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to someone who doesn’t know anything about the relevant science (me) the use of the word “insertions” seems to imply this was engineered. Can someone who actually understands this explain what this document is saying?
Insertions can occur naturally.

https://en.wikipedia.org/wiki/Insertional_mutagenesis

> Because many viruses integrate their own genomes into the genomes of their host cells in order to replicate, mutagenesis caused by viral infections is a fairly common occurrence. Not all integrating viruses cause insertional mutagenesis, however.

This paper does seem to allege that these particular sets of insertions aren't via natural causes, though.

There could be naturally occurring insertions, but they would generally look similar to an associated coronavirus, or something else local, not 4 discrete changes that are all nearly identical to a (very well studied) virus that should be completely unrelated..
Well, the conclusion of this paper is that the odds of this virus coming to be naturally are very small. Which is a very scientific way of saying "we think this was man-made".

But, that is what the paper is saying. Extraordinary claims, extraordinary evidence is what I think. I feel the evidence here is quite small, but I'm not a bio-data-scientist.

Is it an extraordinary claim? The sequence matching should be easy to verify as the genome has been published. If the sequences are short or common enough maybe it would be a more likely coincidence.

That said: What are the priors on a "natural" virus erupting in the only city in China with a level 4 biohazard facility?

Source: http://english.www.gov.cn/state_council/ministries/2018/01/0...

So if it's not extraordinary it's still going to require evidence, which without peer review we still pretty much have none.
This is evidence, but it requires corroboration from other evidence. Peer review doesn't provide additional evidence - it's just a sober second opinion that lends credence (or not) to the proposed evidence and interpretation.

Just wanted to clarify the language here.

Totally right - and thank you for the clarification in language.
Indeed, the paper seems to suggest that the natural occurrence of this virus is the extraordinary claim.
> This indicates that these insertions have been preferably acquired by the 2019-nCoV, providing it with additional survival and infectivity advantage. Delving deeper we found that these insertions were similar to HIV-1. Our results highlight an astonishing relation between the gp120 and Gag protein of HIV, with 2019-nCoV spike glycoprotein. These proteins are critical for the viruses to identify and latch on to their host cells and for viral assembly (Beniac et al., 2006). Since surface proteins are responsible for host tropism, changes in these proteins imply a change in host specificity of the virus. According to reports from China, there has been a gain of host specificity in case 2019-nCoV as the virus was originally known to infect animals and not humans but after the mutations, it has gained tropism to humans as well.

> Our analysis of the spike glycoprotein of 2019-nCoV revealed several interesting findings: First, we identified 4 unique inserts in the 2019-nCoV spike glycoprotein that are not present in any other coronavirus reported till date. To our surprise, all the 4 inserts in the 2019-nCoV mapped to short segments of amino acids in the HIV-1 gp120 and Gag among all annotated virus proteins in the NCBI database. This uncanny similarity of novel inserts in the 2019- nCoV spike protein to HIV-1 gp120 and Gag is unlikely to be fortuitous. Further, 3D modelling suggests that atleast 3 of the unique inserts which are non-contiguous in the primary protein sequence of the 2019-nCoV spike glycoprotein converge to constitute the key components of the receptor binding site. Of note, all the 4 inserts have pI values of around 10 that may facilitate virus-host interactions. Taken together, our findings suggest unconventional evolution of 2019-nCoV that warrants further investigation. Our work highlights novel evolutionary aspects of the 2019-nCoV and has implications on the pathogenesis and diagnosis of this virus.

So, maybe, maybe not. What's the likelihood of natural occurences resulting in these inserts ? Are these novel evolutionary aspects natural or engineered ?

Can't outright say "It was made in a lab" but can say "Something's new here".

A thread by an epidemiologist on the new results:

https://twitter.com/DrEricDing/status/1223305946723704832

What are the geopolitical ramifications if this is indeed a bioweapon?
Perhaps the US and EU will put aside squabbles caused by the trade war to have a united front against China?
I don't think it will be talked about in that way. Especially if this is a bioweapon created in China which accidentally escaped. No one wants the dirty laundry spilled of all the countries who are doing bioweapon research. China is too powerful economically and surely has too much dirt on everyone else to go down alone. So I believe the official position will be that it's either not engineered at all ("inconclusive"), or just an unfortunate accident related to legitimate non-weapon research. Worst case scenario is US, EU, etc. do a little finger wagging that China needs to "stop eating bats" and then it will be let go. Of course, that's just the official/public position.
China is a signatory to the Biological Weapons Convention [1]. The US State Department regularly issues a compliance report about it (and other international agreements). Here [2] is how it summarized China's compliance in August 2019:

"Information indicates that the People’s Republic of China (China) engaged during the reporting period in biological activities with potential dual-use applications, which raises concerns regarding its compliance with the BWC. In addition, the United States does not have sufficient information to determine whether China eliminated its assessed biological warfare (BW) program, as required under Article II of the Convention."

(That's followed by some more details, which you can read about in [2].)

Given this ongoing scrutiny, it would be very surprising if a smoking gun that the PRC has in fact been developing bioweapons were just swept under the rug.

[1] https://en.wikipedia.org/wiki/Biological_Weapons_Convention

[2] https://www.state.gov/wp-content/uploads/2019/08/Compliance-...

One of the issues in treaty monitoring for bioweapons is that so much research is inherently dual-use. The CDC synthesized Spanish flu and infected primates to study why it was so lethal.. they've even tweaked regular strains of flu to make them more lethal, in order to study what genetic factors influence virulence and mortality. There are legitimate, compelling reasons to make even genetically engineered pathogens. Even straight-up engineered bioweapons can be used to study defenses.
Just do not leak and not under communist rule.

Even if this is not, you just cannot trust them. They leak sars in their Beijing lab

“ In fact, the SARS virus had ‘escaped’ multiple times from a lab in Beijing, according to the Nature article.”

I'm making the assumption that there's a MAD situation here with regards to revealing bioweapon programs. I am assuming every major economy has clandestine bioweapon programs and that every major economy has the dirt on everyone else's bioweapons programs, regardless of treaties. So if the US, or someone else, comes out hard against China for an alleged bioweapon program, then China will release information about US programs. That is why, in my opinion, the media headlines and public positions of the major players will be a polite fiction. The truth may wind up buried in some report somewhere, but it won't make the same kinds of headlines that "kooky bat eating" makes.
Maybe this is naive, but I would assume if it was a bio-weapon it would be a lot more deadly.
Viruses which kill too quickly don't spread widely enough to kill a lot of people.

Good viruses kill after a few days of showing few (if any) symptoms so that they can maximise their spread.

This is the difference between epidemic and pandemic viral contagions.

This virus spreads quickly (check) but has a mortality rate of 2%, mostly the old and already immunocompromised. If that's a bioweapon it's a pretty ineffective one.
2% so far, it's very early in the lifecycle of this epidemic and most people go days without showing any symptoms.

The mortality rate will rapidly increase as it spreads to areas where it can overwhelm the local infrastructure. Not every country is capable of creating hospitals in 6 days like China, and China has a lot of experience responding to these crises since the Sars days.

We are only a month in, it's too early to really count mortality.

It might not be a bioweapon. It might be an economic weapon.
If you want to extinct homo sapiens you should probably make a virus that infects everybody and has as little symptoms as possible and then kills them a year later.

We don't know yet if this virus has any long-term consequences. HIV would seem harmless if we estimated its effects after 1 month.

But I don't think bioweapons need to be deadly. If you can make a virus that kills 2% of people but shuts down global trade with your main economic competitor for example - that's quite useful (if you don't care for morality of course).

I'm not persuaded it's human-created, but it's a possibility.

But the point of a bio weapon is not to kill everyone,just your enemy. So i guess you would want it to be very deadly and not spread to far. And i imagine you would want to primarily take out young healthy people (soldiers) not the eldery and sickly. (I assume)
Funny, I would have assumed the opposite. Nobody wins a war by releasing a doomsday virus that indiscriminately kills 5% of the world. But they can win battles by temporarily incapacitating an army, with no fear of loss of their own life if the winds blow in the opposite direction.
This has been pointed out in previous threads, but this Twitter is full of alarmist unscientific BS and it appears to be spammed with some regularity on HN recently.
That largely depends on the credibility of the source of the Twitter posts. The author in the referenced thread does seem to be a legitimate commentator on the subject.
The Twitter user seems legit. The Internet in general is full of BS yet we don't guilt-by-association the entire Internet.
We should question the veracity of the information presented. The nature of this fluid topic is a good example. I read the first part, a few days ago, and most of the information presented tallied with what was presented elsewhere. However, since then Dr. Eric Ding's profile has risen in prominence and the Twitter feed is commingling speculation with credentials, so it is entirely justified to question the validity of your source.

It would seem that there were doubts around the content in the Wikipedia entry.

https://en.wikipedia.org/wiki/Wikipedia:Articles_for_deletio...

From 2K followers to 64K+ followers in less than 7 days! https://socialblade.com/twitter/user/drericding

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Alarmist, yes. Unscientific BS, not really. He’s got the background to make comments from a position of legitimacy. If we can’t trust this guy, even with some healthy skepticism, who should we trust?

https://scholar.harvard.edu/ericding/home

Edit: by trust, I don’t mean blindly believe, but mean one should consider his comments seriously.

From that link, it seems like he is commenting far outside of his expertise in "behavioral interventions" to improve things like "medicare cost."

Don't trust anyone, just weigh their claims and their background. In this case, I have yet to see people with serious credentials in genomics make this claim (outside of the original scientists who published the paper relating it to HIV - IIT is impressive, but I don't really know how to assess their credentials writ large)

How is this outside his area of expertise? He has a doctorate in epidemiology.

He graduated from The Johns Hopkins University with Honors in Public Health and Phi Beta Kappa. He then completed his dual doctorate in epidemiology and doctorate in nutrition, as the youngest graduate to complete his dual program at age 23 from Harvard SPH. Teaching at Harvard for over 15 years, he has advised and mentored 2 dozen students, and lectured in more than a dozen graduate and undergraduate courses, for which he received the Derek Bok Distinction in Teaching Award from Harvard College.

This would be a really scary outcome. As has been commented elsewhere, there's confirmed events of at least four virus leaks from labs in Beijing.

Evidence/article on it here:

https://thebulletin.org/2014/03/threatened-pandemics-and-lab...

Not only that, but just last year there was a case of a Chinese scientist who was banished from a Canadian bio lab level 4 for stealing virus samples, as well as a Harvard Academic found to be taking money from the Chinese gov to help develop the lab in Wuhan.

None of this proves the lab theory, but I do believe that with enough genetic analysis the truth will come out.

I don't like how people are saying that theories regarding it being accidentally leaked are conspiratorial in nature.

Intentional leaking? Sure, I think it's fair to consider that a conspiracy theory. But not accidental.

It would be conspiratorial in nature because it questions the Chinese government's official narrative that the virus emerged from a seafood market, and implies they're covering up the truth.

Of course, people usually use the term "conspiratorial" to be synonymous with "untrue" or even "patently absurd."

We already know for sure that the initial cases did not originate in the seafood market and that the market was just an infection vector for subsequent cases.

Recently available data shows that the first few cases happened in November.

Haha, I like conspiracy theories. While we're at it: <s>Isn't it convenient that it appeared smack bang in the middle of China right about 2x incubation periods before Chinese New Year, the greatest annual migration in human history? Also that it's the first major virus outbreak to be described to the public as driven by asymptomatic carriers? And right after a 'trade war'? Before an election? What's to say it wasn't a ... drumroll please ... foreign or rogue scientist bioweapon?</s> cue for Dr. Evil cat stroking
I just want to know when we're going to start playing Six Degrees of Jeffrey Epstein here...
I know that specifically on reddit, most posts related to the lab theory are deleted on the main pages and subreddits for this virus. For me it's been fascinating to watch the curation and deletion of content that has been evolving over the last few days.

I agree that anything with intentional leaking is really far into conspiracy theory land, but the idea that it was a leak is not so crazy.

> None of this proves the lab theory

The attempted and partially continued cover-up and downplaying of the outbreak does add a significant amount of credence to the theory.

"The finding of 4 unique inserts in the 2019-nCoV, all of which have identity /similarity to amino acid residues in key structural proteins of HIV-1 is unlikely to be fortuitous in nature."

Does this lend support to the theory that the coronavirus was engineered in Wuhan's bioweapons laboratory?

If that is ever proven and a cover up ensues I’d like to think the people would at last slough off their gov.
The Chinese government has done a lot worse to its own people without being "sloughed" off in living memory.
Very true but but people are better informed and are no longer powerless peasants and roboter. They have a bit more self determination.
I'm not sure that realizing your totalitarian government is more dangerous and less principled than you thought is going to encourage rebellion.
>fortuitous

Happening by a lucky chance.

It's implying it was inserted on purpose... (Sorry had to look up that meaning.)

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I thought detecting intelligent design in the genetic code was impossible and bad science.
Detecting intelligent design in things is done all the time. Teacup dachshunds are intelligently designed. So's corn and broccoli.

Throwing your hands up and saying "God must've done it!" when you don't have an immediate explanation and can't be bothered to do some research into one is the bad science part.

Please don't feed egregious comments by replying. This is in the site guidelines: https://news.ycombinator.com/newsguidelines.html.

A religious flamewar on top of whatever else we've got here is the last thing this thread needs!

Fair enough! I don't seem to be able to delete it; please feel free.
How is this religious?
"Intelligent design" is an argument for the existence of God, which is a religious topic.

The issue from an HN moderation point of view isn't religion; it's religious flamewar, which is what internet arguments about religion—at least in large public forums—inevitably degrade into. Therefore we don't go there.

Intelligent design is the theory that it is possible to detect intelligent intervention, as an explanation for specified complexity. Some use the theory to argue for the existence of God, but there are also atheists like Thomas Nagel who promote the theory. So, the theory itself is orthoginal to religion,and is properly a scientific or philosophical topic. Both science and philosophy are well within the scope of HN discussions.
> there are also atheists like Thomas Nagel who promote the theory.

Well, if there are atheists who do so, they are in that respect specifically not like Thomas Nagel. While Nagel does endorse certain criticisms of the consensus models made by proponents of intelligent design (in the same breath as noting that those criticism have also been made by people not promoting intelligent design), he explicitly does not endorse the alternative explanation provided by intelligent design (and does also explicitly point to intelligent design as being motivated by religion.) So, it's beyond ludicrous to cite Nagel as not only a supporter of ID but support for the idea that ID is independent of religion.

Nagel’s also a philosopher best known for advancing the perspective that materialist objectivity is a limiting perspective, that is, he is a skeptic of the framework in which science operates. So he's even a worse example to use to make the argument (even if he supported ID, which he doesn't) that ID is within the domain of science.

Mind and cosmos is one long argument about why we need some sort of teleological principle to explain our reality. He definitely comes across as an ID proponent in that book. Maybe I missed something...

For reference, here is an article Nagel wrote explaining the core of his book. https://opinionator.blogs.nytimes.com/2013/08/18/the-core-of...

"This means that the scientific outlook, if it aspires to a more complete understanding of nature, must expand to include theories capable of explaining the appearance in the universe of mental phenomena and the subjective points of view in which they occur – theories of a different type from any we have seen so far."

That is totally ID in a nutshell. One may then go on to make theological inferences, or not, as Nagel does.

In which case, perhaps he thinks the current paradigm of science as methodological naturalism is lacking. This is the same perspective that ID promotes. If correct, then Nagel and ID are on the side of science.

At any rate, I propose the relationship between ID and religion is not quite as you believe it to be. Happy to discuss the topic further if you are interested.

I totally agree. Intelligent design is about doing the research and good science, not 'god of the gaps'. The only assumption in the field is that detecting intelligent design is possible. If design detection can be done for the recent past, then design detection can be done for the distant past, as well.
That's very, very disturbing.

If this is an engineered virus, why as a race do we keep doing these things to ourselves? Do we _really_ think that weapons of mass destruction won't be turned on us? Is our hubris so high that we think no one else can replicate what we built?

If a horrible weapon can be built, it will be built. And it is better to be the one building the weapon than the one at the mercy of those who built it.
>Is our hubris so high that we think no one else can replicate what we built?

How do we know someone else hasn't already built what we've built? They don't exactly post these things on Facebook...

....which is why we have to build it too.

Our eye and hand was developed mainly to focus against other humans.

Our military has to study this ...

But officially one has to study this as dual use as one has to prepare the natural evolution of say SARS to another strain. Can’t be sitting duck, let evolution run its course (2% death rate is not high but times 1.4 billion it is 28m people). Hence there is a case to study it, even change it. But then ...

Just like we should fight hiv. But then someone in china use human to experiment on it.

It is not there is no case. There are. Just stupidity of human ...

"...unlikely to be fortuitous."

Ignoring the odd word-choice, this ties in to the conspiracy theory that this was a Wuhan biolab containment leak.

I have been writing it off as a crackpot conspiracy until now, depending on peer review.

I think the important things to know here are:

1. A group of scientist have submitted a manuscript for review with a number of exceptionally (and uncharacteristically) bold claims.

2. A huge amount of scrutiny and additional reproducibility will necessarily need to be conducted before conclusions of this nature can be drawn.

3. This manuscript hasn't even passed the normal muster... a biorxiv post isn't much different than a Medium post. Claims like these require many eyes.

EDIT: My sentiment echoed by someone who know more than I https://twitter.com/DrEricDing/status/1223325141364592640?s=...

As regards #3, I agree: the more eyes who see this unconfirmed claim, the better. That's the main reason I upvoted the OP.

A great outcome would be if reputable scientists see this on HN or Twitter or learn about it through colleagues, and subsequently refute it or dismiss it as bad science.

> the more eyes who see this unconfirmed claim, the better.

Isn't it a waste of those eyes' time if it turns out to be false? When there are plenty of confirmed things they could be reading?

If someone with deep pockets may be liable, there will be a well funded effort to debunk this.
You mean like the government of China?
...or a well funded PR campaign to assign blame to somebody else.
This is especially interesting since there have been reports that China was testing HIV treatments on patients with the coronavirus:

https://www.reuters.com/article/us-china-health-abbvie-hiv/c...

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Yes they are BUT it's my understanding those HIV drugs had already been used against SARS and found helpful in an anecdotal way. So it would be an obvious first go-to drug.
I wonder if this could happen because someone with a retrovirus got both infections at once?
It's not even necessarily someone with HIV - HIV is just one virus that is especially well-studied. If horizontal gene transfer in viruses is more common than we expect it to be, this genetic material could've been picked up from just about anywhere and we wouldn't necessarily know about that source.
Does anyone know the extent of the symptoms of 2019-nCoV? Does the virus get fully expelled from a person when they are recovered? Or is there a secondary effect / reemergence?
Maybe we should wait for peer review before we jump to any conclusions.
So what is the probability that a lab that works with HIV normally, now working under extreme pressure, contaminated or mixed up a sample?

And what is the probability that this is not just a third type of major coronavirus, but in fact a secret bioweapon?

Knowing how commonly there are arguments about mixed up samples in the biolabs friends work in, I know where I would place my bets.

It would be a pretty lame bioweapon given how few people it’s killed.
Be advised that there are many posts on Chinese social media claiming the crematoriums are backlogged with people whose listed cause of death is "viral pneumonia" (or just "pneumonia") because hospitals are turning away so many and diagnostics are not catching up. Do not take statistical reporting for granted: The numbers are a best case scenario of definitive knowns. Also, bioweapons have as diverse a variety of use cases as any other class of weapon: They don't need to kill half of a population to be effective weapons.
While I think China is hiding the number of infected, it'd be pretty hard to hide the proportion of dead to infected as the virus has already escaped Wuhan.
The question is not hard but no one really know. Would you test a body died recently?

China is not very reliable in gdp (one top guy told us to look at the electricity and we look at pollution). It is very hard to get stat.

So far touch wood no one died outside of China. The death rate should not be high unless the alternative saying hiv death rate after 1 month is 0%.

The conspiracy theory in a proper sense is accidentally leaked for an experiment, like sars virus leaked (later and during study) by Beijing level 3 lab.

Could easily be "mixed samples" on the other end instead of intentional leaks. You know how old lab equipment could be really useful in a live seafood market.
The article claims that the new coronavirus is an "hybrid" of an usual coronavirus with some parts of HIV. If you mix both virus in a bottle of water, you don't get the hybrid.

If both virus infect a cell simultaneously, there is a small possibility that something like this happens. I think it's so small that is not possible to do it in a laboratory even on purpose, and definitively not by accident but IANAB.

It is easier with other virus. For example mixing variants of flu, because they have (IIRC) 8 strands of DNA. There are avian, swine, human, others flu, and each of them has many subvariants. If some animal get infected with two variants at the same time, a cell may have a double infection and the viral offspring may have a mix.

But the mix is a mix of the strands of DNA, like 3 swine flu + 5 human flu. This is usual, but you must consider that there are millions and millions of animals in the wild and farms. It's more difficult to do it in a small lab, but IANAB.

The main difference is that the article claim that the usual coronavirus and the HIV parts are in a single strain, not a bunch of strains packed together.

Ignoring the political implications, how would HIV insertions change the virulence and epidemiology of the infection?
In the paper they hypothesize:

> Due to the presence of gp120 motifs in 2019-nCoV spike glycoprotein at its binding domain, we propose that these motif insertions could have provided an enhanced affinity towards host cell receptors. Further, this structural change might have also increased the range of host cells that 2019-nCoV can infect.

Have in mind that this paper is not peer reviewed.
My dose of speculation. So far we have strong evidence that this is a biolab virus, probably they were experimenting with this virus on animals the lab personal didn't realize on time how easy this virus could be transmitted by air, probably they were using the public transport from home to work during the incubation period thats how it boomed all of a sudden.
This looks like a whole lot of rubbish to me. They're excited they managed to get blast hits for these short inserts.

But in the spirit of open-mindedness, what do I need to be convinced this is even interesting? First I want to see where on gp120 these inserts align to. Are they receptor/carbohydrate binding regions? Where do they map to on the coronavirus? These structures are known, so I don't know why this isn't in this manuscript.

If somehow this is engineered, I am honestly impressed that someone could take features from one protein and estimate how to engineer those same features in another protein altogether, with little homology. It's like engineering a monkey tail onto an elephant and somehow getting the elephant to swing through the trees.

I appreciate your skepticism (and your sense of humor) but for the benefit of other readers, it is not like engineering a monkey tail onto an elephant and expecting the elephant to swing through the trees.
The amazing thing is last week someone on 4chan posted this: https://i.imgur.com/Jkq8tYK.png Which shows that the virus had been modified. 4chan wins once again at sleuthing.
This lab theory has been systematically censored across the internet for the last week or so. For me it has been fascinating to watch content on it pop up and then disappear.
Maybe I'm missing something obvious but nothing in that image shows the virus has been modified? Or at least the commentary doesn't say that.
I'm not saying I believe the conspiracies, but it would be a pretty scary future if a totalitarian nation decided to quietly immunize their population (or just a selected elite) from a pathogen designed by themselves, and if push comes to shove you have a bioweapon that will do the job for you, which you know the people you care about can't contract. It's like a smart nuke.
Given historical experimentation by the military and intelligence agencies it seems pretty likely that this sort of research is happening.