Hope Not Hype - Third World Network

138 Hope Not Hype
using an already familiar example, imagine the case where the allele of a gene that encodes
a protein more likely to form into a prion was introduced into a recipient by transient
transfection (using a hypothetical DNA vector that could not replicate and would not
recombine 6 ). The DNA for the allele might be lost, but the prion could persist (Caughey
and Baron, 2006; Prusiner, 1998; Weissman et al., 2002; Weld and Heinemann, 2002)
through its own amplification and may pass through organism generations and by infectious
transfer (ERMA, 2006). 7
Another example is common in bacterial genetics. Bacteria are transiently transformed
using DNA that encodes a transposase that may act on a transposon, cause its mobilization
and re-insertion without retention of the transposase (used by Cooper and Heinemann,
2000; Heinemann et al., 1996). A further illustration comes from a genetically modified
corn plant called LY038. This plant was created by the transient expression (through
breeding) of a Cre recombinase acting at loxP sites and causing a DNA deletion that was
heritable. Even when DNA deletion is not the outcome, Cre can cause chromosome
instability and rearrangements (Qin et al., 1994). While this example is based on a GMO,
it derives from a natural recombinase system. This system should be of immediate interest
to regulators because it is seen as becoming a normal way to create GMOs (Ow, 2007). A
final point that this example illustrates is that excision of a transgene, by the actions of a
recombinase or any other event, does not make the resulting organism not a GMO. This is
because the organism’s genes or other material were modified by the original use of rDNA.
In the above examples, the potential for replication or recombination of rDNA is
incidental to evaluating the risk of the genetic modification. ERMA appears to draw this
same conclusion when it states: “It is likely that the [lawmaker’s] intent of the definition
of genetic material, as opposed to heritable material, was to include any nucleic acid
regardless of whether it produced an effect. The effect of such transfer is considered in the
evaluation of the application” (ERMA, 2006, p. 44) rather than in the evaluation of the
necessity of making an application. 8
6
This is the hypothetical vector that was raised as an example by ERMA staff during the 20 August 2007
meeting.
7
Note that I do not think that this is a special case for at least two reasons. First, which proteins can
become prions is not known, and prions are known to exist in many kinds of organisms. Thus, their
environmental implications must be assessed. Secondly, this is one of a number of characters or traits
that may be propagated epigenetically and is not dependent on the stable propagation/amplification of an
instigating nucleic acid (Heinemann and Roughan, 2000; Strohman, 1997; Weld and Heinemann, 2002).
8
However, I do not agree that ERMA or most applicants could prove that there was so little or no replication
or recombination that it would always be irrelevant. While replication may be so inefficient that the DNA
is lost from a population eventually, recombination of all or part of the manipulated genetic material can
never be prevented. This is the outcome of the “massage model” of recombination (Heinemann et al.,
2004). The efficiency of DNA replication can be low enough to escape detection most times, but still
cause persistence of the DNA (Srivastava and Ow, 2003).