Another article from The New Republic online. This one is lengthy but worthy
of your attention. it helped me a lot in forming my convictions on the
essence of all the hooha on the AIDS epidemic.
I hope I'm excused for cluttering your mail boxes with these AIDS postings.
Hamjatta Kanteh

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The End of Aetiology

By JEROME GROOPMAN
Issue date: 11.01.99
Post date: 10.14.99



The River: A Journey to the
Source of HIV and AIDS
by Edward Hooper
Little, Brown, 1070 pp.
(Click here to buy this book.)

Virus
by Luc Montagnier
W.W. Norton & Company, 249 pp.
(Click here to buy this book.)


I.

The story of the AIDS epidemic has been told many times from many vantage
points--biological, clinical, sociological, psychosexual, economic,
geopolitical--and in the many voices of its protagonists--clinicians,
laboratory scientists, epidemiologists, people with HIV, activists,
journalists, public health officials. The multiplicity of perspectives and
personae notwithstanding, each rendering of the disaster discloses in its way
the magnitude of the suffering that has been caused by this pandemic, and the
continued threat that it poses.

AIDS was first recognized in 1981, in Los Angeles and New York. Dr. Michael
Gottlieb, a clinical immunologist at UCLA, informed the Center for Disease
Control in Atlanta that unusual infections, such as Pneumocystis carinii
pneumonia, were occurring in a handful of previously healthy young gay men.
Dr. Alvin Friedman-Kien, a dermatologist at NYU, reported to the same federal
agency on the appearance of a rare cancer, called Kaposi's sarcoma, in a
similar population of young male homosexuals. All these affected men had
impaired immune defenses. It took some three years until the cause of their
immunodeficiency was identified as HIV.

Taxonomically, HIV is a retrovirus, that is, a type of virus whose genes are
composed of RNA, and then "reverse transcribed"--copied back--into a DNA form
upon entering a susceptible blood cell. After this reverse transcription, the
viral DNA permanently integrates itself into the DNA of the host cell,
generally a T-cell or macrophage. (T-cells and macrophages are types of blood
cells that are essential to immune defense.) This means that once you are
infected with HIV, you are infected for life. Over time, the virus eats away
at the host immune system by destroying helper T-cells and disarming tissue
macrophages. Since those are the cells that protect us against fungi, TBlike
bacteria, herpes viruses, and cancers such as Kaposi's sarcoma and B-cell
lymphoma, their loss causes us to fall prey to these infections and these
tumors.

What Gottlieb and Friedman-Kien observed as a medical oddity in 1981 is now
the second most common cause of infectious death in the world, just behind
influenza and respiratory illness. Significantly, in industrialized countries
the death rate has sharply declined over the last two years, due to the
introduction of anti-HIV protease inhibitors. These agents were developed in
part through rational drug design, an approach that wedded high performance
computing with a three-dimensional representation of the desired target. In
the case of HIV, the 3-D topology of its critical protease enzyme was
deciphered; and computers screened drugs in a virtual format to see which
agents docked on the surface of this target enzyme and would prevent it from
working. Six different anti-viral drugs were developed by this method.

Those drugs have restored countless sufferers to a better quality of life and
staved off what previously was a steady decline to death. How long the
protease inhibitors will work, and for how many, is an open question. As with
all anti-microbials, the bug mutates and develops resistance. Moreover, the
protease blockers are cumbersome to take, and in some people they have
significant side effects, such as diarrhea and lipid deposition in the
abdomen and neck. Emerging viral resistance and drug toxicity make the quest
for new and better treatments all the more urgent; but it is unarguable that
the death sentence of AIDS has been stayed for many in the West. In
developing countries, however, the situation continues to be grim. In nations
with yearly per capita expenditures of a few dollars for health care, the
protease inhibitors are too costly to be distributed, and the death toll
climbs unchallenged.

Strategies aimed at the prevention of HIV have not been as successful as
those aimed at its therapy. The prospects for a vaccine are still remote,
given the wide antigenic variability in strains of the virus as well as its
capability of mutating quickly to escape the grip of the immune system.
Educational efforts have clearly had an impact, manifest in the reduction of
sexually transmitted diseases both in the gay and heterosexual communities.
There is appropriate concern about "slippage" in adherence to safer sex
practices, particularly among the young, but the message about AIDS and
condoms and needles continues to be forcefully articulated from high school
hygiene classes to MTV. Funding for HIV research remains a priority within
the National Institute of Health. Pharmaceutical and biotechnology companies
see HIV as a lucrative target, given the need for lifelong daily anti-viral
therapies.

Discussion also continues over the means to best combat the disease: how to
effectively educate different risk groups about the threat; how to coordinate
intellectual and material resources to generate new and more potent
therapies; what breakthroughs are needed to create the long-elusive vaccine;
whether drug companies have a moral obligation to provide expensive therapies
to indigent developing nations. AIDS activists press for better distribution
of drugs and information, and question the profit margins made by the
pharmaceutical companies, and hector candidates who do not support subsidies
for treatments in the developing world. In general, the activists have
effected significant changes within both governmental and corporate
structures. People with AIDS and their advocates are integrated into the
decision-making process in the White House, at the NIH and at other
governmental agencies, and they are often consulted by the drug manufacturers
about the distribution of products in the affected communities.


II.

It was to be expected that some would reject the mainstream view--which is to
say, the scientifically warranted view--of the AIDS epidemic and the progress
made to date, and produce manifestos and books of historical and biological
revisionism. Peter Duesberg, a professor of biology at Berkeley, is a prime
example. He is the champion of the contrarian position that HIV is really an
epiphenomenon, an innocuous fellow traveler, and not a pathogen. Duesberg
contends that the immune system of AIDS victims collapses because of the
destructive effects of excessive sex and illicit drugs, and the toxicities of
anti-HIV agents, such as AZT.

Duesberg's view is simply not supported by the facts. First, HIV acts as a
pathogen in vitro, readily destroying T-cells in the test tube. Second,
people who were sexually conservative and did not use illicit drugs--such as
health care workers who suffered needle sticks while caring for AIDS
patients--contracted HIV and developed immune deficiency. Third, there is an
animal model of AIDS: monkeys carry related retroviruses known as simian
immunodeficiency viruses, or SIV. Pure SIV inoculated into chaste monkeys
produces AIDS-like immune collapse. And most dramatically, the therapy of
people with AIDS by means of anti-HIV protease inhibitors causes a dramatic
reduction in virus production and consequent restoration of immune function.

Given these forceful observations at the lab bench and the patient's bed, the
Duesberg hypothesis is touted by fewer and fewer people. But there has been
also another non-mainstream theory about AIDS, a theory that was aired and
largely refuted, and is now resurrected in Edward Hooper's tome. Hooper
re-visits the scenario that HIV entered the human population by means of
contaminated lots of oral polio vaccine. This is said to have occurred during
the widespread vaccination efforts in Central Africa in the late 1950s.
Hooper is not a crank. He accepts HIV as the etiology of AIDS. He distances
himself from the Duesberg nonsense, as well as from the fringe that in the
past pursued scenarios about the origins of the virus in Caribbean pigs,
secret military biological warfare, or a plot to wipe out homosexuals.
Instead Hooper takes up the cause of a few journalists and medical
researchers who focus on a colony of chimpanzees in the Congo in 1957-1958.

Now, the chimps might have been carrying a strain of SIV, the simian cousin
of HIV. The SIV isolates known so far are not pathogenic for chimpanzees, but
they could be pathogenic upon infection of humans. The oral polio vaccine
hypothesis posits that kidneys were harvested from SIV-infected chimpanzees;
and these kidney cells may have been used for cultivation of polio virus by
Hilary Koprowski at the Wistar Laboratory in Philadelphia to make vaccines.
The SIV-contaminated oral polio vaccine from Philadelphia may have been given
to Africans in the Congo in the late 1950s. The chimp SIV strain then could
have genetically evolved into what we know now as HIV. All of this is
possible. None of this is proven.

The mainstream scenario subscribed to by AIDS researchers is that a
chimpanzee SIV was indeed the progenitor of HIV, but that the transmission of
these chimp viruses occurred via blood contamination of Africans: as uncooked
meat in the diet or during butchering accidents, when chimpanzee blood may
have entered open cuts. Yet Hooper refuses to endorse these quotidian routes
of transmission, and becomes the prosecuting attorney for an iatrogenic, or
medically caused, case.

When I first learned of the OPV/AIDS theory in June 1992, I had been
investigating theories of origin for more than two years. Suddenly, here was
a more plausible explanation than any other I had come across, but I was
still far from convinced. However, when further research consistently pointed
to the same conclusion, I found, after several years, that I was starting to
describe myself as "more than 90 percent persuaded" on the basis of the
steadily accumulating stream of evidence. ... But how is it that so many of
those who should have been searching ... the virologists and vaccine-makers,
the molecular and evolutionary biologists, even the epidemiologists -- have
failed to do their job?

There seem to have been several factors at play. First, most of them were not
on the field trip: they were busy in their labs, peering into microscopes (or
preparing grant applications). Second, there have been so many crackpot
hypotheses of origin, so many silly and spurious conspiracy theories, that
many observers became jaded and skeptical about iatrogenic theories per se.
Third, many of those who had followed the controversy at a distance had read
Koprowski's reply in Science, or heard about the Wistar expert committee's
negative report, and had assumed that the matter had been laid to rest, that
another theory had crumbled when subjected to the fierce light of scientific
examination.

But possibly there was a fourth reaction too--one involving protection of the
profession and fear of peer reaction. Because, if the OPV/AIDS theory was
proved to be true, then the implications--and likely repercussions--were
almost too awful to contemplate.

Some, the virologists and vaccine-makers, might feel that the theory could
turn people against vaccines in general. Some, like primatologists, might be
concerned that it would lead to awful retribution against African primates--
especially chimpanzees. And some--those in certain institutions and
pharmaceutical companies, or public health departments--would simply have
dreaded the glare of unwanted publicity. Beside, they may have felt, why
should they be held responsible for mistakes that occurred forty years
earlier?

Before we assess Hooper's musings on the "awful" consequences, let us first
examine the oral polio vaccine hypothesis. Hooper is 90 percent persuaded of
its truth. Where is the remaining 10 percent? He doesn't exactly say, but the
rest of the evidence, I suppose, is direct rather than circumstantial: the
fingerprints on the smoking gun. Just as DNA fingerprinting is a powerful
tool in criminal cases to nail down the perpetrator, so DNA fingerprinting is
used in virology to determine the identity of pathogens. In this instance,
however, the fingerprints of the chimpanzee SIV and the fingerprints of the
earliest isolates of HIV do not match. They are too dissimilar to posit that
SIV contaminating an oral polio vaccine moved into man and became HIV.

Or, to put it another way, SIV has an alibi. Hooper imagines it at the scene
of the crime--widespread oral polio vaccine distribution--but it is too far
away to be the culprit. Its exculpatory distance is measured in the rate of
genetic change of these retroviruses. The first known HIV strain comes from a
man in the Congo in 1959. It would take twenty to forty years, at a minimum,
for the known chimpanzee SIV to evolve into the human Congo HIV in 1959, and
thus acquire similar DNA fingerprints. But the oral polio vaccine was made in
the United States, and then distributed in the Congo, in 1957-58. The
fingerprints of the chimp SIV do not match the fingerprints of the African
HIV. And there is no evidence that the chimpanzee SIV changed into HIV within
the chimp, before allegedly being passed into a human. No jury would convict.

There are other problems with the prosecution's case, albeit less directly
dismissed. Kidney cells themselves are not supportive of growth of either SIV
or HIV. Blood cells, specifically T-lymphocytes and monocyte-macrophages, are
the sites of virus replication and release; and T-lymphocytes and macrophages
require complex conditions to spawn HIV and SIV. (Indeed, one of the major
hurdles in the study of HIV after it was first found at the Pasteur Institute
was the difficulty in producing the virus in tissue culture; only after the
NIH group identified permanent T-cell lines that resisted the destructive
properties of HIV could the virus be produced in significant quantities.)
Thus, it is unlikely that chimpanzee kidney cell cultures, even if they were
contaminated with a few blood cells, could be the source of much retrovirus.

These retroviruses, moreover, are relatively fragile, despite the devastation
they cause within the host. Their exterior protein shells are easily broken,
rendering the virus inactive. So the survival of a miniscule amount of chimp
virus in the few T-cells or macrophages that might contaminate kidney cell
cultures is difficult to envision, particularly given the shipment of the
tissues from Africa to the Wistar Institute in the United States, and then
back to Africa.

Much to Hooper's credit, he repeatedly acknowledges that the evidence
supporting the oral polio vaccine hypothesis is entirely circumstantial. He
states that it is actually not known whether chimpanzee tissues were used at
the Wistar Institute by Koprowski's team for manufacture of the Congo
vaccine. Also, none of these SIV retroviruses were found in European polio
vaccine lots. As for the lack of matching DNA fingerprints, given the slow
rate of evolution of chimp SIV into Congolese HIV, Hooper raises the question
whether there might be accelerated genetic change when a new pathogen (like
SIV) first enters a naive host (like man).

But there is no clear precedent for this, which rather enfeebles the idea. In
fact, healthy researchers handling SIV-infected monkeys who became infected
themselves, did not show such accelerated mutations in the simian virus.
Similarly, sexual partners or transfusion recipients who contract HIV were
linked to the source of their infection--the sexual contact or blood
donor--by similar DNA fingerprints. The virus did not change its gene make-up
so radically in a short interval. I am unaware of a deviation from this
paradigm in the countless published studies of retroviral transmission.

Writing about Hooper's book in The New York Review of Books, Helen Epstein
recently addressed the issue of how a monkey virus such as SIV could evolve
into HIV. She cited the work of Dr. Opendra Narayan, a researcher in the
University of Kansas. "I ... agreed with Hooper's view that AIDS just didn't
look like an old African disease," Epstein observed. "It looked like HIV had
crossed from primates to people quite recently.




 We should therefore claim, in the name of tolerance, the right not to
tolerate the intolerant.
Karl Popper  1902-1994

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