diff --git a/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief.vtt b/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief.vtt
new file mode 100755
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+++ b/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief.vtt	
@@ -0,0 +1,3956 @@
+WEBVTT
+
+00:00.000 --> 00:09.560
+Through where I think I'm at, now I'm going to give you my hypothesis in a nutshell and
+
+00:09.560 --> 00:15.920
+then I'm going to drink a beer and probably light a fire and see if I can read some comments
+
+00:15.920 --> 00:18.520
+before I go to bed.
+
+00:18.520 --> 00:23.880
+My current hypothesis is this, this likely originated from a laboratory source.
+
+00:23.880 --> 00:29.000
+Number one, laboratory leaks happen and you can look up many different articles including
+
+00:29.000 --> 00:36.060
+a few from Lynn Klotz who will show you definitively through history how leaks have happened through
+
+00:36.060 --> 00:43.080
+unintended infection, through waste products, lots of different ways and lots of different
+
+00:43.080 --> 00:45.440
+places it has happened.
+
+00:45.440 --> 00:50.040
+The second reason I believe this is true is because of the circumstantial bullseye, the
+
+00:50.040 --> 00:56.160
+idea that this broke out in Wuhan where the research on coronavirus was happening where
+
+00:56.160 --> 01:01.360
+the foremost groups were working on the foremost dangerous viruses and even though you want
+
+01:01.360 --> 01:06.160
+to say and people will tell you that this was BSL Level 4, most of the coronavirus work
+
+01:06.160 --> 01:12.600
+that is published in the literature is done in BSL Level 2 or BSL Level 3, even BSL Level
+
+01:12.600 --> 01:19.960
+3 is not a very strict biosafety level, I work in a BSL 3 level lab with my mice.
+
+01:19.960 --> 01:24.600
+And finally, the entangled financial interests I think are also very important to acknowledge
+
+01:24.600 --> 01:28.280
+here the amount of money that was given away to private equity, the amount of money
+
+01:28.280 --> 01:35.040
+that has been given away without context or identification to millions of corporations
+
+01:35.040 --> 01:40.000
+in America and the amount of money that is being given away through the Warp Speed Act
+
+01:40.000 --> 01:47.400
+that's allowing big pharma companies to make products that are guaranteed to be purchased
+
+01:47.400 --> 01:52.560
+or to be supported by government funding under the pretense that we need to bring as
+
+01:52.600 --> 01:56.440
+much of this to bear as possible.
+
+01:56.440 --> 01:59.600
+One of the things that you have to realize here, and I hadn't made this point yet but
+
+01:59.600 --> 02:07.400
+I know I'm glad I remembered, there is a federal law, the Defense Production Act, which allows
+
+02:07.400 --> 02:14.240
+the government to tell companies and corporations that they need to produce certain things at
+
+02:14.240 --> 02:20.120
+cost because it is for the benefit of all of the American people, for the benefit of
+
+02:20.120 --> 02:22.280
+America as a whole.
+
+02:22.280 --> 02:26.560
+This was an act that was designed to change the production of companies during World War
+
+02:26.560 --> 02:34.200
+One or World War Two and we could easily use this to direct pharmaceutical companies to
+
+02:34.200 --> 02:40.800
+develop specific things like, for example, produce hydrochloroquine or produce a vaccine
+
+02:40.800 --> 02:46.880
+of a particular design or a particular type and we could limit and control the amount
+
+02:46.880 --> 02:52.800
+of profit that was made so that nothing was, no one became rich from it.
+
+02:52.800 --> 02:55.840
+We could do the same thing with coronavirus testing.
+
+02:55.840 --> 03:00.960
+We could be using that act to make sure that no one is profiting from the testing, from
+
+03:00.960 --> 03:06.400
+the antibody testing and from the PCR testing, which I'm going to do another whole talk about
+
+03:06.400 --> 03:12.640
+that but PCR as a test is absurd right now and we know that because this test is not
+
+03:12.640 --> 03:18.920
+specific for SARS-CoV-2 but is only specific for SARS viruses in general and that means
+
+03:18.920 --> 03:23.040
+that we could, as I said before, be testing for the endemic version of the descendants
+
+03:23.040 --> 03:27.680
+of the original SARS, which are almost guaranteed to have gone through at least half of our
+
+03:27.680 --> 03:32.120
+population in the last decade and a half.
+
+03:32.120 --> 03:36.200
+So SARS-1 and its descendants have gone endemic, that's what I was just saying.
+
+03:36.200 --> 03:42.560
+The current PCR test is not specific for SARS-CoV-2 and that is known because it's the German
+
+03:42.600 --> 03:46.480
+company that originally produced it, knows that they've chosen a short sequence that
+
+03:46.480 --> 03:47.480
+they think is relevant.
+
+03:47.480 --> 03:53.320
+It is a short sequence that just comes from one of the open reading frame one proteins.
+
+03:53.320 --> 03:58.520
+We are being duped by a non-specific test and we would have gotten these numbers or
+
+03:58.520 --> 04:03.880
+numbers very similar to them with or without this pandemic because we've never looked for
+
+04:03.880 --> 04:07.560
+SARS viruses as they are spread through our population.
+
+04:07.560 --> 04:09.600
+We've just never looked.
+
+04:09.600 --> 04:12.520
+Nobody sampled for it until this year.
+
+04:12.520 --> 04:19.000
+It's a huge point to make because the SARS virus originally appeared in 2003 and disappeared
+
+04:19.000 --> 04:25.120
+in 2004 but it didn't really disappear, it just became not a problem.
+
+04:25.120 --> 04:32.440
+Descendants of that virus of various virulence and infectivity have circulated in the time
+
+04:32.440 --> 04:40.440
+since they didn't disappear and this test is not specific for any one of them and no one
+
+04:40.440 --> 04:45.920
+has ever done a study about how many descendants there are, how many people are infected,
+
+04:45.920 --> 04:51.000
+how many animals have been infected by it, etc.
+
+04:51.000 --> 04:59.280
+So that's a pretty interesting place to be in July of 2020.
+
+04:59.280 --> 05:06.240
+Thinking that there are descendants of the original SARS leak or leaks or zoonotic jumps
+
+05:06.240 --> 05:12.240
+which are building up an endemic signal in the background that could then be turned
+
+05:12.240 --> 05:18.400
+on in the flick of a switch, just kind of like Kevin McCurnan explained it in the video
+
+05:18.400 --> 05:24.480
+interview with me and a few other people where he said you could do it with HKU1.
+
+05:24.480 --> 05:26.600
+Just turn on the PCR and start monitoring it.
+
+05:26.600 --> 05:32.360
+You're going to see patterns of viruses moving through the population according to him.
+
+05:32.360 --> 05:38.040
+So if there are SARS descendants which could be used and misconstrued in that way, certainly
+
+05:38.040 --> 05:41.520
+that was a possibility that should have been considered from the very beginning of the
+
+05:41.520 --> 05:44.520
+pandemic and it was not.
+
+05:44.520 --> 05:50.680
+Certainly wasn't something that Kevin McCurnan brought up during his authorship of the paper
+
+05:50.680 --> 05:57.560
+that was let's say opposing the PCR test, opposing the PCR test by saying that some
+
+05:57.560 --> 06:00.840
+of the primers would make primer dimers.
+
+06:00.840 --> 06:08.880
+Never mind the whole pretense of being specific for a specific virus when the PCR test that
+
+06:08.880 --> 06:15.520
+was designed by the German lab was using sequences that they had found in Germany, sequences
+
+06:15.520 --> 06:19.080
+from German bats.
+
+06:19.080 --> 06:26.280
+I mean there was a lot of other reasons to lash out against the PCR test that was designed
+
+06:26.280 --> 06:32.920
+by Jorsten but primer dimers and this kind of thing was an odd sort of objection and
+
+06:32.920 --> 06:38.080
+if you look back and see who was on that paper, he will see that a number of early objectors
+
+06:38.080 --> 06:41.440
+were all roped in together.
+
+06:41.440 --> 06:45.760
+I think we're going to be coming back to that little gathering of quote unquote dissidents
+
+06:45.760 --> 06:50.240
+many many times in the next year or so.
+
+06:50.240 --> 06:55.080
+And so saying that we're being duped by a nonspecific PCR test is also really not specific
+
+06:55.080 --> 07:01.080
+enough even though right now this particular version of me was not completely queued in
+
+07:01.080 --> 07:06.440
+to the fact that this time that there could have been as many as 150 different variants
+
+07:06.440 --> 07:14.640
+of the test, 150 different variants of the test being utilized and being employed by maybe
+
+07:14.640 --> 07:20.280
+hundreds if not thousands of independent labs with various levels of quality control and
+
+07:20.280 --> 07:23.120
+certainly no oversight.
+
+07:23.120 --> 07:27.520
+And the crazy thing is as many of those small company labs that were doing a lot of the
+
+07:27.520 --> 07:33.520
+local testing especially in places where the testing was mandated, those are all gone.
+
+07:33.520 --> 07:35.920
+They don't exist anymore.
+
+07:35.920 --> 07:39.800
+Those companies took millions of dollars and they're gone.
+
+07:39.800 --> 07:43.720
+Their owners own houses and they're gone.
+
+07:44.720 --> 07:50.360
+And we're supposed to focus on the DNA fragments in the shot and forget about the fact that
+
+07:50.360 --> 07:58.920
+the whole the whole theater in the beginning to make worst case scenario real was wholly
+
+07:58.920 --> 08:01.080
+created out of out of fresh cloth.
+
+08:01.080 --> 08:08.200
+This is not sorry to start the show like this, but this is just the way it happened to be.
+
+08:08.200 --> 08:12.880
+I had this queued up for some reason.
+
+08:12.880 --> 08:17.040
+So the next thing that I want to say is our lack of biological knowledge and the general
+
+08:17.040 --> 08:23.120
+poor health of the of America, the American people is being used to create the crisis
+
+08:23.120 --> 08:26.560
+they need to divide and conquer us to ruin.
+
+08:26.560 --> 08:27.560
+Maybe America.
+
+08:27.560 --> 08:28.560
+I don't know.
+
+08:28.560 --> 08:29.560
+Crash the dollar.
+
+08:29.560 --> 08:30.560
+I don't know.
+
+08:30.560 --> 08:34.480
+Steel the rest of our are what limited treasury value we have left.
+
+08:34.480 --> 08:36.720
+I don't know.
+
+08:36.720 --> 08:42.360
+But I know for sure that they are combining our lack of biological knowledge and our general
+
+08:42.360 --> 08:49.120
+society's lack of good health and access to health care to create a crisis to usher
+
+08:49.120 --> 08:54.640
+in all kinds of changes that would otherwise never be necessary, and more importantly never
+
+08:54.640 --> 08:56.840
+be possible.
+
+08:56.840 --> 09:01.200
+Just like the Patriot acted 9-11.
+
+09:01.200 --> 09:06.760
+Highly profitable control mechanisms based on immunity are the near term goal.
+
+09:06.760 --> 09:11.040
+I believe this firmly now, there are too many people talking about it in the mainstream
+
+09:11.040 --> 09:13.920
+media hinting at it.
+
+09:13.920 --> 09:18.600
+Sound you hear is a single cicada, there are no crickets.
+
+09:18.600 --> 09:23.000
+Highly profitable control mechanisms, I'm talking about apps that you have to have and
+
+09:23.000 --> 09:27.680
+maybe even worse in order to cross state lines, in order to go to work, maybe in order to
+
+09:27.680 --> 09:31.560
+go to the store, you're going to have this happen.
+
+09:31.560 --> 09:36.760
+So there's going to be technology that needs to be distributed, there's going to be laws
+
+09:36.760 --> 09:40.560
+that are going to be need to be passed, there's going to be all kinds of products that need
+
+09:40.560 --> 09:47.000
+to be sold, and the whole idea is going to be to sell you on the idea that antibodies
+
+09:47.000 --> 09:51.960
+are the only evidence of immunity, and the only way to get antibodies is to get this
+
+09:51.960 --> 09:57.840
+vaccine, because a lot of people of course are not showing long lasting antibody levels,
+
+09:57.840 --> 10:02.200
+so even the people who've been infected, and that's what they're hyping right now is that
+
+10:02.200 --> 10:06.760
+you can get infected again, this is the narrative they're bringing to you so that they're going
+
+10:06.760 --> 10:12.480
+to tell you, the only way we're going to be sure is that if everybody gets vaccinated,
+
+10:12.480 --> 10:20.360
+and now we have billions of doses necessary, billions of doses backed by government money,
+
+10:20.360 --> 10:28.320
+backed by government mandate, controlled by apps, distributed yearly, we are talking
+
+10:28.320 --> 10:33.560
+about a very serious change in our healthcare system that will benefit the largest corporations
+
+10:33.560 --> 10:38.400
+and allow them to profit, because there are no controls on that profit right now, none
+
+10:38.400 --> 10:42.560
+at all, we have chosen to do nothing of the sort.
+
+10:42.560 --> 10:47.320
+That's why I'm sure this hypothesis is correct, the other reason why I'm sure this hypothesis
+
+10:47.400 --> 10:51.920
+is correct is, well I'm getting more sure that this hypothesis is correct, I don't want
+
+10:51.920 --> 10:57.200
+to sound like non-scientific here or non-objective, is because the guy that I first really got
+
+10:57.200 --> 11:03.680
+woken up by on the internet besides Dan of Harvard to the big house blog, is Wolfgang
+
+11:03.680 --> 11:09.360
+Wodach, and for some reason I never searched for this guy after I saw this German video
+
+11:09.360 --> 11:14.520
+that I had to get translated by a friend of mine, where he explained that it was likely
+
+11:14.520 --> 11:19.000
+a SARS virus or a SARS-descended virus that has been circulating viruses that have been
+
+11:19.000 --> 11:28.000
+circulating since the original SARS outbreak fizzled out in 2004 that we are testing for,
+
+11:28.000 --> 11:34.840
+and he only released that video in May or in April and it was only in German, and then
+
+11:34.840 --> 11:35.840
+I just never...
+
+11:35.840 --> 11:40.320
+I hope you see how significant it is that Wolfgang and I have now made contact in such
+
+11:40.320 --> 11:42.360
+a significant way.
+
+11:42.360 --> 11:47.880
+I hope you see what kind of forward progress is about to happen, don't be distracted by
+
+11:47.880 --> 11:54.920
+what's going on on Twitter and how people supposedly think that this story of the clones
+
+11:54.920 --> 12:00.480
+is an open and shut case now because there's effectively no swarm.
+
+12:00.480 --> 12:06.300
+He's been going around in circles on this idea for a very, very long time, and the reason
+
+12:06.300 --> 12:11.240
+why he's doing that is because all of RNA virology is dependent on it and no one can
+
+12:11.240 --> 12:12.440
+know that.
+
+12:12.440 --> 12:21.840
+If everybody understands that, that what they speak of as virology is a gross exaggeration
+
+12:21.840 --> 12:28.800
+of fidelity and it's a gross exaggeration of understanding, even the next strain database
+
+12:28.800 --> 12:34.880
+and phylogeny, even the Jed said database or whatever the hell it's called, all of these
+
+12:34.880 --> 12:45.360
+collections of genomes are presented to you as gold standard evidence of and proof
+
+12:45.360 --> 12:49.360
+of something for which they are not proof of.
+
+12:49.360 --> 12:53.360
+All we know for sure is that these people have managed to measure these sequences and
+
+12:53.360 --> 12:58.580
+a lot of these people believe these sequences are real, but we don't have any reason to
+
+12:58.580 --> 13:04.360
+believe that these sequences are somehow related to one another in a progression related to
+
+13:04.360 --> 13:07.960
+one another in an evolutionary way.
+
+13:07.960 --> 13:13.280
+We don't even know, no one is even talking about the possibility that these animals and
+
+13:13.280 --> 13:20.600
+ourselves would emit coronavirus like signals from our immune system or from the outside,
+
+13:20.600 --> 13:24.320
+from our lungs.
+
+13:24.320 --> 13:30.600
+No one's even talking about the possibility that these signals are being produced by the
+
+13:30.600 --> 13:41.160
+bacteria in our lungs or the bacteria in our airways, our GI tracks, wherever.
+
+13:41.160 --> 13:46.600
+No one's talking about the possibility that there's replication of RNA or DNA being carried
+
+13:46.600 --> 13:51.400
+by bacteriophages that's doing these signals, that's causing these signals, which really
+
+13:51.400 --> 13:58.720
+are just signals, genetic signals that are coincident with, well, genetic signals that
+
+13:58.720 --> 14:03.240
+are present and they're coincident with amplicons of PCR.
+
+14:03.240 --> 14:11.920
+It's very difficult at this size scale and at this sensitivity to definitively say that,
+
+14:11.920 --> 14:18.520
+well, this is definitely a something and we must always end up taking the word of somebody
+
+14:18.520 --> 14:20.120
+like Kevin McCurnan.
+
+14:20.120 --> 14:21.280
+They can't prove it to you.
+
+14:21.280 --> 14:24.120
+He's not going to ever teach you how this stuff works.
+
+14:24.120 --> 14:27.760
+He's always going to tell you that it's just too complicated for him to explain it
+
+14:27.760 --> 14:31.280
+to you, but I'm definitely wrong.
+
+14:31.280 --> 14:38.120
+When in reality, the idea that we're fighting about is really very simple and that's why
+
+14:38.120 --> 14:43.600
+it keeps spiraling out of control behind a block where we can't really have this discussion
+
+14:43.600 --> 14:49.040
+and why he keeps saying that we're not really, that he had this discussion a long time ago
+
+14:49.040 --> 14:53.240
+on email or he tried to do this on his sub stack before.
+
+14:53.240 --> 14:57.160
+I've addressed all the papers in his sub stack when they came out.
+
+14:57.160 --> 15:02.120
+I did a show about it several times in a row, which he completely ignored.
+
+15:02.120 --> 15:03.120
+And that's fine.
+
+15:03.120 --> 15:04.120
+He doesn't have to watch it.
+
+15:04.120 --> 15:06.440
+He calls my videos six hours Scooby-Doo videos.
+
+15:06.440 --> 15:07.440
+So that's fine.
+
+15:07.440 --> 15:08.440
+I get it.
+
+15:08.440 --> 15:12.040
+I should write a sub stack for him.
+
+15:12.040 --> 15:13.880
+We're going to figure this out, ladies and gentlemen.
+
+15:13.880 --> 15:14.880
+Don't worry.
+
+15:14.880 --> 15:19.600
+And when we figure it out the way that the ball will move forward, it will move in a very
+
+15:19.600 --> 15:23.200
+different way with a very different direction and a very different momentum.
+
+15:23.200 --> 15:31.000
+I assure you, I assure you, it's taken me a while to get this all straight in my head
+
+15:31.000 --> 15:36.560
+and make sure that we can move forward confidently.
+
+15:36.560 --> 15:47.520
+I've been trying very hard to remain true to my original idea, which was that this biology
+
+15:47.520 --> 15:50.560
+can't be impossible to learn.
+
+15:50.560 --> 15:58.080
+And any of the biology that underlies this phenomenon is worth learning.
+
+15:58.080 --> 16:02.320
+And so in the case of virology, I think all of us are just going to have to peel back
+
+16:02.320 --> 16:11.040
+our roll up our sleeves a little bit and learn some of this biology that they purport to
+
+16:11.040 --> 16:16.600
+have a monopoly on, that they purport to understand so well that you're just going to have to
+
+16:16.600 --> 16:23.280
+take their word for it, that they can't find any of this stuff in 2019 and before,
+
+16:23.280 --> 16:26.280
+but they sure can find a lot of it now.
+
+16:26.280 --> 16:30.840
+And that means that it's something going around and around and around and it couldn't
+
+16:30.840 --> 16:34.060
+be anything else.
+
+16:34.060 --> 16:37.440
+There are a few things in the background that we have to take and keep in mind.
+
+16:37.440 --> 16:40.000
+And there are a few things that we haven't addressed at all.
+
+16:40.000 --> 16:45.680
+And so it's just a real, it's a real mess right now.
+
+16:45.680 --> 16:51.200
+And so what they would like more than anything else for us to do is to rush as fast as we
+
+16:51.200 --> 16:56.040
+can thinking we know where we're going and thinking we know where the opening is to the
+
+16:56.040 --> 16:57.040
+cave.
+
+16:57.040 --> 17:01.320
+And we've got to keep remembering that we've got to keep our flashlights forward and we
+
+17:01.320 --> 17:02.880
+just got to keep working.
+
+17:02.880 --> 17:11.560
+It can't be distracted by the things that are going on, even if it is that you get fired
+
+17:11.560 --> 17:26.800
+or you get laid off or you get unexplainably your position is discontinued.
+
+17:26.800 --> 17:34.280
+And you are offered a non-disclosure agreement in exchange for $8,000.
+
+17:34.280 --> 17:42.760
+And you're left to kind of decide did I really put my neck on the line and put on
+
+17:42.760 --> 17:55.240
+the t-shirt and say that I was fighting for the truth and then now all of this hard work
+
+17:55.240 --> 18:04.480
+and sacrifice was worth a non-disclosure agreement and $8,000.
+
+18:04.480 --> 18:08.640
+I decided not to do that.
+
+18:08.640 --> 18:13.760
+And now I'm guessing I'm at the mercy of the internet for a little while.
+
+18:13.760 --> 18:20.760
+And we're going to try and make this work because I think actually this biology could
+
+18:20.760 --> 18:23.600
+save our kids.
+
+18:23.600 --> 18:35.280
+I actually think that if we can work through the literature and find truth in it, especially
+
+18:35.280 --> 18:44.800
+pre-COVID truth, and we can find biologists that we're working toward what they thought
+
+18:44.800 --> 18:52.600
+was the truth, I think we can find something that will be solid enough to stand on, that
+
+18:52.600 --> 18:58.560
+we can hand down to our children as an understanding of what these people lied about, what these
+
+18:58.560 --> 19:02.080
+people misled us about.
+
+19:02.080 --> 19:08.000
+And I think you're going to find that the illusion goes back farther than we thought.
+
+19:08.000 --> 19:13.240
+I think that's why so many of the interesting players in this are not like your typical
+
+19:13.240 --> 19:21.400
+players, like people who dropped out of grad school to start working on the Human Genome
+
+19:21.400 --> 19:29.200
+Project and then had like patents and companies and companies and ultra success.
+
+19:29.200 --> 19:37.960
+And then their boss went to the White House and was involved in the writing of $65 billion
+
+19:37.960 --> 19:41.000
+proposal for Warp Speed vaccines.
+
+19:41.000 --> 19:49.920
+And now he's been involved from the very beginning with objecting to the PCR test, but not PCR
+
+19:49.920 --> 19:57.720
+testing, and then all kinds of other random appearances for the RNA not being pure and
+
+19:57.720 --> 20:06.920
+then the RNA code on optimizing being responsible for different G quadriplexes and then came
+
+20:06.920 --> 20:14.280
+out later to be the double stranded DNA and the whole time this guy's been right there.
+
+20:14.280 --> 20:19.920
+Why has he been right there when his whole life is right now pot genetics and trying
+
+20:19.920 --> 20:28.520
+to, I don't know, I guess take over the commercial pot market by controlling genetics and virons
+
+20:28.520 --> 20:37.640
+and screening or providing testing materials for pot growers that will eventually become
+
+20:37.640 --> 20:43.800
+required by the government or some other scam.
+
+20:43.800 --> 20:48.720
+I'm sorry, but this is just this game has got to end.
+
+20:48.720 --> 20:57.840
+And these people, whether you like it or not, are not playing a small, tiny game.
+
+20:57.840 --> 21:03.680
+This is a game for all the marbles is for our grandchildren.
+
+21:03.680 --> 21:08.720
+That's why it seems so ridiculous.
+
+21:08.720 --> 21:12.360
+That's why it's being fought on Twitter.
+
+21:12.360 --> 21:19.200
+Do you think that Kevin McCurnan could have a real discussion about this and a group of
+
+21:19.200 --> 21:23.960
+people that all kind of knew about this stuff?
+
+21:23.960 --> 21:28.960
+Or would it would it really always have to be like him and Meryl Nast and then Andrew
+
+21:28.960 --> 21:36.360
+Kaufman and Christine Massey.
+
+21:36.360 --> 21:42.800
+The one time that we had a conversation a year ago, he couldn't really object to it.
+
+21:42.800 --> 21:51.360
+As you will see in tonight's recap, he just basically spit out exactly what I'm pointing
+
+21:51.360 --> 21:55.640
+out when everybody should be pointing out.
+
+21:55.640 --> 22:04.240
+That by making an infectious RNA and significant quantities, you could seed a coronavirus pandemic
+
+22:04.240 --> 22:09.680
+that was highly homogenous across many different places and maybe even would be highly stable
+
+22:09.680 --> 22:11.440
+for a little while.
+
+22:11.440 --> 22:15.840
+Yes, it's possible that clones transmit.
+
+22:15.840 --> 22:20.760
+I never said that they wouldn't.
+
+22:20.760 --> 22:26.920
+My main argument was that infectious clones and the whole principle of how they should
+
+22:26.920 --> 22:33.520
+or theoretically work is that you can create a much more homogenous viral stock that allows
+
+22:33.520 --> 22:35.840
+you to make a higher quantity of it.
+
+22:35.840 --> 22:40.680
+In fact, an infinite quantity of it is really only dependent on how to investment.
+
+22:40.680 --> 22:45.760
+If you wanted to do Jurassic Park, you could just do PCR construction of all the six or
+
+22:45.760 --> 22:53.480
+seven strands of DNA that you're going to use to ligate together and derive your RNA
+
+22:53.480 --> 22:54.480
+from.
+
+22:54.480 --> 23:05.040
+I mean, this guy's the limit if the idea is to just do it right.
+
+23:05.040 --> 23:12.320
+I'm just kind of, it's just kind of sad because this is where we're at, right?
+
+23:12.320 --> 23:18.320
+We have to protect our children from liars.
+
+23:18.320 --> 23:24.800
+Liars like Paul Offit, liars like Tony Fauci, liars like all of the people that work at
+
+23:24.800 --> 23:31.200
+the top levels of these pharmaceutical companies that know better.
+
+23:31.200 --> 23:35.360
+And we also have to protect our children from a bunch of people who don't know any better
+
+23:35.360 --> 23:41.080
+who aren't wise enough, smart enough, or I've turned the other way.
+
+23:41.080 --> 23:44.280
+In the military, they have caught what is called a lookaway doctrine.
+
+23:44.280 --> 23:48.320
+You know, if you're going to waterboard people, just let me close the door and get out of
+
+23:48.320 --> 23:50.840
+here before you start doing it.
+
+23:50.840 --> 23:57.240
+There are a lot of people involved in this little mystery that are also involved in that
+
+23:57.240 --> 23:58.340
+way.
+
+23:58.340 --> 24:00.720
+They know exactly how dangerous this was.
+
+24:00.720 --> 24:04.980
+They knew exactly how nasty this was going to get.
+
+24:04.980 --> 24:08.800
+And they knew that if they were going to get through this, they were going to break
+
+24:08.800 --> 24:18.480
+some eggs, but you know, make no mistake about it, ladies and gentlemen, breaking eggs
+
+24:18.480 --> 24:26.960
+is also going to require people on Twitter that have no business being on Twitter, talking
+
+24:26.960 --> 24:32.400
+about coronaviruses and fidelity of coronavirus replication and all this other stuff in their
+
+24:32.400 --> 24:41.160
+spare time while they're running companies on the genetics of weed.
+
+24:41.160 --> 24:48.520
+I mean, we are very, very, very close to exposing a group of people who some way or another
+
+24:48.520 --> 24:53.840
+were involved in the containing of the narrative at the same time they were involved in the
+
+24:53.840 --> 25:01.680
+perpetuating of the worst case scenario, making absolutely sure that the existence of the transmission
+
+25:01.680 --> 25:07.400
+of a novel virus was never questioned.
+
+25:07.400 --> 25:15.200
+And think about how strange it is that Eric Lander's former protege is the guy who was
+
+25:15.200 --> 25:21.040
+right there from the beginning, from the PCR objection to the RNA purity objection to the
+
+25:21.040 --> 25:27.920
+G quadriplex objections and the codon optimizing objections to the frame shifting objections
+
+25:27.920 --> 25:32.920
+all the way up to the double stranded DNA objections and what's really weird about the
+
+25:32.920 --> 25:40.560
+objections about the clones and about the proofreading in coronaviruses is that this
+
+25:40.560 --> 25:46.360
+thing that they recommended really, really early, that Cina Bavari predicted that they
+
+25:46.360 --> 25:51.040
+would use very, very early, that Rick Brighton knew that they were going to use very, very
+
+25:51.040 --> 25:59.680
+early, that Paul Cantrell knew that they were going to use very, very early, Remdesivir
+
+25:59.680 --> 26:05.040
+messes with the proofreading of coronavirus.
+
+26:05.040 --> 26:08.240
+So the proofreading of coronavirus is actually pretty significant.
+
+26:08.240 --> 26:18.360
+We need, we need to have high fidelity coronavirus replication that can be interfered with by
+
+26:18.360 --> 26:25.840
+Remdesivir and other antivirals so that the, the subtle balance between the mutagenesis
+
+26:25.840 --> 26:32.400
+in the quasi-species swarm and the stability of it is disrupted and you get this collapse
+
+26:32.400 --> 26:35.240
+of genetic stability.
+
+26:35.240 --> 26:36.800
+That's the story that they tell.
+
+26:36.800 --> 26:38.720
+That's the story that Mark Denison tells.
+
+26:38.720 --> 26:41.800
+That's the story that Cina Bavari told in his paper.
+
+26:41.800 --> 26:44.200
+That's the story that Ralph Barrick has told.
+
+26:44.200 --> 26:50.760
+And that's the story that is told when you argue that coronaviruses are very, very stable.
+
+26:50.760 --> 26:56.000
+You're arguing for Remdesivir's mechanism of action.
+
+26:56.000 --> 26:57.000
+Coincidence?
+
+26:57.000 --> 26:59.000
+Yeah, maybe.
+
+26:59.000 --> 27:00.000
+Believe what you want.
+
+27:00.000 --> 27:01.000
+What I want is high morbidity.
+
+27:01.000 --> 27:02.000
+I want people to complain.
+
+27:02.000 --> 27:03.000
+So what do I do?
+
+27:03.000 --> 27:04.000
+I go to Des Moines.
+
+27:04.000 --> 27:05.000
+Ladies and gentlemen, the people on the screen, I have nothing against Des Moines.
+
+27:05.000 --> 27:06.000
+I live there for four years.
+
+27:06.000 --> 27:07.000
+I go to Des Moines.
+
+27:07.000 --> 27:08.000
+I infect a couple of sentinel cases.
+
+27:08.000 --> 27:09.000
+I go to Seattle.
+
+27:09.000 --> 27:12.000
+I infect a couple of cases there.
+
+27:12.000 --> 27:14.000
+I go to North Carolina.
+
+27:14.000 --> 27:15.000
+I go to Wisconsin.
+
+27:15.000 --> 27:23.000
+What I'm doing is I'm using a dispersion methodology to be able to infect sentinel cases with a highly
+
+27:23.000 --> 27:27.760
+morbid condition.
+
+27:27.760 --> 27:37.760
+So I think what I want to do tonight is just quickly put up for a study hall.
+
+27:37.760 --> 27:51.000
+I've got this video queued up, a couple videos queued up on coronavirus replication, but
+
+27:51.000 --> 27:56.640
+I just want to look at...
+
+27:56.640 --> 28:02.040
+I just want to look at a couple things first to make sure that we still cover what we're
+
+28:02.040 --> 28:03.040
+really covering here.
+
+28:03.040 --> 28:12.080
+Let me escape out of this and start the new deck right away.
+
+28:12.080 --> 28:19.200
+I probably should just go really fast through it to bring everybody up to speed, but I hope
+
+28:19.200 --> 28:20.800
+you don't mind if I do that.
+
+28:20.800 --> 28:28.640
+So first of all, make sure you remember that one of the big, big, big things that is obvious
+
+28:28.640 --> 28:35.240
+to me as we move forward and we watch all these people scream and yell about how bad
+
+28:35.240 --> 28:40.680
+Jonathan Cooey is for putting people's names on there or how bad it is that Jonathan Cooey
+
+28:40.680 --> 28:45.400
+doesn't remember why somebody blocked him or whatever it is that they're crying about
+
+28:45.400 --> 28:46.400
+now.
+
+28:46.400 --> 28:51.040
+The one thing that you will remember and what I have been calling for more than a year now
+
+28:51.040 --> 28:55.800
+is that all these people will ignore this slide.
+
+28:55.800 --> 28:59.960
+You could be wrong about the clones, but right about this, and it wouldn't really matter
+
+28:59.960 --> 29:01.360
+now would it?
+
+29:01.360 --> 29:03.840
+And I assure you that I'm right about this.
+
+29:03.840 --> 29:07.880
+Intramuscular injection of any combination of substances with the intent of augmenting
+
+29:07.880 --> 29:13.440
+the immune system is dumb and transfection in healthy humans is criminally negligent.
+
+29:13.440 --> 29:18.920
+And by having me and you and all these people on Twitter that are trying to defend me,
+
+29:18.920 --> 29:25.120
+thank you very much, arguing about clones and whether or not the viral swarm is significantly
+
+29:25.120 --> 29:30.200
+diverse enough to support the idea that clones are different than the regular virus.
+
+29:30.200 --> 29:34.440
+This is all nonsense.
+
+29:34.440 --> 29:38.400
+This is all nonsense because this is true.
+
+29:38.400 --> 29:43.560
+This is all nonsense because this is true.
+
+29:43.560 --> 29:49.120
+And as long as they keep us occupied about whether or not J is right or wrong or whether
+
+29:49.120 --> 29:54.720
+it's okay to believe in J, then we're not going to we're not going to talk about this
+
+29:54.720 --> 29:56.280
+stuff.
+
+29:56.280 --> 29:59.400
+This is my most important message.
+
+29:59.400 --> 30:04.880
+This is the only message that I want to get to our children because if our children understand
+
+30:04.880 --> 30:11.640
+the big picture biology that underpins this statement, who cares about clones?
+
+30:11.640 --> 30:17.040
+Who cares how they do RNA virology and who cares if somebody with a Poch genetics company
+
+30:17.040 --> 30:22.200
+really does understand how they do coronavirus biology or not?
+
+30:22.200 --> 30:31.680
+Clearly he's being encouraged not to understand it because he is neglecting the very prominence
+
+30:31.680 --> 30:40.440
+of infectious clones from the early 90s on and the almost universal praise of how the
+
+30:40.440 --> 30:45.640
+development of infectious clones and their production has allowed the expansion of the
+
+30:45.640 --> 30:51.120
+understanding of how viruses work.
+
+30:51.120 --> 30:56.400
+We would have to be fools to believe that infectious clones weren't involved in this.
+
+30:56.400 --> 31:02.400
+They are the bedrock foundation methodology of all RNA virology, especially RNA virology
+
+31:02.400 --> 31:08.520
+around viruses that are difficult or impossible to culture for whom no infectious material
+
+31:08.520 --> 31:12.800
+is available.
+
+31:12.800 --> 31:20.000
+And so don't be fooled by somebody who can put up a few papers and then say a few sentences
+
+31:20.000 --> 31:23.440
+about why that paper makes them wrong.
+
+31:23.440 --> 31:27.600
+The time I've ever followed up on one of these papers, it doesn't really demonstrate
+
+31:27.600 --> 31:36.520
+what he says it demonstrates except for in a very sliver kind of way, but it's not addressing
+
+31:36.520 --> 31:41.520
+the very big pictures of what the natural phenomenon, what does the natural phenomenon
+
+31:41.520 --> 31:45.520
+look like is exactly the phenomenon that they don't want to talk about.
+
+31:45.520 --> 31:50.400
+They want you to believe and that's what he would like you to believe that the infectious
+
+31:50.400 --> 31:59.360
+clone replicates the natural phenomenon and that is a hundred percent wrong.
+
+31:59.360 --> 32:04.920
+And so they have fooled us into solving this Scooby-Doo and that's exactly what McCurnan
+
+32:04.920 --> 32:06.440
+is on right now.
+
+32:06.440 --> 32:11.720
+He wants you to believe that I'm supposed to have the exact explanation with all the details
+
+32:11.720 --> 32:16.520
+about exactly why the person came into my house, what they were doing there, what they intended
+
+32:16.520 --> 32:20.280
+to steal and why they were stealing it.
+
+32:20.280 --> 32:24.840
+And that's not the way a crime works.
+
+32:24.840 --> 32:32.280
+And our society, my family and yours are victims of a crime.
+
+32:32.280 --> 32:36.120
+We don't have any obligation as victims of a crime to know all the details and have a
+
+32:36.120 --> 32:39.240
+good explanation for everything.
+
+32:39.240 --> 32:47.960
+And we certainly aren't under any obligation to accept the explanation of the people who
+
+32:47.960 --> 32:52.280
+probably did it or are working with them.
+
+32:52.280 --> 32:56.800
+But we were fooled into believing that a worst-case scenario could have happened and we were fooled
+
+32:56.800 --> 33:01.440
+into believing that we could solve them, that we were watching people solve a mystery.
+
+33:01.440 --> 33:08.880
+That Rand Paul and Tony Fauci were arguing because they were on two sides of this mystery.
+
+33:08.880 --> 33:12.560
+And with this Scooby-Doo, the principle of informed consent has been ignored for the
+
+33:12.560 --> 33:13.800
+duration of the pandemic.
+
+33:13.800 --> 33:22.560
+Here we are trapped on our couch watching the whole thing unfold on TV.
+
+33:22.560 --> 33:28.960
+And so we've talked about how the pandemic was created from years ago up until now with
+
+33:28.960 --> 33:35.520
+a team of people or peoples around the world and especially in Western society that were
+
+33:35.600 --> 33:39.600
+there specifically to coordinate and amplify the worst-case scenario.
+
+33:39.600 --> 33:47.440
+The billions of people dead, the amyloid spike, the prion disease, the spike was killing cardiac
+
+33:47.440 --> 33:50.840
+cells, the whole nine yards.
+
+33:50.840 --> 34:00.400
+And the worst-case scenario was very cleverly tainted with aspects that they expected or
+
+34:00.400 --> 34:04.120
+feared would be a result of the transfection.
+
+34:04.120 --> 34:07.280
+They knew they were going to roll out the transfection so they knew that they could
+
+34:07.280 --> 34:12.840
+see this worst-case scenario with the worst-case scenarios of the transfection so that it would
+
+34:12.840 --> 34:20.880
+never really be clear to an unsuspecting and completely compliant populace that they were
+
+34:20.880 --> 34:25.480
+confounding the effects of the virus with the effects of the shot because you were given
+
+34:25.480 --> 34:30.320
+a viral protein and the viral protein turned out to be wicked.
+
+34:30.320 --> 34:34.640
+The people that were co-opted very early on were briefed that this was a national security
+
+34:34.640 --> 34:40.360
+thing and so you couldn't just talk about it.
+
+34:40.360 --> 34:45.000
+But if you go along with our little role here then maybe you can sell a book about Ivermectin
+
+34:45.000 --> 34:52.760
+or you can sell a book about hydroxychloroquine or you can sell a book about the lab leak.
+
+34:52.760 --> 34:57.520
+And in the end the toxicity of the virus, spike protein has been confounded with the
+
+34:57.560 --> 35:03.520
+toxicity of the transfection along with, of course, since we saw through this, since
+
+35:03.520 --> 35:09.160
+we saw through this little ruse a few years ago, a couple years ago, and we stopped believing
+
+35:09.160 --> 35:12.760
+this ruse.
+
+35:12.760 --> 35:16.040
+One of the reasons why we stopped believing this ruse was because we realized that the
+
+35:16.040 --> 35:21.720
+spike protein that's produced by a codon-optimized pseudo-uridine chemically altered RNA is not
+
+35:21.720 --> 35:29.240
+going to be anywhere structurally related in epitopes to that of one by the viral sequence.
+
+35:29.240 --> 35:34.520
+And we came to that conclusion after having Kevin McCurtain on our stream for two times.
+
+35:34.520 --> 35:38.440
+And so if the protein in three-dimensional structure is not equivalent to the protein
+
+35:38.440 --> 35:43.040
+that you're trying to build immunity to, chances are very good that the most damage
+
+35:43.040 --> 35:48.040
+associated immune epitopes there on that are also different.
+
+35:48.040 --> 35:56.480
+And so here we are, we know what the game was, we know how they did it.
+
+35:56.480 --> 36:00.360
+We know how they did it, we know they drove these mass casualty events and coordinated
+
+36:00.360 --> 36:04.600
+them in a way that made sure that nobody could question what actually happened.
+
+36:04.600 --> 36:09.200
+They co-opted a pre-selective group of narrative controllers and they probably brought more
+
+36:09.200 --> 36:15.320
+people on as the narrative went out of control as the compliance wasn't 100% with the uptake
+
+36:15.400 --> 36:21.440
+of the transfection, but a combination of background signal and nonspecific tests.
+
+36:21.440 --> 36:24.640
+And we don't have to figure that out for ourselves, we don't have to take everybody's
+
+36:24.640 --> 36:27.160
+word for it.
+
+36:27.160 --> 36:32.720
+And just because one person published a paper doesn't mean that that is the definitive
+
+36:32.720 --> 36:39.720
+Supreme Court evidence that now a scientific fact has been established, which is often
+
+36:39.720 --> 36:43.520
+how a lot of these rebuttal papers are presented.
+
+36:43.960 --> 36:48.840
+If you say somebody doesn't understand that the RNA, dependent RNA polymerase has a different
+
+36:48.840 --> 36:55.320
+replication capacity and then they cite a paper that doesn't immediately mean that
+
+36:55.320 --> 37:00.920
+that's the end of the discussion and that's really how this has gone from the very beginning.
+
+37:00.920 --> 37:05.400
+I think that they really thought that I was underprepared that I stumbled onto this idea
+
+37:05.400 --> 37:08.960
+and that's why the first three or four times that we had interaction with it, it was really
+
+37:08.960 --> 37:11.080
+pretty weak.
+
+37:11.080 --> 37:16.280
+And the one time we had an interaction live with my Kevin McCurnan and myself, I just
+
+37:16.280 --> 37:21.440
+kept kicking the ball back to him and at some point I just had to let him go because he
+
+37:21.440 --> 37:27.040
+just kept saying things that made it better.
+
+37:27.040 --> 37:31.680
+And so I think after that talk is when everything really peeled out of control and he decided
+
+37:31.680 --> 37:36.520
+that he had to make it appear as though he was slapping me down and used that stupid
+
+37:36.520 --> 37:42.480
+complicated strategy of his, you know, where he says, April back like six times and it
+
+37:42.480 --> 37:47.360
+forces everybody to Google it and so they all feel like fools and they don't want to admit
+
+37:47.360 --> 37:52.920
+that they don't understand what he's writing and then by not admitting that he's not teaching
+
+37:52.920 --> 37:59.920
+them anything, they let him get away with it, make it look like it's a consistent and consensus
+
+37:59.920 --> 38:02.400
+win on his part.
+
+38:02.400 --> 38:08.880
+And he refuses to acknowledge the fact that all of this stuff happened too.
+
+38:08.880 --> 38:12.840
+So there's actually really good reason to believe that there might not have been a real
+
+38:12.840 --> 38:14.000
+active spread.
+
+38:14.000 --> 38:19.860
+There's really good reason to be skeptical and that's part of what I find very funny
+
+38:19.860 --> 38:24.720
+about the one sub stack that actually dresses JJ's hypothesis in that sub stack.
+
+38:24.720 --> 38:31.280
+I think three times Kevin says maybe only twice that again, I'm not trying to decide
+
+38:31.280 --> 38:36.040
+here how much of the all-cause mortality should be attributed to COVID and how much
+
+38:36.040 --> 38:42.120
+of it should be attributed to bad ideas and man-demic.
+
+38:42.120 --> 38:48.160
+He makes the joke man-demic in his sub stack addressed to me from earlier this year, or
+
+38:48.160 --> 38:55.720
+maybe it's late last year, sorry, yes, it could be late 22 or early 23.
+
+38:55.720 --> 39:02.800
+And so I don't like to be accusatory, but in my perspective, we're dealing with someone
+
+39:02.800 --> 39:05.080
+who's behaving dishonestly.
+
+39:05.080 --> 39:11.400
+And from the very beginning, sort of a limited hangout kind of thing, giving as much, only
+
+39:11.400 --> 39:16.560
+as much information as to feel like he's giving a little bit, but never really bringing us
+
+39:16.560 --> 39:17.840
+all the way to the finish line.
+
+39:17.840 --> 39:22.480
+Are you telling me that Kevin McCurnan couldn't have imagined that there would be double-stranded
+
+39:22.480 --> 39:26.800
+contamination from the process two that he didn't know that they were going to use
+
+39:26.800 --> 39:33.000
+process to, that it was an option given the fact that Enovio was on BBC News with process
+
+39:33.000 --> 39:36.600
+two right behind them?
+
+39:36.600 --> 39:38.480
+I mean, how stupid do they think we are?
+
+39:38.480 --> 39:42.160
+How stupid does Robert Malone think we are that he doesn't know that process one and
+
+39:42.160 --> 39:49.160
+process two are very common differences that we knew that they made the joke on Twiv?
+
+39:49.160 --> 39:55.240
+Vincent Rancin-Yello talked about the amazing upgrade from nanograms to kilograms.
+
+39:55.240 --> 39:59.880
+I mean, come on, guys.
+
+39:59.880 --> 40:05.840
+And so these things all happened and they all want you to ignore the fact that they happened
+
+40:05.840 --> 40:10.720
+and they want you to continue to focus on a novel virus that's highly, high fidelity
+
+40:10.720 --> 40:15.960
+and that it can go around the world and change flavors repeatedly and with patterns.
+
+40:15.960 --> 40:20.560
+They want you to believe that passage of viruses gets you places.
+
+40:20.560 --> 40:25.120
+They want you to believe that when you stiff stuff together it gets you places.
+
+40:25.120 --> 40:29.800
+The worst-case scenario is that they made a lot of something and then they spread it
+
+40:29.800 --> 40:30.800
+around.
+
+40:30.800 --> 40:33.880
+That's the worst-case scenario.
+
+40:33.880 --> 40:38.800
+The worst-case scenario is that they made a lot of something that was pure and also toxic
+
+40:38.800 --> 40:40.800
+and fairly good at replicating.
+
+40:40.800 --> 40:43.560
+That would be awful.
+
+40:43.560 --> 40:51.240
+But it wouldn't be natural and none of the attributes of its spread would be natural
+
+40:51.240 --> 40:55.000
+because it would have started from a state that wasn't natural, a purity that wasn't
+
+40:55.000 --> 41:01.440
+natural and I can't understand why they insist on confounding this, ignoring this really
+
+41:01.440 --> 41:03.640
+easy thing.
+
+41:03.640 --> 41:05.560
+People asking me to write papers and stuff.
+
+41:05.560 --> 41:10.160
+It's like trying to write a paper about why cars use wheels.
+
+41:10.160 --> 41:12.840
+What does that mean?
+
+41:12.840 --> 41:18.920
+What does that mean when Alexandros Maranos and Kevin McCurnan say write up a paper?
+
+41:18.920 --> 41:21.080
+What does that mean?
+
+41:21.080 --> 41:26.480
+I'm telling you and it's a biological fact that the DNA can be copied with much higher
+
+41:26.480 --> 41:33.280
+fidelity than RNA and Kevin McCurnan even admitted it that you can make a lot of DNA
+
+41:33.280 --> 41:36.720
+and then you can make a lot of RNA from it and if you did that you would have a lot of
+
+41:36.720 --> 41:37.720
+genomic RNA.
+
+41:37.720 --> 41:42.360
+It'd be a little variable but it'd be a lot higher purity than anything you could ever
+
+41:42.360 --> 41:49.400
+achieve with any other method that we know and if you invested sufficient into the fidelity
+
+41:49.400 --> 41:55.240
+of it, use PCR methodologies, the state of the art technology, you could get purity levels
+
+41:55.240 --> 41:58.240
+heretofore on seed on earth.
+
+41:58.240 --> 42:03.120
+Distribute those everywhere and the signal would be brightest day.
+
+42:03.120 --> 42:07.160
+Not to mention the fact that you would have this all this leftover DNA that would also
+
+42:07.160 --> 42:14.200
+provide PCR signals because PCR is only looking for a very tiny amplicon so you'd
+
+42:14.200 --> 42:20.920
+have made tons of that amplicons too that you could distribute in sewers and in water
+
+42:20.920 --> 42:25.280
+and DNA is much more stable.
+
+42:25.280 --> 42:30.840
+That signal could potentially last for months and months depending on where you put it.
+
+42:30.840 --> 42:35.640
+Cruise ships could be positive for months if you had DNA that you distributed around.
+
+42:35.640 --> 42:41.000
+I mean come on ladies and gentlemen this is this is all obviously a joke thanks to
+
+42:41.000 --> 42:44.120
+James Giordano.
+
+42:44.120 --> 42:49.080
+Thanks to Kevin McCurnan, thanks to Kevin McCairn, thanks to Paul Catrell, thanks to
+
+42:49.080 --> 42:56.920
+Rick Bright, thanks to Tony Fauci, thanks to Ralph Barrick.
+
+42:56.920 --> 43:01.060
+You know one of the things that I think is really funny about Ralph Barrick is that actually
+
+43:01.060 --> 43:07.700
+I think he was a good guy and I think he's being co-opted.
+
+43:07.700 --> 43:16.300
+I want you to listen to this presentation that I think we are being set up to watch.
+
+43:16.300 --> 43:18.460
+That's all I'm going to say.
+
+43:18.460 --> 43:24.300
+I'm not sure if it's an authentic presentation, there are a couple times where it goes silent
+
+43:24.300 --> 43:30.740
+for like five or six seconds and I'm not sure it's an audio glitch, it could be an erasure
+
+43:30.740 --> 43:35.020
+and a couple times when it goes quiet they are talking about very key aspects of the
+
+43:35.020 --> 43:37.660
+infectious cycle.
+
+43:37.660 --> 43:44.860
+So this YouTube video was actually posted in a sub stack of Peter McCullough and this
+
+43:44.860 --> 43:50.020
+John O'leke or something like that and so that's how I found it and so I'm watching
+
+43:50.020 --> 43:54.740
+it for that reason but what I want you to remember is that this is in between SARS-1
+
+43:55.740 --> 44:02.780
+and Ralph Barrick may in theory, I want you to entertain this possibility, Ralph Barrick
+
+44:02.780 --> 44:13.220
+may still be an innocent bystander, a guy who's just part of the of coronavirus biology
+
+44:13.220 --> 44:21.900
+and he could still be in earnest thinking that coronaviruses could be one, a biotechnology
+
+44:21.900 --> 44:32.780
+to a pan vaccine technology and three, some kind of, I already said that, but some kind
+
+44:32.780 --> 44:44.900
+of future genetic modification technology so as they stand, some useful, then also modified
+
+44:44.900 --> 44:50.980
+and then also modified again I mean they were a huge potential in his mind and so I really
+
+44:50.980 --> 44:56.380
+think it's cool to listen to a video like this, even if it's altered, even if we're
+
+44:56.380 --> 45:04.620
+being tricked, I'm willing to bet that you're gonna hear enough of a guy who is fascinated
+
+45:04.620 --> 45:12.500
+by what he believes he is doing and I think he is doing it and that is studying synthetic
+
+45:12.500 --> 45:14.180
+viruses.
+
+45:14.180 --> 45:19.020
+So viruses that they can't culture, that they couldn't really get to grow in a lab and
+
+45:19.020 --> 45:24.580
+sustain themselves but has found another way to do it when we have these sequences
+
+45:24.580 --> 45:29.780
+and we decide on a consensus how can we do it and to really hear somebody explaining
+
+45:29.780 --> 45:36.140
+how they are developing this technology to assemble full coronavirus genomes, I'm confident
+
+45:36.140 --> 45:43.260
+it's gonna help us in terms of moving forward and really breaking the veil of this whole
+
+45:43.260 --> 45:44.260
+thing.
+
+45:44.260 --> 45:53.380
+Well, Carolina, you're gonna tell us about the synthetic genomics of SARS.
+
+45:53.380 --> 45:59.820
+So I also would like to thank the organizers for inviting me to talk, it's been wonderful.
+
+45:59.820 --> 46:02.180
+Now you are gonna be disappointed with the video here.
+
+46:02.180 --> 46:05.380
+Capture some new ideas that can be tried out on viruses.
+
+46:05.380 --> 46:06.620
+Well, this is not very loud.
+
+46:07.620 --> 46:13.420
+I'm gonna talk about today our basic short introduction into SARS biology.
+
+46:13.420 --> 46:17.140
+Talk about the synthetic resurrection and reconstruction of a variety of zoonotic SARS
+
+46:17.140 --> 46:18.780
+viruses and their applications.
+
+46:18.780 --> 46:27.140
+Okay, so already we're talking about synthetic reconstruction and he used the word resurrection.
+
+46:27.140 --> 46:35.220
+So resurrection would be from a sequence, from a partial sequence and it's very important
+
+46:35.220 --> 46:40.740
+to hear that because this is part of the reason why, again, clones are not just nothing.
+
+46:40.740 --> 46:46.820
+They're very special because the vast majority of coronaviruses cannot be easily cultured
+
+46:46.820 --> 46:53.900
+and when they are cultured, they only really barely culture it, they call it extremely
+
+46:53.900 --> 46:59.660
+low tighter, but it's not really culturing that you can't make enough to share and it's
+
+46:59.660 --> 47:00.660
+not culturing.
+
+47:00.660 --> 47:01.780
+So they have a big problem.
+
+47:01.780 --> 47:08.340
+It's not just that they don't have, they don't have them in the right cell culture
+
+47:08.340 --> 47:12.980
+or it's not the right receptor, it's more complicated than that.
+
+47:12.980 --> 47:19.580
+And I think it comes down to the fact that infectious particles are oftentimes replication
+
+47:19.580 --> 47:25.820
+and competent and if you get at the heart of this, you're gonna find that that's really
+
+47:25.820 --> 47:33.300
+where this all peters out, where the rubber meets the road is right there and that's
+
+47:33.300 --> 47:35.620
+where they just do the hand wavy.
+
+47:35.620 --> 47:38.620
+And that's why the no virus people had so much to stand on.
+
+47:38.620 --> 47:46.460
+That's why I think they were so dangerous and I think that's why they were so confusing.
+
+47:46.460 --> 47:52.020
+But are we, do you feel the pendulum swinging back now, do you feel it?
+
+47:52.020 --> 47:56.740
+Where we were almost all the way to no virus and really exploring the possibility that
+
+47:56.740 --> 48:00.820
+wow, did they really only put clones in like four people?
+
+48:00.820 --> 48:05.300
+Like Sohomish County man and a couple other people and sequence those and then the rest
+
+48:05.300 --> 48:09.380
+is all nonsense, it's possible.
+
+48:09.380 --> 48:16.420
+But there's a whole possibility space that expands from that very tiny number of people
+
+48:16.420 --> 48:23.540
+that were infected with clones that never went anywhere to another medium possibility,
+
+48:23.540 --> 48:29.140
+which is that they actually did put a significant a number of and concentration of clones in
+
+48:29.140 --> 48:34.340
+several places so that several people or many hundreds of people would be infected with
+
+48:34.340 --> 48:37.940
+a very pure infectious RNA.
+
+48:37.940 --> 48:42.660
+And I think over the next few days, as we explore these papers together, you're going
+
+48:42.660 --> 48:49.940
+to find a preponderance of evidence as I have, which indicate that these RNAs all by themselves
+
+48:49.940 --> 48:53.220
+do some pretty cool stuff.
+
+48:53.220 --> 49:05.460
+And as far as most virology papers are concerned, these are better than or more reliable than viruses.
+
+49:05.460 --> 49:09.860
+And what they do and how they do it is more reliable and you're going to figure out that
+
+49:09.860 --> 49:18.500
+that's because of the purity of the RNA, the purity of genomic RNA that gets into each cell
+
+49:18.500 --> 49:27.540
+is several orders of magnitude higher than the amount of genomic DNA that gets into a cell
+
+49:28.180 --> 49:30.740
+during passage.
+
+49:30.740 --> 49:35.780
+And that's what's really extraordinary here. That's really what's extraordinary here.
+
+49:36.420 --> 49:40.420
+And therapeutic and vaccine design.
+
+49:40.420 --> 49:45.220
+I'll also touch on codons, the optimization as a way to attenuate SARS pathogenesis,
+
+49:45.220 --> 49:49.940
+but I certainly haven't gone to the depth of studies that Eckerd's group has done.
+
+49:49.940 --> 49:55.620
+And then I'll talk about rewiring SARS-Coronavirus transcription circuits as a way universal strategy
+
+49:55.620 --> 49:59.380
+to attenuate viral pathogenesis.
+
+49:59.380 --> 50:03.060
+So this is a schematic diagram of the SARS-Coronavirus particle.
+
+50:04.020 --> 50:06.420
+It's about 100 nanometers from diameter.
+
+50:06.420 --> 50:09.940
+It contains a helical nucleic acid inside.
+
+50:09.940 --> 50:12.820
+It contains a single-stranded plus polarity RNA genome.
+
+50:14.020 --> 50:17.140
+This nucleic acid structure is surrounded by a lipid bilayer.
+
+50:17.780 --> 50:20.500
+It contains several viral glycoprotein spikes.
+
+50:20.500 --> 50:25.060
+The important ones for today's talk include the M glycoprotein and the E protein,
+
+50:25.060 --> 50:26.260
+which are shown right here.
+
+50:26.820 --> 50:30.900
+These proteins are absolutely essential for maturation and release
+
+50:30.900 --> 50:32.580
+and the production of virus particles.
+
+50:33.220 --> 50:34.260
+So keep that in mind.
+
+50:35.220 --> 50:39.540
+The second viral protein of interest for today's talk is the escolycoprotein gene
+
+50:39.540 --> 50:43.460
+that's shown right here, which gives the virus its unique occurrence in the electron microscope.
+
+50:44.740 --> 50:48.820
+It's the viral passion protein that binds to the receptor to mediate,
+
+50:48.820 --> 50:50.180
+docking, and entry into the cell.
+
+50:51.140 --> 50:55.460
+It regulates tissue tropism, species specificity.
+
+50:55.460 --> 50:58.340
+It contains a large number of important neutralizing epitopes,
+
+50:58.340 --> 51:00.900
+and it's the principal component of protective immunity.
+
+51:01.860 --> 51:08.340
+Now, if you tear this virus particle apart and look at the viral genomic positive-stranded RNA,
+
+51:08.340 --> 51:11.060
+it's about 30,000 base pairs in length.
+
+51:11.060 --> 51:14.180
+It's the largest plus polarity RNA genomes in nature.
+
+51:14.180 --> 51:17.940
+The first 20,000 base pairs are shown to encode the replicase proteins.
+
+51:17.940 --> 51:22.340
+So the job it is to replicate the genome, replicate the genome,
+
+51:22.340 --> 51:26.740
+and express sub-genomic messenger RNA that encode these downstream open reading frames.
+
+51:31.540 --> 51:33.540
+Here's the first blank space.
+
+51:33.540 --> 51:37.460
+Now, these downstream morphs encode the structural genes like the SEM and
+
+51:37.460 --> 51:40.980
+nucleocapsid protein that I just mentioned that were present in the virion
+
+51:40.980 --> 51:43.220
+in a variety of accessory morphs.
+
+51:43.220 --> 51:48.020
+To get these expressed in cells, you find a nested set of sub-genomic messenger RNA.
+
+51:48.580 --> 51:52.580
+They're ranged from the three prime end of the genome so that all the sequences in the smallest
+
+51:52.580 --> 51:56.260
+message are in the next largest message and so on and so forth.
+
+51:56.260 --> 52:01.620
+This organization allows different open reading frames to be placed at the five prime ends of
+
+52:01.620 --> 52:06.100
+different messenger RNAs so they can be efficiently translated and expressed in cells.
+
+52:06.820 --> 52:07.700
+Now, the trans...
+
+52:09.460 --> 52:11.140
+Here, again, is another dropout.
+
+52:13.540 --> 52:13.940
+I don't know.
+
+52:13.940 --> 52:16.740
+How 70 nucleotides shown here are these little blue boxes.
+
+52:18.260 --> 52:21.460
+That is derived from the five prime end of the genome.
+
+52:21.460 --> 52:25.620
+So these are discontinuous stretches of RNA that are joined going transcription.
+
+52:25.700 --> 52:29.940
+And these little red box elements right here are absolutely essential
+
+52:29.940 --> 52:32.420
+for mediating the joining of these two sequences.
+
+52:33.380 --> 52:36.020
+This will become very important later on in the talk.
+
+52:36.020 --> 52:36.980
+So keep the...
+
+52:36.980 --> 52:41.940
+Okay, so what he's explaining here just to kind of to bring you up to speak.
+
+52:41.940 --> 52:44.020
+You can't really see it here and I apologize.
+
+52:44.020 --> 52:46.740
+I told you it was going to be a bad... the graphics are bad.
+
+52:48.660 --> 52:51.060
+It's weird. This was uploaded last year.
+
+52:51.060 --> 52:52.740
+I can't find another copy of it.
+
+52:53.620 --> 52:58.820
+There's those two things that were edited out there or blanked out in the beginning there.
+
+52:58.820 --> 53:02.100
+I can't tell but it sure feels like there was an erasure there.
+
+53:02.660 --> 53:07.700
+And he's talking about these TRSs which are translation regulatory sequences.
+
+53:08.660 --> 53:12.660
+They are small sequences that are repeated throughout the genome.
+
+53:13.380 --> 53:17.140
+And it's not very clear to me upon reading the genome...
+
+53:17.780 --> 53:24.660
+or sorry, the literature exactly how these transcriptional regulatory elements
+
+53:25.380 --> 53:26.660
+interact with one another.
+
+53:26.660 --> 53:36.900
+But it feels like, if I can give you my best impression, it feels like that these TRS segments
+
+53:37.620 --> 53:44.740
+are repeated because the RNA molecule has a three-dimensional interaction with itself
+
+53:45.300 --> 53:50.260
+and makes it not so that this part gets looped over to this part.
+
+53:50.820 --> 53:56.580
+And so then the RNA-dependent RNA polymerase can make a very short RNA that goes bloke
+
+53:56.580 --> 53:57.860
+and then it goes right to here.
+
+53:58.740 --> 54:01.540
+And it goes bloke and then it goes right to here.
+
+54:01.540 --> 54:06.020
+And so every time it gets to a translational regulatory element,
+
+54:06.660 --> 54:12.420
+there's the potential for this part of the five prime end to be looped in over here.
+
+54:12.420 --> 54:16.020
+And so then the RNA-dependent RNA polymerase that's translating it can
+
+54:16.980 --> 54:19.300
+to make this sub-genomic RNA.
+
+54:19.300 --> 54:21.620
+And that's probably completely wrong.
+
+54:21.620 --> 54:26.180
+But I do know that the translation regulatory elements are all the same.
+
+54:27.140 --> 54:33.940
+And it is from these spots in the genome that the recombination is most likely to occur.
+
+54:35.780 --> 54:40.020
+And one of the ways, and Ralph Berwick will explain it in this talk later,
+
+54:40.100 --> 54:44.420
+that they thought to make an attenuated virus that could not
+
+54:45.220 --> 54:49.860
+de-attenuate by recombining with other viruses in the wild
+
+54:50.660 --> 54:56.980
+was to artificially change the translation regulatory segments of the artificial genome
+
+54:57.940 --> 55:04.980
+so that this virus, when co-infecting a cell, would have translation regulatory elements that
+
+55:04.980 --> 55:09.700
+were incompatible with the genomes that would be present in the wild.
+
+55:09.700 --> 55:17.620
+And therefore they could not rearrange their genome to acquire genes from wild coronaviruses.
+
+55:17.620 --> 55:23.460
+So what he's explaining here is an aspect of the coronavirus genome that if you take their
+
+55:23.460 --> 55:29.700
+word for it, as I'm doing right now, is part of the regulatory mechanism by which the
+
+55:30.660 --> 55:36.500
+entire signal genome actually gets translated into these sub-genomic RNAs that we've been talking
+
+55:36.500 --> 55:41.540
+a lot about and that we understand are in abundance of several orders of magnitude more
+
+55:41.540 --> 55:47.300
+abundance than the full genome, whenever they try to find the total RNA in any of these preparations.
+
+55:47.300 --> 55:53.940
+I hope that helped a little bit, especially because you can't see Jack in this sort of blurry thing.
+
+55:53.940 --> 55:58.180
+But we are listening to the great RB, so it's pretty fun.
+
+55:58.740 --> 56:04.020
+The concept of TRS elements, a little red box element, is being essential for regulation of
+
+56:04.020 --> 56:12.420
+messenger RNA synthesis. Now, let's talk about synthetic genomics in the context of a platform
+
+56:12.420 --> 56:17.780
+to control emerging infectious diseases. If you think about emerging viruses, they have tremendous
+
+56:17.780 --> 56:23.940
+potential to cause high morbidity and mortality. They have tremendous potential to cause high
+
+56:24.020 --> 56:31.220
+morbidity and high mortality, meaning that there are small examples of this happening. But again,
+
+56:31.220 --> 56:38.100
+it's the pandemic potential is different. I'm sure that if you had enough clone of a clone
+
+56:38.100 --> 56:42.660
+of an RNA like this and you put it in somebody's lungs, yeah, or squirted it in some,
+
+56:42.660 --> 56:49.940
+an animal's nasal passages, you'd have some problems. If you put that RNA in a cell culture and then
+
+56:49.940 --> 56:54.580
+passage it a few times, you're going to have a lot of RNA in every cell. It's all going to be
+
+56:54.580 --> 56:58.820
+the same. It's all going to do its viral thing. It's all going to package a bunch of stuff up.
+
+56:58.820 --> 57:05.780
+You're going to have a huge concentration of highly homogenous RNA particles, as far as we can tell,
+
+57:05.780 --> 57:12.500
+viral particles, exosomes, whatever, that you would not have if you just started with a sample from
+
+57:12.500 --> 57:17.300
+the bat and then started passageing it and tried to make a lot. And that's the point.
+
+57:21.220 --> 57:26.900
+Let's let it keep playing here. Maybe I should just quick, just let me give you this one thing here.
+
+57:26.900 --> 57:31.220
+I had this queued up and then I just, I just realized we were going way, I was going way off
+
+57:31.220 --> 57:43.060
+balance here. But here's a mini review from a virology in 1994, infectious transcripts,
+
+57:43.060 --> 57:50.020
+CDNA clones of RNA viruses. Recombinant DNA technology makes it possible to analyze and modify
+
+57:50.020 --> 57:55.540
+genomes at the molecular level and thus gain deeper insight into their organization and expression.
+
+57:55.700 --> 58:01.140
+Oops, sorry. In this, in this respect, viruses because of the small size of their genome are
+
+58:01.140 --> 58:06.820
+particularly amenable to such investigations. In spite of this, the study of molecular biology of
+
+58:06.820 --> 58:13.860
+non-retroviral RNA viruses has long been hampered by the fact that these viruses do not encompass a
+
+58:13.860 --> 58:20.740
+DNA intermediate step in their replication cycle. Therefore, since to date, the extremely varied
+
+58:20.740 --> 58:26.020
+and powerful molecular biology techniques aimed at modifying nucleic acids have been directed
+
+58:26.020 --> 58:31.780
+essentially at DNA substrate, new molecular tools had to be developed. The possibility of
+
+58:31.780 --> 58:42.260
+obtaining infectious clones as CDNAs or as in vitro transcribed RNA copies, which is what an RNA
+
+58:42.260 --> 58:50.900
+infectious clone is. Corresponding to the genomes of RNA viruses has greatly enhanced the
+
+58:50.900 --> 58:56.100
+potential of investigations. Indeed, they can facilitate studies of viruses that are present
+
+58:56.100 --> 59:07.940
+only in low titers in infected cells or whose isolation is problematic. Interesting. That's from
+
+59:08.340 --> 59:20.820
+1994. Let's go to 2019 from Cina Bavari and Alison Totura, a former postdoc of Ralph Barrick.
+
+59:22.340 --> 59:30.100
+Section 2, 2.1, reverse genetic systems. Advances in the study of highly pathogenic coronaviruses and
+
+59:30.100 --> 59:35.460
+potential pan-coronavirus drug tech candidates partially depends on the technology to genetically
+
+59:35.460 --> 59:40.180
+manipulate coronaviruses to probe mechanisms of viral pathogenesis and antiviral drug activity.
+
+59:40.820 --> 59:46.740
+Reverse genetic systems synthetically generate viruses from known viral sequences. In situations
+
+59:46.740 --> 59:52.500
+who wear clinical isolates of infectious material unavailable and due to restrictions for collecting
+
+59:52.500 --> 59:57.140
+patient samples, shipping infectious materials, availability of containment laboratories,
+
+59:57.140 --> 01:00:03.220
+reverse genetic systems, provide the essential research materials for studies on viral pathogenesis
+
+01:00:03.300 --> 01:00:09.860
+in model development. Prior to the SARS pandemic, robust reverse genetic systems to manipulate the
+
+01:00:09.860 --> 01:00:17.140
+genomes of Scarsco V2s, sorry, of coronaviruses had already been developed by systematic assembly
+
+01:00:17.140 --> 01:00:23.060
+of cDNA consents to full-length infectious clones, allowing precise and genetic targeted
+
+01:00:23.060 --> 01:00:29.220
+manipulation of viral genes. More importantly, to me, infectious clones allow the creation of
+
+01:00:29.220 --> 01:00:36.900
+near homogenous viral stocks where the traditional viral stocks are prepared by
+
+01:00:36.900 --> 01:00:44.660
+amplification of infectious material in cell culture. Infectious materials, that's the stuff
+
+01:00:44.660 --> 01:00:51.460
+they take from bats, that's the stuff they take from sick people. Over many passages, strategies
+
+01:00:51.460 --> 01:00:56.580
+to build reverse genetic systems were rapidly applied to both SARS and MERS within the first
+
+01:00:56.580 --> 01:01:03.700
+year of identifying these viruses. In addition to reconstructing epidemic,
+
+01:01:03.700 --> 01:01:09.780
+epidemic strains of SARS-CoV-2 with reverse genetic systems allow targeting of mutations
+
+01:01:09.780 --> 01:01:15.860
+to specific viral genes and assembly of these virus when infectious material is not available.
+
+01:01:15.860 --> 01:01:28.260
+So they've seen pretty significant for RNA virology in general, but for some reason or another, a guy who
+
+01:01:30.980 --> 01:01:35.220
+was at the White House when he was what, 25 or something like that? I don't know,
+
+01:01:35.220 --> 01:01:40.420
+how old was he when he was at the White House for the first time and probably because of his dad,
+
+01:01:40.500 --> 01:01:49.300
+maybe, I don't know, but and then his, he drops out of grad school, goes to work for Eric Lander,
+
+01:01:50.260 --> 01:02:01.300
+Eric Lander's in the Biden White House, running stuff for the mRNA, and this guy's involved from
+
+01:02:01.300 --> 01:02:06.660
+the very beginning from the PCR shot all the way through all the objections that were ever made
+
+01:02:06.660 --> 01:02:17.220
+about the transfection and titrating them one by one and we're supposed to believe that
+
+01:02:17.220 --> 01:02:21.860
+clones are just like everything else. It's no big deal. Clones don't do anything. Clones are
+
+01:02:21.860 --> 01:02:31.780
+chemtrails stupid. It's pretty phenomenal, really, if you think about it. And severe economic
+
+01:02:31.780 --> 01:02:37.780
+hardship, good examples are HIV, the 1918 flu, far as coronavirus, H5N1,
+
+01:02:37.780 --> 01:02:43.220
+chicken and guinea virus, probably most recently. Now it's clear that zoonotic introductions are
+
+01:02:43.220 --> 01:02:50.260
+increasing and a large number of these viruses have large reservoir pools of animal strains
+
+01:02:50.260 --> 01:02:56.420
+like SARS and H5 that are maintained as sort of heterogeneous swarms of pools of viruses
+
+01:02:56.420 --> 01:03:01.220
+of which someone may actually emerge in the future to cause epidemic disease in humans.
+
+01:03:01.860 --> 01:03:07.140
+This raises a conundrum in terms of how do you protect the public health against the future
+
+01:03:07.140 --> 01:03:14.340
+occurrence that is hard to predict. I wonder how we would differentiate between a pathogen in bats
+
+01:03:14.340 --> 01:03:21.460
+that doesn't make bats sick. How would we differentiate that from a immune signal?
+
+01:03:22.900 --> 01:03:31.380
+Like let's say that the bats physiology is to emit coronaviruses. Let's say that a lot of
+
+01:03:31.860 --> 01:03:44.180
+mammals emit self replicating RNA packaged in a lipoprotein coat. Just just imagine that for a
+
+01:03:44.180 --> 01:03:51.300
+second. Is that crazy? Is that a crazy idea? Are we crazy? Are we a little crazy to assume
+
+01:03:52.100 --> 01:03:57.780
+that these RNA molecules coated in a lipid dental, a lipid protein, a lipoprotein coat,
+
+01:03:58.020 --> 01:04:03.060
+aren't we a little? Isn't it a little weird to assume that these guys are just all independent
+
+01:04:03.060 --> 01:04:12.740
+actors that are out of the control of the bats, out of the influence of the bats,
+
+01:04:12.740 --> 01:04:20.660
+out of the hands of the, despite the bats best effort, these coronaviruses are thriving inside
+
+01:04:20.660 --> 01:04:23.620
+of the bat population. Why does it have to be like that?
+
+01:04:28.260 --> 01:04:31.300
+Is it, is it really like that? Are we sure it's like that?
+
+01:04:34.340 --> 01:04:41.460
+Are we sure that Simeon virus 40 was really a virus that the monkeys body really wanted to get
+
+01:04:41.460 --> 01:04:47.300
+rid of but couldn't get rid of? Are we assuming that the pangolans have coronaviruses that they
+
+01:04:47.300 --> 01:04:54.020
+don't want that they're not supposed to have but they're just there because despite their best
+
+01:04:54.020 --> 01:05:05.060
+efforts, that's a huge assumption, isn't it? As opposed to it being like a signal or an offgassing
+
+01:05:05.060 --> 01:05:10.660
+or a noise, I like a signal. I like the idea of it being a signal.
+
+01:05:11.460 --> 01:05:15.940
+I don't like the idea so much of it being a pathogen anymore.
+
+01:05:17.940 --> 01:05:22.900
+But I definitely like the idea that Ralph Barrick thinks it's a signal and thinks that what he's
+
+01:05:22.900 --> 01:05:27.620
+working on is important and what he's working on is something that's worth understanding and that
+
+01:05:27.620 --> 01:05:33.540
+he's made a major breakthrough by figuring out how to make these full genomes and start there.
+
+01:05:34.340 --> 01:05:40.820
+I think it's possible. I think your your sliver of understanding, your sliver of specialty could
+
+01:05:40.820 --> 01:05:47.060
+be so great that you could get so fired up about making machine guns that you just don't realize
+
+01:05:47.060 --> 01:05:55.460
+that, wow, I made really, I mean this machine gun is pretty amazing and I'm proud of all the the
+
+01:05:56.340 --> 01:06:02.100
+the ingenious ideas I put into it but I'm a little disappointed with what it did to them all.
+
+01:06:03.060 --> 01:06:05.700
+That's possible. It's totally possible.
+
+01:06:08.420 --> 01:06:13.220
+You know, I was a clock maker but then I got into guns and I just figured out this thing and it
+
+01:06:13.220 --> 01:06:21.460
+was super cool and and then somebody took it to a high school but you could still have your you
+
+01:06:21.460 --> 01:06:27.060
+know if you were really hyper focused on something if you really were interested in making something
+
+01:06:27.060 --> 01:06:31.140
+cool out of coronavirus is because somebody said that something cool could be made out of
+
+01:06:31.140 --> 01:06:35.940
+coronaviruses and you're a clever guy maybe that's who Robert over there that's who Ralph
+
+01:06:35.940 --> 01:06:44.660
+Berwick is. That's why he's trying to attenuate them. That's why he's trying to find combinations
+
+01:06:44.660 --> 01:06:49.220
+of monoclonal antibodies that will neutralize all of them.
+
+01:06:52.580 --> 01:06:57.780
+That's why he's trying to change their translation regulatory sequences so that they can't recombine
+
+01:06:58.660 --> 01:07:07.060
+with with natural viruses and that they can be permanently attenuated. These are all laudable
+
+01:07:07.060 --> 01:07:14.180
+pursuits if viruses are real and and if they are potentially a biotechnology that could be harnessed
+
+01:07:14.180 --> 01:07:22.420
+for good. A endogenous signal that could be that could be used and harnessed as a as a tool.
+
+01:07:22.420 --> 01:07:31.380
+Why not? Sounds great. I think Ralph Berwick might be innocent. I think we might be led to believe
+
+01:07:31.380 --> 01:07:35.940
+that in this little Scooby-Doo this is the guy we're supposed to unmask. This is the bad guy right
+
+01:07:35.940 --> 01:07:42.900
+here. Look at him. I don't think so. How do you develop drugs and therapeutic against an unknown
+
+01:07:42.900 --> 01:07:47.940
+from this heterogeneous swarm of variant strain that will actually work against the unknown that
+
+01:07:48.020 --> 01:07:53.700
+will emerge in the future? How do you target your scarce resources? We think platform technologies
+
+01:07:53.700 --> 01:07:58.420
+like synthetic biology, phylogenomics, structure modeling, high-throughput sequencing really will
+
+01:07:58.420 --> 01:08:04.420
+provide a platform and our goal is to use SARS coronavirus and its large pool of zoonotic viruses
+
+01:08:04.420 --> 01:08:09.940
+as a model to develop rapid response platforms to protect against this broader heterogeneous
+
+01:08:09.940 --> 01:08:16.020
+pool of variants. We also would like to develop strategies that would attenuate all family members
+
+01:08:16.020 --> 01:08:20.580
+so that you could rapidly develop vaccines for the public overall public health.
+
+01:08:20.580 --> 01:08:25.300
+And so that's funny because he's talking about rapidly developing vaccines. I wonder
+
+01:08:25.300 --> 01:08:31.700
+anywhere in this talk he's going to project a time frame. Is he going to say five years?
+
+01:08:33.060 --> 01:08:37.140
+Because if he says two years that would be very interesting, wouldn't it? If he says
+
+01:08:37.860 --> 01:08:42.900
+five years or he says one year anything that he says about development time will be interesting
+
+01:08:42.980 --> 01:08:49.460
+in 2007. This is going to be cool. Keep your ears open. Now a lot of beautiful work in Malek's
+
+01:08:49.460 --> 01:08:55.940
+lab as well as other labs here in China worked out the basic molecular epidemiology of the SARS
+
+01:08:55.940 --> 01:09:01.060
+coronavirus. The virus originated most likely in bat. It probably jumped into civets or humans
+
+01:09:01.700 --> 01:09:07.780
+and in that context set up a transmission cycle between civets and ratoon dogs and marketplaces
+
+01:09:07.780 --> 01:09:13.140
+and humans who frequented those marketplaces. Over time it's selected for strains that were
+
+01:09:13.140 --> 01:09:17.540
+more efficient at infecting human cells and recognizing the human ACE2 receptor for doctor
+
+01:09:17.540 --> 01:09:24.420
+human entry leading to the 2002-2003 epidemic which caused about 8,000 cases and 800 deaths.
+
+01:09:26.500 --> 01:09:30.980
+Now I want you to keep 8,000 cases and 800 deaths in mind as the
+
+01:09:31.060 --> 01:09:44.740
+as a certain quantity of clone. Let's call that one clone unit and so if you release one clone
+
+01:09:44.740 --> 01:09:56.820
+unit in a place in China and it can cover 8,000 trackable or suspected cases and 800 deaths
+
+01:09:57.460 --> 01:10:08.260
+with a few sequences. So let's just call that a single clone unit as 8,000 cases and 800 people
+
+01:10:08.260 --> 01:10:16.820
+dead so that we can think about what we would do if we had two or three clone units, if we had
+
+01:10:16.820 --> 01:10:25.700
+10 clone units released in four places. How many cases would that be? How far would it go?
+
+01:10:26.900 --> 01:10:33.540
+How much molecular change would occur per unit time in that scenario? I want you to start
+
+01:10:33.540 --> 01:10:40.020
+thinking about the possibility that that's what actually was done. The first time single clone
+
+01:10:40.020 --> 01:10:48.340
+unit this time maybe five clone units and the difference is that these five clone units were
+
+01:10:48.340 --> 01:10:55.460
+all so clones right they're the same so instead of having a SARS outbreak originate from a apartment
+
+01:10:55.460 --> 01:11:04.820
+building in China and ultimately end up somewhere in Toronto of all places which was probably part
+
+01:11:04.820 --> 01:11:09.300
+of an exercise again because they were elevated as people who knew what they were talking about
+
+01:11:09.380 --> 01:11:18.420
+at the beginning of this one and so with more clone units you could just have a bigger brighter
+
+01:11:18.420 --> 01:11:26.820
+signal that would be as homogenous as you wanted it to be and so interestingly enough when we were
+
+01:11:26.820 --> 01:11:37.060
+having this argument before Kevin McCurnan and I he brought up the idea that there should be some
+
+01:11:37.060 --> 01:11:44.420
+purity in the thing which I find curious and I just want to throw that up there for people who
+
+01:11:44.420 --> 01:11:54.420
+are listening and watching so this was from earlier this year something you know the things that he
+
+01:11:54.420 --> 01:12:00.260
+says that I ignore this is from a slide that I made for that I think it was in the in the last week
+
+01:12:00.260 --> 01:12:06.180
+of April the first week of May ask yourself why he's making six hour scooby-doo videos instead
+
+01:12:06.180 --> 01:12:11.060
+of downloading data from NCBI and trying to find a signal for his hypothesis in real data
+
+01:12:11.060 --> 01:12:19.060
+if the clones offer some advantage to Dr. Evil surely there is evidence of reduced mutation rates
+
+01:12:19.060 --> 01:12:26.340
+to prove this now interestingly I didn't want to make a big deal about this I went really fast
+
+01:12:26.340 --> 01:12:30.820
+through it because I'm a little scared it's going to disappear I'm a little scared that somebody's
+
+01:12:30.820 --> 01:12:37.460
+going to make an excuse for it to disappear but this is the paper from Alina Chan in May of 2020
+
+01:12:37.940 --> 01:12:46.180
+Alina Chan with the book Alina Chan that works at the Broad Institute that Eric Lander is the head
+
+01:12:46.180 --> 01:12:54.420
+of at MIT Eric Lander the former boss of Kevin McCurnan at the Human Genome Project ladies and
+
+01:12:54.500 --> 01:13:01.860
+gentlemen the one that worked at the White House for Biden yeah him now runs the Broad
+
+01:13:01.860 --> 01:13:06.820
+Institute or still runs the Broad Institute at MIT where Alina Chan works Alina Chan submitted
+
+01:13:06.820 --> 01:13:14.820
+this paper this pre-print to bio archive on May in 2020 and here she has nucleosides nucleotide
+
+01:13:14.820 --> 01:13:22.820
+substitutions in the genome of SARS-1 versus nucleotide substances substitutions in this genome
+
+01:13:22.820 --> 01:13:29.860
+of SARS-CoV-2 and lo and behold what is this it looks like there is evidence of reduced mutation
+
+01:13:29.860 --> 01:13:34.660
+rates at the beginning of the pandemic relative to the beginning of the pandemic of SARS
+
+01:13:36.580 --> 01:13:45.060
+hugely reduced mutation rates publicized and observed by none other than Alina Chan who was
+
+01:13:45.060 --> 01:13:49.780
+incidentally has never published this paper officially under peer review
+
+01:13:50.500 --> 01:13:57.300
+and instead accepted a position at the Broad Institute as a staff scientist and sold a book
+
+01:13:57.300 --> 01:14:06.020
+about the lab leak it's a pretty interestingly tiny circle of monkeys considering the fact
+
+01:14:06.020 --> 01:14:17.300
+that Kevin McCurnan just recently said that I gave him the George Webb treatment like I mean
+
+01:14:17.300 --> 01:14:22.500
+have we are really running out of characters here is it really that many people aren't backstage
+
+01:14:22.500 --> 01:14:31.060
+anymore or what like when we when we spike this football ladies and gentlemen it's going to be
+
+01:14:31.060 --> 01:14:37.380
+quite a spike okay it's going to be quite a spike let's go back to some more traditional virology
+
+01:14:37.380 --> 01:14:43.140
+with the Great Ralph Barrack if you do phylogenetic analysis of the isolates that were sequenced
+
+01:14:45.620 --> 01:14:52.340
+you find they fall into two broad categories these this line indicates the strains underneath
+
+01:14:52.340 --> 01:14:58.020
+that line were identified during the epidemic and you have early phase isolates primarily of
+
+01:14:58.020 --> 01:15:04.260
+January 2003 after a variety of super spreading events you had middle phase isolates shown here
+
+01:15:04.260 --> 01:15:11.460
+by this group of isolates and then following infected physicians who came to Hong Kong and
+
+01:15:11.460 --> 01:15:16.100
+resulted in a super spreading event that some transmitted the virus to the rest of the world
+
+01:15:16.100 --> 01:15:22.100
+these were considered late phase isolates now if anything is suited to a super spreader event
+
+01:15:22.100 --> 01:15:27.780
+it is somebody who is infected with an infectious clone because all their cells will have been
+
+01:15:27.780 --> 01:15:34.020
+infected with a genomic RNA that was identical which means when they start making this swarm
+
+01:15:34.020 --> 01:15:42.180
+of of slightly altered viral genomes and they make this huge collection of sub genomic RNAs
+
+01:15:42.740 --> 01:15:47.860
+the collection of proteins that they produce will be much more homogenous than anything
+
+01:15:47.860 --> 01:15:53.860
+that would have been generated from a typical cultured virus if you could culture it but you
+
+01:15:53.860 --> 01:15:58.340
+can't you see you see what's magical about this you see how beautiful this is
+
+01:16:01.380 --> 01:16:06.340
+and so Ralph knows that he's making something that's super cool Ralph knows that he's making
+
+01:16:06.340 --> 01:16:14.180
+something that is not natural but he's arguing that not only can we make something super pure
+
+01:16:15.380 --> 01:16:22.580
+but if we find a way to alter it so that it's not dangerous so that it's useful to us we can make
+
+01:16:22.580 --> 01:16:31.060
+huge quantities of that useful new synthetic virus from Ralph Barrack's perspective he is on
+
+01:16:31.060 --> 01:16:38.420
+the verge of tapping into a biotechnology that has almost limitless possibilities
+
+01:16:41.060 --> 01:16:46.900
+once he can figure out a way to attenuate them so that they replicate in a way that we want them
+
+01:16:46.900 --> 01:16:53.140
+to that they have no toxic parts to them that the most toxic parts of their replication process
+
+01:16:53.140 --> 01:16:59.860
+are minimized then potentially we would have the ultimate transfection tool the ultimate gene
+
+01:16:59.860 --> 01:17:06.980
+therapy tool the ultimate personalized medicine tool that's what he sees here that's what Ralph
+
+01:17:06.980 --> 01:17:14.420
+Barrack is chasing he's chasing a universal vaccine a universal transfection tool a universal gene
+
+01:17:14.420 --> 01:17:22.580
+therapy that's what he's teaching chasing here and he wants to use this diverse set of coronaviruses
+
+01:17:22.580 --> 01:17:29.620
+in the wild that's present and sustaining in the wild in these populations has a basis for understanding
+
+01:17:29.620 --> 01:17:39.540
+them if this biology is it checks out it's a very noble effort in my humble opinion it's not the
+
+01:17:39.540 --> 01:17:48.820
+Scooby-Doo bad guy we're looking for it's just not the vast pool of heterogeneous zoonotic strains
+
+01:17:48.820 --> 01:17:53.540
+however reside up here most of these were in fact none of these were ever actually successfully
+
+01:17:53.540 --> 01:18:01.460
+cultured they actually exist as sequence signatures in silico so one of the immediate goals that we
+
+01:18:01.460 --> 01:18:08.420
+became interested in during the outbreak was to develop a platform of viruses that captured the
+
+01:18:08.500 --> 01:18:14.340
+heterogeneous that exists within the family of viruses and to do that we identified sort of
+
+01:18:14.340 --> 01:18:19.140
+representative strains for example middle phase early phase isolate or bony we had in the lab
+
+01:18:19.140 --> 01:18:26.740
+middle phase isolate with cohk w1 kzo2 with early phase isolate animal isolates like it's from sivets
+
+01:18:26.740 --> 01:18:34.100
+fc 16 and hc fc 6103 a raccoon dog isolate which is shown down here the sporadic 2004 human case
+
+01:18:35.060 --> 01:18:41.380
+and a couple of other viruses sequences were identified as good candidates that would capture
+
+01:18:41.380 --> 01:18:48.180
+all the diversity that had been identified within the sequence pool this shows the sequence that's
+
+01:18:48.180 --> 01:18:54.100
+the sequence variation within the spike like a protein if it's a blue box amino acid that's an
+
+01:18:54.100 --> 01:18:59.780
+animal associated residue early phase changes are shown here in yellow middle phase changes
+
+01:18:59.780 --> 01:19:05.860
+shown in orange and late phase changes shown in red in addition in 2004 there are a variety
+
+01:19:05.860 --> 01:19:10.580
+of other animal strains of sporadic human cases were identified that had additional variations
+
+01:19:10.580 --> 01:19:16.820
+shown here in white and it's interesting as much i i hope that everybody was paying attention right
+
+01:19:16.820 --> 01:19:25.620
+what i put up here before you were paying attention right um this paper is actually
+
+01:19:26.580 --> 01:19:32.740
+this paper this paper right here
+
+01:19:36.740 --> 01:19:42.660
+broad spectrum coronavirus antiviral drug discovery by allicin totura and cena bivari
+
+01:19:42.660 --> 01:19:48.420
+written in 2019 allicin totura was a postdoc of ralph veric
+
+01:19:48.420 --> 01:19:55.620
+so she's at us amrit
+
+01:19:59.140 --> 01:20:01.620
+you don't think she knows how to make infectious clones
+
+01:20:03.620 --> 01:20:07.300
+you don't think everybody that went through ralph veric's lab knows how to make infectious
+
+01:20:07.300 --> 01:20:13.860
+clones are you kidding me where did these people go off to they're not working at starbucks or
+
+01:20:13.860 --> 01:20:16.980
+something like that you think
+
+01:20:20.500 --> 01:20:25.460
+this paper is not accidental that it talks about a virus getting out of china and needing to use
+
+01:20:25.460 --> 01:20:32.900
+remdesivir as an antiviral for it it's not for nothing that we're defending the proof reading
+
+01:20:32.900 --> 01:20:41.460
+ability of exo x one gene or or our exo and gene uh the the ribonuclea we're not we're not
+
+01:20:41.460 --> 01:20:49.700
+defending these these things for nothing they're all related all these people all their nonsense
+
+01:20:49.700 --> 01:20:58.740
+it's all related don't you remember the the the domain program run by ditra
+
+01:21:00.340 --> 01:21:06.820
+run by robert malone who supposedly made an x-ray crystallography computer model
+
+01:21:06.900 --> 01:21:15.060
+of the three cl protease of the virus and then interface that computer model with all known
+
+01:21:15.060 --> 01:21:20.500
+pharmaceuticals with a volunteer team of researchers in a matter of weeks to identify
+
+01:21:20.500 --> 01:21:29.300
+femotidine and remdesivir as two usefully useful antivirals
+
+01:21:37.460 --> 01:21:40.020
+and cena bivari knew about it a year before that
+
+01:21:41.700 --> 01:21:45.620
+and ralph veric and mark dennison knew about it a few years before that
+
+01:21:46.580 --> 01:21:51.220
+for zika or for for Ebola for whatever else they were trying it on
+
+01:21:56.500 --> 01:21:58.740
+because they're all RNA viruses right
+
+01:22:00.980 --> 01:22:06.660
+don't you see the pattern here there is a mythology that has been laid down there is a
+
+01:22:06.660 --> 01:22:08.500
+mythology that is being defended
+
+01:22:08.900 --> 01:22:20.580
+this paper got in bobbie's book this paper that is in bobbie's book and actually actually
+
+01:22:20.580 --> 01:22:26.500
+right uh uh robert malone sold bobbie's book today on his sub stack which is pretty badass i like
+
+01:22:26.500 --> 01:22:33.460
+that a lot maybe that was part of the deal if you get that you stop that kooie from talking about
+
+01:22:33.540 --> 01:22:40.580
+me on his stream i'll i'll sell bobbie's book on my sub stack maybe that's what it is
+
+01:22:41.780 --> 01:22:46.260
+it's a pretty simple deal right you know robert malone's got a million subscribers if he tweets
+
+01:22:46.260 --> 01:22:49.860
+out a book probably a hundred thousand people buy it or ten thousand people buy it
+
+01:22:52.660 --> 01:22:57.540
+he better sub stack the book he wrote a wrote a review on the back cover
+
+01:22:58.420 --> 01:23:06.900
+i'd say buy a copy i'd say buy a copy and we'll meet and i'll autograph it for you
+
+01:23:07.860 --> 01:23:12.820
+um there's some bad stuff in there there's some good stuff in there it's probably the best
+
+01:23:12.820 --> 01:23:14.820
+document of all the nonsense people said
+
+01:23:18.580 --> 01:23:22.980
+the person who showed me this paper the person who showed me this paper his mark
+
+01:23:23.540 --> 01:23:29.780
+he's the tonic mark kulak it wasn't shown to me by by kevin mccairn it wasn't shown to be by
+
+01:23:29.780 --> 01:23:36.580
+paul katrel it wasn't shown to me by george web wasn't shown to me by kevin mccernan or stephanie
+
+01:23:36.580 --> 01:23:44.580
+sinev or steve kirsch or robert malone the only person that's ever mentioned this paper to me
+
+01:23:44.580 --> 01:23:48.740
+ever shown it to me ever found it and said holy crap dude did you read this
+
+01:23:49.300 --> 01:23:51.780
+this is mark kulak
+
+01:23:55.780 --> 01:24:00.900
+i just can't stress to you how all of these things line up in a way that that can't be
+
+01:24:00.900 --> 01:24:06.340
+discounted anymore all of these people all of their behavior line up in a way that cannot
+
+01:24:06.340 --> 01:24:11.300
+be discounted anymore even if we find out that there's a huge coronavirus background that
+
+01:24:11.300 --> 01:24:18.180
+coronaviruses can transmit for months even if we find out that clones can transmit for months
+
+01:24:19.620 --> 01:24:26.580
+the ultimate conclusion is is that we have been lied to by a group of medlers that sustained
+
+01:24:26.580 --> 01:24:34.980
+a worst-case scenario sustained a confusion and uncertainty and a doubt that allowed the world
+
+01:24:34.980 --> 01:24:41.620
+to be transfected and only after the world was transfected that these people do it about face
+
+01:24:41.620 --> 01:24:47.940
+and pretend like they always knew and the list of these people is long but it doesn't include
+
+01:24:47.940 --> 01:24:55.460
+Ralph Barrick the list of people who lied to us about the worst-case scenario at the beginning
+
+01:24:55.460 --> 01:25:02.020
+of the pandemic only to pivot after our kids had lost two years of school after our kids have
+
+01:25:02.020 --> 01:25:09.220
+been traumatized with masks after we had been locked down for a year and a half that's not Ralph Barrick
+
+01:25:09.220 --> 01:25:21.380
+case you can't tell i'm trying to get Ralph Barrick to come and interview on giga-owned
+
+01:25:21.380 --> 01:25:27.220
+biological wouldn't that be badass much of the variation actually falls within residues or regions
+
+01:25:27.220 --> 01:25:33.620
+that neutralizing epitopes were identified and in fact although the number of residues that are
+
+01:25:33.620 --> 01:25:38.420
+changed aren't that great you can actually reduce neutralization titers by about 20 fold
+
+01:25:39.460 --> 01:25:47.300
+with some of these variants now importantly Farzan's group showed that the two key changes
+
+01:25:47.300 --> 01:25:52.500
+during the epidemic where this life seemed to asparaging change at 4.79 and Assyrian 3
+
+01:25:52.500 --> 01:26:00.340
+change at 4.87 that drove animal adaptation to human strain and so keep that in mind so
+
+01:26:01.060 --> 01:26:10.340
+without access to this pool of strains we decided to synthesize basically a portfolio of
+
+01:26:11.060 --> 01:26:16.980
+spike like a protein genes of about 4k each and then use a molecular clone for the
+
+01:26:16.980 --> 01:26:22.100
+urbani epidemic strain that we had built in the lab basically replacing the urbani spike
+
+01:26:22.100 --> 01:26:26.020
+one at a time with these various spike like a protein from different phases of the epidemic
+
+01:26:26.820 --> 01:26:32.580
+now all of these viruses were viable except for the sc-16 variant this actually can't recognize
+
+01:26:32.580 --> 01:26:38.100
+the humanase receptor so it didn't grow until we made mouth cells that consistently expressed
+
+01:26:38.100 --> 01:26:42.980
+the civetase to receptor and once we did that this virus to grow well before we had those cells
+
+01:26:43.620 --> 01:26:50.260
+since Farzan had identified this 4.79 changes the key residues so be careful there now they
+
+01:26:50.260 --> 01:26:55.620
+just admitted that they use mouth cells which have been genetically altered to express the
+
+01:26:55.620 --> 01:27:02.900
+civetase receptor now i can't stress enough we had this paper come out that everybody's been
+
+01:27:02.900 --> 01:27:07.460
+yelling about it i'm probably gonna have to do a show about it in the next couple days again
+
+01:27:08.260 --> 01:27:14.980
+about this paper that um you know i should do that video tomorrow that's what i'm gonna do
+
+01:27:14.980 --> 01:27:24.980
+tomorrow i'm gonna do i found this video with mccernan and um christine uh parks christina parks
+
+01:27:25.860 --> 01:27:35.140
+and um john bodewin and i've i've been meeting to do john bodewin um on highwire and so i should
+
+01:27:35.140 --> 01:27:41.860
+do john bodewin on highwire this week and then i'll do this this multiple person stream that
+
+01:27:41.940 --> 01:27:46.740
+happened a few days a few a week ago or so with mccernan and parks and bodewin that'll be good
+
+01:27:46.740 --> 01:27:52.900
+that's two good good study halls for this week um so what he's talking about here now is making a
+
+01:27:52.900 --> 01:27:57.940
+number of different clones where he's swapping the spike out um this is of course supposed to get
+
+01:27:57.940 --> 01:28:03.300
+us really excited about making chimeric viruses but here again he's gonna make clones of all these
+
+01:28:03.300 --> 01:28:09.700
+things so if there's a danger the danger is is that he's making clones if he wasn't making clones he
+
+01:28:09.700 --> 01:28:16.740
+couldn't even study these things the regular virus of these things is not attainable won't grow
+
+01:28:16.740 --> 01:28:21.940
+and even if you could grow it the titers would be so low it would be almost unsequitable
+
+01:28:23.300 --> 01:28:30.980
+that's the problem with these guys right and so don't let the the nonsense fool you
+
+01:28:30.980 --> 01:28:38.420
+infectious clones are the bedrock methodology of RNA virology change especially build a recombinant
+
+01:28:38.420 --> 01:28:44.180
+virus with that change and that virus could be cultured uh interestingly enough two of these
+
+01:28:44.180 --> 01:28:50.340
+the gz-o-2 and the uh hcse-61 of three viruses actually caused lethal infection in aged animals
+
+01:28:50.340 --> 01:28:56.020
+they produced an ARDS like disease saw SARS caused ARDS in humans or predominantly in age
+
+01:28:56.020 --> 01:29:01.300
+populations uh that's acute respiratory distress syndrome it's a clinically devastating end stage
+
+01:29:01.300 --> 01:29:06.420
+lung disease with about a 50 mortality rate so these are actually some of the first real good
+
+01:29:06.420 --> 01:29:13.300
+animal models for SARS infection and so remember what I said the other day again you have to
+
+01:29:14.100 --> 01:29:19.380
+take everything with a huge grain of salt if it's an animal model especially a genetically modified
+
+01:29:19.380 --> 01:29:27.700
+one then the expression of the protein that the virus interacts with could be so over or so
+
+01:29:27.780 --> 01:29:39.140
+inappropriate or any other number of of wrong that when exposed to these exosome collections
+
+01:29:39.140 --> 01:29:44.740
+these animals produce a really robust immune response or a really robust infection because
+
+01:29:45.300 --> 01:29:49.780
+these signals go everywhere so if you believe the biology that they need a receptor and that
+
+01:29:49.780 --> 01:29:54.420
+the receptor has to be somewhere and if the receptor isn't there then the virus can't hurt you
+
+01:29:54.980 --> 01:30:01.700
+if you believe this then these animal models are also very scary because you could imagine
+
+01:30:01.700 --> 01:30:07.300
+a scenario whereby genetically altering the animal you create an animal that is hyper
+
+01:30:07.940 --> 01:30:14.740
+susceptible to this manipulation hyper susceptible to the exposure to these signals
+
+01:30:15.700 --> 01:30:22.740
+so if you believe viruses work the way that these people say they do and that they need receptors
+
+01:30:22.820 --> 01:30:27.940
+and then you alter the expression of those receptors or even worse you homogenize them
+
+01:30:27.940 --> 01:30:34.180
+across the whole animal then their susceptibility to exposure to these things could be very different
+
+01:30:34.180 --> 01:30:40.180
+and that that could be great if you're writing grant applications that need an animal model that's
+
+01:30:40.180 --> 01:30:46.900
+very repeatable and very robust and so don't underestimate the stuff that we talked about with
+
+01:30:47.460 --> 01:30:53.620
+with Wolfgang Wodock keeps coming up here where you have academic biologists that are essentially
+
+01:30:53.620 --> 01:31:01.060
+academy-gicians they've been they become so good at doing experiments that are fundable
+
+01:31:02.020 --> 01:31:08.980
+asking questions that are fundable that they have stopped asking useful questions that they have
+
+01:31:08.980 --> 01:31:14.900
+stopped asking questions that actually move the ball forward but they're now asking sort of circular
+
+01:31:14.980 --> 01:31:22.580
+questions they don't want to make any progress they want to make the illusion of motion right
+
+01:31:24.420 --> 01:31:29.140
+and so in this scenario i don't think that's what what Ralph barracks doing at all i think he's
+
+01:31:29.140 --> 01:31:35.460
+actually making forward progress there are these RNA signals which have been very difficult to study
+
+01:31:35.460 --> 01:31:41.940
+in the wild because they're almost unculturable there's no infectious material available it's so
+
+01:31:41.940 --> 01:31:47.300
+rare and if you take this infectious material and try to culture it you often get very low to
+
+01:31:47.300 --> 01:31:58.260
+no tighter so infectious clone overcomes that Ralph barrack is a genius now um these viruses
+
+01:31:58.260 --> 01:32:03.780
+replicate of the human epidemic strains replicate efficiently in human airway epithelial cultures
+
+01:32:03.780 --> 01:32:08.500
+these are cultures that are derived from cells lining the trachea of transplant patients you can
+
+01:32:08.580 --> 01:32:13.780
+actually culture them on liquid air interfaces and they take on the architecture of the human airway
+
+01:32:13.780 --> 01:32:20.420
+stars coronavirus all the epidemic strains actually like to infect ciliated cells and these epidemic
+
+01:32:20.420 --> 01:32:26.900
+strains replicate very efficiently the animal strains however do not and this is just some
+
+01:32:26.900 --> 01:32:33.540
+fluorescent microscope images showing the cilia of the ciliated cells with an expression of the
+
+01:32:33.540 --> 01:32:39.220
+sars nucleic acid protein from an epidemic strain on the ciliated cells and the zoonotic
+
+01:32:39.220 --> 01:32:47.140
+strains se 16 in this and hdse 6103 and replicate however if you passage these viruses on human
+
+01:32:47.140 --> 01:32:52.660
+airway cells and culture you can actually rapidly select out variants that can replicate efficiently
+
+01:32:52.660 --> 01:32:59.540
+in human airways those viruses actually do not contain the mutations that would be had been
+
+01:32:59.620 --> 01:33:05.780
+predicted by mike farson as being which were clearly responsible for the 2002-2003 epidemic
+
+01:33:06.340 --> 01:33:14.100
+rather we saw changes um at positions 442 and 472 and 479 and so this is an interesting
+
+01:33:14.100 --> 01:33:23.300
+presentation of the data where it seems like this single trial of putting a clone on a epithelial
+
+01:33:23.300 --> 01:33:30.100
+cell culture a differentiated epithelial cell culture and then seeing sequence changes in the
+
+01:33:30.740 --> 01:33:37.860
+consensus sequence he seems to talk about it like okay so we put the car on the road and it drove
+
+01:33:37.860 --> 01:33:42.180
+down the road and then that's how it works and so if we did it again that's what would happen
+
+01:33:43.380 --> 01:33:49.300
+and i don't think that that's really how virology works i think if he did this again he would get
+
+01:33:49.300 --> 01:33:57.300
+different results here it might be a similar kind of selection process by which non-infectious
+
+01:33:57.300 --> 01:34:04.580
+particles versus infectious particles are selected and and can be seen in in in subsequent passages
+
+01:34:04.580 --> 01:34:10.660
+or detected in subsequent passages but that selection process is purely based on function
+
+01:34:10.660 --> 01:34:18.020
+then it's not going to be based on fitness nothing is is fitness unless it's number of copies right
+
+01:34:18.020 --> 01:34:23.300
+so then we're talking about a whole different thing and we're really only doing a selection
+
+01:34:23.300 --> 01:34:28.340
+process we're taking the whole supernatant here there's there's no like you know
+
+01:34:29.540 --> 01:34:34.740
+race to see who can make more copies of themselves we're not selecting based on fidelity or anything
+
+01:34:34.740 --> 01:34:38.980
+like that in fact we have the argument that there has to be mutation rate otherwise there would be
+
+01:34:39.060 --> 01:34:46.660
+a collapse so it's interesting um that's it's that's it mediated the cross species transmission
+
+01:34:46.660 --> 01:34:52.500
+event so in reality we've done this a couple of times there's actually several pathways by which
+
+01:34:52.500 --> 01:34:57.940
+the zoonautics are it could actually adapt and recognize the humanase receptor what's interesting
+
+01:34:57.940 --> 01:35:04.340
+is that the epidemic strains actually efficiently use both the humanase receptor and the civetase
+
+01:35:04.420 --> 01:35:10.260
+receptor when we in vitro select for human adapted strains on human airway culture
+
+01:35:11.140 --> 01:35:16.820
+they actually lose the ability to recognize the civic receptor so what this data suggests
+
+01:35:16.820 --> 01:35:22.900
+actually is that ours had existed in a transmission cycle between humans and civets actually probably
+
+01:35:22.900 --> 01:35:28.500
+for several several years prior to the 2002-2003 epidemic allowing the virus to
+
+01:35:28.580 --> 01:35:34.900
+regain the capacity to recognize both receptors okay so those were the easy ones to do
+
+01:35:35.860 --> 01:35:41.700
+oh with an application um so now that we had a large panel of our of uh variant viruses we could
+
+01:35:41.700 --> 01:35:46.500
+use those for therapeutic testing over vaccines in this case i'm going to show you an example of
+
+01:35:46.500 --> 01:35:52.420
+about 30 human monoclonal antibodies that were derived by Antonio lancevechia if you take those
+
+01:35:52.420 --> 01:35:56.820
+30 monoclonals and test their ability to neutralize all the strains that we've made in the laboratory
+
+01:35:56.820 --> 01:36:03.220
+you find some that only neutralize urbani some that neutralize all human strains some that neutralize
+
+01:36:03.220 --> 01:36:08.820
+some civets but not all the animal strain but you do end up with four antibodies that neutralize
+
+01:36:08.820 --> 01:36:14.340
+all strains we have in our portfolio including the ones that were in vitro adapted on human
+
+01:36:14.340 --> 01:36:22.260
+airway culture importantly if you select for escape using these antibodies these antibodies
+
+01:36:22.260 --> 01:36:26.420
+select for changes in different locations of the receptor binding domain
+
+01:36:26.420 --> 01:36:32.020
+and in fact three of them actually don't overlap yes 109 the 230 and the 227
+
+01:36:32.020 --> 01:36:37.380
+don't overlap and so these represent good therapeutic cocktails that would capture most of the
+
+01:36:37.380 --> 01:36:43.460
+diversity that exists in SARS therapeutic cocktail what an interesting story we can tell there so
+
+01:36:44.260 --> 01:36:51.380
+there's a guy by the name of plumber who used to work on AIDS in Canada who died at the beginning
+
+01:36:51.460 --> 01:37:03.140
+of the pandemic he had a postdoc I think she was Chinese and she had a three antibody cocktail
+
+01:37:03.140 --> 01:37:13.620
+called Z map that was trialed against remdesivir and was actually being trialed against remdesivir
+
+01:37:13.620 --> 01:37:20.100
+probably at us amrit right before the pandemic and then it was shut down
+
+01:37:21.700 --> 01:37:30.020
+so the trial comparing remdesivir with Z map was stopped this is all Kevin sorry this is all
+
+01:37:30.020 --> 01:37:39.140
+marcoolax work here that I'm reciting from memory so we have an AIDS expert dying I think he fell
+
+01:37:39.140 --> 01:37:46.980
+on the sidewalk or something crazy like that and we have this spy Chinese lady who supposedly
+
+01:37:48.100 --> 01:37:53.700
+took some samples back to China and so she's a spy she she got put away but actually she was
+
+01:37:54.260 --> 01:38:03.540
+like on the cover of magazines and stuff is being the star of of of biology one year for Z map it's
+
+01:38:03.540 --> 01:38:11.460
+really cool because that was a three antibody cocktail this is also another proposed three
+
+01:38:11.460 --> 01:38:21.220
+antibody cocktail as a as a pan by an antiviral that's pretty that's pretty cool I I'm starting
+
+01:38:21.220 --> 01:38:28.020
+to see Ralph Barrett as a good guy it's weird and probably work in potential patients that would
+
+01:38:28.100 --> 01:38:33.140
+be infected during future epidemics and these also actually protect young and aged animals from
+
+01:38:33.140 --> 01:38:40.260
+lethal infection that was a paper published by Barry Rock in a couple papers now the civet
+
+01:38:40.260 --> 01:38:46.420
+and the raccoon dog strains were the easy ones the true reservoir for SARS is within bat population
+
+01:38:47.460 --> 01:38:52.980
+so if you look at a phylogenetic tree the human strains are shown here in red the civet strains
+
+01:38:52.980 --> 01:38:57.540
+raccoon dog strains are shown in purple but the real variation is within the bat strain
+
+01:38:58.580 --> 01:39:02.340
+um the reservoir it's thought that these were probably the reservoir for the
+
+01:39:03.140 --> 01:39:09.220
+emergence of the virus now these are about 80 to 90 percent identical to SARS they can't be
+
+01:39:09.220 --> 01:39:14.100
+cultured and they exist to sequence signature signatures in silico there's also extensive
+
+01:39:14.100 --> 01:39:20.020
+variation see they can't be cultured they exist as sequence signatures in silico well that just
+
+01:39:20.020 --> 01:39:26.900
+means they're stored on a computer they're keyboard viruses and so clones are really really important
+
+01:39:26.900 --> 01:39:33.940
+because you can take a virus that you've only detected in the wild as a sequence and create
+
+01:39:33.940 --> 01:39:41.060
+large quantities of that RNA and electropyrated into cells and get those cells to run it through
+
+01:39:41.060 --> 01:39:49.460
+their ribosomes and package it the only thing you can't do sometimes is passage it
+
+01:39:49.940 --> 01:39:57.940
+but the cells can be made to take the RNA up they can be it can be electropyrated in
+
+01:40:00.020 --> 01:40:05.540
+you can use lip effectamine to get it in and then those cells will read the RNA and those
+
+01:40:05.540 --> 01:40:09.780
+proteins will produce and the sub genomic RNAs will be produced and everything will be packaged
+
+01:40:09.860 --> 01:40:20.740
+up and then you'll get this this effect this is cool because this is really underscoring
+
+01:40:22.580 --> 01:40:29.700
+that downplaying the clones is just it's absurd it's absurd it is a bedrock methodology of RNA
+
+01:40:29.700 --> 01:40:34.980
+virology through the replicase and elsewhere in the genome so when we decided we were going to
+
+01:40:34.980 --> 01:40:41.620
+synthetically resurrect the entire virus now before we started it's important to note this is a
+
+01:40:44.340 --> 01:40:51.220
+the cryoem reconstruction of the SARS glycoprotein spike notice that there are three receptor binding
+
+01:40:51.220 --> 01:40:57.300
+domains shown here in with bubbles that actually engage the ACE2 receptor if you look at the sequence
+
+01:40:57.300 --> 01:41:03.860
+the receptor binding domain shown here in yellow there's a large amount of sequence variation
+
+01:41:03.860 --> 01:41:09.060
+especially within the contact interface residues that engage the human ACE receptor
+
+01:41:09.060 --> 01:41:13.620
+and in fact there's only four of 13 contact interface residues that are retained in these
+
+01:41:13.620 --> 01:41:18.580
+fat strains but we don't actually think it's going to use the human ACE receptor to get into cells
+
+01:41:19.300 --> 01:41:24.580
+in fact we think we're going to have a tough time culturing the virus now it's important to note
+
+01:41:24.580 --> 01:41:31.700
+that the SARS RBD that is was identified has been proposed by a couple of groups that it may have
+
+01:41:31.700 --> 01:41:37.220
+been introduced by recombination processes from unknown strains that haven't yet been identified
+
+01:41:37.220 --> 01:41:42.820
+and that that led to the initial cross-species transmission events now to get back to the
+
+01:41:42.820 --> 01:41:48.900
+issue of in silico sequences they actually represent hypothetical viruses most synthetic viruses that
+
+01:41:48.900 --> 01:41:55.540
+have been resurrected to this point actually we knew that the sequence was infectious in this case
+
+01:41:55.540 --> 01:42:01.460
+we actually don't know which of the sequences in GenBank were infectious if any so to do that
+
+01:42:01.460 --> 01:42:05.860
+with an error rate in GenBank ranging from about one to five hundred to one to ten thousand depending
+
+01:42:05.860 --> 01:42:12.100
+on the sequence we had to do extensive bioinformatic analysis to identify what we thought was the likely
+
+01:42:12.100 --> 01:42:18.020
+consensus sequence well that sounds like that sequencing is a lot more hairy than i thought it was
+
+01:42:18.740 --> 01:42:22.980
+I just thought sequences were sequences you get one it just kind of spits it out
+
+01:42:22.980 --> 01:42:26.900
+beep beep beep beep beep beep beep beep beep beep beep beep beep beep beep beep beep beep beep
+
+01:42:26.900 --> 01:42:32.660
+then you just kind of read it off right now we're getting back to the Vincent Rancin yellow
+
+01:42:32.660 --> 01:42:41.940
+explanation of consensus sequence the the more traditional Vincent Rancin yellow will say that
+
+01:42:41.940 --> 01:42:50.820
+the consensus sequence might not even actually exist but Kevin McCurnan says that there are 15
+
+01:42:50.820 --> 01:42:57.380
+million SARS-CoV-2 genomes on on gents said they're all real they're all independent they all come
+
+01:42:57.380 --> 01:43:03.140
+from different people so they have to be real what's Ralph Barrick talking about here then
+
+01:43:03.940 --> 01:43:16.500
+I see a battleship size incongruency between pre-COVID virology and post-COVID virology
+
+01:43:19.860 --> 01:43:25.300
+I really do I really think we're on to something here I think with a couple weeks of work
+
+01:43:25.940 --> 01:43:34.260
+this is going to be over and we're going to be able to you know incorporate all of these
+
+01:43:34.260 --> 01:43:40.500
+various factions into a common explanation for why a lot of people were mistaken
+
+01:43:41.460 --> 01:43:47.700
+why a lot of people were fooled why you could be taken all the way by no virus why you could
+
+01:43:47.700 --> 01:43:52.900
+be taken all the way by lab leak why you could be taken all the way by my market zoneosis and
+
+01:43:52.980 --> 01:43:58.660
+why you could be taken all the way by by any of these other in-betweens including
+
+01:44:00.100 --> 01:44:01.700
+including iatrogenic murder
+
+01:44:04.420 --> 01:44:11.460
+but in the end there's only one explanation that fits all of them that lets the most people on
+
+01:44:11.460 --> 01:44:22.660
+earth be right and I think that's why everybody's so angry because the explanation that we are being
+
+01:44:22.660 --> 01:44:28.900
+fooled into believing it's Ralph Barrick and Tony Fauci and eco-health alliance
+
+01:44:30.420 --> 01:44:39.940
+instead of understanding that this technology was actually available available it was available
+
+01:44:40.900 --> 01:44:41.860
+to us Amrit
+
+01:44:44.420 --> 01:44:50.020
+probably for a couple decades right ever since they first did it with the polio virus
+
+01:44:53.540 --> 01:44:57.860
+we have to wake up and apologize to our kids sooner or later we might as well do it now
+
+01:44:58.660 --> 01:45:03.380
+none of the strains that we actually saw we thought was completely correct some of them had
+
+01:45:03.380 --> 01:45:08.980
+deletions in the sequence of the five prime ends that we had to make some educated guess
+
+01:45:10.180 --> 01:45:14.900
+the basic approach that we build coronavirus is using our molecular clone is shown here
+
+01:45:14.900 --> 01:45:21.860
+with the SARS clone shown in blue is the clone is broken into six five kv about five kv thesis
+
+01:45:22.660 --> 01:45:29.620
+each piece is flanked by bagel one restriction endonucleate sites these are class two S restriction
+
+01:45:29.620 --> 01:45:35.060
+enzymes that recognize a palindromic sequence and so this is asymmetric and this is almost
+
+01:45:35.060 --> 01:45:40.020
+certainly one of the enzymes that was mentioned in the foyer request that was recently released
+
+01:45:41.300 --> 01:45:50.580
+and so the release of this enzyme or related enzymes as a list in an email or a supplementary
+
+01:45:50.580 --> 01:45:56.580
+document or something like that is now being misconstrued as evidence that the diffuse proposal
+
+01:45:56.580 --> 01:46:01.060
+is real and that they were making clones and that they were spraying them into bad caves and they
+
+01:46:01.060 --> 01:46:08.980
+put fear and cleavage sites at the joint between S1 and S2 yada yada yada so most likely that's
+
+01:46:08.980 --> 01:46:15.780
+why we're being fed this video is so that we get to this point right here and we see how clones
+
+01:46:15.860 --> 01:46:24.420
+are assembled and now i'm sure he's about to tell us that this right here represents a S2 S1 S2
+
+01:46:26.340 --> 01:46:32.420
+clone junction there so that they can substitute the S1 from other coronavirus is right in there
+
+01:46:32.420 --> 01:46:40.260
+let's listen this allows since these ends are asymmetric they actually will not concatomerize
+
+01:46:40.260 --> 01:46:44.580
+like classic sticky ends left by restriction enzymes but rather they become directional
+
+01:46:45.220 --> 01:46:50.660
+so if you end clone A with a bagel site that leaves one three nucleotide overhags and the
+
+01:46:50.660 --> 01:46:55.060
+five prime end of the B fragment with the complementary three nucleotide overhags they
+
+01:46:55.060 --> 01:46:59.780
+totally get it directly you change different bagel sites at each piece it's midnight
+
+01:47:00.740 --> 01:47:07.940
+assemble up into 30k B chromosomes like tinker toys like tinker toys like tinker toys
+
+01:47:07.940 --> 01:47:13.300
+batching home that we made that's actually a good way to date somebody like do you know
+
+01:47:13.300 --> 01:47:19.140
+what tinker toys man i had tinker toys you know i had lots of them like a lot of them i had a
+
+01:47:19.140 --> 01:47:25.300
+lot of tinker toys i think i had like three of the cylindrical containers i could go down
+
+01:47:25.300 --> 01:47:30.740
+with tinker toys hey by the way it's uh past midnight so technically speaking i just turned
+
+01:47:30.740 --> 01:47:39.860
+52 years old yeah 52 52 years old how's that for old using blue heron and biobasic basically
+
+01:47:39.860 --> 01:47:45.060
+is interchangeable with the urbanic clone the only real difference was that we broke the F
+
+01:47:45.060 --> 01:47:50.180
+fragment into two pieces so that we could play with the receptor binding domain easily if this
+
+01:47:50.180 --> 01:47:56.020
+thing didn't turn out to be infectious and in fact we made this clone we built the fool on cDNA we
+
+01:47:56.020 --> 01:48:00.660
+drove transcripts electroprated that in the cells and we can see evidence of replication by
+
+01:48:00.660 --> 01:48:05.540
+the synthesis of sub-genomic messenger RNA but we couldn't culture the virus and we couldn't pass
+
+01:48:05.540 --> 01:48:10.420
+it from cell to cell ah we couldn't culture the virus we couldn't passage it from cell to cell so
+
+01:48:10.420 --> 01:48:17.460
+they could see that the RNA was being sorted into sub-genomic RNAs but they couldn't passage it from
+
+01:48:17.460 --> 01:48:23.620
+cell to cell does that mean it was not getting packaged or does that mean that it wasn't binding
+
+01:48:23.620 --> 01:48:28.980
+in the next passage i think it wasn't binding in the next passage is the right explanation
+
+01:48:28.980 --> 01:48:35.940
+which means that you could make virus from these clones you just have to have a receptive cell type
+
+01:48:35.940 --> 01:48:40.900
+on the other end that's going to do it so they transfected listen carefully they transfected
+
+01:48:41.540 --> 01:48:49.460
+this clone into that cell culture and it packaged virus for them you know it packaged virus because
+
+01:48:49.460 --> 01:48:54.420
+it made the sub-genomic RNAs those were translated into the many many many copies of the proteins
+
+01:48:54.420 --> 01:48:59.860
+and all this stuff happened it's just that when they took the supernatant off of that cell culture
+
+01:48:59.860 --> 01:49:06.180
+and tried to put it on the next cell culture it didn't propagate and that has to do with the spike
+
+01:49:06.180 --> 01:49:11.860
+protein receptor binding domain compatibility with the cell culture that you're using according to
+
+01:49:11.860 --> 01:49:18.020
+their methodology explanation so let's listen to that again because i want you to hear what he did
+
+01:49:18.100 --> 01:49:22.900
+he electroporated it into a cell culture but couldn't get it to jump from cell culture to cell
+
+01:49:22.900 --> 01:49:30.820
+culture which is what culturing is what passaging is clearly there was RNA the cell and we could
+
+01:49:30.820 --> 01:49:36.100
+clone we built the full-on cDNA we drove transcripts electroprated that in the cell and we can see
+
+01:49:36.100 --> 01:49:40.740
+evidence of replication by the synthesis of sub-genomic messenger RNA but we couldn't
+
+01:49:40.740 --> 01:49:45.380
+culture the virus and we couldn't pass it from cell to cell sub-genomic electroprated that and in fact
+
+01:49:45.380 --> 01:49:50.660
+we made this clone we built the full-on cDNA we drove transcripts electroprated that in the cell
+
+01:49:50.660 --> 01:49:55.380
+and we can see evidence of replication by the synthesis of sub-genomic messenger RNA
+
+01:49:55.380 --> 01:49:59.780
+but we couldn't culture the virus and we couldn't pass it from cell to cell so clearly there was
+
+01:49:59.780 --> 01:50:08.740
+probably a defect in entry to solve that problem we use literature data that has suggested that
+
+01:50:08.740 --> 01:50:14.020
+RBD domains of coronaviruses may be interchangeable between species so we took the human
+
+01:50:14.900 --> 01:50:20.580
+the urbani epidemic receptor-bonding domain that's 210 amino acids and went
+
+01:50:21.620 --> 01:50:28.260
+and dropped that into the bat genome backbone producing a chimera with the receptor-bonding domain
+
+01:50:28.260 --> 01:50:33.940
+driven from the epidemic strains now when we built that clone drove transcripts and electroprated
+
+01:50:33.940 --> 01:50:39.140
+that in the cells we got a virus that could replicate quite efficiently this is just some
+
+01:50:39.140 --> 01:50:46.020
+growth curve data showing I think the black box is the urbani wild type and the white circles are
+
+01:50:46.020 --> 01:50:52.980
+open open symbols are the bat viruses you can see they replicate exactly as good as the urbani
+
+01:50:52.980 --> 01:50:58.900
+epidemic strain at low and high multiplicities of infection they recognize the human ACE2 receptor
+
+01:50:58.900 --> 01:51:04.420
+and dbt cells at low and high multiplicity infections and grow just like the epidemic strains
+
+01:51:04.420 --> 01:51:10.020
+and they also retain the ability to use the CIVID ACE2 receptor just like the epidemic strains
+
+01:51:10.020 --> 01:51:16.500
+low and high multiplicity they also are capable of infecting human airway epithelial cultures
+
+01:51:16.500 --> 01:51:21.380
+and targeting ciliated cells just like the epidemic strain and they grow to similar titer
+
+01:51:23.700 --> 01:51:28.740
+now if you make aniseera just against the bat spike like a protein
+
+01:51:29.620 --> 01:51:36.500
+and use that aniseera to target the SARS wild type virus it will not neutralize that virus
+
+01:51:37.220 --> 01:51:43.140
+so clearly aniseera and vaccines derived against epidemic strains are not going to protect against
+
+01:51:43.140 --> 01:51:49.540
+the bat strains to use that same sera against the RBD chimeric virus you can neutralize it
+
+01:51:49.540 --> 01:51:55.220
+indicating that there are neutralizing episodes that resist that exist outside the RBDs and if
+
+01:51:55.220 --> 01:52:00.340
+you take the human monoclonal to target the epidemic strain RBDs you can neutralize these
+
+01:52:00.340 --> 01:52:05.700
+virus with quite efficient so one thing that I think we all need to learn is exactly what neutralized
+
+01:52:05.700 --> 01:52:13.460
+means in this context because I kind of was under the naive operation or operating under the naive
+
+01:52:13.460 --> 01:52:20.580
+assumption that that neutralized means to bind to the receptor binding domains so that the receptor
+
+01:52:20.580 --> 01:52:24.580
+binding domain is not able to interact with the receptor and therefore you don't get
+
+01:52:25.540 --> 01:52:30.420
+infection so I thought that's what neutralizing was but I think neutralizing has more to do with
+
+01:52:30.420 --> 01:52:38.900
+like precipitation and if you get enough antibodies stuck onto you then you come out of out of solution
+
+01:52:38.900 --> 01:52:46.020
+and I'm wondering if it's something like this too like uh aggregation or something like that
+
+01:52:46.020 --> 01:52:51.460
+that causes neutralization and precipitation so I need to learn that a little bit better because
+
+01:52:51.460 --> 01:52:57.860
+I do know that that people like Mark Bailey and and uh Steven Lanka have been working on trying to
+
+01:52:57.860 --> 01:53:02.900
+understand what it is that virologists are meaning with that and I do think that that is something
+
+01:53:02.900 --> 01:53:11.220
+that we should be masters of here as well so I apologize for that so in summary um certainly
+
+01:53:11.220 --> 01:53:15.780
+synthetic genomics and reverse genetics this can be a platform to recover uncultivatable
+
+01:53:15.780 --> 01:53:20.580
+zoonotic precursors can be used to synthesize this is actually the largest synthetic virus
+
+01:53:20.580 --> 01:53:27.540
+to date it's going to be a short record but it is a record um and you can use it now to identify
+
+01:53:27.540 --> 01:53:33.860
+a broad spectrum antiviral from the vaccine clearly the RBDs are interchangeable uh this is with an
+
+01:53:33.860 --> 01:53:40.980
+89 percent amino acid identity within the spike it's the minimal domain required to host shift
+
+01:53:40.980 --> 01:53:46.420
+coronaviruses what is the phylogenetic limits to RBD interchange we actually don't know
+
+01:53:47.620 --> 01:53:52.580
+clearly the human monoclonals and vaccines targeting the SARS RBD would provide protective
+
+01:53:52.580 --> 01:53:56.740
+immunity against natural isolates that emerge that's not my sound the overall process is in
+
+01:53:56.740 --> 01:54:04.500
+future or unfortunately by deliberate design so now I want to move to the next part of the
+
+01:54:04.500 --> 01:54:09.700
+talk which is synthetic the optimization scheme to attenuate SARS coronavirus pathogenesis
+
+01:54:10.580 --> 01:54:16.420
+this is the maturation pathway okay so after as he explains the maturation pathway I want you to
+
+01:54:16.980 --> 01:54:22.340
+imagine that we're trying to solve the puzzle of the infectious cycle as well and then I also
+
+01:54:22.340 --> 01:54:30.820
+want you to listen carefully to the amount of effort time thought and ideas that are going into
+
+01:54:31.620 --> 01:54:42.340
+the attenuation of coronaviruses and a general strategy to attenuate all coronaviruses specifically
+
+01:54:42.340 --> 01:54:50.580
+in the context of recombination and so he's keenly aware that there's a problem with the
+
+01:54:50.580 --> 01:54:56.100
+oral poliovirus vaccine that when you give the oral poliovirus vaccine it can mix with other
+
+01:54:56.180 --> 01:55:03.460
+polioviruses in the gut of people and then become active polio again and he's at least
+
+01:55:03.460 --> 01:55:09.300
+theoretically aware of the possibility that should you make a de attenuated coronavirus like say
+
+01:55:10.100 --> 01:55:17.300
+take out some genes then it would be very easy for that clone that you're using as an attenuated
+
+01:55:17.300 --> 01:55:24.500
+virus to attain that gene to acquire that gene from a co-infection and so what he's going to explain
+
+01:55:24.500 --> 01:55:32.580
+to you is how these translational regulatory sequences can be altered in such a way to prevent
+
+01:55:32.580 --> 01:55:38.500
+recombination with wild type viruses that's his strategy I think it's a pretty cool idea
+
+01:55:39.300 --> 01:55:46.340
+it suggests that these self-replicating RNAs are are some kind of a real biological phenomenon
+
+01:55:47.220 --> 01:55:52.980
+and it suggests that making infectious clones of them is a really handy way of exploring the
+
+01:55:52.980 --> 01:56:01.140
+variation within them that is otherwise un-intractable by laboratory means so here we go again I
+
+01:56:01.140 --> 01:56:07.540
+apologize that this is such a fuzzy thing but I will try to help you follow along way for how
+
+01:56:07.540 --> 01:56:12.500
+far it gets out of the cell the nuclei caps is the line underneath an intermediate compartment
+
+01:56:12.500 --> 01:56:19.140
+in the ruffiardology with a M glycoprotein and the E-protein are expressed and then these the M
+
+01:56:19.140 --> 01:56:24.900
+and the E-protein actually drive the assembly of virion which then mature in the Golgi and then
+
+01:56:24.900 --> 01:56:31.940
+are released in the cell and secretory vesicles which fuse the last membrane. Now if you knock out
+
+01:56:31.940 --> 01:56:39.780
+E-protein expression this pathway is still viable but you reduce virus yields by about two logs
+
+01:56:39.780 --> 01:56:44.900
+and if you knock out the M glycoprotein expression or M and E together you don't make any virus
+
+01:56:45.460 --> 01:56:51.620
+so M protein will stop without the M protein nothing happens the E-protein will still
+
+01:56:52.660 --> 01:56:57.860
+get some viral production I wonder what they mean by that I guess it's just detectable RNA in the
+
+01:56:57.860 --> 01:57:04.100
+supernatant. So our approach to de-optimize SARS
+
+01:57:04.100 --> 01:57:14.740
+coronavirus the SARS coronavirus genome and to attenuate pathogenesis focused primarily on the
+
+01:57:14.740 --> 01:57:21.460
+E and the M glycoprotein genes of about 350 amino acids in total. The strategy we used was to
+
+01:57:21.460 --> 01:57:26.900
+progressively increase the number of de-optimized codons so we started with serine to produce a
+
+01:57:26.900 --> 01:57:34.180
+D-serve virus serine-loosing R gene to produce the SLR de-optimized strain or a five-set DSLR
+
+01:57:34.180 --> 01:57:39.700
+VA strain basically the idea is you create a real stat where you're increasing the number of
+
+01:57:39.700 --> 01:57:44.020
+de-optimized residues and turning down expression of critical proteins needed for release.
+
+01:57:45.220 --> 01:57:50.100
+So that's an interesting strategy right he's changing the codons
+
+01:57:50.420 --> 01:58:00.180
+not changing the codons like to different different amino acids but he's changing the amino acid
+
+01:58:00.180 --> 01:58:08.500
+codons so that they're not as they're not what they were in the virus which he assumes is optimized
+
+01:58:09.460 --> 01:58:16.580
+which I think is a pretty cool thing because the the assumption for the mRNA
+
+01:58:17.220 --> 01:58:27.780
+transfection is that the viral codon selection the the actual codons used by the virus are not
+
+01:58:27.780 --> 01:58:33.380
+important and in fact we can change them to whatever we want so that we get more protein
+
+01:58:34.180 --> 01:58:41.300
+and we can even chemically alter the RNA with M1 pseudo-uridine alteration so that's fine
+
+01:58:41.300 --> 01:58:49.460
+we don't care about that either even though here Ralph Barrick is saying that just by changing
+
+01:58:49.460 --> 01:58:58.260
+these synonymous codons for one or two or five amino acids he can progressively attenuate
+
+01:58:59.460 --> 01:59:05.940
+viral production he can hamper viral production he can handicap the virus just by changing its
+
+01:59:05.940 --> 01:59:13.620
+codons this is pretty antithetical to the idea that Moderna can just change those codons and
+
+01:59:13.620 --> 01:59:20.980
+it doesn't matter at all right that's that's pretty impressive this is just a cartoon to show
+
+01:59:20.980 --> 01:59:26.340
+amino acid sequence and the wild type virus sequence here so like in the three set at the
+
+01:59:26.340 --> 01:59:32.180
+searing residue which was optimal in the case of SARS we just change it to the most
+
+01:59:32.420 --> 01:59:43.460
+rare codon if you look at the statistics here in general in the wild type E and M gene they're
+
+01:59:43.460 --> 01:59:50.420
+about 39 codons that are de-optimized in the one set this increased to 52 the three set 94 and the
+
+01:59:50.420 --> 01:59:58.900
+five set 134 so they're only de-optimizing the codons of the M or the E protein which is even more of a
+
+01:59:58.900 --> 02:00:06.180
+subtle modification think about that so look at the ct ctb values that Eckerd just talked about
+
+02:00:07.140 --> 02:00:09.780
+by these values here so these are very minimally
+
+02:00:13.140 --> 02:00:20.820
+on the negative side of the codon pair usage we also made random controls where we scrambled
+
+02:00:20.820 --> 02:00:25.780
+the codon usage much like Eckerd did retaining the wild type genome organization lightless and we
+
+02:00:25.780 --> 02:00:33.300
+made three set in the five set this is we made these in a mouse adapted background so they would
+
+02:00:33.300 --> 02:00:40.660
+be pathogenic in mice mouse adapted growth is shown here black the blue lines show the searing
+
+02:00:40.660 --> 02:00:47.860
+de-optimized viruses which also reach high titers by about 24 hours post-infection if you look at
+
+02:00:47.860 --> 02:00:52.020
+the three set mutants however you see about a log log and a half reduction as compared to wild
+
+02:00:52.020 --> 02:00:57.940
+type the three set randomized virus and the five set randomized virus in this case i'm showing
+
+02:00:57.940 --> 02:01:03.060
+two different plaques and the five set randomized viruses through just about like wild type so just
+
+02:01:03.060 --> 02:01:07.940
+like Eckerd had reported if you randomized the sequence it really has very little impact on
+
+02:01:07.940 --> 02:01:15.460
+replication but the optimization does affect final yield now in contrast to what Eckerd talked
+
+02:01:15.460 --> 02:01:22.100
+about we actually deoptimized in the middle of the downstream ores which would potentially affect
+
+02:01:23.140 --> 02:01:28.340
+critical sequences that would affect RNA synthesis we're very careful not to knock out any known
+
+02:01:29.140 --> 02:01:35.780
+sequences regulatory sequences that make messenger RNA however both the searing and the SLR mu knocked
+
+02:01:35.780 --> 02:01:40.740
+out messenger RNA six expression which you can see right here these actually were the messages
+
+02:01:40.740 --> 02:01:46.340
+the genes the messages that encode the gene so this is supposed to be a northern blot where
+
+02:01:46.340 --> 02:01:52.820
+the darkness is supposed to show you RNA so this isn't a very clean blot there's an awful lot of
+
+02:01:54.180 --> 02:02:01.540
+what is this i mean holy balls you're not getting a clear signal here certainly i mean
+
+02:02:02.100 --> 02:02:12.020
+i don't know what i see here but that's not what i would expect to see um he's looking for sub-genomic
+
+02:02:12.020 --> 02:02:18.660
+RNAs i guess so this would be the full genome up here i don't know that that's what i would assume
+
+02:02:18.660 --> 02:02:24.580
+um it's two hours and i don't think he's going to say very much i'm just going to leave it go but i'm
+
+02:02:24.580 --> 02:02:28.980
+going to say very much i'm just going to leave it go but i might put it on a little faster and i
+
+02:02:28.980 --> 02:02:36.420
+got to get to bed holy cow it's my birthday today tomorrow so we deoptimized so we actually found
+
+02:02:36.420 --> 02:02:40.020
+some evidence of long-range RNA RNA interactions that are regulatory elements that we're trying to
+
+02:02:40.020 --> 02:02:45.620
+decipher the five set the optimized trains showed no cpe in culture if you develop primaries to the
+
+02:02:45.620 --> 02:02:49.940
+five prime end of the genome and the leader sequence and a primer down here in the message six
+
+02:02:49.940 --> 02:02:53.460
+that encodes work six you can actually identify leader containing transcripts which are signatures
+
+02:02:53.540 --> 02:02:57.060
+of the messenger RNAs that are made during infected cells in these cultures you can see evidence of
+
+02:02:57.060 --> 02:03:02.260
+message seven i'm sorry message six five four and three this is a day one post-transfection
+
+02:03:02.260 --> 02:03:06.020
+even by day ten you can still see these transcripts infected cells and they continue at that level
+
+02:03:06.020 --> 02:03:09.540
+with about five passages at five-day intervals but you actually never can actually develop
+
+02:03:09.540 --> 02:03:13.140
+a virus you can never plaque a virus you can never actually show a virus is there producing cpe
+
+02:03:13.140 --> 02:03:19.140
+so that's interesting so now he's looking at how the RNA signal develops over days of passage
+
+02:03:19.940 --> 02:03:24.580
+and he he shows how the robustness disappears i think that's kind of cool
+
+02:03:25.460 --> 02:03:32.500
+um i don't see a control here though i don't see how the RNA sustains over in days when it's
+
+02:03:32.500 --> 02:03:39.620
+not attenuated that would be a nice control to have here right um anyway i think this is where
+
+02:03:39.620 --> 02:03:45.060
+he's going to end it he's probably just going to close he had deoptimization he's going to show
+
+02:03:45.060 --> 02:03:50.980
+these three different ways that they did it and the sites that they changed and then he shows
+
+02:03:50.980 --> 02:03:58.260
+pathogenesis of these things in the mice he made a mouse adapted version of it for aged mice um
+
+02:03:58.260 --> 02:04:03.220
+it's an it's an it's an oh these are all papers that we've looked at before they're all relevant for
+
+02:04:03.860 --> 02:04:12.900
+the clone discussion because the clone discussion puts us in um the context of the pandemic and
+
+02:04:12.980 --> 02:04:19.300
+trying to explain what's happening here i want to just leave you with the slide that i put up
+
+02:04:19.300 --> 02:04:30.260
+earlier um with regard to alina chan um and kevin mccurnan's objection that uh maybe there should be
+
+02:04:30.260 --> 02:04:37.940
+some some so ask yourself why he's making six-hour scooby-doo videos instead of downloading data
+
+02:04:38.420 --> 02:04:43.700
+from ncbi and find a signal for his hypothesis in real data if the clones offer some advantage
+
+02:04:43.700 --> 02:04:51.620
+for dr evil surely there is evidence of reduced mutation rates to prove this and i would humbly
+
+02:04:51.620 --> 02:04:59.140
+submit that actually alina chan and employee of the broad institute for whom your uh old boss is
+
+02:04:59.140 --> 02:05:04.980
+now the director for quite some time um has data from the beginning of the pandemic that seems to
+
+02:05:04.980 --> 02:05:15.300
+show a much lower mutation rate in the sars 2 sequences than those found during a similar time
+
+02:05:15.300 --> 02:05:22.980
+frame in the sars pandemic which might be the reduced mutation rate you were looking for um
+
+02:05:22.980 --> 02:05:28.340
+we have a long ways to go we got a lot of stuff to talk about but i'm not really worried the reason
+
+02:05:28.340 --> 02:05:32.500
+why i'm not worried is because people have lose in their minds and when people lose their minds
+
+02:05:32.580 --> 02:05:37.380
+it usually means that you're right over the target have never seen so many people lose their
+
+02:05:37.380 --> 02:05:42.900
+mind at once and i've never seen so many people do it that weren't doing it together before
+
+02:05:43.700 --> 02:05:49.460
+um people are coming together and retweeting and talking to one another and patting each other
+
+02:05:49.460 --> 02:05:55.700
+on the back that heretofore have never really interacted in that way before and that's pretty
+
+02:05:56.020 --> 02:06:03.780
+special not only that but it's brought together a few of these dream team members and uh i think
+
+02:06:04.340 --> 02:06:14.500
+the spontaneous sort of confluence of efforts are going to become obvious what everybody's
+
+02:06:14.500 --> 02:06:19.700
+arguing about is we all got to come together because because because i'm making exactly the
+
+02:06:19.700 --> 02:06:24.740
+opposite argument i don't need to come together with anybody because if we are fighting for the
+
+02:06:24.740 --> 02:06:31.140
+same things then our our efforts will buy necessity and buy natural
+
+02:06:32.660 --> 02:06:38.100
+by natural order where they will they will become a confluence of effort toward the same goals
+
+02:06:38.740 --> 02:06:45.540
+my goal is to have our children realize that the vaccine schedule in america is a criminal
+
+02:06:45.540 --> 02:06:52.420
+enterprise my goal is to have our children realize that virology especially RNA virology
+
+02:06:52.420 --> 02:06:58.180
+is wholly dependent on cloning technology and in fact a pandemic could not have occurred in
+
+02:06:58.180 --> 02:07:02.820
+the way that they said it is no matter how much they insist that the sequences are here and not
+
+02:07:02.820 --> 02:07:09.220
+there or that they're real or they're not they are lying about the fidelity and that's all that i
+
+02:07:09.220 --> 02:07:15.940
+can say and and all this this insistence is not good enough they need to start teaching because
+
+02:07:15.940 --> 02:07:21.780
+that's what we're doing that's what we've been doing for three and a half years no one else is doing it
+
+02:07:21.780 --> 02:07:26.100
+just us just here and so if you like what we're doing you like what we've done
+
+02:07:27.060 --> 02:07:32.180
+please support our work go to get your own biological and subscribe share the work if you can
+
+02:07:33.700 --> 02:07:41.940
+we are gaining momentum tomorrow is my birthday but i will be on i'm going to try and be on as
+
+02:07:41.940 --> 02:07:46.500
+often as literally as often as possible i don't know if it's going to be every day or not
+
+02:07:47.380 --> 02:07:53.940
+um but i really am targeting every day but i also have other things that i'm trying to get
+
+02:07:53.940 --> 02:07:59.060
+regular with including the sub stack i don't think i'm going to make a sub stack and transcript of
+
+02:07:59.060 --> 02:08:03.540
+this one but i want to do it for a lot of them and so i don't know if you've noticed it or not but
+
+02:08:03.540 --> 02:08:11.140
+there is a sub stack now the sub stack has videos that are on vimeo um those videos i've added
+
+02:08:11.700 --> 02:08:19.780
+uh i've added subtitles to and so that makes them also kind of um better to watch you can also
+
+02:08:19.780 --> 02:08:23.860
+share them a little bit better the sub stack maybe is a better way to share them because people can
+
+02:08:23.860 --> 02:08:32.340
+scan the the the transcript as well and so wolf gang wodocks interview is up there um my presentation
+
+02:08:32.340 --> 02:08:38.660
+to the uk doctors is up there um and uh i'm just going to keep trying to do it every time i get a
+
+02:08:38.660 --> 02:08:43.860
+stream that i think is good enough or is worthy of it um we're going to do a sub stack on it i
+
+02:08:43.860 --> 02:08:49.460
+don't think i'm going to do this one because tomorrow i'm going to try and do if all goes well
+
+02:08:49.460 --> 02:08:55.460
+i'm going to try and do a pretty decent show tomorrow um but it's a birthday and i've got two
+
+02:08:55.460 --> 02:08:59.460
+basketball games so i don't know there's going to be a show and it's don't know if it's going to be
+
+02:09:00.660 --> 02:09:06.100
+slam-bam crazy show or if it's just going to be an average show like this one was but anyway
+
+02:09:06.820 --> 02:09:12.180
+we've got the momentum going again or at least i got it going tonight and so hopefully i can get
+
+02:09:12.180 --> 02:09:19.540
+some sleep and uh get it going tomorrow again and uh we'll get this this pace up to speed thank you
+
+02:09:19.540 --> 02:09:35.460
+very much for joining me and i will definitely see you again tomorrow
+
+02:09:49.540 --> 02:10:16.020
+i have no responsibility for the current pandemic
+
+02:10:19.540 --> 02:10:20.820
+you
+
diff --git a/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/README.md b/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/README.md
new file mode 100644
index 0000000..b70152d
--- /dev/null
+++ b/twitch/2045872239 (2024-01-27) - Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief/README.md	
@@ -0,0 +1,5 @@
+# Baric 2007 Synthetic SARS (Study Hall) -- (27 Jan 2024) -- Gigaohm Biological High Resistance Low Noise Information Brief
+
+## Streams
+- https://twitch.tv/videos/2045872239
+