Genetically engineered vaccines 'Inherently unpredictable and possibly dangerous'

Discussion in 'Health and medical' started by John, Apr 7, 2004.

  1. John

    John Guest

       Genetically engineered vaccines

    'Inherently unpredictable and possibly dangerous'

    In recent years, genetically engineered vaccine strategies
    have been rushed into common use within such fields as
    medicine, veterinary medicine and fish farming. Some
    scientists contend that such vaccines are totally innocuous.
    But a recent and major research report by Professor Terje
    Traavik reduces the 'safe technology' to sheer naive
    optimism, and warns in conclusion that 'many live,
    genetically engineered vaccines are inherently unpredictable
    (and) possibly dangerous.' Martin Jalleh highlights the
    compelling findings of the report - which make the arguments
    for genetically engineered vaccines look frail and move
    Traavik to call on the scientific community to go beyond the
    'Holy Grail' of medicine.


    'MODERN molecular biology, recombinant DNA technology and
    genetic engineering have opened the road to a number of
    alternative strategies for vaccine production,' reveals
    Professor Terje Traavik of the Departments of Virology and
    Medical Microbiology, University of Tromso, GENK-Norwegian
    Institute of Gene Ecology, Tromso, Norway. He deems it
    necessary to add: '...from an ecological and environmental
    point of view many first generation live, genetically
    engineered vaccines are inherently unpredictable, possibly
    dangerous...' He emphasises that such vaccines 'should not
    be taken into widespread use until a number of putative
    problems have been clarified'.

    He describes the risks and hazards as 'most certainly within
    the realm of possibility, and according to the Precautionary
    Principle they should be subject to preventive measures'. He
    points out, 'In practice, however, the risks are considered
    to be non-existent, since they have not been supported by
    experimental or epidemiological investigations. This, again,
    is a 'Catch-22' situation, in the sense that such
    investigations have not been performed at all.'

    Traavik's comments and conclusions on genetically engineered
    vaccines can be found in his major study entitled An Orphan
    in Science: Environmental Risks of Genetically Engineered
    Vaccines, written on assignment with the Norwegian
    Directorate of Nature Management.

    According to Traavik, the report attempts to 'address the
    potential ecological and environmental risks posed by some
    types of genetically engineered (GE) or modified vaccines
    that are now being developed, and may soon be in widespread
    use'. (Most of the excerpts from Traavik's report quoted in
    this article and accompanying boxes refer to GE live virus
    vectors. Other quotations are either general in nature or
    refer specifically to  naked DNA vaccines.)

    Traavik's report prompts a rather pertinent question, which
    at the same time effectively brings to the fore the fact
    that genetically engineered vaccines are inherently
    unpredictable - does genetic engineering deserve the
    'technology' label?

    Unpredictable effects

    According to Traavik, the word 'technology' is derived from
    the Greek term 'tekhne' which is connected to handicrafts or
    the arts. It is often associated with predictability,
    control, and reproducibility. He then goes on to say that
    'the parts of genetic engineering that concern construction
    of vectors are truly technology.' On the other hand, and in
    contrast, he argues, present-time techniques for moving new
    genes into cells and organisms mean:

    ·        No possibility of targeting the vector/transgene to
    specific sites within the recipient genomes. In practical
    terms, this means that modifications performed with
    identical recipients and vector gene constructs under the
    same standardised conditions may result in highly different
    genetically modified organisms (GMOs) depending on where the
    transgenes become inserted.

    ·        No control of changes in gene expression patterns
    for the inserted or the endogenous genes of the GMO.

    ·        No control of whether the inserted transgene(s), or
    parts thereof, move within or from the recipient genome, or
    where transferred DNA sequences end up in the ecosystems.

    Traavik also draws attention to the fact that the
    unpredictability of genetically engineered vaccines is
    further increased by the problems posed by some
    environmental pollutants known as xenobiotics.

    'Different xenobiotics have properties and biological
    activities that enable us to envisage at least two different
    sets of possible impacts on the fate of naked DNA in an
    ecosystem. Some xenobiotics can act as mutagenes (this
    applies to radioactive substances, polluting industrial
    chemicals and plant protectants). Mutagenes can result in
    naked DNA that escapes or is released having its sequence or
    structure changed. This, in turn, can affect the
    possibilities for DNA uptake in cells and organisms,
    horizontal transfer and long-term establishment in the
    ecosystems in ways which are totally unpredictable for us.
    (There have been) reported examples of minor changes in a
    DNA sequence altering the host spectrum of a transferable
    genetic element.'

    'Some xenobiotics can affect cell membrane and/or
    intracellular functions in ways which can very well be
    thought to influence the ability of cells to take up and
    horizontally transfer naked DNA. This concerns the structure
    of cell membranes and the content of both surface receptors
    and transport canals, and also for intracellular signal
    conversion and gene expression.

    For instance, xenobiotics which mimic hormones or affect the
    local conditions in the organ systems of mammals (e.g.
    respiratory passages) may change the possibilities for both
    uptake and establishment of foreign nucleic acids in animals
    and people,' the report reveals.

    'There are xenobiotics which are found in both categories,
    and we do not know how the sum of the impacts of such
    substances will turn out. Likewise, up to several
    individual compounds from each category will often pollute
    the same environment. We have no knowledge of how such
    situations affect DNA uptake and dispersal in the
    ecosystems,' it states.

    'Unsafe' definition

    Traavik's study also brings to light what he calls 'the
    deplorable fact' of the very narrow and exclusive definition
    of 'safety' in vaccinology, compared to the putative risks
    and hazards vaccine use may imply.

    'Primarily, 'safety' research is occupied with prospects of
    unintended and unwanted side effects with regard to the
    targeted vaccinees themselves. Secondly, such research may
    be directed towards non-target effects on unvaccinated
    individuals within the same species. Very small efforts
    have been dedicated to unintended and non-target effects
    across species-borders and biologic kingdom-borders,'
    contends Traavik.

    'This narrowing of conception as well as intellectual and
    research strategies may leave many potential hazards and
    harms related to various vaccine categories unapprised,
    until one or more of them actually happen,' he warns.

    'Very few research reports concerning environmental or
    ecological effects of genetically engineered vaccines were
    published as late as January 1999. On the other hand,
    examples of scientists defending the total innocuousness
    of vaccines, without taking environmental and non-target
    effects into consideration, are numerous. Many seem
    totally religious in their belief, and prescribe
    strategies to convert the ignorant public and
    politicians,' Traavik observes.

    'Furthermore, I suspect that the lack of holistic and
    ecological thinking with regard to vaccine risks is
    symptomatic of the real lack of touch between medicine and
    molecular biology on one side, and potential ecological and
    environmental effects of these activities on the other.

    'A frighteningly small number of original research reports
    concerning environmental or ecological consequences of
    molecular biology applications or genetic engineering were
    published until January 1999. I believe that we are here
    dealing with a void in medical education and cooperation
    focus, as well as a dangerous lack of focused research
    efforts,' he writes in his report.

    According to Traavik, genetically engineered self-
    replicating and/or self-expressing vaccines 'may turn out to
    be good equipment in science, but too dangerous for
    practical large-scale use'. It has also become evident to
    him that 'the various putative risk factors and hazards
    related to these vaccines ought to be adequately
    investigated before we and the ecosystems are massively
    exposed to them.'

    'Many of the vaccine constructs may have obvious value
    within basic and applied research, but should be kept
    contained until credible ecological risk assessments are
    possible. Such clarification will demand carefully planned
    investigations and adequately designed model systems for
    experimental research. In addition to basic knowledge
    directly applicable to risk assessments, enhanced insight
    into and awareness of general biologic and ecological
    interactions ranging from the molecular to the ecosystem
    level would be gained,' Traavik strongly suggests.

    Unreliable risk assessments

    Very close to the 'safety' factor is the issue of risk.
    Traavik explains that the term 'risk' is very often confused
    with 'probability', and hence used erroneously. 'Risk', by
    his definition, is 'the probability that a certain event
    will take place multiplied by the consequences arising if it
    takes place'.

    He notes: 'With regard to development and commercialisation
    of genetically engineered nucleic acids, organisms and
    viruses, we often are neither able to define probability of
    unintended events nor the consequences of them.

    Hence, the present state of ignorance makes scientifically
    based risk assessments impossible.' This, according to
    Traavik, calls for invoking the 'Precautionary Principle',
    the need for which, he believes, can hardly be
    overestimated, both for risk management and for generations
    of risk-associated research.

    In the context of gene technology and use of GMOs, he says,
    the principle could be generally defined as follows: 'In
    order to obtain sustainable development, policies should be
    based on the Precautionary Principle.

    Environmental and health policies must be aimed at
    predicting, preventing and attacking the causes of
    environmental or health hazards. When there is reason to
    suspect threats of serious, irreversible damage, lack of
    scientific evidence should not be used as a basis for
    postponement of preventive measures.'

    Traavik adds: 'In order to make reliable risk assessments
    and perform sensible risk management with regard to genetic
    engineering in general, and genetically engineered vaccines
    in particular, much pertinent knowledge is (necessary, yet
    this is) lacking.'

    He strongly feels that risk-associated research should be
    the responsibility of the authorities concerned and not the
    industry: 'The prerequisite for obtaining such knowledge is
    science and scientists dedicated to relevant projects and
    research areas. It must be the responsibility of the
    national governments and international authorities to make
    funding available for such research.'

    'On one hand, this is obviously not the responsibility of
    producers and manufacturers. On the other hand, risk-
    associated research must be publicly funded in order to keep
    it totally independent, which is an absolute necessity for
    such activities,' is his pertinent observation and
    conclusion on this point.

    Unanswered questions

    Traavik, in his report, reviews some fundamental conceptions
    on vaccination and the immune system. Vaccination is seen as
    'a form of prevention or prophylaxis of infectious disease
    and cancers', and Traavik feels the reasons for giving
    priority to prevention and prophylaxis will become stronger
    than ever, 'as development of resistance in  microorganisms,
    viruses and cancer cells are reducing the therapeutic
    opportunities offered by chemotherapeutics and antibiotics.'
    He points out that while vaccination intends to provide
    individuals with immunological protection before an
    infection actually takes place, it is crucial to take
    cognizance of the fact that 'the immune system is very
    complex, and immunity against different infectious agents is
    based on fine-tuned balances between the various types of
    cells, signal substances and antibodies that make up the
    total immune system.'

    When providing the contrast between traditional vaccines and
    modern vaccines, he makes it clear that the latter are not
    without drawbacks such as short-lived general immune
    responses, weak local immune responses, and the most
    prominent being the danger that 'they (live vaccines) may
    revert to their full disease-causing potential'.

    The report also deals with the strategies used to achieve
    various types of vaccines by recombinant DNA techniques and
    genetic engineering and the equally unpredictable outcome of
    the recombination of a genetically engineered vaccine virus
    with naturally occurring relatives.

    His findings on the strategies can be summed up as follows:
    'Genetically modified viruses and genetically engineered virus-
    vector vaccines carry significant unpredictability and a
    number of inherently harmful potentials and hazards.

    'The immunological advantages of such vaccines are related
    to the fact that the viruses are 'live' and infect the
    vaccinated individuals. It has, however, been demonstrated
    that minor genetic changes in, or differences between,
    viruses can result in dramatic changes in host spectrum and
    disease-causing potentials. For all these vaccines,
    important questions concerning effects on other species than
    the targeted one (have been) left unanswered so far.'

    Unearthing knowledge

    In the concluding chapter of his report, Traavik reiterates
    the seriousness of the situation: 'it is not possible for
    the moment to either assess or manage the environmental
    risks (posed by many first generation live, genetically
    engineered vaccines). Most probably we have not even
    conceived all theoretical risks at the present time.'

    He calls to mind the all-too-often-tragic past concerning
    the use of 'technology': 'Recent years have witnessed
    many examples of unforeseen side effects from 'safe
    technology' having led to health risks and threatened to
    disturb the ecological balance. Dogmas concerning absence
    of hazards have often been proven wrong... Absolute
    biological and ecological truths are, however, very rare,
    and rare phenomena may have important consequences when
    they take place.'

    He stresses that to the extent that any prior investigations
    of damaging effects had been undertaken, methods and
    approaches had been used that were only capable of
    disclosing short-term effects, whereas in ecological
    contexts it is the long-term impacts that are most important
    and most serious.

    'Long-term impacts in these contexts, and also in connection
    with the possible damaging effects of the dispersal of
    genetically engineered vaccines means not months or years,
    but at least ten to hundreds of years,' Traavik warns.

    Traavik is of the opinion that 'many of the vaccine
    constructs may have obvious value within basic and applied
    research', but he adds these 'should be kept contained until
    credible ecological risk assessments are possible.'

    'Such clarification will demand carefully planned
    investigations and adequately designed model systems for
    experimental research. In addition to basic knowledge
    directly applicable to risk assessments, enhanced insight
    into and awareness of general biologic and ecological
    interactions ranging from the molecular to the ecosystem
    level would be gained.'

    He believes that there are 'no controversies connected to
    the fact that subunit or peptide vaccines are the inherently
    safest alternatives with regard to unintended side effects,
    as well as unpredictable non-target effects. Such vaccines
    are also, beyond reasonable doubt, the potentially safest
    from an ecological and environmental point of view'.

    He is also optimistic with regard to the intensive search
    for alternative vaccine strategies, which he says will lead
    to 'new insights into basic immunological mechanisms and new
    delivery systems'.

    His final recommendation is that: 'It must always be kept in
    mind that although vaccinology is the 'Holy Grail' of
    medicine, there are other ways of preventing infectious
    diseases in humans and animals that must not be ignored.
    Many of the most burdening infectious agents of mankind and
    its domesticated animals are caused by pathogens that have
    reservoirs and are circulating among wildlife animals.

    'By increasing our knowledge about these reservoirs, their
    occurrence, the transmission routes within and out of the
    indigenous ecosystems, we might be able to break
    transmission chains or keep our activities out of dangerous
    ecosystems. There is a void in knowledge about the
    ecological interactions for many important pathogens. This
    field is to some extent subdued by the confidence in
    vaccines, and hence another scientific orphan.'

    Martin Jalleh is a research officer with the Third
    World Network.

    Box stories:

    Genetically engineered vaccines

    BELOW are some GE vaccines referred to by Professor Terje
    Traavik in his report, An Orphan in Science: Environmental
    Risks of Genetically Engineered


    Subunit vaccines: They represent technologies ranging from
    the chemical purification of components of the pathogen
    grown in vitro to the use of recombinant DNA techniques to
    produce a single viral or bacterial protein, such as
    Hepatitis B surface antigen for example. The disadvantage of
    such vaccines is that immune responses, especially T-
    lymphocyte activation, are too weak.

    DNA vaccines: They employ genes encoding proteins of
    pathogens rather than using the proteins themselves, a live
    replicating vector, or an attenuated version of the pathogen
    itself. They consist of a bacterial plasmid with a strong
    viral promoter, the gene of interest, and a
    polyadenylation/transcriptional termination sequence. The
    plasmid is grown in bacteria (e. coli), purified, dissolved
    in a saline solution, and then simply injected into the
    host. In present versions only very small amounts of
    antigens are produced within the vaccinated individual.

    Recombinant (DNA) vaccines: Made by isolation of DNA
    fragment(s) coding for the immunogen(s) of an infectious
    agent/cancer cell, followed by the insertion of the
    fragment(s) into vector DNA molecules (i.e. plasmids or
    viruses) which can replicate and conduct protein-expression
    within bacterial, yeast, insect or mammalian cells. The
    immunogen(s) may then be completely purified by modern
    separation techniques. The vaccines tend to give good
    antibody responses, but weak T-cell activation.

    Naked DNA vaccines: They are engineered from general
    genetic shuttle vectors and constructed to break species
    barriers. They may persist much longer in the environment
    than commonly believed. Upon release or escape to the wrong
    place at the wrong time. Horizontal gene transfer with
    unpredictable long- and short-term biological and
    ecological effects is a real hazard with such vaccines.
    There may be harmful effects due to random insertions of
    vaccine constructs into cellular genomes in target or non-
    target species.

    Live vector vaccines: These are produced by the insertion of
    the DNA fragment(s) coding for an immunogen(s) intended for
    vaccination into the genome of a 'non-dangerous' virus or
    bacterium, the vector. The insertion is performed in such a
    way that the vector is still infectious 'live'.

    RNA vaccines: This involves the use of in vitro synthesised
    RNA (a single-stranded relative of DNA). RNA are different
    from DNA vaccines in that there is no risk of chromosomal
    integration of foreign genetic material.

    Edible vaccines: These are produced by making transgenic,
    edible crop plants as the production and delivery systems
    for subunit vaccines. Little is known about the consequences
    of releasing such plants into the environment, but there are
    examples of transgenic plants that seriously alter their
    biological environment. A number of unpredicted and unwanted
    incidents have already taken place with genetically
    engineered plants.  


    Unanswered questions

    CONSIDERING the unpredictability of genetically engineered
    vaccines, Professor Terje Traavik has come up with a list of
    questions which he feels have to be answered in a
    satisfactory way before any vaccinia virus vectored GE
    vaccines are released:

    *Can the virus engage in genetic recombination, or by other
    means achieve new genetic material? If so, will the hybrid
    offspring have changed their host preferences and virulence

    *Can other viruses that are present within the ecosystem
    influence the infection with the released virus or its
    offspring?  Can insects or migrating birds or animals
    function as vectors for the released virus or its offspring,
    to disseminate viruses out of their intended release areas?

    *For how long can the virus and its offspring survive
    outside host organisms under realistic environmental and
    climatic conditions?

    *Is the virus and its offspring genetically stable
    over time?

    *Can the virus or its offspring establish long-lasting,
    clinically mute, persistent or latent infections in
    naturally accessible host organisms?

    *Can the virus or its offspring activate or aggravate
    naturally occurring latent or persistent virus infections?

    The stark reality, he points out, is that most of these
    questions are unaccounted for, when they are related to
    vaccinia virus vectored GE vaccines (VV). 'Even when they
    have been answered by experimental investigations,
    ecological non-target effects cannot be excluded because
    even carefully designed model studies will not directly
    reflect the real ecosystem conditions, which in addition are
    dependent on local variable parameters.'  


    Warning signals

    PROFESSOR Traavik provides growing evidence of the
    unpredictability of GE virus recombinants:

    *During the human small pox eradication campaign,
    vaccinia virus vectored GE vaccines (VV) found a new host
    species and established themselves in a new reservoir,
    namely the buffalo.

    *It is a general experience that inserts may change the
    virulence and host preferences of viruses.

    ·        MRV (Malignant rabbit virus) seems to be a
    recombinant between SFV (Shope fibroma virus) and myxoma
    virus. It seems to have arisen by mixed infection in wild
    rabbits. MRV causes an invasive malignant disease and
    profound immunosuppression in adult rabbits, much more
    serious than the diseases caused by any of the parental
    viruses. MRV has received more than 90% of its DNA from one
    parent (myxoma virus) in a coupled recombination and
    transposition event. The MRV story exemplifies the
    unpredictability of virus recombinants with regard to
    biological characteristics and virulence.

    ·        A recombinant field isolate of capripoxvirus has
    also been detected. The new virus was the result of
    recombination between a capripoxvirus vaccine strain and a
    naturally occurring virus strain.


  2. Jeff

    Jeff Guest

    Anything in life is inherently unpredictable and possibly

  3. "Jeff" <[email protected]> wrote in message
    news:[email protected]...
    > Anything in life is inherently unpredictable and possibly
    > dangerous.

    John's information is a perfect example. He spouts dangerous
    information and is inherently predictable in spouting same.
  4. Jan

    Jan Guest

    >Subject: Re: Genetically engineered vaccines 'Inherently unpredictable and
    >possibly dangerous'
    >From: "Jeff" [email protected]
    >Date: 4/8/2004 4:40 AM Pacific Standard Time
    >Message-id: <[email protected]>
    >Anything in life is inherently unpredictable and possibly

    Therefore people have a right to make their own choices.

    If it disagrees with yours, there is no need for name
    calling and belittling.

  5. "Jan" <[email protected]> wrote in message
    news:[email protected]...
    > >Subject: Re: Genetically engineered vaccines 'Inherently
    > >unpredictable
    > >possibly dangerous' From: "Jeff" [email protected]
    > >Date: 4/8/2004 4:40 AM Pacific Standard Time Message-id:
    > ><[email protected]>
    > >
    > >Anything in life is inherently unpredictable and possibly
    > >dangerous.
    > >
    > >Jeff
    > Therefore people have a right to make their own choices.
    > If it disagrees with yours, there is no need for name
    > calling and

    So, stop it already. Practice what you preach.