[To contribute to this conference, send your message to
For further information on the Electronic Forum on Biotechnology in Food and
Agriculture see Forum website.
NB - participants are assumed to be speaking on their own behalf, unless they state otherwise.]
Sent: 26 June 2002 09:28
Subject: 75: Gene flow in animals
My name is David Trus. I am a quantitative geneticist working for Agriculture & Agri-Food Canada on animal breeding issues. I haven't seen much reference to gene flow in animals during this forum so I would like to add a few thoughts. [Many thanks to David Trus for this message, the first one dealing specifically with the issue of gene flow in livestock populations. Remember there are 3 days left for sending messages, the conference closing on 28 June, so additional comments on the livestock situation as well as specific comments about gene flow and GM forest trees and fish are highly welcome...Moderator]
I will start from the issue of "genetic pollution" which was raised by several contributors [see e.g. messages 30 (June 10) and 39 (June 11)...Moderator], as it relates to the concept of purity. In Canada, we have federal legislation under which animal breeds are recognized and breed associations operate. The Act contains a minimum definition for "purebred" of 7/8ths inherited from foundation stock of the breed or from other purebreds. Many breeds impose more rigorous criteria for purebreds. However, in biological systems there is rarely such a thing as absolute purity. Similarly, the concept of "pollution" is a relative one only. Any apparent purity in a breeding population is really a function of the amount of time since the last novel genetic "migrations" (intentional or otherwise), the nature of the novel genetic contributions and the genetic stability of the resulting population. This can be true for conventional or, perhaps in the future, for transgenic animal introductions.
In order to recognize a distinct breed in the first place, we use criteria
similar to the DUS mentioned by Derek Burke (message 64, June 21). A breed
can only be recognized as distinct if it represents a viable population of
1. Common genetic origin and history
2. Distinct characteristics
3. Genetic stability
Once the breed is recognized, if a novel genetic contribution (i.e. outcross) is made to the population then the resulting progeny may only be recognized as "percentage" animals until such time as the purebred criterion is achieved, again through further breeding-up. But what happens when there is no formal system to help maintain segregated populations, as I am sure happens in many countries?
Here in Canada we generally do not have many indigenous animal populations that would be at risk from gene flows from domesticated animals (whether conventional or transgenic). Cross-species flows would also appear to be so low as to be insignificant. Nevertheless, breed to breed gene flows, which can compromise the viability and/or integrity of existing purebred populations, can take place as a result of the following;
1. Intentional crossing
2. Unintentional breedings due to isolation failures
3. Multiple breedings (e.g. due to use of bull batteries, clean-up bulls, double inseminations, pooled semen)
4. Registration, parentage verification and administrative errors
Appropriate process controls need to be in place to limit any negative impact of the above. Ultimately, unintentional gene flow can be further limited by use of neutering, implementation of isolation and other biosafety measures, and through use of tracking systems with built-in monitoring and audit capability. This is the first aspect of risk, which quite likely has additional levels of complexity in developing and bio-diverse countries. In summary, gene flows can and do happen, but they can be limited.
The second aspect of risk is the potential harm that could come from unintentional gene flows, but which we know so little about. I would suggest that the black box that quantitative/population geneticists use to model population changes will remain black for a considerable time yet. However, risk assessment models such as proposed by W. Muir (message 69, June 22) are essential. Meanwhile, as with any good statistical modelling, all the assumptions should be stated up-front. If everyone did that, I wonder if the gene flow issue would look different?
David Trus, P.Ag.
Agriculture & Agri-Food Canada
TRUSD (at) agr.gc.ca
Sent: 26 June 2002 10:16
Subject: 76: Fitness of lab modified organisms in natural settings
This is from Dr Wayne Knibb. I am a geneticist (population and molecular biologist) working on aquacultured species.
Though not theoretically impossible, it is an extraordinary claim to have empirical evidence of laboratory modified organisms with increased fitness in natural settings (Bill Muir, message 69, June 22), if natural settings are taken to mean the wild "natural" environments with natural selective forces including the presence of competitive conspecifics, and fitness is assumed to be Darwinian fitness.
Such novel claims should be examined closely, not only as "extraordinary claims require extraordinary evidence", but as the conditions which satisfy such claims are stringent, namely, the demonstration of gene frequency increases across generations (to reflect the net fitness of the gene) in response to natural selection. Such claims have been mooted in the past (for bacteria), but have not withstood scrutiny.
[Bill Muir in message 69 referred to the paper by Stewart et al. (1997) in Molecular Ecology, in which they describe a field experiment they carried out "in which transgenic and nontransgenic rapeseed plants were planted in natural vegetation and cultivated plots and subjected to various selection pressures in the form of herbivory from insects.". Based on the results, they conclude "where suitable habitat is readily available, there is a likelihood of enhanced ecological risk associated with the release of certain transgene/crop combinations such as insecticidal rapeseed". Quotations are from the paper's abstract...Moderator]
Dr Wayne Knibb
Principal Research Scientist
Bribie Island Aquaculture Research Centre
144 North Street, Woorim
PO Box 2066
Bribie Island Queensland 4507
Ph (07) 34002000 / 2052
e-mail: wayne.knibb (at) dpi.qld.gov.au
Sent: 26 June 2002 10:27
Subject: 77: Re: Models - Human intervention - Developing countries
Hi Professor Muir again (sorry to send in so many comments). This is in reply to Jane Morris (message 74, June 25) questions on utility of our model in developing countries.
Regarding use of the model in developing countries, there are three issues.
First, a model is only as good as the estimates of fitness components put into it. Our model is based on extensions of Prout's (1971a) paper. Prout's (1971b) paper shows the predictions of the model were accurate but attributes the success to the ability to measure fitness components in the environment in which the gene will be released. Thus, in order to get accurate estimates, facilities need to be developed which simultaneously 1) restrict the GM organism to those secure facilities and 2) provide a similar environment to that in which the transgene might escape. This type of facility could be exceedingly expensive to build, depending on the type of GM organism examined.
Second, there is the issue of the receiving population size and magnitude of the GM release (brown bag, etc.). The model as presently developed is deterministic, that is it assumes the receiving population size is infinite, in which case genetic drift (genetic sampling errors) and magnitude of release is not important (release of 1 is the same as 1000, the only difference is the time to fixation or loss). However, with small population sizes stochastic events can be more powerful than natural selection and fix poorly adapted genes which could result in extinction of the local population. See Lynch and O'Hely (2001) for a discussion of this hazard due to release of domesticated fish into natural populations. The model can be made stochastic to include these factors, I just have not had time to do that. Thus we can include impact of magnitude of release in release. However, we are never going to be able to do things on a fine scale. The assumption is that those fine scale deviations only add noise to the system but do not influence the final outcome.
Finally there is the issue of what harms the model can address. The model can only address ecological risk to native species due to spread of a transgene in the native population. It cannot be used to predict human health risks, changes in farming practices, or other such issues unless they result from secondary ecological impacts due to affected species.
Lynch, M. and M. O'Hely. 2001. Captive breeding and the genetic fitness of
natural populations. Conservation Genetics 2:363-378.
Prout, T. 1971a. The relation between fitness components and population prediction in Drosophila. I: The estimation of fitness components. Genetics 68: 127-149.
Prout, T. 1971b. The relation between fitness components and population prediction in Drosophila. II. Population prediction. Genetics 68: 151-167.
William M. Muir, Ph.D.
1151 Lilly Hall
W. Lafayette, IN 47906
bmuir (at) purdue.edu
Sent: 26 June 2002 11:22
Subject: 78: Re: Risks of genetic engineering
This is from Roberto Verzola, Secretary-general, Philippine Greens and former member of the National Committee on Biosafety of the Philippines.
I have earlier made the point (message 67, June 21) that genetic engineering (GE) increases the risk of damaging mutations. I've been asked by the moderator to relate this to gene flow. The connection is simple: the increased risk carried by a genetically-modified organism is passed on to other organisms of the same species (e.g. by cross-pollination) or of another species (e.g. horizontal gene transfer to fungi or bacteria). Because the carriers of the risk reproduce and multiply, then the risk itself will also be increasing over time. Furthermore, with horizontal gene transfer, the foreign DNA sequences will be operating under a totally new genetic and environmental context, creating new unpredictable risks.
These risks are objectionable for several reasons:
*Genetic privatization*: as the engineered genes flow around, ownership claims associated with them attach themselves to farmers' produce, causing contentious issues. This is especially true for developing countries because most biopatents belong to biotech firms from the developed world.
*genetic contamination*: enough has been said on this matter, where the higher risk associated with an engineered gene transfers itself to non-engineered varieties, creating new environmental and health concerns. Just to mention one: by increasing the level of Bt toxin in the fields, whether or not a major corn borer infestation occurs, Bt crops will hasten the development of Bt resistance, rendering useless an important tool of organic farmers for controlling this pest. Organic farming is an important alternative of the developing world to agrochemical dependence and foreign control.
*market rejection*: if the engineered genes are not wanted by consumers, gene flow creates marketing problems not only for farmers who used the gene on purpose, but also those who unknowingly got the genes into their fields through gene flow. U.S. and Canadian farmers, for instance, have lost major markets due to gene flow. The only market for engineered soya and corn today are countries where consumers are not informed about the presence of the engineered genes due to the absence of mandatory GMO labeling laws. Again, this is especially important to developing countries because most of the GM corn and soya rejected in Europe, Japan, Korea or elsewhere ends up being sold or "donated" in developing countries. Philippine scientists are now doing research on GM mangoes, papayas, bananas, etc. If their transgenes escaped into commercial farms - we could lose our markets for these major export products.
I would like to clarify further what these risks are:
* the risks associated with the foreign gene itself (e.g. allerginicity, toxicity, long-term side-effects, resistance development, etc.)
* the risks associated with the marker gene (e.g. antibiotic resistance)
* the risks associated with the promoters (eg, the recombination hotspot in the cauliflower mosaic virus promoter)
* the unpredictable risks associated with the randomness of the insertion process and pleiotrophic effects
I already cited the difference in *actual* damaging mutations in the first generation following conventional breeding (CB) (<0.1%) vs. GE transformation (>99%). That's at least 5 orders of magnitude difference. I do hope that others will post here the more accurate figures from actual industry results.
Here's another way of showing that GE risks are high not only in the first generation of transformed cells but in subsequent generations, using what may be called the input-output method: Introducing foreign genes (Bt gene, marker, etc.) makes the target organism produce proteins that it has not produced in the past. Consider an input-output table: columns represented by amino acids and rows by protein products, with weights as entries (representing amount of each amino acid needed to produce an x amount of a specific protein), with a final row and column of totals, representing the materials balance of all protein production in an organism. A GMO will produce one or more new proteins not found in the non-GM version. These new proteins will require extra amino acids for its production, thus less will be available for the production of other proteins, upsetting the entire material balance of the organism. We cannot possibly predict in advance how the remaining amino acids will be reallotted under the new material balance and how much less of which other proteins will be produced. We can only be certain that the balance has been upset and less of some other proteins will be produced. (Where a protein regulates the production of another substance, a reduction in that protein may very well result in overproduction of the substance it is regulating. This can explain why a side-effect can be *higher* rather than lower levels of another substance (like lignin, or an allergenic substance, for instance).
By introducing such uncertainty, we have added to the system's entropy and raised the risk of abnormal events in the system. Dr. Stewart (message 68, June 22) goes the opposite direction and claims that the risk is lower. How can it be lower when actual results (>99.9% viability in CB and <1% viability in GE) show at least 5 orders of magnitude higher risk for GE in the first generation after transformation? This also immediately falsifies Dr. Knibb's hypothesis (message 63, June 20) that GE is no riskier than CB.
Dr. Stewart claims greater certainty (and therefore lower risk) in GE because the transgenic cassette is known precisely. That may be true, but the insertion point is random, and much of the genome itself is not well-understood by genetic engineers. The risk of increasing the entropy of the genome is surely higher where the insertion point is random, and the system itself is not well-understood and much more complex.
Dr. Stewart says more selection is done after the transformation event, to
reduce the risks associated with unpredictable GE effects. My response:
* The post-transformation selection is done using CB, not GE, supporting the contention that CB reduces risk, while GE increases it
* It is true that no transformed (and very high-risk) cell is immediately commercialized. The first generation engineered mutants go through further CB to eliminate the damaged sections of the genome. But if the side-effects are unpredictable or if they occur only under certain circumstances, perhaps rare, genetic engineers will not know what they are selecting against.
* The fact that unintended side-effects (e.g. higher lignin content, greater tendency to outcross) continue to show up in commercial GMO crops leads us to suspect that more side-effects remain undiscovered. That is, commercial GE organisms continue to carry higher risks.
It is this higher risk carried by GMOs which are transferred to non-GMOs in the process of gene flow. Over time, as the GMO reproduces and multiplies in the field, the risks associated with it also multiplies. The risks associated with GMOs do not have half-lifes; they have doubling times.
rverzola (at) gn.apc.org
Sent: 26 June 2002 19:26
Subject: 79: Re: Fitness of lab modified organisms in natural settings
Professor Muir again in reply to Wayne Knibb (message 76, June 26). Wayne's message contains a number of confuting points.
First my message (69, June 22), that he refers to, only used as it's example rapeseed in natural environments, certainly not a laboratory species. If the rapeseed example was not sufficient, transgenic papaya provides another excellent example (again, not a laboratory species). Because plants and microbes evolve at different rates owing to vastly different generation times, it is not unusual that a virus can destroy a population before a resistant plant is found. GM technology has allowed plants to speed up the evolutionary process. Ferreira et. al. (2002) note that Papaya ringspot virus (PRSV) destroyed nearly all of the papaya hectarage in the Puna district of Hawaii (the native plant in a natural environment). In contrast, these researchers observe that none of the current GM plants have PRSV infection. Again, a clear demonstration that GM organisms can be developed with a greatly enhanced fitness in a natural setting.
Wayne's (Knibb, 1996) position is that all human modifications to an organism will result in a reduced fitness in natural settings. Thus, because, historically, selective breeding and natural mutations have resulted in a reduced fitness of these organisms in natural environments, we should similarly conclude that GM organisms have no risk. As I discussed in message 57 (June 19), these ideas are old fashioned and do not hold up for GM organisms (and clearly refuted by the above example).
His statement that "extraordinary claims require extraordinary evidence" is a two edged sword. Do the claims of no risk requires the same extraordinary evidence as those of risk? Because it is impossible to prove a negative, while easy to disprove a positive (as demonstrated above), Wayne should rethink what evidence should be used to evaluate risk (in either direction). Historical example of risk of non GM organisms (laboratory or other) is not valid.
Ferreira SA, Pitz KY, Manshardt R, Zee F, Fitch M, Gonsalves D 2002. Virus coat protein Transgenic papaya provides practical control of Papaya ringspot virus in Hawaii. PLANT DISEASE 86:101-105William M. Muir, Ph.D.