After tens of thousands of mistakes, they thought they might have done it: They had created 100 seedlings laced with DNA from soil bacteria, a cauliflower virus and a petunia plant. They planned to test them cautiously in their Monsanto Co. labs. But an eager executive decided to test them all, to douse every plant with a highly potent concentration of the herbicide.

The team leader, Stephen Padgette, raced to the greenhouse to plead that some seedlings be spared. But he was too late; the plants were sprayed.

Every one of them survived.

They would go on to become the first blockbuster biotech crop, sweeping across America's farms and into America's diet with astounding speed.

Genetically modified soy has been on the market just five years. Yet it already accounts for two-thirds of the U.S. soybean harvest. Soy products are used in hundreds of processed foods, often to add texture and protein. So the biotech beans end up in pancake mix and baby formula, chicken soup and margarine, crackers and salad dressing, ice cream and granola bars.

From lab to field to table, the story of engineered soy offers a window into the biotechnology revolution. It was the first staple crop to be successfully engineered and widely planted. And it offers the longest-running case study of the biotech experiment.

Five years in, there are signs that the rapid spread of transgenic crops may be upending agricultural ecosystems--throwing colonies of soil microbes out of balance and shifting the types of weeds that crop up most often on fertile fields.

The experience of biotech soy also points up the lack of federal regulation, especially compared with other countries. The soy appeared in processed food even before the manufacturers knew it was there. And though Monsanto conducted extensive safety tests, critics warn that they were inadequate and raise questions about the enormous economic power that a company such as Monsanto wields in this new world.

The United States has not seen the same type of anti-biotech protests that have roiled Europe in recent years. But vandals protesting genetic engineering have destroyed some labs and test fields in their fury.

And there is a small but fierce rebellion brewing among farmers who contend that the biotech business model is strangling the heartland by giving Monsanto too much power over global agriculture.

Though competitors such as DuPont Co. and Dow Chemical Co. are working to catch up, Monsanto dominates the biotech market: Well over 90% of all transgenic crops planted worldwide were developed at the firm's high-tech labs here in suburban St. Louis. Monsanto's scientists have engineered not only two-thirds of the soy crop, but also two-thirds of all the cotton and a quarter of all the corn grown in the United States.

The reason for Monsanto's success is straightforward: The new seed is easier and often cheaper to grow. It can reduce the need for chemicals to control weeds and pests.

Transgenic soy, cotton and corn are now planted on more than 75 million acres in every state except Alaska, Hawaii, Nevada and Rhode Island. Most U.S. livestock eat feed made with biotech grain. And 70% of processed foods have biotech ingredients. Despite bitter European protests, the crops are increasingly popular overseas as well, especially in parts of Asia and South America.

Monsanto executives see genetic engineering as a wonder tool that can help alleviate hunger by making food more nutritious and easier to grow. They take their triumph with these first few crops as proof that they can change the world. Their critics fear just that.

The Search

Biotech soy was born of a business brainstorm.

In the late 1970s, as today, Monsanto's leading product was a herbicide called Roundup, which is made from glyphosate, an incredibly effective chemical that kills almost everything green. Farmers worldwide relied on Roundup to clear their fields before planting. But they could not spray it once their seeds sprouted, because it would kill their crop along with the weeds.

Monsanto set out to boost sales of Roundup by creating crops that would tolerate glyphosate.

It would take 700,000 hours of work.

Padgette's team spent the first seven years on the wrong track altogether, trying to rearrange soybean DNA by hand. "At a certain point," Padgette recalled, "we decided we needed to think outside the box."

Instead of toying with soy's existing genes, they decided to try to add new ones. Glyphosate works by binding to an enzyme in plants that produces proteins critical for growth. With the glyphosate clinging to it, the enzyme can't function and the plant dies. Bacteria have that same critical enzyme. So in 1987, Padgette's group began screening bacteria to see whether any had a natural resistance to glyphosate.

Two years later, with the help of a robot that ran analyses all night, they found one that did. In this bacterium, the enzyme critical for growth had a slightly different chemical structure, so glyphosate could not bind to it. It was, Padgette said, "a great Eureka moment."

Not that he allowed time to celebrate. Working late nights, jazz music blaring, the team turned to the hardest chore: figuring out how to make the bacterial DNA perform its magic in soy.

The key turned out to be a gene packet containing DNA from four sources.

A gene from a cauliflower virus acted as a master control switch. It activated the bacterial enzyme that was able to fend off Roundup while still producing adequate growth proteins. A snippet of petunia DNA made sure those proteins were ferried to the proper location within the soy plant. Another strand of DNA from a different type of bacterium served as a molecular stop sign, preventing overproduction of the proteins.

Padgette's team bundled those four strands of DNA together. Then they used a gene gun to plug the whole packet into individual soybean cells. The process worked like this: DNA strands were wrapped around tiny gold pellets, smaller than dust. The gene gun then fired the pellets at soybean embryos. As the pellets ripped through the embryo, at velocities of up to 1,400 feet per second, the DNA was wiped off, sticking in the nuclei of individual cells.

Trouble was, the gene gun inserted the DNA at random. Sometimes a bundle would splinter before landing in a cell. Or two gene packets would double up. Even worse, the DNA would at times land in a spot that interfered with cellular function. The team had to fire the gun tens of thousands of times to get a few dozen plants that looked promising.

After three years of field tests on these promising plants, a single line of transformed soybean shone as superior. It could resist heavy doses of glyphosate, as the greenhouse experiment proved. And it looked great in the field, matching conventional varieties bean-for-bean in yield, growth and quality. "It was bulletproof," Padgette recalled with pride. In 1993, Monsanto declared it a winner.

The embryo that had been labeled "40-3-2" during the gene-gun trials had emerged as the first transgenic soybean. Monsanto called it "Roundup Ready," because it could be sprayed with the herbicide and suffer no harm. Just one hurdle remained before taking it to market.

Though the Food and Drug Administration did not require any safety tests, Monsanto executives wanted to be sure they had a seal of approval from that agency, as well as from the U.S. Department of Agriculture and the Environmental Protection Agency.

The Testing

But there was no regulatory process in place.

So Roy Fuchs, Monsanto's director of regulatory science, was called upon to invent one. He came up with a list of tests he thought Monsanto should run to prove the soybeans safe. Then he compared notes with government regulators.

Although the FDA did not require any specific safety tests of biotech food, other agencies around the world did. Monsanto plunged ahead.

Roundup Ready soybeans were fed to quail, cattle and rats, to catfish in Mississippi and chickens in Missouri. There were toxicity tests to make sure the bean wasn't dangerous even in huge quantities. There were feed tests to make sure animals gained as much weight on a transgenic diet.

The foreign protein in Roundup Ready soy was matched against a computer database to make sure it did not resemble any known allergen. It was plunked into simulated intestinal juice to see how the human gut would react. Every nutritional component of the biotech bean was analyzed and matched against conventional varieties. In all, Monsanto spent up to $8 million on safety tests. The goal was to show a "reasonable certainty" that the beans would do no harm--the FDA standard used for ordinary food.

"A lot of people who oppose biotech would like us held to a standard of absolute safety, which is not possible," Fuchs said. "We would have to reinvent food, because food is not inherently safe." (Indeed, food produced through conventional cross breeding has at times proved dangerous, from a potato loaded with toxins to a celery that causes a blistering rash.)

Monsanto aimed to show that its transgenic crops were "substantially equivalent" to conventional ones. The FDA and several international groups, including the World Health Organization, have approved this standard. Using it, Monsanto has won approval for its soy from 30 regulatory agencies in 18 countries. Opponents, however, are not reassured.

"You're producing combinations of genes that cannot be made in nature," said Margaret Mellon, a molecular biologist and prominent foe of biotechnology. "You're putting bits of DNA, in some cases whole proteins, into crops when they've never been in the food system before. It seems to me that level of novelty is enough to merit an extra degree of scrutiny."

"It's difficult to say anything is 100% certain, but we have a good handle on what we ought to be looking at" to ensure food safety, responded Laura Tarantino, the FDA's deputy director of premarket approval. "We're trying to use the best set of tests we know."

The FDA has proposed making safety testing mandatory for biotech food. But the agency has no plans to dictate which tests companies should perform. "We're not explicit," Tarantino said, "but we expect them to come in early in the process to consult with us."

To critics, letting biotech companies define and measure safety is akin to letting a student write and grade his own exam.

Even Dan Glickman, former Agriculture secretary, has expressed concern that products such as Roundup Ready beans have not received enough objective scrutiny, though he says he still believes they are safe.

Glickman supervised approval of several biotech products that followed Monsanto's soy. Looking back now, he regrets that industry was allowed to take the lead, as regulators largely ceded their watchdog role. "Regulators even viewed themselves as cheerleaders for biotechnology," he said. "It was viewed as science marching forward, and anyone who wasn't marching forward was a Luddite."

The Concerns

In 1996, their first year on the market, Roundup Ready beans were planted on 1 million acres. The next year, that figure was up to 9 million. The year after, 27 million. This year, the USDA projects biotech soybeans will be sown on 48 million acres. Monsanto estimates 90% of soy growers have tried them, though some have rejected them as not cost-effective for their particular fields.

The transgenic soy (and, later, corn and cottonseed oil) entered the food stream so quickly that most processors did not even realize they were using it. It was not until Europeans began protesting "Frankenfoods" that U.S. makers of processed food began to investigate the safety of ingredients they had been using for at least two years.

"We really learned after the fact, after these ingredients were already in the food supply," said Lisa Katic, director of scientific policy for the Grocery Manufacturers of America.

After a year of intense review, Katic said her group's members are convinced the biotech crops on the market today are safe to eat. And, indeed, no serious scientist has suggested otherwise.

Instead, five years after the introduction of Roundup Ready soy, many critics are turning their attention to the beans' performance in the field--and to possible environmental effects.

Monsanto says its research shows its beans perform every bit as well as conventional varieties. They also have some positive environmental spinoffs. Farmers do not have to churn the soil as much to loosen weeds, which cuts down on erosion. And because glyphosate is so effective, soybean growers have slashed both the number of chemicals they spray and the number of fuel-burning trips they take across their fields.

But there have been some worrisome indicators too.

Research from the University of Georgia suggests that the genetic changes may have affected the soybean metabolism, causing stalks to grow brittle and split in extreme heat. A study at the University of Arkansas found some biotech beans fared badly in drought, perhaps because the Roundup spray damaged the soil bacteria that help soy plants draw in nutrients.

Perhaps most troubling, USDA soil scientist Robert Kremer found in a four-year study that spraying Roundup over biotech beans seemed to touch off wild proliferation of fungi in the soil. Some fungi are fatal to soybeans. But Kremer says it's not short-term crop damage that concerns him. It's long-term shifts in soil ecology if Roundup is sprayed season after season on our most fertile fields.

"These microbes in the soil are in a natural balance with each other, and if we keep putting the same chemicals in year after year, that could lead to a shift in the soil ecosystem, which could lead to problems down the road in terms of the soil's ability to nurture plant life," Kremer said. Monsanto says it is still studying the issue.

Of equal concern are the shifts some farmers have noticed in weed populations.

Since the introduction of Roundup Ready crops, glyphosate use has soared. It was applied on 20% of U.S. farm acreage in 1995; four years later, on 62%. (Though there are competing brands from other companies, the boom has been a windfall for Monsanto: Roundup sales brought in $2.6 billion last year.) Some farmers now plant Roundup Ready crops year-round, rotating corn and soybeans; they may apply glyphosate four to six times a year on a single field.

Though the EPA has determined that spraying crops with Roundup has no ill effect on the consumer, critics worry that such heavy use will speed the emergence of weeds that can tolerate glyphosate--and will force farmers and home gardeners alike to turn to more toxic herbicides.

Some farmers are starting to see morning glory vine and yellow nut sedge, the weeds Roundup has always had the toughest time controlling, moving aggressively into their fields. Some need to mix other herbicides with their glyphosate for total weed control, said Don Schafer, a soybean product manager at Pioneer Hi-Bred International, a major seed company.

"By the time the industry acknowledges a problem, the glyphosate-resistant genes will have spread far enough through the weed population that not much can be done," warns Charles Benbrook, a biotech critic who directs the Northwest Science and Environmental Policy Center in Sandpoint, Idaho. "This is not the kind of thing where you can put the genie back in the bottle."

Monsanto executives point out that Roundup has been on the market for 25 years and there are only two confirmed examples of weeds that can withstand it: one in Australia and one in Malaysia. (They are studying two other recent reports of tolerant weeds in Delaware and Missouri, however.) What's more, they say, Roundup has long been applied four to six times a year on tropical crops such as Florida citrus, without sparking widespread weed shifts.

Many growers, however, seem resigned that weeds will one day outsmart Roundup. "It's happened with every herbicide we have," said Don Latham, an Iowa farmer.

That conviction doesn't stop him from using Roundup Ready beans, though. In fact, Latham loves them. With conventional soy, he makes two passes over each field to spray three different herbicides--and still spends hours pulling stray weeds by hand. With the biotech crop, he sprays glyphosate once and kills every weed. Even factoring in the higher price of Roundup beans, he saves $22.50 an acre on chemicals and fuel. To him, biotech is a bargain.

The Rebellion

Other growers are not so sure.

When a farmer buys a 50-pound sack of Roundup Ready soybeans, enough to plant about an acre and a quarter, he pays an extra $6.50 "technology fee." He also has to sign a two-page contract promising not to save beans from his harvest to plant as seed the following season. This is a radical demand. Traditionally, about a third of U.S. soybean growers have saved some of their harvest for seed, which saves them money.

Monsanto's rationale is clear. It spent at least $80 million to develop biotech soy. It owns eight patents on Roundup Ready beans, plus another two dozen on technologies developed during the 13 years of research and testing it took to bring the soy to market. Now, it's payback time. Or, as Brett Begemann, a vice president, put it: "To make that kind of investment, you have to get a return."

The company operates a toll-free hotline to collect tips about farmers who might be saving seed illegally. And tipsters call by the hundreds, eager to blow the whistle on competitors getting the Roundup gene for free. Monsanto's investigators--the "bean police" to angry farmers--follow up on every tip. Quite often, Begemann said, the cases are resolved with the offending grower agreeing to pay a fine. But Monsanto also has taken scores to court.

Among the pending cases is a suit against Mitchell Scruggs, a 51-year-old soy and cotton farmer near Tupelo, Miss.

Scruggs likes the Roundup trait. But he hates Monsanto's contract. In open defiance, he saved and replanted his biotech seed four years running. Then the company sued him. He has countersued with an antitrust claim, arguing that Monsanto is colluding with seed companies and retailers--who get a cut of the technology fee--to squeeze farmers dry.

"They're trying to control all the food and fiber in the world by monopolizing the seed industry," Scruggs said, an edge to his Southern drawl.

Hoping to spark a farmers' rebellion, Scruggs recruited 200 neighbors not long ago and founded the "Save Our Seed" movement. They advertised their wrath in farm publications and received, Scruggs says, some 18,000 calls from irate farmers nationwide. Scruggs' attorney now has antitrust cases against Monsanto in two other states.

Monsanto also is catching flak from critics over its proprietary attitude toward the genes and technology that made its biotech blockbusters possible and power its $5.5 billion in annual sales.

Monsanto does license its technology widely so other researchers can use its techniques. It also donates its know-how to work on Third World staples such as cassava. But that track record does not reassure critics who warn that Monsanto and a few other biotech leaders have increasing power to choke off competing research.

"Who will determine the future of agricultural research? Are we as a society willing to turn this over to a handful of companies?" asked Hope Shand, research director of the Rural Advancement Foundation International.

Monsanto, of course, stands by its business model. And it stands by Roundup Ready. Among the dozens of biotech crops in its pipeline: Roundup Ready wheat, rice, alfalfa and sugar beets.

Those who fueled this revolution, who spent nights analyzing soil bacteria in the lab and days juggling test tubes with a robot, think of Roundup Ready as a marvel. It has been a profit machine for Monsanto, of course. But they say it has transformed farming as well. They are proud, and still slightly amazed, that they pulled it off.

Padgette tried recently to put the feeling into words. This was the best he could do: "You just sit back and you say, 'Wow.' "

Copyright © 2001 Los Angeles Times

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