What is molecular biology? We need to ask this question right at the beginning. One obvious answer is that it's the study of biology at the molecular level. However, that's not specific enough for what we're going to do in this course. Here's a better definition:
Molecular biology is the study of gene structure and function at the molecular level
At the heart of this definition is the idea of the gene, a concept that dates back to the decade of the 1860's. It is the quest for understanding what a gene is that gave birth to the discipline of molecular biology.
The question was asked by three groups:
The chemists' question: of what (which cellular chemical) is the gene made?
The geneticists' question: what does the gene do?
The physicists' question: what are the thermodynamics of the gene?
Interestingly, this last question was posed by one of the giants of quantum mechanics, Erwin Schrödinger, in his 1945 book "What is Life". This book was of great influence to the young physicist Max Delbrück, the founder of the Phage Group and, in effect, molecular biology.
A brief retrospective by Gunther Stent, one of the founders of modern molecular biology, can be found here.
The decade of the 1860's was, in retrospect, truly remarkable. Here are the key events for our purposes:
|
Date |
Event |
| November, 1859 | Charles Darwin publishes "On the Origin of Species" |
| 1866-1868 | Fr. Gregor Mendel publishes "Experiments in Plant Hybridization" |
| 1869 | Friedrich Miescher discovers DNA ("nuclein") |
While it is clear that Mendel read and knew of Darwin's work, few, if any, biologists paid any attention to the notion of the "gene" until the beginning of the 20th century. And no one had any idea of the relationship of DNA to either genetics or evolution until the middle of the 20th century.
What happened to change this? The key development was the acceptance of DNA as the chemical nature of the gene. The first evidence was obtained in the 1940's by Oswald Avery and his colleagues at Rockefeller University, following on the experiments of Griffith two decades before demonstrating transformation (Fig. 2.2). The culminating demonstration occurred in the 1950's with the famous experiment of Alfred Hershey and Martha Chase, using bacteriophage T2 (Fig. 2.4). This experiment came at the same time as the report of the structure of DNA from the X-ray crystal diffraction patterns of Franklin and Wilkins and the modeling of Watson and Crick. This was the birth of modern molecular biology and what is called the neo-Darwinian synthesis (the gene and mutational variation as the target of natural selection).
Modern biology is the product of 19th century philosophical thought in science. At that time, physics, the most developed of the sciences, was reductionist and deterministic. Modern biology, with its roots in Mendel and Darwin, shares this philosophical outlook. By contrast, modern physics, through the revolution of quantum mechanics, has become holistic and probabilistic. Biology has not yet reacted to these fundamental changes in the perception of the natural world.
What leads to changes such as these? Thomas Kuhn, in his pivotal work "The Structure of Scientific Revolutions" introduced the concept of paradigm shifts.
A paradigm, according to Kuhn, is the set of assumptions that form the current working framework of a discipline. Before a revolution, all work within a discipline is basically in support of the existing paradigm. It is only when anomalies continue to arise that a revolution can occur, leading to a change or shift in the paradigm. A classic example is the Copernican revolution, changing from the Ptolomeic (geocentric) cosmology to the heliocentric picture.
We have had these shifts in biology. Mendelian genetics eventually ruled our "blending inheritance." DNA as the genetic material eliminated consideration of protein, the molecule of choice before Avery and Hershey-Chase. In this case, the anomaly was provided by Chargaff's discovery that DNA, unlike Levene's tetranucleotide hypothesis, was indeed very complex in structure:
| Organism | Percent Composition | |||
|---|---|---|---|---|
| A | T | G | C | |
| human | 30.9 | 29.4 | 19.9 | 19.8 |
| hen | 28.8 | 29.4 | 21.4 | 21.0 |
| turtle | 29.7 | 27.9 | 22.0 | 21.3 |
| sea urchin | 32.8 | 32.1 | 17.7 | 17.3 |
| yeast | 31.3 | 32.9 | 18.7 | 17.1 |
| E. coli | 24.7 | 23.6 | 26.0 | 25.7 |
| phage T7 | 26.0 | 26.0 | 24.0 | 24.0 |
Modern biology may be on the verge of another dramatic shift, this time in basic philosophy. The extreme reductionist view of the current paradigm is represented by workers such as Richard Dawkins. An opposing view is that of Steven Rose. If you're interested in what they have to say, here are two references:
"The Blind Watchmaker," Richard Dawkins, 1996, W. W. Norton & Co.
"Lifelines: Biology Beyond Determinism," Steven Rose, (1998), Oxford University Press
