DNA: A Puzzle That Gave Us Deep Insights About Ourselves

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What color are your eyes? What color is your hair? How tall are you? Sure, the environment you're brought up in plays a big role, but your DNA is largely responsible for your identity along with all other life.

Today, we're going to learn about the story behind the discovery of DNA along with the story behind it.

Show Article/Notes Below


The Story and Science Behind DNA

What color is your hair? What color are your eyes? How tall are you? Maybe you wish that you were just a little bit taller, or shorter for that matter. Does your family have a history of health problems or is your future looking healthy? I hope it’s the latter.

There are so many aspects of our life and who we are that come from our DNA. Sure, our environments play a huge role, but underlying it all is the genetic code that makes us who we are. Behind it all is the winding chemical double helix structure that was only discovered relatively recently when you look at all of humanity’s history.

However, its discovery and all the science behind it allowed the field of genetics to push forward to what it is today. The discovery of the double helix was important because it allowed science to understand what was underlying genetics. It also helped turn biology and molecular biology into global industries.

Today, we’re going to learn the story of how many scientists came together to discover the DNA double helix along with how it works and why it’s so important.

DNA puzzle put together.jpg

Humans Figured Out How Traits Are Passed

Humans have known that traits get passed from parents to offspring for quite some time. I recently did a podcast on plant breeding and learned that as far back as 12,000 years ago, people were selecting plants that had the most desirable traits to keep making improvements generation after generation.

Sure, these people didn’t understand the genetics behind it, but they knew in some way that the plant they chose to sow would lead to offspring that looked more similar to the parent than other random plants.

Then, people started to cross breed plants of different species together and also within  the same species to make the observation that the offspring would be a blend of the parents. Ok, not a big deal by today’s standards but back then, this was a big step in the field of genetics.

Gregor Mendel And His Laws Of Heredity

A scientist and monk named Gregor Mendel came along and in 1866, changed everything. His breeding experiments with peas led to the Laws of Heredity, where he found patterns that could be seen of how traits get passed from parents to the offspring.

Interestingly, at the time of his discovery, he and his colleagues didn’t think much of the discovery and published it in a little known journal. Around 1900, other scientists found the work and realized its value.

From khanacademy.com

From khanacademy.com

This really helped bring about the Green Revolution where crop yields increased across the globe, but at the same time, started the field of genetics. Mendel described some traits being dominant and some being recessive, which is still a main theory today, but much more complex of course.

Anyways, if you want to learn more about that story, make sure to check out the episode I did on it.

The research on genetics went forward following what Mendel had found. Scientists found more complex systems of heredity and were able to track these systems from generation to generation, but there wasn’t a lot of reason behind it. They just knew it happened.

How The DNA Molecule Was Found

Around the same time that these experiments were going on determining how simple genes were passed, in 1869 a Swiss physiological chemist named Friedrich Miescher discovered the DNA molecule.

He requested to have puss-soaked bandages sent to him from a local hospital. I know it’s gross, but it’s all in the name of science. His goal was to extract white blood cells to analyze various proteins within them. However, he came across something that stumped him.

DNA Is a Molecule Unlike Any Other

Inside the nuclei of the cells, there was a molecule that had a much higher phosphorous content that also wouldn’t get broken apart like the rest of the proteins he found among other differences. It was at this point that he realized this was a completely new discovery.

Friedrich wrote, "It seems probable to me that a whole family of such slightly varying phosphorous-containing substances will appear, as a group of nucleins, equivalent to proteins.”

Even though this work was groundbreaking, like the experiments of Mendel, it went largely unnoticed. I guess there was no framework yet to put this discovery in. It was important, but people didn’t know why yet.

DNA Research Slowly Pushes Forward

Despite this, the study of DNA slowly continued as more scientists of the time started to take interest. More specifically, scientists started to study the chemical makeup of DNA. A Russian physician and chemist or biochemist as we would call it today named Phoebus Levene was the first to discover the three main components of DNA in 1919.

In other words, he discovered the chemical building blocks of DNA, mainly that nucleotides are made up of a sugar, a phosphate group, and a nitrogenous base. If that sounds like a different language to you, just hold on, we’ll talk about DNA and how it works soon. He did the same for RNA, the chemical message sent by DNA.

from Quora.com

from Quora.com

This was revolutionary because at this time, nobody knew what DNA was made of. They knew that it was a new molecule unlike any that had been found, but nothing about it. The DNA molecule was itself elusive because there are many different ways that it can bond with other molecules, making it hard to pinpoint exactly what is going on.

DNA Is Made Of A Chain Of Nucleotides

Levene was the first to propose a model that suggested DNA was made up of chains of nucleotides. His reason for stating this came from years of work breaking down nucleic acids from yeast. Nucleic acid is just a more general term for the class of molecule that DNA belongs to.

He found that different conditions would cause the nucleic acids to break down differently, more specifically that there were four different ways that the nucleic acids would break down. This led him to believe that there were four different nitrogenous bases we spoke about earlier, and in the end this was correct.

Levene’s statement goes “New facts and new evidence may cause its alteration, but there is no doubt as to the polynucleotide structure of the yeast nucleic acid.”

The Science Behind The Structure Of DNA

Since we’ve gone a ways without any explanation of the actual science going on, I feel like I owe you a bit of clarity. Let’s break it down piece by piece starting with the acronym ‘DNA’. DNA stands for ‘deoxyribonucleic acid’. The ‘deoxyribo’ part comes from the sugar backbone of DNA.

The Sugar Backbone

When we say sugar, it actually is somewhat similar in structure to what we usually think of when we say sugar like in sweets for example. Sugars are a large class of molecules. Glucose is a simple sugar that is in the sweets we eat, and deoxyribose is a sugar that forms the backbone of DNA.

Now, what do I mean by backbone? Remember how Friedrich Meischer found that phospherous component of DNA? Well, the Deoxyribose molecules are strung together with phosphate in between. So, it goes deoxyribose, then a phosphate, then deoxyribose, then a phosphate, and so on. Phosphate is just a molecule that has a phosphorous and four oxygens attached to it.

The Backbone Is Linked By Phosphate

Now, this is the backbone because the most important part of DNA, the nitrogenous bases, are attached to the deoxyribose part. So every deoxyribose has two phosphates attached to form the chain, and then a nitrogenous base.

From Chemguide.co.uk

From Chemguide.co.uk

Nitrogenous Bases Make The “Code”

These nitrogenous bases are the actual ‘code’ that we talk about that form genes. Instead of the ones and zeros that form code in a computer, there are four different nitrogenous bases that code for the traits that make us who we are.

Don’t worry, you don’t have to memorize this next part, or any of it for that matter, but the names of the bases are adenine, guanine, cytosine and thymine. They are commonly abbreviated with the first letter of their names, so A, T, G and C and are generally called nucleotides.

That should be enough explanation so for now, let’s get back to the story so we don’t get too far ahead of ourselves.

Even though Levene’s discovery was extremely important, he thought that the nucleotides were always in the same order along the chain to form a structure that was part of some other process. However, it turns out that this is way too simplistic. You can’t win them all, I guess.

Scientists Find Out What DNA Actually Does

By the 1930s, scientists knew that DNA was an important part of chromosomes, but not really what chromosomes do. In a nutshell, chromosomes are bigger structures made of coiled up DNA. You get one from your mother and one from your father.

I’m going to give you some insider information that wasn’t known at the time, but it’s important for us to know. Chromosomes hold genes and many times, different species will have a different number of chromosomes, but the same species will have the same number and arrangement.

Another thing, every chromosome holds many different genes that code for traits that make us who we are. At this point in the story, we will have to wait a little bit for scientists to figure this out.

I did a longer explanation of chromosomes in the plant breeding episode if you want to learn more.

Incorrect Theories About Genes

So, like I said, in the 1930’s, scientists knew about chromosomes and that they were made of DNA, but there wasn’t any evidence suggesting that genes and DNA were related. There were some theories at the time though.

One example was a crystallographer who thought that genes were made of proteins that were stuck into the structure of DNA. Another scientist mistakenly discovered that the active part of viruses was a protein, not DNA. This was wrong, but at the time it reinforced the thought that genes were made from proteins and he actually won a Nobel Prize.

It’s kind of funny. At the time, DNA was thought to be a boring thing to study because it was just the four nitrogenous bases and some sugars. Scientists thought that there was no way it could be responsible for the complexity of genes and traits with just the four bases. Proteins were much more complex and therefore can do a lot more right?

Well, it turns out that many mainstream scientists were very wrong. I think we can learn a lesson from this. Just because most scientists or people in general agree that something is true, doesn’t make it true especially when it comes to cutting edge science that is still being explored. Many of these scientists were closed-minded to new ideas and that just doesn’t work for a good scientist or anyone for that matter.

DNA Is Finally Linked To Genes

In comes Oswald Avery, a Rockefeller Institute microbiologist who in 1934 started studying a substance that seemed to transform certain types of bacteria from harmless organisms into virulent beasts. For example, a bacteria that causes pneumonia is harmless until a signal is sent causing it to morph and cause harm. He and his co-workers came out with a paper stating that this substance was actually DNA.

They published their paper in the Journal of Experimental Medicine in 1944 and suggested that it was a gene being activated. Along with this, they also said that it’s likely this was true for other organisms as well. Around this time, other scientists discovered similar findings when studying E. coli.

Here is a good video on the experiments done by Avery.

Interestingly, before Avery came out with his paper, he became extremely sick with a thyroid condition and the two others working in the field died in World War II. Science came close to a major setback if all three of these scientists, along with their research, were lost.

Luckily though, Avery survived and the idea that genes came from DNA started to be widely accepted despite skepticism from those closed-minded scientists. All the way up to the 1960s, some publications and scientists were suggesting genes might be made of proteins.

Pushing The Link Between DNA and Genes Across All Species

Then, in 1944 an Austrian biochemist named Erwin Chargaff read Avery’s paper on the link between DNA and genes and was inspired to launch an entire program around the chemistry of nucleic acids. I guess you never know the ripples your work or creations will have.

Someone might see something you did and use it for inspiration to do even more great things like Erwin and Avery. That’s really motivating to me and I hope it motivates you as well.

Different Species Have Different DNA

To start his work, Erwin wanted to see what differences there were in DNA across species. With the use of new analytical techniques, Chargaff had two main findings. The first was that the sequence of DNA was different across species.

This may seem obvious to us now, but at the time it was a revolutionary idea. Every species had different DNA. Now the question was why and what difference does it make? The second discovery was as important or more important than the first.

There Are Some Characteristics Of DNA That Are Shared Across Species

He found that even though the sequence of nitrogenous bases changes, there are many shared characteristics about DNA across species. The most important shared characteristic is that the amount of Adenine is almost always the same as Thymine and the amount of Guanine is almost always the same as Cytosine.

A nice visual explanation of Chargaff’s Rules

Now, Erwin Chargaff didn’t know why this was, but now it is called Chargaff’s rule. The amount of A is the same as T because they are chemically bound to each other. The same goes for G and C.

So, at this point in the story we know that DNA contains genes and that genes are responsible for the traits we see across species. We also know that that DNA is a chain of four different nitrogenous bases, abbreviated A,T,G and C. A and T are found in the same amounts as each other, which is the same as G and C.

However, the structure of DNA itself wasn’t yet known. This piece of information was really holding the study of genetics back because without the structure, you can’t really know much about how DNA works.

Finding The Structure Of DNA

This all changed in the early 1950’s with photo 51. Photo 51 was taken by Rosalind Franklin with help from Maurice Wilkins at King’s College in London and it was an x-ray diffraction photo of the crystal structure of DNA. In a nut shell, x-ray crystallography works by beaming an x-ray at a crystal sample.

The crystal will scatter the x-rays which are caught on a screen and depending on the pattern of diffraction, you can determine the shape of your molecule. I think that’s relatively close to what goes on, but if I got anything wrong, feel free to know. I feel like I should know more given that I took an entire class on it, but you know how it goes.

Photo 51 Shows a Double Helix Shape

In this case, the shape on the x-ray film was a cross which is typical for a molecule with a helix shape. Some spots on the film are darker and from this, you can determine where there are more dense molecules. This was cutting edge science for the time and this method is still used today even.

From gizmodo.com

From gizmodo.com

In addition to the diffraction pattern, Rosalind was responsible for creating a crystal that could be analyzed which was also a first. Her discovery was crucial to figuring out the structure of DNA, but unfortunately, she died an early death and is sort of lost to history.

James Watson and Francis Crick Find The Double Helix

While there were many scientists involved in the discovery of the structure of DNA up to this point, the two who get the most credit are James Watson and Francis Crick. In 1953, they came out with a one-page paper in the journal called Nature suggesting the 3-dimensional structure of the double helix that is still used today. In case you can’t visualize that, the double helix looks like a twisted ladder.

Their finding was heavily reliant on the x-ray crystallography work of Rosalind Franklin along with advancing chemical knowledge from an American biochemist named Linus Pauling. They actually rushed their paper because they thought Pauling was going to beat them to the discovery, but his 3D model ended up being incorrect.

Interestingly, Watson and Crick didn’t get it correct right off the bat either. They were too excited about their model and the added pressure from Pauling led them to act too quickly. They made some assumptions that proved not to be true and came out with the wrong shape. They were embarrassed by the mistake and their lab manager actually banned them from working on DNA.

Then, Rosalind kept supplying them with x-ray crystallography images that were more and more clear. After collaborating with a few other scientists, they settled on the correct model and Crick’s wife drew it.

Putting All The Data Together

Luckily, they didn’t stop despite the ban. Watson and Crick used cardboard cutouts of the different molecules in DNA and shifted them around until they found a structure that worked. It was sort of like putting together a puzzle, except there was no picture on the box to look at for reference.

So, here’s what they came up with. They decided that the structure was a double-stranded helix where two different strands were connected by hydrogen bonds. The A and T and then G and C nitrogenous bases would be bonded to each other so that it could follow Chargaff’s Rule while also complying with photo 51.

They also decided that the double helix had a right had twist. This means that if you were to hold your right hand out, with your thumb pointed up and your fingers curled, your thumb would represent the axis of the helix and your fingers would represent the curl of the sugar-phosphate backbone.

They also figured out that the structure was anti-parallel, meaning that the strands run the opposite direction of each other while still matching the nitrogenous bases to each other. There’s a lot of biochemistry going on in the background, but for our purposes we don’t really need to get into all that.

From hominins.wordpress.com

From hominins.wordpress.com

The Significance of The Double Helix

While scientists have slightly modified their model as time passed, it has largely stood the test of time. This was a huge milestone in biology and genetics that allowed both fields to push forward. With this knowledge, scientists could now figure out how DNA worked and what it did on a chemical level.

The double helix now symbolizes more than just the structure of a molecule, but rather the beginning of humanity’s understanding of what makes us who we are along with all other life. It’s a symbol of humanity’s scientific achievements and knowledge, but also a reminder of how far we still have to go to get a complete understanding of genetics and biology.

There Are Three Types Of DNA

One of the findings after this was that there are three different types of DNA, called A-DNA, B-DNA and Z-DNA. The main difference between them is that A-DNA is a bit wider and shorter than B-DNA, and Z-DNA twists the opposite way, so it is left-handed.

Crick, Watson, and Wilkins won a Nobel Prize in 1962 for their discovery. Since Rosalind passed away in 1958, she wasn’t eligible. Francis Crick at least acknowledged that Rosalind Franklin’s work was critical to the discovery. Watson, on the other hand, is actually known to have made more than a few racist and sexist remarks throughout his career.

In the end, Watson and Crick really just pieced together all of the data into a structure that agreed with everything we knew at the time. They didn’t do many of their own experiments. This isn’t meant to diminish their work, but we should acknowledge all of the scientists in the background who aren’t in the limelight.

DNA+GIF.jpg

 Deciphering The DNA Code

After finding the structure of DNA, Watson and a physicist named George Gamow founded a group with the goal of deciphering DNA. They wanted to know how you get from DNA to the proteins that make up our bodies and carry out all of the functions that keep us alive.

This was an exclusive group of scientists that was responsible for finding many of the sequences that code for the amino acids that make up proteins. They did this partially by discovering the structure of RNA.

Without getting too far into it, there are certain proteins that make chemical messages from DNA that gets shipped from the nucleus of the cell to protein factories that piece together proteins based off what the message tells them. We call that message RNA and it is sort of like a single stranded DNA molecule.

DNA to Protein.gif

 The Discovery Of DNA & The Double Helix Changed Science & The World Forever

In the 60-plus years after the discovery of the double-helix and the science that led up to it, science has uncovered an unimaginable amount of information surrounding DNA and how it affects our lives. As science pushes forward, the role of the study of genetics will increasingly become more and more important.

We now know all about how DNA gets replicated and expresses itself in our bodies. Molecular Biology, Genetics, Biochemistry and many other fields have become increasingly focused on the study of DNA as it’s importance and relevance becomes more and more clear.

While there has been many discoveries related to DNA and its role beyond what we’ve talked about here, I think we have a good foundation going forward. Maybe in future episodes I’ll talk about some more topics. Let me know if that would be interesting. In the meantime, go check out the episode on CRISPR and plant breeding for similar topics.  

From understanding our individual health risks to how we should eat and exercise to what our children will be like, this science has revolutionized humanity. Now that developments like CRISPR allow us to change our genetics and services like 23andMe give you the ability to look at your genetic code, it’s up to us to determine how we use all this new information.

In the meantime, we can just appreciate all of the hard work and dedication of these scientists who figured out what’s behind life through the discovery of DNA. It shows us how we evolved, how we are born, and how we live.

 

References

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001197

https://www.nature.com/scitable/definition/double-helix-277

https://www.dnalc.org/view/15280-After-the-discovery-of-the-double-helix-structure-Sydney-Brenner.html

https://www.nature.com/scitable/topicpage/discovery-of-dna-structure-and-function-watson-397

https://www.yourgenome.org/stories/unravelling-the-double-helix

https://io9.gizmodo.com/the-unsung-hero-who-discovered-the-double-helix-5761388

https://www.khanacademy.org/science/high-school-biology/hs-molecular-genetics/hs-discovery-and-structure-of-dna/a/discovery-of-the-structure-of-dna

https://www.sciencebuddies.org/blog/celebrating-dna-and-the-history-of-the-double-helix

https://profiles.nlm.nih.gov/SC/Views/Exhibit/narrative/doublehelix.html