NIH Scientists Identify Antibody That Neutralizes Nearly All HIV Strains
niaid.nih.gov
niaid.nih.gov
In essence, an antibody called N6 was extracted from an HIV patient. The patient is a long-term nonprogressor who has had HIV for 21 years, but an exceptionally low viral load of <1000/mL and normal CD4 T-cell count. This indicates that his immune system has kept the virus at bay for all these years with essentially no ill effect.
HIV viruses have a surface protein complex called Env, which binds to the CD4 surface protein to gain entry to T-cells (part of the immune system). HIV cannot transmit without this protein complex, and so certain parts of the complex are very well conserved across different HIV strains.
N6 binds to this part of Env, in some sense "simulating" CD4. However, because it's just an antibody and not a cell, once Env is bound it cannot infect anything. This is what makes N6 a neutralizing antibody.
The thing that makes N6 special (more potent and more broadly applicable) is that it is able to avoid the parts of Env that HIV doesn't need for replication. Imagine Env as a wrench. The head of the wrench is a specific hex shape to mate with CD4 and can't change. Antibodies can grab on to the wrench handle to prevent infection. But the handle can change, and HIV regularly mutates this part to avoid being caught - adding side branches, changing the shape, and so forth. N6 is cleverly arranged so that it can strongly bind to the wrench without grabbing the handle too strongly - in other words, it tightly binds the head of the wrench like a person wrapping a thumb and index finger around it (this hand analogy appears in the paper). The result is that HIV has a much harder time getting out from under the antibody, since mutating itself to alter the head shape would also affect infectivity.
Now that larger HIV screening trials are done, and the technology has advanced to better detect such super-antibodies, more of these clever antibodies may be discovered. We may yet have a good shot at defeating this tricky virus!
It's a game of big numbers, much (very smart) trial and error I suppose, and never finding something meaningful may result in much frustration. Still this has to be done because you simply don't know which path will lead to the solution.
Now if you only do negative research you cannot publish and you if you don;t publish you die.
I wonder how many negative results get repeated because they don't get published. It could save a lot of effort and money publishing negative results.
"He was discovered by the AIDS industry when he had already been HIV-positive for twelve years. His strain of HIV was notpathogenic but was able to kill the lethal strain of HIV. By isolating his mutant strain of HIV it was possible to develop an AIDS vaccine."
It stops HIV from progressing in the body, holding it at bay. Someone with HIV would need to take this medicine for the rest of their lives. It doesn't actually cure it. (not denying that holding it at bay is a significant step forward)
Obviously, curing HIV is an open research question, but also the way to go about curing this retroviral infection is still unknown. When there is sustained virologic response, we know that the virus will come back if drugs are withdrawn. Exactly which niche of cells have integrated HIV into their genome, and how to identify them, is an active area of research at least as of about a year ago when I last looked into it (hint: probably macrophages and T cells).
The Berlin patient shows that cure is possible via treatments that also eradicate the bone marrow, but these are not generalizable across populations due to the high morbidity and mortality.
For prevention, vaccination that can generate antibodies such as the one in the article would be highly valuable. Less valuable but still very beneficial would be a long-lasting monoclonal antibody injection that can be given once a month (or ideally less often) to reduce the likelihood that high-risk individuals become infected.
For cure, I suspect that an approach which pairs replication suppression with genome editing tools, such as CRISPR, may ultimately prove successful in curing individuals of HIV.
Correct me if I'm wrong but I thought that patient got HIV back a year or two after the bone marrow transplant?
The question is whether all humans can produce this, or just some genotypes. If it's the latter, then yes, some people would have to take it as medicine and never stop.
Ahh, of course they do. Thanks for the clarification :)
Either way this seems like an exciting result.
Which is a problem since it would probably be a monoclonal antibody and those are the most expensive drugs to make. Like hundreds of thousands or even millions per year expensive (depending on what dose is needed).
If it really does cost millions per year the US couldn't afford it - it would cost over a trillion per year to treat everyone in the US, and more than 40 trillion to treat everyone (and that's just for the medicine).
(For comparison total healthcare spending in the US is 3 trillion.)
So better hope that either the price goes down, or that it only requires a limited course of treatment. Can you imagine a cure for HIV, and we can't afford it?
If the cure is proven, the society will likely be able to mobilize much more resources, particularly to scale up operations.
Special expertise can be trained to other biologists (the underemployment problem would be mitigated as well). More biologists could be trained. Likewise for factories, materials, etc. Monopolies can be broken.
What factors cannot be scaled up with such an approach? (Honest question. I do not know anything about antibody production.)
The first 3. Monopoly doesn't help I'm sure, but this drug class in inherently very expensive to produce, there's a reason there is little outcry over the prices charged.
It's extremely labor intensive, and very hard to scale up. They are also inherently dangerous, so there is a need for extreme purity. (See: https://en.wikipedia.org/wiki/TGN1412 for what a monoclonal antibody can do, you would not want that to happen by accident.)
As of right now this drug class remains the most expensive of all drugs, I would assume if it were possible to make it cheaper they would have.
But we'll only really know once the first generics enter the market.
You design the monoclonal antibody, figure out its sequence, deliver the sequence back into your own body (via some HIV-like virus), and now your body has an unlimited continuous access to the therapeutic.
Production of the therapeutic-delivering virus could be done in such a way as to produce a global scale for a small amount of money that would never need to be administered again. For example, in lab I can produce enough (lab quality) purified protein for a single one-time dose for a few thousand dollars and a week's work. On the other hand, I could produce enough therapeutic virus for dozens of people to forever produce their own versions of that same protein for a few hundreds dollars and an afternoon's work. This is very unlike any other 'drug' of the 20th century.
as an aside: Curiously, in the lab at least, most of those therapies are delivered using a 'gutted' version of HIV (precisely because it is so good at delivering genetic payloads to humans). So there's a pretty good chance you'd be using an engineered version of HIV's own machinery to deliver a permanent anti-HIV payload to the patient's genome.
I think the most interesting nonprogressors to look at are the ones who refuse treatment. Many of them die within 5 ~ 10 years, but the ones who don't could potentially have a natural resistance to HIV.
Not my area of expertise either, but as I understand it, it really depends on how many strains you are infected with. If it's just one, it'd reduce the infections in the next generation of patients by 99%. If the average patient had 10 strains, randomly distributed, it'd still reduce the infection rate by 90% (because there's a 10% chance of having that one resistant strain).
Only if all HIV patience had all strains (and I'm pretty sure that's not the case) would it bring us back to where we started.
The transmission rate of HIV is not really dependant on the strain but on the behaviour of the affected host.
Since HIV infection can be asymptomatic even for the natural life of a host the transmission rate is then dependant on the environment the social interaction of that host.
A host that has unprotected sex (or any other risky activity as far as blood transmitted diseases go) and does not get tested regularly will have a considerably higher transmission rate than a host that has only protected sex and gets tested when they switch partners.
Most HIV patients are infected with multiple strains, because at this point most new infections are multi-strain ones due to the lifestyle of the hosts and due to the fact that the virus can mutate in vitro.
I'm also not clear how does this press release counts "strains", since it's 16 it's more than just by major types HIV-1 and HIV-2, but then it's the question of what and how they count sub groups.
Most people in the west will get infected by HIV-1 Group M type B, type B itself can have several variations, and there are also host specific mutations, and if you are coinfected with another subtype you can have multiple variations of both and also recombinant (a new form made out of several types of the virus due to coinfection of a single cell) variations that may or may not be unique to each host.
That said effective post infection and pre AIDS outbreak treatments can drastically reduce of new hosts that end up as transmission vectors and carriers, if HIV becomes a considerably more manageable disease that would allow most infected people to carry on with a normal lifestyle (safely have sex with a partner, and have children) once treated more people are more likely to be tested regularly.
If you can also contain the disease to specific subtypes which are regionally locked as sad as it sounds you still doing quite a bit of good since now you can focus your resources on education and containment as well as further research since the transmission rates between say interveinal drug users in Berlin are considerably higher than between a sex worker in nairobi and the same drug users.
We've been able to eradicate or nearly eradicate several viruses from the planet. It starts with getting them down to manageable numbers, then addressing every outbreak. (Granted, HIV is not quite an analagous in terms of spread to viruses like smallpox.)
https://en.wikipedia.org/wiki/Eradication_of_infectious_dise...
I think that reducing the spread alone still could get us to a point where we "manage this out over the long term" as you say. Say you're a person with many sexual partners that has say a 1 out of 100 chance of sleeping with someone infected with HIV on a given day. Say there's a 1 in 10 chance that encounter will lead to transmission of the virus. (These aren't like factual numbers, just examples). That's still a 1 in 1,000 chance per encounter, so it adds up over time. After 1000 encounters chances are you've contracted HIV. But say you're vaccinated against 99% of the serotypes. That reduces your chance per encounter to 1 in 100,000. Even after 1000 encounters your chance of contracting HIV is 1 in 100. Not terrible.
Of course this is not realistic. People like sex, novelty, and having sex with different partners!
Another strange thing, it does not seem all that difficult (relatively) for interspecies transmission to occur: "Scientists have now documented that the SIV virus has jumped from monkeys or apes into humans at least 13 separate times!"[4]
Perhaps those transmissions are due to self-injury while cutting infected meat, etc. The vagina is tissue that expects the presence of foreign human cells, and so has defenses against them. Anal sex, injections, etc are a different story. To me it sounds like an entire cell gets transmitted.
[1] http://m.jid.oxfordjournals.org/content/191/9/1403.full
[2] http://www.ncbi.nlm.nih.gov/m/pubmed/18490657/
[3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614444/
[4] http://evolution.berkeley.edu/evolibrary/news/081101_hivorig...
EDIT: Another possibility is that the vast majority of these variants found floating free in the blood are non-functional and serve as chaff to confuse the immune system.
The various HIV strains inside the body compete with each other over infected cells. Once you kill some of the strains with a treatment it opens up space for the other strains to to fill.
HIV is a very expensive disease to treat and since it's no longer a death sentence, a significant amount of resources go towards a lifetime supply of drug cocktails for long term HIV patients (which is all of them). Even a 10% reduction in the number of infections would free up a massive amount of resources at the NHS, CDC, and other agencies best suited to put them to use dealing with the remaining infections. Like with cancer and drug resistance, there is no single panacea but that doesn't mean we can't make big leaps that help a lot of people. Fighting a virus like HIV takes a lot of victories, big and small, that chip away at the problem until, like with smallpox or polio, there are so few cases left that each can be dealt with individually by the public health infrastructure.
With my tin foil hat on, I've always wondered that now there is a very profitable business (for the big Pharma companies) out of just providing HIV positive people with drugs for years, that there is little appetite (again, inside big pharma) to actually 'cure' the disease...?
The real problem is not pharma trying to turn things chronic but rather people who have less common or less prominent diseases.
That's not entirely true. When Hillary Clinton was running health policy in Washington, the white house threatened to impose trade sanctions on India and South Africa if they manufactured generic drugs to treat their citizens with HIV. This was before it had become an epidemic in those areas. And now that it is an epidemic, the pharma companies get tax writeoffs by working with the Clinton Foundation to provide treatment in those areas at 'reduced cost'.
I agree that insisting that third world countries who are already debtors to first world countries for aid pay huge sums for HIV drugs is problematic at best, but I am not sure why you add Clinton's name into this argument.
http://www.pbs.org/wgbh/americanexperience/features/biograph...
B) The issue you mention does not even fall under health care policy, it falls under IP and trade policy, because the point of objection is when foreign nations nullify or nationalize U.S. pharma patents. That is an ongoing fight to this day, BTW.
Multiple companies could collude to keep a cure off the market. But such cooperation would require all the collaborators to be simultaneously honorable enough to keep the agreement, and dishonorable enough to keep life-saving drugs away from people who are dying. I find that unlikely.
Meanwhile it would only take one traitor to make the deal collapse. Such a traitor could be any person who is in on the secret and also has a family member affected by the disease in question. It takes dozens of scientists, project managers, lab assistants, and random extra staff to create a new drug. I don't believe that many people can keep any kind of secret for any amount of time, let alone a secret as hot as a cure for (in this case) HIV.
This is why I don't believe in the idea that drug companies intentionally keep cures off the market. If no cure is available, it's probably because it genuinely doesn't exist yet.
That's not quite correct. The company with the cure will make more money going forward. But not necessarily overall, and the difference there is important.
Let's say you're a venture investor in biotech, and you're thinking about whether to fund the development of an HIV cure or a better HIV treatment. Both will completely replace the existing market in HIV drugs. When you do the net present value calculation for the treatment however, you'll see that you have some probability of people staying on it basically forever. That means that over time, you can extract more money from it, which means of course that you ought to be willing to invest more money in developing it.
It is through this completely rational, non-evil mechanism that treatments may receive more funding than cures. Nobody here is suppressing anything, it's just that one of them will receive more funding than the other because it has a greater potential ROI.
A market based solution might be allowing pharma companies to charge extremely exorbitant prices for their cures, sufficient to recoup the foregone profits of treatment. But i'm not sure how well that would go down.
So, it may be that sometimes that causes it to make sense to search for a cure (if there is a particularly promising pathway that someone else is likely to explore, for instance), but all else being equal, it probably makes more sense to fund treatments.
The initial cost of developing any new drug is extremely high. We're talking hundreds of millions to billions. That's just to break even. That means if you have a cure for a disease that 100k people have, you have to charge them each $10k just to break even.
That is insane. The numbers of course scale directly with the number of patients, too. If only 10k people in the world have the disease, you need to charge them each 100k, just to break even (the average cost of developing a new drug is actually 2.5 billion, but for these purposes let's say you get lucky and it's 'only' 1 billion).
If you want to actually make a profit, you'll need to charge even more than that.
Also, there does not need to be an evil twist where someone deliberately holds back a developed cure. It is much easier to cut/steer the research in ways that favor treatment/management options, ensuring that a cure would only be found be accident.
No. Stuff like this gets posted to HN all the time but that is just not how things work. In a public corporation, management has broad latitude to make decisions about how to run the company and shareholders have essentially no say in it. They can sell the stock if they don't like it.
If you don't believe me, consider that Tim Cook, CEO of one of the most valuable public companies on Earth, said almost exactly the same thing in a shareholder meeting and nobody batted an eye.
Furthermore, the cost of HIV drugs isn't even the majority of the cost of HIV treatment because the constant monitoring and long term complications are extremely expensive. A single hospital visit for HIV-related pneumonia or another opportunistic infection can cost more than several years worth of the drug cocktails and the visits become more frequent and expensive with age as the weakening immune system contributes negatively to almost every other healthcare issue. The incentives for public health and universal healthcare agencies around the world is pretty cleanly aligned with curing HIV at any cost.
[1] http://store.globaldata.com/market-reports/pharmaceuticals-a...
1. Researchers build careers based on reputation. The reputational value of "cured cancer" (even for some small subset of cancer) is probably worth more than a lifetime of developing treatments.
2. Also, some motivated researchers have lost family or friends to the diseases they're working on.
3. Also, many researchers are simply not working at for-profit companies.
All of the above can be filed under "profit is not the only motive for curing diseases (even if it's a powerful one, it's not the exclusive one)." A different tack:
4. Many lines of research have unpredictable results. Studying a virus to develop a treatment may uncover a key weakness that results in a cure. Foundational research often is too early to prioritize a use, and breakthroughs happen in unpredictable ways.
5. There are a lot of players involved in research. A big mix of for-profit companies, NGOs, and governments might have to collude to avoid developing impending cures. So if there's an reasonable next step for global research, it'd be a bad gamble for a company to avoid it, hoping that no one else would pursue it either. ie, If you can get there, assume others can too, so just claim the credit.
EDIT: OTOH if you want to run with this line of thinking, there's a great classic comedy called "The Man in the White Suit" starring Alec Guinness. He invents an unstainable suit that never needs cleaned, and the garment industry sends people to stop him.
If nothing else, many academics are motivated by ego rather than money (I'd put myself in this category). Having successfully discovered a cure for HIV would do such spectacular things for my career that the level of money that would have to be involved is pretty substantial - and would have to be spread over a large number of people.
This of course brings money and marketshare to the company that owns the cure over the company that owns the treatment patents, and it brings recognition to the scientists involved.
So you can take off that tinfoil hat, if someone would find a cure for HIV, they would absolutely not sit on it.
Of course, in practice, doing so would lead to severe media outrage, calls for regulation, state-sanctioned patent breaching all over the world, etc. So the practical price is capped. Investors know this.
wait..birth control doesn't affect STD transmission. Unless you mean people getting birth control tends to lead to mode education from the medical professionals who prescribe it to them?
Yes, this is something to worry about and is exactly the reason why it is so hard to find a cure for AIDS. HIV mutates inside the body into thousands of different configurations and no matter what treatment you throw at it there will generally be at least a couple of strains that will survive and take over.
> Or is the promise here that we can combine this discovery with another that solves that remaining 1%?
That would be hard. There is always a chance that the additional treatment will only treat 99% of that 1% and even a single surviving virus might be enough to restart an infection with resistant strains.
> Or, do the mutations of that last 1% make HIV less virulent or harder to transmit?
One of the other comments here, from someone that read the paper, says that the antibody found in this study binds very specifically to a part of HIV that is crucial for infection so the 1% of strains that resist the antibody (due to mutations in the binding site) are less virulent. The antibody also binds only to parts of HIV that mutate very slowly so it might mean that it would take longer for virulent resistant strains to evolve.
Support for this work was provided by the Intramural Research Program and the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under contract number W-31-109-Eng-38.
I'm not sure how it applies here, where ~80% of the authors appear to be directly employed by some of the NIH's Institutes.
One of the current challenges being worked on is how to train individuals to make these complex antibodies. We've isolated these from people with long-term exposures to HIV, showing that the body can generate these broadly neutralizing antibodies.
Some current work is focusing on developing a series of peptides that can coax HIV negative individuals to make these complex antibodies.
Your immune system can and does fight the HIV virus, it does loses that fight because HIV attacks the immune system, can hide for years, and has a cell to cell infection vector.
The immune system is also limited to what it can do, and when viruses can spread cell to cell there isn't much it can do since there is little to no attack surface available for the immune system to work with in that case.
Antibody and therapeutic vaccines can be used as post exposure treatments and combined with other regiments to help slow down or even control the progress of HIV and AIDS in already afflicted patients.
A therapeutic vaccine with a regiment of reverse-transcriptase inhibitors and a treatment to control cell suicide upon infection can probably be developed for HIV and for other retroviruses, well excluding the antibodies it is what we already are doing today mostly.
I am an absolute noob in science, but still want to ask out of curiosity. If a biological virus can have a cell to cell infection vector, can't an anti-body or immunogen also have a cell-to-cell "replenishing" factor?
An antibody is just a protein molecule with no ability to create copies of itself. It might move from one cell to another, but that does create a new synthesizer of the antibody at the new location, and so does not trigger a spread of the antibody throughout the tissue or organism.
Cell to call transfer and communication happens all the time, cells share nutrients and many other things, some viruses take advantage of that mechanism allowing them to basically cross cellular and tissue boundaries.
Some can exploit this to the extreme by actually replicating only parts of themselves in each cell and using the cell to cell transfer highway to be finally assembled in another cell, this is often used to prevent cell suicide since one of the intracellular defense mechanism is basically the cell invoking cell death upon detecting an infection.
If you want an analogy from the technology world think about it as staged payloads that some malware use, each payload on it's own is undetectable and even non-functional but when everything reaches the final target all the payloads are assembled into the final piece of malware that takes over the targeted host ;)
If you are interested in cell to cell infections NIH has an article about it
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587356/
There are quite a few other sources on Google, overall viruses are pretty sneaky, some of them even ask the cell politely to establish new cell to cell contacts to facilitate cell to cell infection.
You might also like to look up virus assembly and budding, since it's also a pretty interesting topic, you might have viruses that do cell to cell infection of their naked forms then the final polymerization of their shells happens in another cell and they might even do the final budding in another.
Expect nightmares tho ;)
P.S.
Cell to cell transfers might also be called exocytosis (sometimes also called reversed endocytosis) (exit) and endocytosis (entry) so if you are googling and can't find what you need might need to use the scientific terms.
I see the comments about cell-to-cell infection; I don't know what it is about these controllers but it doesn't seem to be a problem for them.
Actually, a lot of stuff about HIV makes more sense if you assume the majority (all?) of transmissions occur this way.
2) Notice I have no quantification or numbers associated with these ideas. As far as I know, no one has ever spent the time to work this out into a real model that can make precise predictions. Accordingly, consider them wild speculations.
3) According to this sketch of an idea, anything that contributes to identifying and lysing non-self cells should reduce transmission in a given tissue.
Rather, it's the researchers who went looking for them who should be granted any patent rights. They're the ones who could work harder to produce better results and can have their performance improved with more rewards like a patent's monopoly.
There are tricks to developing vaccines without using the pathogen directly, like constructing a decoy with the relevant surface proteins, but they're unlikely to work with HIV because it's so simple. When an antibody finds its antigen, it signals the immune system to consume the pathogen and learn about it if it hasn't seen the invader before. Since antibodies share a chemical structure (like DNA and RNA, except more complex), cells in the immune system can memorize the antibody and produce it even if it isn't present in our genetic code. This process is one of the most amazing adaptations in the animal kingdom, allowing complex organisms to compete with the microscopic in the evolutionary arms race, but the immune system needs to see the antibody and pathogen in order create mature B-cells, which adapt to bind to the same pathogen as the antibody. HIV is small, simple, and doesn't have many unique features on the viral package (which contains the RNA) so it'll likely be very hard to produce a decoy for the antibody to latch on to.
here is an HIV sequence database https://www.hiv.lanl.gov/content/index https://hivdb.stanford.edu/page/who-resistance-list/
if you take medicine, get off them and try to get back on your medicine, you may find your medicine no longer works.
that being said I don't quite know what "neutralize" means in this context, but the NIH seems to feel this result has wide applicability.
Yes.
I think, as a species, we'll master time-travel before consensus...
You might have to eradicate a number of species.
Many species have a similar virus, even cats, and still it only jumped once so far in it's history.
Not true.
http://incubator.rockefeller.edu/jumping-species-how-hiv-ent...
There are four major groups of HIV, HIV1 (likely to have originated in a strain of SIV commonly infecting chimpanzees and gorillas) O and M and HIV2 (likely to have originated in a strain of SIV commonly infecting mangabeys) A and B, it's not cleared how many times it independently jumped, what is clear that this was more or less a single temporal event in modern history (cavemen didn't had to worry about HIV or aids, neither did the Romans, and even the bushmen in africa only have been recently infected) and the jump happened between the late 19th and early to mid 20th centuries.
SIV doesn't jump species all the time, there are plenty of SIV strains that haven't done so even tho humans were and are in contact with primates that are infected by those strains all the time.
Other immuno suppressing viruses also haven't made the jump from other species to humans.
If you eradicate HIV today with a push of a button there is no guarantee that SIV will make a jump again and turn into HIV, and there is little to no evidence that HIV jumped back to primates or has yet to infect another species.
There is also no conclusive evidence that the four groups of HIV happened to jump species on 4 distinct occasions, could have been 4, could have been 2 could have been 1 could have been 400. Heck if HIV1C somehow originated in South America and then was introduced to the human population in Africa half of our models can be thrown down the toilet.
What we do know is that this happened 80-140 years ago, why did a virus that infected primates for 50,000 to 2000000 years suddenly jumped species all of a sudden despite the fact that there was just as much if not more cross species interaction during human history is a better question, in fact if it indeed jumped multiple times all within a pretty small time window that would only raise more questions than give any answer.
Simian AIDS was discovered after human AIDS though: "Examination of the species-specific annual mortality rates of macaques at the center during the previous 4 yr showed a significant increase in deaths in 1980 and 1981" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393899/
I don't see how people really know whether the problem originated in humans and spread to apes or vice versa. If anything you would expect such issues to be detected in highly monitored animals kept in well controlled research facilities first...
We know it didn't originate in humans, because we can estimate how old SIV and HIV are based on their genetic material and other factors.
And we also know how old SIV at least is because we've tested primates on isolated islands and found that they are also infected, so if you find SIV infected primates on an island that was isolated from mainland Africa 30,000 years ago and it's preset within 100% of the primate population you know it's at least that old.
Another thing you can do is look at the DNA of the host and see if any viral DNA has been embedded within it, depending on where it is you can also estimate a timeline based on known processes and mutation rates.
There is very little to no doubt that HIV originated from SIV, the question is why now.
And yes we've discovered SIV later because AIDS happened then we found that it's a virus and not because they are gay, so people started looking at it's source and discovered SIV, FIV, EIAV and others.
You also need to understand that viruses are very hard to find, it's not like you just look at blood samples and see them, there are also not that many generic tests that can simply detect if a virus is present or not, it takes years to decades to isolate, classify and then develop methods to identify a virus and it's not like in the 1980's you could just order a full genome to be sequenced at will.
This sounds familiar, do you remember the ref? From what I remember the degree of "isolation" was questionable.
It's important to note that even if the location is not isolated it doesn't matter, and we do have proof that it is, what we look at is the molecular clock of the virus basically it's molecular structure based on the mutation rate of each virus.
When you calculate the drift between different strains you can estimate the age, more isolated populations help since they tend to have less types of infections, while it's not common to find a primate with multiple strains on the mainland primates in the deep jungles of south america and on isolated islands off the coast of africa usually only have a single strain due to their relative isolation from other primate populations.
"Crucially, he knew from geological records that the island separated from continental Africa around 12,000 years ago. Assuming that the strains had had at least 12,000 years to evolve apart, he determined that the mutation rate of SIV is much slower than originally thought."
I find it difficult to believe that for 10k years a plausible scenario is that nothing happened like eg: A) someone was hunting monkeys from more populated areas and traveled to "isolated" islands/regions to get more. B) monkey on a branch gets thrown out to sea and floats to the island.
Again it doesn't need to have a perfect isolation, and the fact that the island is home to completely different strains which are unique to that island and can be genetically studied for drift and mutation rates does show that there was sufficient isolation to prevent transmission between the mainland and the islands.
All isolation is relative, N. Korea is isolated it doesn't mean that nothing gets in or out, same thing here a monkey on a branch might be thrown out to the ocean but it doesn't mean it will become a transmission vector.
Strain X exists only on Island Y while strain M N and O exist only on Mainland Z but not vice versa is enough proof for isolation for the studies to be valid.
Sure, not only, but according to your source it is dependent on the assumption the island was "isolated" for 10k years. We would have to look at the model to tell what effects relaxing this assumption and definition may have.
We know that the island is isolated sufficiently because of the unique SIV strains, we also know that the populations of the animals were isolated because there are no signs of cross-breeding.
There have also been countless studies to determine the age and the source of the tMRCA between HIV and SIV, and SIV is the source for every genetic study, even those that do not rely on using molecular phylogenetics to ascertain the time scale.
SIV and other primate lentiviruses are old, they are asymptomatic in the vast majority of their natural hosts which suggest coevolution which resulted effectively in cohabitation.
Most of the current work is done in regards to tMRC identification to build an accurate timeframe to understand why did HIV1 jumped from chimps to humans and HIV2 jumped from mangabeys.
We are also studying the divergence of different strains of SIV between different species of primates to better understand the virus, all of these studies find completely different time scale than what you are proposing, in fact other than conspiracy theories that were already disproven no science actually backs up any of your assertions.
Overall even if we take the studies that point to a completely different pathology and estimate the age of SIV at 100's or a few 1000's of years old, the divergence of the different strains still means it came first, spread across the primate population of africa, and then jumped to humans.
The rest of what you wrote is interesting (or will be once I get some sources for your claims), but you start out with this one that blatantly disagrees with what was written in your own source. In your source it says that molecular clock depends on the assumption the island was isolated for 12,000 years.
It would be great if you could:
1) Focus on that one point to clear up why you disagree with your own source, do this without writing about anything else. I am stuck on that issue right now.
2) Bring some links when referring to evidence, so I can tell what has made you believe the things you say. I am getting the sense you are well informed but not quite skeptical enough (perhaps current grad student?). The devil is in the details, as I have seen with the "isolated" island and molecular clock interdependence.
This doesn't really fit with the narrative in the paper I linked. They give this reason: "It was the impression of workers at the New England Regional Primate Research Center that there had been an increase in the number of deaths in its macaque colony."
So what's exactly the surprise in the fact that an article from 35 years ago that was written at the dawn of HIV and AIDS research doesn't exactly fit with our modern understandings of the disease?
As quoted earlier, they say the study was initiated because they noticed the animals dying more often than usual. You don't need genetic/epidemiological data to notice something like that. I do not understand what relevance that should have.
When that research was conducted we didn't even knew what was causing AIDS as neither SIV nor HIV have been identified yet.
Also research animals die all the time in great numbers, if it's a research laboratory then they'll probably die or be put to death way before they'll develop AIDS, if it's a conservation then they die to natural causes all the time, it's more likely that no one bothered to think why primates die to various infectious diseases more frequently than they should beforehand and then when AIDS research began to be published some one made a connection and looked into it.
It's not like in 1983 or prior to that we commonly had 100's of primates locked in for a multi decade research in a state of the art habitat which was constantly monitored, they were either lab rats that lived a very short life or at best simply tracked for conservation purposes on a reservation.
In fact after reading the research fully, it looks to me like they've unintentionally introduced SIV to Asian Macaca Cyclopis from an African species M. Mulatta (commonly known as a rhesus monkey) since SIV is not commonly present in Asia it's no real wonder why an Asian primate species would be considerably more affected as African species would be more or completely immune to AIDS while being SIV carriers.
If anything this paper proves that African primates coexisted with SIV for a long enough time to develop an immunity or high tolerance to the virus while species from other regions that did not have SIV strains did not.
And you can chuck this again to the fact that in 1983 no one knew that AIDS was caused by HIV, SIV, FIV and other similar viruses.
Yes, yet (relatively) soon after human AIDs is discovered people start noticing an increase in macaque deaths in their labs. This was later attributed to a similar cause. I think that is an important aspect of the timeline to keep in mind, that is all on that point. The rest hinges on other evidence which we are discussing in parallel here.
I really don't understand why you are even attempting to quite wrongly interpret the results of a study before HIV or SIV were even discovered that actually disproves your assertion.
This is a borderline conspiracy theory.
There is a huge difference between the NIH announcing a finding and the sensationalist science journalism that is typically inaccurate. I wonder if this divergence erodes the public trust in science.
So instead of seeing news that say specific things like "this might lead to a monoclonal antiboody treatment in 10 years" or "this could help vaccine research" you end up with a bunch of headlines that sound as if AIDS is going to be cured tomorrow.