UPI INVESTIGATIVE REPORT 1987
(BURIED SINCE 1987!)
NUTRASWEET: QUESTIONS SWIRL - PART 2

By Gregory Gordon
UPI Investigative Reporter



Posted 18 April 2004


(Editor's note: UPI Investigative Reporter Gregory Gordon spent eight months examining industry research into popular artificial sweetener, NutraSweet and the Food and Drug Administration's handling of the product permeating the diet food and drink markets. Here is the second in his three-part report.)

Part 2: NUTRASWEET APPROVAL MARRED BY CONTROVERSY

By Gregory Gordon

WASHINGTON (UPI) Pouring over laboratory rat studies in the spring of 1981 in the government's final safety review of a new artificial sweetener, senior statistician Satya Dubey of the Food and Drug Administration was troubled.

Dubey, a member of a special FDA "commissioner's team" formed to help decide the fate of the product to be known as NutraSweet, wrote an internal memo that brain tumor data from the rat tests was so "worrisome" that he could not recommend approval.

Two other statisticians on the six-member team agreed with Dubey that the Chicago-based G.D. Searle Co. had not proved with "reasonable certainty" the safety of the sweetener, known generically as aspartame. A 1980 Public Board of Inquiry had voted 3-0 to ban aspartame because of similar fears.

But a few weeks later on July 18, 1981, new FDA Commissioner Arthur Hull Hayes, Jr., a pharmacologist who had been in office less than three months and had little background in food additives, overturned the board and approved the use of aspartame in dry foods.

The ruling, one of the first regulatory actions of the Reagan presidency, came at a time of growing concern that the most widely used low-calorie sweetener, saccharin, was linked to cancer. Thus Hayes' approval of NutraSweet profoundly changed the eating habits of millions of Americans, handing Searle a financial bonanza.

It also climaxed a topsy-turvy, eight year FDA review process in which the agency approved the sweetener, then banned it and demanded a grand jury investigation of its manufacturer, only to reverse course again after reexamining the issue at least five times.

Now, six years after Hayes' ruling, its uses expanded, the sweetener is widely consumed in diet sodas, puddings, cereal, drink mixes, and even chewing gum and vitamins. Yet NutraSweet and its FDA approval remain at the center of controversy, the sweetener's safety questioned by a small corps of independent scientists; defended by its manufacturer and the diet food and drink industry.

In a recently released report, the General Accounting Office concluded that the FDA "adequately followed" its food additive approval process on NutraSweet.

Congress's investigative arm did not evaluate the sweetener's safety. A federal appeals court also has rejected court suits by consumer groups challenging the NutraSweet approval.

United Press International has learned that more than 10 federal officials involved with the NutraSweet review have taken private sector jobs linked to the industry ­ among them, Hayes, an acting FFDA commissioner and former chiefs and acting chiefs of the agency's Bureau of Foods.

In addition, many of the scientists who have produced favorable studies or served as outspoken advocates of NutraSweet's safety have received grants or consulting fees from Searle and the industry.

Consumer lawyer, James Turner, who has unsuccessfully pressed petitions for a NutraSweet ban as part of an 11 - year campaign against the sweetener, asserted, " NutraSweet is an opportunity for the entire country to look in great detail at how we make food safety decisions. It is a rickety, 19th Century process."

G.D. Searle began to study the artificial sweetener aspartame soon after a company laboratory chemist, James Schlatter, stumbled on the compound when he licked it off his finger while conducting ulcer research in 1965.

In a memo on Dec. 28, 1970, a Searle official laid out a plan for winning FDA approval for the sweetener. " We must create an affirmative atmosphere in our dealing with them," Herbert Helling wrote senior company executives. Helling suggested that Searle representatives carefully order proposals to the FDA to put Bureau of Foods officials "into a yes saying habit." If FDA officials could be swayed to do Searle some favor, he asserted, it would "help bring them into a subconscious spirit of participation."

On July 26, 1974, just 15 months after Searle petitioned for approval, FDA commissioner Alexander Schmidt approved aspartame use in dry foods, allowing a 30-day period for public hearings and comment. He acted on a strong endorsement from the Bureau of Foods, now called the Center for Food Safety and Applied Nutrition (CFSAN).

At that point, consumer attorney Turner, author of a 1970 book about food additives, objected to the short comment period. Turner was joined in his protest by a now-defunct public interest group and by Dr. John Olney, a Washington University neuropathologist who had linked aspartame to brain lesions in mice.

Schmidt promptly froze the approval. In an action that was the first of its kind, he ordered that a Public Board of Inquiry be named to look into aspartame.

Schmidt also had been alerted to conflicts between Searle research reports and conclusions from independent animal studies that the firm's anti-infective drug, Flagyl and its cardiovascular drug Aldactone may cause cancer. He named a Bureau of Drugs task force to investigate.

Philip Brodsky, the unit's since-retired lead investigator, said aspartame was included in a broad inquiry into Searle animal studies on five drugs and the Copper-7 intrauterine device to surprise the company. "We didn't think they'd expect us to cover it."

The task force assailed Searle's conduct of research on most of the products, including aspartame, in a searing, 84-page report.

"At the heart of the FDA's regulatory process," the report said, "is its ability to rely upon the integrity of the basic safety data submitted by sponsors of regulated products. Our investigation clearly demonstrates that, in the G.D. Searle Co., we have no basis for such reliance now."

The task force charged, for example, that the company removed tumors from live animals and stored animal tissues in formaldahyde for so long that they deteriorated. Instead of performing autopsies on rhesus monkeys that suffered seizures after being fed aspartame, the company had financed a new monkey study with a different methodology that showed no problems.

For the next seven years, Searle's petition was tied up in reviews by the task force and other sharply critical FDA panels. At the task force's request, Richard Merrill, the FDA's general counsel, demanded in a letter that Samuel Skinner, the U.S. attorney in Chicago, open a grand jury investigation of Searle and three of its employees.

One Searle official named by Merrill was Robert McConnell, who had been director of Searle's Department of Pathology and Toxicology and oversaw most of the company's aspartame research.

McConnell's Detroit lawyer, Gerald Wahl, said that as the inquiries heated up, his client was suddenly awarded a $15,000. bonus and asked to take a three-year sabbatical by director Wesley Dixon. Wahl said Dixon told McConnell he had become a "political liability," a remark Dixon later denied making.

McConnell received his annual salary of more than $60,000 during the sabbatical at the Massachusetts Institute of Technology, but he never got his job back, and ended up suing the company, Wahl said.

"I've represented hundreds of executives, but I've never seen anybody get the deal that McConnell got," he said. "When you boil it all down, they were looking for continued support from McConnell during the inquiries."

Wahl said McConnell had felt pressure to hurry his research because of the "profit motive," but the company never ordered him to alter test results.

Chief investigator Brodsky said that "politicized" handling of the task force disclosures, at hearings chaired by Sen. Edward Kennedy D-Mass., was one reason he retired in 1977. He said the main witnesses, Searle executives, and top FDA officials uninvolved in the investigation gave "the wrong answers to the wrong questions"...They didn't even let the experts answer the questions.

The FDA, rocked by controversy, established a set of "good laboratory practices" ­ minimum standards for future corporate research work.

Richard Ronk, deputy Bureau of Foods chief, stressed that Searle practices were typical of the industry at the time, "not the worst on the block."

Searle's fortune did not begin to change until 1977, when Donald Rumsfeld, White House Chief of Staff under Gerald Ford, was named its new president.

Turner alleged that Searle chose, with Rumsfeld's hiring, not to redo the questioned studies on belief he could handle aspartame as "a legal problem rather than a scientific problem."

The company also hired another Ford White House official, William Timmons, as a Washington lobbyist.

Before deciding on Merrill's grand jury request, U.S. Attorney Skinner and an aid agreed in February 1977 to meet with lawyers for Searle, including Newton Minow, a partner in the law firm of Sidley & Austin.

A month later, Skinner, a Republican appointee who was looking for a job as a result of Jimmy Carter's election, informed aids in a memo that he had begun preliminary employment discussions with the law firm.

Withdrawing from the Searle matter, Skinner suggested his designated successor, Thomas Sullivan, be left to decide whether to open a grand jury inquiry-a move that delayed action for at least four months. Sullivan took office just 12 weeks before expiration of the statute of limitations for prosecuting alleged false statements on aspartame. While the grand jury inquiry ultimately was convened, those allegations were not explored.

Skinner denies any conflict of interest.

Assistant U.S. Attorney William Conlon worked with the grand jury until October 12, 1977, two days after the statute of limitations expired on the aspartame allegations. No indictments were brought on the few matters investigated. Conlon, who declined comment, joined Sidley & Austin 15 months later.

Following issuance of the task force report back in March 1976 and facing a dilemma as to how to proceed, the FDA sought new reviews of several "pivotal" studies ­ long term animal tests to see whether aspartame causes cancer.

A new five-member internal FDA task force analyzed three of these studies, and Universities Associated for Research and Education in Pathology, Inc., a consortium formed by 15 universities, was contracted to look at another dozen.

Much like the earlier team, the five-member FDA task force, headed by veteran Chicago inspector Jerome Bressler, assailed the quality of animal tests into whether the substance might cause birth defects and tumors.

The report said Searle laboratory employee Raymond Schroeder, who worked on related research, first told investigators the feed in the study of the aspartame breakdown product DKP (diketopiperazine) was so inadequately mixed it appeared the rats could "discriminate" and avoid eating the DKP.

Schroeder, who has worked for another company since 1975, later backed off his statement. He told UPI, "I just didn't feel qualified to speak on something I didn't work on...There's no one twisting my arm."

Bressler criticized the company's "sloppiness" on all three studies. "The question you've got to ask yourself," he said in an interview, "is: Because of the importance of this study, why wasn't greater care taken ? The study is highly questionable because of our findings. Why didn't Searle, with their scientists, not closely evaluate this, knowing fully well that the whole society, from the youngest to the elderly, from the sick to the unsick...will have access to this product?" Howard Roberts, acting director of FDA's Bureau of Foods, appointed a five-person task force to review the Bressler team's findings pending a decision on whether to throw out the three tumor and birth-defect studies.

Jacqueline Verrett, a senior scientist on the review team, said members were barred from stating opinions about the research quality. "It was pretty obvious that somewhere along that line they (bureau officials) were working up to a whitewash," she said. "I seriously thought of just walking off of that task force."

Verrett, now a private consultant, said that she and other members wanted to "just come out and say that this whole experiment was a disaster and should be disregarded."

But on September 28, 1977, the panel reported that deviations between Searle's raw data and its FDA submissions were "not of such magnitude as to alter its conclusion."

Verrett said the bureau's intent seemed to be "to tone down what was really found." She noted the bureau felt pressure because safety concerns also had been raised about cyclamate, another alternative for the cancer-linked sugar substitute, saccharin.

In October, 1978, a year after ordering the review that helped get Searle's petition back on track, Robert's (acting Director of Bureau of Foods) quit to become vice president at the National Soft Drink Association. The NSDA's members later marketed a stream of NutraSweet-flavored diet soft drink products.

Reached at NSDA, Roberts dismissed Verrett's criticism, asserting the task force report "really was of no importance." He said he had no concerns about the appearance of his taking the NSDA job, stressing he does not represent NSDA before the FDA. "I sleep well at night," he said.

Negotiations for an additional, outside review of Searle's studies had begun with an August 4, 1976 meeting between Searle and 10 FDA officials. During the meeting, Searle officials said they desired to help pick the consultant to perform the review, and internal FDA memo said.

Agency memos show the FDA soon was negotiating with the Universities Association for Research and Education in Pathology for a half-million dollar, company-funded "validation" of a dozen Searle studies.

The pathology organization's review concluded that Searle's studies were authentic and the discrepancies largely inconsequential.

Adrian Gross, an investigative consultant to the 1975 task force, later said the 16-month review was "at best, irrelevant" because the group was limited to analyzing "whether Searle lied about the data in its tests".

"It was not our task to challenge the validity of the experimental methods, since the FDA had itself already accepted the methodology", the group's executive director, Kenneth Endicott, said.

Jere Goyan, who was FDA Commissioner in 1980, said he would have put less weight on the review than on the findings of FDA's task forces. Goyan also suggested that, after approving aspartame in 1974, the FDA's Bureau of Foods may have "felt they had to keep their previous position."

Regardless, the pathology groups findings carried major weight in the final approval decision. The chairman of the 1980 Public Board of Inquiry, Dr. Walle Nauta of the Massachusetts Institute of Technology, said the board had to rely on those findings because it was denied access to the task force reports by FDA officials.

"There was absolutely no way in which we could decide who was right here," Nauta said. "We simply had to accept the data as they stood."

Nauta was joined on the panel by Drs. Vernon Young of MIT and Peter Lampert of the University of California at San Diego.

Before voting 3-0 to ban NutraSweet on the narrow cancer issue, the board itself was drawn into allegations of bias because two of the three members came from MIT ­ as did Bureau of Foods Chief Miller and several scientists involved in the controversy.

Between 1979 and 1982, four more FDA officials who participated in the approval process took jobs linked to the NutraSweet industry: Pape; acting FDA commissioner Sherwin Gardner; Albert Kolbye, who was associate director of the Bureau of Foods for toxicology, and Mike Taylor, an FDA lawyer who represented the bureau before the Board of Inquiry. All four denied any conflict of interest.

After the Board of Inquiry ruled against NutraSweet on Sept. 30, 1980, Searle waited until January 21, 1981, the day after President Reagan's inauguration, to press for a reversal of the FDA commissioner ­ assuring the new administration would decide the issue.

Jere Goyan, Hayes' predecessor as commissioner, said he found the delay curious because, after eight years of legal battles, financially struggling Searle "obviously was most anxious to have this thing approved."

Robert Dormer, a lawyer for the NutraSweet Co., said there was nothing special about the Jan. 21 date or the papers filed that day.

But with Reagan's election, it was virtually assured that a republican-appointed commissioner would replace Goyan and decide the appeal- and Searle had strong GOP connections with Rumsfeld at the helm.

Goyan had set up a five-member "commissioner's team" of scientists with no prior involvement in the issue to review the board's ruling.

On May 10 and 13, 1981, a month after Hayes took office, scientists Satya Dubey, Douglas park, and Robert Condon each laid out concerns about the sweetener's safety in memos to team lawyer Joseph Levitt.

Dubey not only expressed reservations about reported incidence of brain tumors in one key Searle rat study, but also said key data in another study appeared to have been altered. Dubey, who still works at FDA, refuses to discuss the matter.

Condon, another statistician on the team, and Park, staff science advisor in the agency's Office of Health Affairs, each said the available evidence failed to prove NutraSweet's safety or lack of safety.

Park said that Levitt hurried the panel to decide the issue. "They wanted to have the results yesterday," he said. "We really didn't have time to do the in-depth review we wanted to do."

Park said Levitt met frequently with Hayes and "was obviously getting the pressure to get a resolution and a decision made."

Sources have said the office of Sen. Howard Metzenbaum, D-Ohio, has received allegations of political influence in Hayes' final decision- making process.

In a letter written after the FDA cleared NutraSweet, one former Searle saleswoman, Patty Wood-Allott, asserted the Rumsfeld told his sales force shortly after Reagan took office that if necessary, "he would call in his markers and that no matter what, he would see to it that aspartame would be approved that year." Rumsfeld declined to return phone calls.

With three of five scientists on the commissioner's team opposing approval, it was decided to bring in a toxicologist for his opinion on isolated issues.

Goyan said if the decision were his, he never would have enlarged the team. While the panel did not vote, it ended up split 3-3.

Levitt, who normally would have been expected to draft an options paper spelling out scientific evidence on key issues, took an unusual tact. He circulated an approval recommendation ­ and only backed off when Dubey, Park and Condon objected, team members said.

Levitt said he was not directed to draft the approval memo, but did so as a "tactical" step to break the team's week-long impasse by forcing each scientist to state his views.

"It worked didn't it?" said Levitt, who later was promoted to a post as an executive assistant to the FDA commissioner.

One team member said that during discussions, Hayes, appeared to be abandoning the agency's traditional standard of "reasonable" proof of safety and looking for "proof of hazard."

Hayes' July 1981 approval decision came in the face of a Searle threat to file a suit challenging the regulatory delays.

His ruling relied in part on a late rat study of brain tumors submitted by Ajinmoto, a Japanese company that manufactures aspartame for Searle. That study, however, tested Wistar rats, a strain that some scientists said is more tumor resistant than the Sprague-Dawley rats used in earlier research.

In his decision, Hayes wrote: "Few compounds have withstood such detailed testing and the repeated close scrutiny and the process through which aspartame has gone should provide the public with confidence of its safety."

In late 1982, Searle petitioned for FDA approval to use the sweetener in diet soft drinks and children's vitamins. On a day when Hayes was away, Novitch approved the petition, increasing the acceptable daily intake level for humans by nearly half, from 34 mg to 50 mg per kilogram of body weight.

Novitch, now in private industry, said he and Hayes had worked together on the matter, but declined to say why he was left to sign the approval.

Just weeks later, Hayes resigned under the cloud of an internal Dept. of Health and Human Services investigation into his acceptance of gratuities from FDA-regulated companies ­ including free rides aboard jets owned by a major NutraSweet user, the General Foods Corp.

Shortly after being named Dean of the New York Medical school, Hayes also became a consultant to the New York-based public relations firm of Burson-Marsteller, which represents the NutraSweet Co. and several major users.

Hayes' former top spokesman, Wayne Pines, who previously had joined the firm, said he approached Hayes because he thought him "an added value" to clients.

Hayes, now president of the E.M. Pharmaceutical Co. in Hawthorne, N.Y., declined comment for this series of articles. He has in the past denied any impropriety in his consulting role, which sources said paid him more than $1000. per day.

Burson-Marsteller vice president, Buck Buchwald stressed that Hayes was not involved in NutraSweet issues and worked but 10 to 15 days a year. But a former Burson-Marsteller employee, who requested anonymity, said Hayes was hired precisely because of his decision on NutraSweet and other issues affecting company clients.

Sen. Metzenbaum said it was "at the very least...unbecoming, at the very most, it probably was inappropriate" for Hayes to accept the position.

In July 1986, Anthony Brunetti, a FDA consumer product officer who drafted the 1983 notice approving NutraSweet use in soft drinks, also took an industry job, joining the soft drink association as a science advisor. Brunetti said he cleared the move with the FDA's ethics officer.

"My situation," he said, "is no different than many, many people...that go through the revolving door. It can be made to look like there is some duplicity going on. In terms of my own conscious, I have no problem."

Ron Lorentzen, an FDA toxicologist who was asked by current Bureau of Foods chief Sanford Miller to perform a separate, internal review of the agency's handling of aspartame, described it as a "tortured" story.

But despite the myriad questions and revolving door issues, he asserted the FDA responded to each issue "in a way, perfectly reasonable." Other questions have arisen over the company and industry's funding of researchers who have invariably supported NutraSweet's safety ­ with the exception of people with the rare disease phenylketonuria. Independent studies have often raised health concerns.

Dr. Lewis Stegink, a pediatrics professor at the University of Iowa who repeatedly has produced studies, that he says, support aspartame's safety, has received more than $1.3 million dollars in research grants and gifts, including lab equipment, from the NutraSweet) company since the early 1970's, limited university records show.

Metzenbaum said, "If it is a fact that no questions were raised and more than a million dollars was spent, you have to wonder whether their job was done thoroughly as it should be done."

Stegink's longtime research collaborator, Dr. Jack Filer, serves as executive director of the ILSI (International Life Sciences Institute), the Washington foundation that funds aspartame research.

Filer said he sees no conflict in his dual roles as ILSI's executive director and a company researcher, but declined to disclose his ILSI consulting fees. He said all the Iowa research money has gone to Stegnik.

Filer also said the company (NutraSweet) paid him and Setgnik "$2,000. to $3,000." to edit a book, "Aspartame," about research on the sweetener, and another $1,000. or $1,500. to each of the contributors, including researchers whose studies helped the company win FDA approval. The book states that "the extensive research program carried out to demonstrate aspartame safety may serve as a new standard for the study of food additives." Filer said he had been "maligned over the years for taking money from corporations," but that the funding source never has influenced his findings.

Dr. David Hunninghake of the University of Minnesota was picked to study aspartame's effect on the liver by former Searle research director Daniel Azarnoff, once Hunninghake's mentor at the University of Kansas, a Hunninghake associate said. He said Searle helped design the study.

Susan Schiffman, named to head a Searle-funded Duke University medical School study into NutraSweet's link to headaches, is a former General Foods and Searle consultant. Her research at Duke, where the medical school has a new Searle Center, has fallen under the office of university vice president William Anylan, a former Searle director. Schiffman said Anylan had no role in Searle's promise to cover all costs of the study, which is expected to cost "hundreds of thousands of dollars." She said she took no salary for her work.

Another industry-backed researcher has been Ann Reynolds, now chancellor of California State University at Long Beach. Dr. John Olney asserted that in a 1971 study, Reynolds confirmed his findings that the sweetener destroyed nerve cells in infant mice, but Searle did not notify the FDA until 1975 or 1976, after the FDA's initial review. Dr. Daniel Azarnoff, Searle's former science director, and other Searle officials have denied withholding any studies from the government.

Reynolds also co-authored a Searle monkey study that contradicted earlier aspartame research leading to seizures in monkeys. Dr. Olney alleged that Reynolds, who did not return phone calls, and several other company-funded researchers "have a pattern of avoiding" scientific peer review. Industry spokesmen contend that few studies by scientific critics of NutraSweet have undergone peer review. But few such clinical studies have been completed because of a funding shortage.

George Liepa, a nutrition professor at Texas Woman's University said he was required to discuss his findings with Searle before reporting that NutraSweet "is safe" for diabetics on hemodialysis. Dr. David Horwitz, an associate professor of medicine at the University of Illinois, who studied NutraSweet and diabetics, said the company did not influence the outcome, But, "The results were favorable... Obviously, that is perhaps why Searle was eager to fund an additional study of ours."

Dr. Richard Wurtman was an ardent defender of NutraSweet's safety at public hearings six years ago (1981). Now he is one of the artificial sweetener's harshest critics.

"I think the likelihood is very strong that NutraSweet does produce serious and potentially damaging brain effects in a number of people," the nationally known neuroscientist from Massachusetts Institute of Technology said in a recent series of interviews.

Wurtman's seemingly enigmatic flip-flop from a position as a G.D. Searle Co. consultant to a role as a foe urging restrictions on marketing the firm's best-selling product appears to be much at the center of the controversy over NutraSweet's safety.

Wurtman says his views simply changed with the evolution of his scientific studies and his growing skepticism of industries attitude toward research.

His sometimes stormy relationships with the company and an industry-funded foundation, the ILSI, provide a glimpse of the maneuverings surrounding research into a major food additive.

Wurtman, a brash-talking, hard-driving head of a major research laboratory, said he unilaterally severed his consulting relationship with Searle in 1985 after he grew concerned about NutraSweet's effects and the company's inaction. He said he rejected several approaches by the firm, (the NutraSweet Co.) since its sale that year to the Monsanto Corp., to rekindle the consulting arrangement.

Wurtman accuses NutraSweet Co. officials of "misrepresenting" the nature of company-financed studies into links between the sweetener, generically known as aspartame, and epileptic seizures, of sidestepping key safety issues, and of threatening to veto his grant application to ILSI's aspartame committee.

A spokesman for the NutraSweet Co. described Wurtman's public attacks as a "political issue," but declined to elaborate.

Wurtman's relationship with Searle, The NutraSweet Co., and many of the companies that sell NutraSweet-flavored products dates to 1978. Beginning that year, according to public records, ILSI provided more than $200,000. to finance his research on caffeine, a common beverage ingredient that was under FDA scrutiny.

Wurtman said he found no ill health effects during his caffeine research, and his relationship was "excellent" with ILSI ­ a spinoff of the National Soft Drink Association.

During the same period in 1978, he said he rejected a Searle offer of financial support for research on amino acids. Phenylalanine and aspartic acid, two such amino acids, are the main components of NutraSweet.

He said Dr. Sanford Miller, chief of FDA's Bureau of Foods, later sought his testimony before a 1980 Public Board of Inquiry because he openly stated his belief that neither glutamate nor aspartic acid, a similar compound to that in NutraSweet, would not cause brain damage. Wurtman strongly defended aspartame at the hearing.

He said he did not focus on phenylalanine until about 1983, when he learned the FDA was considering expanding use of the low-calorie sweetener, approved two years earlier for dry foods, to include carbonated soft drinks.

From his caffeine research, Wutman said, he was aware of the exploding soft drink market and concluded "that the use of aspartame was going to go up considerably."

"I was genuinely concerned that there might be an increase in brain phenylalanine levels."

Wurtman said that, while phenyalanine is vital to the brain, it can serve as a barrier to 20 other amino acids that provide protein.

At a meeting in July 1983, Wurtman said he told National Soft Drink Association officials that "if you put large amounts of aspartame in soft drinks and people drink as much as I think they will, there are going to be problems."

Wurtman said that after the industry accepted his idea for combining NutraSweet with saccharin to cut the danger level, he accepted a Searle offer to serve as consultant and relations were "all very friendly and chummy".

Wurtman said he became "convinced that these people really want to know the extent to which their product may be a real problem".

Shortly after he took the consulting job, he began getting letters from seizure victims who believed their problems stemmed from NutraSweet.

Wurtman said he when advised Dr. Gerald Gaull, Searle vice president for nutrition and medical affairs, in the Spring of 1985 that he thought there was a link, "there was a very rapid souring of their relationship".

During a visit to his MIT laboratory, Wurtman said, Gaull asked him to review a proposal for a seizure study by him and his collaborator, Harvard University neurologist Donald Schomer. He charged that when he advised Gaull the pair would seek funding from ILSI, Gaull "got very angry" and said, "We (meaning Searle), are active members of the ILSI and we will veto your study".

"I was incredulous that he would say it to me, and I was dumbfounded that he would say it in front of a witness," Wurtman said.

Schomer said he did not recall the comment. Gaull said, "There is no way that I can veto anything at ILSI," because Searle has only one of 12 votes on the ISLI aspartame committee. He did not deny making the threat.

Wurtman charged that Gaull later advised ISLI that two company-funded seizure studies already were under way, and the foundation declined to approve Wurtman's grant.

In July of 1985, Wurtman said, he and three other scientists who had expressed concerns about NutraSweet were among a group invited to Gaull's home in Northeast Harbor, Maine, for a two-day conference.

"I left there with the conclusion there was no way these people were going to do an honest job in assessing the possibility that aspartame contributed to seizures," Wurtman said.

He said he also was skeptical because, as a company consultant, Searle had asked him to chair its scientific advisory committee, a role in which the company could use his name to defend the integrity of its own research. But, he said, Searle refused to let him see protocols and data from its studies.

"They wanted the name, but not the reality," he said. Frustrated by these developments, Wurtman said he wrote a letter to Robert Shapiro, president of Searle and later of the NutraSweet Co.

"Dear Bob," the letter said, "I know you'll agree that my value to Searle... derives in part from my telling the company some things that it would rather not hear...and then from helping the company to deal with those things."

"One such thing is that some consumers may develop significant medical symptoms after consuming very large amounts of aspartame, particularly if they happen, concurrently, to be on a low-calorie, low-protein, weight-reducing diets... If Searle-supported studies are going to contribute to our understanding of these people and their symptoms, then the studies have to include them, and not be restricted to people who have a can or two of soda per day."

He said Shapiro never answered the letter.

Wurtman said he resigned his consulting role a short time later and rejected company efforts in the ensuing months to reinstate the arrangement.

Continue on to PART 3