Although the vast majority of the enzymes are removed through the oil-refining process, they’re still in the oil in some quantities. Furthermore, there’s a small chance that these plants could cross-pollinate other varieties of soybean out in the fields whose seeds are harvested to make protein-alternative foods, for instance. These facts are important because critics say there’s a chance that the new enzyme inserted into a plant could produce unwanted effects. Some enzymes are outright toxic, prime examples being the neurotoxins that cause botulism and the enterotoxins (that enter through the human intestine) responsible for the harmful effects of cholera.
Enzymes can also induce allergic reactions. Everyday food allergies, like those involving peanuts, shrimp, and dairy products, are in fact allergies to specific enzymes within the foods. Depending on the type of allergic enzyme, and their genetic makeup, people can suffer bouts of hives, stomachaches, asthma attacks, or, in the most acute cases, they can die.
Not only is there a precedent for inserted allergic enzymes, but the most instructive case involved a soybean. In the early 1990s, Pioneer Hi-Bred, one of Monsanto’s major biotech competitors, inserted into soybeans a Brazil nut gene that would enable them to produce an enzyme rich in methionine, an essential nutrient that helps us break down fats and cleans our livers. But the catch was that this enzyme is also a major allergen. Blood tests confirmed that people allergic to the Brazil nut were also allergic to the methionine-enhanced soybean. The project was soon scrapped. GMO opponents claim that the case highlighted the dangers inherent in genetically modified foods and should be considered a cautionary tale about the whole endeavor. Industry saw things in a different light.
“It showed how the regulatory process works,” said an emphatic Eric Sachs, Monsanto’s director of global scientific affairs, who, at a luncheon at St. Louis headquarters, was inclined to bringing up past biotech controversies only to refute them.
For Monsanto, sound safety protocol starts with knowing the kinds of enzymes they’re inserting into plants. The first line of precaution for Monsanto is its use of a software program that compares the amino acid sequence of potential transgenic protein to those of known allergens and toxins. According to Goldstein, toxins are easily identified. Identifying allergens, on the other hand, requires a little more finesse. One standard method for determining if an enzyme is a potential allergen is to compare its amino acid sequence (the building blocks of enzymes) to known allergens. It’s debatable how many identical amino acids of an allergenic enzyme need to line up with the Omega-3 soybean’s enzymes—the 446 amino acids found in the delta 6 enzyme and the 429 found in the delta 15 enzyme—for there to be concern.
“If you look for six matching acids, you’re going to pick up a lot of matches for enzymes that aren’t even known food allergens,” he said. “Eight is the generally accepted minimum number of amino acids that would give us concern. And we discard those potential enzymes right away.”
In this case, though, it turns out that delta 15 does consists of eight amino acids that match those of an allergen found in wheat. But Sachs asserts that sometimes only a part of an enzyme’s amino acid sequence is allergenic, and that the part of the delta 15 sequence that matched those of the wheat is harmless.
Another major characteristic of allergens is their resistance to digestibility. So one method for finding whether enzymes are possible allergens is to test how quickly they are dissolved in Pepsin, an enzyme our stomachs use in digestion. But critics insist that the results can’t be trusted because the typical proportion of pepsin and proteins doesn’t mimic the interactions in our stomachs.
Doug Gurian-Sherman, senior scientist at the Union of Concerned Scientists, noted in a report that, in one particular test done for one of Monsanto’s Roundup Ready soybeans, scientists dissolved the enzymes—the ones that give those soybeans resistance to the company’s herbicide—in pepsin concentrations 120 times greater than the recommended international standards. At that level, Gurian-Sherman suggests, potential allergens might not be found because they can break down as fast as a non-allergenic protein would.
“With Monsanto, it’s hard to think they weren’t being devious when they did these things,” Gurian-Sherman said.
Goldstein concedes that Gurian-Sherman is right about pepsin levels not always replicating the acidity of the human stomach. Acknowledging that there’s room for debate regarding such levels, he contends an enzyme’s resistance to digestion is only one of several factors that are taken into account, noting that there is debate as to the appropriate pH levels and enzyme amounts. Adding to the complexity is the fact that some allergens are easily digestible while some hard-to-digest enzymes aren’t allergens. To address the uncertainty, other factors are considered, such as heat stability and whether the enzyme in question contains an amino acid sequence similar to other known allergens. Goldstein is confident in the corporation’s methods for avoiding what, in his view, amounts to a very isolated group of problematic enzymes.
“Out of the millions of enzymes out there, only about fifty known allergens exist,” he says. “We know which ones to look out for.”
Nature always finds a way, doesn’t it?
Beyond questioning testing protocol, critics are concerned about the actual enzymes used in all the company’s tests, including the animal feeding trials, because they’re not derived from the transgenic crop—in other words, the soybean itself. Instead, they are derived from bacteria (usually E. coli), which are engineered to produce the enzyme in bulk amounts to make testing easier. According to the opposition, plants and bacteria process enzymes differently. Plants can glycosylate, or add sugar molecules to their enzymes, something bacteria normally do not do. And sometimes those extra sugar molecules can spur allergic reactions, and, in the event that they do, we’d never know beforehand because those enzymes are not the ones being tested.
Monsanto official Goldstein says that using bacterial surrogates is a matter of efficiency, noting that it’s extremely time-consuming and costly to extract enough of the enzymes directly from plants, which are present only in tiny amounts—a few micrograms at most. Using bacteria, scientists are able to produce concentrated amounts. In an attempt to dispel concerns about glycosylation, they change the sequence of the enzymes’ amino acids so they’re prevented from manufacturing those potential allergy-producing sugars.
But in keeping with the novelty of the Omega-3 soybean, Monsanto didn’t use protein surrogates for safety testing. The corporation had no choice but to extract the enzymes directly from the genetically modified plants because bacteria, lacking the right structures to produce these fats, can’t manufacture the enzymes successfully. Plant cells are specially designed to process these fat-producing enzymes. And that’s the source of another controversy that’s unique to the new nutritionally enhanced crops: Not only can plants utilize these unique enzymes to produce Omega-3’s fats—they can also produce potentially other dangerous byproducts.
Fear of these mystery enzymes being inserted into food crops has been a focus of contention since before Roundup Ready soybeans entered the market as the country’s first commercial biotech crop in 1996. But Monsanto’s newest invention—a soybean engineered to improve cardiovascular health—has some opponents ironically even more worried, and it’s because of fears that the omega-3 fatty acid SDA isn’t the only novel oil being produced.
In the complex world of plant metabolism, enzymes normally initiate or accelerate multiple chemical reactions. For example, a certain enzyme can convert ALA (our mother Omega-3) into Jasmonic acid, a critical defense compound that acts as a toxin to plant insect pests. Policy analyst William Freese says he’s not sure if Monsanto, in touting their new nutritional wonder, is aware of all those possible secondary reactions, much less studying their effects on human health.
“What it all comes down to is the wrong fatty acids in cell membranes of plants can cause problems,” he said.
Dave Schubert, a cell neurobiologist at the Salk Institute and an outspoken critic of biotechnology, believes this next generation of nutritionally altered crops could open a Pandora’s Box of new toxic compounds. His 2008 article, “The Problem with Nutritionally Enhanced Plants,” published in the Journal of Medicinal Food, cites examples where enzymes, taken from one plant, produce unexpected byproducts when inserted into another.
But his most high-profile claim was launched against another nutritionally altered food famously (or infamously) known as Golden Rice. In the 1990’s, scientists genetically engineered rice kernels to produce beta carotene, an important precursor to Vitamin A. The discovery of these grains (named for their cornfield yellow color) was touted as a momentous benefit for the poor in South East Asian countries who often go blind because their diets lack this critical nutrient. But biotechnology is particularly controversial internationally, and it took the better part of a decade to convince beneficiary countries of its safety. China only accepted Golden Rice technology last year (now called Golden Rice II because scientists found an enzyme that could produce more Beta Carotene than its predecessor). One reason for the long deliberation might be due to concerns voiced by scientists like Schubert, who argues that the enzymes used to increase Beta Carotene intake in rice could also produce other similar compounds like retinoid that are toxic in excessive amounts.
“Six-hundred naturally occurring compounds exists in the Carotene family, and at least 60 can be precursors to retinoids,” he writes. “Therefore, plants have the potential to make many potentially harmful retinoid-like compounds when there are increased levels of synthetic intermediates to Beta Carotene as in Golden Rice” [namely those produced by the newly-inserted enzymes].
Goldstein agrees that these are “absolutely things that could conceivably happen.” But they don’t happen, he hastens to add, because of scientific thoroughness. Although Monsanto was not directly involved with the Golden Rice project (it was supported by rival company Syngenta), he defends the product as being thoroughly tested, that the Beta Carotene—as produced in the grain—was extensively studied and already widely consumed in the human diet. He is equally confident about the safety of SDA oil, and the evidence that supports the assertion.
“We’re very familiar with the metabolic pathway,” he says, “with what these enzymes are set to do.”
Where are our safeguards?
By engineering a nutritionally modified plant that is not substantially equivalent to its unmodified counterpart, Monsanto finds itself in new regulatory territory. To vouchsafe for the novelty of this new fat, in addition to the usual biotech consultation studies, the corporation submitted a GRAS notification to the FDA in February 2009 to prove that the oil contains nothing new or dangerous. And much like how Monsanto self-affirmed the safety of its previous biotech crops, the company could also have made its own determination that the Omega-3 oil is GRAS by submitting the supporting evidence.
But, for further validation, Monsanto chose a more thorough approach, by convening a panel of independent experts who reviewed and validated the existing data. In accordance with all notifications, the FDA then made the submission publicly available on its website, making the documents far more accessible than the biotech consultation studies, which are accessible only by submitting a Freedom of Information Act request. Those can take months to process.
After reviewing the dossier, the FDA then delivered a decision to the company. Two responses by the agency are possible at this point. The agency could demand more data to support the safety determination, and, if that’s not persuasive, relegate the product to the status of a food additive, which means further testing leading up to a pre-market approval. Or the agency could state that it “does not question the basis for the notifier's GRAS determination,” meaning that the major concerns have been satisfied. Goldstein -- and the panel, for that matter -- believes that Monsanto has answered all relevant concerns.
And in April, the FDA agreed, for now: “Based on the information provided by Monsanto, as well as other information available to FDA, the agency has no questions at this time regarding Monsanto’s conclusion that soybean oil-RP/RL/IO is GRAS under the intended conditions of use. The agency has not, however, made its own determination regarding the GRAS status of the subject use of soybean oil-RP/RL/IO.