11 APRIL 2003 VOL 300 SCIENCE www.sciencemag.org282academic ability, and to home in on that,”says Fuller. “There’s a history of peoplewith no qualifications who are now senior.” Past as prologue At the end of April, hundreds of former LMBresearchers will converge on Cambridge tocelebrate the 50th anniversary of Watson andCrick’s DNA paper. They include numerousNobel laureates whose prizewinning researchcame after their time at LMB, as well asprominent department heads, institute direc-tors, and journal editors. There is no doubt intheir minds that LMB is unique. “I don’tthink if you had put the same people in a U.S.institution that they would have done aswell,” says Rubin.But can it continue to be so special?Thirty years ago, “the field was muchsmaller. It was the place for U.S. postdocs togo, and the best went,” Rubin explains.“Now there are many good places.” Al-though funds still flow relatively freely, pa-perwork, regulations, and other constraintshave crept in, Henderson notes. And whilehe and his colleagues pride themselves ontheir small labs, which range in size from 1to 10 people, they worry that they will fallbehind. “There’s so much more you can dowith more manpower,” says Pelham.To keep pace with the burgeoning sci-entists and staff—about 400, more thantwice the number 30 years ago—the build-ing has doubled in size every decade since1962. A new building is in the works. SaysKlug, “I am worried that we will get toobig and lose the ethos on which the lab hasbeen built.”LMB now relies on a glossy annual re-port rather than word of mouth to publi-cize its accomplishments. Commercialconsiderations are al-so gaining promi-nence. For instance,25 years ago MRCdidn’t bother to patentMilstein’s techniquefor making monoclon-al antibodies, now afundamental tool inmany industries. Thesame was true ofSanger’s sequencingtechnology. Today,patenting is encour-aged, says Henderson,and several compa-nies, such as Celltech,are associated withthe lab. Klug and Henderson suspect that theplace is good for at least a couple of moreNobels. Even today, with universities,medical foundations, and other organiza-tions working to create hotbeds of scien-tific creativity, LMB still earns strong ku-dos. Says Yale’s Joan Steitz: “There havebeen very good research institutions thathave tried to capture the flavor and spirit,but they haven’t got it.”–ELIZABETH PENNISIWhen James Watson and Francis Crickelucidated the structure of DNA, they dis-covered an elegantly simple molecule.With cardboard cutouts, metal, and wire,they showed how DNA’s two chains woundaround each other, with the paired basesinside, one full rotation every 10 bases.Their model immediately suggested howDNA copied itself and enabled geneticinformation to flow from one generationto the next. They boasted that they hadfound the “secret of life”—essentially, bi-ology’s master molecule that controlledthe fate of the cell and, consequently, ofthe organism. Fifty years of research since then hasshown that, despite its precision design, thismolecule can’t dance without a team of cho-reographers. Like a puppet, DNA comesalive only when numerous proteins pull its“strings.” At the time of their discovery,Watson and Crick had only the haziest ofideas about how this double helix interactedwith proteins. But rebuilt today, Watson andCrick’s bare-bones model would be drapedwith proteins that kink and curl, repair, andotherwise animate DNA. DNA ascendantThe age of DNA began well before Crickand Watson were born. In the 1860s,Friedrich Miescher, a Swiss working inTübingen, Germany, isolated a strange,phosphorus-rich material from the cell nu-cleus. Within decades, it was clear that thispeculiar substance—later identified as nu-cleic acids—was fundamental to the cell’schemistry. Somehow.Throughout the early part of the 20thcentury, biochemists argued about DNA’srole. Some postulated that it was the stuff ofgenes; others insisted that proteins carriedCREDITS: (TOP TO BOTTOM) MRC LABORATORY OF MOLECULAR BIOLOGY; SCIENCE AND SOCIETY PHOTO LIBRARYB UILDING ON THE DNA REVOLUTIONS PECIAL S ECTIONImage not available for online use.Naked DNA. Watson and Crick’s first model ofDNA didn’t begin to reveal the complex set ofproteins the molecule needs to do its job.NEWS DNA’s Cast of ThousandsWatson and Crick’s discovery revealed much, suggested more, but leftmany details unanswered. Ever since, researchers have been discoveringthe proteins that unlock DNA and the genetic codeBiological incubator. Hundreds of budding molecular biologists gottheir start at the Laboratory of Molecular Biology, opened in 1962.the genetic code. Even though Oswald Av-ery, Colin MacLeod, and Maclyn McCartyof Rockefeller University in New York Citydemonstrated in 1944 that DNA and notproteins carried the genetic code, the debatecontinued; even Crick and Watson at firstdisagreed on this point.Soon after Watson joined him at the Uni-versity of Cambridge, U.K., in 1951, Crickwas persuaded. Across two continents, theyand others set out to discover just whatDNA looked like. Tapping a newly devel-oped imaging technique called x-ray crystal-lography, Rosalind Franklin and MauriceWilkins of King’s College in London pro-duced images that showed DNA was heli-cal. Others were busy envisioninghow DNA’s bases werearranged to enable it tofunction. Watson andCrick’s discovery set-tled once and for allthat genes weremade of DNA. Butit took eight moreyears—and the efforts of many researchers—tocrack the geneticcode contained in thenucleotide bases. Watson and Crick, par-ticularly Crick, had many ideasabout how DNA worked, somethingtheir landmark 1953 paper hinted at in itslast sentence: “It has not escaped our noticethat the specific pairing we have postulatedimmediately suggests a possible copyingmechanism for the genetic material.” Theidea was that, as the double helix uncoiled,each strand of an existing DNA moleculecould act as a template for building anothercopy of the molecule. In the late 1950s,Matthew Meselson and Franklin Stahl of theCalifornia Insti-tute of Technolo-gy in Pasadenashowed this to bethe case.Shortly after-ward, Arthur Ko-rnberg of StanfordUniversity and hiscolleagues dem-onstrated that anenzyme they haddiscovered severalyears earlier or-chestrates the syn-thesis of each newDNA strand. Theenzyme, DNApolymerase, addsjust the right nu-cleotide base to the separated DNA