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-----Original Message-----
From: Biotech-Mod3
Sent: 29 June 2002 09:37
To: 'biotech-room3@mailserv.fao.org'
Subject: 95: Traditionally bred organisms vs. GMOs

This is Kaare M. Nielsen. I am associate professor of microbiology at the University of Tromso, Norway. I also hold a part-time position at the Norwegian Institute for Gene Ecology, Tromso, Norway. I have studied and published on horizontal gene transfer processes and how they relate to the safe use of GMOs during the last 9 years.

Do traditionally bred organisms and those derived through genetic engineering contribute the same in gene flow?

From my perspective, Dr. Suzanne Wuerthele´s opening statement (message 1, May 31) in this email conference identifies the essential issue regarding the consequences of gene flow from GM organisms. Namely, do transgenic organisms differ fundamentally in their genetic make-up from other traditionally bred organisms? If the answer to this question is no, then no particular concerns are to be raised that would separate the assessment of GMOs as compared to traditionally bred organisms. If the answer is yes, then the unique features should be identified and the consequences of their dispersal by gene flow evaluated.

I believe the answer to the question is dependent on the specific genetic changes introduced into the GMO in focus. Thus, GMOs with simple intra-chromosomal changes are likely to produce few concerns beyond those present for traditionally bred counterparts. By traditional breeding, I refer to processes where selection (of naturally-arising or induced spontaneous genetic variation) is the major mechanism to obtain the desired genetic variation. However, as more species-foreign genes, novel genes, and other genetic changes are introduced into GMOs, they will deviate substantially from what can be achieved by traditional, selection based breeding. These latter organisms have a genetic composition that does not arise from naturally occurring evolutionary processes alone. Thus, they have the potential to introduce previously inaccessible genetic variation (functionally enhanced by different promoters etc.) into wild populations. [This question of whether the nature of the genetic modification (i.e. wide transfer, close transfer or tweaking - see Section 2 of the Background Document) should be considered when evaluating the potential impacts of gene flow from GM populations is something we definitely wished to see raised in this conference. Thus, are the gene flow questions or potential consequences different if we intend to release, for example, a tilapia fish containing a tilapia growth hormone gene genetically modified to alter its level or pattern of expression or containing a gene from a bacteria...Moderator].

Thus, unintended gene flow from GMOs has the potential to significantly change the evolutionary trajectories of their wild relatives. Whereas traditional breeding is largely based on artificial selection, modern gene technology introduces novel genetic variation that is naturally unachievable in the organism in question. Mechanisms providing genetic variability in higher eukaryotes do not combine DNA sequences from several organisms into a compact functional unit within the time scale achieved by genetic engineering. Thus, the argument that genetic engineering is a naturally occurring process cannot be used when the genetic novelty introduced by the transgenes extends beyond simple modifications.

In most cases, engineered genes are unlikely to be positively selected in wild relatives. However, it cannot be assumed that this will always be the case. An awareness of this potential for selection is important as more novel gene constructs are prepared for environmental release. Moreover, I argue (in support of Dr. Muir [see e.g. message 73, June 25...Moderator]) that population genetics methods are the best tools available today to evaluate the consequences of such gene flow into wild relatives. Most crucial parameters needed for the models can be derived from field experiments and improved further (along with the models) after collection of data from focused monitoring efforts. Unfortunately, most field release experiments published so far have been concerned with cultivar performance in a commercial perspective rather than generating and communicating data for enhancing risk assessment.

The important thing to consider in a eukaryotic gene flow perspective (often missed in the debate) is not the rate of transfer but the strength of selection on those individuals who carry the transgene. This is because purifying selection will remove those individuals carrying the transgene(s) from the wild populations if the introduced genetic changes from gene flow do not provide an advantage. However, if selection is positive, even very rare gene flow events may have a major impact as the receiving organisms then may out-compete its neighbors.

Which characteristics would make the consequences of potential transgene flow differ from the consequences of gene flow seen from traditionally grown counterparts? At least the following characteristics may be relevant to consider:

1. Horizontal gene transfer (HGT) to bacteria: Transgenes often contain DNA sequence homology to prokaryotes, thereby significantly increasing their likelihood of integration in bacteria. Many studies have shown that DNA homology is the main barrier to HGT of chromosomal DNA (such as transgenes) in bacteria. Moreover, they are often inserted as a compact genetic unit making transmission a single step process, as compared to host-indigenous quantitative traits they may substitute.

2. Transgenes are often modified to allow broad expression in a variety of hosts; they often lack introns, contain promoters active across a broad range of hosts (e.g. viral or bacterial in origin), and seldom require extensive interactions with other proteins in the host cytoplasm for functionality. Genes from distantly related species are less likely to be retained and to function in the recipient organism due to differences in nucleotide sequence, gene expression, codon usage, and possibly post-translational modification and protein interactions. However, transgenes are often modified to allow broad expression and often require few interactions with the host cytoplasm for activity. Thus, transgenes may have an increased likelihood of expression if transferred by gene flow to wild relatives.

3. The transgenes may represent novel genetic variability due to the use of synthetic genes with new protein domains or encoding novel biochemical pathways that have not been subject to natural selection in their new host environment.

The effect of such genes must be addressed in a population genetics perspective. Thus, when compared to any native gene of related organisms, transgenes may possibly differ with respect to their likelihood of gene flow, expression in the new host, and selection. The relevance of the above characteristics has to be evaluated on a case-by-case basis.

[Eukaryotes (eukaryotic organisms) include animals, plants, fungi and some algae, while prokaryotes include bacteria and blue-green algae...Moderator]

Kaare M. Nielsen
Department of Pharmacy
School of Medicine
University of Tromso
N9037 Tromso, Norway
Email: knielsen (at) pharmacy.uit.no
http://www.farmasi.uit.no/~knielsen/

-----Original Message-----
From: Biotech-Mod3
Sent: 29 June 2002 09:43
To: 'biotech-room3@mailserv.fao.org'
Subject: 96: Re: Policy options when there is no consensus

Mr. Wozniak (message 87, June 28) seems to deny that U.S. regulators use the concept of substantial equivalence in evaluating GMOs. I've heard this term so often from U.S. regulators visiting the Philippines that I am stunned that this is denied.

Mr. Wozniak asks for an example of a "reckless release". He says the overwhelming majority of scientists he interacts with do not have a safety issue with the Bt crops released to date. He seems to deny the lack of a reasonable consensus on the safety or non-safety of GM crops.

My response: U.S. regulators refused to approve Starlink for human consumption due to a safety issue (potential allergenicity). Yet, they allowed its commercial release anyway. Given the scientific consensus that contamination is inevitable after commercialization, this was clearly a reckless release, as was, in fact, borne out by subsequent events and the expensive $1-billion recall.

The British Medical Association has called for a phase out of antibiotic resistance genes. The safety or non-safety of using such genes clearly remains a matter of scientific debate. So is the use of the cauliflower mosaic virus (CaMV) promoter, which some scientists have also questioned on safety grounds.

I think the lack of scientific consensus is understandable because the current batch of GM crops have not been tested at all on human volunteers. If controversies occur even with medicines which have undergone thorough testing on human volunteers, how much more with novel foods which have not yet gone through such tests?

The question is valid: what policy should decision-makers adopt, while their scientists could not yet come to a reasonable agreement on the safety or non-safety of GM products? I've given my answer in an earlier message (82, June 27).

It's a pity we are closing when the debate is just getting to be interesting.

Roberto Verzola
Secretary-general, Philippine Greens
Philippines
rverzola (at) gn.apc.org

-----Original Message-----
From: Biotech-Mod3
Sent: 29 June 2002 09:59
To: 'biotech-room3@mailserv.fao.org'
Subject: 97: Transgenic Fish

Prof. Joe Cummins, Professor Emeritus of Genetics University of Western Ontario, Canada.

Transgenic fish have been launched with optimistic hopes that the fish will grow rapidly, use food efficiently and pose little threat to the native stocks. To insure that patented fish are prevented from spreading their traits to native stocks, "sterile" triploid stocks are a preferred genetic manipulation. Triploids have been produced in a wide variety of fish and the use of triploid grass carp to control lake vegetation has had wide application in North America.

Triploids are frequently produced by suppressing the second meiotic division using a shock such as heat, cold or pressure.(1). A related technique, gynogenesis, employs irradiated sperm to fertilize normal eggs followed by inhibition of the first or second meiotic division of the egg. Triploid embryos are identified by the large cell size, sometimes assisted by rapid identification of nucleolar organizing regions with occasional full karyotypes to verify the chromosome counts(1). Gynogenic embryos are identified using genetic marker. The aim of triploid production or triploid with gynogenesis is to produce sterile fish that can be produced in mass and easily verified (2).

In many instances the use of sterile triploids to contain the transgene while allowing the modified fish to grow in the natural environment has been put forward as if the sterile triploids were "fool proof" while, in reality, a number of studies suggest that sterile triploids may be "leaky" and allow some fertile gametes to be produced. Even though sterile triploid grass carp are used extensively in North America to control lake vegetation there have been few studies on the fertility of feral grass carp. Feral grass carp recovered from the Chesapeake Bay waterway observed gonadal development in two female and one male triplods (3). A study of transgenic Tilapia found that triploid females had no gamete development while males had poorly developed gonads with spermatozoa (4). Anueploids were recovered from among triploid oysters (5) [Aneuploidy is when an organism or cell has a number of chromosomes which is not an exact multiple of the haploid number...Moderator]. Extensive studies on sterile triploid leakiness to produce gametes should be done before any transgenic fish are exposed to the environment.

Triploids may pose special problems. For example, triploid Atlantic salmon had a high prevalence of skeletal deformity and reduced gill surface area (6). Families of triploid salmon were found to have much greater variability in growth than fertile diploids(7). Ocean migration and recoveries of triploid Atlantic salmon were between 12% and 24% of diploid siblings (8).

Turning to transgenic fish, a number of studies suggest that release of such fish to the environment is presently premature. For example, growth-enhanced transgenic Atlantic salmon were found to be negligent in predator avoidance in comparison to normal counterparts (9). The likelihood of growth-enhanced Atlantic salmon achieving maximum growth or even surviving outside intensive culture conditions was lower than non-transgenic salmon (10). Growth-enhanced transgenic Arctic charr were found to partition nutrients in a manner that resembled domestic rather than wild rainbow trout (11). The use of fish that are growth-enhanced using human growth hormone has been attempted frequently, for example, human growth hormone enhanced carp achieved higher growth rates and food utilization efficiency than non-transgenic carp (12). However, the use of human genes to modify animals meant for human consumption bears special scrutiny. Finally, the impact of fertile transgenic salmon, or other transgenic organisms, on natural populations has been found to have conditions for invasion of the natural population that are very broad and if the transgene reduces viability the release can lead to extinction of the natural population (13).

In conclusion, peer reviewed studies on induced triploidy in fish and on transgenic fish indicate that the technology is fraught with uncertainties and problems that have not yet been resolved. The evidence currently available indicates that the risks to the natural fish stocks is far too great to allow transgenic fish to be released to the environment. However, production of transgenic fish can be considered so long as that production is undertaken in inland facilities rather than fish pens. From the point of view of genetics, conditional dominant lethal mutations might achieve a higher level of safety and transgene containment than that achieved by sterile triploids. However, biology seems amazingly resilient in the way that organisms circumvent obstacles to passing on their genes and great caution should be employed in introducing potentially lethal transgenes. Transgenic fish should not be deemed "substantially equivalent" to facilitate their rapid commercialization.

References
1.Felip,A,Zanuy,S,Carillo,M and Piferrer,F. "Induction of triploidy and gynogenesis in teleost fish with emphasis on marine species" 2001 Genetica 111,175-95
2.Pandian,T and Koteeswaran,R "Ploidy induction and sex control in fish" 1998 Hydrobiologia 384,167-243
3.Summer,S,Steinoening,E and Brown,B "Ploidy of feral grass carp in the Chesapeake Bay watershed" 2000 North American Journal of Fisheries Management 21, 96-101
4.Razak,S,Hwang,G,Rahman,M and Maclean,N "Growth performance and gonadal development of growth enhanced transgenic Tilapia following heat-shock-induced triploidy" 1999 Mar.Biotechnol. 1,533-44
5.Wang,Z,Guo,X,Standish,K,Allen,R and Wang,R. "Anueploid Pacific oyster as incidental from triploid production" 1999 Aquaculture 173,347-57
6.Sadler,J,Pankhurst,P and King,H. "High prevalence of skeletal deformity and reduced gill surface area in triploid Atlantic salmon" 2001 Aquaculture 198,369-86
7.Friars,G,McMilan,I,Quinton,M,O'Flynn,McGeachy,A and Benfey,T "Family differences in relative growth of diploid and triploid Atlantic salmon" 2001 Aquaculture 192,23-9
8. Wilkins,N,Cotter,D and Maileidigh,N "Ocean migration and recapture of tagged, triploid,mixed-sex and female Atlantic salmon released from rivers in Ireland" 2001 Genetica 111,197-212
9. Abrahams,M and Sutterlin,A "The foraging and antipredator behavior of growth enhanced transgenic Atlantic salmon" 1999 Animal Behaviour 58,933-42
10. Cook,J,Sutterlin,A and McNiven,M " Effect of food deprivation on oxygen consumption and body composition of growth-enhanced transgenic Atlantic salmon" 2000 Aquaculture 188,47-63
11.Krasnov,A,Agren,J,Pitkanen and Molsa,H "Transfer of growth hormone transgenes into Arctic charr II. Nutrient partitioning in rapidly growing fish" 1999 Genetic Analysis:Biomolecular Engineering 15,99-105
12.Fu,C,Cui,Y,Hung,S and Zhu,Z "Growth and feed utilization by F4 human growth hormone transgenic carp fed diets with different protein levels" 1998 J Fish Biol 53,115-29
13. Hederick,P "Invasion of transgenes from salmon or other genetically modified organisms into natural populations" 2001 Can.J.Fish.Aquat, Sci. 58,841-4

Professor Joe Cummins,
University of Western Ontario.
Canada
jcummins (at) uwo.ca

-----Original Message-----
From: Biotech-Mod3
Sent: 29 June 2002 10:09
To: 'biotech-room3@mailserv.fao.org'
Subject: 98: Managing gene flow in the South.

From Glenn Ashton, Cape Town, South Africa.

It is clear this conference remains polarised and that consensus is unlikely in the immediate future. This is unfortunate, especially given the proven genetic pollution in Mexico and Canada as well as pollution of conventional and organic farms in the USA and Canada. Supporters of transgenics have shown remarkable reluctance to accept responsibility. This reinforces concerns raised in this conference, relevant to gene flow in developing nations.

In developing nations, the major issue that needs to be addressed is the paucity of oversight, both commercial and institutional, based on political and economic will and reality. Genetic pollution has only come to light in North America due to legal challenges or from comprehensive scientific oversight. These are absent in Africa and in other developing nations.

The present drought in Southern Africa is a prime example of the risks of inadvertent pollution. It is highly likely that much of the whole-grain food aid contains GE contaminants from a wide variety of sources. The potential for contamination for the entire region is significant and there is little possibility of containment or oversight in monitoring this problem.

Scientific investigation struggles to interrogate multiple simultaneous hypotheses and events that have random and unpredictable permutations. We must look beyond the narrow scientific perspectives that clearly limit our investigation of these simultaneous events in the matter of unconfined gene flow.

Wally Menne's suggestions (message 84, June 28) on four criteria on which to base our investigations, namely ecological, economic, social and cultural would form a good starting point to broaden our perspectives on how gene flow is manifested and monitored. We cannot depend on science to investigate issues that are driven by economic needs rather than by scientific or social need. A recent report out of Zambia* (see below) emphasises the above by showing that there is a complete lack of capacity to even grow GE crops efficiently, not to mention manage them.

Laboratory theory and practice is all good and well and must be continued. However we will need a far broader perspective to determine the practicalities behind GE crops. More urgent are the far more complex challenges raised by gene flow from transgenic animals, fish and insects.

It is strange for me, as a non-scientist, that some scientists can remain so robustly confident about the safety of transgenic organisms yet simultaneously discount the multiple concerns outside their disciplines. The song "blinded by the science, servant of technology" springs to mind.

We must be cautious about using technology just because we can; it must be needs driven and not profit driven. It must also be judged against a far wider, multidisciplinary background. Sustainable development, particularly of the south, should encourage tested and sustainable agricultural modalities that are predominantly advantageous with minimal risk. Transgenics cannot yet be placed in this category. We need to learn a lot more before we foist transgenic organisms on the south.

Furthermore, if risks are to be taken with food and crops by the introduction of transgenic organisms, let them take place in developed nations where capacity, oversight and tort can deal with the consequences and where starvation is not a daily reality. We cannot further risk the fragile fabric of existence in the South by introducing the risks of GMOs into completely unregulated environments.

Before we use questionable technological innovations that carry incalculable risk, we must first deal with political, economic, environmental and social challenges of the South, not exacerbate them.

Glenn Ashton,
Cape Town,
South Africa.
ekogaia (at) iafrica.com

*Chiluba's ASIP Was A Total Failure - FAO
TITLE: UN works on emergency food appeal for Zambia
SOURCE: The Post, Zambia, by Bivan Saluseki
http://www.zamnet.zm/zamnet/post/post.html
DATE: June 19, 2002
Chiluba's ASIP Was A Total Failure - FAO
Richard Fuller, Zambia's representative to the Food and Agricultural Organization of the United Nations, asserts that the Agriculture Sector Investment Program (ASIP), initiated by the Zambia government and funded by international donors, "was a total failure." He cites mismanagement of funds and the inability to address small-scale farmers' needs as factors contributing to ASIP's poor performance. Fuller explains that due to the donor community's experience with ASIP, direct funds to the Ministry of Agriculture are being withdrawn. However, donors will support communities or community based organizations directly to include small-scale farmers in planning and implementing programs. Fuller asserts that agricultural biotechnology is not an appropriate method for improving the agricultural sector in Zambia, because the low national agricultural production is due to lack of political will, not poor production technologies. He adds that agricultural biotechnology is suited for countries with well-developed agricultural systems, which includes a regulatory framework for biotechnology.