Introduction
Most people know that DNA carries genetic information that codes for proteins influencing our traits. If you’ve taken a biology course, you perhaps know DNA is a double helix made of nucleic acids. In addition, you have likely learned that the molecule is found in the nucleus and is passed on from parents to offspring once it self-replicates. What isn’t taught extensively to students is the story behind DNA’s discovery to begin with. This story is a very recent one as well. Before the mid-20th century, most scientists believed that proteins were the cell’s genetic material due to their high complexity. It would take more than a dozen scientists’ efforts (many of whom are severely under-credited for their contributions) throughout a century to finally discover the role of DNA. This is the story I want to tell today, not what DNA is; for that purpose, your textbook is a much better resource, but instead, how we as a species came to learn about what makes us us.
History
Our story begins in 1844 with the birth of Friedrich Miescher in Basel, Switzerland. Miescher was born into a family of scientists and developed a keen liking for science very early in his life. He thus continued his education by studying medicine at Basel. Despite his medical education, Meischer had little interest in practicing medicine, and paired with his hearing handicap, which made interacting with patients difficult, he decided to pursue a research career instead, specifically in biochemistry.
After acquiring solid background knowledge, our hero joined Hoppe-Seyler’s laboratory in 1868, where he studied lymphoid (white blood) cell composition. Hoppe-Seyler’s lab was the first to focus on tissue chemistry, meaning they isolated the molecules that made up cells. Miescher’s job was to conduct tests on leucocytes from pus (which he found on used medical bandages) to study the various types of proteins considered “promising targets for understanding how cells function.” It is during these tests that Miescher noticed and obtained a crude deposit of DNA. In 1869, Miescher had just become the first person to isolate DNA from the cell nucleus, consequently labeling it as nuclein. With further experimentation, he concluded that this new material could not be a protein due to the large amount of phosphorous. In his words, “We are dealing with an entity Sui generis not comparable to any hitherto known group.”
He found that nuclein consisted of carbon, hydrogen, oxygen, nitrogen, and phosphorus, which we now know are the elements that make up nucleic acids. After finding nuclein in the cells of other tissues, he suspected that this family of phosphorous-containing substances would prove “tantamount in importance to proteins.” He could not have been more right. Despite all these exciting discoveries, the role of nucleic acids in the cells would take many decades to be recognized. Many scientists still believed proteins to be the genetic material, including Meischer himself. Nevertheless, Meischer’s work laid the groundwork for the work of many scientists who would precede him and discover the wonderful world of nucleic acids.
Next up in our journey through time is Phoebus Levene. When Levene is mentioned in the history of DNA, it’s often due to his incorrect tetranucleotide hypothesis of DNA. Despite being wrong about DNA’s structure, Levene accomplished much to help further the understanding of nucleic acids. Phoebus Levene was a Russian physician who resettled to the US with the rise of anti-semitism in Russia. He started practicing medicine in 1892 and, by 1905, was appointed to the Rockefeller Institute of Medical Research to lead the biochemical laboratory. After some experimentation, Levene and his student J.A. Mandel identified the nucleic acid base thymine and concluded that nucleotides consisted of a phosphoric acid, a sugar, and a base. He had also just become the first to isolate nucleotides.
Levene and his assistant Walter A. Jacobs also identified the sugar in yeast nucleic acid, or RNA, as d-ribose. This is when they made an error. The duo incorrectly asserted that DNA and RNA share the same sugar, d-ribose. Despite this error, Levene was able to redeem himself when he successfully identified the sugar from DNA to be a deoxy-pentose rather than the previously accepted hexose (6-carbon sugar). In the same experiment, where dogs were used to isolate nucleotide components, he identified the bases guanine and thymine. Levene furthermore announced the tetranucleotide hypothesis, which proposed that DNA comprised equal amounts of the four bases and was organized into repeating tetranucleotides that could not carry genetic information. In spite of his hypothesis being ultimately flawed, his work with DNA helped identify nucleotides and their components. It provided the necessary knowledge for future scientists not only to correct his work but also to experiment further to answer questions regarding DNA’s structure and function.
So far in our story, we’ve explored two scientists whose work helped reveal the structure of DNA, but not much has happened to reveal the function of DNA in organisms. Specifically, the property of DNA that allows it to be passed on between organisms and express traits not present before. The first scientist to discover the transformation properties of DNA was a microbiologist named Frederick Griffith.
Prior to Griffith’s experiments, the world had just experienced a worldwide epidemic: the 1918 Spanish Influenza. Consequently, many governments worldwide worked ceaselessly in hopes of finding vaccines for other diseases. Finding a vaccine just so happened to be our friend Frederick Griffith’s goal as well. Specifically, Griffith examined two strains of Streptococcus pneumoniae, the bacteria known for causing pneumonia. One of the strains, dubbed the S strain due to its smooth capsule, was capable of causing disease, while the other strain, dubbed the R strain due to its, you guessed it, rough appearance, was incapable of causing any harm. When Griffith injected the S strain into mice, they would perish within a few days; however, mice injected with the R Strain would not. Fueled by curiosity, Griffith discovered heat would destroy the S strain’s capsule, which previously stopped the mice’s immune system and, thus, the strand’s ability to harm mice. Things took a mindboggling turn when Griffith learned that mice would die when exposed to both R and heat-killed S strains. In addition, he noticed, upon taking blood samples from the miracle mice, living S-strain bacteria!
Our story begins in 1844 with the birth of Friedrich Miescher in Basel, Switzerland. Miescher was born into a family of scientists and developed a keen liking for science very early in his life
History of DNA
Conclusion
Once Griffith gave the scenario more thought, he concluded that the R Strain bacteria must have taken up some mystery material from the killed S strain, allowing them to “transform” into the latter strain. He was correct; however, he could never conclude what, as he called it, the “transforming principle” behind the change. With our knowledge today, we know that DNA is behind magician-like strains, as bacteria can take up DNA from the foreign environment through transformation. At the time, however, this wisdom was unknown, and it would take the efforts of many scientists to finally gain an accurate understanding of DNA’s qualities and function.
