... I discovered that Narayan had actually succeeded in turning an apparently
harmless monkey virus into an AIDS virus in his own laboratory.
Narayan works with a genetically engineered virus called a SHIV (simian human
immunodeficiency virus), which is a version of HIV that is used to infect lab
monkeys. This SHIV grows in monkeys but does not cause disease in those
monkeys, and it is not passed to other monkeys through sex, biting, or other
natural means. However, this SHIV can be passed from one monkey to another
artificially in laboratories, for example through blood transfusions or
through bone marrow transplantation. If the SHIV is transmitted artificially
from one monkey to another rapidly enough, through a process known as
"passaging," it can turn into a virus that spreads easily and causes AIDS in
monkeys.
Something similar may have happened with HIV. If a hunter or monkey-meat
butcher became infected with a harmless monkey virus and then shortly
afterward passed it on to someone else, who then passed it on to someone else
in a few weeks later, it is possible that the monkey virus might have turned
into HIV.
Epstein's interpretation of Narayan's work on SHIV, to argue for a short
time-frame of SIV evolution, betrays a lack of understanding of the
underpinnings of the experiment. SHIV is a chimera, an artificial product of
genetic engineering whereby large pieces of a clone of the human virus HIV
are grafted in the laboratory into the backbone of the monkey virus SIV. SHIV
does not exist in nature, in monkeys or in man. It is not "a monkey virus,"
but something akin to a griffin or a minotaur. Its genetic elements would not
arise through the normal course of transmission from primates to man. SHIV is
not a precedent for a "harmless monkey virus" turning into HIV in "a few
weeks"; it is, rather, a hybrid creation that can only be spawned in a test
tube. And it is a sign of Hooper's probity in his lay analysis of the
scientific literature that he does not make the error that Epstein does.
And so, after 843 pages of often vivid and flowing prose about the AIDS
epidemic and its social impact, and the parallel stream of circumstantial
evidence, Hooper prudently makes his closing arguments not for conviction but
for further research studies to settle the issue. But those studies are
relatively simple: they would consist in an examination of the records of
production of the accused oral polio vaccine lots to see if they were made
from virus grown in chimpanzee kidneys, and in rigorous assays of any
remaining stocks of vaccine, for DNA fingerprints of either chimpanzee SIV or
Congo HIV. Such studies would take little time and would consume scant
resources. If the Wistar group chooses, it can respond with the data to
solidify their previous published rebuttals.
As to Hooper's listing of potential repercussions as "almost too awful to
contemplate," he underestimates the merciless ethic of scientific inquiry.
The vast majority of scientists pursue the truth regardless of where it leads
and whom it offends. The falsification of data, and the suppression or
neglect of experimental results, could not be sustained in the research
community. A worldwide cover-up abetted by hundreds or thousands of
researchers is almost impossible even to imagine, except in pulp fiction.
Indeed, the best researchers relish challenges to dogma and encourage
contrarian views. They are eager to wrestle with opposing data--so long as
the struggle is on a plane of rationality, and the contest is played by the
rules of the scientific method: cause and effect and reproducibility of
results. I am of the opinion, obviously, that the oral polio vaccine
hypothesis is incorrect; but I would change my mind if I were provided with
solid experimental data that verify it, and under those intellectual
circumstances I would have to accept that genetic evolution of retroviruses
can be radically accelerated under certain conditions. And every scientific
colleague I know who is dedicated to authentic inquiry would respond in
precisely the same way. This is not an idealistic picture of how science
works; it is a realistic picture.
Hooper is anxious that some people would be turned against vaccines in
general, but surely not a greater number of people than those who now debate
the safety and the need for vaccination, particularly among children. The
weight of expert opinion in public health is strongly on the side of
vaccines, invoking their great value in preventing past scourges such as
polio, measles, and diphtheria. If forty years ago a lot of oral polio
vaccine was contaminated, then let us know it, and let us safeguard all
current vaccines, and use the knowledge wisely in the development of future
vaccines.
As for the rampant slaughtering of primates, especially chimpanzees, as an
act of revenge, this is a bit farfetched. It is already widely accepted in
the scientific community that African primates are the reservoir of this
family of retroviruses, and that SIV was transmitted to man in Central and
West Africa and evolved into HIV-1 and HIV-2. The oral polio vaccine
hypothesis does not make the animals more culpable--since no one sees them as
"responsible" now for the pandemic.
What about the "glare" of unwanted publicity for universities, pharmaceutical
companies, and public health departments? Surely none of them enjoys being
trapped in such a spotlight, but all of these institutions have matured
greatly, and surely they know that cover-ups bring only calumny, in the end,
and nothing like a frank and open articulation of error, particularly error
that occurred four decades ago. In sum, my bet is strongly against Hooper's
hypothesis.
III.
Luc Montagnier's book carries us away from hypothetical scenarios of the
iatrogenic origins of HIV, and back to the actual historical record of the
discovery and the spread of HIV. Montagnier, of the Pasteur Institute in
Paris, as well as Queens College in New York, is largely credited with the
discovery of HIV. He has produced a book that is part autobiography, part
personal musing about the events surrounding the early days of AIDS, and part
primer on AIDS biology, its clinical manifestations, and its treatment and
prevention.
A good deal of Montagnier's book is devoted to the scientific and
nationalistic competition that marked the discovery. Teams of scientists
around the world were racing to identify the cause of AIDS. The epidemiology
of the disease, which is spread by sexual contact, intravenous drug use, and
blood transfusions, made an infectious etiology likely. Since T-cells were
lost in afflicted patients, it was presumed that the microbe had a tropism
for these cells. Most laboratories, therefore, sought to isolate the
remaining Tcells from people with AIDS and to examine them, in tissue
culture, for evidence of a new pathogen.
The obstacle proved to be the complexity in successfully propagating T-cells
outside of the body, particularly in the presence of a destructive microbe
that caused their rapid demise. Montagnier's group at the Pasteur Institute
secured a lymph node from a man with the disease and succeeded, short term,
in propagating the T-cells from this node. Using sensitive and specific
assays for enzymes unique to retroviruses, the Pasteur group provided the
first evidence that the T-cells harbored a new human retrovirus, which they
named LAV. Pictures of the LAV retrovirus were taken, using an electron
microscope, and its morphology resembled that of so called lentiviruses, or
slow viruses, which were known to cause disease in horses and sheep. Yet the
Pasteur group was frustrated in its effort to produce enough of this novel
virus for more detailed characterization.
Meanwhile Robert Gallo at the NIH was also culturing T-cells from blood and
lymph nodes of people with AIDS. He had long worked on techniques to grow
T-cells, and had developed in his laboratory so-called permanent cell lines,
or immortalized T-cells that grow in a relatively autonomous fashion. Gallo
reasoned that these hardy T-cell lines might be able to support the AIDS
retrovirus without being destroyed by it. He requested a sample of the novel
virus isolated by Montagnier's laboratory, and (so the story goes) a
researcher in Gallo's group, Mika Popovic, succeeded in making the French
virus grow on the NIH's immortalized T-cell lines. As Montagnier recounts:
He [Popovic] was about to characterize it and notified Robert Gallo of this,
but was told to keep silent. When ... Popovic called me ... he was careful
not to tell me that he had learned how to cultivate our virus on a continuous
cell line, and only laconically remarked: I know how to grow your virus.
In late March of 1984, Robert Gallo telephoned me to say he had isolated a
new virus that was growing very well. ... In his opinion, it was the AIDS
agent. Had he compared it with LAV [the Pasteur virus]? I asked. I could not
hear the answer.
In fact, the primary isolate grown in the NIH laboratories that was to be
used in the lucrative HIV detection tests ultimately proved to be the Pasteur
virus, which presumably had inadvertently contaminated Gallo's own T-cell
cultures. This was not realized at the time, and Montagnier says that such
information might have changed the presentation of Gallo's work at a press
conference held on April 28, 1984, in Washington:
Gallo, sounding very tense, telephoned me before and after the event. I
advised him to make sure to mention the work we at Pasteur had done. In fact,
the press conference, as it was reported on the teletypes and later over the
radio, proclaimed a great victory for American science. The Secretary of the
U.S. Department of Health and Human Services, Margaret Heckler, lost her
voice at an unfortunate moment, preventing her from reading the paragraph
that was supposed to give credit to the work of the Pasteur team. Even after
fifteen years, these events still leave a bitter taste in my mouth, even
though I am aware that the extraordinary publicity Gallo rallied around his
virus reflected onto ours.
Montagnier writes gently about this once vitriolic controversy; and his soft
tone reflects more than a decade of slow reconciliation. The band-aid was a
joint document prepared and signed by the Pasteur Institute and National
Institutes of Health in March, 1987, elaborating a consensual account of the
discovery and the sharing of royalty rights for the very lucrative HIV
diagnostic tests. The clash of egos and the mutual accusations of the
"French" team and the "American" team about who deserved credit for the
identification of HIV received considerable media attention at the time, and
was featured by many journalists as the acme of unsalubrious scientific
behavior; and there is little new in Montagnier's recounting, alas, except
his very negative view of the superstructure of French science.
Montagnier roundly criticizes the academics with whom he trained, the
bureaucrats in the French government, and the senior faculty of the Pasteur
Institute. He protests their shackling of young, aggressive, and
independent-minded researchers.
The Pasteur Institute has many talented immunologists. Most, however, are
interested only in fundamental problems and work on mice: humans are too
"complicated" and the research we wanted to conduct was too "applied" for
these researchers, which might seem surprising in an institution founded by
Louis Pasteur.
I organized a seminar on AIDS retroviruses at the Pasteur Institute.
Francoise Barre-Sinoussi [a young researcher] presented our findings. Being
prudent, we only put forth a hypothesis: the virus whose characteristics we
were presenting might be the AIDS agent. But we were also proud of ourselves,
and certain that our Pasteur colleagues would welcome our findings with
enthusiasm. The reaction was clearly colder than that. It's "the Montagnier
gang" crowing again! said some.
This criticism has some merit, and it is corroborated by the contemporary
brain-drain of French (and other European) researchers to America.
(Montagnier's own move to New York occurred much later in his life, after he
was well established at the Pasteur, and cannot be attributed to a snuffing
of his nascent talent.)
But Montagnier's criticisms of French science are just about all that holds
his reader. Otherwise there is not enough to make this book into an
illuminating assessment of either the process of scientific inquiry or the
logistics whereby government, industry, and academia can best coalesce around
a seminal discovery like that of HIV. The book suffers from much unexplained
detail, in scientific terminology and in the identities of the players in the
early days of the AIDS drama; it is inside baseball, and there is no program
roster. This is unfortunate. A genuine memoir from a person of Montagnier's
learning and stature could have shed much light on the unmasking of the role
of viruses in the pathogenesis of immune deficiency and cancer.
The second part of Montagnier's book is a primer on AIDS, and it is presented
in a fluent and balanced fashion. The unknowns about precisely how HIV
destroys the immune system--whether infections other than HIV (so-called
co-factors, like herpes viruses and mycoplasma) augment the pernicious
potential of the retrovirus, and the differences in virulence among different
HIV strains--are all well covered. The impact of the protease inhibitors, as
well as the clinical limitations of such treatments, are also accessibly
delineated for a lay audience.
Montagnier's focus is on a vaccine, and he clearly articulates the daunting
complexities involved in developing such a prophylactic. The virus's exterior
coat is so changeable that it quickly eludes the grasp of the immune system.
So a person vaccinated using protein from a single isolate of HIV would not
be protected from infection by other isolates. Moreover, the initial virus
isolate used to prepare the vaccine will likely so change over time as to be
able to infect the person. Montagnier also rightly emphasizes that currently
ninety percent of all new HIV infections occur among heterosexuals in
under-developed countries, primarily Africa and South East Asia, and that
health care in such areas is so limited that virtually none of the benefits
of combination protease therapy or prophylactic antibiotic therapy against
opportunistic infections are realized.
Montagnier does not deal with the oral polio vaccine hypothesis--an
indication, perhaps, of how the notion had fallen off the radar screen of the
scientific community before Hooper's attempt to revive it. But Montagnier
does battle with Peter Duesberg. In forceful language, Montagnier asserts
that such unfounded theories are more than parlor debates, because they
endanger the health of the people who subscribe to them and who would
otherwise benefit from anti-HIV therapy, if they accepted the virus as the
underpinning of AIDS:
I did not think, when I first began writing this book, that I would have to
explain once again why AIDS is an infectious, communicable disease caused by
a retrovirus, HIV. ... A few scientists, however, led by Peter Duesberg ...
persist in defending the indefensible--that AIDS is not an infectious disease
but the result of aberrant behavior patterns, especially drug use. ... such a
theory can lead to irresponsible behavior and may, as with cancer, prompt
patients to seek treatment from charlatans ... I ... believe that, lacking a
medical education [Duesberg], ... did not take into account the complexity of
this immunological disease of viral origin, and confused the co-factors
(drugs, other infections) with the primary cause.
Beliefs can make the difference between life and death. Science demands that
our beliefs about disease, its cause and its treatment, be weighed against
empirical data; that our conceptions be examined and re-examined under the
sharp light of the experimentalist. It is not enough for prominent scientists
to invoke arguments from authority, and to rely upon the rhetoric of derision
in the struggle against fallacious views such as Duesberg's. The most
persuasive rebuttals are those that explain the facts. And the impartiality
of science is also a matter of humaneness, because false and fantastical
beliefs inflame the psychology of desperation and denial that grips people
with serious illness. The only consequence of false hope is true anguish. In
the shadow of deathly disease, ignorance does not end in bliss. Reality is
not only the domain of suffering and loss; it is also the domain, the only
domain, where genuine hope may exist.
JEROME GROOPMAN is the Recanati Professor of Medicine at Harvard Medical
School. His new book, Second Opinions: Stories of Intuition and Choice in the
Changing World of Medicine, will be published by Viking next spring.
We should therefore claim, in the name of tolerance, the right not to
tolerate the intolerant.
Karl Popper 1902-1994
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