The Gene - Saying Simple to a Thing Makes It Really Simple?
The Secret in the Crowd
Valuable things are often simple, but they don't like to be seen easily. They prefer to stay silent, without being disturbed. They use "the crowd" as their cloak and their wisdom to enlighten others without spotlighting themselves.
The concept of inheritance is ancient, with ideas dating back to Pythagoras, but for centuries, the molecule that carried the blueprint of life remained a mystery. Even though DNA, RNA, and their building blocks (A, T, G, C, U) were discovered in the 19th century, DNA was largely overlooked. For a long time, it just sat there with its four humble elements: Adenine, Thymine, Guanine, and Cytosine. Using only these four "notes," it composed the wonderful and unique song for every living creature, but no one was listening. It was as if DNA was using its simplicity to hide in plain sight.
Some scientists were openly dismissive. One, Max Delbrück, famously called DNA a "pretty stupid molecule." Another complained it was too boring, just a repetitive sequence of A, G, T, A, G, T... Most scientists believed that proteins, with their complex structures, had to be the carriers of genetic information.
But it doesn't matter who says what or how many times they say it. The truth is always there, waiting to be discovered. And eventually, it is.
The Transformation
The path to the truth was illuminated by Frederick Griffith's "transformation" experiment. In his lab, Griffith worked with two strains of Streptococcus pneumoniae bacteria:
- R-strain: Has a Rough surface and is harmless.
- S-strain: Has a Smooth coat and is deadly.
Here’s a summary of his groundbreaking experiment:
- He injected a mouse with the harmless R-strain. The mouse lived.
- He injected another mouse with the deadly S-strain. The mouse died.
- He killed the S-strain bacteria with heat and injected them into a mouse. The mouse lived, because the bacteria were dead.
Now, here's where the magic begins. Griffith mixed the heat-killed S-strain (deadly but dead) with the live R-strain (harmless) and injected the mixture into a mouse. The mouse died.
How was this possible? Griffith theorized that some "transforming principle" was passed from the dead S-strain to the live R-strain, turning it into a killer. This phenomenon was like something out of a sci-fi show—think of the shapeshifters in Fringe.
The Hero Steps In
In 1933, a 55-year-old scientist named Oswald Avery read about Griffith's experiment and thought something was wrong. How could genetic information be transferred from a dead bacterium through a simple chemical reaction? He decided to repeat the experiment, hoping to prove Griffith wrong. Instead, he got the exact same results.
If this was reality, then there had to be an explanation. Avery asked the right question: how?
In 1940, after validating Griffith's results, Avery set out to identify the "transforming principle." He knew the main molecules in the cell were:
- Proteins
- Lipids (Fats)
- Carbohydrates (Sugar)
- RNA
- DNA
His strategy was simple: eliminate them one by one. He prepared a batch of the heat-killed S-strain and used enzymes to destroy just one type of molecule in each sample.
He started with the top candidate, proteins. He destroyed the proteins and mixed the remaining material with the live R-strain. The mouse died. Transformation still occurred.
He tried again, destroying the lipids and sugars. The mouse died. Then he destroyed the RNA. The mouse still died.
Hope was fading. The last, seemingly hopeless, molecule left was DNA. Avery isolated the material from the S-strain and destroyed only the DNA. He mixed what was left with the live R-strain and injected it into a mouse.
The mouse lived.
Without DNA, there was no transformation. The mystery was solved. After seeing the result, Avery may as well have said, "The stupid one wasn't DNA, but us."
The paper can be read from this link for those of you who want to deep dive into this big hole.
The Race for the Structure of DNA
Once DNA was crowned the carrier of genetic information, the race was on to discover its structure. Four names are central to this part of the story:
- Maurice Wilkins
- Rosalind Franklin
- James Watson
- Francis Crick
Wilkins pioneered using X-ray crystallography to take pictures of DNA, but his images were blurry. To get a better picture, his lab hired Rosalind Franklin, a brilliant but notoriously difficult colleague. Despite the friction between them, Franklin did her job perfectly, capturing a crystal-clear X-ray image of DNA, famously known as "Photo 51."
In contrary to Wilkins and Rosalind, Watson and Crick were perfect team. They failed many times while trying to build a physical model of DNA, but they never gave up. Eventually, they did it by a little "help" of Franklin's DNA picture as seen in Fig-2. In Fig-3 you see all those 3 important legends who had piece on the pie!
Crick was a brilliant theorist. He believed that the key was to figure out which molecules liked to pair together, rather than running thousands of lab tests. As he put it, trying to determine the structure of DNA from experiments alone was like "trying to create the structure of a piano from the sound it makes falling down the stairs."
The paper published by Watson and Crick can be found in nature journal.