The stories behind two groundbreaking books that reveal how science really happens.
We often imagine scientific breakthroughs as solitary "Eureka!" moments—a lone genius making a discovery that changes the world. The reality is far more complex and fascinating. Scientific innovation emerges from a rich ecosystem of social interactions, institutional pressures, technological capabilities, and even business considerations.
Two remarkable books—Paul Rabinow's Making PCR and Joan H. Fujimura's Crafting Science—pull back the curtain on this process, taking us inside the laboratories and minds of scientists to explore how revolutionary biological concepts and tools came into being.
Their work reveals that science is not just discovered, but painstakingly crafted through the collective efforts of diverse actors working within specific social and historical contexts.
Paul Rabinow's Making PCR: A Story of Biotechnology (1996) provides a fascinating ethnographic account of the invention of the polymerase chain reaction (PCR) at Cetus Corporation during the 1980s 4 6 .
PCR revolutionized molecular biology by allowing scientists to amplify specific DNA sequences millions of times in just hours, making abundant what was once scarce.
Rather than a straightforward narrative of discovery, Rabinow reveals PCR's development as a "contingently assembled practice" composed of distinctive subjects, their workplace, and the object they invented 4 .
Joan H. Fujimura's Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (1996) tells a different but equally compelling story—the rise of proto-oncogene research in the late 1970s and 1980s 3 .
During this period, cancer underwent a remarkable conceptual transformation from a set of heterogeneous diseases marked by uncontrolled cell growth to a disease of our genes 1 .
Fujimura demonstrates how this transformation was not inevitable but resulted from careful work by scientists to make proto-oncogene research a "doable problem" 3 .
Fujimura introduces the powerful concept of the "theory-methods package"—a combination of methods (like recombinant DNA technologies), instruments (such as nucleotide sequencers), materials (including molecular probes and engineered animals like the OncoMouse™), and conceptual tools (like "genes" and "cancer") that together enabled scientists to ask new questions about cancer at the molecular level 3 .
This standardized package allowed methods to travel between laboratories, facilitating connections between different institutions and disciplines and helping create a massive scientific "bandwagon" 3 .
Both stories highlight how technological advancements made new research possible. The table below details key components that formed the essential toolkit for molecular biology research during this period:
| Research Tool | Function | Significance in Research |
|---|---|---|
| Taq DNA Polymerase | Thermostable enzyme for DNA synthesis during PCR cycles 2 | Eliminated need to add fresh polymerase each cycle, making PCR automation possible 2 7 |
| Proto-oncogenes | Normal cellular genes that could mutate into cancer-causing oncogenes 3 | Provided a material entity—a specific DNA fragment—as the putative genetic cause of cancer 3 |
| Recombinant DNA Technologies | Methods for cutting and splicing DNA from different organisms 3 | Enabled cloning and sequencing of genes, fundamental to both PCR and cancer genetics 3 |
| OncoMouse™ | Transgenic mouse engineered to carry specific oncogenes 3 | Provided standardized animal model for studying cancer development in living organisms 3 |
| Hot-Start Techniques | Methods to inhibit DNA polymerase activity at room temperature 2 | Reduced nonspecific amplification in PCR, leading to cleaner results and higher yields 2 |
DNA strands separate at 94-98°C
Primers bind at 50-65°C
DNA synthesis at 72°C
Repeat 25-35 times
A central insight from both books is that scientific work requires making problems "doable." Fujimura particularly develops this concept, showing that scientists don't just solve problems—they first have to construct them as solvable within existing technical, social, and institutional constraints 3 .
Creating protocols that can travel between laboratories and produce comparable results
Developing terminology and frameworks that multiple research groups can utilize
Obtaining financial and institutional support for research programs
Establishing connections across disciplines, organizations, and institutions
Rabinow observed similar processes in the development of PCR, where the concept had to be transformed into an experimental system, which then became a technique, which in turn became new concepts—a fascinating process of "curious and wonderful reversals" 6 .
Fujimura's discussion of cancer genetics is grounded in foundational experiments that reshaped how we understand cancer development. One of the most elegant examples is Alfred Knudson's "two-hit hypothesis" for retinoblastoma, a rare childhood eye cancer 8 .
In 1971, Knudson performed a careful statistical analysis of data from retinoblastoma patients, examining family histories and the number of tumors present in each patient 8 .
He compared cases of:
His analysis revealed that bilateral cases followed a pattern of autosomal dominant inheritance, yet not everyone who inherited the predisposition developed tumors 8 .
Knudson proposed that two specific mutations ("hits") were required for retinoblastoma to develop in a single cell 8 .
The statistical distribution of tumors matched what would be expected if:
This hypothesis brilliantly explained why hereditary cases appeared earlier, were often multiple/bilateral, and followed familial patterns, while sporadic cases were typically single, unilateral, and occurred later 8 .
| Characteristic | Hereditary Retinoblastoma | Sporadic Retinoblastoma |
|---|---|---|
| Typical presentation | Bilateral, multiple tumors | Unilateral, single tumor |
| Age at diagnosis | Younger (average 15 months) | Older (average 27 months) |
| Family history | Often present (or de novo mutation) | Usually absent |
| Predisposition in offspring | 50% risk if parent affected | Minimal risk |
| Proposed genetic mechanism | One germline mutation + one somatic mutation | Two somatic mutations in same cell |
| Type of Evidence | Finding | Significance |
|---|---|---|
| Cytogenetic evidence | Constitutional deletions at 13q14 in bilateral retinoblastoma patients 8 | Mapped putative retinoblastoma gene to specific chromosomal region |
| Loss of heterozygosity | Tumor cells lost the wild-type RB1 allele 8 | Supported that both copies of the gene must be inactivated |
| Gene cloning | RB1 gene successfully cloned in 1987 | Confirmed Knudson's hypothesis at molecular level |
First Hit: Germline mutation inherited in all cells
Second Hit: Somatic mutation in retinal cell
Result: Tumor development (often multiple/bilateral)
First Hit: Somatic mutation in single retinal cell
Second Hit: Second somatic mutation in same cell
Result: Tumor development (usually single/unilateral)
The powerful lesson from both Making PCR and Crafting Science is that scientific knowledge is constructed through social processes. Rabinow shows us that PCR emerged not just from a brilliant idea but from the specific environment of Cetus Corporation, with its unique mix of personalities, management styles, and business pressures 4 6 . Fujimura reveals how cancer genetics became a massive research bandwagon through the careful packaging of theories and methods that made genetic approaches to cancer "doable" across multiple laboratories 3 .
These accounts remind us that science advances not through solitary genius but through collaborative effort, institutional support, technological innovation, and social negotiation.
The tools and concepts that become foundational in our understanding of biology—whether PCR or proto-oncogenes—carry with them the social histories of their creation. Understanding these histories gives us not only a richer appreciation of how scientific knowledge develops but also a more nuanced perspective on contemporary scientific debates, from gene editing to personalized cancer therapies. In the end, these stories reveal science as a profoundly human endeavor—less a sudden breakthrough than a carefully crafted achievement.