Re: UK: Research centre admits GM failure

[David Tribe <detribe@unimelb.edu.au>]

Response (from Agbio View) to previous posting,
The bolded sections below explain forcefully the serious misinterpretation of this biology by Ho et al.

>Research centre admits GM failure
>
>ISIS Press Release
>26 Jan. 2001
>
>UK Top Research Centre Admits GM Failure
>
>Scientists in UK's top GM crop research institute, the John Innes
>Centre, are finally admitting to the public that GM crops are no 
>good.
>It amounts to pronouncing the death sentence on GMOs. Mae-
>Wan Ho,
>Angela Ryan and Joe Cummins report.
>
// SNIP//

>
>Contacts:
>Ms. Angela Ryan: 44-20-8441-6481; mobile: 44-07833-114525 e-mail:
>I-sis@dircon.co.uk Dr. Mae-Wan Ho: 44-20-7272-5636; e-mail:
>m.w.ho@I-sis.org Prof. Joe Cummins: 1-519-681-5477; e-mail:
>jcummins@julian.uwo.ca


RESPONSE ON AGBIOVIEW

Following is the response from the Director of John Innes Center, UK to
the ISIS REPORT of Mae-Wan Ho entitled "UK Top Research Centre Admits GM
Failure: ISIS Press Release 26 Jan. 2001" that was posted on our group
http://agbioview.listbot.com/cgi-bin/subscriber?Act=view_message&list_id=agbioview&msg_num=968&start_num=


=========
RESPONSE TO THE ISIS REPORT FROM PROFESSOR CHRIS LAMB, DIRECTOR OF THE
JOHN INNES CENTRE 

The ISIS is absolute nonsense and is a rehash of tired old non-issues.
Neither issue, use of the CaMV 35S promoter or stability of transgene
expression in some transgenic lines is at all new. Both have been
extensively discussed and shown to have no merit with respect to safety or
performance of commercial GM crops which have gone through very extensive
evaluation.Ý 

Please let me know if you need additional information. 

Chris Lamb Director, JIC
---------------------------------
CaMV PROMOTER

RESPONSE FROM ROGER HULL, JI EMERITUS FELLOW, INITIATOR OF CaMV RESEARCH
AT JIC 

1. All comparisons of transgenics should be made against the baseline of
the current and predicted short-term future situation. 

2. There is nothing new in her comments about the 35S promoter which Phil
Dale, Simon Covey and I answered in our paper in the Swedish journal that
published her original critique of the promoter. 

##Once again, major points
include: most people eat brassicas and consume relatively large quantities
of CaMV; there are many other similar promoters in integrated
pararetrovirus and retrotransposon sequences in plants; there is natural
recombination in plants bringing together various promoters and coding
sequences. I know of no case where this natural situation has been blamed
for health, cancer or any other problem. 

3. It would be interesting to have some examples of problems that have
arisen from the generally accepted "natural" breeding programmes including
radiation mutagenesis, embryo rescue and other advanced techniques. These
could be used as examples of what has been accepted in the past. 

4. The screening of transgenics is far more intense than that of the
products of conventional breeding. TGs have to go through many more hoops
before they are even considered for field release. 

5. The work described in the Annual Report, and in much of the scientific
literature, is on understanding potential problems that may arise from the
new technology so that these problems can be avoided. In this, scientists
are being responsible to society. Any new technology goes through this
phase of understanding the cons as well as the pros, and it is better to
do this before the product is let loose and major problems arise. There
was much done on the 35S promoter before it was used and much of what she
criticises was known and assessed some time ago. 

6. One further point on instability of the promoter or transgene - if a
company releases such material to the farmer it is the company that will
suffer - there are some examples of this from conventional breeding. 

RESPONSE FROM PAUL CHRISTOU, LEAD SCIENTIST ON THE RECENT JIC CaMV WORK


Mae Wan Ho et al. have earlier misinterpreted our results (Kohli et al.
1999) regarding 'recombination hot-spots within the CaMV35S promoter'(Ho,
et al., 1999). With the recent press release they continue to misinterpret
our results. Extensive information is now available over the Internet
(http://www.gene.ch/cgi-bin/htsearch. search string "A few replies to Ho
and Cummins") and in print, to convince any reader that the reported
recombination hot-spot in the CaMV35S promoter poses no danger to any
crop, animal or person. A number of scientists have not only clarified why
Mae Wan Ho et al are wrong in predicting great dangers about to befall
humanity, but have also explained the technical and scientific issues
which dispel beyond any doubt the remotest possibility of such scenarios.
For the benefit of readers of this rebuttal we would like to once again
state that: 

a) The reported recombination event within the CaMV35S promoter actually
destroys the promoter and renders it incapable of driving expression of
any gene. It is therefore totally irrelevant to speculate that the
promoter will recombine through such an event and give rise to harmful new
genes or viruses! 

b) 
##The event occurs before the integration of the transgene into the plant
genome. If the recombination hot-spot was functional after stable
integration of the construct into the plant genome then we would observe
different recombined products in the progeny. We have instead observed and
reported stable inheritance of the transgenic locus, (Gahakwa et al.,
2000) however, Mae Wan Ho et al. chose to ignore these reports. 

c) 
##The event was most likely facilitated by the fact that there were two
copies of the promoter on the same construct, running in opposite
directions. GM crops do not have such an arrangement. 

Instead of using our report to understand the mechanisms of a certain
event Mae-Won Ho et al used it to make misinterpreted sweeping statements
and indulge in scare mongering. A typical example of how Ho et al. pay
little attention to detail is their statement that "Our fiercest critic
was leader of a research group in the JIC that had discovered that the
promoter has a 'recombination hot-spot'". No doubt the views of Ho et al
would be fiercely debated but the scientist who is most capable of
refuting their claims, Professor Roger Hull. In his comments to Ho et al
Professor Hull alluded to his role in the discovery of the CaM virus and
not in the specific hot-spot, recombination at which was being debated.


Expert virologists from around the world have condemned this attitude of
Ho et al. and commented on how and why our report cannot be the basis of
such scary scenarios as painted by Ho et al.
(http://www.gene.ch/cgi-bin/htsearch. search string "A few replies to Ho
and Cummins"). After reading those comments it does not take a genius to
see that the views of Ho et al. (1999), are biased against GM crops and
that they will distort and extrapolate any situation to campaign against
GM crops. 

It is exactly this stance which makes them leverage the latest JIC Annual
Report content on page 30 for 'demise of GM crops'.
## As a result of a
logical extension of our earlier studies, we have used constructs, which
have minimal amount of foreign DNA required for gene expression, thus
reducing the availability of any sequences that can potentially recombine
prior to integration (Fu et al., 2000). This strategy leads to increase in
efficiency of obtaining transgenic plants with intact constructs. Safety
is not at issue here, rather more efficient and stable expression of
transgenes in plants. 

Our report does not compromise GM crops on the market because again, these
crops contain stably integrated DNA and not floating DNA. Our report
describes a method to create the next generation of transgenic crops that
is more efficient. One such efficiency factor is to cut down on the
production of plants that result from pre-integration recombination events
and one way to do this is to reduce the potentially recombinogenic
sequences. Again safety arguments are irrelevant as we explained
previously. 

Ho et al have used statements taken from page 30 (and not page 29 as again
incorrectly quoted by Ho et al) of the JIC Annual Report to predict the
'Demise of GM crops'. They have again failed to notice that we are
referring to processes involved in the generation of the plants and not to
those after the plants have been generated. 

References:

Fu X, Duc LT, Fontana S, Bong B, Sudhakar D, Tinjuangjun P, Christou P,
Kohli A (2000) Particle bombardment-mediated delivery of minimal transgene
cassette leads to generation of transgenic rice with simple integration
patterns. Transgenic Research. 9 (1): 11-19. 

Gahakwa D, Maqbool SB, Fu X, Sudhakar D, Christou P, Kohli A (2000)
Transgenic rice as a system to study the stability of transgene
expression: Multiple heterologous transgenes show similar behaviour in
diverse genetic backgrounds. Theoretical and Applied Genetics.101 (3): 388
- 399 

Ho, M.-W., Ryan, A. and Cummins, J. (1999). Cauliflower mosaic virus
promoter - a recipe for disaster. Microb. Ecol. Health Dis. 10: 33-59.


Kohli A, Griffiths S, Palacios N, Twyman RM, Vain P, Laurie DA, Christou P
(1999) Molecular characterization of transforming plasmid rearrangements
in transgenic rice reveals a recombination hotspot in the CaMV 35S
promoter and confirms the predominance of microhomology-mediated
recombination. Plant Journal, 17 (6): 591-601 

RESPONSE FROM PHIL DALE, (JIC) MEMBER OF AEBC: Roger Hull, Simon Covey and
I published a review which considered some of Mae Wan Ho's comments last
year (R. Hull, S.N. Covey, P. Dale "Genetically modified plants and the
35S promoter: assessing the risks and enhancing the debate" Microbial
Ecology in Health and Disease 2000, 12: 1-5).Ý 

Our conclusion was that "any risks are no greater than those encountered
in conventional plant breeding". There are several millions of hectares of
crops containing the 35S promoter across the world and there have not been
any instances that would raise concerns, from its presence in crops that
are currently commercialised. 

BARLEY TRASNGENICS: COMMENTS FROM JOHN SNAPE, HEAD OF CROP GENETICS
Contrary to the views expressed in the ISIS article JIC scientists are not
saying that GM crops are no good, quite the contrary. All the evidence
from the field trials of barley transgenics is that the performance is no
different from that observed in a conventional breeding programme.
Although there are slight changes in traits such as flowering time or
plant height (which are shown to be due most likely to the tissue culture
process and not the transformation process, anyway) none of the changes
observed in any character influences the safety of the crop. The plants
are not invasive, it does not affect their reproductive behaviour (there
was no change in yield) and barley doesn't have any UK relatives with
which it could outcross. It is utter rubbish to say that these data have
the potential to create new recombinant bacteria or viruses.Ý 

It is well established that the expression of transgenes is not yet
entirely predictable and that more information is needed on transgene
stability so that we can make the technologies more predictable. Thus, we
are investigating the structure of transgenic plants at the molecular
level with a view to developing technologies where plants have a more
predictable level of expression of a transgene. The changes in transgene
expression observed between independent transformation events and over
generations have no implications with respect to changing the
environmental safely of the lines, and essentially, demonstrate the
'substantial equivalence' of barley transgenic lines. 

---
Prof. Chris Lamb,
Director. John Innes Centre
Norwich Research Park, Colney, Norwich, NR4 7UH, Norfolk, UK 

******************************
David Tribe Ph.D.
Senior Lecturer,
Department of Microbiology and Immunology
University of Melbourne
Parkville, Australia 3010
Fax 61 3 9347 1540
Ph. 61 3 8344 5703