Let's take a look, what Seymour Benzer did, okay? At that time, there was a strategy to make the mutants off of the Drosophila. You just used those chemicals, and you excrete to induce the mutations of this gene. And then you screen, because decent mutation you cannot control. It's just random. You don't know which gene affected at first, okay? It's just actually a bunch of mutants. And then you're screw in the phenotype. So if you are interested in the time, the circadian, right? When the fly, the deep waves of the fly awake. So if you check this kind of pattern and then you can find some genes mutation maybe will affect this behavior, indeed. This is actually a very famous paper in 1975. They published in P&S. This study is, okay, so this is the behavior of the animal. This behavior is called, actually, the monitor the activity of the fly, or the movement of the fly. What they did is very simple, okay? So you just use a tube, a plastic tube, transparent. And then you take one fly, put inside. And then put the tube under the control for the lighting. Sometimes maybe few the light conditions, sometimes dark, okay? And then you monitor the activity of the fly. How you monitor the fly activity? You cannot use your eye just directly of result. Because these take a long time, days, weeks, you will maybe, even longer amounts. Then what you can is do is, actually they just used, because he was very clever at the time, he has a very strong background in physics. Of course, they just used the dy is the infrared ping, a y-shift. Now and then that infrared beam actually pops the tip. So if the fly move, breaks the beam, and then you have a detector, and then you can automatically record the activity. Then you know when the fly move once, and then they'll record the way, record fly activity. And the thesis, you can see, each of these individual line, horizontal line, is one day or maybe two days, yeah, put together. And then you can see, these thick lines actually is the activity monitor. That means actually the fly here is very active, move around, okay? And then for this period actually, then the fly actually not much activity. Use the genes and then [INAUDIBLE] you see. This is 24 hours, okay? 24 hours and then, this maybe a 12 hour in the dark, 12 hour in the light. And then this is actually in the light condition. This is in the dark. So the fly actually makes a lot of movement in the light, because you want to show how, you want activity. And then, in the dark, actually that's activity, okay. This is kind of you can see quite interesting. The flies actually maintained about actually this kind of 24-hour cycle. Because you have the light condition, your control, these 12 hour light, 12 hour dark. So things 24 hours, the cycle, right? And then, I'm sorry, here is actually they change the condition. The first, actually they change the animal actually in this 24 hour, 12 hour, 12 hour, the cycle. And then the experiment actually is then you put this fly in complete darkness without any light cue, 24 hours in the dark, okay? And then you see these animals actually maintained their activity about 24 hour period, okay? So then it means actually this animal has intrinsic clock in the brain. They know actually when they should actually move around, when to rest. This is called circadian rhythm, okay? This rhythm actually, they don't need the external input. It's intrinsic. Without any cue you can maintain. And then, quite interestingly, on this screen, it is a mutant animal. The fly, actually, some animals you see the purity is much shorter. This is in the wild obviously about 24 hours circadian in the dark, intrinsical clock. But it isn't anymore, actually only about 19 hours. Apparently, something changed, right, changed the behavior. And then she also found, some animals, deep in the mutants has a longer period, about 29 hours. And of course, some animals actually, just no any reason, just awake and asleep actually, quite disrupted. And then later, actually, they mapped this, okay. So right now you have this mutant. You know the phenotype, because you have the chemical-induced mutation. And then you know there is some kind of phenotype deficit for the circadian. And then the next thing is actually you want to find which gene actually really are responsible for this kind of behavior, right? Then they did the mapping, okay. How you do the mapping, actually the chromosome mapping and determine which gene actually was disrupted in this mutant animal. And what they found, actually quite interesting, for this one, the map to a protein called. And then there was some amino acid actually was changed, notated, and then this one again is. But it's different amino acid mutations. So it tells you, right now it tells you it's one gene. You change a different amino acid to different locations it can affect the behavior differently. One can make this circadian rhythm shorter. Another one make it longer. So they are very excited, because this is the first time to demonstrate to you a single gene can change their behavior, okay? And at that time, as I told you, nobody believe this is what happened. But it did, they did demonstrate at this point. Okay, so this is actually the first clock gene discovered ever. And the later then follow similar strategy, and the people found more and more clock gene. So for example in the fly, the Drosophila, is really a good model to study this kind of gene and the behavior relationship. And later a lot of different genes actually were discovered, also affect the circadian rhythm. For example, the first one is the [INAUDIBLE] period, right? We talk about [INAUDIBLE] in 1971. And then there was another one called a [INAUDIBLE] team. There's another gene, also, if you mix the mutations, the circadian rhythm will be changed. And also there is another one, the cycle. Cycle also another gene.
