Hershey and Chase conclusively show DNA genetic material

In the last video, we began to see some pretty good evidence that DNA was the molecular basis for inheritance. We saw that from the work of Avery, McCarthy, and Mlead, where they tried to identify whether it was DNA or proteins that acted as a transformation principle in Griffith's experiments. I encourage you to watch that video if all of this sounds unfamiliar.

But even their work in 1944 was not viewed as conclusive evidence. It was viewed as strong evidence but not conclusive evidence because, remember how they did it? They took the heat-killed smooth strain. The smooth strain, you might remember from Griffith's experiment, was the virulent one. The heat killed it. When you heat-kill it and inject it into a mouse, it didn't do anything to the mouse. But if you took the heat-killed smooth strain and put it with the rough strain, it somehow transformed the rough strain into the smooth strain, into the virulent strain.

So they took the heat-killed smooth strain and they took out its different components. They eventually were able to isolate one that was able to transform the rough strain into the smooth strain by itself. Then they applied all sorts of chemical tests to it and said, "Hey, there's pretty good evidence that this is DNA." But it wasn't conclusive because, well, maybe they didn't purify it properly, or maybe there was still a little bit of protein. Maybe it was mostly DNA, but maybe it was a little bit of protein that was still left there that actually did the transformation.

The scientific community, they weren't just saying, "Hey, that looks pretty good, let's move on. Let's just assume." They wanted to continue to test it, especially test it in different ways. The conclusive evidence didn't come until a few years later, until 1952, when Alfred Hershey and Martha Chase decided to study T2 bacteriophage.

So let me write this down: T2 bacteriophage. This is a phage that infects bacteria, bacteriophage. When you hear the word "phage," we're referring to viruses. Now, they knew that T2 bacteriophage was composed of proteins and DNA. We now know that it's a protein shell and there's DNA inside, but from their point of view, they said, "Okay, it's made up. If we look at the stuff that this virus is made of, it's protein and DNA."

So protein plus DNA. They knew that this virus, when it infects bacteria, injects something into that bacteria. So it injects something, and that something is what hijacks that bacteria's genetic information to start producing more of the T2 bacteriophage. If they could identify the something that gets injected, if they could figure out if that something was either protein or DNA, then they would have conclusively proven that either the protein or the DNA forms the molecular basis.

They were actually quite skeptical of Avery, McCarthy, and Mlead's experiments. Hershey and Chase actually thought that they were going to show that it was the protein. Remember, this whole time, people said, "You know, protein—we know it's these complex molecules that have these different shapes and all these different amino acids. It seems like that's much more likely to encode the complexity of genetic information than DNA." They didn't have an appreciation for the structure of DNA at this time.

So they devised an experiment to figure out, "What is that something that the T2 bacteriophage is injecting? Is that something protein, or is it DNA?" So this is the question. What they do is they take two batches or they develop two batches of T2 bacteriophage. One batch of the T2 bacteriophage they do in the presence of radioactive phosphorus-32. In the other batch, they grow that T2 bacteriophage in the presence of another radioactive isotope, but this time it is sulfur-35.

So why are they doing that? Well, phosphorus is found in DNA, so in this first batch, the radioactive marker, you could say, is going to incorporate itself into the DNA. In the second batch, sulfur is found in the protein and not in the DNA. This would actually tag the protein parts. If you’re wondering, "Well, how do you develop these radioactive batches?" Well, you let the viruses hijack cells in a medium that has either the radioactive sulfur or the radioactive phosphorus.

As they reproduce, they are going to incorporate that radioactive material into either the protein or the DNA of the new viruses that get produced. So anyway, they were able to produce some of the T2 bacteriophage in the presence of the radioactive phosphorus. They knew that the DNA would get that radioactive material in it. Then with the radioactive sulfur, they said the protein would have that radioactive sulfur.

Then for each of those batches, they infected bacteria with them and said, "Okay, they're going to inject something into the bacteria, and to figure out what that something is that was injected into the bacteria phage," they took the products in either of the two scenarios. They first blended them up so that all the stuff that's left outside gets taken off of the surface of the bacterial cells. Then they stuck it into a centrifuge.

The centrifuge, you can imagine, is kind of just a big spinning machine. If you were to take a test tube and orient it sideways, put maybe a stopper in it so nothing leaks, and then you spin it around really fast, what you're going to find is that you can actually generate significant G-forces. The heavier stuff is going to gravitate to the bottom of the test tube, or to the right when it's on its side, and the lighter stuff is going to gravitate to the left.

It turns out that the bacterial cells are heavier, so the bacterial cells are going to go toward the bottom of the test tube and they're going to form a material that we call the pellet. Then all the other stuff, all of the fluid and the leftover phage parts, those are going to go up to the top of the test tube and we call that the supernatant. I always have trouble pronouncing that—supernatant.

So they said, "Look, if we look at the pellet, which they knew had the bacterial cells in there or you could even say the remnants of the bacterial cells, if we look at the pellet here, if the pellet contains phosphorus, that means that the DNA, our radioactive DNA or our tagged DNA, made it into the bacteria. But if it contains sulfur, that means that the protein made it into the bacteria."

What they found is they found that the radioactive phosphorus was in the pellet, which allowed them to conclude that, hey, it's the DNA from the virus that made it inside of the bacteria and not the protein. Then they said, "Well, it must be, wow, the, you know, Avery, McCarthy, and Mlead were correct. It's actually the DNA that is this transformation principle that can go in and hijack the genetic machinery of the bacteria to produce more of the actual virus."

So this is a really, really, really big deal. Once again, we started with Mendel saying, "Hey, we have these inheritable factors and they seem to segregate and assort in certain ways. They seem to be discrete." Boveri and Sutton said, "Hey, chromosomes seem to kind of—their behavior during meiosis when cells split seemed to kind of match up to that." Morgan starts to provide some evidence. We have Griffith's experiments with the mice and the bacteria saying, "Hey, look, there's some transformation principle."

Avery, McCarthy, and Mlead say, "Hey, it looks like when we try to really purify this transformation principle, it seems like DNA is what really matters." Then Hershey and Chase validate that even more conclusively.