and their university counterparts, whoearned up to 10% more. The differential wascausing a “brain drain of CSIC scientists” tothe universities, Tarrach says. He found himself under increasing pressure from theranks: In a 4 December letter, 10 directors
and scientists of CSIC institutes urged him
to deal with a series of concerns about his
management of the agency.
Tarrach’s woes intensified after the oilspill. In a 24 January letter to Science (p.
511), 422 scientists accused the governmentof failing to adequately take into account theviews of the scientific community. Although
no government official was singled out inthe letter, some researchers pin at least partof the blame on Tarrach. He has shown an“incapacity of leadership,” charges Juan
Eugenio Iglesias of the Institute of Materials
Science in Madrid. Tarrach, he says, hasdemonstrated that “he serves the govern-ment rather than the scientists.”
If that’s the case, the government has
found an odd way to express its appreciation. On 24 January, the conservative newspaper ABC announced Tarrach’s resignation.
Tarrach himself says he learned of his resignation from the news article; he blames hisfall on the Science letter, which generated
widespread press coverage in Spain that day.
In a written statement, the science ministry explained that Tarrach resigned because
he “wished to return to the academic life.” A
spokesperson declined to comment on suggestions that the Science letter precipitatedTarrach’s departure. Ironically, the CSIC official most responsible for dealing with the oilspill—Emilio Lora-Tamayo, CSIC vice president and head of the agency’s scientific commission on the spill—is being tapped as Tar–XAVIER BOSCHrach’s successor.
Xavier Bosch is a writer in Barcelona.

N E U RO S C I E N C E

Buried deep within the brain, the sickle- ory and learning. Although it was originallyshaped hippocampus helps determine what a discovered as a general facilitator of neuron
person learns and remembers. Now, re- growth and maintenance, over the past few
searchers have identified a tiny genetic varia- years, numerous groups, including Lu’s,tion that may influence just how effectively have linked it to the neuronal remodelingthe hippocampus functions. The genetic twist that underlies learning and memory. In parmay also affect a person’s susceptibility to ticular, they have found that it enhances abrain diseases such as Alzheimer’s.
phenomenon called long-term potentiation
People carrying a particular variation in (LTP), in which synapses, the connections
the gene for a protein
called brain-derived
neurotrophic factor(BDNF) didn’t perform
as well on a memory
test as people with thestandard version of thegene did, according toa report in the 24 January issue of Cell byMichael Egan, Bai Lu,
Daniel Weinberger, and Delivery error. The red stain identifies the secretory vesicles, and thecolleagues at the green stain identifies either the valine (top) or methionine (bottom)
National Institutes of variant of BDNF in these hippocampal neurons. Merging the greenHealth (NIH) in Beth- and red-stained images (top and bottom right) shows that only theesda, Maryland. Brain- valine variant ends up in BDNF’s normal location in the vesicles.
imaging and otherstudies point to abnormal functioning of between neurons, are strengthened when
hippocampal neurons in those with the vari- their neurons are stimulated simultaneously.
ation, which changes just one amino acid in
In the first phase of their work, WeinBDNF, replacing valine with methionine at berger and his colleagues searched gene
position 66 of the protein. Neurobiologist databases for variations in BDNF thatSusan Patterson of Columbia University in might influence the protein’s function.
New York City says that the work “provides They also wanted to see if any variations
a very nice demonstration that BDNF plays could be linked to schizophrenia, which isa role in some forms of human memory.”
associated with derangements in hippoThe NIH team had ample reason to sus- campal function.
pect that BDNF might be involved in memThe valine-to-methionine switch at▲

CREDITS: (TOP TO BOTTOM) WORLD HEALTH ORGANIZATION; SOURCE: M. F. EGAN ET AL., CELL 112, 257 (2003)

Minor Variation in Growth-Factor
Gene Impairs Human Memorywww.sciencemag.org

SCIENCEVOL 299

31 JANUARY 2003

ScienceScope
Insider to Lead World HealthOrganization
A relatively unknown insider, Jong Wook Lee(right), has been tapped as the next director-general of the World Health Organization (WHO).The South Korean tuberculosis expert has
worked at WHO for nearly 20years, most recently as headof WHO’s Stop TB antituberculosis program.
The 28 January vote by
the organization’s Executive
Board at WHO’s Geneva,
Switzerland, headquarters
was close: Lee received 17
votes to 15 for runner-up
Peter Piot, head of UNAIDS. Three otherfinalists—Pascoal Manuel Mocumbi, prime
minister of Mozambique; Ismail Sallam,
Egypt’s former health minister; and Mexico’s health minister Julio Frenk—wereeliminated in a first round of voting.
Lee has said he will work to decentralize WHO and strengthen its country andregional offices. Lee’s current boss, DavidHeymann, executive director of WHO’sdivision of communicable diseases,praised the board’s choice. Lee “hasshown great skills in working with partners in the private sector,” he said, which
will be important for the organization incoming years. The WHO General Assembly is expected to approve Lee’s nomination at its meeting in May. He will takeover from current Director-General Gro
Harlem Brundtland at the end of June.
–GRETCHEN VOGEL

Indian Animal ActivistsDropped From Oversight PanelNEW DELHI—In a move likely to please theIndian biomedical community, ardent animal
activists have been pushed off a committeethat supervises animal experimentation.
Under animal-welfare activist and former union minister Maneka Gandhi, theCommittee for the Purpose of Control andSupervision of Experiments on Animals conducted a series of inspections that founddeficiencies at several well-known science
institutes. But Gandhi lost her Cabinet postin July after a squabble with the former
health minister, and her committee post
last month. Now the panel has shed 10 of28 members and been recast into a body ofscientists and government officials.
Immunologist Satyajit Rath of the National Institute of Immunology in New
Delhi welcomes the changes as a move toward more balanced oversight. But Gandhi
sees it as “the end of the road for surpriseinspections and rigorous oversight.”–PALLAVA BAGLA639

NEWSO FT H E

WEEK

site 66 looked promising, Weinberger
says. It’s a fairly common variant: Of 600
people the researchers examined, 32% hadat least one copy of the oddball gene. And
the variation is located in the so-called ZIP
code of BDNF, a sequence that directs theprotein to its correct destination in the cell.
Thus, the amino acid change wouldn’t alter BDNF function directly, but it could do
so indirectly by causing the protein to end
up at the wrong place.
Subsequent testing revealed no link between the methionine variant and schizophrenia risk. But the researchers did findthat both schizophrenic and healthy subjects
who carried the variant fared worse on a test
that measures episodic memory—the ability
to remember past experiences—than didpeople who had two copies of the valineversion. Results on the test, in which subjects are asked to recall the elements of ashort story that they have read, have been

linked to activity in the hippocampus.
Brain-imaging studies confirmed thathippocampal function was abnormal in people with the methionine variant. In a different memory test, in which the hippocampus
is normally deactivated, functional magnetic
resonance imaging showed that activity inthis brain region was actually turned up inpeople with the variant.
In addition, Weinberger’s group used
another imaging method to look at levelsof a chemical called N-acetyl aspartate(NAA), an indirect measure of the richnessof synaptic connections among neurons.
Hippocampal NAA levels were lower inpeople with the methionine variant. All inall, Weinberger concludes, “the form of
the gene you have influences how wellyour hippocampus works.”
Further studies by the NIH team point toa possible reason for the impaired hippocampal function in people who make thevariant BDNF. Normally, neurons secrete
BDNF when they are stimulated. This isthought to help strengthen synapses, as in
LTP. But studies of cultured hippocampal
neurons showed that the methionine variant
wasn’t transported to the nerve endings as
it should be. As a result, BDNF wasn’t
secreted when the neurons were stimulated.
Neuroscientist Mu-ming Poo of the University of California, Berkeley, describes
these findings as “very intriguing … a very
bold link of a molecular defect with a defectin cognitive function.”
Even so, Egan and others note that thevariant’s effect on memory is small, and it has
no apparent effect on one’s IQ. But the findings raise the possibility that people with thevariant may be more vulnerable to memory
loss that may come with advanced age orbrain injury. “Everybody may not have thesame genetic toolbox to deal with additional–JEAN MARX
insult,” as Weinberger puts it.

M E TA B O L I C E N G I N E E R I N GPeter Schultz is dissatisfied with the number 20. That’s the number of amino acids
that virtually all organisms use to constructproteins, the molecules that carry out the lion’s share of chemistry within cells. Twoyears ago, a team led by Schultz, a chemist

into the bacterium’s growth medium.
Now, in a paper scheduled to appear inthis week’s issue of the Journal of the American Chemical Society, Schultz’s team reports going one step further by engineering
an E. coli that not only incorporates a 21st
amino acid into its
makeup but also
manufactures thecompound by itself.
“These results
are very exciting,” inpart because they
provide researcherswith a new way toexplore evolution,says David Liu, achemist and specialist in molecular evolution at Harvard
University in Cambridge, Massachusetts. “It’s tantalizingto ask how can thisorganism evolve,
now that it isExtra edge? Tests should show whether bacteria engineered with a 21st equipped with amethod for not only
amino acid (green) outcompete those with 20 (light blue).
using a nonnaturalat the Scripps Research Institute in La Jolla, building block but also for creating that
California, engineered the genes of a live building block,” says Liu.
organism—an Escherichia coli bacterium—
Getting an organism to expand its stanto incorporate a 21st amino acid into its dard amino acid repertoire took some doproteins. That made the bug the first syn- ing. Schultz’s team has had to reengineer
thetic life form with a chemistry unlike any- the basic machinery that cells use to makething found in nature. To make proteins proteins. That machinery starts with trioswith unnatural amino acids, however, the re- of nucleotide bases, called codons, thatsearchers had to put that new amino acid make up DNA. Each codon directs a par-640

31 JANUARY 2003

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SCIENCEticular amino acid to be added to a protein
chain. To create its first synthetic bug,
Schultz’s team co-opted a little-usedcodon—known as the amber stop codon—and reengineered the cellular enzymes
to add a new amino acid, O-methyl- L tyrosine, whenever it saw that codon.
In the latest work, Schultz—with students and colleagues at Scripps, the University of California, Berkeley, and theGenomics Institute of the Novartis Research
Foundation in La Jolla—followed thatsame strategy with a new amino acid,p-aminophenylalanine. To enable the microbes to make the new amino acid on theirown, they also spliced a trio of enzymeproducing genes from a strain of Streptomyces bacteria into the E. coli. Together withanother enzyme already present in E. coli,
these enzymes enabled the bugs to turn acommon compound in E. coli called chorismate into p-aminophenylalanine, which
protein-building enzymes then picked up
and inserted into growing proteins.
What difference does the altered chemistry make? To find out, Schultz says, his
team is randomly inserting amber stopcodon mutations into the E. coli genome.
Next, they plan to put these E. coli and the
20-amino-acid variety under selective pressure by changing their food supply and otherfactors, to see whether the bacteria with a21st amino acid fare better than natural ones
do. If so, he says, it would suggest that although biology has made do with 20 aminoacids for billions of years, evolution could
make use of plenty more.

www.sciencemag.org–ROBERT F. SERVICECREDIT: J. CHRISTOPHER ANDERSON AND ALAN MCPHEE/BIOMEDICAL GRAPHICS

Researchers Create First Autonomous Synthetic Life Form