History of molecular biology facts for kids

Kids Encyclopedia Facts

The history of molecular biology is about how we learned to understand life at its most basic level. It started in the 1930s when different science fields like biochemistry (the chemistry of living things), genetics (how traits are passed down), microbiology (the study of tiny living things), virology (the study of viruses), and physics (the study of matter and energy) all came together. Many physicists and chemists became interested in this new field, hoping to uncover life's deepest secrets.

Today, molecular biology tries to explain how living things work by looking at tiny building blocks called macromolecules. The two most important types of macromolecules for molecular biologists are:

Nucleic acids: The most famous one is deoxyribonucleic acid (or DNA), which makes up our genes.
Proteins: These are the active workers in living organisms, doing many jobs.

So, molecular biology mainly focuses on understanding what these two types of macromolecules look like, what they do, and how they work together. This helps us understand when the "molecular revolution" began and how it developed.

What is Molecular Biology?

The term "molecular biology" was first used by Warren Weaver in 1938. Back then, it was more of an idea about explaining life using physics and chemistry, rather than a clear science field. After we understood how genes are passed down (in the 1910s) and learned more about atomic theory and quantum mechanics (in the 1920s), it seemed possible to explain life at a tiny level.

Weaver and others encouraged and funded research that mixed biology, chemistry, and physics. Famous physicists like Niels Bohr and Erwin Schrödinger also started thinking about biology. In the 1930s and 1940s, scientists weren't sure which new areas of research would be most successful, but many fields like biophysics and crystallography looked promising.

Key Discoveries

In 1940, George Beadle and Edward Tatum showed that there's a clear link between genes and proteins. They used a fungus called Neurospora crassa for their experiments, which was a new and useful model organism (a simple organism used for research).
In 1944, Oswald Avery proved that genes are made of DNA. (You can read about this in the Avery–MacLeod–McCarty experiment).
In 1952, Alfred Hershey and Martha Chase confirmed that the genetic material of a bacteriophage (a virus that infects bacteria) is also DNA. (This was shown in the Hershey–Chase experiment).
In 1953, James Watson and Francis Crick discovered the amazing double helix shape of the DNA molecule. Their discovery was based on important work by Rosalind Franklin.
In 1961, François Jacob and Jacques Monod showed that some genes control the activity of other genes. They also suggested there was a go-between molecule, which they called messenger RNA (mRNA), that carries instructions from DNA to make proteins.
Between 1961 and 1965, scientists figured out the "genetic code." This code explains how the sequence of nucleotides (the building blocks of DNA) tells the cell which amino acids (the building blocks of proteins) to use.

In April 2023, new information showed that Rosalind Franklin was a very important and "equal player" in the discovery of DNA's structure.

Most of the big discoveries in molecular biology happened in just about 25 years. It took another 15 years for new, advanced tools, now called genetic engineering, to allow scientists to find and study specific genes, especially in complex organisms.

Exploring the Tiny World

Molecular biology is the result of a long journey that began with the first observations through a microscope. Early scientists wanted to understand how living things work by looking at their tiny parts. Later, in the 18th and 19th centuries, scientists started focusing on the chemical molecules that make up living beings. This led to the birth of physiological chemistry and then biochemistry.

There was a mysterious area between the molecules studied by chemists and the tiny structures seen under a microscope, like the cell nucleus or chromosomes. This was called "the world of the ignored dimensions." It was filled with substances like colloids, whose structure wasn't well understood.

Molecular biology succeeded by exploring this unknown world using new tools from chemists and physicists. These tools included X-ray diffraction (using X-rays to see atomic structures), electron microscopy (using electrons to see tiny details), ultracentrifugation (spinning samples at high speeds to separate molecules), and electrophoresis (using electricity to separate molecules). These studies helped reveal the structure and function of macromolecules.

A key moment was in 1949, when Linus Pauling showed for the first time that a specific gene change in patients with sickle cell disease led to a change in a single protein, hemoglobin, in their red blood cells.

Biochemistry Meets Genetics

Molecular biology also grew from the meeting of two fields that made big progress in the early 1900s: biochemistry and genetics.

Biochemistry

Biochemistry studies the structure and function of molecules in living things. Between 1900 and 1940, scientists described important processes like metabolism (how bodies use food for energy) and digestion. Every step in these processes is helped by a special protein called an enzyme. Enzymes are like tiny helpers that speed up chemical reactions. Proteins also include antibodies (which fight off sickness) and proteins that make muscles contract. So, studying proteins became a main goal for biochemists.

Genetics

Genetics started to take shape after the rediscovery of Mendel's laws of inheritance around 1900. In 1910, Thomas Hunt Morgan began using the fruit fly (Drosophila melanogaster) as a model organism for genetic studies. Morgan soon showed that genes are located on chromosomes. He and other groups continued to work with Drosophila and confirmed how important genes are for life and development. However, scientists still didn't know what genes were made of or exactly how they worked. Molecular biologists then focused on finding the structure of genes and how they relate to proteins.

The growth of molecular biology wasn't just a natural step; it was also shaped by historical events. The amazing progress in physics in the early 1900s made biology seem like the "new frontier" for discovery. Also, new ideas from information theory and cybernetics in the 1940s (developed partly for military needs) brought many useful ideas and ways of thinking to biology.

The Phage Group

Choosing bacteria and their viruses (bacteriophages) as models to study life's basic mechanisms was a smart move. They are the smallest known living organisms. This approach became very successful thanks to Max Delbrück, a German physicist. He created a strong research group in the United States called the phage group, which focused only on studying bacteriophages.

The phage group was a network of biologists who studied bacteriophage T4 and made many important discoveries in microbial genetics and the early days of molecular biology. In 1961, Sydney Brenner, a member of the phage group, worked with Francis Crick and others. They did experiments that showed the basic nature of the genetic code for proteins. They found that for a gene that makes a protein, three DNA bases in a row (called a codon) specify each amino acid in the protein. This means the genetic code is a "triplet code." They also learned that these codons don't overlap and are read from a fixed starting point.

Between 1962 and 1964, phage T4 researchers studied almost all the genes needed for the bacteriophage to grow in the lab. This was helped by finding two types of "conditional lethal mutants" (mutants that die only under certain conditions). Studying these mutants helped scientists understand many basic biological problems. They learned about how proteins work together in DNA replication (making copies of DNA), DNA repair, and genetic recombination (mixing DNA). They also learned how viruses are built from protein and nucleic acid parts. And they figured out the role of "stop codons," which tell the cell when to stop making a protein. One important study showed that the sequence of amino acids in a protein is directly determined by the sequence of nucleotides in its gene. This proved that the gene and its protein are "co-linear" (they line up).

The places where this new biology grew were influenced by earlier work. The US, where genetics developed quickly, and the UK, which had advanced genetics and biochemistry, were leaders. Germany, a leader in physics, should have played a big role, but the rise of the Nazis in 1933 caused many scientists to leave. Most of them went to the US or the UK, giving a boost to science in those countries. These movements made molecular biology a truly international science from the start.

The Story of DNA Biochemistry

Studying DNA is a core part of molecular biology.

Francis Crick, lecturing around 1979

First DNA Discovery

In the 1800s, biochemists first separated DNA and RNA (mixed together) from the center of cells. They quickly realized these "nucleic acids" were long chains, but only later discovered that nucleotides (their building blocks) came in two types: one with ribose sugar and one with deoxyribose sugar. This led to identifying DNA as separate from RNA.

Friedrich Miescher discovered a substance he called "nuclein" in 1869. Later, his student, Richard Altmann, named it "nucleic acid" in 1889. This substance was found only in chromosomes.

In 1919, Phoebus Levene identified the parts of DNA: the four bases, the sugar, and the phosphate chain. He showed that these parts were linked in the order phosphate-sugar-base. He called each unit a nucleotide and thought DNA was a chain of nucleotides linked by phosphate groups, forming the "backbone." However, Levene incorrectly thought the chain was short and repeated in a fixed order. Later, Torbjörn Caspersson and Einar Hammersten showed that DNA was a long polymer (a large molecule made of many repeating units).

Chromosomes and Inherited Traits

In 1927, Nikolai Koltsov suggested that inherited traits are passed down by a "giant hereditary molecule" made of "two mirror strands that would copy themselves using each strand as a template." In 1935, Max Delbrück and others published work suggesting that chromosomes are very large molecules whose structure can be changed by X-rays, and that these changes could alter inherited traits. In 1937, William Astbury produced the first X-ray diffraction images of DNA. He couldn't figure out the exact structure, but the images showed that DNA had a regular shape, meaning its structure could be discovered.

In 1943, Oswald Theodore Avery and his team discovered that traits from one type of bacteria could be transferred to another type just by adding killed bacteria of the first type. The living bacteria changed into a new type, and these new traits were passed down. Avery called the transfer agent the "transforming principle" and identified it as DNA, not protein, as was thought before. He basically redid Frederick Griffith's experiment. In 1953, Alfred Hershey and Martha Chase did an experiment (Hershey–Chase experiment) that showed DNA is the genetic material in a virus called T2 phage.

Finding DNA's Structure

In the 1950s, three groups aimed to find the structure of DNA.

One group at King's College London was led by Maurice Wilkins and later joined by Rosalind Franklin.
Another group at Cambridge included Francis Crick and James Watson.
A third group at Caltech was led by Linus Pauling.

Crick and Watson built physical models using metal rods and balls, including what was known about the chemical structure of nucleotides. At King's College, Maurice Wilkins and Rosalind Franklin used X-ray diffraction to study DNA fibers. Only the London group (Franklin and Wilkins) was able to get high-quality diffraction patterns, which provided important information about the structure.

Helix Shape

In 1948, Pauling discovered that many proteins have spiral (helical) shapes. He figured this out from X-ray patterns and by building models. Even in the first DNA diffraction data from Maurice Wilkins, it was clear that DNA had a helical structure. But this was just the beginning. Questions remained: How many strands were there? Did the bases point inward or outward? What were the exact angles and positions of all the atoms? These questions drove Watson and Crick's modeling efforts.

Complementary Bases

Watson and Crick made sure their models were chemically and biologically sensible. A big breakthrough happened in 1952 when Erwin Chargaff visited Cambridge. He told Crick about his experiments from 1947. Chargaff had noticed that while the amounts of the four nucleotides (adenine, thymine, guanine, and cytosine) varied between different DNA samples, the amount of adenine always equaled thymine, and the amount of guanine always equaled cytosine.

The Crick and Watson DNA model built in 1953. It was rebuilt in 1973 and given to the National Science Museum in London.

Using X-ray diffraction data, especially information from Rosalind Franklin that the bases were paired, James Watson and Francis Crick created the first accurate model of DNA's molecular structure in 1953. Rosalind Franklin herself accepted their model after seeing it. The discovery was announced on February 28, 1953. The first paper by Watson and Crick appeared in the journal Nature on April 25, 1953. In 1962, Watson, Crick, and Maurice Wilkins shared the Nobel Prize in Physiology or Medicine for figuring out the structure of DNA.

"Central Dogma"

Watson and Crick's model immediately sparked great interest. In 1957, Crick presented the "central dogma of molecular biology." This idea explained the flow of genetic information: DNA makes RNA, and RNA makes proteins. It also included the "sequence hypothesis," stating that the sequence of bases in DNA determines the sequence of amino acids in a protein. A key confirmation of how DNA copies itself (implied by the double helix) came in 1958 with the Meselson–Stahl experiment. Later work by Crick and others showed that the genetic code was based on non-overlapping groups of three bases, called codons. Har Gobind Khorana and others soon figured out the entire genetic code (by 1966). These discoveries mark the true beginning of molecular biology.

The Story of Protein Biochemistry

First Protein Discoveries

Proteins were first recognized as a special group of biological molecules in the 1700s. Scientists noticed that these substances (like egg whites or milk curd) would clump together when heated or treated with acid. The name albumen for egg-white protein came from the Latin for "egg white."

With advice from Jöns Jakob Berzelius, the chemist Gerhardus Johannes Mulder analyzed common animal and plant proteins. Surprisingly, all proteins had almost the same basic chemical formula. Mulder suggested there was one basic substance for proteins, made by plants and absorbed by animals. Berzelius supported this idea and suggested the name "protein" in 1838, from a Greek word meaning "primitive" or "principal substance," because it seemed to be the main part of animal nutrition.

Mulder also identified products from protein breakdown, like the amino acid leucine.

Cleaning and Measuring Proteins

The smallest weight Mulder's analyses suggested for proteins was about 9,000 times larger than other molecules being studied. So, understanding the chemical structure of proteins was a big research area until 1949, when Fred Sanger figured out the sequence of insulin (a protein). The correct idea that proteins are long chains of amino acids linked by peptide bonds was proposed in 1902 by Franz Hofmeister and Emil Fischer. However, some scientists doubted that such long molecules could be stable.

Proteins were finally shown to be large molecules with a clear makeup (not just random mixtures) by Theodor Svedberg using a tool called an analytical ultracentrifugation.

Most proteins are hard to get in large amounts, even with modern methods. So, early studies focused on proteins that could be easily purified, like those from blood, egg whites, or enzymes from slaughterhouses. Many ways to purify proteins were developed during World War II to purify blood proteins for soldiers. In the late 1950s, the Armour Hot Dog Co. purified a huge amount of a protein called ribonuclease A and made it available cheaply to scientists worldwide. This helped make RNase A the main protein for basic research for decades, leading to several Nobel Prizes.

Protein Folding and Models

The study of how proteins fold began in 1910. Scientists showed that when a protein clumps, it first goes through a process called denaturation, where it becomes less soluble and loses its activity. In the 1920s, scientists suggested that denaturation could be reversed, a correct idea that was joked about as "unboiling the egg."

In 1929, Hsien Wu suggested that denaturation was simply the protein unfolding, changing its shape and exposing parts of it to the water around it. This made the protein less soluble and changed its activity. This idea was plausible but not immediately accepted because so little was known about protein structure. In the early 1960s, Christian B. Anfinsen showed that a protein called ribonuclease A could fold back into its correct shape by itself, proving that the folded state is the most stable state for the protein.

Scientists then looked into what physical interactions help proteins fold correctly. The important role of hydrophobic interactions (where water-hating parts of the protein hide from water) was suggested. Linus Pauling believed that protein structure was mainly held together by hydrogen bonds. Amazingly, Pauling's ideas about hydrogen bonds led him to correctly propose the main shapes found in proteins: the alpha helix (a spiral) and the beta sheet (a folded sheet). The importance of hydrophobic interactions was confirmed later.

Early studies of protein structure used methods like ultracentrifugation and special light techniques. The first detailed, atomic-level structures of proteins were figured out using X-ray crystallography in the 1960s and by NMR in the 1980s. As of 2019, there are over 150,000 atomic-level protein structures available in a database. More recently, cryo-electron microscopy can also show atomic details of large protein groups, and computer programs are getting very good at predicting protein structures.

Images for kids

Francis Crick, lecturing around 1979
The Crick and Watson DNA model built in 1953. It was rebuilt in 1973 and given to the National Science Museum in London.