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From: B. Harris)
Subject: The AIDS Heresies ((all articles, combined))
Date: 22 Dec 1996



   The following paper, _The AIDS Heresies_, was written in
response to a large recent increase in unscientific and frankly
paranoid theorizing about HIV and AIDS.  The recent publication
of a book by prominent retrovirus researcher Peter Duesberg,
Ph.D., claiming that HIV does not cause AIDS, and the well-
publicized statements of a Nobel Prize-winning chemist (Kary
Mullis, Ph.D.) also publicly questioning the HIV-AIDS theory,
have both contributed to a certain amount of skepticism within
the HIV-infected community, if not the general public.  It has
become clear that some kind of detailed response is needed to
Duesberg and his followers, to be used by professionals and
laymen alike in the always difficult question of what to do about
AIDS.  This essay was begun at the end of 1994 with this end in

   The issue of whether or not HIV causes AIDS is a life-and-
death one.  Until recently, the treatments for HIV infection were
only moderately better than doing nothing, but there was still
the question of prevention.  It seems likely that the sexual
behavior of someone who knows themselves to be infected with a
virus which is deadly, versus the behavior of someone who is
convinced his or her infection is less serious than a cold, will
be quite different.  To this end, it is likely that skepticism
about the cause of AIDS has already contributed to many HIV
infections, and many deaths, as people carrying HIV simply lie to
themselves and their partners about carrying the virus.  "Sex
will not kill you," states Peter Duesberg, who recommends that
people worry only about previously known, non-fatal sexually
transmitted diseases.  But such a low and inappropriate level of
concern will be expected to be a disaster in a venereal plague
which is, in fact, deadly.

   Progress against AIDS continues, and in late 1995 and early
1996 a new class of antiviral drugs (HIV protease inhibitors) was
introduced.  These antivirals have shown the remarkable ability
to inhibit HIV replication almost completely, for periods of up
to a year and a half, and perhaps far longer.  Addition of these
new drugs to the medical regimen of tens of thousands of people
dying of AIDS has already caused many to regain weight and
health, and, to their astonishment, the will to continue with
their previous lives.  Smaller AIDS wards across the country are
literally being shut down for lack of sick patients.  Yet in the
face of such gains the critics continue to tell HIV-infected
people that if they take no drugs of any kind they will surely
live, but that if they agree to medical treatment, they will
surely die.  Never before has the question of belief in one of
the more difficult theories of medicine been so important to so
many people.

   This essay tells the story of the discovery of HIV and its
lenitvirus relatives.  The reader who perseveres will gain an
understanding of not only HIV epidemiology and history, but also
some understanding of the difficulties of using the inferential
scientific method.  When does a critic of science become a crank?
What makes the establishment so sure about the role of HIV?  How
much room does the evidence give for alternate theories?  All
these questions will be addressed.

   This essay, written as it is for net distribution, is a work-
in-progress.  The author would be glad for any feedback from any

                            Steven B. Harris, M.D.
                            Salt Lake City, Utah
                            December, 1996

N.B.  The author is an internist, clinician, and experimental
gerontologist who receives no grant money from the government
AIDS research establishment, and does not feel himself
constrained in his opinion on this subject in any way by his
academic status or occupation.

   This draft information brief may be freely reproduced and
distributed in this ASCII form by anyone without license, so long
as the ENTIRE contents are reproduced, including author copyright
information and notes, and so long as reproductions are not sold
for money (this does not include normal connect time charges on
computer nets for downloading, but would include any special
charges for the article itself on a BBS).  Those seeking other
arrangements should contact the author.  Illustrations and
figures for some of the concepts are available, and can be
obtained by contacting the author.  A shorter edited and
illustrated version of this paper appeared in SKEPTIC Magazine in
vol. 3 no. 2, 1995, with follow-up letters and an author reply in
SKEPTIC vol. 3 no. 3.  For SKEPTIC information call
(818) 794-3119.

                   THE AIDS HERESIES

         A Case Study of Skepticism Taken Too Far

           (c) 1994-1996 Steven B. Harris, M.D.

        _Felix qui potuit rerum cognoscere causas._
 [Fortunate is the man who understands the causes of things.]


        "It's the virus, stupid."
                                    Dr. David D. Ho
                                    AIDS Researcher

A Dialogue In Inductive Frustration

   Let us suppose that you have a bright and iconoclastic friend
who smokes three packs of cigarettes a day.  You remark one day
that you would like to see your friend quit the habit, since he
is certainly increasing his chances of lung cancer.

    "Prove it,"  says your friend.

    "Well," you begin, "the Surgeon General and a lot of
scientists and doctors say you should quit...."

   "Come now!" says your friend, "Since when did you become a fan
of The Argument From Authority?  I can find you scientists who do
NOT believe I necessarily should quit, too, as well as a lot of
intelligent business executives."

    "Sure, but all those scientists and all those executives are
paid by tobacco companies or grants from the Tobacco Institute,"
you protest.

    "Well, what do you expect?" says your friend, lighting up and
taking a satisfying drag.  "Whenever any scientist takes an
anti-establishment, anti-government position like that, all
grant funding is cut off.  Didn't you know that?   The poor
scientists then don't have anyone else to support their research
_but_ the Tobacco Institute.  Do you expect them to starve or
drop out of research just because they hold unpopular opinions?"

     "Okay, let's look at the facts," you say.  "What about the
fact that 90% of lung cancer occurs in smokers?"

    "Yes," says your friend, "and that means that 10% of it
occurs in non-smokers, doesn't it?  Obviously the `cigarettes =
lung cancer' hypothesis doesn't explain all lung cancer, and even
for smokers there must be `co-factors.'  Heck, my
grandfather smoked 3 packs a day right up to the day he was hit
by a drunk driver at the age of 92.  A lot of people smoke for a
whole lifetime and never get cancer."

    "Look, I didn't say the association was statistically
perfect!"  you protest.  "But it is certainly there.  Two-pack-a-
day people have 13 times the lung cancer risk of non-smokers."

    "Oh, really?"  your friend says, "Now, where do you get that
number?  I suppose somebody did an experiment where they got
together a group of nonsmokers and randomized them to start
smoking, or else stay smoke-free, and then made sure each and
every person did as told for the next 40 years, so as not to bias
the results.  I must've missed that study."

    "You know there is no such study.  That experiment would have
been impossible, since you can't enforce a random protocol like
that. People will start or stop on their own.  And besides, any
experiment where you try to keep people from quitting would be
immoral, since smoking causes cancer."

    "Sort of circular argument there," sighs your friend,
admiring a smoke ring, "since that is what remains to be proved.
So you admit you don't have any study where the two groups of
smokers and nonsmokers are exactly equivalent, and only differing
by chance or random draw?  In every study the smokers and the
nonsmokers are self-selected for their behavior, aren't they?
And bound to be different not only in smoking behavior, but also
because of whatever made them smoke or not smoke to begin with!
So your experimental `controls' are inadequate, even if I do say
so.  Not exactly great science, if you ask my layman's opinion."

    "But darnit, when smokers quit, we know their risk of dying

    "You mean with regard to the smokers who don't quit?  So
what?  The people who quit smoking did so for a reason other than
chance or the experimental flip of a coin, I'm sure, and again
that means they will differ in some way OTHER than their not
smoking.  Again you don't have a proper "control group" of non-
smokers who had that very same reason, but were _prevented_ from
quitting.  Look here: did you know that for the first year after
quitting, the risk of death for a new quitter actually goes UP
with regard to his fellow smokers who keep right on smoking?"

    "I knew you'd bring that up.  The mortality goes up for the
quitter group for a while after they quit only because those
people who quit are quite often sick, and that's WHY they quit."

    "If so that makes my point about self-selection, doesn't it?
These aren't true controlled experiments.  You're saying that in
that first year of quitting, the higher death rate of quitters is
caused by another factor in our study other than smoking--
namely, sickness.  Well, so long as we're talking about such
third factors, I have a hunch that _stress_ causes cancer, and
stressed-out people take up smoking to try to relieve the stress,
and that's why there is more cancer in smokers, not because of
smoking.  Moreover, maybe the act of quitting stresses people
out, and that's really why quitters die faster in that first year
after quitting.  Smoking is just a marker for stress, you see--
what you statistics people call a "proxy variable."

   "All this is ridiculous!  You're just using your intellect to
make you believe something you want to believe for other reasons.
There is experimental evidence!  Smoking causes lung cancer in
lab animals!  Are THEY stressed?"

   "Actually, yes-- have you seen what they do to them in a
modern lab?   Ever seen one of those rabbits with a leather
muzzle over its nose, and a cigarette stuck in it which it can't
take out?  But anyway, I don't even believe you can find me a
report of an experiment in which smoking causes lung cancer in

    Back you go to the scientific literature.  And you find----
nothing.  There is no such paper....


Medical Induction.

     Because there are many intellectual steps which are not
perfectly secure in any generalization, even the most detailed
inductive argument only goes so far toward proof, as our fictio-
nal dialogue, which is based on facts, demonstrates.  It is also
unavoidable that the same evidence will mean different things to
different people.  In particular, it is more difficult to induce
a person to follow a complicated inductive-reasoning trail when
they dislike, or are threatened by, the conclusion at the end.

    In the medical sciences, assembling an irrefutable argument
for causation is sometimes an impossible task for the same reason
it is in astronomy or paleontology: the direct and definitive
experiment cannot be done.  Scientists cannot travel back in time
to watch dinosaurs, nor can they influence the behavior of
planets or stars.  In medicine, a common difficulty is that the
necessary human interventive experiments to perfectly assess
"risk factors" for harm may be unethical, and so these risks
cannot be studied directly by experiment either [1].  How, then,
do we come to "know" (or confidently believe) what things cause
lung cancer or AIDS?  For that matter, how do we come to know
with any confidence that tyrannosaurs ate meat, or what generates
the sun's energy?  In other words: how _do_ we ever infer
causation from looking at events (or records of events) which we
cannot influence?

    However we do it, it does seem that it can (to some extent)
be done.  Modern science depends on the fact that "correct"
causal relationships can often be guessed entirely from logical
and indirect observational tests of competing theories, even
where direct experimentation is not possible.  This is done using
help from knowledge of simpler causal mechanisms which we have
gained from similar systems in which experimentation _is_
possible.  One of the most amazing things about the universe is
that this kind of inference is possible at all, as Einstein once

    Of course, the overall results of this kind of theorizing,
like those of any inductive process, are never certain.  Still,
whenever inferential theories in science finally _do_ become
directly testable by some new experimental technique, they often
prove to be surprisingly sound (or "robust," as scientists say).
Why this should be true remains the deep mystery that it was for
Einstein.  We are only little more than re-stating the mystery
when we note that the universe seems to have a certain degree of
uniformity and symmetry at many levels, allowing us to correctly
guess at the structure of some levels of uniformity, on the basis
of knowledge of others.  Human intuition, trained by a core of
more secure direct experimental knowledge, does seem often an
adequate tool for doing some of this kind of guessing.  On the
basis of our past success, we expect (on the basis of the
symmetry of past and future) that the present inferential methods
of science will _continue_ to result in progress toward truth in
many fields of knowledge.  This progress in understanding will
occur even before final experimental "proof beyond all reasonable
doubt" arrives in each case.

    It is because of an inferential process, based on many lines
of evidence, that we can be reasonably confident of the tobacco
causation of much of lung cancer, even in the absence of a
definitive experimental study.  In the same way, an examination
of a large body of related facts allows us reasonable confidence
about the causation of other diseases-- even a disease far more
complicated than lung cancer, and with even more money and
passion involved on either side of the issues.

The HIV-AIDS Hypothesis, and Its Challengers.

   Recently, several popular lay publications (Reason Magazine,
Spin Magazine, the New York Native) have run articles calling
into question the theory that the viral agent with the conclusi-
on-asserting name, the "human immunodeficiency virus (HIV)," is
the cause of the epidemic of human acquired immune deficiency
disease, known as AIDS.

    What do we mean by talking of the "cause" of AIDS?  We know
that the common cold or the flu-- indeed all infectious diseases-
- are in some sense "caused" not only by the pathogenic organism.
Also important in the causal chain are host factors (such as
immune response), and even simple host-overwhelming factors, such
as the infectious dose of organism which enters the body (called
the "inoculum").  These additional causal factors, which have
nothing to do with the microbe itself, can be extremely
important.  They may in some cases outweigh everything else.
Because (for example) the smallpox virus is necessary for
smallpox, if not sufficient, medical science still regards it as
"causal" in the sense that if there is no microbe, there is no
illness.  Eliminate the smallpox virus from the population and
one eliminates the disease, as was in fact done in the 1970's.

   Yet even this kind of "causal" connection between a disease
syndrome and infectious agent is what is under attack in recent
articles about HIV and AIDS.  Some skeptics have claimed not only
that HIV is not the only external factor necessary for AIDS, but
perhaps even that HIV is not always necessary for AIDS, so that
if HIV were eliminated from the Earth, at least some AIDS would
still be with us.  Still others have gone further and claimed
that HIV infection is totally harmless and never even _contribut-
es_ to the development of AIDS.  These people believe that if HIV
were to disappear, AIDS would continue exactly as before.

    In what follows, we will examine the best evidence behind
what most researchers believe is the role of HIV and other
factors in AIDS.  We will also examine leading skeptical views on
the causation of AIDS.  Because a great deal of published
research is available on this issue, our examination of AIDS will
also let us illustrate how science closes in on cause and effect,
even when direct experimental "proof" is not available.

    We will thus be interested in not only AIDS, but also larger
questions about science, and scientific debate.  What makes a
good scientific theory, and what makes a poor one?  Are there
reasons for hope in looking at the disease of AIDS in particular,
and the workings of the biomedical scientific "establishment" in
general?  Or has science been completely corrupted in working on
the cause and cure of AIDS, as many critics suggest, so that with
this particular medical problem the scientific method has ceased
functioning?  Are we making any progress with AIDS, or just
wasting billions each year chasing fantasies?

    This essay will argue that we are not wasting our money, and
that when it comes to critics of the HIV/AIDS hypothesis, we have
a practical case in which scientific skepticism has been taken
too far.  Science, we are happy to report, still works, and it is
making progress with AIDS.  That some critics have failed to
recognize this only highlights the fact that science is only
partly an empirical enterprise, and that it also has an intuitive
and aesthetic side which is subject (to a certain extent) to
arguments over taste.  This is not a thing which is taught about
science in school, but it is a concept key to understanding most
scientific controversies.

What Is This Thing Called AIDS?

    Scientific problem-solving begins with definitions, and in
choosing a definition for AIDS we run immediately into the
HIV/AIDS controversy.  Some of the difficulty is that
definitions, even in science, are chosen partly on aesthetic

    There are utilitarian principles, too, of course.  In medical
science we rarely know in detail at the molecular or even
cellular level what causes most human illness, and so in our
ignorance we are often forced to work with "disease syndromes,"
which are collections of symptoms and sometimes lab tests which
seem to "go together."  In order to usefully define a "disease
syndrome," (which gets promoted to a "disease" after it stands
the test of time and we get used to it) we need to pick our
defining characteristics so as to include all of the sick people
who we are interested in for good clinical reasons, and exclude
everyone else.

   What are "good clinical reasons"?  In medicine there isn't
much point (other than pleasing some doctor's vanity) in defining
a new "disease" which, when present, makes no difference in
either prognosis or treatment.  Nor is there much point in
defining a disease so poorly that it fails to capture all the
sick people who seem to have pretty much the same thing wrong
with them from the prognosis or treatment viewpoint.  If (as
always happens) we lack information about what impact certain
definitional characteristics _have_ upon treatment or prognosis,
then we are forced to _guess_, as best we can, what disease
definition will be most useful.  It is at this point, in deciding
whether two people have "pretty much the same thing wrong with
them," that aesthetic and intuitive considerations unavoidably
enter into medical science.

    Utility imposes other constraints, too.  A disease definition
which is to be used during a hunt for the disease's causation,
should not assume any cause which is in question.  To be
specific, if we choose a definition for "AIDS" which in some
cases requires evidence of infection with the HIV virus (the
current way it is done in many countries, including the U.S.),
then we will have chosen our terms so as be of little help in the
question of whether HIV causes AIDS.  Obviously, it would be
nothing remarkable if we "discovered" that almost all people with
AIDS were infected with HIV, if we had previously chosen our AIDS
definition to make sure that it was so.

    In re-opening the question of the cause of AIDS, what we need
then is a modified AIDS definition which does not involve HIV, so
that the question of whether or not all AIDS cases are infected
with HIV is an empiric one, not simply a semantic one.  When we
have a suitable HIV-free candidate definition for "AIDS," we can
then ask two critical questions about it:

1) Have we captured with our definition all of the people with
the new medical problem that we historically came up with the
"AIDS" label, in order to describe and encompass in the first

2) If we test our defined group, are very nearly 100% of the
people encompassed by our AIDS definition found to be infected
with HIV, an otherwise rare virus in the population?

   If the answer to both these questions is yes, then HIV is
promoted to a good candidate for the cause of the AIDS epidemic.
If either answer is no, then our version of the HIV/AIDS
hypothesis obviously has severe problems right from the start.

    Fortunately, it turns out that we can easily construct a
workable definition of AIDS which does not include any reference
to HIV, but which still describes the new epidemic we are
interested in.  Such a definition will not be the standard one,
of course, but since the standard modern "HIV-containing" AIDS
definition is unusable for this purpose, both we and the HIV/AIDS
critics are required to construct special AIDS definitions, even
to continue to talk about the problem of causation.  It's

   Finally, we should note that in no infectious disease known to
man is it possible to possible to define the disease syndrome
clinically (i.e., by things observable at the bedside) or by any
laboratory means which don't include direct tests for the causal
organism, and YET still be able to achieve 100% specificity
("100% specificity" means that in no case before testing for the
microbe is the physician ever fooled about whether or not the
patient REALLY has the disease).  We're not pefectly 100% sure we
are seeing ANY infectious disease without a test for the disease
causing organism.  Since this is true for any infectious disease,
we should expect this to be true of AIDS also.  Simply put: no
definition of AIDS which does not depend on HIV (as the critics
insist it must not) can ever be expected to be perfect, and thus
NEVER capture anyone who actually does not have HIV.  But, as
with all infectious diseases, a 99.9% score will be quite good
enough for us.

_AIDS Is An Acquired Immune FAILURE Syndrome_.

    What is the best way to define AIDS without reference to HIV?
First, the term "AIDS" stands for Acquired Immune Deficiency
Syndrome, but it has always been understood (except by certain
critics, who we will come to presently) that the amount of immune
deficiency we are interested in, is not a trivial one.  AIDS is
the name historically chosen for a new medical syndrome which is
essentially 100% fatal, and thus in defining "AIDS" we are
looking for people with an immune deficiency in the range which
is life-threatening, and which will continue to grow relentlessly
worse until life is impossible.

   One possible way to define immune deficiency would be to
define it by what secondary health problems it causes-- for
instance, one could pick people who have gotten so-called
"opportunistic infections," which are strange infections which
are seldom if ever seen in people whose immune systems are fully
functional.  In the early days of AIDS, before HIV was
discovered, the syndrome was indeed defined using such opportuni-
stic diseases (Fig. 1a), and people with these infections are
still included in the latest 1993 Centers for Disease Control and
Prevention (CDC) clinical surveillance definition of AIDS (but
now, in most cases, such people are only included if they are
also HIV infected).  We will not be able to use this CDC definit-
ion of AIDS (Fig. 1c).  Not only does it require HIV infection in
many (though not quite all) cases, but for historical, political,
and technical reasons, it also is constructed in a way which does
not assess current immune status in the best way for our

    Why is this?  The basic problem is that only a limited amount
of information about a person's immune system function flows from
the bare fact that they have an "opportunistic" infection.
Certainly there is a good correlation between immune function and
what kind of opportunistic infections occur, but the correlation
is far from perfect, since opportunistic infection risk is
influenced by not only immune status, but also by the quality of
what we may term the infectious "assault" to the system.  The
infectious assault in turn is influenced by a person's physical
location, infection contacts, personal habits, and other exposure
factors both known and unknown.  In the end, infection assault
differences insure that _some_ unlucky, highly-infection-exposed
people manage to contract opportunistic infections when only
mildly immune compromised (though these are rarely fatal).  By
contrast, the same assault differences insure that _other_ people
who are badly immunologically impaired may escape opportunistic
infections for an amazingly long time, simply by missing the
microbes which can kill them.

   When it comes to immune function, then (what we are interested
in with AIDS), it is better to have a direct test which is not
subject to uncontrolled variables, such as which microbes happen
to be in the air or drinking water, and how many.  We would like
a more direct test.

    Such a test exists.  Quite early in the history of AIDS, it
was found that the immune defect in this disease is peculiar, and
that it most visibly involves a particular kind of cell in blood
and lymphatic tissues (lymph "nodes"), called "T-lymphocytes."
In the syndrome of AIDS, certain T-lymphocytes gradually disapp-
ear from both blood and lymph tissues, and a simple T-lymphocyte
count in the blood can tell how serious the reduction has been in
both places (since blood lymphocytes come from the lymphatics).
The arm of the immune system which is controlled most directly by
T-lymphocytes (the body's defense against viruses and fungi) is
what is most defective in AIDS, and viral and fungal infections
are (not surprisingly) the main opportunistic infections which
appear and cause death in AIDS.

     AIDS is so specific in its attack that scientists eventually
found that only one _subset_ of T-lymphocytes was initially
hardest-hit.  This was the so-called CD4+ or "helper" T-lymphocy-
te, which has the job of stimulating the immune system.  The
other major type of blood T-lymphocyte, the CD8+ or "suppressor"
lymphocyte, is involved in shutting the immune system down; in
AIDS, CD8+ lymphocyte blood numbers increase early in the
disease, and are not decreased until near the very end of the
disease process, when they may also disappear.

[See appendix: "What is a CD4+ Lymphocyte"].

    CD4+ lymphocyte blood counts tell much of the story in AIDS
and other immunodeficiencies involving the T-lymphocyte immune
system.  A healthy adult might have a CD4+ lymphocyte count of
800 to 1000, with a CD8+ count half of this.  These are normal
values.  Under physical stress, injury, or chronic infection,
CD4+ lymphocyte count might drop to 500 (to even less than the
CD8+ count), and mild, non-fatal opportunistic infections might
be the result.  A CD4+ count less than the CD8+ count was once
used as a crude marker for AIDS, but today with progress we know
that this immune state is non-specific.  In AIDS, things eventua-
lly become much worse than this, and the worse things get, the
fewer possible other causes besides AIDS there are for the

   In full-blown AIDS, as defined by opportunistic infections and
other problems, the CD4+ count is usually below 200.  It is at
such count levels that Kaposi's sarcoma (a tumor perhaps caused
by a virus) and life-threatening infections begin to appear,
although approximately 95% of AIDS patients survive beyond this
level of decline [2].  Another feature of AIDS, however, is that
inevitably the count grows worse over time.  Today, in the modern
era of antibiotics and more knowledgeable care, 85% of AIDS
patients live to see their CD4+ lymphocyte count drop below 50,
which is also near the average point at which most AIDS patients
in the modern era now suffer their first opportunistic infection
[3].  Famous AIDS sufferer Kimberly Bergalis, for instance, had
her CD4+ count drop to 41 before her disease was discovered [4].
Many AIDS patients today go all the way to CD4+ counts of zero
before the inevitable final infection or other complication.  It
is because of the implacable and more or less irreversible loss
of vital T-cells that AIDS remains a fatal condition, with an
average time of less than two years between the first opportunis-
tic infection and death.

    If we wish to define AIDS in terms of immune failure, the
essential question is this: where do we draw the line, so as to
include almost all people with the new immunodeficiency epidemic,
who are going to die from it, but exclude everyone else?  If we
simply define "immune deficiency" as a CD4+ lymphocyte count of
less than 200 (where death begins to become more likely), we will
capture about 95% of people who die of what the CDC now defines
as "AIDS" (Fig. 1b).

    Previous to the epidemic of AIDS, of course, people did die
of immune failure with low T-lymphocyte counts (including low
CD4+ counts) for other reasons, and they continue to do so now.
Thus, we must also exclude from our AIDS definition all those
people who have one of the classic reasons for a very low T-
lymphocyte count-- reasons which were well-known before the AIDS
era (cancer, malnutrition, tuberculosis, radiation, chemotherapy,
etc).  These people don't have AIDS, because the historical
epidemic of AIDS consisted of people with no T-lymphocytes for no
other known reason.  These people had appeared (more or less)
newly on the scene in the 1980's with evidence of a fatal kind of
immune failure which was _acquired_, meaning that it was an
epidemic problem of something "picked up" by previously healthy

   So let us simply collect all the people we can find with
sustained CD4+ counts below 200 without known reason, and test
them for HIV.  When we do, we find that almost all are HIV
infected, and any who aren't, don't look at all like typical AIDS
patients (as we will see).  This, despite the fact that only 0.3%
of the general population of the U.S. carries the HIV virus,
giving a huge population free of this virus which should still be
at risk for any other causes of severe immune problems.  Thus, at
this point we have no evidence yet to directly contradict the
simple theory that HIV causes almost 100% of our conservatively
defined "AIDS."  In fact, things are looking quite suspicious for

AIDS Heresies,  Part 2

_Enter the Critics_    Not everyone will agree to use the above
definition of AIDS, of course.  Before we go further, we will
introduce two major critics of the HIV/AIDS hypothesis.  Both are
scientists who hold Ph.Ds.  Neither one is a physician.

[See Appendix: "Two Critics: Duesberg and Root-Bernstein"]

   The view that HIV plays no role in AIDS has been most notably
put forth by Peter H. Duesberg, a molecular biologist spe-
cializing in a group of viruses which are related to HIV.
Duesberg's view, promulgated since 1987, is that HIV is harmless
and has no causal role in AIDS, and that AIDS instead is caused
by drug use and by immunosuppressive blood products (page
references to Duesberg's views will be from his major 1992 paper
on the subject, and to a recently published book by Ellison and
Duesberg [5]).

    At the other end of the skeptic spectrum are hybrid
arguments raised by Robert Root-Bernstein, an associate professor
of physiology and author of _Rethinking AIDS_ [6], the most
carefully-documented work to yet assail the prevailing medical
views on HIV and AIDS (Root-Bernstein references will be given in
the form of a page reference from this book).  Root-Bernstein is
less radical than Duesberg, arguing for a somewhat less central
role for HIV in AIDS than is generally given it, but still
allowing for the virus to have some part in the etiology of the

    Since Duesberg's original challenge, which has been the cause
of much formal debate in the literature [7], a number of
scientists, physicians, and lay persons have taken up the cause
for a "re-appraisal" of the idea that HIV is THE major causal
factor, or even _one_ of the major causal factors, in AIDS.  Most
respectable is an organization called "The Group for the Scienti-
fic Reappraisal of the HIV/AIDS Hypothesis," which has collected
over 300 signatures of physicians and scientists, including those
of Nobelists Walter Gilbert and Kary Mullis.  This group has
campaigned to remove the requirement for HIV infection from any
medical definition of AIDS, feeling that using this criterion is
at best premature, and prejudices any hunt for alternative
explanations for the disease.

    Almost all critics of the AIDS/HIV hypothesis have one thing
in common: they insist on using a much broader definition of AIDS
than we have proposed, a definition which virtually guarantees
that some people who fit the critics' "AIDS" definition will
_not_ be HIV infected.

    To be fair, there is some historical precedent for using a
definition of AIDS which relies solely on the patient developing
certain of the most serious and specific opportunistic infectio-
ns, since this was the way the disease was diagnosed before HIV
testing became available in 1985 (Fig. 1d).  Today we know that
almost all such people with pre-1985 defined "AIDS" are infected
with HIV---indeed this was known in late 1983, before the
official announcement of viral cause was made the following year.
But today we know this figure would not quite be 100% [13].  As
we will see below, there is evidence that the few HIV-negatives
in this group will be people with lesser degrees of immune
suppression (higher CD4+ counts), who will _not_ progress to
worse immune function, or quickly die.  It seems reasonable,
then, with what we know today, to simply exclude them-- since we
know that this is not the characteristic picture of AIDS.  Again,
it is most reasonable for our purposes to diagnose AIDS on the
basis of immune function (CD4+ levels) only, since it is immune
function, not infection status, which correlates with prognosis
in CD4+ immunosuppressed people.

   The critics, however, will have none of this, and in their
definitions are seemingly less interested in clinical utility
than they are in collecting ammunition for an argument.  The more
broadly AIDS is defined, the more "HIV-free AIDS" cases critics
can assemble, and these can in turn be used as evidence to the
lay public that HIV cannot be the cause of "AIDS."

    Duesberg, for instance, has insisted upon retaining the early
1980's observation that a CD4+/CD8+ lymphocyte count ratio of
less than 1.0 is often seen in AIDS, and he has decided that such
a ratio, even in the absence of opportunistic infection, is
synonymous with AIDS (Duesberg, p. 260).  Duesberg now calls this
ratio an "AIDS-defining immunodeficiency," and counts people with
this lab result as part of "HIV-negative AIDS," in his shocking
and too-often repeated statistic that there are "3000 documented
HIV-free AIDS cases" [8].  Here again, Duesberg's chosen definit-
ion of AIDS is less than useful epidemiologically or clinically,
because people with such mild immunosuppression as he uses to
define "AIDS" are not the people who are dying, or are shortly
destined to die (as will be made clear below).  AIDS is nothing
if not a fatal epidemic, and insisting that mildly compromised
persons who may or may not eventually get any worse be labeled as
having "AIDS," as Duesberg routinely does, only serves to confuse
the issue (Fig 1e).

    Perhaps following Duesberg, there is a general trend for
HIV/AIDS skeptics to overdramatize levels of immune deficiency
which are not clinically very significant.  For example, Root-
Bernstein (p. 262), in characterizing a study of HIV-negative
(HIV infection free) men newly infected with CMV virus, notes
that for a time, some of the men had CD4+/CD8+ cell ratios of
less than 0.4, a figure which he claims "represents extreme
immune suppression."  It would take a medically sophisticated
reader to know that in AIDS this ratio would typically be far
less than 0.3, and thus these men would not be mistaken for the
current CDC immunological definition of AIDS, even if they were
HIV-positive.  The reader would also need to know that the level
of immunosuppression associated with a ratio of only 0.4 is not
associated with significant risk of death by opportunistic
infection.  Such a reader might wonder how we are justified in
calling a ratio of 0.4 "extreme immune suppression," if people
rarely die from it, as they are known to do in AIDS.  Root-
Bernstein does not say-- indeed, does not even raise the issue.
An tendency toward overdrawn interpretation of the clinical
significance of lab results, is one of the places in which the
absence of medical training in the chief HIV/AIDS skeptics shows
most clearly [9].

    Duesberg's paper [5] and Root-Bernstein's book [6] each
contain descriptions of groups of HIV-free people who are
somewhat immunosuppressed due to low CD4+ counts, but not
severely so, as defined by our straightforward criteria of having
a significant risk of infectious death due to T-lymphocyte loss.
These immune deficient patients in HIV/AIDS skeptic literature
are presented along with the inference that perhaps somewhere
there exist people with these immune suppressive factors, or
combinations of them, who are _severely_ permanently T-lymphocyte
immunosuppressed (as AIDS patients generally are), and yet still
without having HIV.  Duesberg and Root-Bernstein only have one
difficulty in this argument-- neither has been able to actually
_find_ more than a handful of such people in a country where AIDS
sufferers infected with HIV have passed through this clinical
phase by the hundreds of thousands [9].

_HIV-Free AIDS?_   Hypotheses may be disproved by the right data
with relative ease, and cases of HIV-free AIDS would disprove the
idea that HIV causes AIDS, in proportion to how often these are
found (i.e., if 10% of AIDS cases were HIV-free, this would prove
that HIV is not the cause of AT LEAST 10% of AIDS).   Thus,
Duesberg and Root-Bernstein aren't the only ones who have been
looking for HIV-free people who are badly CD4+ lymphocyte
immunosuppressed without any classic reason (i.e., good
candidates for HIV-free AIDS).  Very recently the CDC reported
that after a massive search it had only been able to find less
than 100 people without HIV infection across the country whose
CD4+ counts were, at one measurement, less than 300 (not quite in
the AIDS-class immunosuppression range of 200, but drawing
close).  This group of people, for ease of reference, was given a
special syndrome name: "ICL" (idiopathic CD4+ lymphocytopenia),
meaning "people with low CD4+ lymphocyte counts without a
medically-defined disease, or other known immunosuppressive

    Why wasn't ICL simply called "HIV-free AIDS"?  Sometimes it
is.  The 1987 and 1993 CDC AIDS definitions do allow for AIDS to
be diagnosed in the absense of HIV, and even with a negative HIV
test.  This requires certain infections and a CD4 count less than
400, and these things happen extremely rarely in the absense of
HIV (fewer than 1 in 1000 cases of AIDS are tested for HIV and
found repeatedly negative).   Critics have darkly suggested that
the reason "ICL" is not called AIDS, is simply a matter of
politics, but in fact there were problems with considering these
people as AIDS cases, which had nothing to do with AIDS politics
or the HIV theory.

    One difficulty was that two thirds of people labeled as
having "ICL" were found not to come from the AIDS risk groups.
They did not use illicit drugs, had not been exposed to blood
products, and had no evidence of sexual behavior which would have
exposed them to a special infection risk.  Thus, as we will see,
the most popular alternative AIDS hypotheses did not explain the
majority of these people _either_ --- a fact which did not keep
them from being mentioned in nearly every skeptical treatment of
the HIV/AIDS issue.  What the skeptics had forgotten (or hoped
their readers would not notice) was that the immune deficiency of
people with ICL did not seem to be _acquired_ in any obvious way
[10].  What justification was there, then, for calling it "AIDS"?
To call a disease "acquired" it is not enough simply to show that
it appears in adults without previous problems, for even some
genetic diseases do this (Huntington's disease).  A bona-fide
acquired disease must have evidence of an etiology which is not
genetic.  The classic epidemic we know as "AIDS" does.  Most ICL
does not.  The two syndromes are evidentally not the same thing,
even looking at them from basic epidemiology.

     Moreover, people with ICL were not only epidemiologically,
but often immunologically very much distinguishable from AIDS
cases:  their CD4+ lymphocyte counts swung widely in response to
infections and were often much higher than 300 (in contrast to
people with AIDS, whose CD4+ lymphocyte counts tend to stay low,
and heading on an ever-downward trend).  ICL people also often
had low total lymphocytes or low CD8+ lymphocyte counts, again
indicating that their type of immune failure did not make much
distinction between CD4+ and CD8+ lymphocytes, as AIDS always
does.  Clearly, these people did not belong to the classic AIDS
groups which began suffering with epidemic immune problems about
1980.  They are not part of the new phenomenon of AIDS, something
underscored also by the fact that, although suffering from
opportunistic infections, ICL victims did not even seem to share
the implacable death rate of AIDS [10].

   Searches for HIV-negative people who have AIDS-type severe
immune suppression have also been taken specifically within AIDS
risk groups.  Vermund reported in the United States Multicenter
Cohort Study that of the 2713 persistently HIV-negative homosex-
ual men in the study, who had had a total of 22,643 blood tests,
only one significantly immunosuppressed man (CD4+ lymphocyte
counts persistently less than 300) was found.  This man was
taking chemotherapy and radiation for cancer, and thus had a very
good immunosuppressive reason other than his lifestyle to explain
his lab results [11].  A similar review of another cohort of
homosexual and bisexual men found no persistently lowered CD4+ T
cell counts among 756 HIV-seronegative men who had no other cause
of immunosuppression [11].   Finally, in the San Francisco Men's
Health Study (a population-based cohort recruited in 1984) it was
found that among 206 HIV-seronegative heterosexual and 526
HIV-seronegative homosexual or bisexual men, only one had
consistently low CD4+ lymphocyte counts, and this man also had
low CD8+ T cell counts, suggesting that he had general
lymphopenia rather than the selective loss of CD4+ lymphcytes
characteristic of AIDS [11].  If these three studies are
indicative-- and there is no reason to think they are not-- then
most, if not all, male homosexuals with AIDS-range immune failure
are HIV-positive, since it has proved very difficult to find any
who are HIV-negative.

    Much the same seems to be true in IV drug users:  in a study
of 1246 HIV-negative injecting drug users in New York City from
1984 to 1992, for example, only 4 were found with CD4+ lymphocyte
counts less than 300 (if IV drug use per se was a major cause of
AIDS, the number should have been far higher).  In this small
group of 4 people, even though infected with multiple other non-
HIV viruses, and with a history of heavy drug use, immune
function was stable and without the steady decline in CD4+
lymphocyte counts over a time span of years which is characteris-
tic of all unselected HIV-positive cohorts [12].  A second study
by others found much the same result [12].  Thus, in these
studies also, the few HIV-negative people who could be found with
even near-AIDS range immunodepression, were _still_ not behaving
medically like people with AIDS.

    Studies of recipients of blood and blood products, and
household contacts and sexual partners of transfusion recipients,
also suggest that persistently lowered CD4+ cell counts are very
rare or nonexistant in the absence of HIV infection [12a].  So
far as we know, then, in the United States more than 99.9% of the
people who are a part of this new phenomenon of permanently very
low (and declining) CD4+s in high risk groups, have been infected
with  HIV. This does not prove that HIV causes AIDS, but it is
surely an important clue.

Why Not Merely Use the CDC Definition For AIDS, With HIV Taken

    A persistent suggestion by critics is that it would be proper
to use as an AIDS definition the current CDC definition (which
includes all HIV-infected people with a much expanded list of
infections and other problems), but with the HIV criteria
removed.  The problem with this suggestion is that definitions of
diseases are chosen by the CDC for maximum clinical utility, and
the HIV infection criteria in the CDC AIDS definition were not
put there only to insure that there would be less HIV-free AIDS.
Rather, HIV infection in a person with opportunistic infection is
known to be (alone among all other viral infections) a very good
predictor of whether immune status will continue to decay until
the person eventually succumbs to opportunistic infections.  In
people with mildly compromised immune systems, the prognostic
value of an HIV infection is large.  Even critics admit that the
prognostic value is large, without admitting causation.  Thus, we
cannot simply remove HIV status from the CDC definition and still
have the definition do what it was designed to do, which is
_predict_ impending death by immune failure.

    Critics know that if "AIDS" is defined only in terms of
today's much broader list of "AIDS-defining" diseases and
infections (which are meant to be used only in conjunction with
HIV status), it is sure to be quite true that the definition will
then become far too broad to be prognostic.  Such opportunistic
infections, as critics well know, sometimes happen occasionally
even without the most severe CD4+ immunosuppression which is
characteristic of people who die with AIDS.

    A study by Salvato illustrates this point [13].  In the
study, medical records covering 6 years for 1500 HIV-positive
patients were compared with records for 1000 HIV-negative
patients who had Chronic Fatigue Immunodeficiency Syndrome
(CFIDS) and evidence of immune suppression.  It was found that
the CFIDS patients had a syndrome much like that seen with early
HIV infection  -- fatigue, lymphadenopathy (swollen lymph
"nodes") and low grade fevers-- but that over the course of 6
years their problems were not severe.  Only one of them developed
CD4+ lymphocyte counts less than 300 ("ICL").  Still, two had
yeast esophagus infections, a severe opportunistic infection
rarely seen other than in AIDS, and other people severely
immunosuppressed.  Three had active CMV virus disease of various
tissues-- another disease very often seen in AIDS.  A total of
486 patients had evidence of yeast infection of the mouth on
exam, a condition suggestive of mild immune problems but one not
limited to AIDS.  The average CD4+ lymphocyte count in these
patients (not including the single ICL patient) ranged from
500-1400, with an average of 650.  This was significantly lower
than normal, but much higher than typical for AIDS.

    In this study, 95% of the HIV-negative patients had previou-
sly been infected with the EBV, CMV or HHV-6 viruses, and 48% had
evidence for continued viral infection (critics such as Root-
Bernstein have suggested that these viruses have roles in AIDS at
least as important as that of HIV, but this study provides
evidence against this idea).  Most interestingly, these immuno-
compromised HIV-negative patients were followed from 2 to 6
years, and none experienced progressive CD4+ lymphocyte decline
(except for the one patient with ICL, who, with treatment of CMV
infection, showed increased CD4+ lymphocyte counts again).  Such
CD4+ count stability is never seen in any random group of HIV-
positive people, where an average CD4+ count decline over time
would be inevitable.  The study authors' conclusion:

   "Even after a methodical search in a practice that sees a
large number of patients with immune problems, only 1 patient was
found to have ICL.  However, this study demonstrates that
patients with normal CD4 counts can develop AIDS defining
opportunistic infections [...] Upon long-term follow-up these
patients do not appear to experience progressive CD4 depletion."

    Most importantly, no HIV-negative person died in the study,
which illustrates the extent to which chronically virally
infected, immune-suppressed people can _approach_ the clinical
picture of AIDS, without crossing into the deadly long term
immune failure which is characteristic only of people with HIV

    The reader who is a bit confused at this point should keep in
mind simply that the most important thing about the syndrome of
AIDS (by any good definition) is that it inevitably and rapidly
destroys the immune system, and then kills people by means of the
infectious and other diseases they get as a result of having no
working immune function.  Thus, mild CD4+ cell depression and
opportunistic infections are not always AIDS, for only some of
these people (as it turns out, the HIV+ ones) will progress to
immune failure, and death.   It is immune failure (almost
complete CD4+ lymphocyte loss) and death by opportunistic
infection which is characteristic of AIDS; and it is only such
people who are almost _always_ HIV infected.

How and Where AIDS First Appeared

    The story of the detective hunt for the cause of AIDS is told
with wit and clarity by Randy Shilts (an author who in 1994, at
the age of 42, ultimately became a casualty of the disease
himself), in the best-selling book _And the Band Played On_.
Other good histories of the early AIDS epidemic are also availa-
ble [14].

    Historically, what happened in the U.S. in 1981 was that
homosexual men began presenting to physicians in increasing
numbers with very, very low CD4+ lymphocyte blood counts (but not
lowered counts for other subtypes of lymphocytes), a destroyed
immune system with lymphatic tissue destruction, opportunistic
infections, and Kaposi's sarcoma.   Almost no one who had treated
diseases in the male homosexual community could remember having
seen anything remotely like what had began happening on an
increasingly large scale in the early 1980's.

     The year 1981 was not (in retrospect) exactly when the
problem started, but rather when the problem first grew large
enough in the U.S. to be brought to the attention of the
federally-run Centers for Disease Control and Prevention (CDC) in
Atlanta.  It was in the Summer of 1981 that alert physicians
brought to the attention of the CDC a mini-epidemic of immunod-
eficiency and pneumonia caused by unusual organisms (A fungal
organism called _Pneumocystis carinii_, and a virus called CMV)
in homosexual men in Los Angeles.  Before the epidemic of AIDS,
there were only 50 to 60 cases of pneumocystis pneumonia reported
to the CDC per year, in the United States.  After ten years of
the AIDS plague, this number had risen to tens of thousands of
cases per year, and almost all of these in adults who had never
previously been targets for this organism.

     Because many of the first people to contract AIDS had had
sexual contact with each other, CDC researchers thought they
might be looking at an unknown sexually-transmitted infectious
disease.  They also toyed for a time with the idea that sex-
stimulant-chemical use or illicit narcotic use, both very common
among the first cases of AIDS, might be somehow causing
immunosuppression.  Perhaps sexual contact was a red herring-- or
merely a marker for a small and fairly tight-knit sub-community
of people who shared common interests in non-sexual activities
which might be damaging their immune systems.

   Those physicians treating infectious diseases in homosexual
men thought not, however.  Dr. Joel Weisman, one of the first
doctors to put the AIDS puzzle together, noted that initially,
within the male homosexual community, the disease seemed to
follow lines of sexual contact more than it did drug or sex
habits.  Not all homosexual men were so promiscuous as to make
contact-tracing impossible; Weisman observed that
promiscuous men did not always contract the disease, but on the
other hand, that even men with few sexual contacts were coming
down with the disease if they had had sexual contact with the
wrong person.  In fact, men with severe immunodeficiency were
eventually found to form sexual contact networks, of the kind
that have always been seen by researchers using the classic
epidemiologic tools for tracing sexually transmitted disease
chains.  The difference, however, was that for AIDS the contact
networks stretched over years, indicating an infectious agent (if
there was one) with a very long latency.  Still, investigators
found that of the first 19 cases of AIDS reported in Los Angeles,
9 had direct or indirect (one intermediate partner) sexual
contact with a single French-Canadian airline steward, a man who
was also sick with immunodeficiency.

    Then, starting in 1982, reports began to come into the CDC of
the same CD4+ lymphocyte and lymphatic-tissue-destroying immune
failure syndrome occurring this time in U.S. citizens who had
received transfusions.  Soon also came reports that an identical
immune deficiency of a new severe variety was now being seen in
men with hemophilia, a genetic disease in which sufferers must be
injected with concentrates of protein clotting factors made from
donated blood plasma.  Reports of the first people with hemophi-
lia and AIDS emphasized that, in these people, none of the same
drug or male-homosexual behavioral factors were present that had
been seen in the first group of AIDS sufferers [15].

   Further, the same was true of those with "transfusion-related
AIDS," who also did not fit into drug-using or male-homosexual
lifestyles, and did not resemble them in sex or age either.
Former tennis star Arthur Ashe is a well-known modern example.
Ashe, like many of those with transfusion-related AIDS, had never
had an intimate connection with anyone else with an immune
problem, EXCEPT for a history of a blood transfusions years in
the past, during the time in which transfusions were associated
with AIDS.

    In late 1982 all this worried epidemiologists as the reports
continued to come in.  They knew that another viral disease
called hepatitis B ("serum hepatitis") was also
transmitted epidemically as a sexually transmitted disease in
homosexual men, but much more rarely in homosexual women or
heterosexuals in the U.S.  Hepatitis B had historically also
shown up early in people with hemophilia, who because of their
large pooled blood-product exposure have historically seemed to
be first to suffer from any new organism infecting the blood
supply.  Hepatitis B had also been known to be one of the worst
disease-causing contaminants in donated blood for general
transfusion.  Thus, the same 3 groups of people who had
historically been infected with hepatitis B in the 1970's, had
now started coming down with AIDS.  Hepatitis B was also a
disease of IV drug users who shared needles, and it was not long
before the first reports of IV drug users with AIDS came in.

    By 1983, the CDC was sure it had a new infectious disease on
its hands, similar in epidemiology to hepatitis B, but with a
longer latency period.  Analysis of the habits of donors of the
blood components that were transfused into people who had later
developed AIDS, indicated one thing different about the donors:
it was found that blood products AIDS patients had received had
more often come from people who themselves were at "high-risk"
for AIDS due to promiscuous male homosexual behavior.  On the
other hand, matched case-controls who had been transfused
identically from the same blood bank but had _not_ developed AIDS
after transfusion, were found to be not nearly as likely to have
gotten blood components from anyone in a "high-risk group."

    This initial study concluded that there was only a 1% chance
that the statistical association of transfusion-associated AIDS
with the lifestyle of the blood-donor would be as close as it was
found to be, if only chance had determined the lifestyles of the
donors of blood to people who later became sick.  Such a chance
association would have been expected if there was no contamin-
ation, and instead there was something about normal transfusion
blood itself, or perhaps some other factor unrelated to trans-
fusion, that was causing AIDS in transfusion recipients [16].
The remarkable fact-- from which there was no escape-- was that
AIDS in a transfusion recipient PREDICTED the lifestyle of a
blood-donor he or she had never met (a donor which generally
turned out to be a promiscuous homosexual man who had thought
himself to be perfectly healthy).  Nothing but an infectious
agent (or more than one) could explain a statistical connection
between a blood donor's sexual habits, and risk to the person
receiving the blood.  As for drugs or immune toxins, it was
impossible to believe that any chemical toxin could be present in
a relatively small amount of blood component coming from a single
nominally healthy person, in sufficient quantities to cause total
immune failure in the recipient, and do it years after the

    Eventually, with many cases like Arthur Ashe's on record (but
showing up in the early 1980s, earlier than Ashe's did), AIDS
looked epidemiologically _very_ much like hepatitis B.  The hunt
was on for the microbe, or microbes, which caused the new
syndrome.  When the virus now known as HIV finally hit the world
news in the Spring of 1984, there was a great deal of skepticism
in the scientific and lay communities alike.  With the ability to
test for antibodies to HIV in 1985, however, there came a way of
powerfully sifting through putative causal factors for AIDS, and
comparing them with the factor of past HIV infection.  HIV
infection has emerged from these tests as the clear champion of
competing AIDS-causation theories, convincing at present all but
the most die-hard skeptics [14].

[See Appendix: "What is an Antibody? and What Does HIV-positive

AIDS Heresies, Part 3

The Skeptics and the History of HIV and AIDS

     But what if AIDS and immune failure are not really new--
perhaps (as some critics suggest) we just look harder for them
now that we recognize them?  Could our new theories be warping
our views so completely that by now that we have made a new
"plague" out of something that was here all the time?
Epidemiologically, what can we fairly say about the period before
1980, keeping this possible bias in mind?

     With the new ability to test old preserved tissue specimens
for HIV, the first thing that becomes apparent is that AIDS is
indeed older than 1981-- perhaps far older.  Deaths from what has
since been recognized as HIV infection with immune failure have
been seen clinically, without being understood, for at least 35
years, and probably much longer.  An HIV-infected British sailor,
who had traveled widely, was once thought to have died with
severe immune deficiency and HIV infection in 1959, the earliest
proven case of modern AIDS.  The diagnosis was made by means of
preserved autopsy tissue specimen HIV testing, 30 years after the
fact, although this case is still not without controversy.  [Note
added in Jan. 1996-- this case has finally been disproven.
Apparently reports of this man's tissues containing HIV were in
error, see ref 17].

     This man's death alone would have provided good evidence
that HIV is not a product of deliberate genetic engineering, for
in 1959 biologic science was simply too unsophisticated to work
with lymphotropic (lymphocyte-infecting) retroviruses like HIV,
let alone engineer them [103].  HIV appears still to be an
accidental infection of humans with an African primate virus, if
it is anything at all. The genetic material of the most common
HIV-1 strain is most similar to that of a virus known to natura-
lly infect chimpanzees, and it may be that HIV's ancestors have
been present in Africa, perhaps even in humans, for a very long
time-- perhaps thousands of years [18, 121].  In West Africa, a
close cousin of the U.S. HIV-1 strain, called HIV-2, is almost
identical to several indigenous African monkey viruses, and
almost certainly has been derived from them quite recently in
virus evolutionary time (less than several centuries).

   In the U.S., AIDS-like deaths have been reported as far back
as 1934, as Root-Bernstein notes.  The first AIDS or AIDS-like
death that we believe could have been associated with HIV infect-
ion was that of a 17 year-old possibly homosexual male, who died
of strange opportunistic infections in St. Louis in 1968 [19].
This early AIDS-sufferer had never been out of the country,
showing that the virus was already active in the Western Hemisph-
ere in 1968. Unfortunately this case is the clearest on record,
and even it has not resulted in recovery of HIV DNA sequences
(which would provide absolute proof).  Some reports of early HIV
are frankly errors: for instance a 4% fraction of preserved serum
samples from IV drug users in this era (1971-2) in the U.S.,
found to be "HIV-positive," were apparently false-positives as
shown by later followup [20].  It is possible that HIV viral
infection has been present in small contingents of both drug
users and homosexual men for some time in the United States, but
the case has yet to be absolutely proven.

    Let us suppose that preserved specimens finally show that HIV
was present in America long before the late 1970's.  Why, then,
was the U.S. first hit with an AIDS epidemic only in the 1980's,
with HIV infection quickly rising to 50% in some risk-groups?
The answer may be that if it was not the simple presence of HIV
virus in the United States that changed, perhaps it was the
social milieu.

    In the late 1960's drug use became far more widespread in the
U.S., and the invention of the disposable plastic injection
syringe about 1970 made IV drug abuse possible for the first time
on a large scale.   Also beginning around 1969 (the date of the
New York City "Stonewall riots"), homosexuals in the U.S. began
to take open political power, and concomitantly one faction of
male homosexuals began to engage in the high-infection risk
"bathhouse lifestyle" chronicled by Shilts.  In addition, the
American homosexual-male community was apparently many times re-
infected by many world-traveling disease "vectors" from other
countries in the 1970's, including the previously mentioned
airline steward (described in Shilts as the CDC "patient zero")
who traveled widely in Europe, Canada, and the U.S., died of
AIDS, and is known to have had sex with no less than 40 of the
first 248 Americans to be diagnosed with AIDS by April, 1982

   What happened in the late 1970's in the U.S. is that when a
large enough fraction of the American homosexual-male population
became infected with HIV, the U.S. blood supply, maintained with
volunteer donations only, finally became contaminated with the
virus. (This started in 1978, as we know from later testing of
archived serum samples taken from homosexual men originally for
hepatitis B studies).  Similar archived samples tell us that in
1978 the U.S. plasma supply used to make clotting factor for
hemophilia treatment became HIV contaminated, no doubt primarily
by IV drug users selling plasma to support a drug habit.  The
dates are not coincidental-- a crossover between initial HIV
infected groups occurred as some homosexual men experimented with
IV drugs in the late 1970's, and male IV drug users in large
cities turned to homosexual prostitution in order to obtain
drugs.  The resulting new epidemic of transfusion and hemophilia-
associated AIDS, beginning in 1982 and rising sharply in 1984,
helped to bring the acquired nature of AIDS into focus.

    The small incidence of AIDS in the American homosexual-male
and IV drug-user communities before the late 1970's in no way
subtracts from the reality of the dramatic increase in AIDS which
took place in the early 1980's on the heels of exploding HIV
infection rates in these groups.  Although relatively mild immune
suppression has apparently always been widespread in many AIDS
risk groups, the more complete and deadly immune failure
characteristic of AIDS itself has been sporadic and very rare in
young cancer-free people in any of these groups, until the 1980s.

     It is, to be sure, difficult to retrospectively evaluate the
health of male homosexuals before the first prospective studies
of gay men's health were done in the 1980's AIDS era, but we can
be reasonably sure that an epidemic of deadly immune failure
among young American men before 1980 would have been duly noted
by epidemiologists.  The HIV/AIDS skeptic Root-Bernstein docume-
nts a few cases of unexplained opportunistic infection deaths
from the medical literature before 1980, but clearly an epidemic
of immunosuppressive deaths cannot be seen in the historical
record before 1980 by any act of imagination.

     By contrast, at present "AIDS" (a new epidemic of
immunodeficiency deaths) shows a high and rapidly rising incide-
nce among young men and women in the U.S., and these deaths
cannot be simply a new label for an old problem.  The reason is
that _total_ mortality and cumulated years of life lost to
premature death in young persons are observed to be rising
rapidly, with all of the change due to "AIDS" deaths, _at_ _the_
_same_ _time_ other leading categories of mortality remain
stable.  If mere re-labeling of deaths into different categories
was a problem, these "newly recognized" AIDS deaths would come
out of other previously defined mortality categories, and this
clearly isn't happening [21].  AIDS, the disease, may be old, but
AIDS, the epidemic, is indeed something new.

[See Appendix: "Hemophilia and Life Expectancy in the 80's"]

   People with hemophilia, unlike homosexual men, represent a
well-defined group with long-term documentable changes in
morbidity and mortality, since they had been well-studied as a
group before the era of AIDS.  This research shows that people
with hemophilia began to die of dramatically different things,
starting about 1982 [22] See Fig 2.  A recent check shows little
evidence of a special incidence of opportunistic diseases in
people with hemophilia in the U.S from the turn of the century up
to 1979, although a low incidence of AIDS could not be ruled out
in this study, mostly because some cases of fatal pneumonia had
no identified infecting organism [23], and because people with
hemophilia as a group are immunosuppressed enough to be somewhat
more susceptible than normal to bacterial infections.  Signifi-
cantly, however, in the years before AIDS, people with hemophilia
had never been noted to be particularly susceptible to the more
obvious _fungal_ infections, such as candida esophagitis, common
to AIDS patients and others with low-lymphocyte type immune
deficiency.  After 1984, however, this type of AIDS-associated
opportunistic infection and immune failure rapidly became the
single most common cause of death in people with hemophilia in
the U.S. [24].

     The rise in total mortality risk in people with hemophilia
was sudden: total mortality in this population, which had been
stable in 1982 and 1983, suddenly increased by a factor of
approximately 900% in the first quarter of 1984 [25].  Such an
increase in raw numbers of deaths was consistent with an epidem-
ic, or some new very toxic contamination of the clotting factor
supply.  It is not consistent with slower social changes, slower
toxin or immune suppression models, multifactorial causation
models, or the idea that people with hemophilia were actually at
no greater risk than before (i.e., that again perhaps there had
been some kind of "cause of death" re-labeling in response to
AIDS hysteria).   Mortality figures in hemophilia patients also
showed something else important, which was that the new deaths of
the late 1980s, by virtue of all being judged "AIDS," demonstra-
ted that most or all of them occurred in people with hemophilia
who were HIV-positive.  Since these deaths accounted more or less
for the entire new increase in mortality, it could be inferred
that the mortality rate for HIV-negative people with hemophilia
did not increase much in the 1980's, if at all.

   How significant was the increase in death rate for HIV-
positives in this group?  In one _Journal of the American Medical
Association_ study it was found that in a cohort of 111 people
with hemophilia infected with HIV in the early 1980's, one third
had died by 1992 [26].  The reader is asked to imagine any group
of this age (a high school class, perhaps) and imagine an overall
33% mortality rate in less than 10 years.  Of the estimated
10,000 people with hemophilia to have been infected with HIV in
the early 1980s in the United states, a quarter had been reported
to the CDC to have died of AIDS by July of 1993.

    Such death rates were especially shocking in view of strides
in hemophilia treatment which had been made in the years before.
Total life expectancy in people with hemophilia had risen as
clotting factor treatment became available through the 1970's,
until by 1980 it was nearly normal [23].  After 1984, however,
life expectancy in this group began a steep decline, and by the
early 1990's was at a lower level than at any time since before
World War II [24].  In the 1980's, total mortality for hemophilia
increased in all age groups above 9 years of age, and age at
death shifted markedly to lower ages, decreasing from 57 years of
age in 1979-1981 to 40 years of age in 1987-1989 [27].

    About 50% of people with hemophilia in the U.S. had been HIV
infected by early 1986, when screening and treatment of the
clotting factor concentrate stopped HIV spread [28].  Still, the
long latency of the virus (as long as 15 years for 50% progress-
ion to AIDS in this group) caused death rates to rise for long
after the window of new HIV infection closed (they are still
rising as of this writing, although clinical AIDS or severe
lymphocyte loss (ICL) has yet to be reported in children with
hemophilia born after 1986).

    The fact that there was a massive and silent HIV infection of
half of the people with hemophilia in the early 1980's is beyond
question.  The HIV/AIDS skeptics' quest to divorce this event
from the epidemic of deaths by AIDS in this same group over the
next decade has resulted in some remarkable and curious stateme-
nts about hemophilia mortality.  Duesberg, for instance (p. 216)
quotes only older statistics for hemophilia patients from the
pre-1986 period, before AIDS deaths became very large. His
practice of using randomly reported AIDS and mortality data for
people with this disease (which is often notoriously unreliable
in the best of circumstances [29]) instead of the much more
reliable cohort study data, also results in figures which
minimize the impact of AIDS.  Cohort data shows mortality in
hemophilia patients to be far higher than Duesberg acknowledges

     Duesberg has not been alone in ignoring major trends in
hemophilia mortality in the last decade.  The very misleading
statement that people with hemophilia are living "longer than
ever" today is one of the standards among the HIV/AIDS skeptic
community.  Root-Bernstein does no better than Duesberg at
providing updated information in this area, offering one paper's
1979 pre-AIDS statistics [23], without update and without qualif-
ication, to represent _contemporary_ life expectancy in people
with hemophilia in 1993 (p. 247).  This represents very sloppy
scholarship (something which stands out particularly in Root-
Bernstein), but the oversight does allow the author to skip
discussion of the pronounced and otherwise awkward peak in life
expectancy for hemophilia in the middle 1980's.

    Duesberg, though he seems to believe that people with
hemophilia have suffered no mortality increases in the age of
AIDS, does suggest that people with hemophilia live longer than
ever due to recent factor concentrate development, and thus live
long enough to die of immunosuppression caused by longer treatme-
nts with clotting factor concentrate, instead of from hemophilia
(Duesberg, p. 220).  Although clotting factor does indeed appear
to be mildly immunosuppressive (albeit in a different way than
AIDS-- see appendix hemophilia section), the main problem with
the hypothesis that clotting factor itself causes AIDS is that
two studies of HIV-positive people with hemophilia have found
that HIV infection and not clotting factor use is the critical
risk for AIDS.  These studies found that once a person is HIV-
positive, risk of AIDS is _not_ related to amount of clotting
factor used or severity or type of hemophilia---effects that
would have been expected if clotting factor carried a significant
immune risk independent of its HIV content [31].  Available
statistics thus strongly suggest that the known association of
clotting factor use and AIDS risk is merely due to the increased
risk of being infected with HIV the more clotting factor has been
consumed; once HIV infection has occurred, it doesn't matter how
much clotting factor is used.

Can a Viral Epidemic Explain the Historical Timing and
Epidemiology of AIDS?: Attacks on Straw Men.

    It is an unfortunate fact that a great deal of the debate
over AIDS and HIV has been over what rhetoricians call "straw-
men."  A straw man is an argument or viewpoint set up in a debate
only for the purpose of being knocked down, and one which the
opposite side never really defended or held; or one which is not
very important to the central issue of the debate, even if it
_has_ been held.   Straw man arguments often result from debaters
talking "past each other," without understanding the opposing
side's position (straw man arguments may also, of course, be used
deliberately solely for rhetorical purposes-- a practice genera-
lly considered beneath respect in scientific debates).  In the
HIV/AIDS debate, straw men set up by heretics have most often
been medical hypotheses which have previously been put forth in
the context of the HIV theory and which have turned out to be
wrong, but which were never important corollaries necessarily
deduced from the idea that HIV causes AIDS, or were in other any
other way central to it.  Other straw men are ideas that the
orthodox scientific "establishment" never put forth seriously at
all, though they may be attacked vigorously by heretics as though
they are current medical dogma.  We will presently see samples of

   An example of an epidemiologic straw man is the timing of HIV
arrival in the Western hemisphere.  Root-Bernstein discusses
cases of possible AIDS as far back as 1932, notes documented HIV
infection with AIDS as far back as 1968 in the US, and argues
that these data are anomalous (p. 2) if the virus was transferred
for the first time to the Western hemisphere around 1978, as was
originally thought (and which is the "just-so story" told by
Shilts).   And so they are.  But if the HIV virus was transferred
much earlier than 1978 to the new world, and remained at low
levels in male homosexuals and injecting drug users in America
until changing social factors in the 1970's encouraged its spread
(exactly as Root-Bernstein himself indirectly suggests), no real
damage would be done to a suitably modified HIV/AIDS theory.

    An example of a bad prediction made by the orthodox medical
establishment which is not necessarily derivative of the HIV
theory, was (or is) the official idea that AIDS is due to be a
heterosexual pandemic in America _any_ _time_ _now_.  It is
argued by Duesberg (p. 203), that the "viral hypothesis" has
failed to predict the course of the AIDS epidemic-- namely that
AIDS has (at least so far) shown no clear inclination to spread
rapidly by a complete heterosexual-sexual-transmission mechanism
in the U.S., even though it apparently does so in Africa.  It is
also asserted in a related argument by Root-Bernstein that the
HIV/AIDS hypothesis does not explain the generally-low measured
levels of HIV virus in semen, the low (but not zero) rate of HIV
infection in mates of HIV-positive men with hemophilia, or the
nearly zero rate of infection in U.S. heterosexual prostitutes
(unless they are drug users).  If AIDS is an infectious disease,
ask the critics, then why doesn't HIV infect very well?

    All these arguments are against straw men, so far as the
cause of AIDS goes.  There is nothing in the HIV/AIDS theory
which demands that any particular transmission mechanism be the
chief cause of the spread of HIV infection in any given place, or
which demands that the HIV virus be as infectious in one locality
as another.  For example, it now seems likely from many studies
that efficient sexual transmission of HIV requires mucosal tissue
trauma, which is much more likely with anal intercourse, and/or a
concomitant inflammation or ulcer from a second sexually transmi-
tted disease.  Because transmission may be inefficient even so,
promiscuity also greatly enhances the chance of HIV spread.
These requirement(s) for efficient HIV sexual transfer easily
explain the difference between spread of HIV in tropical Africa
vs. the developed counties.  They also adequately explain why a
disease which spreads well sexually only in populations with an
extreme level of both promiscuity and rectal mucosal trauma
(i.e., one sub-segment of American homosexual men) has not yet
become a generally spreading epidemic in the U.S.

   It isn't that the HIV/AIDS heretics haven't come across such
explanations.  Root-Bernstein, in a good discussion of the
epidemiology of AIDS, admits that there is nothing especially
strange about a sexually transmitted disease which spreads easily
in homosexual males but not heterosexuals.  Both syphilis and
hepatitis B in the 1970's have been examples of such a phenomen-
on, and the "odd" differential epidemiology of both diseases with
regard to sexual-preference groups is easily explained by
differential _behavior_ in the homosexual and heterosexual
populations in those years.

    Thus, Duesberg argues that a disease which restricts itself
to classes of people in America, but not in Africa, cannot be
explained by a micro-organism.  But while he is doing so, fellow
heretic Root-Bernstein (pp. 281-303) is noting that infectious
epidemiology in one group of American homosexual males (who may
have ulcerative sexually transmitted diseases and in addition be
sexually infected with giardia, parasites, amoebas, hepatitis A,
and B, shigella, salmonella, etc.), may resemble far more the
disease epidemiology of some African countries than that of
heterosexuals living next door (p. 290).  In this, an AIDS caused
by an infectious agent such as HIV may behave just as AIDS
statistics suggest it does, and yet merely follow a pattern
already amply demonstrated before AIDS, with many another
infectious disease.  Root-Bernstein is sometimes too competent a
scholar for his own good:  his Chapters Eight and Nine-- which
address the epidemiologic differences and commonalities of U.S.
homosexual men and African heterosexuals due to sexual practices
and social changes which appeared newly in the 1970's and 1980s--
not only believably explains and refutes most of Duesberg's
epidemiologic problems with AIDS (Duesberg, p. 209), but also
does the same with many of Root-Bernstein's own epidemiological
problems, raised in Chapter One.

    Unfortunately, Root-Bernstein is willing to let lifestyle and
habit differences explain epidemiologic differences when it suits
his argument's needs, but much less willing to consider them when
they don't.  An illustrative example occurs as Root-Bernstein
discusses the rectal traumas and infections which occur during
certain male homosexual practices, writing of these (p. 283-4):

   "It is now accepted that such injuries and infections greatly
increase the risk of con-current infections (HIV or otherwise)
and of semen gaining access to the immune system following anal

   Yet when Root-Bernstein discusses the statistical association
of AIDS with receptive anal intercourse (p. 225) he shows an odd
difficulty with the same concept:

   "One possibility is that it is much easier to transmit HIV to
a receptive partner than from a receptive partner.  No other
sexually transmitted disease behaves this way, however. [...]
HIV would be the first disease agent to be able to make the
discrimination, unless some other factor is involved."

    Here, unfortunately, Root-Bernstein is wrong, and wrong for
the very reasons that he himself discusses in the quote
preceding the last.  Much like HIV, hepatitis B infection in
homosexual men _also_ correlates with rectal trauma and receptive
anal intercourse [32], and there is little reason to believe that
the "other factor" is anything other than the fairly straight-
forward mechanical injury that Root-Bernstein has already
helpfully identified for us (see [33] for statistical development
of a "rectal trauma index" which partly predicts risk of HIV
infection).  It is a characteristic of Root-Bernstein's style of
argument that it makes causal mechanisms as mysteriously complic-
ated as possible-- very often far more complicated than required
to explain the facts.

    Here is another example of Root-Bernstein's difficulties with
simple explanations: The known fact that HIV is difficult for an
asymptomatic HIV carrier to transmit to another person by needle
stick, or by heterosexual contact between married couples, does
_not_ necessarily argue for the need for additional unknown co-
factors or immune suppression in the more common cases of HIV
transmission.  Low infection rates for needle sticks may just as
easily be explained by the known fact that virus blood levels in
"healthy" HIV-infected people are low.  Similarly, the known fact
of low HIV infection risks during some kinds of heterosexual
intercourse similarly admits to several interpretations, but one
which requires no additional hypotheses is surely (and simply)
that certain kinds of _homosexual_ behavior are more dangerous
from an infection transmission standpoint (as discussed above) by
their very _mechanical_ nature, without need to resort to the
dubious and insupportable idea that the individuals who practice
them must also be grossly immunologically compromised for HIV
infection to occur.

     Root-Bernstein, eager to draw attention to any factor other
than HIV in the causation of AIDS, does not take into account the
most obvious physical factors.  "...what is clear from existing
studies," he asserts (p. 45), "is that HIV is extremely difficult
to transfer to a healthy individual."  In fact, existing studies
establish no such thing.  Studies quoted by Root-Bernstein never
demonstrate that only "unhealthy" people in known risk groups
contract HIV, only that certain traumatized risk groups
(promiscuous gay men, hemophiliacs, transfusion recipients) are
_on average_ somewhat unhealthy to begin with.  This, of course,
is not the same thing.  Indeed, there is evidence that within
risk groups, even the healthiest of individuals (immunologically)
are capable of contracting HIV. Although men with hemophilia and
homosexual men are on average mildly immunosuppressed even in the
absence of HIV, it is by no means true that all are.  A study of
army recruits (surely a carefully screened group for health)
shows that those who seroconvert to HIV (demonstrating HIV
infection) may initially (by the criterion of CD4+ count) have
immunity which is in the normal range.  This is true in other
groups as well [34].

    Perhaps the most bloated straw man assailed by Root-Bernstein
(and the one that provides the major theme of his book) is the
idea that the causal agent of an infectious disease such as AIDS
must be both _necessary_ and _sufficient_ to cause the disease in
every sense of the terms; and moreover that since Dept. of Health
and Human Services Secretary Margaret Heckler's dramatic announc-
ement in 1984, most scientists have considered HIV to play this
very role for AIDS.  Root-Bernstein spends much time attacking
what he calls the "HIV-only" theory of AIDS, an idea which
actually has never flown, except possibly in the popular press or
(at worst) occasionally when some scientist expresses a rash
opinion without considering his formal training.  (Dr. Robert
Gallo, official co-discoverer of HIV, must by now badly regret
his remark about HIV being able to cause AIDS in Clark Kent [35];
but this is hardly the N.I.H. official position).  The subtitle
warning of Root-Bernstein's book is _The Tragic Cost of Premature
Consensus_, and it appears from the book that it is upon the
"HIV-only" theory of AIDS that the "premature consensus" of the
establishment is in dire danger of settling, if it hasn't

   Fortunately, it can safely be said that no such thing is
occurring in the biomedical consensus, or about to.  This does
not prevent Root-Bernstein (p. 331) from logically blasting the
somewhat cartoonish view he attributes to medical science:

    "Two of the most important implications of the HIV-only
theory of AIDS are that all the risk groups should develop AIDS
at approximately the same rate following HIV infection and that
the symptoms they manifest should, on the whole, be the same."

    Alas for Root-Bernstein, however, since AIDS has from the
beginning involved opportunistic infection organisms which vary
in prevalence among populations, and since there has been reason
to believe from the first that AIDS risk varies greatly with the
biological _age_ of the HIV-infected person, scientists have
never, even at the beginning, seriously considered such a theory
as Root-Bernstein here lays out.

    "One logical implication [continues Root-Bernstein] is that
the immunological status of an infected person should be
irrelevant to susceptibility to contagion or to the progression
from infection to disease.  Acquisition of the retrovirus should
be the sole factor determining whether an individual develops
AIDS.  Everyone should be at equal risk for AIDS, just as
everyone is at equal risk for hepatitis B virus, syphilis, or

    The most troubling thing about such writing is that an unwary
lay reader may leave Root-Bernstein's book with the impression
that the author has single-handedly discovered that infectious
disease risks depend partly on host immune defenses and host
behaviors and environments.  The reader might well decide further
that the biomedical community today does not in general think in
terms of individuals having differing resistances to various
diseases, and is accepting such advanced ideas only under duress,
due to political pressures resulting from the penetrating logic
of popular writers such as Root-Bernstein who are "re-thinking

    The facts are more mundane.  Obviously, since no microbe
infects 100% of people exposed to it, or even causes disease in
100% of the people it infects (not even HIV has been shown to do
this), there must be other factors to explain why some exposed
people become ill with ANY infectious agent (viral, bacterial or
parasitic), and some do not.  Medical science certainly recogni-
zes such factors, but does not use them to argue that there is in
general something badly wrong with the germ theory of disease.
Instead, as discussed earlier, medical scientists regard "caus-
ality" in infectious disease in merely the sense of "necessity"
(i.e., the "causal" microbe is necessary, but not sufficient).
Medicine has not regarded the pathogenesis of any natural
infection in terms of a "germ only" theory such as Root-Bernstein
describes, since Pasteur, referring to disease, said that "The
seed is nothing, and the soil is everything."  Thus, Root-
Bernstein spends many chapters assailing an idea that physicians
have not held since the late 19th century, and certainly have
never generally held in the case of AIDS.

     No infectious agent is usually "sufficient" to cause disease
in a natural host, although in a laboratory (or perhaps very
occasionally in nature) it may be sometimes true that inoculum
(microbe "dose") may be so high as to make host resistance almost
irrelevant.  Naturally-occurring infectious disease organisms at
reasonable doses, however, always rely on a chink of some kind in
host immunity, with regard to that particular microbe (this is
not to say that we must consider any host that is successfully
infected to be "immuno-compromised"-- that would cheapen and
overly broaden this useful term).  The idea that deficiencies in
host defense in some sense "permit" all or most infections is
indeed a standard medical teaching [36], although a lay reader of
Root-Bernstein might be surprised to learn of it after Root-
Bernstein finishes misrepresenting the standard views of modern

AIDS Heresies, Part 4

    "Why is there such a huge and medically unprecedented
variation [in time between HIV infection and death from AIDS]?"
asks Root-Bernstein (p. 89).  The answer to this rhetorical
question is that such variation is _not_ medically unprecedented.
Other infectious diseases, from malaria to syphilis to tuberculo-
sis to viral hepatitis, may kill years after initial infection--
or within a much shorter time.  In a cohort of newly-infected
people, any  study of a chronic infectious disease cannot help
but produce steady increases in the "average" time between
infection and death, as deaths accumulate slowly while the study
follows the infected cohort prospectively onward in time.

    Once again, medical science has long assumed that there must
exist host factors and other factors which explain why some
people die of (say) tuberculosis or serum hepatitis 3 months
after infection, and others not until after 3 decades-- but again
these factors have nothing to do with our standard way of
speaking of infectious disease "causation."  The question of
whether eventual liver failure from chronic infectious hepatitis
is "caused" by the viral infection, is medically simply another
way of asking whether or not it would occur _without_ the virus.
It does not mean that other causal elements in the chain are
being denied by medicine-- only that for very practical and
necessary reasons they are being ignored at present (we will
return to these reasons later in discussing polio).

    "No theory based solely on HIV can explain the phenomenon [of
variable times of death]," writes

	[[ part lost ]]

		was explained as being merely an early warning of
impending immune failure in these groups.  (In HIV/AIDS skeptic
lore, HIV is a harmless bellwether virus which can tell when
certain members of modestly immunosuppressed groups are headed
for future immune failure, and rapidly infects them ahead of

   The process of multiplying causal theories in order to
minimize HIV responsibility for AIDS has finally culminated in
the work of Root-Bernstein, which contains an eclectic "multifac-
torial" view of AIDS which is so formless and complicated as to
be epidemiologically unfalsifiable, even in Root-Bernstein's view
(see his p. 92, quote below-- we will turn to this theory later).

   At the time of the early drug/toxin theories of AIDS, the
leading toxin candidates were the inhaled amyl and butyl nitrite
street drugs ("poppers") used heavily and almost universally as
sexual-experience enhancers in the 1970's and early 1980's by the
same fraction of homosexual men who indulged in high risk,
promiscuous sexual practices causing injuries to mucosal tissue,
and who also historically were the first U.S. group to develop
AIDS as an "epidemic" [14].

    Since this group was the one that suffered the first major
impact of AIDS, a number of early studies found high statistical
correlations between AIDS risk and nearly everything to do with
this group's lifestyle.  Later, after the HIV virus was
identified, the CDC found that HIV was universally present and
active in such men who developed AIDS.  Almost as prevalent were
a number of other chronic viruses, such as CMV (cytomegalovirus),
HZV (Herpes Zoster virus), EBV (Epstein-Barr virus), and HSV-1,
2, and 6 (Herpes Simplex viruses 1,2, and 6).  Many of these
chronic viruses were found to be replicating actively in homos-
exuals with AIDS.  This state of "viral re-activation" (a product
of immune suppression) was less common in AIDS sufferers from
other risk groups, mainly because other groups had not been
infected with as many chronic viruses in the first place.
Sorting through the drug and infection variables among promiscu-
ous homosexual men with AIDS was a statistical nightmare,
although it became easier to separate out important AIDS risks
when AIDS in other groups with different lifestyles was consider-

    Epidemiologists fought it out in scholarly journals.  After
the main battle was over, they even tried to decide who hadn't
guessed from the beginning on epidemiologic grounds that the
problem might be infectious, even before a specific causal virus
was proposed--- occasionally lambasting each other's past methods
in print with words like "Neanderthal" [37,38].  Before HIV was
identified, however, the basic problem for epidemiologists was
that statistical methods could not by themselves suggest which
lifestyles or practices (if any) were causal for AIDS, and which
were merely an associative marker for some other causal factor
which (perhaps) had not been measured.  _After_ HIV was identif-
ied, however, a second statistical appraisal could be taken using
HIV status as a statistical factor, in an attempt to see if HIV
had a closer associational (and therefore presumably more likely
causal) relationship with AIDS, than other previously identified
factors [39].  It did [40].

    Much the same thing happened with other viruses, especially
when statistics were extended across different risk groups.
Infectious HIV was finally found to be present in essentially
100% of AIDS cases in ALL risk groups-- a higher proportion than
was seen with any other virus [41].  Furthermore, although the
prevalence of HIV was high (as much as 50%) in certain risk
groups, such as homosexual males in some cities, or in people
with hemophilia, the difference in HIV status for a risk group,
and those who actually contracted AIDS within the risk group, was
by far the largest _change_ associated with any virus, increasing
from 50% to 100%.

    Furthermore, as noted, most of the change in HIV infection
status had occurred before 1984 in people with hemophilia [28],
long before the worst incidence of immunosuppression and in-
creased death rate in this community, proving at least that HIV
positivity was not derivative of _severe_ immunosuppression,
since it preceded it.  As judged by CD4+ lymphocyte counts in
people who were followed over time, most of the loss of immune
function in _individual_ HIV-positive people with hemophilia,
came after HIV infection, as well [42].

    Finally, it was found in several studies that while HIV-
negative homosexual males might be mildly immunosuppressed, their
immune function was never seen to drop as low as AIDS-class-
immunosuppression (immune failure), as defined by CD4+ lymphocyte
counts below 200.  Moreover, when followed over time, HIV-
negative homosexual men did not become MORE immunosuppressed, but
HIV-positive ones did, and in prospective studies when men were
followed by blood tests as they actually contracted HIV, this
same slow and steady decay in immune status happened to the newly
infected group after contracting HIV infection, starting immedia-
tely after infection.  HIV, when contracted by men being followed
in studies, was generally contracted during a time when immune
status (CD4+ lymphocyte count) was reasonably good [43].  Men who
were severely immunosuppressed (CD4+ lymphocyte counts below 200;
essentially immune failure) with no other explanation (such as
cancer), invariably had become HIV positive already, or in other
words, had become HIV-positive _first_ [44].  Such tight corre-
lations between timing of immune failure and time of infection do
not hold for any other known viral infection in immunosuppressed

   Lifestyle factors such as non-injected drug use and exposure
to blood products (as in transfusions or hemophilia treatments)
did correlate with risk of developing AIDS, but this association
could be completely explained in the statistics by the fact that
these behaviors (including even perhaps nitrite ("popper") use
[45]) also increased risk of contracting HIV.  To discover which
was most important to risk, HIV or drug use, epidemiologists
statistically "controlled" for HIV status (i.e., compared people
with each other only within HIV status groups), attempting to
discover if drug use or blood product exposure was important to
AIDS risk AFTER the HIV virus was contracted, or independently of
it.  The answer, it turned out, was generally no.  By and large,
drug use and promiscuity were not independent variables after HIV
infection was taken into account (with two exceptions, to be
discussed).  Important studies finding this included the followi-

* With regard to risk of AIDS in homosexual men, Susan Buchbinder
followed 588 men in the San Francisco Men's Health Study who were
infected with HIV at well documented times in the early 1980's
(this is known because their sera was being stored for use in a
hepatitis study).  Of 588 men, 51% had developed AIDS by 10
years, and 69% had developed AIDS within 14 years of becoming
HIV-positive.   The San Francisco study also found that HIV-
negative controls (both homosexual and heterosexual) had stable
immune status, and did not develop AIDS, nor AIDS defining

     Of 538 men who became HIV-positive before 1983 in this
study, only 8% were "healthy" HIV-positives as of Jan 1, 1993.
This group of 1 person in 12, who for reasons still not underst-
ood possibly will be long term survivors of HIV infection, was
found to be quite time-stable in immune function, though mildly
abnormal in immune status with respect to HIV-negative controls.
[Italics]: _Significantly, the long term healthy HIV-positive men
were as likely to have had sexually transmitted diseases or been
users of illegal drugs as the other HIV-positive men in the study
who became ill_ [46].   Those who progressed to AIDS and those
who remained healthy, reported equal and significant use of
marijuana, nitrite inhalants, and amphetamines.  Both groups had
similar herpes and hepatitis B infection immunity on lab testing-
- objective markers for risky sexual behavior [46].  Regarding
people already infected with HIV, there is no support from this
study for the idea that either of the two possible outcomes
(eventual progression to AIDS, or the long term health which may
be possible for a small subset of HIV-infected people) has
anything to do with non-injected drug use or sexual habits
_after_ HIV infection, within a fairly wide range of behavior.

   A specific re-analysis of non-injected illicit drug use in
this study [40] showed that 3 stratifications of drug use groups
into low, moderate and heavy use, had NO statistical effect on
risk of progression to AIDS in groups (even if done imperfectly,
as Duesberg contends, some effect should still have been seen).
[Fig. 2].  All 3 HIV-positive drug-use groups over several years-
time lost CD4+ lymphocytes with equal rapidity and developed AIDS
with equal probability; and all 3 HIV-negative drug use groups
did not lose CD4+ lymphocytes at all, and did not develop AIDS
defining diseases.  Crude death rates in groups agreed with CD4+
loss rates and AIDS diagnosis rates, suggesting no bias problems
with any of these markers, as has been suggested by critics.
Statistical association of nitrite use with AIDS disappeared when
only homosexual men, or only HIV-positive men, were examined, and
thus nitrite use was seen to be merely a marker for homosexual
behavior or HIV risk in San Francisco men, not an independent
AIDS risk. Previous investigators in this study had also examined
the statistical effect on AIDS risk of reported recreational non-
injected drug use, and certain sexually transmitted infections,
while controlling for other variables, and also found no associa-
tion [47].

* In the Multicenter AIDS Cohort Study following a group of 1835
HIV-positive homosexual men, it was found that the 59 men who
developed AIDS over 15 months during the course of the study were
no more likely to have used inhaled nitrite "poppers" in the
previous two years than were 295 matched controls picked from the
same group, who did not develop AIDS [48].  In another paper from
this study entitled "No evidence for a role of alcohol or other
psychoactive drugs in accelerating immunodeficiency in HIV-1-pos-
itive individuals..." Kaslow and coworkers found that the
proportion of HIV-positive men at enrollment who developed AIDS
during the following 18 months ranged from 5% to 8%, and that
among HIV-positive men with low CD4+ lymphocyte counts, those who
continued to use drugs showed no significantly higher 18-month
risk of AIDS than non-users. No other manifestations of
immunodeficiency were positively associated with substance use
prior to enrollment in this study.  Prior use of non-injected
drugs was not associated with low mean CD4+ lymphocyte counts at
enrollment, and continued drug or alcohol use after enrollment
was not associated with greater subsequent decline in CD4+
lymphocyte counts.  The authors conclude that as used in a large
cohort of homosexual men, psychoactive substances did _not_
enhance the progression of HIV infection to lower CD4+ counts or
AIDS [49].

* Likewise, the Vancouver Lymphadenopathy-AIDS Study (VLAS)
comparing HIV-negative to HIV-positive men found no sexual
behavior variables which correlated with CD4+ lymphocyte counts
independent of HIV status, and for the 25 men who developed AIDS
during the study found no significant differences in sexual
behavior or illicit non-injected drug use as compared with 80
controls who were HIV-positive but remained AIDS free [50].
These studies included 78 HIV-negative men who were heavy users
of many drugs who did not lose CD4+ lymphocytes or develop AIDS
defining diseases, and also 19 HIV-positive men who reported no
recreational drug use of any kind (and who were followed,
incidentally, before AZT became available, yet lost CD4+ lymphoc-
ytes steadily [51]).

   Again, AIDS risk in all studies correlated highly with the use
of both intravenous and also certain non-injected drugs in
homosexual men, but just as highly with promiscuity and high-risk
sex in such men. If non-injected drug abuse (particularly nitrite
use) was simply part of the lifestyle which caused one to
contract the HIV virus, we would expect the correlation between
non-injected drugs and AIDS to be high, without necessarily being
causal.  To separate out any independent effects of orally
administered, inhaled, or intravenous illicit drug use, it is
necessary to look at only men who had been infected with HIV
while still showing reasonably good immune function (CD4+
lymphocyte count), and ask the question of whether drug use THEN,
after infection, had any effect on the risk of later AIDS (which
in most cases, appeared years later).

    The statistical answer was that after HIV infection, contin-
ued injection of narcotics did seem to increase risk of AIDS, but
that use of no other drug had any effect at all.  Specifically,
several early (pre-HIV) studies found connections between nitrite
use by male homosexuals and Kaposi's sarcoma; but (in addition to
the many studies cited above) later studies found that this
association between nitrite use and AIDS disappeared after
controlling for HIV status [52].  If recreational nitrite
inhalants or oral drugs caused AIDS or Kaposi's sarcoma, and HIV
was harmless, there should be some continued statistical associa-
tion between AIDS risk and nitrite or other drug use, even when
looking only at HIV-positive men, or only at HIV-negative men.
No such association has been found in more than half a dozen
studies [37-40, 46-52].

    Illicit drugs did not cause AIDS, with the qualification that
injection of drugs was implicated as a cofactor (see below).  In
the end, the "drug-only" hypothesis of AIDS pathogenesis failed
all careful epidemiologic scrutiny.  Even among IV drug users,
although short term overdose deaths tend to swamp any necessarily
long-term consequences of HIV infection [53], studies have
generally shown that HIV infection is an additional risk factor
for IV drug users [54-56].

   Injected or IV drug use, of course, proved an excellent way to
_contract_ HIV, if needles were shared.  There was no evidence,
however, that injected drugs themselves ever led to severe AIDS-
type immunosuppression (CD4+ lymphocyte counts less than 200), in
the absence of HIV.  There was some evidence that IV narcotic use
could be quite immunosuppressive (leading at least in part to
fatal infections), and a co-factor for rapid AIDS development in
people HIV-positive.  Some studies found that continued IV
injection of heroin, but not use of other drugs, hastened
progression to AIDS in HIV-positive people [57], but other
studies have suggested that heroin does not decrease CD4+ counts
as AIDS does, so the immunosuppression of heroin users is
apparently not due to heroin itself, but possibly drug
impurities, or to other factors in drug-injectors [22].  One
study [58] suggested that HIV-positive IV drug users who switch
to methadone (an oral heroin substitute) may have slower
progression to AIDS, but there was no mortality difference
between using methadone and quitting narcotics completely, so IV
injection per se, rather than narcotic use, was possibly the
offending practice.  Studies of IV drug users who continued IV
drug might be implicating not drugs themselves in the rapid
production of AIDS, but rather simply continued needle-sharing
leading to acquisition of more virulent strains of HIV.  The same
was possibly true of extreme promiscuity, which also continued to
be a risk factor after HIV-infection, in one study [59].
Acquisition of CMV was also a possible consequence of risky
behavior, although the role of this virus as cofactor was limited
at best [60].

    In summary, the search for controllable cofactors in develop-
ing AIDS, once HIV infection is present, was disappointing.
Needle-sharing  and extreme promiscuity very possibly hastened
AIDS in HIV-positive people, but if they did so, it wasn't by
much.  Nor was there any evidence that avoiding these behaviors
led to significant delays in AIDS, as compared with risk groups
such as HIV-positive hemophiliacs, who still had a 50% chance of
developing AIDS over 15 years.

The Critics Don't Give In

    The above results have not convinced those who champion the
drug hypothesis as the cause of much of AIDS.

     Duesberg, for example, accepts a causal role for drugs in
AIDS (and for that matter, also for smoking in the causation of
lung cancer: Duesberg, p. 213) on much the same grounds which he
rejects for assigning a causal role to HIV-- namely, epidemiol-
ogical correlations and suggestive lab experiments.
The irony of this position is that the correlations are not
nearly as good statistically for drug use and AIDS as they are
for HIV infection and AIDS, and lab animal experiments with
retroviruses mimic human AIDS immunodeficiency far more precisely
than lab animal experiments with drugs have.  Nitrite recreatio-
nal drugs, for instance, do not cause lymphocyte abnormalities,
lymphadenopathy, or the almost complete disappearance of CD4+
lymphocytes at the same time as CD8+ lymphocytes counts rise, as
all happen in AIDS.  Yet chronic retrovirus infection of
experimental animals routinely causes these odd and specific
phenomena.   Nor have opportunistic infections or lymphomas ever
been seen in a nitrite treated animal, and yet these are hallma-
rks of lentivirus infections.   Apparently, Duesberg's standards
of evidence change greatly with the hypothesis he likes.

    Duesberg actually accused a group of scientists of data
fabrication [61] after a paper in _Nature_ reported findings not
in line with Duesberg's drug hypothesis [40].  Duesberg's letter
to _Nature_ calling some results of the paper from the San
Francisco Men's Cohort study less than honest, was refused print
by _Nature's_ editor, with an accompanying editorial [62].  An
independent institutional review board cleared the researchers of
Duesberg's charges, which have been answered in print by the
authors [63].

    In the study printed in _Nature_, the authors had found in
the San Francisco cohort men no connection between the four most
commonly reported kinds of illicit drug use and later progression
to AIDS, after results were controlled for HIV status (i.e.,
heavy drug users had the same likelihood to progress to AIDS as
light users, if HIV-positive, but HIV-negative men did not
progress toward immune failure, no matter what their drug use).
[See Fig 3].  Moreover, these results held also for the 1985-1986
period before the drug AZT (the use of which Duesberg has
suggested may cause AIDS to develop in HIV-positive people) was

    Duesberg's objections were that the study had not controlled
carefully enough for drug use between HIV-positive and HIV-
negative groups in the study, but Duesberg did not address the
obvious question of why such considerable controlling for drug
use as _was_ done, had absolutely no effect on differential AIDS
risk seen.  Duesberg also complained after seeing the raw data
that supposedly "AIDS-defining" diseases in the HIV-negative
group had not been counted as "AIDS," despite the author's denial
that this had happened.  Here apparently much depends on a
disagreement between Duesberg and others as to what constitutes
clinical AIDS.  A recent article in _Science_ suggests that one
difficulty is over the question of whether mild opportunistic
conditions such as oral candida (thrush) constitute clinical
"AIDS."  Duesberg, ever ready to define AIDS broadly, argues they
should [22].  In any case, the specifics of Duesberg's reanalysis
of the Nature paper have never been printed, and death rates in
this study again underscore the fact that Duesberg's broadly
defined "AIDS," which strikes HIV-negative people, somehow does
not kill nearly as well as the standard variety.

    As for worsening immune failure in groups over time (seen as
declining CD4+ counts in the HIV-positive men, independent of
drug use, but not in HIV-negative men, no matter how much drug
use), Ellison and Duesberg have noted that this phenomenon isn't
so clear before the data is reduced to averages.  This, however,
seems a odd complaint (making group trends clear is _why_
scientists calculate group averages).

    The bottom line is that, for now, the drug hypothesis of AIDS
has no epidemiologic associational evidence behind it which is
independent of HIV infection.  HIV infection, by contrast, is
heavily associated with AIDS risk, independent of drug use.

[See AZT Section in Appendix on the question of whether AZT
contributes to AIDS]

Previously Known Viruses

    Because Duesberg does not regard any virus as being capable
of causing a fatal disease long after the body has generated an
antibody immune response to the microbe, he rejects a causal role
for any virus in AIDS.  The evidence for multiple viral infecti-
ons in many of the early victims of AIDS, however, has caused
many such "non-HIV virus" theories to be generated and tested.
For example, though Root-Bernstein does not regard HIV as always
a bystander virus in AIDS, he does regard other viruses in AIDS
to be just as important as HIV.  Are the other viruses (CMV, EBV,
Herpes, etc.), or at least their antibodies, present as often in
AIDS as those of HIV?

    Here statistics can help.  According to Root-Bernstein,
evidences of replication of the viruses CMV and EBV "are just as
frequent concomitants of AIDS as is HIV replication" (p. 260).
Unfortunately Root-Bernstein fails to note that this is true only
in homosexual men with AIDS (where co-infection with EBV and CMV
along with HIV is nearly universal).  In science, situations in
which several possible causes are all nearly 100% associated with
a particular effect do not help us to differentiate causality, a
point that Root-Bernstein makes (p. 279-280) without taking the
next logical step.  What are needed with viral studies and AIDS,
obviously, are AIDS cases where some of the putative viral causes
are present less frequently than 100% of the time.  Such cases
are available.  In both hemophilia and transfusion-associated
AIDS, HIV infection is universal, whereas infection and re-
activation with other viruses, such as CMV and EBV, is variable
[64].  In short, some people with AIDS in these groups have never
been infected with CMV or EBV viruses at all in the past-- but
all have been infected with HIV.

    Much the same is seen to be true when people in AIDS _risk_
groups are examined for antibodies to various viruses.  EBV or
CMV antibodies alone, in themselves, are not predictive for
development of AIDS in risk groups where exposure prevalence of
CMV and EBV is much less than 100% [60,65], a fact that eludes
Root-Bernstein, who writes with too much generality that CMV and
EBV antibodies are "synonymous with AIDS" (p. 103).  In fact, as
we have noted, CMV and EBV antibody are not unusually common in
either HIV-positive people, or AIDS patients, from groups such as
transfusion recipients, and people with hemophilia, in some
countries [66].  Nor are antibodies to these viruses a clear
extra risk factor for development of AIDS, even in HIV positive
people [60].  Cases of people multiply infected with many chronic
viruses, but not HIV, are also well known, and such people are
easily differentiable from AIDS on clinical and laboratory
grounds (see the study of Salvato [13] above).  Despite Root-
Bernstein's suggestions, statistical associations clearly
differentiate HIV from other viruses in AIDS.

    It is necessary for heretics to come to grips with the
crucial point (hard to explain if HIV has no causal role in AIDS)
that the utility of HIV antibody screening is _exactly_ that a
positive HIV screen, found in only 0.3% of the population, is
predictive of risk for development of severe immunodeficiency,
i.e., 50% risk of developing severe, life-threatening immunodef-
iciency within less than 15 years.  By contrast, EBV and CMV
viral immunity and antibodies are acquired by most (well over
50%) of any normal, healthy population of humans during a
lifetime, and thus are not predictive of future severe immunod-
eficiency and death, except to the extent that they are markers
for membership in particular risk-groups (such as gay men).
Like many other factors, the association of viral antibodies with
AIDS across risk groups disappeared when people were compared
within groups-- except for HIV, where the association persists.

    The fact that HIV antibody is even 50% predictive of disease
or death within 15 years is exactly the burden that those who
argue that HIV is not causal must labor under, if they are to
face the evidence.  Other viral hypotheses fail this most simple
test of prognostic value.  As any life or medical insurance
company knows, HIV infection status (HIV-positivity status) is
more surely predictive of future death due to future severe
immune failure than any other known piece of medical information
related to viral infection.  In science, if one has a list of
factors which are independently statistically associated with an
effect (such as AIDS), this does not prove that any of them are
causal.  If one of these factors (such as HIV infection) is far
more highly associated than any of the others, however, it
becomes difficult to argue convincingly that it is no more
important than the others are.  We will return to this point

AIDS Heresies, Part 5

Why Did Medical Science Historically Implicate HIV?

    The standard method of trying to identify a new virus in a
new disease suspected of being caused by a new virus, is to
attempt to culture a new virus from an infected person, then show
that antibodies to this virus are present in all people with the
disease, but less often in people who are not ill.  It is also
helpful to show that persons develop antibodies to the virus
during the acute illness.

   Sometimes viruses can be very difficult to culture in lab
glassware.  This is especially true of viruses which grow in
human T-cells-- cells which could not be grown well without
certain growth factors only discovered in the 1970's.   In 1980,
Dr. Robert Gallo of the NIH formally reported isolating a virus
he named "Human T-cell Leukemia Virus," (HTLV) which infected T-
cells and which was thought to cause some cases of T-cell
leukemia in humans.  This virus was a retrovirus (a virus type
associated with cancer causation), and it was a distant relative
of the "Feline Leukemia Virus" (FeLV) which caused leukemia in

    Because the transfusion results had shown that AIDS could be
infectious, and because AIDS patients had abnormal-looking T-
cells which looked something like those from retrovirus-infected
animals, or T-cells in cultures infected with retroviruses, early
AIDS researchers began hunting a T-cell retrovirus.  In early
1983, a team of French scientists led by Dr. Luc Montagnier
isolated a new retrovirus which they reported in May of that
year, calling it eventually Lymphadenopathy-Associated Virus
(LAV), because it had been isolated from tissues of a French
patient with enlarged lymph tissues, or "lymphadenopathy" (this
man died of AIDS in 1988).  The French had been alerted to the
possibility of a retrovirus in AIDS patients by an American team,
led by Gallo, which was convinced that the AIDS virus was another
variety of HTLV.  It wasn't.

[See appendix: "Montagnier, Gallo, Slip-Ups and Wrong Paths"]

    The new virus discovered by the French was a tiny, spherical,
membrane-coated, protein-studded virus 1/100th the diameter of a
lymphocyte, with an inner protein viral core shaped like a
truncated cone, with a dense base.  Under the electron microscope
it didn't look like the feline FeLV or the human HTLV leukemia
viruses (Fig 4), which had no distinct cores.  Eventually, the
LAV virus was correctly understood that Summer by the French team
not to be a leukemia virus as they had thought, but rather to be
the first human "lentivirus."  This hypothesis was first formula-
ted when Montagnier, at a suggestion from a colleague, began
reading about "lentiviruses" or "slow viruses" -- a class of
animal retroviruses he'd never previously heard of.  In one book
was an electron micrograph of the "equine infectious anemia
virus," a virus which sometimes produced a familiar-sounding
immunodeficiency and lymphadenopathy disease, after long latenci-
es, in horses.  Montagnier found himself looking at a tiny
membrane-coated virus shaped like a sphere, containing a protein
viral core in the shape of a narrow cone [67].  Antibodies
against the horse virus cross-reacted with Montagnier's new
virus, but not with Gallo's HTLV.

    Most importantly, coded AIDS patient serum provided by the
CDC contained antibodies to LAV, but not HTLV-III, and Montagnier
proved his lab could easily pick out AIDS samples from normal
samples in the CDC material, without knowing the codes.  Thus,
Montagnier had his answer (his "LAV" was our modern HIV), but
nobody would believe him for almost a year.

Lentiviruses and Latent Diseases

    Most readers will remember that viruses in some sense are not
complete living organisms.  Animal viruses when outside cells
don't metabolize, and cannot reproduce or grow by themselves.
Instead, most viruses are little more than tiny floating packages
of genetic material, sometimes without much other equipment.
Viruses can reproduce themselves only by entering a living cell
and commandeering the cell's synthetic machinery to subvert it
into making more virus particles, which are then, in turn,
released to infect more cells.

    A metaphor for a virus would be a truck-load of blueprints
which rolls into a completely automated factory, and once there,
is somehow able to use the blueprints to control the factory's
machinery to cause it to make more sets of blueprints and more
trucks to carry them, all of which are then assembled and sent
out to take over more factories.

[See appendix: "How Do Viruses Hide From the Immune System?" and
"What is a Retrovirus?"]

    Members of one class of viruses use RNA as their genetic
material, and are called "retroviruses," because their synthesis
of DNA from RNA proceeds retrograde, in the opposite direction to
what is "normal" in the rest of biology.  Retroviruses avoid the
body's immune system by inserting themselves into the DNA of the
host cell.

    Most retroviruses cause no major disease, but not all are
harmless.   A sub-class of retroviruses, called "lentiviruses" is
capable of slow infections resulting in death.   Lentiviruses
typically spend lengthy waiting periods in hiding in the cell
nucleus (music lovers will recognize the Latin root _lento_,
meaning "slow"), and even lentiviruses may never cause overt
disease in their natural hosts.  Sometimes, however, the
lentivirus disease produced after a latency period can be
devastating, though sometimes difficult to detect
epidemiologically, due to the delay between initial infection and

   Lentiviruses were named in 1954 in honor of several very slow-
acting brain infections of farm animals.  The classic example was
a sheep disease with a latency as long as a decade, called
"visna" (an Icelandic word for "shivering").  Visna wiped out
most of the sheep population of Iceland in 1939 because it had
not been realized in 1933 that apparently-well sheep brought to
the island from Germany had actually been carrying a latent
disease.  The ability of visna to cause disease many years after
infection has since been demonstrated in a series of controlled
experiments with sheep [68].  The visna agent proved eventually
to be a retrovirus and a lentivirus, and the ominous pattern of
the visna epidemic will become familiar to the reader during the
course of this essay, as we discuss other better-known viruses in
this unique class.  HIV, our main subject, is a lentivirus.  It
is clearly related to the visna sheep lentivirus in structure and
genetics, and more closely to "equine infectious anemia virus" a
lentivirus which infects macrophages in horses.  It is yet more
closely related to FIV and SIV, two other immunosuppressive
lymphocyte-infecting (lymphotropic) animal lentiviruses which the
reader is shortly to meet.

How To Dismiss All Laboratory Animal/Virus Experiments

    Before we meet these viruses, we should note that molecular
biologist Peter H. Duesberg's scientific heresies do not only
extend to his views on HIV.  Duesberg, for instance, is unable to
believe that any disease which confines itself relatively rigidly
to classes of susceptible people, can qualify as a genuine
communicable disease caused (in any sense) by a treatable
microbe.  In these diseases, Duesberg tellingly prefers to focus
entirely on the host, refusing to consider the role of the
microbe at all (as we will see, the issue of "causation" is a
difficult one for HIV/AIDS skeptics).  Thus, Duesberg and Ellison
dismiss (for example) Legionnaire's disease and hepatitis C as
fantasy diseases made up by the biomedical establishment for
purposes of profit and self-aggrandizement (pp. 35-38, 57-59).

    Duesberg also does not believe in slow infections in general.
The modern physician perusing Ellison and Duesberg's AIDS book
will be astounded to read that syphilis microbes do not cause
neurosyphilis, and that leprosy is not an infectious disease nor
is it caused by the organism the medical textbooks say causes it
(Ellison and Duesberg, p. 35).  Nor does Duesberg believe in slow
viruses at all, in the sense that he does not believe that any
virus is capable of causing general infection or fatality years
later in an organism which had been healthy prior to the initial
viral infection (Duesberg, pp 209, 233).  "There are no slow
viruses," says Duesberg, "only slow virologists" (Ellison and
Duesberg make it clear that they consider one of these to be D.
Gajdusek, who won the Nobel Prize in 1976 for slow virus work,
see pp 50-54).

    Nor does Duesberg believe that viruses cause cancer in
animals, with a single kind of exception, the partial mechanism
for which was co-discovered, as it happens, by Duesberg himself.
Rous Sarcoma Virus (RSV), a retrovirus, causes muscle tumors in
chickens (this fact won F. P. Rous the Nobel Prize in 1966).  In
1970, Duesberg and P. Vogt showed that RSV caused tumors by
carrying a cancer gene into the cell.  (Thus, Duesberg's conten-
tion that cancer is never caused by chronic viruses which have no
cancer genes, such as HTLV and HIV, perhaps coincidentally has
the effect of magnifying Duesberg's own discovery).

    A review of the evidence that Legionnaire's disease, leprosy,
and hepatitis C are real infectious diseases, or that viruses
other than RSV cause cancer, is beyond the scope of this article.
With regard to other latent diseases it is worth noting that
Duesberg's rejection of all current theories that viruses are
causal in any latent cancer or disease of normal animals or
humans requires that he reject not only all epidemiological
evidence, but also all experimental laboratory animal evidence
for viral cancer causation and fatal viral immunosuppression.
Thus, cancer and immune failure in virally infected lab animals
are uniformly dismissed as being responses of weak, inbred lab
animals under "odd conditions" (Ellison and Duesberg, p. 91).

    The reader should note that, if valid, Duesberg's view about
lab animals would have the effect of making almost any claim for
a virus-caused cancer or immunodeficiency nearly impossible to
prove.  Epidemiology, after all, can always be dismissed in the
absence of lab data.  Moreover, it is difficult to impossible to
collect experimental lab infection data on animals which have not
been bred in captivity to be free of infections other than the
ones being studied.  In short, if infection-free lab animals were
useless for the very infection experiments in which they are
needed and now used, this would leave scientists with no good way
to study infectious processes at all.

    Fortunately, however, enough experimental data is available
to reject Duesberg's claims in the matter.  With the exception of
rodents, most animals used in laboratories are in fact no more
highly inbred than are pets or domestic animals (or many
societies of humans, for that matter).  Modern science works with
many tumor-virus models, and there is no reason to regard (for
instance) the "specific pathogen free" cats used in feline viral
leukemia experiments [69], or the woodchucks used in hepadnavirus
liver tumor experiments [70], as being inbred, weak, or in any
way intrinsically immunologically abnormal.  Moreover, although
Ellison and Duesberg (p. 84) say that feline leukemia virus and
all other retroviruses only cause disease in young inbred lab
animals, experiments have proven them wrong.  In the next section
we will discuss a retrovirus which causes fatal immunodeficiency
and cancer, even when injected into so-called "random-source"
domestic cats, such as one might obtain from a pet store or
animal shelter [71].

Animal Lentiviruses Suitable For Laboratory Study

    In this section we will examine two very similar
animal lentiviruses called FIV and SIV, and will note something
of their effects in different animal hosts.  The details about
these two virus/host systems are given because all are crucial to
a pattern which will be apparent by the end of our survey.   The
two viruses we are about to describe were actually discovered
several years _after_ HIV, but it is more illuminating to tell
about them first, for nature seldom provides her good clues in
proper order.

    The reader should again bear in mind that our modern idea of
the cause of AIDS is based on induction and inference, and
inference depends on recognition of common _patterns_.  Some of
the crucial information for one of these patterns follows.  By
the end of the discussion, the reader should have some idea for
why the "odd" effects of HIV in humans are no longer a surprise
or shock to most scientists who study the matter.  They've seen
it all by now in animals, under controlled conditions, and
realize that the way HIV works is much the way other viruses in
its family work.

_They Call It "Cat AIDS"_.  The feline immunodeficiency virus
(FIV) is a lentivirus discovered in Petaluma, California in 1986,
where it was first obtained from the blood of two domestic cats
living in a household in which there had been a number of deaths
of cats from a strange immune deficiency disorder.  The virus was
isolated from the housecats by experimentally infecting special
disease-free laboratory cats with their blood, then isolating the
resulting infectious virus in tissue culture.  The FIV microbe,
once characterized, has since been identified in many species of
cats around the world.

   The FIV virus is a tiny ball of lipid and protein, measuring
four millionths of an inch in diameter, which is less than the
span of 1000 hydrogen atoms laid next to each other in a line.
An FIV virus particle is thus 1/10th the length of a small
bacterium, or 1/100th the diameter of a white blood cell.  The
electron microscope shows the virus to be composed of a roughly
spherical coat of phospholipids stolen from the host cell
membrane when the newly made virus particle leaves or "buds" from
the cell.  This outer membrane is studded with protein molecule
spikes, a bit like cloves stuck in a Christmas orange.  The
membrane closely covers a protein capsid shell which is a sphere
or icosahedron (20-sided spheroid object made of triangular
protein faces).  The shell, in turn, contains within it a protein
lozenge (called the viral core) in the shape of a blunt or
"truncated" cone-- a cone which has a base which shows up notice-
ably darker (denser) in the electron microscope views.  The final
result is a complicated structure not seen in any other virus
class but the lentiviruses (Fig. 4).

    Inside the hollow protein cone which makes up the core of FIV
are packaged two identical (or close to identical) coiled strands
of viral genomic RNA, each containing 9 genes (a gene is a region
of RNA which codes for and controls production of a main functio-
nal virus protein, or set of proteins).   Also present along with
the RNA in the FIV viral core are molecules of a particular
variety of reverse transcriptase enzyme peculiar to several
previously known lentiviruses, including HIV.  This reverse
transcriptase functions best with a particular concentration of
magnesium ion, and does not work (as this enzyme from other
retroviruses sometimes does) with ions of the chemically somewhat
similar mineral manganese.

   The RNA molecule genome of FIV is organized very closely along
the lines of several other lentiviruses and is clearly related to
them, with most genes and proteins having identifiable analogues
from one strain of lentivirus to another.  FIV, however, infects
only the cat family.  It causes disease in domestic cats (pets,
feral cats, and lab cats), but apparently infects lions without
causing disease.  Not surprisingly, once FIV infects a cat, a DNA
virus copy finds its way into the cat DNA, and stays with the
animal for life [72].

    It is what happens to FIV-infected domestic cats, however,
that makes the FIV virus most interesting: in late life, ap-
parently many years after being first infected, some FIV-infected
cats come down with an immune deficiency syndrome.  Older cats
infected with the virus are worst affected.  The presence of
antibody in the cats' blood is not protective against damage,
since the presence of FIV antibody makes no difference in later
development of severe symptoms and death in older cats.  Indeed,
even with antibody present, the immune system of infected cats
was found to be declining in a peculiar way--  CD4+ lymphocyte
were disappearing while CD8+ lymphocytes were relatively unaffec-
ted [72].

    The lymphocytes of cats also happened to be the cells
preferentially infected by the FIV virus in cell culture (a
incubated glass dish containing cells and a nutrient solution).
FIV virus infection sometimes killed cells in culture and
sometimes not, depending on the strain of the virus and the type
of cat cell.  In FIV-infected cats, immune systems began to
malfunction (sometimes years after infection) as CD4+ lymphocytes
numbers declined.  As scientists followed naturally-infected
older cats, they saw some cats begin to waste away and develop
lymphadenopathy (swollen, enlarged lymphatic organs or "nodes"--
the filtering structures which hold immune cells and trap
invading microorganisms). Infected cats also developed fevers,
diarrhea, and chronic neurological dysfunction-- the last a
result of direct brain infection by the FIV virus.   Finally,
after a year or two of being ill, the unfortunate felines usually
died of opportunistic feline infections [73].

    Naturally, scientists wished to prove once and for all that
FIV was the entire cause of the disease syndrome which they were
seeing in FIV-infected cats, now informally dubbed "feline AIDS"
(i.e., a life threatening immunodeficiency syndrome caused by a
retrovirus, in cats without cancer).  With experimental cats in
the laboratory setting, experimenters were able to do what could
not be done in humans, which was to cause deliberate infections
in an animal with a lentivirus.  FIV experiments with cats have
taught us much, and allowed us to infer still more.

   When young cats were infected with FIV by injection in the
laboratory, they suffered lymphadenopathy, coat and skin
problems, and lethargy.  They also developed very slow and
progressive and specific loss of CD4+ lymphocytes and a decline
in immune response over a period of years.  The FIV virus was
also active in the brains of deliberately infected cats, and they
suffered various abnormalities in neurological function [74].
Older cats were worst affected, just as with HIV in humans [75].
Cats experimentally infected with FIV were observed to sometimes
enter a carrier phase after infection, but this might progress to
lymphadenopathy, wasting, and death as long as 3 years after
infection.  It didn't happen in uninfected control cats.
Experimentally infected specific-pathogen-free lab cats (domestic
breed cats raised in the lab without many microbes or parasites
that affect pet housecats) often developed lymphomas eventually.
"Random-source" domestic cats, exposed to and carrying many more
normally-present "cat germs" from the outside world, not surpris-
ingly were more likely to develop immunodeficiency and AIDS-like
opportunistic cat infections when brought to the lab and given
FIV [71,76].  Domestic cats infected with FIV are known to
develop candidiasis and cryptococcosis, rare cat microbial
infections also seen in human AIDS.  Toxoplasmosis, a common cat
parasite usually benign in both cats and people with good immune
systems, was another organism deadly in both human and feline
retrovirally acquired immune deficiency.

    In all FIV-infected cats, destruction of lymphatic tissues in
a manner similar to that seen in AIDS patients (but no other
human infectious disease) was found, with FIV virus growing
actively in the lymphatic tissues [76].  What was really needed
for further study, however, was an animal even more closely
related to man, which could be infected with a similar
immunosuppressive lentivirus.

_A Tale of Two Colonies: Simian AIDS._

   The needed non-human animal model of AIDS arrived by chance, a
decade before it could be recognized or put to use.  In 1976, a
colony of stump-tailed macaque monkeys at the California Regional
Primate Research Center (University of California at Davis)
developed a disease epidemic-- an infectious syndrome of immunos-
uppression, lymphocyte loss, lymphadenopathy, wasting, and death.

Scientists at that time had no idea what kind of infection was
killing the monkeys, but they did preserve some of the obviously
diseased lymphatic tissue of one dead monkey in 1977.  Many years
later, in the mid 1980's, they isolated from this frozen tissue a
virus which was by then familiar in both structure and function.
In 1977, however, nobody recognized simian AIDS [77].

   Macaque monkeys infected with the new agent developed a
peculiar and severe immunodeficiency, and sometimes they develo-
ped it after unprecedented delays, causing mistakes to be made in
assuming that monkeys were recovered and well, when they were in
fact chronically infected and doomed.  At the primate colony at
the Yerkes Primate Center (Emory University, Atlanta, GA), which
had previously been "closed" to contact with other lab primate
colonies since 1964, four apparently healthy stump-tailed
macaques were introduced from the apparently "clean" California
Regional Primate Research Center in 1981 [78]. In retrospect this
was to prove as much a disaster as the visna-infected sheep which
passed the quarantine in Iceland.  The California Primate Center
colony was not discovered to be still infested with its old
1970's immunodeficiency plague until 1986, when the plague broke
out in California again.  At that time, newly available antibody
survey tests showed that two of the animals previously
transferred to the Yerkes colony in 1981 were indeed infected
with the latent retrovirus, but (in 1986) were still without
symptoms after 5 years in their new home.

    It was not until 1988 that much of the Yerkes colony, still
"closed" to other contact with other lab primates, began to die
of an immunodeficiency syndrome, with loss of half of the animals
in the colony over the next year.   Many of the Yerkes macaques,
including the two infected transferred animals, began to first
develop immunodeficiency more than 7 years after first being
exposed to the infectious agent from the other colony, and their
disease syndrome consisted of opportunistic infections,
lymphadenopathy, and selective loss of CD4+ lymphocytes.
Scientists found that all the dead adult animals (including the
transferred monkeys) had antibody in their blood to the newly
identified viral agent, so again, antibodies had not conferred
immunity to the immunodeficiency disease.

    The agent responsible for the Yerkes disaster was by this
time known to be a lentivirus, a virus that has since become
known as Simian Immunodeficiency Virus, or SIV.  Eventually, a
number of different SIV strains were isolated from both captive
and wild African monkeys, each with its own story of detection,
and sometimes also disaster in an expensive commercial colony

   The SIV virus strains, like FIV, turned out to be interesting
in a number of ways.   SIV was, by the mid-1980's era of AIDS,
also a horribly familiar-looking virus.  It was a tiny sphere,
1/100th the diameter of a lymphocyte, and it had a lipid membrane
studded with proteins, and an inner protein core that was a
truncated protein cone with a dense base.  Inside were two
identical or near-identical RNA molecules, associated with a
peculiarly magnesium-dependent reverse transcriptase enzyme. The
organization of its 9-gene genome was similar to other
lentiviruses, and much like that of FIV.

   Like many other viruses in many classes, SIV turned out to be
very host-specific in its ability to cause disease.  SIV infected
its natural hosts (apparently a number of species of _African_,
not Asian, monkeys) without causing any obvious sickness or
immunosuppression in them.  The hosts developed antibodies to the
virus, but in the case of SIV, like FIV in cats, these antibodies
did not signal immunity, since the virus went on quietly hiding
in the nuclei of cells until ready to reproduce and infect other

    Only when transferred to genetically different _Asian_
species of primates (several species of macaque monkeys) did SIV
cause illness.  It killed animals quickly when antibodies did not
develop, but of more interest was that it was quite capable of
killing monkeys after more than a year, long after a strong
antibodies response did appear.  SIV had originally been trans-
ferred to Asian macaques perhaps by housing primates from Africa
and Asia in the same cage (in retrospect, not a good idea).
Apparently, the African SIV virus did not know quite how to
behave in the Asian macaques (which do not carry it naturally),
and in these monkeys SIV caused both rapid and slow syndromes of
immunosuppression and death, depending on the host's immune
response.  If the virus from a dying macaque was transferred back
into African monkeys, however, it went right back to being
benign-- infecting and reproducing without causing sickness.

    Again, all this was an old story to virologists, who had long
known that severe viral disease and death syndromes usually
result from mismatched duets between a virus and a "new" species
of host for which the virus is not yet adapted.  Viruses, after
all, do not evolutionarily "want" to make their hosts deathly
ill-- they want their hosts to be up-and-about, and spreading
virus.  Generally, a virus does not kill its normal host.

   For SIV, the consequences of mal-adaption to Asian monkeys
caused the scientific interest--- for SIV infection in macaques
caused what looked more like human AIDS than anything seen yet.
Again, in SIV infection, T-lymphocytes were infected, and CD4+
lymphocytes were preferentially killed, leaving CD8+ lymphocytes.

Again, simian lymphatic tissues became swollen, and were even-
tually destroyed during SIV infection.  Again, the disease
progressed inexorably in some infected animals, even in the face
of antibody "immunity," and without showing much active virus in
the blood (progression was in the lymphatic tissues, which became
damaged in a way sometimes indistinguishable from the stereotyp-
ically-destroyed lymphatic tissues found in human AIDS patients).

    Again the SIV virus paradoxically caused little damage to
lone CD4+ cells in culture, but obviously also did something in
the host which totally destroyed the CD4+ system in the living
animals.   At the end of the SIV disease course, the CD4+
lymphocyte-depleted primates developed not only a few monkey-
specific diseases, but also an eerie number of the same opportun-
istic fungal and parasitic infections that were familiar from
human AIDS:  oral candidiasis (yeast infection of the mouth),
_Pneumocystis carinii_ pneumonia (a fungal pneumonia), cryptos-
poridium diarrhea (a protozoal intestinal infection), cytomegalo-
virus (CMV) retinitis (a herpes-type viral eye
disease), and _Mycobacterium avium_ (a tuberculosis bacterium
relative).  SIV also caused a "retroviral encephalitis" -- a
brain infection caused directly by the SIV virus which was
microscopically similar to the disease changes seen in human AIDS
brains.  Macaques with SIV also developed lymph-cell-associated
tumors (lymphomas), a frequent AIDS complication in humans [80].

   Many monkeys, like cats, have been sacrificed in scientific
studies to learn about infections that could not be studied in
humans, but in the history of science few monkeys have been
sacrificed so usefully as the laboratory monkeys deliberately
infected with the various strains of SIV.  Again, scientists
wondered if the SIV virus was itself capable of all the immune
pathologies seen in SIV infected macaques.  Was the SIV virus
necessary to simian AIDS?  Was it sufficient for simian AIDS, or
were other infectious agent co-factors (perhaps even other
viruses) being accidentally transferred with SIV from animal to
animal, in experiments?

    At Harvard and elsewhere, the question was answered using the
techniques of molecular biology.  Teams using harmless viruses
and bacteria as "carriers" were able to clone, and thus purify, a
provirus, or DNA-copy of the SIV genome.  They were even able to
clone half of the virus genome in each of two cultures of bacter-
ia, and then reconstruct and piece together a working SIV virus
pro-genome (set of DNA-based instructions), out of the two cloned
parts of the virus DNA.  No other infectious agent but SIV could
have survived this specific manufacture of SIV.  The resulting
cloned SIV genome, after being used as "instructions" to manuf-
acture fresh whole SIV virus in cell culture, was found to cause
immune destruction with lag periods of up to 11 months in rhesus
macaques [81].  Whatever viral information was being cloned in
the SIV genome, that genetic information was enough to cause
deadly immune destruction in Asian primates.

    SIV "molecular clone" experiments proved that SIV was
sufficient to cause the AIDS-like syndrome it produced in
macaques, with no co-factors or co-infections being required
(other than those that all healthy macaques normally possessed).
Uninfected primates remained healthy; primates infected with SIV
genomes manufactured by cloning often died deaths of
immunosuppression or cancer months later [82].   Thus, SIV genes
alone somehow held the key to, or perhaps--metaphorically-- the
fuse to, the total immune destruction seen in the lab animals.
Science was able to prove this much, simply because deliberate
and pure infections could be carried out.  When it came to simian
AIDS in the laboratory, the SIV virus was capable of being the
sole inciting culprit which made the difference between health
and death.  Although SIV and FIV were discovered after HIV, there
remains a lesson for us from each of them:  Lentiviruses alone in
some circumstances is quite capable of causing slow immunos-
uppressive death.

AIDS Heresies, Part 6

The Critics Again

    Or, at least they are for those who are willing to look.  Dr.
Peter Duesberg spends very little time on the monkey SIV experim-
ents in his writings, and what time he spends is spent on select
experiments.  Concerning SIV, Duesberg notes that in one experim-
ent, lack of good antibody response to a cloned strain of SIV in
monkeys predicts simian death, suggesting that the virus is
powerless against a good immune response.  Unfortunately,
Duesberg fails to note that this finding applies only in the
short term in a paper where animals were not followed for the
long term [81].  Thus, while it is true that experimentally
infected monkeys die quickly of SIV in the short term if they
cannot mount an antibody response, it is also true that they can
also often be expected to die of SIV-caused immune suppression
after 1 to 3 years of infection, despite good antibody response
[83].  This has also been seen in naturally transmitted infectio-
ns: a long SIV infection progressing to AIDS even with good
antibody response has been observed after experimentally-monito-
red sexual transmission of SIV from animal to animal [84].  Also,
as noted previously, the natural latency period for SIV before it
causes immune disease and death has been observed to be as long
as 7 years in animal colonies, and such long-latent disease, when
found, also occurs in the presence of good antibody response

    Duesberg believes that the presence of antibodies to a
retrovirus confers immunity on the host (p. 233), and thus that
it is unlikely that those people infected by HIV who develop
antibodies (making them "HIV-positive"), should develop active,
damaging HIV infection later on.  But it has long been known in
general that antibody response does not protect against long
delayed immune failure in the slow but fatal immune deficiency
disease caused not only by SIV and FIV, but also by many retro-
viruses, such as the simian leukemia virus and feline leukemia
virus [85].  Nor does antibody response protect against the
persistent and sometimes later damaging infection in lentiviral
diseases in sheep and goats [86].

    In writing of SIV infection, Duesberg is also at great pains
to emphasize differences between the infection and human AIDS,
pointing out that SIV infected monkeys do not get dementia (how
would we know if they did?) and Kaposi's sarcoma, but failing to
note that monkeys do get most of the other human AIDS infections,
and have much the same basic pathology evident in their destroyed
lymph tissues and immune systems as do human AIDS patients.
Indeed, Ellison and Duesberg (p. 135) go so far as to character-
ize simian infections with SIV as not resembling AIDS at all,
instead merely being " all respects, very traditional viral
flu-like diseases..."  This is a pathological absurdity which we
have already addressed and refuted at length.

    If Duesberg fails to discuss the relevant animal work with
any degree of care or detail, Root-Bernstein does not even try.
Any argument based on induction must turn on standards of
evidence, and bias in standards of evidence abounds in arguments
about the cause of AIDS, just as it does in all scientific
arguments (the arguers being human).  Thus, Root-Bernstein (p.
330) asserts: "The entire case for HIV as the cause of AIDS rests
upon epidemiologic correlations..."  He knows better.  Root-
Bernstein himself is willing to use a wide range of animal
experimental evidence in indirect support for his own multifacto-
rial AIDS hypotheses, yet he steadfastly maintains a peculiar
blindness for the same kind of evidence when it supports the
HIV/AIDS hypothesis.

   For instance: Root-Bernstein is quite capable of noting for
purposes of inference many instances where a possible non-HIV
causal factor of AIDS causes relatively mild unselective lymphoc-
yte suppression, or even relatively mild selective CD4+/CD8+
ratio suppression, in laboratory animals (p. 117, 121, 124, 127,
130, 137, 138).  Yet there is total silence from Root-Bernstein
about the immunological effects of infection by animal lentiviru-
ses like SIV and FIV.  Indeed, the gap in Root-Bernstein's
discussion of causes of immune suppression is so glaring that one
is left wondering how it is that a literature search as careful
as that represented by his book entirely failed to note the
effects of certain viruses on immune parameters.  Root-Bernstein
discusses the effects of many micro-organisms, including viruses,
on immune function, and even gives us the effects of CMV, EBV,
and hepatitis B viral infection on CD4+/CD8+ ratios (p. 151,152,-
153).   The results: the ratios may change as in AIDS, but not
nearly as drastically.  Yet Root-Bernstein writes nothing about
the effects of any _retrovirus_ of any kind on these immune
parameters, whatsoever.  This, even though lymphotropic retrovir-
uses are the only organisms known which in the laboratory mimic
the especially severe CD4+ lymphocyte loses, severe CD4+/CD8+
lymphocyte ratio suppressions, lymph node destruction and
opportunistic infection susceptibility found in AIDS.

     Nor does Duesberg mention such effects, except in one
instance in which he makes an observation that SIV retrovirus
"barely reduces the T-cell levels of ill monkeys" (p. 232), a
statement which is false as a generalization, since there are in
fact a number of studies which have found significant T-cell and
CD4+ lymphocyte depletion in some SIV-infected monkeys [80].
Note that it is not that the effects of retroviruses on immunity
are discussed and dismissed in heretical literature; rather, they
are generally not discussed at all.  In reading the AIDS here-
tics-- even those heretics doing detailed surveys of the bio-
medical literature about AIDS-- it is as though information on
the effects of lymphotropic retroviruses on animal immune
function did not exist.

The Retrovirus From the Human Epidemic

    SIV clearly caused immunosuppression and death in monkeys,
but no such simple answer was forthcoming with humans when it
came to the question of what was causing AIDS, although certain
lab and blood donation incidents came close to being controlled
experiments with HIV.  At the NIH, three workers have so far been
accidentally infected with pure molecularly-cloned HIV, with the
result that two are running abnormally low CD4+ counts some years
later, and the third has lost almost all CD4+ cells, and develo-
ped opportunistic infections.  (Though many of Duesberg's "HIV-
free" AIDS cases are based on nothing more than slightly abnormal
CD4+ counts, in a display of double standards Duesberg reportedly
refuses to acknowledge two of the lab HIV infections as AIDS by
the same criteria) [22].

     In another example, an African study found that children who
had been HIV infected by blood transfusion given for malaria and
other reasons, had a far higher death rate than matched children
who had received the same amount of blood for the same illnesses
but did not contract HIV [87].  In this study, 6% of patients who
received HIV-positive blood and had been infected, but no HIV-
negative transfused controls, had developed clinical AIDS after
one year.  Such studies underscore the close relationship between
HIV-positivity of blood and risk to the recipient of dying.
Duesberg has claimed [88] that no study shows a higher death rate
in HIV infected people than in matched HIV-uninfected people--
yet here is such a study.

    With the new infectious immunodeficiency syndrome in humans
first identified before FIV and SIV were known, science at first
had only epidemiologic correlations to work with.  Later, some
results from viral cultures and matched clinical studies arrived.
Nevertheless, the scientific community decided early that it was
working with a viral disease of unusually long latency.  After
HIV was identified, statistical studies quickly picked it as the
most likely answer yet proposed for the cause of AIDS.

     But there was more than statistics-- also present in HIV and
AIDS was an overall pattern of viral structure and immune failure
which proved far from unique as time wore on.  HIV had the
typical lentivirus structure, identical to that of FIV and SIV.
Inside its cone-shaped core were two more or less identical RNA
molecules, each containing 9 genes, and associated with a
peculiarly magnesium-dependent reverse transcriptase enzyme.
People infected with HIV were found to develop antibodies to it
in the blood usually a month or two after infection, and keep
them for life (although levels of antibody "targeted" to stick to
the core proteins of the virus often did decline toward the end,
in full-blown AIDS, as numbers of virus particles in the blood

     The presence of antibodies in the blood for years did not
seem to keep people with HIV from eventually becoming very ill,
however.  Since HIV was discovered before the many careful
studies with FIV and SIV, the progression of HIV infection to
serious illness in the face of serum antibody "immunity" to it,
puzzled some scientists quite a lot.  Today, we know from much
closer experimental study that lentiviruses are routinely able to
mutate to escape host antibodies, so that antibodies found in the
same blood with these viruses often do not neutralize them,
especially late in the course of disease [86].

    The HIV virus proved to have a special affinity for CD4+
lymphocytes, the very cells which disappeared in AIDS patients
(and, as we have seen, disappeared also in many
lentivirus-infected animals).  The HIV virus grew readily in CD4+
lymphocytes in culture (not usually causing them harm, but
sometimes doing so [89]), and with the ability to grow the HIV
virus in cultures of cells and to detect antibodies to it, came
the ability of scientists to detect infections caused by it.

    Because HIV infection almost always resulted in HIV antibody,
but since the antibody did not signal cure or the end of virus
infection, the HIV antibody test was later used to track cases of
transfusion-associated AIDS.  In nearly all cases where archived
samples of transfused blood could be tested later, people with
transfusion AIDS were found to have gotten units of
"HIV-positive" blood.  In the U.S., 28,000 people received HIV-
positive blood products before testing halted such transfusions
in 1985, and of these, 5,879 have developed AIDS as of July,
1993.  These figures, allowing for less than 100% transmission of
HIV by this route, are quite similar to the AIDS rate in HIV-
infected people with hemophilia.  HIV-positive blood was later
shown to hold not just antibodies to HIV, but also the infectious
HIV virus itself.

The Slow Development of HIV Infection in the Body.

   Although people could not be deliberately infected with HIV
for ethical reasons, antibody testing to see who had been
infected with HIV suggested that HIV was indeed transmitted
sexually (though with very low efficiency), and also through
contaminated blood products.  In time, the virus was "caught in
the act," as a number of people were identified by antibody
testing and viral culture as they were first undergoing
infection.  This "primary" infection turned out to sometimes be
rather like an attack of infectious mononucleosis ("mono") -- a
long and severe sore throat, swollen lymphatic tissues, fever,
and tiredness for weeks.  Sometimes it was less severe, and was
not even noticed (a good sign which was found to predict a longer
time to development of AIDS [90]).  After the initial onslaught,
however, the infected person developed HIV-antibodies (i.e.,
become "HIV-positive," or as epidemiologists say:
"sero-converted"), and then began recovering.

    Occasionally a person newly infected with HIV would rapidly
seroconvert, lose most CD4+ lymphocytes in the blood, and go on
to develop full-blown AIDS in as little as 8 weeks [90], so
scientists knew this could happen (just as some monkeys developed
AIDS in a few months after SIV infection).  Most people, however,
apparently recovered completely after initial HIV infection, and
felt well.

   But only apparently.  The virus was not gone, but had only
gone underground, into the DNA of many of the host's cells.  As
with other lentiviruses, the long latency period of HIV before
secondary disease was striking.  Throughout the largely symptom-
less latency period the antibody against HIV always continued to
be detectable in the blood, making the infected person HIV-

    But there was always more than antibody.  Even years after
infection, viral DNA could still be detected essentially 100% of
the time in an HIV-positive person's CD4+ lymphocytes, and other
cells as well.  Especially easily infected were immune system
cells called monocytes and macrophages.  In a person with AIDS,
up to 13% of lymphocytes and monocytes in the blood were found
infected [91].  From 93% to 100% of the time (depending on the
study), infectious virus and viral DNA could be recovered from
the blood of asymptomatic people who were HIV-positive, and 100%
of the time from people with AIDS [41].  Higher levels of virus
could be cultured from the lymphatic tissues of such people,
where it was multiplying actively, even in people who appeared
healthy [92].

    Like SIV-infected monkeys and FIV-infected cats doomed to
future immune failure, HIV-positive people were still infected,
and most were still slowly losing immune cells in lymphatic
tissues.  In some sense they were still "sick," even though they
might feel and appear healthy.  By following large groups of HIV-
positive volunteers with blood tests and exams over more than a
decade, scientists began to piece together what was happening.
Over time, the average numbers of CD4+ lymphocytes in the blood
of groups of such people (but not in HIV-negative people) were
slowly falling at a steady rate, although not at the same rate in
everyone.  At the same time, until late in the disease, levels of
CD8+ lymphocytes actually rose.

    The lymphatic tissues of some infected people were found to
be under viral attack, and after some years began to show this by
enlargement, as was also often seen in lentivirus-infected
animals.  This phase had early been called the "AIDS related
complex" or ARC syndrome.  In the lymphatic tissues, a particular
stringy virus-trapping cell called the "follicular dendritic
cell" disappeared, and with this loss came dysfunction of the
other immune cells which depended on the follicular cells to
catch and digest viruses for evaluation.  (Cells in the immune
system evaluate infectious organisms by partly digesting them
into smaller pieces and then "tasting" and sharing the fragment-
ary results among themselves, for later recognition).  Even-
tually, in an HIV-positive person with lymphadenopathy, most of
the CD4+ lymphocytes in the lymphatic organs (where 98% of the
CD4+ lymphocytes in the body were normally to be found) were
gone.  Exactly what had happened to them was not clear, but they
had disappeared from the blood as well, and had obviously been

     At about the time the lymphatics were reaching the end stage
of destruction, the HIV virus, escaping filtration by the
now-destroyed immune system in the lymphatics, began to enter the
blood in larger numbers once again.  The largely asymptomatic and
reasonably healthy latent period was now at an end [93].  Levels
of CD4+ lymphocytes had been falling at an average rate of 60 per
year, and when levels of CD4+ lymphocytes in the blood reached
the critical count of 250 to 200 (about a quarter of normal
levels), fevers and other symptoms began.  Opportunistic
infections often also appeared, such as candida yeast infection
in the throat (often the first infection), or the unusual fungal
pneumonia caused by _Pneumocystis carinii_ (this organism is
particularly suppressed by CD4+ lymphocytes, and so is one of the
first infections to arrive when their numbers fall).  In homosex-
ual men, but much more rarely in other AIDS patients, a
peculiar vascular tumor called Kaposi's sarcoma might appear on
the skin. (This disease has long been thought to be caused by a
second infectious agent, which only recently has been detected by
DNA sequence and antibody detection [93a], and suggested to be a
new virus in the herpes class, called HSV-8).  With the
appearance of these markers of secondary disease, now the
infected person was said to have "full-blown AIDS," or simply,

    Estimates of the time between initial HIV infection and later
AIDS were found to vary strongly with the age of the person, and
to a lesser extent on the group infected (homosexuals, with many
other concurrent infections, developed opportunistic infections
sooner, and also Kaposi's sarcoma).  The latency time did not
depend heavily (if at all) on the sex of the infected person
[93b].  Generally, the period taken for half of a given infected
group to become sick with full-blown AIDS was about 10 years--
with perhaps a few more years for younger people, and a few less
for older people.

    The development of AIDS signaled a permanent loss of much of
the body's ability to effectively fight viruses and fungal
diseases, although the ability to fight bacteria was only mildly
impaired.  This gave the immune deficiency in AIDS a very
different character from the kind of immune deficiency caused by
many cancers, drugs, and other diseases.  In AIDS, as, first,
CD4+ lymphocyte count dropped toward zero, then finally at the
end of life, even CD8+ lymphocyte count dropped sharply, finally
even more devastating infections arrived, such as viral diseases
of the retina and brain.  Chemotherapy-resistant lymphomas became
common.  By the time AIDS suffers died, usually a year or two
after first developing full-blown AIDS, it was not uncommon for
them to have no CD4+ lymphocytes in the blood at all, and for
them to have lymphatic tissues which had been essentially

    Before scientists became acquainted with the lymphotropic
(lymphocyte-infecting) lentiviruses, they had never before seen
_any_ disease, toxin, or condition specifically destroy nearly
every CD4+ lymphocyte in an animal, while leaving CD8+ cells
relatively untouched until near the end.  The specificity of
lentiviruses in causing destruction of one part of the immune
system, while leaving another part relatively intact, was awesome
and very strange.

    It remains so today, not least because scientists still have
not discovered exactly why it happens.  One good guess is that
the body's immune system somehow destroys infected CD4+
lymphocytes (as it does other virally infected cells) before they
have time to make it into the blood, until eventually they are
all gone.  Many other possible mechanisms for destroying these
cells have been proposed, and limited evidence for each proposed
mechanism exists.  That infection with a lentivirus can destroy
an immune system is not the issue, since lentiviruses are known
for certain to have this capability in animals, and thus a
mechanism for this certainly exists.  The only issue left is what
this mechanism is.

Telling Nature How Her Viruses Must Behave

    It is unfortunate that HIV/AIDS skeptics spend so little time
on the behavior of lentiviruses in animals, for HIV is a typical
lentivirus, and many of the things critics are saying HIV cannot
do in humans are things which lentiviruses are known quite well
to do in animals.  The inference is not difficult to draw.  It is
one thing to assume that HIV cannot cause disease long after
there has been a good antibody response to its initial infection,
and another thing to assume this even though many examples are
known in animals of the viruses' cousins operating in exactly
this way.  Animal models quite often provide "existence proofs"
of mechanisms which overconfident scientists, on the basis of
limited understanding of biology, might otherwise dismiss as
being unlikely or impossible.  That is one important function of
animal models: to provide humility to biologists.  Usually models
are successful in this, but not always.

    The status of Dr. Peter Duesberg as a leading retrovirologist
has made it easier for him to be taken seriously when he expres-
ses disbelief at the way in which HIV is hypothesized to damage
the immune system.  Duesberg's objections of disbelief are made
possible by the fact that we do not presently understand every
step in the process by which lentiviruses (or indeed most
viruses) cause disease.  This does not prevent Duesberg from
dictating how it should, or must, happen.  "If HIV were the cause
of AIDS," writes Duesberg, "T-cells would drop and AIDS would
appear during the primary infection, when HIV titers [amounts of
HIV virus in the blood] are high and there is no viral immunity"
[8].  Unfortunately, based on the way both FIV and SIV are
documented to kill animals after long intervals with good
antibody production responses, it would appear that Duesberg has
no good grounds to believe that HIV should not, or could not, do
the same as a pathogenic agent in humans.

    Similarly, a great number of other properties of HIV which
Duesberg believes argue against HIV's pathogenicity, also happen
(to the detriment of his argument) to be properties of the
demonstrably pathogenic "simian-AIDS" virus SIV, which (as we
have seen) closely resembles HIV.  There is, for instance, no
question that SIV infection alone is sufficient to cause simian
CD4+ cell-loss immunodeficiency and death, and that this may
happen with delays of up to 3 years in experimental infection
[81, 83].  In short, much of Duesberg's inference that HIV is
probably harmless is built upon the very shaky proposition that
HIV-1 is not likely to be able to do in humans what FIV, SIV, and
(as we will see) HIV-2-- all very similar retroviruses-- are
already known both observational and experimentally to do,
without assistance, in animals.

    Properties of SIV infection, in common with HIV, include:
similar low level viral titers in animals which are doomed to die
later of retrovirus infection, lack of pure CD4+ lymphocyte cell
killing by SIV in culture [89], with paradoxical profound loss of
CD4+ lymphocytes and lymph organ destruction in SIV-infected
animals [94], and finally, absence of any obviously special SIV
genes which might confer virulent properties with regard to other
retroviruses (instead, the infection latency and eventual death
with SIV infection in some monkeys is a property of the host-
virus system as a whole, and can be seen with one strain of HIV-2
or SIV, and not another).

    All these viral properties or infection characteristics have
been claimed by skeptics to indicate that HIV is probably
harmless, and yet we know that their presence with both SIV and
FIV certainly does not indicate harmlessness for these organisms.

By analogy it would seem, if anything, that HIV is not necessar-
ily harmless either.

The Koch Postulates of Disease

    The parallels between SIV and HIV turn out to be useful also
in an odd debate involving the "Koch postulates" of disease
causality, which has lately been resurrected by HIV/AIDS skepti-
cs.  Duesberg, almost alone among virologists, believes that
viruses must fulfill these postulates to be proven to cause
disease.  Koch's postulates, named after a 19th century
physician Robert Koch, date from a time before viruses or
antibody testing were known, and have been discarded by most
scientists in the modern era, since they can lead to bad inferen-

    To repeat a theme of this essay: statistical correlation
causes many difficulties in trying to infer causation, yet it is
still useful.  For instance, there are many people with sore
throats who are not infected with the micro-organism popularly
known as "strep," and many people are infected with strep for
decades who don't have sore throats.  However, we could not
legitimately conclude from these data that strep does not cause
_any_ sore throats.  Rather, the issue is what fraction, if any,
of sore throats are caused by strep.  In order to even begin to
answer this question, we need to know at minimum how "tight" are
mathematical correlations between the presence of the putative
infectious agent (strep), and the disease syndrome (sore throat)
we think it may cause.

    Dr. Robert Koch postulated some simple rules which he felt
should be fulfilled for an organism to be proven to cause a
disease.  The first was that the organism be findable in essenti-
ally all cases of the disease.  Strep would fail the first Koch
test as the "cause" of the syndrome of sore throat, but today we
would not say that this was proof that strep did not cause sore
throats.  Rather, we would measure the prevalence of strep in
various populations of asymptomatic and sore-throated people, and
then employ statistical methods in order to arrive at a probabil-
istic estimate of what fraction of sore throats strep was likely
to cause.   Koch, too, would use such statistical methods later
in life when he was forced to abandon his own rules in order to
inductively guess the cause of cholera.  In short, the world has
moved beyond Koch's postulates, and even Koch in his own life
time did so.

    But not Duesberg.  We have examined Duesberg's attempts to
define AIDS in such a way that many AIDS cases would be HIV-free,
rather than define it in any clinically useful way.  These are
misguided attempts to disprove the HIV/AIDS hypothesis using
Koch's simple un-statistical laws.  Another of Duesberg's
arguments relating to the first Koch postulate holds that HIV is
not present in _sufficient quantities_ to cause disease in humans
who have AIDS.  But how do we know what "sufficient quantity" is,
when it comes to lymphotropic lentiviruses?  This ought to be a
case where animal models should help.  HIV is in fact present in
the blood of AIDS patients in quantities very similar to the
amount of SIV in the blood of SIV-infected monkeys, and we know
that without doubt SIV is sufficient to cause severe immune
deficiency disease leading to death in monkeys [82].  (During
much of both SIV and HIV infections, most of the body's retrovi-
rus is present in the lymph tissues, not the blood).  Thus,
animal experiments tell us that there seems to be something wrong
with Duesberg's intuition regarding how much retrovirus "should"
be observed in the blood, during a retrovirus infection which
will eventually be fatal.  We also know that the replicating HIV
virus is indeed present in high quantities in the lymph tissues,
where the destruction in AIDS is primarily seen [122].

    Another of the Koch postulates requires that an organism be
isolated in pure culture (not even close to possible for a virus
when Koch was alive, but possible now with modern viral culture
and molecular cloning), and that this culture then be used to
transmit the disease to a susceptible host.  Duesberg has pointed
out that HIV does not cause disease in non-human primates, and
has not been demonstrated by deliberate and controlled direct
transfer to cause disease in man.  However, we should note that
failure to cause disease by experimental transmission is true
only for HIV-1, since recent experiments have now succeeded in
producing animal disease with another strain of HIV, called HIV-

    HIV comes in two strains, HIV-1 and HIV-2.  HIV-1 is the
"familiar" strain isolated from almost all American patients;
HIV-1 does infect and replicate in chimpanzees, but except for
lymphadenopathy does not cause noticeable illness in them (this
is not strange behavior for a virus-- deadly yellow fever and
hepatitis B viruses behave in the same benign way in chimpanzee-
s).  Quite recently, however, when researchers were able to
isolate a different lentivirus from AIDS patients in West Africa
(with a few cases in other parts of the world), they found that
the new virus, eventually dubbed HIV-2, was only 50% identical in
genome to the more familiar HIV-1, but was genetically almost
indistinguishable from the SIV family of monkey viruses (The
figure of 50% may seem a significant amount, but it is for
instance similar to the difference between the two common
varieties of herpes simplex, either of which can infect the mouth
or the genitals, and both of which cause very similar diseases).
If HIV-1 and HIV-2 are as close genetically as Herpes-1 and
Herpes-2, then the question of whether or not HIV-2 causes an
AIDS-like syndrome in monkeys would become somewhat relevant to a
causal debate involving HIV-1.

   Since HIV-2 is the only retrovirus isolated from some West
African AIDS cases [95] it was natural for researchers to see if
the HIV-2 virus, so similar to SIV, killed Asian monkeys (but not
African monkeys) in the manner of SIV.  They found, by injecting
HIV-2 into Asian monkeys, that this virus does indeed behave like
SIV [96].  HIV-2 destroys the immune system in Asian monkeys,
somehow causing lymphadenopathy, depletion of CD4+ lymphocytes
over time periods of up to a year, and fatal opportunistic
infections.  In other words, HIV-2 infection gives the monkeys
the simian version of AIDS [97]. Further, the longer the chain of
infection in monkeys, the more deadly the human virus becomes for
them.  HIV-2 also causes an AIDS-like condition when injected
into baboons [97a].  In all this work, clues have emerged about
where the HIV-2 virus came from originally.  Humans appear not to
be the natural hosts of this virus, just as they are not the
natural or earliest reservoir for HIV-1.

    The result of this work is a chain of inferences, but with
help of the new HIV-2 results, not a difficult chain to follow.
The retrovirus known as HIV-2 has been found by direct experiment
to cause low CD4+ lymphocyte counts in animals, destruction of
animal immune systems, opportunistic infections, and death.  This
HIV-2 virus had been isolated from humans dying in Africa from an
epidemic of something that destroyed CD4+ lymphocytes, destroyed
immune systems, and as a result allowed opportunistic diseases
resulting in death (in other words, AIDS).  If HIV-2, which
causes AIDS-like CD4+ immune destruction in monkeys, is not
causally involved in the severe human immune problems in West
Africa where it is isolated from AIDS cases, it would rank as one
of the greatest scientific coincidences of all time.  The
magnitude of the coincidence would be similar if HIV-2 does
indeed cause AIDS, but the 50% genetically homologous HIV-1,
already implicated for many other reasons in AIDS, does NOT cause
disease in the human AIDS cases from which _it_ is isolated.

    The art of scientific inference lies in deciding how many
coincidences it is wise to believe in.

AIDS Heresies, Part 7

The Ultimate Proof

   The HIV/AIDS hypothesis has not been proved by experimentally
infecting completely healthy humans deliberately with HIV under
controlled conditions.  Thus, many of the standards of proof
required by those who are skeptical of the HIV hypotheses would
seem to be impossible in an ethical age. Apparently no organism
but man becomes significantly ill with HIV-1, just as is the case
with a number of other viruses, such as hepatitis B and yellow
fever virus (both of which historically were proved to be human
disease organisms in direct human experiments which would never
pass a human subjects protection review board today).  Root-
Bernstein notes that human-specific viral diseases satisfy Koch's
postulates only by being transferred deliberately and experiment-
ally from a sick person to a healthy one (p. 95), and sometimes
such a trial appears to be what skeptics demand for HIV.  Root-
Bernstein states:

   "..correlation, no matter how good, is never grounds for
asserting causation.  One must have experimental control over the
disease." (p. 101).

    It is not clear what Root-Bernstein means by "experimental
control over the disease."  Should enough of the extreme HIV
skeptics (which, to be fair, Root-Bernstein is not) take a page
from the notebooks of self-experimenting disease-hunting doctors
like John Hunter (who died after inoculating himself with
syphilis) or Walter Reed's brave colleagues James Carroll and
Jesse Lazear (who allowed mosquitos carrying yellow fever to bite
them, resulting in the death of Dr. Lazear) and deliberately
infect themselves with HIV-1, we might have something.  Many
physicians have historically risked and even given their lives
for science and their beliefs, when there was no other way to
continue an experimental program on human subjects [1].

    Peter Duesberg has indicated unwillingness to be inoculated
with HIV, saying it would prove nothing if he survived in good
health, as he expects to.   Duesberg is probably right in this,
but since HIV is thought to cause steady and implacable immune
decline in more than 90% of people infected with it, highly
statistically significant results would be generated if even two
healthy skeptics infected themselves with HIV, and both survived
without any evidence of increasing immune deficit, for 5 years.
Thus, it may be that putting together the necessary experiment
lacks only some organization.  One Florida physician named Robert
E. Willner, author of an amazingly misinformed AIDS heresy book
called _Deadly Deception_ [98]  has already performed at least
two TV-televised needle inoculations on himself with the blood of
an HIV-positive man with hemophilia (no word yet on Willner's HIV
antibody status, but from what we know of viral blood burdens, he
is inoculating with too little blood to realistically be of much
risk from a non-ill HIV-positive person).  Such cases will
probably remain too scarce for conclusions, especially if the
adequate pre-testing necessary for good science is not done.
Still, if any self-inoculating heretic does contract HIV, and
then AIDS, this way, it will certainly make news [98].

    Meanwhile, how far can we go with the AIDS statistical
results that we have?  How does associative statistics, coupled
with knowledge of related mechanisms, actually work in guiding
formation of a good scientific theory?

Induction: Telling Causation From Mere Correlation

   Since the writings of the 18th century philosopher David Hume
it has been known that certainty about physical causes and
effects is not to be had from mere association, even if the
temporal sequence is correct.  (In fact, according to Hume,
absolute certainty about positive causation is not to be had even
when we can do direct experiments.  Most scientists ignore this
most extremely pessimistic view of causal knowledge, or else they
view the high degree of inductive certainty gainable with
experiment to be "good enough.")

    It seems that Hume is at least correct that to some extent
the causal conclusions of science are always uncertain, because
they involve mechanisms and rules we can never be completely sure
of understanding, even if we had some way to guarantee that
future events will continue to be bound by any "rules" we _could_
be sure we understand now.  A favorite fable, which philosophers
tell to illustrate the problems of induction, features a turkey
on a family farm who observes that every time the farmer comes to
his turkey-run, he comes to feed the turkey.  The turkey thus
hypothesizes a causal connection, and predicts feeding each time
the man comes-- and as time goes on, sees this theory "verified"
many times.  But on the fourth Thursday of November the turkey's
well-verified theory suddenly becomes mal-predictive, because the
universe is a much more complicated place than turkeys can
comprehend.  Humans are sometimes in the same position with
human science: unfortunately, the universe is such a complicated
place as to sometimes make turkeys of us all.

    Nevertheless, to the extent that today's future, which we
cannot know, continues to be like "yesterday's future," which we
can check, progress can be made.  A turkey's existence is made
easier for a time by having even an incomplete model of reality,
and we may ourselves say that even partial understanding of
causes brings partial "knowledge."  Inductive knowledge is
uncertain the way a weather forecast is uncertain, but this does
not mean that science does not uncover a certain kind of truth.
A weather forecast may not guarantee the future, but the point is
that it is usually better than the results of flipping a coin or
guessing.  Probabilistic knowledge, therefore, is still genuine
knowledge of a special kind.  Indeed, it is the only kind of
knowledge we can have about what events will occur in the future.

    Because the association of events may be always controlled by
a third factor we do not suspect, the problems with induction
become most acute in trying to tease out causal relationships in
systems where we cannot experimentally influence events in order
to rule out possible causal relationships.  In such systems,
statistics help us tell which factors are important and independ-
ent of each other in _predicting_ future events, but such
associations only _suggest_ causation when present.  This is
because any factor "predictive" of an event may still only be
merely a good "proxy," or marker, for an even more predictive,
mechanistically causal factor.  Thus, the strength of statistical
associations between events and possible causes are far more
helpful in ruling _out_ possible causes than ruling them _in_.
Obviously it is very difficult for a factor to be causal of an
event if its presense is not _at least_ independently predicative
of the event.

    Here an example may be helpful: If we find from a multivari-
ate analysis of (say) food sales and crime, that weekly ice cream
sales during a calender year predict juvenile delinquency arrests
from week to week, but spaghetti sales do not, this is reasonably
good evidence on the face of it that spaghetti sales are NOT
causally connected to juvenile delinquency.  On the other hand,
for ice cream and juvenile delinquency, the associative connect-
ion found by the statistics is merely suggestive-- here we may be
looking at cause and effect, _or_ in the case of ice cream may be
looking at a variable which is a proxy for something else which
is more directly causal of delinquent behavior.  But if we doubt
ice-cream causation of delinquent behavior for other reasons, we
must guess what the real causal variable is, before statistics
can help us further.

    If we find that, say, the daily average _temperature_
predicts juvenile behavior even better than ice cream sales
predict it, and that knowledge of ice cream sales gives no
predictive power independent of knowledge of temperature, then we
now have evidence that ice cream is not causal, but is _merely_ a
proxy, or marker, for _temperature_ during the year.  Even with
this better association, we are not still not assured of the
causal role of temperature, although we might guess for
"mechanistic" and even indirect experimental reasons that we are
closer to the right track for temperature than we were with the
ice cream sales.  So we've made headway.  This story, though
silly, illustrates a major path by which science in general makes

Good and Bad Theory-Making: Occam's Razor and the Multiplication
of Hypothetical Causes.

    As in the example above, to make progress in science requires
that we continue to propose new and better causal factors for
effects which interest us, and then test these putative causal
factors statistically and experimentally.  Independent prediction
serves as the best statistical test for factors which we cannot
vary experimentally.  The power of prediction is thus all-
important in evaluating candidate causal factors for the cause of
effects which we cannot directly manipulate, such as AIDS.

    As noted, statistics cannot do independent thinking for us,
and we must rely on something other than statistics to come up
with our list of possible causal factors (such as the average
temperature in the example) to test with our statistical methods.
This is the business of the human imagination, and very possibly
also the human sense of order and beauty.  It has been observed
by the late Karl Popper, noted philosopher of science, that
almost no theory is ever ruled out by experiment, because with
enough imagination, nearly any theory can be tinkered with after
the fact, so that it continues to "explain" all data.  Thus, if
one causal factor does not explain results statistically in a
given situation, it is not necessary to drop it-- one may instead
postulate an additional factor which explains results in the case
where the first one fails.  In fact, if one persists in hypo-
thesizing new factors each time an old factor fails, one need
never drop any old hypotheses at all.  At some point, however,
doing this makes any theory simply too ugly and ungainly to be
believed, and at that point (if a better alternative is in view)
many scientists may decide to discard the old theory [99].  (Or,
at least, most scientists will-- for as physicist Max Planck
pointed out, only death removes the last die-hard believers in
_some_ theories).

   When it comes to AIDS, it is of course possible to construct a
theory in which AIDS is NOT caused by an infectious agent, but a
theory with so many causal agents that it still covers all the
available evidence.  To do so, however, requires that a newly
emerging simultaneous and significant cause of mortality in many
diverse groups of people be explained rather "unnaturally" (at
least to this author's sense of such things) in a great number of
different ways.  For example, Duesberg suggests that AIDS in
Africa is caused by malnutrition and tuberculosis and new
misclassification (p. 220), in U.S. male homosexuals by a new
habit of recreational nitrite use (p. 248), in female IV drug
abusers and their newborn children, by newly popular drugs other
than nitrite (p. 215), and in many of those HIV-positive people
who do not use illegal drugs, by use of prescription AZT since
1987 (p. 241), etc. [100].  Deaths in non-drug-using groups like
people with hemophilia in the era before 1987 are explained as
being due to immune suppression and extra life extension by
clotting factor concentrate, new since the early 1970's (p. 219)

    For none of these suggested causes of AIDS is there any
mechanistic or experimental evidence of good quality, since none
of the agents proposed, or anything related to them, causes in
animals the severe and specific suppression of CD4+ lymphocyte
numbers characteristic of AIDS.   In Duesberg's theory, AIDS
deaths from transfusions are argued to be non-existent (p. 214),
rejecting the orthodox idea that simple transfusion or trauma-
associated mortality usually covers them up (but see [87]).  AIDS
deaths in contaminated hospital workers are rejected as anecdotal
and perhaps due to something else, such as personal drug abuse
(p. 211).  AIDS deaths in wives of men with hemophilia (and their
children) are dismissed as being due to normal aging and misclas-
sification (p. 219), etc.

   One of the chief arguments against this kind of theorizing may
be aesthetic, but a less subjective matter has to do with
utility.   Because there are no statistical data to estimate a
quantitative role for many non-orthodox postulated risk factors
for AIDS (such as immunosuppression from undiscovered viruses or
from certain behaviors) the problem with very complicated _post
hoc_ explanations is that they are retrodictive, but not
predictive.  If HIV is only a proxy factor, or marker, for a
number of habits or practices which are supposed to "explain"
immune failure better than HIV infection does, then it follows
that the quantitative and even the qualitative presence of such
problems should be usable to predict future development of AIDS
in asymptomatic people, to even better accuracy than HIV status
does.  Nothing of the kind has been shown, however.  On the
contrary, cohorts of HIV-positive people have been shown to
develop AIDS at a predicable rate, fairly _independently_ of most
of the factors that have been suggested by heretics to be the
real causal factors for which HIV is merely a marker. (The reader
may see [100] and internal references, and also the review in
[102] for studies of the development of AIDS over time in
prospectively tracked cohorts of HIV-positive male homosexuals,
people with hemophilia, and transfusion-infected people).

   Duesberg's hypothesis, as compared with Root-Bernstein's,
actually has the charm of a certain simplicity, since for
Duesberg immune failure is said to be due to only two categories
of toxins: foreign blood proteins or drugs.  In Duesberg's view,
these two causal factors are supposed to have independently (and,
apparently, coincidentally) begun producing an epidemic of immune
deficiency in 1) people with hemophilia and 2) everyone else--
both starting in 1982 or so.

    "Multifactorial" hypotheses such as Root-Bernstein's,
however, posit so many different contributing causes of severe
immunosuppression (again, failing to differentiate between
significant ones and non-significant ones) that one or more of
the putative additional risk-factors identified by Root-Bernstein
is likely to be present in addition to HIV, in almost every AIDS
case.  _Rethinking AIDS_ argues the case that besides HIV
infection, AIDS might be caused by blood product infusion (both
whole blood infusion and clotting factor concentrate injection),
by surgery and/or anesthetics, by accidental trauma, by age (both
extreme youth and old age) by use of any and all common illicit
drugs and most pharmaceuticals (especially antimicrobials used in
AIDS), by concurrent infection with any of dozens of
microorganisms (known and unknown), by rectal insemination, by
malnutrition, and even by sunlight exposure.  Considering all
these hypothetical cofactors, Root-Bernstein writes (p. 92): "If
such agents exist... it is not enough to demonstrate that HIV is
present and highly correlated with AIDS.  It is also necessary to
demonstrate that these other agents are not present in AIDS
patients. That is impossible."

    Here Root-Bernstein somewhat overstates the case, since the
epidemiologic statistics contains methods for testing putative
risk-factor contributions in ways far more subtle than looking
for people with simple presence or total absence of all factors
being assessed.  Far more important to the issue of causation,
for those putative risk-factors which can be quantitated, is what
the mathematical effect of a larger "dose" of one factor is upon
the total risk, independently of the others.  Example: looking at
statistics, is cancer risk smoothly increased by smoking more
cigarettes per day, other factors being equal?  If so, that tells
us something very suggestive.  On the other hand, are smokers who
spend various amounts of time in the sun, from a little to a lot,
at larger risk with each larger increment of sun exposure, all
other factors (such as cigarettes smoked) held equal?  If not,
this tells us something, too.

  In general, it is not necessary statistically to find cases
where each factor which is a possible cause of a disease is
totally absent, in order to amass evidence that the factor in
question is not causal.  It is merely enough to show that the
increasing or decreasing _quantitative_ presence of the factor in
any "experiment of nature" has no independent statistical effect
on probability of the disease.  Such a demonstration never rules
out causation completely (due to annoying problems with induction
which always allow for the insertion of additional hypotheses to
"explain" failures in prediction), but it does make causation
much less likely-- at least for those who like their causal
hypotheses as simple as possible.

    Such statistical tools (i.e., multivariate analysis) are
among the most powerful which scientists can use for exploring
initial possibilities for causation, in complicated and
difficult-to-manipulate systems.  Without such statistical tools,
for instance, it would never be possible to exonerate any one of
any common set of behaviors (such as drinking coffee, walking, or
eating certain foods) from a causative role in ANY disease.  The
reason is that we live in a complicated world, and participation
to some extent in one or more of a certain set of behaviors
describes ALL of us, and certainly all of us who develop
diseases.  But we are fairly certain that walking and driving a
car (for instance) do not contribute to (say) lung cancer,
because of multivariate analysis of life-style, NOT because
somebody has described a group of lung cancer sufferers who never
left their houses.

   The following example may illustrate how, if too many
un-quantitated factors are postulated to explain an effect,
statistical science cannot help us sort through them, since only
quantitation can separate effects or lack of effects of possible
risk factors which are widely prevalent.

    For our example, consider a new hypothetical "multifactor"
theory that (say) lung cancer is not caused by smoking alone, but
also by "hidden immunosuppression," caused by certain behaviors.
This immunosuppression might be generated (say) by: certain kinds
of sexual contact, exposure to unshielded sunlight, exposure to
recreational and pharmaceutical drugs, chronic stress from
depression and urban life, previous surgeries, and concurrent
infections (including lung infections and infections by herpes
and other chronic viruses).  If we generate a long enough list of
hypothetical co-factors for lung cancer, we will have found, for
almost everyone who smokes and develops lung cancer, some other
hypothetical "risk-factor," other than smoking, which has never
been measured quantitatively in relevant groups.  If, in additi-
on, the very few people with cancer who smoke but deny all of our
new hypothetical risk factors, can be dismissed as being of
questionable veracity, we will have constructed a brand new
"multi-factorial" hypothesis of lung cancer.  This theory will be
complicated, difficult to test, and not possible to evaluate
statistically immediately, because the data do not exist to do
it-- nobody having previously bothered to measure them.

    But just what good have we done by constructing such a new
theory?  Just how useful would our new model be?  If, for none of
our new hypothesized risk factors, can the extent of exposure to
these risks be used now to statistically predict lung cancer
rates independently of smoking (in the way that, say, fruit
intake, age, or radon exposure can)-- then none of our newly
hypothesized risk-factors are useful at all.  Perhaps they may be
useful in the future when measurements are done.  Or perhaps not.
But would we be justified _now_ then in using their _possible_
existence to berate those scientists who would like to focus
study on known statistically independent explanatory risk-factors
for lung cancer-- such as smoking, age, diet, and radon-radiation
exposure?  Would we be justified, having done nothing more than
having constructed a new hypothesis of lung cancer involving new
un-quantitated variables, in writing books on our new causal
proposals with chapter subtitles like: "How could so many
scientists be so wrong?" (Root-Bernstein, page 350).

    The answer is no.  Nor is Root-Bernstein justified in this
kind of thing, based on what evidence he has.  Formless
hypotheses involving large numbers of unknown etiologic factors
which will be prohibitively expensive to search for until we have
some better indication of where it will be most profitable to
look, do not help the cause of human knowledge.  When considering
complicated multi-factorial hypotheses, where most of the
multiple factors are unquantitated, missing, or un-named, one is
reminded of the great physicist Wolfgang Pauli being asked if he
thought the theory in a new scientific paper was wrong, and his
remark that that would be too kind.  Said Pauli: "It isn't even
wrong." [99].

    In the case of the AIDS heretics, actually, the situation is
even more extreme than in our lung cancer example, since in the
case of AIDS, statistical data DO exist to evaluate some of the
heretically proposed "co-factors" for AIDS.  The statistical
influence of many of these (illicit non-injected drug use, AZT
use, total clotting factor concentrate use) have been found to be
statistically _not_ independent of HIV exposure, and their AIDS-
risk predictive power disappears completely in study after study,
when HIV status is controlled as a variable.  All these proposed
co-factors, then, are proxy variables.  There is thus very little
justification in continuing to advance hypotheses which involve
them, since none have passed even the most basic initial statist-
ical standards used by epidemiologists.

AIDS Heresies, Part 8

Impact of Belief on Action: Do More Complicated Theories Gain Us

   As we have seen, epidemiologic criteria implicate HIV as a
necessary causal agent in all AIDS cases, so long as AIDS is
defined most narrowly (and most usefully) as the newly epidemic
syndrome of life-threatening immune _failure_ (_not_ mild immune
suppression) which occurs in certain groups of body-fluid exposed
people known to be at risk for this new acquired disorder.
Moreover, an examination of the pathogenesis of virally-caused
CD4+ immune failure and slow death in animals infected with
viruses related to HIV, demonstrates that it is quite possible
biologically that HIV operates in humans to cause the same
sequence of pathologic events as we see in AIDS.

    As regards the last point, our retrovirus "proof of
mechanism" information is useful, if only in a negative way.  As
we have seen, because of such information it does no good for
heretics to express disbelief that there could be any mechanism
for retroviruses to do the immunologic damage which orthodox
medicine thinks they do (perhaps the common theme of every
heretical HIV/AIDS argument).  Since we know from direct
experiment that retroviruses _do_ in fact do this kind of immune
damage in animals, even in the presence of serum immunity and
with low blood viral levels, we _know_ a such a mechanism must
exist in animals.  Thus, such a mechanism is _not_ unlikely to
exist in humans as well.  The fact that we have not found yet
what we logically know must be there in animals, should not
bother us too much, and by extension, _the same is true of our
lack of success so far in humans_.

    Let us frankly admit it: we know very little of the actual
molecular mechanisms behind _most_ of the causal sequences which
we have identified by experiment in biology.  Thus, at this point
the fact that we don't yet know exactly how HIV and the other
retroviruses "work," is no more and no less odd than the fact
that we don't yet know exactly how cancer, or fetal development,
or memory, or the aging process works.  Complaining in 1995 that
we've spent a decade and lots of money on AIDS-- or for that
matter the aging process, or embryo development, or cancer, or
the basis of biological memory-- and only gotten more bogged
down, is childish.  This list of biological problems includes
some of the most complex problems science will ever face-- so
complex, in fact, that in the 20th century we're simply out of
our league as regards most of them [103].

    Again, (pace Root-Bernstein) _all_ infectious diseases are
known to be influenced by inoculum and host defense, and there is
certainly no reason to believe that HIV infection is an
exception.  _Intrinsic_ qualities of the host which are important
in all known diseases, and so too presumably for an HIV-caused
AIDS, would include ordinary variations in genetically-determined
immune response, and also things like host age. These qualities
we may term "intrinsic host factors."  Root-Bernstein refers to
host age as a "cofactor," but for purposes of our discussion it
may be more useful to differentiate intrinsic host factors which
cannot be changed, from those more conjectural environmental
cofactors which might be subject to manipulation--- such as diet,
dangerous habits, or infection by other organisms which are
susceptible to antibiotics.  The reason, of course, is that the
last are where the treatment payoffs lie.

   It is, I believe, generally assumed by orthodoxy that risk of
HIV infection is influenced by such standard infectious disease
variables as virulence of the HIV strain, amount of the HIV virus
inoculated, and route of inoculation into the body (which will
not be independent of amount inoculated).  The role of none of
these things is fully understood for HIV infection, but the idea
that there is a large role to be found for each of them, when we
finally understand AIDS more completely, is not really
controversial.  Possible cofactors in the acquisition of HIV and
development of AIDS have been discussed in the mainstream
scientific literature for years, and are not in any danger of
being dismissed any time soon.  Real controversy in the clinical
treatment of AIDS is almost entirely centered about the role of
conjectural extrinsic cofactors which are manipulatable _after_
the time of HIV infection, and thus not related to sexual
mechanics, the genetics or age of the host, or the inoculum and
virulence of the HIV strain in question.

    Again, Root-Bernstein differentiates between AIDS theories in
which HIV 1) plays a necessary role _along with_ such additional
_and also necessary_ conjectural extrinsic cofactors; and 2)
those theories in which HIV may play a role in AIDS, but is not
necessarily required.  The latter theories in which HIV may
contribute to AIDS, but is not required, all suffer, like
Duesberg's hypothesis that HIV is totally harmless, from this
problem: full-blown AIDS, as defined by very low CD4+ lymphocyte
counts seen epidemically in groups at risk for acquired immune
failure, is essentially never seen without HIV being present.
Again, this is true for no other infectious agent.  It would be
odd indeed if an infectious agent which is not really necessary
for AIDS, is the only agent found always to be present in those
who die of it.  And if HIV is so good at finding out and
infecting _all_ those who are immunosuppressed before they die,
why is HIV not also found in most or all people who are somewhat
CD4+ immune-suppressed for classical reasons, such as cancer or

    By contrast, theories which posit that HIV is necessary for
AIDS-- but that other immune-suppressive "extrinsic" or change-
able cofactors are necessary ALSO, are more difficult to evalu-
ate.  We have examined a number of the arguments against specific
proposals for hypothetical necessary extrinsic co-factors-- such
as licit and illicit drugs, specific micro-organisms, and blood-
product-effects on the immune system--and noted that studies do
not find these ideas borne out by independent statistical
regression, controlled for HIV status.  This is not to say that
we will not one day identify an important extrinsic risk factor;
only that the evidence is against the ones so far proposed.

    We have also argued that intrinsic host factors, viral
strain, viral dose, plus extrinsic cofactors like sexual mechan-
ics factors and the presence of other mucosal lesions (as from
sexually transmitted diseases) at the time of HIV infection, are
sufficient to explain most broad variations in AIDS epidemiology.
Of course, there is no guarantee that here again nature will not
prove to be more complicated than our simplest theories.  If
extra complexity proves necessary to describe the risk of
contracting HIV, however, we shall have to wait for clues that it
does, in order to know how best to proceed toward a more compl-
icated hypothesis.  Such clues, as argued above, have not arrived
so far.

    How important is it that we understand causation in AIDS as
fully as we can, and as soon as we can?  Obviously, having a more
realistic view of the pathogenesis of AIDS matters, in that it
partly determines where we put research dollars into prevention
and treatment studies, to say nothing of insurance dollars into
standard clinical practices.  If HIV is merely a bystander virus,
it won't be very helpful to study it, and it may even be
counterproductive to treat it, if the treatment carries some risk
on its own (as AZT and similar drugs certainly do).  Similarly,
even if HIV is only partly causal in AIDS, if another cofactor
modifiable after HIV infection is necessary to development of
AIDS as well, then (as Root-Bernstein points out) AIDS might be
prevented or cured by treating something which we have some
control over, even after a person shows up HIV-positive. This
would give us something to do to improve or even guarantee health
in HIV-positive people, and that something might be more
effective, and not as dangerous, as taking long term
antiretroviral medications.

    The correct view of the pathogenesis of AIDS should also
important in prevention as well.  If HIV is merely a bystander
virus, there would be no more reason for an HIV-positive person
to tell a prospective sexual partner about a previous infection
with HIV than there would be to tell about a childhood case of
chicken pox.  And there would be no more (and no less) reason to
use a condom if one was HIV-positive than if one was not.
Obviously, an incorrect view of the pathogenesis of AIDS might be
dangerous and expensive to many people with the wrong idea (and
their sexual partners), no matter which view ultimately turns out
to be correct.

    Prevention, of course, does not only apply to sexual transmi-
ssion: if viral theories of HIV causation are correct, we should
shortly see the positive effects on crude mortality rates, as a
result of preventing people with hemophilia from becoming HIV-
infected from their clotting factor concentrate, an intervention
begun in 1985-1986.  If this does not happen (and because of the
long latency of this disease it is too early to tell now), we
will know that we missed something very important.  Duesberg has
already proposed that we save the money that the HIV test for
every pint of donated blood costs us, and stop doing it.  If we
cannot with time prove that halting blood-borne HIV infection has
stopped transfusion-associated AIDS, to say nothing of almost all
AIDS in younger people with hemophilia, we will have little
excuse for continuing to test blood or clotting factor

    Alternative views of the cause of AIDS are probably becoming
more popular today, simply because they offer more hope than
conventional views of the cause of this disease.  A virus is
implacable-- especially one hiding in the DNA so intimately that
it is part of the genetic fiber of one's being.  It would be much
preferable to some to believe that AIDS is due to a combination
of more tractable problems.  This possibility has led to some
unusual biomedical research suggestions: Root-Bernstein suggests
(p. 369):  "If the multifactorial, synergistic theory of AIDS is
valid, then treating mice, rats or rabbits with some combination
of, say, multiple blood transfusions, cytomegalovirus infection,
anesthetics and surgery, and opiate painkillers could well result
in the immunological suppression typical of AIDS."

    And maybe not.  The idea that a lot of small immuno-
suppressions might add up to a large one, is an interesting idea,
but thin fare to base anything but a grant proposal on, until the
experiment is actually done.  In this author's opinion, it would
certainly be inexcusable to base a book which advocates changes
in the standard management of an often fatal disease on such
theorizing (Root-Bernstein stops just short of this, but many of
his readers will not).

    By contrast to experimental models of a multifactorial immune
suppression "hypothesis" (if such a vague entity is worth of the
term) of AIDS, we know experimentally that infecting Asian
primates with SIV or HIV-2 virus DOES IN FACT sometimes result in
exactly the type and severity of immunological suppression
typical of AIDS.  We have the added bonus in these experiments of
producing this interesting result with nothing more than a single
virus, quite similar to the one we always find in AIDS patients
with immune failure (and the very same virus, in fact, as we find
in West African AIDS patients).  One would think that this kind
of animal model would excite skeptics who wish understanding of
the nature of this disease to come to science-- but for some
reason it does not.  Skeptics are silent about HIV-2.  Perhaps
the reasons have to do with other than pure logic.

    In _Rethinking AIDS_ Root-Bernstein ironically quotes
Einstein's version of William of Occam's philosophic "razor":
"Keep hypotheses as simple as possible, but no simpler."
Failure to follow this maxim can be very costly in the real
world.  Resources for research are not infinite, and in practice,
diversion of resources toward experiments to test _a priori_
epidemiologically unlikely hypotheses, can result in much wasted
time and (of course) lives lost.

    One can imagine for instance, how long-delayed might have
been the program to control polio (a disease which was also, for
a long time, refractory to the "one agent--one disease" approach
criticized (p. 108) by Root-Bernstein) had multifactorial
theories of disease been pursued on all fronts for polio paralys-
is.  To this day we still cannot explain why the polio virus
causes paralysis in some few, but not most, infected people---
yet science succeeded in finding an effective preventive strategy
for polio paralysis, nevertheless.  We long ago stopped polio by
simply stopping the polio virus, which we had found was a
necessary element in the disease.  We _ignored_ the other
cofactors (whatever they were) which caused some people to be
paralyzed, and not others.  There is perhaps a simple lesson

   Root-Bernstein, in the concluding paragraphs of his book,
brings us to the crux of this practical issue (p. 372):  "Assura-
nce in science, he writes, "comes only through elaborating as
many possible explanations as can be imagined for a phenomenon
and eliminating all that can be possibly eliminated."  A
historian of science ought to have inserted major qualifications
in such a statement.  There are actually an infinite number of
possible explanations which can be imagined for any phenomenon,
and trying to eliminate them all would leave both science and
government paralyzed and bankrupt.  Real scientists, and the real
government agencies that fund them, need a better plan.

    In practice, only a certain relatively small segment of
possible kinds of theories are accepted or acceptable in science,
and these are based mostly on the success of previous small
classes of theories.  As both evolutionary biologists and
successful businessmen know, no efficient search of any large set
of possibilities proceeds by random search of all possibilities,
but rather must succeed (if it is to succeed) by exploration of a
much more limited set of combinations (randomly chosen or not) of
previously successful possibilities.  Major hypotheses worthy of
the expense and time of experimental testing in science are not
generated by elaborating every possible explanation.  Rather they
come through a still mysterious process of mentally narrowing
down certain classes of possible explanations to a few "good
ones," and then testing those. (If there were no mystery about
this process of narrowing down millions of theories into a few
good candidates, it would not be necessary to speak of scientific

    Again: "assurance" in science comes not from "eliminating all
possibilities that can be eliminated," as Root-Bernstein seems to
unwisely suggest, for (again) the resources for this do not exist
in the real world.  Assurance in science comes from publicly
testing for "prediction power" a relatively *few* leading
candidate explanatory theories, in ways that will usefully
differentiate them from each other, and THEN finding that one
particular theory (or small class of theories) repeatedly
survives such tests, while the other likely theories do not.

   At present, there is no getting around the fact that the HIV-
infection theory of AIDS is the leading and most predictively
successful causal hypothesis for AIDS.  Progress is thus most
likely to be made by continued testing of this theory, and likely
variations of it suggested to us by various kinds of statistical
evidence.  Testing of a causal theory of disease, of course, is
most profitably done by testing its prediction of the occurrence
of disease, or by its usefulness in preventing disease.  A theory
is not "tested" by requiring that it provide the route to a
successful treatment for disease as well.  Our present failure to
cure either AIDS or lung cancer does not speak to the truth or
usefulness of theories about their causation.

    Allocation of resources for the testing of more radical
causal theories for any disease (of which there are, of course,
an infinite number) must be made on the basis of some prior
likelihood of their being more useful or more explanatory (our
only current tests for "truth"), since otherwise much money would
be spent uselessly chasing moonbeams and bad guesses [104].  When
a new causal theory "predicts" (retrodicts) a phenomenon only
after the fact, and predicts it no better than our current best
theory, which is much simpler and already available for no more
money-- then our current theory is to be preferred.  On the
public level of funding, there would seem little reason to waste
money on the infinite number of alternate theories of disease
which may be more comforting than the standard one, but which
have (given current knowledge) too little chance of being true to
bet much money on.  It is to this point that we have come with

    In AIDS research, as in most research, science is now heading
generally (though never perfectly) toward the area of
investigation in which the largest number of medical scientists
and epidemiologists think maximum payoff is most likely to lie.
This is the research direction which seems likeliest to most
experts to save the most lives, with some caveats (see appendix
on biomedical funding problems).  We all wish there were modifia-
ble necessary extrinsic cofactors for AIDS, but we also know that
(in keeping with a saying as old as the metaphor) if wishes were
horses, then beggars would ride.  It is a long way from postulat-
ing such modifiable co-factors for AIDS and thinking how useful
they would be if there, to actually finding them.

    The bottom line is that, since there are an infinite number
of such possible co-factors, those who wish for change in
research direction policy in AIDS had best come up with better
arguments for why we should divert a great deal of our limited
attention and resources to look for things that we presently have
too little reason to believe may exist.  Nobody cares, of course,
if a small fraction of research money is diverted to wild ideas
and bold guesses (it's impossible to keep this from happening,
actually); but survey funding is one thing, and major policy
changes are another.

    In the meanwhile, is there any legitimate and useful and
honorable role for the scientific heretic in matters of
life-or-death public policy?  That depends on whether said
heretic publishes his contrary views in scientific journals, or
_Spin Magazine_.  There is a great difference between debate
within the scientific and medical community, which may be (and o
often must be) quite freewheeling, and the recommendations which
this community should formally offer the lay public, which
ethically must emerge from a better consensus of the best minds,
and be somewhat more conservative in nature.  From the workings
of Darwinian evolution to the workings of business; from speaki-
ng, to writing, to work in any field of science, there is no
creative act in which the selection/editing process is not
critical.  Attempts to circumvent the particular expert-review
editing process which produces progress in science certainly do
not help matters.  In particular, initiating biomedical scienti-
fic debates at the lay public level, where most chemical,
immunological, and mathematical or statistical evidence for one
view versus another is bound to be lost, is to invite public
policy disaster.  [Footnote]

Footnote:    It is not best that medical treatment debates be
kept secret, but perhaps it is best that they sometimes be left
confined to professional journals where those especially-well
motivated lay people who work hard enough to root them out and
decode them will probably in the process also gain enough
knowledge to begin to see the data in perspective.

    Certainly, the idea of partly shielding debate may sound
patronizing, especially as it involves the field of medicine,
which has come under intense criticism of late for this very
flaw.  And certainly, questioning authority is reasonable when
one's interests are at stake.  (One is reminded of Napoleon's
remark to a famous beauty that he did not approve of women
involving themselves in political discussion, and her reply that
in a country where women were having their heads cut off, that it
was natural for some of them to want to know why).  Although the
struggles of medicine in this area have been especially controve-
rsial, the problem of the "expert" does not only arise in
medicine, for we are all experts at something, and we are all
ignorant of most things.  Any expert asked for advice holds a
special obligation (knowing that the asker may not have the time
or the power to check conclusions), to edit knowledge, and to
pass along only conclusions which are relatively sure, and which
have been independently checked by other good minds.  The asker
_trusts_ the expert to do this, and indeed the essence of
relationship between the knowledge-seeker and the expert is one
of this kind of trust.

    When the expertise and the advice involves a life-or-death
matter, the level of obligation and the level of trust are
amplified, and this can result in behavior in those trained in
the medical profession which may appear more paternalistic than
it is.  More often, such conservative behavior is better underst-
ood as a manifestation of the wisdom, understood by responsible
adults, to refrain from saying everything one thinks, in situa-
tions where what one says really matters.  The person who gives
medical advice about life-and-death matters to the lay public in
popular publications is under an ethical obligation to refrain
from pushing a private theory with which most experts disagree,
no matter what it is (no rational person, after all, can be so
certain of his own conclusions as to bet other people's lives on
them before his theory has been well-checked by others).  Linus
Pauling, to his credit, probably did no harm with his popular
common cold suggestions, or probably even with this suggestion to
give mega-dose vitamin C to terminal cancer patients.  The AIDS
heretics, however, are in a different ball game.
End Footnote

The Future and AIDS in the U.S.:  Many Reasons for Hope

    The HIV viral plague is the great plague of the 20th century,
infecting as many as a million people in the U.S. alone, with 1/3
of a million people already having developed AIDS.  Almost all of
the people with AIDS now alive can be expected to die within a
few years, barring some immediate major technical advance or
discovery.  What about the rest of people with HIV?  If there is
no evidence that converting to a drug-free, medication-free
lifestyle assures the harmlessness of subclinical HIV infection
(and there most assuredly is NOT), then what can be done?  And
what about those people who are still HIV-free?  Are they
destined to see the disease sweep through their communities,
eventually catching everyone who is not perfectly chaste,
careful, and lucky?

    Let us, for the moment, follow William of Occam and assume
that there are no important post-HIV-infection modifiable cofact-
ors for AIDS left to identify, since at present we really don't
have much reliable AIDS epidemiologic data that cannot be
explained in broad terms under the headings of host and behavio-
ral cofactors that we assume exist already.  Suppose HIV is
indeed the major culprit for development of AIDS, exactly as
appears, and that risk of AIDS, once HIV infected, is more or
less predetermined already by the virus and host, with only minor
modifications in AIDS risk possible though modifications of the
most extremely risky behavior, such as discontinuance of IV drugs
and the more extreme forms of promiscuous behavior.  Studies show
that very long-term HIV survivors, as we have discussed, are NOT
saints [46], and thus there is no evidence that saintly behavior,
once a person is HIV-positive, does any significant good for
survival (however psychologically appealing for some this thought
may be).  Is there much hope for the population of the world,
even on these grounds?

    Perhaps.  I believe there is reason for optimism, even if the
simplest AIDS hypothesis which fits the facts (which is the one
now commonly accepted) turns out to be substantially correct.

     The first bit of optimism is on behalf of people who do not
have HIV yet.  It appears that the HIV virus is very hard to
catch, with favorable odds seen so far, even for U.S. call-girls
who report that even they do not use condoms with some trusted
regular customers.  The risk for transmission from a woman to a
man is particularly low in the absence of other sexually transmi-
tted diseases-- so low, in fact, that when American women
contract HIV from men, the men they contract the virus _from_
almost never contracted the virus themselves from other women,
but rather from needle-sharing during injected drug use, or from
male homosexual contact.  Since it is usually difficult to hide
the scars and the lifestyle which are corollaries of the kind of
illicit drug use which involves drug injection equipment-sharing,
it follows that a discriminating American woman's major risk of
AIDS is from heterosexual contact with a secretly bisexual man.
Even this risk can be greatly reduced by avoidance of anal
intercourse, and sexual contact with men who do not appear per-
fectly healthy. (As we have seen, HIV is far more transmissible
in the acute early "mononucleosis-like" stage of the disease, and
also much later in the final ARC and AIDS stages of the disease).
As for men's risks, exclusively heterosexual men in America who
have sexual partners at low risk for other concomitant sexually
transmitted diseases, have a very low risk of acquisition of HIV.

    These facts alone are probably enough to insure that in the
present sexual climate, condom use or not, HIV will not spread to
any great further extent by exclusively heterosexual transmission
in U.S.  The heterosexual AIDS pandemic we have been warned of
for a decade, in other words, is not clearly coming at all [105].
Indeed, there is every reason to believe that such an epidemic
would be here already if it was destined to arrive soon.
Constant numbers of HIV infected persons in the U.S. for the last
several years point strongly to the probability that at an
infection prevalence of only 0.3% of the total population, HIV
has largely run its course in most populations susceptible to it
in this country [101]. (Because of latency delays between
infection and disease, new yearly AIDS cases will continue to
rise rapidly for years, even so).  In the farther future, sexual
mores may yet change greatly, of course-- and it may be that even
now, among select groups of heterosexuals (inner city teens, for
instance) promiscuity and lack of treatment for other sexually
transmitted diseases will allow for a future small heterosexual-
ly-transmitted AIDS mini-epidemic.  Much remains to be seen.
What does seem likely, however, is that for the near future, most
of the U.S. population will escape AIDS--- even should no vaccine
or treatment be found.

   [Note from 1996: recent results suggest that strains of HIV
transmitted heterosexually in the Eastern hemisphere may be
different from the HIV "B" strain transmitted primarily
intravenous drug use and homosexual contact in the U.S.
If some strains of HIV really do prove to be far more easily
transmitted by heterosexual sexual contact, and these strains
have not yet reached the U.S., the assumptions made above may yet
prove optimistic.  We do not yet have enough data to be sure.]

AIDS Heresies, Part 9

   For any individual, use of a condom during heterosexual
contact further greatly decreases the odds of HIV transmission,
so much so that the odds of HIV transmission after condom failure
with a carefully-chosen heterosexual partner, are probably on the
order of the risk of dying on a routine freeway excursion, or
perhaps even as low as fatality from a commercial passenger jet
airline flight [footnote].  In short, conservative protests that
use of condoms gives heterosexuals a "false" sense of security,
are incorrect.  For the American heterosexual, use of a condom
and common sense probably results in at least as much security
from accidental fatality as is the norm for participation in many
other activities such as driving, swimming, skiing or boating.
Certain homosexual behaviors, by contrast, are indeed considera-
bly more dangerous, unless extraordinary precautions are taken.

   The estimated risk of transmission of HIV (at least for the
familiar U.S. HIV "B" strain) from male to female during vaginal
intercourse in the absence of other sexually transmitted disease
is estimated to be about 1 in 250 to 500 per act of intercourse,
and around half this for transmission from female to male (this
data comes from married couples discordant for the virus).  If a
properly used condom fails 1% of the time, this figure would
result in an infection risk of 1 in 50,000, even with an HIV-i-
nfected partner. (These figures are consistent with studies of
HIV-discordant married couples which show that consistent condom
use even over several years time reduces HIV infection rate to
essentially zero).  Since far less than 1% of non-IV drug using
women will be infected with HIV (prevalence is less than this,
even for many classes of prostitute), total HIV-infection risk of
heterosexual contact for an American man should be less than 1 in
5 million, which is the range for mortality-risk on an average
commercial jet airline flight.  Again, the "new sexual partner"
risk is very much greater for women, who must exclude contact
with bisexual men in order to bring risks into the same range of
risk as for men.

    Concomitant sexually transmitted disease other than HIV also
contributes to HIV transmission risk in a significant way.
Studies of healthy Thai soldiers who acquire HIV heterosexually
from prostitutes suggest that transmission risk for HIV in the
presence of other sexually transmitted disease(s), may approach 1
in 10.  In light of such facts the Surgeon General would of
course remind us that limiting one's number of lifetime sexual
partners is a time-honored (if not always followed) way of
decreasing one's chance of acquiring sexually transmitted
diseases, including HIV.  Statistically, however, this strategy
works only if one's partner(s) are doing the same.  Requiring
formal HIV testing before the beginning of any monogamous sexual
relationship helps these statistics.  For those demanding life by
a shorter timetable, a rapid saliva HIV test is under development
in Thailand, and may be on the U.S. market in a few years.

    For those people already infected with HIV, there is much
hope as well.  Very long-term HIV survivors do tend to be people
who have avoided long-term early treatment with AZT alone [46],
but it is hard to know if this is a cause or effect of good
health.  In any case, although it seems likely that AZT
monotherapy for long periods is worth avoiding, the same does not
necessarily follow for combinations of anti-retrovirals.  New
antiviral drugs are being developed at a rapid pace, and even a
mutating virus may have difficulty keeping up with many different
antiviral drugs administered at a time, or in combinations in a
rotating fashion.   For example, preliminary reports indicate
that the new antiviral drug 3TC/lamivudine is particularly
effective in combination with AZT at eliminating replicating HIV.
The newly approved protease inhibitor drugs also appear to add to
the effectiveness of nucleoside analogues such as AZT and 3TC,
and have recently been shown to decrease viral loads drastically
in AIDS patients, and improve survival over simple combinations
of nucleosides.  Other interesting combinations of antivirals,
and even rotating combinations of combinations, are sure to come.

    Protease inhibitors are examples of the new drugs which are
are continuously being tested against viral replication steps not
affected by the AZT-like drugs.  Other preliminary data suggest
that an old anticancer drug called hydroxyurea might even be able
to do the "impossible" and remove HIV viral genes inserted into
the DNA of infected cells.  For all these treatments and others
yet to come, rapid assays of HIV viral reproduction, such as the
RNA PCR test for HIV, can be used to rapidly pre-screen the
effectiveness of new candidate treatments, without requiring the
large and long trials which employ clinical endpoints such as
morbidity (illness), or death.

    Other ways of controlling viral infection are also being
tried by medicine, including methods of "booby-trapping" body
cells by inserting a gene for a poison which is controlled by a
virus gene, so that cells self-destruct before making any more
new virus (the author has suggested inserting a poison gene in
cells which is constructed so that it can be properly translated
only after being copied by the viral reverse transcriptase
enzyme).  One or all of these techniques may buy much time, since
the body can well afford to lose a few cells, if doing so stops
viral replication.  (Indeed, the word "cytotoxic," so vilified by
skeptics in describing AZT, is an excellent description of the
body's own chemical defenses against viruses, such as those
provided by the sometimes cell-killing interferons).

   As long-term animal and human survival with retroviruses
demonstrates, immune failure as a consequence of retroviral
infection is a host-specific response to infection, and has
little to do with any property of the virus itself.  Almost
certainly, AIDS is an evolutionary "mistake,"  caused by a
particular (and perhaps unnecessary interaction of HIV virus and
host [106].  We know that retroviruses survive well in many of
their natural hosts without causing illness. We also know that in
SIV infection of macaques, deletion of a single viral regulatory
gene (called _nef_) can give rise to SIV viruses which replicate
well enough to produce antibody, but produce no disease (just as
they do not in African monkeys).  It is thus very probable that
HIV will be successfully dealt with eventually by finding a way
to turn it into the kind of harmless infection it is in chimpanz-
ees, long before a way is found of removing the virus wholesale
from the body.  In Australia, scientists have followed for some
years a group of 5 people who are HIV-positive but healthy (save
for one who died of AIDS after being treated with immunosuppress-
ant drugs for lupus erythematosus), after all being infected by a
blood donation from a single healthy HIV-positive donor who may
harbor a more or less harmless strain of HIV [107].  There seems
little doubt for many reasons that such a thing is possible,
though perhaps rare.  The particular HIV virus strain carried by
these long-infected-but-well people no doubt has much to teach

    There is also much to learn from the 8% of HIV positive
people harboring conventional strains of HIV, who are also still
healthy after 14 years of infection, with no sign of becoming
more immunosuppressed [46].  Do these people have less pathogenic
strains of HIV, or are their own immune systems simply better?
We know their blood load of virus is smaller than HIV-positive
people who are progressively deteriorating in immune status.
Recently identified is an interferon-like factor made by CD8+
cells in HIV "non-progressors" and other healthy people, which
suppresses HIV infection in CD4+ cells without killing the cells.
The factor is being intensively studied, and should it prove
useful, may one day be commercial produced by genetic engineering
techniques [108].

    Of all examples of evolution we know of, viruses are the most
spectacular, since they evolve so quickly that new species are
seen on Earth regularly on the scale of a human life-time, and
some of these newly "emerging" viruses emerge as plagues.
Indeed, with HIV, there is good reason to think that the average
human HIV host is infected by not one, but rather many closely
related strains or subspecies of the HIV virus, all evolving
furiously in parallel.  During the asymptomatic phase of HIV
infection, virus cultured from the host reproduces slowly in
culture, but at the end of the disease when the virus is more
active, cultured viruses have often turned into strains that are
able to reproduce rapidly in culture.  It is even possible to
track the immune system as it attempts to produce antibody to a
changing virus, and watch the virus as it attempts to escape by
transforming itself.

    Usually, after a long time, the virus gains the upper hand in
this battle with the immune system, but does so only because it
infects the host slowly enough to give the virus time to evolve
over a decade into something the host's defenses finally cannot
handle.  Even so, the virus can win only by slowly destroying the
body's ability to deal with any invader, including itself.
Possibly the attack on the immune system and the viral evolution
are both needed to cause HIV's exceptionally high mortality rate
after a long delay (at least 50% in 15 years, depending on host

    The fact that the HIV virus only prevails after it has
destroyed the host immune system is itself a hopeful sign that
the virus can be kept at bay for years, as long as an immune
response can be maintained.  Most interesting is the fact that in
AIDS, cell-mediated immunity is not the only host immune defense
against HIV which is destroyed by the virus at the end of the
disease course:  levels of antibodies against the core of the
virus also decline during AIDS (perhaps due to loss of immune
cells which stimulate antibody-making cells to produce them).
Antibodies against the antibody envelope remain, but are often
not neutralizing (do not stop the virus from infecting cells).
If antibodies are not being made in AIDS, or the wrong antibodies
are being made because the virus has mutated, it seems a natural
treatment to try infusing anti-HIV antibodies from other AIDS
patients who are in an earlier phase of the disease.

   Indeed, such experiments have recently been reported and
confirmed: transfer of sterilized plasma, containing immune
factors and anti-HIV antibodies, from early HIV-infected patients
into AIDS patients, considerably cuts their risk of opportunistic
infection, and raises their numbers of lymphocytes.  Such
primitive adoptive immune system therapy, using first antibodies
targeted against HIV, and later soluble cell-growth factors and
immune modulators (cytokines), seem likely to play an increas-
ingly large role in the treatment of AIDS in the future.

   _The Future_.  What will the future bring in the way of new
diseases like AIDS?  To the question of whether or not we will
see more viruses newly evolving to be able to infect humans with
new plagues, the answer is that no doubt we will.  We know from
the examples of viruses like Ebola Zaire that a virus can be as
deadly as HIV without needing a latency period.  But a short
incubation and less than maximum infectivity was the undoing of
Ebola, or otherwise modern world civilization might indeed have
been destroyed by it [121].  The real question is: what kinds of
viruses can manage greater spreading capability by having a long
infectious latency period, yet be able to cause high mortalities
as well?

    It may be that all viruses with as long a latency period as
HIV must, in order to escape the active and tracking immune
system over that time, either replicate in a place hidden from
the immune system (such as the brain), or must be able to attack
the immune system itself, in order be able to eventually emerge
in enough force to cause host death.  Perhaps only retroviruses
can manage these feats.  The only variable which may be possible
to change is communicability, and one can imagine a "super-flu"
which is as communicable as influenza or measles in the initial
stages, but has a latency period followed by the long-term
consequences of HIV, years down the line.  At present we know of
no retroviruses which are that infectious, but we don't know
enough about biology yet to say whether or not this fact is due
to necessity or luck.  Certainly the fact that all known retrovi-
ruses are membrane-coated and fragile-- easily destroyed by the
environment outside the host-- has been a blessing.

    Let us hope that lymphotropic retroviruses are all forever
somehow necessarily constrained in communicability, and that
biotechnology progresses rapidly enough to find a way of
suppressing our current crop of these microbes.  Finally, let us
also hope biotechnology does not progress in such a way as to let
molecular bioengineering of such a virus become a possible
basement hobby project (as it surely will one day) before we
understand how to protect against the possibility of such a
deliberately-caused, or deliberately-modified plague.

AIDS Heresies, Part 10


1. "What Are CD4+ and CD8+ Lymphocytes?"

     T-lymphocytes are lymphocytes which mature in the thymus (T
is for "thymus") and which coordinate the immune response.  They
make up most (about 80%) of the lymphocytes in the blood in
humans.  The particular T-lymphocytes now known as "CD4+
lymphocytes" are known also as T-helper cells, because they help
the immune system respond to invaders.  CD4 (Cluster Designation
number 4) is one of various "CD" designations referring to
protein marker molecules found on the cell surfaces.  CD4 is the
cell surface molecule upon which the HIV virus "docks" and binds,
before being taken inside by the cell (HIV can get into cells in
other ways, though).  The positive (+) sign for a given cell type
(such as "CD4+") indicates that CD4 is present.  T-Lymphocytes
may be CD4+ or not.  CD4+ lymphocytes make up about 2/3 of T-
lymphocytes in the blood, with most of the remainder being T-
lymphocytes classed as "CD8+ lymphocytes."  The normal numerical
ratio of CD4+ to CD8+ lymphocytes is about 2, but in stress can
fall below 1, and in AIDS almost always falls below 0.3.

Two HIV/AIDS Critics: Duesberg and Root-Bernstein

    Dr. Peter H. Duesberg is professor of molecular and cell
biology at the University of California at Berkeley.  A German
emigree, he was originally trained in chemistry.  On arriving in
the U.S. in 1964 he began work in the field of viral molecular
biology at Berkeley, where in 1970 he co-discovered the genetic
basis for the carcinogenic action of the Rous sarcoma retrovirus.

In 1987 he began publicly questioning the role of HIV in AIDS, a
stand which has made him the center of the present HIV/AIDS

    Duesberg's most recent book is called _Why We Will Never Win
the War on AIDS_ (1994), co-authored by a Berkeley graduate
student and one-time protege Bryan J. Ellison.  The book has been
plagued by trouble.  According to a message issued October 13,
1994 by the Group for the Scientific Reappraisal of the HIV/AIDS
Hypothesis, this manuscript was published unilaterally by Ellison
without Duesberg's consent, following failed editorial negotiati-
ons with the original contracting publisher (St. Martin's Press).
According to Duesberg, the editor had asked for additional
documentation, clarification, and elimination of material which
might be considered unfair to individuals.  Duesberg was willing
to cooperate but Ellison was not.  Following Ellison's publicat-
ion of the manuscript at Inside Story Communications (a political
newsletter edited by Ellison), Duesberg severed relations with
Ellison and is seeking an injunction against further publication
of the book.  In fact, Ellison and Duesberg are at this writing
suing each other, with Ellison claiming injury from being forced
to leave his Ph.D. track.  The cooperation of James Tabulse,
publisher of the Group's newsletter _Rethinking AIDS_, with
Ellison, has meant that the Duesberg's Group has decided to
severe relations with this publication as well.  They now publish
a new newsletter called _Reappraising AIDS_.   Since Duesberg has
questioned only publication and editorial rights for the new book
and has not repudiated any of its contents, the book is also used
in this review as an additional source of Duesberg's views.

    Robert Root-Bernstein is associate professor of physiology at
Michigan State University (East Lansing).  He held a MacArthur
Prize Fellowship (the famed MacArthur "genius award") from 1981
to 1986, as the result of work in which he analyzed public policy
and scientific creativity.  He is the author of the recent book
_Rethinking AIDS_ (MacMillan, 1993), and also author of numerous
scientific articles dealing with the immunology of AIDS and other

2. What is an "Antibody" and What Does "HIV-Positive" Mean?

    Antibodies are blood proteins made by immune cells, which
stick very specifically to microbial invaders, targeting them for
destruction by the immune system.  For many years after an
infection by a microbe, antibodies specific to that microbe can
be detected in the blood.  A person who tests positive for
antibodies to HIV by two different kinds of lab tests, is said to
be "HIV-positive."

    In the case of infection with the average microbe, a person
may test antibody positive for years or even a lifetime after the
microbe is completely gone from the body.  For the chronic
viruses which hide in cell nuclei, however (retroviruses like
HIV; and also CMV, EBV, and other herpes-class viruses), the
presence of antibody is generally a clue to the continued
presence of the virus, active or inactive, somewhere in the body.

In some cases modern sensitive tests for viral DNA can actually
detect these hidden viruses directly.

   Recently, development of sensitive tests for viral mRNA are
able to test for continued viral activity, or "reactivation."
The presence of viral mRNA indicates protein manufacture, which
indicates virus reproduction.  It is now known that chronic
viruses often reactivate when the immune system is suppressed,
but only sometimes cause illness as a results (well known
examples of illness are cold sores and shingles).  Tests for HIV
RNA show HIV to be active in essentially all HIV-positive people,
in blood cells and especially lymph nodes.  This is true even if
the person is asymptomatic.  Continued reproduction of the HIV
virus at all times after infection is thought to underlie the
gradual immune decline seen over many years' time in 11 out of 12
HIV-positive people.  The remaining 1 in 12 people with HIV show
antibodies but no immune decline, indicating an immune system
which is somehow able to keep replication to very low levels.
This small subsegment of HIV-infected persons may be long-term
survivors of HIV; at present with less than 15 years of tracking,
it is still too early to tell.

    Over the years since the discovery of HIV, critics of the
HIV/AIDS hypothesis have had to struggle to keep up with sensiti-
vity increases in HIV testing.  Initially, critics complained
that HIV virus was not present in most HIV-positive people.  When
it became clear that infectious virus could be found in almost
100% of such people, if cultures were done correctly, critics
claimed that most HIV was dormant until reactivated in culture.
With new sensitive tests for HIV RNA showing that HIV virus is
active in the body's lymph nodes, critics have fallen back to the
position that it may be active, but not active _enough_.  This is
a question which can only be answered indirectly, by other
studies.  In the case of HIV, however, Ellison and Duesberg
assert (p. 124), that HIV is rarely to be found budding from
cells in patients, and that " most individuals with AIDS, no
virus particles can be found anywhere in the body," implying that
this absolves the virus from any disease role.  Actually,
however, even actively reproducing HIV may spend very little of
its total life-cycle actually budding through a cell membrane or
floating free as a particle in the blood before being picked up
by another cell.

   Studies of viral RNA in the body show that there may be
anywhere from roughly 10 million, to as much as 1 billion
particles or actively replicating HIV genomes in a gram of lymph
tissue-- a significant amount by the standards of most other
kinds of virus [122].  Furthermore, a number of studies now show
that amount of free HIV virus in the blood plasma, shown by more
sensitive tests to be much larger than previously thought,
correlate with rate of progress of HIV infection to AIDS [123].

3. Hemophilia and Life Expectancy in the 80's.

    Hemophilia is a collection of genetic diseases which have in
common an inability to make sufficient amounts of active blood
clotting proteins.  Many people with hemophilia require
transfusions of active clotting factor proteins in order to avoid
bleeding episodes.  Just before the era of AIDS, such treatment
had resulted in nearly normal life expectancies for people with
hemophilia in the U.S., though the average age of the population
was still low and had not yet recovered to U.S. normal.

   Approximately half of all people with hemophilia in the U.S.
were infected with HIV in a silent plague beginning in 1979,
peaking in 1982, and ending in 1985 when factor sterilization and
testing ended new HIV infection.  AIDS was first identified in
people with hemophilia in 1982, with a sharp rise in AIDS deaths
after 1984.

    Since the beginning of the AIDS plague, about 1/3 of HIV
infected people with hemophilia have died of AIDS. This has
resulted in the life expectancy of people with hemophilia falling
sharply since 1984, during the same period that the average age
for this population has been rising.  These seemingly disparate
trends represent the effects of the AIDS plague and advancing
medical technology acting in opposing directions.  The _average
age_ of a population is an integrated effect of mortality risks
over many previous decades: this is still increasing rapidly for
hemophilia patients  because of hemophilia treatment gains over
much of this century, particularly in the 1970s.  The _life
expectancy_ for a population reflects the sum of current mortal-
ity risks for people of all ages at a given time: this number has
been decreasing continuously for hemophilia patients over the
last decade because of increasing losses to AIDS.

   Duesberg and other HIV/AIDS critics have chosen to emphasize
average age in their discussions, a very bad index of how risks
are changing in a population on a year to year basis (as they are
in the AIDS plague).  Worse still, Ellison and Duesberg confuse
life expectancy with average age (pp. 123, 188), further making
things even more difficult for their unwary readers.

     _Hemophilia and Immune Suppression._  HIV/AIDS critics have
recently emphasized the fact that hemophilia itself is immunosup-
pressive, without emphasizing that this immunosuppression does
not resemble that of AIDS, since it is a product mostly of higher
CD8+ (suppressor T-cell) counts, rather than lower CD4+ (helper
T-cell) counts [22].  Critics have also suggested that the much
higher death rates in HIV-positive people with hemophilia are due
to AZT use, despite direct survival statistics showing the
reverse, and also the fact that this trend was well-established
long before 1987, when AZT became available (see section on AZT).

   Although most hemophilia is found in men, approximately 3% of
those with the disease are women, and female patients
have a quite different spectrum of clotting factor use.
Female hemophilia sufferers thus provide another piece of
evidence that it is HIV, not clotting factor use, which causes
AIDS, since male and female hemophilia patients have different
factor usages and different AIDS risks, but the differences are
entirely explained by HIV.  This is easily seen in the fact that
in people with hemophilia, average clotting factor use by type is
different for HIV-positive males and females, yet AIDS risk over
time is the same [109].

4. AZT: Panacea-- Pandora Plague--- or Perfectly Pedestrian
Pharmaceutical? [110]

_The Drug and How it Works_   It is a greater task to find
antimicrobials which interfere with virus reproduction than
bacterial reproduction, simply because viruses use much of the
cell's machinery to do their work, and thus it is difficult to
find inhibitors of the viral reproductive process which are not
poisons to cells as well.  Viruses which use their own special
enzymes, different from cell enzymes, may have Achilles heels.

   Retroviruses (including their subset, the lentiviruses)
contain the unique enzyme "reverse transcriptase," which transcr-
ibes the RNA instructions of these viruses into newly-made DNA.
Since normal cells do not contain this enzyme (or at least not
much of it), reverse transcriptase has been a natural target for
antiviral drug developers.  Eventually it was found that this
particular enzyme is both the strength and weakness of
lentiviruses when it came to AZT-like drugs.  Advantage came in
the fact that lentiviruses had a transcriptase enzyme which has
no proof-reading capability, which a cell's reproductive enzyme
systems have.  The virus enzyme was thus prone to making mistakes
in copying virus genes, giving retroviruses a high mutation rate
which helped them evolve rapidly to adapt to new drugs, or to new
hosts.  The disadvantage to the virus was related:  the viral
enzyme would pick up and put into viral DNA altered or wrong
building-block chemicals which the cell's enzymes were too
fastidious to use for cellular DNA.  Some of these synthetic
chemicals, once inserted into a growing virus DNA chain, made the
chain useless for further building, and so reproduction of viral
genes was selectively stopped while cellular DNA could continue
to be replicated.  The first such chemical found to act this way
was 5'-azidothymidine, or AZT.  AZT had first been synthesized in
the 1960's as a possible chemotherapeutic agent, but it had
proved too toxic to normal cells at doses that interfered with
cancer (at high doses, even the cell's enzymes could be fooled,
particularly the DNA synthesizing enzymes in mitochondria).
However, AZT proved less toxic at smaller doses which still
inhibited HIV.

    The initial 1986 placebo-controlled trial of AZT in AIDS
patients was so dramatic that the independent ethical monitors of
the study (who had the codes for the otherwise double-blinded
experiment) stopped the trial early so that AZT could be given to
all the participants.  The study was halted when 19 people had
died in the group of AIDS patients receiving placebo, but only
one patient had died in the equal-sized group receiving AZT
[111].  A second study of AZT vs. placebo in Europe also showed
that AZT delayed progression of HIV-positives to AIDS [112].

    AZT was not benign, however.  In the initial trial the 1500
milligram daily dose, 3 times what later became standard, was
enough to cause some patients to require transfusions due to
AZT's toxicity to their blood-forming bone marrow.  The drug also
caused side effects in the GI system and muscles.  A number of
placebo-controlled trials at lower doses showed that AZT did
indeed delay the onset of AIDS and lengthen survival when given
to immunosuppressed HIV infected men (both male homosexuals and
people with hemophilia [113]), although the earlier the drug was
given in the course of the HIV disease, the more the toxicity of
the drug counterbalanced any symptoms of immunodeficiency that
were delayed [114].

   In the end, AZT alone turned out to represent a few extra
months of life to the average AIDS patient, nothing more.  Nor
did (in smaller studies) early use of the drug before AIDS
appeared seem to offer clear survival benefits over waiting until
later stages of HIV disease [115].  Eventually it became clear
that the reason for this was that the fast-mutating HIV virus was
capable of evolving enough under the pressure of toxicity to
escape the effect of AZT after approximately one to two years of
treatment [116].  Because of this, many physicians began to
suspect that this relatively short time of effective viral
suppression was probably best left until late in the course of
the disease, when the virus was causing the most damage, since
AZT itself could damage quality of life in HIV-infected people
who still had good immune function and were feeling well [117].

    This suspicion was confirmed by the Concorde Trial, the
largest trial of AZT ever done and one which had more patients
and statistical power than all the other trials combined. When
Concorde examined the benefits of AZT started quite early in the
course of HIV infection, as opposed to waiting for AIDS or severe
immune problems before starting AZT, there was a disturbing trend
toward greater mortality on early AZT than deferred AZT.  Some of
the excess AZT group deaths, however, came from auto accidents,
and it wasn't clear if these should be counted; AZT is accused of
modulating immune problems, after all, not causing traffic
accidents.  However, with the study showing an 85-87% chance that
the drug had done more harm than good when started earlier vs.
later in HIV disease, it was finally apparent to most physicians
that AZT was at best a short term drug, and a drug to be used
later rather than earlier in HIV disease, at least when used
alone [118].

    Critics had thus scored a point in suggesting long ago that
immense political and economic pressures had introduced AZT too
early into clinically well people, a group for whom overall
benefit was never well documented, and who in fact (as now
appears) were being very expensively treated without being
helped.  The Concorde trial, however, proved also a blow to the
severest critics of AZT, since it made clear once and for all
that AZT at the proper doses was not a very toxic drug, and
certainly was not a major AIDS-producing drug.  In particular,
Concorde proved that AZT could NOT be used to explain the large
numbers of extra AIDS cases in HIV positive groups which are
routinely seen in studies.

    This work of improving AZT-like drugs continues.  Along with
better and more specific treatment of the fungal and viral
opportunistic diseases which AIDS patients develop, especially
the previously often fatal pneumocystis pneumonia, the new
anti-viral drugs have apparently slowly increased the time from
the diagnosis of AIDS to death.  Starting in 1987, the year AZT
was introduced and began wide distribution, the average survival
time of AIDS patients began to steadily increase.  It continues
to increase today: the average survival time after first diagno-
sis of full-blown AIDS (the last stage of HIV infection) is now
18 to 24 months.  Unfortunately, AIDS is still, by and large, a
fatal condition.

_The Controversy_.  Despite the results of the Concorde trial
which showed no significant evidence of any AIDS-producing effect
of AZT, the effects of AZT are routinely discussed in heretical
literature as though they might somehow be mistaken for the
immunologic losses normally seen in the AIDS syndrome.  But AZT
does not cause selective loss of CD4+ lymphocytes with severely
skewed CD4+/CD8+ ratios, nor does AZT at standard doses cause the
kind of immunosuppression which can in any way be compared with
that in AIDS [119].  This does not slow critics, who simply lump
all kinds of immune deficiency together.  Duesberg writes of one
study:  "Although the AZT-specific diseases were not diagnosed as
AIDS, neutropenia generates immunodeficiency, and thus AIDS." (p.
242).  Here Duesberg generates yet one more definition of AIDS of
his own.  Physicians, however, know that neutropenia, a
deficiency of different kind of blood cell than the lymphocyte,
predisposes to very different kinds of infectious problems than
classic AIDS does, so again Duesberg's proposed definition is
hardly clinically useful.

    Despite the complete lack of any findings showing that AZT
causes selective CD4+ lymphocyte loss, or that AZT treated groups
have significantly more deaths or immunological deaths than
placebo or non-AZT groups (something that one would think might
be an important point), skeptics led by Peter Duesberg have
continued to characterize AZT as "AIDS by prescription" (p. 252)
[120].   Thus, in heretical AIDS literature, AZT has become the
scapegoat which "explains" modern studies which find a great deal
of AIDS in HIV-positive people who do not use drugs.  Duesberg
blames AZT, for instance, for much of the increase in AIDS in HIV
positive people with hemophilia, despite the fact that statistics
show that HIV-positive hemophilia patients who take AZT are less
likely to contract AIDS, not more likely [113].

    Duesberg has also publicly blamed AZT and other AIDS drugs
for AIDS-diseases in non-illicit-drug-using, non-hemophiliacs who
have died of AIDS after contracting (supposedly harmless) HIV.
He has, for instance, blamed AIDS medications for the death of
clean-living transfusion-HIV-infected tennis star Arthur Ashe,
despite the fact that Ashe's rare brain toxoplasmosis (thought
initially to be a stroke) and his low T-cell count, proved the
destruction of his immune system had taken place long before he
was diagnosed with HIV, or took any drugs to treat it.

    Most famously, Duesberg has blamed AZT for the AIDS problems
and death of Kimberly Bergalis, the non-drug using Florida
college student who contracted HIV either sexually from a
boyfriend, or else from her HIV-infected dentist during a dental
procedure in December, 1987.   According to Duesberg (in a
favorite story which he has repeated in many interviews, and has
included in his book), Bergalis began only with a non-pathologic
oral yeast infection (one of Duesberg's medical eccentricities is
his apparent belief that oral thrush is "AIDS-defining" in men
but non-pathologic in women).  In Bergalis, thrush was followed
by what Duesberg describes only as "a brief pneumonia," after
which Bergalis was inexplicably tested for HIV by her doctors
"out of the blue," and when found positive, finally poisoned to
death by her physicians who treated her with AZT and other AIDS
drugs (Ellison and Duesberg, p. 217).

    According to a recent book-length account of the incident by
Runnells, however [4], the complete story is a quite different
than Duesberg's macabre account of a basically healthy woman
being killed by her doctors.  Bergalis had months of severe
fatigue, wasting, chronic yeast infections, and a CD4+ lymphocyte
count of only 41 just 5 days before entering the hospital, in
December, 1989, where she was diagnosed by broncho-alveolar
lavage with bilateral _Pneumocystis_ pneumonia, an AIDS-defining
disease (the reader will remember that a CD4+ count of 41 signals
nearly complete immune failure, and defines AIDS also by the more
strict criteria proposed in this review).  Only at this point
(and hardly out of the blue) was Bergalis tested for HIV, on
suspicion of AIDS, and only after testing HIV-positive, was she
treated with AZT.  But her immune system was nearly destroyed

    Bergalis ultimately survived another 24 months after her
_Pneumocystis_, comfortably longer than similar patients in the
era before AZT (average survival less than a year).  Arthur Ashe
lived more than 3 years from his first opportunistic infection
and diagnosis of AIDS.  There is no reason whatsoever to believe
that AZT drugs shortened the life of either Bergalis or Ashe.
Nor is the experience of these two AIDS celebrities unique, for
there are quite enough studies of both average incubation time
and survival time for AIDS in the era before AZT (eg, [113],
[102] to be sure that (whatever else AZT does) it does not hasten
either the onset of AIDS, or death from AIDS.

   What about studies in which people taking AZT have fewer AIDS
diseases than people on placebo?  For Duesberg this is only
reason to suspect that placebo patients are using more illicit
drugs-- even when the AZT and placebo groups have been matched by
collecting them from a randomizing process.  The chance of
getting more illicit drug-users into one randomized group versus
another, when the groups are picked by the equivalent of coin
toss, is obviously low.  This does not prevent Duesberg (p. 242)
from grasping at a statistical straw and suggesting that this
might somehow have happened in each of two separate studies, even
though the chance of _this_ is "low" squared.

5. Montagnier, Gallo, Slip-Ups and Wrong Paths

    In the first weeks after the first AIDS cases were reported
in 1981, the brilliant Don Francis of the CDC (played by actor
Matthew Modine in the TV-movie version of Shilts' _And the Band
Played On_), a scientist who had spent years working with the
FeLV virus, hypothesized that AIDS was "feline leukemia in
people." [ref. 14, p. 73]  This was an inspired guess, but as it
turned out, not quite correct (FIV, the actual cat analogue of
HIV, would be discovered only in 1986).  Sometime later Bob Gallo
of the NIH (Alan Alda) would at Francis' suggestion make
essentially the same assumption, thinking that AIDS was caused by
a human leukemia retrovirus in the virus family that he himself
had discovered.

    The French researcher Luc Montagnier isolated the correct
virus in early 1983 from a French patient who later died of AIDS.
However it wasn't until Gallo's lab cultures were contaminated
with one of Montagnier's generously provided virus strains, which
was then mistakenly identified as coming from an American AIDS
patient, that the Americans were ready to also announce in 1984
that this virus (Montagnier's virus) was the AIDS virus [67].
Incredibly, the French-provided virus was also "re-isolated"
after a similar lab contamination in England, as well.  These
fortuitous lab incidents, which tended to rob the French of sole
credit and sole patent rights, were later proven by genetic
fingerprinting of viruses; but government hearings failed to
convict Gallo or anyone else of any misconduct (helping the
American and English cases for accident was the fact that even
Montagnier's own lab had been accidentally contaminated by the
same fast-growing strain, which was not his original first
isolate).  Meanwhile, however, the American team led by Gallo had
discovered a way to grow the virus in quantities which permitted
an economical screening test to be produced from it, and had
shared formal credit in 1987 with the French for the discovery of
what became known as HIV, and by international agreement shared
royalties for the HIV antibody test as well.  The Americans and
Gallo have since made far more money at this than the French, and
thus, particularly in the eyes of HIV/AIDS skeptics who see a
capitalist conspiracy in AIDS, have emerged as the clear villains
of the tale.  The personable Montagnier, despite his prime role
in discovering HIV, has been granted partial absolution even by
HIV/AIDS skeptics, due to his more recent speculations that HIV
might not be able to cause AIDS without help from other microbes.

6.  How Some Viruses Hide From Your Immune System

    The actual blueprints used by both viruses and cells to
reproduce themselves, are long tape-like molecules called DNA and
RNA.  Either DNA or RNA is capable of carrying genetic
information, and this information is coded by the linear
sentence-like structure of the molecule.  There exist viruses
which use DNA, and others that use RNA, to carry their own
instructions for making themselves.  DNA and RNA as chemicals are
a bit like recording media: biologic information can be copied
from DNA to RNA in all living systems, and sometimes (in retrovi-
ruses) even from RNA back to DNA, as we shall see.  It is the
genetic information, not the medium that holds it (DNA or RNA),
which is important.

    Animal and plant cells use only DNA to archive their
information.  Some DNA-containing viruses are able to place their
own DNA into close association with the cellular DNA located in
the nucleus of the host cell, so that viral and cell DNA are
regulated together.  This is a survival tactic: virus DNA
sometimes associates with cell DNA before halting new virus
production and going into "hiding."  The normal immune system of
an animal can seek out and destroy actively virus-infected cells,
and infected cells themselves also make antiviral substances
called interferons, which destroy active viruses within other
cells.  The very effective strategy of associating non-active
viral DNA with cellular DNA, however, sidesteps both these
defenses, and results in infected cells which harbor virus DNA,
but which are apparently very difficult for either the outside
immune system, or the cell's internal defense systems, to detect.

     The virus which produces "cold sores" on the mouth and lips
(a type of herpes simplex virus) is a familiar example of a virus
which uses this trick, and which the immune system, despite all
efforts, sometimes can never get rid of.  Many people who are
afflicted with a cold sore propensity are afflicted for life
because there is no known way to remove herpes virus DNA
chromosomes from association with the DNA of nerve cells, with
which it is sequestered.   Each outbreak of cold sores represents
an event in which "sleeping" herpes DNA, hiding in nerve cells
near the base of the brain, re-activates and directs the cell's
biochemical machinery to now produce more virus DNA.  The newly-
made virus DNA then uses the nerve cell's inner transportation
machinery like a subway train to move down through a long branch
of the cell to the mouth, where it breaks free of the cell to
infect and destroy skin cells to form a blister.  Such outbreaks
may occur sporadically for life.  Each time the normal immune
system stops an outbreak, the virus simply goes back into hiding
inside the nerve cells.

    Certain viruses called retroviruses hide in cells in an even
more intimate fashion, by making DNA genes and then inserting
them directly into the cell's DNA.  By directly controlling and
influencing cell DNA activity in this manner, retroviruses may
cause cancer or cell death after long latency periods.

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