The Discovery of DNA

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Podcast Transcript

One of the most important advancements in the 20th century was the identification of the structure of the DNA molecule.

However, that discovery didn’t appear out of nowhere. It was part of a century-long process that included many advancements in biology, chemistry, and physics. 

Solving the secret of the DNA molecule was a major accomplishment, but it wasn’t without controversy.

Learn more about the discovery of DNA and how its structure was solved on this episode of Everything Everywhere Daily.

It is hard to stress just how important DNA is. 

DNA stands for Deoxyribonucleic acid, and it is the foundation of all life as we know it. You have DNA, your pets have DNA, trees have DNA, amoebas have DNA, and so do viruses. 

DNA literally defines what life is on Earth. 

Analyzing DNA has been used to diagnose illnesses, solve crimes, and create new drugs. 

The discovery of DNA and how it functions is one of the most important scientific discoveries of all time. 

Yet, it wasn’t discovered in an ah-ha moment.  It was a process that spanned a century and, in some respects, is still going on today. 

Two discoveries made in the 19th century seemed to have nothing to do with each other at the time, but it later turned out they were intimately related. 

The first discovery is one you might have heard of. It was made by an Austrian monk named Gregor Mendel. He conducted experiments with pea plants at his abbey in Brno, in what is today the Czech Republic.  

For centuries, humans have known that certain physical traits can be passed from one generation to the next, whether it is in humans, animals, or crops.

Through the meticulous cross-breeding of 28,000 pea plants from 1856 to 1864, he observed how traits were passed down through generations, leading him to formulate the laws of inheritance, including the concepts of dominant and recessive traits and the segregation of pairs of traits.

Mendel’s work was largely ignored during his life but was rediscovered later when its importance was realized.

The second discovery was made by a Swiss biochemist named Friedrich Miescher. 

Meischer was investigating the nuclei of white blood cells when he isolated several chemical compounds found inside. The chemicals he isolated were rich in phosphates, and he dubbed them nucleic acids.

Meischer’s process for collecting the cells and isolating the nucleus was very innovative. It began with collecting pus from discarded surgical bandages.

Meischer had no idea what nucleic acids did, and Mendel had no idea of the molecular process by which the traits he discovered were transmitted. 

In 1902, a Danish biologist named Wilhelm Johannsen demonstrated that discrete units of heredity determine inheritance through experiments on pure lines of beans. He showed that while environmental factors can influence the phenotype (observable traits) of an organism, the genotype (the genetic makeup) remains unchanged and is responsible for hereditary transmission. 

Johannsen’s work helped to distinguish between the genetic constitution of an organism and the expression of those genes, emphasizing the role of genetics in determining hereditary traits and laying the groundwork for the field of genetics as a scientific discipline.

It was Johannsen who coined the terms gene, phenotype, and genotype.

In the 1910s and 1920s, Phoebus Levene, a researcher at the Rockefeller Institute in New York, identified the basic components of nucleic acids which he dubbed nucleotides, each oneconsisting of a sugar, a phosphate group, and a nitrogenous base.

In DNA, there were four known as adenine, guanine, cytosine, and thymine.

The next big advancement came in 1928. Frederick Griffith, a British bacteriologist, made a groundbreaking discovery in the field of genetics through his experiments on Streptococcus pneumoniae, the bacteria responsible for pneumonia. 

Griffith conducted what is now known as the Griffith Experiment, where he demonstrated the phenomenon of transformation. He found that a harmless strain of the bacteria could be transformed into a virulent one when mixed with heat-killed virulent bacteria. This transformation was due to the transfer of genetic material from the dead bacteria to the living ones, making them virulent. Griffith’s work provided the first evidence of horizontal gene transfer and suggested that some “transforming principle” was responsible for heredity. 

That transforming principle had to be a molecule.

In 1927, Russian biologist Nikolai Koltsov proposed that whatever transmitted heredity information had to be transmitted via a very large molecule using “two mirror strands that would replicate in a semi-conservative fashion using each strand as a template.”

So, at this point, there were researchers who had identified DNA and even figured out what it was composed of. Other researchers identified how heredity worked and how heredity had to be transmitted via a molecule. 

What was needed was someone to tie the two things together. 

That happened in 1944. A team of researchers who worked at the Rockafeller Institute, Oswald Avery, Colin MacLeod, and Maclyn McCarty, made the leap that put everything together. 

They set out to find the molecule that was responsible for encoding and passing heredity. They did something similar to Frederick Griffith’s experiments almost 20 years earlier. 

In their experiment, they extracted various biochemical components from the virulent strain of Streptococcus pneumoniae and treated non-virulent bacteria with these components. They discovered that only the purified DNA from the virulent bacteria could transform the non-virulent strain into a virulent form. This transformation demonstrated that DNA, and not protein or other molecules, was the substance carrying genetic information. 

Their work marked a pivotal moment in biology by providing the first clear evidence that DNA was the molecule of heredity, setting the stage for the future discovery of the structure of DNA and the development of molecular genetics.

In fact, many people believe that this discovery is one of the most important discoveries of the 20th century that never was awarded a Nobel Prize.

In 1952, Alfred Hershey and Martha Chase conducted a different experiment that confirmed the findings of Avery, MacLeod, and McCarty. DNA is the genetic molecule.

Also in the late 40s and early 50s, Erwin Chargaff, working at Columbia University, developed a series of rules for how the components of DNA fit together.

He found that in any given DNA molecule, the amount of adenine (A) always equals the amount of thymine (T), and the amount of guanine (G) always equals the amount of cytosine (C). This 1:1 ratio (A=T and G=C) held true across various species and became a crucial piece of evidence for the structure of DNA.

Chargaff’s rules suggested that A pairs with T and G pairs with C, which helped explain how genetic information is stored and replicated in living organisms, contributing significantly to the understanding of DNA’s role in heredity.

So, by the early 1950s, a big part of the mystery of heredity had been solved. Deoxyribonucleic acid had been identified as the molecule that transmitted genetic information. 

Many of the laws of heredity had been figured out, and even the chemical components of DNA were known. 

However, there was much they still didn’t understand. How exactly did DNA transmit genetic information? If it was indeed a large molecule that replicated itself using two identical strands, how did that work? 

To understand all of this, it was necessary to determine the shape and structure of the DNA molecule. 

One team that took this problem on was two researchers at Cambridge, Englishman Francis Crick and American James Watson.

They developed a model for the structure of DNA that involved a double-helix shape. They used the rules developed by Chargaff to build physical models of the molecule that would fit the known rules of how the molecule was built and worked. 

On February 28, 1953, Crick got up at a pub in Cambridge and announced to the patrons there that he and Watson had discovered the secret to life. 

On April 8, they made the first public presentation in Belgium at a conference, where they announced their findings. However, their discovery didn’t warrant a mention in the press. 

It wasn’t until an article was published in the journal Nature on April 25 that attention was given to their discovery. 

At the top of the show, I mentioned that the discovery of DNA had controversy, and it was in Watson and Crick’s announcement that the controversy set in. 

Perhaps the key piece of evidence used by Watson and Crick was a photograph taken by another Cambridge researcher, Rosalind Franklin, using X-ray spectrography. The historic photo became known as Photograph 51. 

The image was able to put Watson and Crick on the right path in creating a DNA model, and by their own later admission, it probably wouldn’t have been possible without it.

However, they didn’t get Franklin’s permission to use her research, nor did they even notify her that they had used it. The photograph was given to them by Maurice Wilkins, another researcher in the same lab who was doing X-ray spectrography on DNA. 

Rosalind Franklin died in 1958, and Watson, Crick, and Wilkins were awarded the Nobel Prize in physiology in 1962. The Nobel Prize committee doesn’t award prizes posthumously, so Franklin couldn’t have gotten the award, but her contributions to the discovery of the shape of the DNA molecule weren’t made public until well after her death. 

The discovery of the double helix wasn’t the end of DNA discoveries. In fact, it marked the beginning of an entirely new field of study.

In 1958, American molecular biologists Matthew Meselson and Franklin Stahl conducted an experiment that confirmed that DNA could replicate via a process known as semiconservative replication. 

They showed that each strand in a double helix of DNA could split and be paired with a new strand, thus replicating into two new DNA molecules. 

The first full DNA sequence was performed by the British biochemist Frederick Sanger in 1977. Sequencing is when the complete ordering of all of the A, T, C, and G nucleotides is recorded. Sanger did a DNA sequence for simple bacteria and was awarded his second Nobel Prize in 1980. His first Nobel Prize came in 1958 for determining the amino acid sequence of insulin.

It wasn’t until 2003 that the first human genome sequence was finally conducted. It took 13 years, from 1990 to 2003, to sequence the human genome, and it was one of the largest collaborative science projects in history. The very last gaps in the genome weren’t completed, however, until January 2022….32 years after the project started. 

In 2012, a technique was developed for editing and changing DNA molecules. Known as CRISPR, it was a technique taken from the immune system of bacteria. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. The name was created in 2001 to make it easier to understand. 

Jennifer Doudna of the United States and Emmanuelle Charpentier of France were awarded the 2020 Nobel Prize for their development of CRISPR technology. 

In many ways, DNA research and technology are just getting started. The techniques for manipulating and editing DNA are still recent developments, and there are plenty of discoveries and advances yet to be made. 

However, all of the modern uses of DNA stem from discoveries made in the 19th century by researchers who had no clue about the importance of what they had stumbled upon.