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.