
Walgreens' CEO talked about the flip side of investing in increased security on a recent earnings call.
Ah wow they're actually doing it. They're doing a...do they know they doing it? Has no-one played? There's always a lighthouse? Always a boat? Brow sweat hoarding?? Family values??? Tonics?!?0
This biohacking company is using a crypto city to test controversial gene therapies
Under bespoke “innovation-friendly” regulation in Próspera, Honduras, Minicircle is conducting trials to try to find the keys to longevity.
Regular visior/customer is Brian Johnson the billionaire (ex?) mormon claiming he's doing science to live forever and uhh look, he hears your criticisms, but us humble ole humanity's totes gonna benefit from it if successful and won't be locked out through aggressively class-based gatekeeping, pinky promise! Though if his recent interviews are anything to go by: with claims like *there's just no science oh why hasn't they done the science??" responding to COVID vaccine question along with dodgy supplement product business, there's chance his grifting and intelligence stats conflict too much to stumble into success. If we're lucky.
its bioshock, ok there said now!
I'm explaining how the algorithm works, not whether I like it or not.
Sounds like they have to choose, do they want to sell more but also have higher losses from theft, or lose more to theft but also sell more? Seems like they've realized the difference in theft is smaller than the difference in sales. I imagine there are scenarios where price of goods and differences in theft/sales could swing that the other way, but I'm not shocked that it doesn't apply to any commonly stolen goods from Walgreens.Walgreens CEO describes drawback of anti-shoplifting strategy: ‘When you lock things up…you don’t sell as many of them’
Walgreens' CEO talked about the flip side of investing in increased security on a recent earnings call.fortune.com
I shouldn't not be seeing things because they got tagged as misinformation, that's the thing. Facebook or whoever shouldn't be deciding what gets downgraded outside of what the algorithm already does as that's the algorithms job.
So you aren't just talking about how it works. You're talking about how you think it should work.
And how it works now is that stuff is still deprioritised depending on whether you've shown interest.
But you've said that if something isn't being boosted, that's the same as being censored. So you want things you're not interested in to be censored?
... or other people have shown interest. or other people have decided to deprioritize arbitrarily.
Can you read what I say? I never said any of that. Stuff gets deprioritized to you based on what YOU interact with. Stuff getting deprioritized to you because Facebook deems it such without input from you is censorship. Just like if I go to the library and only check out and read superhero graphic novels, I'm censoring myself, but if the library was purposefully not buying DC superhero graphic novels, that would be a 3rd party censoring me. You do realize if Facebook or Twitter or whatever social media platform was publicly owned and did this, it would be a blatant violation of the 1st amendment, right?And how it works now is that stuff is still deprioritised depending on whether you've shown interest.
But you've said that if something isn't being boosted, that's the same as being censored. So you want things you're not interested in to be censored?
neither of these things are censorship. Good lord, man.But let's go with the analogy for a moment. The library still contains all those comics, it never stopped. It's just that the library has stopped actively suggesting them to you. Tell me: Is a library "censoring" a certain genre if it has it readily available, but doesn't actively suggest it to you?