The First Principle of Transcriptomics
An Analog of the First Law of Thermodynamics
Sungchul Ji, Ph.D. (with ChatGPT assistance)
Emeritus Professor of Theoretical Cell Biology
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ
1. Introduction: From Thermodynamics to Transcriptomics
In the 19th century, physicists discovered the First Law of Thermodynamics: energy can neither be created nor destroyed, only transformed from one form into another. This insight revolutionized our understanding of the physical world, uniting heat, work, and energy under a single principle of conservation.
In the 21st century, transcriptomics—the study of gene expression at a genome-wide scale—has reached a similar turning point. Increasingly, evidence shows that living systems respond to diverse stressors and interventions not with infinite variety, but with conserved patterns of gene expression. These patterns represent what I call the First Principle of Transcriptomics (FPT):
Across biological, social, and pharmacological domains, the human genome responds with conserved transcriptional programs, reflecting a principle of conservation of information.
2. The Building Blocks: CTRC, CTRA, and CTRI
Three well-established phenomena illustrate this principle:
Conserved Transcriptional Response to Cancer (CTRC)
Despite differences in tissue of origin and mutational profiles, many cancers exhibit a shared transcriptional signature: upregulation of stress and proliferation pathways, downregulation of metabolic and differentiation genes.Conserved Transcriptional Response to Adversity (CTRA)
Social genomics has shown that chronic stress, loneliness, and low socioeconomic status induce a predictable leukocyte transcriptional profile: increased pro-inflammatory gene expression, reduced antiviral responses, and altered antibody synthesis.Conserved Transcriptional Response to Intervention (CTRI)
Pharmacological agents, from beta-blockers to antidepressants, also trigger stereotyped shifts in gene expression, reflecting the cell’s finite repertoire of response pathways.
Together, CTRC, CTRA, and CTRI demonstrate that gene expression is constrained by conserved, system-level rules.
3. The First Principle of Transcriptomics (FPT)
Just as the First Law of Thermodynamics unifies physical transformations, the FPT unifies biological responses:
Inputs: Biological insults (cancer), social adversity, pharmacological interventions.
Process: A conserved transcriptional machinery (DNA → RNA → protein) operating under universal rules.
Outputs: Health, behavior, and systemic adaptation.
In short, the genome does not improvise infinitely—it plays variations on conserved themes.
And just as energy conservation provides a bedrock principle for physics, information conservation provides a bedrock principle for transcriptomics.
4. Energy, Information, and Gnergy
To fully capture the analogy, we must recognize that Energy and Information are complementary aspects of a deeper, third entity, which I have termed Gnergy.
Energy represents the capacity to do work.
Information represents the capacity to control work.
Gnergy unifies these dual aspects, much as wave and particle are complementary in quantum physics.
The First Principle of Transcriptomics thus reflects a gnergic conservation principle: conserved transcriptional responses are the biological manifestation of the conservation of information, just as energy transformations express the conservation of energy.
5. Visual Representation of the FPT
Figure: Cancer, adversity, and interventions all converge on a conserved transcriptional response, which in turn shapes health and behavior. This cycle parallels the conservation of energy across physical systems, but here highlights the conservation of information as a manifestation of Gnergy.
6. Why This Matters
Integrative Biology: The FPT links oncology, social genomics, and pharmacology into one framework.
Predictive Medicine: Understanding conserved transcriptional responses enables better biomarkers for disease risk, resilience, and treatment response.
Philosophical Implication: Just as thermodynamics reshaped physics, the FPT may reshape biology by providing a universal principle of transcriptomic conservation—rooted in Gnergy.
7. Conclusion: Toward a New Biology
"If the First Law of Thermodynamics is the cornerstone of physics, the First Principle of Transcriptomics may become a cornerstone of 21st-century biology. By recognizing that cancer, social adversity, and interventions converge on shared gene expression programs, we can begin to unify the molecular language of life under a principle of conservation of information."
In this light, gene expression is not chaos—it is choreography. The genome responds to the world not with randomness, but with conserved transcriptional dances, echoing the deeper unity of Energy and Information within Gnergy.
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