House of Numbers - First Impressions

Well, I've been busy of late, and quiet on the blogosphere, but what started out as a denialist deception has turned into a frightening assault on knowledge and public health.

I'm talking of course about the film "House of Numbers" by Brent Leung, a pretense of investigative journalism that is, in fact, a mish-mash of interview excerpts and misrepresentations that is out to promote the AIDS Denialist agenda.

Leung isn't doing this alone - a considerable amount of money is behind the effort, not only in the slick production graphics that appear in the movie, but to bankroll his travels across the globe to promote the film at festivals and universities, including my own Alma Mater, Cambridge.

And here is where it really gets me. You see, I got involved in combating AIDS denial because I frankly can't stand ignorance. If someone is wrong, I will point it out and teach them. To have someone deliberately seek out people who want to learn (i.e. students) and feed them dangerous bullshit is the epitome of evil.

A few prospective venues have stood up to Leung - who has pulled out when told he has to face reputable scientists on his panel "debate" that ubiquitously follows the showing, which actually consists of Brent saying his thing and taking questions. Journalists covering the story have apparently been asked to sign contracts to the effect that they will say that HoN is "potentially beneficial" in their article before being allowed to see the film for themselves.

Some have supported their decision to show the film based on the concept of 'freedom of speech' or a misguided attempt to 'present both sides'. However, this only holds true if there truly is more than one side, and just as Leung does indeed have freedom to tell whatever lies and misrepresentations he sees fit, the venues have their freedom not to show it.

Unfortunately we live in a media age, where spin is everywhere, and opinion outweighs fact (the popularity of stations such as Fox "News" is testament to this). We are used to interviews and cutaways that are supposed to be linked together in context, but of course the wonders of video editing mean that what we see doesn't necessarily have anything to do with how the footage was actually shot.

A case in point.





This is basically what Leung has done, although probably not to the extent of actually dubbing in additional footage. Maybe. I'm curious for example where he got the audio that accompanies the black-and-white footage where a nameless outraged man asks that the "...Press stop calling it GRID" - gay related immune deficiency. Presumably someone at the 1982 scientific conference in Washington saw fit to tape the event. In black and white. To be honest it looks more like archive footage of the League of Nations than any scientific meeting I've attended, but what do I know. Maybe I just shouldn't take that particular segment literally...but then what CAN I trust about this film?

The short answer is "not much after the first 5 minutes", judging from a preliminary viewing. One of his biggest cons is in splicing in well-known AIDS denialists between legitimate AIDS scientists as if their opinions are equally valid and all part of the same story. 17 of the scientists who were interviewed by Leung signed a letter stating that the film misrepresents their views, effectively undermining his entire premise that there is any form of internal debate about HIV and AIDS among the scientific community.

I will be addressing specific points about this film in the next few posts. I have a sincere belief that a small number of people will see this film, believe it, and acquire HIV or stop treating their infection as a result.

And it will be left to people like me to pick up the pieces.

HIV Kills T cells...and doesn't need help to do it

Recently I've had cause to want to post again. Two things: an amusing comparison, and the an alarming take-over of a once-useful Society.

A certain Clark Baker (one-time cop and marine by his own account - a good reason to brush up on my Karate for self defence if ever there was one...as it also appears his 'retirement' from the LAPD may have been spurred by an assault charge made by an immigrant) has started making noise and touting the same old disproven denialist lies (such as HIV is a harmless retrovirus, originally stated by Duesberg based on Duesberg's extensive personal experience working on HIV in the lab - ie none). Baker went one step further though. Taking advantage of what sounds like fundamental apathy in the society, he managed to infiltrate the Semmelweiss Society International (SSI) with other AIDS denialists, gain control of their bank account, and throw out the non-denialist board members. The SSI's remit was certainly honorable enough - to protect medical practitioners who are wrongfully accused of malpractise, but it has certainly lost its way. The takeover is all outlined in court documents filed against Baker which I have read. This infiltration certainly explains why the SSI saw fit to 'honor' Duesberg and Farber with whistle-blower awards.

The SSI website is now filled with the slightly hysterical, ill-informed, self-grandiosing propaganda that passes for AIDS denial these days.

The sad thing is that AIDS denial is no different from the Fiber One breakfast cereal. WTF I hear you say? Consider this:


The wife here is pissed, because "everyone knows" that foods high in fiber don't taste nice, therefore since Fiber One tastes nice, it can't have much fiber in it.

This is no different from Duesberg stating that "everyone knows" that retroviruses don't kill cells, and since HIV is a retrovirus, it can't kill cells.

The Fiber One commercials are funny. AIDS denial is resposible for killing hundreds of thousands of people.

Baker, on one of his recent rants, asks for proof that HIV kills T cells. Well, I pointed this out the AIDS denialists over a decade ago, but keeping up with the literature was never a strong point of AIDS denialism (denying the current science is what makes then denialists, after all). Incidentally this bit of research also explains a comment made by Montagnier (one of the original discoverers of HIV) where he states that a co-factor, along with HIV, may be responsible for AIDS - suggesting that HIV by itself might be relatively harmless. This, if it were true, wouldn't necessarily detract from the HIV->AIDS hypothesis, but it might have had an impact on how to treat or prevent AIDS, so it was well worth looking into.

Specifically, in this 1992 paper by Montagnier, they state that

Following infection of lymphoblastoid (CEM) or promonocytic (U937 and THP1) cell lines with HIV-1 cytopathic effect was observed only in association with mycoplasmal contamination. Moreover, HIV-1 infection of U937 cells after experimental inoculation with a human isolate of M. fermentans led to pronounced cell killing. We have verified that this effect is not merely an artifact caused by arginine and/or glucose depletion in the cell culture medium. These results confirm that mollicutes, in particular M. fermentans, are able to act synergistically with HIV-1 to kill infected cells in some in vitro systems.

He had noticed that doxycycline could protect against HIV-induced cytotoxicity back in 1990. The mycoplasma detected here is a common problem in laboratory cell culture systems - they are notorious for upsetting experiments. I wonder if this notoriety came about because of results like this. It is not surprising that a mycoplasma, or some other co-factor, might be considered in AIDS causality, and the denialists are all over results like this as proof that HIV is harmless. But Montagnier only looked for cytopathic effect - i.e. what do the cells look like under the microscope. Look at this paper, from a couple of years afterwards. I'll post the abstract - basically they showed that the cell line Montagnier used (CEM in his original 1990 and followup 1992 paper) was not a pure line - it was partly CD4+ and partly CD4-. HIV can only infect CD4+ cells as that is what its envelope proteins (gp120 and gp41) bind to. It will come as no surprise to those who actually follow HIV science that in CEM lines, all the CD4+ cells get killed, but the CD4- cells grow to fill in the gaps (i.e. no cytopathic effect for Montagnier to observe).

CEM cells were infected with three HIV-1 non syncytium-inducing (NSI) strains obtained from AIDS patients or seropositive individuals. The surviving cells were followed for several months in the persistently infected cultures designated 65870/CEM, 65871/CEM and 3929/CEM, and analyzed for virus expression using light and electron microscopy, immunofluorescence, reverse transcriptase assay, polymerase chain reaction amplification (PCR), nucleic acid hybridization and flow cytometry. The virus isolates induced relatively few syncytia and other cytopathic effects in the corresponding cell lines and the number of cells positive for virus expression never rose above 44%. Distinct peaks of antigen-positive cells were obtained, coincident with high levels of reverse transcriptase activity. The cultures were strongly resistant to superinfection by laboratory strain Lai, with the exception of 65870/CEM which expressed HIV antigens in up to 15% of the cells for a few days. However, cell lysis was minimal in all cases. After long-term cultivation of the three cultures, no antigen-positive cells were detected and no trace of virus expression could be observed. The remaining cells consisted entirely of CD4-negative cells. PCR analyses indicated that cells harboring a provirus were progressively eliminated from the cultures, leaving only virus-free cells. In this system, cells carrying a latent provirus survive for a limited period of time before virus activation induces cell lysis. These results suggest that at least three types of cells exist in the CEM cell line: CD4-positive cells which are rapidly killed by the virus, a second type harboring a latent viral genome after the infection and which grow normally until activation of the resident genome by external or internal signal(s), and a third type which represents rare CD4-negative cells present in the initial CEM population and which are selected for by the NSI isolates. This is the first study documenting specific interactions between NSI strains of HIV-1 and distinct subpopulations of CEM cells grown as a single cell culture.

This is a great example of how papers that apparently 'disprove' a hypothesis actually confirm it if you look at the science in greater detail.

To wrap up the story, it's well known that monocytes/macrophages like the U937 and THP-1 lines are responsible for longterm infection with HIV, the "reservoir" of infection that is hard to kill. But this makes sense - HIV doesn't deplete CD4+ macrophages to cause AIDS, so HIV wouldn't be expected to kill monocyte cell lines in the lab...unless perhaps the cultures were contaminated with mycoplasma... Maybe Duesberg was half-right.

In any case, just as Fiber One is a tasty source of fiber, HIV kills cells.

This whole story is a great example of why AIDS denialism has moved from a legitimate question-asking exercise, through inexplicable stubborness and willfull ignorance, to downright evil. When AIDS denial is touted by homophobic, ignorant, arrogant people who (allegedly) lie and steal in order to further their devastating agenda, then it's really fallen about as far as it can go.

Bennett


Disclaimer: I have never bought Fiber One, nor do I endorse them. I have however worked with HIV in the lab in short and long-term culture systems and witnessed its cytopathic effect. I use the word "allegedly"above as Baker is so far accussed, but not proven, to be a homophobic, racist, ignorant, arrogant, liar and thief. However, anyone who calls AIDS patients "a small group of promiscuous, addicted, nitrite-huffing, gonorrheal and syphilitic bath house veterans" probably needs no further said of them.


Lemaitre M. Guetard D. Henin Y. Montagnier L. Zerial A. Research in Virology. 141(1):5-16, 1990 Jan-Feb Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells.

M Lemaître, Y Henin, F Destouesse, C Ferrieux, L Montagnier, and A Blanchard
Infect Immun. 1992 March; 60(3) 742–748. Role of mycoplasma infection in the cytopathic effect induced by human immunodeficiency virus type 1 in infected cell lines.

Yelle et al Arch Virol 1994;139(1-2):155-72 "Analysis of long- term viral expression in CEM cells persistently infected with non syncytium-inducing HIV-1 strains.

Maggiore

"Why did she remain basically healthy from 1992 until just before her death?" asked David Crowe,

Good question David. Perhaps because 16 years isn't too far outside the normal progression for untreated HIV infection. At 10-15 years (depending on the study) she might have been classified as a long-term non-progressor (about 10% of people with HIV do), but then only if her CD4 counts were normal, and we have no idea about that. In one long-term followup of so-called LTNP's at 10 years, by 18 years of being HIV+ 86% of those LTNP's had progressed to AIDS. The strongest individual predictor of progression rates has consisently been viral load and/or anti-HIV killer T cell responses, so even reaching one breakpoint (10 year survival) doesn't easily predict the chances of reaching another (15 year survival).

This is all hand-waving though - the only facts are that someone lost a mother and someone lost a wife, and that's terrible. My personal thoughts are that this is a tragedy that might well have been preventable. She lays the blame herself squarely at the feet of one man:

"All that changed in 1994, she said, when she spoke to UC Berkeley biology professor Peter Duesberg..."

And really, that's all I have to say on the matter. For what it's worth, I really, really hope that Robin and Charlie can find some kind of peace after this second loss. What a mess.

Message for the lawyer

For the LA lawyer who tried to call me - I managed to accidentally delete voicemail with your number, and since there's more than a fair chance that someone connected to the EJ story might read this, I'm posting this up here.

I can however give an easy answer to your question - basically when I wrote the EJ commentary I was a resident physician, and according to NYS law:

"If you did not graduate from a NYS-registered or LCME- or AOA-accredited medical program, you must complete at least three years of postgraduate hospital training in an accredited residency program approved by the Accreditation Council for Graduate Medical Education, the American Osteopathic Association, or the Royal College of Physicians and Surgeons of Canada."

http://www.op.nysed.gov/medlic.htm

Since I graduated from Cambridge, England I couldn't get a NYS license until after residency - which I am now done with and my application is in the works :o)

The point though is irrelevant. In my commentary I am merely an observer and bringer of facts - the facts are irrefutable. I offer my opinion in only a few places, mostly in regards to speculation about a kidney disease that is neither necessary nor sufficient to explain the story, and in hindsight most of the findings regarding EJ's fluid in various organs can be explained by the resuscitation she recieved.

Al-Bayati on the other hand offers nothing but personal opinion and speculation, laced with a heavy dose of over-interpreted, cherry-picked literature to suit his pre-conceived idea that EJ must have died from something other than what the LA coroner found.

A side-by-side comparison of the coroner's report and Al-Bayati's report will reveal just how often Al-Bayati misrepresents it - and that's all I really did.

Conspiracy!

So there isn't really much to say once the conspiracy ideas start flowing (most sensible readers will ignore anything further from that side of things), but I thought it would be fun to pose a few questions:

Who is more inappropriate to comment on medical research regarding HIV, a physician with a research background in HIV, or an online "journalist"?

Since the commentators are quite right that an "email club" couldn't possibly convince the BBC to retract their program on the ICC, is it perhaps more likely that they simply saw they had been duped once the Re-Appraising AIDS denialist group started praising the story (and they realized that the "experts" quote in the story were in fact merely AIDS denialists)?

I leave the reader to judge.

A good question

Ironically this was posted by the (of late disruptive) Liam Scheff, although of course it's not his words - they are far too sane.

This was emailed to me by a non-Blogspot member. Consider:


1. Fundamental assumption: accept medicine the way it is. Therefore, your attempts to improve it are unwanted.

Who really knows how long those kids will live? Maybe all of them will die in their 20's due to ARV's? Who knows, there is evidence that ARV's prolong lives that are Th2 imbalanced, with respect to their immune system balance among Th1 and Th2 (helper T-cell inversion). The reason, the drugs depress the production of the cells that make these cytokines by killing them, and thereby abating an autoimmune condition.

But there is much evidence that these are harmful:

It has been about 7 years since it was published in The Journal, AIDS, that children born to ZDV-treated mothers "are more likely to have a rapid course of HIV-1 infection compared with children born to untreated mothers, as disease progression and immunological deterioration are significantly more rapid and the risk of death is actually increased during the first 3 years of life" [12. de Martino et al., Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AIDS. 13 (8):927-933, May 28, 1999.The Italian Register for HIV Infection in Children. AIDS, 13:927-933, 1999].

Therefore, it behooves us to think about at least improving the situation for the children involved, don't you agree?

Discussion is warranted. Can we suppress the Th1-2 population by non-toxic means, or perhaps by interference. Suppose we invent a peptide that interferes with the harmful effects of Th2 cytokine-driven storms on the tissues and especially on other immune cells (since the Payer's patches go first finally, indicating complete disruption of the lymph system).

Are we really expected to believe that there is no room for growth in medicine? Critical analysis, and then discussion regarding weaknesses and strengths in a hypothesis are required.

Whomever this is raises a number of good points. Firstly, the assumption that medicine is good enough is obviously entirely wrong. Medics and scientists in general (or let's broaden the scope to include the entire human race) have been wrong in the past, are probably wrong about some things now, and will be wrong about new things in the future. We cannot accept the status quo and expect that there's no room to improve. In the case of HIV for example, monotherapy led to dual therapy which led to hit-hard-hit-early with triple therapy, and now we're looking at monitoring and waiting until it's worth treating (if at all). Each step appeared to be the "best" approach at the time, but in hindsight they weren't the best way to go. Hindsight of course is 20/20. In another decade or so no doubt we'll look back and wonder how we managed the way we did...

The Th1/Th2 imbalance is also a feature of any chronic viral infection - HIV included. The antivirals don't actually kill off the T cells, but HIV-induced immune activation certainly does, and there is HIV-induced impaired T cell replacement. If anything the meds improve both of these actions, which is why they result in increased T cell counts over time.

The AZT study mentioned was important, although there is a large caveat in that the survival hit was in those who were HIV-infected _despite_ AZT prophylaxis. Obviously there were fewer HIV-infected kids than there would normally be without AZT. The questions that arise are: is this an effect of AZT directly? Is this because "tougher" clones of HIV made it through the AZT and were therefore worse to acquire (this would confound the results and make it appear as if AZT correlated with a worse outcome, even though it wasn't causal)? Does the AZT prophylaxis actually _select_ for more difficult viral clones? I don't think anyone yet has an answer to those questions, but all are potentially valid.

The real issue for me, and which denialists, well, deny, is that untreated HIV infection is so goddam awful in kids. Fully 25% or more will die by age 5 years. In the era of decent therapy and prophylaxis, risks of opportunistic infections and death are much less.

PEDIATRICS Vol. 120 No. 1 July 2007, pp. 100-109 (doi:10.1542/peds.2006-2052)

Could more be done - I certainly hope so, and the idea presented here about some kind of immune modulator sounds intriguing, and not the first time it's been suggested. We know that CCR5-delta32 mutations severely hamper viral replication but don't seem to hurt the human host, so if a way could be found to mimick that without buggering up the normal immune function, they why not? There is strong evidence that somewhere along the way cytokine signaling is wrong in HIV infection, and whether something abnormal needs to be turned off or something normal needs to be turned back on, it's far from a bad idea to look into that.

Further falls in my estimation

Oh the irony - Liam Scheff arrives on my blog firstly challenging me to post his comments, then to reply on his own blog, and through it all taking pot-shots at my personal and professional ethics.

So I take the unusual step of actually going to his site and writing in.

And after receiving two posts which he presumably either cannot refute, or which unfortunately don't fit his perception of me as an evil Pharma-Nazi, he shuts down discussion with two further posts fading into the ether...

However, since I assumed (rightly) that Liam would do such a thing, I saved the posts for posterity. Here are the comments that Liam would rather not have on his blog, saved as screenshots of the fact that these comments were in the moderation queue while he let other posts through.

Cheers

Bennett