FDA Followed Paper Trail in Hunt for Potent Tobacco : Smoking: Tip led to what agency says is industry project to cultivate ‘Y-1’ plant that is high in nicotine levels.

When the tip crackled over the speaker phone, the half a dozen Food and Drug Administration investigators gathered for the call did not become terribly excited.

“I think you should check the patents,” said a source familiar with the inner workings of the tobacco industry.

The tip was so vague that investigators didn’t expect much. Nevertheless, they ordered a routine computer search of the worldwide patent database.

It was Friday, May 13, a day that turned out to be anything but unlucky for the FDA team--a group that had been working nonstop for months investigating nicotine and tobacco.

Within four days, the tip had touched off an intense investigation to unravel the story of “Y-1,” a quiet, decade-long project to create a tobacco plant with unusually high levels of nicotine. The startling findings, disclosed by the FDA on June 21, will almost certainly serve as the underpinnings for the agency’s case to regulate tobacco.

The search of patent databases paid off on May 17, when FDA librarian Carol Knoth turned up a citation that led to a document in Portuguese. It had been filed by Brown & Williamson Tobacco Corp., the third-largest U.S. cigarette maker.

Even to those who did not understand Portuguese, the words were riveting.

“Variedade de fumo geneticamente estavel e planta de fumo . . . nicotina . . . 6% ou maior.”

It was obvious the patent involved some kind of new tobacco plant, most of it grown in Brazil, with nicotine levels of 6% or greater--unheard of until that moment.

“I remember we were all standing around outside the commissioner’s office staring in amazement at this piece of paper,” said Mitchell Zeller, an FDA official involved in the inquiry. “We knew there had been breeding efforts but, as far as we knew, the highest they’d ever gotten the nicotine up to in flue-cured tobacco was 3.4% So this was quite a leap.”

From the FDA’s perspective, Y-1 was evidence that the industry would go to extraordinary lengths to control the levels of nicotine in cigarettes. Any such efforts are important because the FDA is trying to prove nicotine is an addictive drug and determine whether the industry can control its levels in cigarettes. If so, cigarettes could be subject to FDA regulation.

The Industry’s Position

Industry officials insist that they do not believe nicotine is addictive, and they deny that they manipulate nicotine levels to keep smokers hooked. They say, however, that they do blend various tobaccos to control nicotine levels--but only to maintain taste.

The FDA team actually began its work in March, after FDA Commissioner David A. Kessler announced that the agency was going to explore the possibility of regulating cigarettes. On May 3, FDA investigators traveled to Macon, Ga., for a meeting with Brown & Williamson officials, a session that would later become a source of friction over whether B&W; had tried to cover up the Y-1 project--and whether the FDA knew about Y-1 in advance.

During the meeting, FDA investigators asked general questions about plant breeding for high nicotine levels.

B&W; said it was not “feasible” because of agreements among U.S. cigarette companies that set limits on the nicotine yield of tobacco plants grown in this country. No one asked about growing such plants outside the United States, and Y-1 never came up.

FDA officials say they believe that B&W; deliberately concealed Y-1, a charge the company denies. Moreover, B&W; officials claim that the FDA knew about Y-1 before the meeting but withheld questions about it so that the agency could later accuse the company of hiding the project.

Complete Document

FDA officials say they knew nothing about Y-1 until they followed the tip, which came 10 days after the meeting.

On the day Knoth found the patent citation, she was unable to call up the full document because it was not in English. “No abstract available,” the computer screen flashed.

The agency asked a local patent search company to track it down. The next day, Liz Berbakos, the FDA’s policy coordinator, strode into Kessler’s office, wide-eyed, shaking a piece of paper at him.

“Boss,” she said, “you won’t believe it.”

She had the complete document. It was barely legible and in Portuguese. Nevertheless, it was evident that B&W; and a sister company in Brazil, Souza Cruz Overseas, had been involved in growing a new kind of tobacco plant with at least twice the standard levels of nicotine.

Agency officials were flabbergasted.

“I remembered all of those papers we had read on plant-breeding that we thought didn’t go anywhere,” one FDA official recalled. “Now, all of a sudden, we had something--the first piece of paper that made it real.”

But more work needed to be done. The patent showed that the industry had been exploring ways to increase nicotine in tobacco leaves, but there was no evidence yet that the experiment had gone far beyond its early stages.

Major Questions Left

Had large quantities been grown? Had any come into the United States? Did any cigarettes on the market contain the new leaf? A yes answer would further bolster the FDA’s case.

The agency began checking U.S. Customs Service records to see whether any of the leaves had entered the country. One FDA investigator “spent weeks doing computer searches in customs databases and manually going through customs records in various locations in the Southeast,” Zeller said.

At the same time, FDA officials decided to visit Dr. Janis Bravo, a scientist employed by DNA Plant Technology. Bravo’s name was among those listed on the patent as an inventor of the new plant.

DNA Plant Technology, or DNAP, is an agricultural biotechnology company that had been contracted by B&W; to work on the new plant. The company, which had been based in Cinnaminson, N.J., had recently moved its headquarters to Oakland.

On May 25, Zeller and another FDA investigator drove to New Jersey to see Bravo. They did not tell her they were coming and had no idea if she would let them into her house. They pulled into her driveway about 7:30 p.m. in the middle of a drenching rainstorm.

“Her husband answered the door and let us in,” Zeller recalled with amazement. “I think he actually felt sorry for us because we were standing there, getting soaked.”

Bravo agreed to talk. During the next two hours, she disclosed that Y-1 already had a high nicotine gene in its seed when DNAP’s work began and that her job was to make the new plant male sterile--that is, unable to produce seeds on its own without the addition of pollen. A plant thus rendered sterile presumably could make it harder for competitors to obtain seeds.

The two FDA investigators also asked her if she had ever traveled to Brazil to see it grown and whether she had ever shipped the seeds anywhere. The answer to both was yes, Zeller said. This was important because, until 1991, federal law prohibited the export of tobacco seeds, except for extremely small quantities for research. If large numbers of seeds were exported before the law changed, it is possible that someone had broken the law.

“We asked her if she had ever shipped seeds to Brazil, and she said yes,” Zeller said. “How much had she shipped? She was having trouble recalling. In one year, she said she may have shipped 10 pounds of seed,” most of which had gone to Brazil, the rest to B&W; headquarters in Louisville, Ky.

It is still unclear whether she shipped the seeds before the law was changed and whether she was the one responsible for sending enough seeds to Brazil to grow commercial quantities of tobacco.

Bravo did not return a reporter’s phone call. But her boss, David Evans, DNAP’s vice president for business development, told The Times that the company did not violate any federal laws in shipping seeds. He refused to elaborate.

On June 1, the FDA investigators had another breakthrough. Berbakos received a call from the individual who had been checking customs records.

“I think I’ve found what you were looking for,” he said.

He had uncovered two invoices filed with the Customs Service in 1992, addressed to Brown & Williamson Tobacco Corp. in Louisville, Ky., from Souza Cruz Overseas. They referred to “your order Project Y-1,” and said that more than half a million pounds of Y-1 tobacco had been shipped to B&W; on Sept. 21 of that year.

Berbakos ran into Kessler’s office.

“Boss, we found it,” she said.

Even so, agency officials were not certain whether the company had used the new high-nicotine tobacco in any cigarette brands.

Lawyers Complain

That same day, Eugene Pfeifer, an attorney with King & Spaulding, a law firm hired by B&W;, dispatched an angry letter to Kessler. The company had heard that FDA officials were visiting and calling its employees at home, and didn’t like it.

“I am writing to urge that agency inquiries . . . be made through official channels in a businesslike manner,” Pfeifer wrote. He complained that “employees found these extraordinary contacts extremely disturbing.”

Zeller responded that the agency’s efforts were justified because of the company’s reluctance to cooperate. He reminded Pfeifer that the May 3 visit to Macon, which had been scheduled to last two days, was ended by B&W; after the first day.

On June 9, the FDA spoke to DNAP’s Evans. After initially refusing to answer most questions because of a confidentiality agreement with B&W;, he later cooperated to the extent possible.

“Our job was to make it seedless when it was growing,” Evans said in a recent interview with The Times. “At the time, it appeared to be a chance to help make a safer tobacco product (with low tar), which is why we got involved in it. They came to us with a line that they wanted to have protected.”

‘No Real Proof’

The FDA wanted to know whether Y-1 had ever been used commercially.

“We had the invoices but no real proof that anything had ever been done with the stuff,” Zeller said.

The agency says DNAP indicated that the plant was never used commercially. Kessler told Congress that DNAP officials had told the FDA that B&W; “had said it was OK to tell us that Y-1 had never been commercialized.”

Evans later insisted that he told the FDA only that “as far as we knew, Y-1 had not been commercialized,” not that B&W; had instructed him to say this.

The agency also wanted to know who had developed the seed with the high-nicotine gene.

On June 10, FDA investigators spoke by telephone with Dr. James F. Chaplin, a former Department of Agriculture official regarded as a pioneer in the field of plant breeding. FDA officials, in doing their research, had read much of Chaplin’s published work and knew he had tried to develop a high-nicotine plant.

On June 13, they went to Oxford, N.C., to meet with him. He told them he was responsible for developing the high-nicotine seeds that ultimately became the basis for the Y-1 line.

Moreover, Chaplin “acknowledged that he had taken his work farther than the published literature and actually had grown some experimental varieties on a (Wilson, N.C.) farm, owned by an L.V. Jones, under a contract with Brown & Williamson,” one FDA official said.

But he said he had trouble getting his plants to grow well.

“They didn’t stand up in the field,” the FDA official said.

Enter DNAP, a company with the advanced technology to make the fledgling plants thrive.

“Here you have the traditional geneticists, like Chaplin, taking years . . . and then you have DNA Plant Technology . . . light years away from anything Chaplin could do,” one senior FDA official said.

Another Inventor

At the same time, FDA officials also reached Hugh Hardison, a retired North Carolina tobacco grower, another name listed as an inventor on the patent. Hardison, who had worked for Export Leaf of Wilmington, N.C., an affiliate of B&W;, told the FDA that he had obtained seeds from Chaplin. He said he had tried to grow at least five experimental lines on the Jones farm.

While FDA officials were at Chaplin’s home, he told them that the Jones farm was only an hour away by car and gave them directions. The two investigators decided to go.

There, they met a farmhand and some neighbors who remembered the project well.

“They said: ‘Oh yeah, we remember Y-1. . . . It was in the early ‘80s. There was even a sign that said Y-1,’ ” Zeller said.

Hardison said the five plant lines eventually were narrowed to two, dubbed Y-1 and Y-2. Hardison recorded his plants by alphabet letters, Zeller said.

Foul Smell of Y-2

The FDA was curious about the fate of Y-2.

“Did you ever smell a dirty sock?” Zeller quoted Hardison’s reply. “That’s what Y-2 smelled like when it was smoked.”

On Monday, June 13, B&W; asked for a meeting with the FDA. Thomas E. Sandefur Jr., the company’s chief executive officer, later told Congress that B&W; was concerned about the escalating Y-1 inquiry and was upset that the FDA had not asked company officials directly about it.

FDA officials readily agreed. They say they had been seeking a second meeting all along.

On Friday afternoon, June 17, B&W; sent several officials to Washington. They met with FDA investigators for four hours in the agency’s 13th-floor conference room.

“We want to hear the Y-1 story from start to finish,” Zeller told them.

Used in 5 Brands

To the FDA’s astonishment, B&W; gave them two new--and critical--pieces of information.

The company said it had 4 million pounds of the leaf in storage in the United States--far more than the half a million pounds described in the two invoices filed with the Customs Service.

And the company said it had used Y-1 in five brands of cigarettes.

Until that moment, “we didn’t have evidence that more than a half-million pounds had come into the country, or that it actually was being used,” Zeller said.

Berbakos left the meeting abruptly and climbed the stairs to Kessler’s office.

“There’s 3 to 4 million pounds here,” she told him. “And they used it in five brands of cigarettes.”

The following Monday, June 20, FDA officials went to Capitol Hill to brief the staff of the House Energy and Commerce subcommittee on health, where Kessler would testify the next day and disclose the Y-1 findings.

Rep. Henry A. Waxman (D-Los Angeles), its chairman, said the news was “beyond anything I thought would ever come out of this.”

Ironically, on April 14, as the chief executives of the seven leading U.S. tobacco companies were testifying before the subcommittee--a hearing televised live nationwide--an individual identified only as a former B&W; employee called Waxman’s office.

“This person said the company had been growing genetically altered tobacco in South America that lowered tar and increased nicotine,” recalled Phil Schiliro, a spokesman for Waxman.

“The caller said the company was test-marketing the tobacco in the United States and suggested we ask Sandefur about it. The caller couldn’t remember the name of the project.”

The staff decided against having Waxman ask the question. They felt it was too risky.

“There’s an old lawyer’s saying: You never ask a question you don’t know the answer to,” Schiliro said, adding that Waxman “always takes the approach that if it’s good information, it will come out eventually.”