The debate of genetically modified organisms (GMOs), agricultural crops in particular, has raged for decades. But while the debate has been raging, and passions flare, GMO plantings are up and we're feeding a growing population around the world, observes Alex Daley of Casey Research.

Last month, a group of Australian scientists published a warning to the citizens of the country and of the world who collectively gobble up some $34 billion annually of its agricultural exports. The warning concerned the safety of a new type of wheat.

As Australia's number-one export, a $6-billion annual industry, and the most-consumed grain locally, wheat is of the utmost importance to the country. A serious safety risk from wheat-a mad wheat disease of sorts-would have disastrous effects for the country and for its customers.

Which is why the alarm bells are being rung over a new variety of wheat being ushered toward production by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) of Australia. In a sense, the crop is little different than the wide variety of modern genetically modified foods. A sequence of the plant's genes has been turned off to change the wheat's natural behavior a bit, to make it more commercially viable (hardier, higher yielding, slower decaying, etc.).

What's really different this time-and what has Professor Jack Heinemann of the University of Canterbury, NZ, and Associate Professor Judy Carman, a biochemist at Flinders University in Australia, holding press conferences to garner attention to the subject-is the technique employed to effectuate the genetic change. It doesn't modify the genes of the wheat plants in question; instead, a specialized gene blocker interferes with the natural action of the genes.

The process at issue, dubbed RNA interference or RNAi for short, has been a hotbed of research activity ever since the Nobel Prize-winning 1997 research paper that described the process. It is one of a number of so-called "antisense" technologies that help suppress natural genetic expression and provide a mechanism for suppressing undesirable genetic behaviors.

RNAi's appeal is simple: it can potentially provide a temporary, reversible off switch for genes. Unlike most other genetic modification techniques, it doesn't require making permanent changes to the underlying genome of the target. Instead, specialized siRNAs-chemical DNA blockers based on the same mechanism our own bodies use to temporarily turn genes on and off as needed-are delivered into the target organism and act to block the messages cells use to express a particular gene. When those messages meet with their chemical opposites, they turn inert. And when all of the siRNA is used up, the effect wears off.

The new wheat is in early-stage field trials (i.e., it's been planted to grow somewhere, but has not yet been tested for human consumption), part of a multi-year process on its way to potential approval and not unlike the rigorous process many drugs go through. The researchers responsible are using RNAi to turn down the production of glycogen. They are targeting the production of the wheat branching enzyme, which if suppressed, would result in a much lower starch level for the wheat.

The result would be a grain with a lower glycemic index-i.e., healthier wheat.

This is a noble goal. However, Professors Heinemann and Carman warn, there's a risk that the gene silencing done to these plants might make its way into humans and wreak havoc on our bodies. In their press conference and subsequent papers, they describe the possibility that the siRNA molecules-which are pretty hardy little chemicals and not easily gotten rid of-could wind up interacting with our RNA.

If their theories prove true, the results might be as bad as mimicking glycogen storage disease IV, a super-rare genetic disorder, which almost always leads to early childhood death.

"Franken-Wheat Causes Massive Deaths from Liver Failure!"

Now that is potentially headline-grabbing stuff. Unfortunately, much of it is mere speculation at this point, albeit rooted in scientific expertise on the subject.

What they've produced is a series of opinion papers-not scientific research nor empirical data to prove that what they suspect might happen, actually does. They point to the possibilities that could happen if a number of criteria are met:

.If the siRNAs remain in the wheat in transferrable form, in large quantities, when the grain makes it to your plate. And.

    If the siRNA molecules interfere with the somewhat different but largely similar human branching enzyme as well.

Then the result might be symptoms similar to such a condition, on some scale or another, anywhere from completely unnoticeable to highly impactful.

They further postulate that if the same effect is seen in animals, it could result in devastating ecological impact. Dead bugs and dead wild animals.

Luckily for us, as potential consumers of these foods, all of these are easily testable theories. And this is precisely the type of data the lengthy approval process is meant to look at.

Opinion papers like this-while not to be confused with conclusions resulting from solid research-are a critically important part of the scientific process, challenging researchers to provide hard data on areas that other experts suspect could be overlooked. Professors Carman and Heinemann provide a very important public good in challenging the strength of the due-diligence process for RNAi's use in agriculture, an incomplete subject we continue to discover more about every day.

However, we'll have to wait until the data comes back on this particular experiment-among thousands of similar ones being conducted at government labs, universities, and in the research facilities of commercial agribusinesses like Monsanto and Cargill-to know if this wheat variety would in fact result in a dietary apocalypse.

That's a notion many anti-genetically modified organism (GMO) pundits seem to have latched onto following the press conference the professors held. But if the history of modern agriculture can teach us anything, it's that far more aggressive forms of GMO foods appear to have had a huge net positive effect on the global economy and our lives. Not only have they not killed us, in many ways GMO foods have been responsible for the massive increases in public health and quality of life around the world.

The Past Isn't Prologue

The science of GM food has advanced considerably since the dark ages of the 1920s. Previous versions of mutation breeding were akin to trying to fix a pair of eyeglasses with a sledgehammer-messy and imprecise, with rare positive results. And the outputs of those experiments were often foisted upon a public without any knowledge or understanding of what they were consuming.

Modern-day GM foods are produced with a much more precise toolset, which means less unintended collateral damage. Of course it also opens up a veritable Pandora's box of new possibilities (glow-in-the-dark corn, anyone?) and with it a whole host of potential new risks. Like any sufficiently powerful technology, such as the radiation and harsh chemicals used in prior generations of mutation breeding, without careful control over its use, the results can be devastating. This fact is only outweighed by the massive improvements over the prior, messier generation of techniques.

And thus, regulatory regimes from the FDA to CSIRO to the European Food Safety Authority (EFSA) are taking increasing steps to ensure that GM foods are thoroughly tested long before they come to market. In many ways, the tests are far more rigorous than those that prescription drugs undergo, as the target population is not sick and in need of urgent care, and for which side effects can be tolerated. This is why a great many of the proposed GM foods of the last 20 years, including the controversial "suicide seeds" meant to protect the intellectual property of the large GM seed producers like Monsanto (which bought out Calgene, the inventor of that Flavr Savr tomato, and is now the 800-lb. gorilla of the GM food business), were never allowed to market.

Still, with the 15 years from 1996 to 2011 seeing a 96-fold increase in the amount of land dedicated to growing GM crops and the incalculable success of the generations of pre-transgenic mutants before them, scientists and corporations are still in a mad sprint to find the next billion-dollar GM blockbuster.

In doing so they are seeking tools that make the discovery of such breakthroughs faster and more reliable. With RNAi, they may just have found one such tool. If it holds true to its laboratory promises, its benefits will be obvious from all sides.

Unlike previous generations of GMO, RNAi-treated crops do not need to be permanently modified. This means that mutations, which outlive their usefulness, like resistance to a plague, which is eradicated, do not need to live on forever. This allows companies to be more responsive, and potentially provides a big relief to consumers concerned about the implications of eating foods with permanent genetic modifications.

The simple science of creating RNAi molecules is also attractive to people who develop these new agricultural products, as once a messenger RNA is identified, there is a precise formula to tell you exactly how to shut it off, potentially saving millions or even billions of dollars that would be spent in the research lab trying to figure out exactly how to affect a particular genetic process.

And with the temporary nature of the technique, both the farmers and the Monsantos of the world can breathe easily over the huge intellectual-property questions of how to deal with genetically altered seeds. Not to mention the questions of natural spread of strains between farms who might not want GMO crops in their midst. Instead of needing to engineer in complex genetic functions to ensure progeny don't pass down enhancements for free and that black markets in GMO seeds don't flourish, the economic equation becomes as simple as fertilizer: use it or don't.

While RNAi is not a panacea for GMO scientists-it serves as an off switch, but cannot add new traits nor even turn on dormant ones-the dawn of antisense techniques is likely to mean an even further acceleration of the science of genetic meddling in agriculture. Its tools are more precise even than many of the most recent permanent genetic-modification methods. And the temporary nature of the technique-the ability to apply it selectively as needed versus breeding it directly into plants which may not benefit from the change decades on-is sure to please farmers, and maybe even consumers as well.

That is, unless the scientists in Australia are proven correct, and the siRNAs used in experiments today make their way into humans and affect the same genetic functions in us as they do in the plants. The science behind their assertions still needs a great deal of testing. Much of their assertion defies the basic understanding of how siRNA molecules are delivered-an incredibly difficult and delicate process that has been the subject of hundreds of millions of dollars of research thus far, and still remains, thanks to our incredible immune systems, a daunting challenge in front of one of the most promising forms of medicine (and now of farming too).

Still, their perspective is important food for thought...and likely fuel for much more debate to come. After all, even if you must label your products as containing GMO-derived ingredients, does that apply if you just treated an otherwise normal plant with a temporary, consumable, genetic on or off switch? In theory, the plant which ends up on your plate is once again genetically no different than the one which would have been on your plate had no siRNAs been used during its formative stages.

One thing is sure: the GMO food train left the station nearly a century ago and is now a very big business that will continue to grow and to innovate, using RNAi and other techniques to come.

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