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Let's transport ourselves to the 1930s for a moment. The Wall Street Crash has just happened, the planet Pluto has recently been discovered, and Adolf Hitler has become chancellor of Germany. In biology, there is intense interest in the structure and function of cells, and bacteria have become the model organism of choice to perform these studies. The nature of hereditary cellular material was one of the most fascinating questions of the time. Can you imagine a time when people didn't know that DNA contained our hereditary information?
Around this same time, the |. He had two strains (types) of bacteria: a virulent strain, that would cause pneumonia and death in mice, and a non-virulent strain, which didn't make mice sick. Griffith discovered that when the non-virulent bacteria were mixed with parts of virulent bacteria, the non-virulent strain suddenly became virulent. This was incredible because it meant that the bacteria were now expressing characteristics that they didn't have before. This is analogous to you spending time with a friend and having your hair change color to match theirs!
How could this be possible? Griffith proposed that one bacteria was injecting a transforming principle, a fancy term for an unknown molecule or compound, into the other bacteria and thus changing their nature. This transforming principle might be the hereditary material that they had all been looking for! But what was the chemical nature of this transforming principle? Now, researchers had a good experimental model to look deeply into this question.
Oswald Avery was an American scientist who made several important contributions to the fields of bacteriology, immunology, and molecular biology. He was extremely productive and hard-working his whole life, and his most important scientific discovery didn't occur till he was more than sixty years old! In 1944, together with Colin MacLeod and Maclyn McCarty, Dr. Avery conducted a series of elegant experiments that showed that DNA (and not protein, the top candidate at the time) was the molecule responsible for bacterial transformation and thus the molecule of heredity.
So, how did these three great scientists prove that DNA was the transforming principle? Well, think about what they wanted to find out. They knew that something in the virulent bacteria could act on the non-virulent bacteria and make it virulent. But how could they identify exactly which component of the virulent bacteria was responsible for this? Bacteria contain lipids, proteins, sugars, nitrogenous bases, organelles… Which one of these is the transforming principle?
So this is how they went about it: Imagine that you have an allergy to a component in your favorite salad, but you don't know what it is. Then, you go ahead and make the salad without one component and see if it causes a reaction. If it does, then you know that the component you removed was not the one responsible for the allergy. If it doesn't, then you know that the component that you were allergic to is the one that you removed.
Avery, MacLeod, and McCarty used this exact same logic in their experiments. As we go through the process, we'll call the virulent bacteria the S strain, as these bacteria had smooth walls, and the non-virulent bacteria the R strain, as these had rough walls.
Step 1:
They took a mixture of the S-strain bacteria and broke the cells up and then separated the mixture into different tubes. (This is you making many salads that all have identical components).
Step 2:
They treated each tube with a specific enzyme that would degrade one single type of chemical compound. The enzymes included DNAses, RNAses, proteases, lipases, etc. (Akin to removing tomato from one of the salads, lettuce from another one, etc.)
Step 3:
They added R-strain bacteria to each of the tubes and then injected them to different mice. (This is you tasting the different salads. Or to be more precise, many copies of you eating a salad each, but you get the idea.)
Step 4:
They examined what happened to the mice. The mice that survived would be the ones that were injected with the R-strain bacteria treated with the mixture missing the transforming principle. (The one salad that didn't cause an allergic reaction is the one missing the allergenic component.)
Step 5:
When they analyzed their results they saw that the only group of mice that had survived was the one injected with the R-strain bacteria that had been exposed to the DNAse treated mixture. DNAse degrades DNA while leaving all other chemical components intact.
Conclusion:
DNA is the transforming principle!
Since 1928, scientists knew that there was a chemical compound in bacteria that could transform one kind of bacteria into another thanks to the Griffith experiments. This chemical compound was called the transforming principle, but its chemical nature was unknown. Through their experiments, Avery, MacLeod, and McCarty were able to identify that the transforming principle was DNA. This experiment set the stage for the subsequent experiments by DNA researchers.
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| Events & Discoveries |
|---|
| Frederick Griffith: English scientist of the 1930s makes incredible finding working with pneumonia-inducing bacteria |
| Transforming principle: an unknown bacteria molecule or compound being injected into another bacteria thus changing its nature |
| Oswald Avery: an American scientist who made several important contributions to the fields of bacteriology, immunology, and molecular biology |
| Avery: in 1944, together with Colin MacLeod and Maclyn McCarty conducted a series of experiments that showed that DNA was the molecule responsible for bacterial transformation |
| Virulent bacteria: S strain, shows smooth walls |
| Non-virulent bacteria: R strain, has rough walls |
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