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« Two-fer Tuesday! | Main | A Chorus of Mathematicians Joins Lang and Duesberg (and Hank) in Questioning Establishment AIDS »

September 12, 2006

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Leo Kaplan, MD

Is there anyone who thinks that the elevated hazard ratios seen by the physicians and researchers in the Goedert et al. '94 Lancet report should not have raised several red flags, or that the obvious risks of administering AZT to hemophiliacs can be swept under the rug by the kind of waffle that DT writes?

If so, there is a bridge in my beloved Brooklyn I can sell you cheap.

(BTW I suspect that Dr. Knobless has several tongues in several cheeks, as clearly the disingenuous and rather charming "Recent Grad" of indeterminant gender does.)

Pharma Bawd

Well Darin, science is about the search for truth.

If you say the authors never mention X and the authors do mention X, it’s a relevant part of a debate to point out such untruths.

It’s called impeaching the witness. Hank can tell you all about it if you’re unfamiliar with the technique and its value in establishing veracity.

I saw no analysis relevant to this discussion at your site.

If HIV positive hemophiliacs are dying at a rate 11X higher than HIV negative hemophiliacs, and HIV positive hemophiliacs on AZT are only dying 2X higher than those not taking AZT, how do you explain the excess deaths among HIV positive non-AZT using hemophiliacs?

I explain it by the immune disabling retrovirus they’re infected with.

ps. I’m sorry if I offend you by sharing things I’ve learned from previous HIV “debates”. That you have not, and that you find such knowledge pedantic, explains your ability to maintain your erroneous position.

McDonald

I was working off memory when I wrote my comments, and the message gleaned from the paper was that it was likely that AZT had been administered to the most needy cases, who would also by reason of their clinical condition, be the ones likelier to die. The paper gives no indication as to the reasons for patients being given AZT

Dt, so let me get this straight, you 'were working off memory' when you wrote that the 'message gleaned from the paper' suggested it was '"likely" that AZT was administered to the most needy cases'. But as it turns out 'the paper gives no indications as to the reasons why patients were given AZT'

And on this background you feel confident to administer logic lessons here?

In all seriousness, I respect you for staying on point. But your TB analogy is still... 'lame' I think is the coolhip word in Skeptico's lingo.

If it turns out on empirical investigation that the clinicians put only the people with all the symptoms of full blown Aids on AZT, you may have a point however awkwardly put.
In any event I think you should go back and re-read the Organon with your mentor

Darin

PB,

If you found that one pager by Goedert more convincing than the analysis by Maver, more power to you and the companies you work for.

This is not a debating farm, and even if it were, some animals are more equal than others.:) And even so, can you actually defend the logic of what Goedert et al. wrote as a full and complete, and all that was required "discussion" of the major cause of death in their subjects?

Maybe you need to debate with Recent Grad?

Pharma Bawd

Darin,

I've now searched your site for "Maver", 3 hits, none relevant.

Got any more hints for me?

Andrew Maniotis


About the hemophilia topic. Let us consult with the experts who make the package inserts complete with the post-marketing experience. For instance, if I were a hemophilic who had just been convicted of being "HIV-positive," I'd be at least slightly concerned about bleeding out if a the first thing a drug's package insert said:

"WARNING: RETROVIR (ZIDOVUDINE, AZT) MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING GRANULOCYTOPENIA AND SEVERE ANEMIA PARTICULARLY IN PATIENTS WITH ADVANCED HIV DISEASE."

"PROLONGED USE OF RETROVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY SIMILAR TO THAT PRODUCED BY HUMAN IMMUNODEFICIENCY VIRUS. RARE OCCURRENCES OF LACTIC ACIDOSIS IN THE ABSENCE OF HYPOXEMIA, AND SEVERE HEPATOMEGALY WITH STEATOSIS HAVE BEEN REPORTED WITH THE USE OF ANTIRETROVIRAL NUCLEOSIDE ANALOGUES, INCLUDING RETROVIR AND ZALCITABINE, AND ARE POTENTIALLY FATAL."

Other side effects of AZT that have been listed on the denialist AZT package inserts also include:

"Persistent headaches lasting longer than 1 month, anemia, dementia, diarrhea, muscle wasting, candidiasis, non-specific oral lesions, severe fatigue, enlarged liver and liver failure, heart failure, diabetes, unmasking of opportunistic infections including CMV retinitis, spontaneous bleeding in hemophiliacs, lymphoma, severe skin rashes, Stevens-Johnson syndrome, and other toxic reactions, back pain, body odor, chest pain, chills, edema of the lip, fever, flu syndrome, hyperalgesia, syncope, vasodilation, BLEEDING GUMS, constipation, dysphagia, edema of the tongue, eructation, flatulence, mouth ulcer, rectal hemorrhage, lymphadenopathy, arthralgia, muscle spasm, tremor, twitch, anxiety, confusion, depression, dizziness, emotional lability, loss of mental acuity, nervousness, paresthesia, somnolence, cough, dyspnea, epistaxis, hoarseness, pharyngitis, rhinitis, sinusitis, acne, changes in skin and nail pigmentation, pruritus, rash, sweat, urticaria, amblyopia, hearing loss, photophobia, taste perversion, dysuria, polyuria, urinary frequency, urinary hesitancy."

There also have been numerous mutagenesis studies regarding AZT and drugs with similar mechanisms of action that have been published. For example, among infants of mothers given AZT "to prevent the vertical transmission of "HIV"', the peer-reviewed literature has reported physical deformities result including:

"misshapen heads, triangular faces, misplaced ears, extra fingers, albinism, cavities in the chest, webbed fingers, spontaneous abortion, and "congenital" birth defects of the heart, chromosomal damage and various cancers. "

A couple of examples on the package insert include:

"In two in vivo micronucleus studies (designed to measure chromosome breakage or mitotic spindle apparatus damage) in male mice, oral doses of zidovudine 100 to 1000 mg/kg/day administered once daily for approximately 4 weeks induced dose-related increases in micronucleated erythrocytes. Similar results were also seen after 4 or 7 days of dosing at 500 mg/kg/day in rats and mice."

"In a study involving 11 AIDS patients, it was reported that the seven patients who were receiving Retrovir (1200 mg/day) as their only medication for 4 weeks to 7 months showed a chromosome breakage frequency of 8.29±2.65 breaks per 100 peripheral lymphocytes. This was significantly (P< 0.05) higher than the incidence of 0.5±0.29 breaks per 100 calls that was observed in the four AIDS patients who had not received Retrovir.


Wouldn't you be concerned with these warnings if you had a bleeding disorder?

Posted by: Andrew Maniotis | September 14, 2006 at 06:40 PM

Andrew Maniotis

Blog was truncated: sorry....

" In the presence of metabolic activation, the drug was weakly mutagenic at concentrations of 1000 µg/ml and higher. In an in vitro mammalian cell transformation assay, zidovudine (AZT) was positive at concentrations of 0.5 µg/ml and higher. In an in vitro cytogenetic study performed in cultured human lymphocytes, zidovudine induced dose-related structural chromosomal abnormalities at concentrations of 3 µg/ml and higher."

"In two in vivo micronucleus studies (designed to measure chromosome breakage or mitotic spindle apparatus damage) in male mice, oral doses of zidovudine 100 to 1000 mg/kg/day administered once daily for approximately 4 weeks induced dose-related increases in micronucleated erythrocytes. Similar results were also seen after 4 or 7 days of dosing at 500 mg/kg/day in rats and mice."

"In a study involving 11 AIDS patients, it was reported that the seven patients who were receiving Retrovir (1200 mg/day) as their only medication for 4 weeks to 7 months showed a chromosome breakage frequency of 8.29±2.65 breaks per 100 peripheral lymphocytes. This was significantly (P< 0.05) higher than the incidence of 0.5±0.29 breaks per 100 calls that was observed in the four AIDS patients who had not received Retrovir.

Hank Barnes

Pharma Ditz,

Why the need to get so snippy?

I believe the item Dr. Brown is referring to can be found on the homepage of the AIDS Wiki under a well lit box labeled "Featured Document".

I do not think anyone wishes to enter into what you call "debate" on this topic, however.

Anyone can read the reference you provided and the one he did, and can make his or her own determinations much better than by having one or another of us play games of logical misdirection, rhetoric or otherwise posture for an imagined internet audience.

Pharma Ditz

That article doesn't address the issue at all Darin. WTF?

Yes, I take Dr. Goedert's familiarity with his own work over an insurance actuary's analysis of epidemiologic data that doesn't even refer to the specific patient group involved in the two Goedert papers.

That's (one of the reasons) why I refer to this nonsense as a "debate" Hank.

McDonald

I saw no analysis relevant to this discussion at your site.

If HIV positive hemophiliacs are dying at a rate 11X higher than HIV negative hemophiliacs, and HIV positive hemophiliacs on AZT are only dying 2X higher than those not taking AZT, how do you explain the excess deaths among HIV positive non-AZT using hemophiliacs?

I explain it by the immune disabling retrovirus they’re infected with.

ps. I’m sorry if I offend you by sharing things I’ve learned from previous HIV “debates”.

Pharma,

You've learned to refute the claim that

'AZT doubles the death rate among HIV+ hemophiliacs.'

by arguing that,

'AZT only doubles the death rate among HIV+ hemophiliacs.'

Amazing.

Did you 'learn' that in Skeptico's logic classes by any chance?

DT

McDonald, I think the word you have failed to see in PB's post is the little one begining with I and ending in F.

Now how about answering his point how: "IF HIV positive hemophiliacs are dying at a rate 11X higher than HIV negative hemophiliacs, and HIV positive hemophiliacs on AZT are only dying 2X higher than those not taking AZT, how do you explain the excess deaths among HIV positive non-AZT using hemophiliacs?"

Pharma Ditz

While your at it, instead of concocting absurd little conspiracies about coverups because of one line from a table, that was addressed in the body of the text, why don't you look at the published literature on when hemophiliacs are prescribed AZT?

"Patients are given zidovudine because they are ill

It is not true that most British haemophilic patients infected with HIV have been given zidovudine since 1987. Initially patients were given zidovudine after the development of AIDS. Subsequently, since around 1989, patients have been given zidovudine once their CD4 count has fallen below 0.2x109/l or after the development of symptomatic disease. Similar recommendations are made for pentamidine or co-trimoxazole as prophylaxis against Pneumocystis carinii pneumonia. Consequently, by the time patients begin zidovudine and pentamidine they have low CD4 cell counts and are usually symptomatic.

Observational studies often show that patients given zidovudine have a worse prognosis than untreated patients.7 Patients receiving zidovudine are selectively treated because they are ill. The interpretation of findings from these studies should not therefore be that zidovudine increases the risk of AIDS. Of the nine patients developing AIDS in our study, seven received zidovudine only after an initial AIDS diagnosis when immunological deterioration had already occurred. There is no possibility, therefore, that either zidovudine or pentamidine had a causal role in the initial development of symptomatic disease in these patients."

http://bmj.bmjjournals.com/cgi/content/full/312/7025/211

So Duesberg, and the rest of you, are doing exactly what DT said above and blaming meningitis deaths on antibiotics rather than an infection.

In fact some of you, notably Duesberg, are blaming the infection on the antibiotics prior to their administration to the patient!

George

Ditz,

Who exactly are you writing your comments to?

Hank makes posts like this one to enlighten people like Dr. Pato, and other serious, thinking human beings, who until now have been relatively unaware of both the scientific arguments themselves as well as the quality of discourse represented by the "lay" advocates of each side.

So who are you trying to "win a debate with" and to what purpose?

Need I say "Moore"?

Pharma Ditz

"Debate" was Darin's word. See above.

You and Hank are not trying to enlighten people like Dr. Pato, you're trying to repeat Duesberg's failed arguments to convince people who aren't familiar with the literature.

This is sophistry, not science.

George

Ditz,

At the risk of being *overly* pedantic -- something of which I been accused on more than one ocassion -- let me make it abundantly clear that no one here on the questioning side is trying *to convince* anyone of anything other than there are serious unanswered questions about HIV/AIDS that have been buried for too long EXACTLY as the chorus of mathematicians who wrote the letter to the Notices wrote.

Au contraire, Ms. Ditz, it is your unquestioning, self-serving and entrenched positions which are exposed in your own well chosen words and held up to world wide ridicule time and time again.

Need I say "Moore"?

Pharma Ditz

George,

"there are serious unanswered questions about HIV/AIDS"

Sure there are. This, however, is not one of them. Hemophiliacs get AIDS first and AZT second. This has been clear for a long time. Bringing it up again in such a one-sided manner is simply an attempt to deceive, or evidence that someone hasn't done enough research to comment intelligently on the matter.

What "Moore" do you have to say?


George

I have this to write, Ditz,

This post has exposed to people who may not have known about it before that indeed there are some who question this aspect as well of the HIV/AIDS paradigm.

As important, or more, they have been given sufficient pointers to the actual scientific literature on the subject to do the hard, and often tedious, work necessary to inform oneself, as Dr. Diallo wrote in the "Read Me" to the hyperlinked Duesberg monograph at the AIDS Wiki I linked above, and which you have never read, and that, quite frankly, are *totally* incapable of reading.

Now I think I have written more than sufficent so that all who are not Moore clones understand --as my wife likes to pronounce it -- per-fectly.

Hank Barnes

Pharma Ditz,

The chorus of mathematicians, Duesberg, Hank and a few others agree. So do you.

"there are serious unanswered questions about HIV/AIDS"

"Sure there are," you write.

Well, now we're getting somewhere. What are these serious unanswered questions from your perspective?

Hank B.

McDonald

DT, The little word 'IF' covers all premisses equally, it does therefore not change anything.
So EVEN 'IF' HIV+ 1000 doubled hemophiliac deaths, AZT would still double that figure, and that's what we were talking about in this thread 'IF' you hadn't noticed.

McDonald

Next up, we can discuss the 'IF' itself.
You may care to remember, I said you could have had a point, IF the patients put on AZT already had AIDS.

You've read the study in question, or rather the one line in it. It says:

Sujects who had started AZT had an increased risk of AIDS, probably because Zidovudine was administered first to those whom clinicians considered to be at highest risk.

This may be a bad formulation, who knows since it's merely a handwave and NOT a discussion, but it would seem patients were put on AZT BEFORE they had developed AIDS but consequently developed it at a rate 4.5 times greater than other HIV+ patients.

Andrew Maniotis

Maniotis here.

Some interesting discussion above from different viewpoints. Maybe a different view might be appreciated?

When I posted the post-marketing experience package insert about AZT above, I assumed that folks would get my point, but I need to briefly elaborate given the the pointed discussions that followed.

First, allow me to edit the AZT package insert I posted above to only include two of the warnings to make my point clear:

The warnings, "spontaneous bleeding in hemophiliacs, and "bleeding gums" should constitute some kind of a warning to those who suffer from coagulopathic symptoms of any kind, and to the doctors who treat and prescribe drugs to these folks. First, do no harm, I believe, is the protocol.

Nobody wants a hemophiliac like Ryan White to bleed out from the liver (said to be in his case a complication from AIDS at the time as if "HIV" had a tropism for liver as does hepatitis A virus) because they have a condition that could kill them independent of taking a failed chemotherapy drug that induces spontaneous bleeding in hemophilicas and bleeding gums in non-hemophiliacs.

As a physician who must treat patients according to certain Nazi-like protocols or risk disbarment from "the profession," and especially if folks have a severe form of the "hemophilia," wouldn't you want to warn them about the package insert? Even if you believed for some strange reason that "HIV" is an exogenous retrovirus that causes immune suppression, and that AZT, a poorly designed drug that failed as a chemotherapy agent, has some inhibitory effect on "HIV" replication, wouldn't you at least want to warn the patient (or the patient's parents) about the adverse event warnings, so that in the event that any adverse events began occurring to the subject consistent with the package warning insert, the "treatment" could be discontinued immediately by the subject him/herself, or the subject's parents, at the first indication of trouble?

Regarding the statement that:

"IF HIV positive hemophiliacs are dying at a rate 11X higher than HIV negative hemophiliacs, and HIV positive hemophiliacs on AZT are only dying 2X higher than those not taking AZT, how do you explain the excess deaths among HIV positive non-AZT using hemophiliacs?"

I don't think these figures are correct (see Papadopulos-Eleopulos et al. FACTOR VIII, HIV AND AIDS IN HAEMOPHILIACS: AN ANALYSIS OF THEIR RELATIONSHIP. Genetica 95: 25-50, 1995; Also see Peter Duesberg.
FOREIGN-PROTEIN-MEDIATED IMMUNODEFICIENCY IN HEMOPHILIACS WITH AND WITHOUT HIVGenetica 95: 51-70, 1995; Also see Robert Root-Bernstein, AIDS-The Tragedy of a Premature Consensus where he talks about hemophilia).

But let's assume these figures are correct. How can they be explained?

In the broad context of how the symptoms of hemophilia are expressed in different sufferers, it should at least be put onto the discussion table that hemophilia is known to be one reason to test positive on an "HIV" ELISA or Western Blot, or PCR test as is pregnancy, recent flu vaccines, etc.

In addition, despite the fact that hemophilia is a reason to test positive on "HIV" tests, it might be worth considering that
hemophilia, and I'm no expert on the subject, is a coagulopathy. I'd bet anyone a month's pay, however, that like cancer (which also is a complex series of disease symptoms with which I do have some first hand direct experience with), that from what I've read about hemophilia, that hemophilia is (like cancer) a complex array of disease symptoms. In addition, coagulopathies are known to accompany a wide range of human afflictions including allergy, cancer, certain viral infections, late-stage alcoholism, parisitic diseases, to name a few. Like the catch-all term, encephalitis, thrombocytopenia in the general sense, and the seemingly more predictable syndromes called hemophilia A, B, are approximations of a diverse class of symptoms, for which factors XIII and IX are indeed sometimes helpful, as I believe Robert Root Bernstein, Peter Duesberg, Eleni Papadopulos, and others pointed out many years ago, and which permitted many more "HIV-positive" hemophiliacs after the concentrates were available, to live longer with severe forms of hemophilia, than they did before the concentrates were available, and despite the fact they "had HIV."

From first hand knownledge, let me give one example of a cancer like syndrome known as Kasabach-Merritt Syndrome which kills because it is a coagulopathy, which develops from hemangiomas, the most common tumors of infancy. In this disorder, platelets are successively trapped in the growing hemangioma lesion, until the infant bleeds out into the brain because there are no platelets left in the blood vessels to initiate clotting, or to support their patency.

Because of the diversity of coagulopathies and thrombocytopenias, it is likely that the disease symptomology described as hemophila A or B, is for convenience, not to be taken as a simple 0 or 1 computer-like description of a disease state.

From the literature, we find that some acute hemophiliacs can't walk down a stairway without their knees bleeding from the normal trauma of supporting the body's weight during the descent, and must dose themselves heavily with morphine to kill the pain (also an immune-suppressive drug like AZT), while others could cut themselves shaving and stop the bleeding with some toilet paper and pressure.

Because multiple pregnancies, the H1N1 epitope in the flu vaccines, and about 70 other factors can cause a positive reaction on "HIV" specific tests, there is no basis for stating that there is any meaning behind "the 11X excess deaths among HIV positive non-AZT using hemophiliacs" Their "HIV" positive status, or their advanced coagulopathy, may be attributable to the other dimensions of altered blood, such as "sticky blood," high ESR rates (erythrocyte sedimentation rates), and other "coagulopathic" features of persons who test "HIV" positive. If you are talking about "AIDS patients" with advanced disease such as Kaposi's sarcoma, it is easy to see how this would apply to Gallo's earlier statement regarding the diversity of AIDS:

"The association of Kaposi's sarcoma with AIDS deserves special mention. This otherwise extremely rare malignancy occurs predominantly in a restricted group, that is, the homosexuals, and can occur in the absence of any T-cell defect in the patients" (Flosie Wong-Staal & Robert C. Gallo. Nature Vol 317, 3 Oct 1985).

Here we have an "AIDS-defining cancer (not really an AIDS-defining illness), without any cytopathology of T-cells. Anemia and other blood disorders of persons who took AZT are manifested in approximately 1/3 to 1/2 of low-dose AZT takers, and these folks require transfusions (did Goedert take this into consideration)? Other folks feel better, at least for awhile on AZT, like Judge Edwin Cameron, as he described in his book, Witness to AIDS. If some persons feel better, then they should be helped by us to feel better, even if it means taking rat poison, which AZT is. However, let us not forget that even in the approval trail for AZT, Fischl reported that almost 1/3, to 1/2 of patients taking AZT in the trial, and in many others trials reported since, required transfusions in order to stay alive. Doesn't this count for something?

Pharma Ditz

Here’s a few:

What is it about long-term non-progressors that allows them to maintain healthy levels of CD4 cells over time?

Can these people be identified by genotypic or other markers?

http://jvi.asm.org/cgi/content/abstract/80/16/8236
I’ve cited a paper here previously about the destruction of gut associated lymphoid tissue by HIV. This paper followed patients beginning HAART during primary or during chronic infection, and found that those who began HAART during primary infection were able to re-establish the population of CD4 cells in the gut. (about 70% of the CD4 cells in a healthy person are found in the gut) So this paper is important to me and leads to a genuine rethinking of how AIDS and HIV are treated, what is the best way to prevent the destruction of this population of CD4 cells during primary infection? Obviously, maintaining mucosal CD4 cells could have major improvements on the prognosis of HIV+ people, better absorption of nutrients, stronger immune system, etc.

There are numerous questions about how to improve the medications, reduce side effects, toxicity etc.

There are issues of genetics and drug efficacy for AIDS ie: Are there genetic markers associated with efficacy or tolerability for certain drugs? By finding these you can prescribe the right drugs to the right patients.

Vaccine? I’m not hopeful but it should be pursued.
...

George

Well done Ditz,

You have reproduced, with the newest additions, essentially ALL of the "mysteries of the virus" as my old fiend (sic) Jay Levy once called the unresolved questions about the HIV-AIDS hypothesis in the pages of Nature.

So let me add two that he thought pretty important 10+ years ago, and still are.

How does the virus kill T cells?

Why don't antibodies protect from disease since they are perfectly neutralizing?

And I will add the question of the day from 'Grad Student':

If the virus is constantly mutating to avoid drugs and the immune system's defenses, why are the same patented proteins used today to detect presumed antibodies to HIV that were patented 20 years ago?

George

Ditz,

Not that I wish an answer because everyone has sufficient data (or a way to obtain them) to answer for themselves, but do you, personally, still maintain that the quote you mined from the Goedert one-page of Lancet correspondence is definitive experimental proof of the contention that hemophiliacs are "AIDS"-free unless they are HIV antibody reactive, and that all of their "AIDS" diseases, complications and their eventual death are the indirect result of infection, and have nothing to do with inotxication by the "highly specific" poison, AZT?

I just want EVERYBODY to know, if they didn't by now because maybe they are blind and cannot read your comments and their surrogate reader mispronounces the big words, exactly what kind of an open and questioning and thoughtful mind you have, just like your guru JP Moore.


That's all. Grand kids visit today. :)

Harvey Bialy

A True Story about the Father of AZT, Sam Broder, MD.

This happened at the afternoon session of the Cold Spring Harbor Vaccine meeting where it was agreed, as a gentlemen's (sic) agreement between Gallo, Levy, and Montagnier during a luncheon presided over by Jim Watson, that from 2 PM henceforth HTLV-III/LAV/ARV would forever be known far and wide as "HIV, the virus that causes AIDS".

I was sitting to the immediate left of Sam (and I think that maybe George was to his right but I cannot be certain of this)trying to listen to Simon Wain-Hobson explain how he had found the "AIDS nucleotide" by sequencing isolates from Gabon (where the Pasteur had an outpost that I visited once, but that's another story, as they say). It was way before power point, and DNA sequencing was still sexy and done by hand so the slides were difficult to see and very confusing too.

Following Simon was not made any easier by the fact that Sam kept jumping out of his seat every 10 minutes, disrupting my ferocious note taking by making for the stage left exit.

I thought it was an unfortunate result of the luncheon, especially when he took his seat for the final time with a satisfied smile.

At the coffee break I asked him what was going on, and he told me proudly,in the presence of several of his colleagues, that he had been on the phone with his lab at the NCI and had learned that the first AZT trial had *just* been prematurely terminated because the results (still coming in until today) were so impressive that it would be unethical to continue the placebo arm past the few months the trial had been ongoing.

And with a Cheshire cat grin he added - "No mistakes here, the endpoint was death".

I will never forget the chill that ran down my spine as I realized I was standing next to Dr. Mengele.

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