The Gene

1. The Gene: A Unit of Heredity Discovered and Defined.

Just as physics and chemistry go back to molecules and atoms, the biological sciences have to penetrate these units [genes] in order to explain . . . the phenomena of the living world.

Fundamental unit. The gene is the basic unit of heredity and biological information, analogous to the atom in matter or the byte in digital information. Understanding this irreducible unit is crucial to understanding the whole organism. Early thinkers like Pythagoras and Aristotle debated how traits were passed, proposing theories like male semen carrying all information or a mix of male "message" and female "material."

Mendel's discovery. Gregor Mendel, an Austrian monk and gardener, discovered the fundamental principles of heredity through meticulous experiments with pea plants in the 1850s and 60s. He showed that traits are determined by independent, indivisible particles (later called genes) that are inherited from parents, with some being dominant and others recessive. His work, published in 1866, was ignored for decades.

Rediscovery and definition. Mendel's work was independently rediscovered by three scientists in 1900. William Bateson championed Mendel's ideas and coined the term "genetics" in 1905. Wilhelm Johannsen coined the term "gene" in 1909, defining it as a functional unit of heredity, even though its physical nature was unknown. This marked the birth of modern genetics.

2. Early Misunderstandings Led to the Perversion of Genetics into Eugenics.

When power is discovered, man always turns to it.

Galton and eugenics. Francis Galton, Darwin's cousin, sought to apply principles of heredity to improve the human race, coining the term "eugenics" in 1883. He believed that desirable traits like intelligence were inherited and could be enhanced through selective breeding, advocating for "positive eugenics" (encouraging the fit to breed). His ideas were based on flawed statistical models of inheritance, not Mendelian genetics.

Descent into negative eugenics. Eugenics quickly shifted from encouraging the "fit" to breed to preventing the "unfit" from reproducing ("negative eugenics"). Fueled by anxieties about class, race, and immigration, particularly in the US and Europe, this led to state-sponsored programs.

• Forced sterilization laws were enacted in many US states, targeting individuals deemed "feebleminded," criminals, or mentally ill.
• The Buck v. Bell Supreme Court case in 1927 upheld forced sterilization, famously stating, "Three generations of imbeciles is enough."

Nazi racial hygiene. The most horrific manifestation of eugenics was the Nazi program of "racial hygiene." Based on distorted genetic theories, it led to the forced sterilization and mass murder of millions deemed genetically or racially "unfit," including Jews, Gypsies, and the disabled. This period permanently stained the reputation of eugenics.

3. DNA: The Chemical and Structural Basis of the Gene.

The most important biological objects had to come in pairs.

Searching for the molecule. For decades, the gene remained an abstract unit. Scientists knew genes were on chromosomes, but not what they were made of or how they worked. Proteins were initially favored as the carriers of genetic information due to their complexity. DNA was considered a "stupid molecule."

Avery's transforming principle. In 1944, Oswald Avery's experiment with bacteria showed that DNA, not protein, carried the "transforming principle" of heredity. Heat-killed virulent bacteria could transfer genetic information to harmless bacteria, making them virulent, and the active agent was DNA. This provided the first strong evidence that DNA was the gene molecule.

The double helix. In 1953, James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin solved the three-dimensional structure of DNA: a double helix. This structure, with its complementary base pairing (A with T, G with C), immediately suggested how genetic information could be stored and copied, revealing the physical basis of heredity.

4. How Genes Work: Regulation, Replication, and Development.

The genome contains not only a series of blue-prints [i.e., genes], but a co-ordinated program . . . and a means of controlling its execution.

Gene action. George Beadle and Edward Tatum showed that genes "act" by encoding proteins, specifically enzymes that control metabolic processes. This established the link between genetic information and biological function.

Regulation. Jacques Monod and François Jacob discovered that genes are not always active but can be turned "on" and "off" by regulatory proteins in response to environmental cues. This gene regulation explains how different cells in an organism, despite having the same genes, perform different functions.

Replication and development. The double helix structure suggested how DNA replicates, with each strand serving as a template. Arthur Kornberg isolated the enzyme (DNA polymerase) that copies DNA. Genes also orchestrate the complex process of embryonic development, acting in cascades and hierarchies to specify cell fates and build organisms, as shown by studies in flies and worms.

5. Reading and Writing Genes: The Revolution in Technology.

By learning to manipulate genes experimentally, you could learn to manipulate organisms experimentally.

Gene cloning. In the early 1970s, Paul Berg, Herbert Boyer, and Stanley Cohen developed techniques to cut and paste DNA fragments from different organisms, creating "recombinant DNA." They could insert foreign genes into bacterial plasmids and use bacteria as factories to make millions of copies of these genes ("gene cloning"). This allowed scientists to isolate and amplify specific genes.

Gene sequencing. Frederick Sanger developed methods to "read" the precise sequence of bases (A, C, T, G) in a DNA strand. His method, perfected in the late 1970s, made it possible to decipher the genetic code of any organism, starting with small viruses.

Transformative impact. These technologies revolutionized biology. Genes, once inaccessible, could now be read, written, and manipulated in test tubes and living cells. This enabled the study of gene function with unprecedented detail and led to the birth of the biotechnology industry, producing medicines like insulin from genetically engineered bacteria.

6. Human Genetics: Mapping Disease and Diversity.

The proper study of mankind is man.

Mapping human genes. The ability to read and write genes spurred the study of human genetics. Victor McKusick cataloged thousands of human diseases linked to genes. Techniques like linkage analysis and positional cloning, pioneered by scientists like David Botstein and Nancy Wexler, allowed researchers to map disease-causing genes to specific locations on human chromosomes, leading to the identification of genes for diseases like Huntington's and cystic fibrosis.

The Human Genome Project. The ultimate goal was to sequence the entire human genome. Launched in 1990, the Human Genome Project, led by James Watson and later Francis Collins, aimed to read all 3 billion base pairs. A parallel private effort led by Craig Venter used a faster "shotgun" sequencing method. The draft sequence was announced in 2000, providing a reference map of human genes.

Human origins and diversity. Genomic studies revealed that modern humans originated in Africa relatively recently (~200,000 years ago) and migrated globally. Genetic diversity is highest in Africa and decreases with distance from Africa. While we are genetically very similar as a species, most genetic variation exists within traditional racial groups, not between them, making race a poor predictor of individual genetic traits.

7. Genes, Identity, and the Complexity of Fate.

So, we’s the same. Just a different color.

Genes and identity. Beyond disease, genetics began to explore the influence of genes on identity, behavior, and temperament. Studies on twins reared apart showed striking similarities in personality, attitudes, and even specific behaviors, suggesting a strong genetic component independent of environment.

Sex and gender. Genes play a fundamental role in determining biological sex (XY vs. XX chromosomes, with the SRY gene on the Y chromosome being a master switch for maleness). While gender identity is complex, studies suggest genes are highly influential, challenging purely environmental explanations.

Temperament and behavior. Genes are linked to aspects of temperament like novelty seeking and impulsivity, often through variants in genes affecting brain signaling. However, these links are often probabilistic, influencing propensities rather than rigidly determining outcomes. The effect of genes on complex traits is often polygenic (involving multiple genes) and heavily influenced by environment and chance.

8. The Future of the Genome: Editing and Ethical Challenges.

Those who promise us paradise on earth never produced anything but a hell.

Gene therapy returns. After setbacks like Jesse Gelsinger's death, gene therapy has advanced with safer viral vectors and better targeting, showing success in treating diseases like hemophilia. This involves altering non-reproductive cells.

Epigenetics. Beyond the DNA sequence, chemical marks on DNA and associated proteins (epigenetics) can influence gene expression and be heritable, showing how environment can leave its mark on the genome and potentially across generations.

Genome editing. New technologies like CRISPR/Cas9 allow scientists to make precise, intentional changes to specific genes. This offers unprecedented power to correct mutations or introduce new genetic information.

Germ-line engineering. The ability to edit genes in human embryonic stem cells and potentially convert them into sperm and eggs raises the prospect of permanently altering the human genome for future generations. This technology, while still developing, is becoming feasible. It raises profound ethical questions about "enhancing" humans and who decides what constitutes an improvement, echoing the dark history of eugenics.

Last updated: May 3, 2025