Cisgenics- Transgenics without the Transgene

posted in: Science | 12

Recently at the International Horticultural Congress in Lisbon, Portugal, a workshop was dedicated to transgenic crop biology and its integration with public perception.  As mentioned in previous posts, the central theme is to placate the misinformed public opinion by using clever technologies to circumvent traditional unfounded criticisms of biotechnology.

Dr. Franz Krenz was the first speaker of the session.  His focus was in describing what have been known as cisgenic technologies, or the moniker sometimes applied to allele-specific marker assisted selection, precision breeding.*  Dr. Krenz and colleagues have adopted a very strict interpretation of what cisgenic means.  By his definition, a cisgenic plant contains regulatory regions and protein-coding regions from the same species, shuttled by biotechnological means.  There are no bacterial genes for resistance, no viral promoters, no other genic sequences. Corn to corn, rice to rice, quince to quince.  It would be like moving a gene that controls eye color from one person to another to another to make their blue eyes brown.  Homo sapiens to Homo sapiens.  Nothing fancy.

In plants naturally-occurring beneficial gene variants are quite common, yet oftentimes occur in unimproved species with limited commercial potential.  Specific gene variants confer resistance to disease, variation in flowering time and production traits like fruit size and yield.  These have been described in many horticultural and agronomic crops.  To breed these traits into existing lines using traditional crossing methods might take decades, depending on the crop.  For example, apple scab prevention requires 20-30 sprays per season, sprays that weigh on the environment, the farmer’s bottom line, and place more chemicals into consumer products.  For a long time science has searched for a solution. In 1946 scientists identified natural resistance to scab in Malus floribunda, a wild apple relative.  The gene was identified years later.

Back in the 50’s, crosses were made, and the resistance to scab moved to new commercial lines- along with >30,000 other genes that were potentially inconsistent with commercial apple qualities.  This phenomenon of linkage drag means that you can’t easily just breed in a single desired trait, that you bring the rest of the non-commercial qualities along for the meiotic ride into subsequent generations.  To get the apple-scab resistance gene into plant lines with commercial apple potential took almost fifty years!

Imagine if that single beneficial gene could be picked up and moved to a new line without all the deleterious genetic baggage?  Certainly modern transgenic technologies could do (and did) just that.  Yet to survive the non-scientific onslaught of anti-transgenic interests, scientists had to work around the traditional means of transgenic technologies to make it acceptable.  Over the last decade, scientists have isolated that one beneficial gene, and only that gene, and moved it alone to commercial plants.

The process took a few years rather than five decades and the cost to achieve this and deregulate was about €6M instead of ten times that and many scientist careers.   Dutch consumers do find this form of genetic engineering acceptable, as it provides a healthy product with less chemical intervention and lower environmental impact.  Plus, it is apple genes into apples.  We do that already with crosses.

Still there are opponents to the technology, but most of their their weak arguments disabled via these techniques.  Unfortunately, the end product is the same, maybe even less effective, than if traditional transgenic approaches were used, and it takes a lot more time and money to make it happen.

This is just one example of how scientists are cleverly working around warped public perception problems to solve real issues, and enhance sustainable production.  Cisgenics will be at least a stop-gap solution in the European Union until public education and perception refocus real problems in sustainable agriculture.  For now, the practices of cisgenics may be the central means of introducing traits to plants that can benefit the consumer and environment without the lengthy breeding process, and most of all without raising the ire of those that seek to stop transgenic technology.

*Precision Breeding has also been used to refer to marker assisted selection (MAS), which is a tool for checking the results of breeding experiments, not a type of genetic engineering.

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Kevin is a public scientist that enjoys illuminating hot-button scientific issues for non-scientists using an evidence-based approach. Kevin is always uncomfortable referring to himself in the third person.

  • Pam Ronald

    great post.

    Some cisgenics will introduce genes that are more diverse than transgenics. Eg. A wild apple gene into apple can be something completely new to the genome.

  • It is good to hear more opinions about Cisgenics, because there are some very specific places where it can help plant breeders. Fruit trees are a great example because of the long time it takes to go from seed to flower. If you are just trying to introgress one gene into your favorite apple variety, why not snip it out and put it in instead of going through the lengthy process? The likelihood of reproducing your exact Honeysweet apple is very low, and could be 40 years too late.
    One of the objections people have to genetic engineering is about what the side-effects could be. It is assumed that plant breeding is automatically safe or has no non-target effects when compared with transgenics (or cisgenics as the case may be). But I have a great example of published research that shows the opposite – for fungus-resistant apples, no less:
    http://onlinelibrary.wiley.com/doi/10.1111/j.1570-7458.2009.00942.x/abstract
    They compared apples that had a fungus resistance gene bred into an apple variety versus transformed with the gene through genetic engineering. It turns out that the other genes dragged into the apple through breeding were negatively affecting insect species that lived on or around the tree, while the genetically engineered version did not. (or rather, did much less) Imagine a future wherein genetic engineering is common practice on an everyday basis – The Center for Food Safety would be citing this study to argue that plant breeding should be banned!

  • Andre

    1. The last but one para seems odd to me and may warrant some redrafting.

    2. “Cisgenics will be at least a stop-gap solution in the European Union until public education and perception refocus real problems in sustainable agriculture.” I’m afraid this is wishful thinking.

    The destruction of a grapevine trial in Colmar (to test a resistance against the grapevine fanleaf virus (GFLV) that can easily be explained as a kind of vaccination — same as for your transgenic papaya) shows that new objections are invented, or old ones recycled despite their lack of relevance.

    “GMO testing fields, the Faucheurs volontaires said, are the first step of a commercial venture aiming at imposing, with the backing of the European Commission, crops that are currently not authorised and more particularly rejected by the population and the professionals.” What would be the ultimate purpose of a test if it were not a step towards commercial use? What about a test the conditions of which were discussed with and agreed upon by a broad panel of stakeholders, including the professionals (of course those not adhering to the extremist positions of the Faucheurs volontaires and their altermondialiste and other anti=corporate allies)?

    “This test is useless and deficient: the flowers having been suppressed, it cannot conclude on the possible move of transgene elements into the fruit or wine.” The facts are, one, that the transgene is in the rootstock and, two, that the flowers were removed precisely to meet concerns from opponents.

    They requested (well, curious way of making requests…) that “public funds be used to finance research on alternative ways of combating the grapevine fanleaf virus, rather than GMOs which are known to generate not only dependence of farmers, winegrowers and land workers on patents on life, but also extraordinary profits for the private sector represented here by agrochemical industry.”

    3. Karl, you cannot introgress one gene into your favorite apple variety, or into any vegetative reproduced variety. You can introgress the gene into the apple gene pool, but then you must breed entirely new varieties. The traditional method is extraordinarily difficult.

    • Good points, Andre. What I meant by introgressing a gene into a favorite apple variety was that you could cross an apple tree with the gene of interest with the variety you want it to be like, and then each generation cross it again to the same variety (backcrossing for those non-geneticist types). Each generation, you remove half of the non-favorite DNA and replace it with DNA from your favorite variety. You are right in saying that you cannot introduce just one gene, as even if you get something very close to the original variety (plus your gene) there will be other linked genes dragged along in the process with potential harmful or beneficial effects. This would be relatively easy to do in maize, but apples would take forever! The process can be sped up with molecular markers, but I don’t know how to speed up the juvenile-to-adult development of fruit trees!

    • I understood Karl’s comment to mean backcrossing as well, but perhaps that’s because I’m used to maize where bringing one gene (along with some linked unwanted stuff) into a line is fairly common. For example, we usually backcross transgenic events into 3 maize inbred lines.

      Andre, unfortunately I think you are right. Every time the questions of opponents of genetic engineering or other ag technology are addressed, they move the goal posts. Still, I have hope that cisgenics will be more accepted, especially as more papers like the apple paper Karl mentioned come out.

  • Kevin Folta

    Hi Andre, Good points, as always. I guess the one ray of hope here is that Dutch consumers do find this acceptable. I didn’t see any data, nor do I know the questions, and I have no idea if the rest of Europe was polled and found it unacceptable. All I know is that Dr. Krenz indicated that the public acceptance of cisgenics was surprisingly high.

    Kevin

  • Speaking of cisgenic acceptance – any one have an idea why the genetically engineered salmon aren’t cisgenic? I guess it’s because cisgenics weren’t common 10 years ago when they started developing the fish, but it wouldn’t have been that hard to redo the process. They could have picked an ubiquitous promoter from the same species rather than one from ocean pout which would mean the news couldn’t say things like “The inventors of the genetically engineered fish took some of the genetic code that acts as a switch for the pout’s antifreeze machinery and put it in their salmon to keep the growth hormone on. (NPR)” All this is true, but I bet it makes people think of antifreeze in their tomatoes and gets people all riled up. If I have time later I plan to write a post about GM salmon.

  • Eric Baumholder

    Interesting that cisgenics is considered not to be genetic engineering. It’s not conventional breeding, that’s for sure.

    It’s not genetic engineering for several reasons. It’s not Monsanto, and the activists aren’t protesting it yet. And it’s not resulting in products that compete with existing products in the European Union.

    The sad thing is that promoters of cisgenics tout the value of the technology by alleging various failures and shortcomings of genetic engineering.

    The moment they run afoul of the organic industry, they’ll discover in short order that it’s genetic engineering after all.

  • Can someone clarify: are the cisgenic apples referred to above actually on the market? I mentioned the abstract idea of cisgenics recently to an opponent of GM, as a way of illustrating how imprecise the notion of a “GMO” is. He called this a fantasy.

    So, is it real?

    Thanks,
    Chris MacDonald
    Food-Ethics.com

    • Great question! Cisgenic plants exist, but as far as I know none have been deregulated, possibly due to the barriers that smaller companies, universities, and individual researchers have to pursuing commercial transgenic plants, namely cost, that big companies can easily meet.

      One cisgenic plant that is on it’s way to deregulation is the Arctic apple developed by Okanagan Specialty Fruits to not turn brown. I learned about the apple in the article “Modifying Plant Growth the Cisgenic Way” by Venkatesh Viswanath and Steven H. Strauss that appeared in the September 2010 issue of the Information Systems for Biotechnology Report. The article discusses some of the regulatory complications of cisgenic crops – such as whether they should they be regulated as stringently as transgenic crops.

  • Andre

    Chris,

    Cisgenics have not yet come across my radar screen. Thereofore, I cannot tell.

    Kevin,

    The story about the panel of consumers is also here in French. However, to my knowledge, the technology has not yet hit the public with a practical achievement. So I remain pessimistic (which allows me to have good surprises…). As a matter of fact, Greenpeace Netherlands says in a myths and facts page:

    Q.: But cisgenics is different from genetic engineering?

    A.: No, cisgenics is genetic engineering with the species’ own genes. The risks of genetic engineering stem from the unpredictable techniques that are used to manipulate plants. The risks do not lie solely in the origin of the genes. Therefore, cisgenics is just another word for genetic manipulation.

  • Nick Larsen

    It would seem that cisgenics could be the solution to problems surrounding bananas, which are incredibly difficult to breed. There are several cultivars that are resistant to black sigatoka and numerous cultivars that are resistant to Panama disease. If one could just insert the resistance genes into Cavendish bananas, you would save banana growers from having to spray over 30 times per year. What I don’t know is:

    Can you use cisgenics when you are dealing with multiple genes? Can you move 4 or 5 genes at a time?

    Of course, this is just one more tool in the arms race with nature. I have documented failures of Bt corn in Belle Glade and it only took a few years for that to happen.