Transcript COLOMBO-BERGEN-02-07

GENIMPACT SYMPOSIUM
Bergen, 2 – 4 July 2007
Genetic engineering in aquaculture:
possibilities
and limitations
possibilities and limitations
Lorenzo Colombo
Department of Biology
University of Padova, Italy
[email protected]
Trying to be good
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Transgenesis into the germinal line of fish is a consolidated
technology displaying significant achievements, like 2-11-fold
growth rate enhancement by fish-GH-gene transfer (autotransgenesis)
in more than 30 teleosts, mostly of aquaculture interest.
GH-transgenic fish need less time, water and energy to reach market
size and convert food more into protein and less into fat.
Food safety issues for consumers are presently deemed to be
negligible, as GH-transgenic fish are substantially equivalent to nontransgenics.
Private companies have invested for the mass culture of transgenic
fish (mainly salmon).
According to FAO, fast-growing fish may help to meet future animal
protein demand.
On the brink of extinction ?
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Why the cultivation of transgenic crops, which are mainly
allotransgenic, have conquered 100 million hectares since 1997
and are presently expanding globally at 10% per year, while the
commercial farming of fast-growing GH-transgenic fish is not
yet allowed and viewed with widespread skepticism ?
Is the opposition against the mass cultivation of transgenic fish
based on sound science, traditional culture or mass mediainfluenced attitude ?
Are transgenic fish an example of reckless manipulation of life
and, hence, doomed to extinction, or the result of inadequate
application of otherwise useful technology ?
BIODIVERSITY
BIOREPERTOIRE
Evolutionary mechanisms
Evolution by natural selection
and speciation
Metaevolution by domestication
and genetic improvement
Selective parameters
Fitness
(reproductive success)
Performance
(production or service capacity)
Agents
Natural forces
Biological interactions
Reproduction control
Reproduction manipulation
Courses
Unplanned and undirected
No design
Planned and directed
Intelligent design
Percent of total species domesticated
1
Time (years before present)
Land versus water. Most land species were domesticated earlier than aquatic
species but, in the past 100 years, many more aquatic species than land species
have been domesticated.
Duarte et al. (2007), Science, 316, 382-383.
Global pace of species domestication
Species groups
Time since domestication
(years before present)
Number of
50% species
species
domesticated
domesticated
90% species
domesticated
Land plants
250
4000
2000
Land animals
44
5000
146
Freshwater animals
180
22
4
430
Marine animals
250
19
4
Marine Plants
19
32
<10
Duarte et al. (2007), Science, 316, 382-383.
Traditional domestication process
Domesticated biodiversity
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Development of rearing practices providing shelter, food,
care and assisted reproduction in exchange for confinement
and terminal sacrifice.
Broodstock open to exchanges with wild-type genetics.
Domesticated biorepertoire
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Application of selective breeding, either empirically or
according to quantitative genetics to improve progeny
performance.
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Broodstock belonging to a selected race or line.
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Sale of progeny without further royalties.
Production improvement in aquaculture
Genetically holistic approaches
Selective breeding
Sequential genetic gains
Interspecific hybridization
Single genetic gain
Polyploidization
Single genetic gain
Integrated expression of
novel allele combinations
Integrated expression of
combined heterospecific genomes
Integrated expression of
high-ploidy (>2) genomes
Recommended management of genetic resources
Biodiversity
Biorepertoire
Gene flow
Wild populations
Farmed stocks
Evolution by
natural selection
Domestication by
genetic improvement
Biotechnological approaches in aquaculture
Genetically reductionistic approaches
Gene transfer
into the germinal line
DNA vaccination
Transgene with perpetuated
transmission and expression
Plasmids with indipendent
and transient expression
The third phase of domestication
Transformed biorepertoire
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Application of gene transfer technology to jump start a trait
of interest without progressing through small genetic gains
along multiple generations.
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Broodstock belonging to a stabilized transgenic line.
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Right to patent and license a transgenic line.
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Possible monopolistic control of the product market.
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Risk of transgenic
crossbreeding.
contamination
of
wild-life
by
A big leap for mankind
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Application of gene transfer technology in agriculture marked a
transition from domesticated biorepertoire to transformed
biorepertoire, while in fish culture it would be a leap from
domesticated biodiversity to transformed biorepertoire.
For this transfer, two main safety issues must be satisfied:
Nutritional equivalence: when food transgenic components are
identical or comparable to those of traditional food.
Ecosystemic compatibility assessed by:
 fitness
estimate: probability that
population be established in the wild;
a
transgenic
 dynamic
impact estimate: level of harm imposed on
recipient biocommunities;
 genetic
impact estimate: probability of transgenic
contamination of feral conspecifics.
How transgenic crops got their way
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Nutritional equivalence: not given for granted because of the
prevalent transfer of transgenes from other taxa
(allotransgenesis); consumers’ safety issue resolved
pragmatically.
Ecosystemic compatibility: debated as an affair internal to
agriculture rather than biodiversity because:
 the
genetic interface with isospecific wild plants is
minimized due to their absence, rarefaction or genetic
incompatibility with polyploid genomes of cultured plants;
 fear of possible cross-contamination with conventionally or
organically cultivated crops;
 supposed cross-contamination with agricultural weeds.
Why GH-transgenic fish flopped
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Public perplexity because growth-enhanced GH-transgenic
fish would be the first animal product for human
consumption to be genetically engineered.
Nutritional equivalence: generally conceded for GHtransgenic fish because integration of autotransgenes, like
fish-GH-transgenes, should not alter qualitatively the host
transcriptomic and proteomic profiles, at least not in a way
to represent a health hazard for consumers.
Ecosystemic compatibility: strongly contested to safeguard
biodiversity because:
 due
to the recent domestication process of a great
number of aquatic species, the genetic interface with
wildlife is vast and still permeable in both directions.
Transgenic contamination
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Although gene transfer between fish species can occur
naturally, as in introgressive hybridization, transgene trade
with wild fish is not be equivalent to the passage of native
genes, because transgenes are products of intelligent design
and patentable.
The hazard of transgenic contamination of feral conspecifics
is double-faced:
 if
they are indigenous, it represents a contamination of
biodiversity;
 if they are naturalized from alien escapees, it may entail
exacerbation of non-genetic impacts on other species, but
not a loss of genetic integrity in truly natural biodiversity.
Entering the wrong way
 Since
transgene insertion in wild genomes may be
irreversible, ecosystemic risk assessment based on field tests
is the currently obligatory step for approving applications
for the mass culture of possibly fertile transgenic fish.
 This precautionary measure determined a deadlock because:
 fish
tested in natural ecosystems are essentially
unrecoverable;
 tests
in secluded environments are of limited
significance and can provide only circumstantial
estimates with limited predictive capacity.
 Hence, endless moratoria have been the only outcome.
An industrial miscalculation
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To overcome the impasse, the only option is to solve the
problem about how to maintain the fertility of confined
spawners to perpetuate a transgenic line, while securing
complete reproductive sterility in transgenic fish for grow-out
Surprisingly, private companies interested in developing
transgenic fish culture for commercial purposes have not
promptly realized that complete sterility of marketed transgenic
fish was a top priority also for them because it is required:
 to safeguard aquatic wildlife;
 to ensure full market control on their product;
 to
avoid being sued at later times for
unforeseen transgenic contaminations.
Coolest inventions 2003
No more sex
 Apparently, the rush in the implementation of gene transfer
in agriculture instigated the belief that this was also possible
in fish culture.
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remedy this misconception, triploidy induction by
pressure or heat shocks was proposed to secure sterility, but
this claim was soon dismissed for lack of consistent 100%
efficiency, while fish have high reproductive capacity and
may escape in large numbers from culture facilities.
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the options at hand, the simplest is the double
sterility approach where triploidy induction is combined
with other techniques to fill up the gap in its per cent
effectiveness, such as allotriploidization of infertile
interspecific hybrids.
Let’s make it better
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Whatever the best sterilizing solution, it would be deplorable
to dump gene transfer technology as inapplicable to fish
culture, just because the first attempts were inadequate.
In the past, geneticists have made wonders by platonically
gazing at the shadows of genes as reflected in the realized
phenotypes. Now, in the era of genomics, we have the
privilege of admiring life in full shining in order to
responsibly take care of our growing needs.
Given the fact that the human population is presently
increasing at the rate of half billion people every 6 years,
transgenic fish may provide a convenient source of cheap
animal protein from non-carnivorous species in countries
most afflicted by heavy demographic pressure.
A bomb in the alcove
1650 : 0,5 billion people
+ 0,5 BL / 150 years
1800 : 1 billion
+ 1 BL / 130 years
1930 :
2 billion
+ 1 BL / 30 years
1960 : 3 billion
+ 1 BL / 15 years
1975 : 4 billion
+ 1 BL / 12 years
1987 : 5 billion
+ 230.000 / day
Present increment rate: + 7 milioni / month
+ 84 milioni / year
Picture above x 170.000
+ 1 BL / 12 years
1999 : 6 billion
+ 0,5 BL / 6 years
2005 : 6,5 billion