Pat Gibbs Rosenstiel, School of Marine and Atmospheric Sciences, University of Miami, Miami, Florida 33149, USA. pgibbs@rsmas.miami.edu
To the editor:
Your editorial in the January issue (Nat. Biotechnol. 22, 1, 2004) rightly raises concerns over the regulatory oversight of the GloFish marketed in the United States by Yorktown Technologies (Austin, TX, USA). But the most pertinent question is what exactly is the transgenic content of this animal?
In fact, analyses in my laboratory have revealed that GloFish® contain four or five tandem duplicated copies of the DsRed1 shuttle vector from BD Biosciences Clontech (Palo Alto, CA, USA) with a zebrafish muscle promoter inserted into the multiple cloning site ( http://www.bdbiosciences.com/clontech/techinfo/vectors_dis/pDsRed1-1.shtml ). In addition to a minimal transcription unit for red fluorescent protein expression, the fish contains six extra unnecessary segments of DNA. These consist of the following: f1 bacteriophage, pUC and simian virus 40 (SV40) origins of replication; a 'universal' expression cassette with the -lactamase/SV40 promoters; and the herpes simplex virus thymidine kinase polyA site and terminator driving expression of the kanamycin/neomycin resistance transgene (nptII).
The decision not to excise the antibiotic resistance marker nptII from GloFish is particularly troubling, given that kanamycin is sold over-the-counter for home aquarium use and is also commonly used in ornamental fish aquaculture. As GloFish appear likely to come into contact with kanamycin, the presence of prokaryotic and eukaryotic origins of replication together with 'universal' expression of antibiotic resistance is likely to positively select for rare horizontal gene transfer events, raising the potential for horizontal gene transfer from this genetically modified organism (GMO).
As far as I can tell, nothing like this animal has ever been approved for release as a GMO into the environment in either the United States or the European Union. Yet, all we have from the US Food and Drug Administration (FDA; Rockville, MD, USA) on these fish is an ambiguous three-sentence ruling:
"Because tropical aquarium fish are not used for food purposes, they pose no threat to the food supply. There is no evidence that these genetically engineered zebra danio fish pose any more threat to the environment than their unmodified counterparts which have long been widely sold in the United States. In the absence of a clear risk to the public health, the FDA finds no reason to regulate these particular fish."1
Neither the antibiotic gene nor the regulatory sequences contained in the fish are even mentioned. More importantly, the statement gives the impression that the FDA was not aware of the precedent-setting nature of this particular release.
The lack of lucidity at the FDA is mirrored by equal confusion at the level of US state's rights-driven regulation. Already, California has banned the GloFish on the basis of apparent 'ethical' reasons. Florida, in contrast, has decided that GloFish can continue to be cultivated, but that regulatory guidelines will be formulated for further release of new varieties of transgenic ornamental fish. The United States thus appears in danger of promulgating an incoherent regulatory patchwork on these products.
The FDA, or some federal GMO umbrella organization, should clarify the situation by describing the transgenic content of all GMOs before they are released and providing an up-to-date list of allowable genetic sequences/functions and combinations.
Nature Biotechnology responds: We are aware of neither studies on gene transfer between individuals within a zebrafish population nor studies on gene transfer between teleost species. As yet, the genomes of Fugu and zebrafish have not been sufficiently analyzed to ascertain the presence of horizontally transferred gene sequences in either fish genome.
REFERENCES US
Food and Drug Administration. FDA Statement Regarding GloFish®. (USFDA, Rockville, MD) (December 9, 2003).
source: email 2apr04
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