Gene Splicing and the Molecular Biology Revolution - The Rediscovery of Mendel and the Concept of Mutation

Dr Zahra Mohebi-Pourkani, Countercurrents, November 23, 2025 :  The mid-twentieth century marked a transformative period in biology, spurred by advances in genetics and molecular biology. The aftermath of World War II and the atomic bombings of Hiroshima and Nagasaki had made scientists acutely aware of the dangers posed by radiation to the genetic pool of humans and other organisms. Amid this climate, genetic research accelerated, culminating in a detailed understanding of heredity at the molecular level. The foundation was laid by Gregor Mendel, whose classic experiments with pea plants established that inherited traits are controlled by discrete units called genes. Mendel’s experiments demonstrated that crossing tall and dwarf plants produced hybrid offspring, and that subsequent generations followed predictable patterns of dominant and recessive traits.

Mendel’s work, published in 1865, went largely unnoticed due to political upheavals in Austria and his responsibilities as Abbot of his monastery. It was not until 1900 that Hugo de Vries, along with Correns in Berlin and Tschermak in Vienna, independently rediscovered Mendel’s laws while studying other plant species. De Vries also identified genetic mutations, sudden heritable changes in form, some of which were passed to subsequent generations. Although mutations had been observed anecdotally, for example in livestock breeding, de Vries was the first to systematically study their significance, noting that most mutations are harmful, while rare beneficial mutations may endure and contribute to evolution.

Genes, Chromosomes, and the Physical Basis of Heredity

Following these rediscoveries, scientists began to suspect that chromosomes were the carriers of genetic information. Edouard van Beneden demonstrated that sperm and egg cells each receive half the standard set of chromosomes, which are restored to a complete set upon fertilisation. This mirrored Mendelian inheritance patterns and strongly suggested a direct link between genes and chromosomes. Thomas Hunt Morgan expanded this understanding through experiments with fruit flies, showing that genes on the same chromosome tend to be inherited together, while occasional crossovers create new gene combinations. Hermann J. Muller further revealed that radiation could induce mutations in fruit flies, providing the first experimental evidence that environmental factors could directly alter genetic material. These findings highlighted both the mechanics of heredity and the potential dangers of radiation exposure.

DNA as the Carrier of Genetic Information

Until 1944, most scientists believed that proteins carried genetic information. O.T. Avery and his colleagues at the Rockefeller Institute overturned this notion, demonstrating that DNA, rather than protein, encodes heredity. Using experiments with pneumococci bacteria, they showed that DNA extracted from one strain could permanently transform another strain. Subsequent research elucidated the chemical composition of DNA as a chain of nucleotides — adenine (A), thymine (T), guanine (G), and cytosine (C) — organised along a sugar-phosphate backbone. In 1953, Watson and Crick, building on X-ray diffraction data from Rosalind Franklin and Maurice Wilkins, proposed the double-helix model of DNA, revealing that complementary base pairing allows DNA to replicate itself and provides a precise mechanism for transmitting genetic information across generations.

Protein Structure and the One-Gene–One-Protein Hypothesis

Parallel to DNA research, scientists explored protein structure. Proteins, polymers of twenty amino acids, fold into three-dimensional shapes dictated by their amino acid sequences, which in turn determine their biological functions. Dorothy Crowfoot Hodgkin, Max Perutz, John Kendrew, and Frederick Sanger elucidated the structures of penicillin, vitamin B12, haemoglobin, myoglobin, and insulin. Their studies showed that hydrophilic amino acids are typically positioned on the protein surface, while hydrophobic residues reside inside. Archibald Garrod’s one-gene–one-protein hypothesis, later confirmed by George Beadle and Edward Tatum in mould experiments, linked genes directly to enzyme production. Linus Pauling extended this framework to human genetics, demonstrating that sickle-cell anaemia results from a defect in haemoglobin synthesis.

The Flow of Genetic Information: DNA to RNA to Protein

By the mid-1950s, the role of RNA in translating genetic information became evident. RNA, structurally similar to DNA but containing uracil (U) instead of thymine (T), is found in both the nucleus and the cytoplasm, where protein synthesis occurs. Francis Crick proposed that amino acids are first attached to adaptor molecules called tRNA, which then interact with mRNA to guide protein synthesis. George Palade confirmed that ribosomes are the sites where mRNA directs the sequential addition of amino acids to a growing protein chain. This hierarchy — DNA controlling RNA, RNA guiding protein synthesis, and proteins regulating cellular metabolism — established a conceptual framework for understanding life at the molecular level.

Deciphering the Genetic Code

The genetic code, the language in which DNA encodes amino acid sequences, was unravelled through a series of landmark experiments. Severo Ochoa and Arthur Kornberg developed enzymes capable of synthesising RNA and DNA chains. Marshall Nirenberg and Heinrich Matthaei demonstrated that poly-U RNA sequences code exclusively for the amino acid phenylalanine, while Sydney Brenner and Francis Crick’s bacteriophage experiments revealed that the code is read in three-letter words, or codons. H. Gobind Khorana completed the deciphering of the genetic code by identifying codons for all twenty amino acids. Remarkably, the code is universal across species, confirming Darwin’s insight that all life shares a common ancestry.

The Dawn of Genetic Engineering

The discoveries surrounding DNA and the genetic code laid the foundation for genetic engineering. In 1970, Hamilton Smith observed that bacteria could cut DNA from invading viruses, a phenomenon mediated by restriction enzymes. This insight led to the development of recombinant DNA technology by Paul Berg, Peter Lobban, Dale Kaiser, and David Jackson, who created the first recombinant DNA molecules by adding cohesive ends to DNA fragments. Eco RI, another restriction enzyme, produced sticky ends that could be rejoined by DNA ligase, enabling the combination of DNA fragments from different organisms. Concurrently, Joshua Lederberg’s work on plasmids and antibiotic-resistance genes (R-factors) revealed mobile genetic elements that could be manipulated to carry foreign DNA. Herbert Boyer, Stanley Cohen, and their colleagues used these tools to create gene-spliced bacteria, capable of producing novel proteins, and developed methods to select and clone these bacteria using antibiotic resistance markers.

Applications and Implications

The revolutionary implications of these techniques were immediate. Recombinant DNA technology enabled scientists to produce medically essential proteins, such as human insulin, interferon, clotting factors, and hormone proteins, on a large scale. Industrial and agricultural enzymes could also be manufactured, enabling the production of substrates and compounds previously inaccessible. By combining insights from DNA, RNA, and protein structure with gene-splicing techniques, scientists gained the ability to manipulate life at its most fundamental level, creating a new era of biotechnology. As microbiologist Richard Novick observed:

“Appreciation of the role of plasmids has produced a rather dramatic shift in biologists’ thinking about genetics. The traditional view was that the genetic makeup of a species was about the same from one cell to another, and was constant over long periods of time. Now a significant proportion of genetic traits are known to be variable, labile, and mobile — all because those traits are associated with plasmids or other atypical genetic systems.”

These advances not only transformed biology into a creative and applied discipline but also raised important ethical and safety considerations regarding the manipulation of genetic material. From understanding heredity to producing life-saving proteins, the discoveries of the 1950s through the 1970s laid the foundation for modern molecular biology and biotechnology, providing tools and insights that continue to shape science and medicine today.

Dr Zahra Mohebi-Pourkani is a distinguished General Practitioner and Family Physician with a distinguished career in medical service and public health leadership. Since 2008, she has accrued extensive clinical experience across diverse regions and currently serves as the Head of a government clinic in Kerman province, Iran. Beyond her clinical and administrative responsibilities, Dr Mohebi is deeply engaged in scholarly and humanitarian pursuits. She maintains a strong academic interest in amateur astronomy, development studies, and the dynamic relationship between science and society. This interest extends to her work as a contributor to reputable Iranian and international newspapers and magazines. Dr Mohebi is passionately committed to education and capacity building. She dedicates significant effort to pedagogical activities,