From discovering DNA polymerase to creating one of the world's most influential biochemistry departments
In 1959, just as he was receiving the Nobel Prize for his groundbreaking discovery of DNA polymerase, Arthur Kornberg was simultaneously embarking on an equally ambitious project: building a new biochemistry department at Stanford University from the ground up. This dual triumph marked a pivotal moment in science history, where the biochemical understanding of life's blueprint converged with the creation of an unparalleled scientific environment. Kornberg's journey from a childhood in Brooklyn sweatshops to the pinnacle of scientific achievement is a story of relentless curiosity, experimental brilliance, and a profound belief that "if a cell can do it, then a biochemist can do it" 9 .
Arthur Kornberg's origins were unlikely for a future Nobel laureate. Born in 1918 to Jewish immigrant parents, his father worked for nearly 30 years as a sewing machine operative in New York's Lower East Side sweatshops before opening a small hardware store 5 7 . The young Kornberg worked in the store from age nine, learning the value of diligence and precision that would later define his scientific career 7 .
A brilliant student, he graduated from high school at 15 and earned a BS from City College of New York before receiving his MD from the University of Rochester in 1941 5 6 . His first research paper, published during medical school, documented his discovery of a mild form of jaundice (later identified as Gilbert's syndrome) in himself and fellow students 7 9 .
Graduated high school at age 15
BS from City College of New York
MD from University of Rochester
Recruited to NIH by Rolla Dyer
This early work caught the attention of Rolla Dyer, Director of the National Institutes of Health, who recruited Kornberg to the NIH in 1942 7 9 . It was at NIH that Kornberg's fascination with enzymes began, leading him to postdoctoral work with Severo Ochoa at New York University where he mastered enzyme purification techniques 5 7 . His growing expertise culminated in 1956 with his landmark discovery of DNA polymerase I—the first enzyme shown to synthesize DNA in a test tube 7 9 . This achievement, which earned him the Nobel Prize in 1959, demonstrated that genetic replication was fundamentally a chemical process, finally putting to rest the notion of vitalism in genetics 9 .
Despite the monumental discovery of DNA polymerase, a major mystery remained: how does DNA replication begin? For years, Kornberg and his team struggled with this question, experiencing what he described as "10 man-years of utter frustration" 1 . The breakthrough came in 1981 in a seminal paper by Roberta Fuller, Jon Kaguni, and Arthur Kornberg that developed the first cell-free system capable of initiating DNA replication at the bacterial origin of replication, oriC 1 .
The key to their success began with the then-recent cloning of the E. coli origin of replication (oriC) 1 . This specific DNA sequence provided the essential starting point that the researchers needed to study initiation.
The final masterstroke was adding molecular crowding agents like polyethylene glycol 1 . These compounds simulated the packed intracellular environment by excluding volume, effectively increasing the concentration of enzymes and their DNA targets to biologically relevant levels.
| Reagent | Function | Significance |
|---|---|---|
| oriC-containing plasmids | DNA template with specific origin sequence | Provided defined starting point for replication |
| Fraction II | Concentrated protein extract | Contained essential initiation proteins |
| Polyethylene glycol (PEG) | Molecular crowding agent | Mimicked intracellular conditions |
| ATP with regeneration system | Energy source | Fueled the energetically demanding process |
| Anti-DnaB/Anti-SSB antibodies | Specific protein depletion | Validated essential components |
The system's validity was confirmed through multiple controls: replication required a functional oriC sequence, was sensitive to RNA polymerase inhibitors, and depended on known replication proteins like DnaB helicase and SSB 1 . When they used extracts from dnaA mutant cells—lacking the crucial initiator protein—the system failed, further confirming its biological relevance 1 .
| Test | Procedure | Result | Interpretation |
|---|---|---|---|
| Antibody depletion | Removed DnaB or SSB with antibodies | Replication halted | Confirmed protein requirements |
| Template specificity | Tested non-oriC plasmids | No replication | Demonstrated origin dependence |
| Genetic validation | Used dnaA mutant extracts | System inactive | Confirmed DnaA requirement |
| Electron microscopy | Visualized replication bubbles | Bidirectional from oriC | Confirmed authentic initiation |
This elegant experiment didn't just solve a biochemical puzzle—it opened the floodgates for understanding the precise mechanism and regulation of chromosomal replication initiation in bacteria 1 .
As Kornberg was revolutionizing DNA biochemistry, Stanford University was preparing to move its medical school from San Francisco to the main Palo Alto campus 9 . They invited Kornberg to chair the new Biochemistry Department, a offer he considered carefully before famously responding, "I must return to St. Louis to consult my colleagues" 9 .
Kornberg didn't just bring a department to Stanford—he brought an entire philosophy of how science should be conducted. He recruited key colleagues from Washington University, including Paul Berg, Bob Lehman, Dave Hogness, and Dale Kaiser, forming the nucleus of what would become one of the most productive biochemistry departments in history 9 .
His innovative organizational principles created an environment unlike any other:
| Innovation | Implementation | Impact |
|---|---|---|
| Mixed laboratory spaces | Students and postdocs from different groups working together | Fostered collaboration and cross-pollination of ideas |
| Shared research resources | Enzymes and major instruments available to all | Eliminated resource competition |
| Flexible funding model | Grants shared without strict accounting | Reduced administrative burden |
| Small group sizes | Faculty worked directly in labs with few trainees | Enhanced mentorship quality |
| Consensus decision-making | Faculty meetings only for important issues | Streamlined governance |
| Regular research gatherings | Monthly home meetings, later Asilomar retreats | Strengthened scientific community |
The department maintained an intense focus on research, with faculty personally working in laboratories and teaching through the apprentice method 9 . The famous Tuesday/Thursday noon seminars became a department ritual, initially featuring only faculty and visiting scientists, though later expanded to include postdoctoral fellows and senior students 9 .
"If a cell can do it, then a biochemist can do it"
This unique environment produced extraordinary results. The department became a cradle for molecular biology, with faculty making pioneering contributions across multiple fields. Paul Berg's work with recombinant DNA, which earned him the 1980 Nobel Prize in Chemistry, was emblematic of the department's innovative spirit . The collaborative, focused atmosphere was so effective that former members often recalled their Stanford days wistfully when they moved to other institutions 9 .
Arthur Kornberg's influence extends far beyond his own research discoveries. His "ten commandments" for enzymology and his conviction that biological processes could be understood through purified components inspired generations of biochemists 9 . The "Kornberg school" of biochemistry—his intellectual descendants through trainees and their trainees—spreads across the global scientific community 5 .
Even after shifting his research focus to inorganic polyphosphate in 1991, Kornberg remained actively involved in research at Stanford into his eighties 6 . When he died in 2007 at age 89, he left behind a transformed scientific landscape—both in our understanding of DNA replication and in how biochemical research is conducted 9 .
The department he built continues to honor his legacy through the Arthur Kornberg and Paul Berg Lifetime Achievement Award in Biomedical Sciences, recognizing Stanford alumni who have made significant contributions to the field . Current recipients like W. Kimryn Rathmell continue the tradition of excellence that Kornberg established .
Through his experimental brilliance and organizational genius, Arthur Kornberg proved that great science requires not just great discoveries, but also great environments where curiosity can flourish. His dual legacy—unraveling the chemical basis of genetic inheritance and creating a model for collaborative science—continues to shape biochemistry more than half a century after he first arrived at Stanford.
1918-2007
American biochemist who won the Nobel Prize in Physiology or Medicine in 1959 for discovering DNA polymerase.
Kornberg's 1956 discovery of DNA polymerase I was the first enzyme shown to synthesize DNA in a test tube, fundamentally changing our understanding of genetics.
Kornberg built Stanford's Biochemistry Department into one of the world's most influential centers for molecular biology research.
Kornberg's intellectual descendants through his trainees and their trainees form a vast network across the global scientific community.