Mix-up leaves biotech project at CSUS withering on the vine

By Edie Lau -- Bee Science Writer

Published Wednesday, December 31, 2003

A project in genetically engineering crops to produce medicines began with exuberant hopes at Sacramento State. Now all that remain are two disheveled plants with one wrinkled red tomato.

After five years, the biologist who led the project, Nicholas Ewing, is giving it up. The experiments didn't work. Ironically, the very tool he was trying to employ -- biotechnology -- spoiled the studies.

The problem lay in the seeds. Ewing and his students tried to genetically engineer seeds they thought were from an ordinary tomato. Trouble was, the seeds were mislabeled; they arrived with genes already altered.

It was another case of agricultural biotechnology appearing to be out of control.

"This is a significant thing," Ewing said in an interview this week in his office at California State University, Sacramento, where he is chairman of the department of biological sciences.

"It illustrates that these (biotech) genes can be difficult to contain unless we have practices in place to better detect them."

Ewing was one of 34 people around the world who may have received the misidentified seeds over the past seven years. The seeds came from the University of California, Davis, C.M. Rick Tomato Genetics Resource Center -- a repository of seeds from more than 3,600 varieties of wild and domesticated tomatoes.

Like other such seed banks, the Rick Center is a sort of Library of Congress for crops -- a place where the genetic diversity of important plants is catalogued and preserved.

The Rick Center doesn't knowingly keep genetically engineered seed in its stock. When officials recognized the error this fall, the embarrassed center issued a recall and apology, followed in mid-December by a public announcement.

The seeds traveled widely: to Africa, Asia, Australia, Europe, North America and South America. Most recipients were scientists, though not all. A recipient in England used the tomatoes in a display garden. The use by a recipient in Ethiopia could not be determined.

UC Davis officials emphasized that the mistake in no way endangered the food supply. The biotech gene, or "transgene," in the tomato was approved for human consumption by the U.S. government in 1994.

The transgene is designed to slow the fruit's decay. It is essentially the same as that in the Flavr Savr tomato, the world's first genetically engineered commercial crop, created by the Davis biotech company Calgene.

Since the consequences of the mistaken distribution so far appear to be minor -- nothing more serious than botched experiments in assorted labs -- Ewing looks upon the incident as something of a useful warning.

"In a way, I think it was good it happened at this time in this way. It's indicative of what can happen, and maybe," he said, pausing, his normally lively voice growing soft, "even what will happen."

Ewing, who earned a doctorate in plant physiology at UC Davis in 1993, started exploring making pharmaceuticals in crops in 1998. He was inspired by a student who became intrigued by the idea of making inexpensive vaccines out of plants, which could be especially beneficial in poor countries.

But now, not wanting to be party to a more serious biotech accident, Ewing is putting the project on indefinite hold.

Students in his lab were just beginning to attempt to engineer into tomatoes the components of an antibody derived from mouse cells, as well as a bacterial protein that binds to antibodies.

In both cases, the products appear to be safe to eat, Ewing said, but he can't say so positively.

"In light of this (seed accident), we thought, 'Let's back up on this,' " he said. "... I want to look more carefully at safety and the regulatory process."

One idea Ewing has to better contain biotech genes is to require all engineered organisms to possess a universal genetic signature, a DNA bar code of sorts, that identifies them as transgenic.

Jim Rogers, a spokesman for the U.S. Department of Agriculture, which is investigating the UC Davis seed accident, said the agency is receptive to suggestions for improvement. "We're always interested in new ideas and new techniques," Rogers said.

The UC Davis seed mix-up is just the latest in a string of mishaps involving the escape of genetically engineered genes.

In 2000, StarLink, a variety of transgenic corn approved only for animal feed, was discovered widely in taco shells, corn chips and other human food, forcing a massive recall. Traces of the StarLink protein reportedly remain in some corn products today.

In 2001, researchers from UC Berkeley reported finding biotech genes in native corn from the mountains of rural Oaxaca, Mexico, where growing genetically engineered corn is illegal.

In 2002, a Texas biotech company, ProdiGene, was found to have contaminated 500,000 bushels of soybeans with corn engineered to make pig vaccine. The soybeans had to be destroyed.

In all cases, no obvious harm was done to public health or the environment, though there were economic repercussions and, perhaps, some erosion in consumers' confidence.

The UC Davis gene escape differed from the others in one particularly notable way: It brought more trouble to genetic engineers -- the people who typically feel the most comfortable with the science -- than to anyone else.

"The consequences of the mix-up were a loss of time and money for our laboratory," Patricia Drevet, a researcher at Université Blaise Pascal in France, said in an interview by e-mail. "... All our experiments with those materials failed."

At CSUS, Ewing and his students were confounded because the seeds contained a bacterial gene for antibiotic resistance, which is a tool genetic engineers use to distinguish transformed plants from untransformed plants.

Usually only a small fraction of plants that are manipulated actually incorporate the transgenes. Scientists treat all manipulated plants with antibiotics, and those that survive -- those that are resistant to antibiotics -- are the ones that have taken up the transgenes.

In Ewing's case, even the tomato plants that didn't take up his target gene carried the antibiotic resistance gene. Later, when he and his students checked the plants' DNA, they were perplexed: The gene they thought they'd introduced wasn't there.

Figuring the mistake was theirs, they ordered a second batch of seeds from UC Davis. "The last thing you want to do is blame somebody else," Ewing said.

When the same thing happened again, Ewing realized something was wrong with the seed. Just as he was set to call the seed bank, the seed bank called Ewing.

The mix-up had been detected through a similar experiment failure at a UC Davis lab.

Since then, most of CSUS' misidentified tomato plants have been bagged up to be destroyed. Soon, the last two standing plants will join the rest in an orange plastic garbage bag marked "biohazard."


About the Writer The Bee's Edie Lau can be reached at (916) 321-1098 or elau@sacbee.com.