From genes tobiochemistryGeorge Beadle, an UncommonFarmer: The Emergence ofGenetics in the 20th Centuryby Paul Berg & Maxine SingerCold Spring Harbor Laboratory Press: 2003.383pp. $35, £25

Benno Müller-Hill

Genetics is a young science, having its rootsjust 100 or so years ago in the rediscovery of Gregor Mendel’s work on inheritance inpeas. These days, this history is left out ofmost textbooks and is rarely taught at uni-versity. Today’s students learn only aboutwhat has happened in the past five years,not about the pioneering work that openedup their field — they know nothing of thegiants on whose shoulders they stand. Ifyou ask today’s advanced genetics studentsabout George Beadle (1903–1989), youwould be met with a deafening silence. So it is fortunate that Paul Berg and MaxineSinger took the time to write a book aboutthis great pioneer.

They describe Beadle’s family and hischildhood and youth on a farm close toWahoo, Nebraska. His father prevented hiselder brother from going to agricultural col-lege, but when this brother died after beingkicked by a horse on the farm, George wasallowed to go the agricultural college in Lincoln, where he developed an interest in maize genetics. His intelligence and hardwork impressed his teachers, who sent him to Cornell University in Ithaca, New York,where he continued to work on maize genet-ics. There he met Barbara McClintock, whodemonstrated that maize has ten chromo-somes. But her supervisor was not amusedwhen she published this under her ownname without including him as a co-author.

Beadle’s work on maize genetics earnedhim a PhD in 1929, after which he moved tothe California Institute of Technology,whichwas an exciting place to be. Thomas HuntMorgan had just moved there, and theauthors describe his fly group in a separatechapter that is a must for students. I wouldhave liked to hear more. For example, theauthors mention that the undergraduateAlfred Sturtevant produced the first linearmap of five genes of the fruitfly’s X chromo-some, and that Morgan allowed him to publish his results without demanding hisown name on the paper. Berg and Singerdon’t comment on this, but how many professors would allow this today?

Beadle started collaborating with BorisEphrussi, who was on sabbatical there, to tryand understand what a gene produces. ForMorgan and his group, the gene was abstract,but Beadle and Ephrussi wanted to comecloser to biochemistry. They concentrated on Drosophila mutants with different eyecolours, vermilion and cinnabar. After fiveyears they concluded that tryptophan is con-verted by the vermilion gene into a substanceof unknown structure.So it was a blow in 1940when they read in the journal Naturwissen-schaften that Adolf Butenandt had identifiedthe compound as 3-hydroxykynurenine.Fiveyears’work and then scooped!

Ephrussi then moved into a different field but Beadle stuck tothe problem. During a lecture byhis postdoc Edward Tatum, Beadlehad the idea of treating micro-organisms with mutagens and iso-lating mutants that are unable toproduce amino acids, hormones or other substances.These mutantswill then show that one gene produces one enzyme. Tatum didthe experiment using the fungus Neurospora. It worked like a charm,and hundreds of such mutantswere isolated and analysed. Whatworked well with Neurosporaworked even better with the bac-terium Escherichia coli. One ofTatum’s students, Joshua Leder-

berg, showed that such mutants could be isolated,and demonstrated genetic exchangebetween two mutants of E. coli. In 1958,Beadle,Lederberg and Tatum shared a Nobelprize for their work. As Ephrussi wrote to afriend:“I suddenly felt my life wasted.”

But the story does not end here. When the experimental problem was solved andBeadle had convinced the sceptics, he movedinto the field of administration at Caltech,first as chairman of the biological faculty andthen as president. He excelled at hiring excel-lent faculty and defended Linus Pauling whenhe was attacked as a communist. Even afterhis retirement, Beadle returned to a familiarproblem: was teosinte, a wild grass from Mexico,really the predecessor of maize?

The book tells us in detail about Beadle’stwo marriages, the salaries he earned (butnot their equivalent values today), his jour-neys by ship and by train, and the fact that he succumbed to Alzheimer’s disease. Thereis plenty here for everyone. Those interested in the history of genetics will want to read the whole book, but today’s students wouldbenefit from just a few chapters. ■

Benno Müller-Hill is at the Institute of Genetics,Cologne University, Weyertal 121,50931 Cologne, Germany.

A recipe forsuccess?Organic Syntheses DatabaseWiley/Organic Syntheses, Inc: 2003.http://www.interscience.wiley.com/db/osAvailable through a site licence.

John Mann

The total synthesis of complex natural products remains one of the most tangibleand often elegant demonstrations of thechemist’s craft. Some practitioners haveturned these endeavours into somethingapproaching an art form. It is also often

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subtitle “Tracing evolution from moleculesto genes to phenotypes”.Most authors wouldhave gone from genes to phenotypes withoutbothering with the molecular level. But notCraig, who states that one of her goals is “toillustrate the ease with which evolutionarystudies of spiders and silk proteins can crosstraditional molecular and organismal bor-ders”. Thus silk proteins are “the perfect system through which to study evolutionaryconflicts among molecular genetic con-straint,protein architectural constraint,pro-tein diversity and selection”. Indeed, silk hasevolved to function as a dead material out-side the animal’s body. And silk is only onestep (spinning) removed from the protein inits native form; the chain from gene to rawprotein to dehydrated protein fibre is brief.

But more importantly, the fibre, oncedrawn — whether as a simple drag safety lineor as a structural member in a web — is thephenotype that is selected more or less on itsown,distinct from its creator.This is unusualfor a protein and suggests that silk mightallow for shortcuts in the study of proteinevolution — yet another reason why studyingsilk might provide interesting insights intothe more general aspects of protein folding.

Be that as it may, Craig’s Spider Webs and Silks brings a fascinating and important subject to a potentially broad audience. Andit might even turn some arachnophobes into arachnophiles. ■

Fritz Vollrath is in the Department of Zoology,South Parks Road, University of Oxford,Oxford OX1 3PS, UK.

Field work: at Cornell, George Beadle (kneeling) studiedmaize genetics with Barbara McClintock (right).

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the only route by which quantities of rare compounds such as eleutherobin or bryo-statins can be made available for biologicalevaluation. Any synthesis, whether of a rare,highly potent natural product or of a moremundane yet equally important intermedi-ate for a prescription drug, requires the careful selection of starting materials andpotential synthetic routes.

Synthetic chemists already have a num-ber of information sources, including onlinesearch sites such as Crossfire Beilstein(www.beilstein.com) and the AmericanChemical Society’s SciFinder (www.cas.org).There are also printed reference works suchas Fieser’s Reagents for Organic Synthesis(Wiley), Comprehensive Organic Synthesis(Pergamon, now Elsevier) and of courseOrganic Syntheses (Wiley).

Organic Syntheses is the ‘Mrs Beeton’ forsynthetic chemists. If you can find a ‘recipe’for the reaction or compound you wish tomake in these volumes, you can guaranteethat the chemistry will work, because eachentry is checked for accuracy, safety and

reliability. There is a cumulative index for the first 70 volumes, although many librariesdo not have either this index or a complete set of 80 volumes. The release of the OrganicSyntheses Database now provides access to all 80 on your computer screen.

So how does it perform? The user cansearch for structures and part-structures byimporting these from one of their own draw-ing packages into a display box, and this isprobably the most useful function. I triedseveral structures I wanted to synthesize andothers that I knew to be within the volumesof Organic Syntheses, and obtained accuratelinks to the full text for all of them. Much lessuseful is the search for reaction types andnamed reactions. An enquiry about the aldol reaction elicited just one response, andno response was returned for queries on theReformatsky and Heck reactions. Yet theterm palladation produced two responses,both referring to syntheses submitted byHeck, and there are many others within the80 volumes that have clearly been missed by this route.

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Searches that use either keywords orauthor were generally very good, so search-ing for methodology associated with a keyreagent, such as osmium tetroxide or palla-dium acetate, will elicit a large number of citations although, irritatingly, reactionnames (Heck or Mitsunobu, for example)elicit nothing. The utility of the database isextended by the ability to search other Wileydatabases, including EROS, the Encyclo-paedia of Reagents for Organic Synthesis(although my login and password deniedme access to explore these possibilities),and access to Organic Reactions will follownext spring.

Overall, the database is easy to use andwill complement rather than replace theother existing online search tools. The onemajor advantage of the Organic SynthesesDatabase is that it provides access to aninstant recipe that will work, rather than to a list of literature references in which thechemistry may or may not work.John Mann is at the School of Chemistry,Queen’s University Belfast, Belfast BT9 5AG, UK.

Built specifically for the vast, multistorey spaceof the Turbine Hall at Tate Modern in London,Olafur Eliasson’s installation The Weather Projectis mesmerizing. A huge sun blazes at the far end of the hall, its light diffused by artificial fog,creating a dynamic microclimate.

The Danish–Icelandic artist’s work investigatesthe dichotomy between nature and culture. Herehe tackles the weather, a ubiquitous topic ofconversation, which he says “somehow definesa sense of community, within which conflictingviews can be accommodated, such as liking ornot liking rain”. By introducing meteorologicalvariables — water, light, temperature andpressure — into artificial, built environments, he encourages viewers to reflect on theirunderstanding of the natural world and theirrelationship to it. Eliasson is intrigued byperception and describes the moment whenpeople pause to consider what they areexperiencing as “seeing yourself sensing”. Buteven though all is not as not seems, his aim is toheighten people’s awareness of their perception,not to deceive them.

At ground level, visitors can clearly seemachines pumping artificial haze into the halland the bank of mono-frequency lamps thatpowers the semicircular ‘sun’. From above, they can observe that the reflective ‘sky’ issuspended from the ceiling, both doubling thehall’s apparent height and reflecting the half ‘sun’ to form a whole. Colin MartinThe Weather Project can be seen at Tate Modernin London until 21 March 2004. The work is thesubject of an extensively illustrated book, Olafur Eliasson: The Weather Project, edited by the installation’s curator, Susan May (TatePublishing, £19.99).

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