Biomedical Engineering Reference
In-Depth Information
The production of any marketable commodity
requires a great deal of investment in terms of
research and development. Most commodities
are not self-renewing, so manufacturers can
recover their investments through long-term
sales. Transgenic plants, however, are capable of
reproduction. Farmers have to make an initial outlay
for seed purchase, but, by saving a proportion of
seeds from each harvest, they need never return
to the manufacturer again. For producers who
have invested heavily in development, this is
unacceptable. So how can the producers protect
their investment?
Until recently, this was achieved through the use
of contracts that obliged farmers not to save any
seeds. However, such contracts are difficult to
enforce, particularly in developing countries. A
novel strategy is to modify the plants so that the
seeds are sterile, thereby forcing the farmer to return
to the manufacturer year after year for fresh supplies
of seeds. This strategy, which has been termed
technology protection
by the biotechnology
companies and
terminator technology
by disgruntled
consumers and opponents, is perhaps the most
controversial potential use of genetically modified
plants. In essence, the technology works rather like
the anti-copying devices now incorporated into video
recorders - the industry is protecting its investment
by preventing unauthorized duplication of its
products. The principle of terminator technology is
the expression of a toxic transgene, the terminator
gene, at a critical stage of embryonic development,
thus killing the embryo and rendering the seeds
incapable of germination. Several variants on this
technology were described in a patent application,
granted in March 1998, to Pine Lands Corporation,
which has since been bought by Monsanto. One of
the variations is discussed below.
In this example, the terminator gene encodes a
ribosomal-inactivating protein and is expressed
under the control of a promoter that is active in late
embryogenesis, such as the promoter of the
lea
(late embryogenesis abundant) gene. Seeds produced
from such plants are sterile, but, since seed storage
products (e.g. starch and oil) accumulate in early
and mid-embryonic development, the seeds are
nutritionally unimpaired. In order to maintain a stock
of fertile plants, the terminator gene is controlled by
inducible site-specific recombination, as described in
detail in Chapter 13. The gene is rendered inactive by
inserting a blocking element between the gene and
its promoter. This blocking element is flanked by
loxP
sites. The transgenic plant also contains a
cre
recombinase gene, which is controlled by a
tetracycline-inducible promoter, and a third
transgene encoding the tetracycline repressor
protein, which is constitutively expressed. In the
absence of tetracycline, the repressor prevents
cre
expression, the terminator gene is not activated
and the plants can be grown as normal, allowing
the producer to grow plants and produce seeds in
unlimited quantity. Before distribution, however, the
seeds are soaked in tetracycline, which causes the
repressor to release the
cre
promoter, thus inducing
the
cre
gene, leading to excision of the blocking
fragment and activation of the terminator gene.
Since the terminator gene is controlled by an
embryonic promoter, it is not switched on until
the following generation of developing seeds.
The advent of terminator technology was met by
a public outcry, particularly from farmers and from
environmentalists concerned that terminator genes
could spread from the transgenic crops into wild
plants, with unknown consequences. Perhaps in
response to this, Monsanto has since pledged not
to implement the technology now at its disposal.
(a)
No tetracycline
TET
R
P
LCA
P
Tet R
P
Cre
RIP
tetO
TET
TET
R
(b)
Tetracycline present
Cre
P
LCA
P
Tet R
P
Cre
tetO
Oliver
et al.
(Pine Land Corporation) United States Patent 5 723765, 'Control of Plant Gene Expression', 3 March 1998.
