The Secret of Life: How Proteins are Made

You’ve heard of proteins. With the exception of water and fat, over 80 percent of the human body is made up of proteins. Skin is made of proteins called collagen and elastin, fingernails consist of a protein called keratin, and your stomach has a digestive protein called pepsin.

Given the importance of proteins in allowing life to function, a fundamental question arises: Where do all these proteins come from? They certainly don’t come from the food we eat (after all, we aren’t eating hard-plasticlike foods to get keratin for our fingernails). And they don’t just appear from thin air, either.

In fact, it took scientists over 100 years to answer this question. From the time proteins were first discovered under the microscope in 1838, it wasn’t until 1958 when scientists had determined where proteins actually come from. And the funniest part is— the scientists who discovered the answer.. actually weren’t trying to research proteins at all.

Our story starts in 1847. Morse code had just been invented, Queen Victoria had just started her reign, and Lincoln wasn’t even president yet.

But in the small town of Göttingen, Germany scientists Matthias Jakob Schleiden, Rudolf Virchow, and Otto Bütschli made a discovery. Now, these three weren’t even interested in protein synthesis— in fact, Schleiden was a plant expert and Virchow was a physician.

But as scientists, these three looked at cells under microscopes a lot. And as they did this over the years, they all began to notice something strange. Because cells mostly consist of water and are therefore hard to see under the microscope, Schleiden, Virchow, and Bütschli often used dyes to stain the cells so that the colors appeared more distinct.

However, while most of the cell was colored rather lightly, the scientists realized that, in the nucleus, there were strange shapes that were stained very strongly, colored bodies that no other scientist had noticed before.

Schleiden, Virchow, and Bütschli were excited— they had discovered something new! So naturally, they decided to give these colored bodies a name. It turns out that, in Greek, the word “color” is chroma, and “body” is soma, so these colored bodies were (uncreatively) named chromosomes.

While Schleiden, Virchow, and Bütschli didn’t solve the question of how proteins are synthesized, their discovery turned out to provide crucial information for the scientists of the next generation.

In 1950, Austro-Hungarian-born American biochemist Erwin Chargaff was experimenting with chromosomes. Specifically, he wanted to figure out what chromosomes were made of chemically. So Chargaff literally grinded cells open, extracted the chromosomes, and dissolved the chromosomes into individual molecules.

But how did Chargaff figure out what these chemicals that make up chromosomes were? Well, Chargaff had a clever idea. He reasoned that some molecules dissolve in water better than others. For example, salt easily mixes with water, but oil does not. So using this simple logic, he put his chromosomal components into water and checked how well they dissolved! To be more accurate, he allowed the water to run up a piece of paper so that he could physically measure how well the compound mixed with water— that is, the better the compound dissolves, the higher up it will travel together with the water.

And when Chargaff did this experiment with the chromosomal components, he found that they ran up with the water in very specific amounts, amounts that were unique to four chemicals that had been discovered before. These chemicals were known as Adenosine (A), Thymidine (T), Cytidine (C), and Guanosine (G), and collectively, they were called nucleotides. Today, we say that these four nucleotides combine to form a molecule called DNA, which is a major constituent of chromosomes.

Specifically, Chargaff found that these four compounds were found in very specific ratios. For any given cell, the amount of Adenosine always equaled the amount of Thymidine, and the amount of Cytidine always equaled the amount of Guanosine. Though Chargaff was unable to explain what this data meant, it was discovered that chromosomes are simply made of four different types of chemicals.

(As an aside, the experiment that Chargaff performed with water is what scientists call paper chromatography, and it is still used in many scientific research laboratories to this day.)

Chargaff helped figure out that chromosomes and DNA consisted of Adenosine, Thymidine, Cytidine, and Guanosine, but scientists wanted to figure out the exact structure of chromosomes. That is, how did A, T, C, and G combine? What was the exact shape of DNA?

On May 6, 1952, 31-year-old scientist Rosalind Franklin was interested in answering this question. To do so, she had a fancy technology by her side: x-ray crystallography. Though it sounds complicated, the idea behind x-ray crystallography is simple. She used a machine to shoot x-rays at DNA. If you think of x-rays like lasers, you know that the x-rays will bounce off the DNA at very specific angles depending on the shape of the molecule. Thus, by measuring the angles at which the x-rays bounced, she could essentially go backwards and determine the shape of the DNA molecule.

So Franklin did crystallography on DNA, and she got this picture.

Franklin, a crystallography expert, immediately realized that this photo meant that DNA must be a double helix, as can be seen in the animation below.

However, as history puts it, Franklin was very cautious and didn’t like to prematurely come to conclusions, so she wanted more data to be sure. But while Franklin was collecting this extra data, scientists James Watson and Francis Crick managed to get hold of Franklin’s photo. The details are complicated— some say that Watson and Crick stole the photo, others say that they had fair access to it. But regardless, Watson and Crick had Franklin’s photo, and they, too, realized: DNA is double helix. So they published their paper entitled “A Structure for Deoxyribose Nucleic Acid,” which is now one of the most famous research papers to date.

It was none other than Francis Crick himself who put everything together. After he and Watson determined that DNA was a double helix, he noticed that if you look at the type of nucleotide that is on one strand of DNA, then the DNA can be read as a sort of code. For example, maybe ATG was an instruction for the cell to make one part of a protein, and maybe CAC meant to make a different part of a protein.

And this turned out to be true! DNA is simply a code— a recipe book, if you will— that the body uses to make proteins. For example, if you need to make collagen proteins for your skin, then your skin cells will refer to the section of DNA that contains instructions to make that protein, and it will synthesize the protein itself!

In 1958, just 5 years after proposing his double helix model, Francis Crick published his “Sequence Hypothesis” for Protein Synthesis, in which he stated in his own words, “the [DNA] sequence is a simple code for the... sequence of a particular protein.”

DNA contains the instructions to make proteins.

An individual recipe to make a single type of protein is called a gene.

The set of all genes contained in DNA is called the genome.

Cells can choose which genes to use at what times depending on which proteins they need, a process called gene regulation.

If a gene becomes damaged so that a protein cannot be correctly made, this is called a mutation.

When you are cooking, you might avoid taking the entire cookbook to the kitchen in order to prevent accidentally damaging the entire book. You might instead make a photocopy or transcript of the specific recipe that you need, and take that copy to the kitchen. Similarly, when cells use DNA to make proteins, they often don't directly use the DNA but instead first create an intermediate transcript. This transcript is similar to DNA but exactly identical; it is made of RNA.

The process of creating this transcript is called transcription, and the process of using the RNA to then actually create the protein is called translation.

While scientists were originally just trying to find proteins come from and how they are made, the journey to get there led to the discovery of an arguably even more important molecule: DNA. We have already established the importance and abundance of proteins in the human body and in life in general, and the fact that DNA contains the instructions to make proteins means that DNA is truly a vital component of human life. That is, small changes in our DNA lead to differences in our body. In fact, over 90% of human diseases are caused by damage to DNA, as this prevents essential proteins in our bodies from being formed. Even nowadays, many targeted therapies against cancer are drugs that work to activate or repress particular segments of DNA known to be affected in cancer patients.

This realization has led the field of biology to experience a revolution, one centered around the idea of editing our DNA. Theoretically, if we could edit our DNA, we would be able to change the protein composition of our body, allowing us to potentially cure many diseases and even make smaller cosmetic changes such as changing our eye color (since eye color is determined by proteins. In the past decade, many DNA editing technologies have arisen, including zinc finger nucleases, TALENs, and most famously, CRISPR-Cas9.

In the past, many biology classes focused on just plants and animals. However, the discovery that DNA and proteins underlie all of life has led biology to turn into a field that is centered more at the molecular and cellular level rather than the organismic level, and this has the potential to change the way humans live forever.

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