Go at it

So, I moved the malaria entry to another post--since all the comments focused on Culshaw's post (noted in the first comment below), might as well have a more focused discussion on it. I'll be back tomorrow with a somewhat related post, but until then, feel free to chat amongst yourselves.

More like this

"I don't have an account with NEJM, so can't read the study you would like me to see."

In fact the NEJM allows you to read the article Tara cited as well as many others just by setting up a free registration. You have to fill in contact details but you don't have to pay them anything.

Does this have anything to do about malaria? Is that all y'all can do--spam for your own sites? I saw it, and noticed she quote-mined me. Remind you of anyone?

I love it -- the Battling Science Babes! Smith v. Culshaw in a steel cage, wielding sharpened slide rulers and hurling flaming Bunsen Burners at each other!

White lab smocks or polka-dotted bikinis, your choice!

We could make a veritable fortune on this. Who's with me?

Hank Barnes

By Hank Barnes (not verified) on 22 Mar 2006 #permalink

Rebecca Culshaw has nothing to do with malaria. And her statements about the mysteries of modeling the effects of HIV on the immune system, which clearly show no understanding whatsoever of the immunological parameters involved, rather undermine the notion that her opinion carries any more weight than the opinion of someone like, say, Hank Barnes. If you're going to make a mathematical model of HIV's effects on the immune system, you need to be able to plug in the relevant parameters regarding:

naive CD4 T cell production
naive CD4 T cell activation
naive CD4 T cell death
naive CD4 T cell homeostatic division
conversion of naive CD4 T cells to memory
memory CD4 T cell homeostatic division
memory CD4 T cell activation
memory CD4 T cell death
total body memory CD4 T cell distribution

- and that's just for CD4 T cells, without even beginning to get into antigen specificity. A lot of assumptions are involved simply because the understanding of T cell immunology in humans is incomplete. Can you point me to where Rebecca Culshaw addresses these issues?

Richard,

How's the vaccine coming? We've been waiting since 1984:)

Also, could you please advise when you're wearing your scientist cap as opposed to your propagandist cap? It makes it easier to respond.

Hank B.

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

Tara said, "I saw it, and noticed she quote-mined me. Remind you of anyone"?

Tara, maybe you can correct me. I always thought that the notion of "quote mining" was that you take a solitary quote and use it to try to prove a point that, taken with greater context, might have revealed a different thought.

Here's what Culshaw said the comment about her was (and she didn't say it was you. Never mentioned you by name at all) -

"That's rich. First, as I mentioned, she's a mathematician. I don't know what her background is in infectious disease epi[demiology] (I contacted her but she did not respond), and she obviously shows little understanding of molecular biology in her comments about PCR (by her logic, any microbe shouldn't cause us harm because they are so tiny)."

So if she quoted you out of context to prove her point, what did you REALLY MEAN to say? Also, what are your thoughts on the notion that she was simply giving a couple of examples of the feedback she has received since turning her back on the model, and that the above quote might simply typify a lot of what she has been hearing?

Thanks in advance of your thoughtful, non-defensive, non-attacking response.

By the way, say what you will about Hank but he is one FUNNY dude!

"White lab smocks or polka-dotted bikinis, your choice"!

Well, those are some extraordinary contributions. I actually regret participating in dragging this thread further off-topic and would not mind in the least if Tara deleted it and started over.

Richard said, "Well, those are some extraordinary contributions. I actually regret participating in dragging this thread further off-topic and would not mind in the least if Tara deleted it and started over"

It's a BLOG Rich. Blogs aways do that. But I like your very creative thinking on how to handle it when it goes in a direction you don't care for.

Tara, maybe you can correct me. I always thought that the notion of "quote mining" was that you take a solitary quote and use it to try to prove a point that, taken with greater context, might have revealed a different thought.

That's the most extreme. She simply created a strawman of my position. It's not because she's "just a mathematician;" it's because she's a mathematician basing her arguments on areas which I've not seen evidence that she understands--and indeed, see evidence by her characterization of PCR and pathogen isolation that she doesn't understand molecular biology nor have a broad understanding of infectious disease epidemiology--which were the areas she discussed in her first post on "why I quit HIV." I elaborated on both of these later in the thread, which she chose to ignore and instead paint a strawman. Additionally, she throws out another Duesberg line:

Ever more convoluted explanations for HIV pathogenesis and epidemiology are not the signs of a mysterious virus, but rather the signs of a theory that is being shaped to fit the facts.

Again, by this logic, every infectious disease should be in the same category as AIDS--as we delve deeper into the mechanisms of disease causation and epidemiology of the disease, we also find "more convoluted explanations." She says the same thing later for Koch's postulates--that saying they're "outdated" is a sign that science is somehow lax today, when Koch himself realized they weren't universal and that we shouldn't be legalistic about their application! This shows that she's speaking too far from her area of expertise, and she simply doesn't have the background to discuss the topics she is.

It's a BLOG Rich. Blogs aways do that.

Well, no, they don't--at least not as far off-direction as you've taken it. I commented previously about what poor netiquette that was when Harvey did it; guess that didn't register. If you want to draw my attention to something totally off-topic, I've given you my contact information, and it's also available above.

John,

Hmmm. Was that the "thoughtful, non-defensive, non-attacking response" you were looking for?:)

...that saying they're "outdated" is a sign that science is somehow lax today...

Laxity is the least of the problems. The sheer indoctrination and pervasive intellectual (and financial) corruption is way beyond mere laxity.

Frankly, I'd kill for mere laxity.

Hank

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

Hank, I don't think you're exactly the one to lecture me on "thoughtful" responses. I didn't attack John--in fact, I split off the comments into a new post just for him (well, and others) to discuss. The fact remains that is is, well, rude to pop into an unrelated thread and say, "hey, here's something completely unrelated that I'm discussing on my own blog," and I've mentioned previously that type of behavior annoys me.

Regarding your "indoctrination" comment--Hank, have you had scientific training? It's really laughable to say it's "indoctrination." Scientists know better than anyone about the fluid nature of scientific facts and paradigms, and to be open to evidence that counters your assumptions. That certainly doesn't mean we'll buy it on initial glance--we're also skeptics and require a high burden of evidence--but as has been mentioned many times, it's often the "paradigm shattering" notions that win Nobels. Indoctrination, indeed...

Well, sometimes the indoctrinated, doesn't understand how they've been indoctrinated or, in your case, that they've been indoctrinated.

...we're also skeptics and require a high burden of evidence..

No, you are sometimes skeptical, but only against ideas with which you have already developed pronounced biases.

It is easy to be skeptical of ID proponents

It is easy to be skeptical of thimerisol-autism proponents.

It is easy to be skeptical of anti-vaccine activists.

On things that matter (AIDS, Cancer, excessive pharmaceutical influence, corruption at NIH, stem cells) or on your own pet issues, you exhibit no skepticism, and act as compliant little lambs.

That's the problem. Scientists who don't do science.

Hank Barnes

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

or on your own pet issues, you exhibit no skepticism, and act as compliant little lambs.

I'm sure it's comforting for you to think that, Hank, just like it's easier for me to wish that Culshaw and IDists had simply been "brainwashed" or are too "stupid" to understand the issues. Alas, life isn't so black and white--many creationists/IDists are highly intelligent but choose to maintain their position, and similarly, many very smart people deny HIV for many reasons. But if it helps you categorize the world into your little boxes, go right ahead--life is, of course, always messier.

Ok, Tara, prove me wrong:

1. Are you skeptical of any aspect of the current HIV=>AIDS paradigm?

2. If so, What?

Hank Barnes

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

"BTW, I am not certain about the science." Hank Barnes

Neither is McKiernan. In fact McK is usually shrugged off by Barnes as without vested interest in the subject matter. Like the only people that can discuss the issue with Barnes is anyone that knows p-reviewed literature and comfortably agrees with his position. The AIDS fatalities through 1987 are 16000 deaths, thats pre-AZT. Now, it seems to be consistent with Barnes that Gallo and company and their ilk require burning at the stake in front of the altar of his self-appointed overlordship. Standard fare for Barnes ask a question.

This is a better forum Barnes. You committed to offering a paper on the validity of endogenous retrovirus.

Where is it ?

By McKiernan (not verified) on 23 Mar 2006 #permalink

I'm making progress here, McKiernan, go the $@%@ away!! And, stop following me around the internet:)

Barnes

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

Hank,

Sure, I'm skeptical of all of it. Does HIV really cause AIDS? Does it work alone? Are there other factors necessary? Is our treatment strategy the best method to go currently? Is advising all HIV+ people to take drugs optimal, or should some kind of screening--such as for the CCR5 delta 32 mutation--be provided first? I've mentioned all this on here previously, Hank. Despite what you say, my mind certainly is open to other alternatives--but as I've mentioned, show me the evidence. What I've read from Duesberg et al. are poor arguments based on a misunderstanding of the lit--as has been mentioned many times, Duesberg seems to craft his own laws of epidemiology that simply aren't applicable to most diseases. So show me another virus that's present in people currently diagnosed with AIDS, that works with or instead of HIV. Show me that HIV is, as has been suggested, a "harmless passenger virus." Show me that something else was present in, say, health care workers that experienced a needle stick after treating an HIV+ patient and then developed AIDS. If I see something persuasive, I'm happy to re-address my understanding--and most scientists will be as well. The key is evidence--evidence powerful enough to overturn the HIV-->AIDS paradigm, which is very well-supported.

This isn't just theoretical: let me give you a very current example. For many years--up to my own training--it was thought that pandemic influenza viruses were almost exclusively the result of a recombination event between an animal and human virus, and that the pig was the main "mixing bowl" for this recombination--an "antigenic shift" event. Now, it's certain that this can happen--for example, the 1968 H3N2 virus was a recombinant--and it's still a worry that something similar will happen with H5N1 and a human influenza virus, resulting in a "humanized" avian virus capable of H2H transmission. But by determining the sequence of the 1918 virus, it appears this had no such recombination event--it's essentially an all-avian virus that entered the human population, and adapted solely by small mutations--antigenic drift. So this has caused influenza virologists to change some of their assumptions about influenza pandemics, based on this new information. What changed their minds wasn't some list of "dissenting scientists" or a political campaign--it was the accumulation of evidence to support the modification of the "recombination as main way of pandemic virus development" paradigm. That's how science works, and despite almost 20 years of "dissent," Duesberg et al. have yet to present compelling evidence for their claims. When/if they do, I'll entertain them in light of the new evidence. Until then, I see no reason to abandon the current understanding of AIDS causation.

Very nicely put Tara.

Tara,

This is good. This is progress.

Sure, I'm skeptical of all of it. Does HIV really cause AIDS? Does it work alone? Are there other factors necessary? Is our treatment strategy the best method to go currently? Is advising all HIV+ people to take drugs optimal, or should some kind of screening--such as for the CCR5 delta 32 mutation--be provided first?

If you had stopped here, you woulda hit a home run a la Barry Bonds, but nonetheless this is exceedingly fair and reasonable.

Despite what you say, my mind certainly is open to other alternatives--but as I've mentioned, show me the evidence.

"Open to other alternatives" -- "show me the evidence"

Beautiful construct, I love it. Can't ask for more.

What I've read from Duesberg et al. are poor arguments based on a misunderstanding of the lit--as has been mentioned many times, Duesberg seems to craft his own laws of epidemiology that simply aren't applicable to most diseases.

Duesberg was the leading virologist in the world in 1987. He had just been elected to the NAS. He had just rec'd an NIH 850K/year investigator grant. He and Gallo were buddies on sabatical at NIH. He was the man.

And, then, in a journal called Cancer Research, he published a critique of the entire field of retrovirology. This is a scholarly, seminal, peer-reviewed, opus maximus on everything to do (at the time) with viruses causing cancer and AIDS. But, politically, it wrecked him. It would be like, say, Bill Clinton coming out as a Republican.

Please read this one paper honestly, openly, without a jaundiced eye, highlighting the good points, highlighting the bad points -- Hell, e-mail Duesberg himself with your critiques, he's easy to reach -- and we will be buddies, without my silly shenanigans or ad homimen quips, or anything else.

Now, I don't expect you a priori to agree with everything Duesberg said in the paper -- because that would be unscientific and unfair. But, surely -- based purely on the evidence you require -- you will have to accept many of his points, no matter how hard they hurt certain pet theories of certain well-established scientists.

If I see something persuasive, I'm happy to re-address my understanding--and most scientists will be as well.

Perfect. I can't ask for anything more. I don't know about "most" scientists (many are making too much $$ off AIDS), but I do not doubt your personal sincerety.

Dr. Smith, I believe the fever has broke. I apologize for some of my juvenile tactics. Henceforth, I will answer and ask questions based on civility and mutual respect.

And I hope to continue the dialogue. But, promise me 1 thing: That you will read the Cancer Research paper by Duesberg, stripped of any preconceptions, Yes, skeptically, but fairly and squarely. Don't presume that retroviruses cause cancer and don't presume that HIV kills T4-cells. Just follow the evidence where it leads.

And, then open 1 thread on it to discuss with civility here at this fine blog.

Henry J. Barnes

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

Duesberg was the leading virologist in the world in 1987.

And where was he in 1981, 1982, 1983, 1984, 1985, 1986 ?

One is not challenging the gentlemans credentials, but what are the clinical applications of his science ?

The last, some have heard, David Rasnick, his co-worker is working with a vitamin salesman in South Africa to treat the ill.

16,000 deaths due to AIDs occurred by the end of 1987, for the majority of which AZT was not an option.

Now we are told that Aetiology will be an appropriate format for discussion by Mr. Barnes if she reads Duesberg and promises to open the subject matter to discussion with clarity.

What answers can you give to the thousands on retro-virals that are keeping themselves alive with their meds ?

Ms. Culshaw says, don't take an HIV test. How does that fit into a clinical setting with ill people ?

For myself, Duesberg went off the radar screen with the Scovill child and the LA Examiner's report. I fail to see how reading a peer-reviewed article will help the debate.

By McKiernan (not verified) on 23 Mar 2006 #permalink

Rebecca Culshaw's citations on HIV/AIDS mathematical modelling (from PubMed):

1: Culshaw RV, Ruan S, Spiteri RJ.
Optimal HIV treatment by maximising immune response.
J Math Biol. 2004 May;48(5):545-62. Epub 2003 Oct 27.
PMID: 15133623 [PubMed - indexed for MEDLINE]

2: Culshaw RV, Ruan S, Webb G.
A mathematical model of cell-to-cell spread of HIV-1 that includes a time
delay.
J Math Biol. 2003 May;46(5):425-44.
PMID: 12750834 [PubMed - indexed for MEDLINE]

3: Culshaw RV, Ruan S.
A delay-differential equation model of HIV infection of CD4(+) T-cells.
Math Biosci. 2000 May;165(1):27-39.
PMID: 10804258 [PubMed - indexed for MEDLINE]

- David Crowe

Sure, I'm skeptical of all of it. Does HIV really cause AIDS?

You realize you just made yourself vulnerable to some potential quote mining?

On AIDS-denialists blogs everywhere: Dr. Tara Smith is skeptical that HIV causes AIDS. ;)

By Miguelito (not verified) on 23 Mar 2006 #permalink

Hank, I've read the Duesberg paper. Several times. I have it in his "Infectious AIDS" book as well. Again, you assume too much when you make assumptions that I'm not familiar with his work. Indeed, recall that I mentioned another one of his papers--also included in the "Infectious AIDS" collection--in another post, where you chided me for not calling him Dr. Duesberg. It's the fact that I have read so much of his and others' writing--with an open mind, checking their claims against the scientific lit--that I find so much of it unconvincing. They make assumptions and mistakes that even an undergraduate microbiology major shouldn't make regarding the development and spread of infectious disease.

I'm out of town as I mentioned, so my copy of the paper is about a thousand miles away, but I can indeed write up my criticisms of it if that will help--but most of them have been covered ad nauseum in the previous threads on this topic with little response from y'all except ignoring or dismissing them out of hand. I'll essentially be repeating myself, so I don't really know what the point would be.

You realize you just made yourself vulnerable to some potential quote mining?

On AIDS-denialists blogs everywhere: Dr. Tara Smith is skeptical that HIV causes AIDS. ;)

Ha! Sad but true.

The papers that Dr Culshaw wrote are by her own admission not relevant to her reasons for "quitting" HIV.

The arguments that she does present are just regurgitations of Duesberg. You do not need any scientific training or critical thinking to regurgitate Duesbergian Dogma. Hank Barnes demonstrates this very effectively (Yes, that was an ad hominem. It is also true).

She also writes If the AIDS establishment is so convinced of the validity of what they say, they should have no fear of a public, adjudicated debate between the major orthodox and dissenting scientists to settle the matter once and for all. Yet all the major AIDS researchers have averted such a public debate, either by claiming that the "overwhelming scientific consensus" makes such a debate superfluous, or by saying that they are "too busy saving lives."

She again tells the same story that there has never been a debate in the literature. This is simply not true. You can go back and search the literature and find this debate that according to the revisionists never happened.

The revisionists themselves point to the papers that Duesberg has published. Duesberg was even given a whole edition of Genetica to present all the "dissident" ideas. Duesberg was himself the editor of this edition. Duesberg was also allowed to publish his articles in PNAS despite them failing peer review. The responses to these articles are also published in various journals.

Importantly several authors have gathered evidence that directly contradicts Duesberg's hypothesis that recreational drugs, factor VIII and AZT were responsible for AIDS in homosexuals, drug users and haemophiliacs.

Does drug use cause AIDS? Ascher MS, Sheppard HW, Winkelstein W Jr, Vittinghoff E. Nature. 1993 Mar 11;362(6416):103-4.

The lack of association of marijuana and other recreational drugs with progression to AIDS in the San Francisco Men's Health Study. Di Franco MJ, Sheppard HW, Hunter DJ, Tosteson TD, Ascher MS. Ann Epidemiol. 1996 Jul;6(4):283-9.

The next group is a cohort of homosexual men in Vancouver.

HIV-1 and the aetiology of AIDS. Schechter MT, Craib KJ, Gelmon KA, Montaner JS, Le TN, O'Shaughnessy MV. Lancet. 1993 Mar 13;341(8846):658-9.

The last set is from studies of people with haemophilia in the UK

Comparison of immunodeficiency and AIDS defining conditions in HIV negative and HIV positive men with haemophilia A. Sabin CA, Pasi KJ, Phillips AN, Lilley P, Bofill M, Lee CA. BMJ. 1996 Jan 27;312(7025):207-10.

Mortality before and after HIV infection in the complete UK population of haemophiliacs. UK Haemophilia Centre Directors' Organisation. Darby SC, Ewart DW, Giangrande PL, Dolin PJ, Spooner RJ, Rizza CR. Nature. 1995 Sep 7;377(6544):79-82.

Response: arguments contradict the "foreign protein-zidovudine" hypothesis. Sabin CA, Phillips AN, Lee CA. BMJ. 1996 Jan 27;312(7025):211-2.

The responses made by Duesberg and responses to these responses can be found in various journals. The claim that this never happened is bewildering.

In Duesberg's responses to these challenges he insistently claims that because many of the "drug-free AIDS" patients took AZT that this supports his theory that AZT causes AIDS. Sabin and Ascher make it perfectly clear that patients were put on AZT after they had either progressed to clinical AIDS or their CD4 count had decreased to below 200 cells/ml. It is therefore completely unfounded and illogical to claim that the observed decrease in CD4 cells is due to AZT. The decrease came before the AZT. This has been pointed out to Duesberg several times in the literature and yet Duesberg continued to make the same claim.

Duesberg also claimed that Ascher had fabricated the data in his paper and that Ascher had lied about the drug-free AIDS cases. This arose because Duesberg misread the paper. The issue was reviewed by an independent panel of scientists at Berkely and Duesberg's slurs were found to be baseless.

Duesberg made a big deal out of the way that Ascher used a light/none drug use group compared to a heavy drug use group. The first important detail is that the first group included those who had reported no drug use. Even if this were not the case Duesberg frequently talks about a dose response effect. If this were true then we would expect a difference between the heavy drug users and the light drug users. None could be found.

Duesberg goes to extraordinary lengths to make the inconvenient drug-free AIDS cases go away. Firstly he discounts patients that were given AZT as not being drug-free despite the fact that they were only given AZT after they progressed to AIDS. Then he includes alcohol,marihuana and tobacco as drug use. Of course you can "eliminate" more drug-free AIDS cases this way but it also weakens then whole hypothesis that the drugs cause AIDS. Do all recreational drugs that have vary different chemistry all cause AIDS? If you include the use of these drugs and antibiotics then just about everybody should get AIDS. They don't.

Duesberg also goes to incredible lengths to find HIV-negative AIDS cases. He does this by widening the definition of AIDS to include various conditions such as Herpes-Zoster and oral candidasis that frequently occur in non immune-comprised individuals. These conditions were never AIDS defining. It is hypocritical for people that claim that AIDS is poorly defined to then ignore the CDC definitions when it suits them.

Another 10 years has gone by and the evidence that we have completely refutes the hypothesis that recreational drug use and AZT rather than HIV cause AIDS. The evidence connecting HHV-8 with Kaposi's sarcoma is getting stronger and stronger. The evidence that nitrites cause KS is still weak. Harry Haverkos who originally championed the nitrites connection concedes that HHV-8 and HIV do play a causal role in KS although he apparently does not rule out nitrites as a factor.

The debate has happened. It is recorded in print for anyone to read. To claim that it didn't happen is historical revisionism. Duesberg has not given up his ideas but history is also filled with scientists that cling to their pet theories years and decades after they have been demolished.

I doubt that Duesberg will ever admit defeat. This does not mean he is correct. What matters is that a debate has taken place. Duesberg has presented his ideas. Other scientists have responded to these ideas with evidence that contradicts his claims. Duesberg made very poor responses to these challenges. The vast majority of scientists concluded that Duesberg was wrong.

Let's just revise exactly why Duesberg was judged to be wrong. In his responses to evidence that contradicted his claims he falsely accused Ascher of fabricating data, he claimed that AZT taken after depletion of CD4 cells and progression to AIDS caused the AIDS and loss of CD4 cells, he "reinterpretted" the data to include alcohol, marihuana and tobacco as drugs that cause AIDS and he "reinterpretted" the data to include patients with Herpes-Zoster and other non-AIDS defining illnesses as AIDS.

Of course Duesberg's defenders will ignore all of this because I am someone that blindly follows the "orthodoxy". If I were really a skeptic I would accept everything that Duesberg writes as gospel.

By Chris Noble (not verified) on 23 Mar 2006 #permalink

Dr. Smith,

No, I certainly won't be quote mining you. You have expressed some ordinary skepticsm, but are firmly in the HIV=>AIDS camp, which is fine.

I make no assumptions about whether you've read his work or not. I've merely asked you to evaluate Duesberg's 1987 paper with a fresh, unbiased approach, without assuming that HIV causes AIDS. And, of course, offer a fair-minded critique, acknowledging both his strong points and weak points.

That is all anyone can ask.

Hank Barnes

By Hank Barnes (not verified) on 23 Mar 2006 #permalink

Hank writes:I make no assumptions about whether you've read his work or not. I've merely asked you to evaluate Duesberg's 1987 paper with a fresh, unbiased approach, without assuming that HIV causes AIDS. And, of course, offer a fair-minded critique, acknowledging both his strong points and weak points.

Now you assume that Tara and everybody else that has read the paper and found Duesbergs arguments to be thoroughly unconvincing hasn't read the paper with an unbiased approach.

Please do not attempt to present yourself as an unbiased observer. You are consistently antagonistic to any one that presents evidence that HIV causes AIDS and you are universally credulous of anything that Duesberg claims.

For a group of people that like to call themselves skeptics "HIV rethinkers" display very little if any skepticism towards their fellow "rethinkers".

Anyone that claims there are no flaws in Duesberg's theory that HIV is a harmless passenger virus and that recreational drugs cause AIDS is seriously deluded. "Rethinkers" normally avoid this issue by attempting to reframe the "debate" so that everybody else has to prove to them personally that HIV causes AIDS. While people like Duesberg cling to their pet theories the "rethinkers" can still claim that nobody has proven that HIV causes AIDS.

Duesberg claims that HIV is a harmless retrovirus spread predominantly by perimatal transmission. Yet the CDC serosurveilance reports that Duesberg cites show that in the US the majority of people infected with HIV are in high risk groups such as IVDUs and homosexuals (the proportions have also changed over time). In these particular subgroups the prevalence of HIV has been up to 70%. Does this support Duesberg's claim that HIV is predominantly spread by perinatal transmission? Are the mothers of homosexual men and IVDUs all HIV positive?

The mathematically competent "rethinkers" can attempt to answer this paradox.

Duesberg accepts the studies that show that the efficiency of perinatal transmission is somewhere around 50%.

If the proportion of a population infected with HIV at time 0 is p0 then we would predict that this proportion as a function of generation n should follow this equation.

pn = p0 * (0.5)^n

ie the proportion of people infected with HIV should follow an exponential decay.

My conclusion is that it is impossible for a virus to maintain a steady prevalence in a population if it is predominantly spread by perinatal transmission with an efficiency of 50%.

There are many more paradoxes like this in Duesberg's theories yet for some reason HIV "rethinkers" are only interested in "rethinking" "orthodox" claims.

You also get strategic alliances between groups like The Perthies who claim that HIV does not exist and therefore cannot cause AIDS and Duesberg who claims that HIV does exist but it cannot cause AIDS because retroviruses do not cause disease.

The situation in South Africa is comical. Mathias Rath believes that HIV exists and causes AIDS and that vitamin C is an effective antiretroviral. His scientific advisor - David Rasnick - believes that HIV exists but that it doesn't cause AIDS. His spokesperson - Anthony Brink - apparently does not believe that any virus causes disease in humans.

If HIV "rethinkers" are all honest, unbiased and arguing scientifically why can't they at least convince each other?

By Chris Noble (not verified) on 23 Mar 2006 #permalink

I mentioned above that "rethinkers" only appear to rethink everybody elses claims and not their own.

They appear to be exceedingly credulous of the claims made by fellow "rethinkers".

Dr Culshaw cites this article as evidence that Ho and Shaw's math is all wrong. It appears to have gone through the same critical appraisal and fact checking as most of the articles on the virusmyth website - ie. none.

The author Mark Craddock writes:

To begin with, a few oddities and yet another remark about QC-PCR. In the Shaw paper (Wei et al) they study 22 patients with CD4 counts between 18 and 251 . They claimed that plasma viral RNA levels in the 22 subjects at baseline ranged from 10^4.6 and 10^7.2 with geomteric mean 10^5.5. (The notation 10^4.6 is 10 to the power of 4.6, which you can work out on any scientific calculator. 10^4.6 =39810, or 19,905 virions per ml of blood. 10^7.2 = 15848932, or 7924466 virions per ml. 10^5.5 = 316228, or 158114 virions per ml. Of course the accuracy given here is ludicrous. They can't really mean that they can measure things this accurately) Note that they say geometric mean. What is the geometric mean I hear you ask? Well this is obtained by multiplying the numbers together and taking the nth root. So for two numbers you multiply them together and take the square root. For 3 numbers you take the cube root of the product and so on. The Geometric mean is always less than the arithmetic mean, or average , except when the numbers are identical, in which case the two means are equal. Why have they used the geomteric mean here? Well the only reason we could think of (myself and my colleague Sylvano Lucchetti, who is a statistician) is that the geometric mean smooths out ratio changes. This might be important to make their estimates of viral load by QC-PCR look more consistent than they really are. If they are estimating changes in viral load by taking ratios of QC-PCR measurements at different times, then the geometric mean of these variations will show less variability than the arithmetic mean. It makes their results look more consistant than they really are.

Craddock starts of by converting the geometric mean viral load of 10^5.5 to 316228 per 2ml or 158114/ml and then appears to berate the authors for claiming a ludicrous degree of precision. But Shaw et al aren't claiming that degree of accuracy. They only have 2 signicant figures in the viral load in log scale. If they had intended to claim six significant figures they would have written the viral load as 10^5.50000.

If I type the following line into my computer
> units "pH(7.1)*avogadro*ml"
the answer 4.7835574e+13 pops out

However a pH measurement of 7.1 does not imply that the number of H+ ions in 1 ml of water is exactly 4.7835574e+13. You don't suddenly gain significant figures by transforming the data from a log scale to a linear scale. 4.8e+13 would be a more realistic number.

Craddock then goes on to express amazment that Shaw et al use the geometric mean. Craddock is a mathematician?

Quantitative PCR like any technique has errors. The multiplicative nature of the PCR process means that the error distribution will not be normal but rather lognormal. It is a skewed distribution with a tail on the high value side. Error analysis based on a normal distribution is not appropriate for this technique.

The typical errors for viral load measurements is about 0.5log10. This means that a measurement of 10^5.5 could really be between 10^5.25 and 10^5.75. Hence a viral load of 300,000 could really be between 180,000 and 560,000. Note that the error range is not symmetric about the value.

For this reason in determining the progress of ARV treatment you can realy only consider changes in viral load that are greater than a factor of 3.

The easier method is to transform the measurements to a log scale. The viral load could then be given as 5.5+-0.25 log10.

If repeated measurements of the same sample are made a lognormal distribution of results is expected. For this distribution a geometric mean is applicable. The alternative is to transform the measurements to a log scale and use the arithmetic mean on the transformed data. The two methods are mathematically identical. A lognormal distribution is converted into a normal distribution when plotted on a log scale.

Craddock says he can't understand why a geometric mean is used. I say that this reflects poorly on his understanding.

If the "rethinkers" are correct then why don't they use better arguments?

By Chris Noble (not verified) on 24 Mar 2006 #permalink

FYI, the three cites posted by David Crowe represent the entirety of Dr. Culshaw's published work, at least according to PubMed. Here is the abstract for the most recent:

J Math Biol. 2004 May;48(5):545-62. Epub 2003 Oct 27.

Optimal HIV treatment by maximising immune response.
Culshaw RV, Ruan S, Spiteri RJ.

Department of Mathematics, Clarke College, 1550 Clarke Drive, Dubuque, IA 52001, USA.

We present an optimal control model of drug treatment of the human immunodeficiency virus (HIV). Our model is based upon ordinary differential equations that describe the interaction between HIV and the specific immune response as measured by levels of natural killer cells. We establish stability results for the model. We approach the treatment problem by posing it as an optimal control problem in which we maximise the benefit based on levels of healthy CD4+ T cells and immune response cells, less the systemic cost of chemotherapy. We completely characterise the optimal control and compute a numerical solution of the optimality system via analytic continuation.

Hmmm. "Our model is based upon ordinary differential equations that describe the interaction between HIV and the specific immune response as measured by levels of natural killer cells" - problem with that sentence is that the adaptive immune reponse is specific, while natural killer cells are part of the non-specific innate response. I will try and track down a copy of the full paper before commenting further.

This whole issue seems connected to the strange "speaking from authority" thing given that Culshaw, a mathematical biologist from Clarke College in Dubuque Iowa who has published a total of three papers, is now being lauded for both her expertise and courage by denialists. Would it be churlish to suggest that Culshaw's change in research priorities might relate to the slow progress she has made thus far? I think these papers might better be used in an argument about wasteful, pointless HIV-related research; there is certainly a considerable amount of it.

In terms of the Ho/Shaw papers, I don't think math was the problem, it was the immunology. The follow up letters in Nature by Don Mosier and Jonathan Sprent immediately pointed this out, and subsequent data has proved them right. Cytopathicity is not driving CD4 T cell death in HIV infection, immune activation is - how many times can that be said before the denialists take it on board?

Would it be churlish to suggest that Culshaw's change in research priorities might relate to the slow progress she has made thus far?

I think she has simply moved on to do other things, but it would still seem a bit thoughtless to renounce all of your previous work in a single web page. I can see how a student could decide to finish a PhD and get it over with, even if she had doubts about the theoretical base. But in that case she could have said cleanly "disregard all of my previous work", or even better, try to publish a real article on it.

It would seem that she treats them as purely theoretical work, but the titles imply they might have implications in AIDS treatment.

One of the other authors has a PDF up:

http://www.math.miami.edu/~ruan/MyPapers/CulshawRuanSpiteri-jmb04.pdf

Well, I have made a pact to conduct myself with civility here, so I respond gently as follows:

Chris: We don't get along. But, I do acknowledge that your cites to the literature are valuable, and much better than most. But, we should probably part ways for a bit.

Richard: You certainly know a lot about the "black box" known as immunology. Out of respect for this blog, though, we will have to air our significant differences elsewhere.

Windy: I'm sorry I've lost track of who you are.

McKiernan: We have ample opportunity to discuss this at Dean's World.

For the record, there are 4 likely hypotheses:

1. The Gallo hypothesis: HIV kills T4-cells (aka CDC4 cells) in some manner unknown, causing 1 of 29 diseases

2. The Duesberg hypothesis: HIV is neither necessary, nor sufficient to kill T4-Cells.

3. The Root-Bernstein/Montagnier hypothesis: HIV is necessary to kill T4-cells, but not sufficient.

4. The Perth hypothesis: HIV has not even been properly isolated, so it may not even be a distinct retrovirus, let alone one that kills T4-cells.

I believe that I have fairly described the competing hypotheses. If I haven't, feel free to offer corrections. Clearly, No. 1 is the dominant hypothesis or, rather, the most popular in the world.

My personal view is that I think No. 1 has significant flaws and counterfactual evidence to warrant a proper, unbiased evaluation of the other 3 hypotheses.

Yes, I admire Duesberg and his work. He published over 200 papers in the literature before his seminal piece in Cancer Research in 1987, that wrecked his career.

But, all of this work has withstood massive scrutiny, so when I hear somebody attack him, to me, it tells me much more about the attacker, than Duesberg.

So, you cannot divorce this massive body of outstanding work, from the work he has conducted since 1987 on AIDS and aneuploidy.

No, this is not Duesberg worship. I fully recognize that he may be wrong. But, his work, historically, has been impeccable.

Gentlemen, we are making progress.

Hank Barnes

By Hank Barnes (not verified) on 24 Mar 2006 #permalink

Thanks for the link to the paper. It's a bit confused. It offers four out of date references regarding CD4 T cell depletion, two from 88, one from 91 and one from 2000. None of them relate to immune activation. It seems to confuse natural killer cells and CTLs in several places:

"The impact of the depletion of CD4+ T cells on the host is that although the natural killer cells may be fit to perform their function of eliminating infection, they are never deployed."

Natural killer cells to do not require CD4 T cell help.

"Although HIV does not target the CTLs directly, it has been noted clinically for some time (see Carr et al. [4], Cocchi et al. [5], Gray et al. [10], Arnaout, Nowak, andWodarz [1], Musey et al. [20], Ogg et al. [22],Walker et al. [26],Weine et al. [28],Wodarz et al. [29], and references cited therein) that individuals who maintain a high level of CTLs remain healthy longer."

This had already been disproved when this paper was written, it is not the magnitude of the CTL response that matters, but functional parameters like proliferative capacity. >50% of the CTL pool can be HIV-specific in a person with AIDS, but these cells are demonstrably funcionally impaired. CTLs do depend on specific CD4 T cell help to develop full functionality.

Other than that, it makes a reasonable argument for studying immunotherapies designed to enhance the HIV-specific T cell response. I'm not qualfied to comment on the mathematical equations other than to note that the parameters and variables included are inadequate to encompass T cell homeostasis. And the values assigned to the parameters they do use are questionable assumptions, at best. They could probably have avoided all these problems if they'd run the paper by an immunologist.

I wrote above: "HIV kills T4-cells (aka CDC4 cells)"

It should be CD4 cells (no extra "c")

Hank

By Hank Barnes (not verified) on 24 Mar 2006 #permalink

Oh Hank. I think your post of "The Four Hypotheses" (the four horsemen of the hypotheses?) may be a bit of a classic. This idea that Bob Gallo's work or ideas underpin all subsequent HIV research is beyond ludicrous. As is your continued assumption that competing hypotheses regarding pathogenesis say something about causation (as I've said before, go check out current hypotheses regarding TB pathogenesis). The current thinking about HIV pathogenesis, backed up by reams of data (and not reflected anywhere in your post), is pretty clear:

HIV causes persistent immune activation that typically:

1) depletes the naive T cell pool (both CD4 and CD8 cells, ruling out direct killing as being important)

2) leads to a severe peturbation of the memory T cell pool, loss of memory responses to common opportunistic pathogens and, thus, clinical reactivation of those pathogens.

You can recapitulate this in mice by overexpressing the T cell activating molecule CD70 (the mice end up dying of PCP).

You yourself Hank almost certainly have memory T cells targeting more than 29 different pathogens. You have a team of memory T cells targeting herpes zoster, if that team gets depleted you'll be at risk for shingles. You have a team of memory T cells targeting PCP, if that team gets depleted you'll be at risk for PCP. On and on, there's no mystery about the multiplicity of diseases because they're pathogens that most of us are latently infected with, our immunlogical memory keeps them in check. Mess with immunological memory, and you're in trouble. The memory T cell pool is huge (several billion cells) and fairly resilient, so it takes some time to derange it sufficiently that clinical reactivations occur, hence the generally slow course of disease. Declining CD4 T cell numbers in peripheral blood are just a surrogate marker for the peturbations of the immune system that are occuring, not some direct reflection of T cell killing as David Ho erroneously proposed.

The one thing your four horsemen have in common is this: none of them are able to definitively state whether or not HIV is capable or sufficient to cause immunodeficiency because - like the rest of the human race - none of them know enough about the workings and vulnerabilities of the human immune system. The more we learn about how the T cell immune system works, the more we understand how HIV undermines it. I can foresee one big ironic outcome to all this: at some point Duesberg develops a disease which is treated with a therapy that wouldn?t have existed but for what HIV has taught us about the human immune system.

I think she has simply moved on to do other things, but it would still seem a bit thoughtless to renounce all of your previous work in a single web page.

I'm not sure she's "renouncing all her previous work". The mathematics stands fine, given the assumptions behind them. There is nothing contradictory in her (a) renouncing the HIV theory, and (b) standing by her dissertation and papers which demonstrate her abilities in mathematical modeling and mathematical biology. If you can't separate the two, that's just evidence that you don't understand what an implication statement is.

Any mathematician reading this post would immediately understand what I'm talking about...say lots of people believe conjecture X implies big unsolved problem Y, but no-one has proved it. Suppose researcher R proves the implication. This gains R a lot of notoriety and acclaim. Now, suppose researcher P (for "party-pooper") finds a counterexample to conjecture X so that conjecture X isn't true after all. This does nothing to invalidate the original work of R, whose methods and techniques can often be applied elsewhere. In fact, this has actually happened in mathematics at several points.

I think all Culshaw is saying is, "I've spent the past 10 years of my research career working on X implies Y, and now I no longer believe X to be true." This doesn't do anything to invalidate the work on "X implies Y" though. In fact, the work on "X implies Y" stands for itself and could very well have applications outside of HIV or even outside of biology.

I can see how a student could decide to finish a PhD and get it over with, even if she had doubts about the theoretical base. But in that case she could have said cleanly "disregard all of my previous work", or even better, try to publish a real article on it.

What is "it" -- "AIDS"?? But that was her whole point -- "AIDS" is a phoney construct, based on flawed assumptions, and any attempt to "publish a real article on it [HIV]" would necessarily be flawed, as well. You're so wound up in the HIV "mindset" you can't even fathom that the best solution might be just to throw away the HIV theory and look for specific reasons why individual people are getting sick.

I think you missed her main point -- it's not that she's renouncing all of applied mathematics or even mathematical biology. She's just saying that in researching the biology required for her work, she found certain things that were just too weird or didn't add up. Now, maybe she thinks this way because she's not a biologist or because she hasn't studied the relevant areas enough. Or it could be that maybe she thinks this way because the standards used to educate mathematicians haven't plunged to the depths they have in biology, and so she can recognize horse-poopy when she sees it, regardless.

This whole issue seems connected to the strange "speaking from authority" thing given that Culshaw, a mathematical biologist from Clarke College in Dubuque Iowa who has published a total of three papers, is now being lauded for both her expertise and courage by denialists.

Obviously, you're not a mathematician. Three papers in mathematics (and yes, mathematical biology is a subfield of mathematics) is not the equivalent of 3 papers in biology. It can take 2-3 years just to write a single paper, and 2-3 years for it to go from submission to referreed peer review to publication. Moreover, mathematicians simply publish fewer papers than biologists in terms of number, and 3 papers is actually quite a lot. (At most schools except the highest research-level institutions, 2-3 publications is often enough for tenure. At many, 1-2 is enough.)

Would it be churlish to suggest that Culshaw's change in research priorities might relate to the slow progress she has made thus far? I think these papers might better be used in an argument about wasteful, pointless HIV-related research; there is certainly a considerable amount of it.

Actually, I think Culshaw might agree with you here, but from her 2 posts at Rockwell, I think she might say that similar things can be said about *EVERY* mathematical paper ever published on HIV. In other words, the whole research area [mathematical modeling of HIV] is flawed and wasteful. If you came to conclusion that the entire research area you work in is based on flawed assumptions and is very wasteful of time and resources, wouldn't *you* consider leaving, too? Would it be churlish to suggest that the entire research field itself is "slow" and that Culshaw simply discovered the reason why -- that the whole basis is wrong?

In terms of the Ho/Shaw papers, I don't think math was the problem, it was the immunology.

Again, I guess you're not a mathematician. Any mathematician can see there were mathematical problems, as well. In particular, the statistical analysis was laughable, there were mathematical assumptions that were hidden from the reader, and the models used assumptions not based on any observation.

And I might add that yes, as you point out, the biological problems with Ho/Shaw were eventually pointed out. I think Culshaw's contention was that the flaws in the papers were obvious just by looking at them, and should have been flagged immediately. Why not?

Thanks for the link to the paper. It's a bit confused. It offers four out of date references regarding CD4 T cell depletion, two from 88, one from 91 and one from 2000.

The paper was 2004, I believe. How is 2000 "out of date"?? Again, I can only assume you're not a mathematician. It takes about 2 years to get a paper published in math, and I suspect they started work 2 years before that, so the 2000 paper would have been practically "state of the art" at the time they began their research.

And the fact that the papers from 88 and 91 are "out of date" would only seem to validate Culshaw's claims in her 2 posts. It seems that one thing that frustrated her was that the "explanations" for how HIV was supposed to work kept changing every 2-3 years. It's one thing to not have everything worked out, and questions remain, but when "knowledge" is continually "out of date" every 2-3 years, you have to ask how good is it in the first place?? In mathematics, knowledge is forever -- if something is done well and correctly in 1988 or 1991, then it's just as good and correct in 2006. Nothing goes "out of date". My question would be -- if the 1988 and 1991 papers are now "out of date", then why wasn't what was "wrong with them" found out by the peer reviewers at that time?? It's not as if you guys are steadily building a growing body of knowledge based on accumulated and secure theory. It's more like you're just knocking the whole thing down every 2-3 years and starting over again.

Another thing...if a paper from 2000 is "out of date", then surely you don't have the right to quote the "130,000+" papers written on HIV as evidence for HIV? You can't have it both ways. You can't say all these old papers are "out of date" and then continue to use them to say they're part of the "massive overwhelming evidence in favor of HIV".

This had already been disproved when this paper was written, it is not the magnitude of the CTL response that matters, but functional parameters like proliferative capacity.

See, this is what I don't get. I'm going to assume what you say is true. Given that it's true, how is it that 9 different papers were published, and apparently within each of these, several more were referenced, so that possibly *dozens* and dozens of papers were published in peer reviewed journals asserting (and I'm sure some of the researchers at the time would say "proving") exactly what you just said above is now wrong??

I know that science is self-correcting and things are always open to be questioned, but this seems pretty ridiculous. Did AIDS change that much in 15 years? If it was wrong then, why were so many people able to publish papers "proving" just the opposite?

I'm not qualfied to comment on the mathematical equations other than to note that the parameters and variables included are inadequate to encompass T cell homeostasis. And the values assigned to the parameters they do use are questionable assumptions, at best.

I think this was the point she was making...that the mathematical modeling was based on inadequate biological knowledge and assumptions.

By George Kaplan (not verified) on 24 Mar 2006 #permalink

I think all Culshaw is saying is, "I've spent the past 10 years of my research career working on X implies Y, and now I no longer believe X to be true." This doesn't do anything to invalidate the work on "X implies Y" though. In fact, the work on "X implies Y" stands for itself and could very well have applications outside of HIV or even outside of biology.

Sure, but she said she had had doubts for a long time that X was not true. You think I said the mathematics was flawed, when I said the opposite: the mathematics is probably superb, but was it not part of her task to try to find the right starting parameters (X) as well? If she has doubts on X, why not try to publish her evidence against X.

What is "it" -- "AIDS"?? But that was her whole point -- "AIDS" is a phoney construct, based on flawed assumptions, and any attempt to "publish a real article on it [HIV]" would necessarily be flawed, as well. You're so wound up in the HIV "mindset" you can't even fathom that the best solution might be just to throw away the HIV theory and look for specific reasons why individual people are getting sick.

WTF is the "HIV mindset"? She _did_ publish articles that were based on flawed theory, in her opinion. What I suggested was writing a real article on why AIDS is flawed and submitting it for publication, instead of some half-assed essay.

Hypothetical example:

Let's say I am trying to model the management of some animal population, and initially it is suggested that I should keep the inbreeding level to a minimum. I develop a flawless model, but while working on it, I fail to find evidence of any ill effects of inbreeding. Slowly I begin to suspect that outbreeding is actually more harmful for this species. However, I choose to publish my article titled "Optimal management of species X by minimising inbreeding" because the model itself is good.

I wash my hands of the research, but later write an opinion page on the WWW stating that most of the work put into management of species X is a waste of money, and the scientists who worry about inbreeding are being silly. (I don't say whether my recommendations are still to be followed, but it would seem not.) Meanwhile, the population of species X continues to dwindle.

Is this scientifically the best way to go?

I think this was the point she was making...that the mathematical modeling was based on inadequate biological knowledge and assumptions

About human immunology. Why is it the fault ot HIV researchers that we don't know enough about human immunology to fully understand how HIV causes immunodeficiency? The way you're articulating it, Culshaw's quibble is really with T cell immunologists.

The focus of the rest of your comments seems to be on suggesting that people in HIV & human immunology research have been too wrong somehow. I'm not sure what the threshold is for that, but it seems a bit subjective. The kinds of technologies being used to study T cell responses in recent years (and in the papers cited by Culshaw) are new, and before these technologies came on the scene T cell function was remarkably opaque. So, inevitably, there have been issues around interpretation which have been addressed as the science has progressed. This to me, is normal and commendable. Read the papers and see what you think.

In terms of the cites, they reflect an ignorance of the field which is surely only the fault of the authors. The role of immune activation in disease pathogenesis had been widely discussed and published on when this paper was written. So why pick Miles Cloyd's obscure homing theory from 2000? The paper simply does not bespeak of a firm grasp of the topic at hand. If you're concerned about the quality of peer review, perhaps the statements about natural killer cells should not have slipped through?

Dean writes:

1. The Gallo hypothesis: HIV kills T4-cells (aka CDC4 cells) in some manner unknown, causing 1 of 29 diseases
2. The Duesberg hypothesis: HIV is neither necessary, nor sufficient to kill T4-Cells.
3. The Root-Bernstein/Montagnier hypothesis: HIV is necessary to kill T4-cells, but not sufficient.
4. The Perth hypothesis: HIV has not even been properly isolated, so it may not even be a distinct retrovirus, let alone one that kills T4-cells.

You forgot the Flying Spaghetti Monster hypothesis. Please give it equal time.

Seriously. Everything is a hypothesis if you want to use the word in that manner. That doesn't mean that all hypotheses are equal.

Don't you find it a bit strange that proponents of hypotheses 2 and 4 spend their time trying to tear down hypothesis 1 rather than doing real research to support their own theories.

That reminds me of another group of people ...

By Chris Noble (not verified) on 24 Mar 2006 #permalink

George Kaplan writes:
In mathematics, knowledge is forever -- if something is done well and correctly in 1988 or 1991, then it's just as good and correct in 2006. Nothing goes "out of date".

Truth is Constant

By Chris Noble (not verified) on 24 Mar 2006 #permalink

Whoops.
I apologise to all Deans in the world for falsely attributing Hank Barne's words to one of them.

By Chris Noble (not verified) on 24 Mar 2006 #permalink

Just some quick Saturday night thoughts (sorry to all of you people with real lives, but I've been a lot more excited about the NCAA games - Go Bruins!) Yes, Tara, I know that was WAY OFF topic. But if I may brag, "John's Special Post" 45 "Tara's Malaria" 1 (and that was YOU commenting to your own post)!

Chris - I completely agree with "Don't you find it a bit strange that proponents of hypotheses 2 and 4 spend their time trying to tear down hypothesis 1 rather than doing real research to support their own theories". I agree with it being STRANGE that such research seems to have such an incredibly difficult time getting funded even though you seem to agree that it would at least be worth the off-chance effort. You said before that you can't really speak to WHY funding has been unavailable unless you could review the grant requests. Maybe they were crap. Maybe. But do you find it in the least bizarre that Duesberg never had one REFUSED - EVER until he became the "hated one" in all this? Strange indeed.

Tara, over at my blog you were asked by one of our many anonymous guests on SEVERAL OCCASIONS to cite your examples of your statement below. In fact, I believe she asked for just ONE EXAMPLE, so that should be easy enough. Maybe so easy that you thought it ridiculous. Knowing as little as I do, it would help clarify at least this one thing for me. Could you comment here?

"in, say, health care workers that experienced a needle stick after treating an HIV+ patient and then developed AIDS".

Thanks, as always for treating me so kindly in my ignorance.

Oh, one other thing...

As busy as things have been on this topic, it does seem to have grown a little quieter, at least on the issue of Culshaw and her "arithmetic", ever since the highly knowledgeable interjection on the part of George Kaplan.

Just an observation. Maybe because you were all busy cheering on my Bruins.

ever since the highly knowledgeable interjection on the part of George Kaplan.

I will be polite and just note that we disagree about the degree of "knowledgable" in the comment in question.

By Kristjan Wager (not verified) on 25 Mar 2006 #permalink

As busy as things have been on this topic, it does seem to have grown a little quieter, at least on the issue of Culshaw and her "arithmetic", ever since the highly knowledgeable interjection on the part of George Kaplan.

You mean the rant about us criticising Culshaw's math, which was never the issue?

He seems to be right about articles in J.Math.Biol. taking a long time to reach publication, though. And one year from online to print, what's up with that? Maybe they should try PLoS instead.

According to mr George "you're obviously not a mathematician" Kaplan

"(At most schools except the highest research-level institutions, 2-3 publications is often enough for tenure. At many, 1-2 is enough.)"

cough *bullshit* cough. I am a biologist and the theoreticians (aka "modelers", sometimes mathematicians or physicists, sometimes biologists who studied some math) in my field (ecology, evolution) often publish at least 5 papers *PER YEAR* in high-quality peer-reviewed journals. Papers just as technical as the ones of Culshaw. Many of those guys do not have tenure, even though they'd love to have it. So where are those institutions that give away tenure so easily?

John, could you point out something substantive that George Kaplan said that hasn't been addressed? Did you notice that he ignored certain criticisms of the Culshaw papers and focused on points about:

-the date of the cites
-peer review of Ho/Shaw and some other papers being somehow inadequate (they were so bad they should never have been published seems to be the gist, although he stretches his expertise in mathematics by suggesting this is true for several papers on T cell immunology)

And he chastises us for not knowing how maths papers are published and in a more general way for things in biology being so damn uncertain compared to the comforting predictability of math. Correct me if I'm wrong.

Also, you could do a Pubmed search for the information you're looking for regarding needlesticks, this is one example but there were multiple pages of results.

Wallace MR, Harrison WO.
HIV seroconversion with progressive disease in health care worker after needlestick injury.
Lancet. 1988 Jun 25;1(8600):1454.

John, as I've pointed out several times, I'm simply not online much on the weekends--weekends are family time. I've stayed too long today, and I've not been back over to your blog since my last comment there. I'll try to check back into your conversation tomorrow if I have time.

Thanks Tara. I'll look forward to your reply. I hope it's a bit stronger than Richard's. "Lancet"? I don't understand much, but I'm pretty sure this article doesn't represent some peer reviewed evidence.

By the way, Richard, "you could do a Pubmed search for the information you're looking for"... I think I'll leave the heavy work to Tara. It was her assertion, not just Poor John coming up with a dumb question he wanted answered. And, just for fun... let's leave this one to Tara. If she can't find it, she can request assistance, but let her give it a try. OK?

John,

You've taken half a sentence and quoted out of context: (...in, say, health care workers that experienced a needle stick after treating an HIV+ patient and then developed AIDS).

If you read above: Tara March 23, 2006 07:20 PM, you will find that she is requesting :

"So show me another virus that's present in people currently diagnosed with AIDS, that works with or instead of HIV. Show me that HIV is, as has been suggested, a "harmless passenger virus." Show me that something else was present in, say, health care workers that experienced a needle stick after treating an HIV+ patient and then developed AIDS."

She wasn't addressing peer-reviewed literature on sero-conversion from needle sticks but it certainly does occur.

So what exactly is your question ?

By McKiernan (not verified) on 26 Mar 2006 #permalink

John writes:
By the way, Richard, "you could do a Pubmed search for the information you're looking for"... I think I'll leave the heavy work to Tara. It was her assertion, not just Poor John coming up with a dumb question he wanted answered. And, just for fun... let's leave this one to Tara. If she can't find it, she can request assistance, but let her give it a try. OK?

If you were interested in the answer to your question you would not care who answered it.

If you cared about the answer to the question you would have made some attempt to do your own research. Pubmed would be a good start.

Have you bothered to read the studies that I cited by Ascher et al, Sabin et al, Schechter et al and Darby et al? I don't think so.

Did you bother to read the letters and articles where these authors and Duesberg exchanged opinions?

By Chris Noble (not verified) on 26 Mar 2006 #permalink

"Lancet"? I don't understand much, but I'm pretty sure this article doesn't represent some peer reviewed evidence

The Lancet is one of the most respected medical journals in the world. In terms of impact factor (a rough measure of how influential a journal is), it's third only to the New England Journal of Medicine and the Journal of the American Medical Association.

That, of course, does not mean the article should be taken as gospel, but it does mean you don't want to immediately dismiss it.

Sorry, this is from way up there in the comments...

It is easy to be skeptical of ID proponents

It is easy to be skeptical of thimerisol-autism proponents.

It is easy to be skeptical of anti-vaccine activists.

On things that matter (AIDS, Cancer, excessive pharmaceutical influence, corruption at NIH, stem cells) or on your own pet issues, you exhibit no skepticism, and act as compliant little lambs.

I strongly disagree. Remember, the MMR vaccine-autism link had credibility for a while when a medical journal (actually, I think it was the Lancet) said it was a legitimate hypothesis. It was considered and rejected.

Re: things that matter. There are many outspoken medical groups that are skeptical of drug company influence. See this article (in a medical journal) as an example.

I don't know what you're referring to when you say there's no skepticism about cancer or stem cells (there's research going in all sorts of different directions in these areas), so I con't really respond. And about AIDS, I also don't know what to tell you-- even if the forces that be are aligned against you, if you do good research and get some better evidence behind you, the "scientific establishment" will be happy to claim your ideas as its own. Good luck.

Another case of a lab worker infected with HIV and developing AIDS is detailed here.

Fulfilling Koch s Postulates

You can also read Duesberg's responses.

My question is if you are just goinf to ignore these cases why ask for them in the first place?

By Chris Noble (not verified) on 26 Mar 2006 #permalink

I see one of the anonymouses at EM has dismissed the references given above as "jokes" and "antecdotes" (isn't the latter what case reports generally are?) So I don't know exactly what one's looking for here, if all case reports in the literature are going to be summarily dismissed, but here's another one from Brazil, identifying the first known occupationally-acquired case of AIDS there. This NY Times article obviously isn't peer-reviewed, but it suggests some numbers (this is almost 10 years ago, mind you):

There are no statistics on the number of H.I.V. cases related to needle- stick injuries, but the Federal Centers for Disease Control and Prevention in Atlanta said that as of June, 52 health care workers had contracted H.I.V. while on the job and 114 health care workers with AIDS may have contracted the virus as the result of an on-the-job needle puncture. Because of assumed underreporting, the actual numbers are probably higher, the C.D.C. said.

JP said (in regards to the Lancet): "That, of course, does not mean the article should be taken as gospel, but it does mean you don't want to immediately dismiss it".

Of course not. I recognize that the Lancet is a time-honored mag of science. I believe it was around even back in Darwin's day. I'm not rejecting it. I'm just pointing out that it wasn't a peer-reviewed article and was asking for something more.

It seems to me (and I could be wrong), that if there are numerous examples of health care workers who have received a needle-prick transmission of HIV and later died of AIDS, then there should be numerous, authoritative, undebatable examples of it.

I see quite a few things that aren't proven about the HIV/AIDS model and would like clarification if I'm wrong, and if there is indeed ungoing lack of clarity, then having a non-hostile environment and funding for scientist who would like to clarify it.

Wait, why do you say the Lancet paper hasn't been peer-reviewed? According to their author instructions:

Every Article, Case Report, Hypothesis, Seminar, and Review papers that are published have been peer reviewed.

I don't have a hard copy of the article--does it say it was bypassed for peer review?

It seems to me (and I could be wrong), that if there are numerous examples of health care workers who have received a needle-prick transmission of HIV and later died of AIDS, then there should be numerous, authoritative, undebatable examples of it.

There are numerous problems with this--the privacy of the health-care worker and their family at the forefront. Case reports can be difficult and sensitive. There are better examples showing HIV transmission via needle-stick without follow-up documenting AIDS development (such as this study).

Chris writes:

"If you were interested in the answer to your question you would not care who answered it".

You are right. I was perhaps being uncharacteristically peevish, due to the fact that someone asked her the question at least twice and she didn't respond. But you are right. I now would like the answer and it really doesn't matter if Tara has it or not.

And - "If you cared about the answer to the question you would have made some attempt to do your own research. Pubmed would be a good start".

Again, the question was not originally mine and as long as it was being asserted, I was curious if she had an answer. Maybe not so curious as to do my own research on the matter.

And - "Have you bothered to read the studies that I cited by Ascher et al, Sabin et al, Schechter et al and Darby et al? I don't think so".

Chris, you're a funny guy. Let me say a few things about you that I hope you'll take the way they are meant.

1. Many of your comments are extremely wordy. Not all. But you occasionally go five hundred words or more. There is a lot to read and a little time in the day. I can be very wordy myself. But I try to do so when posting on my blog and not in replying in comments. I know that it will cut down in how much gets read.

2. As Hank has said, thanks for the references. They are helpful. I should do it more myself.

3. I have clicked on (I think) every reference you have ever given me, and many that you have given others.

4. I have read parts or all of each. Admittedly, if it's technical, it's over my head and I often go to the summary.

5. Some of them end up being repetitions of other links you provided previously.

6. Some didn't really prove your point. Others certainly seem to, though I know there are people who disagree and that's my biggest interest in all of this.

7. Why would you assume I don't read your links?

Tara said, "There are numerous problems with this--the privacy of the health-care worker and their family at the forefront. Case reports can be difficult and sensitive".

I don't have an account with NEJM, so can't read the study you would like me to see. But this comment above, taken on it's own and as gospel (I know - it's not meant to be), would mean there is nothing more than imaginary anecdotal stories of it happening. I'm quite sure that people in the situation you gave, would be more than happy to participate in studies that would be helpful, even if they had to be described anonymously. At least some of them. At least enough to show a correlation.

Looking closely at the examples you and Chris gave, would still leave a reasonable person in doubt. Chris, "3 Lab workers", 13 years ago? Tara, you admit that your example was from 10 years ago. Chris, unless I read it wrong, only one of the 3 actually developed (and I'm assuming EVER - since it's now been 13 years and you provide no more current update) "an AIDS defining illness", of which we know that millions of people get annually and it's only "AIDS" if they are additionally HIV positive. Chris, my own wife has had pneumonia twice in the past 5 years. She is not HIV positive.

Tara, when people deride the "anecdotal evidence" in this case, you can see why. If you were to quickly give me links to dozens of such cases, it would be a lot stronger. But Chris having 3 lab workers, one who got sick, from a reasonably common illness, and the other two who did not (admittedly, with lower T Cell counts, though) is hardly STRONG anecdotal evidence.

Just to clarify my position - I'm not "anti-anecdotal evidence" and use it myself at times. I'm very careful about using it, and how I look at it.

Again, if there were hundreds of cases of technicians, nurses, doctors, etc. who had been both infected with HIV and later died of AIDS, I'd accept that. But when I come to a blog like this, where I'm dealing with highly informed individuals in this field, and in response to a challenge can only come up with what I saw above - I'm not accepting that as evidence of anything. And if that makes me a "denialist" or whatever other derrogatory name someone wants to call me, I'll live with it.

John, one question first--do you understand what a "case report" is in the literature? Just asking, because I'm not sure what your background is in all this.

And no, the paper I cited was from 2002. It's the *NY Times* article I cited that was from 1997.

Tara, when people deride the "anecdotal evidence" in this case, you can see why. If you were to quickly give me links to dozens of such cases, it would be a lot stronger.

How so? First, even with needlesticks seroconversion to HIV+ status is fairly rare (the NEJM article I cited said .3 percent). So it's not going to be a common event in any case. Second, most of these people will be on some kind of post-exposure antiviral medication, lessening their chance of developing AIDS (and indeed, their chance of developing HIV infection in the first place). We don't expect many cases, and those we have are frequently published as case reports, which you dismiss as "antecdotes." Third, such case reports are less likely to be 1) written up and submitted to a journal and 2) accepted for publication once it's already known something can happen. Early case reports of health care workers seroconverting to HIV and subsequently dying from AIDS were novel; later ones, tragically, are not as interesting unless there's some other pathology involved. That's likely why the Brazilian one I cited was published--it's the first such report in that country. It's novel. The second, the third, the fourth, the fifth etc. are much less likely to see publication.

And what kind of pneumonia did your wife have? I'd bet 10 to 1 that it wasn't PCP.

Again, if there were hundreds of cases of technicians, nurses, doctors, etc. who had been both infected with HIV and later died of AIDS, I'd accept that.

But John, we don't expect that--you're setting up a strawman. That's why I linked the NY Times article--a scant 52 cases of HIV seroconversion are known in health care workers, where all other exposures could be ruled out and a needlestick carefully documented, and another hundred or so assumed to have contracted the virus on the job but there may be somewhat more ambiguity. We aren't dealing with "hundreds" of cases in the first place, as far as carefully documented cases go. Then to add in that many of these workers, being medically trained, would begin antiviral regimines, expecting similarly a large percentage to have died of AIDS in the time since they've been observed is simply not going to happen; the only people who suggest this type of unrealistic burden of evidence are Duesberg et al.

John, it seems you are moving the goalposts.

In fact, I believe she asked for just ONE EXAMPLE, so that should be easy enough.

You ask for one example, you get one example, plus a few more, what's not to like?

If those case studies weren't what you wanted, simple one-minute googling (HIV + needlestick + "progressed to AIDS") produced the following:

http://www.cdc.gov/ncidod/EID/vol11no07/04-1038.htm#21

To date, 26 (46%) of 57 US healthcare workers with voluntarily reported, documented, occupationally acquired HIV infection have progressed to AIDS, as have 121 (88%) of 138 healthcare workers with possible occupational transmission.

I'm surprised you weren't interested enough to try Google, but were interested enough to ask here repeatedly. (As for "why couldn't Tara/Chris/Santa answer me before, then", I'm sure they are not mindreaders and didn't know you were asking for lots of cases instead of one.)

There have not been hundreds of confirmed cases of occupational transmission in the US because health workers are trained to be careful; because it is sometimes difficult to be confident about the transmission route; and because not all health workers report their infection through the necessary channels. The CDC says that:

"Of the adults reported with AIDS in the United States through December 31, 2002, 24,844 had a history of employment in healthcare . These cases represented 5.1% of the 486,826 AIDS cases reported to CDC for whom occupational information was known (information on employment was missing for 362,954 reported AIDS cases)... Overall, 73% of the healthcare personnel with AIDS, including 1,407 nonsurgical physicians, 3,962 nurses, 385 dental workers, 328 paramedics, and 92 surgeons, are reported to have died."

Of these:

"Fifty-seven healthcare personnel in the United States have been documented as having seroconverted to HIV following occupational exposures... Twenty-six have developed AIDS."

As for the UK:

"There have been five documented cases of occupationally acquired HIV infections in healthcare workers in the UK. A further 14 probable cases of occupational acquisition of HIV in healthcare workers have been diagnosed in the UK. The majority of these healthcare workers had worked in countries of high HIV prevalence, and are presumed to have been infected outside of the UK."

(References are PDFs so I won't give direct links.)

In any case, I don't see why this topic is relevant. The vast majority of HIV infections are believed to be the result of sexual transmission, for which there is abundant evidence.

Whoops, didn't see Tara's answer before I posted, but the above link should be free to access and is dealing with the same 52 (or more recently 57?) verified cases.

Tara queried: "John, one question first--do you understand what a "case report" is in the literature? Just asking, because I'm not sure what your background is in all this".

I thought I have always been very upfront that I am probably, by far, the least informed person on any of the subjects you cover here. That's why I ask. That's why I point out peculiarities between what I am told and what I see - to find out what your version is of what I'm seeing. Still, I think I can figure out the significance of a "case study".

Windy said, "John, it seems you are moving the goalposts.

"In fact, I believe she asked for just ONE EXAMPLE, so that should be easy enough.

"You ask for one example, you get one example, plus a few more, what's not to like"?

Yes, yes. I didn't think the quality of the answer was strong, pointed out that if there were dozens or hunderds of such weak examples, it would strengthen them COLLECTIVELY, so now I'm cheating. You are sharp, Windy. You caught me.

Windy continues: "but were interested enough to ask here repeatedly".

I asked once, referring to the fact that she was "asked repeatedly" about it at my blog. I then responded to the answers given.

So, why don't you quit being so "courteous", Windy? What do really want to say to me? I'm a cheater and I'm lazy?
I'll be more honest than I think you are:

I believe you and some others here would rather come up with snappy, cutting replies to people like me than deal with the MANY oddities of the HIV/AIDS model. And even if the model is accurate (I FULLY admit this is a possibility - I don't know enough to be certain EITHER way), there are plenty of things that on the surface don't make sense if you accept the model as is.

Tara piles on with: "we don't expect that--you're setting up a strawman". (another form of cheating)

and

"and those we have are frequently published as case reports, which you dismiss as "antecdotes." (really needless to point out that I misspelled a word - unless you would like to create a environment where I'm the inferior intellect).

To review "between the lines" (which will all be denied, I predict)

1. I cheat
2. I'm lazy
3. I cheat another way
4. I spell poorly (stupid)

I have no idea why you would bother to reply to me at all. I'll try to stay off of your blog Tara, because it's clear that you and your friends are annoyed by me. I'll be posting over at mine about my questions and concerns on the subject of the HIV/AIDS Model and you are free to comment. I can't speak for everyone you'll run into over there, but you won't be treated rudely by me. It?s just the way I try to be with people. Because...

5. I'm weird

you didn't spell "anecdotes" incorrectly, john. I think that was a typo on Dr. Smith's part.

anyways, you've asked for examples of needlestick AIDS, now you have them. note that there is no way to perform a controlled experiment on needlestick AIDS; it's just not ethical. But the cases you have seen cited here are one of the lines of evidence in support of the HIV->AIDS connection.

you didn't spell "anecdotes" incorrectly, john. I think that was a typo on Dr. Smith's part.

Indeed. It was in scare quotes because the anonymous folks on your blog had said the studies linked were "jokes" because they were anecdotal. I'm far from a spelling nazi--I misspell and make typos all the time. I think you're reading too much into the posts here. Additionally, saying that you're creating a strawman isn't saying you're "cheating" or being lazy--it's simply pointing out that you're using a logical fallacy. I think that's fair game to note.

I have no idea why you would bother to reply to me at all.

Because I'd like to help you understand the evidence that supports the HIV model of AIDS causation. Sincerely. You said, "there are plenty of things that on the surface don't make sense if you accept the model as is." So let's start here. We've given you plenty of evidence for transmission of HIV to health care workers with no other risk factors that went on to develop AIDS. Why don't you list what things you think don't make sense, and we can go from there?

I can't speak for everyone you'll run into over there, but you won't be treated rudely by me.

John, that is patently false. You mocked me on your blog simply because I moved this into a new thread, apart from the malaria post. You ask me not to be defensive, then "read between the lines" of the posts of others to make them seem outright hostile. How about we all take a step back and move forward in a different direction?

"I don't have an account with NEJM, so can't read the study you would like me to see."

In fact the NEJM allows you to read the article Tara cited as well as many others just by setting up a free registration. You have to fill in contact details but you don't have to pay them anything. You can even invent the contact details if you're keen to protect your privacy.

John wrote :What do really want to say to me? I'm a cheater and I'm lazy?

I don't think you "cheat", I think you either erect strawmen unconsciously which is understandable, or you are consciously trolling.

I'll be more honest than I think you are:
I believe you and some others here would rather come up with snappy, cutting replies to people like me than deal with the MANY oddities of the HIV/AIDS model.

Nope, personally I can't wait to embrace Hank's endoretrovirus theory, whenever he posts the evidence.

If I'm also allowed to "read between the lines" and "notice all of the things people fail to respond to", I didn't notice John addressing the dozens of documented cases of occupational AIDS?

John wrote:

1. Many of your comments are extremely wordy. Not all. But you occasionally go five hundred words or more. There is a lot to read and a little time in the day. I can be very wordy myself. But I try to do so when posting on my blog and not in replying in comments. I know that it will cut down in how much gets read.
2. As Hank has said, thanks for the references. They are helpful. I should do it more myself.
3. I have clicked on (I think) every reference you have ever given me, and many that you have given others.
4. I have read parts or all of each. Admittedly, if it's technical, it's over my head and I often go to the summary.
5. Some of them end up being repetitions of other links you provided previously.
6. Some didn't really prove your point. Others certainly seem to, though I know there are people who disagree and that's my biggest interest in all of this.
7. Why would you assume I don't read your links?

I apologise for being wordy and presenting evidence from the literature. I should follow the methods of "anonharvey" and restrict myself to insults and snide comments.

Some of the links were only to abstracts. Some of them had no abstracts on pubmed. I went to the trouble of getting these references from the library and reading them. In most western countries like the US and Australia anyone can walk into a university library go to the shelves and read the journals.

Part of the purpose of posting the references that I did was to dispel the idea that Dr Culshaw espoused in her essays - that no debate had taken place. This is demonstrably false. There are several research articles that have been published in the literature that directly concern Duesberg's hypotheses. I posted some of these. I also posted links to Duesberg's responses to these articles and the author's responses to Duesberg, Duesberg's responses to these etc. It is all there in the literature. Anyone can read it.

It is not true that Duesberg was simply ignored. It is not true that no evidence was produced to refute his hypotheses.

You can also read the arguments that Duesberg used to argue against studies such as Ascher et al. Dr Culshaw writes As a mathematician, I was taught early on about the importance of clear definitions. and yet Duesberg ignores the CDC definition for AIDS defining conditions and uses Salmonella and Herpes-Zoster to invent 45 HIV-free AIDS cases.

I didn't see any reponses from "anonharvey" that attempted to justify Duesberg's stretching of the CDC definitions to create HIV-free AIDS cases. All I saw was insults and derisions.

By Chris Noble (not verified) on 28 Mar 2006 #permalink