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On the Cutting-Edge

Annual Meeting Highlights

A M E R I C A N S O C I E T Y F O R B I O C H E M I S T R Y A N D M O L E C U L A R B I O L O G Y

w w w . a s b m b . o r gAUG UST 2004AUG UST 2004

Constituent Society of FASEB


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f e a t u r e s4 NIH Gets Just Over 2% in Subcommittee Markup

6 House Panel Holds Third NIH Oversight Hearing

8 Publishing Symposium Sheds More Light than Heat

10 Professional Society’s Take On Access to ScientificLiterature

16 Reflections of a Fortunate Biochemist

19 JLR Inaugurates New Series

20 Undergraduate Poster Competition

21 MAC Symposium Addresses Obesity

23 Finding Might Explain Psychiatric Disorders

27 ASBMB Council’s New Members

d e p a r t m e n t s4 News From the Hill

24 Biotech Business

26 NIH News

28 Calendar


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O N T H E C O V E R :

12 Cutting-EdgeSymposiaHighlightedIUBMB/ASBMBMeetingAnnual Meeting Photos byEllen Dallager Photography

16

AUGUST 2004, Volume 3, Issue 5

12

BRONZE AWARD WINNER 2003

AWARDS OF EXCELLENCE:MOST IMPROVED MAGAZINE

COLUMNS & EDITORIALS

DESIGN & LAYOUT

ASBMBToday AUGUST 20042

Dear Editor:I wish to respond to the recent arti-

cle in the ASBMB Today by Peter Farn-ham regarding ASBMB’s position thatthere is a shortage of scientists in theU.S. and that more relaxed immigra-tion policies are needed to increase thenumber of foreign scientists to meetthis demand.

Having been in both academia aswell as industry for the past 25 years Ifind the ASBMB’s assertion to be verydifficult to believe, if not completelypreposterous. to the point of being dis-honest. The ‘real’ data are distorted orignored and the conclusions aremerely self serving by academia. Let usface reality here, foreign scientists ‘intraining’ provide a cheap labor pool foracademic researchers. There is no cur-rent or future shortage of well trainedscientists from the U.S. This is at leasttrue in my field of biochemistry. Infact, I have found quite the opposite.

Jobs for good, well trained scientistsborn in the U.S. are extraordinarily dif-ficult to come by and they have beenfor the past 20 years. Many of my col-leagues, with Ph.D. degrees from majoruniversities with productive trackrecords, have shared with me theirdesire NOT to encourage their ownchildren to go into to science becausethere is no reward at the end of a longjourney of hard work and dedication.

Industry is also blame for this per-ceived ‘shortage.’ Many of my col-leagues at the ripe old age of 40 to 50find themselves to be ‘too senior’ to beemployed by U.S. companies. I knowthis for a fact. My own company of 10

years said “there simply are notenough jobs for senior scientists here.”

There are many outstanding scien-tists who could contribute immenselyto solving this country’s problems, butthey are just sitting idle at home. Or,they are so underemployed that theydo not use their training or scientificacumen. Getting an advanced degreewas a waste of time. Our countryshould be ashamed that it treats its sci-entists like disposable plastic bags.Once used, discard in the landfill.

The ASBMB is severely out of touchwith reality and serves only its owninterests. Why doesn’t the ASBMBspend its efforts trying to encourage thegovernment to hire home trained scien-tists that are unemployed, rather thanjust amplifying an already abysmal jobmarket? Why is the ASBMB not moreaggressive about seeing that experi-enced scientists are not thrown by thewayside, not because they didn’t do agood job or that they didn’t help theircompanies make money, but simplybecause they got older?

Wake up ASBMB, be honest, there isa great labor pool out there already,willing and able to contribute. I won-der why the NSB report to the govern-ment doesn’t solicit input from thosemultitudes who currently need jobs?

It is truly shameful.

Sincerely,Thomas G. Warner, Ph.D.

ASBMB member for many years.541 Wellington Dr

San Carlos, CA 94070 Phone: 650-592-9566

Member Sees ‘No Shortage’of Scient ists in U.S.

A S B M B C o u n c i l

OfficersJudith S. Bond PresidentBettie Sue Masters Past-PresidentPeggy J. Farnham SecretaryKenneth E. Neet Treasurer

Council MembersThomas Blumenthal CouncilorWilliam R. Brinkley CouncilorJoan W. Conaway CouncilorRobert A. Copeland CouncilorLila M. Gierasch CouncilorFrederick P. Guengerich CouncilorWilliam J. Lennarz CouncilorPeter J. Parker Councilor William S. Sly CouncilorWilliam L. Smith Councilor

Ex-Officio MembersGeorge M. CarmanChair, Meetings CommitteeCecile Rochette-EglyDennis R. VoelkerCo-chairs, 2005 Program CommitteeJ. Ellis BellChair, Education and ProfessionalDevelopment CommitteeJuliette BellChair, Minority Affairs CommitteeWilliam R. BrinkleyChair, Public Affairs Advisory CommitteePeter A. RubensteinChair, Publications CommitteeHerbert TaborEditor, JBCRalph A. BradshawEditor, MCPEdward A. DennisEditor, JLR

ASBMB Todayis a monthly publication

of The American Society for Biochemistry and Molecular Biology

Editorial Advisory BoardIrwin FridovichRichard W. HansonBettie Sue MastersEvan J. SadlerRobert D. Wells

CommentsPlease direct any comments or questionsconcerning ASBMB Today to:

John D. ThompsonEditor, ASBMB Today9650 Rockville PikeBethesda, MD 20814-3996Phone: 301-634-7145; Fax: 301-634-7126E-mail: [email protected]

For information on advertising contact FASEB AdNet at 800-433-2732

ext. 7157 or 301-634-7157, or email [email protected].

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N E W S F R O M T H E H I L L


medical inflation. Dr. Bond noted,“This is, in effect a cut in the NIHbudget. It is likely that this will lead toa loss of as many as 640 grants this fis-cal year. This has serious implicationsfor biomedical research. For one thing,it makes it even more difficult for newideas to be pursued. It is the Americanpeople who ultimately suffer from thisslowdown in total effort to explorenew strategies that might lead toprogress in the war against disease.”

The Centers for Disease Control andPrevention would receive $4.2 billion,$138 million less than fiscal 2004 but$15 million more than the Bushrequest. The decrease reflects reducedspending on infrastructure projects.

Subcommittee Chairman Ralph Reg-ula of Ohio acknowledged that hispanel was operating under tightbudget constraints, which limitedincreases for politically popular pro-grams such as medical research, fund-ing for Title I schools servinglow-income students, and state grantsfor education of disabled children.

“We would all like to have moremoney,” Regula said. He added that

the bill represented “the best use of thefunds available” under the proposedFY 2005 budget resolution.

The Obey AmendmentRegula opened the mark-up hearing

by asking if there were any memberswho wanted to comment on the bill.Ranking Democrat Dave Obey of Wis-consin complained bitterly about thebill’s shortcomings, although heacknowledged that Regula had done thebest he could with the allocation he hadreceived under the budget resolution.

Obey mentioned that the NIHincrease in the bill was the smallest in19 years and did not keep up with theBiomedical Research and DevelopmentPrice Index (a measure of biomedicalinflation, commonly referred to as the“Bird-Pie”). Obey, quoting NIH-pro-vided statistics, said that the proposedfunding level would require NIH to cutthe number of new and competinggrants by 640 from last year if theywere all to be funded at the level ofmedical inflation.

When Obey was finished, Regulanoted the increases for education in

he House Labor-HHS-Educa-tion Appropriations Subcom-mittee marked up its FY 2005

spending bill July 8. The subcommit-tee unanimously approved $200 mil-lion more than President Bush hadrequested for 2005 education andhealth programs, with a Democraticbid for even more education spendingquashed along party lines.

The Labor-HHS Appropriations Sub-committee voted 18-0 to send the$492.3 billion spending bill to the fullappropriations committee, whichplanned to mark it up the followingweek. The measure contains $142.5billion in discretionary funding, a $3billion, 2.2 percent increase over fiscal2004. This is slightly higher, just $202million more, than the amount Presi-dent Bush requested in February. Thebill includes $349.8 billion in manda-tory spending for entitlement pro-grams such as Medicaid.

The bill funds NIH at the President’slevel, $28.5 billion, or about $727 mil-lion more than FY 2004. All institutesand centers are funded at the Adminis-tration’s requested levels. This appro-priation was far short of the $30.6billion advocated for by ASBMB andthe rest of the biomedical researchcommunity for FY 2005.

ASBMB President Judith Bond, Penn-sylvania State University College ofMedicine, stated that “We all realizethat public funds are needed to sup-port many worthy projects, but thenation’s health is an investment, notan expenditure.” She expressed con-cern that the subcommittee-approvedlevel of funding for NIH does not evenequal the increased cost due to bio-

N I H Gets Just Over 2% inT

by Peter Farnham , CAE , ASBMB Pub l i c A f fa i rs O f ficer

Thi s i s , in e f f e c t a cu t in the NIH budge t . I t i s

l i k e l y that th i s w i l l l ead to a l o s s o f a s many as

640 g rant s th i s f i s ca l y ear. Th i s has s e r i ous

impl i ca t i ons f o r b iomed i ca l r e s earch . Fo r one

th ing , i t makes i t e v en more d i f f i cu l t f o r new

ideas to be pur sued . I t i s the Amer i can peop l e

who u l t imate l y su f f e r f rom th i s s l owdown in

to ta l e f f o r t t o exp lo re new s t ra t eg i e s that might

l ead to p rog re s s in the war aga ins t d i s ease .

—ASBMB Pre s ident Jud i th Bond

AUGUST 2004 ASBMBToday 5

the bill and added that “NIH has tolook at how they spend the money wegive them.” He said that giving auto-matic increases to NIH does not auto-matically guarantee quality.

Obey then offered his amendmentto add $7.4 billion to the bill, includ-ing a $5.6 billion increase for educa-tion and about $500 million morefor NIH. This was the same amend-ment he brought to the House floorin late June during debate on thebudget resolution. Obey proposed a30 percent reduction in tax cutsenacted in 2001 and 2003 for those

with annual incomes of more than$1 million.

During discussion of the amend-ment, Rep. Randy “Duke” Duke Cun-ningham (R-CA) told a somewhatlaborious story about two pig farmerswho raised their pigs on their own andthen were taxed by the government.The story appeared to be a metaphor,representing how the amendmentwould hurt small businesses.

Cunningham’s story, although notexactly the rhetorical high point of theday, seemed nonetheless to have beeneffective, as the Obey amendment

failed on a party-line vote of 7-11.While Obey may again try to attach itto the bill when the full committeemeets, realistically, there is little chanceit will pass.

The bill was scheduled to go to theHouse floor the week of July 19.

A press release and a table detailingthe subcommittee’s bill are available onthe ASBMB website, www.asbmb.org,under the “What’s New” column onour homepage. Click on the link andyou will be connected to a HouseAppropriations Committee page givingfull details.


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House Subcommittee Markup



For a more detailed explanation ofthese rules, see Dr. Zerhouni’s testimonyat: http://energycommerce.house.gov/108/Hearings/06222004hearing1312/Zerhouni2076.htm

Zerhouni’s actions were well receivedby the committee. CongressmanStearns said that NIH will be better[because of these rules] and ChairmanGreenwood commended Dr. Zerhounion his efforts, “your work meets myapproval.” During questioning, somemembers of the panel brought up pastproblems that have lead to previoushearings, such as those that werereported in the December 2003 LATimes article. A few members askedhow these rules would have changedthose events. Zerhouni said that manyof those problems would have beentaken care of under the proposedguidelines.

Another point of interest revolvedaround the issue of NIH reauthoriza-tion. While the topic was not men-tioned frequently, two members—JoeBarton and Michael Bilirakis—didbring it up. During opening state-ments, Chairman Barton said that dur-ing his Chairmanship he wants tohold government agencies accountablefor their actions and that the subcom-mittee is uncovering problems thatwill build a roadmap to solutions as wego forward with reauthorization. Con-gressman Bilirakis said that during thereauthorization he and Chairman Bar-ton wanted to make the Directors posi-tion stronger and suggested thatZerhouni submit to the committee, inwriting, what can be done.

During the final round of question-ing of Dr. Zerhouni, Congresswoman

DeGette asked Chairman Greenwoodto hold open the option for a futurehearing to examine the effect of thenew rules.

N IH , Hosp ita l ProbesCou ld ProduceLeg is lat iveResponses

House Energy and Commerce Over-sight and Investigations Subcommit-tee Chairman Jim Greenwood, R-Pa.,said today he is considering draftinglegislation to address findings of allthree of the panel’s ongoing healthinvestigations. Greenwood has beenexamining potential conflicts-of-interest at the National Institutes ofHealth, hospital billing practices andthe use of anti-depressant drugs inchildren. Greenwood told healthreporters he is closest to readying leg-islation in response to the NIH inves-tigation, which has uncovered casesof questionable awards and speakingfees given to scientists involved ingrant-making and the extensive use ofa federal law that allows highersalaries for temporary employees.After a series of discussions, NIHDirector Zerhouni is making changes,Greenwood said, including barringawards to scientists involved in thegrant-making process.

These changes also include forbid-ding some scientists from serving oncorporate boards or owning stock indrug or biotechnology companies,and increasing public disclosure oftheir outside income. Greenwoodsaid he wants to remove existingsalary caps and “let it go to marketrate” but with an open and transpar-

he House Energy and Com-merce Subcommittee onOversight and Investigations

held a third hearing, June 22, on theissue of NIH Conflicts of Interests. Theevent was titled “NIH Ethics Concerns:Consulting Arrangements and OutsideAwards”.

During opening statements by mem-bers of the committee a themeemerged: NIH is the crown jewel of thefederal government, but these prob-lems have cast a luster on this organi-zation. Thus, something must be doneto preserve the integrity of NIH. Con-gresswoman DeGette said that evenrare cases must be prevented becausethe public trust of NIH is at stake andCongresswoman Schakowsky said thatAmericans must have faith in the bio-medical research infrastructure. Dr.Zerhouni even commented that theseincidents have lowered moral at NIHand that people want to fix the prob-lem quickly. To accomplish that, Dr.Zerhouni laid out additional new poli-cies; some which he said could bedone internally while others mayrequire new legislation. These include:◆ A ban on ownership of drug com-

pany or biotech stocks by some keyemployees.

◆ Restricted stock ownership for allother employees.

◆ No membership on corporateboards.

◆ The creation of a centralized registryof all outside arrangements and apublic list of the awards thatemployees may receive.

◆ A prohibition of all paid consultingor speaking engagements at institu-tions that receive NIH funding.

House Subcommittee HoldsT

by Peter Farnham , CAE , ASBMB Pub l i c A f fa i rs O f ficer


to social conservatives’ questioningof some NIH grants.

Greenwood said he also is ready todraft legislation to limit what hospi-tals can charge uninsured patientsand require them to offer charitycare to eligible uninsured patients ifhospitals do not change their proce-dures. “No one who qualifies forcharity care should end up payingcharges” that are frequently inflated,he said. “I don’t have a problem withpeople being asked to pay their [hos-pital] bill. I have a problem with peo-ple being asked to pay twice what

everyone else does.” Legislation, hesaid, might limit what hospitalscould charge the uninsured toMedicare’s rate plus a specified per-centage. Greenwood was less certainabout legislation in response to theinvestigation of the use of anti-depressants in children, whichuncovered cases of clinical trials thatproduced negative results that werenever published. “You can imaginehow delicate this is.” If legislation isneeded, it might require the publica-tion of all clinical trial results, Green-wood added.

ent system. “I want to set up a systemin which you ought to be able to paypeople what you need to get them,”he said. Finding a vehicle for suchlegislation could be difficult. Theobvious place would be an NIH reau-thorization bill, which Energy andCommerce Chairman Barton has saidhe wants this year. “So would I,” saidGreenwood. “I’d like to fly, too. But Idon’t think it’s going to happen.” Hesaid an NIH bill faces not only a fightover embryonic stem cell researchbut also “people will want to play the‘don’t study sex’ game,” a reference

Third N I H Oversight Hearing



presently lacking and what the likelychanges will be downstream.”

The symposium was also notable,several panelists and observers toldASBMB Today, for its generally tem-perate tone. This has not always beenthe case in symposia on scientific pub-lishing, particularly in the last severalyears. The mostly reasonable discus-sion was directly tied to the originaldesign, and the questions the panelistswere asked to consider: the qualities ina journal that would lead one to rec-ommend to a junior colleague thatthey publish in it, the scientific com-munity’s unmet needs that wouldwarrant significant change in currentpublishing models, how well served isthe public by the existence of differing

models for publication of scientific lit-erature, and what should the scientificpublishing world look like in tenyears’ time?

“Interestingly,” Dr. Bradshawnoted, “the sense that emerged, atleast from my perspective, is that‘availability’ of the literature is less aproblem than ‘fundability’ of the lit-erature, and that the established lit-erature and journals, which are morelikely to be around in the future, aremore desirable as places to publish,providing they maintain high stan-dards of peer review. No onethought that any particular businessmodel or ‘open access’ approach waslikely to be a predictor of thesedesired characteristics.”

he ASBMB Public Affairs Advi-sory Committee (PAAC)enjoyed a major success at

the recent Society annual meeting inBoston when its public affairs sympo-sium, “Where Should Scientists Pub-lish: The Future of ScientificCommunication,” played to a stand-ing-room only crowd. PAAC memberRalph Bradshaw, Editor of the Society’sjournal, Molecular and Cellular Pro-teomics, said, “The forum was con-ceived as an opportunity to look at themany issues presently confronting thisenterprise from the point of view ofscientists’ needs. Hence the emphasiswas not directly on business modelsand ‘open access,’ although both issueswere certainly raised, but on what is

T

Boston Publishing Symposium By Peter Farnham , ASBMB Pub l i c A f fa i rs O f ficer

The University of California, Davis,School of Medicine has establishedan annual lectureship to honor thefounder of the school’s Department ofBiological Chemistry. The Edwin G.Krebs Lectureship in Molecular Medi-cine celebrates the scientific contribu-tions of Dr. Krebs, who in 1968 wasthe founding Chair of the Depart-ment of Biological Chemistry at UCDavis. The Department (now namedBiochemistry and Molecular Medi-cine) launched the lectureship March24, with a day-long symposium fea-turing graduate students/ postdoctoralfellows, all of whom were here withDr. Krebs during part of his tenure,which lasted until 1977.

Krebs, who is now Emeritus Profes-sor of Pharmacology and Biochemistryat the University of WashingtonSchool of Medicine and an HHMIInvestigator, unraveled the complexpathways by which hormones and

drugs regulate cellular functions. In1955, he and Dr. Edmond Fischer,working in the Department of Bio-chemistry at the University of Wash-ington, discovered the process ofprotein phosphorylation and dephos-phorylation, which mediates hormonestimulation with the metabolism ofglycogen, a complex carbohydrateused as energy storage in the cell. Theyidentified the enzyme phosphorylasekinase, which represented the firstexample of a protein kinase, a familyof enzymes now known to regulatecritical cellular functions.

In 1968, Dr. Krebs and his associatesdiscovered cyclic AMP-dependent pro-tein kinase, an enzyme central to amyriad of cellular activity. This worklaunched the scientific field of proteinkinases. Members of the protein kinasefamily regulate cell growth, develop-ment, malignant transformation, andlearning and memory in the nervous

system. He and Dr. Fischer shared the1992 Nobel Prize in Physiology andMedicine for their pioneering discov-ery of protein phosphorylation anddephosphorylation.

Currently, Dr. Krebs laboratory atthe University of Washington is con-cerned with the mechanisms involvedin the intra-cellular transmission ofhormone and growth factor signals.Of particular interest are mechanismsthat involve the phosphorylation anddephosphorylation of proteins. Onespecific area of research addresses thequestion of how growth factor recep-tors possessing protein tyrosine kinaseactivity, e.g. the insulin, epidermalgrowth factor, and the platelet-derivedgrowth factor receptors, regulate thephosphorylation of cellular proteinson serine or threonine residues. Thelaboratory is also interested in themechanisms that are involved in pro-grammed cell death or apoptosis.

UC Davis Lectureship Honors Founder Of Biolog ical Chemistry Department


important research not being pub-lished; almost 70 % of authors in arecent survey believed access to the lit-erature was better (or much better)than it was five years ago; and that lessthan 5% of authors believed the gen-eral public was their primary audience(conversely, almost 90% wrote for fel-low researchers).

The third speaker, Dr. Pat Brown,Stanford University, one of thefounders of the Public Library of Sci-ence, gave an impassioned presenta-tion advocating for the open accessmodel. He cited a number of recentpapers published in PLOS Biology andPLOS Medicine by eminent scientists,including an ASBMB award winner, asevidence that the PLOS model wasworking and attracting qualityauthors. He summed up by character-izing the PLOS model as “unassailable”in concept and design.

Few if any other members of thepanel agreed with this assessment,however. Dr. Martin Frank, ExecutiveDirector of the American PhysiologicalSociety, noted his organization’s strongsupport for the Washington, DC, Prin-ciples for Free Access to Science. Theprinciples outline the commitment ofnot-for-profit publishers to work inpartnership with scholarly communi-ties such as libraries to ensure thatthese communities are sustained, sci-ence is advanced, research meets thehighest standards and patient care is

enhanced withaccurate andtimely informa-tion. The DCPrinciples providewhat has beencalled the needed“middle ground”in the debatebetween those

who advocateimmediate unfet-tered online accessto medical and sci-entific researchfindings and advo-cates of the currentjournal publishingsystem.

It was clear from the discussions thataccess to the scientific literature,already as broad as it has ever been, isonly likely to get broader in the com-ing decade. This does not mean, how-ever, that there will be no place fortraditional publishing. The well-estab-lished, well-cited journals will nodoubt continue to be around, and sci-entists will no doubt continue to wantto publish in them. The issue will behow to ensure that smaller, butnonetheless important, specialty jour-nals will survive in the new environ-ment. Dr. Catherine Drennan, MIT,another discussant, noted that “jour-nals such as Biochemistry and MolecularBiology Education would not be able tosurvive with an author-pays model,and we need to consider the effects onall journals before making any drasticchanges in publishing models.”

Outgoing ASBMB President BettieSue Masters said, “the Public AffairsAdvisory Committee should be justifi-ably proud of the Public Policy Forum.My personal opinion is that theASBMB case was clear, convincing, andcorrect. Thanks again for this excellentaddition to our meeting program.”

Each of three main speakers dis-cussed the questions that framed thediscussion from a unique perspective.Dr. Robert Simoni, Stanford Universityand deputy editor of the Journal of Bio-logical Chemistry, discussed JBC’s excel-lent track record in science publishingand (not surprisingly) recommendedthat scientists should publish theirwork in JBC “or journals like it”.Among his points: on average, JBC

makes a first deci-sion on a submit-ted paper within25 days, andaccepts within 60days (both wellbelow HighWirePress averages as awhole); Google is

becoming an increasingly importantsearch engine for the JBC (the numberof JBC hits originating in Googleincreased ten-fold from April 2003 toApril 2004); having a wide variety ofcompeting publishing models is goodbecause the competition drives innova-tion; only 7 % of JBC authors supportthe “author pays” model of fundingscientific publication. Dr. Simoni alsoexpects fewer print journals in 10 years’time, and that on-line journals willbecome the “journals of record”.

Michael Mabe, from Elsevier, gavean overview of journal publishingfrom the first scientific journal (pub-lished in 1665) and noted that for thefuture, he expected the journal modelto remain viable (increases in co-authorship would not begin to affectjournal viability for many years); thetechnology will continue to develop;and economic models will continue todevelop as well. He estimated the aver-age cost of publishing a scientific arti-cle to be in the $3,000 - $4,000 range;the author-pays model can result in

Sheds More Light than Heat

Michael Mabe

Pat Brown

Robert Simoni

For A SBMB’s t ake

o n a c c e s s t o s c i e n t i f i c

l i t e r a t u re s e e

n e x t p a g e .


The concept of publishing by scien-tific societies has been a long-standingone, beginning in the late 1800s for thebiological sciences, to meet the obviousneed of an area of scientific expertisewith unique knowledge and skills todisseminate information to those whoshare an interest in the results of scien-tific inquiry and to promote furtherresearch in the specific area. It is impor-tant to maintain the depth of expertiserepresented by these learned societiesfor true peer review of science withinthe respective disciplines.

ASBMB has been highly innovativein the publishing arena. It was the firstbiomedical journal to be available elec-tronically - in 1995. This resulted froman alliance between the JBC and High-Wire Press that arose out of conversa-tions among Robert Simoni (deputyeditor of the JBC), Michael Keller andJohn Sack, all of Stanford University.ASBMB took on the financial risk ofsuccess or failure. Scientists and soci-eties rapidly saw the potential for newforms and features of scientific com-munication, and Science and Proceed-ings of the National Academy ofSciences USA soon joined JBC online.

In 2001, JBC introduced Papers inPress (PIPs), which makes manuscriptsavailable online the day they areaccepted for publication, and permitsfree access to JBC papers to anyone. PIPsremain online even after the final editedand printed version of the manuscriptappears, which takes around 8 weeks.The original date of publication of amanuscript is when it appears as a PIP,and PIPs remain on-line even after theeditorial process is completed and the

final form is published. Thus, the con-tent of JBC publications is freely avail-able online to everyone, and meets thecriteria of a truly ‘open access’ journal.

More recently, JBC has provided free,on-line, full text searchable access toevery published article since its incep-tion in 1905. The JLR now also providesfree, on-line access to every publishedarticle since its founding in 1959. Manyother journals are now following suitbut only a few have succeeded inachieving the goal of making theirentire contents available in such a form.This activity was undertaken with theview of providing a vital service to thebiological sciences community but itwas not done without considerablethought and concern about its financialimplications. The cost of this processwas in excess of $700,000. The financialstability of the ASBMB and our businessmodel for publishing has allowed ournon-profit organization to take on suchexpenses, to serve our readers, authorsand science. Our expenses are paid by acombination of sources, primarily bypage charges to authors and subscrip-tions to individuals and libraries. In arecent survey of over a 1,000 JBCauthors, over 80 percent preferred thismode of covering expenses to othermodels, such as authors or institutionspaying all the costs.

In the end, the open access, coststructure and the quality of the JBCpeer-review system, have been appreci-ated by our readers, authors, librariesand scientific institutions. Submissionsto the Journal continue to increase, asdo citations. These capabilities of JBCare now available for other journals of

he Journal of Biological Chem-istry (JBC), the flagship jour-nal of the American Society

for Biochemistry and Molecular Biol-ogy (ASBMB), will celebrate its centen-nial in 2005. The JBC predated theASBMB by one year. This is notable inthat a professional scientific societygrew out of the need for a discipline-oriented scientific publication. Theexpertise represented by a discipline isa very important consideration in theestablishment and/or maintenance ofthe scientific literature.

The JBC has been a premier scientificpublication with a prestigious scientificfollowing. It is known for the high qual-ity of its peer-reviewed publications offundamental advances in biochemistryand molecular biology. The ASBMB isnow an international organization withover 12,000 members and approxi-mately half of the JBC’s publishedauthors are from foreign countries.

This growing international perspec-tive has redefined the missions of theSociety and its journals, which includeASBMB Today, the monthly magazineof the society, a newly established jour-nal Molecular and Cellular Proteomics(MCP), the newly acquired Journal ofLipid Research (JLR); and the educationjournal Biochemistry and Molecular Biol-ogy Education (BAMBED), whichASBMB publishes in collaboration withthe International Union of Biochem-istry and Molecular Biology. ASBMB isresponsible financially for the successor failure of BAMBED, which has beenundertaken as a service to the commu-nity of teachers and students of thediscipline throughout the world.

T

A Professional Socie ty’s Take onThe fo l lowing statement by ASBMB Pres ident Jud ith S . Bond

and Past-Pres ident Bett ie Sue Masters was pub l ished Ju ly 1 4 on the journa l Nature ’s on l ine Web Focus s i te ,

http : / /www.nature .com/nature/focus/accessdebate/27 .html


actual maintenance of servers, theAssociate Editor offices (secretarial,computer and telephone services),hands-on training sessions for onlinereviewing, and editorial and print costs.

The subject of editorial independ-ence cannot be ignored. Dependingupon the business model, unless largesubmission charges are levied, theremay be a tendency to lower the stan-dards of review to permit more manu-scripts to be published. There is risk,for example, in an author-pays-all-costs publication model that standardscould be influenced by the acceptancerate of manuscripts.

This is not the case with society-based, not-for-profit publishers, partic-ularly if the business model does notrely solely on page charges to authors.The maintenance of high standards is,indeed, the creed for these publishers,since there is pride in knowing thatpublishing in their journals is held inhigh regard. The major safeguard is theselection of editors with the appropri-ate expertise and the knowledge thatone’s peers are overseeing the stan-dards of the publication.

There are many challenges remain-ing in the publishing industry. One ofthese is the archiving of digital infor-mation in a safe, permanent and easilyretrievable medium. There have been

many attempts to address this problembut none has surfaced as the satisfac-tory answer. It would seem that allpublishers should be making efforts toachieve an effective archiving systemand that much of the energy beingexpended by various factions in thepresent debate would be better spentin answering this need.

It is difficult to estimate how mucharchiving will cost because we do notyet know the modality that will beused ultimately. Most agree that thereprobably should be multiple sites forarchiving, and that the systems mustbe updated and corrected continually.There is probably no single solutionand innovations of various typesshould be pursued and implemented.Regardless of which publishing modelone espouses, the fact that the industryis moving toward predominantly digi-tal publication will necessitate a viableand redundant archiving system.

As any believer in the free enterprisesystem would espouse, it is better toallow and, indeed, to encourage com-petition among various modes of publi-cation. Societies, for the most part,believe that their discipline-based jour-nals offer a high standard of review andgreat depth and breadth of scrutiny dueto the expertise represented by the soci-ety members or by those chosen toserve on their respective editorialboards, whether members or not.

ASBMB welcomes the involvementof all publishers in making the scien-tific literature more openly accessibleto all interested readers and challengesthose who would say otherwise toprove that such competition is not ahealthy incentive to new innovationsin submission, review and publication.The burden of such progress rests uponall, and the ASBMB submits that it hasbeen a prime contributor to thisprogress and intends to remain so.

ASBMB as they have become incorpo-rated into the publication network. Itis important to note that societies,such as ASBMB, have been providingthese innovations and that a measureof competition in continuing to pro-vide such in the market place is vital tothe success of the industry.

In order to handle the large volumeof manuscripts that the fields of bio-chemistry and molecular biologyencompass, it has been necessary tomaintain a sizeable panel of associateeditors (21) with editorial offices thathandle approximately 600 manuscriptseach per year. The editorial board con-sists of over 600 members to cover thevarious areas of expertise needed forpeer review of the variety of manu-scripts. These individuals each handlebetween 20-60 manuscripts per year toproduce more than 50,000 printedmanuscript pages in the JBC. In organ-izing a journal of any type, it is impor-tant that the reviewing board be willingand qualified to review. In addition,there are approximately 16 full-timestaff in the Society office that supportthe ASBMB publication mission.

To quote Declan Butler, editor of thisNature Web Focus series, ‘the core func-tions of publishing at its best share acommitment to impose intellectualrigour and high editorial standards onan exponentially increasing body ofknowledge. As the flood of informationgrows, more and not less human edito-rial skill will be needed to focus andmake sense of it’ (our emphasis). Weassert that this is one of the primeresponsibilities of all publishers,whether for-profit or not-for-profit. Theincentives to serve as an editor includethe prestige of Editorial Board member-ship because, in the case of society-based publications, there is noremuneration for such service. There-fore, the major costs are to pay for the

Access to Scient i f ic Li terature

A S B M B h a s b e e n

h i g h l y i n n o v a t i v e i n

t h e p u b l i s h i n g a re n a .

J B C w a s t h e f i r s t

b i o med i ca l j ou r na l t o

b e a v a i l a b l e

e l e c t ron i ca l l y

—in 1995

with our international colleagues.Attendees were treated to special cut-ting-edge symposia that focused onadvances in science and public pol-icy issues that are challenging ourprofession. The sessions captured thepulse of the fundamental basis of thelife sciences, as did the enthusiasticpresentations of our next generationof scientists, the undergraduates andgraduate students.”

Robert J. Lefkowitz of Duke Univer-sity Medical Center, opened the meet-

ing with the Herbert Tabor/Journal ofBiological Chemistry Lecture. His topicwas “Seven Membrane SpanningReceptors.” Dr Lefkowitz is known forhis seminal research on this group thatconstitutes by far the largest and mostubiquitous family of receptors innature. Continuing research on thesereceptors in the Lefkowitz laboratory iscontributing to the development of awide range of drugs to treat disordersincluding heart disease, high bloodpressure, and asthma.

rom the opening day’s Her-bert Tabor/Journal of BiologicalChemistry Lectureship to the

final day’s symposia, IUBMB/ASBMBwas an outstanding experience forsome 3,000 attendees who came toBoston from institutions in the UnitedStates and all around the world.

Reflecting on the meeting, ASBMBPresident Judith S. Bond said, “I wasdelighted with the scope andstrength of the science at the Bostonmeetings, and the vigorous dialogue

F

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On the CuOn the CuSymposia Highlighted I U BM B/AS BM B Annual Meet ing


topic for Dr. Davis whose lab was instru-mental in the development of phagelambda vectors, which are now themost common method for the primarycloning of cDNA molecules using E. coli.

Schering-Plough Research InstituteAward recipient Pehr A. B. Harbury ofthe Stanford University School of Med-icine, spoke on “DNA Display in vitroEvolution of Combinatorial ChemistryLibraries.” Dr. Harbury has developednew methods for characterizing thefolding determinants and foldingbehavior especially of larger proteinsand has used them to characterize thefolding of yeast triosephosphate iso-merase. These methods are expected tobe widely used and speed the develop-ment of proteomics.

The recipient of the ASBMB-AvantiAward in Lipids, William L. Smith, Uni-versity of Michigan Medical School, isknown as an outstanding experimen-talist whose prolific career has yieldedseminal work in the areas of eicosanoidbiosynthesis, the physiology of polyun-saturated fatty acids, and the action ofprostaglandins. The topic of his lecturewas “Prostaglandin Endoperoxide HSynathses/Cyclogenases.”

“The Structure of MHC Proteins andthe Therapy of Multiple Sclerosis” wasthe topic for Harvard’s Jack L. Stro-minger, recipient of the 2004 ASBMB-Merck Award for outstandingcontributions to research in biochem-istry and molecular biology. Dr. Stro-minger has been a pioneer in thediscovery of the structures of bothclass I and class II human major histo-compatibility complex antigens andtheir recognition of self and foreignpeptides for presentation to theimmune system.

In addition to the awards lectures,the meeting’s 10 separate symposiaprovided a rich diet of research find-ings while special sessions focused onsuch topics as minority affairs, publicaffairs, the future of education andprofessional development for youngscientists, undergraduate grant writingand networking, the ASBMB digitallibrary, and other areas.

Other award-winning lecturers were:Steven Almo, Albert Einstein College

of Medicine, recipient of the ASBMB-Amgen Award, is a world leader instructural biology who has developinga unique program in the cytoskeletonand functional analysis of contractileand allergenic proteins. His lecturetopic was the “Structural Basis for T-cellCostimulation.”

“Cytochrome c Oxidase and the Par-ticulate Methane Monooxygenase”was the topic for William C. RoseAward recipient Sunney I. Chan, Cali-fornia Institute of Technology. Hismost recent research interests havebeen broadly based in the area of phys-ical biochemistry, with particularemphasis on bioenergetics and thestructure and function of membraneproteins, magnetic resonance spec-troscopy, and bio-inorganic chemistry.

Stanford University School of Medi-cine’s Ronald W. Davis, a world leaderin biotechnology, delivered the HerbertA. Sober Lecture. “New Genomic Tech-nology for Yeast and Human” was he

tting-Edgetting-Edge

At left: Undergraduate Poster Competition wascenter of attention on exhibit floor.

ASBMB Booth was busy throughout the meet-ing with staffers answering members’ questionsand providing others with membership applica-tions and explanations of the Society’s services

for members.


AS

BM

B

HO

NO

RS Robert J. Lefkowitz, who opened the

meeting with the Herbert Tabor/Journalof Biological Chemistry Lecture, with JBCEditor Herbert Tabor (left) and BruceThomas, President and CEO of Cadmus,who presented the award.

Above: ASBMB-Avanti Award in Lipids recipientWilliam L. Smith of the University of Michigan Med-ical School with Alexandra Newton, University ofCalifornia, San Diego, who presented the award.

Left: Schering-Plough Research InstituteAward recipient Pehr A. B. Harbury, Stan-ford University School of Medicine, withASBMB Past-President Bettie Sue-Masters.

Above Right: Steven Almo, Albert Einstein College of Medicine, receivedthe ASBMB-Amgen Award from Amgen representative Joe Kim.

Below Center: Philanthropist JohnWhitehead (at left) was presented with

Howard K. Schachman Public ServiceAward by Public Affairs Advisory Com-

mittee Chair William Brinkley. Theaward recognized Schachman’s diligent

and constant efforts to promote con-gressional support for NIH funding.

Below: Ronald W. Davis, Professor inthe Department of Biochemistry, Stan-

ford University School of Medicine,accepts the Herbert A. Sober Lectureship

from, at left, Robert Simoni, Deputy Edi-tor of The Journal of Biological Chem-

istry. The award recognizes outstandingcontributions to biochemical and molec-ular biological research, with particular

emphasis on development of methodsand techniques to aid in research.

William C. Rose Awardrecipient Sunney I.Chan, California Insti-tute of Technology, cen-ter, was presented withplaque by Jack Dixon, atright, who received theaward in 2003. At left isMinor J. Coon, professor,University of MichiganHealth Center.

Below Right: Harvard’s Jack L. Strominger, with the 2004 ASBMB-MerckAward which was presented by Merck’s Nancy Thornberry.

M e e t i n g O r g a n i z e r sDennis R. Voelker, National Jewish Medical Research Center

Cecile Rochette-Egly, IGBMC, Strasbourg

and the 2005 ASBMB Program Planning Committee

2 0 0 5 A S B M B A n n u a l M e e t i n gH e l d i n c o n j u n c t i o n w i t h E B 2 0 0 5

S y m p o s i a T h e m e sDynamics of Protein—Protein Interactions (Bumping in the Night)Chair: Ben Margolis, HHMI, University of Michigan

DNA Replication and Interactive Repair and Recombinational ProcessesChair: Charles S. McHenry, University of Colorado HealthSciences Center

Coordinate Regulation of TranscriptionChair: Cecile Rochette-Egly, IGBMC, Strasbourg

Interactions and Functions ofGlycoconjugatesChair: Mark A. Lehrman, University of Texas SouthwesternMedical Center

Integration and Organization of SignalingPathwaysChair: Alex Toker, Beth Israel Deaconess Medical Center

Minority Affairs Committee SymposiaChair: Phillip A. Ortiz, Empire State College

Biochemistry and Molecular Biology of LipidsChair: Charles O. Rock, St. Jude Children’s Research Hospital

Organelle Biogenesis and DynamicsCo-Chairs: Carla Koehler, UCLA and Danny Schnell, University ofMassachusetts, Amherst

Proteolysis and DiseaseChair: Charles Craik, University of California, San Francisco

Catalysis: Structure, Function, and EvolutionChair: John A. Gerlt, University of Illinois, Urbana-Champaign

Metabolic Regulatory CircuitsChair: M. Daniel Lane, Johns Hopkins University School of Medicine

Genomes and ProteomesChair: Andrew J. Link, Vanderbilt University

Education in the Biomolecular Sciences: The Next GenerationCo-Chairs: Judith G. Voet, Swarthmore College and Marion O’Leary,California State University at Sacramento

w w w . a s b m b . o r g / m e e t i n g s

April 2-6, 2005San Diego, CA

Amer ican Society fo rB iochemistr y and Molecular B Io logy


radical chain mechanism, but I did notknow this and had to discover it formyself. Thus I found that sulfite couldreduce cytochrome c and, of course, atthe same time cytochrome c could oxi-dize sulfite. When this was done anaer-obically the stoichiometry was 2cytochrome c reduced per sulfite oxi-dized, as expected. However, in thepresence of dissolved O2 thousands ofsulfites were oxidized per cytochrome creduced. This could be rationalized byassuming that each time sulfite trans-ferred an electron to cytochrome c, theresulting sulfur trioxyradical started achain reaction between sulfite and O2.

The truly impressive amplification pro-vided by this chain reaction fascinatedme and so I played with it to see what itcould be used for. Sulfite oxidation ulti-mately provided: an ultrasensitive mano-metric assay for xanthine oxidase; amethod for detecting long lived flavinradicals generated photochemically; amethod for ultrasensitive manometricactinometry; and much more.

Xanth ine Ox idase It was sulfite oxidation that led to

xanthine oxidase, which in turn led tosuperoxide and to the superoxide dis-mutases. Thus, a soluble fraction ofliver, able to catalyze the oxidation ofsulfite, lost this activity upon dialysis,and adding back the concentrateddialysate restored that activity. A searchfor the dialyzable cofactor of sulfiteoxidation yielded hypoxanthine.Because hypoxanthine is a substratefor xanthine oxidase we were led tothat enzyme. In time we realized thatxanthine oxidase, when acting on itssubstrates aerobically, could initiate theoxidation of sulfite. This should havetold me that xanthine oxidase wasgenerating a radical from O2, and thatradical (O2

-) was initiating the oxida-tion of sulfite. However, I was woefully

slow and that illumination was notachieved for several more years.

A D ivers ion toAcetoacet icDecarboxy lase

Work with xanthine oxidase wasinterrupted in 1962 by a year-long sab-batical spent with F. H. Westheimer inthe Department of Chemistry at Har-vard University. At our first meeting heinvited me to work on anything Ichose to do, but I wanted to exploresome of his interests, which includeddecarboxylation.

When I returned to Duke MedicalSchool, Philip Handler indicated that Ishould quit working on xanthine oxi-dase and branch out into other areas.

Steady state kinetic studies ofenzyme action were then fashionable,and I had noticed that urea and guani-dinium could competitively inhibitxanthine oxidase and could do so atconcentrations far below those neededfor unfolding proteins. The inhibitorypower of guanidinium salts was foundto vary markedly from lot to lot. I thenisolated the symmetrical triazine thatwas responsible for this variability.While working with triazines I foundsome that were powerful inhibitors ofuricase and was pleased to see thisinformation applied to raising theurate level of mice by feeding them myuricase inhibitor.

Acetoacetic decarboxylase was notentirely abandoned, and we foundthat the activity of the isolated enzymecould be irreversibly doubled by mildheating. An incident that reveals thestature of Frank Westheimer deals withthis autoactivation of acetoaceticdecarboxylase. After exploring the phe-nomenon I submitted a descriptivemanuscript to the Journal of BiologicalChemistry. Editor John Edsall sent it forreview to Westheimer, who called me

hile contemplating the writ-ing of this article I rereadsome of my early publications

and in so doing was appalled at myprofound ignorance. That, of course, isthe advantage of hindsight. It is alsoan indication of how much has beenlearned by me and by others duringthe intervening half-century. That isthe beauty of science; it is a collabora-tive work in progress that buildsknowledge and understanding of thereal world. I hope it may be interesting(for readers concerned with the processas well as with the results) to recounthow we progressed from abysmalnaiveté to our current informed viewof the biology of oxidation stress.

Su l fi te Ox idat ionIn 1949, Abraham Mazur introduced

me to the wonders of biochemistry in anundergraduate course and then during ayear spent working in his laboratory atCornell Medical School. At the end ofthat year he recommended graduatework and sent me to Duke to work withPhilip Handler, Chairman of the Depart-ment of Biochemistry. Handler was themost impressive person I ever met. Hewas blessed with a photographic mem-ory, an incomparable mastery of lan-guage, and excellent judgment. Heassigned me to work with Murray Heim-berg, a senior graduate student.

We worked long hours, measuring O2uptake with Warburg microrespirome-ters, and methylene blue bleaching inevacuated Thunberg tubes, with a Cole-man colorimeter. We found thatµhydroxysulfonic acids dissociated tocarbonyl compounds plus sulfite andthat sulfite was then oxidized to sulfatein the liver extracts we were studying.Thus began my long infatuation withsulfite oxidation.

It had already been established thatsulfite was readily oxidized by a free

W

Reflect ions of a Fortunate BiochemistBy Dr. Irwin Fridovich


was very much a function of the con-centration of xanthine oxidase.

Previous misconceptions were sweptaway, and it was immediately clear thatxanthine oxidase was releasing O2

- intofree solution, where it could reducecytochrome c, initiate sulfite oxidation,or be intercepted by the proteininhibitors of cytochrome c reduction. Itwas also clear that those inhibitors ofcytochrome c reduction must be actingcatalytically, and the only feasible waythey could do so was by dismutatingO2 into H2O2 + O2. Bravo Joe McCord!

Now we knew exactly what to do,and the SOD activity in bovine erythro-cytes proved to be abundant and stableand it was soon purified. Moreover itsactivity was demonstrated using elec-trochemically generated O2

- in place ofthe flux of O2

- made by xanthine oxi-dase and using tetranitromethane inplace of cytochrome c. Joe and I feltlike kids in a toy shop. We could anddid use the newfound SOD to explorethe role of O2

- in diverse reactions andto measure the effect of reaction condi-tions on the proportion of univalentover divalent O2 reduction by xan-thine oxidase. We recognized that ourCu,Zn-SOD had long been studied byothers as an abundant cuproprotein ofunknown function and given thenames hepatocuprein, cerebrocuprein,hemocuprein, etc.

Phys io log ica lFunct ion of SODs

If O2- could be made in quantity by

xanthine oxidase, it seemed obviousthat it would be made by otherenzymes as well, and if it could readilycause the oxidation of sulfite and ofepinephrine, it could surely causeunwanted oxidations within cells. IfSODs were so active and abundant, itseemed to us that they must serve as adefense against O2

-, much as catalasesdefend against H2O2. Those viewsdemanded support, which was soonforthcoming. Thus a survey ofmicroorganisms revealed that aerobescontained abundant SOD, whereasobligate anaerobes contained little ornone. In addition SOD was seen to beinduced by aerobic growth, and theinduced level of SOD protected againstthe lethality of hyperbaric O2. Moredefinitive evidence was provided bythe phenotypic deficits of the SOD-null mutants produced by DanielleTouati. In the fullness of time SOD-null mutants were prepared in a vari-ety of prokaryotes, in yeast, and thenin mice.

An I ron-conta in ingSOD

We had seen the blue-green Cu,Zn-SOD from erythrocytes and the red-dish Mn-SOD from E. coli and from

to say that he had the manuscript; thathe had noticed the same autoactiva-tion; that I was somewhat ahead onthis project; and that he was recom-mending publication without revision.Would that everyone was as honestand generous as Frank Westheimer.

On to Superox ideD ismutase

All the foregoing pales to insignifi-cance beside the discovery of SOD.That xanthine oxidase might univa-

lently reduce O2 had been enunciated,and the differences between the reduc-tion of O2 to H2O2 and the roles of O2

-

in mediating cytochrome c reduction,initiating sulfite oxidation, and elicitinglucigenin luminescence had beennoted. However, such were the miscon-ceptions among radiation chemists andphysical chemists concerning the prop-erties of O2

- that it seemed foolhardy topropose free O2

- as a product of thexanthine oxidase reaction. A fallbackposition that could still explain ourmany observations was to proposebound O2

-. In that case cytochrome cwould have to bind to xanthine oxi-dase, as would the protein competitiveinhibitors of cytochrome c reduction.

At this point, Joe McCord joined mylaboratory as a graduate student in1967 and was asked to measure thatpresumed binding. After several heroicefforts provided no evidence for bind-ing he decided to prove that there wasno binding. He asked me whether Kmwas independent of enzyme concen-tration. I responded that it was, so longas substrate concentration exceededenzyme concentration. With thatassurance he produced kinetic datashowing that Km xanthine was, asexpected, independent of the concen-tration of xanthine oxidase. In contrastKm cytochrome c or Ki for theinhibitors of cytochrome c reduction

Irwin Fridovich, seen here at his desk, wasPresident of ASBMB in 1982 when it was stillthe American Society of Biological Chemistry.


reduce cytochrome c or O2. Thisseemed bizarre because CN had beenused with such compounds to synthe-size sugars for over a century. Had noone noticed the oxidation? Perusal ofold literature on the Fischer-Kilianisynthesis, in which aldose sugars wereincubated with CN yielding acyanohydrin that could then behydrolyzed and reduced to the iso-meric pair of longer chain sugars,finally led to a paper whose authorspecified filling the flask to the top andsealing it tightly with a rubber stopperbefore incubating it overnight. Hemust have noticed a decrease in yieldwhen these simple means of excludingoxygen were not used. Subsequentstudy of the mechanism of thiscyanide-catalyzed oxidation of sugarsrevealed a role for enediolate tau-tomers and radical intermediates. Thischemistry is now pertinent to theprocess of non-enzymic glycationthought to be important in diabetesmellitus and in aging.

How Super IsSuperox ide?

Increasing intracellular productionof O2

- by raising pO2 alone, or byadding a redox cycling compounds, orby mutational deletion of SOD,imposes nutritional auxotrophies, suchas the need for branched chain aminoacids. O. R. Brown suggested that thiswas because of inactivation of thedihydroxyacid dehydratase that cat-alyzes the penultimate step in the rele-vant biosynthetic pathway. Thepossibility that O2

- could directly inac-tivate this dehydratase was excitingbecause there were still those who wereasserting that O2

- was a biologicallybenign species. We found that O2

- didinactivate this enzyme and other [4Fe-4S] cluster-containing dehydratases,such as the 6-phosphogluconate dehy-dratase and aconitase.

Motivation and FundingThe work that led to the discovery of

the superoxide dismutases did notseem, at the time, to have any rele-vance to human health or disease. Itwas merely interesting, and we weremotivated purely by curiosity. At thetime, that was enough justificationand one could get funding from theNational Institutes of Health to sup-port such work. Alas that is no longerenough and one has to envisionhealth relevance or not get funded.

In recent years we have been: explor-ing the role of oxidative stress in heatshock and stationary phase death; find-ing a Cu,Zn-SOD in the periplasm of E.coli; clarifying the subcellular distribu-tion of SODs in liver cells; making lowmolecular weight catalysts of the dis-mutation reaction, that may be usefulas pharmaceuticals for treating reperfu-sion injuries and inflammations;exploring the role of oxygen-derivedradicals in adaptive mutagenesis;explaining the nutritional auxotrophiesimposed by lack of SOD activity; study-ing the basis of the oxygen-dependenttoxicity of short chain sugars; adding tothe list of enzymes that are known to becontrolled by the soxRS regulon; andwondering whether the univalent oxi-dation of carbon dioxide to the carbon-ate monoanion radical is a factor inoxidative stress. Curiosity remains undi-minished at age 74 and so there will bemore, if health and strength allow.

The author of this article, Irwin Fridovich,Department of Biochemistry, Duke UniversityMedical Center, received his doctorate fromDuke University in 1955 and was Presidentof ASBMB in 1982 when it was still theAmerican Society of Biological Chemistry. Dr.Fridovich is the author of 440 articles 389 ofwhich can be retrieved on PubMed.

Portions of this article were previ-ously printed in The Journal of Biologi-cal Chemistry.

liver mitochondria. Yet it was clear thatthere was another SOD in E. coli. Thiswas revealed by the activity staindevised by Charles Beauchamp in1972. Fred Yost launched into the iso-lation of this new E. coli SOD. As heapproached the successful isolation ofthis SOD I noticed that the normallyoutgoing Yost was going out of his wayto avoid me. When I asked his goodfriend Mick Gregory about this I wastold that Fred’s SOD had the wrongcolor and he was afraid I would notlike this result. I was delighted withthis new SOD, which proved to con-tain iron. In E. coli the Fe-SOD provedto be constitutive and was present inaerobic or anaerobic cultures. The Mn-SOD, in contrast, was expressed onlyin aerobic cultures and was subse-quently shown to be regulated as partof the soxRS regulon.

An O ld Bott le ofG lycero l

During the summer of 1980 mydaughter Sharon was working in mylaboratory to isolate an SOD fromplant mitochondria. Each morning onthe way to the laboratory we stoppedat a market and purchased a head ofcauliflower. Because Sharon’s goal wasthe mitochondrial Mn-SOD, sheincluded CN- in the assay mixtures tosuppress activity due to the Cu,Zn-SOD. After a while she found that theplant Mn-SOD was unstable and I sug-gested that 10% glycerol might stabi-lize it. Sharon soon reported that CN-

plus glycerol could reduce cytochromec. The only possible explanationseemed to be an impurity in the glyc-erol, which had been on the shelf forover 10 years. Glycerol from a freshbottle did not support the reduction ofcytochrome c so we tried an oxidationproduct of glycerol, glyceraldehyde.CN- plus glyceraldehyde, or a varietyof other µhydroxycarbonyls could


ingly high LDL val-ues. Even among pop-ulations treated witheffective hypolipi-demic agents, such asthe statins, thereremains a very largeresidual of diseaseactivity, a point oftenlost sight of. Clearly,the complexities oflipid and lipoproteinmetabolism, and thediffering responses ofvascular wall cells tothe interplay of lipoproteins and to thevast array of circulating cellular andblood elements, are enormous. To addto the complexity, there is an enor-mous contribution of both environ-mental and genetic factors thatindividually and synergistically affectdifferent aspects of the disease process,effecting both protective andproatherogenic consequences in theface of LDL values above the ideal.

The initial paper in this ThematicSeries provided a detailed review andcomprehensive bibliography of atimely subject, namely, the status ofthe oxidation hypothesis. In futurereviews, JLR will explore the role ofinfection and inflammation, the roleof nuclear hormone receptors, andhow the use of genetic studies can helpsort out the immense complexitiesthat mediate these aspects of atheroge-nesis. Future series will focus on themany other biological factors thataffect atherosclerosis, such as the roleof immune function and the emergingevidence of the enormous contribu-tion of adipose tissue to disturbancesin lipid metabolism and inflammation.

In coming issues, JLR will also presenta fascinating insight into the History

of the CholesterolHypothesis, as seenfrom the perspectiveof Dr. Daniel Stein-berg, one of the lead-ers in the “cholesterolwars,” who hasplayed a pivotal rolein bringing to recog-nition the now widelyaccepted notion thatthe “lower the choles-terol level the better.”The initial installmentin this series will be

found in the September issue.Titles in current series, The Patho-

genesis of Atherosclerosis, coordinatedby Joseph L. Witztum, are:

June – The oxidation hypothesis ofatherogenesis: the role of oxidizedphospholipids and HDL, by Navab etal.

July – Effects of infection and inflam-mation on lipid and lipoprotein metab-olism: mechanisms and consequencesto the host, by Khovidhunkit et al.

September – An interpreted historyof the cholesterol controversy: part 1,by Daniel Steinberg

October – How do we unravel thecomplex genetics involved in athero-genesis? by Aldons J. Lusis

November – The role of nuclear hor-mone receptors in cardiovascular dis-ease, by Christopher Glass

A new thematic series, The ImmuneSystem and Atherogenesis, is sched-uled to begin in December 2004,accompanied by an editorial from itscoordinator, Godfrey Getz. Topics to becovered in this series include:Macrophages and Scavenger Receptors,Acute Phase Proteins, Toll-Like Recep-tors, Natural Antibodies, Unusual Lym-phocyte Subsets, and Cytokines.

he June 2004 issue of TheJournal of Lipid Research inau-gurated a new Thematic

Series, The Pathogenesis of Atheroscle-rosis, which highlights the etiology ofthe disease that results from distur-bances in lipid and lipoprotein metab-olism. Atherosclerosis, with itscomplications of myocardial infarc-tion, stroke and peripheral vasculardisease, is still the major source of mor-bidity and mortality in the industrial-ized world, and has been forecast to bethe major cause of death from diseasein the entire world by the year 2020.

Atherogenesis is a disease that, at itsearliest phase, appears to be presenteven in fetal life, and it evolves slowlyover decades, impacted by a myriad ofenvironmental and genetic factors.Clearly, hypercholesterolemia is a dom-inant risk factor for this disease, andinnumerable clinical trials of varioushypolipidemic agents now documentthe efficacy of cholesterol-loweringtherapy. However, atherosclerosis is acomplex and multifactorial disease,and even if one accepts the “new”dogma that any LDL value above 50mg/ dl is potentially atherogenic, it isnot likely that this target will beachieved in a large percentage ofpatients anytime soon, and, moreimportantly, will not be achieved in thepopulation as a whole.

Furthermore, there still remains anenormous degree of heterogeneity indisease expression among individualswith equivalent LDL values and evenequivalent degrees of other known riskfactors. This is emphasized by the twoto three decade differences, or more, inexpression of CVD that have beenobserved even among subjects withHomozygous Familial Hypercholes-terolemia, who uniformly have exceed-

The Journal of Lipid ResearchInaugurates New Series of Themat ic ReviewsT


First Prize winners who received$100 and a certificate were:Jimmy Hernandez, California State

University, Fullerton.Lee S. Jacobson, Wesleyan University

and University of Regensburg, Ger-many.

Kathryn McCulloch, Ball State Uni-versity, Indiana

Nijee Sharma, Lake Forest College, Illi-nois.

Nicole Wick, Ball State University,Indiana.

The University of Delaware has over80 undergraduate research studentsworking in faculty laboratories thissummer (about half have partial or fullHHMI sponsorship). They were sched-uled to present their work at the uni-versity’s summer UndergraduateResearch Symposium on August 11. Itis from this larger group that studentswill emerge to present at next year’sASBMB undergraduate poster competi-tion in San Diego, April 2-6, 2005.

The undergraduate Poster Compe-tition was sponsored by The Bio-chemical Journal and the GraduatePoster Competition was sponsoredby Cell Press.

n HHMI-sponsored student,Amanda Peters from the Uni-versity of Delaware, was one

of the first place winners at the annualASBMB Undergraduate Poster Compe-tition at the Annual Meeting inBoston. This is the fourth year in a rowthat undergraduate students from theUniversity of Delaware have receivedASBMB first place poster awards in thiscompetition and cumulatively theyhave received more such awards thanstudents from any other school duringthis period. Funding from HHMI hasmade it possible for these students toattend the ASBMB meetings and hassupported the research of most of thestudents. In addition to her success inthe poster competition and based onher submitted abstract, Peters wasselected to present her work in a sym-posium on cholesterol homeostasis.

Grand Prize Winner in the competi-tion was Francesca Mendoza, Califor-nia State University, Fullerton, whoreceived a $500 prize and a certificate.

A

Four in a Row for Delaware AtUndergraduate Poster Compet it ion

Grand Prize Winner Francesca Mendoza of Cal-ifornia State University, Fullerton, and mentor.

Competitors from the University of Georgia formed one of the largest group of entrants at the event.

Phot

os c

ourt

esy

of J.

Elli

s Be

ll


insulin sensitivity, on adipose cells infa/fa obese Zucker rats (a commonly-used genetic model for obesity).

As expected, obese mice that weregiven oral rosiglitazone showedimprovements in whole body glucosedisposal and insulin sensitivity. Theseobese mice also experienced increasesin the fraction of small adipose cells,adipose cell proliferation, and apopto-sis. The gene expression pattern of var-ious adipose cell-derived proteins thatplay a role in insulin sensitivity wasalso altered in the treated mice. “In anutshell,” said Dr. Hunt, “adipose cellsplay a critical role in regulating wholebody insulin sensitivity.”

Turning the focus from biology tonutrition, Dr. Betty Kennedy of thePennington Biomedical Research Cen-ter described the “Rolling Store” project—a unique approach to providingaccess to healthy foods for poorwomen in the Lower Mississippi Delta.This six month pilot project was cre-ated to examine the impact of theavailability of better food choices onpreventing weight gain in the residentsof a region that has one of the nation'shighest rates of households withincomes below the federal poverty line.

Forty low-income, African Americanwomen participated in the study andwere given weekly information onhealthy eating and exercise. Half thewomen were also allowed to shop, costfree, at the Rolling Store – a food deliv-ery truck stocked with healthy foodchoices such as fruits and vegetables.Dr. Kennedy found that the womenwho only received information contin-ued to gain weight, while thosewomen who received information andhad access to healthy foods once a

week not only lost weight but alsoexperienced improved self-esteem. Dr.Kennedy believes these findings indi-cate that the Rolling Store approach isa realistic and inexpensive means toovercoming both economic and geo-graphic barriers to healthy diets inpoor, rural communities.

In addition to biology and nutrition,culture and environment can contributeto the problem of obesity, especially inminority populations. Dr. Kristie J. Lan-caster of New York University addressedthis issue in her discussion of why Blackand Latino Americans have a higherprevalence of obesity and obesity-relateddisease than White Americans.

Dr. Lancaster found that culturalinfluences play a large role in dictatingbody image and eating habits in Blackand Latino populations. For example,both cultures tend to be more accept-ing of larger body size and both viewfood as a huge component of culturalidentity. Unfortunately, traditionalAfrican American dishes tend to behigh in sodium, sugar, and fat, but lowin fruits and vegetables.

Environmental influences such aslower socioeconomic status and a lackof healthy food choices also affectweight negatively in Black and Latinopopulations. Dr. Lancaster indicatedthat we need to understand the cul-ture, traditions, and environment ofminority populations in order to betteraffect change in eating habits.

The last scheduled speaker, New YorkState Assemblyman Felix W. Ortiz, norelation to Dr. Ortiz, was unable toattend the session due to a family emer-gency, but his slides were presented forthe audience in his absence. Assembly-

he 2004 Annual Meetingmarked the first scientificsymposium for the ASBMB

Minority Affairs Committee (MAC).Breaking from the tradition of holdingissues-based symposia, MAC ChairPhillip A. Ortiz of Empire State Collegeand member Thomas D. Landefeld ofCalifornia State University, DominguezHills, organized a series of talks toexplore the problem of obesity fromfour different perspectives, resulting ina hybrid issues-scientific symposium.

This change in focus was motivatedby a variety of factors. “Over the pastfew years we had delivered a bunch ofexcellent issues sessions, had masteredthe issues symposium, and felt that wehad an obligation to address issues ofheath disparities,” said Dr. Ortiz.

Dr. Ortiz opened the symposium bysharing some alarming facts on obesitytrends. Currently, 65% of Americanadults are either overweight or obese,and the obesity epidemic is the numberone health threat in the United States.According to the Centers for DiseaseControl, approximately 300,000 peopledie each year from obesity-related dis-eases including cardiovascular disease,diabetes, and cancer. For a variety ofreasons explored in the symposium,women, children, and minorities areparticularly affected by obesity.

In most people, obesity is associatedwith insulin resistance. The firstspeaker, Dr. Desmond Hunt, a postdoc-toral fellow in the laboratory of Dr.Samuel Cushman at the National Insti-tutes of Health, discussed his work ondeciphering the link between insulinresistance and adipose cells. Dr. Huntlooked at the effects of rosiglitazone,an anti-diabetic drug that improves

T

MAC Symposium Addresses the Problemof Obesity from Different Perspect ives

By N ico le Kresge , S taf f Wr i ter

Continued on next page


Undergraduate Aff i l iate NetworkLaunches Newsle tter

This past June, ASBMB’s Under-graduate Affiliate Network (UAN)launched the first issue of its nationalnewsletter, Enzymatic. The newsletter,whose motto is “Success comes fromhaving a community,” is edited byDr. Ellis Bell, Professor of Chemistryat the University of Richmond andco-chair of the ASBMB Education andProfessional Development Commit-tee (EPD).

Dr. Bell said Enzymatic was createdbecause, “there is a community ineducation in biochemistry andmolecular biology all across the coun-try in small schools where often onlyone or maybe two faculty are in thesame general area of biochemistryand molecular biology. There are alsostudents out there in a similar posi-tion—only a few of them interestedin biochemistry and molecular biol-ogy. The newsletter is a way to keepthem informed of what is going on,to help them feel as though they arepart of a larger community.”

Enzymatic will be published sixtimes a year and will contain features

on UAN participants and highlightsfrom regional and national meetings.The newsletter will also focus on out-reach activities, teaching and learninginnovations, and how to assess whatstudents learn. Dr. Bell hopes thatEnzymatic will eventually become aforum for discussions about what stu-dents really need to know and howbest to assess that.

The UAN was formed last year bythe EPD to create a community forundergraduates interested in bio-chemistry and molecular biology. “Inmany ways the UAN goals have reallydefined what Enzymatic is aiming toachieve—we are trying to connect stu-dents and faculty. A famous politicianonce said ‘it takes a village’ to raise achild. In this day and age ‘it takes anational and international commu-nity’ to raise a science student! Enzy-matic and the UAN are aiming tobuild that community,” said Dr. Bell.

Enzymatic is available on theASBMB website, www.asbmb.org,under the “Education” heading onour homepage.

man Ortiz’ presentation detailed hisefforts to address the problem of obesityat school, at home, and in the commu-nity via legislation. The majority ofthese bills focus on children, as theAssemblyman believes that it is moreeffective to prevent obesity rather thantreat it later on in life. Some of the obe-sity-related legislation AssemblymanOrtiz has sponsored includes creating aChildhood Obesity Prevention Pro-gram, requiring fast food chains to dis-play nutrition information, prohibitingthe sale of un-nutritious foods in schoolvending machines, and imposing a “FatTax” on video games, movies, and cer-tain unhealthy foods.

Overall, Dr. Ortiz felt the symposiumwas a great success. “I expect that thiswill be the first of a series of symposiain which the MAC extends its impacton the ASBMB,” said Dr. Ortiz. “Wehave been in a tremendous period ofgrowth and transition – over the pastfew years the MAC has split away fromthe Education and Professional Devel-opment Committee, has gained a seatat the executive council table, is begin-ning to bring attention to the issuesfacing people of diverse backgrounds,and is working to draw in (and engage)scientists from diverse backgrounds. Ibelieve that if one examines all thesefactors, as a whole, it becomes apparentthat the MAC is on the verge of enter-ing another era of significant growth.”

Because of the success of their firstscientific symposium, the MAC plans,for the first time in its history, on hav-ing two symposia next year – oneissues-based symposium on mentoringand one scientific symposium onglobal nutrition. The symposium onglobal nutrition will be co-organizedby Dr. Lancaster and Dr. Ortiz.

2ND Int. Conference on Phospholipases A2 and 8TH Int. Congresson Platelet-Activating Factor and Related Lipid Mediators

October 6-9, Berlin , Germany

Contact: Dr. Santosh Nigam, Eicosanoid & Lipid Res. Div., Univ. Medical

Centre Benjamin Franklin, D-12200 Berlin, GermanyPh: +49-30-8445 2467; Fx: +49-30-8445 2467

Email: [email protected]: http//:userpage.fu-berlin.de/~nigam

http://www.fu-berlin.de/info/konferenzen

Obesity … Cont inuedontinued from page 21


(Zoloft) and fluoxetine (Prozac). Theinfluence of the serotonin enzymeraises the possibility that a genetic testto distinguish which version of the genea patient has could predict the patient’sresponse to the drugs, Dr. Caron said.

The brain is a network of billions ofneurons. When stimulated, neuronsfire, sending a wave of electrical chargefrom one end to the other. To bridge thegap between nerves, the neurons releasechemical neurotransmitters, SUCH ASserotonin, that set off an impulse inreceiving neurons. Once the originalcell has passed its message on, it sops upthe chemical it released to damp thatsignal and prepare for the next.

If serotonin levels are decreased, asmay occur in patients with depressionand other psychiatric disorders, com-munication among neurons stalls. SSRIscounteract the breakdown by slowingthe re-uptake of serotonin, allowing thebody to make the best use of abnor-mally low levels of the chemical mes-senger, the researchers explained.

Scientists had long considered theenzyme known as tryptophan hydrox-ylase (Tph1) to be the sole enzymegoverning serotonin synthesis in thenervous system, Dr. Caron said. Lastyear, however, researchers at anotherinstitution found that a secondenzyme, tryptophan hydroxylase-2(Tph2), is present in the brain, whilethe earlier discovered Tph1 is foundprimarily in peripheral nerves.

The Duke team screened the brainsof several mouse strains for the Tph2gene. To their surprise, said Dr.Xiaodong Zhang, lead author of thestudy, they found not one version ofthe gene, but two.

The two gene variants differed in asingle DNA unit, called a nucleotide.

That difference altered the gene so thatit produced a variant of the enzymewith a different amino acid unit andraised the possibility that the changemight alter the protein function andproduction of serotonin, he added.

Studying the effects of the enzymevariants in cultured cells, theresearchers found that they had amajor effect on the amount of sero-tonin the cells produced, the teamfound. That difference was also evidentin the mice, the researchers reported. Amouse strain with one variant pro-duced 50 to 70 percent less serotoninin their brains than did mice with theother variant.

“This single genetic difference has ahuge impact on serotonin levels, con-firming that the gene is fundamentalin the synthesis of brain serotonin,”reported Dr. Zhang.

The findings will have an immediatepractical impact, the researcher added,“Mouse strains that are the subject ofmuch biomedical research have beenknown to have behavioral differencesrelated to serotonin levels. Now we’veidentified a major gene responsible.”

Exploiting these findings might pro-vide a useful approach to developinganimal models of serotonin-related dis-orders, added Dr. Martin Beaulieu, aco-author on the study.

The team plans to look for similargenetic differences and their influenceon brain chemistry in humans withpsychiatric disorders. In contrast to theinbred mouse strains, Caron suspectsthat humans likely bear many versionsof the serotonin gene.

Collaborators on the researchinclude Tatyana Sotnikova, Ph.D., andRaul Gainetdinov, M.D.

* ASBMB member.

esearchers at Duke UniversityMedical Center have pro-vided the first direct evidence

in mice for the role of an enzyme thatspecifically controls the production ofserotonin in the brain. Different ver-sions of that serotonin enzyme have amajor effect on brain levels of thechemical messenger, which has beenlinked to many basic behavioral andphysiological functions includingmood, emotion, sleep and appetite,the researchers reported in the July 9,2004, issue of Science. The finding hasmajor implications for understandingpsychiatric disorders and their treat-ment, the researchers said.

Serotonin is a neurotransmitter, achemical that one neuron uses to trig-ger a nerve impulse in its neighbors.Serotonin levels can profoundly affectbrain function, and therefore behavior.

“For the first time, we’ve identified anaturally occurring genetic differencethat controls the production of sero-tonin in the brain,” said HowardHughes Medical Institute investigatorMarc Caron,* James B. Duke Professorof Cell Biology at Duke and seniorauthor of the study.

The finding in mice sets the stage fornew insights into the role the sero-tonin-producing enzyme and the genethat encodes it might play in animalbehavior and human psychiatric disor-ders, said the researchers. Low levels ofserotonin have been implicated inmany disorders such as depression, anx-iety, post-traumatic stress disorder andattention deficit hyperactivity disorder.

The enzyme might also influencepatients’ responses to the class of drugsknown as selective serotonin re-uptakeinhibitors or SSRIs, they added. SSRIsinclude paroxetine (Paxil), sertraline

Brain Serotonin Enzyme FindingMight Explain Psychiatric DisordersR

B I O T E C H B U S I N E S S N E W S


America’s Biotech and Life Science Clusters Who’s the Leader?

Spurned across the continent byfood-fastidious Europeans, thebiotechnology industry has turnedin its quest for converts to the ulti-mate ice breaker—genetically modi-fied beer. A consortium of theworld’s largest biotech companiesled by Monsanto Co. helped fund aSwedish brewer’s new light lagerthat’s produced with the usual hopsand barley—and touch of geneti-cally engineered corn. Brew masterKenth Persson hopes to profit from

the notoriety his biotech brew isgenerating, while biotech companieshope it can gently sway consumersas European regulators slowlyreopen the continent to geneticallyaltered foods.

The brewer won’t say how manybottles have been sold since the beerwas unveiled earlier this year in Den-mark and Sweden. However, in July hetold the Associated Press in that 4,000bottles were on their way to stores andpubs in Germany, and was in talks

with stores in the United Kingdom. Mattias Zetterstrand, a Monsanto

spokesman based in Stockholm,wouldn’t say how much the biotechconsortium contributed to the proj-ect, but said the companies have notpurchased equity in the smallSwedish brewer and won’t share insales of the beer. In addition to Mon-santo, the companies involved in theproject are Bayer CropScience,DuPont, Plant Science Sweden, Sval-oef Weibull and Syngenta.

Biotech Brew Hits European Marke t

by John D . Thompson , Ed i tor

advantage in a knowledge-based econ-omy, clustering innovative activity isimperative.”

According to the study’s BiotechIndex, the top 12 metros (and theircomposite scores) are:1. San Diego (100) 2. Boston (95.1)3. Raleigh-Durham-Chapel Hill (92.5)4. San Jose (87.8)5. Seattle-Bellevue-Everett (83.8)6. Washington, DC (79.4)7. Philadelphia (76.5)8. San Francisco (75.8)9. Oakland (74.3)10. Los Angeles-Long Beach (66.5)11. Orange County, CA (54.1)12. Austin-San Marcos (47.8)

The rankings are based on two fac-tors: An infrastructure that allows ametro area to capitalize on its biotechknowledge and creativity, such as thequality of its workforce and amount ofresearch and development dollars itreceives; and the area’s success in bring-ing ideas to the marketplace and creat-ing companies, jobs, and products.

The study, prepared in cooperationwith Deloitte & Touche LLP, focuses onthe index’s top metro, San Diego. Thatcenter’s life sciences industry is directlyand indirectly responsible for 55,600jobs and $5.8 billion in income – 5.3percent of the metro area’s output.

The study measures each metro’sstrength in five categories: R&Dinputs, risk capital, human capital,biotech workforce, and currentimpact. San Diego placed first in R&Dinputs and current impact. San Josewas first in the risk capital category,while Raleigh-Durham-Chapel Hillwas first in the human capital andbiotech workforce categories.

If life sciences (which includes phar-maceuticals and medical devices) areincluded in the measurements, Bostonwould rank number one, followed by:San Diego (2), San Jose (3), Raleigh-Durham-Chapel Hill (4), Philadelphia(5), Seattle-Bellevue-Everett (6), San Fran-cisco (7), Washington, D.C. (8), Oakland(9), Los Angeles (10), Orange County(11) and Austin-San Marcos (12).

June 2004 Milken InstituteReport, “San Diego’s Positionand Economic Contributions,”

found San Diego to be the leader in therace among the nation’s science-ori-ented regions to latch on to what theysee as the growth industry of thetwenty-first century—biotechnology.

Regional centers from all across theU.S. are fighting hard in this race to gen-erate high-paying jobs and local prosper-ity. However, according to the report’sauthors, Ross DeVol, Perry Wong, Jung-hoon Ki, Armen Bedroussian and RobKoepp, only a handful of metropolitanareas have succeeded on a scale neces-sary to ensure industry sustainability. Atthe top of that list is San Diego, followedclosely by Boston and the Raleigh-Durham-Chapel Hill metro area.Another nine are also in the running.

“Clusters of existing and emergingscience-based technologies are crucialfactors in shaping the economic win-ners and losers of the first half of the21st century,” the authors state. “Tocreate international comparative

A


That way, someone prone to gettingheart disease in his 60s could start tak-ing preventive pills in his 40s. Dr.Hood described this kind of early diag-nosis and intervention as one of theupcoming “enormous revolutions”and opined that blood was poised tobecome a “window on disease.” How-ever, he warned, that this kind of biol-ogy represents a new way of thinking,one that current administrative struc-tures aren’t set up to handle.

Thomas J. Perkins, founding chair-man of Genentech and co-founder ofKleiner Perkins Caulfield & Byers,agreed, adding that generally his ven-ture capital firm builds companiesaround a technology. That way, he said,the company grows around the needsof the technology, and the best-fittingmanagement can be brought in later.

Dr. Hood calledon the federalresearch programs tofocus on integratingresearch instead ofsimply funding indi-vidual researchers’projects. “There arethe study sectionsthat still view science the way we did ityesterday, so the proposals are evaluatedin a way that reflects the past, ratherthan a way that predicts the future.”

Perhaps the biggest challenge for phar-maceutical companies, claimed Dr. Hood,is that personalized diagnostics will shrinkthe markets for individual drugs. To con-tinue to develop new therapies for suchniche markets would require bringingdevelopment costs down.

*ASBMB member

ccording to BiotechnologyHeritage Award winner LeroyHood,* within 10 years nan-

otools will allow an individual’sgenome to be sequenced in less thanhalf an hour at a cost of under $1,000.Hood, President and Cofounder of theInstitute for Systems Biology in Seattle,a non-profit research institute estab-lished to pioneer systems approachesto biology and medicine, made his pre-diction during the Industry Pioneersplenary session at BIO 2004, theannual meeting of the BiotechnologyIndustry Organization (BIO) in June.

The Chemical Heritage Foundation(CHF) and BIO presented the 6th AnnualBiotechnology Heritage Award to Hood,one of the world’s leading scientists inmolecular biotechnology and genomicsand one of the first advocates of theHuman Genome Project, in June at BIO’sannual meeting in San Francisco.

“Award-winning researcher, giftedentrepreneur, and brilliant innovator,Leroy Hood pioneered the techniquesthat made the rapid pace of the HumanGenome Project possible,” said ArnoldThackray, president of CHF. “Withouthis contribution, the sequencing of thehuman genome could have taken yearsor even decades longer.”

Speaking in a panel discussion at theplenary session, Dr. Hood said he envi-sions the creation of handheld devicesthat perform many of the functions ofthe standard annual check-up with aphysician, only with higher sensitivity.These devices will prick a person’sthumb and subject a drop of blood to“dozens of measurements,” whichwould be taken at regular intervals andtransmitted to a physician electronically.

Looking Ahead at B IO 2004

LigoCyte Pharmaceuticals, Inc.has executed an exclusive optionfrom Baylor College of Medicine fora license to technologies related tonorovirus vaccines and therapeutics.

“We are very excited to work withBaylor on the development of anti-norovirus strategies,” said Dr. RobertGoodwin, LigoCyte’s Chief Operat-ing Officer. “Scientists at Baylor havebeen in the forefront of this field forover a decade.”

With support from the Departmentof Defense, LigoCyte is developingproducts to combat norovirus infec-

tions. Researchers at Baylor College ofMedicine, led by Dr. Mary K. Estes,successfully cloned the Norwalk virusgenome in 1990 and have madeconsiderable progress, culminatingin a Phase I clinical study of an oralNorwalk vaccine. “It is wonderful tobe able to join forces with Baylorand combine our programs in thenorovirus field,” commentedCharles Richardson, Ph.D., Ligo-Cyte’s Vice President of Research &Development. “This relationshipwill allow us to quickly move newproduct candidates into the clinic.”

LigoCyte Pharmaceut icals Signs AgreementWith Baylor College of Medicine

A

B I O T E C H B U S I N E S S N E W S

Dr. Leroy Hood


died. In April 2004, a small outbreak inChina is suspected to have begun as aresult of negligent laboratory practices.

In the current study, Dr. ElisabettaTraggiai, and Dr. Antonio Lanzavec-chia, from the Institute for Research inBiomedicine, Bellinzona, Switzerland,together with an international researchteam, generated human antibodiesagainst SARS more quickly and effi-ciently than with current methods.Collaborators Dr. Kanta Subbarao andDr. Brian Murphy, both in NIAID’s Lab-oratory of Infectious Diseases, demon-strated for the first time that humanSARS antibodies, when injected intomice, effectively prevent the virus frommultiplying in the respiratory system.

“The antibodies from people whohave recovered from SARS may targetdifferent parts of the virus than anti-bodies generated by other animals,such as mice,” explained Dr. Subbarao.“For this reason, antibodies from recov-ered patients that may have a proveneffectiveness in fighting the disease areconsidered most desirable for a possibleserotherapy against SARS.”

Antibodies are made by specialimmune system cells called B cells that,to do their job, must first be switchedon. In nature, this occurs when the bodyencounters a new or repeat foreign“invader.” In the laboratory, researchersconventionally accomplish this byexposing the B cells to Epstein Barr virus(EBV), a herpes virus that infects B cells,which in turn activates them. Unfortu-nately, this process is very inefficient,and only one or two B cells out of onehundred are activated this way.

Dr. Lanzavecchia and his team added anew ingredient to the mix that signifi-cantly boosts efficiency. Beginning withB cells from a recovered SARS patient, theresearchers added a short stretch of syn-thetic DNA that mimics DNA found inbacteria and viruses. From 30 to 100 per-cent of the B cells—in this case called“memory” B cells because they had beenexposed to the SARS virus before—wereswitched back on, enabling them tochurn out SARS antibodies at a fast pace.In only a few weeks, the researchersscreened hundreds of antibodies andobtained 35 that could neutralize theSARS virus in the laboratory. All the neu-tralizing antibodies targeted a key SARSprotein, the spike protein, found on thevirus surface.

Furthermore, when Dr. Subbaraoand Dr. Murphy injected one of theneutralizing antibodies into mice, theyfound that these antibodies effectivelythwarted the SARS virus from multi-plying in the lower respiratory tract,which includes the lungs, and, to alesser extent, in the upper respiratorytract, which includes the nasal cavity.According to Dr. Subbarao, theseresults are very promising becausereplication of SARS in the lungs ofhumans can result in pneumonia.

A primary benefit of the new activa-tion technique is that it generates a largepool of prospective antibodies fromwhich to choose, so only the most effec-tive SARS fighters can be chosen for usein a possible immune serum. Becauseviruses can mutate, however, more thanone antibody will most likely be needed

N I H N E W S

uman antibodies that thwartthe SARS virus in mice can bemass-produced quickly using a

new laboratory technique developed byan international research team collabo-rating with the National Institute ofAllergy and Infectious Diseases (NIAID).The new technique could become animportant tool for developing a cocktailof SARS-specific antibodies that mighthelp protect people recently exposed tothe SARS virus or at high risk of expo-sure. The technique could also makepossible the development of a similarapproach to prevent or treat other ill-nesses, such as HIV/AIDS and hepatitis C.

The report describing these findingsappeared in the July 11, 2004, onlineissue of Nature Medicine.

“While much has been accomplishedin our quest for a vaccine against SARS,a vaccine may provide little benefit tosomeone already infected,” saysAnthony S. Fauci, Director of NIAID.“Human SARS antibodies could offer adouble benefit: they could be used as apotent frontline defense for health careworkers and others at high risk of expo-sure and as an effective treatment forthose individuals newly exposed to thevirus.” Currently, there is no specificeffective treatment for SARS.

SARS is caused by a coronavirus, afamily of viruses named for their spiky,crown-like appearance. Highly conta-gious, SARS typically begins with flu-likesymptoms, such as fever, headache andmuscle aches, and generally progressesto pneumonia. In the 2003 global out-break, more than 8,000 people wereinfected with SARS, 9 percent of whom

H

New Method Enables Researchers toMake Human SARS Ant ibodies Quickly

Continued on next page

New Members of AS BM B Council


ing to be held in Granlibakken this fall,and the meeting on redox signaling tobe held at Kiawah. I’d very much like tosee the small meetings program con-tinue and grow.

I’ve also been very impressed withthe development of the nationalmeeting. I think the recent changes inmeeting format (i.e. having up to 10concurrent themes or small “meetingswithin the meeting” that togethercover a significant number of areas ofinterest) pioneered by Claudia Kentand Vern Schramm when they organ-ized the national meeting two yearsago have really energized the meeting.I hope in future years we can findways to enhance the meeting evenmore, perhaps by increasing theopportunities for informal interactionsamong attendees.

Dr. Copeland: Biochemistry hasalways been a discipline that bridgesthe chemical and biological sciences,and working at the interface betweendisciplines has been a constant featureof my career in science. Working as abiochemist in the pharmaceuticalindustry requires me to speak the com-mon language of chemistry and tointerpret this in the context of cellularand organismal biology, and humanmedicine. Actively maintaining anadjunct appointment at the Universityof Pennsylvania School of Medicinehas allowed me toalso be at the inter-face of academicand industrial sci-ence. This hasafforded me manyopportunities tointeract with adiverse group of sci-

entists including students, postdoc-toral fellows and faculty, in addition tomy industrial colleagues. I believethese experiences provide me with aunique perspective on the status, con-cerns and needs of the biochemistryand molecular biology community atlarge. I am excited to bring this uniqueperspective to my work on the ASBMBgovernance council.

Dr. Sly is an internationally knownphysician and scientist with fourdecades of experi-ence in medicaleducation, biomed-ical research, andadministration. Hiscareer was evenlysplit between Wash-ington University,where he began hisacademic career, and Saint Louis Univer-sity, where he has spent the last 20 yearsas Chair of the Department of Biochem-istry and Molecular Biology. In this posi-tion, he directs a vigorous faculty, whichis active in research and medical educa-tion, and in graduate teaching through adepartmental and interdepartmentalgraduate program.

He has served 10 years on differentNIH study sections and six years onscientific advisory panels for HHMI.He has been funded by the NIHthroughout his academic career andcurrently directs two active researchprograms, both supported by R01grants. He was elected to the NationalAcademy of Sciences in 1989. Hisinterests outside science include pro-moting justice and human rights,advocacy for the poor, and promotingunderstanding and tolerance in ourincreasingly polarized society.

hree new members named tothe ASBMB Council at theJune meeting are Joan

Conaway, Investigator, Stowers Insti-tute of Medical Research; Robert A.Copeland, Director, Enzymol andMechanistic Pharmacol Department,GlaxoSmithKline; and William S. Sly,Professor and Chair, Biochemistry &Molecular Biology Departments, St.Louis University School of Medicine.

ASBMB Today asked them to sharetheir thoughts about the Society andwhat they will bring to the Council.Following are there comments.

Dr. Conaway: I believe two of themost important things ASBMB does for

its membership areto publish excellentjournals and tosponsor scientificmeetings. As a meet-ing attendee, I’ve ingeneral had a prefer-ence for smallermeetings because of

the increased opportunities for personalinteractions with other scientists at themeeting. As a member of ASBMB’s meet-ings committee, I’ve been a strong sup-porter of the idea that ASBMB shouldsponsor small, focused meetings such asthe transcription and chromatin meet-

T

Dr. Robert Copeland

Dr. Joan Conaway

Dr. William Sly

to achieve the optimal protection ortreatment, the researchers contend.

The researchers’ next goal is to findadditional antibodies against the SARSvirus, focusing on those that attachmost readily to the virus, are mostpotent against the virus, and canattach to more than one site on thespike protein.

Continued from previous page

C a l e n d a r o f S c i e n t i f i c M e e t i n g s


O C T O B E R 2 0 0 4

Brain Uptake and Utilizaton of Fatty Acids

Sponsored by the Kennedy Krieger Institute and Departmentof Neurology, Johns Hopkins University School of MedicineOctober 7–9 • Holiday Inn Select, Bethesda, MarylandOrganizers: Paul Watkins, Kennedy Krieger Institute; JamesHamilton, Boston University; Cecilia Hillard, Medical Collegeof Wisconsin; and Arthur Spector, University of IowaEmail: [email protected]

Cytokines in Cancer and Immunity:Joint Conference of ICS and ISICR

October 21–25 • San Juan, Puerto RicoAn exceptional meeting bringing together leading investiga-tors in cytokine biology, cancer and immunology. Keynote speakers: Michael Karin and Tak Mak.Abstract deadline: June 11, 2004Email: [email protected]; Fax: 706 228-4685 Website: www.cytokines2004.org

An ASBMB Sponsored Symposium:Redox Signaling in Biology and Disease

October 21–24 • Kiawah Island, South CarolinaOrganized by Larry Marnett, Vanderbilt U. and Roy J.Soberman, Harvard Med. SchoolPlenary Lecture: Regulation of Mammalian Clock GenesSteven L. McKnight, U. of Texas, Southwestern Medical CenterContact: Joan Geiling, Ph: 301-634-7145; Fax: 301-634-7126Email: [email protected]; Website: www.asbmb.org

An ASBMB Sponsored Symposium: Transcriptional Regulation by Chromatin and RNAPolymerase II

October 29–November 1 • Granlibakken, Lake Tahoe,CaliforniaOrganized by Ali Shilatifard, St. Louis U. School of Med.Keynote Speakers: Joan Conaway and Ronald ConawayContact: Joan Geiling, Ph: 301-634-7145; Fax: 301-634-7126Email: [email protected]; Website: www.asbmb.org

N O V E M B E R 2 0 0 4

4th International Congress on Autoimmunity

November 3–7 • Budapest, HungaryDeadline for Receipt of Abstracts: June 20, 2004 Contact: 4th International Congress on Autoimmunity KenesInternational—Global Congress Organisers and AssociationManagement Services,17 Rue du Cendrier, PO Box 1726,CH-1211 Geneva 1, SWITZERLAND Ph: +41 22 908 0488; Fx: +41 22 732 2850 Email: [email protected]: www.kenes.com/autoim2004

A U G U S T 2 0 0 4

8th International Symposium on the Maillard Reaction

August 28–September 1 • Charleston, South CarolinaFor detailed information about the meeting, including abstractsubmission, a call for papers and deadlines.Website: http://Maillard.chem.sc.eduEmail: [email protected]

International Congress on Biocatalysis 2004

August 29–September 1 • University of Technology,Hamburg, GermanyContact: Gerlinde Loebkens; FON +49-40-76618012FAX +49-40-76618018; e-mail: [email protected]: www.biocat2004.de

5th Meeting on Methods in Protein Structure Analysis

August 29-September 2 • University of Washington, SeattlePh: 206-706-8118; Email: [email protected]: http://depts.washington.edu/biowww/mpsa2004/

S E P T E M B E R 2 0 0 4

Relaxin 2004: Fourth International Conference onRelaxin and Related Peptides

September 5–10 • Grand Teton National Park, Jackson Hole, WYThis conference will present recent advances on the chemistry,physiology, and pharmacology of relaxin, related peptides, andtheir receptors.Email: [email protected]: http://www.life.uiuc.edu/relaxin2004/

Stem Cell Biology: Development and Plasticity

September 16–19 • Scheman Continuing Education BuildingIowa State University, Ames, Iowa.Abstracts due July 16, 2004; Registration deadline: August 16, 2004 Student Travel Grant Applications due July 16, 2004 Contact: Growth Factor and Signal Transduction ConferencesSymposium OfficePh: 515-294-7978; Fx: 515-294-2244; Email: [email protected]: http://www.bb.iastate.edu/-gfstlhomepg.htmi

Cellular and Molecular Basis of RegenerationEuroConference on the Molecular Pathways Leading toRegeneration

September 18–23 • San Feliu de Guixols, SpainContact: European Science Foundation, EURESCO OfficePh: +33(0)3 88 76 71 35; Fx: +33 (0)3 88 36 69 87Email: [email protected]; Website: http://www.esf.org/euresco

American Association of Pharmaceutical Scientists AAPS Annual Meeting and Exposition

November 7–11 • Baltimore, MarylandPh: 703 243 2800; Fx: 703 243 9650Website: www.aapspharmaceutica.com/meetings/futuremeetings/

First Latin-American Protein Society Meeting

November 8–12 • Hotel do Frade, Rio de Janeiro, BrazilSponsored by The Protein Society, The Wellcome Trust, andBrazilian research funding agencies.For more information: Dr. Alberto SpisniBrazilian Synchrotron Light Laboratory, Campinas, Brazil,and Dept. Experimental Medicine, University of Parma, ItalyCaixa Postal 6192 - CEP 13084-971, Campinas, SP, BrazilPh: +55 19 3287-4520; Fx: +55 19 3287-4632 Email: [email protected]; Website: www.lnls.br/lapsm

Second National Meeting of the American Society forMatrix Biology

Nov 10–13 • San Diego, CaliforniaContact: ASMB, 2019 Galisteo Street, Building I-1, Santa Fe,NM 87505; Ph: 505 989-4735; email: [email protected]: http://www.asmb.net

D E C E M B E R 2 0 0 4

American Society for Cell Biology, 44th Annual Meeting

December 4-8 • Washington, DCPh: 301-347-9300; Fx: 301-347-9310Website: http://www.ascb.org/

A P R I L 2 0 0 5

American Society for Biochemistry and MolecularBiology Annual Meeting in Conjunction with EB2005

April 2 – 6 • San DiegoContact: Experimental Biology 2005, 9650 Rockville PikeBethesda, MD 20814-3008; Ph: 301-634-7010Fax: 301-634-7014; www.faseb.org/meeting

J U LY 2 0 0 5

30th FEBS Congress — 9th IUBMB Conference, 2005 The Protein World; Proteins and Peptides: Structure, Function and Organization; Science is Fun: A Conference for Your Creativity

July 2–5 • Budapest, HungaryContact: Ms. Franciska Morlin, Chemol Travel Congress Dept.H-1366 Budapest, P.O.Box 28, HungaryPh:+36-1-266-7032, Fx: +36-1-266-7033Email: [email protected]; www.febs-iubmb-2005.com

Department Heads Take Note:

AS BM B Offers Free Membership to

New Ph.D.s ASBMB is now offering a free one-year

Associate membership to all students whohave, within the past year, earned a Ph.D.

degree in the molecular life sciences or related areas.

ASBMB implemented this program as away to recognize the significant

accomplishment of earning the Ph.D., and toprovide new Ph.D.s with something tangible

and of economic value. Membership inASBMB brings with it a free subscription to

the online versions of the Journal of BiologicalChemistry and Molecular and Cellular

Proteomics, as well as subscriptions to TheScientist and the Society’s magazine, ASBMBToday, discounts on other publications, and a

host of other benefits.

The Society is asking department chairs to provide ASBMB with the names and

addresses of each new Ph.D. recipient fromtheir institutions. Upon receipt of this

information, we will write the new Ph.D.s tocongratulate them on their accomplishmentand offer the free one-year membership inASBMB. Names and addresses of the new

Ph.D.s should be sent to:

Membership at ASBMBAmerican Society for Biochemistry

& Molecular Biology9650 Rockville PikeBethesda, MD 20814Email: [email protected]

This is an ongoing project; please advise uswhenever a student in your department earns thePh.D., so that we can make this free membershipoffer to him or her.

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