For HIV, there are plenty of estimates for the mutation rate based off a mixture of statistical bioinformatics and knowledge of genetics. But they are all inferences because we don't have many sequences from before 1988. This relatively ancient genome allows scientists to see how good their estimates are by looking at a genome that will have -20 years worth of mutations. Turns out the estimates are really good. I would then draw the link back to Covid where the mutation rate is estimated in the same way. So it's a good bet that the date estimated for Covid's emergence is pretty close to the mark.
You can see the paper here[0]. I think the actual paper would make a better link on HN, but I guess the press release is useful for those without a molecular biology background.
From the abstract:
"Our phylogenetic analyses date the origin of the pandemic lineage of HIV-1 to a time period around the turn of the 20th century (1881 to 1918)."
At that time humanity didn't even know what the virus really is -- they just knew that something in some liquid transmits some illness. The most advanced lab at that time could only get that liquid using the filters.
The two are different in likelihood by perhaps two orders of magnitude and one is malicious while the other not.
When we lump all accusations together and dismiss them all together based on their most radical claim, then we do ourselves a disservice.
While it's important to be fact based, it's also important to be investigate theories of greater likelihood.
Imagine a murder investigation where a detective won't interview suspects because there's no evidence against them. It becomes a catch-22.
Don't waste your time with them. You cannot reason people out of something they were not reasoned into.
That was already pretty much a certainty from the already known fragmentary genomes (also mostly from the DRC), as well as the phylogenetic analysis of known strains, groups and subtypes.
If it got out before the second half of the 20th century it apparently didn't manage to gain enough of a foothold to go pandemic[0]. Though the long incubation rate and somewhat mixed symptoms also make it somewhat uncertain.
[0] as may have been the case for Robert Rayford who looks to have been something of a terminal case rather than vector or victim of a more widespread infection
"There are older fragments of HIV out there, one from 1959 and one from 1960, also from DRC. But those pieces aren't as complete, and thus can't offer as much information about the virus' mutations. "
'Philadelphia' a fictional movie that touches on the social stigma associated with HIV and 'And the band played on' captures the politics of why it was ignored by Reagan and his supporters for so long and the sad politics and scientific infighting in the chase for a cure.
Both are incredible movies.
He said that even after it was understood that AIDS was not transmissible by touch, morgues would refuse to accept the bodies of gay men. When people knew they were at the end of the rope, they would ask their friends to throw their ashes over the fence into the white house lawn. That way as their final act, they could tell the government that their active silence was literally killing people and that even if they considered them others, they wouldn't be ignored.
It's heartbreaking, but I'd recommend anyone to listen to the interview if you don't know much about that period in history.
[1] https://www.stitcher.com/podcast/shame-on-you/e/66787240
We had very little idea of what constituted "transmissible" and what did not for a period of time, and so while our parents had "free love" and The Pill, with the biggest risk being herpes, at least a section of my generation got "sex = death" internalized on top of all of the other apocalyptic gloom.
Of course, even what would be transmissible was subject to propaganda: on one side, you had people arguing for any gay sex being a risk, but on the other side, some activists insisted that heterosexual intercourse was exactly and precisely as risky as homosexual (male) intercourse. Quite a lot of misinformation floating around.
do you have any source for what you believe?
It shows the challenges of the press to have serious conversations about the disease with the Reagan administration.
Human nature at its most unfiltered.
The video really seems like par for the course and not surprising in the slightest...
Yes, the governments refusal to act on the AIDS crisis and the substantial stigma around the disease - resulting in hundreds of thousands of dead is "much different" from jokes about oral herpes on SNL.
A 90's film telling the story of how AIDS was ignored.
One thing worth being aware of with "And The Band Played On": it's quite old, and science advanced a lot after the book it's based on was written, so it's sometimes factually inaccurate (Gaetan Dugas didn't personally cause the pandemic, and the incubation period is longer than they thought then). It's not a work of history or a documentary, but it makes for fascinating viewing precisely because it was made so close to the events that the story it tells is not neat and polished with the benefit of decades of hindsight and narrative shaping. It's chaotic and emotional and raw and authentic and, inevitably, sometimes wrong about stuff that wasn't known then.
And out of the small portion of the book that talks about Dugas, I never got the impression that Schilts was trying the blame him for causing the pandemic, but rather that he was using him as a real life example of the type of man that existed in that era, who flew around the country having sex with thousands (yes thousands) of other men, whose behavior doubtlessly and unknowingly sped the spread of AIDS.
I have Bruce Springsteen’s Streets of Philadelphia (the titular song of that film) playing right in this instant.
I’m not sure why I write this. I never really spoke of it before. I think I found your comment deeply moving.
The only other thing I do recall was some concern on this first case about folks showing up to disrupt the Funeral in part because most of the mourners were from the gay community. So I think they hired the an officer from the local PD to provide security but nothing happened.
In the podcast, the interviewee talks about how in some major cities there was only one funeral home which would serve that population. Those places have now become the only place some gay men want to handle their body when they pass as a sign of appreciation for their compassion during the AIDS epidemic.
It looks like the white house lawn is home to the remains of at least 18 gay men that died from AIDS.
[1] https://www.vice.com/en_us/article/vdqv34/why-the-ashes-of-a...
The similarity with corona in 2020 is that so little was known, but for years, not months. The difference was that AIDS was 100% fatal until drugs were developed, and AIDS killed a generation of young adults rather than older people.
(There were interviews with a handful of men who were immune to the AIDS virus, but had to endure all of their friends and partners dying, and had to deal with inheriting a lot of possessions that reminded them of dead people.)
Almost all hemophiliacs in North America used pooled blood products from thousands of donors, so just about all of them died. (There's a Canadian film on Youtube that covers this.)
Because of that whenever I see those I think of the bigoted attitude that lead to their deployment and won't use them.
It's an area under the graph thing.
You are comparing a sprinter to a marathon runner. It's hard to do the comparison justice using just one statistic.
I truly hope we manage a better response than the AIDS crisis, because a similar response to COVID-19 would be incredibly devastating.
Think about how often the average person has sex vs how often they’re around tons of strangers who are exhaling, coughing, etc.
Not to mention it takes quite some time for someone to die from an opportunistic infection as a result of being immunocompromised from AIDS.
In NY alone there have been 23K deaths due to covid 19.
911 had about 3K dead.
This was over 7 911 events in a matter of 3 months.
Nationally it's about 33 911s in 3 months.
I read that, looked at their statistics and backed out an estimate of number of years of life lost for AID and Heart disease. And yeah AID's was a really big deal unless you were a sociopathic old white male editor at the WSJ.
Reading what the Wall Street Journal thinks about SARS-COV2 shows they haven't changed a bit in 35 years.
Receptive penile-vaginal intercourse* at 0.05–0.30% Receptive anal intercourse* at 0.04–3.0%
Given the error bars ...
The fact that it was downvoted sort of underscores my point, that people prefer reinforcing their feelings, rather than know the truth.
I’m not sure that prophylactics really would be the deciding factor. Condoms are older than you might think, but on the other hand usage rates are still relatively low.
And humanity keeps bouncing back from things: for example, the plague (multiple times!)
I think the relatively long incubation time is probably what would have made it especially bad if it had taken hold earlier - say, in the 1800s when our understanding would have been limited and our ability to track it worse. It might have been much, much worse then.
That's why it erupted in the gay community first.
Effective HIV suppression is not cheap, and usually out of reach of developing countries or poor communities such as… pretty much all of sub-saharan africa, where the AIDS pandemic remains essentially unchecked.
According to wikipedia, as of 2016, 8 countries had more than 10% of the population infected and two of them (Swaziland / Eswatini and Lesotho) were above 25%: https://en.wikipedia.org/wiki/HIV/AIDS_in_Africa#/media/File...
Given mother-to-child transmission is somewhere between 15 and 45% without mitigation measures (which are unlikely to be in place in a country where a quarter of the population is infected), we're talking 5~10% of children born infected.
Combine that with AK, 2002 - I would guess somewhere in the southern half of Africa.
I guess that it was combination of medicine not being cheap and IIRC some political leaders in the region were downplaying HIV by that time.
https://www.politicsweb.co.za/news-and-analysis/the-virodene...
https://www.telegraph.co.uk/news/2016/03/16/historys-greates...
"Based on the theories of Dr William Campbell Douglass, many believe that that HIV was genetically engineered"
"William Campbell Douglass, M.D. Education: BS, University of Rochester, New York; MD, University of Miami School of Medicine; Graduate, U.S. Navy School of Aviation and Space Medicine" (1)
"Survey data from the United States (US) and South Africa (the only countries for which quantitative data exists) suggest that a significant minority of people endorse such beliefs and that this matters for public health." (2)
And "we know who" now spreads the disinformation about the COVID-19 virus (I won't intentionally mention him, he has too much fans here).
(Additionally, the biggest stockpiles of chemical and biological weapons were always in the U.S., apparently more of 10% of the chemical weapons are still not destructed.)
1) http://ncoic.com/aidswar.htm
2) https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-9566...
Are you referring to President Xi?
Take a step back:
We've been collecting useful yeasts for brewing and cheese production for a very long time, reusing those who yielded better results.
Same as with plants and animals.
So while I don't believe it is man made or synthetic or anything it is smart to have multiple lines of defense against conspiracy theories.
[1]https://www.newsweek.com/dr-fauci-backed-controversial-wuhan...
But we know for certain that SARS-CoV-2 was not created through gain-of-function experiments. It doesn't use any of the standard viral backbones used in such experiments, it has a receptor binding domain that computational chemistry algorithms would not have predicted to work (meaning that nature "invented" it, not scientists), and the virus contains seemingly random differences throughout its genome from all known viruses - that would not be the case for a lab-created virus.
The boring answer is the correct one: this virus evolved in nature, and then spilled over into the human population late last year.
I don't think there is any evidence of this, despite the usual suspects (neocon types on our side, and militarists on the Chinese side) ginning up the case for an "escape from lab" casus belli, but let's get the facts straight.
For example they make gum disease a lot worse (which then in turn is linked to Alzheimer's for example) https://onlinelibrary.wiley.com/doi/abs/10.1034/j.1600-051x....
Note that there is a ton of other HSV-*, for example HSV-6 https://hhv-6foundation.org/what-is-hhv-6 I think there is just not enough research yet on what is caused or made worse by which herpes virus.
I was not trying to diminish the atrocity that is how the AIDS epidemic was handled, I was only trying to illuminate that people (and the super-majority of our lawmakers) are immature and uninformed when talking about all infectious diseases.
Edit: just look at our President’s response to Covid... it is bumbling and moronic.
No. It isn't. Stop trivializing HIV. I don't know what you're getting out of it, but it comes across as incredibly tone deaf.
Edit: grammar
It's not a song that gets played much at home, when she's about :(
In the UK, some schools are refusing to reopen and some people are refusing to return to work in spite of government orders.
Only most of recently infected have no symptoms, whereas most of infected do develop symptoms, but typically after they already transmitted the illness to other people. According to what it is currently known, from all infected around 80% do eventually develop some symptoms, up to 10% need hospital, up to 5% need intensive care and around 1% of all infected eventually die. That is when observed across all age groups, among the older it's much worse.
And as soon as the health system can't cope the percentages of dead increase rapidly to even higher values -- i.e. those that need hospital need it because half of them will need intensive care (and nobody knows before it's critical who), those that need intensive care need it because most of them will need oxygen in some form and half of these will need:
https://en.wikipedia.org/wiki/Tracheal_intubation
That's why it's undesired to have non-functioning health system, and to avoid overwhelming the existing health systems.
I remember how much of a hero Magic Johnson was presented as being for simply publicly admitting he got it during surgery and advocating.
It was brave for a multi-millionaire celebrity to admit publicly that he got it by accident. If he'd have been gay too my gosh... what scandal...
Terrifying indeed.
Of course, that gratuitous pint gave some of them AIDS or liver disease for no useful purpose.
More and more you realize hospitals are the most dangerous place to be, emphasized by corona, but the CDC maintains a list of about 18 infectious diseases rampant in hospitals today.
I still remember that poster with KS and other symptoms on it, some 35 years later. Folks outside of biology have no idea how slow the time frames of some disease treatments can be.
Yeah it was a major scandal here in Canada. The Red Cross lost the right to handle blood a new organization called Canadian Blood Services was created.
Many people with hemophilia died but I think people at the tail end of it were around when the new drug cocktails slowed the disease.
As a teen in the 80s AIDS was pretty scary even for a straight kid with no girlfriend. It seemed like everyone was talking about it, getting it, scared of people with it, or denying it existed.
Anthony Fauci had a hard time getting Pres. Reagan to even take it seriously (sound familiar!?). Many conservatives saw it as the "gay disease" and dismissed it as irrelevant.
I just want to caution you that making these forms of equivalences is a common tactic to derail and discount the impact of HIV or the experience of populations disproportionately harmed, in the same way that people derail discussions about the disproportionate killing of black people by police with statements like "why focus on black people? nobody should be killed by police."
I believe that you were not intending to do so, but I also hope that you understand and can be cognizant of that dynamic.
The problem with that theory is that the virus contains thousands of mutations throughout its genome, which would take decades of evolution to accumulate. In the wild, this virus jumps to a new host every few days, meaning that decades of evolution amount to thousands of generations of virus. No lab has the time to pass virus through so many animals.
fauci was conducting coronavirus gain of function experiments in wuhan in 2019 trying to go from bat to human, so at least some scientists didn't consider the evolutionary distance to be so great
UPDATE: newsweek article on fauci https://www.newsweek.com/dr-fauci-backed-controversial-wuhan...
That is the answer you get from the experiments, if it jumps then it can, if it doesn't jump, keep trying different strains and generations selectively bred in mice/ferrets/etc. (in addition to using human cells in vitro to filter the candidates at various stages, an interesting modern possibility is to use mice seeded with human cells with the receptors of target type like ACE2 in this case and/or with human cells from respiratory surfaces). In general it is like you'd selectively breed new type of apple or grain, condensing the decades of chaotic natural selection into managed selection over few years or even months when it comes to fast iterating objects like for example viruses and bacteria.
So far it looks like the experiments did succeed. China is a country where prison inmates voluntarily donate organs while still alive, and in general it sounds like their prisons are very harsh, comparable or even worse than for example in Russia. Compare to that getting infected with a flu and spending few weeks in a nice lab hospital being well fed and relieved from the hard labor and abuse by the guards and other prisoners - i suspect there would be a line to sign up for those experiments.
No, a chimeric virus created in a gain-of-function experiment would look extremely similar to known viruses, because these chimeras are created by combining elements of known viruses. It would not be 4% different from the closest known natural virus. Accumulating thousands of mutations throughout the entire genome takes decades of evolution. In the wild, that means thousands of generations of hosts.
A virus created in a gain-of-function experiment would also use a well-known backbone. It would not be based on some virus that nobody had ever heard of.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797993/
https://norkinvirology.wordpress.com/2015/12/04/genetically-...
https://www.pnas.org/content/113/11/3048
I don't know what your purpose is in regurgitating verifiable but admittedly realistic-sounding bullshit on hacker news, but virtually every statement you have made here is obvious bullshit.
I don't even particularly believe the "possibly released from a lab" meme, and am generally against the shadowy dipshits that push it. But you're not helping here.
Are you saying that a chimeric virus created in a lab was found to have thousands of seemingly random mutations throughout its genome?
Or are you claiming that a chimeric virus was created using a backbone that nobody had ever heard of?
Be specific, because it's impossible to respond if you vaguely call what I'm saying BS.
https://www.newsweek.com/dr-fauci-backed-controversial-wuhan...
If I understand your argument, you claim sars2 is too genetically different from the closest public sequences to have been lab engineered. But, what precludes a lab from discovering a virus in the wild that is close to making the jump, and then pushing it the rest of the way? I am not understanding the argument that we have to limit the range of possibility to only the publicly disclosed virus sequences.
For example, if you line up the ace2 site between sars2 and sars, they have a lot of similarity. This author claims the section is essentially copied over, although I don't know if it is statistically significant enough to not just be an accident. https://nerdhaspower.weebly.com/blog/scientific-evidence-and...
So, a "lab origin" theorist could say they isolated a virus in the wild, and copied over the ace2 section from sars, and then ran it through human tissue until it gain enough function to spread effectively in the human population. Is that less or more likely than a coronavirus in the wild mutating enough to make such a lethal jump to humans? Is there any way to put a probability on the two theories?
Saying they were trying to generate SARS-CoV-2 in a lab is a very polemical way of saying that they were studying viral transmission in cell culture. They didn't create SARS-CoV-2. They created viruses that are extremely different from SARS-CoV-2.
> But, what precludes a lab from discovering a virus in the wild that is close to making the jump, and then pushing it the rest of the way?
The Wuhan Institute of Virology publishes identifying genetic sequences of the viruses it samples from the wild. SARS-CoV-2 is not among those viruses. The closest virus (RaTG13) that the WIV found before the pandemic was 4% different from SARS-CoV-2. If SARS-CoV-2 were engineered from RaTG13, then the two viruses would be virtually identical throughout most of their genome. The only differences would be those introduced by the researchers. Yet the two viruses have seemingly random differences throughout their genomes - the types of differences you would not get in gain-of-function experiments. A 4% difference corresponds to many years of divergent evolution. The two viruses might have split as far back as the late 1800s.
So it's certain that SARS-CoV-2 is not engineered on the basis of RaTG13. If you want to claim that the WIV secretly found a different virus, then for unknown reasons didn't publish about that virus, and then started doing gain-of-function experiments on it without telling anyone (including their American scientific collaborators), you're just so far out in the realm of evidence-free conspiracy land that it's not worth responding to.
> copied over the ace2 section from sars
The receptor binding domains of SARS-CoV and SARS-COV-2 are very different from one another. The blog you're looking to is nonsense.
Listen to actual experts, like the virologists at This Week in Virology, not bloggers making wild claims.
regarding the binding sites, clearly they are quite different. but, the similarities seem greater than possible by chance, and i am not sure how that could happen. maybe a variant of sars mutated into sars2?
the sites are at least similar enough that researchers are trying to use sars vaccines to engineer sars2 vaccine
Instead of reading conspiracy blogs, go read scientific papers. If you don't understand them, then there is really good introductory course material on virology available from several universities.
Using a uniform distribution over the 20 proteins, and saying the probability of two proteins matching is 1/20, then the binomial probability of getting 7 or more matches out of 55 is 0.02, whereas the probability of getting 20 or more matches is less than 0.000001.
I can see 0.02 being achieved by chance, but 0.000001 seems pretty unlikely to happen by accident. So, there is some sort of non accidental relationship between sars and sars2. Maybe 1) sars2 is descended from sars, or maybe 2) it is lab engineered.
If the bat coronavirus is likely the more proximate ancestor to sars2 than sars, then #1 seems unlikely, which makes #2 the more plausible hypothesis.
Also, to return to your argument about restricting our 'lab origin' hypothesis to known viruses, it seems that if WIV found a very effective bat coronavirus, and intend to create a bioweapon from it, this is exactly the situation when they would not share the sequence. I do not understand why you think people creating a bioweapon would want to share their materials with the world.
You may also find this other article by the same author interesting, pointing out the evidence strongly points to RaTG13 being faked. https://nerdhaspower.weebly.com/ratg13-is-fake.html
There is also this interesting tweet from Jonathan Jacobs that the sample data for RaTG13 does not match the assembled genome. https://twitter.com/bioinformer/status/1252813532850081792
Yeah, they're both betacoronaviruses. You've just discovered something called "common descent." Charles Darwin published about it in 1859.
I'm sorry, but this is getting comical. You really have to step back and learn some basics about biology before you go on this dive into conspiracy theories.
I blasted sars2 against sars and against ratg13. 88% coverage for the first and 99% for the second, so ratg13 seems to be a much more recent ancestor.
- sars2 v. sars: https://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Get&RID=D7WE9PB...
- sars2 v. ratg13: https://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Get&RID=D7WGNJG...
Why would ace2 be much better preserved between sars2 and sars than between sars2 and ratg13?
Apologies for being dense :) As you notice, I'm pretty new to bioinformatics. Just trying to understand what your argument is.
UPDATE: Sorry, I see a mistake I've been making that is confusing. I should be referring to Bat_CoV_ZC45 and Bat_CoV_ZXC21, not ratg13. ratg13 is the one that also has a close match to ace2, but the author claims is a forgery. The bat coronaviruses also seem to be more evolutionarily close to sars2 than sars, and they don't have the ace2 binding sites.
I'm saying that it's complete nonsense to say that there's a (1/20)^7 chance of 7 amino acids matching. We're talking about viruses that are descended from a common ancestor, not random, independently distributed coin flips.
> ratg13 seems to be a much more recent ancestor.
RaTG13 is not an ancestor of SARS-CoV-2. The two viruses share a common ancestor.
> Why would ace2 be much better preserved between sars2 and sars than between sars2 and ratg13?
ACE2 is a human protein. Neither SARS-CoV-2 nor SARS-CoV have ACE2. If you're talking about the RBD of the S protein, then note that the RBDs of SARS-CoV-2 and SARS-CoV are only 73% homologous, which is a pretty massive difference.
Stepping back for a second, you're diving down the conspiracy-theory rabbit hole with very little prior knowledge of the subject. That's just going to make you easy prey to a lot of nonsense. Really, instead of reading blogs that claim to have found the secret truth about SARS-CoV-2, listen to what respected virologists have to say about it. Do some basic background reading on virology and coronaviruses. Read some review articles from scientific journals.
- https://www.nature.com/articles/s41591-020-0820-9
Their two claims are:
1) ace2 binding is much better than humans can engineer with computer simulations
2) virus does not come from any known backbones
Regarding #1, I've found another article where the author was able to induce zoonosis from a feline coronavirus to a mouse by exposing the virus to mouse genetic material. So, the fact humans cannot directly engineer zoonosis very well does not preclude lab induced zoonosis.
- https://www.nature.com/articles/news030331-4
In fact, this is a theory posited at the end of another debunking article, which doesn't actually debunk that particular theory.
- https://www.livescience.com/coronavirus-wuhan-lab-complicate...
Regarding #2, as I mentioned before, it seems this line of reasoning is a non sequitur. A virus backbone used to create a bioweapon is exactly the sort of sequence you are not going to upload to NCBI.
The fact the reasoning does not seem very solid in what is considered the official and definitive debunking of the conspiracy theory is itself odd.
So, it is my reading of some respected virologists that in part motivates me down this rabbit hole.
Anyways, I greatly appreciate your feedback. I'll keep learning more about virology, and hopefully get some clarity on the whole matter.
I'm going to suggest to you that the reason you don't find the reasoning in the debunking to be solid is that you don't understand the field very well. I don't know what your specialty is, but imagine someone who has no experience in it. They might have a lot of weird conceptions about your specialty, they might have no idea how things work in your field, they might find a lot of things surprising. Things that you find obvious might seem dubious to a novice. The arguments made in the debunking are considered very strong by experts in the field. That's what matters.
