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

Part One of Three:

UPI Investigative Report 1987

NutraSweet:Questions Swirl

Part 1:   DID SEARLE IGNORE EARLY WARNING SIGNS ?

By GREGORY GORDON

 WASHINGTON (UPI) ≠ A University of Illinois scientist says he warned

the G.D.Searle Co. years before NutraSweet swept the diet food and soft

drink markets that the companyís new artificial sweetener could heighten

risks of brain damage in fetuses and small children.

 Dr. Reuben Matalon, a pediatrician and geneticist, said that between

1976 and 1984, he prodded Searle officials several times to do more

research on the issue, but Searle never performed the studies suggested.

 The Chicago-based company did, however, pursue U.S. government approval

for the low-calorie sugar substitute, and got it in a controversial

ruling in 1981.

 Today, tens of millions of Americans guzzle diet soft drinks stamped

with the NutraSweet "Swirl", dump packets of the NutraSweet  tabletop

sweetener, "Equal" in their coffee and consume NutraSweet-flavored

cereal, puddings, gelatins, cheesecake, chewing gum or vitamin tablets.

 The Food and Drug Administration, despite receiving more than 3,600

consumer complaints, is so confident of the sweeteners safety that it

recently expanded uses to frozen and chilled fruit juices.

 Matalon, however, has remained skeptical. In May, he reported that his

initial, federally funded tests on 51 adults suggests heavy NutraSweet

consumption may increase blood levels of a key amino acid enough to

affect attention span, memory and concentration in some people,

particularly small children. Pregnant women who are sensitive to the

sweetenerís main component, the amino acid phenylalanine, also may face

heightened risk that their infants will have birth defects, Matalon

said.

 More than a dozen other scientists, some of whom are conducting

clinical studies, also say they suspect that subtle effects of the sweet

powder could pose a major health problem. They believe NutraSweet ≠

known generically as aspartame, is linked to brain damage, epileptic

seizures, eyesight problems, allergic reactions, headaches or dizziness.

 "The likelihood is very strong that aspartame does produce serious and

potentially damaging brain effects in a number of people", said Richard

Wurtman, a neuroscientist at the Massachusetts Institute of Technology

who is studying scores of people who suffered seizures after using

NutraSweet.

 Facing continuing controversy, The NutraSweet Co., the name adopted by

Searleís NutraSweet Division following its 1985 sale to the giant

Monsanto Co., vouches for the sweetener.

 The firmís president, Robert Shapiro, rejects criticism voiced by

Matalon and others, saying, "The fact is that the world scientific

community has considered these very specific allegations repeatedly, and

has come to the same conclusion as the FDA."

 An eight-month United Press International investigation not only turned

up scientific concerns, but also raised questions about the way the

product 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 commissioner

Arthur Hull Hayes Jr. and the food and drink industries.

 Shapiro, who obtained an advance copy of this UPI report, said, "Taken

as a whole, the effect of the article is likely to be a thoroughly

misleading impression of the state of knowledge of the subject." Company

spokesman Thym Smith said the firm is contemplating litigation.

 Senator Howard Metzenbaum, D-Ohio, a leading skeptic of the FDAís

approval who plans to hold a hearing on NutraSweet in the next few

weeks, 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 is

safe."

 FDA officials stress they have yet to see hard data disproving the

sweeteners safety. For that reason, the agency last year rejected a

consumer groupís petition to ban it on grounds that 140 users suffered

seizures and eye problems.

 NutraSweet has been at the center of intense controversy almost since

July 18, 1981, the day Hayes approved its use in dry foods. Indeed, in

rendering his decision, Hayes overrode six of the nine scientists on two

agency review panels who felt studies on itís possible links to brain

tumors in rats has been inadequate.

 Since then, some independent scientists have become unusually

outspoken.

Drs. Louis Elsas of Emory University and William Pardridge of the UCLA

Medical School charged that the diet food and drink industry has engaged

in a "whitewash" by rejecting health concerns, manipulating research

studies and wining and dining scientific critics.

 These and other researchers describe a world of subtle, high-stakes

strategy in which the availability of corporate funds and the design of

research protocols may have influenced the course of a multibillion-

dollar industry and potentially affected the safety of millions of

people.

 The NutraSweet Co. and a non-profit industry group reject these

allegations, asserting they have commissioned scores of studies to test

the product's safety and that decisions on research funding are made

solely on merit. Company spokesman Smith said NutraSweetís "phenomenal

safety record is the result of the well known nature of the product

rather than manipulations of management." Consumer complaints about

NutraSweet surged in 1983, after Hayesí deputy, Mark Novitch, with the

commissioners support, approved its use in soft drinks such as "Diet

Coke" and "Crystal Light", sending consumption soaring.

 UCLAís Pardridge noted in a letter to the American Medical Association

Journal last year that, with aspartame, the food industry now is adding

about five million pounds of phenylalanine ≠ "a known neurotoxin" to the

food supply every year.

 Roy Burry, an analyst with Kidder-Peabody, Inc., said the exploding

diet market now accounts for 24 percent of soft drink sales, compared

with 10 percent in the 1970ís, and is growing at 20 to 25 percent a

year.

 The NutraSweet Co.ís sales are no longer public, but last year revenues

were believed to have exceeded previously stated levels of $700 million.

 So intense has been the NutraSweet advertising campaign that the diet

food and beverage industry created a "NutraSweet World Professional

Figure Skating Championship."

 "Taking good care of oneself makes life a little better- and NutraSweet

makes 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 employee

said Burson Marsteller has hired numerous scientists and physicians,

often at $1,000 a day, to defend the sweetener in media interviews and

other 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 by

the AMA and other scientific bodies worldwide. Actually, the AMAís

Council of Scientific Affairs gave a qualified endorsement based on

"available evidence", including company-funded studies that were

challenged by FDA task forces during investigations of the firmís

laboratory practices in the 1970ís.

 Of 69 scientists who responded to a recent General Accounting Office

survey, 28 said they felt more research was needed on NutraSweet and a

dozen of those questioned considered it a major health problem.

 An "aspartame victims" group has formed, a consumer group has pressed

legal challenges and the company faces at least three personal injury

suits. In one suit, Jim Stoddard, 32, a diabetic in Grand Rapids,

Michigan, charged that his heavy NutraSweet consumption triggered a

dozen seizures-the last one so violent he dislocated his shoulder and

fractured his collar bone.

 Stoddardís lawyer, and his sister, Cynthia, alleged he suffered brain

damage and now has trouble understanding words because he consumed a

product inadequately tested by Searle. She said she withdrew the suit

recently for tactical reasons but would refile it early next year. The

company denies the allegations.

 Wurtman, who quit his job as a Searle consultant and became a vocal

NutraSweet opponent, said he has been contacted by more than 200 persons

who suspect they suffered seizures as a result of NutraSweet use.

 He said Dr. Gerald Gaull, a Searle vice president, visited his

laboratory in 1985 and threatened to veto funding by ILSI(International

Life 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 ILSI

panel, could veto a grant decision, but he did not deny making the

threat.

 ILSI ultimately turned away Wurtman on grounds that Searle already had

arranged for seizure studies at Yale University and New Yorkís Mount

Sinai Hospital ≠  studies that have drawn criticism because human

volunteers were given aspartame only once or twice.

 Wurtman said he is now tapping his laboratoryís budget, which is

extremely limited, slowing progress on his own studies. "Aspartame may

be a serious health hazard," he said, "Itís critically important that

high quality research now be done to assess this hazard." In his letter

to the AMA Journal,  Pardridge said no one has fully researched the

degree to which aspartame raises phenylalanine levels on the brain and,

if so, what the possible effects are. He said in an interview, after he

raised questions about the sweetenerís effects on children, that ILSI

rejected his two grant proposals in 1985. Last year, he said, Gaull

pressed him at a conference in Colorado to prove that phenylalanine, one

of twenty-one amino acids, causes brain damage.

 "It was incredible for him to ask that," Pardridge said. "That was the

basis 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 the

true safety of its product."

 Elsas, who publicly assailed NutraSweet in 1985, said he was put off

for a year before ILSI rejected his proposal without stating a reason.

ILSIís executive director, Jack Filer, asserted research proposals were

rejected 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 whom

they have long-running relationships. A number of industry-funded

scientists acknowledged that company and ILSI officials originated ideas

for their studies or participated in the research design. These studies

generally have reported the sweetener is safe.

 Consumer lawyer Turner said, "The notion that an industrial company

would take large sums of money and parcel it out to scientific

consulting firms and university departments, who they consider to be

personal and commercial allies is an unconscionable way to ensure the

safety of the American food supply."

 He said the NutraSweet experience shows that "the entire system of the

way scientific research is done needs to be carefully investigated,

evaluated, and revamped."

 Food industry officials also said most studies financed by Searle or

the NutraSweet Co. have been arranged as contracts, rather than grants.

Smith said the company often uses contracts "to accomplish a specific

research task."

 James Scala, former director of health sciences for the General Foods

Corp., a major NutraSweet user, said that a scientist working under

contract became "more of an arm of the Searle research group than a

grantee."

 Scala, now with the Shaklee Corp., also said that most early NutraSweet

research consisted of short-term studies that ignored possible "subtle,"

long-term effects.

 Matalon said, "Let us say cigarettes were invented today, and you give

20 people two packs a day and after six weeks, no one has cancer, would

you say that it was safe? Thatís what they did with NutraSweet."

 Dr. Martha Freeman, who was a medical officer at the FDAís Bureau of

Drugs in the early 1970ís, argued in 1973 that the substance (aspartame)

was "a new chemical...that doesn't occur naturally" and should only be

approved after long-term clinical studies, as if it were a new drug. Her

arguments were rejected.

 Despite these complaints, the NutraSweet Co. has insisted that the

company-funded studies prove that except for people with the rare

disease, phenylketonuria, the human body processes phenylalanine in

aspartame just like any other food, Thomas Stenzel, a spokesman for the

International Food Information Council, a public relations arm for

NutraSweetís manufacturers and biggest customers, contended scientific

adversaries comprise a small minority.

 He said he found it "very important that the leading professional

health organizations" have found NutraSweet to be safe.

 For example, the American Academy of Pediatrics concluded in 1985 that

studies on people given massive aspartame doses showed no dangerous rise

in blood phenylalanine levels; the Epilepsy Institute has reported the

sweetener "to be safe for people with epilepsy."

 Filer, executive director of the industryís main organ, the

International Life Sciences Institute, suggested that problems blamed on

aspartame 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 physical

condition, said he often drank up to a gallon of aspartame-sweetened

products when he finished his daily, five-to-eight mile jogs in Nevadaís

desert heat. After noticing slight trembling in his hands over several

weeks, he collapsed unconscious with a seizure on Oct.4, 1985, a lawyer

for Collings said.

 Because of the seizure, Collings is grounded as a pilot for life, is on

medication and was ordered transferred to Maxwell Air Force Base in

Alabama at a $400-a-month pay reduction, said attorney Bryan Gould, who

charged in a state court suit last year that NutraSweet caused the

seizure.

 "He tells me thereís no way to describe the feeling of flight," Gould

said. "He loves to fly and now he can't." The NutraSweet Co. denies any

link between the sweetener and Collings medical problems.

 FDA officials, while publicly endorsing aspartame, are watching the

situation closely. In late 1985, the agency took the unusual step of

asking doctors nationwide to report adverse reactions to NutraSweet, and

another food additive, sulfites ≠ a move normally reserved for drugs.

Sulfites since have been banned from the market. A FDA spokesman said

about 25 doctors filed reports suggesting aspartame links to varying

health problems.

 The FDA approved NutraSweet products on the condition they carry a

compulsory warning to phenylketonurics, individuals sensitive to its

phenylalanine component. But Matalon, Elsas and others worry about

millions of "carriers" of the disease who are unaware of their

sensitivity. They say NutraSweet could damage fetuses of pregnant women

whose bodies have trouble processing the amino acid.

 Matalon, on releasing his new study, urged that products be labeled

with the amount of NutraSweet they contain so consumers can monitor

their intake. In Canada, aspartame is the only food additive for which

such quantity food labeling is required.

 With consumption soaring, Sanford Miller, chief of FDAís Bureau of

Foods, has acknowledged considering a labeling requirement in this

country.

 Dr. Gary Flamm, the FDAís top toxicologist overseeing food additives,

said that beyond labeling, once a food additive such as NutraSweet has

won approval, it is far more difficult to restrict its marketing.

 "If...our approval of it was a mistake, we couldn't rectify that

without data showing that aspartame was unsafe," said Flamm, an

aspartame defender.

 Even then, he said, the agency would face a new regulatory thicket

unless it could be shown NutraSweet posed "an imminent hazard." Consumer lawyer James Turner, who has campaigned for more than a decade for a

NutraSweet ban, assailed the FDAís treatment of such safety issues.

"Once a product is on the market, whether there by nefarious or honest

means," he said, "it is impossible to get it off the market until it has

caused severe, undeniable damage that has probably lasted over many

years."

 Several independent scientists have alleged that the industry has

steered research money to allies in the scientific community, while

denying funding to those who have raised health concerns.

 A number of scientists who pressed for more studies into possible brain

damage told UPI they were turned away by Searle and the International

Life Sciences Institute, a tax-exempt industry foundation supported by

the company, its Japanese aspartame-manufacturing partner and 10 sellers

of NutraSweet-flavored products.

 In interviews, Drs. Matalon, Wurtman, Elsas, Pardridge, and John Olney

of Washington University in Illinois charged that the industry has paid

millions of dollars for studies that have skirted the real issues about

NutraSweet.

 "There are virtually no studies," Turner said, "that have been done by

individuals using resources other than the industryís that have given a

clean bill of health to aspartame."

 University of Illinois researcher Matalon recalled that he couldnít

persuade Searle to do the kind of research necessary to put to rest

lingering health concerns, neither on his first approach in 1976 nor

when he submitted specific grant proposals to more four more company

officials beginning in late 1980.

 After NutraSweet won FDA approval and began changing the dietary habits

of millions of Americans, Matalon said he lost patience in 1984 with the

usual encouragement from Searle officials about prospects for future

funding. "I felt they were just stringing me along," said Matalon, who

obtained a $180,000 grant from the National Institutes of Health.

 Company spokesman Smith said the NutraSweet manufacturer has "not

discouraged Dr. Matalonís work, nor anyone elseís." While declining to

comment on the decision not to fund Matalonís study, Smith said the

company spends "between $30 million and $35 million annually on

research."

"We do make decisions based on how we understand a study will be

conducted and, reasonable scientists may disagree on study designs," he

said.

The company has alleged that a number of its critics are seeking to

pressure the industry to fund their laboratories.

  Faced with sharply differing opinions on the sweetenerís safety, the

FDA and the National Institutes of Health, the governmentís chief

funding mechanism for private research, have financed few studies on its

effects. One former ranking NIH official, Artemis Simopoulos, argued the

agency "should have a very extensive program on aspartame so people

would know" whether it is safe.

 Yet some NIH scientists have served as consultants to the ILSI

foundation, helping decide the awards of $500,000 in annual NutraSweet

research grants in recent years. Even Simopoulos was a non-paid member

of the foundationís board.

 But ILSIís "aspartame technical committee," consisting of the

NutraSweet Co. and 11 other manufacturers and users of sweetener, have

been accused of discriminating against NutraSweet critics in granting

awards.

 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 despite

its U.S. monopoly on the sweetener. "The NutraSweet Co. is one of our

members," said ILSI administrator Sharon Senzik. "Committees operate by

Robertís Rules of Order."

 Filer collaborated for several years on NutraSweet research with a

colleague at the University of Iowa, Dr. Lewis Stegink. Filer pledged

that, despite his past ties to the company, as ILSIís head he would "let

the chips fall where they may" on research results. Samuel Molinary, co-

chairman of ILSIís panel, is Searle's former director of scientific

affairs and now Pepsicoís research director. Molinary insists that ILSI

is not a "lacky and tool" of the NutraSweet Co.

 Peter Dews, a Harvard University psychobiology professor named to

ILSIís original board of trustees in 1978, has served as an ILSI

consultant since then. Dews recently took the trouble to write and

promote an article declaring that, based on scientific presentations at

an ILSI aspartame conference in Spain last year, "there is now a mass of

evidence" 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 filed

with 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 status

for the foundation in 1983, that the organization "does not have any

plans to engage in commercially sponsored scientific research." Attorney

Roger Middlekauff advised the IRS that ILSI would "direct the research

toward benefiting the public" and would release all research results.

 But Elsas charged that ILSI "is definitely a front organization to try

to make the public believe that there is some non-directed, non-biased

research going on," when ILSI studies actually are likely to support

NutraSweetís safety.

 The industry has invited scientific critics for paid visits to company

laboratories, sometimes offering courtesy "honorariums," an industry

source said.

 The NutraSweet Co. also hosted critics at conferences in resort

settings. Matalon briefed ILSI on his research at the meeting in the

Costa 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 afternoon

was spent on a yacht, participants said. "This was industry wooing the

concerned to shut up." Elsas said.

 Pardridge said he was the only strong aspartame critic to accept an

invitation in June 1986 to a heavily-attended Searle sponsored

conference at a picturesque ski resort in Keystone, Colo. Pardridge said

when he tried during the conference to raise his concerns about

phenylalanine, the discussion was cut off. "It was just another typical

industry whitewash," he said.