I don't think the question is whether viruses are real, the question is whether scientific studies have yet to show transmission of infection that leads to disease.
There isn't a scientific definition for "real" that I'm aware of. Do you know of any studies that have isolated a virus, or a virus plus host cells, and successfully introduced those into a novel population to reproduce disease? All I've ever managed to find are epidemiological studies after an assumed viral outbreak, but I really am interested to see a more controlled study that helps prove a more direct link.
I agree with the people saying this is impressively kooky, but just in case here's a pretty overwhelming number of examples of common viruses in mice, how they're isolated, and how laboratory populations are then directly infected with them: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150319/
(There's plenty more out there, but that source is just so dense with examples that it seemed like a nice go-to.)
To be clear, there are a ton of studies listed there but all the ones I chased down (maybe 25%) they aren't isolating the virus.
My message you were replying to specifically called out Koch's Postulates [1] and the fact that virologists had to first redefine it then abandon it for epidemiological and modelling studies.
You effectively proved my point here, everything I see in the survey you linked fits into that description. I'm not arguing that viruses do or don't exist, only that I've never seen a study successfully isolate viral particles in a substrate, introduce it to a novel population, and re-isolate the virus from the novel population after they begin showing signs of disease.
> the question is whether scientific studies have yet to show transmission of infection that leads to disease.
We literally make adenovirus derivatives for cell therapy, and a lot of technical and engineering effort went into making the derivatives non-disease agents. I, personally, have made baculovirus derivatives for protein expression. E.g. https://www.addgene.org/kits/peters-bigbac/#?
The same with vaccine-induced polio and the like from attenuated live virus vaccines. How do you think scientists made those attenuated live viruses in the first place without isolating, engineering, bulking up, and then "infecting" (vaccinating) people with them?
I'm specifically referring to Koch's Postulates here, and as far as I'm aware the viruses you're referring to weren't isolated. I've always seen them being used either in models or in some other host cells from cows, monkeys, etc. though I've never worked directly in the field so please point me to a study if you've seen one truly isolate a virus.
> Virus propagation in cell culture. Heart tissue from freshly dead Atlantic salmon (Salmo salar L.) was collected from a clinical outbreak of CMS (the diagnosis was confirmed by histopathological examination). The heart tissue was homogenized, followed by centrifugation at 4,000 g and 4°C for 20 min to remove cellular debris, before being processed through a 0.22-m filter. The homogenate was subsequently inoculated onto GF-1 cell cultures (5). The GF-1 cell line, derived from the fin tissue of orange-spotted grouper, Epinephelus coioides, was grown in plug seal cap culture vessels at 15°C after inoculation in Leibowitz 15 supplemented with 1% L-glutamine (2 mM final concentration), 0.1% gentamicin sulfate (50 g/ml final concentration) (all from Sigma Aldrich), and 10% fetal bovine serum (Invitrogen). Development of cytopathic effect (CPE) was monitored at 6, 14, and 21 days postinoculation (p.i.). At 21 days p.i., the supernatant was harvested and passaged further in cell culture.
Notice that since this wasn't a stringent purification they used a subsequent passage to further dilute out anything carrying over. As stated in the other comment it would also be possible to use something such as tangential flow filtration or size-exclusion techniques in order to get an even purer first sample.
> the viruses you're referring to weren't isolated
They're made de novo (adenovirus and baculovirus derivatives, and yes, I've done this for baculovirus), which is better than isolation as even with isolation it's difficult to prove a pure sample. Even Koch couldn't prove an isolated sample back in the day. Not to our standards, at least.
Throw a GFP protein in the modified adenovirus or baculovirus genome and you can literally see the exact specific virus that you made move from cell to cell while the cells start dying.
Human challenge studies are used to test the efficacy of therapeutics and vaccines, not to test the pathogen itself. I was specifically referring to the abandonment of Koch's Postulates in virology, which again has nothing to do with challenge studies where the virus is not isolated from the host.
: Due to begin in the next few weeks, it will involve up to 90 carefully selected, healthy adult volunteers being exposed to the virus in a safe and controlled environment.
: The safety of volunteers is paramount, which means this virus characterisation study will initially use the version of the virus that has been circulating in the UK since March 2020 and has been shown to be of low risk in young healthy adults.
Note that this study was in 2021, after the virus had already mutated. In order to ensure that the volunteers are infected with a specific virus version they would have to have cultured it.
: Once this initial study has taken place, vaccine candidates, which have proven to be safe in clinical trials, could be given to small numbers of volunteers who are then exposed to the Covid-19 virus, helping to identify the most effective vaccines and accelerate their development.
As shown here, the first cohort would not have been given a vaccine. But would have been used to characterize the activity of the virus on healthy humans.
> Human challenge studies are used to test the efficacy of therapeutics and vaccines, not to test the pathogen itself.
These are the same thing. The only way to demonstrate the efficacy of a vaccine is if the control group gets sick, otherwise there can't be a relative improvement.
(That's why reported vaccine efficacy goes down over time; as people naturally get the disease it appears to be relatively less effective as some of them get natural immunity.)
> These are the same thing. The only way to demonstrate the efficacy of a vaccine is if the control group gets sick, otherwise there can't be a relative improvement.
That's simply not true. A vaccine efficacy study specifically validates how well the introduction of a vaccine prevents disease, it does nothing to show the specific link between disease and the pathogen itself.
Prior studies are needed to link the pathogen to disease, and the most accurate way to do this is to first isolate the pathogen then show that introducing it to a novel population recreates the disease. After symptoms show up, if the pathogen can again be isolated from the newly infected hosts you have a pretty strong case for causation. Moving on to reproducing the results in follow up studies would go a long way. At that point you know the likely pathogenic cause and can move on to developing a vaccine based on that pathogen and run efficacy studies to see how well the vaccine works to prevent infection, disease, or transmission.
In general this line of argument is questioning how we can know that a particular virus causes a particular disease. It ignores decades of technological improvements developed toward actual viral bulkup, purification, and infection.
Is it easy to know that a particular virus causes a particular disease? Not always, particularly if the disease syndrome is complex. Is it possible to link particular viruses to particular diseases? Definitely. For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.
> For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.
I'd be really interested what this work would look like. Koch's Postulates have always made logical sense to me and I've never understood why they where abandoned for virology. How can we prove a high likelihood of causation when at best we only have data of hosts that already showed signs of disease?
Aside - this thread seems to have gone down a rabbit hole where many are assuming I'm claiming viruses don't exist or don't cause disease. I get that viruses have been made a political topic these days, but I'm only raising that as far as I'm aware viruses have never been isolated in the same way as bacteria or fungi. We've never, again as far as I'm aware, isolated a virus from a sick person, exposed a healthy person to it, and seen the same disease symptoms show up with the virus now present in their system.
One could point to vaccines for this proof, but even those include other adjuvants that are present specifically to inflame the host and help promote a stronger immune response. I'm not claiming that including those adjuvants is a problem as far as the vaccine goes, only that it doesn't fit the definition of introducing an isolated virus.
Have we found plenty of evidence that a specific virus is present in a host after symptoms are shown? Absolutely. But have we ever successfully checked the box on Koch's Postulates with a virus? Not that I know of.
Perhaps, a better way to traverse this would be to look at the history of virology, trace main events, starting from the discovery of bacteriophage, and check out associated work. It is hard to say what kind of evidence would satisfy you. Viruses have been isolated many times, and transmissibility has been shown on cell cultures and animal models.
You can't purposely infect real people with disease-causing viruses in research so you won't find much studies like that. But there is no doubt that viruses are transmissible and can cause disease, and there is plenty of evidence to support that. Check out studies on yellow fever virus and flu done more than a hundred years ago.
Viruses, and some unculturable bacteria and other organisms, are simply unique with regard to Koch's second postulate, in that they literally can't be cultured in a pure manner. Hierarchical and tangential flow filtration can, however, get them incredibly pure (as quality controlled by electron microscope) after culturing. I'm not an expert here. This is probably not routinely done as it would be costly and to no purpose for the particular experiment. But it can be done, and I'd be extraordinarily surprised it it hadn't been done.
> We've never, again as far as I'm aware, isolated a virus from a sick person, exposed a healthy person to it, and seen the same disease symptoms show up with the virus now present in their system.
Yes, we also don't typically expose healthy people to disease-causing bacteria either. This is a hard sell post-WWII.
Typically when you culture a virus you'll also have a separate culture that is exposed to everything else minus the virus. You'll "purify" both in the same manner, expose some animals or cultured cells to the purified virus culture, and expose other animals or cultured cells to the purified control culture. The only thing that differs is the presence of the virus.
> > For the more straightforward diseases it's even relatively straightforward to show that a particular virus causes that particular disease, with enough work.
> I'd be really interested what this work would look like.
A stringent example:
1) Replicate the virus in cell culture and ensure you're isolating the virus while doing so.
- A: homogenize and passage a virus containing sample.
- B: passage it through cell culture.
- C: dilute the supernatant from cell culture until the dilution, on average, has less than one virus per aliquot.
- D: Use these aliquots to inoculate further cell culture.
2) Analyze all cultures
- A: As, on average, some of the aliquots contained no virus, there should be a number of cultures which look identical to the uninfected controls.
- B: Any cultures which show morphology or pathology distinct from the uninfected controls should contain specific virus particles and show specific viral RNA/DNA on a PCR test. Likewise, any cultures which look like the uninfected controls should be free of virus based on these tests.
- C: If any cultures show morphology or pathology distinct from the uninfected controls but do not contain virus particles (given sufficient time for the virus to propagate and emerge from the cells), then you've got a thinker on your hands. Triage for contaminants or another disease causing agent.
3) After demonstrating that virus is the causal agent of the infected culture morphology or pathology, use multiple of these infected cultures to infect animals (and have control "infections" from the uninfected cultures). Then repeat this process from the infected animals to demonstrate that it is indeed the identified virus which causes the disease.
If you can't use an animal model for the disease then you're stuck doing this in cell culture and comparing the infected culture cell morphology and pathology to that of cells in biopsies of diseased people.
Pretty darn good evidence that it is a virus, and a particular virus at that, which causes the disease.
Realistically it's much more convenient just to use 2B as evidence. You get some issues with natural immunity and lysogenic versus lytic viral stages (these have different terms in Eukaryotic viral infection), but it's pretty decent for showing things like HIV being the causative factor of AIDS even prior to showing the effect of HIV presence in immune cells.
Koch's Postulates have since found new life among conspiracy nuts as indisputable proof that viruses aren't real.