Fwd: Science Advisors Abusing Science [UPDATED!]

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Fri, 17 Jan 2003 01:25:54 GMT

Science Advisors Abusing Science [uPDATED!]

 

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ISIS’ Reply to ACRE’s Response on Chardon LLScience Advisors Abusing Science

Dr. Mae-Wan Ho shows how the government’s science advisors are abusing science

in their recent report that dismisses all scientific evidence of GM hazards.

 

A version of this article has been sent to UK Chief Scientist David King and his

Science Panel as part of the National Science Review. You may like to this

article and the accompanying, " Science Advisors Abusing Public Trust " to your

government representatives.

 

" Good scientists go astray when they leave their area of expertise to offer

opinion when they have not studied the literature, when they selectively ignore

information, or when they let their politics and beliefs interfere with the

objectivity of their science… "

 

That could well describe our government’s science advisors, who in addition to

their " politics and beliefs " , may be allowing vested interests to cloud their

judgements. Instead, it is a concerted attack [1] launched by 18 pro-biotech

scientists against another scientist who tries to tell the truth.

 

David Schubert, cell biologist from the Salk Institute in La Jolla, California

argued [2] that " GM food is not a safe option, given our current lack of

understanding of the consequences of recombinant technology " , based on three

kinds of observations in the scientific literature. First, introducing the same

gene into two different types of cells can produce two very distinct proteins;

second, a single transgene usually significantly changes the expression of many

genes; and third, enzymatic pathways introduced to synthesize small molecules

such as vitamins could interact with other pathways in the host to produce

entirely new molecules. Molecules could be made that are " toxic, allergenic, or

carcinogenic. "

 

He called for " all GM plant products destined for human consumption to be tested

for long-term toxicity and carcinogenicity before being brought to the market. "

 

Some of those attacking Schubert are from the John Innes Centre (JIC), which has

a strong presence on the Advisory Committee on Releases to the Environment

(ACRE). ACRE has recently issued its response [3] to concerns raised in both the

public hearing and at its own hearing on T25 (Chardon LL) GM maize.

 

This response shows how ACRE dismisses scientific evidence by evasive tactics

that add up to a serious abuse of science: bland denial, false assertions, false

reassurance, omission of key references and facts, persistent failure to respond

to critical questions, misrepresentation, refusal to interpret experiments

correctly by excluding obvious possibilities, restricting the scope of

investigations, and taking the absence of evidence as evidence of absence. I can

only deal with a fraction of all the examples in that document.

On horizontal gene transfer

ACRE claims there is " no evidence " that transgenic DNA can spread from GM crops

to unrelated species, such as bacteria and mammalian cells, but covers its

tracks with the following statement (p.7): " This is not to say that that

horizontal gene transfer between plants and bacteria could not happen, but the

evidence suggests that if it does, it is a very rare event. "

 

That’s false reassurance. A rare event is sufficient to trigger a catastrophe,

as, in contrast to chemicals that degrade and disappear, genes and genetic

material multiply and recombine. All major disease epidemics are due to such

" very rare " events.

 

ACRE has ignored and omitted to mention most of the evidence we sent [4], and

concentrated on two key papers by Gebhard and Smalla [5, 6]: " The authors of

these publications did not demonstrate, nor did they claim to provide evidence

of horizontal gene transfer under laboratory conditions or in field studies. "

 

ACRE is selectively referring to the authors’ apologies in interpreting their

own results, but as I have shown, in a detailed review of the work submitted to

ACRE [7], the results offered prima facie evidence of horizontal gene transfer.

The authors themselves had indeed considered that possibility, first and

foremost. ACRE is guilty of misrepresentation, and failing to interpret the

experimental results correctly by excluding obvious explanations. At the very

least, ACRE should have called for further investigations, as that was the only

field monitoring experiment ever carried out.

 

ACRE continues,

 

" Horizontal gene transfer between plant and bacterial cells can be achieved by

using forced conditions in the laboratory and by supplying pressure to select

for the gene product and consequently the transgene itself. "

 

That is pure obfuscation. So-called " forced conditions " and " pressure to

select " , are nothing of the sort, they are laboratory techniques to enable us to

detect rare events, much as antibiotic resistance and other marker genes (eg,

green fluorescent protein) are used to detect rare transformed cells or track

their fate, in making GMOs, or following the developmental fate of stem cells.

 

Among the many ignored research reports on horizontal gene transfer submitted to

ACRE [8] are some commissioned by the UK government showing that transgenic DNA

in food has transferred to gut bacteria after only a single meal, and that the

Agrobacterium vector system used in making most GM plants can be a vehicle for

gene escape in the soil. Agrobacterium was found to transfer genes into human

cells in much the same way that it transfers genes into plant cells. This work

has not been followed up, nor has ACRE called for further research.

 

ACRE has also omitted to mention that transgenic DNA can pass through the gut

and placenta into the blood stream ending up in some blood cells, liver and

spleen cells, and some cells of the foetus and newborn. This work goes back to

the early 1990s and is still continuing [9, 10]. ACRE has not called for similar

studies to be carried out. Tracking the passage of transgenic DNA into the blood

stream and blood cells could have been part of the experiment that monitored the

fate of transgenic DNA in food eaten by human volunteers, but it was not [11].

 

By not calling for more definitive experiments to follow up positive findings,

and by not acknowledging the restrictive scope of the investigations, ACRE

continues to take the absence of evidence as evidence of absence.

The hazards of CaMV 35S promoter

ACRE ‘s continuing denial appears on pp.14-15 of their response, which focuses

on a paper we wrote [12], and according to ACRE, " no new data or direct

experimental evidence is presented to support the authors’ hypothesis that the

CaMV 35S promoter, used in many GM plants, is inherently dangerous. "

 

This bland denial can only be justified by ignoring all the papers we published

subsequently that have demolished the argument - which ACRE is unashamedly

repeating - that people have been eating the virus for all these years without

harm: " For many thousands of years CaMV and its relative have infected plants;

consequently humans and animals have been eating plant material containing the

35S promoter via natural CaMV infection. No ill effects due to the activity or

recombination of the virus promoter have been reported and in particular, no

reports of cancer. "

 

But people have not been eating CaMV 35S promoter plucked from its natural

genetic and evolutionary context and incorporated into transgenic DNA. We

published at least two further papers demolishing the criticisms [13, 14]. These

were submitted to ACRE and other science advisory committees on numerous

occasions, and neither ACRE nor any of our critics has ever been able to reply

to them.

 

Roger Hull from JIC who led the attack on us, was asked to reply to us by a

local group, " Concerned Citizens of Wivenhoe " .

 

Hull initially promised to do so, but after a long delay, wrote back to say that

he had discussed the whole matter with the Director of JIC and decided not to

reply, and instead, " to draw up a briefing document targeted [sic] towards

decision and opinion makers " .

 

We have pointed out to our critics that although the CaMV (virus) is specific to

cruciferae, the CaMV 35S promoter is utterly promiscuous, and is active in

species across the entire living kingdom, from bacteria up to human cells.

 

ACRE has selectively ignored that information, which cannot have escaped notice,

as its invited experts to its open hearing confessed their ignorance that the

CaMV 35S promoter was shown to be active in human cell systems in the scientific

literature dating to 1989, when I challenged the panel with that information

[15]. Have those experts been guilty, like ACRE, of having " not studied the

literature " sufficiently?

 

On page 7 of the Report, ACRE claims, " the expression of genes regulated by the

CaMV 35S promoter in bacteria is minimal " . This is obfuscation, because the

claim is being justified by the base sequence modification of the gene

controlled by the promoter (described following the quote), which supposedly

biases it against expression in bacteria. But the case is weak, and certainly

not supported by data.

 

ACRE goes on, " Ho et al., speculate that the 35S promoter has a tendency to

recombine with other DNA which could have harmful consequences. However, there

is no evidence for this, or any reason why 35S CaMV DNA would be more prone to

recombination than other DNA that does not have elements associated with

insertion and excision. "

 

Its claim of " no evidence " and no reason why CaMV 35S would be more prone to

recombination is false. Our first paper [12], the only one ACRE cites, was

precisely provoked by a paper reporting a ‘recombination hotspot’ associated

with the CaMV 35S promoter published by a research team in JIC [16], which ACRE

has failed to cite. Not only that, a second group has confirmed the finding

[17], and showed that another promoter used did not have the same propensity for

recombination as the CaMV 35S promoter. That information was in one of our later

papers [14] submitted to ACRE.

 

The JIC team that discovered the recombination hotspot in CaMV 35S promoter

later admitted to the need to avoid the CaMV 35S promoter as well as other bits

of DNA containing recombination hotpots. They stated in JIC’s annual report in

2001 [18]:

 

" Analysis of junctions between genomic and transforming DNA, and between

individual plasmid molecules at integration sites, demonstrates the predominance

of microhomology-mediated illegitimate recombination events involving regions

with secondary structure. One such region occurs in the CaMV 35S promoter,

widely used to drive transgene expression in plants. The plasmid backbone

provides other such regions, including the origin of replication …..The

influence of transgene rearrangements on expression and silencing has been

understated in the past, but our research may allow improved construct design to

discourage rearrangements and improve transgene-expression stability. "

 

This 40-strong research team has mysteriously disbanded last April, in the midst

of the controversy over GM contamination of Mexican maize landraces. The most

controversial finding was not the contamination itself, but molecular data

suggesting that the transgenic DNA containing the CaMV 35S promoter may be

" fragmenting and promiscuously scattering throughout the genome " of the

landraces. Such observations would be totally consistent with our expectations

given the existence of the recombination hotspot in the promoter [19]. Of

course, ACRE has selectively ignored all of that too.

 

This is also the place to address ACRE’s denial that promoters like CaMV, which

shows a propensity to fragment, and could therefore jump around the genome, has

the potential to cause cancer. Roger Hull has recently issued the same denial in

attacking pathologist Stanley Ewen’s concern that GM crops may trigger cancer

[20].

 

In fact, insertion of foreign DNA into genomes is known to be associated with

cancer, so much so that ‘insertion carcinogenesis’ is a clinical entity [21].

The recent cancer victim of gene therapy [22] should make us wary about eating

anything that has transgenic DNA, and more so, transgenic DNA containing CaMV

35S promoter that has an increased propensity to fragment and recombine with, ie

insert into, DNA of the human cell genome [23]. GM constructs are similar,

whether used for genetic modification of human cells in gene therapy or for

genetic modification of plants and animals.

 

ACRE has ignored all of that as well, and continues its comments on our first

paper,

 

" A prominent concern raised in this paper is that the 35S promoter in GM plants

could inadvertently activate dormant viruses or non-target genes in plants or

other organisms. ACRE is aware that the 35S promoter has the potential to alter

the expression of host genes neighbouring the site of its insertion. This is one

of the reasons why ACRE require applications for marketing consents to describe

the host DNA that flanks the site into which the transgene has inserted. …There

are no reported incidences of a dormant plant virus being unintentionally

activated by the insertion of a transgene with a 35S promoter. In particular,

there is no evidence that the T25 insertion event has altered the maize line in

any way that makes it less safe to human health or the environment than its

conventional counterparts. "

 

ACRE is admitting the 35S promoter in GM plants could alter the expression of

neighbouring host genes and says it requires marketing applications to describe

the site of transgene insertion. But these requirements have been very weak in

the past, and do not satisfy the more stringent " event-specific " molecular

characterisations that also document genetic stability in successive

generations, which ISIS has demanded from the first (see below).

 

Similarly, the bland assurance of " no reported incidence of a dormant plant

virus being unintentionally activated " and " no evidence that T25 insertion event

(in Chardon LL) has altered the maize line in any way that makes it less safe "

is not justified, as there has been no attempt to obtain such evidence

empirically.

 

On the contrary, several recent papers from the JIC, co-authored by Roger Hull,

have described dormant viruses discovered in the genome that can be reactivated

by a variety of treatments. One of these papers [24] expressed explicit concern

about new viruses emerging, " As an unforeseen hazard of plant breeding or genome

manipulation, and of plant and insect movement, there must be concern that new

viruses will emerge… " (italics mine).

 

ACRE continues,

 

" Ho et al., have suggested that there is a ‘close relationship’ between CaMV and

human viruses such as the hepatitis B and that CaMV 35S promoter DNA inserted

into transgenic plants will recombine with DNA from these viruses. However, CaMV

and human retroviruses are not members of the same genetic family and the degree

of similarity between their DNA sequences is low. "

 

CaMV belongs to the pararetrovirus supergroup that includes the Hepadnaviridae

family infecting vertebrates, of which the hepatitis B virus is a member.

Whether one considers that a close relationship is a moot point, as

pararetroviruses share many distinctive features in their life cycle [25].

Sequence homology is also irrelevant given that the recombination mechanism of

the CaMV 35S promoter depends on breaks in the double stranded DNA, which allows

it to rejoin to non-homologous DNA [16, 17].

 

It has also become increasingly evident that the CaMV 35S promoter can

substitute for the promoter of most if not all viruses, plants or animals not

withstanding, and is active in all living things [13, 14]. It is truly

promiscuous and dangerous. It is being quietly phased out behind the scenes,

judging by its almost total absence in newer transgenic crops under development.

The JIC plant geneticists claim that’s because the CaMV 35S promoter compromises

agronomic performance on account of the transgenic instability it causes, and

has nothing to do with safety. I have just presented the arguments as to why the

instability is above all a safety issue.

Transgenic DNA and transgenic instability

ACRE states, " There is also no evidence in the literature to support the idea

that transgenic DNA is inherently less stable than native DNA. " This statement

is false.

 

Instability of transgenic DNA is so well known that it is a textbook topic, as I

have pointed out to ACRE and other government science advisors time and again.

Furthermore, there is such a vast literature on transgenic instability [26] that

ACRE’s denial here is embarrassing. I will only cite the report by another group

in JIC [27] documenting instability arising in later generations of transgenic

barley lines:

 

" Data from the 1998 trial showed that transgenic barley lines performed as well

as non-transformed control plants and controls from tissue culture-derived

parents for several agronomic traits, including yield. For other traits, a

significant difference was seen between transgenic and control lines. The

transgenic lines were significantly shorter and also slightly later flowering….

When we examined the next generation of the same transgenic line in the field

during 1999, there was evidence that the transgenic plants were more variable

compared to the controls than those in the 1998 field trial. This could be

because somaclonal variation, resulting from the tissue culture and

transformation procedures, and was more obvious in later generations. These

results show that transgenic lines need to be examined over a number of

generations under field conditions to obtain the necessary data on transgene

stability and agronomic performance. Further field trials …. combined with

detailed molecular and genetic analysis will allow us to increase our

understanding of the transformation process so that we are better able to assess

the long term effects of genetic modification. " (italics mine)

 

The findings on transgenic barley have been replicated in different forms in

every species of transgenic plants investigated with the appropriate molecular

techniques.

 

Despite that, the only criterion on which ACRE asserts transgenic lines are

stable is transgene expression, and even here, it has simply accepted the

company’s word, with no numerical data nor independent verification. It states

on p.11,

 

" The transgene has been expressed under different genetic and environmental

conditions through numerous generations without any evidence of instability " .

And in a supporting footnote 28, " Bayer CropScience estimate 23 generations of

breeding, with 40 different maize varieties world-wide now containing the T25

insert. "

 

There is still no event-specific characterisation in successive generations to

document true genetic stability. If the company had submitted event-specific

characterisation in its original application for commercial approval, it would

be an easy test to carry out on Chardon LL maize today, to see if the insert has

remained unchanged in structure and location in the plant genome.

 

Such a test was applied to Roundup Ready soya in 2001. Roundup Ready soya failed

the test, the foreign insert was considerably scrambled compared to Monsanto’s

original submission [28, 29].

 

Will ACRE carry out such a test on Chardon LL maize and other GM crops currently

field trialed or seeking commercial approval?

 

Beachy R, Bennetzen JL, Chassy BM, Chrispeels M, Chory J, Ecker JR, Noel JP,

Kay SA, Dean C, Lamb C, Jones J, Santerre CR, Schroeder JI, Umen J, Yanofsky M,

Wessler S, Zhao Y and Parrott W. Divergent perspectives on GM food. Nature

biotechnology 2002, 20, 1195-6.

Schubert C. A different perspective on GM food. Nature biotechnology 2002,

20, 969.

The Advisory committee on Releases to the Environment’s (ACRE’s) response to

concerns raised in written representation and submissions associated with the

CHARDON LL public hearing and to statements made at ACRE’s open hearing relating

to the safety assessment of T25 GM maize conducted under Directive 90/220/EEC.

www.defra.gov.uk/environment/acre, e-mail: gm

Reviewed in many past reports, see Horizontal Gene Transfer, ISIS Reprints

March 2002, ISIS Members’ website, also available in hardcopy, enquire

sam

Gebhard, F., and Smalla, K. (1998) Transformation of Acinetobacter sp. strain

BD413 by transgenic sugar beet DNA. Appl. Environ. Microbiol. 64: 1550-1554.

Gebhard, F., and Smalla, K. (1999) Monitoring field releases of genetically

modified sugar beets for persistence of transgenic plant DNA and horizontal gene

transfer. FEMS Microbiol. Ecol. 28: 261-272.

" Horizontal gene transfer happens, a practical exercise in applying the

precautionary principle " by Mae-Wan Ho, ISIS News 5, 2000

See my latest attempt to put evidence before ACRE and ACNFP. Ho MW. Recent

Evidence Confirms Risks of Horizontal Gene Transfer ISIS’ Written Contribution

to ACNFP/Food Standards Agency Open Meeting 13 November 2002

Hohlweb U. and Doerfler W. On the fate of plant or other foreign genes upon

the uptake in food or after intramuscular injection in mice. Mole. Genet

Genomics 2001, 265, 225-33.

" Suppression & denial " in Horizontal gene transfer special series, by Mae-Wan

Ho, SiS16, 2002.

" Stacking the odds " by in Horizontal gene transfer special series, by Mae-Wan

Ho, SiS16, 2002.

Ho MW, Ryan A and Cummins J. Cauliflower mosaic viral promoter – a recipe for

Disaster? Microbial Ecology in Health and Disease 1999 11, 194-7.

Ho MW, Ryan A and Cummins J. Hazards of transgenic plants with the

cauliflower mosaic viral promoter. Microbial Ecology in Health and Disease 2000,

12, 6-11.

Ho MW, Ryan A and Cummins J. CaMV35S promoter fragmentation hotspot confirmed

and it is active in animals. Microbial Ecology in Health and Disease 2000, 12,

189.

" GM maize approved on bad science in the UK " by Mae-Wan Ho, SiS 15, 2002.

Kohli A, Griffiths S, Palacios N, Twyman R, Vain P, Laurie D and Christou P.

Molecular characterization of transforming plasmid rearrangements in transgenic

rice reveals a recombination hot spot in the CaMV 35S promoter and confirms the

predominance of microhomology mediated recombination. Plant.J. 1999, 17,591-601.

Kumpatla SP and Hall TC. Organizational complexity of a rice transgenic locus

susceptible to methylation –based silencing. IUBMB Life 1999, 48, 459-67.

Christou P, Kohli A, Stofer E, et al. Transgenic plants: a tool for

fundamental genomics research. John Innes Centre & Sainsbury Laboratory Annual

Report 1999/2000, p.29.

See " Who’s afraid of horizontal gene transfer " and other articles in GM maize

wars series, SiS 15, 2002

Roger Hull’s letter to editor, Sunday Herald, 19 Dec 2002.

See Ho, MW, Ryan A, Cummins J and Traavik T. Slipping Through the Regulatory

Net. ‘Naked’ and ‘Free’ Nucleic Acids, Third World Network Biotechnology and

Biosafety Series 5, TWN, Penang, 2001. Available from the ISIS online store

" Gene therapy a suspect in leukemia-like disease " , by Eliot Marshall, Science

Oct 4 2002, 34-35.

" Predicted hazard of gene therapy a reality " by Mae-Wan Ho, ISIS Report,

October 2002 ; " Gene therapy’s first cancer victim " by Mae-Wan Ho SiS 17, 2003.

Hull R, Harper G and Lockhart B. Viral sequences integrated into plant

genomes. Trends in Plant Science 2000, 5, 362-5.

Haas M, Bureau M, Feldreich A., Yot P and Keller M. Cauliflower mosaic virus:

still in the news. Molecular Plant Pathology 2002, 3, 419-29.

See Transgenic Instability, ISIS reprints, ISIS members’ website, also

available in hardcopy, enquire sam

Harwood, WA, Hardon J, Ross SM, Fish L, Smith J and Snape JW. Analysis of

transgenic barley in a small scale field trial. John Innes Centre & Sainsbury

Laboratory Annual Report 1999/2000, p.28.

Windels P, Taverniers I, Depicker A, Van Bockstaele E and De Loose M (2001).

Characterisation of the Roundup Ready soybean insert. Eur Food Res Technol DOI

10.1007/ s002170100336, © Springer-Verlag.

" Scrambled genome of Roundup Ready soya " by Mae-Wan Ho, ISIS News 9/10, July

2001, ISSN: 1474-1547 (print), ISSN: 1474-1814 (online)

 

 

 

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