A History Of DNA, Part III: The Code is in DNA

In my last post we saw how Avery and his colleagues demonstrated (but not conclusively to the scientific community) that the molecule which holds the genetic material in living things is DNA. Now I want to look at a very interesting experiment that really changed the minds of biologist in the matter. In the early 1950’s, Hershey and Chase took a novel approach in trying to found out what the genetic material might be made of, by looking at how a particular kind of virus worked.

Let me give you some background. Viruses are not true cells. They are made of an outer coat of protein with an inner core of nucleic acid. Viruses are made of just two things. The way a virus makes its living is by attaching to a cell, say a bacteria cell, injecting something into that cell and taking over the machinery of the cell. Here is a great introduction to viruses by Salman Khan(Sal), I really recomend you to watch it to understand viruses better.

Hershey and Chase were working with a particular kind of virus, called the T2 phage. This is a bacteria-eating virus, which makes its living by taking over a bacteria and using the protein-synthesizing machinery of the bacteria to make more viruses. Viruses can’t replicate themselves, they have to take over another cell. Clearly, then, what a virus must be doing, is injecting some information. It’s the information that would cause the cell to be taken over. What Hershey and Chase set out to do was to ask, what is it that these T2 viruses are actually putting inside the bacteria? There were only two candidates, proteins and nucleic acids.

The trick was to figure out how to determine which part was being injected. It is a very simple experiment to propose conceptually, but like many experiments in science, the devil is in the details. Hershey and Chase developed a very clever way to figure that out. They did this by radioactively labeling the proteins and the DNA that the virus was made of. In proteins, sulfur is a fairly common element. There is a radioactive form of sulfur (S-35). So, they could grow some T2 viruses in a medium that had a lot of this radioactive sulfur in it. What would happen is that as the viruses reproduce, they would incorporate sulfur into their protein codes. That meant that you could ask not where did the protein go, but where did the radioactivity go.

Alternatively, they could label the DNA. They could grow the same kind of virus in a medium that had radioactive phosphorus (P-32). Phosphorus is not found in proteins, but it is a major chemical constituent of DNA.

So, they grew viruses in a medium that either had radioactive sulfur or radioactive phosphorus. This resulted in some viruses having their proteins radioactively labeled, and others their DNA radioactively labeled.

In separate experiments, they added either the radioactively labeled sulfur viruses (with the radioactive protein), or the radioactively labeled phosphorus viruses (with the radioactively labeled DNA). In both cases they would give these viruses just a couple of minutes. Enough time for them to attach to bacteria and inject whatever they are injecting. Then they would stop the whole process. They were given enough time to inject but not enough time to take over the cell and cause it to build more viruses.

They gave the viruses just 20 minutes, and then they would put the solution in a blender. Then they put this solution in a centrifuge, which spins it around. Because of the action of the centrifuge, the heavier stuff would go down to the bottom of the tube. This would be the relatively large bacterial cell bodies. The lighter stuff, which would be the outer coats of the tiny viruses, would remain up in the solution. If you centrifuge them just right, you’ll get a little lump of stuff at the bottom of the tube, that’s going to be all the bacteria. Then you’ll have the rest of the fluid in the tube, which would include the viral coats.

They then would ask, where is the radioactivity? Is the radioactivity at the bottom, or at the rest of the fluid? What they found was that if they radioactively labeled the sulfur, marking the proteins, the radioactivity was found in the fluid, where the viral coats were. If you radioactively labeled the DNA with phosphorus, the radioactivity was found at the bottom, where the bacteria were. This was a very simple result but took the world by storm, because it showed incontrovertibly that what these viruses were injecting in the bacteria (and happened to be the genetic material), was DNA.

Hershey and Chase published these results in 1952, and it really caused a lot of interest. Biologists began to take a closer look at nucleic acids. That is what I want to do in my next post, look at the structure of DNA.

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