Biochemistry and immunology have seen major paradigm shifts since 1945, with some fields and theories becoming obsolete due to new discoveries. Here are some notable examples:
1. One Gene–One Enzyme Hypothesis (1940s–1960s) → Replaced by Modern Gene Regulation Theory
- What it was: Originally proposed by Beadle and Tatum, this theory stated that each gene codes for a single enzyme.
- Why it collapsed: Further research showed that genes can code for multiple proteins through alternative splicing and post-translational modifications. Additionally, non-coding RNA (e.g., microRNAs) plays a crucial role in gene regulation.
2. Protein-Only Hypothesis of Enzymes (Pre-1980s) → Replaced by Ribozymes & RNA Catalysis
- What it was: It was believed that all biological catalysts were proteins (enzymes).
- Why it collapsed: The discovery of ribozymes (catalytic RNA molecules) in the 1980s by Sidney Altman and Thomas Cech showed that RNA itself could catalyze reactions, revolutionizing our understanding of molecular biology.
3. Central Dogma as a One-Way Flow of Genetic Information (1950s–1970s) → Revised with Reverse Transcription & Epigenetics
- What it was: Francis Crick’s “Central Dogma” suggested that genetic information flows from DNA → RNA → Protein, in a unidirectional manner.
- Why it collapsed: The discovery of reverse transcriptase (enzyme used by retroviruses like HIV) in the 1970s showed that RNA can convert back into DNA. Later, epigenetics revealed that external factors (like methylation) can regulate gene expression without changing DNA sequences.
4. Warburg Hypothesis of Cancer as a Metabolic Disease (1920s–1970s) → Shifted to Genetic Basis of Cancer
- What it was: Otto Warburg suggested that cancer was caused primarily by metabolic dysfunction (abnormal glucose metabolism).
- Why it collapsed: While metabolism plays a role, the discovery of oncogenes and tumor suppressor genes in the 1970s–1980s (e.g., p53, RAS mutations) showed that cancer is primarily a genetic disease, not just a metabolic disorder.
5. Lock-and-Key Model of Enzyme Function (Early 20th Century–1960s) → Replaced by Induced Fit Model
- What it was: The idea that enzymes and substrates fit together like a key in a lock, with a rigid structure.
- Why it collapsed: Daniel Koshland’s Induced Fit Model (1958) showed that enzymes are dynamic and change shape upon binding to substrates, improving catalytic efficiency.
6. “Junk DNA” Concept (1960s–1990s) → Replaced by Functional Non-Coding DNA
- What it was: Scientists once thought that large portions of the human genome (over 90%) were “junk” with no function.
- Why it collapsed: Research (especially from the ENCODE Project in the 2000s) found that much of this non-coding DNA has regulatory functions, including enhancers, promoters, and microRNAs.