Note that in general low-transmission rates aren’t that good an argument against it. First of all, a lot of transmission in the US occurred through other forms, especially early in the epidemic (intravenous needle sharing and transfusion of infected blood being two major ones). As others have noted the transmission issue is also generally higher for homosexual rather than heterosexual intercourse.
Frankly, the thing that I most don’t understand about people who are skeptical about the HIV-AIDS link is how one explains the fact that anti-virals tailored to deal with HIV work. Even the first-gen treatments such as AZT were used due to the biochemistry of HIV (often targeting reverse transcriptase). And they worked in delaying the onset of AIDS and worked for giving people with AIDS higher life-expectancy. I don’t see how one can easily reconcile that with HIV not being the cause of AIDS and I’ve never heard anything remotely resembling a coherent explanation about this.
The extremely low official transmission rates indicate that HIV is probably not a sexually transmitted disease, as typically understood. According to the published transmission data, it’s only effective natural means of transmission is vertical—from mother to child. From what we know about symbiosis and parasites, this should lead one to suspect it is not that lethal.
However that doesn’t destroy the hypothesis that HIV could be a unique disease of civilization—a mutation of a formerly limited retrovirus into a more damaging form that spreads horizontally only through extremely unnatural novelties of the modern world—needle sharing and epic promiscuity in some subgroups. It does of course make the overall hypothesis more complex and overall less likely, but it doesn’t destroy it outright.
Frankly, the thing that I most don’t understand about people who are skeptical about the HIV-AIDS link is how one explains the fact that anti-virals tailored to deal with HIV work.
This is very difficult to prove ethically, and certainly hasn’t been shown to satisfaction. Consider how immensely difficult it has been to understand the real health effects of fat in the diet, for example. In the 80′s and 90′s, we thought it was oh so simple. Today we (the wise) realize how profoundly ignorant we were then, and still are today. I think part of the rational reappraisal for the strength of the HIV hypothesis should come from a similar update.
In other words one can only cling to a high degree of certainty about the HIV hypothesis when one is profoundly ignorant concerning the depth of one’s ignorance about the complexity of human health.
Even the first-gen treatments such as AZT were used due to the biochemistry of HIV (often targeting reverse transcriptase).
That’s the theory.
And they worked in delaying the onset of AIDS and worked for giving people with AIDS higher life-expectancy.
Ahh the world would be so simple if that was true. The AZT clinic trial was ended prematurely and double-blindness could not be maintained due to side effects. The skeptics claim that later studies show that AZT increases long term mortality, not the other way around.
I don’t see how one can easily reconcile that with HIV not being the cause of AIDS and I’ve never heard anything remotely resembling a coherent explanation about this.
You need to realize how impossible it would be to concretely show what you presume to high certainty. You would basically need a double blind study with two control groups, one receiving plazebo, and compare total mortality. One immediate problem is any noticeable side effects would immediately end the blindness—and the retrovirals certainly have side effects.
And even showing that AZT or drug X reduces mortality in HIV+ patients does not lead to the conclusion that HIV is the cause, or that AZT or drug X has any effect on HIV. Supplementing patients with vitamin D, or changing their diet, or feeding them aspirin, or any number of other changes could also decrease mortality, but have nothing to do with the viral theory.
This is very difficult to prove ethically, and certainly hasn’t been shown to satisfaction.
Ahh the world would be so simple if that was true. The AZT clinic trial was ended prematurely and was generally bogus. The skeptics claim that studies show that AZT increases mortality, not the other way around.
So I don’t know what evidence you have for these claims. The original AZT study can be found here. It handled placebos just fine.
And AZT is just one example of many anti-retrovirals. 3TC and ABC have also been used. Moreover, there are studies which show that the the standard drug cocktails work better than AZT or 3TC alone. That makes sense for the standard model of HIV as the cause of AIDS.
And even showing that AZT or drug X reduces mortality in HIV+ patients does not lead to the conclusion that HIV is the cause, or the AZT or drug X has any effect on HIV. Supplementing patients with vitamin D, or changing their diet, or feeding them aspirin, or any number of other changes could also decrease mortality, but have nothing to do with the viral theory.
There seems to be an issue here involving what level of evidence is necessary. From a Bayesian stand point you can’t ever “show” anything in the sense that you want. But the overall pattern of evidence can still give you a probability close to 1 that HIV is the primary cause of AIDS.
Notice that it has serious toxicity side effects, including bone marrow supression, and thus it can massively damage the innate immune system.
This is evident in the abstract itself:
We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001).
The original AZT study could not possibly be placebo controlled, due to the high toxicity—this is basically chemotherapy. Now chemotherapy can be effective, but it can not be double blind.
Furthermore, due to high toxicity, only a fraction of patients actually completed the intended trial:
The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks
Only 27 out of 245 AZT subjects completed the full 24 weeks! One in the AZT group of 245 died in this period, but how many more in the AZT group would have died if they had been able to complete the full 24 week chemotherapy trial?
These were crazy times. These patients were very ill and very worried. It was a full scale terror panic. It was obvious who was on placebo and who wasn’t, and from what I have read, placebo patients were swapping and trading pills with AZT patients who couldn’t finish. It was many things, but not double-blind.
There seems to be an issue here involving what level of evidence is necessary.
Here is what would be required to prove with > 99% certainty that HIV is the sole cause of AIDS:
Take a random sample of perfectly healthy test subjects. Now inject half of them with HIV and half with a placebo, and follow their health over the long term. That is about the only test that could get you 99% accuracy, and it is obviously not ethical.
So, instead we have to make due with what we have.
And again, showing that AZT improves long-term mortality—which the AZT trial clearly did not show, only shows that AZT improves mortality in sick AIDS patients. It doesn’t tell you much else about HIV as a theory.
It’s important that we agree on that subpoint—for it has nothing to do with the level of evidence.
There are many, many things that could improve mortality in sick AIDS patients. Stoss therapy, better diet, more sex, aspirin, etc etc. Do you think that proving a mortality decrease correlation in any of these categories would ‘prove’ they are the true cause of AIDS?
Moreover, there are studies which show that the the standard drug cocktails work better than AZT or 3TC alone. That makes sense for the standard model of HIV as the cause of AIDS.
It also makes sense for the common sense model that reducing AZT doses down from outright lethal to mildly poisonous but tolerable ‘works better’.
Take a random sample of perfectly healthy test subjects. Now inject half of them with HIV and half with a placebo, and follow their health over the long term. That is about the only test that could get you 99% accuracy, and it is obviously not ethical.
There have been documented cases of accidental HIV infection of lab workers and dental patients that are not too terribly far from such a controlled experiment. See: S.J. O’Brien and J.J. Goedert, “HIV causes AIDS: Koch’s postulates fulfilled,” Current Opinion in Immunology, Vol. 8, Issue 5, October 1996, pp. 613-618.
The article (listed as a “guest editorial”, I note for completeness) has the following citations in the relevant section:
52. Weiss SH, Goedert JJ, Gartner S, Popovic M, Waters D, Markham P, Veronese FD, Gall MH, Barkley WE, Gibbons J et al.: Risk of human immunodeflciency virus (HIV-1) infection among laboratory workers.Science 1988, 239:68-71.
53. Reitz MS Jr, Hall L, Robert-Guroff M, Lautenberger J, Hahn BH, Shaw GM, Kong LI, Weiss SH, Waters D, Gallo RC, Blattner W: Viral variability and serum antibody response in a laboratory worker infected with HIV-1 (HTLV-IIIB).AIDS Res Hum Retroviruses 1994, 10:1143-1155.
54. Guo HG, Waters D, Hall L, Louie A, Popovic M, Blattner W, Streicher H, Gallo RC, Chermann JC, Reitz MS: Nucleotide sequence analysis of the original isolate of HIV-1.Nature 1991, 349:745-746.
55. Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guetard D et al.: LAV revisited: origins of the early HIV-t isolates from Institut Pasteur.Science 1991, 252:961-965.
56. Wolinsky SM, Wike CM, Korber BTM, Hutto C, Parks WP, Rosenblum LL, Kunstman KJ, Furtado MR, Munoz JL: Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants.Science 1992, 255:1134-1137.
57. Morbidity Mortality Weekly Report of the Center for Disease Control: Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults (1993). 1992:1-19.
I’m not a skeptic, but I am a bit surprised that three infected lab workers is considered evidence worth mentioning. I’m accustomed to seeing clinical studies with fewer than 100 patients treated as merely suggestive, and several hundred or even thousands of patients necessary to convince regulatory authorities that there is a real phenomenon. So when I read that “three laboratory workers...became infected”, it strikes me as anecdotal. Of course you take what you can get, but still, it seems a small group.
My experience is with pharmaceuticals, which could explain the difference. But still, there’s a difference to be explained.
On the upside, if three is worth mentioning, then maybe one is worth mentioning, which would mean that Seth Roberts’s self-experimentation may be worthwhile.
Ok, so I have finished reading O’Brien and JJ Goedert. I think the accidental lab worker cases probably have low utility in distinguishing between pathologic HIV and passenger HIV theories, but the animal SIV studies potentially fulfill the ideal experiment design. If animals injected with pure close SIV analogs to HIV develop AIDS-like illness, that is about as good as evidence as one could hope for.
For the lab worker infections, they say that the genomes are close to the clonal strain used in the lab, but they don’t have a good probalistic model for this:
The sequence divergence
between LW virus envelope genes and clonal HTLV-IIIB
is <3%, which is the same genetic distance from LAV-LAI
to HTLV-IIIB, viral strains now agreed by all to have
been derived from a single patient [54,55]. This low
level of sequence divergence is equivalent to the variation
observed between HIV-infected infants and their mothers,
and threefold less than the extent of variation of HIV
between unconnected patients [56].
threefold more or less variation doesn’t sound like much to me, and regardless even assuming they did all get infected via the lab, it doesn’t mention treatment, so we don’t know if they were treated with AZT or what.
I think the animal models are more interesting—as all the drug cofounding variables are eliminated and everything is controlled.
The authors discuss 3 animal models—baboons, some wierd knockout mice with human t-cell graphs, and finally SIV injected into rhesus monkeys. They spend the most time discussing the latter paper so I looked into it.
“Induction of AIDS in Rhesus Monkeys by Molecularly Cloned Simian Immunodeficiency”.
In short, all 5 of the monkeys injected later become seropositive, and 50% of them progress to AIDs-like illnesses and die. Presumably some are naturally resistant.
There is a potential issue to this otherwise smoking gun, which is that it appears they had to inject whole culture of T-cells, as the virus can not be isolated directly into plasmid vectors:
We, and others, have experienced considerable considerable difficulty in subcloning the full-length proviral DNA into plasmid vectors.
SIV mac239-cloned DNA was transfected into primary macaque PBLs and into Hut 78 cells (a human CD4+ T cell line) by a DEAE-dexxtran procedure, and stock virus was frozen for subsequent animal inoculations
But if all they had then was provirus integrated into PBL ( peripheral blood lymphocytes ), then one must wonder about the risk of graft versus host disease, and transfusion reaction in general. Basically, the foreign T-cell line can actively invade and cause all kinds of havoc. Perhaps they have controlled for that and I’m completely off, but I don’t see where they mention it.
OBrien and Goodart conclude:
Control macaques inoculated with
saline, with inactivated SIVMAcA239 or with SIVMACA239
carrying mutations/deletions in the nef gene failed to
induce AIDS in the same macaque species [80,83,84].
Because SIV strains cause AIDS in monkeys and because
they are the closest phylogenetic relatives of HIV, they
provide an animal model fulfillment of Koch’s transmission
I haven’t seen mention of ‘inactivated’ sivmaca239 yet in 80, but maybe it is in 83 or 84. However, if they are forced to infect live T-cells because they can’t produce viable clonal plasmid, this seems to have a major confounding factor in graft vs host disease. I’d like to find a knowledge skeptic take on this—perhaps Duesberg confronts it, not sure yet.
If he doesn’t confront it, then that doesn’t look so good for his position.
It appears to me that you are noting different weaknesses, different alternative explanations of the results, in each experimental protocol. I imagine that could appear to happen if there were a strong publication bias for results in favor of the hypothesis (e.g. with medicinal prayer studies), but that has not been demonstrated.
From what I understand, there is strong reason to suspect such bias in the animal models, as many other animal tests were conducted previously attempting to show SIV causing AIDS, and they uniformly failed. From what I have read, the SIV injections failed to do anything in chimps. We don’t know how many other rhesus monkeys were injected, but I find it highly unlikely that the five in this study (3 out of 5 of which developed immune defeciency) were the first.
That bias is interesting and it would be useful to have a metastudy covering all the animals that have been injected, but of course most naturally occuring strains of species specific virus should be expected to be harmless. So the ‘bias’ doesn’t really tell you much and is expected either way.
I’ll look to see if there is any skeptic review of the SIV injections which did succeed, because in my mind that is fairly strong evidence. If HIV analogs cause AIDS-like illness in primates when they hop species or traditional barriers, this is a good experiemental model for HIV crossing over into humans and causing illness, and is far stronger in my mind than the murky epidimelogical data with all of it’s drug cofactor issues.
The lab monkeys are in a controlled environment—we know they weren’t using drugs, weren’t fed AZT, etc etc.
Yes, but were they treated with chemotherapy agents such as AZT which cause bone marrow and immune supression? (I am asking before I read the article)
For the controlled experiment example, it would have to be double blind the entire time. Nobody would ever know who got placebo and who didnt’, and no difference in treatment regimens either way—all on the same diet, same lifestyle, etc etc. I highly doubt the accidental cases fit that profile.
Yes, but were they treated with chemotherapy agents such as AZT which cause bone marrow and immune supression?
From what I see, O’Brien and Goedert don’t report about this. However, Cohen’s Science article to which I linked above provides more details about the cases of infected lab workers, claiming that two of them didn’t receive any antivirals until the progress of AIDS was well underway: http://www.sciencemag.org/feature/data/cohen/266-5191-1647a.pdf
I have seen that, but I don’t take it as strong evidence of anything either way.
Clearly HIV antibodies are correlated with ill-health, poor immune function and low CD4 counts—that was established in the very beginning by Gallo et all and is the entire basis of their original claim.
But the competing hypothesis is not the null hypothesis, the competing hypothesis is that the HIV presence is a marker of some severe immune function failure, and that HIV itself is a largely harmless vertically transmitted retrovirus—like all the others. If it does become active, it is because something is already seriously wrong.
So of course if you have a lab, and you are testing lab-workers deathly afraid of contracting HIV, in either theory some may come up HIV+, and in either theory those that test positive will be ill.
This is very different than the intentional infection test you need to establish strong causation along a koch’s postulate principle. I think one of the stronger flaws in current HIV theory is the chimpanzee models—they have many HIV similar retroviruses (SIV’s), they are common in wild chimps, are all vertically transmitted, and don’t appear to be problematic for chimps. If HIV killed chimps outright, the mainstream theory would have some more ammo.
Instead the theory is that HIV came from a chimp SIV and somehow became lethal and horizontally transmissable at the same time in humans. But from the studies of sexual transmission—it is only weakly blood transmissable. So overall, it’s alot to swallow. I think it is plausible that this happened and HIV causes novel problems in humans, but it certainly has not been well demonstrated, mainly because HIV doesn’t cause specific symptoms and it is extremely difficult to properly dissociate other causitive factors. As Duesberg notes, the cocaine/meth craze boomed in the 80′s right as the AIDS epidemic started—they overlap perfectly.
Deusberg’s theory is that drugs specifically are a major cause of the immunosupression, which I think has some absolute validity, but we should also notice that there are other causes, and some people just have poor immune health, and this has been the case for long before HIV came on the scene.
I think one of the stronger flaws in current HIV theory is the chimpanzee models—they have many HIV similar retroviruses (SIV’s), they are common in wild chimps, are all vertically transmitted, and don’t appear to be problematic for chimps. If HIV killed chimps outright, the mainstream theory would have some more ammo.
I think that, in general, viruses that jump species barriers are more lethal in their new hosts than their old ones. Selection pressure tends to make viruses that are transmitted from individual to individual less dangerous over time, not more, because a dead host can’t spread the virus. So the fact that chimps tolerate SIV better than humans tolerate HIV isn’t a strike against the “HIV is mutated SIV” theory.
Also, there exists a more direct counterexample: FIV, feline immunodeficiency virus, is an HIV-like virus that is commonly found in lions. It doesn’t harm lions very much, but it’s lethal to domestic cats, which haven’t co-evolved with the virus the way lions have. (Specifically, lions compensate for the loss of T-cells to the virus by producing them in much larger numbers than other animals do.)
Perhaps not all viruses that jump species barriers are more lethal, but we care most about the lethal ones for sure, and lethality or host damage is a side effect of high replication, so yes I agree with your analysis.
I also said:
I think it is plausible that this happened and HIV causes novel problems in humans, but it certainly has not been well demonstrated, mainly because HIV doesn’t cause specific symptoms and it is extremely difficult to properly dissociate other causitive factors.
I’m reading the OBrien Goddert response now that cites some animal studis showing how some animal HIV analogs do fulfill koch’s postulate now. I am reading into the sources, but I wasn’t aware overall that they had found animal HIV analogs that caused AIDS like symptoms. I’ll have to update towards the ‘HIV is more pathogenic’ stance if this all checks out.
But the competing hypothesis is not the null hypothesis, the competing hypothesis is that the HIV presence is a marker of some severe immune function failure, and that HIV itself is a largely harmless vertically transmitted retrovirus—like all the others. If it does become active, it is because something is already seriously wrong. So of course if you have a lab, and you are testing lab-workers deathly afraid of contracting HIV, in either theory some may come up HIV+, and in either theory those that test positive will be ill.
According to O’Brien and Goedert, however, the strains of HIV found in these accidentally infected individuals were effectively identical to those from the source of their accidental infection, showing much less difference than is usual for strains taken from two random patients. This looks like powerful evidence against the competing hypothesis. On the other hand, it seems like there have been disputes about the validity of these identification procedures, and Duesberg and other skeptics raised some specific objections to them back then. However, this gets into technical issues that I’m definitely not competent to judge on.
(I should add that I haven’t delved into the references provided by O’Brien and Goedert, which Robin has conveniently listed in his above comment, to see if their summary of the facts is accurate and complete.)
Also, while we are looking at evidence for one side or the other, I should present some of the recent evidence that supports the Deusberg hypothesis, namely that cocaine use can cause HIV progression and AIDS-defining illness. Heavy cocaine use and HIV+ status are extremely correlated, the question is one then of causation.
Just search for “cocaine cd4 counts”|
From a rat study linked here
We noted a 200- to 300-fold increase in HIV RNA copy numbers in the peripheral blood obtained from cocaine-treated, HIV-infected animals when compared with HIV-infected controlsExposure to cocaine alone did not affect the implantation of PBL, suggesting a specific interaction between cocaine and HIV. This report describes a model for evaluating HIV cofactors and supports cocaine’s role in the development and progression of AIDS.
Even more interesting—an abstract from a more recent study showing that crack cocaine can cause AIDS independently (in women at least)
CONCLUSION: Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.
I was under the impression that there was only 2 HIV strains, and only HIV-1 is of concern in the west, but I’m no expert on this.
Do you have the O’Brien/Goedert paper link or any of this discussion? Your earlier link was just an editorial summary. Sounds interesting, I’d like to read more into it. (i am going to search now, but if you have the link . . .)
If O’Brien and Goedert are right, it would depend on how many strains there are and what their prevalence is ahead of time—I think Bayes’ Theorem would apply, no? Also, I guess we just have to presume that no other sick people from the sample were not reported. And finally, the sample size of 1 or 2 raises some theoretical issues, but still it would be interesting.
I was under the impression that there was only 2 HIV strains, and only HIV-1 is of concern in the west, but I’m no expert on this.
No. There are two major HIV strains, HIV-1 and HIV-2, with the vast majority of infections in the US being HIV-1. However, there are many substrains of both. In general, since HIV has a high mutation rate, there are individual genetic markers for different people. No one who has HIV for more than a few weeks has a single form of HIV in them but already will have a population of slightly distinct forms. This is part of what makes HIV so pesky for the immune system, for developing vaccines, and for developing drugs to combat it. Note that this isn’t that rare. For example, influenza does something similar although my impression is that this is not nearly as extreme an example.
Frankly, this is a very basic aspect of HIV biology, which you could find on any primer on the subject. If one doesn’t know about this, this suggests major gaps in one’s knowledge base about HIV and I’m not at all sure that one who doesn’t know about this has enough background to discuss issues related to whether HIV causes AIDS.
and I’m not at all sure that one who doesn’t know about this has enough background to discuss issues related to whether HIV causes AIDS.
Because he said “2 HIV strains” rather than “2 major HIV strains with many substrains”? He should be disqualified from participating in debate on a topic because he failed to use sufficiently precise language on a point not relevant to the current discussion?
I’m a non-partisan on this issue, having not researched it enough to have a firm opinion… but the consistent use of these kinds of dark side debate tactics by one side makes me seriously tempted to update in the opposite direction.
the strains of HIV found in these accidentally infected individuals were effectively identical to those from the source of their accidental infection, showing much less difference than is usual for strains taken from two random patients.
It seemed pretty clear from context that Vlad was talking about substrains. If there’s anything that went wrong here, judging from Jacob’s followup remark, it was an illusion of transparency failure on my part in that Vlad’s meaning seemed clear to me, and I then made the (erroneous) conclusion that someone with a basic background would also get what Vlad was talking about.
Note incidentally, that using heuristics about whether or not someone has enough background to understand or discuss something is not intrinsically a dark side issue to start with. Indeed, sometimes it is very necessary. See for example some of the discussion on cousin it’s recent post where it seemed that some individuals (well, primarily one individual) were making repeated subtle but highly relevant errors about certain ideas related to Godel’s theorems and Turing machines. After repeated attempts to explain, the mathematicians in the thread (including myself) started trying to explain that the errors in question were basic enough that further attempts to explain would likely be fruitless. That’s not a dark side tactic, sometimes that’s just true.
Note incidentally, that using heuristics about whether or not someone has enough background to understand or discuss something is not intrinsically a dark side issue to start with
Yes, I absolutely agree. But that’s not the tactic I was referring to. The tactic in question consists of finding some nitpicky objection to something your opponent said, something not directly relevant to the issue at hand, and something which isn’t even wrong, just insufficiently precise, and discounting the substance of their argument on that basis.
The tactic in question consists of finding some nitpicky objection to something your opponent said, something not directly relevant to the issue at hand, and something which isn’t even wrong, just insufficiently precise, and discounting the substance of their argument on that basis.
Hrrm? Imprecision if anything occurred on Vlad’s part, not Jacob’s. Again, see issue of illusion of transparency matter. See also Vlad’s remark below.
It seemed pretty clear from context that Vlad was talking about substrains.
Yes, of course. I’m not familiar with the finer points of terminology in this area, but the O’Brien-Goedert paper uses the term “strain” both for the two major strains and their sub-strains, and I’ve noticed the same in many other papers too. So I don’t think this was imprecise in any way.
Vlad originally used the word ‘strains’, not substrains, and I have only ever heard ‘strains’ used in reference to HIV1 and HIV2 as you say. But yes I am at least somewhat aware of sub-strains through protein coding variation in viruses in general, and how mutations lead to new epidemics.
I’m not sure what the proper ‘background’ is just to discuss an issue, but I probably don’t have it, regardless.
(I initially posted an excerpt from the paper in this comment, but in the meantime, I found an ungated version. The stuff about the accidental transmissions is on page 615.)
Do you have the O’Brien/Goedert paper link or any of this discussion? Your earlier link was just an editorial summary. Sounds interesting, I’d like to read more into it. (i am going to search now, but if you have the link . . .)
The article cited here? I downloaded a copy if anyone wants to PM me an email address.
For the controlled experiment example, it would have to be double blind the entire time. Nobody would ever know who got placebo and who didnt’, and no difference in treatment regimens either way—all on the same diet, same lifestyle, etc etc. I highly doubt the accidental cases fit that profile.
If you want absolute certainty, you need to fulfill koch’s postulates, which is the medical disease variant of experimental physics, and is well grounded.
So yes, in questions of science, we do demand specific evidence for near-certain proof, but naturally when that is not possible for whatever reason, we can still update based on other evidence and reach well grounded conclusions.
First of all, you never have absolute certainty. Proof is for math and alcohol. You may also want to read the Sequences relevant to Bayesian reasoning especially about how 0 and 1 are not probabilities.
Note also that even outside a Bayesian context, Koch’s postulates are a rough framework. For example, sometimes there is great difficulty growing an organism in a culture (Koch’s second postulate requires this), and sometimes only a fraction of a population may be symptomatic. Even Koch was willing to treat the first postulate as a guideline rather than a hard and fast rule; he worked with multiple examples of microorganisms that showed up in some healthy people but didn’t cause disease In fact we know now that this very common. Many causes of minor infections, such as staph, are present on everyone. It then takes some problem, such a wound, or disruption of the immune system to cause the person to become unhealthy. For viral examples, look at asymptomatic herpes or HPV.
Frankly, referring to Koch’s postulates like this are one of the things that makes many people with medical knowledge not take the HIV-AIDS skeptics very seriously. As a general heuristic, cranks like to take old ideas and try to use them to argue against some modern result even when that idea isn’t used in the current form or isn’t as absolute as they make it out to be. This seems for example to occur frequently with creationists who use an oversimplified form of Mendelian genetics that seems to date prior to the work of Hardy, Weinberg, and Fisher. As a way of preventing this signal, referring to such things as Koch’s work can be done, but you need to be clear that you understand the limitations it has. Otherwise, it just sets off alarm bells.
As a general heuristic, cranks like to take old ideas and try to use them to argue against some modern result even when that idea isn’t used in the current form or isn’t as absolute as they make it out to be.
Note also that even outside a Bayesian context, Koch’s postulates are a rough framework. For example, sometimes there is great difficulty growing an organism in a culture (Koch’s second postulate requires this), and sometimes only a fraction of a population may be symptomatic.
It is also difficult to empirically test elements of String Theory or evolutionary history. This difficulty isn’t taken to be evidence for against those theories. Lack of easy clear cut empirical tests is just that—lack of a simple theorem discriminator. I am not claiming that it is some magic pass required for any theory to be credible.
On the other hand, nor can one use lack of said simple theorem discriminator to get a free pass and somehow claim to have extra certainty—that most come from evidence regardless.
However, in this case I do think that the general idea of Koch’s postulate is highly relevant, it is not ‘cranky’ to invoke it, and in fact it is probably the single strongest piece of evidence for the mainstream position—as Vlad M pointed out to me.
I am currently reading:
”
HIV causes AIDS: Koch’s postulates fulfilled”
Guest editorial
Stephen .I O’Brien* and .lames ,i Goederff
It reviews SIV models where SIV can be prepared and injected into monkeys and in some cases does cause AIDS like disease progression (usually more quickly than HIV).
So I don’t think your associations between “referring to Koch’s postulates” and cranks, and your general heuristic are valid at all, not when the mainstream is listing this as a centerpiece of evidence.
I haven’t read the editorial yet, but I’m not sure where the notion that this was a centerpiece of evidence comes from. I was vaguely aware of this result but never have paid it much attention. I suspect that if one talked to active AIDS and HIV researchers they’d say that there was a very strong case even without this. But yes, conservation of expected evidence does come into play here, so you have a valid point. In any event, the upshot that Koch’s postulates are not seen as any sort of absolute is very much relevant.
S.J. O’Brien and J.J. Goedert (1996) (the paper cited by Vladimir_M) specifically references Koch’s postulates. The accidental infection of laboratory workers is only one of five items cited in reference to (I believe) #3, “The cultured microorganism should cause disease when introduced into a healthy organism.”
Ever since I’ve read in Guinea Pig Zero about test subjects who feel that they’ll never be able to afford medical care and cheat on the requirements of an experiment (for example, not following dietary changes they’ve signed on for), I’ve been that little bit more dubious about drug studies.
Note that in general low-transmission rates aren’t that good an argument against it. First of all, a lot of transmission in the US occurred through other forms, especially early in the epidemic (intravenous needle sharing and transfusion of infected blood being two major ones). As others have noted the transmission issue is also generally higher for homosexual rather than heterosexual intercourse.
Frankly, the thing that I most don’t understand about people who are skeptical about the HIV-AIDS link is how one explains the fact that anti-virals tailored to deal with HIV work. Even the first-gen treatments such as AZT were used due to the biochemistry of HIV (often targeting reverse transcriptase). And they worked in delaying the onset of AIDS and worked for giving people with AIDS higher life-expectancy. I don’t see how one can easily reconcile that with HIV not being the cause of AIDS and I’ve never heard anything remotely resembling a coherent explanation about this.
The extremely low official transmission rates indicate that HIV is probably not a sexually transmitted disease, as typically understood. According to the published transmission data, it’s only effective natural means of transmission is vertical—from mother to child. From what we know about symbiosis and parasites, this should lead one to suspect it is not that lethal.
However that doesn’t destroy the hypothesis that HIV could be a unique disease of civilization—a mutation of a formerly limited retrovirus into a more damaging form that spreads horizontally only through extremely unnatural novelties of the modern world—needle sharing and epic promiscuity in some subgroups. It does of course make the overall hypothesis more complex and overall less likely, but it doesn’t destroy it outright.
This is very difficult to prove ethically, and certainly hasn’t been shown to satisfaction. Consider how immensely difficult it has been to understand the real health effects of fat in the diet, for example. In the 80′s and 90′s, we thought it was oh so simple. Today we (the wise) realize how profoundly ignorant we were then, and still are today. I think part of the rational reappraisal for the strength of the HIV hypothesis should come from a similar update.
In other words one can only cling to a high degree of certainty about the HIV hypothesis when one is profoundly ignorant concerning the depth of one’s ignorance about the complexity of human health.
That’s the theory.
Ahh the world would be so simple if that was true. The AZT clinic trial was ended prematurely and double-blindness could not be maintained due to side effects. The skeptics claim that later studies show that AZT increases long term mortality, not the other way around.
You need to realize how impossible it would be to concretely show what you presume to high certainty. You would basically need a double blind study with two control groups, one receiving plazebo, and compare total mortality. One immediate problem is any noticeable side effects would immediately end the blindness—and the retrovirals certainly have side effects.
And even showing that AZT or drug X reduces mortality in HIV+ patients does not lead to the conclusion that HIV is the cause, or that AZT or drug X has any effect on HIV. Supplementing patients with vitamin D, or changing their diet, or feeding them aspirin, or any number of other changes could also decrease mortality, but have nothing to do with the viral theory.
Health is complex.
So I don’t know what evidence you have for these claims. The original AZT study can be found here. It handled placebos just fine.
And AZT is just one example of many anti-retrovirals. 3TC and ABC have also been used. Moreover, there are studies which show that the the standard drug cocktails work better than AZT or 3TC alone. That makes sense for the standard model of HIV as the cause of AIDS.
There seems to be an issue here involving what level of evidence is necessary. From a Bayesian stand point you can’t ever “show” anything in the sense that you want. But the overall pattern of evidence can still give you a probability close to 1 that HIV is the primary cause of AIDS.
http://www.ncbi.nlm.nih.gov/pubmed/3299089
Ah you read this while I was editing it.
Yes I have browsed that abstract, although I can’t see if there is a full copy of the whole thing. Notice the link to the toxicity right next to it:
The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.
Notice that it has serious toxicity side effects, including bone marrow supression, and thus it can massively damage the innate immune system.
This is evident in the abstract itself:
The original AZT study could not possibly be placebo controlled, due to the high toxicity—this is basically chemotherapy. Now chemotherapy can be effective, but it can not be double blind.
Furthermore, due to high toxicity, only a fraction of patients actually completed the intended trial:
Only 27 out of 245 AZT subjects completed the full 24 weeks! One in the AZT group of 245 died in this period, but how many more in the AZT group would have died if they had been able to complete the full 24 week chemotherapy trial?
These were crazy times. These patients were very ill and very worried. It was a full scale terror panic. It was obvious who was on placebo and who wasn’t, and from what I have read, placebo patients were swapping and trading pills with AZT patients who couldn’t finish. It was many things, but not double-blind.
Here is what would be required to prove with > 99% certainty that HIV is the sole cause of AIDS:
Take a random sample of perfectly healthy test subjects. Now inject half of them with HIV and half with a placebo, and follow their health over the long term. That is about the only test that could get you 99% accuracy, and it is obviously not ethical.
So, instead we have to make due with what we have.
And again, showing that AZT improves long-term mortality—which the AZT trial clearly did not show, only shows that AZT improves mortality in sick AIDS patients. It doesn’t tell you much else about HIV as a theory.
It’s important that we agree on that subpoint—for it has nothing to do with the level of evidence.
There are many, many things that could improve mortality in sick AIDS patients. Stoss therapy, better diet, more sex, aspirin, etc etc. Do you think that proving a mortality decrease correlation in any of these categories would ‘prove’ they are the true cause of AIDS?
It also makes sense for the common sense model that reducing AZT doses down from outright lethal to mildly poisonous but tolerable ‘works better’.
jacob_cannell:
There have been documented cases of accidental HIV infection of lab workers and dental patients that are not too terribly far from such a controlled experiment. See: S.J. O’Brien and J.J. Goedert, “HIV causes AIDS: Koch’s postulates fulfilled,” Current Opinion in Immunology, Vol. 8, Issue 5, October 1996, pp. 613-618.
UPDATE: Ungated link to the paper here.
The article (listed as a “guest editorial”, I note for completeness) has the following citations in the relevant section:
52. Weiss SH, Goedert JJ, Gartner S, Popovic M, Waters D, Markham P, Veronese FD, Gall MH, Barkley WE, Gibbons J et al.: Risk of human immunodeflciency virus (HIV-1) infection among laboratory workers. Science 1988, 239:68-71.
53. Reitz MS Jr, Hall L, Robert-Guroff M, Lautenberger J, Hahn BH, Shaw GM, Kong LI, Weiss SH, Waters D, Gallo RC, Blattner W: Viral variability and serum antibody response in a laboratory worker infected with HIV-1 (HTLV-IIIB). AIDS Res Hum Retroviruses 1994, 10:1143-1155.
54. Guo HG, Waters D, Hall L, Louie A, Popovic M, Blattner W, Streicher H, Gallo RC, Chermann JC, Reitz MS: Nucleotide sequence analysis of the original isolate of HIV-1. Nature 1991, 349:745-746.
55. Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guetard D et al.: LAV revisited: origins of the early HIV-t isolates from Institut Pasteur. Science 1991, 252:961-965.
56. Wolinsky SM, Wike CM, Korber BTM, Hutto C, Parks WP, Rosenblum LL, Kunstman KJ, Furtado MR, Munoz JL: Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 1992, 255:1134-1137.
57. Morbidity Mortality Weekly Report of the Center for Disease Control: Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults (1993). 1992:1-19.
I’m not a skeptic, but I am a bit surprised that three infected lab workers is considered evidence worth mentioning. I’m accustomed to seeing clinical studies with fewer than 100 patients treated as merely suggestive, and several hundred or even thousands of patients necessary to convince regulatory authorities that there is a real phenomenon. So when I read that “three laboratory workers...became infected”, it strikes me as anecdotal. Of course you take what you can get, but still, it seems a small group.
My experience is with pharmaceuticals, which could explain the difference. But still, there’s a difference to be explained.
On the upside, if three is worth mentioning, then maybe one is worth mentioning, which would mean that Seth Roberts’s self-experimentation may be worthwhile.
Ok, so I have finished reading O’Brien and JJ Goedert. I think the accidental lab worker cases probably have low utility in distinguishing between pathologic HIV and passenger HIV theories, but the animal SIV studies potentially fulfill the ideal experiment design. If animals injected with pure close SIV analogs to HIV develop AIDS-like illness, that is about as good as evidence as one could hope for.
For the lab worker infections, they say that the genomes are close to the clonal strain used in the lab, but they don’t have a good probalistic model for this:
threefold more or less variation doesn’t sound like much to me, and regardless even assuming they did all get infected via the lab, it doesn’t mention treatment, so we don’t know if they were treated with AZT or what.
I think the animal models are more interesting—as all the drug cofounding variables are eliminated and everything is controlled.
The authors discuss 3 animal models—baboons, some wierd knockout mice with human t-cell graphs, and finally SIV injected into rhesus monkeys. They spend the most time discussing the latter paper so I looked into it.
“Induction of AIDS in Rhesus Monkeys by Molecularly Cloned Simian Immunodeficiency”.
In short, all 5 of the monkeys injected later become seropositive, and 50% of them progress to AIDs-like illnesses and die. Presumably some are naturally resistant.
There is a potential issue to this otherwise smoking gun, which is that it appears they had to inject whole culture of T-cells, as the virus can not be isolated directly into plasmid vectors:
But if all they had then was provirus integrated into PBL ( peripheral blood lymphocytes ), then one must wonder about the risk of graft versus host disease, and transfusion reaction in general. Basically, the foreign T-cell line can actively invade and cause all kinds of havoc. Perhaps they have controlled for that and I’m completely off, but I don’t see where they mention it.
OBrien and Goodart conclude:
I haven’t seen mention of ‘inactivated’ sivmaca239 yet in 80, but maybe it is in 83 or 84. However, if they are forced to infect live T-cells because they can’t produce viable clonal plasmid, this seems to have a major confounding factor in graft vs host disease. I’d like to find a knowledge skeptic take on this—perhaps Duesberg confronts it, not sure yet.
If he doesn’t confront it, then that doesn’t look so good for his position.
It appears to me that you are noting different weaknesses, different alternative explanations of the results, in each experimental protocol. I imagine that could appear to happen if there were a strong publication bias for results in favor of the hypothesis (e.g. with medicinal prayer studies), but that has not been demonstrated.
From what I understand, there is strong reason to suspect such bias in the animal models, as many other animal tests were conducted previously attempting to show SIV causing AIDS, and they uniformly failed. From what I have read, the SIV injections failed to do anything in chimps. We don’t know how many other rhesus monkeys were injected, but I find it highly unlikely that the five in this study (3 out of 5 of which developed immune defeciency) were the first.
That bias is interesting and it would be useful to have a metastudy covering all the animals that have been injected, but of course most naturally occuring strains of species specific virus should be expected to be harmless. So the ‘bias’ doesn’t really tell you much and is expected either way.
I’ll look to see if there is any skeptic review of the SIV injections which did succeed, because in my mind that is fairly strong evidence. If HIV analogs cause AIDS-like illness in primates when they hop species or traditional barriers, this is a good experiemental model for HIV crossing over into humans and causing illness, and is far stronger in my mind than the murky epidimelogical data with all of it’s drug cofactor issues.
The lab monkeys are in a controlled environment—we know they weren’t using drugs, weren’t fed AZT, etc etc.
Yes, but were they treated with chemotherapy agents such as AZT which cause bone marrow and immune supression? (I am asking before I read the article)
For the controlled experiment example, it would have to be double blind the entire time. Nobody would ever know who got placebo and who didnt’, and no difference in treatment regimens either way—all on the same diet, same lifestyle, etc etc. I highly doubt the accidental cases fit that profile.
jacob_cannell:
From what I see, O’Brien and Goedert don’t report about this. However, Cohen’s Science article to which I linked above provides more details about the cases of infected lab workers, claiming that two of them didn’t receive any antivirals until the progress of AIDS was well underway:
http://www.sciencemag.org/feature/data/cohen/266-5191-1647a.pdf
I have seen that, but I don’t take it as strong evidence of anything either way.
Clearly HIV antibodies are correlated with ill-health, poor immune function and low CD4 counts—that was established in the very beginning by Gallo et all and is the entire basis of their original claim.
But the competing hypothesis is not the null hypothesis, the competing hypothesis is that the HIV presence is a marker of some severe immune function failure, and that HIV itself is a largely harmless vertically transmitted retrovirus—like all the others. If it does become active, it is because something is already seriously wrong.
So of course if you have a lab, and you are testing lab-workers deathly afraid of contracting HIV, in either theory some may come up HIV+, and in either theory those that test positive will be ill.
This is very different than the intentional infection test you need to establish strong causation along a koch’s postulate principle. I think one of the stronger flaws in current HIV theory is the chimpanzee models—they have many HIV similar retroviruses (SIV’s), they are common in wild chimps, are all vertically transmitted, and don’t appear to be problematic for chimps. If HIV killed chimps outright, the mainstream theory would have some more ammo.
Instead the theory is that HIV came from a chimp SIV and somehow became lethal and horizontally transmissable at the same time in humans. But from the studies of sexual transmission—it is only weakly blood transmissable. So overall, it’s alot to swallow. I think it is plausible that this happened and HIV causes novel problems in humans, but it certainly has not been well demonstrated, mainly because HIV doesn’t cause specific symptoms and it is extremely difficult to properly dissociate other causitive factors. As Duesberg notes, the cocaine/meth craze boomed in the 80′s right as the AIDS epidemic started—they overlap perfectly.
Deusberg’s theory is that drugs specifically are a major cause of the immunosupression, which I think has some absolute validity, but we should also notice that there are other causes, and some people just have poor immune health, and this has been the case for long before HIV came on the scene.
I think that, in general, viruses that jump species barriers are more lethal in their new hosts than their old ones. Selection pressure tends to make viruses that are transmitted from individual to individual less dangerous over time, not more, because a dead host can’t spread the virus. So the fact that chimps tolerate SIV better than humans tolerate HIV isn’t a strike against the “HIV is mutated SIV” theory.
Also, there exists a more direct counterexample: FIV, feline immunodeficiency virus, is an HIV-like virus that is commonly found in lions. It doesn’t harm lions very much, but it’s lethal to domestic cats, which haven’t co-evolved with the virus the way lions have. (Specifically, lions compensate for the loss of T-cells to the virus by producing them in much larger numbers than other animals do.)
Perhaps not all viruses that jump species barriers are more lethal, but we care most about the lethal ones for sure, and lethality or host damage is a side effect of high replication, so yes I agree with your analysis.
I also said:
I’m reading the OBrien Goddert response now that cites some animal studis showing how some animal HIV analogs do fulfill koch’s postulate now. I am reading into the sources, but I wasn’t aware overall that they had found animal HIV analogs that caused AIDS like symptoms. I’ll have to update towards the ‘HIV is more pathogenic’ stance if this all checks out.
jacob_cannell:
According to O’Brien and Goedert, however, the strains of HIV found in these accidentally infected individuals were effectively identical to those from the source of their accidental infection, showing much less difference than is usual for strains taken from two random patients. This looks like powerful evidence against the competing hypothesis. On the other hand, it seems like there have been disputes about the validity of these identification procedures, and Duesberg and other skeptics raised some specific objections to them back then. However, this gets into technical issues that I’m definitely not competent to judge on.
(I should add that I haven’t delved into the references provided by O’Brien and Goedert, which Robin has conveniently listed in his above comment, to see if their summary of the facts is accurate and complete.)
Also, while we are looking at evidence for one side or the other, I should present some of the recent evidence that supports the Deusberg hypothesis, namely that cocaine use can cause HIV progression and AIDS-defining illness. Heavy cocaine use and HIV+ status are extremely correlated, the question is one then of causation.
Just search for “cocaine cd4 counts”| From a rat study linked here
Even more interesting—an abstract from a more recent study showing that crack cocaine can cause AIDS independently (in women at least)
CONCLUSION: Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.
A blog discussion of this here
Perhaps the tide’s are turning in Deusberg’s favor?
I was under the impression that there was only 2 HIV strains, and only HIV-1 is of concern in the west, but I’m no expert on this.
Do you have the O’Brien/Goedert paper link or any of this discussion? Your earlier link was just an editorial summary. Sounds interesting, I’d like to read more into it. (i am going to search now, but if you have the link . . .)
If O’Brien and Goedert are right, it would depend on how many strains there are and what their prevalence is ahead of time—I think Bayes’ Theorem would apply, no? Also, I guess we just have to presume that no other sick people from the sample were not reported. And finally, the sample size of 1 or 2 raises some theoretical issues, but still it would be interesting.
No. There are two major HIV strains, HIV-1 and HIV-2, with the vast majority of infections in the US being HIV-1. However, there are many substrains of both. In general, since HIV has a high mutation rate, there are individual genetic markers for different people. No one who has HIV for more than a few weeks has a single form of HIV in them but already will have a population of slightly distinct forms. This is part of what makes HIV so pesky for the immune system, for developing vaccines, and for developing drugs to combat it. Note that this isn’t that rare. For example, influenza does something similar although my impression is that this is not nearly as extreme an example.
Frankly, this is a very basic aspect of HIV biology, which you could find on any primer on the subject. If one doesn’t know about this, this suggests major gaps in one’s knowledge base about HIV and I’m not at all sure that one who doesn’t know about this has enough background to discuss issues related to whether HIV causes AIDS.
Because he said “2 HIV strains” rather than “2 major HIV strains with many substrains”? He should be disqualified from participating in debate on a topic because he failed to use sufficiently precise language on a point not relevant to the current discussion?
I’m a non-partisan on this issue, having not researched it enough to have a firm opinion… but the consistent use of these kinds of dark side debate tactics by one side makes me seriously tempted to update in the opposite direction.
This isn’t a “dark side” tactic. Vlad wrote:
It seemed pretty clear from context that Vlad was talking about substrains. If there’s anything that went wrong here, judging from Jacob’s followup remark, it was an illusion of transparency failure on my part in that Vlad’s meaning seemed clear to me, and I then made the (erroneous) conclusion that someone with a basic background would also get what Vlad was talking about.
Note incidentally, that using heuristics about whether or not someone has enough background to understand or discuss something is not intrinsically a dark side issue to start with. Indeed, sometimes it is very necessary. See for example some of the discussion on cousin it’s recent post where it seemed that some individuals (well, primarily one individual) were making repeated subtle but highly relevant errors about certain ideas related to Godel’s theorems and Turing machines. After repeated attempts to explain, the mathematicians in the thread (including myself) started trying to explain that the errors in question were basic enough that further attempts to explain would likely be fruitless. That’s not a dark side tactic, sometimes that’s just true.
Yes, I absolutely agree. But that’s not the tactic I was referring to. The tactic in question consists of finding some nitpicky objection to something your opponent said, something not directly relevant to the issue at hand, and something which isn’t even wrong, just insufficiently precise, and discounting the substance of their argument on that basis.
Hrrm? Imprecision if anything occurred on Vlad’s part, not Jacob’s. Again, see issue of illusion of transparency matter. See also Vlad’s remark below.
JoshuaZ:
Yes, of course. I’m not familiar with the finer points of terminology in this area, but the O’Brien-Goedert paper uses the term “strain” both for the two major strains and their sub-strains, and I’ve noticed the same in many other papers too. So I don’t think this was imprecise in any way.
Vlad originally used the word ‘strains’, not substrains, and I have only ever heard ‘strains’ used in reference to HIV1 and HIV2 as you say. But yes I am at least somewhat aware of sub-strains through protein coding variation in viruses in general, and how mutations lead to new epidemics.
I’m not sure what the proper ‘background’ is just to discuss an issue, but I probably don’t have it, regardless.
Ok. Seems to be an error in communication more than anything else then.
FWIW, you seem to have a much better understanding of a lot of this material than most of the HIV-AIDS skeptics I’ve interacted with in the past.
(I initially posted an excerpt from the paper in this comment, but in the meantime, I found an ungated version. The stuff about the accidental transmissions is on page 615.)
The article cited here? I downloaded a copy if anyone wants to PM me an email address.
I’m not sure you are allowed to demand that specific piece of evidence.
If you want absolute certainty, you need to fulfill koch’s postulates, which is the medical disease variant of experimental physics, and is well grounded.
So yes, in questions of science, we do demand specific evidence for near-certain proof, but naturally when that is not possible for whatever reason, we can still update based on other evidence and reach well grounded conclusions.
First of all, you never have absolute certainty. Proof is for math and alcohol. You may also want to read the Sequences relevant to Bayesian reasoning especially about how 0 and 1 are not probabilities.
Note also that even outside a Bayesian context, Koch’s postulates are a rough framework. For example, sometimes there is great difficulty growing an organism in a culture (Koch’s second postulate requires this), and sometimes only a fraction of a population may be symptomatic. Even Koch was willing to treat the first postulate as a guideline rather than a hard and fast rule; he worked with multiple examples of microorganisms that showed up in some healthy people but didn’t cause disease In fact we know now that this very common. Many causes of minor infections, such as staph, are present on everyone. It then takes some problem, such a wound, or disruption of the immune system to cause the person to become unhealthy. For viral examples, look at asymptomatic herpes or HPV.
Frankly, referring to Koch’s postulates like this are one of the things that makes many people with medical knowledge not take the HIV-AIDS skeptics very seriously. As a general heuristic, cranks like to take old ideas and try to use them to argue against some modern result even when that idea isn’t used in the current form or isn’t as absolute as they make it out to be. This seems for example to occur frequently with creationists who use an oversimplified form of Mendelian genetics that seems to date prior to the work of Hardy, Weinberg, and Fisher. As a way of preventing this signal, referring to such things as Koch’s work can be done, but you need to be clear that you understand the limitations it has. Otherwise, it just sets off alarm bells.
This bears repeating.
It is also difficult to empirically test elements of String Theory or evolutionary history. This difficulty isn’t taken to be evidence for against those theories. Lack of easy clear cut empirical tests is just that—lack of a simple theorem discriminator. I am not claiming that it is some magic pass required for any theory to be credible.
On the other hand, nor can one use lack of said simple theorem discriminator to get a free pass and somehow claim to have extra certainty—that most come from evidence regardless.
However, in this case I do think that the general idea of Koch’s postulate is highly relevant, it is not ‘cranky’ to invoke it, and in fact it is probably the single strongest piece of evidence for the mainstream position—as Vlad M pointed out to me.
I am currently reading: ” HIV causes AIDS: Koch’s postulates fulfilled” Guest editorial Stephen .I O’Brien* and .lames ,i Goederff
It reviews SIV models where SIV can be prepared and injected into monkeys and in some cases does cause AIDS like disease progression (usually more quickly than HIV).
So I don’t think your associations between “referring to Koch’s postulates” and cranks, and your general heuristic are valid at all, not when the mainstream is listing this as a centerpiece of evidence.
I haven’t read the editorial yet, but I’m not sure where the notion that this was a centerpiece of evidence comes from. I was vaguely aware of this result but never have paid it much attention. I suspect that if one talked to active AIDS and HIV researchers they’d say that there was a very strong case even without this. But yes, conservation of expected evidence does come into play here, so you have a valid point. In any event, the upshot that Koch’s postulates are not seen as any sort of absolute is very much relevant.
S.J. O’Brien and J.J. Goedert (1996) (the paper cited by Vladimir_M) specifically references Koch’s postulates. The accidental infection of laboratory workers is only one of five items cited in reference to (I believe) #3, “The cultured microorganism should cause disease when introduced into a healthy organism.”
Ever since I’ve read in Guinea Pig Zero about test subjects who feel that they’ll never be able to afford medical care and cheat on the requirements of an experiment (for example, not following dietary changes they’ve signed on for), I’ve been that little bit more dubious about drug studies.