GENET archive


9-Misc: New model to assess risks of GMOs

genet-news mailing list

-------------------------------- GENET-news --------------------------------

TITLE:  Potential environmental risks and hazards of biotechnology
SOURCE: Information Systems for Biotechnology, by William M. Muir
DATE:   November 5, 2001

------------------ archive: ------------------

Part I: Risks and Hazards

Part II will look at methods to address those hazards

Harm, Risk, and Hazard

A concern related to genetically modified (GM, transgenic) organisms is the 
potential environmental harm if these organisms escape or are released into 
the environment. Harm can take many different forms from transient to 
permanent in time frame and from local to global in scope. Thus, to define 
harm it is first necessary to distinguish between the terms risk and 
hazard, which are often confused. In this context, William Muir and Richard 
Howard (Purdue University, Lafayette, Indiana) define transgene risk as the 
probability that a transgene will spread into natural populations once 
released and hazards as the probability of species extinction, 
displacement, or ecosystem disruption given that the transgene will spread 
into the population.(1) To show lack of harm from transgenic organisms, 
either the risk [Risk = P(E) where P(E) represents the Probability that 
Exposure will occur] or hazard [Hazard = P(H/E) where P(H/E) is the 
conditional Probability of a resulting Harm (H) given that exposure has 
occurred] must be close to zero; that is, P(E) is approximately equal to 0 
or P(H/E) is approximately equal to 0. Long-term hazards to the ecosystem 
are difficult to predict because not all non-target organisms may be 
identified, species can evolve in response to the hazard, and a nearly 
infinite number of direct and indirect biotic interactions can occur in 
nature. Muir and Howard conclude the only way to ensure that there is no 
harm to the environment is to release only those transgenic organisms whose 
fitness is such that the transgene will not spread, i.e., P(E) is 
approximately equal to 0, in which case the hazard, P(H/E), is irrelevant 
because the transgene is lost from the population.(1)

Factors Affecting Risk

In this context, long-term ecological risk can be determined from the 
probability that an initially rare transgene can spread into the ecosystem. 
Spread of the transgene into natural populations may result in a number of 
ways, including 1) vertical gene transfer as a result of matings with feral 
animals, 2) invasion of new territories as with introduction of an exotic 
species, and 3) horizontal gene transfer mediated by microbial agents, or a 
combination of these factors. The relative importance of each factor is 
dependent on species, transgene inserted, and method used to insert the 
transgene, respectively.

Vertical Gene Transfer: The first mechanism of spread, vertical gene 
transfer, is dependent on species modified. Highly domesticated stock 
developed for poultry, swine, and cattle are not well adapted to the 
natural setting and may not be able to survive and reproduce there. 
However, if feral populations are locally available, then local adaptation 
is not a major barrier to gene spread, as the domesticated GM stock may be 
able to mate with the highly adapted native populations. Aquatic species 
present the greatest concern in this regard because aquatic environments 
are highly connected throughout the world and readily available feral 
populations exist for all domesticated species. Although feral populations 
do not exist locally for every domesticated species, if the GM organism has 
an economic advantage, we must assume that human intervention will 
transport such organisms to area(s) of the world where native populations 

Invasion of New Territories: The second mechanism of spread, invasion of 
new territories, depends on the functionality of the transgene. The 
anthropogenic introduction of any exotic organisms into natural communities 
is a serious ecological concern because exotics could adversely affect 
communities in many ways, including eliminating populations of other 
species.(2) The release of transgenic organisms into natural environments, 
however, poses additional ecological risks÷although transgenic individuals 
retain most of the characteristics of their wild-type counterparts, they 
may also possess some novel advantage. A transgene for enhanced 
environmental adaptation, such as heat tolerance, would allow cold water 
fish with this gene to invade cool and warm water environments while 
maintaining populations in current habitats. As such, GM fish could 
reproduce at a faster rate; their population may increase unchecked and 
adversely affect other species. As a consequence, transgenic organisms 
might threaten the survival of wild-type conspecifics as well as other 
species in a community.(3)

Horizontal Gene Transfer: The third mechanism of spread, horizontal gene 
transfer, occurs naturally through viruses and transposons, but at such low 
rates that it would not normally be an additional concern. However, if a 
virus or transposon is used to insert the transgene construct, even if the 
virus is disabled, it may be possible for the element to recombine with 
other naturally occurring viruses and spread into new hosts.

Evaluating Risk

Regardless of the mechanism of gene spread, the ultimate fate of the 
transgene will be determined by the same forces that direct evolution, 
i.e., natural selection acting on fitness. Thus, risk assessment can be 
accomplished by determining the outcome of natural selection for increased 
fitness. This conclusion assumes that the natural populations are large 
enough to recover from such introductions, i.e., natural selection will 
have time to readjust the population to its previous state. Fitness in this 
context is not simply survival to market age but all aspects of the 
organism that result in spread of the transgene. Muir and Howard reduced 
these aspects to six net fitness components: juvenile and adult viability, 
age at sexual maturity, female fecundity, male fertility, and mating 
success.(1,4,5) Mating success is often overlooked because it is not a 
factor in artificial breeding programs but is often the strongest factor 
driving natural selection.(6)

Potential Hazards

Extinction Hazard: Muir and Howard found that pleiotropic effects of 
transgenes that have antagonistic effects on net fitness components can 
result in unexpected hazards, such as local extinction of the species 
containing the transgene.(7,1) Such transgenes were referred to as Trojan 
Genes. A Trojan Gene is a gene that drives a population to extinction 
during the process of spread as a result of destructive self-reinforcing 
cycles of natural selection. For example, if a transgene enhances mating 
success while reducing juvenile viability, the least fit individuals obtain 
the majority of the matings while the resulting transgenic offspring do not 
survive as well. The result is a gradual spiraling down of population size 
until eventually both wild-type and transgenic genotypes become locally 
extinct.(7) These results were later theoretically verified by Hedrick.(8) 
Local extinction of a wild-type population from a transgenic release could 
have cascading, negative effects on the rest of the community.

The interaction of mating success and juvenile viability is not the only 
mechanism that can produce a Trojan Gene effect. Muir and Howard have shown 
that there are other ways in which a Trojan Gene can result, such as if the 
transgene increases male mating success but reduces daily adult viability, 
or the transgene increases adult viability but reduces male fertility.(1) 
The latter case is of particular interest because transgenes for disease 
resistance or stress tolerance can increase offspring viability and 
transgenes can also reduce male fertility, as has been reported for 
transgenic tilapia containing the growth hormone (GH) gene.(9) Extinction 
hazards predicted in this case parallel the use of sterile males to 
eradicate pest insects. However, in the latter program, males are 
completely sterile and must be reintroduced repeatedly to cause extinction. 
In effect, the viability of sterile males is near 1.0 (due to repeated 
introduction) while male fertility is 0%. Such population extinction, as a 
result of the antagonistic pleiotropic effects of transgenes on viability 
and fertility, represents a new class of Trojan Genes, which suggests that 
attempts to reduce transgenic male fertility that do not result in complete 
male sterility may increase hazard rather than reduce it.(9)

Invasion Hazard: Muir and Howard also confirmed that, as expected, if any 
of the net fitness components are improved by the transgene, while having 
no adverse side effects, the transgene will invade a population.(1,4) 
However they showed that advantages in one fitness component can offset 
disadvantages in another and still result in an invasion risk. Experimental 
evidence that transgenes have multiple effects on fitness components was 
presented by Muir and Howard with the Japanese rice fish, medaka (Oryzias 
latipes).(4) They found that insertion of a growth hormone gene resulted in 
a 30% reduction in juvenile viability, a 12.5% reduction in age at sexual 
maturity, and a 29% increase in female fecundity, relative to wild type. 
Our model predicted that advantages in both age at sexual maturity and 
fecundity are sufficient to overcome the viability disadvantage produced by 
the transgene and would present an invasion risk if released. The model 
also predicted that for a wide range of parameter values, transgenes could 
spread in populations despite high juvenile viability costs if transgenes 
also have sufficiently high positive effects on other fitness components.

This research clearly shows that all six net fitness components must be 
estimated to determine risk. Simple models, such as those presented by 
Mclean and Laight that are based on viability or other single fitness 
components, are very misleading.(10) Also, those components need to be 
integrated into a model that combines them into one prediction of risk. In 
the next part, I (W. M.) will examine experiments to estimate net fitness 
components and review development of the model.


1. Muir WM and Howard RD. 2001. Environmental risk assessment of transgenic 
fish with implications for other diploid organisms. Transgene Research. In 
2. Bright C. 1996. Understanding the threat of biological invasions. In 
State of the World 1996: A World Watch Institute report on progress toward 
a sustainable society, ed. L Starke, 95-113. New York: WW Norton.
3. Tiedje JM et al. 1989. The planned introduction of genetically 
engineered organisms: Ecological considerations and recommendations. 
Ecology 70: 298-315.
4. Muir WM and Howard RD. 2001. Fitness components and ecological risk of 
transgenic release: A model using Japanese medaka (Oryzias latipes). 
American Naturalist 158: 1-16.
5. Muir WM and Howard RD. 2001. Methods to assess ecological risks of 
transgenic fish releases. In Genetically engineered organisms: Assessing 
environmental and human health effects, eds. DK Letourneau and BE Burrows, 
355-383. CRC Press.
6. Hoekstra HE et al. Strength and tempo of directional selection in the 
wild. PNAS USA 98: 9157-9160.
7. Muir WM and Howard RD. 1999. Possible ecological risks of transgenic 
organism release when transgenes affect mating success: Sexual selection 
and the Trojan Gene hypothesis. PNAS USA 24: 13853-13856.
8. Hedrick PW. 2001. Invasion of transgenes from salmon or other 
genetically modified organisms into natural populations. Canadian Journal 
of Fisheries and Aquatic Sciences 58: 841-844.
9. Rahman MA and Maclean N. 1999. Growth performance of transgenic tilapia 
containing an exogenous piscine growth hormone gene. Aquaculture 173: 333-
10. Maclean N and Laight RJ. 2000. Transgenic fish: An evaluation of 
benefits and risks. Fish and Fisheries 1: 146-172.

William M. Muir
Department of Animal Science 
Purdue University


|                   GENET                     |
| European NGO Network on Genetic Engineering |
|                                             |
|             Hartmut MEYER (Mr)              |
|               Kleine Wiese 6                |
|           D - 38116 Braunschweig            |
|                 Germany                     |
|                                             |
| phone: +49-531-5168746                      |
| fax:   +49-531-5168747                      |
| email:                    |