Kornberg Essay, Research Paper
A. Personal Information
Arthur Kornberg (1918-), American biochemist and physician, claims
he has never met ?a dull enzyme.? He has devoted his life to pursuing
and purifying these critical protein molecules. His love of science did
not spring from a family history rooted in science. He was born on
March 3rd, 1918, the son of a sewing machine operator in the
sweatshops of the Lower East Side of New York City. His parents,
Joseph Aaron Kornberg and Lena Rachel Katz, were immigrant Jews
who made great sacrifices to ensure the safety of their family. They
had fled Poland, for if they had stayed, they would have been
murdered in a German concentration camp. His grandfather had
abandoned the paternal family name Queller, of Spanish origin. This
was done to escape the fate of the army draft; he had taken the
name of Kornberg, a man who had already done his service. His father
used their meager earnings to bring and settle his family in New York
City and was thrust into the sweatshops as a sewing machine
operator. He, along with his brother Martin, 13 years older and sister
Ella, nine years older, was encouraged by loving parents to obtain a
good education. The public school reinforced this ideal. Education was
the road of opportunity for social and economic mobility out of the
sweatshops.
His early education in grade school and Abraham Lincoln High School
in Brooklyn was distinguished only by his ?skipping? several grades.
There was nothing inspirational about his courses except the teachers?
encouragement to get good grades. When he received a grade of 100
in the New York State Regents Examination, his chemistry teacher
glowed with pride. It was the first time in over twenty years of
teaching that a student of his had gotten a perfect grade. Arthur was
a brilliant student who graduated from high school at the age of
fifteen. He enrolled in City College in uptown Manhattan. Competition
among a large body of bright and highly motivated students was
fierce in all subjects. His high school interest in chemistry carried over
into college. After receiving his B.S. degree in biology and chemistry
in 1937, and since City College offered no graduate studies or
research laboratories at that time, he became one of two hundred
pre-med students at the University of Rochester. All through college
he worked as a salesman in his parents? furnishing store, and earned
about $14 a week. This along with a New York State Regents
Scholarship of $100 a year and with no college tuition to pay he was
able to save enough money to pay for the first half of medical school.
While a student, he became aware of a mild jaundice (yellowing) in
his eyes. He observed a similar condition among other students and
patients at the hospital and published these findings, his first
professional paper, in the Journal of Clinical Investigation.
He enjoyed studying to become a doctor, and his goal was to practice
internal medicine, preferably in an academic setting. The medical
school curriculum was uncrowded and close contact with a
distinguished faculty was encouraged, but to his shock anti-Semitism
was rampant in the academic circles. He was denied academic awards
and research opportunities because he was Jewish. He had hoped to
receive one of the fellowships from the medical school which allowed
a few outstanding students to spend a year doing research, even
though the idea of spending a significant amount of his days in the
laboratory had no appeal at that time. To his disappointment he was
passed over in every department, due to the ethnic and religious
barriers which existed during that time, even though his grades were
the highest. Although one professor at Rochester stood out, William
S. McCann, Chairman of the Department of Medicine, the only one who
made any effort to help Kornberg. William McCann persuaded a
wealthy patient to endow a scholarship of which Kornberg was the
recipient. This enabled Kornberg to pursue his first research project
(on jaundice), and allowed him to be appointed to an internship in
medicine, and then to an assistant residency, which would groom him
for a career in academic medicine. Following his graduation in 1941,
Kornberg enlisted in the U.S. Coast Guard, being assigned duty as a
medical officer in the Caribbean. Officials at the National Institute of
Health in Maryland, aware of his brief clinical study on the subject of
jaundice, arranged for Kornberg?s transfer to the institute. He spent
the remainder of World War II carrying out research in the nutrition
laboratory. In 1943, Kornberg married Sylvy Levy; he enjoyed not only
companionship with Sylvy but also laboratory collaboration with a
gifted wife. Her suggestions and advice would play major roles in his
research. He has also enjoyed the privilege of fathering three sons,
Tom, Ken, and Roy who have exhibited extraordinary scientific and
professional achievements.
B. Professional Information
The National Institute of health was founded by Joseph Goldberger,
one of the first scientists to recognize that a vitamin deficiency could
cause an epidemic disease. Dr. Goldberger discovered the vitamin
niacin, a member of the B complex of vitamins. Dr. Goldberger
emerged as one of the greatest vitamin hunters. During Kornberg?s
stay at the institute, from 1942 to 1945, his work contributed to the
isolation of another vitamin in the B complex, folic acid. He always
felt that he had come to the nutrition research in its twilight, decades
too late to share the excitement and adventures of the early vitamin
hunters who had solved riddles of diseases that had plagued the
world for centuries. His envy of their exploits would eventually impel
him to search for a new frontier. Having fed rats a purified diet for
three years, he became frustrated with not knowing what vitamins
really did and decided on a leave of absence. Kornberg wanted to
immerse himself in the new biochemistry and study enzymes.
A new breed of hunters tracking down the metabolic enzymes
intrigued him. He spent a year, 1945, with Severo Ochoa at the New
York University School of Medicine and a year with Carl and Gerty Cori
at the Washington University School of Medicine. This is where he got
to know enzymes for the first time and was captivated with them. In
Ochoa?s lab he learned the philosophy and practice of enzyme
purification. To attain the goal of a pure protein, the cardinal rule is
that the ratio of enzyme activity to the total protein is increased to
the limit. Despite initial failures, the immersion in enzymology was
intoxicating to Kornberg; he discovered the momentum of
experimental work exciting. Although enzymes were recognized in the
nineteenth century as catalysts for certain chemical events in nature,
their importance was not fully appreciated until their role in alcohol
fermentation and muscle metabolism was defined. Then it became
clear that virtually all reactions in an organism depend on the high
catalytic potency of a cast of thousands of enzymes, each designed to
direct a specific chemical operation. Deficiency of a single enzyme-as
the results of mutation-could spell disaster for the cellular or human
victim. It was at this time Kornberg realized that enzymes are the
vital force in biology, the sites of vitamin actions, and the means for
a better understanding of life as chemistry. Kornberg decided to take
summer courses offered at Columbia University to better understand
organic and physical chemistry. On completing these courses, he
returning to Ochoa?s lab. He was luckier in his second attempt at
enzyme purification. He joined Ochoa and Alan Mehler, who was a
graduate student, in studies of a certain liver enzyme and its effects
upon malic acid. Alan Mehler became Kornberg?s devoted tutor. At the
end of 1946, while working side by side with Ochoa, Kornberg
overturned a cylinder, which had a domino effect that destroyed the
entire experiment. Returning the next morning, Kornberg noticed one
vile in the centrifuge. The remains had separated, and he collected
the solid material. This fraction had the bulk of the enzyme activity
and was several-fold purer than the best of all previous preparations.
This step (without the cylinder breakage) became part of the
published procedure on enzyme purification. During his time spent
with Severo Ochoa at New York University School of Medicine in 1946,
and time spent with Carl and Gerty Cori at the Washington University
School of Medicine in St. Louis in 1947, Kornberg refined his
knowledge of enzyme production, as well as isolation and purification
techniques.
C. Specific Information on a Specific Contribution
In 1948, Kornberg returned to the National Institute of Health as chief
of the enzyme and metabolism section and established his own
laboratory. He continued his work in the purification of enzymes. It
was four years later (he calls these years ?his golden working years?)
that Kornberg had purified an enzyme from potatoes. He called the
enzyme ?nucleotide pyrophosphatase? and discovered how to cleave
the complex coenzymes gently enough to leave their component
halves intact. He was able to advance his knowledge of the location
of one of three phosphate groups of NADP (nicotinamide adenine
dinucleotide phosphate). Cleaving NAD (nicotinamide adenine
dinucleotide) gave him the key to the discovery of the wondrous
enzyme that makes NAD. With the discovery of an enzyme goes the
privilege and burden of naming it. Kornberg named the enzyme NAD
synthetase. This discovery gave him instant recognition among
biochemists and set him on a career devoted to the enzymes that
assemble DNA, genes, and chromosomes. His pursuit of this particular
enzyme would lead him to the synthesis of coenzymes, to the origin
of inorganic pyrophosphate, and eventually to the replication of DNA.
During his time spent at the
National Institutes of Health (1942-1953), he helped elucidate the
reactions leading to the formation of two important coenzymes: flavin
adenine dinucleotide (FAD) and diphosphopyridine nucleotide (DPN).
During the summer of 1953, Kornberg enrolled in a microbiology
course offered by Cornelius van Niel in Pacific Grove, California.
Kornberg recently accepted a position as chair of the Department of
Biochemistry at the Washington University School of Medicine in St.
Louis, and he felt the need for a more formal instruction in the
subject. Kornberg became intrigued with bacteria as a source of
enzymes for his research. In particular, he became interested in
biosynthetic pathways for the building blocks of deoxyribonucleic acid
(DNA). It was also in 1953 that James Watson and Francis Crick
reported their discovery that DNA is a pair of chains spiraling about
each other-a double helix. Within two years of Watson and Crick?s
historic report, Kornberg had found, in juices extracted from cells, an
enzyme that synthesizes the huge chains of DNA from simple blocks.
But it was not until 1956 that Kornberg?s interest in the replication of
DNA became the focus of his research. It was after the enzyme that
assembles the nucleotide building blocks into a DNA chain was
already in his hands. Much of his research during 1953 and 1954 dealt
with purification of the enzymes that synthesize the precursors of
DNA. By 1954, Kornberg?s team had firmly established how the
nucleotides are synthesized. The next step was to study how they are
assembled into DNA or RNA.
Initial experiments with extracts from animal cells were unsuccessful,
and Kornberg turned to extracts from the bacterium Escherichia coli
(E. coli). This was the first major discovery his team had made, and
was the chemical catalyst responsible for the synthesis of DNA. They
discovered the enzyme in the common intestinal bacterium Escherichia
coli, and Kornberg called it DNA polymerase. This was an important
discovery because DNA is the construction manual, and RNA
transcribes it into reading form, but the proteins, particularly the
enzymes, carry out all the cellular functions and give the organism its
shape. In 1957, Kornberg?s group used this enzyme to synthesize DNA
molecules, but they were not biologically active. This proved that this
enzyme does catalyze the production of new strands of DNA, and it
explained how a single strand of DNA acts as a pattern for the
formation of a new strand of nucleotides-the building blocks of DNA.
In 1959, Kornberg along with Ochoa shared the Nobel Prize for their
?discovery of the mechanisms in the biological synthesis of ribonucleic
acid and deoxyribonucleic acid.? His work established the basic
mechanism of all DNA polymerases in nature and the capacity of
these polymerases to make genetically active DNA in the test tube.
The same year Kornberg accepted an appointment as professor of
biochemistry and chairman of the Department of Biochemistry at
Stanford University. He continued his research on DNA biosynthesis
along with Mehran Goulian. The two researchers were determined to
synthesize an artificial DNA that was biologically active. By 1967 the
two researchers announced their success.
This research would help in future studies of genetics, as well as in
the search for cures to hereditary diseases and the control of viral
infections. The Stanford researchers have continued to study DNA
polymerase to further understanding of the structure of that enzyme
and how it works. Kornberg has used his status as a Nobel Laureate
on behalf of various causes. Arthur Kornberg is an expert in DNA
replication, and in particular DNA polymerases. He is currently an
active Professor Emeritus in the Department of Biochemistry at
Stanford University School of Medicine, and he holds memberships in
several scientific associations, including the National Academy of
Sciences, the Royal Society, and the American Philosophical Society.
He has also authored over 300 scientific publications from 1956 to
1994 relating to DNA replication, DNA polymerases, and other aspects
of nucleic acid enzymology. Arthur Kornberg?s accomplishments still
continue today, and the list is growing. Many of the enzymes that he
isolated are also used in modern genetic engineering today. His work
has help spawn a new generation of research in molecular medicine,
has completely transformed the nature of medical research, and has
enabled scientists to make great strides in the diagnosis and
treatment of immune disorders. His research has laid the foundation
for the clinical advances in the treatment of many devastating human
disorders.
D. Conclusion
Professor Kornberg finds time to travel and lecture at many
universities and research centers. He calls for a return of simple
curiosity. He lectures that? scientists need to be able to study
science for curiosity?s sake and not be driven by the possible dollar
benefits-and governments should encourage them.? He is adamant
that research into science should proceed, despite public concerns
that new discoveries, especially in genetic engineering, could be
abused. ?There is often a focus on the alarmist possibilities of any
new technology; however it is foolish to try and predict where science
will take us.? He states? there hasn?t been a single instance of
biotechnology being misapplied. It?s safer than driving.?
Professor Kornberg is a remarkable individual, and his devotion to his
field of study is inspirational. His contributions have advanced medical
knowledge. Medical knowledge needs to constantly advance because
of the challenges of new problems- such as novel toxins and resistant
organisms that are constantly arising. I believe that research is the
lifeline to medicine; we should continue to question and search for
answers.