GREG GORDON, UPI INVESTIGATIVE REPORT ON ASPARTAME 10/87:...

GREG GORDON, UPI INVESTIGATIVE REPORT ON ASPARTAME 10/87:
Part One of Three:
UPI Investigative Report 1987NutraSweet:Questions SwirlPart 1:   DID SEARLE IGNORE EARLY WARNING SIGNS ?By GREGORY GORDON WASHINGTON (UPI) ≠ A University of Illinois scientist says he warnedthe G.D.Searle Co. years before NutraSweet swept the diet food and softdrink markets that the companyís new artificial sweetener could heightenrisks of brain damage in fetuses and small children. Dr. Reuben Matalon, a pediatrician and geneticist, said that between1976 and 1984, he prodded Searle officials several times to do moreresearch on the issue, but Searle never performed the studies suggested. The Chicago-based company did, however, pursue U.S. government approvalfor the low-calorie sugar substitute, and got it in a controversialruling in 1981. Today, tens of millions of Americans guzzle diet soft drinks stampedwith the NutraSweet "Swirl", dump packets of the NutraSweet  tabletopsweetener, "Equal" in their coffee and consume NutraSweet-flavoredcereal, puddings, gelatins, cheesecake, chewing gum or vitamin tablets. The Food and Drug Administration, despite receiving more than 3,600consumer complaints, is so confident of the sweeteners safety that itrecently expanded uses to frozen and chilled fruit juices. Matalon, however, has remained skeptical. In May, he reported that hisinitial, federally funded tests on 51 adults suggests heavy NutraSweetconsumption may increase blood levels of a key amino acid enough toaffect attention span, memory and concentration in some people,particularly small children. Pregnant women who are sensitive to thesweetenerís main component, the amino acid phenylalanine, also may faceheightened risk that their infants will have birth defects, Matalonsaid. More than a dozen other scientists, some of whom are conductingclinical studies, also say they suspect that subtle effects of the sweetpowder could pose a major health problem. They believe NutraSweet ≠known generically as aspartame, is linked to brain damage, epilepticseizures, eyesight problems, allergic reactions, headaches or dizziness. "The likelihood is very strong that aspartame does produce serious andpotentially damaging brain effects in a number of people", said RichardWurtman, a neuroscientist at the Massachusetts Institute of Technologywho is studying scores of people who suffered seizures after usingNutraSweet. Facing continuing controversy, The NutraSweet Co., the name adopted bySearleís NutraSweet Division following its 1985 sale to the giantMonsanto Co., vouches for the sweetener. The firmís president, Robert Shapiro, rejects criticism voiced byMatalon and others, saying, "The fact is that the world scientificcommunity has considered these very specific allegations repeatedly, andhas come to the same conclusion as the FDA." An eight-month United Press International investigation not only turnedup scientific concerns, but also raised questions about the way theproduct was approved, about the independence and depth of the industry-funded research efforts into its safety, and about "revolving door"relationships between FDA officials including former FDA commissionerArthur Hull Hayes Jr. and the food and drink industries. Shapiro, who obtained an advance copy of this UPI report, said, "Takenas a whole, the effect of the article is likely to be a thoroughlymisleading impression of the state of knowledge of the subject." Companyspokesman Thym Smith said the firm is contemplating litigation. Senator Howard Metzenbaum, D-Ohio, a leading skeptic of the FDAísapproval who plans to hold a hearing on NutraSweet in the next fewweeks, said, "I don't have hard evidence that the product is not safe.But, I am convinced that there is no hard evidence...that the product issafe." FDA officials stress they have yet to see hard data disproving thesweeteners safety. For that reason, the agency last year rejected aconsumer groupís petition to ban it on grounds that 140 users sufferedseizures and eye problems. NutraSweet has been at the center of intense controversy almost sinceJuly 18, 1981, the day Hayes approved its use in dry foods. Indeed, inrendering his decision, Hayes overrode six of the nine scientists on twoagency review panels who felt studies on itís possible links to braintumors in rats has been inadequate. Since then, some independent scientists have become unusuallyoutspoken.Drs. Louis Elsas of Emory University and William Pardridge of the UCLAMedical School charged that the diet food and drink industry has engagedin a "whitewash" by rejecting health concerns, manipulating researchstudies and wining and dining scientific critics. These and other researchers describe a world of subtle, high-stakesstrategy in which the availability of corporate funds and the design ofresearch protocols may have influenced the course of a multibillion-dollar industry and potentially affected the safety of millions ofpeople. The NutraSweet Co. and a non-profit industry group reject theseallegations, asserting they have commissioned scores of studies to testthe product's safety and that decisions on research funding are madesolely on merit. Company spokesman Smith said NutraSweetís "phenomenalsafety record is the result of the well known nature of the productrather than manipulations of management." Consumer complaints aboutNutraSweet surged in 1983, after Hayesí deputy, Mark Novitch, with thecommissioners support, approved its use in soft drinks such as "DietCoke" and "Crystal Light", sending consumption soaring. UCLAís Pardridge noted in a letter to the American Medical AssociationJournal last year that, with aspartame, the food industry now is addingabout five million pounds of phenylalanine ≠ "a known neurotoxin" to thefood supply every year. Roy Burry, an analyst with Kidder-Peabody, Inc., said the explodingdiet market now accounts for 24 percent of soft drink sales, comparedwith 10 percent in the 1970ís, and is growing at 20 to 25 percent ayear. The NutraSweet Co.ís sales are no longer public, but last year revenueswere believed to have exceeded previously stated levels of $700 million. So intense has been the NutraSweet advertising campaign that the dietfood and beverage industry created a "NutraSweet World ProfessionalFigure Skating Championship." "Taking good care of oneself makes life a little better- and NutraSweetmakes it a little sweeter!" boasted one ad during a TV fitness program. The NutraSweet Co. also has paid up to $3 million a year for a 100-person public relations effort by the Chicago offices of Burson,Marsteller, a former employee of the New York PR firm said. The employeesaid Burson Marsteller has hired numerous scientists and physicians,often at $1,000 a day, to defend the sweetener in media interviews andother public forums. Burson Marsteller declines to discuss such matters. Dismissing safety fears, The NutraSweet Co. stresses that its product,which in raw form, is 180 times sweeter than sugar, has been endorsed bythe AMA and other scientific bodies worldwide. Actually, the AMAísCouncil of Scientific Affairs gave a qualified endorsement based on"available evidence", including company-funded studies that werechallenged by FDA task forces during investigations of the firmíslaboratory practices in the 1970ís. Of 69 scientists who responded to a recent General Accounting Officesurvey, 28 said they felt more research was needed on NutraSweet and adozen of those questioned considered it a major health problem. An "aspartame victims" group has formed, a consumer group has pressedlegal challenges and the company faces at least three personal injurysuits. In one suit, Jim Stoddard, 32, a diabetic in Grand Rapids,Michigan, charged that his heavy NutraSweet consumption triggered adozen seizures-the last one so violent he dislocated his shoulder andfractured his collar bone. Stoddardís lawyer, and his sister, Cynthia, alleged he suffered braindamage and now has trouble understanding words because he consumed aproduct inadequately tested by Searle. She said she withdrew the suitrecently for tactical reasons but would refile it early next year. Thecompany denies the allegations. Wurtman, who quit his job as a Searle consultant and became a vocalNutraSweet opponent, said he has been contacted by more than 200 personswho suspect they suffered seizures as a result of NutraSweet use. He said Dr. Gerald Gaull, a Searle vice president, visited hislaboratory in 1985 and threatened to veto funding by ILSI(InternationalLife Sciences Institute), the Washington-based tax-exempt foundation,for his planned study into whether NutraSweet changes brain chemistry,lowering some humansí seizure thresholds. Gaull said, "thereís no way" Searle, with one of 12 votes on the ILSIpanel, could veto a grant decision, but he did not deny making thethreat. ILSI ultimately turned away Wurtman on grounds that Searle already hadarranged for seizure studies at Yale University and New Yorkís MountSinai Hospital ≠  studies that have drawn criticism because humanvolunteers were given aspartame only once or twice. Wurtman said he is now tapping his laboratoryís budget, which isextremely limited, slowing progress on his own studies. "Aspartame maybe a serious health hazard," he said, "Itís critically important thathigh quality research now be done to assess this hazard." In his letterto the AMA Journal,  Pardridge said no one has fully researched thedegree to which aspartame raises phenylalanine levels on the brain and,if so, what the possible effects are. He said in an interview, after heraised questions about the sweetenerís effects on children, that ILSIrejected his two grant proposals in 1985. Last year, he said, Gaullpressed him at a conference in Colorado to prove that phenylalanine, oneof twenty-one amino acids, causes brain damage. "It was incredible for him to ask that," Pardridge said. "That was thebasis for my ILSI grant (proposal)." "Thereís an internal conflict of interest," he said, "when a company,which has profit at the bottom line, is charged with finding out thetrue safety of its product." Elsas, who publicly assailed NutraSweet in 1985, said he was put offfor a year before ILSI rejected his proposal without stating a reason.ILSIís executive director, Jack Filer, asserted research proposals wererejected because they cost too much or lacked scientific merit. While denying funding for these aspartame skeptics, the company(G.D.Searle/NutraSweet Co.) and ILSI have financed researchers with whomthey have long-running relationships. A number of industry-fundedscientists acknowledged that company and ILSI officials originated ideasfor their studies or participated in the research design. These studiesgenerally have reported the sweetener is safe. Consumer lawyer Turner said, "The notion that an industrial companywould take large sums of money and parcel it out to scientificconsulting firms and university departments, who they consider to bepersonal and commercial allies is an unconscionable way to ensure thesafety of the American food supply." He said the NutraSweet experience shows that "the entire system of theway scientific research is done needs to be carefully investigated,evaluated, and revamped." Food industry officials also said most studies financed by Searle orthe NutraSweet Co. have been arranged as contracts, rather than grants.Smith said the company often uses contracts "to accomplish a specificresearch task." James Scala, former director of health sciences for the General FoodsCorp., a major NutraSweet user, said that a scientist working undercontract became "more of an arm of the Searle research group than agrantee." Scala, now with the Shaklee Corp., also said that most early NutraSweetresearch consisted of short-term studies that ignored possible "subtle,"long-term effects. Matalon said, "Let us say cigarettes were invented today, and you give20 people two packs a day and after six weeks, no one has cancer, wouldyou say that it was safe? Thatís what they did with NutraSweet." Dr. Martha Freeman, who was a medical officer at the FDAís Bureau ofDrugs in the early 1970ís, argued in 1973 that the substance (aspartame)was "a new chemical...that doesn't occur naturally" and should only beapproved after long-term clinical studies, as if it were a new drug. Herarguments were rejected. Despite these complaints, the NutraSweet Co. has insisted that thecompany-funded studies prove that except for people with the raredisease, phenylketonuria, the human body processes phenylalanine inaspartame just like any other food, Thomas Stenzel, a spokesman for theInternational Food Information Council, a public relations arm forNutraSweetís manufacturers and biggest customers, contended scientificadversaries comprise a small minority. He said he found it "very important that the leading professionalhealth organizations" have found NutraSweet to be safe. For example, the American Academy of Pediatrics concluded in 1985 thatstudies on people given massive aspartame doses showed no dangerous risein blood phenylalanine levels; the Epilepsy Institute has reported thesweetener "to be safe for people with epilepsy." Filer, executive director of the industryís main organ, theInternational Life Sciences Institute, suggested that problems blamed onaspartame may stem from "water load" on the brain resulting from over-consumption of liquids. Maj. Michael Collings, who was an Air Force F-16 pilot in top physicalcondition, said he often drank up to a gallon of aspartame-sweetenedproducts when he finished his daily, five-to-eight mile jogs in Nevadaísdesert heat. After noticing slight trembling in his hands over severalweeks, he collapsed unconscious with a seizure on Oct.4, 1985, a lawyerfor Collings said. Because of the seizure, Collings is grounded as a pilot for life, is onmedication and was ordered transferred to Maxwell Air Force Base inAlabama at a $400-a-month pay reduction, said attorney Bryan Gould, whocharged in a state court suit last year that NutraSweet caused theseizure. "He tells me thereís no way to describe the feeling of flight," Gouldsaid. "He loves to fly and now he can't." The NutraSweet Co. denies anylink between the sweetener and Collings medical problems. FDA officials, while publicly endorsing aspartame, are watching thesituation closely. In late 1985, the agency took the unusual step ofasking doctors nationwide to report adverse reactions to NutraSweet, andanother food additive, sulfites ≠ a move normally reserved for drugs.Sulfites since have been banned from the market. A FDA spokesman saidabout 25 doctors filed reports suggesting aspartame links to varyinghealth problems. The FDA approved NutraSweet products on the condition they carry acompulsory warning to phenylketonurics, individuals sensitive to itsphenylalanine component. But Matalon, Elsas and others worry aboutmillions of "carriers" of the disease who are unaware of theirsensitivity. They say NutraSweet could damage fetuses of pregnant womenwhose bodies have trouble processing the amino acid. Matalon, on releasing his new study, urged that products be labeledwith the amount of NutraSweet they contain so consumers can monitortheir intake. In Canada, aspartame is the only food additive for whichsuch quantity food labeling is required. With consumption soaring, Sanford Miller, chief of FDAís Bureau ofFoods, has acknowledged considering a labeling requirement in thiscountry. Dr. Gary Flamm, the FDAís top toxicologist overseeing food additives,said that beyond labeling, once a food additive such as NutraSweet haswon approval, it is far more difficult to restrict its marketing. "If...our approval of it was a mistake, we couldn't rectify thatwithout data showing that aspartame was unsafe," said Flamm, anaspartame defender. Even then, he said, the agency would face a new regulatory thicketunless it could be shown NutraSweet posed "an imminent hazard." Consumer lawyer James Turner, who has campaigned for more than a decade for aNutraSweet ban, assailed the FDAís treatment of such safety issues."Once a product is on the market, whether there by nefarious or honestmeans," he said, "it is impossible to get it off the market until it hascaused severe, undeniable damage that has probably lasted over manyyears." Several independent scientists have alleged that the industry hassteered research money to allies in the scientific community, whiledenying funding to those who have raised health concerns. A number of scientists who pressed for more studies into possible braindamage told UPI they were turned away by Searle and the InternationalLife Sciences Institute, a tax-exempt industry foundation supported bythe company, its Japanese aspartame-manufacturing partner and 10 sellersof NutraSweet-flavored products. In interviews, Drs. Matalon, Wurtman, Elsas, Pardridge, and John Olneyof Washington University in Illinois charged that the industry has paidmillions of dollars for studies that have skirted the real issues aboutNutraSweet. "There are virtually no studies," Turner said, "that have been done byindividuals using resources other than the industryís that have given aclean bill of health to aspartame." University of Illinois researcher Matalon recalled that he couldnítpersuade Searle to do the kind of research necessary to put to restlingering health concerns, neither on his first approach in 1976 norwhen he submitted specific grant proposals to more four more companyofficials beginning in late 1980. After NutraSweet won FDA approval and began changing the dietary habitsof millions of Americans, Matalon said he lost patience in 1984 with theusual encouragement from Searle officials about prospects for futurefunding. "I felt they were just stringing me along," said Matalon, whoobtained a $180,000 grant from the National Institutes of Health. Company spokesman Smith said the NutraSweet manufacturer has "notdiscouraged Dr. Matalonís work, nor anyone elseís." While declining tocomment on the decision not to fund Matalonís study, Smith said thecompany spends "between $30 million and $35 million annually onresearch.""We do make decisions based on how we understand a study will beconducted and, reasonable scientists may disagree on study designs," hesaid.The company has alleged that a number of its critics are seeking topressure the industry to fund their laboratories.  Faced with sharply differing opinions on the sweetenerís safety, theFDA and the National Institutes of Health, the governmentís chieffunding mechanism for private research, have financed few studies on itseffects. One former ranking NIH official, Artemis Simopoulos, argued theagency "should have a very extensive program on aspartame so peoplewould know" whether it is safe. Yet some NIH scientists have served as consultants to the ILSIfoundation, helping decide the awards of $500,000 in annual NutraSweetresearch grants in recent years. Even Simopoulos was a non-paid memberof the foundationís board. But ILSIís "aspartame technical committee," consisting of theNutraSweet Co. and 11 other manufacturers and users of sweetener, havebeen accused of discriminating against NutraSweet critics in grantingawards. Represented on the ILSI committee are General Foods, the Coca Cola Co.,PepsiCo, Inc., the Royal Crown Cola Co. and Seven-Up, Inc. ILSI insists that the NutraSweet Co. carries no special weight despiteits U.S. monopoly on the sweetener. "The NutraSweet Co. is one of ourmembers," said ILSI administrator Sharon Senzik. "Committees operate byRobertís Rules of Order." Filer collaborated for several years on NutraSweet research with acolleague at the University of Iowa, Dr. Lewis Stegink. Filer pledgedthat, despite his past ties to the company, as ILSIís head he would "letthe chips fall where they may" on research results. Samuel Molinary, co-chairman of ILSIís panel, is Searle's former director of scientificaffairs and now Pepsicoís research director. Molinary insists that ILSIis not a "lacky and tool" of the NutraSweet Co. Peter Dews, a Harvard University psychobiology professor named toILSIís original board of trustees in 1978, has served as an ILSIconsultant since then. Dews recently took the trouble to write andpromote an article declaring that, based on scientific presentations atan ILSI aspartame conference in Spain last year, "there is now a mass ofevidence" that NutraSweet is safe if consumed at FDA-recommended levels. Dews declined to discuss his ILSI consulting fees, except to say it is"not enough to make any difference in my life." ILSIís 1984 return filedwith the Internal Revenue Service showed payments to Dews that year of$31,000. A lawyer for the ILSI pledged to the IRS in obtaining tax-exempt statusfor the foundation in 1983, that the organization "does not have anyplans to engage in commercially sponsored scientific research." AttorneyRoger Middlekauff advised the IRS that ILSI would "direct the researchtoward benefiting the public" and would release all research results. But Elsas charged that ILSI "is definitely a front organization to tryto make the public believe that there is some non-directed, non-biasedresearch going on," when ILSI studies actually are likely to supportNutraSweetís safety. The industry has invited scientific critics for paid visits to companylaboratories, sometimes offering courtesy "honorariums," an industrysource said. The NutraSweet Co. also hosted critics at conferences in resortsettings. Matalon briefed ILSI on his research at the meeting in theCosta del Sol region on Spainís southern coast. In the summer of 1985, the firm flew Wurtman, Elsas, Matalon,Pardridge, several of their wives and other NutraSweet critics to a two-day meeting at a luxurious home in Northeast Harbor, Maine. An afternoonwas spent on a yacht, participants said. "This was industry wooing theconcerned to shut up." Elsas said. Pardridge said he was the only strong aspartame critic to accept aninvitation in June 1986 to a heavily-attended Searle sponsoredconference at a picturesque ski resort in Keystone, Colo. Pardridge saidwhen he tried during the conference to raise his concerns aboutphenylalanine, the discussion was cut off. "It was just another typicalindustry whitewash," he said.