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Massimo Dr. Glenn 🧬🧠👽💪🏻📈 Here’s CNBC’s great piece which explains in layman’s terms what exactly is CRISPR-Cas9, interviews its co-inventor & Nobel prize winner Emmanuelle Charpentier, how $CRSP transformed this Gene Editing tool into the first ever FDA approved therapy - CASGEVY & its future plans $XBI
16,897 次观看 • 7 个月前 •via X (Twitter)
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![An interview by VERY DARK AND CORRUPT Wall Street Journal aired today [1] WSJ's terrible "journalists" (and I use that term lightly) made many false statements about Sarepta's worthless, dangerous drug and Vinay Prasad's firing [1,2] I explain how the FDA sausage is made in excruciating detail Buckle up To get readers up to speed -> In June, corrupt pharma company Sarepta Therapeutics paid $40,000 to lobbying group Michael Best Strategies (MBS) to deal with a problem [3] -> MBS had recently hired Chris LaCivita, who had close connections with "MAGA" influencer Laura Loomer [4] -> With stock down 88%, Sarepta needed to sell their very bad, very dangerous drug or the company would go bankrupt [5] -> After several deaths from the drug this year, FDA official Vinay Prasad said "no way" and kicked the drug to the curb [2,6] -> Sarepta panicked and paid MBS (we believe) to deal with Prasad [3,4] -> If this story is right, LaCivita recruited Laura Loomer to take down Prasad [4,7] -> Loomer said she was defending Trump, but she was lying [7] -> She was defending taxpayer-funded payouts to a worthless, corrupt company [7] -> Laura Loomer so brave A history of bad drugs and regulatory failure -> This is one of the worst pharma scandals in American history and corrupt mainstream media isn't covering it -> Sarepta has a very long, troubled history [8] -> For more than a decade, every major Sarepta FDA drug approval has required INTENSE political intervention [8,9] -> Scientists at FDA have been repeatedly overruled [8,9] -> Many scientists have resigned, very publicly, over these POLITICAL decisions, some writing scathing public criticisms of these terrible decisions [10,11] -> The most recent resignation by Vinay Prasad is not something new; it follows in a long tradition [2,10] -> In fact, standards have dramatically deteriorated since the first controversies about the company's drugs in the 2010s [8,9] -> Prasad was trying to hold the line in the face of rapidly deteriorating standards at the agency [2,6] -> For that, pharma launched a coup--a literal coup of a drug regulator [4,6] -> This is unprecedented -> Banana republic sht, unbelievably corrupt 2016: first Sarepta drug approval and the "highly unusual" decision -> The first Sarepta drug approved by FDA was called Exondys 51 [8] -> This drug was for patients with mutations in dystrophin, a muscle protein [8] -> This is a debilitating and fatal disease affecting children [8] -> Exondys 51 increased dystrophin by 0.2% of normal levels [8,12] -> Unsurprisingly, there was no good evidence the drug worked [8,12] -> Why would it? It increases the protein from zero to 1/500th of normal levels -> One reviewer wrote: "I can find no precedent of an accelerated approval for a marketing application where the effect size on the surrogate endpoint is as small as 0.3%." [12] -> The study submitted by the company included no proper control group [12] -> The techniques used were so bad not even a first-year PhD student would do a study that way -> This the level of work you would expect from a mediocre undergraduate with no guidance -> It's almost like it was so bad on purpose -> (Narrator: it was on purpose) -> Nerd time: -> One reviewer wrote: "The Western blots submitted by the applicant for Study 201 were oversaturated, unreliable, and uninterpretable." [12] -> Another wrote: "Because CDER also determined that the conditions under which the original IHC analysis was performed were inadequate, including that the reader was not masked to sequence and time, the Center requested a re-reading of the stored images by three masked pathologists under different conditions. The IHC results from the reread were not nearly as favorable, as compared to the initial IHC results reported by Sarepta." [12] -> "The lack of concordance between the IHC and the Western Blot results is 'striking'" [12] -> "Study 201/202 had fundamental flaws, including baseline biopsies from external controls who could differ in unknown ways from study subjects, Week 180 biopsies from different muscles than baseline, and potential protein degradation in stored baseline samples." [12] -> And on and on. -> FDA commissioner Robert Califf wrote at the time: the submitted study was "characterized by major flaws in the clinical study design" and "Blinded experts assembled by the FDA fundamentally debunked this study, which has yet to be retracted and continues to be cited" [9,12] -> That's right, the FDA commissioner expressed dismay that the study that the company used to gain approval hadn't yet been retracted, it was so bad [9] -> Senior FDA official Janet Woodcock decided to approve before scientific review team had even voted [9,12] -> Woodcock be like: yeah i'm going to decide before you guys can because i know what you're going to say lol -> Despite external intense pressure, FDA scientists voted against Exondys 51's efficacy [9,12] -> They then voted against its accelerated approval [9,12] -> The review team filed an appeal with FDA commissioner after "passionate" disagreement with Woodcock [9,12] -> One reviewer called Woodcock's decision "unprecedented" [12] -> In a 126-page report, FDA commissioner Califf called Woodcock's decision "highly unusual" [9] -> The FDA board wrote: "[Woodcock's] involvement here appears to have upended the typical review and decision-making process. ... Care should be taken to avoid the appearance of interfering with the integrity of scientific reviews at the lower levels of a Center." [9] -> Again, the data were unbelievably bad, literally every technique in the study was inappropriately used [12] -> I would fire an undergraduate student who did science like this, immediately -> FDA's chief scientist accused Sarepta of "serious irresponsibility" for selectively publishing only some of the data [9] -> Even Woodcock, who approved the drug, called the research "seriously deficient" [12] -> Yes, even the person who approved the drug over the heads of FDA's scientists said the research was horrible [12] -> Still, FDA tried to bury their heads in the sand and beg that, basically, Sarepta pretty please do a better job next time -> FDA commissioner: "The utmost attention should be paid to optimizing the methodological rigor of [future] trial[s]" [9] -> FDA also demanded a clinical trial "to verify the benefit" of the drug [8] -> Welp, this was in 2016 [8] -> The trial results are supposed to be available in 2026, maybe [13] -> Or maybe later, depending on how much money needs to be made first -> As an article published in Nature three years later despaired of the decision: "The approval was conditional on the company agreeing to conduct a two-year post-approval trial to show Exondys 51’s efficacy. But by August 2019, the company had yet to begin such a trial and in the meantime had profited from sales of $300 million in 2018." [13] -> If it sounds like Sarepta used political pressure to get its drug approved and then tried to avoid actually publishing the study showing it didn't work, it sounds that way because that's exactly what happened [13] -> FDA commissioner after deferring to Woodcock: "I am confident this unique situation will not set a general precedent for drug approvals under the accelerated approval pathway, as the statute and regulations are clear each situation must be evaluated on its own merits based on the totality of data and information." [9] -> This statement was profoundly naive, and the historical record bears this out [8,14] -> Three FDA scientists resigned, including the lead reviewer of the drug, understanding the grave implications of the collapse of scientific standards and where they would lead [10,11] -> One was John K. Jenkins, M.D. Director, Office of New Drugs Center for Drug Evaluation and Research/FDA [10] -> In a presentation given just before his resignation, he wrote: -> "Path taken by Sarepta NOT a good model for other development programs" [10] -> Crucially: -> "Upholding statutory standards for approval in face of hopes and desires of patients, families, sponsors, and investors is a very difficult job" [10] -> "Personal attacks on FDA reviewers creates an atmosphere of distrust and isolation rather than collaboration" [10] This brings us to WHY Sarepta's drug was approved Facebook FDA -> So why did the drug get approved? -> Basically, Sarepta propagandized extremely desperate patients [9,15] -> They used miraculous snake oil promises and patients believed them -> Remember that this is life or death for patients, and they are extremely vulnerable -> Sarepta also professionally trained some patients to give testimonials to FDA and congress [15] -> The patients then went to congressmen who don't have time to understand the science [15] -> They gave emotional stories to congressmen [15] -> The result: -> Letter from 109 House members [15] -> Letter from 24 Senate members [15] -> And a media circus documented in the New York Times [16] -> Patients screaming at scientists during meetings [9] -> 2,792 emails written to FDA urging approval [12] -> One of them: "Dear Dr. califf: How is it that everyone in and around DMD understands this simple Idea and the science geniuses at FDA don't? You stupid fckers are costing each and every DMD kids days of their lives with your Moronic Dystrophin dance. Time to get a fcking clue" [12] -> Upon approval, a journalist for Reuters wrote: "owing to pressure from patient advocates, the U.S. Food and Drug Administration on Monday approved a treatment for Duchenne muscular dystrophy even though an outside panel of experts and the agency's own reviewers questioned the drug's efficacy" [17] -> A commentary in Nature Medicine was also published called "Railroading at the FDA" [9] -> Its author wrote: "In the words of one FDA committee member, Exondys lowers the agency's evidentiary standard for drug effectiveness 'to an unprecedented nadir.'" [9] -> A highly critical commentary was also published in Science, titled "Sarepta gets an approval - Unfortunately" [18] -> The article's author pharma veteran Derek Lowe wrote: "The company... called up Duchenne-affected boys and their families to plead with the FDA, and won over Janet Woodcock, and that appears to be enough. Is this going to be the new way to get a drug approved? Run a trial in a dozen people, generate unconvincing data, and then lobby Janet Woodcock? I share the worries that this might open the floodgates, because after all, Sarepta got their drug through." [18] -> One FDA reviewer ended in an equally grim note: ". Approval of this NDA would send the signal that political pressure and even intimidation – not science – guides FDA decisions, with extremely negative consequences. The public is well aware of this development program: the meager size of the study population, the marginal (at best) effect size, the Division’s dim view of the efficacy data, and the robust activism of some members of the DMD community. Many would be amazed at an approval action, because other DMD drugs, recently turned down for approval, appeared to provide stronger evidence of efficacy. ...The ramifications here are profound. The public will perceive that it was their unprecedented lobbying efforts that made the difference and earned eteplirsen its accelerated approval. For the future, this will have the effect of strongly encouraging public activism and intimidation as a substitute for data, which is one of the worst possible consequences for communities with rare diseases. This type of activism is not what was envisioned for patient-focused drug development." [12] -> A new era was born -> Activism had replaced data -> Facebook had fried people's brains -> And now Facebook-fried brains had fried FDA too -> FDA's credibility as a regulatory agency would now be hollowed out -> FDA's Facebook age had begun -> But the worst was yet to come Sarepta approvals: 2016 to present -> Three more drugs were approved from Sarepta on the same shoddy basis, proving Califf's promises that Exondys 51 was an isolated case empty [8,14] -> But things would take a turn for the worse with Sarepta's newest drug Elevidys in 2024 [19] -> At last a rigorous clinical trial looking at actual clinical outcomes was published [19,20] -> All would be put to rest -> At long last the issue could be resolved with HARD CLINICAL DATA -> There was only one problem -> The trial failed to show any benefit according to the primary outcome [19,20] -> The surrogate biomarker of micro-dystrophin meant absolutely nothing; it wasn't actually helping patients [19,20] -> What did FDA scientists do? They voted against approval. Of course [19] -> How could they not? The drug didn't actually work in the clinical trial [19] -> It's the only thing that made sense, since FDA is a scientific agency -> AND THEY WERE OVERRULED AGAIN BY PETER MARKS [19] -> YES THAT'S RIGHT, OVERRULED YET AGAIN -> PHARMA WINS AGAIN -> HAHAHAHAHAHA PHARMA ALWAYS WINS YOU FOOLS -> What happened is that Marks crossed his eyes somewhat, trying to make the words on the page blurry -> He prayed really hard, "my god please give me a sign, something, anything, I need this for my career" -> lzzosolsolzzolzozlslzolosllslozllzlzl -> Marks was trying really hard to see SOMETHING, come on come on, give me SOMETHIGN he said -> And he said: wait, look, there are these secondary, exploratory endpoints and a two of them look pretty good, I'LL APPROVE [19,20] -> AHAHAHHAHAHA YES PHAMRA WINS AGAIN -> And Marks said, "Thank you pharma go- I mean god, not pharma god, why did I just say that, FCK" -> The trial was explicitly designed for what Marks did NOT to happen [20] -> Once the primary endpoint was not met, the secondary endpoints couldn't even be statistically tested [20] -> And the trial explicitly said that they could not be interpreted the way Marks interpreted them [20] -> They were not adjusted for multiplicity and they were, like expression of dystrophin, simply bad endpoints [20] -> These two secondary endpoints were time to rise from lying on the floor and the 10-meter walk/run tests [20] -> Subjects who received the Elevidys performed, on average, about 0.5 seconds better than placebo recipients on these tasks [20] -> However several facts must be borne in mind when interpreting these: -> 1. At the time of testing, patients receiving the drug were receiving more corticosteroids than placebo patients, biasing the results [20] -> 2. Blinding might have been broken because those receiving the drug experienced lots of nausea and vomiting from the drug (~70%) [20] -> 3. These differences were tiny and may be attributable to chance, since the natural course of the disease varies widely [20] -> Marks knows this but who cares? Pharma I mean Facebook needed to be placated Elevidys: the drug -> To understand why this is so messed up, one must understand a few things -> On a Bayesian basis, one must assume that Elevidys is harmful until proven otherwise, for two reasons: -> 1. All drugs are potentially "toxic", but some toxins heal: by default you must assume it is a toxin that does not heal because this is what is actually usually the case; you need evidence that it actually heals -> 2. Elevidys IN PARTICULAR must be assumed to be harmful until proven otherwise because of the very nature of the drug -> Let's do a breakdown of the basic science of Elevidys that supports this (Bayesian) hypothesis: -> Gene therapy that permanently integrates into human genome [21] -> Meant to replace dystrophin, the protein that these patients cannot produce themselves [21] -> Preferentially targets muscle but gets expressed everywhere [21] -> Killed three people this year [6,21] -> Costs $3.2 million per injection [21] -> Truncated version of the protein it is supposed to replace [21] -> 3X shorter than the real protein [21] -> Has to be truncated because the technology cannot create the full protein [21] -> Because it's an abnormal protein, it's foreign, so immune system attacks it [21] -> Patients injected with drug are basically given an autoimmune disease [21] -> Patients have to be given anti-inflammatories to fight the disease that the drug causes [21] -> Causes terrible muscle inflammation [21] -> Inflames the heart, heart walls thicken because of the inflammation [21] -> Blows up the liver, causes acute liver injury and death [21] Drug should actually be assumed harmful, not beneficial -> Given all of the above, since the drug failed to meet its primary endpoint, it should actually be considered harmful by default, not beneficial [19,20] -> In other words, what we would actually expect if we added more patients and did an even larger study... -> Is that the drug would do worse than placebo, i.e., patients taking the drug would do worse than those taking placebo -> Why isn't this the default interpretation? -> They are reading the study with an intervention bias -> An intervention bias is natural, which is why "do no harm" is such a central tenet of medicine -> If I may put forward a thesis: most of Vinay Prasad's 500+-paper body of work has been dedicated to demonstrating the "do no harm" principle empirically [22] -> Rose-colored glasses study interpreters are simply not applying this principle properly and are thus failing scientifically in the most fundamental way -> Incomprehensible -> Back in 2016, scientists were adamant that the approval of Sarepta's first drug indicated the profound deterioration of scientific standards [8,9] -> But this latest approval is even worse: actual clinical data is now being overruled -> No standards at all are being enforced anymore; anything can now be approved based on any evidence whatsoever -> What Vinay was trying to do was simply to stop the unrelenting downslide -> And his firing punctuated that downslide for what it was The WSJ segment -> When Elevidys was approved, former FDA chief scientist and one of the original reviewers of Sarepta's first drug Luciana Borio said: -> "I don’t know what to say. Peter Marks makes a mockery of scientific reasoning and approval standards that have served patients well over decades. This type of action also promotes the growing mistrust in scientific institutions like the FDA." [23] -> To return to this video, these two WSJ reporters show an incredible level of ignorance and arrogance -> Finley says that the drug is "clearly" beneficial by misreading the secondary endpoints, just like Marks did -> An FDA memo from last year says about these endpoints: "Under these circumstances, they are misleading and cannot guide any stakeholders—including patients, family members and caregivers, and prescribers—in making informed decisions about the potential benefit of treatment with ELEVIDYS." [20] -> It really doesn't get any clearer than that -> But these two journalists are overruling the actual scientists, just like Marks did -> One of the most incredible comments during this interview was the complaint that "90% of clinical trials fail", as if that's bad thing [1] -> It's actually a good thing; most drugs suck; failing in clinical trial actually allows us to use only the drugs that don't suck -> These people don't understand the most fundamental purpose of the clinical trial -> They think clinical trials failing is a bad thing, as if it means that patients now won't get to use a useful drug -> No, it's a good thing, because it means that patients won't be exposed unnecessarily to a useless drug that might harm them -> The level of ignorance really is unbelievable -> What's worse is that these "journalists" defend their decision -> But what they did is exploit social media hysteria caused by Laura Loomer [1,7] -> Following up on her heels with editorials, using her as pharma attack dog [1,4] -> This is a huge blow to WSJ's credibility, and they know it -> Unbelievably shameful Where do we go from here? -> The Vinay Prasad firing creates a serious crisis of credibility at FDA [2,6] -> Up to this point, we could call these approvals a difference of opinion, but as we've seen, that's a huge stretch -> But any illusion of that is now shattered: the firing shows that drug regulation is explicitly political -> Janet Woodcock: approve, keep job -> Peter Marks: approve, keep job -> Vinay Prasad: block, transparently fired -> Make a decision that is anti-pharma and lose your job: that's the message -> Who can trust any decision at FDA anymore? -> RFK Jr. and Marty Makary both stand behind Vinay Prasad [24] -> Trump went along with lockdowns, he went along with mask mandates, he went along with all of the Covid pseudoscience that he now decries -> He should reverse course and not go along with this -> Trump has created a profound crisis of credibility at FDA and needs to fix it](https://image.24vids.com/tw-1952294845248114806/amplify_video_thumb/1952292444621451264/img/SPXp7ZpvQZ3FQV7_.jpg)
!["We have sequencing from a colon [tumor] biopsy from a patient who was 4 times vaccinated...we can find [DNA] plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." Kevin McKernan (Kevin McKernan), Chief Scientific Officer and Founder of Medicinal Genomics, as well as former R&D lead of the Human Genome Project, describes for Nick Jikomes (Nick Jikomes) how he and his colleagues have sequenced a colon tumor biopsy from a person who took four COVID injections and have found DNA plasmids—almost certainly from Pfizer's COVID-injection manufacturing process—at a ratio of 100 per cell. McKernan notes that the plasmids, however, are "not exactly the same as Pfizer's," which "is a real head-scratcher." "We haven't published the work yet, but we have sequencing from a colon biopsy from a patient who was 4 times vaccinated. A year after vaccination, they had a colon cancer. They biopsied it that day, and then 30 days later, they died, and then they biopsied after, and we have sequencing on both the pre-mortem and post-mortem samples," McKernan says. The scientist and entrepreneur, often cited as the first person to find DNA contamination in the mRNA COVID injections, adds, "we can find plasmids in there a hundred copies per cell. They're not exactly the same as Pfizer's, which is a real head-scratcher, but they're in there." "There's two of them," McKernan says of the plasmids. "And one encodes spike and one encodes nucleocapsid. We don't know where the hell the nucleocapsid one's coming from." (For reference, a nucleocapsid of a virus is the protein shell or capsid that encloses the nucleic acid—DNA or RNA—content, providing protection and structure to the viral genome.) When asked why the plasmids wouldn't exactly match those used in Pfizer's mRNA-injection manufacturing process, McKernan speculates: "Do they have more than one [DNA plasmid] in circulation? Like, BioNTech got a different manufacturing plasmid than the manufacturing plant out here in the US because they're making these in two different locations? It's possible. Is there contamination in their laboratory, in the manufacturing of this, they get the wrong plasmid in their E. coli vat, and suddenly they've got a different background there?" "And we've gotta do everything on our end to make sure we didn't introduce it, which we're doing. We're running all types of experiments to show that there's spike expression going on. But there's any number of reasons that could explain this," McKernan adds. Note that DNA plasmids—small, circular, double-stranded DNA molecules capable of replicating independently within a bacterial cell—were understood to be used in the manufacturing of the mRNA injections, but should've been removed below a certain threshold established by regulatory authorities such as the FDA. (The DNA contamination may be present in vials at 1,000 times higher than allowable according to one article published by the Brownstone Institute covering this issue. Article title: "The Vax-Gene Files: An Accidental Discovery") "We've got a case now that we're zeroing in on that looked like the SV40 poly-A signal, which is a termination signal. It's a transcription termination signal. We've got a piece of that integrating into chromosome 21, and it's breaking a gene that's involved in cancer. So, that one looks really interesting," McKernan tells Jikomes. "That could be maybe the driver of this whole thing. But the program spits out a long list of potential integrations that we have to go through and verify which ones are real and which ones are artifacts and all that. So I don't wanna get ahead of ourselves on that. That hasn't been Sanger verified yet." (For reference, Sanger sequencing is a method used to determine the precise order of nucleotides in a DNA molecule; the SV40 promoter is a strong regulatory region from the Simian Virus 40 that drives high levels of gene expression in mammalian cells when used in genetic constructs; a poly-A signal is a sequence in DNA or RNA that signals the end of a gene, prompting the addition of a polyadenine tail to the mRNA during processing, which stabilizes the mRNA and aids in its export from the nucleus.) "But the copy number alone suggests that these things aren't fully fragmented. Right? These plasmids really shouldn't be replicating to a hundred copies per cell," McKernan adds. "They couldn't, they shouldn't be in there at that level, because if you just do the math on how much is in the vaccine, when you do an injection of this, this person has four vaccines...1.2 ml of Pfizer...went into about 87,000 mls [of] body volume. So you should have a massive dilution into your body. Yet when we're sequencing this and doing qPCR off the tumor, the CTs coming back off the tumor are almost as high as they are straight out of the vial." (For reference, qPCR—or quantitative Polymerase Chain Reaction—is a technique used to amplify and simultaneously quantify a targeted DNA molecule. "CTs" is a reference to cycle threshold; PCR cycle threshold is the number of cycles at which the fluorescence signal from the reaction exceeds the background level, indicating that the target DNA amplification has occurred.) McKernan goes on to say: "And even if it were an integration event [that is, the DNA plasmid integrated into the genome]...I think there could be two things going on here: There could be plasmids replicating episomally [in the cell] and there could be parts of them integrated. But if it were purely integrated and the plasmid was gone, we would not expect to see the copy number of what integrated to be higher than the copy number of the genome. Right? You'd get one integration into one chromosome probably. So it would be half the signal of what you get amplifying a human house gene like RNAP, which is what we use. You would get a similar CT if it integrated. Because if it were a driver mutation, the cells would take off, and it would maybe have one copy of that mutation with it. And as a tumor advanced, you would probably you expect to see a CT score in PCR for that region that was similar to the actual genome background. But we're not seeing that. We're seeing CTs that are that are way ahead. If it's a hundred fold up there, it's around six to seven CTs ahead of the RNAP gene, which is the human gene. And then when we do sequencing, we see the same thing. "The coverage of sequencing is like 100 to 200X in the plasmids [vs.] 1X of the human genome. So they're in this tumor at really high levels. And that tells us that it has to be replicating. And this was a formalin fixed tissue. So it's not like we could sprinkle plasmids on it from our laboratory to contaminate that and have them be translationally active. Formalin is like this process when you take a tissue and you Formalin fix it. It's like...carbon freezing Han Solo. Alright? So you can't add plasmids after the fact and get it to replicate on cells, and you can't add plasmids on the fact afterwards and get it to integrate. Like those things can only occur if the cells are live. So we're pretty certain we've ruled out that, alright, this isn't coming from us. The anti-vaxxers aren't pouring plasmids on this to create a story. "This has certain biological signals that show this was present in the patient when they were alive. We don't know the source of it. They were four times vaccinated, and one of the vaccines that they used was one of the earliest vaccines from December 30th 2020."](https://image.24vids.com/tw-1863041263756624246/ext_tw_video_thumb/1863040923929571328/pu/img/RqpWM1Dr-laLIXD0.jpg)
!["[The UN's Agenda 2021/2030 says] they [want] the...population reduced to 500 million...If you [make] something that [harms the] ovaries, it's...guaranteed to impair...fertility. [That's] why they wanted...young people to get these shots...[they want to] reduce the population." Dr. Charles Hoffe, a practicing family physician in BC, Canada, describes for Maryann Gebauer how the intent behind the COVID injections is to "impair...fertility," specifically by targeting women's ovaries for "micro[clotting] and gene editing and clots and bleeding and...inflammation." Hoffe notes that the United Nations has declared via its now-infamous Agenda 2021 and Agenda 2030 documents—which are plans for achieving so-called "sustainable development goals"—how the international organization aims to decrease the world's population from approximately 8 billion people to only 500 million. Hoffe notes this wouldn't be the first time that the UN has, through its subsidiary World Health Organization (WHO), aimed to damage women's fertility via ostensible "vaccines." "The World Health Organization has used vaccines five times before this pandemic to reduce fertility," the physician says. "They did it in Brazil and Mexico and India and Kenya and one other country that I now can't think of. They did it in five countries. And in every case, they gave these people vaccines for some other reason, [ostensibly] to keep them safe. In Kenya, it was a tetanus vaccine—[they used] different vaccines in different places. And this was an injection to keep these people safe or their children safe [ostensibly], but was actually designed to reduce fertility." "I think these COVID vaccines are no different," Hoffe says. He goes on to say: "The fact that they mandated these shots for university students, for school kids, [who] couldn't play sport. They couldn't go on school field trips. University students who had been, you know, for example, studying medicine. You're four years in and you're told unless you get these COVID shots, you're done. You forget it. Go and go and deliver pizzas. You will not be a doctor. And...in other words, they forced young people for whom COVID was almost no risk to have a shot that had the worst safety record in human history. So you can think, well, so did they just make a mistake? Because there seems to be no benign explanation for that." Hoffe adds: "We know that the shots didn't keep anyone safe because it didn't stop people getting COVID. So this idea that, well, you're putting other people at risk if you're unvaccinated was nonsense because they knew by the time they mandated any of these things that these shots didn't stop transmission or infection. So they couldn't possibly keep out anyone safe. So that reason was clearly fraudulent. So there was no other benign explanation for why these should be mandated for young people other than the fact that we knew from the Pfizer biodistribution study using the messenger RNA particles where they tested it on mice. They found that the ovaries were in the top four destinations for those spike proteins. "And when a baby girl is born, she is born with all of the eggs in her ovaries that she will ever have. Guys make sperms every day from puberty till they die. But girls are born with eggs in their ovaries that are created when they're in their mother's womb. And from the time they're born, they cannot get new eggs. So if you can design something that goes into their ovaries, that causes microclots and gene editing and clots and bleeding and whatever else, inflammation. If you can design something that will harm that person's ovaries, it is pretty well guaranteed to impair their fertility. Which explains why they wanted all the young people to get these shots that they didn't need... The only explanation is to try and reduce the population."](https://image.24vids.com/tw-1902037506071077311/ext_tw_video_thumb/1902031693222952960/pu/img/a5g837cUGbNtKwFQ.jpg)
![The most epic 13 minute AI rant I've heard in 2026 PS: My parent's heard this when I was playing it in the car and thought Jason ✨👾SaaStr.Ai✨ Lemkin went OFF like Stephen A Smith does on first take PPS: Full transcript below [17:00] Harry Stebbings: I I just wanted to ask Jason, if the people that we want are fundamentally different, the developers that we used to hire, we don't because AI writes the code for us. The marketers we don't want, the sales people we don't want—who who do we want genuinely? Like what is the attractive profile? Because your Anthropic’s and your OpenAIs are hiring, so so what are the people that we want in the companies of the future? [17:18] Jason Lemkin: Look, I know it sounds trite, but but the answer is simple. It's just the expression each year changes. We want folks that are genuinely AI fluent. It's pretty simple. Now you know, maybe last year we called them prompt engineers, right? That used to be a job. I don't know if you remember that actually used to be the hottest job on planet earth. Now no one needs a prompt engineer because it's pretty easy to prompt all these tools. That job died. Okay. Um and now we need go-to-market engineers. Um I think that job's going to die. We need—everyone needs so many forward deployed engineers. Like you can't hire enough forward deployed engineers. But uh you know um but Palantir just announced in whatever their their big their big event—they've gotten their deployment times down over 90% with forward deployed engineers. So that may become—so the this wave of disruption for the titles and the specificity, it's also exhaustingly accelerating. But it's really simple. You meet anyone for any role—sales, marketing, engineering, product, QA—they're they're either they're either they can't keep all of the ways they use AI to accelerate their job from spewing out of their mouth, or they're staring at you. It's there's nowhere in the middle. Like, and the person that comes in and says—it's it's it sounds Captain Obvious—but like, you know, you just had the whatever from Lovable, the the marketing head that was super popular on the show, right? She's just spewing AI-native insights into Lovable, right? It's not that complicated. You hire her, Elena, or whatever it is. You just hire her. It doesn't matter whether she's still in college or a junior or a senior or a middler, a left or right. And honestly, if you interview people, I would say of all even of the best startups I've invested in, maybe 30% of the management team meets this standard at best. 30%. Maybe less. And of the interviews I do in general, it's single-digit percents. It's just and in in that sense, it's the same as ever. Like you either lower the bar in hiring or you hire someone that's actually great. And someone that's actually great is so far ahead of you in how to apply to to employ the efficiencies of AI in their role, your jaw falls on the table. The difference is we used to need warm bodies. That's what's changing. We used to need warm bodies to answer the call, to do QA, to do code review, to to get the blue pixel to go from the upper left to the lower right. You laugh, but you need you literally needed to brute force this with humans. With AI, every day that goes by, the AI—you do not need brute force human beings on your team. And that's another reason they're shrinking. Why are all these new companies so efficient? They're just not brute forcing things with humans. They're just not. They're choosing not to. And so these team—all the brute forcers out there—everyone talks about how bloated teams got in 2021. I don't agree with that. I think they got as big as they needed to be when growth was high and you needed humans to do everything. All you look at these teams that that doubled—well if growth continued at 60% like the rate in early 2021 for 5 years or can help me do the math and every single thing a software company did required a human. You were understaffed by your 2021 headcount. You'd be sitting here in 2026. You every office in SoMa would be triple packed and you there wouldn't be enough humans to staff your company. It's just the world changed. [20:33] Harry Stebbings: Jason, you live on the bleeding edge. I think me and Rory see that and I think the world sees that when they hear you every week in terms of how you run SaaS. For all of the CEOs and execs who listen to the show, what would you advise them in terms of determining whether someone is AI fluent when they meet them for jobs, for talent? [20:51] Jason Lemkin: Here's I realized I was just asked this. I just did a review with a super fast startup growing just crossing 100 million and I was asked this question. And one of my favorite executives, I thought his answer was pretty dated and because he gave me an answer that was about 6 months old. The answer 6 months old is: "I look for folks in my team, I look for you know at what tools they play with." Okay, that was a great answer in like summer of 2025. Okay, I tried Lovable last week. Okay, the answer in 2026 is: "What commercial AI tool have you brought into your organization this month?" That's the test. Anyone that is on the bleeding edge that you would want to hire—now there are so many great products in the market. Okay, there is no excuse in any role to have not brought one tool a month into your organization. Okay, there—now there's going to be better and better tools and better and better products as the year goes on. What's the one you did? And you will see folks with their deer in the headlights to this question. What what sales tool? What marketing tool? What product tool? What engineering tool? What did you bring in? Why did you pick it? How does it working? Because if you're at remotely at the cutting edge, you're all over this. You're looking for the next agentic tools that will radically improve how you do business. This is—you think everyone thinks SaaS is at the bleeding edge, right? You know, you know, all we do is we're just looking for the tools and trying them. Okay? Okay, we're one year ahead of everybody else because we did the simplest thing in the world. Like we tried the tools early and we trained them. We trained them for a month. Okay, I'll give you—want hear a horrible example from this week? Super hot AI company valued at 6 billion. Okay, I'm not going to name it. Um, this week yesterday told us we had to quadruple what we spent on their product. Okay, their agent told us, right? And why did this happen? Okay. Well, at this $6 billion company, no one had trained the agent on its pricing properly. No one had tested it. They said, "Well, well, we've been in beta." And we said, "Well, when did the beta launch? A year ago." Okay, these are people asleep at at the wheel. You want somebody who the instant this comes up, they exactly know what the issue is. And "Hey, when I was at Lovable Replit, we trained the agent. This is how we did it. I brought in this tool. I brought in this tool that that Rory invested in last week. It solved all these issues." That's what you want to hear. And if they haven't brought in a tool in the last 30 days, at least deeply evaluated it. I don't really care whether they bought it, but gone so far down the funnel they can tell you—pick whatever tool: Fixie, Regie, GC, AIGC—I don't care how you went through it, you looked at it, you can tell me the eight ways it would improve the productivity of your business and three you didn't. Just don't hire that person because they're going to run your company to the ground. This is the job today. The job today is not to screw around on ChatGPT and to be a prompt engineer. The job today is to bring the best AI and agentic products into your organization and leverage all the hard work that the engineers have done building those products. That's your job. You don't have to screw around. You don't have to be a prompt engineer anymore. You have to be an agent deployment expert. A—this is the new job we're making up today. An Agentic Deployment Expert. That's your job from C-level to junior. Agentic Deployment Expert. Don't hire anybody else. You're going to regret it. They're going to stare at the camera. He's good. Stare at the camera. He's honorable. We could probably just I could slip away, get a coffee, and come back. No. And I I sound exasperated, Rory. And I—but the reason I am is I can just see I can see my best companies doing it. And I can see some companies I've invested in not doing it. And I want to cry. I just want to cry when they have no ADs on their team. I just—like you're flushing your years of your life down the toilet by not approaching your how you're building this company this way. [24:33] Rory: Yes. And at the risk of being positive, it's worth pointing out two things he didn't say. Well, something implicit why he said—Jason didn't do the only hire, you know, he didn't commit the um employment law, I think it's a civil penalty of saying only employ people below X who get the new new thing because he implicitly said anyone can do it provided you're willing to learn. And I think that's the big aha that's one of the positive statements to make here right? Look and I think it applies—I'm always wary of being "Hey, coming across, hey this this is the things that you all have to do." I think it applies to everyone including investors right? I mean I will say I have found that unless you're willing to invest the time learning these tools you actually shouldn't be investing in them. One of my partners Andy had this expression: "You know, if you decide you want to stop learning new things you probably should retire within 6 to 12 months and never write another check again." Maybe that's down to 3 to 6 months at this stage, right? And I think, you know, it's— [25:27] Harry Stebbings: Yeah, I actually I actually had a meeting with mine and Jason's biggest investor the other day and I—pretend he's not here—I said I think he's the most equipped investor for this generation of investing because I don't think anyone quite sits at the bleeding edge like he does on the investor side. [25:42] Harry Stebbings: Why in terms of using the equip stuff? Yeah. Yeah. In terms of using the stuff, understanding understanding bottlenecks, constraints. For sure. [25:51] Jason Lemkin: But can I just add one point? We can just cuz it's so important if it helps people. Okay, we are—and thank you Harry. We're going through these phases. Okay, and when AI started to blow up for real for us, uh call it early 2024, right? Maybe late '23, I wasn't equipped. It was too technical. I wasn't going to go in and figure out—I wasn't smart enough to figure out how to deal with a massively hallucinating LLM API and turn that and turn that into something magical. Kudos to investors and others that that got it in early '23, '22. I mean I remember I—I guess it was maybe SaaStr Annual '23. I was with David Sacks and I did a Q&A and I said, "How you thinking about AI at Craft?" He's like, "Well we're all in. We want 80% of '23 of investments to be AI." I'm like, "Great but like show me the show me the great ones in market." He's like, "They're all prototypes. We're all they're all they're all proof of concepts but we're all in anyway." That's where you kind of had to be in '23 if you weren't investing at like the LLM level. Okay, I wasn't smart enough. Then we went through this weird-ass prompt engineer era where like you you could torture these products to do something good, right? But you had to torture them. You had to like craft these crazy things that made no sense. Now we are in the era where mere ordinarily smart generalists can make these tools do magical things. And literally I go to these meetings and people be like, "I don't know how to like this is so scary. I don't know how to do this." And we show them our backends. Do you know how to do a workflow generator? Do you know how to do a a decision tree? Like we've been building these since software in the '90s. Okay, if you—I can show you all of our agents. The how they work is novel. They do have to be trained. You can't be lazy and have these agents work. But honestly, the the UI, the UX, the way we interact with them, it's just software. And so my point is: Pick yourself off the ground. This is your time now. If you felt lost in AI era, if you felt like you're behind, you don't understand what all these people are saying on X and Twitter and their Claude and and their and talking about all the 4.6 point Nano point and it's over—like you just it's not your world. This is your time. This is your time for the generalist that knows how to use software tools really really well. And I—this is my last point but it's so important. If ever in your recent life—and this is why you could be all you need to be is young at heart to Rory's point—if in the last three to five years you have successfully deployed a piece of enterprise software of any sort you yourself, not some agency you hired, but if you have deployed it, you can deploy any agentic tool. Any. And you can become the hero in your company and you can become the hero in your functional area. But I watch folks—I'm literally helping a company now that they're adding hundreds of sales folks this year with a new pre-IPO COO—he's not hasn't brought in a single tool, totally scared of it. Okay, it's not that hard. Did you use SalesLoft? Did you use Outreach? Did you use HubSpot? Do you know these tools? If you can deploy these tools, you can deploy a world-changing AI agent. And so this is the time for people like the folks that that were shut out of the AI revolution right now. The generalist folks that are not that know how to deploy software that don't even know how to build software. Like vibe coding for me was folks who knew how to build software, but you didn't have to be an engineer. Now, you just need to know how to deploy software to win with AI agents. That's all you need to know. So many people have these skills and they're petrified of AI. "How did you do that? How did you deploy an AI BDR?" Well, we bought a piece of software, we figured out how it worked for a day, we set it up in an afternoon, and then and then we did spend 30 months training it, which you didn't do with this old software because in the old days, we just had to manually upload all the data, right? And there was no training. The the only non-intuitive part is training these things. And it's it's it's just work. So that's why when I see folks on the management team not doing this, there's no excuse. You do not need to be technical to win with AI agents in Q2 of '26. You do not need to be even 1% technical. Not at all. So it's your time. Or you're going to get laid off. Or you're going to get laid off because you're not going to matter.](https://image.24vids.com/tw-2036795243681423518/amplify_video_thumb/2036794127560613888/img/52_cdbzzL6_foTSI.jpg)
