Biotherapy 9: 17-26, 1996.
AIDS and transfer factor: Myths, certainties and realities
Laboratoire d'Immunobiologie, URA 1294 CNRS, Faculté de
Médecine, Paris, France
Key words: AIDS, cancer, cell mediated immunity, cytotoxic
T-lymphocytes, HIV, normal science, transfer factor, vaccines
At the end of the 20th century, the triumph of biology is as indisputable
as that of physics was at the end of the 19th century, and so is
the might of the inductive thought. Virtually all diseases
have been seemingly conquered and HIV, the cause of AIDS, has been
fully described ten years after the onset of the epidemic. However,
the triumph of biological science is far from being complete. The
toll of several diseases, such as cancer, continues to rise and
the pathogenesis of AIDS remains elusive.
In the realm of inductive science, the dominant paradigm can seldom
be challenged in a frontal attack, especially when it is apparently
successful, and only what Kuhn calls "scientific revolutions" can
overthrow it. Thus, it is hardly surprising that the concept
of transfer factor is considered with contempt and the existence
of the moiety improbable: over forty years after the introduction
of the concept, not only its molecular structure remains unknown,
but also its putative mode of action contravenes dogmas of both
immunology and molecular biology. And when facts challenge
established dogmas, be it religion, philosophy or science, they
must be suppressed. Thus, results of heterodox research become
henceforth nisi - i.e., valid unless cause is shown for rescinding
them, because they challenge the prevalent paradigm. However,
when observations pertain to lethal disorders, their suppression
in the name of dogmas may become criminal. Because of the
failure of medical science to manage the AIDS pandemic, transfer
factor, which has been successfully used for treating or preventing
viral infections, may today overcome a priori prejudice and rejection
more swiftly. In science, as in life, certainties always
end up by dying and Copernicus' vision by replacing that of Ptolemy.
Abbreviations: CMI=cell-mediated immunity; CTL=cytotoxic T-lymphocytes;
HIV=human immunodeficiency virus, HSV = herpes simplex virus; MuLV
= murine leukaemia virus; SIV = simian immunodeficiency virus;
VZV = varicella zoster virus.
The syndrome or the virus
Examining certain aspects of science policies and politics, leading
to conceptual obstructions, is not a pure philosophical or idle
intellectual exercise. Indeed, sometimes deadly diseases
are involved, and AIDS offers a timely example.
Despite the identification of HIV, the causative agent of AIDS,
only three years after the onset of the epidemic and its near complete
dissection today, the pathogenesis of the syndrome is still not
understood, the therapeutic approach remains ineffective, and the
clinical results totally disappointing. A hiatus between
knowledge and clinical results is becoming apparent and the gap
widens with time. However, despite the therapeutic failure,
only those leads within the dominant stream of thought are explored. Thus,
for over a decade, neither the fact that some patients are able
to resist infection , nor encouraging preliminary results, reported
as early as 1987, using transfer factor for the treatment of AIDS
, have drawn the attention of the investigators, the funding
agencies and research policy makers, who apparently cannot see
the disease for the virus.
Discordance between the quantity of available analytical data
and solutions requiring a synthetic approach, as well as deliberate
disregard of facts or ideas, is more common than expected in science,
especially in biomedical disciplines. The failure in treating
AIDS, after that in controlling cancer, is an illustration of a
dominant trait of "normal science" : results are never
proportional to the amount of knowledge gathered by accretion,
following the rules of inductive research.
The kernel of my contention here is that existing funding could
produce far more significant results if it were partially used
to finance extraordinary science [3, 4]. To substantiate
this assertion, I shall review some aspects of AIDS research and
discuss why certain facts and seemingly rational approaches are
at times neglected, whilst cul-de-sacs may be investigated with
unmitigated ardour. In this context, censorship, i.e., selective
consideration of facts and ideas -- a natural constituent of normal
science -- becomes a decisive factor in transforming research into
a closed system. Transfer factor may be cited as a typical
example of an a posteriori factual rejection, i.e., rejection of
established facts when ossification of the consensual thought does
not allow for their existence.
Normal science as religion
Thomas Kuhn has called science carried out routinely and not challenging
the paradigm, "normal science" [3, 4]. Despite
disagreements among philosophers, by and large, normal research proceeds
by induction: it is a linear process of collecting and comparing
factual observations, increasing knowledge by accretion. Today's
biological research closely follows the kuhnian model, and the
fact that both Kuhn and Popper condemn progress by accretion, does
not change reality [3-9]. Cancer research, and more recently
the human genome project, are examples of a mere collection of
observations by skilled technicians, where the construction of
new, daring, falsifiable hypotheses is deemed unnecessary for achieving
Normal science is organised around central hypotheses,
which have evolved to consensual truths or paradigms, and the majority
of scientists are transformed into their hidebound guardians. Such
a system is gradually closed, becoming quasi-impermeable to outside
reality, the belief in the perfection of its dogmas being its defence
against the challenge of unwelcome conjectures, and even observations. Many
barriers protect the citadel. Peer review committees of gatekeepers
are created to make certain that the rules are respected and that
heretics do not find their way to the core of the system to challenge
the existing order from within; support is offered for projects
within the dominant paradigm, and publications will be screened
for their conformity to it; funding in turn will be reserved for
those who can prevail with a high number of printed reports supporting
the paradigm. The outcome of this policy has been described
as the Saint Matthew effect .
The consequence of this
policy is that the number of paradigmatic publications cannot but
increase, whereas the risk of printing controversies cannot but
decrease, to the utter satisfaction of the control bodies and funding
agencies: all approaches being within the limits of the accepted
tenets, no major controversial observations or errors would easily
appear, but neither would unexpected discoveries. By introducing
the "impact factor", which was supposed to measure the
penetration of a publication in the scientific community by the
number of its citations, Eugene Garfield produced a tool for identifying
and measuring an important aspect of normal science . Gradually,
with time, it became a means to increase the closure of the system
and the effectiveness of the gatekeepers. Thus, only observations
within the limits of the existing thought would be readily published
in high impact journals, read, consensually appraised, and subsequently
acquire a high impact. The Vatican's imprimatur, although
lacking today's computer power, was just as efficient in preventing
the diffusion of heretical ideas and in enforcing orthodox beliefs.
This type of science is far from the idealistic, close to myth
description of Sir Karl Popper, who believes that science progresses
through conjectures and refutations, and that each hypothesis,
being by definition falsifiable, should be repeatedly tested until
proven false and replaced [7-9]. Nearer to reality, Kuhn
contends that the paradigm is overthrown only in exceptional circumstances
of "essential tension" - when the gap between reality
and belief becomes untenable - leading to a scientific revolution [3-6].
In his attempt to condemn
the concept of normal science, Watkins accurately describes it:
normal scientists are "under some mysterious compulsion to
preserve the current theories against awkward results. Close
examination shows that those theories lose their scientific status
and degenerate into something like metaphysical doctrines";
thus, scientific normalcy amounts to "a closed society of
closed minds" . The reasons for such behaviour producing
this state of affairs, although fascinating, are study matter for
disciplines such as psychology and sociology, Suffice to say that
scientists, even when medically qualified, are not psychologically
better prepared to deal with reality and social issues than
politicians, the military, or the clergy.
Be that as it may, it is obvious that it is always more comfortable
to dwell in certainty than in doubt - religion was invented for
this purpose - and that certainty is not only the effect of passion,
often it is also associated with reason. Resistance to change,
in this case to consensual framework, is a natural tendency and
one way of averting or delaying essential tensions and revolutions. More
often than not, it is achieved by unconscious and subtle manipulation
of facts and ideas, a bona fide adaptation of new observations
to existing theories. The Ptolemaic system is a classical
example. Thus, until Copernicus revolutionary ideas, Ptolemy's
coherent construction remained valid and operational after introduction
of ad hoc corrections - epicycles on epicycles on deferents - to
account for new, challenging the system observations. Thus,
the system remained functional, despite the falsity of the underlying
model, that of geocentricism .
When this method is not successful, i.e., when adaptations of
the conceptual framework are not sufficient to integrate the challenging
observations, facts may be discredited and discarded as observational
errors. Barbara McClintock's observations on the "jumping
genes", contravening the entrenched idea of genome's stability,
were considered ludicrous for years, before receiving the recognition
of the Nobel Prize Committee .
In their struggle for power, via dogmas, followers and opponents
of the paradigm may resort to fraud, faking or misappropriating
experimental evidence. The controversy over a potential Nobel
Prize for discovery of the AIDS virus is a recent example of blatant
fraud, which despite wide publicity had no consequences on the
culprits' careers. In contrast, in the 70's, the fraud of
a Nobel prize-candidate's assistant, who, under extreme pressure
to produce results resorted to the use of paint to prove successful
allogeneic mouse skin grafts, destroyed both careers . Scientists,
wooing peers' approval rather than solely embracing reality, are
not immune to passion, nor to the lures of power; rather, they
tend to succumb too easily to both.
Not only are scientific beliefs in our era substitutes for religious
dogmas, but the underlying mechanisms of their formation and survival
seem similar. When the Church had the power to censor scientific
observation, the latter could not evolve outside the Aristotelian
framework. However, when censorship became insufficient to
secure stability and survival of the credos, like the henchmen
of an endangered scientific tenet, the clergy tried to preserve
the dogmas by adapting them to the scientific reality. But
before accepting change, the temptation has always been to negate
reality. The creationists' present struggle to save their
faith in the biblical myths may seem ludicrous and contemptible,
but in an analogous situation, pro-life supporters use murders
to defend their beliefs i.e., save life.
In theory, rejection of facts in science is condemnable on the
grounds of objectivity and unbiased observation, which supposedly
govern research. In reality, observational filters are present
at all levels and they do not pertain solely to marginal phenomena
such as parapsychology. Although, even in such a case, even when
the rejection of facts seems an appropriate measure for spooky
topics, it is objectionable, since "it operates before considering
the evidence". But "similar things happen constantly
even where there is no suspicion of metaphysics. For instance,
the theory of continental drift was long dismissed as unscientific,
and so for a time were James Lovelock's suggestions about damage
to the ozone layer" . Lovelock's text is a fascinating
illustration of a subconsciously programmed fact-rejection. "It
is a scandal that the vast sums spent on expensive big science
of satellite, ballon, and aircraft measurement failed to predict
or find the ozone hole. Worse than this, so sure were the
computer programmers that they know all that mattered about the
stratosphere, they programmed the instruments aboard the satellite
that observed atmospheric ozone from above to reject data that
were substantially different from the model predictions. The
instruments saw the hole, but those in charge of the experiment
ignored it, saying in effect, 'Don't bother us with facts; our
model knows best'. The Ozone War is littered with stories
of this kind of military incompetence" .
Obviously, operating in this fashion appears simpler, time and
energy saving. Closer examination shows counterproductivity,
contradiction with the system's fundamental premises of objectivity
and obfuscation of the mind, which can lead to disaster.
It thus appears that the only distinction between a credible
and a non-credible observation is whether or not it fits with the
consensually accepted reality, not with the factual experimental
data. Logically, when "confronted with the unexpected,
the scientist must always do more research in order further to
articulate his theory in the area that has just become problematic";
in fact though, "no exclusively logical criteria can entirely
dictate the conclusion he must draw" . In other words,
irrational psychological impulses may inspire scientific conclusions
and rejections. But as soon as a phenomenon moves outside
the boundaries of the accepted reality, it becomes marginal, comparable
to metaphysical phenomenology, and subject to irrational treatment,
e.g. to derision and rejection.
AIDS: A syndrome outside the paradigm
There are instances where factual rejection may have immediate
disastrous consequences. For instance, rejection of the evidence
for the infectious aetiology of AIDS for ten years would have resulted
in an epidemiological catastrophe.
This is not pure speculation. It is plausible to imagine
that Duesberg's arguments [17-20] might have prevailed
for a few years, and that the role of HIV was relegated to that
of a co-factor. Under this scenario, retroviral research
funding would have been minimal, and diagnostic tests would not
have been developed nor would educational efforts have been undertaken
to prevent the spread of HIV. Thanks to transfusions of unscreened
blood, the number of seropositives would be at par today with that
The early history of
unravelling the AIDS aetiology makes this scenario even more plausible. Indeed,
the infectious aetiology of AIDS was called a "simplistic
hypothesis" as late as 1984 , whilst, even to this day,
Duesberg continues to claim the unimportance of HIV in the aetiopathology
of the syndrome [17-20].
The hypotheses produced by respected scientists at the beginning
of the AIDS epidemic to account for its aetiology, negating the
existence of a new infectious agent, were ingenious and --- complex. They
had to be, to remain viable and discount reality with some credibility
[21-26]. Nonetheless, despite the scientific and medical
community's lack of formal philosophical training, one may contend
that it was not difficult to conceive and investigate the hypothesis
of the existence of a new infectious agent as early as 1981. Instead,
ignoring the rather recent teachings of Legionnaire's disease,
the infectious hypothesis was discarded with vehemence.
If from the beginning AIDS appeared strange, it was mainly because
it was confined to certain groups: homosexuals, haemophiliacs,
Haitians, and heroin addicts. Homosexuals being the first
and largest identified population, inductive thinking had to propose
a plausible hypothesis compatible with observed facts and existing
certainties. Formulating theories to incriminate homosexuality
was certainly a complex task, but more within the realm of the
known, and it benefited from the undercurrent support of the moral
majority: incriminate what has been for other reasons condemned,
was more comfortable and consensus nurturing. Religious neurotics
were quick to jump to the rescue of the untenable hypothesis, and
to remind us that homosexuality was a behaviour condemned by the
commands and the representatives of the Judeo-Christian God. Thus,
AIDS became God's justification in the 80's, of his very early
The homosexual hypothesis was the first naive construction to
account for the pathogenesis of AIDS. It was simple, obvious
and it appeared correct, since in the early years, almost all known
cases were homosexuals. As usual, when prima facie simplistic
explanations are apparently flawless, logic recedes and it is easily
forgotten that a phenomenon in biology can seldom receive a simple
and univocal explanation. Interestingly, followers of the
homosexual theory were not bothered by stumbling logical difficulties,
the main one being that homosexual practices have always been present
in human societies, but not AIDS. Thus, the attempt to account
for the sudden outbreak of the epidemic in the 80's as a consequence
of sperm's immunosuppressive properties should have seemed utterly
preposterous. But proponents of the ludicrous hypothesis
were stubborn, and adjustments were devised to save it. The
existence of adjuvant factors was postulated and recreational or
hard drugs were proposed to that effect. The presence of
the syndrome among haemophiliacs was explained by the immunosuppressive
properties of the blood by-products, whereas the high prevalence
in Haitians was attributed to their homosexuality and/or drug addiction. The
analogy with the adaptation of the Ptolemaic system to the heliocentric
reality is striking. But, errors of the past never become
lessons for the present.
It may be significant that the homosexual explanation is not dead
today, even among non-believers in revealed biblical truths, i.e.,
among scientists who still see the semen playing a major role in
the pathogenesis of AIDS , whilst others  have decided
to widen the argument and include additional factors, but exclude
the HIV. When a seemingly successful research has not produced
the expected tangible results -- here a therapy -- , it is tempting
to seek the solution in the irrational collation of data rather
than by exploring alternative new hypotheses.
The cancer blueprint
As a consequence of the failure to show significant clinical results,
those who have vested interests in uttering statements of hope,
have often suggested that the pattern of AIDS therapy would follow
that of cancer, implying that it is unrealistic to expect the discovery
of an antiviral drug capable of eradicating the HIV infection in
the near future. Thus, a strategy using antiviral poly-chemotherapy
should be developed which, after several randomised clinical trials,
might eventually produce some long lasting effects.
Unfortunately, the analogy between AIDS and cancer is pertinent. Quasi-consensually,
cancer has been accepted as the result of an irreversible malignant
change in the normal cell. The alteration producing the malignant
cell -- be a mutation or a viral insertion -- being irreversible,
it follows that the only evidently rational therapeutic strategy
would be the eradication of the mutant cell and its progeny. Notwithstanding
contradicting observations -- several reports in the 60's and 70's
had unequivocally challenged the irreversibility of the cancer
cell dogma [30-32] -- these conjectures gradually became certainty
determining the therapeutic methods, all aiming at the extermination
of the tumour cell: surgery, radiotherapy, chemotherapy, immunotherapy. Refined
with time, these techniques are the ones still in use today, with
results far below the promises of politicians and scientists. Indeed,
Nixon's cancer campaign launched in 1971, made cancer a target
to conquer in the 70's, as the moon was conquered in the 60's. The
subsequent RFP (requests for proposals) programme launched by the
NCI was supposed to ask scientists to produce the answers to the
problems defined by the thinking elites of the paradigm. The
apology of this "war" is summarised in a NCI publication,
with a significant title attempting to exorcise the cancer cell: "Contrary
to Nature" . However ridiculous this title may seem
today, it is the explicit epitome of a credo, and an illustration
of the absurdities that certainty can produce.
Despite claims of politicians and fundraisers, and the enormous
research budgets, cancer mortality statistics look worst today
than at the beginning of the century or 20 years ago . But
in normal research, failure does not determine change swiftly. It
is, nevertheless, candidly admitted that "the main conclusion
we draw is that after 35 years, the intense efforts to improving
treatments [for cancer] must be judged a qualified failure ...
we are losing the war against cancer" . Obviously,
such statements have no effect on the cancer paradigm and the underlying
policies, which will continue unswayed until its death, but make
R. Gallo's assertions that "AIDS is following almost too neatly
the history of cancer chemotherapy, and one could almost predict
exactly what will happen next", seem piteous and asinine,
if not cynical. Cancer is an illustration, a forcible example
of predictable and predicted failure of research confined within
the boundaries of consensual paradigmatic certainties . It
is reminiscent of what is happening with AIDS: the scientists and
politicians' boastful claims [e.g., 37, 38] and, several years
later, the paucity of results.
AIDS and cancer seem to have
something fundamental in common indeed: they share the same conceptual
errors -- i.e., facts ignored to save theories. And the results
are comparable: failure to produce tangible clinical results. It
is thus ironical, and it would be cynical, if it were not pathetic,
to present as promising the fact that the pattern of AIDS treatment
will follow that of cancer.
Transfer factor a concept outside the paradigm
The evolution of transfer factor's
perception by the scientific community has followed a rather unusual
career. Here, previously accepted facts and hypotheses are
not rejected because they are refuted by new experimental evidence,
or by alternative explanations, but simply discarded, deliberately
placed into oblivion. Forty-five years after its existence
has been postulated, because its structure remains elusive and
its putative mode of action apparently does not fit within the
boundaries of the current certainties of immunology and molecular
biology, it has been implicitly decided by steeped-in-orthodoxy
guardians to do away with the concept, together with the underlying
supportive evidence, by ignoring them. Consequently, over
1200 reports printed in the past twenty-five years  should
be scraped, not because an alternative explanation to the described
observations can be proposed, but precisely because none seems
adequate to account for them.
The implicit negation of transfer factor's existence may be a
mirror image to the previous proposed scenario of refuting
the AIDS infectious aetiology for a decade. But this time,
the setting is real: all research on the subject has been stifled
and funding dried up. However, continuing the analogy with
the non-viral aetiology of AIDS, if the preliminary results reported
on the use of transfer factor in AIDS were to be confirmed, the
consequences of deliberately ignoring not only theoretical considerations,
but also factual evidence, could prove to be as disastrous as ignoring
the evidence for HIV for ten years, and as criminal as dispatching
for commercial reasons contaminated blood by-products to haemophiliacs. One
can imagine what adequately funded research would have produced
since 1987 (the first data using transfer factor in HIV infected
patients were published that year [2, 40] ), and the toll that
patients had to pay because of the deliberate decision not to explore
this therapeutic approach.
Transfer factor's rejection is, in certain aspects, reminiscent
of that of DMSO. Because it was empirically utilised for
the treatment of miscellaneous and unrelated pathological conditions
(from eczema to arthritis, and from burns to psoriasis or to mental
disorders), based on unsubstantiated rumours of toxicity, the FDA
decided to ban its medical use. It is true that reductionist
thought profoundly dislikes compounds with pleiotropic effects. Thus,
research on the molecule withered, notwithstanding its extraordinary
properties on cell differentiation [e.g., 41-44], while the toxicity
issue remains unresolved to this day, despite its use for cryopreservation
of embryos, tissues, or cells injectable into patients. A
recent report indicates that after a decade of procrastination,
NIH experts accepted the products lack of carcinogenicity, albeit
no study has shown that the non-toxicity impression was
any more valid than that of toxicity . Rumours versus
rumours. Once again, we are closer to religious beliefs than
to scientific objectivity. Such irresponsible attitudes --
often tolerated by the editors of the scientific press -- are common
and indicative of the role that lack of courage plays today. For
it is always safer to say no, and there are no sanctions
against procrastination or refusal. A behaviour described
by Samuel Butler in 1872: "...it seemed to be counted the
perfection of scholarship and good breeding among them not to have
-- much less to express -- an opinion on any subject on which it
might prove later that they had been mistaken. The art of
sitting gracefully on the fence has never been brought to greater
perfection than at the Erewhonian Colleges of Unreason..." .
Under the crack of reality
Despite the early discovery of its causative virus, the pathogenesis
of AIDS is still not understood. Inter alia, the pace of
progression to the full-blown syndrome varies from one patient
to another, but it is unclear whether the preponderant role should
be attributed to the changing virulence of the various viral strains,
to individual differences of the immune system, or to co-factors,
e.g. other viruses and microorganisms. What seems certain
is that cell-mediated immunity (CMI), as in most viral diseases,
plays a key role in the progression of the HIV infection. However,
one had to wait until 1992 for clear prompts that attention should
be shifted to the immune system . It was the time when
the failure of the research, so far focused on the description
of the virus, to produce clinical results became obvious and inspired
eloquent editorials, inviting scientists to remember that uncertainty
is always present in our world .
Because the success of virology, associated with that of molecular
biology in identifying the virus has been remarkable, because it
made intuitive sense that antivirals preventing viral replication
should curtail the CD4 cell loss, because the evolution of a viral
disease is, we used to think, well understood and cure is synonymous
with viral elimination, it seemed logical, and it is still intellectually
tempting to many, to believe that the solution lies in the discovery
of the miraculous antiviral compound.
However, it now seems univocal that CMI is responsible for the
observed resistance to disease progression [49-53] and in certain
cases to infection [54-57]. Although known, potent in vitro
antivirals fail to cure and antibodies to protect, these observations
should be sufficient to suggest that the HIV infection is not outside
the realm of our repertoire of the known, even if it does not fit
within the ad hoc framework we have created for it. For instance,
herpes patients suffer relapses despite the presence of anti-HSV
antibodies, the defect lying in the CMI arm of their immune system
[58-60]; once this is corrected, relapses subside [61-62], whilst
mice can be protected from lethal HSV infection by specific transfer
factor . It is thus hardly surprising that all attempts
to produce anti-HSV vaccines have failed since they were soliciting
the B cell compartment of the immune system [64-72].
That anti-viral antibodies may in certain cases remain ineffective,
and that CMI mechanisms may be efficacious is, therefore, in no
way novel, unusual, or specific to HIV infection. Rather,
what is astonishing is the enormous effort stubbornly deployed
to manufacture a vaccine addressing humoral immunity, despite past
experience and repetitive failures to produce a herpes vaccine,
and notwithstanding the evidence that the presence of anti-HIV
antibodies does not abate AIDS progression. This enterprise
continues uncurtailed, in spite of the recurrent failures to produce
results [73, 74].
The evidence for the role of CMI in the control of AIDS is as
overwhelming as the failure of humoral immunity to neutralise the
virus. Recent reports have substantiated this contention,
suggesting a plausible mechanism: HIV-specific cytotoxic T-lymphocytes
(CTL) would be responsible for controlling the infection [54-57]. Several
observations support this view. The presence of HIV-specific
CTL in the blood of an uninfected child, born to an infected mother,
implies successful resistance mechanisms induced by contact with
the virus , as does the presence of HIV-specific CTL in seronegative
partners of HIV-infected individuals . Not only these
findings offer a plausible mechanism for the resistance to the
disease, but also suggest that certain individuals, who have developed
cellular immunity to HIV, are able to prevent infection and destroy
the virus with such speed and efficiency that no antibody formation
takes place , whereas others are capable of resisting progression
of the infection  or even of clearing the infection and eventually
becoming seronegative . Rowland-Jones et al. reported
that certain prostitutes, daily exposed to the virus, remain uninfected,
as shown both serologically and by PCR, but they do develop HIV-specific
CTL . One major implication of this observation is that
CMI, contrary to neutralising antibodies, may protect against several
viral strains: the Gambian prostitutes seem to be resistant to
all HIV strains presented by their clients. Yet, the existence
of uninfected homosexual or heterosexual partners of HIV-infected
individuals has been known for many years. But as long as
the failure of the consensual solution i.e., the use of neutralising
antibodies to combat the virus was not recognised, the CMI track
was left unexplored.
Transfer factor acts on CMI, and it is known to be efficacious
in treating viral infections. Indeed, CMI plays a key role
in controlling such infections [61-63,73-78]. Observations
using HIV or SIV-specific transfer factor have provided insights
leading to the formulation of similar hypotheses: the possibility
for CMI, probably via the CTL subpopulation, to control lentiviral
infections. Indeed, a monkey model provided evidence that
SIV-specific transfer factor can hinder disease progression, and
furthermore that transfer factor extracted from CD8 cells is the
most potent . More recent studies by Clerici et al. corroborated
these observations: low dose, below threshold seroconversion level,
SIV injections induce a T-cell mediated response capable of conferring
resistance to subsequent virus challenge in macaques. And
the authors contend: "AIDS vaccines should be designed to
optimise the cellular arm of the immune response".
The fact that transfer
factor may induce cytotoxic lymphocytes is not new: it was reported
twenty years ago . This observation, together with the
above cited evidence that CTL may be able to control the HIV infection,
and the first encouraging data from the transfer factor use in
AIDS, should have prompted an active investigation; but did not. Only
recently has CMI received serious consideration for inclusion into
the AIDS management paradigm, whereas transfer factor is still
ostracised and remains off limits of the orthodox territory.
Yet, in several instances, transfer factor has been used
not only for treatment, but also for prophylaxis against viral
infections. Steele et al. utilised a VZV-specific transfer
factor to protect leukaemic children from varicella infection . Our
own studies with a HSV mouse model have also shown that HSV specific
transfer factor, injected prior to a lethal HSV challenge, has
a prophylactic effect . Since animal models using the
HSV or the MuLV in mice, or the SIV in macaques are relatively
inexpensive and simple to operate, this crucial issue, viz. the
possibility of employing specific transfer factor to prevent viral
infections, could easily be investigated. A vaccine, based
on an oral administration of specific transfer factor, would be
the simplest, least expensive and least toxic type of vaccine known
Criticising a posteriori contentions and certainties, when facts
have proven them mistaken, might seem presumptuous and the exercise
futile, if it were not in the hope to draw some insights and lessons
for the future. Indeed, retropredictions i.e., predictions
explaining the unfolding of the past, are easy: retrospectively,
reality almost always makes sense, and more often than not facts
become predictable; but "predictions are difficult, especially
if they concern the future" . Nonetheless, I shall
try to make a few; they are always easier when they do not intend
to flatter or to fool. Thus, the gloomy forecasts, foretelling
the failure of inductive research to swiftly solve the cancer problem
and reduce mortality, were proven correct fifteen years later [36,
Imagining in 1995 strategies for coping with the HIV infection
is not an extremely hazardous enterprise. The humeral vaccine
track seems to be an impasse, whereas prophylactic vaccines based
on CMI stimulation, viz. specific CTL induction, should become
reality in the years to come. Combination of antiviral poly-chemotherapy
to reduce the viral load, with immunotherapy to boost CMI defences
and eliminate the HIV-harbouring cells, seems a plausible approach,
the most plausible. This type of intervention should be started
as early as possible: the time of a quiescent asymptomatic phase
reflecting the inactivity of a dormant virus, is a myth of the
past. We now know that the immune system launches a paramount
struggle against the virus from the beginning of the infection
[85, 86] and it is precisely at this stage that the immune system
is in dire need of help, and outside intervention will be the most
efficacious. This strategy should significantly reduce mortality
Predicting transfer factor's future is a different affair. It
seems highly probable that it will have a favourable effect on
the evolution of AIDS. In the absence of alternative efficacious
therapies, it is plausible to predict that it will be used in association
with antivirals for treating this syndrome. Hopefully, its
preventative potential will also be investigated, and it is equally
probable that the data will prove its effectiveness. Results
obtained with the HIV infection should then re-focus attention
on this challenging immunological oddity, and provide funding for
further research to solve its biochemical and immunological riddle. Thus,
it should be possible to associate a structure to the concept and
a mode of action to the molecule.
No doubt, the use of transfer factor for the prevention of viral,
parasitic and mycobacterial infections will then be the object
of unbiased clinical investigation. For both prevention and
therapy, the main advantages pleading for this compound are low
cost of production, absence of toxicity and easy administration. For
countries with limited technological and financial resources, plagued
with viral and parasitic infections, these features are additional
and important arguments pleading for its wide use.
If transfer factor contributes, as I predict with undeterred
optimism, to the solution of the AIDS problem, it will prove its
value even to its adversaries, and will unerringly solve its own
problems. It should also advance the formulation of new paradigms
to accommodate its mode of action. All this, encouraging
as it may sound, will not change the structure and functioning
of biomedical research. It is within the ken of predictability
that a many-valued logic approach will not be acceptable, at least
for another half century, in biology; and also that it is forlorn
to hope for scientists to spontaneously evolve and follow precepts
of an ideal approach to unbiased investigation and "search
their minds beforehand to find out what they would like to be true
or false, and having got that clear, constantly discount their
natural tendency in that direction" . Thus, biomedical
science will continue to be normal, plagued with certainties
and controlled by the guardians of orthodoxy, those who managed
to acquire the power to command funding and printing, and who believe
that some crank has written that "through purely logical thinking
we can attain no knowledge whatsoever of the empirical world" .
The only way to counterbalance this depressing kuhnian vision
is to secure funding for alternative, popperian-style research. Only
politicians could impose such a change with affirmative action,
but there is little probability that an event of the sort will
ever occur, and at any rate not before it has been convincingly
demonstrated that alternative research is not only intellectually
more gratifying, but also able to produce answers faster, and not
least, at lower costs.
It is possible that private initiative might support such alternative
systems and succeed in proving a prediction made several years
ago: if 20% of the research budget were used to finance alternative
research, the results would be comparable to those obtained with
the remaining 80% . Until then, scientists opting against
the consensual comfort must continue to fight established paradigms,
as they used to fight religious creeds when the Church was mighty. However,
their task today is far more arduous: instead of fighting evident
irrational myths on the name of reason, they must fight
on the name of reality rationally established certainties, which
have degenerated into dogmas.
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Einstein A; Cited by F. Crick.
Eight years after the publication of this article, very little
has changed. Despite the repeated promises, AIDS can't be cured,
nor can HIV infection be prevented by a vaccine, the imminent discovery
of which has been presented as certainty for the last fifteen years.
If the Church, following... God's will, continues to oppose homosexuality
and the use of condoms, if some half-witted politicians find it
convenient, whenever they are not promising an imminent breakthrough,
to doubt the role of HIV in the pathogenesis of the disease, the politically
correct scientific and political majorities persist in opposing
the exploration of alternative paradigms. Following the example
of politicians, spin has become a widely used practice in biomedical
science in order to secure funding or kudos, and an academic degree
does not seem to prevent one from becoming a spin-expert.
As with cancer research, failure seems to be inescapable, unless
we find ways to encourage the exploration of alternative approaches.
This has not been the case so far, even when the evidence has invited
it. Thus, the cases of resistance to the viral infection failed
to inspire new leads. And although the role that CMI may play in
controlling the virus that drugs are unable to eradicate is now
accepted, the potential of Transfer Factor, despite several encouraging
reports continuously supported by fresh data, remains unexploited.
Maybe it is now time to give serious consideration to Popper's
contentions for implementing a continuous evolution in scientific
thought, if we wish to avoid paying the price of the Kuhnian model
of scientific revolutions. For revolutions in science or elsewhere
can be very costly. But to this end, we have first to accept that
we are incapable of spontaneously changing our predetermined ways
of thinking, and admit wilful funding of unorthodox ideas, whose
sole merit may be to challenge the existing ones. "New
types of experiments have to be invented"1,
and not only for solving the genome problems. For many riddles
in modern medical science are "systems' problems" and "one
must know how parts work together, having only the list is not
insufficient"1. It becomes obvious that the
new challenge lies in understanding the function of systems and
not in the mere listing of gene products, the so reassuring butterfly
Because our genetic and cultural makeup renders certain types
of psychological limitations impossible to avoid, change seems
often a dramatic and fearful event. The survival of our primitive
and barbaric religious beliefs is one astounding example, as is
the significant success of Fukuyama's thesis claiming the reassuring
advent of "The End of History". It therefore may be more
appropriate to consider pacific ways for paradigm change or rather
coexistence. Making funding available to alternative approaches
is one way to break the boundaries we have placed around ourselves
hoping to limit the dangers of change, but by doing so we ignore
that such limitations also curtail creativity. One may wager that
the windfall results of such a new policy would be higher than
those produced by abiding by the rules of today's orthodoxy.
1 Robert Laughlin, Nobel Prize laureate, 1998. In:
Nobel Technology, BBC, 2003.