I read with interest the message from Ulrich Melcher about Gus de
Zoeten's talk. I also was concerned by the paper from Greene and Allison and
sent a letter to Science. I do not know if they will publish it but I
enclose it so that, hopefully, it can add to the discussion on this topic.
The recent report by Ann Greene and Richard Allison on recombination
between a viral RNA and transgenic plant transcripts (Science 11th March 1994
Vol. 263, p. 1423) raises various safety issues concerning the field release of
transgenic plants. In their commentary on this paper in the same issue of
Science (p. 1395), Bryce Falk and George Bruening focused on some of the risks
of recombination and came to the conclusion that there was probably no more
chance of this happening in a transgenic plant than in the joint infection of
two viruses in a non-transgenic plant. What was not brought out in the
commentary was that recombination is just one of the potential risks and that
there are ways of minimizing undesirable effects.
The expression of viral sequences in transgenic plants is designed to
confer protection against the donor virus and related strains. The major
question that arises is what is the possibility of an interaction between the
products of a transgene and an unrelated superinfecting virus? There is a
wide range of approaches to the non-conventional protection strategy (for
review see 1) and at least one of them, that of crop plants expressing viral
coat proteins to give viral protection, will be commercialized soon. The coat
protein of many viruses confers the specificity of interaction with the vector (
e.g. insect, nematode or fungus) which naturally transmits the virus.
This raises the possibility of the transgenically produced coat protein
encapsidating the genome of the superinfecting virus thus changing its vector
specificity. There are examples of this heteroencapsidation between related
and even unrelated viruses occurring in transgenic plants (2, 3). Thus,
recombination is not the only interaction between the product of a transgene
and a superinfecting virus which could lead to potential risk.
The argument that these interaction phenomena rarely happen in natural
joint infections and that this can be extrapolated to the transgenic situation
is open to question on several counts. Firstly, most of these phenomena,
except for that of heteroencapsidation between related viruses (4), have not
been sought experimentally and molecular studies which can reveal such
interactions have not been widely applied to field situations. Secondly,
heteroencapsidation or recombination will only take place when the viral genome
is exposed, that is when it is being expressed or replicated. There is strong
evidence that this occurs in different cellular compartments for different
viruses but there is no information as to whether the products of transgenes
are similarly compartmentalized. Thirdly, the use of transgenic plants will
involve their widescale deployment thus increasing the potential for risk (risk
= hazard x frequency). This leads to the dilemma as to whether to undertake
widescale field releases of such transgenic plants as this is the only situation
in which the current issues can be resolved. If a problem did arise it would
then be too late.
Is there any way that these problems can be bypassed? There is
evidence, at least with some viruses, that the region of the coat protein
involved with vector specificity is not important in protecting against viral
infection (see 5). Thus, one can effect biological containment by rendering
the protein incapable of vector interactions while maintaining its capacity to
afford viral protection. This approach of biological containment could have
application to all virus-related transgenes. What is needed is an
understanding of the interactions giving the potential undesirable properties
of the transgene product so that the gene can be refined or tailored to remove
the 'bad' features while retaining those which would give the desired
protection effects. In the absence of information on potential risks it would
seem prudent to minimize any chance of a risk rather than perform the grand
field experiment.
Roger Hull,
John Innes Institute,
John Innes Centre,
Colney, Norwich NR4 7UH, UK
References
1. R. Hull and J.W. Davies, Crit. Rev Plant Sci. 11, 17 (1992).
2. H. Lecoq et al., Molec. Plant Microbe Interns. 6, 403 (1993).
3. P. Candelier-Harvey and R. Hull, Transgenic Res., 2, 277 (1993).
4. C.D. Atreya et al., Virology 178, 161 (1990); P.L. Atreya et al., Proc. Natl.
Acad. Sci. USA 88, 7887 (1991); J.A. Lindbo and W.G. Dougherty Virology 189,
725 (1992).
5. W.F. Rochow, Science 167, 875 (1970); D. Bourdin and H. Lecoq, Phytopathol.
81, 1459 (1991).
