Video Transcript
In this video, we will learn about the different experiments performed by scientists in the 20th century to study the genetic material of living organisms. We will trace the timeline over which DNA was conclusively proven to be the genetic material.
Every living organism is made up of microscopic individual units called cells. Some organisms, like bacteria, only have one cell. Others, like human beings, have trillions of cells. Regardless of how many there are, every cell in an organism’s body performs a very specific function. You can think of the body kind of like a factory with the cells as employees. Every employee knows exactly what job to perform, and this is what keeps the factory running smoothly. So the question is “How do cells know exactly what their function is in the body?”
Today, of course, we know that the answer is DNA. DNA, or deoxyribonucleic acid, is the double-stranded molecule that carries the genetic information in the cells of all living organisms. The genetic information is what controls the function of every system in the body, from their appearance to the substances they produce to their location in the body. The most crucial function of DNA however is to pass on the information it carries. When an organism reproduces, the offspring cells need to have genetic information too so that their cells and systems can function smoothly. So aside from being able to store genetic information, DNA also transfers it from one generation to the next.
We mentioned earlier that today we know that DNA is the genetic material. But this wasn’t always an accepted fact. At the beginning of the 20th century, it was widely accepted that genetic information was passed on from parents to offspring. Scientists knew that this was how children shared characteristics with their parents and that this could perhaps be how certain genetic disorders were inherited. But the key fact was missing. Nobody knew exactly what molecule carried this genetic information. In this video, we’re going to trace the scientific discoveries and theories that led people to understand the fact that we know today that DNA is the genetic material.
Let’s go way back to 1869 when DNA was first discovered. In 1869, a scientist from Switzerland called Friedrich Miescher studied immune cells that he isolated from used bandages from a nearby hospital. He discovered a new molecule in the nuclei of these immune cells. He found that it was acidic and contained phosphorus. He named this molecule nuclein, but we now know that it was in fact DNA. At this point in time, Miescher didn’t know what the function of this molecule was. Let’s place Miescher’s discovery at the beginning of a timeline. We’ll come back to this timeline every so often so we can see how scientists pieced together their discoveries over time.
A few decades later, two scientist called Walter Sutton and Theodor Boveri contributed another important piece of the puzzle. In 1902, Walter Sutton studied inheritance in grasshoppers. And in 1903, Theodor Boveri conducted similar experiments in sea urchins. Although they didn’t work together, they both reached a similar conclusion, which is now called the chromosome theory of inheritance. They proposed that chromosomes were responsible for carrying genetic information from one generation to the next in all living organisms.
Let’s take a quick look at chromosomes and understand their function. As you can see in this diagram, chromosomes are linear structures, and they are found in the nucleus of cells. Sutton and Boveri both proposed that chromosomes carry genes and that they were copied and passed on when organisms reproduce. We now know that chromosomes are composed of DNA molecules packaged using proteins called histones. When the chromosome theory was put forth however, Sutton and Boveri didn’t know whether it was the protein or nucleic acid that actually carried the genes. Let’s mark this theory in our timeline as well. We can see that the pieces of the puzzle are slowly coming together.
In the early 1900s, several scientists believed strongly that proteins were responsible for carrying the genetic information rather than DNA. Over the next few decades, several crucial experiments were performed that helped scientists settle the debate. Let’s trace this journey beginning in 1928.
Frederick Griffith was an English scientist who conducted experiments on bacteria called Streptococcus pneumoniae. This is a type of bacteria that can cause pneumonia. There are several different types or strains of this bacterium. For his study, Griffith selected two contrasting strains. One was the smooth strain or the S strain. The bacteria belonging to the S strain have smooth surfaces because they synthesize a smooth polysaccharide coating over their outermost layer. The other strain was the rough strain or the R strain. As you may have guessed, these bacteria have no polysaccharide coating over their surfaces.
There is another important difference between the S strain and the R strain, which is what Griffith was particularly interested in. The S strain is the virulent strain of the bacteria, which means it is capable of causing a harmful infection in other organisms. The R strain on the other hand is the nonvirulent strain and does not cause a harmful infection.
Let’s see how Griffith applied this knowledge in his experiments. He began with two groups of mice. We’ll just use one mouse to represent each group. He injected the S strain of bacteria into the first group of mice and the R strain into the second group. He observed that the mice injected with the R strain remained healthy, but the mice that were given the S strain developed pneumonia and eventually died.
Next, Griffith separated a group of S strain bacteria and used heat to kill them or inactivate them. We’ll call these heat-killed S strain. When these bacteria were injected into mice, the mice remained healthy. This meant that once they had been heat killed, the S strain bacteria were no longer able to cause pneumonia in the mice.
Now, here’s the interesting part. Griffith made a mixture containing heat-killed S strain bacteria and live R strain bacteria. Remember, according to his previous experiments, neither of these should have had the ability to cause pneumonia. However, when he injected this mixture into mice, he found that they all developed pneumonia and died. What’s more, when he examined the blood of these dead mice, he found live S strain bacteria, which he had not injected. So how did this happen? Had the S strain bacteria somehow come alive and killed these mice?
This might sound a bit like a scary movie, but the explanation is actually quite simple. What had actually happened was that some mysterious substance from the heat-killed S strain bacteria had entered the R strain bacteria causing them to transform. This substance had given the living R bacteria the ability to synthesize a smooth protective layer and to cause pneumonia in mice. This phenomenon, called bacterial transformation, had never been recorded before. Griffith named this mysterious substance the transforming principle. Let’s quickly note down Griffith’s observations on our timeline.
Before we move on, let’s think back to that question that needed to be answered. Was it proteins or nucleic acids which carried the genetic information? While Griffith’s experiment showed some incredibly interesting results, he didn’t actually find an answer to settle this debate. In 1944, a group of three scientists Avery, MacLeod, and McCarty brought us a step closer to answering this question. They used Griffith’s results as a basis for their experiments.
Just like Griffith, they procured S strain and R strain Streptococcus pneumoniae and used heat to kill the S strain bacteria. Now remember, they were trying to determine whether the transforming principle was a protein or a nucleic acid. You might recall that there are in fact two types of nucleic acids: DNA and RNA. Avery and his group divided the heat-killed S strain bacteria into three groups. They added enzymes to each group: proteases to the first, RNase to the second, and DNase to the third. The names of these enzymes give us a clue about what they do. Proteases break down or digest proteins, RNase digests RNA, and DNase digests DNA. This would mean that the first group of S strain bacteria had no proteins, the second group had no RNA, and the third group had no DNA.
They then mixed each of these groups with live R strain bacteria, just as Griffith did. When they examined these mixtures, they spotted signs of bacterial transformation in the first and second groups. However, in the third group, which had no functioning S strain DNA, they saw no signs of transformation. This led them to conclude that Griffith’s transforming principle was actually DNA. The first two groups would have had intact DNA, enabling the bacteria to transform.
Let’s put this discovery down in our timeline as well. Avery, MacLeod, and McCarty had proven for the first time that DNA was the transforming principle, and it caused bacterial transformation. But several scientists weren’t convinced that DNA was actually the genetic material. In 1952, Alfred Hershey and Martha Chase finally provided solid evidence that this elusive molecule was indeed DNA. Let’s take a look at their experiments.
Hershey and Chase used a type of virus called a bacteriophage in their experiments. They’re named bacteriophages because they infect bacteria by injecting their genetic material into bacterial cells. Each bacteriophage has a shell called a capsid made of proteins. This capsid contains DNA. Remember what Friedrich Miescher discovered way back in 1869. He found that nuclein was a phosphorus-containing molecule. From this, Hershey and Chase knew that DNA contained phosphorus. Proteins do not contain phosphorus. But they often contain sulfur, which DNA does not have. They used this difference between proteins and DNA in their experiments.
Hershey and Chase produced two sets of bacteriophages in their laboratory. For the first set, they used a medium that contained radioactive sulfur. This would mean that the protein capsid in these bacteriophages would contain radioactive sulfur. Similarly, they used radioactive phosphorus in the second set so that any DNA in these bacteriophages would also contain radioactive phosphorus. They then allowed these bacteriophages to infect two separate sets of bacteria. Remember, they do this by injecting their genetic material into the bacterial cells.
Once they had been infected, they agitated each mixture in a blender. They then spun each mixture in a centrifuge. This separated the infected bacterial cell from the part of the bacteriophage that had been left outside. Once this had been done, they were left with two sets of infected bacterial cells. They then checked for radioactivity in these infected cells. They found that the bacteria that had been infected with viruses that contained radioactive proteins showed no radioactivity, while the ones that had been infected with viruses containing radioactive DNA did show radioactivity.
Let’s think about what this meant. The viruses had injected their genetic material into the bacteria, which would mean that the remaining portion of the virus would’ve been left outside the bacterial cells. In the first set of bacteriophages, the radioactivity was in their proteins, whereas in the second set the radioactivity was in their DNA. The fact that the second set of bacteria was the one showing radioactivity after infection was clear proof that DNA was the genetic material that had been injected into the bacteria.
Let’s add this final contribution to the timeline. We can now see how over the years several scientists worked together, each group contributing a new piece to the puzzle until a clear picture formed: DNA as the genetic material.
Let’s go over the key points that we have covered in this video. In 1869, Friedrich Miescher discovered an acidic, phosphorus-containing molecule in immune cells. He called this molecule nuclein. In 1902 and 1903, Sutton and Boveri proposed the chromosome theory of inheritance, which stated that genetic material was carried in linear structures called chromosomes. In 1928, Frederick Griffith demonstrated bacterial transformation for the first time and discovered a substance called the transforming principle. In 1944, Avery, MacLeod, and McCarty demonstrated that this transforming principle was in fact DNA. In 1952, Hershey and Chase used bacteriophages to provide conclusive evidence that DNA is the genetic material.
