The enzyme is the heart of biochemistry.
DNA Polymerase
Nobel Prize 1959
Stanford University
In 1959, just a year after one of the most transformative discoveries in modern science, Arthur Kornberg was awarded the Nobel Prize for his discovery of DNA polymerase, the enzyme that assembles the building blocks of life into DNA1 . This breakthrough did more than just solve a fundamental mystery of heredity; it placed the self-replication of genes on a solid biochemical footing, effectively putting an end to vitalism—the notion that life processes are driven by a force beyond physics and chemistry1 .
"If a cell can do it, then a biochemist can do it and I can do it"1
Kornberg's creed was simple yet powerful. This conviction not only led to his Nobel Prize but also guided him as he built one of the most productive and collaborative biochemistry departments in the world at Stanford University, forever changing the landscape of molecular biology.
Discovered in 1956, this enzyme faithfully copies DNA templates, enabling genetic replication.
Nobel Prize in Physiology or Medicine
Enzyme that assembles DNA
Life processes explained by biochemistry
Born in New York to a Jewish immigrant working-class family. His father, though without formal education, spoke at least six languages1 5 .
A precocious student, Kornberg graduated high school at 15 and City College of New York at 191 .
His entry into research was almost accidental; a paper he wrote as a medical student caught the attention of the Director of the National Institutes of Health (NIH), leading to his recall from sea duty to join the NIH1 5 .
Working with Severo Ochoa, Kornberg converted into a "passionate advocate of using enzymes to deconstruct how cells work"1 . His early work on the enzymatic synthesis of coenzymes and nucleotides laid the groundwork for his later discoveries.
The same year Watson and Crick unveiled the structure of DNA, Kornberg left the NIH to chair a new Department of Microbiology at Washington University in St. Louis1 .
In 1959, Kornberg faced a pivotal decision: an offer to chair the new Biochemistry Department at Stanford University's medical school, which was moving from San Francisco to the main campus near Palo Alto. Characteristically, he did not immediately say yes. Instead, he replied:
"I must return to St. Louis to consult my colleagues"1
His loyalty paid off; several of his key colleagues from St. Louis moved with him to Stanford, forming the core of a department that would stay together as a cohesive unit for forty years1 .
Students and postdoctoral fellows mixed together in common laboratories to foster collaboration.
Research grants were pooled with no strict accounting or financial deadlines.
Faculty meetings only for important decisions; issues decided by consensus.
Monthly gatherings at Kornberg's home and twice-a-year retreats at Asilomar.
By the 1970s, the basic mechanism of DNA synthesis was understood, but a major problem remained: how does the replication of an entire chromosome begin? Understanding the initiation of DNA replication was a "tall order" and a problem that had led to "10 man-years of utter frustration"2 . Kornberg and his team were determined to crack this code.
In a seminal 1981 paper, Roberta Fuller, Jon Kaguni, and Arthur Kornberg reported a breakthrough: a cell-free enzyme system that could replicate DNA in a manner dependent on the bacterial origin of replication, a specific DNA sequence known as oriC2 . The success of this experiment hinged on a series of meticulous biochemical steps.
| Reagent | Function |
|---|---|
| oriC-containing Plasmid | Specific DNA template containing the origin of replication2 |
| Fraction II | Concentrated protein extract containing replication machinery2 |
| Ammonium Sulfate | Salt used to precipitate active replication proteins2 |
| Polyethylene Glycol (PEG) | Molecular crowding agent mimicking cell interior2 |
| ATP-regenerating System | Provided continuous energy supply for replication2 |
The results were clear and compelling. The system was entirely dependent on the oriC sequence; other circular DNA molecules could not substitute2 . Furthermore, the reaction was sensitive to rifampicin, an antibiotic that inhibits RNA polymerase, providing the first biochemical clue that an RNA primer might be essential for initiating DNA synthesis2 .
This cell-free system opened the floodgates for discovery. It allowed scientists to biochemically dissect the intricate process of initiation, leading to the identification and characterization of the DnaA protein—the key initiator that binds oriC and unwinds the DNA to start the replication process2 . For Kornberg, this was the culmination of a long struggle, a triumph made possible by perseverance and brilliant biochemistry.
Arthur Kornberg's influence extended far beyond his own laboratory. The department he built at Stanford became a model for collaborative, innovative science. His trainees, his "intellectual children and grandchildren," spread his philosophy across the globe5 . Even after his death in 2007, his legacy continues1 .
The story of Arthur Kornberg and the Stanford Biochemistry Department is a testament to the power of a single-minded pursuit of knowledge, the importance of building a supportive community, and the profound impact that a deep love for enzymes can have on our understanding of life itself.
Kornberg's trainees became leaders in biochemistry worldwide, extending his influence for generations.
Fundamental mechanism of genetic inheritance
Using enzymes to deconstruct cellular processes
Model for productive, cooperative research departments