Let Uncle Ralph educate you
Synthetic Viral Genomics:
Risks and Benefits for Science and Society
These enzymes can be used to create unique interconnecting junctions, which can be subsequently removed from final assembly product allowing seamless reconstruction of an exact sequence
The pathogenicity of these chimeric coronaviruses is unknown
The pathogenicity of these chimeric coronaviruses is unknown
The pathogenicity of these chimeric coronaviruses is unknown
This powerful technique provides bioterrorists with a “scapegoat” option; leaving a sequence signature that misdirects efforts at tracking the true originators of the crime. Even better, the approach could be used to build mistrust &/or precipitate open warfare
Hence Ecohealth DARPA/DTRA spooks & virus thieves collaboration with Baric (UNC) Lipkin (Mailman) NIchols (Atlanta CDC) and USAMRIID (Bavari, Totura et al) & Jonathan Epstein's palpable concern about dual use references in the @USRightToKnow FOIA emails
Delving into the cold and calculating mind of a twisted genius?
https://t.co/MrwxYK93cx
Bring Uncle Ralph and his transgenic mice in for questioning!
unroll @threadreaderapp
https://t.co/rjNZ8aDNDl
1. Synthetic Genomics: Options for Governance (2008) https://t.co/A32jEfL1TQ
2. Sequence Screening - Robert Jones (2005)
https://t.co/zOqMroYbVU
3. Synthetic Biology as a Field of Dual-Use Bioethical Concern - Alexander Kelle
https://t.co/Va1movPqvs
4. Sanghvi Y. A Roadmap to the Assembly of Synthetic DNA from Raw Materials.
https://t.co/4kWu4vzcXC
5. Collett MS. Impact of Synthetic Genomics on the Threat of Bioterrorism with Viral Agents.
https://t.co/OcaTmuCUBy
6. Fleming DO. Risk Assessment of Synthetic Genomics: A Biosafety & Biosecurity Perspective.
https://t.co/JBcLVLr005
7. Risk Governance of Synthetic Biology
https://t.co/9BE9X5s0Fb
8. US Competitiveness in Synthetic Biology
https://t.co/OCZJdsXSjl
9. Ensuring security of synthetic biology
https://t.co/7kPE1OpbrS
10. Synthetic biology: emerging research field in China
https://t.co/T3BcaDvUsa
11.
What rough beast? Synthetic biology, uncertainty,& the future of biosecurity (2016)
https://t.co/XTlBXILEWh
Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus (2003)
https://t.co/k8PI1rbcm8
Systematic Assembly of a Full-Length Infectious Clone of Human Coronavirus NL63 (2008)
https://t.co/bWhAv1wsC0
In 2016, Shi and her team at the WIV, in conjunction with the New York-based EcoHealth Alliance, constructed a full-length clone of a bat coronavirus called SL-CoV WIV1. They assembled it in discrete segments.
“Thus, several options exist to remove the desired insert DNA with a single restriction digestion.”
This shows that researchers at the WIV have the ability to genetically engineer viruses and remove the signatures of the genetic engineering.
They showed how they can insert new spikes into viruses. The researchers state:
“Then any spike could be substituted into the genome of SARSr-CoV WIV1 through this strategy.”
COVID 19: The Spike and the Furin Cleavage
https://t.co/bDOMmhpJ1t
More from Billy Bostickson 🏴👁&👁 🆓
@EricTopol @NBA @StephenKissler @yhgrad B.1.1.7 reveals clearly that SARS-CoV-2 is reverting to its original pre-outbreak condition, i.e. adapted to transgenic hACE2 mice (either Baric's BALB/c ones or others used at WIV labs during chimeric bat coronavirus experiments aimed at developing a pan betacoronavirus vaccine)
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 30, 2021
"we generated a mouse model expressing hACE2 by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young & aged hACE2 mice sustained high viral loads... pic.twitter.com/j94XtSkscj
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
1. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2!
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 2, 2021
2 papers:
Human\u2013viral molecular mimicryhttps://t.co/irfH0Zgrve
Molecular Mimicryhttps://t.co/yLQoUtfS6s https://t.co/lsCv2iMEQz
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o
1/ Directed Evolution and Serial passage of RNA Viruses
A quick (I hope) thread on RNA viruses & some others, mainly for my own learning process, but also as evidence (as if it was needed) of what modern virology & microbiology is capable of doing to viruses in their laboratories
2/ In Vivo Continuous Directed Evolution
1 Recent advances in the field of in vivo continuous evolution
2 Advances in continuous culture of microbes enable continuous evolution
3 Viruses, prokaryotes, & eukaryotes mediate in vivo continuous evolution
https://t.co/BfR0B2Hwsf
3/ Continuous Directed Evolution of Biomolecules
By greatly accelerating laboratory evolution, PACE may provide solutions to otherwise intractable directed evolution problems and address novel questions about molecular evolution.
https://t.co/G3mIptI54H
4/ CDE for Strain & Protein Engineering
Inducible hypermutator systems accelerate strain evolution without compromising genome integrity.
Site-specific in vivo mutagenesis strategies have facilitated continuous protein engineering.
Automation
5/ Targeted mutagenesis:
A sniper-like diversity generator in microbial engineering
https://t.co/wdKyXghRYe
Advances in the directed evolution of proteins
https://t.co/1xXTtw1i3i
In vivo continuous directed evolution
https://t.co/xKRVSjVvo4
A quick (I hope) thread on RNA viruses & some others, mainly for my own learning process, but also as evidence (as if it was needed) of what modern virology & microbiology is capable of doing to viruses in their laboratories
2/ In Vivo Continuous Directed Evolution
1 Recent advances in the field of in vivo continuous evolution
2 Advances in continuous culture of microbes enable continuous evolution
3 Viruses, prokaryotes, & eukaryotes mediate in vivo continuous evolution
https://t.co/BfR0B2Hwsf
3/ Continuous Directed Evolution of Biomolecules
By greatly accelerating laboratory evolution, PACE may provide solutions to otherwise intractable directed evolution problems and address novel questions about molecular evolution.
https://t.co/G3mIptI54H
4/ CDE for Strain & Protein Engineering
Inducible hypermutator systems accelerate strain evolution without compromising genome integrity.
Site-specific in vivo mutagenesis strategies have facilitated continuous protein engineering.
Automation
5/ Targeted mutagenesis:
A sniper-like diversity generator in microbial engineering
https://t.co/wdKyXghRYe
Advances in the directed evolution of proteins
https://t.co/1xXTtw1i3i
In vivo continuous directed evolution
https://t.co/xKRVSjVvo4
Smoking Chinese Anomalies!
@interne41914499 compares the influenza diagnosis & treatment plan by China NHC on 13 Nov 2019 with the 2018 plan.
Medical staff training manuals for influenza were also issued & included similar changes between 2019 &
Taking this research as a starting point, I will look at the people responsible for drafting the influenza plan in 2019
1. The National Health Commission (NHC)
国家卫生健康委员会
Guójiā Wèishēng Jiànkāng
2. Cabinet-level executive department of State Council which is responsible for formulating health policies in Mainland China.
Formed on 19 March 2018.
Its predecessor was the National Health and Family Planning Commission.
Here is the leadership list:
https://t.co/0vJRvbxjMl
Boss is Ma Xiaowei
Current Minister in charge of the Commission and Party Branch Secretary.
https://t.co/Ldcfuve0N0
https://t.co/L1QDdVSRXY
https://t.co/yZtCjLPApI
https://t.co/DSlwXgl3cw
Ma Xiaowei sucks Xi's dick for
In memo discussed here:
https://t.co/TPWey3oKFd
Ma demanded officials unite around Xi because social stability was priority in the lead up to the upcoming March CCP State Meetings:
Emphasize politics!
Emphasize discipline!
Emphasize science!
Avoid causing panic among the masses!
@interne41914499 compares the influenza diagnosis & treatment plan by China NHC on 13 Nov 2019 with the 2018 plan.
Medical staff training manuals for influenza were also issued & included similar changes between 2019 &
Taking this research as a starting point, I will look at the people responsible for drafting the influenza plan in 2019
1. The National Health Commission (NHC)
国家卫生健康委员会
Guójiā Wèishēng Jiànkāng
2. Cabinet-level executive department of State Council which is responsible for formulating health policies in Mainland China.
Formed on 19 March 2018.
Its predecessor was the National Health and Family Planning Commission.
Here is the leadership list:
https://t.co/0vJRvbxjMl
Boss is Ma Xiaowei
Current Minister in charge of the Commission and Party Branch Secretary.
https://t.co/Ldcfuve0N0
https://t.co/L1QDdVSRXY
https://t.co/yZtCjLPApI
https://t.co/DSlwXgl3cw
Ma Xiaowei sucks Xi's dick for
In memo discussed here:
https://t.co/TPWey3oKFd
Ma demanded officials unite around Xi because social stability was priority in the lead up to the upcoming March CCP State Meetings:
Emphasize politics!
Emphasize discipline!
Emphasize science!
Avoid causing panic among the masses!
1. The mysterious case of Eddie Holmes and the SARS-COV-2 genome sequence publication delay
https://t.co/ahWcudTbxd
Seems that Eddie was playing the "innocent card"
@TheSeeker268 @franciscodeasis @ydeigin @AntGDuarte @edwardcholmes @K_G_Andersen
2. Was the motive of https://t.co/nu7hNVhiwP’s rush release due to competition to get the first releaser credit for the sars-cov-2 genome?
3. @GISAID claims 'the access credentials of some of the persons listed as authors of Wuhan-hu-1 were among the access credentials used on January 10, 2020 to access the first genomes available on GISAID'
4. @GISAID formally wrote to the authors who acknowledged Virological,org’s post as the world's first release of the SARS-COV-2 genome, and penalised the authors of MN908947
5. but @GISAID didn't identify who exactly from Fudan University or University of Sydney ACCESSED and KNEW about IVDC's 'initial' submission of IVDC-01/05 on GISAID on 10th Jan, 2020, via login records of their GISAID account credentials.
https://t.co/ahWcudTbxd
Seems that Eddie was playing the "innocent card"
@TheSeeker268 @franciscodeasis @ydeigin @AntGDuarte @edwardcholmes @K_G_Andersen
Edward Holmes on being asked why they didn't release the SARS-CoV-2 genome when they got it: "...essentially there were instructions that there's no publicizing the outbreak, so we kept it to ourselves, we told the key people in China..but we were told not to release the data..." pic.twitter.com/mAGUUrsiet
— The Seeker (@TheSeeker268) April 9, 2021
2. Was the motive of https://t.co/nu7hNVhiwP’s rush release due to competition to get the first releaser credit for the sars-cov-2 genome?
3. @GISAID claims 'the access credentials of some of the persons listed as authors of Wuhan-hu-1 were among the access credentials used on January 10, 2020 to access the first genomes available on GISAID'
4. @GISAID formally wrote to the authors who acknowledged Virological,org’s post as the world's first release of the SARS-COV-2 genome, and penalised the authors of MN908947
5. but @GISAID didn't identify who exactly from Fudan University or University of Sydney ACCESSED and KNEW about IVDC's 'initial' submission of IVDC-01/05 on GISAID on 10th Jan, 2020, via login records of their GISAID account credentials.
More from Science
Recently I learned something about DNA that blew my mind, and in this thread, I'll attempt to blow your mind as well. Behold: Chargaff's 2nd Parity Rule for DNA N-Grams.
If you are into cryptography or reverse engineering, you should love this.
Thread:
DNA consists of four different 'bases', A, C, G and T. These bases have specific meaning within our biology. Specifically, within the 'coding part' of a gene, a triplet of bases encodes for an amino acid
Most DNA is stored redundantly, in two connected strands. Wherever there is an A on one strand, you'll find a T on the other one. And similarly for C and G:
T G T C A G T
A C A G T C A
(note how the other strand is upside down - this matters!)
If you take all the DNA of an organism (both strands), you will find equal numbers of A's and T's, as well as equal numbers of C's and G's. This is true by definition.
This is called Chargaff's 1st parity rule.
https://t.co/jD4cMt0PJ0
Strangely enough, this rule also holds per strand! So even if you take away the redundancy, there are 99% equal numbers of A/T and C/G * on each strand *. And we don't really know why.
This is called Chargaff's 2nd parity rule.
If you are into cryptography or reverse engineering, you should love this.
Thread:
DNA consists of four different 'bases', A, C, G and T. These bases have specific meaning within our biology. Specifically, within the 'coding part' of a gene, a triplet of bases encodes for an amino acid
Most DNA is stored redundantly, in two connected strands. Wherever there is an A on one strand, you'll find a T on the other one. And similarly for C and G:
T G T C A G T
A C A G T C A
(note how the other strand is upside down - this matters!)
If you take all the DNA of an organism (both strands), you will find equal numbers of A's and T's, as well as equal numbers of C's and G's. This is true by definition.
This is called Chargaff's 1st parity rule.
https://t.co/jD4cMt0PJ0
Strangely enough, this rule also holds per strand! So even if you take away the redundancy, there are 99% equal numbers of A/T and C/G * on each strand *. And we don't really know why.
This is called Chargaff's 2nd parity rule.
Hard agree. And if this is useful, let me share something that often gets omitted (not by @kakape).
Variants always emerge, & are not good or bad, but expected. The challenge is figuring out which variants are bad, and that can't be done with sequence alone.
You can't just look at a sequence and say, "Aha! A mutation in spike. This must be more transmissible or can evade antibody neutralization." Sure, we can use computational models to try and predict the functional consequence of a given mutation, but models are often wrong.
The virus acquires mutations randomly every time it replicates. Many mutations don't change the virus at all. Others may change it in a way that have no consequences for human transmission or disease. But you can't tell just looking at sequence alone.
In order to determine the functional impact of a mutation, you need to actually do experiments. You can look at some effects in cell culture, but to address questions relating to transmission or disease, you have to use animal models.
The reason people were concerned initially about B.1.1.7 is because of epidemiological evidence showing that it rapidly became dominant in one area. More rapidly that could be explained unless it had some kind of advantage that allowed it to outcompete other circulating variants.
Variants always emerge, & are not good or bad, but expected. The challenge is figuring out which variants are bad, and that can't be done with sequence alone.
Feels like the next thing we're going to need is a ranking system for how concerning "variants of concern\u201d actually are.
— Kai Kupferschmidt (@kakape) January 15, 2021
A lot of constellations of mutations are concerning, but people are lumping together variants with vastly different levels of evidence that we need to worry.
You can't just look at a sequence and say, "Aha! A mutation in spike. This must be more transmissible or can evade antibody neutralization." Sure, we can use computational models to try and predict the functional consequence of a given mutation, but models are often wrong.
The virus acquires mutations randomly every time it replicates. Many mutations don't change the virus at all. Others may change it in a way that have no consequences for human transmission or disease. But you can't tell just looking at sequence alone.
In order to determine the functional impact of a mutation, you need to actually do experiments. You can look at some effects in cell culture, but to address questions relating to transmission or disease, you have to use animal models.
The reason people were concerned initially about B.1.1.7 is because of epidemiological evidence showing that it rapidly became dominant in one area. More rapidly that could be explained unless it had some kind of advantage that allowed it to outcompete other circulating variants.
