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.