MEET THESE
GREAT WOMEN
WHO HAVE
WON
SCIENTIFIC
NOBELS
THROUGHOUT HISTORY
CHEMISTRY
Irène Joliot-Curie
Irène Curie, born in
Paris, September 12, 1897, was the daughter of Pierre and
Marie Curie, and since 1926 the wife of Frédéric Joliot. After
having started her studies at the Faculty of Science in Paris, she served as a
nurse radiographer during the First World War. She became Doctor of Science in
1925, having prepared a thesis on the alpha rays of polonium. Either alone or
in collaboration with her husband, she did important work on natural and
artificial radioactivity, transmutation of elements, and nuclear physics; she
shared the Nobel Prize in Chemistry for 1935 with him, in recognition of their
synthesis of new radioactive elements, which work has been summarized in their
joint paper Production artificielle d’éléments radioactifs. Preuve chimique
de la transmutation des éléments (1934).
Dorothy
Crowfoot Hodgkin (1964)
Born: 12 May 1910, Cairo, Egypt. Died: 29 July
1994, at Shipston-on-Stour, United Kingdom
Affiliation at the time of the award: University
of Oxford, Royal Society, Oxford, United Kingdom
Prize motivation: "for her determinations by
X-ray techniques of the structures of important biochemical substances."
Prize share: 1/1
Life
Dorothy Crowfoot Hodgkin's life as a researcher
began when she received a chemistry book containing experiments with crystals
as a child. After studying at Oxford University and despite graduating with
good grades, as a woman, she had difficulty finding work. Finally, J.D. Bernal
of Cambridge University, a pioneer of modern molecular biology, gave her a
chance. After receiving her PhD from Cambridge University, Dorothy Crowfoot
Hodgkin returned to Oxford University in 1934 where she remained for the rest
of her career, achieving a host of brilliant discoveries in the field of
molecular biology.
Work
When X-rays pass through a crystalline structure,
the patterns formed can be captured as photographic images, which are then used
to determine the crystal's structure. During the 1930s, this method was used to
map increasingly large and complex molecules. A mass of X-ray diffraction
images, extensive calculations, and astute analysis helped Dorothy Crowfoot
Hodgkin to successfully determine the structure of penicillin in 1946 and, in
1956, also the structure of vitamin B12, which has the most complex structure
of all vitami
The Nobel Prize
in Chemistry 1964 was awarded to Dorothy Crowfoot Hodgkin "for her
determinations by X-ray techniques of the structures of important biochemical
substances."
Ada Yonath (2009)
This is her autobiography. I
was born in Jerusalem in 1939 to a poor family that shared a rented four room
apartment with two additional families and their children. My memories from my
childhood are centered on my father’s medical conditions alongside my constant
desire to understand the principles of the nature around me. The hard
conditions didn’t dampen my enormous curiosity. Already at five, I was actively
investigating the world. In one of my experiments I tried to measure the height
of our tiny balcony using the furniture from inside the apartment. I put a
table on another table, and then a chair and a stool on top, but did not reach
the ceiling. Hence, I climbed up on my construct, fell down to the back yard on
the ground floor and broke my arm … Incidentally, the results of this
experiment are still unknown, since the current tenants in the apartment have
remodeled the ceiling.
My parents were raised in religious families,
being educated mainly in Judaism (my father) and women household skills (my
mother). All of the schools in my immediate neighborhood were based on the same
principles as those of my parents. However, despite the poverty of my parents
and the lack of formal education, they went out of their way so that I could
obtain a proper education in a very prestigious secular grammar school, called
“Beit Hakerem”.
My father was frequently hospitalized and
operated on, and when I was 11 years old he died. My mother barely coped, and I
started to help her at that age. I had all types of jobs, cleaning, babysitting
and providing private tuition to younger children. But both of us could not
earn enough to support our little family, and consequently a year later my
mother decided to move to another city, Tel Aviv, in order to be closer to her
sisters. There I completed my high school education, and my mother, despite her
tough life, supported my desire to keep on learning.
Indeed, after I spent my compulsory army service
in the “top secret office” of the Medical Forces, where I was fortunate to be
exposed to clinical and medical issues, I enrolled to the Hebrew University of
Jerusalem. There I completed my undergraduate and M.Sc. studies in chemistry,
biochemistry and biophysics. My doctoral work was carried out at the Weizmann
Institute. I tried to reveal the high resolution structure of collagen. I
continued to work on fibrous proteins (muscle) in my first postdoctoral year at
the Mellon Institute in Pittsburg, Pennsylvania and then moved to the
Massachusetts Institute of Technology (MIT) to study the structure of a globur
protein staphylococcus nuclease. After completing my postdoctoral research, at
the end of 1970, I returned to the Weizmann Institute. There, I initiated and
established the first biological crystallography laboratory in Israel, which
for almost a decade was the only laboratory for such studies.
At the end of the 1970s, I was a young researcher
at the Weizmann Institute with an ambitious plan to shed light on one of the major
outstanding questions concerning living cells: the process of protein
biosynthesis. For this aim I wanted to determine the three-dimensional
structure of the ribosome – the cells’ factory for translating the instructions
written in the genetic code into proteins – and thus reveal the mechanics
guiding the process. This was the beginning of a long quest that took over two
decades, in which I was met with reactions of disbelief and even ridicule in
the international scientific community. I can compare this journey to climbing
Mt. Everest only to discover that a higher Everest stood in front of us.
I began these studies in collaboration with Prof.
H.G. Wittmann of the Max Planck Institute for Molecular Genetics in Berlin, who
supported these studies academically and financially. In parallel I maintained
my laboratory at the Weizmann Institute, initially with a very modest budget
and a grant given by the USA National Institute of Health (NIH). Over the
years, a center for macromolecular assemblies was established by Mrs. Helen
Kimmel at the Weizmann Institute, and consequently I came to lead a large team
of researchers from all corners of the globe. Though my research began as an
attempt to understand one of the fundamental components of life, it has led to
a detailed understanding of the actions of some of the most widely prescribed
antibiotics. My findings may not only aid in the development of more efficient
antibacterial drugs, but could give scientists new weapons in the fight against
antibiotic resistant bacteria – a problem that has been called one of the most
pressing medical challenges of the 21st century.
Because the ribosome is so central to life,
scientists around the world had been trying for many years to figure out how it
works, but without an understanding of its spatial structure there was little
hope of forming a comprehensive picture. To reveal the three-dimensional
structure at the molecular level, crystals are required, but when dealing with
ribosomes, there are added challenges. The ribosome is a complex of proteins
and RNA chains; its structure is extraordinarily intricate; it is unusually
flexible, unstable and lacks internal symmetry, all making crystallization an
extremely formidable task.
At the start of the 1980s, working at both the Weizmann
Institute in Israel and the Max Planck Institute in Germany, we created the
first ribosome micro crystals. The procedure, which I developed especially for
this aim, included a method for the preparation of the crystallizable ribosome
that had been developed at the Weizmann Institute by Prof. Ada Zamir, Ruth
Miskin and David Ellison. My inspiration came from an article on hibernating
bears that pack their ribosomes in an orderly way in their cells just before
hibernation, and these stay intact and potentially functional for months.
Assuming that this is a natural strategy to maintain ribosomal activity for
long time, I searched for ribosomes from organisms that live under harsh
conditions, first of semi thermophiles, given by Dr. V. Erdmann and later I
developed a unique experimental system based on ribosomes taken from the hardy
bacteria living the extreme environments of the Dead Sea, thermal springs and
atomic piles. In this way we managed to produce the initial micro crystals of
ribosome in a fairly short time. However, even after obtaining preliminary
diffraction indications, when I described my plans to determine the ribosome
structure many distinguished scientists responded with sarcasm and disbelief.
Consequently I became the World’s dreamer, the village fool, the so-called
scientist, and the person driven by fantasies.
In the mid-1980s we visualized a tunnel spanning
the large ribosomal subunit and assumed, based on previous biochemical works
(Malkin & Rich, 1967, Blobel & Sabatini, 1970) that this is the path
through which the nascent protein progresses as it is being formed – until it
emerges out of the ribosome. In the course of my research, I developed a number
of new techniques that are today widely used in structural biology labs around
the world. One of these is cryo-bio-crystallography, which involves exposing
the crystal to extremely low temperatures, –185°C, to minimize the crystalline
structure’s disintegration under the X-ray bombardment. The day we conducted
this experiment was special and unique. One of the rare “Eureka!” events. In
retrospect, it was second only to the great pleasure I had when seeing our
first high resolution structure a dozen years later. In fact the “Eureka type”
of an experiment was not common, although we frequently had a great pleasure of
overcoming complicated challenges.
In the mid-1990s, once we proved the feasibility
of ribosome crystallography, several groups from leading universities or
research institutions initiated parallel efforts. As they could repeat our
procedures, I was no more alone in this field. At the end of the 1990s, we as
well as those who used our experimental systems succeeded in breaking the
resolution barrier, thanks to improvements in the crystals, in the facilities
for detecting the X-ray diffraction and in ways to determine the diffraction
phases. The first electron density map of the ribosome’s small subunit was a
real breakthrough, and for me, a tremendous excitement. Then, in 2000 and 2001,
we published the first complete three-dimensional structures of both subunits
of the bacterial ribosome.
These discoveries are clearly a high point in 20
years of research, but my quest to understand the ribosome is still far from
complete. Armed with new insight into ribosomal structure, I can afford moving
on to revealing what else these structures can tell us about the ribosome
actions, and how antibiotic drugs block those actions in bacterial ribosomes.
Because ribosomes are so essential to life, many antibiotic drugs work by
targeting their actions. The advances we made in our long quest to solve the
structure and function of the ribosome may also pave the way toward improving
existing antibiotic drugs or designing novel ones. We therefore crystallized
bacterial ribosomes that can serve as pathogen models, complexed with each of
over two dozens antibiotic compound. We found that the drugs bind in specific
“pockets” in the structure, located at or close to functional centers, thus can
block them and prevent the ribosomes from manufacturing proteins. Since these
findings were published in Nature, in 2001, we have revealed the means
of action of almost all of the antibiotics that target the ribosome, and our
research in this area is ongoing.
For all scientists, the true scientific discovery
is the top. In my case I can recall saying things like: ‘why work on ribosomes,
they are dead … we know all what can be known about them’, or: ‘this is a dead
end road’, or: ‘you will be dead before you get there’. Indeed, to my
satisfaction, these predictions were proven wrong, the ribosomes are alive and
kicking (so am I) and their high resolution structures stimulated many advanced
studies.
And in the future? We plan on looking to the
distant past. Ribosomes are found in every living being – from yeast and bacteria
to mammals – and the structures of their active sites have been extraordinarily
well-preserved throughout evolution. We have identified a region within the
contemporary ribosome that seems to be the vestige of the primordial apparatus
for producing peptide bonds and essentially giving rise to life. How did these
first ribosomes come into being? How did they begin to produce proteins? How
did they evolve into the sophisticated protein factories we see today in living
cells? We plan on answering these and related questions in our future work.
Awarding the Nobel Prize exposed the ribosome to
the public. It stimulated true scientific interest and turned on the
imagination of many youngsters. As I have curly hair, there is a new saying in
Israel: “Curly hair means a head full of ribosomes”. Furthermore, our studies
added to the buzz around the lovely North Pole Bears, which inspired my own
research and are now endangered by the changing climate.
These studies could not be performed without the
help and/or active participation of many individuals. Thanks are due to the
Weizmann Institute, particularly its presidents Michael Sela and Haim Harari,
for keeping up with me for over two decades and for allowing me to work; to the
Max Planck Society, especially the late Prof H.G. Wittmann for co-initiating
this project, for producing the ribosome and their crystals and for financing
my dream; to Ms. Helen Kimmel for establishing and maintaining the Kimmelman
Center, thus paving the road for us from the early stages of our studies; to my
colleagues in Hamburg (e.g. Frank Schluenzen, Heike Bartels, Joerg Harms and
Ante Tocilj) and in Israel (especially Anat Bashan, Ilana Agmon, Tamar
Awerbach, Ziva Berkovitch-Yellin, Raz Zarivach and Shulamit Weinstein), as well
as my collaborators in Berlin (especially Francois Franceschi) for their
devotion and enthusiasm in good and bad periods.
Above all, to my family who supported me with no
questions or complaints despite my frequent disappearances and although at
times my mind was not solely with them. These include my parents, who were
brought up far away from science, especially my mother, who experienced
enormous difficulties in raising and educating me after my dad’s death when I
was still a child; my young sister Nurit, and my daughter Hagith, who had to
tolerated me in my presence as well as in my absence; and to my granddaughter
Noa, who at the age of five invited me to her kindergarten to talk about the
ribosome!
Frances Arnold (2018)
The Linus Pauling Professor of Chemical
Engineering, Bioengineering and Biochemistry, has won the 2018 Nobel Prize in
Chemistry for "the directed evolution of enzymes," according to the
award citation. Directed evolution, pioneered by Arnold in the early 1990s, is
a bioengineering method for creating new and better enzymes in the laboratory
using the principles of evolution. Today, the method is used in hundreds of
laboratories and companies that make everything from laundry detergents to
biofuels to medicines. Enzymes created with the technique have replaced toxic
chemicals in many industrial processes.
Arnold shares the prize with George P. Smith of
the University of Missouri in Columbia, who developed a "phage display"
method for evolving proteins, and Sir Gregory P. Winter of the MRC Laboratory
of Molecular Biology in Cambridge, United Kingdom, who used phage display for
evolving antibodies. One half of the prize, which comes with an award of 9
million Swedish krona (about $1 million), goes to Arnold, with the other half
shared by Smith and Winter.
Arnold received the call at a hotel in Dallas,
Texas, at around 4 a.m. local time; she was scheduled to give a lecture
today at UT Southwestern, but had to reschedule to fly back to California. She
says she was in a "deep, deep sleep" when awakened by the call.
"I am absolutely floored. I have to wrap my head around this. It's not
something I was expecting."
"Frances's work on directed evolution is a
beautiful example of an enterprise that has both deep scientific significance
and enormous practical consequences," says David A. Tirrell, Caltech's
provost, the Carl and Shirley Larson Provostial Chair, and the Ross
McCollum-William H. Corcoran Professor of Chemistry and Chemical
Engineering. "Through decades of commitment to exploring a powerful
idea, Frances has transformed the fields of protein chemistry, catalysis, and
biotechnology. She has changed the way we think about things and the way we do
things."
"Directed evolution has transformed how we
make proteins and how we think about new protein catalysts," says
Jacqueline K. Barton, Caltech's John G. Kirkwood and Arthur A. Noyes Professor
of Chemistry and the Norman Davidson Leadership Chair of the Division of Chemistry
and Chemical Engineering. "Through this work, she has broadened the
repertoire of nature's catalysts."
"Life—the biological world—is the greatest
chemist, and evolution is her design process," says Arnold. "I may
not be the best chemist but I do appreciate evolution."
Arnold was born on
July 25, 1956, in Pittsburgh, Pennsylvania. She received her undergraduate
degree in mechanical and aerospace engineering from Princeton University in
1979 and her graduate degree in chemical engineering from UC Berkeley in 1985.
She arrived at Caltech as a visiting associate in 1986 and was named assistant
professor in 1987, associate professor in 1992, and professor in 1996. In 2000,
she was named the Dick and Barbara Dickinson Professor of Chemical
Engineering, Bioengineering and Biochemistry; she became the Linus Pauling
Professor in 2017. She became the director of the Donna and
Benjamin M. Rosen Bioengineering Center at Caltech in 2013.
Directed evolution works in the same way
that breeders mate cats or dogs to bring out desired traits. To perform the
method, scientists begin by inducing mutations to the DNA, or gene, that
encodes a particular enzyme (a molecule that catalyzes, or facilitates,
chemical reactions). An array of thousands of mutated enzymes is produced and
then tested for a desired trait. The top-performing enzymes are selected and
the process is repeated to further enhance the enzymes' performances. For
instance, in 2009, Arnold
and her team engineered enzymes that break down cellulose, the main
component of plant cell walls, creating better catalysts for turning
agricultural wastes into fuels and chemicals.
A number of additional enzymes produced through
directed evolution are now used for a host of products, including biofuels,
agricultural chemicals, paper products, and pharmaceuticals. For example, the
method led to a better way to produce a drug for treating type 2 diabetes.
More recently,
Arnold and her colleagues used directed evolution to persuade bacteria to make
chemicals not found in nature, including molecules containing silicon-carbon or boron-carbon bonds,
or bicyclobutanes,
which contain energy-packed carbon rings. By using bacteria, researchers can
potentially make these chemical compounds in "greener" ways that are
more economical and produce less toxic waste.
"My entire career I have been concerned about
the damage we are doing to the planet and each other," said Arnold when
she won the 2016
Millennium Technology Prize, granted by the Technology Academy Finland.
"Science and technology can play a major role in mitigating our negative
influences on the environment. Changing behavior is even more important.
However, I feel that change is easier when there are good, economically viable
alternatives to harmful habits."
Arnold was the first woman to receive the 2011
Charles Stark Draper Prize from the National Academy of Engineering
(NAE). She is among the small number of individuals, and the first woman,
elected to all three branches of the National Academies: the NAE (2000), the
National Academy of Medicine (2004; it was then called the Institute of
Medicine), and the National Academy of Sciences (NAS; 2008). She received the
2011 National Medal of Technology and Innovation and was inducted into the
National Inventors Hall of Fame in 2014. She has won numerous other awards,
including the 2017
Sackler Prize in Convergence Research from the NAS and the Society
of Women Engineers' 2017 Achievement Award.
She is a member of the American Academy of Arts
and Sciences and the American Philosophical Society, and is a fellow of the
American Association for the Advancement of Science and the Royal Academy of
Engineering.
"Frances's methods have been adopted by scientists
and engineers around the world, and many more have been inspired by her vision
and her impact on chemical science and technology," says Tirrell.
"Her extraordinary accomplishments reflect the unconventional research
environment at Caltech, where scholars are encouraged to dream, to take risks,
and to venture beyond the constraints of disciplinary boundaries."
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