Cech, Thomas R. WORLD OF MICROBIOLOGY AND IMMUNOLOGY102•
separate—that there was a delicate division of labor. Cech and
his colleagues at the University of Colorado established, how-
ever, that this picture of how RNA functions was incorrect;
they proved that in the absence of other enzymes RNA acts as
its own catalyst. It was a discovery that reverberated through-
out the scientific community, leading not only to new tech-
nologies in RNA engineering but also to a revised view of the
evolution of life. Cech shared the 1989 Nobel Prize for
Chemistry with Sidney Altman at Yale University for their
work regarding the role of RNA in cell reactions.
Cech was born in Chicago, Illinois, to Robert Franklin
Cech, a physician, and Annette Marie Cerveny Cech. Cech
recalled in an autobiographical sketch for Les Prix Nobel,he
grew up in “the safe streets and good schools” of Iowa City,
Iowa. His father had a deep and abiding interest in physics as
well as medicine, and from an early age Cech took an avid inter-
est in science, collecting rocks and minerals and speculating
about how they had been formed. In junior high school he was
already conferring with geology professors from the nearby uni-
versity. Cech went to Grinnell College in 1966; at first attracted
to physical chemistry, he soon concentrated on biological chem-
istry, graduating with a chemistry degree in 1970.
It was at Grinnell that he met Carol Lynn Martinson,
who was a fellow chemistry student. They married in 1970 and
went together to the University of California at Berkeley for
graduate studies. His thesis advisor there was John Hearst who,
Cech recalled in Les Prix Nobel,“had an enthusiasm for chro-
mosome structure and function that proved infectious.” Both
Cech and his wife were awarded their Ph.D. degrees in 1975,
and they moved to the east coast for postdoctoral positions—
Cech at the Massachusetts Institute of Technology (MIT) under
Mary Lou Pardue, and his wife at Harvard. At MIT Cech
focused on the DNA structures of the mouse genome, strength-
ening his knowledge of biology at the same time.
In 1978, both Cech and his wife were offered positions
at the University of Colorado in Boulder; he was appointed
assistant professor in chemistry. By this time, Cech had
decided that he would like to investigate more specific genetic
material. He was particularly interested in what enables the
DNA molecule to instruct the body to produce the various
parts of itself—a process known as geneexpression. Cech set
out to discover the proteins that govern the DNAtranscription
process onto RNA, and in order to do this he decided to use
nucleic acids from a single-cell protozoa, Tetrahymena ther-
mophila. Cech chose Tetrahymenabecause it rapidly repro-
duced genetic material and because it had a structure which
allowed for the easy extraction of DNA.
By the late 1970s, much research had already been done
on DNA and its transcription partner, RNA. It had been deter-
mined that there were three types of RNA: messenger RNA,
which relays the transcription of the DNA structure by attach-
ing itself to the ribosome where protein synthesisoccurs; ribo-
somal RNA, which imparts the messenger’s structure within
the ribosome; and transfer RNA, which helps to establish
amino acids in the proper order in the protein chain as it is
being built. Just prior to the time Cech began his work, it was
discovered that DNA and final-product RNA (after copying or
transcription) actually differed. In 1977, Phillip A. Sharp andothers discovered that portions of seemingly noncoded DNA
were snipped out of the RNA and the chain was spliced back
together where these intervening segments had been removed.
These noncoded sections of DNA were called introns.
Cech and his coworkers were not initially interested in
such introns, but they soon became fascinated with their func-
tion and the splicing mechanism itself. In an effort to understand
how these so-called nonsense sequences, or introns, were
removed from the transcribed RNA, Cech and his colleague
Arthur Zaug decided to investigate the pre-ribosomal RNA of
the Tetrahymena,just as it underwent transcription. In order to
do this, they first isolated unspliced RNA and then added some
Tetrahymenanuclei extract. Their assumption was that the cat-
alytic agent or enzyme would be present in such an extract. The
two scientists also added small molecules of salts and
nucleotides for energy, varying the amounts of each in subse-
quent experiments, even excluding one or more of the additives.
But the experiment took a different turn than was expected.
Cech and Zaug discovered instead that RNA splicing
occurred even without the nucleic material being present. This
was a development they did not understand at first; it was a
long-held scientific belief that proteins in the form of enzymes
had to be present for catalysis to occur. Presenting itself was a
situation in which RNA appeared to be its own catalytic moti-
vator. At first they suspected that their experiment had been
contaminated. Cech did further experiments involving recom-
binant DNA in which there could be no possibility of the pres-
ence of splicing enzymes, and these had the same result: the
RNA spliced out its own intron. Further discoveries in Cech’s
laboratory into the nature of the intron led to his belief that the
intron itself was the catalytic agent of RNA splicing, and he
decided that this was a sort of RNA enzyme which they called
the ribozyme.
Cech’s findings of 1982 met with heated debate in the
scientific community, for it upset many beliefs about the
nature of enzymes. Cech’s ribozyme was in fact not a true
enzyme, for thus far he had shown it only to work upon itself
and to be changed in the reaction; true enzymes catalyze
repeatedly and come out of the reaction unchanged. Other crit-
ics argued that this was a freak bit of RNA on a strange
microorganism and that it would not be found in other organ-
isms. The critics were soon proved wrong, however, when sci-
entists around the world began discovering other RNA
enzymes. In 1984, Sidney Altman proved that RNA carries out
enzyme-like activities on substances other than itself.
The discovery of catalytic RNA has had profound
results. In the medical field alone RNA enzymology may lead
to cures of viral infections. By using these rybozymes as gene
scissors, the RNA molecule can be cut at certain points,
destroying the RNA molecules that cause infections or genetic
disorders. In life sciences, the discovery of catalytic RNA has
also changed conventional wisdom. The old debate about
whether proteins or nucleic acids were the first bit of life form
seems to have been solved. If RNA can act as a catalyst and a
genetic template to create proteins as well as itself, then it is
rather certain that RNA was first in the chain of life.
Cech and Altman won the Nobel Prize for chemistry in
1989 for their independent discoveries of catalytic RNA. Cechwomi_C 5/6/03 2:04 PM Page 102