How a Failed Experiment Revealed the Secret of Cell Division
Every day, your body performs approximately 330 billion cell divisions—that's about 3.8 million every second . This astonishing cellular choreography enables growth, healing, and maintenance of all living organisms. Yet, for much of scientific history, the mechanisms controlling this fundamental process remained shrouded in mystery.
Cell divisions occurring in the human body each day
The story of how we came to understand cell division is not one of straight-line progress but rather a twisting path filled with failed experiments, chance discoveries, and brilliant insights—most notably through the work of Nobel laureate Paul Nurse, whose career began with a spectacular laboratory failure that would ultimately lead to revolutionary discoveries about life itself.
Before delving into Nurse's story, it's essential to understand what scientists were trying to uncover. Cell division is part of the cell cycle, a repeating series of events that include growth, DNA synthesis, and division 1 .
The cell's "daily life" phase, where it grows and performs normal functions 9
What controls this precise sequence? The key regulators are cyclin-dependent kinases (CDKs), enzymes that activate or deactivate other proteins through phosphorylation, and cyclins, whose levels fluctuate throughout the cycle 4 . These molecules form the core engine of the cell cycle, ensuring that each phase proceeds in the correct order and that the cell only advances to the next stage when ready.
| Phase | Primary Function | Key Regulators |
|---|---|---|
| G1 | Cell growth and normal functions | CDKs, G1 cyclins |
| S | DNA replication | CDKs, S cyclins |
| G2 | Preparation for division | CDKs, G2 cyclins |
| M | Nuclear and cellular division | CDKs, mitotic cyclins |
Paul Nurse's path to scientific glory almost ended before it began. As a student in the 1960s, despite having excellent grades and university offers, he failed elementary French six times 8 . This language deficiency threatened to derail his academic career before it started.
"The University Senate insisted I study French in my first year!" Nurse recalls 8 .
Under the guidance of zoology lecturer Jack Cohen, Nurse undertook a project measuring the respiration rate of dividing fish eggs 8 . He was fascinated by cell division as the basis of all growth and development.
"I soon saw that the respiration rate oscillated every fifteen minutes or so, which is also roughly the time needed for the fish eggs to divide. Strangely this pattern persisted no matter what I did to the system—it seemed incredibly robust." 8
Just one week before he was due to present his findings, Nurse ran what he thought would be a routine control test—and the results left him stunned.
"I ran the experiment with no eggs in the chamber and I measured the same, perfect oscillation. Rather than measuring the respiration rate of the eggs, all the time I had been monitoring the effects of a thermostat in my apparatus. It was a complete failure from beginning to end." 8
This failure taught Nurse a crucial lesson that would guide his future research: "Do controls early on in your study, as soon as it becomes interesting!" 8
Despite this inauspicious start, Nurse remained captivated by the mystery of cell division. "The cell is the simplest thing that demonstrates life," he explains. "Key to understanding that is knowing how information is managed in the cell to generate order in space and time." 8
Inspired by earlier genetic studies on budding yeast, Nurse turned to a familiar subject from his Guinness laboratory days: brewer's yeast (Saccharomyces cerevisiae). This simple organism would become his key to unlocking one of biology's fundamental secrets.
Simple eukaryotic cells that revolutionized our understanding of cell division
By studying mutant strains, Nurse identified a gene called cdc2 that appeared to play a crucial role in initiating key stages of the cell division cycle 8 . This gene encoded a protein kinase—an enzyme that adds phosphate groups to other proteins to modify their activity.
Nurse and colleagues used classical genetics approach, treating yeast to induce random mutations 8
They looked for cells that divided abnormally—either unusually slowly or quickly 8
Identification of cdc2 gene as crucial regulator of cell division cycle 8
Nurse's team took an audacious approach: they took a human gene library and added it to yeast that lacked the functional cdc2 gene. Astoundingly, after one of the human genes was added to the yeast, the cells began dividing normally again 8 .
This simple yet elegant experiment demonstrated that a fundamental engine driving the cell cycle was the same in all species, a mechanism that had traversed 1 to 1.5 billion years of evolution.
| Researcher | Experiment | Key Finding |
|---|---|---|
| Paul Nurse | Genetic screening of yeast mutants | Identification of cdc2 gene as cell cycle regulator |
| Paul Nurse | Human gene complementation in yeast | Conservation of cell cycle mechanism across evolution |
| Tim Hunt | Protein analysis in sea urchin eggs | Discovery of cyclins and their cyclical nature |
| Hartwell et al. | Genetic studies of cell division cycle | Identification of multiple cdc genes |
The work of Nurse and his colleague Tim Hunt (who discovered cyclins in sea urchin eggs) revealed the exquisite regulatory system that controls cell division 4 . Their discoveries earned them the Nobel Prize in Physiology or Medicine in 2001.
Enzymes that activate or deactivate other proteins through phosphorylation, working in concert with cyclins to regulate the cell cycle 4
Proteins whose levels fluctuate throughout the cell cycle, binding to and activating CDKs 4
This system includes crucial checkpoints that ensure the cell doesn't advance to the next phase until the previous one is properly completed 3 . For example, the G1-S checkpoint checks for appropriate cell size and undamaged DNA, while the G2-M checkpoint verifies that DNA replication is complete 3 .
| Reagent/Technique | Function | Application Example |
|---|---|---|
| Colchicine | Inhibits spindle formation | Arresting cells in metaphase for chromosome analysis 5 |
| Acetocarmine stain | Stains chromosomal material | Visualizing chromosomes in squashes 5 |
| siRNA/CRISPR-Cas9 | Gene knockdown/knockout | Studying function of specific cell division genes 4 |
| FUCCI system | Fluorescent cell cycle indicator | Real-time monitoring of cell cycle phase 4 |
| Cyclin-specific antibodies | Detect specific cyclin proteins | Monitoring cyclin expression throughout cell cycle |
While Nurse's work revealed the core engine of the cell cycle, recent research shows that evolution has continued to add new regulatory layers. A 2025 study published in Cell Genomics found that recently evolved genes—some unique to primates—play crucial roles in human cell division .
When disabled, cells struggled to copy their DNA correctly, and growth slowed
Helps regulate when specific parts of the genome are duplicated before mitosis
This discovery shows that even processes as ancient as cell division continue to integrate new genetic players, which may help explain why certain cancers or developmental disorders behave differently in humans than in other mammals.
Paul Nurse's journey from French failure to Nobel Prize illustrates the often-tortuous path of scientific discovery. His story reminds us that setbacks and accidental findings often pave the way for breakthroughs.
"It is important to know the real stories behind science and the failures and successes that are part and parcel of our work to inspire the next generation of scientists." 8
The understanding of cell division has profound implications for human health, particularly in cancer research, where uncontrolled cell division is a hallmark of the disease. Many cancer therapies specifically target rapidly dividing cells, and understanding the regulatory mechanisms of the cell cycle has been crucial for developing these treatments.
From a faulty thermostat in a fish egg experiment to the universal mechanisms governing life itself, the story of cell division discovery exemplifies how science often advances through persistence, curiosity, and the willingness to learn from failure.
The cell cycle continues to fascinate researchers, with ongoing studies investigating how recently evolved genes fine-tune this ancient process and how disruptions can lead to disease.