Biology: Linking Genes & Chemicals Cont'd

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If A.E. Garrod gave the world their first glimpse into what genes might do, it was only a glimpse. It was based on family histories. There were no test tube studies. There were no lab studies. But nevertheless, in looking back, that's kind of cool stuff. But I want you to understand something. We still were not sure even that genes and the hereditary material were chemical in nature.
Well in the 1920s, a serious link between chemistry and genetics finally happened. And it was by the work of H.J. Mueller. Now Mueller worked with an organism that had become popular by the work of another biogeneticist who you are going to hear a lot about later on, a guy by the name of Morgan. And they worked with an organism called Drosophila melanogaster, the common fruit fly. And what Muller was doing was he was documenting and creating mutations of fruit flies. One of the things about fruit flies is they reproduce very quickly. And because they do, there is a lot of variance of fruit flies. So we like to use them in genetics experiments. What Muller did was he used to create mutants using x-rays. So he'd irradiate the flies, let them reproduce, and see what came out. And quite often he would get lethal mutants, mutants that didn't survive say past the maggot stage.
Well here's the thing. That was nice. And the fact that he was creating mutants was a good thing, but that kind of pales when we see what he really realized. And it was this, that warmer temperatures created more mutants. Well what does that mean? We need to think of our basic biochemistry. When you warm things up, what happens to their chemicals? They move faster. So therefore, if genetics has anything to do with biochemistry, then genetics should follow some of the basic rules of biochemistry. For example, a rule of thumb that biochemists use is something like this. If you warm a solution up approximately ten degrees Celsius, it doubles the chemical rate. So if you have an enzymatic reaction going, and you warm it up by ten degrees, you get about a doubling of the amount of enzymatic product, kind of a rule of thumb. Well guess what. Muller found out that when you warmed up the medium that the fruit flies were in ten degrees, it doubled the mutation rate when they were irradiated with x-rays, or spontaneously, doubled mutation rate. What is this? Folks this is a direct link between genetics and chemistry. Genes are chemicals.
Well I want to jump ahead in time a little bit about 30 years after Garrod published his paper and his book to the late 1930s, where a now famous work was done by Beadle and Tatum. This could be a very long story, but let's summarize what they did. They worked with fungal systems. They worked with a fungus. And the great thing about a fungus is they produce with spores. And what you can do is you can grow the spores in something called a minimal medium. And it's important to get this idea of the minimal medium. So what they would do is they would take spores of a fungus, and they would put it in a dish. And they'd put those spores in that dish, and the dish would contain minimal medium. Minimal medium is just the minimum amount of stuff they need to grow. You know fungus, like many organisms, make their own amino acids, make their own materials. They literally, if you just get them the basics, they can produce materials that they need. That's important. Keep that registered right there. So this is their control, if you will. Grow the spores in the minimal medium. Yeah, they can grow. Okay, that's great.
Now they took some spores and they irradiated them. Remember late 1930s, so x-rays, they zapped these spores. And what they believed they were doing is they were mutating the spores. Well what's in the spores is the organism itself. Remember a spore is a structure that is almost like an asexual, if you will, seed. It's kind of a contradiction in terms there, but basically a spore is something that plants itself in the ground and gives rise to an organism. What they did was they put these irradiated spores into minimal medium. And guess what they found. Some of them grew, fungus, fungus, fungus. What they found was some of them didn't grow. Why would that be? They're mutants. They mutated them.
So they said, "Wow! What did we do to these spores when we mutated them?" Now I've got to tell you the patience of this experiment blows me away, because I'm sure they had like, "Let's take some of these spores out. Let's grow them. Oh, they're not growing. Let's try it another way. Oh, they're not growing. Let's try it a third way. They're not growing." So some of these spores were just like history. But here's what they did. They filtered the spores through cheesecloth, and they basically got the irradiated spores. Now what did they do with those spores? Well here's what they did.
They took those spores and they put them in a different medium. For example, they would take minimal medium. Now you're saying to yourself, "Well wait a minute. They already tried minimal medium. We know these spores aren't going to grow." So we'll put the spores in here, and they don't grow. But to that minimal medium they would add something, perhaps a vitamin, perhaps an amino acid. So I'll give you one example. Let's add alanine. Alanine is an amino acid that a fungus generally can produce. So they're asking themselves, "I wonder if there are any of these spores that just plain old can't produce alanine." Well how would you know if it can't produce alanine? Well give it some alanine. Then if it grows, we know that this thing, its variation, its mutation was the inability to produce alanine, because when I give it alanine, it grows. You see? And if that's true, and if giving it the alanine caused it to grow, well then we know what we mutated. And sure enough, some of these would grow in the presence of alanine. Now let's take the ones that didn't grow and let's give them something else. Let's give them tyrosine. Let's give them a vitamin. Let's give them this.
And here's what they came up with. They realized that their mutation was not in the nutrient. You don't mutate nutrients. These were simply nutrients. Their mutation must have been something in the pathway of synthesis, something in the pathway of the synthesis, in this case, of alanine, in another case of tyrosine, in other words, the synthesis of a material.
And you know what? They knew something that you and I know. You synthesize materials with enzymes. They knew that the mutation had something to do with enzymes. Have we solved the problem? Of course not, because enzymes are proteins. And we know that proteins must be the genetic material, at least some people did. But what's the key here? Once again, Garrod, inborn errors of metabolism, somehow linking the genetic material to heredity, the genetic material to enzymes, Mueller linking the genetic material to chemistry. Beadle and Tatum, back to Garrod, linking that genetic material to enzymes. As you may have guessed, there's still a whole lot more to this story.
Molecular Genetics
Discovering DNA
Continuing to Link Genes to Chemicals: Mueller, Beadle, and Tatum Page [1 of 2]