DEBATING AZT
AZT: A Medicine from Hell

By Anthony Brink

October 1998

The more ignorant, reckless and thoughtless a doctor is,
the higher his reputation soars, even amongst powerful princes.

Praise of Folly, Desiderius Erasmus (c. 1466-1536), Dutch humanist.

National Health Minister Nkosazana Zuma has been condemned by just about everyone recently for her heartless decision not to make a drug called AZT available at State expense to HIV-positive pregnant women. It reduces the risk, so it’s said, of the transmission of HIV from mother to child. Politicians and journalists from left to right have joined moist-eyed, hand-wringing doctors in pleading for the free provision of AZT to these women, their babies cruelly deprived and doomed to die, they say.

In all the fuss about the minister’s decision on AZT, no one, it seems, has stopped to ask, “So what the hell is this stuff anyway?”

In 1964, a chemist called Jerome Horwitz synthesised a sophisticated experimental cell poison for the treatment of cancerous tumour cells (1). It was called Suramin, or Compound S. Its formal title is 3’-azido-3’-deoxythymidine - zidovudine for short - but everyone knows it by its nickname, AZT.

It works like this. Thymidine is one of the four nucleotides (building blocks) of DNA, the basic molecule of life. AZT is an artificial fake, a dead ringer for thymidine. As a cell synthesises new DNA while preparing to divide in order to spawn another, AZT either steals in to take the place of the real thing, or else disrupts the delicate process by interfering with the cell’s regulation of the relative concentrations of nucleotide pools present during DNA synthesis. That’s the end of the cell line. Cell division and replication, wrecked by the presence of the plastic imposter, comes to a halt. Chemotherapeutic drugs such as AZT are described as DNA chain terminators accordingly (2). Their effect is wholesale cell death of every type, particularly the rapidly dividing cells of the immune system and those lining our guts. Horwitz found that the sick immune cells went, but with so many others that his poison was plainly useless as a medicine. It was akin to napalm-bombing a school to kill some roof-rats. AZT was abandoned. It wasn’t even patented. For two decades it collected dust, forgotten - until the advent of the AIDS era.

As soon as Dr Robert Gallo made his famous announcement at a press conference on 23 April 1984 that his virus was the probable cause of AIDS, the race was on to find a pharmaceutical weapon against it. The stratospheric profit potential (since borne out) of being the first past the post was on everybody’s mind. Obviously, if an already synthesised drug could be applied to the malady, it would short-cut most of the road-race there. AZT was fished off the shelf, along with numerous other abandoned brews, and put to some in vitro tests. It demonstrated a bright alchemical sparkle. On the basis of a reassuring but fallacious assertion that AZT was specifically antagonistic to HIV, and a thousand times more toxic to the latter than human cells generally, the drug went to clinical trials. The chaos into which the trials degenerated is a tale too long to tell here. It wouldn’t be extravagant to call them fraudulent (3). (Subsequent trials consistently turned in opposite results.) At best, they were so incompetently staged that the data gathered under them were useless, save to note that one in five of its subjects taking AZT needed repeated blood transfusions to keep going. Small surprise, since the label on bottles of AZT supplied to laboratories bears a skull and cross-bones and cautions, “Toxic by inhalation, in contact with skin and if swallowed. Target organ(s): Blood, bone marrow…Wear suitable protective clothing.”

Four months after the trials started, they were called off prematurely, on an interpretation of provisional results deemed positive for the drug by the trial overseer. Which is odd for a drug claimed to be on double-blind test, with neither doctor nor patient supposed to know who was on what, but there we are. Next, it went before the FDA, to be approved in record time under huge political pressure from the gay lobby. Strong reservations were expressed at the hearing about its dreadful toxicity. The chairman’s vote against it was defeated. As the most poisonous drug ever licensed by the FDA for indefinite use, and with the conviction apparently that the terrible new disease needed a terrible medicine, AZT was approved for use in extreme AIDS cases only - for which you might want to read, in cases of people very ill with their presenting AIDS indicator disease, fungal pneumonia or what have you. Scarcely a year later, in the orgy of stupidity that characterises the AIDS age, AZT was officially recommended for administration to entirely healthy people, whose misfortune it was to register positive to an HIV antibody test. Since the drug destroys the very immune cells allegedly attacked by HIV, the introduction of AZT as a treatment regimen for asymptomatic HIV-positive people saw the AIDS mortality rate among the previously well take off like a rocket. Five years and countless deaths later, and only after the disastrous results of the European Concorde and St Mary trials, was this murderous treatment recommendation reversed. AZT, it was found, did no good. Of course not. On any intelligent consideration of its pharmacological action, AZT could never be ‘antiviral’, any more so than arsenic could have cured the scurvy for which it was administered to sailors, and later, to troops in the trenches in the First World War.

In Europe and the US, HIV-positive ‘long term survivors’ quietly gather to form groups, having sloughed off the terror of the death sentences imposed on them by their doctors. Here’s the strangest thing. Without exception, what they find they all have in common is that they all eschewed (or quickly gave up) AZT, related nucleoside analogues like 3TC, and protease inhibitors. Some have pondered the unthinkable: that nearly all medically managed AIDS cases, always terminal, represent that balefully familiar phenomenon in the history of medicine, iatrogenocide - to be killed by the cure. Their reasoning becomes less obscure when one reads the AZT package insert. To do so might tempt one to wonder impertinently whether AZT isn’t AIDS by prescription. Indeed, such perverse conjecture is actually confirmed in capitals: AZT use “MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING GRANULOCYTOPENIA AND SEVERE ANEMIA” (destruction of white and red blood cells respectively), and “PROLONGED USE OF RETROVIR HAS BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY (gross atrophy of muscle tissue) SIMILAR TO THAT PRODUCED BY HUMAN IMMUNODEFICIENCY VIRUS”. As to the latter claim, history will judge whether the thousands of healthy HIV-positive people who embarked on their metabolic poison treatment and wasted away (just as the AZT insert predicted) would have died had they ignored doctor’s orders and thrown their pills away. Here the syphilis story is instructive.

Before the introduction of mercury and arsenic salts as a treatment for this clap, the organic brain damage and dementia that signalled ‘tertiary-’ or ‘neuro-syphilis’ was quite unknown to medicine. When penicillin replaced the older decoctions, it then disappeared. The moral is hard to miss.

One sane notion in that otherwise mad dance with death that chemotherapy for cancer involves is that you stop before you drop. Since healthy cells are always killed in the crossfire, the idea is to rescue the patient from going over the cliff along with the target bad cells, by taking him off the drug in the nick of time. That iron rule is broken in AIDS treatment. You’re going to die, you’re told, so better take the bitter medicine to the bitter end, to stave off the evil day. But as AZT heads like a heat-seeking missile for one’s immune and energy transporting cells (“target organs: blood, bone marrow”, remember?) dying of AIDS on AZT is a racing certainty. No one has ever been cured by AZT, but it sells like hot cakes all the same, still the most widely prescribed AIDS drug, and it reaps profits counted in billions.

Ever irrepressible as a medicine following one failure after another, in 1994 AZT was proposed as a treatment for pregnant women to prevent the transmission of HIV from mother to child, or so it was touted. Until then, it had been staunchly contraindicated during pregnancy. Generously underwritten by the drug’s manufacturer, the study, ACTG 076, in which this startlingly novel use of AZT was tried, epitomises the junk-science that characterises so much AIDS research. Of 477 babies born to HIV-positive mothers in the trial, 13 in the AZT-treated group were born antibody-positive, against 40 in the placebo group. Apart from the lunacy of basing a decision to dose HIV-positive mothers with a cell-toxin as lethal as AZT on such feeble numbers, the underlying assumption that an HIV-positive test result predicts inevitable illness and death is a canard of modern medicine which, surprisingly, wants for evidence. Most babies ‘seroconvert’ to HIV-negative in any event, medicated or not. The other overarching myth is that the mere presence of antibodies in one’s bloodstream signifies an active infection. Isn’t it elementary that we carry antibodies to all sorts of pathogens that we have met and defeated? Isn’t this first-year stuff? Advocates of AZT confess to being completely in the dark to account for the vaunted HIV blocking effect they claim. The reason why administering vitamin A instead works precisely the same magic might be a pointer to something less interesting: stressed health, thanks to chronic poor nourishment and living conditions. As for the positive immune signals a ‘short course of AZT’ can generate, poison ingestion provokes an immune reaction as the body rises to the insult. This is old hat.

Thrown to the wind have been all the safeguards set up to ensure that the Diethylstilbestrol and Thalidomide tragedies would never happen again. Before the hysteria of the AIDS age, women were enjoined even to avoid drinking beer during pregnancy. A recently reconfirmed active carcinogen, and teratogen too - cells not killed outright are nastily maimed - AZT freely crosses the placental barrier, so the package insert tells us cheerfully. Has anyone here paused to question whether a growing foetus comprising rapidly dividing cells should be exposed to a random terminator of DNA chain synthesis? Apparently not. Certainly not the recipients of GlaxoWellcome’s largesse from its slush fund of millions for those who make AIDS their business in this country. Nor our doctors carrying out bold medical experiments on the foetuses of pregnant black women - whose unlucky dice gives them a positive registration to the irredeemably and hopelessly non-specific ‘HIV-antibody’ test. Of course anyone in the game crying foul, and drawing attention to the reams of literature in the medical journals about the harm caused by AZT, especially to the young, is going to find himself sent off and defunded, for keeps. Were it not for the amazing collapse of critical intelligence in the AIDS age, GlaxoWellcome’s heart-warming contributions to ‘the fight against AIDS’, with its research grants and cut-prices - described by the Mail and Guardian as a “bouquet of assistance” - might have been seen less as philanthropy than commerce, pure and simple. As it has achieved so successfully abroad, what better way to fix its local market than by buying off our medical establishment and ‘AIDS activist’ crowd with lolly aplenty to fund their dumb projects? And by enticing our government with current discounts for its rancid wares, in order to hook longer-term contractual commitments.

The AIDS Law Project at Wits currently busies itself with plans to sue the minister in the High Court for an order compelling her to respect ‘pregnant women’s rights to AZT’, and dole it out on the house. Then again, its ‘AIDS activist’ lawyers gratefully take junkets to AIDS conferences in holiday cities overseas at GlaxoWellcome’s expense. The ‘human rights’ they pursue might be better served were these legal crusaders to call off their foolish case and think of ways best to bite the hand that feeds them. Several actions for loss of support have been launched against GlaxoWellcome in England and the USA, arising out of the deaths of family members killed by their doctors’ prescriptions of AZT (5).

Although she has justified her perplexing decision on AZT on the basis of financial considerations exclusively, saying she would rather spend her money on ‘AIDS education’, one day Health Minister Nkosazana Zuma will be praised for her great prescient wisdom in keeping AZT away from pregnant women and their foetuses. A bit like much-lauded Dr Francis Kelsey, whom Kennedy honoured for her wise perspicacity in sparing the USA the European Thalidomide calamity, when in truth her only notable trait was her fortuitously inefficient foot-dragging in obstructing the start of the FDA approval process.

It’s high time that everyone involved in this nightmarish mess went off to do some basic homework in the subject in which they have so much to say for themselves.

(1) Horwitz, J.P., Chua, J. and Noel, M: Nucleosides. V. The monomesylates of 1-(2’-Deoxy-beta-D-lyxofuranosyl)thymine, Journal of Organic Chemistry 29: 2076-2078 (1964). However, an American biochemistry professor with whom I have corresponded privately makes a documented prior claim to the first synthesis of AZT in the autumn of 1961. He prefers both to remain anonymous and not to upset the settled history - based on the first to publish. He mentioned to me that he employed AZT as an experimental cell-poison against leukaemic blood cells, and against the bacteria Salmonella Potsdam and E. coli. (Studies in the ‘90’s have confirmed AZT’s activity against all three.) He pointed out that after publishing his paper, Horwitz investigated the activity of AZT against Jensen tumour cells, and not against leukaemic blood cells as I reported originally in line with the conventional history. He also criticised my repetition of the claim that Horwitz abandoned AZT because of its toxicity (see for example the excerpt from Radford’s article immediately below). He said the reason was its inactivity against target cancer cells, while the acute toxicity of AZT emerged only later. Actually, Horwitz has made contradictory statements about this. Reviewing this essay, he remarked, “…you are justified in sounding a warning against the long-term therapeutic use of AZT, or its use in pregnant women, because of its demonstrated toxicity and side effects. Unfortunately, the devastating effects of AZT emerged only after the final level of experiments were well underway, that is, the experiments which consisted of giving AZT to large numbers of human patients over a long period of time. Your effort is a worthy one… I hope you succeed in convincing your government not to make AZT available...”

In an enthusiastic article about the pharmaceutical industry in the UK, Tim Radford wrote in the Guardian on 30 March 2000, “They settled on an anti-cancer drug which had proved too toxic to use against cancer: It was AZT… Since DNA is a ubiquitous part of life, compounds that act against it can potentially stop life forms like bacteria, like viruses, like humans. Of course, they can cause cancer as well, so balancing the risks is an essential part of the fascination.” The fascinating risks for the development of cancer posed by the administration of AZT are examined extensively in my reply to Dr Martin, AZT and Heavenly Remedies.

(2) DNA chain formation termination - described in this paragraph - is generally understood to be the basic pharmacological action of AZT. GlaxoWellcome asserts in its PRODUCT INFORMATION release about AZT, “In vitro, zidovudine triphosphate has been shown to be incorporated into growing chains of DNA by viral reverse transcriptase. When incorporation by the viral enzyme occurs, the DNA chain is terminated.” In a glitzy CD dished out at the 13^th International AIDS Conference in Durban, GlaxoWellcome claims similarly: “Nucleoside Reverse Transcriptase Inhibitors – NRTIs – [like AZT are] phosphorylated by cellular enzymes… competitively inhibit viral DNA synthesis [and are incorporated] into the DNA thus terminating DNA synthesis.”

This conventional model of AZT pharmaco-kinetics is accepted by a vociferous critic of the drug, Dr Peter Duesberg, professor of molecular biology at the University of California at Berkeley. His criticisms go principally to the unacceptable toxicology profile of AZT, and do not take issue with its manufacturer’s claims about its mode of action.  Accordingly, in Inventing the AIDS Virus he writes, “While on AZT, Bergalis once told a reporter she hoped to also get dideoxyinosine (ddI), another experimental AIDS drug. This drug and ddC, two products of cancer chemotherapy research, work in precisely the same way as AZT. Chemically altered building blocks of DNA, they enter the growing chain of DNA while a cell is preparing to divide and abort the process by preventing new DNA building blocks from adding on… So, like AZT, ddI and ddC kill dividing cells and have similar toxic effects. They destroy white blood cells and therefore can cause AIDS.” Jay Levy, professor of medicine and director of the Laboratory for Tumor and AIDS Virus Research at UCSF (and unlike Duesberg, a vocal protagonist of the orthodox HIV-AIDS model) said in Newsday on 12 June 1990, “AZT can only hasten the demise of the individual. It’s an immune disease and AZT only further harms an already decimated immune system.” Duesberg’s most recent and most detailed critique of AZT, co-authored with pharmacology biochemist David Rasnick Phd, is contained in The AIDS Dilemma: Drug diseases blamed on a passenger virus, published in Genetica in mid-1998. It can be read on the internet.

As Mycek et al put it in their text Pharmacology (2nd ed), it is trite that before the drug can be incorporated into DNA, “AZT must be converted to the corresponding nucleoside triphosphate by mammalian thymidine kinase in order for it to exert its antiviral activity.” Recognising this, GlaxoWellcome claims, “Within cells, zidovudine is converted to the active metabolite, zidovudine 5’triphosphate (AztTP), by the sequential action of cellular enzymes.” But numerous investigations since AZT was approved by the FDA in the US have found that AZT is triphosphorylated in vivo very inefficiently, and at least one order of magnitude lower than necessary for its claimed anti-HIV effect. Consequently viral DNA chain termination by the incorporation of metabolically altered AZT into DNA in place of natural thymidine is insignificant in relation to other activities of the drug, inter alia as a potent oxidising agent. This subject will get a close look in my reply to Dr Martin, AZT and Heavenly Remedies. AZT also disrupts cell division by perturbing the relative levels of natural nucleotide pools, with the drug acting as a ‘sink’ and sponging up phosphate molecules essential to the process. Starved of these molecules and denied the energy they provide, dividing cells die.

This pivotal criticism of the conventional model of the pharmacology of AZT - namely that AZT is not in fact triphosphorylated as GlaxoWellcome claims it is - is made and elaborated extensively in a paper discussed in my reply to Dr Martin, A Critical Analysis of AZT and its Use in AIDS by Papadopulos-Eleopulos et al, published in mid-1999 as a special supplement to the academic medical journal Current Medical Research and Opinion. Like Duesberg and Rasnick’s paper mentioned above, it is archived on the website www.virusmyth.com. Librapharm also has it posted at: http://www.librapharm.co.uk/cmro/vol_15/supplement/main.htm

(3) The way in which AZT was approved and reached the market as an AIDS drug has been closely researched and reported by John Lauritsen (Poison by Prescription: The AZT Story, and The AIDS War), Celia Farber (Sins of Omission, The AZT Scandal), Bruce Nussbaum (Good Intentions), Elinor Burkett (The Gravest Show on Earth), Peter Duesberg (‘With therapies like these who needs disease’ in Inventing the AIDS Virus) Martin Walker (Dirty Medicine and HIV, AZT, Big Science & Clinical Failure) and Steven Epstein (Impure Science: AIDS, Activism, and the Politics of Knowledge). It’s an amazing story, and is certain to haunt GlaxoWellcome in litigation sooner or later. Some of this writing can be read on the website mentioned above.

(4) In his address to the National Council of Ministers on 28 October 1999, during which he ordered an investigation into the safety of AZT, President Mbeki mentioned these lawsuits. GlaxoWellcome’s representatives in South Africa immediately denied them. A few days later, the President’s office asked me for details. I referred to the English cases of Threakall and others, and the American Nagel and McDonnell cases, all of which had been reported in the press. A month later however, in a telephone call from Susan Threakall’s English solicitor Graham Ross, I was informed that her action, his lead case, had been withdrawn a couple of months earlier. In March 2000, Paul Headlund, the American attorney who had handled the Nagel and McDonnel cases, told me that the claims had not been pursued. GlaxoWellcome was therefore technically correct in disputing Mbeki’s statement that there were cases concerning AZT pending against it at that time. What GlaxoWellcome omitted to mention was that a month earlier a court in Maine in the US had dismissed a bid by health authorities to compel Valerie Emerson to administer AZT to her son after her daughter had died on the drug, and held, “She feels that she has willingly and in good faith surrendered up the life of one child to the best treatment medicine has to offer and does not want to do the same with the next. Nikolas has made significant strides recently in gaining weight and overcoming developmental deficits, and appears happy and healthy. She does not want to see this child take on the pallor and pain of a sick and dying child.”

I am currently briefed in a claim against GlaxoWellcome for the widow and minor son of an attorney killed by a single month’s course of AZT and 3TC treatment. The action will be the first world-wide in which the integrity of GlaxoWellcome’s claims about the molecular pharmacology of AZT and the adequacy of the information provided about its hazards will be examined by a trial court in the light of the Papadopulos-Eleopulos et al review paper and others canvassed in my reply to Dr Martin. It will be the plaintiffs’ case that AZT is an unreasonably dangerous drug with no therapeutic or palliative value as an ‘antiretroviral’ whatsoever. This action is my lead case. I have since been instructed to represent two other plaintiffs, one who suffered permanent leg muscle damage and another liver damage after treatment with the drug. For another action I am handling involving AZT poisoning, but brought on a different basis, see An AIDS Case in the appendices to this debate.