C M Y KID NAME: EE02,2006-02-12,BU,001,Bs-4C,E1 YELO MAG CYAN BLK 3 7 15 25 50 75 85 93 97

Sunday, February 12, 2006

NJCommercial Real Estate, Pages 20-22

By TIMOTHY L. O’BRIEN

FOR sci-fi movie fans, the opening titles of “Alien,”Ridley Scott’s 1979 voyage through interstellardread, perfectly evoke the film’s ensuing themes.

As a series of white rectangles gradually align to formthe movie’s title, the camera pans across the expanse ofan enormous planet floating in the numbing, ominous,infinite void of outer space.

For visual effects aficionados, Coca-Cola’s 1992television commercial featuring Paula Abdul hoofing itwith digitally inserted film clips of Groucho Marx and

Gene Kelly presaged time-traveling lures of lateraward-winning works like the movie “Forrest Gump,”in which Tom Hanks was digitally transported into theKennedy White House.

And for contemporary digital interaction buffs,Nike explored fresh marketing and communicationsterrain last year when it deployed a towering electronicbillboard in Times Square that allowed shoppers to dialcommands from their cellphones to customize footwearappearing on the giant screen above them.

The creative thread linking all these efforts — thesekindlings of mood, persuasion and pitch — takes shapein Robert M. Greenberg, a 57-year-old with the specta-cles and visage of Benjamin Franklin; the eclectic, Ren-

aissance interests of Leonardo da Vinci; the fashionsense of a well-turned-out ninja; the obsessive tics andserpentine conversational habits of Woody Allen; andthe legerdemain of a hands-on businessman whose firstjob was running his uncle’s mirror factory in Chicago.

Nestled for almost 30 years in the Manhattan neigh-borhood called Hell’s Kitchen, Mr. Greenberg’s ad-vertising and communications agency, R/GA, makes itshome in a rambling, spare Bauhaus nest set far backfrom the curb on West 39th Street. Mr. Greenberg’sjourney — from titlemeister of “Alien” to Ms. Abdul’sdigital choreographer to Nike’s Times Square showoff— has been a mixture of wandering curiosity and pro-fessional reinvention. He now oversees a diverse team

of about 450 people trying to wed design and marketingin groundbreaking ways.

The background music in Mr. Greenberg’s littlesymphony is, of course, the Internet and other techno-logical leaps like the cellphone, which are upending theadvertising and marketing industries in much the sameway that they have begun to turn businesses as variedas media, entertainment, retail and communications ontheir heads.

“I think technology is going to wreak havoc on theagency business,” Mr. Greenberg predicts of an in-dustry that plans to give him its most prestigiousaward, a Clio for lifetime achievement, in May. “Be-

Continued on Page 8

MadisonAvenue’s

30-SecondSpot

RemoverHere’s to the crazy ones.

The misfits. The rebels.

The troublemakers. The round

pegs in the square holes – the

ones who see things differently.

They’re not fond of rules and

they have no respect for

the status quo. You can praise

them, disagree with them,

quote them, disbelieve them,

glorify or vilify them.

About the only thing that you

can’t do is ignore them.

Because they change things.

– Apple Computer ad, 1997

Fred R. Conrad/The New York Times

Robert M. Greenbergis redefining

advertising bymaking the delivery

of the message atwo-way street

between marketersand consumers.

By MELANIE WARNER

WHEN Dr. Morando Soffritti, a cancer research-er in Bologna, Italy, saw the results of histeam’s seven-year study on aspartame, he

knew he was about to be injected into a bitter contro-versy over this sweetener, one of the most contentiouslydebated substances ever added to foods and beverages.

Aspartame is sold under the brand names Nutra-Sweet and Equal and is found in such popular productsas Diet Coke, Diet Pepsi, Diet Snapple and Sugar FreeKool-Aid. Hundreds of millions of people consume itworldwide. And Dr. Soffritti’s study concluded thataspartame may cause the dreaded “c” word: cancer.

The research found that the sweetener was associ-ated with unusually high rates of lymphomas, leuke-mias and other cancers in rats that had been given dos-es of it starting at what would be equivalent to four to

five 20-ounce bottles of diet soda a day for a 150-poundperson. The study, which involved 1,900 laboratory ratsand cost $1 million, was conducted at the EuropeanRamazzini Foundation of Oncology and EnvironmentalSciences, a nonprofit organization that studies cancer-causing substances; Dr. Soffritti is its scientific di-rector.

The findings, first released last July, prompted aflurry of criticism from the Calorie Control Council, atrade group for makers of artificial sweeteners that hasspent the last 25 years trying to quell fears about aspar-tame. It said Dr. Soffritti’s study flew in the face of fourearlier cancer studies that aspartame’s creator, G. D.Searle & Company, had underwritten and used to per-suade the Food and Drug Administration to approve itfor human consumption. “Aspartame has been safelyconsumed for more than a quarter of a century and isone of the most thoroughly studied food additives,” read

Continued on Page 7

Pigi Cipelli for The New York Times

Dr. Morando Soffritti, who led tests of aspartame on 1,900 rats, calls it a possible carcinogen.

The Lowdown on Sweet?

A Study Rekindles Debate Over Aspartame

VETERAN investors have learned the hardway that for a company in crisis, even thesmallest moves by its executives can mean a

lot. Shrewd investors also know to question WallStreet’s quick pronouncements that the company’scrisis, whatever it involved, has passed.

And yet, a primal urge remains among manyinvestors to heed all spin that is positive. Peoplewho buy stocks are optimists, after all.

Shareholders of SFBC International, the na-tion’s largest administrator of clinical trials fordrug makers and medical device manufacturers,face just such a conundrum. The company, still re-covering from deep and wide-ranging turmoil, hasrecently installed new management, and WallStreet analysts are recommending its shares, bray-ing that the worst is over.

But a closer look indicates that the company’smanagers seem interested in silencing critics andavoiding the kind of sweeping changes to their op-erations that some investors would prefer.

You may not know SFBC, but the company hasconducted trials for many of the world’s leadingpharmaceutical companies and generic drug mak-ers. Bristol-Myers Squibb has been a major cus-tomer, and SFBC conducted studies for Merck onVioxx, the arthritis painkiller, after it was ap-proved by the Food and Drug Administration.Vioxx was withdrawn from the market in 2004.

SFBC’s woes began last November, whenBloomberg News published an extensive reportquestioning its practices and its behavior towarddrug trial participants — some of them poor, non-English-speaking immigrants — at its Miami facil-ity, a former Holiday Inn. In December, a drug trialat the company’s Montreal unit collapsed when oneparticipant infected others with tuberculosis.

Senator Charles E. Grassley, an Iowa Republi-can and Finance Committee chairman, opened aninvestigation into SFBC, and the Securities and Ex-change Commission came calling.

Not surprisingly, SFBC’s shares plummetedon these unhappy events. It hired an independentlaw firm to investigate its operations, but it turned

Continued on Page 4

GRETCHEN MORGENSON

Wanting It

To Be Over

Isn’t Enough

INSIDE

OPENERS

What chefs have longed to

bake: fake Twinkies. The Goods,

by Brendan I. Koerner. 2

INSIDE THE NEWS

What you can’t find at Amazon.

Digital Domain, by Randall

Stross. 3

When white knights turn hostile.

DealBook, by Andrew Ross

Sorkin. 3

The never-ending search for full

employment. Economic View,

by Louis Uchitelle. 4

SUNDAY MONEY

Bargain hunting for charity.

By Alexandra Peers. 5

Farewell, my lovely bearer bonds.

By Ken Belson. 5

SPECIAL SECTION

Your Taxes. 23

C M Y KID NAME: NYTx,2006-02-12,BU,007,Bs-4C,E1 YELO MAG CYAN BLK 3 7 15 25 50 75 85 93 97

BU 7THE NEW YORK TIMES, SUNDAY, FEBRUARY 12, 2006

The Quality of Body ArmorTo the Editor:

Re “All’s Not Quiet on the MilitarySupply Front” (Jan. 22): We wouldlike to again emphasize, as we statedin the article, that the bullet-resist-ant vests that DHB Industries manu-factures and supplies to the Armyand Marine Corps save lives, andthere are no reports from the field ofour vests failing to perform as de-signed.

There are numerous testimonialswhich credit body armor manufac-tured by DHB Industries with savingthe lives of soldiers serving in Af-ghanistan and Iraq. In fact, on thevery same day the article was pub-lished, The Times also ran a front-page article that gave an account ofwounded soldiers returning homefrom the war in Iraq. It said thatmany soldiers “suffered wounds thatwould have been fatal in earlier warsbut were saved by helmets, body ar-mor, advances in battlefield medi-cine and swift evacuation to hospi-tals.”

Since the Sunday Business articlewas published, DHB has been award-ed two new contracts to supply bodyarmor components to our troops. Webelieve this demonstrates the con-

tinuing confidence of our customersin the quality and effectiveness ofour products.

DHB takes great pride in the qual-ity, design and workmanship of all ofits products, particularly those thathave saved and will continue to savethe lives of many of this country’sarmed forces.

GEN. LARRY R. ELLIS, retiredWestbury, N.Y., Feb. 4

The writer is president of DHB In-dustries.

The Smaller ApproachTo the Editor:

“Carmakers’ Big Idea: ThinkSmall” (Feb. 5) described the plantin Dundee, Mich., where a relativelysmall number of workers are mak-ing four-cylinder engines to be usedby Chrysler, Mitsubishi and Hyun-dai.

Interestingly, Dundee was the siteof one of the 19 “village industries”established by Henry Ford as an al-ternative to the very large factoriesthat he, more than any other Ameri-can, established in southern Michi-gan earlier in the 20th century. Fordpioneered decentralized technologyin Dundee and nearby towns in orderto make auto manufacturing morehumane, if not more efficient, than inhis famous Highland Park and RiverRouge plants. It is interesting that in

some ways Ford’s generally forgot-ten experiment is now being adopted.

HOWARD P. SEGALOrono, Me., Feb. 5

The writer, a history professor at theUniversity of Maine, is the author of“Recasting the Machine Age: HenryFord’s Village Industries” (Univer-sity of Massachusetts Press).

•

To the Editor:Re “Carmakers’ Big Idea: Think

Small” (Feb. 5): If they can begin to think in terms

of smaller cars with smaller-dis-placement fuel-efficient engines,G.M. and Ford may well survive.

Last week, our rental car in Den-ver was a Chevrolet Aveo, a 1.6-literfour-door. At the rental counter, theagent tried to have us change to anS.U.V. after hearing that we weredriving to Aspen over two mountainpasses in a minor blizzard. But wekept the Aveo, folded down half of theback seat and slid our skis, boots andtwo large pieces of luggage into thetrunk. We had no problems with sta-bility and traction. During our weekwe drove 558 miles, including trips tothe stores and high-altitude lower-gear driving up Vail Pass, and aver-aged 30.2 miles a gallon. Statisticslike that will sell cars.

BURT RICHMONDChicago, Feb. 6

LETTERS

Letters for Sunday Business may besent to sunbiz@nytimes.com.

one news release from the council.At the same time, Dr. Soffritti’s

findings have energized a vociferousgroup of researchers, health advo-cates and others who say they areconvinced that aspartame is a toxinassociated with a variety of healthtroubles, including headaches, dizzi-ness, blindness and seizures.

DR. SOFFRITTI, who oversees180 scientists and researchersin 30 countries who collab-

orate on toxin research, says thatsince last July, he has been contactedby some of these critics, including amember of Parliament in Britainand a number of conspiracy theo-rists, some of whom say they havesuffered from “aspartame poison-ing” and filled Web pages with cloak-and-dagger speculation about whythe F.D.A. approved aspartame forsale a quarter-century ago.

No regulatory agency has yet act-ed on Dr. Soffritti’s findings, al-though Roger Williams, a member ofParliament, called for a ban onaspartame in Britain last December.Last month, the European FoodSafety Authority, an advisory bodyfor the European Commission, beganto review 900 pages of data from Dr.Soffritti; the goal is to finish by May.A commission spokesman, PhilipTod, said it was too early to knowwhat the next steps would be if thescientists reviewing the data con-curred with Dr. Soffritti’s findings.

In the United States, the Food andDrug Administration says it has alsotaken note of the study, which isavailable online (http://ehp.niehs.nih.gov/docs/2005/8711/abstract.html) and is scheduled tobe published next month in a medicaljournal financed by the National In-stitutes of Health. F.D.A. officialssay that they, too, intend to conduct athorough review.

But both the F.D.A. and the Euro-pean Commission have cautionedthat there is no need for people toavoid aspartame. “We don’t see anyconcerns at this stage,” said GeorgeH. Pauli, associate director for sci-ence policy in the F.D.A.’s Office ofFood Additive Safety. “We’ve gonethrough a humongous amount ofdata on aspartame over the years.”

Putting restrictions on aspartamewould come at a significant cost.Food companies and consumersaround the world bought about $570million worth of it last year. Newregulatory action on aspartamewould also jeopardize the billions ofdollars worth of products sold with it.Already, in the United States, manycompanies are opting to use sucra-lose, or Splenda, in their new low-calorie products, in part because it isless controversial.

Lance Collins, chief executive ofFuze Beverage in Englewood Cliffs,N.J., said that safety concerns aboutaspartame were a “major contribut-ing factor” in his decision to usesucralose in his tea and juice drinks.Sucralose, however, is made by un-der a patent by just one company,Tate & Lyle of London, and is in des-perately short supply.

Dr. Soffritti, who has spent 28years doing research on potentialcarcinogens, said he was trying tosteer clear of the growing politicalmaelstrom. But he added that he wasconcerned about the large numbersof people who use aspartame, partic-ularly children and pregnant women.“If something is a carcinogen in ani-mals,” he said, “then it should not beadded to food, especially if there areso many people that are going to beconsuming it.”

Lyn Nabors, executive vice presi-dent of the Calorie Control Council,said Dr. Soffritti’s study was not val-

id because the rats used in it hadbeen allowed to live longer than thetwo-year standard established by theUnited States government’s NationalToxicology Program. “It’s difficultto determine if the cancers you findare due to something else,” Ms.Nabors said. “Just as in humans, therat’s body slows down later in life,and the aging process causes allkinds of things.”

But John R. Bucher, deputy di-rector of environmental toxicologyat the National Toxicology Program,the government’s agency for re-search on toxic chemicals, called thedesign of the Ramazzini study “im-pressive” and “thorough,” and saidthat he did not think the fact that ratswere allowed to live until their natu-ral deaths had skewed the results.

Dr. Jose Russo, director of thebreast cancer and environmental re-search center at the Fox Chase Can-cer Center in Philadelphia, says thatlifetime studies are “ideal” but thatthey are not done often, partly be-cause they are more expensive thanlimited-time tests. Dr. Russo, howev-er, criticized the Ramazzini study fornot allowing outside pathologists toanalyze all of the tissue sampleswhere cancerous tumors were found.“People need to see every tumor,” hesaid.

Dr. Bucher of the National Toxicol-ogy Program said pathologists at theprogram, with which Ramazzini col-laborates, looked at 70 tumor slides.But with the study producing over9,000 tumor-containing slides, JamesSwenberg, professor of environmen-tal science at the University of NorthCarolina at Chapel Hill, says that thisfalls short of standard practice.

While Dr. Soffritti’s methods havedrawn some criticism,the Ramazzini cancerlab, which is financed byprivate bank founda-tions, governments and17,000 individual mem-bers, has earned consid-erable credibility sinceit was founded in 1971for its pioneering re-search on chemicals. Itwas the first researchbody to do studies show-ing that vinyl chlorideand the gasoline addi-tive methyl tertiary-butyl ether, orM.T.B.E., are carcinogenic, researchthat eventually encouraged the Unit-ed States to strictly regulate vinylchloride and that led 21 states to banM.T.B.E.

Dr. Soffritti said he was inspired tolook at aspartame because of whathe calls “inadequacies” in the cancerstudies done by Searle in the 1970’s.He said that those studies did not in-volve large-enough numbers of ratsand did not allow them to live longenough to develop cancer.

The Ramazzini study was conduct-ed with 1,900 rats, as opposed to the280 to 688 rodents used in Searle’sstudies, and the rats lived for up tothree years instead of being sacri-ficed after two, which is the humanequivalent of age 53. “Cancer is a dis-ease of the third part of life,” Dr. Sof-fritti said. “You have 75 percent ofcancer diagnoses for people who are55 years old or older. So if you trun-cate the experiments at 110 weeksand the rats are supposed to surviveuntil 150 to 160 weeks, it means youavoid the development of cancer atthe time when cancer would be start-ing to arise.”

Others have also challenged Sear-le’s studies. Documents from theF.D.A. and records from the FederalRegister indicate that, in the yearsbefore the F.D.A. approved aspar-tame, the agency had serious con-cerns about the accuracy and credi-bility of Searle’s aspartame studies.From 1977 to 1985 — during much ofthe approval process — Searle washeaded by Donald H. Rumsfeld, who

is now the secretary of defense;Searle was acquired by Monsanto in1985. Monsanto later spun Searle’sassets out into two companies: Mer-isant, which owns the brands Equaland Canderel, and NutraSweet,which is owned by J. W. Childs Equi-ty Partners, an investment firm inBoston.

A 1976 report from an F.D.A. taskforce, for example, found that Sear-le’s studies on aspartame and sev-eral of the company’s pharmaceu-tical drugs were “poorly conceived,carelessly executed, or inaccuratelyanalyzed or reported.” It cited whatit called a lack of training by the sci-entists analyzing tissue samples, a“substantial” loss of information be-cause of tissue decomposition and in-adequate monitoring of feeding dos-es.

In response to the re-port, the F.D.A. askedthe Justice Departmentto open a grand jury in-vestigation into whethertwo of Searle’s aspar-tame studies had beenfalsified or were incom-plete. In a 33-page letterin 1977, Richard A. Mer-rill, the F.D.A.’s chiefcounsel at the time, rec-ommended to Samuel K.Skinner, then the United

States attorney for the Northern Dis-trict of Illinois, that a grand jury in-vestigate the company, which wasbased in the Chicago suburb of Sko-kie, for “concealing material factsand making false statements in re-ports of animal studies conducted toestablish the safety of the drugAldactone and the food additiveaspartame.”

A grand jury was never convened,however. Shortly after the letter wassent, Mr. Skinner left the Justice De-partment to join Sidley & Austin, alaw firm that represented Searle. Af-ter 12 years at that firm, now Sidley,Austin, Brown & Wood, Mr. Skinnerwas appointed to be PresidentGeorge H. W. Bush’s transportationsecretary; later he became his chiefof staff. In 1978, a year and half afterMr. Skinner left the United States at-torney’s office in Chicago, his depu-ty, William F. Conlon, also left towork at Sidley & Austin.

Mr. Skinner, now a lawyer atGreenberg Traurig LLP, said that assoon as he began looking for a newjob and interviewing with Sidley &Austin, he recused himself from theSearle investigation. Mr. Conlon, whois still at Sidley & Austin, did not re-turn phone calls.

Over the next few years, Searle’spetition for aspartame approval ledto much disagreement within theF.D.A. The commissioner at thetime, Alexander M. Schmidt, con-vened a three-member public boardof inquiry, which concluded that oneof Searle’s studies on rats showed anincrease in brain tumors from aspar-

tame. The board members — all ofthem scientists at universities — vot-ed to withhold approval of aspar-tame until more studies were done.

But yet another F.D.A. review, thisone of Searle’s tumor tissue slides —paid for by Searle and conducted byan academic group that is now de-funct — concluded that Searle’s stud-ies had demonstrated that aspar-tame was safe. In 1981, a new F.D.A.commissioner, Arthur Hull Hayes,concurred with this assessment andgranted approval to aspartameshortly after President Ronald Rea-gan appointed him to run the agency.

And in a move that fueled the con-spiracy theories, Mr. Hayes left theF.D.A. a little more than a year afterapproving aspartame and took a jobas a consultant to Burson-Marsteller,which at the time was Searle’s publicrelations agency. Mr. Hayes did notreturn calls seeking comment.

Ms. Nabors of the Calorie ControlCouncil said that suggestions or innu-endoes that Searle was trying to in-fluence government officials with lu-crative job offers were baseless. Ar-tificial sweeteners are unfairly tar-geted for suspicion, she said, citingthe government’s decision to ban thesweetener cyclamate in 1969 afterstudies showed that it caused cancerin animals. “Cyclamate was banned,saccharin was required to have awarning label for a while, and there’sall these conspiracy theories onaspartame,” she said.

She added that there were morethan 100 published scientific studiesshowing no adverse effects from

aspartame, and said that in 2002, theEuropean Commission reviewedmany of these studies and re-affirmed the sweetener’s safety. Thebulk of the studies investigated neu-rological effects; none were animalcancer studies, which are lengthyand expensive.

In any case, critics say that mostof these studies were financed eitherdirectly or indirectly by manufactur-ers of aspartame, and that the re-sults of aspartame studies tend to de-pend on who paid for them. In ananalysis of 166 articles published inmedical journals from 1980 to 1985,Dr. Ralph G. Walton, a professor ofpsychiatry at Northeastern OhioUniversities College of Medicinefound that all 74 studies that were fi-nanced by the industry attested tosweetener’s safety.

Of the 92 independently funded ar-ticles, 84 identified adverse health ef-fects. “Whenever you have studiesthat were not funded by the industry,some sort of problem is identified,”said Dr. Walton, adding that he hasnot looked at studies performedsince 1985. “It’s far too much for it tobe a coincidence.”

Dr. Walton, who, like some otherpsychiatrists, has studied aspartamefrom a neurological perspective, saidhe had also seen problems from thesweetener firsthand. At Safe HarborBehavioral Health, a mental healthfacility in Erie, Pa., where he is clin-ical director, Dr. Walton said he hadobserved that for many people withmood disorders, such as depressionor bipolar disorder, aspartame ex-

acerbates the condition. “For peoplewith panic disorders, for instance,we’ve seen that when we eliminateaspartame, it’s much easier to con-trol their illness,” he said. “The num-ber of panic attacks goes down.”

Dr. Walton and others say that thisis probably attributable to aspar-tame’s phenyalanine component.(Aspartame is made up of two aminoacids, phenyalanine and asparticacid.) He said that an excess of phe-nyalanine could upset the body’s bal-ance of neurotransmitters, causing arange of neurological symptoms.

Defenders of aspartame oftenpoint out that phenyalanine is natu-rally present in many protein-inten-sive foods. But Dr. William M. Par-dridge, a professor of endocrinologyat the David Geffen School of Medi-cine at the University of California,Los Angeles, says that when it comesfrom food, phenyalanine is absorbedinto the brain more slowly.

“If your blood phenyalanine levelwas increased five times, in my viewthere would be a safety concern,” Dr.Pardridge said. “The question iswhether aspartame use could everincrease levels that much, and theanswer is yes. We’ve known that for20 years.”

Dr. Soffritti said he had not studiedthe effects of phenyalanine. He theo-rized that the tumors in his studywere related to the methanol, orwood alcohol, that is produced as thebody metabolizes aspartame. Whenthe body breaks down methanol, theresult is formaldehyde, a known car-cinogen. “I know that when I treatanimals with methanol, you end upwith lymphomas and leukemias,” hesaid.

BUT Dr. Kenneth E. McMartin,a methanol expert and profes-sor of pharmacology, toxicol-

ogy and neuroscience at the Louisi-ana State University Medical Center,said he believed that it was unlikelythat someone could consume enoughaspartame to let harmful levels offormaldehyde build up in the body.

Dr. Soffritti said he thought thatmore research and open debate wereneeded on whether aspartame was acarcinogen. “It is very important tohave scientists who are independentand not funded by industry looking atthis,” he said.

Michael F. Jacobson, executive di-rector of the Center for Science in thePublic Interest, a nutrition advocacygroup, said he did not think that Dr.Soffritti’s study could be considereddefinitive, but that it should promptan “urgent re-examination.

“For a chemical that is used byhundreds of millions of peoplearound the world, it should be abso-lutely safe,” Mr. Jacobson said.“There shouldn’t be a cloud ofdoubt.” Ø

Pigi Cipelli for The New York Times

A study conducted at an Italian cancer research center, above, has rekindled the debate on aspartame.

What’s the Lowdown On Sweeteners?Continued From Page 1

A study is atodds with theF.D.A.’s viewof aspartameas safe.

Dr. Soffritti’s journal article on hisfindings is at nytimes.com/business.

Slow and steady and completely focused.

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