Monsanto’s new Omega-3 soybean:
Healthy or hazardous? Part II
HONOLULU—Last year, soybeans provided 69 percent of the edible consumption of fats and oils in the United States.
Soy consumption is big in America. It’s even bigger around the rest of the world, particularly in Asia. In an effort to capitalize on the soy market, Monsanto Company has genetically engineered a “healthy” soy bean that has a critical compound our bodies can convert to a heart-healthy fat. The agricultural biotechnology corporation says it has created a seed that could provide a sustainable alternative to a very in-demand nutrient.
Monsanto’s Omega-3 soybean seed has passed all but the final stage of the U.S. regulatory process and will almost certainly be approved within a matter of months.
The idea for the new product began in the mind of biologist Virginia Ursin 12 years ago. Ursin was working at Calgene before Monsanto bought out the biotech company in 1997. Situated near the UC Davis campus in California, this comparatively small facility had a history of expertise in plant oil manipulation.
One of the projects Ursin worked on before the takeover involved successfully engineering a Canola plant to produce gamma-linolenic acid (GLA), also known as a fatty acid, or fat, or just plain oil. While that project was abandoned for commercial reasons, she got to thinking of other ways Monsanto could utilize Calgene’s knowledge of food oil production.
“We had a really robust toolbox for modifying plant [fats],” Ursin says. “We realized the tools, the pathways we were manipulating to modify these genes, could also manipulate Omega-3s.”
Not all fats are created equal. Much like how we’ve come to know that the once-healthy trans-fats are now the worst kind, we now understand that Omega-3 fats are accountable for a variety of positive health outcomes. A certain kind of Omega-3 called EPA is responsible for producing prostaglandins, compounds that reduce blood clotting, thus helping to prevent a range of ailments, like thrombosis, atherosclerosis, and heart attacks—all linked to thickened arterial walls. Women with high-risk pregnancies are given EPA as natural supplements to lower high blood pressure. Preliminary studies also show its effectiveness in helping prevent certain kinds of cancers and aid in the treatment of mental disorders.
Ongoing research continues to demonstrate the fatty acid’s potential for a lot of good. Now the question is centered less on its value than its availability in sufficient quantities.
The original manufacturers of EPA are seagoing algae, which use the fats to keep their cell membranes functioning in frigid waters. These plants are eaten by small fish that are then eaten by larger fish, like mackerel and salmon. These “fatty” fish, which also use EPA to survive the cold, store plentiful amounts of EPA in their bellies. This is how Eskimos, for example, get their daily intake—by living wholly on fish and seals, whose diets also enable them to accumulate lots of the fat. But not everybody likes fish. And if everybody did, that would present another problem.
“There’s not enough fish to go around,” says Ursin. “If everyone started to fish, by 2013 and 2014, the demand would exceed the supply.”
Bigger fish to fry
For Monsanto scientists, the rapidly diminishing supply of fish-derived Omega 3 represented a great opportunity. They knew a lot about soybeans, and they knew, theoretically, at least, that they could engineer the plant to produce an Omega-3 that could give people an important nutrient while preserving the world’s fish stocks. The idea took off. Understanding the idea first requires a light lesson in biochemistry.
The thing to remember about EPA is that it’s just one of a family of Omega-3 fatty acids. And all the different Omega-3s are derived from one mother acid: Alpha Linolenic Acid (ALA). This is the Omega-3 that’s currently advertised on salad dressings and other foods. ALA is found in most plants, and it’s the job of human enzymes to spur along the chemical reactions that transform ALA into EPA. But our enzymes are sorely inefficient. Studies suggest that, at best, it takes thirteen ALA molecules to produce one EPA, resulting in the average American ingesting less than 100 mg of EPA a day—only a fifth of the amount that the American Heart Association recommends we consume.
The obstacle to producing EPA lies early in the chain of chemical reactions that are necessary to turn ALA into EPA. Specifically, human enzymes do a poor job of converting ALA into SDA (stearidonic acid), the fatty acid that then, in turn, becomes EPA. Ursin and her team’s solution to this dilemma was very clever. Simply stated, they genetically engineered soybeans to produce extra amounts of SDA. Eat the beans, goes the logic, and the difficult early chemical reaction has already taken place. This is key because our bodies are fairly efficient at converting SDA into EPA. For every three molecules of SDA consumed, we generate one molecule of EPA.
The soybean is also a perfect crop for extracting oil because of its high fatty acid content: 60 percent of its composition is fat, compared to most other legumes, which measure in at roughly two to 14 percent. And to stroke its ego further, its fats are largely healthy, with 63 percent comprised of Linoleic acid (LA) and our own much coveted mother Omega-3, ALA.
But the problem, for the purposes of Ursin and her team, is that ALA comprises a mere seven percent of the total. They needed to find a way to induce the bean to produce more of the mother ALA so more SDA could be created. To solve the problem, the soybean needed not just one, but two genes inserted into it: one that creates an enzyme that converts LA to ALA, and another whose enzyme then takes all that ALA and transforms it into SDA. The first step in the development of a soybean containing greater amounts of Omega 3 was finding the right genes for the two jobs.
In the plant and animal world, many species possess enzymes that perform similar functions. But some do a better job of igniting chemical reactions than others. For instance, our body has a relatively poor-performing Delta 6 enzyme, the protein needed to convert ALA to SDA (with a dismal 13-to-one ratio). Ursin needed to find what she calls the “super” Delta 6 enzyme, some plant that could convert ALA to SDA with maximum efficiency. To do so, she needed to harvest its corresponding gene—a segment of DNA that tells an organism to manufacture the enzyme. Likewise, she scoured everywhere looking for the Delta 15 enzyme that could churn out the most ALA. She inserted the enzymes into yeast, which have fast-multiplying cells (perfect for quickly evaluating the most efficient enzymes), and tested hundreds of plants, phytoplankton, and fungi.
“We surveyed the universe looking for the best reactions,” Ursin says.
Sometime later (she couldn’t disclose how long the process took), Ursin finally uncovered the species with these super enzymes: Primrose flower for Delta 6 and a bread mold fungus for Delta 15. These were the best in their class, able to convert oils from one to another type with the greatest efficiency. Now that they had the right enzymes, it was time to isolate the genes that coded for them then insert the genes into the soybean seed.
A new seed is born
In 2001, Ursin and her colleagues embarked on phase I of Monsanto’s development pipeline: the transformation, or insertion of the genes into the soybean. And it began with extracting the Delta 6 and Delta 15 genes from their primrose and bread mold hosts. To do this, they used so-called restriction enzymes. Found in bacteria, these enzymes act as defense mechanisms by cutting into the DNA strands of invading viruses, preventing them from infecting the bacteria. Scientists mimic this function by embedding DNA markers at the ends of the desired genes. The markers act like homing beacons, drawing the restriction enzymes toward them, cleaving the genes at just the right places.
With both the genes that coded for the delta 6 and delta 15 enzymes extracted, they were then inserted with codons, sequences of DNA that optimize the genes’ performance in their new host, kind of like greasing the wheels on a bike to make it go faster. Then it was on to the actual transformation.
Scientists took soybean seedlings and applied heat and spun them in centrifuges to make them more vulnerable to being ‘infected’ by a gene-transferring organism called agrobacterium tumefaciens. In nature, this bacterium infects a plant with crown-gall disease by injecting its own DNA directly into the plant’s genome. This DNA is malignant and forces the plant to grow tumors near its roots. Scientists are able to remove the tumor-causing DNA from the bacterium and insert their gene of choice in its place. So, instead of disease-genes, the soybean took in the two genes that helped it produce ALA and SDA. Well, that’s what’s supposed happen to the successfully transformed beans. Truth be told, inserting a gene into a plant’s DNA doesn’t require a surgeon’s precision as much as a lottery winner’s luck.
“It’s like pinning the tail on the donkey,” Monsanto spokesman Gary Barton explains.
That’s one of the reasons the bacterium is inserted into as many as 10,000 bean seeds. The chances of a commercial failure are very high. In the end, Monsanto will often choose only a single superior seed that has taken in the genes and produced the right amount of ALA and SDA—all the while still behaving like an unmodified soybean.
Known as the post-transformation stage, phase II is all about Monsanto weeding out the inferior seeds. For this, the 10,000 transformed soybean plants were shipped from their home at Calgene in California to another Monsanto facility outside Madison, Wisconsin. Scientists monitored the plants, which were embedded in nutrient-rich gelled petri dishes, as they were kept in climate-controlled growth chambers (the Chesterfield facility boasts a seemingly endless corridor of 75 labs and 108 growth chambers).
It’s while they were housed in these chambers that the vast majority of the seedlings were discarded. Many suffered from the hormonal roller coaster they endured during the transformation process. Before genes were inserted, the seedlings were pried from their outer coatings, which contained the hormones and instructions that help the seedlings grow into a plant. In its absence, scientists had to play the surrogate by inserting different hormones.
But the technique is risky. Seedlings can misread the cues and develop mutations, like double-shooting stalks and misshapen leaves.
And yet others were tossed because the new genes landed somewhere badly in the soybean’s strand of roughly 30,000 genes, and scientists had no control over where they embedded themselves. While the best spots for these newbies are “blank” areas of the strand, some were inserted right-smack in the middle of another gene, potentially silencing a trait that regulates a critical plant function, whether it be its flowering time, the numbers of seeds its pods produce, even photosynthesis. Sometimes, the new gene combined with another and created fusion enzymes that take on the traits of both genes (certain drugs are created using this process, and certain cancers are promoted by these fusions). At other times, more than one copy of a gene was inserted, causing excessive production of the protein.
From the 10,000 soybean seedlings that started out in the growth chambers, only a startling three to four hundred survived the ravages of hormone therapy and gene insertion and were moved to the greenhouses. The plants continued to be monitored for their health and for the amount of SDA and ALA they synthesize. Even if the genes landed in a safe place along the DNA strand, some places are more optimal for oil production than others. Some plants end up not producing enough oil, making them commercially useless. Yet others synthesize too much (over-producing plants do not stand up well to hot climates). All of these fell to the wayside.
The remaining plants survived a gauntlet of challenges, and because of their stressful journeys many appeared brittle and puny. But they were hardy enough to pollinate and sprout new pods. Monsanto harvested these seeds and planted them, and scientists checked to see if the new genes “shut off,” or no longer produce the new enzymes. These flops were tossed, and this method of weeding-out of inadequate seedlings was repeated again and again for a few successive generations.
Three generations of transformed soybeans later, this last group of around forty survivors made it to the last stage of elimination. By this time, all the remaining soybeans produced sufficient amounts of SDA. The issue was no longer about the effectiveness of the new genes—but the heartiness of the plant.
One seed to rule them all
As with all crops, some lines perform better than others when they’re taken from the ideal climates of the greenhouses to the vicissitudes of the open fields. To test for this, they were whisked away for field trials. Normally grown in places that have yearlong warm temperatures like Hawaii, Puerto Rico, and Mexico (which just approved of GM crop tests on their soil after an eleven-year ban), these plants are grown and monitored for their agronomic stability. Some of them might not stand up as well to the heat, others won’t yield enough beans, and yet others might simply be too puny.
But two years, six generations, and 79 worldwide field locations later (Monsanto wanted to make sure this widely grown crop was suitable everywhere), there was one cream of the crop: a single line of soy plants that has withstood all the rigors and challenges. This line was the most healthy and resilient, and its seeds produce suitable quantities of SDA for the market. This is the winner we all can consume—in one food product or another—in the next few years.
By 2012, we could be getting most, if not all, of our recommended EPA through Monsanto’s Omega 3 soybean. Because the bean does the tough part, converting ALA into SDA in sufficient quantities, our bodies can do the rest and convert the oil to EPA at a workmanlike three-to-one-ratio (compared to our 13-to-one rate with ALA). And the thing about it is you probably wouldn’t have to change much of your diet at all. Monsanto, in partnership with Solae, a major soy innovator, is selling the oils to food companies that can add it to virtually any processed product. It’s entirely possible that you could be getting part of your daily EPA intake by eating Twinkies
But before that happens, Monsanto must demonstrate that the new product is safe. And it’s the regulatory oversight, or rather the lack thereof, that forms the center of critics’ arguments against the safety of this eccentric soybean.
In Part III of our exclusive report “Monsanto’s New Omega-3 Soybean: Healthy or hazardous?,” The Hawaii Independent‘s Samson Kaala Reiny will look into the process of federally approving the Omega 3 soybean for consumption.