WORLD OF MICROBIOLOGY AND IMMUNOLOGY Chaperones113•
made available for civilian use. The ethics of whether to make
penicillin research universally available posed a particularly
difficult problem for the scientific community during the war
years. While some believed that the research should not be
shared with the enemy, others felt that no one should be denied
the benefits of penicillin. This added layers of political intrigue
to the scientific pursuits of Chain and his colleagues. Even after
the war, Chain experienced firsthand the results of this
dilemma. As chairman of the World Health Organizationin the
late 1940s, Chain had gone to Czechoslovakia to supervise the
operation of penicillin plants established there by the United
Nations. He remained there until his work was done, even
though the Communist coup occurred shortly after his arrival.
When Chain applied for a visa to visit the United States in
1951, his request was denied by the State Department. Though
no reason was given, many believed his stay in
Czechoslovakia, however apolitical, was a major factor.
After the war, Chain tried to convince his colleagues
that penicillin and other antibiotic research should be
expanded, and he pushed for more state-of-the-art facilities at
Oxford. Little came of his efforts, however, and when the
Italian State Institute of Public Health in Rome offered him the
opportunity to organize a biochemical and microbiological
department along with a pilot plant, Chain decided to leave
Oxford.
Under Chain’s direction, the facilities at the State
Institute became known internationally as a center for
advanced research. While in Rome, Chain worked to develop
new strains of penicillin and to find more efficient ways to
produce the drug. Work done by a number of scientists, with
Chain’s guidance, yielded isolation of the basic penicillin mol-
ecule in 1958, and hundreds of new penicillin strains were
soon synthesized.
In 1963, Chain was persuaded to return to England. The
University of London had just established the Wolfson
Laboratories at the Imperial College of Science and
Technology, and Chain was asked to direct them. Through his
hard work the Wolfson Laboratories earned a reputation as a
first–rate research center.
In 1948, Chain had married Anne Beloff, a fellow bio-
chemist, and in the following years she assisted him with his
research. She had received her Ph.D. from Oxford and had
worked at Harvard in the 1940s. The couple had three children.
Chain retired from Imperial College in 1973, but con-
tinued to lecture. He cautioned against allowing the then-new
field of molecular biologyto downplay the importance of bio-
chemistryto medical research. He still played the piano, for
which he had always found time even during his busiest
research years. Over the years, Chain also became increas-
ingly active in Jewish affairs. He served on the Board of
Governors of the Weizmann Institute in Israel, and was an out-
spoken supporter of the importance of providing Jewish edu-
cation for young Jewish children in England and abroad—all
three of his children received part of their education in Israel.
In addition to the Nobel Prize, Chain received the
Berzelius Medal in 1946, and was made a commander of the
Legion d’Honneur in 1947. In 1954, he was awarded the PaulEhrlich Centenary Prize. Chain was knighted by Queen
Elizabeth II in 1969. Chain died of heart failure at age 73.See also Antibiotic resistance, tests for; Bacteria and
responses to bacterial infection; Chronic bacterial disease;
Staphylococci and staphylococcal infectionsCChaperonesHAPERONES
The last two decades of the twentieth century saw the discovery
of the heat-shock or cell-stress response, changes in the expres-
sion of certain proteins, and the unraveling of the function of
proteins that mediate this essential cell-survival strategy. The
proteins made in response to the stresses are called heat-shock
proteins, stress proteins, or molecular chaperones. A large num-
ber of chaperones have been identified in bacteria(including
archaebacteria), yeast, and eukaryotic cells. Fifteen different
groups of proteins are now classified as chaperones. Their
expression is often increased by cellular stress. Indeed, many
were identified as heat-shock proteins, produced when cells
were subjected to elevated temperatures. Chaperones likely
function to stabilize proteins under less than ideal conditions.
The term chaperone was coined only in 1978, but the
existence of chaperones is ancient, as evidenced by the con-
servation of the peptide sequences in the chaperones from
prokaryotic and eukaryotic organisms, including humans.
Chaperones function 1) to stabilize folded proteins, 2)
unfold them for translocation across membranes or for degra-
dation, or 3) to assist in the proper folding of the proteins dur-
ing assembly. These functions are vital. Accumulation of
unfolded proteins due to improper functioning of chaperones
can be lethal for cells. Prionsserve as an example. Prions are
an infectious agent composed solely of protein. They are pres-
ent in both healthy and diseased cells. The difference is that in
diseased cells the folding of the protein is different.
Accumulation of the misfolded proteins in brain tissue kills
nerve cells. The result for the affected individual can be
dementia and death, as in the conditions of kuru, Creutzfeld-
Jakob disease and “mad cow” disease (bovine spongiform
encephalopthy).
Chaperones share several common features. They inter-
act with unfolded or partially folded protein subunits, nascent
chains emerging from the ribosome, or extended chains being
translocated across subcellular membranes. They do not, how-
ever, form part of the final folded protein molecule.
Chaperones often facilitate the coupling of cellular energy
sources (adenosine triphosphate; ATP) to the folding process.
Finally, chaperones are essential for viability.
Chaperones differ in that some are non-specific, inter-
acting with a wide variety of polypeptide chains, while others
are restricted to specific targets. Another difference concerns
their shape; some are donut-like, with the central zone as the
direct interaction region, while others are block-like, tunnel-
like, or consist of paired subunits.
The reason for chaperone’s importance lies with the
environment within cells. Cells have a watery environment,
yet many of the amino acids in a protein are hydrophobicwomi_C 5/6/03 2:04 PM Page 113