12 December 2011

Brave new wheat

By
Booming populations, new disease threats and a changing climate are forcing scientists into a desperate race to boost wheat yields and avoid a global crisis. And yet, it’s a race some environmental activists seem intent on thwarting.
GM wheat

This high-yield wheat - made especially for noodles - grew faster, taller and had more seeds than non-GM controls. Yet in July 2011, Greenpeace mowed down this and other GM wheat varieties at a CSIRO experimental facility in Canberra, sparking outrage in scientific communities. Credit: CSIRO

LIKE A BIBLICAL pestilence, it spread unchecked across India and China, turning golden oceans of wheat into blackened wastelands. Then, blown by the winds, the great red cloud swept across the Indian Ocean to continue its easterly creep across Australia.

Yet the fields stayed golden. The only evidence of the passing rust plague was the occasional shrivelled roadside specimen of old varieties escaped from the paddock. It’s 2050, and Australia’s bounteous wheat harvest has been saved. The hundred dollar notes printed that year bore the images of Jeff Ellis, Evans Lagudah, Wolfgang Spielmeyer, Peter Dodds, and Mick Ayliffe, the CSIRO scientists whose teams had genetically modified wheat to resist the rust plague.

The only farfetched aspect of this scenario is that it probably won’t be India and China that miss out on these protective crops. It will be Australia – that’s if the enemies of genetically modified crops have their way.

Groups like Greenpeace, committed to a struggle against GM foods, are keeping the rage alive. In fact, they’re becoming more adamant even as the evidence goes the other way and public acceptance grows. Twenty-five years after the first GM crop was sown and 15 years after their introduction into the human food chain, anti-GM activists decry genetic modification of foodstuffs as the arch-enemy of human health and the environment. Their thinking goes something like this: GM foods are unnatural, inadequately tested, unsafe and a tool for the corporations of the world to control our food supply and get rich.

So what’s the evidence for this? Mostly, the opinion of a minority of scientists, who are lionised and feted by anti-GM campaigners. At the same time, the opinion of thousands of scientists, the evidence of hundreds of reports and 25 years of studies concluding GM food is as safe as conventional food – are ignored.

Sound familiar? It mirrors the heated battle over climate change, with a minority of expert opinion (and many not-so-expert) confusing the issues and waylaying good policy.

And it’s the kind of thing we’ve seen before: Peter Duesberg, a professor of molecular and cell biology at the University of California at Berkeley – famed for being the first to isolate a cancer gene – has long maintained that AIDS isn’t caused by the HIV virus: a review of his evidence in the respected journals Nature and Science found his citations selective and his argument “lacking credibility”. Then there’s former British surgeon Andrew Wakefield, who helped ignite anti-vaccination hysteria by claiming in a paper that autism was linked to the measles/mumps/rubella (MMR) vaccine; a claim refuted by many studies since. His theory led the British Medical Journal, following an investigation, to call his original paper “an elaborate fraud”, and eventually led to Wakefield being deregistered as a physician in Britain.

Greenpeace doesn’t champion fringe scientists when talking about climate change. But when it comes to GM food, it does. Of course, just because you’re in the minority doesn’t mean you’re wrong: in the 1980s, Australian physician Barry Marshall claimed bacteria caused stomach ulcers – and nobody believed him. But he and colleague Robin Warren developed a strong body of evidence and, eventually, proved it – and both collected a Nobel Prize.

In science, fringe players who back their claims with good scientific evidence, eventually win out. And when they can’t, they stay in the fringe; while the mainstream view, rightly, holds sway.
But that’s not how Greenpeace sees it.

In the wee hours of 14 July 2011, three women clad in hazmat suits took whipper-snippers to a plot of the Australian science organisation, the CSIRO’s, GM wheat, growing in Ginninderra, Canberra. They damaged hundreds of thousands of dollars of taxpayers’ money and set the scientists’ work back by a year. One of them, brandishing her motherhood in a choreographed interview, told us: “GM wheat is not safe, and if the government can’t protect the safety of my family, then I will.”

So what was this monster wheat that led the Greenpeace mum to don a hazmat suit and break the law? It wasn’t rust-resistant wheat she destroyed – that wheat is still years away from testing. The breeds she destroyed may not save the world’s wheat in one dramatic stroke, but they could make a big contribution to growing enough food to feed nine billion people – the world’s estimated population by 2050 – while also improving their health, and doing it more sustainably.

Let me tell you a tale of three wheats.

IN LAUDING the power of food science to prevent colorectal cancer, CSIRO scientist David Topping is something of an evangelist. “If we’re right, 60-80% of colorectal cancer is preventable.”

Topping’s faith in science stems from personal experience. As a 12-year-old in post-war England, his bout of rheumatic fever would have been fatal were it not for penicillin procured from Howard Florey’s lab in Oxford. It was, at that time, “more expensive than gold,” he says.

But Topping’s strategy to prevent colorectal cancer promises to be a lot cheaper – indeed, it should end up in our daily bread if his team at CSIRO Food and Nutritional Sciences in Adelaide are successful. “This is an important story”, he exclaims many times in our interview.

The story begins in the late 1950s in southeast Africa, when several doctors realised that there was a dramatic difference in the bowel health of their Caucasian and black African patients. The Caucasian patients suffered from constipation, appendicitis and colorectal cancer; their African patients did not. When they looked at the differences in what the two groups ate, one factor stood out. The Africans had a lot more roughage in their diet: fruit, vegetables and cereals, particularly corn cereal known as mealies.

And so the fibre theory was born: indigestible plant fibre was protective against bowel disease. From the 1980s onwards, the fibre message entered the public consciousness and food product marketing. Bread went from soft white to wholemeal and Australians’ fibre intake doubled. With the dramatic jump in fibre intake, you would also expect to see a dent in the incidence of colon cancer. But, as Topping says: “Things are not always what they seem”. After 20 years of high-fibre diets, Australian colorectal cancer rates were still rising. This became known as ‘the Australian paradox’.

LOOKING MORE CLOSELY at the traditional African diet, CSIRO researchers found it wasn’t actually that high in indigestible fibre. But it was rich in something called ‘resistant starch’. Africans consumed 20-30 g per day, much of it from corn meal porridge.

Corn meal has an interesting property after it has been cooked and allowed to cool. Its stringy starch molecules get tangled up, resist digestion in the stomach and travel intact to the large intestine where they are digested by the resident microbes, rather like the way the cellulose of grass is digested in a cow’s rumen.

Topping and colleagues are convinced resistant starch offers major health benefits to the Western bowel. One way to boost its levels is to increase the amount of a starch called amylose in the grains we eat. In rats and humans who’ve been fed grains high in amylose, the bowel becomes more acidic, absorbs more water and calcium, develops a thicker layer of mucus and does a better job at culling precancerous cells.

Most of these beneficial effects are thought to be due to a short-chain fatty acid called butyrate, which is produced when the intestinal bacteria ferment the resistant starch. And there is one more dramatic piece of evidence to add. Rats predisposed to colorectal cancer are protected when their diets contain grain enriched in amylose. “The bottom line is that we are now trying to put back the resistant starch that is missing,” says Topping. To do so, the Adelaide team joined forces with the crop breeders at CSIRO Plant Industry. The first fruit of their collaboration is BARLEYmax, a barley variety produced by traditional breeding that has high levels of amylose and is now available at local supermarkets as a breakfast cereal.

Other foods also provide resistant starch: cooked and cooled corn meal and potatoes, bananas, brown rice and baked beans. But to really affect the average diet, amylose needs to get back into a staple, like bread. “This is the opportunity,” says Topping.

While barley was relatively easy to modify by traditional means, wheat is not. Which is why CSIRO Plant Industry used a form of genetic modification known as RNA interference (see “GM recipe” p52). They successfully generated wheat with a starch content that is 70% amylose. When tested in rats and pigs, it showed many of the same properties as BARLEYmax. It would have taken more tests before the researchers were ready to try it in humans to answer a compelling question: might it protect people against colorectal cancer?

Thanks to the Greenpeace break-in, it will now take a year longer to find out.

THE SECOND ‘MONSTER’ wheat in the sabotaged plot at Ginninderra was distinctive even as a seedling; larger and greener than the plants surrounding it. This is a remarkable wheat, and you need to know a smidgeon of wheat history to understand why.

In the 1960s, Asian and South American countries were struggling to feed their growing populations. Then the Green Revolution turned things around: phenomenally productive new wheat varieties – bred in Mexico by Norman Borlaug, a U.S agronomist and Nobel-prize winner – doubled yields. Annual wheat yields continued climbing at about 2-3% per year through the 1980s; but by the 1990s, they plateaued. They are now rising at about 0.7% per year, while the world population jumps 1.1% per year. You begin to see the problem. If we do nothing, the food mountains created by the surpluses of the 1980s will be replaced by empty granaries in 2050.

Which is why wheat breeders around the world have put wheat back on their drawing boards, to see what can be done to raise yields. Some, like those who are part of the International Wheat Yield Consortium, are planning to take the wheat photosynthetic engine apart and rebuild it to behave more like a turbo-charged corn engine. Imagine wheat with heads the size of corn! It’s a long shot that will require some very hefty genetic engineering and a decade or more to prove its worth.

But at CSIRO Plant Industry, the plant breeders have ‘accidentally’ produced wheat whose yields are 20-30% higher. “I’ve never seen anything like it,” Bruce Lee, director of CSIRO Food Futures Flagship, told me. Lee should know what he’s talking about. Before taking up the CSIRO position, he spent 22 years in both academic research and agri-business, eventually as head of Global Licensing Biotechnology for Syngenta AG, in Basel, Switzerland.

Matthew Morell, a geneticist at CSIRO Plant Industry in Canberra, didn’t set out to create super wheat. He just wanted to make better noodles. His expertise lies in understanding how wheat starches can be modified to better suit the characteristics of the final product.

Wheat comes in many varieties, and food manufacturers have long taken advantage of this. High protein or ‘hard’ wheat makes elastic dough that is good at trapping carbon dioxide during baking. Pastry wheat on the other hand, has higher levels of starch and produces a more crumbly texture.

Australian wheat growers were interested in optimising their wheat for noodle flour, which is why Australia’s Grains Research and Development Corporation – a statutory body funded by the Australian government and grain growers – supported Morell’s team to explore how to modify wheat starches.

Morell’s past research had shown that the viscosity, or ‘gooeyness’, of wheat starch was influenced by its chemistry: the more phosphate groups it carried, the gooier it became. Morell also knew the enzyme that tacked these phosphate groups onto the starch: it was called glucan water dikinase. He knew all this from the test tube. But could this enzyme actually be used as a lever to modify the starch? Perhaps lower levels of the enzyme would result in better noodle starch?

So his team tested the idea using GM. Again, they used the technique of RNA interference to wind down the activity of the enzyme that tacked on the phosphate. Once the GM seeds were planted in the greenhouse, Morell didn’t expect to pay them much attention until months later when the starches from their grain would be analysed.

So he got quite a surprise when the scientist working with the plants told him his plants were bigger than the controls. As they lived out their half-year lifespan, the wheat grew faster, taller, had larger ears and those ears contained more seed. Morell is very measured in his response. Yes, he says, they do produce a 20% greater yield. “But that was in pots in the greenhouse, where they are treated like princesses. Our agronomist colleagues won’t believe it ’til they see them growing out in the fields.” And they too will have to wait another year to find out.

THE GREEN REVOLUTION doubled wheat yields and saved untold hundreds of millions of people from starvation. But it also racked up a hefty nitrogen bill. Since the 1960s, the use of nitrogen fertiliser has increased seven-fold.

Plants need nitrogen to build their tissues. But while they breathe air that is 78% nitrogen, they have no way of trapping it, unless they are legumes and have partnered with nitrogen- fixing bacteria. Most plants must rely on nitrogen released from animal or plant manures, or since 1913, on artificially-produced ammonia made by reacting nitrogen with hydrogen at high temperature and pressure – the Haber-Bosch method. Without this method, some three billion people would go unfed; but it’s a costly process that requires 1% of world energy supply to manufacture.

Yet plants are very profligate with the nitrogen we give them. They use only about half; the rest goes to soil microbes, or leaches into waterways where it spurs algal blooms that strip oxygen from the water, creating dead zones. Or, it escapes back into the atmosphere as nitrous oxide, a potent greenhouse gas whose release from the soil is responsible for some 5.2% of global greenhouse gas emissions. Atmospheric levels have climbed 16% since 1750, largely due to the increased use of fertiliser. Clearly we need plants that are more efficient at using nitrogen.

“Nitrogen has taken over my life,” Allen Good tells me. But in 1995, the Canadian plant geneticist at the University of Alberta had no intention of solving the world’s nitrogen problem: he was trying to engineer a canola plant that would survive flooding. Which is why he supplied it with a copy of a barley gene called alanine aminotransferase. The gene produces alanine, an amino acid that plants rely on as a nitrogen store to revive themselves after drowning.

Good was stunned to find the engineered plants used 40% less nitrogen, yet grew just as big. But he wasn’t stunned for long. “The minute we thought they might be more nitrogen efficient, we did the numbers on the back of a napkin. The world spends $100 billion a year and another $50 billion on the associated environmental costs. If we used 20% less, that could mean a $30 billion dollar-a-year saving. The numbers are staggering!”

The company Arcadia Biosciences, based in Davis, California, thought these numbers staggering enough to license the technology. They have since sub-licensed it to researchers who are testing it in canola and rice, and also to the CSIRO and the Australian Centre for Plant Functional Genomics (ACFPG) in Adelaide, to try it out in wheat. According to plant geneticist Andrew Jacobs at the ACPFG, early trials show this wheat is performing well using 15-25% less fertiliser. This nitrogen-efficient wheat was also in the Ginninderra plot, and was also destroyed by the Greenpeace action.

IF EVER THERE WAS A GM plant to please environmentalists, this was it. So why did Greenpeace try to destroy it?

In a video on the group’s website, Greenpeace’s concerned mother tells us the Ginninderra wheat was about to turn up in Australia’s daily bread; that Australians were to be guinea pigs and that if the government wouldn’t protect her family, she would.

That is far from true. Trials for the high amylose wheat have been conducted in rats and pigs – showing beneficial effects. Australia’s Office of the Gene Technology Regulator (OGTR) had approved human trials on a small group of volunteers. But before the wheat would end up in our bread supply, it would have had to jump many more regulatory hurdles, says Lee.

Those hurdles are set by the environment protection officers at the OGTR, and the toxicologists at Food Standards Australia and New Zealand (FSANZ) – experts who are surely better equipped than Greenpeace to decide if the wheat is safe and offers benefits to Australians.

But it’s hard to blame Greenpeace for being concerned when a letter from eight scientists and doctors, sent to CSIRO chief Megan Clarke a couple of weeks before the Ginninderra attack, sounded an alarm over the possibility of people eating GM wheat. The concerned experts included one person from the Maharishi University of Management in Iowa – an unlikely authority on the safety of GM crops – but also persons whose expertise is less easily dismissible: one from the Salk Institute, one from King’s College London School of Medicine and one from the Newcastle University School of Agriculture. Their concerns are largely the same ones that have been directed against GM corn, canola and beta-carotene-rich ‘golden rice’ for the last two decades. The gist of these concerns is this: GM techniques could produce novel proteins or small molecules. These might cause allergies or toxicity, perhaps over the long term. All true. But the question that has been raised since the beginning of the GM food era is this: if you take a piece of DNA whose function you understand and splice it into a plant’s DNA, is this intrinsically more hazardous than if you introduce or alter a piece of DNA by any number of traditional breeding techniques? The answer, according to 25 years of investigation by the European Food Safety Authority, is no.

And let’s be clear about what is involved in traditional breeding. Ever since we started picking our favourite varieties of wild wheat and rice and crossing them during the birth of agriculture 10,000 years ago, not much of what we do is ‘natural’. We’ve also been bombarding plants with mutagenic chemicals or radiation for decades to alter their genes and find useful new traits.

According to Bruce Chassy, professor of food microbiology and nutritional sciences at the University of Illinois at Urbana-Champaign, “the leading durum wheat [pasta wheat] variety in Italy was produced in a reactor near Rome in 1958.” And plant breeder Wayne Parrott at the University of Georgia points to other common examples: “Clearfield rice, sunflower, wheat and canola are major and current examples of crops from mutagenesis [where the plants' genes were exposed to a chemical to produce a mutation].”

MANY OF OUR COMMERCIAL wheats that were produced by ‘traditional breeding’ have also had a dramatic birth. They carry chunks of chromosomes from wild relatives like Middle Eastern goat grass or Thinopyrum from the steppes of Asia, that protect them from fungal and viral diseases. These chunks carry hundreds of genes from the wild ancestor. To get offspring from a cross between modern wheat and a wild relative requires the embryo to be rescued and grown in tissue culture. Then some brutal techniques are required to trim away most of the wild chromosomes, while leaving the chunks carrying disease resistance. It’s called chromosome engineering, and breeders around the world have been fortifying our wheat this way ever since American breeder Ernie Sears figured out how to do it in the 1950s.

It sounds pretty wild, but all plant breeding is potentially hazardous, as Wilford Mills at Pennsylvania State University, discovered. In the 1960s, Mills bred a pest-resistant potato by crossing the popular Delta gold variety with a wild Peruvian variety. The resistant potato, called Lenape, had already been released to commercial breeders and was even being made into potato chips when a breeder based in Ontario, Canada, cooked some and ate them. He got nauseous, and sent the potatoes to a biochemist at the nearby university. They were loaded with glycoalkaloids, natural toxins. Decades of breeding to remove toxins from wild potatoes had been returned in one stroke by Wilford Mills.

So plants can be hazardous. What hundreds of studies have now shown is that manipulation by GM is no more hazardous than traditional methods of plant breeding. The good news is that decades of food science has taught the scientists what hazards to look for. Any GM crop is subjected to a so-called ‘compositional analysis’. The plant is pulverised and levels of potentially problematic molecules such as glycoalkaloids are checked by mass spectrometry. Further tests assess the potential of modified proteins to cause allergies, usually indicated by a protein that resists digestion.

OF COURSE, there’s a flaw in the logic here. You can only test for what you know. What if the plant makes something weird and unexpected? It’s possible. But that same possibility applies to all newly bred plant varieties. We’ve accepted that hazard for 10,000 years.

Besides compositional analysis, GM crops have been subject to feeding trials in rats, something that non-GM new varieties (like the Lenape potato) don’t automatically require. Some studies have famously suggested that rats fed GM food suffered harmful effects. Arpad Pusztai, then at Britain’s Rowett Research Institute, published a controversial study in The Lancet in 1999 showing rats fed insect-resistant GM potatoes showed changes to their intestines and immune system. Gilles-Eric Seralini, molecular biologist, found changes in the organs of rats fed herbicide-resistant GM corn.

The signatories to the CSIRO letter also raised these rat-feeding studies as a concern. And this was a warning light. Because these studies have been roundly rejected by mainstream science: Pusztai’s work was reviewed by a specially convened panel of experts, the Royal Society and food safety experts around the world, and rejected. As for Seralini’s claims, Chassy commented “EFSA [the European Food Safety Authority] has reviewed every claim he has made, and concluded that they are without scientific merit … Expert histologists, physiologists and toxicologists have looked at the data, and concluded that there were no meaningful differences. In short, Seralini is playing games with differences in numbers that mean nothing.”

Towards the end of 2010, the European Commission released a mammoth study into the safety of GM foods, summarising 50 studies carried out between 2001 and 2010 and involving more than 400 independent research groups. Their previous report spanned 15 years. So after a total of 25 years of research involving 500 independent research groups and costing €300 million, their conclusion is “that biotechnology, and in particular GMOs, are not per se more risky than [for example] conventional plant breeding technologies.”

IT’S UNSETTLING WHEN scientists disagree. But it’s not uncommon. When they do, the prudent choice is to take the view espoused by the majority of the experts in the field. As a 2002 letter in Nature Biotechnology by Chassy, Parrott and 16 other food toxicology experts and plant breeders, put it, “Good scientists go astray when they leave their area of expertise to offer an opinion when they have not studied the literature, when they selectively ignore information, or when they let their politics and beliefs interfere with the objectivity of their science.”

Will the anti-GM fringe players derail the development of technologies that could one day save a global wheat harvest, that could dent the rise of colorectal cancer, raise flattened yields, make plants guzzle less nitrogen and be more drought and salt tolerant?

Maybe.

A recent trip to my local Coles supermarket was not very heartening. I went to the shelf trying to buy some GM canola oil, something that Australian farmers could at last plant after a moratorium in four Australian states was lifted in 2008.

I searched in vain. All the bottles proudly proclaimed ‘GM-free’.

GM RECIPE

 GMrecipe
Computer model of an amylopectin molecule

Wheat is a complex beast with six copies of most of its genes. That makes it difficult to reduce the activity of any one gene, which CSIRO researchers had to do to raise amylose levels. Lowering the levels of a gene that makes ‘starch branching enzyme’ would flick a switch and cause the wheat to make amylose rather than its sister starch amylopectin. They dialled down the activity of the gene for this enzyme using a technique called RNA interference. A piece of lab-synthesised DNA was transferred into the DNA of the wheat cells, where it produced a strand of ‘interfering RNA’. This interrupted the activity of the gene.

Elizabeth Finkel, a contributing editor of Cosmos, is an award-winning Melbourne science writer whose latest book is The Genome Generation, available in February 2012.
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