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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.).
Franken-Wheat?
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 come 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 Roots of
the GMO Food Debate
The debate over genetically modified (GM) food is a
heated one. Few contest that we are working in
somewhat murky waters when it comes to genetically modified anything, human
or plant alike. At issue, really, is the question of whether we are prepared
to use the technologies we've discovered.
In other words, are we the equivalent of a herd of
monkeys armed with bazookas, unable to comprehend the sheer destructive power
we possess yet perfectly capable of pulling the trigger?
Or do we simply face the same type of daunting
intellectual challenge as those who discovered fire, electricity, or even
penicillin, at a time when the tools to fully understand how they worked had
not yet been conceived of?
In all of those cases, we were able to probe, study,
and learn the mysteries of these incredible discoveries over time. Sure,
there were certainly costly mistakes along the way. But we were also able to
make great use of them to advance civilization long before we fully
understood how they worked at a scientific level.
Much is the same in the study and practical use of GM
foods.
While the fundamentals of DNA have been well understood
for decades, we are still in the process of uncovering many of the inner
workings of what is arguably the single most advanced form of programming
humans have ever encountered. It is still very much a rapidly evolving
science to this day.
For example, in the 1990s, an idea known simply as
"gene therapy" – really a generalized term for a host of
new-at-the-time experimental techniques that share the simple characteristic
of permanently modifying the genetic make-up of an organism – was all
the rage in medical study. Two decades on, it's hardly ever spoken of. That's
because the great majority of attempted disease therapies from genetic
modification failed, with many resulting in terrible side effects and even
death for the patients who underwent the treatments. Its use in the early
days, of course, was limited almost exclusively to some of the world's most
debilitating, genetically rooted diseases. Still – whether in their
zeal to use a fledgling tool to cure a dreadful malady or in selfish, hurried
desire to be recognized among the pioneers of what they thought would be the
very future of medicine – doctors chose to move forward at a dangerous
pace with gene therapy.
In one famous case, and somewhat typical of the times, University
of Pennsylvania physicians enrolled a sick 18-year-old boy with a liver
mutation into a trial for a gene therapy that was known to have resulted in
the deaths of some of the monkeys it had just been tested on. The treatment
resulted in the young man's death a few days later, and the lengthy
investigation that followed resulted in serious accusations of what can only
be called "cowboy medicine."
Not one of science's prouder moments, to be sure. But
could GM foods be following the same dangerous path?
After all, the first GM foods made their way to market
during the same time period. The 1980s saw large-scale genetic-science
research and experimentation from agricultural companies, producing
everything from antibiotic-resistant tobacco to pesticide-hardy corn. After
much debate and study, in 1994 the FDA gave approval to the first GM food to
be sold in the United States: the ironically named Flavr
Savr tomato, with its delayed ripening genes which
made it an ideal candidate for sitting for days or weeks on grocery store
shelves.
Ever since, there has been a seeming rush of modified
foods into the marketplace.
Modern GM foods include soybeans, corn, cotton, canola,
sugar beets, and a number of squash and greens varieties, as well as products
made from them. One of the most prevalent modifications is to make plants
glyphosate-resistant, or in common terms, "Roundup Ready." This
yields varieties that are able to stand up to much heavier doses of the
herbicide Roundup, which is used to keep weeds and other pest plants from
damaging large monoculture fields, thereby reducing costs and lowering risks.
In total it is estimated that modern GM crops have
grown to become a $12 billion annual business since their commercialization
in 1994, according to the International Service for the Acquisition of Agri-biotech Applications (ISAAA). Over 15 million farms
around the world are reported to have grown GM crops, and their popularity
increases every year.
They've brought huge improvements in shelf life, pathogen
and other stress resistance, and even added nutritional benefits. For
instance, yellow rice – which was the first approved crop with an
entirely new genetic pathway added artificially – provides
beta-carotene to a large population of people around the world who otherwise
struggle to find enough in their diets.
However, the race for horticulturalists to the genetic
table in the past few decades – what could be described accurately as
the transgenic generation of research – has by no means been our
first experiment with the genetic manipulation of food. In fact, if anything,
it is a more deliberate, well studied, and careful advance than those that
came before it.
A VERY Brief
History of Genetically Modified Food
Some proponents of GMO foods are quick to point out
that humans have been modifying foods at the genetic level since the dawn of
agriculture itself. We crossbreed plants with each other to produce hybrids
(can I interest you in a boysenberry?). And of course, we select our crops
for breeding from those with the most desirable traits, effectively
encouraging genetic mutations that would have otherwise resulted in natural
failure, if not helped along by human hands. Corn as we know it, for example,
would never have survived in nature without our help in breeding it.
Using that as a justification for genetic meddling,
however, is like saying we know that NASCAR drivers don't need seatbelts
because kids have been building soapbox racers without them for years.
Nature, had the mix not been near ideal to begin with, would have prevented
such crossbreeding. Despite Hollywood's desires, one can't simply crossbreed
a human and a fly, or even a bee and a mosquito, for that
matter – their genetics are too different to naturally mix. And
even if it did somehow occur, if it did not make for a hardier result, then
natural selection would have quickly kicked in.
No, I am talking about real, scientific genetic mucking
– the kind we imagined would result in the destruction of the world
from giant killer tomatoes or man-eating cockroaches in our B-grade
science-fiction films. Radiation mutants.
Enterprising agrarians have been blasting plants with
radiation of all sorts ever since we starting
messing around with atomic science at the dawn of the 20th
century. In the 1920s, just when Einstein and Fermi were getting in their
grooves, Dr. Lewis Stadler at the University of
Missouri was busy blasting barley seeds with X-rays – research that
would usher in a frenzy of mutation breeding to follow.
With the advent of nuclear technology from the war
effort, X-rays expanded into atomic radiation, with the use of gamma rays
leading the pack. The United States even actively encouraged the practice for
decades, through a program dubbed "Atoms for Peace" that proliferated nuclear technology throughout various parts
of the private sector in a hope that it would improve the lives of many. And
it did.
Today, thousands of agricultural varieties we take for
granted – including, according to a 2007 New York Times feature
on the practice, "rice, wheat, barley, pears, peas, cotton, peppermint,
sunflowers, peanuts, grapefruit, sesame, bananas, cassava and sorghum"
– are a direct result of mutation breeding. They would not be
classified as GM foods, in the sense that we did not use modern transgenic
techniques to make them, but they are genetically altered nonetheless, to the
same or greater degree than most modern GMO strains.
Unlike modern GM foods – which are often closely
protected by patents and armies of lawyers to ensure the inventing companies
reap maximum profits from their use – the overwhelming majority of the
original generations of radiation-mutated plant varieties came out of
academic and government sponsored research, and thus were provided free and
clear for farmers to use without restriction.
With the chemical revolution of the mid-20th
century, radiation-based mutations were followed by the use of chemical
agents like the methyl sulfate family of mutagens. And after that, the
crudest forms of organic genetic manipulation came into use, such as the uses
of transposons, highly repetitive strands of DNA discovered in 1948 that can
be used like biological duct tape to cover whole sections the genome.
These modified crops stood up better to pests, lessened
famines, reduced reliance on pesticides, and most of all enabled farmers to
increase their effective yields. Coupled with the development of commercial
machinery like tractors and harvesters, the rise of mutagenic breeding
resulted in an agricultural revolution of a magnitude few truly appreciate.
In the late 1800s, the overwhelming majority of global populations lived in
rural areas, and most people spent their lives in agrarian pursuits. From
subsistence farmers to small commercial operations, the majority of the
population of every country, the US included, was employed in agriculture.
Today, less than 2% of the American population (legal
and illegal combined) works in farming of any kind. Yet we have more than
enough food to feed all of our people, and a surplus to export to more densely
populated nations like China and India.
The result is that a sizable percentage of the
world’s plant crops today – the ones on top of which much of the
modern-era GMO experiments are done – are already genetic mutants.
Hence the slippery slope that serves as the foundation of the resistance from
regulators over the labeling of GM food products. Where do you draw the line
on what to label? And frankly, how do you even know for sure, following the
Wild-West days of blasting everything that could grow with some form or
another of radiation, what plants are truly virgin
DNA?
The world's public is largely unaware that many of the
foods they eat today – far more than those targeted by anti-GMO
protestors and labeling advocates – are genetically modified. Yet we
don't seem to be dying off in large numbers, like the anti-RNAi researchers project will happen. In fact, global
lifespans have increased dramatically across the board in the last century.
The Rise of
Careful
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.
The Casey Extraordinary Technology team has been
tracking the leading lights of the RNAi medical
industry for some time. Recently, one of our small biotech upstarts struck a
potentially massive, exclusive deal with an agricultural giant to seed its
own RNAi research program. Success could mean
billions for both firms. If you'd like to know what company we believe will
profit most from the next generation of GM food development, subscribe to CET.
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