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From: ((Steven B. Harris))
Subject: Re: AZT, Psoriasis, and HIV-
Date: 11 Jun 1995

In <> (Todd Miller -
Pharmacology) writes:

>>Comment: I think they'll get wise about this, though. Much vertical
>>transmission happens at the time of birth, and is presumably related to
>>how viremic the mother is at that time (there is some evidence for
>>this). So the thing to do is stay off AZT until near the time of
>>zero-extra risk early delivery, at 35 weeks or so, give AZT for a week
>>to knock viral levels down maxially (we know it happens that fast now),
>>and then induce labor. Damage to fetal cell division then should be
>>minimal, and no chance for the virus to come back up with mutants before
>>the child can get born.
>>                                          Steve Harris, M.D.
>	But Loveday et al (Lancet 345: 820, 1995) found that the slow
>rise seen after the rapid drop could not be explained by the frequency
>of mutants in the population of virus (the "swarm" in lingo).  Seems
>the virus that had mutated to AZT resistance made up only a small
>portion of the population.  They speculate that there must be other
>mechanisms, besides effects on RTase, for the reduction seen shortly
>after beginning AZT treatment.  These in general must act on endogenous
>cell machinery.  I wonder what the effects of AZT are on levels of
>actin?  The rapid drop of "HIV RNA" followed by a slow rise is more
>similar to what one would observe in response to any toxin that can
>affect transcription.

Interesting.  Well, whatever the cause, you want the mother to deliver
at the viral titer nadir, and it doesn't last that long.   Thus, I would
certainly think it would be best to save the stuff until near the end.
Here is a classic case of what do you do when you have something you
know works after a fashion, and you have something you're pretty sure
will work better for mechanistic reasons, but cannot be perfectly sure
until you try it.  Obviously trials are of the utmost priority, but what
do you do with your regular *patients* in the mean time.  Possibly tell
them the two options and let them choose.

Myself, I do NOT trust an antimetabolite like AZT around a developing
brain.  We know very well that things like head radiation for leukemia
early in a child's life can show NO differential effects for YEARS, but
nevertheless cause an IQ drop later on.  If a long course of AZT doesn't
do something like this, it'll be a surprise to me, frankly.  But, as
always, Nature must be the arbitrator of opinion.  Let's get those
trials on the road, folks! (and P.S., since we think that ddC has a
great preference for poisoning mitochondria in nerves, let's NOT do the
equivalent long term trial in pregnancy with ddC; we've got lots of
other things to do).

                                          Steve Harris, M.D.

From: B. Harris)
Subject: Re: HIV and AIDS and AZT Action (Previously Torture fantasy, etc)
Date: 25 Dec 1996
Newsgroups: alt.politics.homosexuality,alt.true-crime,,,

In <59pd6l$> (John
Lauritsen) writes:

   >> I'll post separately a longer description of the way that
AZT "works" -- by randomly terminating DNA synthesis.<<

     >> Although AZT is described by its promoters as a "reverse
transcriptase inhibitor", the description is highly misleading.<<

    Comment: On the contrary, the description is a good one.  AZT
does inhibit the reverse transcriptase enzyme of HIV, and keeps
it from doing its job, which is to make HIV cDNA strands from HIV
RNA.  This inhibition has been specifically shown in lab studies
(for instance, see Antimicrob Agents Chemother: 32:1733, 1988).
Whether AZT has its effect on retroviral replication by causing
termination of viral DNA (with the enzyme then freed), or whether
it has its effect by simply stopping viral DNA synthesis by
competitive inhibition of thymidine triphosphate, with the
inactivated enzyme still bound to the DNA chain, has not been
answered (see the Reardon monograph on HIV RT in J Biol Chem
265:20302, 1990).  But whichever effect (or both) are antiviral,
the fact that AZT is anti-retroviral with a mechanism of action
that involves reverse transcriptase, is clear.  For one thing,
AZT is effective on many different retroviral infections of cells
in culture, but has little or no effect on replication of most
other viruses (with the few exceptions, like hepatitis B, being
viruses with replication enzymes that have reverse transcriptase
activity)-- see Biochem Pharmacol 29:1849, 1980).  A specific
action against retroviruses, but not other viruses, or mammalian
cells, in culture, means that AZT is acting SELECTIVELY.

    If Lauritsen wants us to believe otherwise, it is his job to
go to the literature, review the papers which find AZT acting
selectively on retroviruses (see the many citations in this
message), and tell us where the authors erred or lied, and why he
thinks so.  It's not enough for Lauritsen to simply state that
all these scientists are mistaken.  Too many scientists, unfortu-
nately, have all reported the same results (see below).

   >>The biochemical mechanism of AZT is extremely simple; it is
a random terminator of DNA synthesis, the basic life process.
Since reverse transcriptase requires DNA synthesis, it could be
argued theoretically that terminating DNA synthesis would inhibit
reverse transcriptase.  But that is like dropping a napalm bomb
in someone's back yard, observing that insects had been killed,
and then marketing napalm bombs as insecticides.  AZT, despite
claims made a decade ago, cannot distinguish between human
cellular DNA and retroviral DNA.<<

   Comment: Note that Lauritsen gives no citation of any
experimental work to back this remarkable (and false) statement.
Since selective inhibition of reverse transcriptase by comparison
with cell enzymes has been found in a number of independent
studies (for instance, see J Biol Chem 266:1754,1991; J Biol Chem
265: 11914, 1990), Lauritsen again needs to tell us why he thinks
what many groups of scientists have reported independently, is
wrong.  Again, what experimental studies can Lauritsen cite to
support his views here?

   Note that the idea that AZT is selectively toxic to retroviral
replication, is supported by not only by enzyme kinetic studies,
but also by in vitro studies in which cell division in culture is
not inhibited at certain concentrations of AZT, but retrovirus
production IS-- as in the classic paper by Mitsuya: Proc Soc Natl
Acad Sci (USA) 84:2033, 1987.

   Furthermore, that AZT is effective against retroviruses but
not cell division at certain dosages, is demonstrated by the fact
that AZT inhibits retroviral activity in a number of in vivo or
*animal* models, improving outcomes (disease and death).  This is
not the behavior of a toxin.  For instance, AZT administration
prevents murine leukemia virus (a retrovirus) from causing immune
deficiency and death in C57B10 mice (Antimicrob Agents Chemother
34:605, 1990).  For people like Duesberg, who have been arguing
that AZT causes immune deficiency but retroviruses do not, papers
such as the one above need explaining.  It's not enough to claim
that (say) M. Fischl cooked the human data so that the
retrovirus-infected patients who didn't get AZT died, instead of
the ones that did get AZT.  The Fischl study was a big sexy
study, but Lauritsen also has to explain why a bunch of Japanese
scientists half way around the world are playing the same games
with their MICE.  And why other groups have found the same kinds
of results in SIV infected monkeys.  At some point the world-wide
conspiracy in favor of AZT which Lauritsen and Duesberg want us
to believe in, is just a little too large.

   Laurentsen (in another message, with the promised explanation of how
AZT works:
>>By its very nature AZT is cytotoxic -- a killer of human cells.<<

   Comment: nothing by it's "very nature" is cytotoxic.
Cytotoxicity is a function of dose, period.  No chemical is toxic
at any concentration.

     >> Peter Duesberg's new book, INVENTING THE AIDS VIRUS
(Regnery 1996) has an entire chapter on AZT ("With Therapies Like
This, Who  Needs Disease?"), in which there is a clear explanat-
ion of how AZT works.<<

    Comment: The problem here, however, is that Duesberg has not
a clue about how AZT works.  The scientists who've studied the
mechanisms of action of AZT (Duesberg has not) don't even know
exactly how it works (see citations above, especially the Reardon
monograph).  So if Duesberg thinks he knows, he's full of it.

    >>Later in this chapter Duesberg discusses the early
estimates  of AZT's toxicities relative to both human cells and
HIV.  On the  basis of laboratory experiments conducted by
researchers working for the manufacturer of the drug, AZT was
allegedly found to be much more toxic to the virus than to human
cells, enabling the claim that AZT specifically attacked reverse
transcriptase, and could therefore be considered an anti-retrov-
iral drug.  However, no independent researchers have ever been
able to replicate these results.<<

    Comment: This statement is completely false, as will be seen
by reading the many papers already cited.  I suppose that
Lauritsen is going to claim that dozens of groups of scientists
all over the planet getting the same results as regards AZT
specificity for retroviruses, are somehow not "independent"?

  >> More recent studies by small laboratories have consistently
found that AZT is every bit as toxic to human cells as to the
virus: AZT may be as much as 1000 times more toxic to human cells
than had been believed at the time the drug was  precipitously
and improperly approved for marketing by the Food and Drug

   Comment: The only grain of truth in the above statement is
that AZT does indeed have toxicity which varies incredibly widely
depending on the kind of cell being tested, the species, the
culture conditions, etc., so that AZT is indeed far more toxic to
certain of the most sensitive human cell lines than the first
studies (using other cell lines) showed.  It's not a question of
studies being unreplicable.  This is where the truth ends,
however, and Lauritsen and Duesberg begin.  Unfortunately for
their thesis, even at AZT doses far LESS than needed for any
toxicity in the most AZT sensitive cell lines known, AZT is STILL
capable of inhibiting AZT-sensitive HIV strain replication (see
numerous citations to primary literature below).  If there ARE
any papers, from small labs or not, which show the opposite (that
AZT is just as toxic to cells as to AZT-sensitive HIV virus
replication), neither Lauritsen or Duesberg have yet to cite them
anywhere, so far as I can see.  Prove me wrong, Lauritsen.  The
Duesberg paper you do cite does not study HIV.

     >> The question of AZT's toxicities to human cells is very
thoroughly analyzed by D.T. Chiu and P.H. Duesberg in the
chapter,  "The toxicity of azidothymidine (AZT) on human and
animal cells in culture at concentrations used for antiviral
therapy", in the book, AIDS: VIRUS- OR DRUG INDUCED? (Kluwer
1996). <<

   Comment: the last time Lauritsen brought up this pitiful
Duesberg paper, I posted a discussion of the many errors in the
paper, and promised I'd repost that discussion every time
Lauritsen brought it up.  Lauritsen has either a short memory, or
a very thick skin when it comes to being made a fool of, in

   For those readers who are new, or who cannot remember the
Chiu/Duesberg paper, again, it is a paper which doesn't study
HIV.  Rather, it's a study of AZT toxicity on cultured cells.  It
finds that its cells, under certain conditions, are inhibited by
AZT concentrations of 25 uM, and have evidence of minor toxicity,
which they eventually escape, at 10 uM.  That's all.  From this
data, Duesberg argues that since AZT is given to humans at
concentrations of 20-60 uM, that it must be very toxic.

   Except AZT isn't given in those doses to humans.  Wups.  I
discuss this little problem with Duesberg's argument extensively
below.  In short, medically-speaking, Duesberg doesn't know what
he's talking about.  AZT isn't given to humans to produce
concentrations of 25-60 uM, but rather to produce concentrations
far lower: 1.5 to 10 uM peak, with averages less than this.   And
there are many independent studies which show that AZT sensitive
strains of HIV are inhibited at AZT concentrations far less than
1 uM.  Thus, Duesberg's paper shows NOTHING.  His partial data
are good as far as they go (no evidence that Chiu fudged them),
but Duesberg's big conclusions from these few data are based on
silly errors he makes in pharmacology, which I've completely
detailed below.  So Lauritsen's reliance on Duesberg is thus a
case of the blind being led by the blind.

   How do you like the ditch you've fallen into, Lauritsen?

   What follows is a reposting of an earlier discussion about the
Chiu/Duesberg paper, after Lauritsen had tried to sell it earlier
this year as saying something significant.  EVERY time you try to
do this, Lauritsen, I'm going to repost.  Hell, there ought to be
a website specifically for refuting Lauritsen bullshit, since
he's so good at putting it up again and again, no matter how many
times it's shot down.

>     No, it's true in the sense that viral DNA synthesis can be
stopped before cell DNA synthesis, because the viral RT enzyme >
is less finicky about putting AZT into the DNA chain than are
cellular enzymes.  That's not only theory, it's also observed
fact.  Read a book.<

Lauritsen:	>>This is not true.  The early studies, by research-
ers employed by or close to Burroughs Wellcome, claimed to find
that AZT strongly preferred to terminate viral DNA synthesis as
opposed to human cellular DNA synthesis.  Their "findings" could
not be replicated.  Later, independent studies found that AZT is
a *nonselective* terminator of DNA synthesis -- as much as 1000
times more toxic to human cells as had been estimated by the
BW-connected researchers.  (Reference: D.T. Chiu and P.H.
Duesberg, "The toxicity of azidothymidine (AZT) on human and
animal cells in culture at concentrations used for antiviral
therapy" in __AIDS: Virus- or Drug Induced?__, Kluwer 1996)<<

   Comment: On the contrary, this is what comes of Lauritsen's
reading Duesberg instead of the studies themselves. That will
always get a person into trouble, because Duesberg is a master at
leaving out information which goes against his thesis, ending up
saying by implication that which is false.  Duesberg also has a
problem with arguing that his *theories* mean that certain
experimental *results* cannot be true, and therefore such results
should be ignored.  Good scientists, however, know that theory
must ever bow before observation (unless possibly the observation
is unrepeated and the theory is rock solid cornerstone of
physics--all of which does not describe any theory that Duesberg
spins, or any of the studies he attacks).

   In the study you quote above, Chiu and Duesberg find that AZT
is toxic to their cell lines at 25 uM (= micromolar,
"u" = mu for "micro"), but only marginally so at 10 uM (here,
interestingly, the cells eventually grow resistant and escape the
toxic effects).  Some other recent studies have found the same
result at about the same concentrations (though there is wide
variation, with some other studies finding much higher inhibitory
concentrations, and a few lower concentrations), but in any case
there is no reason to question Chiu and Duesberg's results.  The
interesting question is not what Chiu and Duesberg did, but what
they didn't do: why do Chiu and Duesberg perform no experiment at
5 uM or 1 mM, to find what the toxicity limit actually is?  I
suspect (on the basis of a number of other studies, some of which
Duesberg even quotes) that such concentrations show no toxicity,
and so Duesberg and Chiu don't publish them.  What-- we are to
believe that they didn't really try any lower concentrations that
those they report on? (Give me a break!)  Had lower concen-
trations been toxic, Duesberg and Chiu would certainly be telling
us about it (this is I suspect an example of Duesberg's tendency
to leave out facts which don't support his argument).  The fact
is that nobody, neither Duesberg or anyone else, has reported AZT
toxicity to cells in culture (including marrow cells) at below 1
uM.  But AZT was initially reported to stop HIV replication at
05 to 0.5 uM, as Duesberg notes [but does not say that this has
been many times confirmed].  The implied therapeutic index of 2
to 20 is quite in accord with what is seen clinically-- ie, that
doses of AZT only a few times larger than therapeutic are too
toxic to useful.  But we knew that already.

   Now for the fun.  Duesberg cannot get around the fact that AZT
has been reported to inhibit HIV at concentrations well below
toxic range in cell culture, including his own cultures.
Duesberg answers this embarrassing problem in three ways:

   1) He states that AZT doses are chosen to fall in [some]
therapeutic window between .5 uM and 1000 uM, with 500-1500
mg/d/patient corresponding to 20-60 uM/Kg, which to the unwary
would appear to be the toxic range, *unless* you notice that
uMoles/Kg are not the same as uM (micromoles/liter = microMolar).
Later, at the end of the Genetica paper, Duesberg actually
forgets himself and DOES equate 20-60 uM/Kg with concentrations
of 20-60 uM.  Wups.  This is very bad and ignorant reasoning, and
Duesberg should be very embarrassed about it.  It betrays the
problems of a chemist trying to do pharmacology [NB-- it sounds
sort of like Duesberg mutating "average age" of hemophiliacs into
"average life-expectancy" -- does it not?]

    Micromoles/(Kg of subject) are generally not equivalent to
micromoles/liter in the subject's serum.  Thus, an oral dose of
20-60 mMole/Kg does *not* generally equate to serum concent-
rations of 20-60 uM (uMole/liter) for oral drugs.  This for two
reasons: First, no orally given drug is absorbed instantly and
completely.  Second, even if the drug were given IV, the drug may
not have a volume of distribution of 1 liter/Kg.  The partly
protein bound AZT actually has a volume of distribution of 1.6
liters/Kg, and is not given IV, but orally (where the bioavaila-
bility is 65% or so, and absorption time is a significant
fraction of the half-life).  Thus, actual studies of the subject
(NOT theory or Duesberg guesswork) show that 200 mg oral doses of
AZT produce mean peak concentrations in real volunteers of
between 1.5 and 10 mM, with a lot of individual variation (Clin
Pharmacol Ther 41:407, 1987; J Infect Dis 159:745, 1989), and
even lower levels when the drug is given with food.

   Moreover, the short pharmacological half life of AZT (close to
1 hour) ensures that 200 mg administered two or three times a day
will not produce peak levels significantly higher than the peak
for a single 200 mg dose (ie, more than 99% the drug is gone
before the next dose is given), and that average levels across 24
hours will be far lower, around 3 mM (see above studies) [...].

   This experimental pharmacological FACT that actual AZT
concentration peaks in humans at standard doses range from 1.5 to
10 uM (implying mean concentrations of 0.5 to 3.4 uM) is, or
should be, somewhat embarrassing for Duesberg and Chiu, who found
escape from toxicity at 10 mM (essentially continuous concent-
ration) in their cultures, and did not look (or report) at lower
concentrations, or at the effect of AZT concentrations which
varied with large peaks and troughs.  But Duesberg, of course,
does not address this problem with his argument.  He's apparently
not sophisticated enough to know the problem even exists (nor is
Lauritsen, needless to say).  We know that Duesberg has read the
package insert for AZT (see Physician's Desk Reference for
zidovudine), where most of this pharmacologic information can be
found, and we know from his writing that Lauritsen has also.  The
problem is that neither *understands* what they were reading.
This is yet another reason why laymen should be wary of what they
read in package inserts, written by lawyers and medicinal-
chemists and meant for doctors and pharmacists, without guidance
from such professionals.

   2) Duesberg reports the Furman study's conclusion that AZT
inhibits HIV in cell culture at .5 to .05 uM, and gives
theoretical arguments why it cannot be true.  Alas, one will not
read in Duesberg that this result has been replicated many times
at many labs, which find 50% inhibitory concentrations of AZT for
HIV replication as low as 0.01 mM.  See the original Furman study
in P.N.A.S., USA 82:7096, 1985; but also see confirming studies
in Antimicrob Agents Chemother 30: 933, 1986 and AIDS Res Hum
Retroviruses 3:87, 1987, as well as confirming control studies
performed in Science 243: 1731, 1989; Antimicrobial Agents
Chemother 32:997, 1988 and J Exp Med 166:1144, 1987.  These six
studies together represent the findings of 18 scientists at 5
institutions, and do not conflict with Duesberg's study, which
does not involve HIV.  They are real.  Once again I urge
Lauritsen, who has written a book about this, but missed reading
the relevant literature, to get off his butt and visit a library.

    3) Duesberg uses theoretical arguments that AZT cannot be
doing anything.  These theoretical arguments, besides conflicting
with reality, are not very good (surprise).

[A] Duesberg's argument that the observed difference in sensitiv-
ity to DNA replication and HIV replication is wiped out by the
much larger mass of cell DNA forgets that it is CELL replication
which is being directly measured already in such studies, so this
effect has already been accounted for in the direct studies
(wups).  How dumb does Duesberg think his readers are?

[B] Duesberg's argument that numbers of infected cells do not
correlate with AIDS ignores the perfectly reasonable possibility
that it is not the absolute numbers of infected cells which are
important in immune function, but rather the total number of
cells remaining in the body.  Numbers of infected cells tell only
how fast the cells are disappearing, not how many are left (not
the same thing).

[C] Duesberg's argument that AZT inhibition of HIV replication is
unnecessary because HIV "does not spread" in the presence of
antiviral antibody, is also directly contradicted by numerous
experiments which show that sera from an HIV infected person may
NOT prevent HIV isolated from the same person from replicating
and spreading in culture.  This is due to the appearance of HIV
mutants able to escape antibody neutralization (AIDS 3: 777,
1989; AIDS 4: 107, 1990).  Indeed anti-HIV antibodies have been
described which actually enhance HIV infectivity in vitro,
presumably by allowing antibody coated virus to bind to antibody
receptors one target immune cells.  Presence of these antibodies,
interestingly, correlates with progression to AIDS (J Virol
64:1437, 1990). We have already summarized sheep, cat, and monkey
studies which clearly show advance of retroviral disease in the
face of seroconversion, even if one does not believe the numerous
studies of HIV patients in which viral loads are observed in late
disease to escape the antibody response also.  Once again,
Duesberg's pet theories run up against a large mass of experimen-
tal fact from many spheres.

[D] Finally, Duesberg's quaint argument that AZT must be toxic
because it must kill 999 cells for every HIV infected cell,
relies on the idea that AZT works by killing infected cells.  The
argument is not relevent if AZT works by inhibiting HIV
replication [without killing cells], replication which (once
again) can be expected to be pathologic even in the presence of
antibodies, as shown above.

Abstract included below for a treat.  More of the giant world
conspiracy, no doubt.

AU  - Eiden L ; Murray E ; Rausch D
TI  - Continuous AZT treatment of rhesus macaque infants infected
      perinatally with SIVsmm/B670.
AB  - Infant rhesus monkeys were inoculated i.v. with SIVsmm/B670
      within 48 hours of birth, as a model for intrapartum transmission

      of HIV. 5 animals were treated continuously (AZTc, 1 mg/kg/hr,
      s.c.), and 3 animals were treated intermittently (AZTi, 6 mg/kg
      four times daily, s.c.) with AZT for six months. Motor and
      cognitive performance was compared to 5 uninoculated and 5
      SIV-inoculated but untreated animals. All virus-inoculated
      animals were productively infected. 4/5 of the untreated animals
      succumbed to SIV disease, with wasting and opportunistic
      infection, within one year, and 2/5 exhibited transient motor
      impairment. These animals succumbed to disease before cognitive
      testing could be initiated. 4/5 of the AZTc and 3/3 of the AZTi
      animals have survived to 15-18 months of age. No animals in the
      AZT groups exhibited motor or cognitive impairments relative to
      controls. Serum chemistry, general health and development of all
      of the AZT survivors was normal throughout and following
      treatment. All of the animals in the untreated inoculated group
      showed a transient p26 antigenemia within two weeks of
      inoculation (peak levels 15 +/- 4 ng/ml). There was a significant

      reduction in initial antigenemia in the AZTc (2.6 +/- 2 ng/ml).
      The single non-survivor in that group also had the highest peak
      antigemia (9.4 ng/ml). The SIV-infected neonatal rhesus monkey
      may be useful to determine minimal perinatal treatment regimens
      for AZT and other antivirals, and examining viral disease in the
      neonatal host.
SO  - Int Conf AIDS. 1993 Jun 6-11;9(1):27 (abstract no. WS-A11-3).

From: B. Harris)
Newsgroups: gay-net.aids,,,
Subject: Re: Immunocal- setting the record straight
Date: 16 Jul 1998 07:11:21 GMT

In <> fred <> writes:

>Harris, can you cite the Federal law that says others
>can bring a copyright suit without the consent of the
>copyright grantee, or is this just more Harris The Chimp-doo?

   Since copyright continues for 50 years after the author is dead
(1976 revision), it's really rather obvious that somebody other than
the grantee can file such suits.  But you are probably correct that the
person filing for infringement must do so on behalf of the legal
copyright owner.

>Sure -- they put their money on Margaret Fischl, who they put
>in charge of the trials with Douglas Richman -- funny though,
>prior to the fraudulent and outrageously corrupt early AZT trials,
>Fischl had NEVER published anything that had to do with
>Isn't that interesting, Bonzo?

   Not really.  Fischl was an unknown, but she wasn't in charge,
either.  There was plenty of clinical experience to run a clinical
trial which ran at 13 centers at once.  And there was plenty of prior
experience in analyzing clinical trials data.

>> The Feds have no mechanism for bringing drugs
>> they discover to market.
>Sure they do -- they pick up the phone, call their drug company
>golf buddies, set up the deal, receive the bribe and they're off
>to the races!!!

   Not really.  AZT was not developed by the government per se, but
rather discovered in 1964 by a guy named J. Horowitz working at the
Detroit Cancer Institute (private insitute), on a government grant.
Not the same thing.   Governemnt grants are just that: grants.  They
don't come with stings attached.  Horowitz could have patented AZT in
his own name (doing something on government grant money doesn't mean
the government has any rights to it), but he didn't bother to.   So
nobody owned AZT, and it was long in the public domain, waiting for
somebody to come along with a use patent.  It had been known since
about 1974 that AZT had activity against retroviruses in animals (FeLV
in cats, for instance) and Burroughs Wellcome did research with it and
actually considered it as a vertinary drug in that time.  Their
exclusive license came when they became the first to apply to use it
against HIV under the orphan drug act.  That came out of some NCI work
with AZT on HIV (the AZT supplied by Burroughs Wellcome), which in turn
came out of Wellcome's long experience with the stuff with animal
retroviruses, before anybody had any inkling that there were nasty
retroviruses in humans.  No golf deals were involved at all.

>> In the meantime, this activity (development of a possible
>> pharmaceutical for human use) is granted to the highest
>> private bidder.
>Is it, Dr. Harris? Are you sure that there aren't "gentleman's
>agreements" as to who will bid and who won't?
>Do you believe that's how Burroughs Wellcome got the
>exclusive license for AZT in 1986-1987?

    No, what I believe about that is printed above.  In this case,
Wellcome was first to apply for orphan drug license (read what I mean
about highest bidder), was the company that had the experience with the
drug on retroviruses long before there was any such thing as HIV, and I
suppose had some extra inside track because they had supplied the drug
for the initial positive tests on HIV virus-- proding the Feds to look
at it.

>> Bidding here being understood as willingness to risk large
>> sums of capital development money for a
>> product which may be worthless.
>No, dummy -- that isn't "bidding" ... that's known as risk
>assessment through drug development and testing.

   With the Orphan drug act it's known as a bid.

>>    Sounds like fairness to me.  Where were these other companies
>> when the development costs were being assigned?
>Perhaps wondering why they weren't able to bid competitively?

   They were.  They could have beat out Burroughs if they'd been
working with AZT for years anyway, and if they'd been the ones to pushd
the government to do the in vitro antiviral research with AZT, and if
they'd supplied the drug to do it, and if they'd applied first under
the Orphan drug act to use it.  Except, they didn't.  Wah, they wanted
their mommies later.  It was so unfair that Burroughs Wellcome got that

>I have no dispute with the small gifts, just the big ones.
>Naturally, knowing how Frankenharris rationalizes, the free
>pens, coffee mugs and pizza are probably waiting for him
>at the reception center when he steps off the plane in
>Bali Bali for his drug company-paid "Continuing Education"
>cruise in the South Pacific!

    Right, Fred.

>> What have you taken, Fred?
>Nothing. I give.
>> Who pays your bills,
>I do.

    With money you get where, Fred?  Rich uncles?  Dutch Uncles?  Sugar
daddies?  Government handouts?  What?   It's a cinch you don't work for

                                   Steven Harris, M.D.

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