[***Moderator's Note: In considering the impact of HIV/AIDS on
education,it is important to grasp some of the technical issues
related to the spread of HIV/AIDS. The following message is
considerably longer than those we usually post; our apologies to
members who have difficulty downloading it. However, we felt that this
information is rarely available to a lay audience, and is important in
considering approaches to addressing the impact of HIV/AIDS on
ducation, particularly strategies to reduce rates of infection. The
message suggests that the dynamics of "slow viruses" indicate why
certain groups are susceptible, e.g., teachers in Sub-Saharan
Africa. It also addresses the issue, raised earlier in this
discussion, regarding other factors, in addition to HIV, which
contribute to a patient succumbing to AIDS. Finally, it suggests that
there is hope for developing a vaccine, if "slow viruses" are
understood by researchers and the public alike.***]
Dear HIV-impact members,
This forum has been remarkable for the clarity and wealth of
information provided from all sectors in the world and particularly
for its implications pertaining to HIV and AIDS in sub-Saharan Africa.
The Moderators are to be commended for providing this service and
keeping it on target. As the forum winds down, I wish to inject into
our discussions two often overlooked key elements (i.e.,
ethnomethodological and slow virological elements) that have an
extraordinary impact on nations and cultures in sub-Saharan Africa,
and worldwide. Before launching into this discussion, a few words
about me and my organization, the Institute for Postgraduate
Interdisciplinary Studies (IPIS).
I am an interdisciplinarian, trained in medicine, virology (especially
slow viruses), molecular biology, psychology, education, mathematics,
statistics, computer sciences, and research methods. I have been a
founding co-editor of two international journals (Instructional
Science and Health Policy, both initially published by Elsevier), a
university professor (University of California, California State
University, and the Institute of Transpersonal Psychology), department
head (Testing Officer), scientific advisor to the Hepatitis C Virus
(HCV) Global Foundation, and Director of IPIS since the early-1980s.
IPIS conducts ongoing research in four areas: the molecular biology of
long-term memory in living systems (LTM); HIV, AIDS and HCV;
psychoviruses" and the impact of "transmissible negativism" on
commonsense (in Japan, Germany and the USA); and, how to help the
"unknowingly needy" and "worried well." My research takes me to all
sectors of the world, and especially islands and isolated groups.
My investigations of HIV and AIDS began before they were known. In
1977, I observed that all slow viruses (including the agents of
scrapie and kuru, prions, lentiviruses, and others), without
exception, cause the loss of long-term memory (LTM) in one or more
organ systems - and especially in brain and the immune system. Three
questions emerged. First, why would a class of viruses "knock out"
LTM, selectively? Second, why are these viruses "slow" and can one
"speed up" or "slow down" slow viruses to facilitate early or rapid
detection/diagnosis and/or to increase research throughput? Third, are
underlying molecular mechanisms among various manifestations of LTM
parsimonious? These questions were answered, albeit tentatively, in a
little reported presentation [Smith, R. W. (1979). Long-Term Memories:
Where Does the 'Buck' Stop? - Toward a Testable Theory of Debugging
the Molecular Basis of Long-Term Memories in Living Organisms.
Abstracts, Seventh Meeting of the International Society for
Neurochemistry (Jerusalem, ISRAEL - September 2-6), p. 590]. What now
is known as AIDS was dubbed, at the time and in theory, an "immune
dementia," even before descriptions of GRIDS, AIDS, and "slimming"
emerged. This label arose because no known neutralizing immune
response had ever been reported for any slowly progressive
transmissible infection, though one investigator (Bjorn Sigurdsson)
examined perplexing immune responses in Icelandic sheep (see below).
Prior to that time most slow viral pathology was associated with
lesions in brain, though arthritis or other immune manifestations were
reported.
Now to the terms ethnomethodology and slow viruses: Generally
speaking, ethnomethodology is the study of what we know, how we know
it, and "taken-for-granted" assumptions. Adjuncts to
ethnomethodological studies are general studies of "sense-making"
(i.e., how we make sense of information) and erotetic logic (i.e., the
study of the logic of asking questions, especially in discourse).
A precise definition of slow viruses (or slow virology) is
considerably more complex, and, for many years, quite elusive. The
term and definition arose in the third of three seminal papers based
on a lecture series, "Some observations on three slow infections in
sheep" [Sigurdsson, B. (1954a). Maedi, a slow progressive pneumonia of
sheep: An epizoological and a pathological study. British Veterinary
Journal 110:254-270; Sigurdsson, B. (1954b). Paratuberculosis (Johne's
disease) of sheep in Iceland. British Veterinary Journal 110:307-322;
Sigurdsson, B. (1954c). Rida, a chronic encephalitis of sheep. British
Veterinary Journal 110:341-354]. These articles describe AIDS-like
diseases in sheep from 1933 to 1954, even in the absence of
technologies for characterizing T-cell pathology. Evidence of AIDS-
like disease is only possible if the three articles are considered as
a whole. Infected sheep initially were derived from a stock of 20
karakul sheep imported from Halle, Germany. There was no evidence of
prior diseases in Iceland or Germany, or the karakul region of
Uzbekistan from which the sheep descended. This observation has
profound importance because it raises the question of why disease
arose rapidly in Iceland, but not in native stocks. Similarly, why did
AIDS arise rapidly in the late-1970s? Sigurdsson's second article, on
Johne's disease, provides the first clue that vaccines against
opportunistic pathogens may cure AIDS-like diseases.
Sigurdsson's articles are largely unrecognized, with only 27
citations to all three articles from 1980 to the end of 1996 and only
23 citations between 1974 and 1992. There are likewise few references
and citations to other lentivirus studies. These reports illustrate
the need for a broader purview on slow viruses, and the history,
philosophy and sociology of sciences of slowly progressive phenomena.
From an ethnomethodological perspective, do investigators not see a
bigger picture? Alternatively, do publishing related articles in
separate issues of a journal, possibly to benefit the business of
publication, affect scholarship adversely?
Because definitions of slow viruses remained elusive throughout the
1980s, we at IPIS undertook a study to characterize incontrovertible
features common to all slow viruses. It is important to understand
that controversy and internecine behaviors always have characterized
studies of slow viruses. Indeed, discussions in this forum, on other
HIV/AIDS list-servers, and especially in South Africa under the Mbeki
government are somewhat comic "replays" of issues slow virologists
faced during the 1960s through 1990s (cf., http://www.virusmyth.com).
For example, the recently released Mbeki government list of
distinguished scientific advisors has no representative with
demonstrated expertise on slow viruses - not one on either side of the
perceived "scientific divide"! Hence, it is important to identify
features of slow viruses that are immutable. This can potentially
reduce controversy while bringing an important foundation to research
on HIV and other slow viruses, especially in view of the long time
periods often required for slow virus experiments and challenges by
so-called peers [cf., Horrobin, D. F. (1982). Are the good the enemies
of the best? Journal of Research Communication Studies 3(4):327-334].
It should not escape the reader's attention that there are no
incentives for journal editors and publishers to promulgate
controversial findings, even though the underlying controversies often
have significant pedagogical value. Likewise, it is not too surprising
that the most important findings pertaining to slow viruses are in
unpublished reports, obscure journals, or in personal communications
at conferences, by telephone, and, now, by e-mail. One must never lose
sight of conferences, journals and scientific publications being
businesses - driven by "Rule of Two," Ingelfinger rule, page limits,
"peer" review (even if those peers have conflicts-in-interest or
little understanding of underlying issues), advertisers, etc. Indeed,
Sigurdsson's articles are much longer than would be published today,
and, even so, appeared in three separate issues of the British
Veterinary Journal.
Eleven rules or "near-axiomatic" principles now have been identified
that distinguish slow viruses from all other viruses or transmissible
agents [Smith, R. W. (1994). On Mechanisms of Slowness and
Progressiveness in Slowly Progressive Processes. Annals of the New
York Academy of Sciences 724:430-434]. This is especially important in
distinguishing lentiviruses, such as HIV, from other retroviruses,
such as oncoviruses and spumaviruses. "Slowness" is a functional
distinction, and not necessarily a structural one and with no known
structural feature characterizing slowness. The axioms focus
exclusively on functional issues germane to underlying slowness and
progressiveness. Combinations of these "axioms" can be used to derive
inferences, regardless of experimental outcomes. In other words,
contradictory findings are likely to have been derived from flawed
premises, poor experimental design, inadequate experimental controls,
and/or scientific naivete. Perhaps most interesting, virtually all
progress and lack of progress to date was accurately anticipated in
numerous published and unpublished reports by this author or other
slow virologists, in some instances even prior to the onset of AIDS.
Again, this poses another ethnomethodological challenge: why would so
many investigators, even with tools like the polymerase chain reaction
and the Internet, not recognize these prior findings and/or cite them?
Let us examine some of these rules or axioms. First, the number of
slow virus particles in a host or "herd" (infected group) is inversely
correlated with incubation periods, though activating co-factors must
also be considered. In other words, the more viral particles (titer or
load) the shorter the time to symptom onset. Some call this as a dose-
dependent phenomenon. In fact, this axiom is the basis for extant
measures of "viral load" (quantitative estimates of virus particles in
peripheral circulation). An underlying presumption is that this axiom
applies in the absence of prior intervention. Several special
considerations are very important. In HIV/AIDS, diseases are
associated with relatively uncommon "opportunistic" pathogens, not
common pathogens. Of course, what are common and uncommon pathogens
are host and environmentally defined. Indeed, evidence emerges
supporting Sigurdsson's clue that vaccines against opportunistic
pathogens have merit. At a semantic level, "AIDS" really is a
syndrome of abnormal tolerance for nascent (relatively uncommon)
opportunistic pathogens, not pathogens for which the host has a viable
immune response. Probably the most important implication of this first
axiom is a clue to the answer to the controversy that divides the AIDS
research community, AIDS activists and others. To wit, what is the
cause of AIDS, and what role does HIV play in AIDS, if any? I believe
I was the first person to raise this question in 1983 and 1984, and
directed attention to the Henle-Koch postulates not being relevant in
elucidating causality. The answer is that HIV and all opportunistic
pathogens (i.e., co-factors) are causes of AIDS, not HIV alone -
claims by Duesberg, Mullis and others on both sides of the scientific
divide, notwithstanding. Several investigators (notably Luc Montagnier
and David Ho) pursued this line of reasoning throughout the 1980s,
though they lost sight of considering opportunistic pathogens as the
elusive cofactors. We shall see that this issue has relevance in a
later axiom that accounts for mechanisms of slowness and
progressiveness. This matter also has obvious relevance for a
question about quarantines that arose in earlier discussions in this
forum and a more recent discussion on vaccine development.
Frthermore, policies on notification may be impacted, particularly in
island and isolated environments.
Second, slow viruses may infect many bodily fluids and cells
in many tissues. This is especially true of the central nervous system
and immune system, and any other systems involving LTM. Pathology most
often is associated with tissue possessing "memory potential," with
this propelling my LTM research. Third, unconventional agents (e.g.,
prions, "autotoxins" and "autovirions"; see [Smith, R. W. (1984). AIDS
and 'Slow Viruses'. Annals of the New York Academy of Sciences
437:576- 607]) may be associated with lentiviruses, and especially in
brain or associated with end-stages in disease. Autotoxins are toxic
products of "self," whereas autovirions are transmissible toxic hybrid
products of "self" and viruses or other infectious agents (e.g.,
including some small ribonucleoprotein complexes known as "snRNPs").
Substantial clinical and circumstantial evidence suggests that
autotoxins and/or autovirions contribute to Kaposi Sarcoma,
autoimmune sequelae in AIDS, and production of acid-labile alpha
interferon, the latter comprises an important viral countermeasure
against natural host defenses. These observations are extremely
important because no laboratories or experimental reports that I am
aware of control for autotoxicity or autovirulence. Additionally, it
signals a need for vigilance regarding concomitant pathology
associated with any gamma-herpesvirus (e.g., EBV, HHV-6 and HHV-8) in
the HIV-infected person, with the association between Kaposi sarcoma
and AIDS being reasonably anticipated.
This brings us to another significant observation. A fourth axiom is
that lentiviruses may have unusual synergistic relationships with
herpesviruses and especially gamma-herpesviruses. Herpesviruses often
activate lentiviruses by pathways other than trans-activation (i.e.,
being indirectly activated). Because herpesviruses often are activated
by stress, this may have profound implications for HIV-infected
persons in cultures and societies without adequate therapeutic support
for stress. Furthermore, autoimmune sequelae and abnormal clinical
chemistries should not be too surprising in HIV-infected persons,
specially when there are unusual stresses at hand.
Many investigators have noted the high mutation rate in HIV,
lentiviruses and other slow viruses. This is the fifth axiom. The
mutation rate in lentiviruses is often attributed to intrinsic
unreliability in reverse transcriptase. Other factors include host
mechanisms for generating diversity (including DNA changes in brain),
host genetic susceptibility, types of infected tissue, and
environmental factors. What is highly significant is the lack of any
neutralizing vaccines or immune responses to any slow virus. Equally
important, the rates of mutations (often called "microheterogeneity")
are an exponential function of the quantity of viruses in the host
and/or herd. That is, as the number of viral particles increase,
mutations rates in HIV and other lentiviruses increase manifold.
Mathematics demonstrates the low probability for a successful vaccine
against HIV or any slow virus. To place this in context, think of the
many years and billions of dollars spent in pursuit of vaccines
against HIV. Also recall pronouncements in the mid-1980s by leading
investigators and politicians that a vaccine would be developed in two
years. The same underlying mathematical model reveals the greater
therapeutic potential for killed multivalent vaccines against
opportunistic pathogens. This offers hope. Clinical demonstration of
causality in AIDS must await such vaccines almost as a straightforward
analogue to a syllogism in elementary sentential logic (i.e., modus
tollens [the method of "denying"]: "if 'HIV' implies 'opportunistic
disease'", and one has "not 'opportunistic disease'", the inference is
"not 'HIV'"). Furthermore, consider the economic implications
associated with developing killed vaccines against pathogens that are
opportunistic in AIDS contrasted to costs for research and development
of pharmaceutical preparations such as protease inhibitors. Not
surprisingly, this model also helps explain the limited successes and
failures of "drug cocktails" (e.g., HAART). The latter provides
discrete therapy, whereas killed multivalent vaccines against
opportunistic pathogens provide continuous therapy, while
circumventing trans-activating HIV. Biological attrition then may
reduce viral load. Notice the optimism!
Three other axioms are particularly important to this forum. One is
that of "recessive functioning." A study of prevalence rates of all
slow viruses worldwide and records of slow viral diseases revealed
that prevalence rates are almost always higher in island
or isolated environments. Exceptions to this observation virtually
always have clear explanations that are not inconsistent with the
underlying finding. If one reflects on the distinctions between
dominant and recessive genes, on the implication of Charles Darwin's
theory of evolution deriving from observations in the Galapagos, and
particularly on the very clean mathematics underlying the classic
principle/law of Hardy - Weinberg, it is clear that the basis of
slowness and progressiveness in slow viral disease is largely a
function of "recessive-functioning." No, HIV is not a recessive gene!
Rather, HIV generally requires "trans"-activation (i.e., indirect
activation) by its "opportunistic" co-factors, with HIV possibly
being opportunistic itself. Again, this speaks to the issue of
causality: HIV and opportunistic cofactors are the cause of AIDS, not
HIV alone. This is in contrast to other viruses that, at most, are
"cis"-activated. The significant exceptions to this principle in AIDS
and for all lentiviruses are the herpesviruses which have unusual and
special synergistic roles.
The recessive functioning axiom changes the dynamics of discussions on
the origin and evolution of HIV and AIDS. It now is essential that we
revisit claims of an African origin for AIDS. This is particularly
important because many studies challenge ease in cross-species
transfers of slow viruses. Moreover, the immediate challenge is to
identify "sociotechnological" factors that contributed to increased
numbers of HIV particles in islands, isolated groups and other
"herds." The term sociotechnological refers to technological, social,
political, economic and/or other changes impacting the ecology of the
slow virus. Indeed, participants in this forum have noted several
sociotechnological considerations contributing to the alarming spread
of HIV and AIDS in, say, teachers. The challenge in Iceland was to
identify aspects of animal husbandry and other sociotechnological
factors that contributed to the rapid onset of AIDS-like disease,
causing precipitous increases in quantities of the maedi-visna virus.
An analogous challenge in humans is to identify factors that caused
the rapid rise in HIV load. The evolution of HIV, itself, is
relatively irrelevant because its mutations depend exponentially on
numbers of viral particles. Notice an emerging confluence among issues
contributing to the perceived scientific divide. If nothing else, the
underlying controversies should be viewed as an appropriate part
of the business of science. Indeed, I applaud the Mbeki government's
initiative, even if we scientific dinosaurs remain buried in the
chasm.
Our findings reveal an important mathematical and statistical analog
to the Law of Hardy - Weinberg characterizing any modeling of HIV and
general lentiviral lineage. These models fundamentally rely on non-
linear graph-theoretical models, not the linear graph-theoretic models
promulgated heretofore. Linear models cannot account for the rapid
onset of AIDS-like disease in Iceland or the rapid onset of AIDS
worldwide. This also is the basis of the second of these three
important axioms, the island phenomenon. Slow viruses always may be
expected to cause greater harm or damage on islands or in isolated
groups unless adequate intervention exists. Measures of how avidly
circumscribed isolated groups are can be exceedingly important.
The third axiom also follows what I call the "counter-intuitive"
axiom. Success in clearing or curing slow viral diseases is best
accomplished by mitigating sociotechnological factors. That is,
resolving slow viral disease most often requires more than medical or
virological intervention. Contributions to this forum make this
abundantly clear in AIDS. In kuru, for example, this was accomplished
by changing mortuary rituals. In Icelandic sheep, 'mad cow' disease
and AIDS-like disease in primate colonies, changes in animal husbandry
and business practices were necessary. In HIV and HCV infections,
especially in prisons, it involves rapid, proper and effective
surveillance, education and intervention. Not least in importance, in
science, religion and other professions or cultures, it must involve
education. This is particularly true of the allied health professions
that owe much to discoveries by non-traditional medical practitioners,
herbalists, buyers' clubs, activist groups, NGOs and other groups.
Note that the island and counter-intuitive axioms urge caution in some
sociotechnological activities, especially when island or isolated
groups are highly circumscribed.
In summary, I set out with four unstated objectives. The first
objective is to increase general awareness about slow viruses because
HIV and other slow viruses are poorly understood. I hope that my
comments facilitate discussing a broader range of underlying issues
without recriminations or internecine behaviors characteristic
of past research in slow virology. A second objective is to
"level" the playing "field" by providing "peers" with knowledge of
axiomatic systems central to all slow viruses. An obvious goal is to
reduce instances of controversy common to research on slow viruses. An
anticipated corollary is increased harmony and collegiality among
parties having vested interests in HIV and AIDS. A third objective is
to establish the basis for appropriate mathematical models and
"gedanken studies" (i.e., thought studies and experiments) in research
on slowly progressive infectious processes. This is aimed at reducing
costs of research in time and funds. An additional benefit is to
narrow the "scientific divide" and controversies surrounding research
on slow viruses using the axiomatic scheme to foster scientific "good"
sense in sense-making studies. Finally, I hope that by citing
instances of psychodynamics and sociodynamics in slow virus research,
and particularly their impact on the business and culture of sciences,
we all can move forward with greater awareness and self-awareness of
factors likely to contribute to needless aggressive, aversive or
counterproductive behaviors.
I tried to portray a variety of ethnomethodological and slow viral
findings that impact studies of HIV and AIDS in sub-Saharan Africa and
worldwide, thereby going a step beyond the initial mandate of this
forum. On the other hand, I hope this relatively brief overview of
past research will broaden the discussion on the impact of HIV on sub-
Saharan Africa to now include discussions of the impact of this forum
on scholarship and science, particularly as they relate to
consequences of HIV and AIDS in sub-Saharan Africa. Stated
differently, I hope we appreciate the potential impact this forum may
have on revisiting and rethinking all aspects of HIV and AIDS,
including our own roles in research, care-giving, and providing real
hope to all "impacted" by this dread pandemic. In the end, I am
particularly grateful to the Moderators of this forum for
disseminating this longer than usual perspective. I am equally
grateful to forum participants who examine past postings in the
context of this posting.
Post Script: A virologist colleague described lentivirologists and
slow virologists as living dinosaurs. We largely are endangered
species, creatively resorting to crude investigatory tools. The
axiomatic scheme is but a mere example, as is the application of modus
tollens. I sincerely hope this posting has awakened readers to the
exciting problems to which living dinosaurs must contend, and
of the fossilized remains yet to be unearthed! Although this forum
will cease shortly, possibly burying a scientific dinosaur and a
contribution of potential value, where else can or should these views
be promulgated?! As noted earlier, some of the most significant
contributions in slow viral research are personal communications
having value if a participant survives to carry a message forward.
I look forward to our further interactions in Durban and/or by e-mail!
Dr. Ricki A. Lewis and Nicole M. Smith provided invaluable editorial
assistance.
Roulette Wm. Smith, Ph.D. - Director
Institute for Postgraduate Interdisciplinary Studies
P. O. Box 60846
Palo Alto, CA 94306-0846 USA
***Also***
Testing Officer
Testing Office, SCC 11207
California State University, Dominguez Hills
1000 East Victoria Street
Carson, CA 90747-0001 USA
E-Mail: Roulette@research.csudh.edu
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