Converted Expression Patterns for Cancer
The First Principle of Transcriptomics and the Bhopalator
Sungchul Ji, Ph.D.
Emeritus Professor of Theoretical Cell Biology
Rutgers University
September 15, 2025
1. From Normal Tissue to Cancer
Every healthy tissue—liver, lung, brain, skin—expresses a unique genetic program.
These tissue-specific expression patterns allow the heart to beat, the liver to detoxify, and neurons to fire. But when cells undergo malignant transformation, their finely tuned tissue-specific programs are converted into a generic, cancer-associated profile.
2. The Conserved Transcriptional Response to Cancer (CTRC)
Researchers have identified a Conserved Transcriptional Response to Cancer (CTRC) [1]: a shared set of gene expression changes observed across many cancers, regardless of their tissue of origin.
Features of CTRC:
- Downregulation: Genes tied to normal tissue identity and differentiation.
- Upregulation: Genes tied to cell proliferation, wound healing, inflammation, and immune suppression.
In effect, cancer cells shed their tissue “accent” and adopt a common molecular dialect—a strategy for unchecked growth and survival.
3. The First Principle of Transcriptomics (FPT)
This convergence exemplifies what I call the First Principle of Transcriptomics [2]:
Diverse biological perturbations—cancer, chronic stress, or therapeutic interventions—converge on conserved gene expression programs.
Just as the First Law of Thermodynamics states that energy is conserved across transformations, the FPT reveals that information is conserved in biology through shared expression programs.
4. Beyond Cancer: Stress and Drugs
Figure 1. The conserved Transcriptional Response of the human brain to environmental inputs. Adapted from [1].
The phenomenon of “conversion” is not unique to cancer.
- Psychosocial stress induces a Conserved Transcriptional Response to Adversity (CTRA).
- Pharmacological interventions often trigger conserved sets of transcriptional adjustments.
Together, CTRC, CTRA, and drug responses suggest the existence of a universal biological principle: different challenges funnel into a few deeply conserved expression patterns, like streams joining a river.
5. The Structural Basis: The Bhopalator Model [3]
Figure 2. The Bhopalator: A molecular model of the living cell.
The Bhopalator consists of a total of 20 major steps: 1 = DNA replication; 2 = transcription; 3 = translation; 4 = protein folding; 5 = substrate binding; 6 = activation of the enzyme-substrate complex; 7 = equilibration between the substrate and the product at the metastable transition state; 8 = product release contributing to the formation of the intracellular dissipative structure (IDS); 9 = recycling of the enzyme; 10 = IDS-induced changes in DNA structure; 11 through 18 = feedback interactions mediated by IDS; 19 = input of substrate into the cell; and 20 = the output of the cell effected by IDSs, which makes cell function and IDSs synonymous (see Section 10.1 for more details). Reproduced from [3].
Why should cancer, stress, and drug exposure trigger such conserved transcriptional responses?
The answer must lie not only in the genes themselves, but also in the architecture of the living cell.
In 1983, I proposed the Bhopalator model of the cell at the International Conference on Self-Organization in Bhopal, India (published in 1985).
The Bhopalator treats the cell as a self-organizing dynamical system sustained by chemical concentration gradients—conceptualized as standing waves of chemical activity.
Key implications of the Bhopalator:
- Wave-based organization: Cellular functions emerge from the interference and resonance of chemical concentration waves.
- Universality: Just as Fourier or Fibonacci series can generate diverse forms from simple rules, the Bhopalator explains why different perturbations converge on the same transcriptional basins.
- Resonant plasticity: Perturbations—whether mutations, stress hormones, or drugs—shift the Bhopalator into alternative attractor states, which appear to us as conserved transcriptional responses.
6. Linking Expression Patterns to Structure
The composite figure below integrates these ideas:
- Left panel: The Bhopalator model of the cell, providing the wave-structured, self-organizing framework.
- Right panel: How normal tissue programs are converted into conserved responses (CTRC/CTRA/drugs), which in turn settle into attractor states—stable basins of transcriptomics supported by the Bhopalator.
7. A Unified Theoretical Framework
The First Principle of Transcriptomics describes the law-like conservation of information across perturbations, while the Bhopalator provides the structural and dynamical framework that makes this law possible.
- Genes are not isolated determinants but operate within a larger wave-driven, self-organizing systome (system + environment).
- Conserved transcriptional programs are the natural attractor states of this dynamical system.
- This framework unifies molecular biology, mathematics (Fourier/Fibonacci), physics (wave mechanics), and philosophy (cosmese as universal language).
8. Closing Reflection
If the First Law of Thermodynamics [4] is the cornerstone of physics, the First Principle of Transcriptomics (FPT) may become a cornerstone of 21st-century biology.
And if the FPT expresses the “law,” then the Bhopalator supplies the geometry and dynamics that underlie it.
Together, they suggest that the living cell is not a bag of molecules, but a wave-structured, self-organizing system whose responses to stress, cancer, and drugs are constrained by deep universal principles.
References:
[1] Cole, S. W. (2012) Nervous system regulation of the cancer genome. Brain Behav Immun 30(Suppl): S10–S18.
[2] Ji, S. (2018). The Cell Language Theory: Connecting Mind and Matter. World Scientific Publishing, New Jersey. Pp. 330-332.
[3] Ji, S. (2012). Molecular Theory of the Living Cell: Concepts, Molecular Mechanisms, and Biomedical Applications. Springer, New York. Pp. 62-64.
[4] First law of thermodynamics. https://en.wikipedia.org/wiki/First_law_of_thermodynamics