SARS-CoV-2 contains part of a patented genetic sequence
frontiersin.org
frontiersin.org
Huh? I just run BLAST (blastn, specifically) with that nucleotide sequence and found several eukaryotic genomes containing it in non MutS-like contexts, aligning sense and anti-sense strands, with 100% coverage and 100% identity. Besides, there is no “BLAST” database (I used the non-redundant -nr- one, for instance; BLAST is just the name of the tool). One possible reason they didn’t find the sequences is that BLAST, by default, only returns the first 100 hits, which in their case might have been prokaryotic ones. I didn’t check viral genomes but might later.
Disclaimer: I know and have used BLAST since my undergrad years, about a decade and a half ago.
BLAST is used on a daily basis by a lot of scientists (its paper is among the most cited of all time), but many of them lack the theoretical knowledge to analyze in depth their results. This paper doesn’t have a single line about methodological details, such as the parameters used in their BLAST runs. The authors don’t even refer to P- or E-values either, despite being prominently displayed on the output table of every run!
Serious virologists went over the furin cleavage site in close detail already and none of them seemed very convinced it was anything but natural in 2020.
Also, stick any 13 bp dna sequence into BLAST and you will find some strange matches if you include the right databases. That this particular 13 base pairs matches some bit of the human genome (inverted, mind you) is not really that surprising.
"Serious virologists" isn't proof.
Which virologists think it's natural, and which think it's unnatural?
Now lets see the data and thorough reasoning by each, and see the rebuttals of each for their opposition's reasoning, etc.
Until this is laid out clearly it's all shallow discussion - that no one should blindly trust or believe.
The above is the scientific process, method.
There clearly isn't consensus yet.
Literally no one, including the authors of this paper, contends the sequence is "unatural".
You realize that their saying "natural" or "unnatural" completely changes what they're saying to the polar opposite, right?
So now clarity is pedantic?
Seriously?
If HN had subreddits there'd be one similar to /r/WatchRedditDie
unatural + n == correctly spelled unnatural
unatural - u == correctly spelled natural
How the hell are you supposed to guess as if the context of viral sequencing is somehow easy to parse correctly?
Furin cleavage sites are rare in coronaviruses, and even rarer in the closest ones to SARS-CoV-2. It's the case that there was a research proposal to put a furin cleavage site into bat coronaviruses to fuck around and find out precisely because they are rare in most classes but conspicuous (and possibly related to pathogenicity) in others (https://www.documentcloud.org/documents/21066966-defuse-prop...).
(Ps i am also a former molecular biologist that worked in gain of function for non pathogenic bioengineering and I used to look at dendrograms to steal ideas from nature to improve enzyme function -- and I was successful: https://jbioleng.biomedcentral.com/articles/10.1186/1754-161...)
Edit: clarified that betacoronaviruses contains SARS-CoV-2, because some armchair analysts don't stop to understand figures
https://en.m.wikipedia.org/wiki/Frontiers_Media
The fact is that the state of research, peer review, and publication in academia is in complete shambles, in my professional opinion. The amount of system gaming in research has lead me to question most publications and claims I see anymore, unfortunately. I know the system, many of pressures / incentives, and I know a lot of the games played to optimize around these. It's impossible to be any bit lazy and give into any semblance of authoritative findings anymore unless you too just want to play the publication ranking game to stay afloat or get ahead in your career.
We need a massive overhaul of research culture in the US, IMHO.
While Wikipedia has never been a source, the particular linked wiki page clearly links to multiple controversies in the footnotes. Take a look starting at [37] https://en.m.wikipedia.org/wiki/Frontiers_Media#cite_note-37
A relatively newer policy implemented through their MediaWiki project is a "feature" whereby an edit can be permanently hidden from view, so future editors cannot go back and see what edits were removed or reverted. This goes completely against the original concept of a wiki and bolsters my claims that Wikipedia should never be used as a source because in the most contentious articles they will hide removed edits containing information they don't like.
The result of this is editors who have contradicting opinions from the Wikipedia-approved opinion will stop editing simply because it isn't worth the effort as Wikipedia always wins (because it is Wikipedia's website).
Wikipedia is a dumpster fire full of bias, pettiness, and structured manipulation. Linking there or using those pages demonstrates laziness and a near complete lack of higher reasoning.
If you throw the baby out with the bath water, you lose the good parts of something as well as the bad parts, because you reject it as a whole instead of just removing what is bad. [2]
The meaning is that you were throwing out the clear links in the wiki article due to them being presented at wikipedia.org. Footnote 37 and onwards.
[1] https://www.dictionary.com/browse/throw-out-the-baby-with-th...
[2] https://www.collinsdictionary.com/dictionary/english/to-thro...
Your points do not acknowledgement this central thesis. Wikipedia is garbage, using it as a base of aggregated links is ignorant or naive.
To put it more bluntly: I don't care about the opinions you express regarding this topic, as you are demonstrating very arrogant behavior, particularly in linking to a dictionary dot com article on a common English phrase, as if I've demonstrated some lack of understanding in English require some assistance there. Then completely ignoring my points. You are terrible at discussion.
We are done.
https://www.projectveritas.com/news/military-documents-about...
DoD analysts letter: https://assets.ctfassets.net/syq3snmxclc9/2mVob3c1aDd8CNvVny...
Whoa, that says a lot about what kind of scientist you are ...
I have a published paper under the "Frontiers in" brand and can assure you that the people behind it (staff and editors) are among the most professional in what they do. "Frontiers in" does not publish fringe science, they are quite rigorous in their process.
Also the paper is written by quite reputable people and backed by several institutions. If their claims were "stupid" (as you arrogantly put it) they would have spotted it before you, trust me.
http://retractiondatabase.org/RetractionSearch.aspx#?jou%3df...
That's actually quite a good record for a publisher with 80 or so journals and ~270,000 published papers.
Edit: you're right @flobosg, I was looking at another comment with a similar username and my mind just squashed them together :P.
You are confusing me with someone else.
It seems the presence of the furin cleavage site in any other Coronavirus would be enough to invalidate this paper’s comparison to pure random chance.
Why would the authors misuse statistics comparing this to random chance when there are published examples of the furin cleavage site appearing elsewhere? It doesn’t make any sense.
I do not see the substack author among the paper authors or references to that writeup. I wonder if there was any collaboration or if this was an independent finding?
That substack made the rounds here about 5 weeks ago. While it was heavily critiqued for being a rather poor writeup, there was a fair bit of discussion about the observation itself that should be relevant here: https://news.ycombinator.com/item?id=29938732
I have a close friend who works w/ population genetics and basically does phylogenies all day. For those who don't know, a phylogeny is an analysis where you study how similar/dissimilar are sequences between known things in order to infer what are the most plausible evolutionary relationships that (could have) happened.
So, this friend of mine has been taking a look at some of the published sequences ever since they came out and his personal conclusion is that there is no way that SARS-CoV-2 came to be in a "natural" way.
Among other interesting things, he claims that the virus does not seem to have a single "origin". I'll try to explain, so while you're figuring out what the "history" of something is (i.e. ancestors, lineage), you usually get some sort of tree-like arrangement where some structural rules are strongly (but not completely) preserved, like if A -> B and B -> C then A -> C, you get the idea. In SARS-CoV-2's case, such rules (or lack thereof) suggest that different regions of the sequence cannot be assumed to have followed the same evolutionary history; which is kind of weird, honestly. This is something that has been observed naturally, but under very specific constraints which are unlikely to apply to SARS-CoV-2 and how it has spread throughout the world.
Anyway, I'm happy that these sort of studies are finally coming to light and that, for whatever reason, people are now allowed to talk about it. The whole point of science is to engage in rational discussion and build on each other's knowledge in order to attain the truth.
PS: I have degrees in Genomics and Molecular Biology, and have worked for around 15 years on the field.
Sure, but that can also indicate it's a virus resulting from natural stitching together of DNA sequences from multiple infections in one living host, like HIV.
How do we disambiguate novel virus arising from multi-infection interference from human synthesis?
Best you can do is work with probabilities and try to infer which theory is more plausible than others.
This is because of recombination, which is extremely common among coronaviruses.
If you look at the phylogenetics of the relatives of SARS-CoV-2 (forget about SARS-CoV-2 for a moment), you get different trees if you look at different genes. Did the Wuhan Institute of Virology engineer all the different viruses found in nature in bats? That's the conclusion your friend would have to draw, based on the logic you've presented.
I don't like "this is very rare"
How rare?
It's a database. Query it, and confidently give numbers to support your statement.
Zero other exact matches, in the database.
An n of 1 has infinite variance. The relevant rarity, though is not the database, but rather "in the universe of viral sequences. The database biases for sequences that we've sequences, so at best you can give a really shitty estimate.
Fwiw I believe the story that this was a stack overflow copy-paste operation from the moderna sequence, but I can only ever call this a strong belief[0], with no numbers behind it, unless someone comes forward and admits having done it.
[0] why strong? Because it follows the scientific method. If the hypothesis is that it's a lab leak, then your prediction is that existing sequences would bleed through. A bit crazy that we only found this now, hell I could have done this blast search years ago, but it is what you would expect to find.
https://www.washingtonpost.com/archive/politics/2001/03/30/f...
https://web.archive.org/web/20200212011902/http://english.wh...
2017 conference at (Wuhan Institute of a virology) with gain of function research being top priority:
http://web.archive.org/web/20200221213643/http://english.whi...
Ecohealth Alliance partnership:
https://web.archive.org/web/20210323171425/http://english.wh...
US Gov from state department:
http://web.archive.org/web/20210116001621/https://www.state....
EcoHealth Alliance Peter Daszak discussing gene editing in coronaviruses in december 2019 - https://www.youtube.com/watch?v=5-Y843FFJvI
Can someone tell me what the real implications of this are, and what the totally reasonable explanations might be?
That seems like a pretty small number.
In an "average" COVID-19 infection course in an adult human, it is estimated that at peak infection a person has 10^9 to 10^11 virion particles in their body alone. Multiply by the all the people infected, + all the animals, + parallel gene transfer with other viruses in the ecosystem...
Going back and finding the “odds” of an event that already happens is mostly meaningless. Extremely unlikely things happen constantly, see any particular game of poker.
What I think would have been at stat that would be interesting is what are the odds of ANY patented sequence appearing in this genome.
Imagine this same analogy for computer programs. Instead of genetic code, considers bits. Some author without understanding of how code works finds a small matching bit sequence in two different executables, then implies that the shared sequence is evidence of some conspiracy.
As a programmer you’d know that the bits of a program aren’t random because they actually do something specific for the programs execution, so it’s not surprising that different programs would share short bit sequences. But someone who doesn’t understand programming might assume it’s legitimate evidence of a conspiracy.
Same thing is happening here. Genetic code isn’t random because it corresponds to specific functions. It’s not surprising that different viruses would end up sharing bits of genetic sequence if they have similar functions.
The author is misusing statistics for random distributions on something that isn’t random. Don’t take them seriously.
Yeah... I don't need statistics for that one. The bloody tooling speaks, and the chart of human agency/interest speaks for itself. To be honest, ai find it amazing the backflips people are doing to justify that there's no possible way that an interested grad student with the right tools would have tried something like this.
I'd have. Of course I avoid doing science in those types of areas because Murphy finds a way.
A somewhat more honest question would be to look at what they did, which is look at a length 12 sequence (and it's complement) that they apparently found interesting and see if it showed up in a library of 24712 sequences with an average length of 3300.
You can estimate this probability by calculating the average number of matches you'd expect to find. This can be done by taking the number of positions a match could be in, approximately 24712*3300 - 24712*11, times 2 to account for its complement showing up, and multiply this by the chance two length 12 sequences will match, estimated by them at (1/4)^12 (in reality this probability should probably be higher since base pairs aren't uniformly random). Since this is an expected value we can ignore that matches at adjacent positions aren't independent.
This suggests you'd expect to find about 10 matches. So I'm not sure if they simply picked the longest one or if there was just the 1 match. You do get a lowish number of 0.000059 of matching sequences of length 19, that said this chance would be significantly higher when you know there exists a match of length 12, especially if the sequences aren't simply uniformly random.
Basically: please be careful here, a lot of people are going to want to treat this as a smoking gun, and it's not. It sure is interesting though.
Is this more like a naturally occurring sequence that has been documented before, isolated, and then claimed by the team that isolated it?
MolBio 102 for software engineers: each amino acid is coded for by 3 RNA bases. However, the number of possible RNA triplets (4^3=64) is greater than the number of amino acids (20), so some amino acids have multiple triplets assigned to them. For instance, both UUA and CUG code for the same amino acid (leucine), but one of them is more efficient to express. The implicit argument is that consistent preferential use of these optimal codons is evidence of genetic engineering rather than natural evolution.
This is just going to feed more conspiracy theory nutters.
First, a 1 in a 100 billion chance is absolutely nothing. There have been hundreds of millions of infections in humans, each representing billions upon billions of replications of the virus. Every replication carries the chance of mutation. Given that,
Second, mutations, whether random or not, are subject to selective pressure and incremental progress. A mutation that moves a sequence just slightly in the right direction, coding for a slightly different but close protein, will be selected for. Basically, evolution optimizes some structures (and therefore sequences) by hill climbing, accepting mutations that improve fitness and discarding mutations that don't. It doesn't roll all the dice at once and start over every time.
This article is of course based on an early sequence of SARSCov2, from before the pandemic spread.
Which means you didn't even begin to understand the question before spouting off, and everything you say on this subject can be disregarded. Do better.
Which apparently had never replicated before and thus was not subject to evolution...? My point was just to illustrate how many trillions of replications happen for viruses in the wild. 100 billion is absolutely nothing for biology.
The snide ad hominem that makes up the rest of your comment doesn't belong here. If you had just left it out, this would be a conversation and not an unnecessary source of anger and stress.
You came straight out the gate with "conspiracy nutters", then typed two paragraphs of misleading nonsense which did nothing to further the conversation.
This isn't a dialogue, this is me tagging you for other's sake as someone to ignore on this subject. Which is an important subject.
I stand by everything I wrote. It will definitely feed the conspiracy theory people. I was on r/conspiracy last night and saw a link to a similar article that had identified the stop sequence of the Moderna vaccine, part of the non-protein-coding RNA, as a patented sequence. Well, of course the stop sequence could be patented. It's non-coding DNA. The comments were filled with totally bizarre ranting by people who literally had no understanding.
> two paragraphs of misleading nonsense
Wonderful dynamic here. If you want to actually engage with the ideas I wrote above, please do, but I'd rather assert that the entirety of what you have written here is subtractive and unhelpful. And you're literally and by your own omission not trying to "further the conversation" but stamp it out and have literally zero constructive dialog to offer other than "this person is crazy."
> This isn't a dialogue
So good, please don't continue to reply then. There's [-] for you to click on. You're welcome to downvote. It'll be less effort than firing off half-cocked, completely misunderstanding what I wrote, and creating a stinky atmosphere which devalues all of HN.
[0]: https://old.reddit.com/r/science/comments/sysag6/msh3_homolo...
https://seqdata.uspto.gov/?pageRequest=viewSequence&DocID=US...
What has to be done with this scientific paper, from a scientific journal is to read it, maybe go to scholar.google.com to look for its references or other sibling papers. And maybe go to science.reddit.com askscientists.reddit.com or any other internet forum were people educated in the subject interact, to get some good quality dialogue.
Over here at HN? we are just speculating.
In this case, it’s accurate to say that the same sequence found in SARS-CoV-2 is indeed found in a patent. That’s valid and accurate.
The claim that the occurrence is an impossibly unlikely random chance is the flawed part, though. Generic fragments aren’t actually random because they correspond to actual functions of the virus, and it shouldn’t be surprising that viruses with similar functions have similar genetic code fragments.
It’s like if someone examined the binaries of two executables from different companies, identified a small sequence of bits that was common to both, then tried to imply that they were secretly written by the same author because it’s statistically unlikely for that random sequence of bits to appear twice. As a programmer you’d immediately dismiss the claim because that small sequence of bits could be common code like a standard library part or a common algorithm. But the claim may appear to be proof of a conspiracy to the uneducated.
That’s basically what’s going on with this article, but swap bits for genetic code.
But people keep falling back on political arguments which have nothing more compelling than an argument from some authority. Programmers can see that the media and govt lies when there is a “hack” which was just a result of poor management, and extend that to literally anything reported on by the news.
There is a QTQTN deletion in circulating SARS-CoV-2 at the flanking region at 675-679 which has been observed in circulating human strains at the level of a few percent along with mouse-adapted strains. RmYN02 is closer in nucleotide sequences to those variants of SARS-CoV-2 than to ancestral (the SARS-CoV-2 variants carrying that deletion not show in that figure).
If there are variants of RmYNO2 which retain the QTQT sequence at 675-679 then that virus would be one amino acid insertion away from a functioning QTQTNSPRAAR FCS sequence. Then flipping another amino acid would give the SARS-CoV-2 sequence. The relative probably would be discovered with a higher level of surveillance and sequencing of sarbecoviruses in wildlife.
And the rest of the argument in this paper is some weird genetic numerology.
It was something to consider last summer but now it is a dangerous idea again.
We have become such a total joke intellectually.
However, that's all speculation, not fact.
> 14. The method of claim 13, wherein the route of administration is intramuscular
This does not match how sars-cov-2 is administered
I'm thinking about certain mathematically expressed concepts and ideas which are nonetheless patented and treated as property nowadays; I don't see why DNA would be any different.
It's silly for anybody to "own" (with the exclusivity, royalties deserving modern way it is being done) a gene sequence.
I think that whomever has it already owns it and these things can and in reality are non-exclusively owned. because what is next? "oh you have so and so patented genes hence you must pay the owners royalties?"
I like thinking about who really owns the English (or any natural) language to try and makes sense of how it ought to be....
then again who wouldn't like to come up with some idea and then keep getting paid for this until they die? this is similar to rent-seeking, it is rent-found.
This is exactly how new plant foods are created. Here is a potato as an example:
https://ctl.cornell.edu/wp-content/uploads/plants/Cornell_po...
His company M-Cam is copied all the patents in the world, and making intelligence reports based on that.
They made an analysis about all the DNA sequences of SARS-CoV-2, and came to the conclusion that it was manipulated by man.
Someone would have to request them the scripts and the patents to be able to reproduce their assessment. Which was flagged as 'complotist'.
https://un-denial.com/2021/07/20/dr-david-martin-covid-is-a-...