WEBVTT 00:00:00.030 --> 00:00:02.400 The following content is provided under a Creative 00:00:02.400 --> 00:00:03.830 Commons license. 00:00:03.830 --> 00:00:06.860 Your support will help MIT OpenCourseWare continue to 00:00:06.860 --> 00:00:10.510 offer high-quality educational resources for free. 00:00:10.510 --> 00:00:13.390 To make a donation or view additional materials from 00:00:13.390 --> 00:00:17.490 hundreds of MIT courses, visit MIT OpenCourseWare at 00:00:17.490 --> 00:00:18.740 ocw.mit.edu. 00:00:20.920 --> 00:00:21.271 PROFESSOR: All right. 00:00:21.271 --> 00:00:22.000 It's 11:05. 00:00:22.000 --> 00:00:23.910 OK, let's get started. 00:00:23.910 --> 00:00:28.930 Last day we talked about protein structure. 00:00:28.930 --> 00:00:33.220 We talked about composition, which is the primary structure 00:00:33.220 --> 00:00:36.955 of proteins, and that's the instant R group sequence, as 00:00:36.955 --> 00:00:38.520 you go down the backbone. 00:00:38.520 --> 00:00:42.500 The secondary structure proteins is all about packing, 00:00:42.500 --> 00:00:45.070 and we saw that there were three different structures, 00:00:45.070 --> 00:00:48.190 the alpha helix, the beta pleated sheet, 00:00:48.190 --> 00:00:49.380 and the random coil. 00:00:49.380 --> 00:00:52.480 And the gambit here is to maximize hydrogen bonding. 00:00:52.480 --> 00:00:56.440 And why you choose alpha, beta, or random coil depends 00:00:56.440 --> 00:00:59.790 upon the instant R group sequence, which is why in some 00:00:59.790 --> 00:01:01.260 instances, you can't form the coil. 00:01:01.260 --> 00:01:03.450 Because the R groups won't allow it. 00:01:03.450 --> 00:01:07.280 And then lastly, we talked about tertiary structure, and 00:01:07.280 --> 00:01:10.080 that's conformation, and that talks about our group 00:01:10.080 --> 00:01:14.390 interactions, and ultimately explains protein folding. 00:01:14.390 --> 00:01:17.040 Today I want to talk about denaturing of proteins, which 00:01:17.040 --> 00:01:21.610 is disruption of secondary and tertiary structures. 00:01:21.610 --> 00:01:24.360 But before we do so, I wanted to show you. 00:01:24.360 --> 00:01:27.440 I found another movie reference to chemistry. 00:01:27.440 --> 00:01:29.585 This comes from 1957, and the movie 00:01:29.585 --> 00:01:30.990 is called Silk Stockings. 00:01:30.990 --> 00:01:33.770 It's based on an old Cole Porter play. 00:01:33.770 --> 00:01:36.950 And this stars Cyd Charisse and Fred Astaire, who were 00:01:36.950 --> 00:01:38.680 both fantastic dancers. 00:01:38.680 --> 00:01:40.360 And I want you to see in this film clip 00:01:40.360 --> 00:01:41.900 how she carries herself. 00:01:41.900 --> 00:01:43.140 And she actually sings this. 00:01:43.140 --> 00:01:44.600 She didn't have somebody dub it over. 00:01:44.600 --> 00:01:45.510 So the singing is OK. 00:01:45.510 --> 00:01:48.610 It's not great, but you've got to see her posture. 00:01:48.610 --> 00:01:49.840 She's so graceful. 00:01:49.840 --> 00:01:52.320 And Fred Astaire is a terrific dancer, but he doesn't dance 00:01:52.320 --> 00:01:53.300 in this sequence. 00:01:53.300 --> 00:01:56.120 And last thing you need to know here is, this is set 00:01:56.120 --> 00:01:57.510 during the Cold War. 00:01:57.510 --> 00:02:00.920 So she's playing Ninotchka Yoschenka, a good Ukrainian 00:02:00.920 --> 00:02:03.810 name, and she's a Soviet representative. 00:02:03.810 --> 00:02:06.450 And she's fighting with Fred Astaire, who 00:02:06.450 --> 00:02:09.950 is an American agent. 00:02:09.950 --> 00:02:12.620 And they're talking about the differences between the Soviet 00:02:12.620 --> 00:02:15.780 and the American systems. So that's the background. 00:02:15.780 --> 00:02:17.280 It's 1957. 00:02:17.280 --> 00:02:18.810 I guess we better get some volume up here 00:02:18.810 --> 00:02:19.690 so we can hear it. 00:02:19.690 --> 00:02:23.050 And she will explain to you-- and remember, just 00:02:23.050 --> 00:02:26.740 parenthetically, that my particular interest in 00:02:26.740 --> 00:02:29.150 chemistry is, of course, electrochemistry, which is the 00:02:29.150 --> 00:02:30.730 highest form of chemistry. 00:02:30.730 --> 00:02:31.530 Now she'll explain it to you. 00:02:31.530 --> 00:02:31.855 [BEGIN FILM PLAYBACK] 00:02:31.855 --> 00:02:33.550 -If you studied, Kamachev, you would know what 00:02:33.550 --> 00:02:35.250 I am talking about. 00:02:35.250 --> 00:02:36.580 -Who's Kamachev? 00:02:36.580 --> 00:02:38.660 -He was one of our greatest scientists. 00:02:38.660 --> 00:02:41.100 He has proved beyond any question that physical 00:02:41.100 --> 00:02:44.270 attraction is purely electrochemical. 00:02:44.270 --> 00:02:45.360 -You don't say. 00:02:45.360 --> 00:02:46.995 -Kamachev has proven it! 00:02:46.995 --> 00:02:48.970 -For 30 years, he worked. 00:02:48.970 --> 00:02:51.090 -I happen to have worked on the same subject for about the 00:02:51.090 --> 00:02:53.330 same amount of time, and I have very good reasons for 00:02:53.330 --> 00:02:55.600 believing otherwise. 00:02:55.600 --> 00:02:57.450 -Facts are facts 00:02:57.450 --> 00:02:57.830 [SINGING] 00:02:57.830 --> 00:03:01.990 -When the electromagnetic of the he-male meets the 00:03:01.990 --> 00:03:07.229 electromagnetic of the female, if right away, she should say, 00:03:07.229 --> 00:03:12.860 this is the male, it's a chemical reaction, that's all. 00:03:12.860 --> 00:03:16.560 And though you Fascists may answer with kisses, the same 00:03:16.560 --> 00:03:20.970 applies when your Mr. And Mrs. Hey-diddle-diddle with 00:03:20.970 --> 00:03:26.430 middle-class kisses, it's a chemical reaction, that's all. 00:03:26.430 --> 00:03:30.470 Say in love, with you, I fall. 00:03:30.470 --> 00:03:34.970 And in love, with me, you also fall. 00:03:34.970 --> 00:03:38.430 Though the uninstructed faction calls it mutual 00:03:38.430 --> 00:03:44.636 attraction, it's a chemical reaction, that's all. 00:03:44.636 --> 00:03:45.064 [END SINGING] 00:03:45.064 --> 00:03:47.400 -You don't believe in Kamachev? 00:03:47.400 --> 00:03:47.810 -No, ma'am. 00:03:47.810 --> 00:03:50.420 [END FILM PLAYBACK] 00:03:50.420 --> 00:03:51.480 PROFESSOR: See the posture? 00:03:51.480 --> 00:03:54.150 It's just unbelievable. 00:03:54.150 --> 00:03:54.860 Fantastic. 00:03:54.860 --> 00:03:55.130 OK. 00:03:55.130 --> 00:03:57.920 So let's talk about denaturing of proteins. 00:03:57.920 --> 00:04:02.550 So we want to talk about how we can alter the structure. 00:04:02.550 --> 00:04:06.640 And we do so by invasive means. 00:04:06.640 --> 00:04:08.130 So let's get to the next slide. 00:04:08.130 --> 00:04:09.760 So here's the tertiary structure, and I 00:04:09.760 --> 00:04:11.150 can point to that. 00:04:11.150 --> 00:04:14.720 The first thing I wanted to draw attention to, is we can 00:04:14.720 --> 00:04:17.480 disrupt that structure by change in temperature. 00:04:17.480 --> 00:04:22.560 So temperature is the first agent that we can use in 00:04:22.560 --> 00:04:26.220 disrupting, or denaturing, protein. 00:04:26.220 --> 00:04:30.040 And the whole idea here is to break bonds. 00:04:30.040 --> 00:04:33.295 But we're only going to break secondary or tertiary bonds. 00:04:33.295 --> 00:04:35.330 We're not going to do anything to the backbone. 00:04:35.330 --> 00:04:40.400 And a good example is what happens when we fry an egg. 00:04:40.400 --> 00:04:42.560 The egg has protein in it. 00:04:42.560 --> 00:04:43.910 One of them is ovalbumin. 00:04:43.910 --> 00:04:47.510 It's about 90% water, about 10% protein. 00:04:47.510 --> 00:04:51.095 And its native state, its natural state, conformation is 00:04:51.095 --> 00:04:52.500 a tight ball. 00:04:52.500 --> 00:04:56.710 And the diameter of that ball is small enough that uncooked 00:04:56.710 --> 00:04:59.060 egg is transparent to visible light. 00:04:59.060 --> 00:05:01.620 Egg white is transparent to visible light in its natural 00:05:01.620 --> 00:05:05.340 form, but when we heat beyond the denaturing temperature, 00:05:05.340 --> 00:05:09.210 that changes the bonds in here, and it unpacks. 00:05:09.210 --> 00:05:11.760 And when it unpacks, two things happen. 00:05:11.760 --> 00:05:15.090 First of all, the length scale changes to be great enough 00:05:15.090 --> 00:05:16.530 that it scatters light. 00:05:16.530 --> 00:05:18.440 So now the egg white appears white. 00:05:18.440 --> 00:05:22.220 And secondly, those various chains entangle, and that 00:05:22.220 --> 00:05:24.450 gives it its rubbery character. 00:05:24.450 --> 00:05:29.200 So all of that is happening as a result of the increase in 00:05:29.200 --> 00:05:30.350 temperature. 00:05:30.350 --> 00:05:36.610 So second way that we can operate, is to change pH. 00:05:36.610 --> 00:05:40.120 And what that does, is it changes hydrogen bonding and 00:05:40.120 --> 00:05:41.190 electrostatic interactions. 00:05:41.190 --> 00:05:44.040 Now I draw your attention to zone two here. 00:05:44.040 --> 00:05:48.490 In zone two, imagine if we take that proverbial drink of 00:05:48.490 --> 00:05:52.190 cola, and now the pH in here goes way, way down. 00:05:52.190 --> 00:05:56.090 You can see this N has got a hydrogen bond over to here. 00:05:56.090 --> 00:05:59.140 Now, if there's a proton excess, the proton can cap, 00:05:59.140 --> 00:06:01.270 because this is a proton attachment site. 00:06:01.270 --> 00:06:05.590 If the proton caps this carboxyl, then this hydrogen 00:06:05.590 --> 00:06:08.750 bond is broken, and now this thing can unfurl. 00:06:08.750 --> 00:06:11.620 Over here, you see, this is an electrostatic attraction. 00:06:11.620 --> 00:06:15.550 Again, the carboxyl could be kept by a proton, and now the 00:06:15.550 --> 00:06:19.650 plus minus electrostatic attraction is lost. So by 00:06:19.650 --> 00:06:22.900 change of pH, we could denature what we see here. 00:06:22.900 --> 00:06:23.990 So there's a good example. 00:06:23.990 --> 00:06:26.120 And in fact, I think we do this. 00:06:26.120 --> 00:06:28.390 We pickle our foods. 00:06:28.390 --> 00:06:31.590 And then this one I have, because of my interest in high 00:06:31.590 --> 00:06:34.220 temperature electrochemical processing of metals, I've 00:06:34.220 --> 00:06:35.600 been to Norway many times. 00:06:35.600 --> 00:06:39.270 And this is a food that they will never let me eat, because 00:06:39.270 --> 00:06:40.570 they're afraid if I ever taste this, I'll 00:06:40.570 --> 00:06:41.690 never return to Norway. 00:06:41.690 --> 00:06:45.400 But this is lutefisk, which literally means lye fish. 00:06:45.400 --> 00:06:47.020 And lye has high pH. 00:06:47.020 --> 00:06:49.970 And this is an example of denaturing protein by going to 00:06:49.970 --> 00:06:51.930 very, very high pH. 00:06:51.930 --> 00:06:55.070 And then you soak it and draw back out and so on. 00:06:55.070 --> 00:06:57.790 So there's a good example of food. 00:06:57.790 --> 00:07:01.730 Now the third one I want to talk about is oxidizing 00:07:01.730 --> 00:07:04.450 reducing agents to denature proteins. 00:07:15.050 --> 00:07:20.760 And what they do, they can either create or destroy the 00:07:20.760 --> 00:07:24.640 sulfide linkages, the sulfur-sulfur linkages. 00:07:24.640 --> 00:07:27.720 So for example, you see at position number one. 00:07:27.720 --> 00:07:30.310 Position number one, we can use oxidizing 00:07:30.310 --> 00:07:31.440 and reducing agents. 00:07:31.440 --> 00:07:34.790 And a good example, that comes from hair. 00:07:34.790 --> 00:07:36.123 So first of all, I want to talk to you. 00:07:36.123 --> 00:07:37.410 Hair is protein. 00:07:37.410 --> 00:07:42.270 And this first example is just, how protein can, one 00:07:42.270 --> 00:07:44.980 strand can bond to the other by hydrogen bonding. 00:07:44.980 --> 00:07:48.195 So up here you have one strand and a second strand, and there 00:07:48.195 --> 00:07:50.230 are hydrogen bonds in your hair. 00:07:50.230 --> 00:07:54.680 Now, what you do when you want to change your hair by blow 00:07:54.680 --> 00:07:57.020 drying is first you wet the hair. 00:07:57.020 --> 00:07:59.820 And the water goes in and interrupts these hydrogen 00:07:59.820 --> 00:08:01.540 bonds between strands. 00:08:01.540 --> 00:08:05.460 So now each of these cross-links that want to form 00:08:05.460 --> 00:08:08.220 instead terminate with a water molecule. 00:08:08.220 --> 00:08:11.450 And now with the water molecules, now you can move 00:08:11.450 --> 00:08:15.340 the hair one strand versus the other, hold it in place, blow 00:08:15.340 --> 00:08:19.630 dry, get rid of the water, and form new hydrogen bonds. 00:08:19.630 --> 00:08:23.700 So what, on the basis of what I've just told you, how can 00:08:23.700 --> 00:08:25.430 you account for a bad hair day? 00:08:25.430 --> 00:08:27.290 What is a bad hair day? 00:08:27.290 --> 00:08:30.880 A bad hair day is a day in which it's rather humid. 00:08:30.880 --> 00:08:35.120 And so water can get in from the atmosphere and interrupt 00:08:35.120 --> 00:08:38.460 these bonds, and then the hair will relax, and go back to a 00:08:38.460 --> 00:08:41.790 native state that is unfavorable vis-a-vis what you 00:08:41.790 --> 00:08:44.840 tried to achieve with the blow dryer in the mirror. 00:08:44.840 --> 00:08:46.710 So you want to combat this. 00:08:46.710 --> 00:08:47.590 So what do you do? 00:08:47.590 --> 00:08:49.900 Well, you bring out covalent bonds. 00:08:49.900 --> 00:08:53.710 So here's two strains of hair, and there are disulfide 00:08:53.710 --> 00:08:55.990 linkages between the strands of hair. 00:08:55.990 --> 00:09:00.730 So now with a reducing agent, reducing agent is going to be 00:09:00.730 --> 00:09:02.460 a proton donor. 00:09:02.460 --> 00:09:08.340 And can you see, these disulfide linkages are capped 00:09:08.340 --> 00:09:10.940 with hydrogen, and now they're terminated. 00:09:10.940 --> 00:09:14.380 And so now the two strands of hair are free to move relative 00:09:14.380 --> 00:09:15.640 to one another. 00:09:15.640 --> 00:09:18.500 And now when you're at the beauty parlor or the 00:09:18.500 --> 00:09:22.700 hairdresser, now you can take this hair, for example, and 00:09:22.700 --> 00:09:25.150 wrap it around-- 00:09:25.150 --> 00:09:26.280 what do you call this thing? 00:09:26.280 --> 00:09:28.530 It's a mandrel in the metallurgical word. 00:09:28.530 --> 00:09:29.680 What do you call this thing? 00:09:29.680 --> 00:09:30.890 Curling iron or something? 00:09:30.890 --> 00:09:31.110 Yeah. 00:09:31.110 --> 00:09:31.430 OK. 00:09:31.430 --> 00:09:32.740 So here you are. 00:09:32.740 --> 00:09:33.510 You wrap this around-- 00:09:33.510 --> 00:09:34.520 I know what it does. 00:09:34.520 --> 00:09:35.800 I don't know the terms, all right. 00:09:35.800 --> 00:09:39.090 So now you see, we've got the hair now wrapped around in 00:09:39.090 --> 00:09:41.710 this fashion, and now we use an oxidizing agent. 00:09:41.710 --> 00:09:43.830 The oxidizing agent is peroxide here. 00:09:43.830 --> 00:09:46.130 You know the derogatory term, peroxide blonde. 00:09:46.130 --> 00:09:47.290 There it is, right here. 00:09:47.290 --> 00:09:49.610 So the peroxide goes in, and now it 00:09:49.610 --> 00:09:51.880 removes these hydrogens. 00:09:51.880 --> 00:09:55.100 The peroxide takes the hydrogens away and reforms the 00:09:55.100 --> 00:09:57.590 disulfide linkages, but now the hair is 00:09:57.590 --> 00:09:59.350 in this curled state. 00:09:59.350 --> 00:10:01.400 You know, you might have the opposite. 00:10:01.400 --> 00:10:04.190 Maybe in your native state, your hair, because of the way 00:10:04.190 --> 00:10:07.350 the R groups are formed along the length of your hair, you 00:10:07.350 --> 00:10:09.910 know, it's always, the ones with the curly hair want the 00:10:09.910 --> 00:10:11.660 straight hair, the ones with the straight hair want the 00:10:11.660 --> 00:10:12.230 curly hair. 00:10:12.230 --> 00:10:14.290 And so, you know, maybe you could be running this sequence 00:10:14.290 --> 00:10:14.890 in reverse. 00:10:14.890 --> 00:10:17.870 But in this case, somebody obviously wants curly hair. 00:10:17.870 --> 00:10:20.290 Now they form the disulfide linkages. 00:10:20.290 --> 00:10:22.680 So this is the object, here, of denaturing. 00:10:22.680 --> 00:10:25.770 So now when we go over to here, we have a disulfide 00:10:25.770 --> 00:10:29.410 linkage, which is forcing this run of the random 00:10:29.410 --> 00:10:30.960 coil to stay straight. 00:10:30.960 --> 00:10:36.660 But if we get, in this case, the oxidizing, the reducing, 00:10:36.660 --> 00:10:39.390 and what will happen is that we will break this. 00:10:39.390 --> 00:10:46.340 So the reducing agents will destroy disulfide linkages, 00:10:46.340 --> 00:10:50.830 and the oxidizing agents will create disulfide linkages, and 00:10:50.830 --> 00:10:56.940 thereby we can distort the natural form of the protein. 00:10:56.940 --> 00:10:58.290 And here's a fourth example. 00:10:58.290 --> 00:11:01.260 There are many others, but I'll just give you four here. 00:11:01.260 --> 00:11:02.990 In the fourth one, we can use detergents. 00:11:06.880 --> 00:11:12.060 And last day, I showed you the example of 00:11:12.060 --> 00:11:14.270 how to do your laundry. 00:11:14.270 --> 00:11:18.800 And so you've got this long aliphatic tail and the 00:11:18.800 --> 00:11:23.330 hydrophobic head, and you can imagine if you take such 00:11:23.330 --> 00:11:27.660 species and you've got this hydrophobic pocket, the 00:11:27.660 --> 00:11:32.460 species will operate in such a way as to pull these non-polar 00:11:32.460 --> 00:11:34.730 entities out, and then destabilize 00:11:34.730 --> 00:11:36.290 this hydrophobic pocket. 00:11:36.290 --> 00:11:40.190 So depending on what the nature is of the protein, 00:11:40.190 --> 00:11:46.300 these various chemical and thermal actions can lead to 00:11:46.300 --> 00:11:46.860 denaturing. 00:11:46.860 --> 00:11:53.870 So this destabilizes hydrophobic pockets. 00:11:59.180 --> 00:12:00.250 All right. 00:12:00.250 --> 00:12:02.150 So that's pretty good. 00:12:02.150 --> 00:12:03.390 All right. 00:12:03.390 --> 00:12:05.880 Well, I think this is where I want to leave it with the 00:12:05.880 --> 00:12:07.500 treatment of proteins. 00:12:07.500 --> 00:12:11.790 And I want to move on to a second biomolecule, 00:12:11.790 --> 00:12:13.790 and that's the lipid. 00:12:13.790 --> 00:12:15.240 We'll say a few words about lipids. 00:12:15.240 --> 00:12:18.200 Lipids are not classified on the basis of their 00:12:18.200 --> 00:12:20.660 composition, but rather by their properties. 00:12:20.660 --> 00:12:25.970 So they are defined their properties, 00:12:25.970 --> 00:12:27.480 which is kind of unusual. 00:12:27.480 --> 00:12:30.330 Normally we define things in terms of their chemical 00:12:30.330 --> 00:12:31.210 compositions. 00:12:31.210 --> 00:12:33.975 And in particular, they're soluble in 00:12:33.975 --> 00:12:35.225 solvents of low polarity. 00:12:40.620 --> 00:12:44.930 Some of the books say nonpolar solvents, but even something 00:12:44.930 --> 00:12:48.580 that's polar but only mildly so will work, in solvents of 00:12:48.580 --> 00:12:51.240 low polarity. 00:12:51.240 --> 00:12:52.320 So that's the example. 00:12:52.320 --> 00:12:55.300 They're insoluble in water, they're oily to the touch. 00:12:55.300 --> 00:13:01.840 And this includes things like fats, oils, 00:13:01.840 --> 00:13:02.790 these are all lipids. 00:13:02.790 --> 00:13:09.710 Cholesterol, hormones. 00:13:09.710 --> 00:13:13.430 These are all members of the lipid class. 00:13:13.430 --> 00:13:17.410 And so let's look at some examples. 00:13:17.410 --> 00:13:19.190 We've got some slides. 00:13:19.190 --> 00:13:22.100 So if you start over here with the glycerol, this is a 00:13:22.100 --> 00:13:23.590 trialcohol. 00:13:23.590 --> 00:13:24.900 And you can see the OH. 00:13:24.900 --> 00:13:27.170 We're going to drop the H's, and we're going to put these 00:13:27.170 --> 00:13:30.290 long aliphatic chains on. 00:13:30.290 --> 00:13:32.635 There's 14 carbons here, plus the two, so 00:13:32.635 --> 00:13:34.380 it's 16 carbons long. 00:13:34.380 --> 00:13:37.620 And this also is seven plus seven, and 00:13:37.620 --> 00:13:39.340 then the two carbons. 00:13:39.340 --> 00:13:42.420 And the difference here is that in this case, it's all 00:13:42.420 --> 00:13:43.430 straight chain. 00:13:43.430 --> 00:13:46.830 In this case, we go for seven, then we put in a double bond. 00:13:46.830 --> 00:13:49.220 And by doing so, when we get to the double bond, that 00:13:49.220 --> 00:13:53.560 forces everything to go into planar 120 degree arrangement. 00:13:53.560 --> 00:13:56.030 So you go for seven however you want, and then there's 00:13:56.030 --> 00:13:59.030 this rigid 120 degree placement, and then you go for 00:13:59.030 --> 00:14:00.370 seven however you want. 00:14:00.370 --> 00:14:04.140 Well, clearly, the one in the middle is going to pack better 00:14:04.140 --> 00:14:05.270 than the one on the left. 00:14:05.270 --> 00:14:08.850 And so even though they have seemingly the same chemical 00:14:08.850 --> 00:14:11.430 composition, the one in the middle is a solid. 00:14:11.430 --> 00:14:12.050 It's a fat. 00:14:12.050 --> 00:14:14.790 The one on the right is a liquid, because it doesn't 00:14:14.790 --> 00:14:15.480 pack well enough. 00:14:15.480 --> 00:14:17.250 The bonds aren't strong enough. 00:14:17.250 --> 00:14:19.110 So these are both examples. 00:14:19.110 --> 00:14:21.150 And this is called a palmitic acid. 00:14:21.150 --> 00:14:23.510 And you can see here oxygen acting as a 00:14:23.510 --> 00:14:25.330 bridge, as an ester. 00:14:25.330 --> 00:14:29.710 So oxygen, over and over again, acting in this way to 00:14:29.710 --> 00:14:35.930 give us the ability to make these other longer structures. 00:14:35.930 --> 00:14:38.840 Now we can replace that oxygen bridge with a dibridge. 00:14:38.840 --> 00:14:41.380 So instead of having just an oxygen here, we're going to 00:14:41.380 --> 00:14:42.660 put a phosphate. 00:14:42.660 --> 00:14:46.720 So with the phosphate, we've got a phosphodiester linkage. 00:14:46.720 --> 00:14:50.030 There's one ester, there's a second ester. 00:14:50.030 --> 00:14:51.310 And why we doing this? 00:14:51.310 --> 00:14:53.720 Because nature wants to get the spacing right. 00:14:53.720 --> 00:14:55.900 And remember what I just said, because by the end, you're 00:14:55.900 --> 00:14:58.460 going to see that spacing is everything. 00:14:58.460 --> 00:15:02.110 So we can use this, and we can even lose that oxygen, and put 00:15:02.110 --> 00:15:03.350 something else here. 00:15:03.350 --> 00:15:04.090 So here's a-- 00:15:04.090 --> 00:15:06.060 I'm not expecting you to know these by heart. 00:15:06.060 --> 00:15:09.740 I would give you the structure and tell you what it is, tell 00:15:09.740 --> 00:15:11.890 you its name, and then we can go on from here. 00:15:11.890 --> 00:15:13.090 So what do you see here? 00:15:13.090 --> 00:15:15.340 Well, this is called a phosphatide. 00:15:15.340 --> 00:15:18.580 And this one is a phosphatidylethanolamine, 00:15:18.580 --> 00:15:20.720 because there's the amine here. 00:15:20.720 --> 00:15:22.140 And look at this thing. 00:15:22.140 --> 00:15:23.600 Well, you've got a phosphate in the 00:15:23.600 --> 00:15:24.690 center that's the bridge. 00:15:24.690 --> 00:15:27.310 This is the glycerol, the three carbons. 00:15:27.310 --> 00:15:29.430 In its most primitive form, we could just 00:15:29.430 --> 00:15:30.900 have hydroxyls here. 00:15:30.900 --> 00:15:33.380 This is the fatty acid off the one end. 00:15:33.380 --> 00:15:35.990 Long chains here, not to scale. 00:15:35.990 --> 00:15:38.590 So these things should be way, way over to here. 00:15:38.590 --> 00:15:40.480 And over here, we have an ethanol amine. 00:15:40.480 --> 00:15:42.540 But look more closely. 00:15:42.540 --> 00:15:45.220 Well, this is a hydrophilic head, this is 00:15:45.220 --> 00:15:47.020 twin hydrophobic tails. 00:15:47.020 --> 00:15:48.520 Look, this is just hydrocarbon. 00:15:48.520 --> 00:15:50.220 It's not soluble in water. 00:15:50.220 --> 00:15:52.250 So now you've got this amphipathic molecule. 00:15:52.250 --> 00:15:54.250 It looks like a detergent, doesn't it? 00:15:54.250 --> 00:15:58.160 This long, hydrophobic tail could stab the grease, and 00:15:58.160 --> 00:16:00.330 this hydrophilic head can bond to the water. 00:16:00.330 --> 00:16:03.760 And now if we shake things up, we'll release the grease 00:16:03.760 --> 00:16:06.320 that's binding the soil to your T-shirt. 00:16:06.320 --> 00:16:09.170 Got the phosphate bridge here, and look even more closely. 00:16:09.170 --> 00:16:11.420 There's a minus, and there's a plus! 00:16:11.420 --> 00:16:15.210 This is zitterionic, on top of everything else. 00:16:15.210 --> 00:16:18.160 So this can function as a zwitterion, too. 00:16:18.160 --> 00:16:20.300 And everything we learned about zwitterionic chemistry 00:16:20.300 --> 00:16:23.540 and buffering, this thing can do. 00:16:23.540 --> 00:16:25.290 That's cool. 00:16:25.290 --> 00:16:25.580 All right. 00:16:25.580 --> 00:16:28.120 So now I want to show what happens when I take a whole 00:16:28.120 --> 00:16:29.330 bunch of those. 00:16:29.330 --> 00:16:29.640 All right? 00:16:29.640 --> 00:16:30.370 So let's go back. 00:16:30.370 --> 00:16:33.830 I want to keep this one up, and I want to want to do is 00:16:33.830 --> 00:16:37.810 take a whole bunch of those, and show how lipids can 00:16:37.810 --> 00:16:41.110 actually operate in order to build complex 00:16:41.110 --> 00:16:42.150 structures for us. 00:16:42.150 --> 00:16:43.440 So what I'm going to do, is I want to 00:16:43.440 --> 00:16:45.100 represent that molecule. 00:16:45.100 --> 00:16:47.600 So here's the hydrophilic head. 00:16:47.600 --> 00:16:49.420 That's the amine, right? 00:16:49.420 --> 00:16:52.470 And then we've got twin hydrophobic tails. 00:16:52.470 --> 00:16:55.970 And that's your carbon sp3 chains. 00:16:55.970 --> 00:16:57.540 And I don't want to write that so much. 00:16:57.540 --> 00:17:03.400 So I'm just going to simplify that as simply hydrophilic 00:17:03.400 --> 00:17:05.640 head and hydrophobic twin tails. 00:17:05.640 --> 00:17:07.640 So this now represents the twin tails. 00:17:07.640 --> 00:17:10.550 Now if I put a whole bunch of these in water, 00:17:10.550 --> 00:17:11.660 what's going to happen? 00:17:11.660 --> 00:17:14.600 First of all, this is hydrophilic. 00:17:14.600 --> 00:17:18.320 And what if I were to just pour this into a beaker? 00:17:18.320 --> 00:17:20.660 What do you think would happen if I introduced this into a 00:17:20.660 --> 00:17:21.900 beaker of water? 00:17:21.900 --> 00:17:24.860 Well, this is hydrophobic, this is hydrophilic. 00:17:24.860 --> 00:17:27.070 Can you imagine that they would all sort of 00:17:27.070 --> 00:17:28.060 line up like this? 00:17:28.060 --> 00:17:33.970 We're trying to stick the hydrophobic 00:17:33.970 --> 00:17:35.870 tails up into the air. 00:17:35.870 --> 00:17:37.350 Because they don't want to be down in here. 00:17:37.350 --> 00:17:38.720 This is hydrophobic. 00:17:38.720 --> 00:17:39.910 Doesn't want to be here. 00:17:39.910 --> 00:17:42.470 So now suppose I put a whole bunch of these in water. 00:17:42.470 --> 00:17:44.500 More than four, right? 00:17:44.500 --> 00:17:46.220 With only four, that's the best can do. 00:17:46.220 --> 00:17:48.860 What if I put some molar? 00:17:48.860 --> 00:17:50.790 So then what it does, is it forms a pocket. 00:17:50.790 --> 00:17:52.290 It's going to do this. 00:17:52.290 --> 00:17:55.560 All the heads are going to find each other, and all of 00:17:55.560 --> 00:17:57.620 the tails are going to find each other. 00:17:57.620 --> 00:18:00.760 Because now they're going to form a hydrophobic pocket. 00:18:00.760 --> 00:18:05.120 So they'll do it this way, because they can-- can you see 00:18:05.120 --> 00:18:10.580 how the heads can sort of make a wall against the water? 00:18:10.580 --> 00:18:13.455 And you go on and on and on, not to scale, and then finally 00:18:13.455 --> 00:18:15.370 you have some end effects here. 00:18:18.560 --> 00:18:20.250 So what have I formed here? 00:18:20.250 --> 00:18:24.590 I've got something, first of all, I've got a lipid layer 00:18:24.590 --> 00:18:26.240 here, and a lipid layer here. 00:18:26.240 --> 00:18:29.210 So together, I have a lipid bilayer. 00:18:33.360 --> 00:18:35.407 In here, there's a pocket. 00:18:47.100 --> 00:18:50.490 And now, what I can do with this whole thing, is I can 00:18:50.490 --> 00:18:53.000 build a cell wall with this. 00:18:53.000 --> 00:18:54.800 I've got a cell wall. 00:18:54.800 --> 00:18:57.990 I've got an outside and an inside. 00:18:57.990 --> 00:19:02.050 So what happens is, when we put all these things together, 00:19:02.050 --> 00:19:04.720 because of the clustering of the hydrophobic and 00:19:04.720 --> 00:19:07.835 hydrophilic, we say this thing is endowed with the property 00:19:07.835 --> 00:19:09.085 of self-assembly. 00:19:13.020 --> 00:19:18.010 Very hot topic in material science. 00:19:18.010 --> 00:19:20.860 And that leads to cellular structure, and I think we've 00:19:20.860 --> 00:19:23.150 got a nice cartoon here. 00:19:23.150 --> 00:19:25.650 So this is taken from one of the readings. 00:19:25.650 --> 00:19:29.420 So you can see this with the plurality of these. 00:19:29.420 --> 00:19:32.570 They're actually showing the twin tails. 00:19:32.570 --> 00:19:34.960 Now, this was taken from another text. 00:19:34.960 --> 00:19:40.040 I like this one, because it shows the hydrophilic top, 00:19:40.040 --> 00:19:43.470 hydrophilic bottom, and the hydrophobic interior. 00:19:43.470 --> 00:19:45.920 And then this thing is called an integral protein. 00:19:45.920 --> 00:19:46.510 Why? 00:19:46.510 --> 00:19:49.560 Because it's integrated into the cell wall. 00:19:49.560 --> 00:19:52.330 And let's think about this protein for a second. 00:19:52.330 --> 00:19:55.680 What must be the nature of the R groups in this vicinity of 00:19:55.680 --> 00:19:58.430 the protein, that it sits where it does? 00:19:58.430 --> 00:20:01.810 The R groups around here must be dominantly hydrophilic, 00:20:01.810 --> 00:20:05.170 otherwise it would get dumped out of that zone. 00:20:05.170 --> 00:20:08.450 And in here, it must be dominantly hydrophobic, so 00:20:08.450 --> 00:20:12.050 that it feels at home with all of these hydrophobic tails. 00:20:12.050 --> 00:20:14.300 And over here, it must be hydrophilic. 00:20:14.300 --> 00:20:15.860 Now imagine what happens. 00:20:15.860 --> 00:20:18.090 I'm going to go back to that drink of Coca Cola. 00:20:18.090 --> 00:20:19.500 Forgive me, no brand names. 00:20:19.500 --> 00:20:20.100 Cola. 00:20:20.100 --> 00:20:25.370 And now the this zone here gets flooded with protons, 00:20:25.370 --> 00:20:26.910 because the pH is dropping. 00:20:26.910 --> 00:20:29.940 So that could cause conformational changes, 00:20:29.940 --> 00:20:34.480 because pH changes the conformation of the protein, 00:20:34.480 --> 00:20:37.540 and it could cause this thing to change shape. 00:20:37.540 --> 00:20:41.230 It could unfold, or it might unfold in such a way as to 00:20:41.230 --> 00:20:44.880 open a channel down the center here. 00:20:44.880 --> 00:20:49.220 And so in response to a change in pH here, we open up a 00:20:49.220 --> 00:20:53.900 channel, which means this is acting as a chemical gate. 00:20:53.900 --> 00:20:56.970 This is how things are animated! 00:20:56.970 --> 00:20:58.980 It responds. 00:20:58.980 --> 00:21:02.290 And then once the proton concentration has been 00:21:02.290 --> 00:21:06.440 depleted and you're back to a more neutral pH, then this 00:21:06.440 --> 00:21:08.840 thing changes back to its old confirmation, 00:21:08.840 --> 00:21:10.920 and the gate closes. 00:21:10.920 --> 00:21:12.310 It's that simple! 00:21:12.310 --> 00:21:15.980 The secondary bonding explains animation. 00:21:15.980 --> 00:21:16.830 That's what's happening. 00:21:16.830 --> 00:21:18.310 And there's one other cool thing. 00:21:18.310 --> 00:21:18.970 Look at this. 00:21:18.970 --> 00:21:21.500 If they all have the same head, They're 00:21:21.500 --> 00:21:22.750 going to close pack! 00:21:27.100 --> 00:21:28.610 It's fantastic. 00:21:28.610 --> 00:21:29.630 Everything. 00:21:29.630 --> 00:21:32.090 Everything you need to know, 3.091 here. 00:21:32.090 --> 00:21:32.430 All right. 00:21:32.430 --> 00:21:36.240 So what is the key to animation? 00:21:36.240 --> 00:21:38.520 The key to animation is self-assembly. 00:21:38.520 --> 00:21:40.850 And why do we have self-assembly? 00:21:40.850 --> 00:21:43.360 Because we have these molecules with the hydrophilic 00:21:43.360 --> 00:21:45.320 head and the hydrophobic tail. 00:21:45.320 --> 00:21:47.070 These molecules are called amphipathic. 00:21:56.580 --> 00:21:56.910 OK. 00:21:56.910 --> 00:21:59.790 So this has hydrophobic and hydrophilic components. 00:21:59.790 --> 00:22:03.820 So if you take amphipathy, you end up with self-assembly. 00:22:03.820 --> 00:22:05.660 That's the key. 00:22:05.660 --> 00:22:06.910 All right, good. 00:22:09.910 --> 00:22:10.190 All right. 00:22:10.190 --> 00:22:12.640 I think that's all I want to say about lipids. 00:22:12.640 --> 00:22:14.630 That's all you need to know about lipids, is lipids will 00:22:14.630 --> 00:22:15.910 give you cellular structure. 00:22:15.910 --> 00:22:17.870 Now we've got a little bit of time left, and we're going to 00:22:17.870 --> 00:22:19.880 talk about nucleic acids. 00:22:26.160 --> 00:22:28.170 So what do I want to say about nucleic acids? 00:22:28.170 --> 00:22:30.950 Nucleic acids carry information. 00:22:30.950 --> 00:22:33.850 They carry information that directs metabolic activity, 00:22:33.850 --> 00:22:36.120 including replication. 00:22:36.120 --> 00:22:39.490 And something can be animated, but it doesn't count as a life 00:22:39.490 --> 00:22:41.730 form unless it replicates. 00:22:41.730 --> 00:22:46.890 That's the characteristic of life forms. So nucleic acids 00:22:46.890 --> 00:23:00.540 carry information that directs metabolic activity, including 00:23:00.540 --> 00:23:01.790 replication. 00:23:11.950 --> 00:23:14.430 So these are macromolecules. 00:23:14.430 --> 00:23:16.020 Not polymers, but macromolecules. 00:23:19.406 --> 00:23:22.500 We'll take a look in a moment at their structure. 00:23:22.500 --> 00:23:26.810 They're macromolecules, and the basic structural unit is 00:23:26.810 --> 00:23:28.060 called a nucleotide. 00:23:37.230 --> 00:23:40.140 And it's got three building blocks. 00:23:40.140 --> 00:23:44.520 Every nucleotide has three building blocks. 00:23:44.520 --> 00:23:46.880 See, what we're doing right now, is we're really tying 00:23:46.880 --> 00:23:50.270 together all of that chemistry you've been learning the 00:23:50.270 --> 00:23:52.750 entire semester. 00:23:52.750 --> 00:23:55.330 And it's fun to see it actually go to use. 00:23:55.330 --> 00:23:57.260 So what are the three building blocks? 00:23:57.260 --> 00:23:59.460 Every nucleotide has a sugar. 00:23:59.460 --> 00:24:02.810 And we didn't study carbohydrates, but I'll just 00:24:02.810 --> 00:24:04.480 show you the structure the sugar. 00:24:04.480 --> 00:24:05.790 It's got an amine. 00:24:05.790 --> 00:24:06.570 You know what that is. 00:24:06.570 --> 00:24:09.360 That's the NH something group. 00:24:09.360 --> 00:24:10.610 And it's got a phosphate. 00:24:13.350 --> 00:24:16.720 So the nucleotide has those three components, 00:24:16.720 --> 00:24:17.860 So let's take a look at the sugar. 00:24:17.860 --> 00:24:23.480 There's really two types of sugars found in amino acids. 00:24:23.480 --> 00:24:25.400 There's the ribose-- 00:24:25.400 --> 00:24:27.240 and the only reason I'm showing you this, is so that 00:24:27.240 --> 00:24:29.180 you'll understand the terminology. 00:24:29.180 --> 00:24:30.430 There's the deoxyribose. 00:24:33.200 --> 00:24:39.910 So if you look here, the sugar on the left has this five-fold 00:24:39.910 --> 00:24:41.880 symmetry, the five-fold ring. 00:24:41.880 --> 00:24:44.830 And there's hydroxyls at the number one position, number 00:24:44.830 --> 00:24:46.810 two position, number three position. 00:24:46.810 --> 00:24:50.060 The deoxyribose is missing the hydroxyl at 00:24:50.060 --> 00:24:51.520 the number two position. 00:24:51.520 --> 00:24:52.710 That's the difference. 00:24:52.710 --> 00:24:55.150 The reason I'm showing you this, is this is called 00:24:55.150 --> 00:24:59.170 deoxyribose, and ultimately this is the D in DNA. 00:24:59.170 --> 00:25:02.850 So you'll be able to at least hold your own with your course 00:25:02.850 --> 00:25:05.160 seven major friends, if you have any 00:25:05.160 --> 00:25:06.150 friends in course seven. 00:25:06.150 --> 00:25:09.870 And you can say, I know what the D is. 00:25:09.870 --> 00:25:11.100 It's deoxyribose. 00:25:11.100 --> 00:25:11.790 OK. 00:25:11.790 --> 00:25:13.900 So then the amines. 00:25:13.900 --> 00:25:19.320 The amines we've got, there's five of these. 00:25:19.320 --> 00:25:25.000 And they split for RNA and DNA. 00:25:25.000 --> 00:25:26.250 And they're shown here. 00:25:28.880 --> 00:25:30.140 So it's interesting. 00:25:30.140 --> 00:25:33.530 There's two of them that are called purines, because 00:25:33.530 --> 00:25:35.920 they've got this ring structure. 00:25:35.920 --> 00:25:38.270 And then the six fold, and then the five fold. 00:25:38.270 --> 00:25:42.050 So these are the purines, and then the pyrimidines have just 00:25:42.050 --> 00:25:43.210 the six fold structure. 00:25:43.210 --> 00:25:44.410 There are three of those. 00:25:44.410 --> 00:25:47.290 So A, G, C, U, and T. 00:25:47.290 --> 00:25:49.840 Those are the five different amino acids. 00:25:49.840 --> 00:25:55.620 And the difference is that in DNA, you only have A, G, C and 00:25:55.620 --> 00:25:59.730 T, whereas in RNA, you have A, G, C, and U. 00:25:59.730 --> 00:26:00.670 This is the chemistry. 00:26:00.670 --> 00:26:03.430 If you take 7012, you'll figure out how all of this 00:26:03.430 --> 00:26:04.310 other stuff goes. 00:26:04.310 --> 00:26:05.820 And this thing here is phosphate. 00:26:05.820 --> 00:26:07.300 And why is phosphate present? 00:26:07.300 --> 00:26:11.570 Because it's acting as the bridge and a spacer. 00:26:14.480 --> 00:26:18.230 So let's take a look at the structure. 00:26:21.090 --> 00:26:21.430 OK. 00:26:21.430 --> 00:26:23.320 There's more of the amines in nucleic acid. 00:26:23.320 --> 00:26:24.760 So this is what it looks like. 00:26:24.760 --> 00:26:27.960 So you have a backbone that consists of sugar phosphate, 00:26:27.960 --> 00:26:30.630 sugar phosphate, sugar phosphate, shown here. 00:26:30.630 --> 00:26:33.710 So in this case, you've got the deoxyribose. 00:26:33.710 --> 00:26:36.250 So there's the sugar, there's the five-fold symmetry. 00:26:36.250 --> 00:26:39.350 Then the spacer, the phosphate, then the sugar, and 00:26:39.350 --> 00:26:41.260 then the spacer, the phosphate. 00:26:41.260 --> 00:26:46.140 And you can see that the sugars are acting as hangers 00:26:46.140 --> 00:26:48.310 for these amine groups. 00:26:48.310 --> 00:26:50.700 And they're called bases, because in fact they act as 00:26:50.700 --> 00:26:51.760 Bronsted bases. 00:26:51.760 --> 00:26:55.300 They're proton acceptors, and in the early days of molecular 00:26:55.300 --> 00:26:59.090 biology, people determine the chemical composition by wet 00:26:59.090 --> 00:27:00.930 assay, and these were determined 00:27:00.930 --> 00:27:03.340 to be Bronsted bases. 00:27:03.340 --> 00:27:06.960 And so to this day, people refer to them as base pairs, 00:27:06.960 --> 00:27:08.880 et cetera, et cetera, even though now we know they're 00:27:08.880 --> 00:27:10.100 amines, et cetera. 00:27:10.100 --> 00:27:12.150 So this is the structure going up. 00:27:12.150 --> 00:27:14.750 And you see, at one end, you've got the three, and 00:27:14.750 --> 00:27:15.705 going up to the five. 00:27:15.705 --> 00:27:18.800 The three is, you have the carboxylic acid end, and at 00:27:18.800 --> 00:27:21.650 the other end you have the amino end. 00:27:21.650 --> 00:27:21.970 OK. 00:27:21.970 --> 00:27:24.270 So there the structure. 00:27:24.270 --> 00:27:25.950 And you have a choice here. 00:27:25.950 --> 00:27:29.230 So again, the sugar hanger, the phosphate spacer, the 00:27:29.230 --> 00:27:31.070 sugar hanger, the phosphate spacer. 00:27:31.070 --> 00:27:34.580 And you have a choice of one of these four. 00:27:34.580 --> 00:27:38.440 Any one of these four is what's found in a DNA strand, 00:27:38.440 --> 00:27:40.055 as you go up the strand. 00:27:46.120 --> 00:27:48.440 Now, how is information encoded? 00:27:51.170 --> 00:27:53.540 Well, the information is encoded-- 00:27:53.540 --> 00:27:55.490 first of all, we have to recognize what 00:27:55.490 --> 00:27:56.810 the structure is. 00:27:56.810 --> 00:28:00.450 Know that the structure, turns out that it forms a double 00:28:00.450 --> 00:28:06.020 helix, which is the first secondary structure, right? 00:28:06.020 --> 00:28:09.370 It doesn't have. The primary structure is this instant A, 00:28:09.370 --> 00:28:12.380 C, G, T sequence all along. 00:28:12.380 --> 00:28:14.760 And then the secondary structure is, in order to 00:28:14.760 --> 00:28:18.960 maximize hydrogen bonds, this forms a double helix with a 00:28:18.960 --> 00:28:22.310 second chain. 00:28:22.310 --> 00:28:26.940 And furthermore, the pairing is such that A always pairs 00:28:26.940 --> 00:28:30.460 with T, because they have two hydrogen bonding sites between 00:28:30.460 --> 00:28:34.280 them, whereas C pairs with G, because they have three 00:28:34.280 --> 00:28:36.780 hydrogen bonding sites between them. 00:28:36.780 --> 00:28:38.580 And furthermore, look at the spacing here. 00:28:38.580 --> 00:28:41.420 This always just stuns me. 00:28:41.420 --> 00:28:43.990 If you look down the center of the strand-- 00:28:43.990 --> 00:28:47.970 so I've got two strands of nucleic acid. 00:28:47.970 --> 00:28:53.590 The center to center spacing is 1.085 nanometers between A 00:28:53.590 --> 00:28:58.380 and T, and it's 1.085 nanometers to four significant 00:28:58.380 --> 00:29:01.170 figures between C and G. 00:29:01.170 --> 00:29:05.450 And you might say, well, is it possible that I could take two 00:29:05.450 --> 00:29:09.810 of these hydrogen bond sites and line them up to two of the 00:29:09.810 --> 00:29:11.550 three hydrogen bond sites? 00:29:11.550 --> 00:29:14.690 And the answer is no, because the spacing is wrong. 00:29:14.690 --> 00:29:17.830 You can't, these two are far enough apart that they won't 00:29:17.830 --> 00:29:18.450 line up here. 00:29:18.450 --> 00:29:23.561 So it's guaranteed that it's always A to T, C to G. 00:29:23.561 --> 00:29:24.140 All right. 00:29:24.140 --> 00:29:25.960 So now you see the double strand. 00:29:25.960 --> 00:29:27.600 You have one strand moving up. 00:29:27.600 --> 00:29:31.230 You see the pentagon is pointing up, and here you see 00:29:31.230 --> 00:29:33.590 the pentagon is pointing down, and we have the 00:29:33.590 --> 00:29:34.870 base pairs in between. 00:29:34.870 --> 00:29:38.960 C pairs to G, and T pairs to A. 00:29:38.960 --> 00:29:42.730 And down here is the basic end, the acidic end, the basic 00:29:42.730 --> 00:29:44.060 end, the acidic end. 00:29:44.060 --> 00:29:46.800 And so the secondary structure is the double helix. 00:29:46.800 --> 00:29:47.750 Why? 00:29:47.750 --> 00:29:51.580 To maximize hydrogen bonds in between, and then to keep 00:29:51.580 --> 00:29:53.130 maximizing hydrogen bonds. 00:29:53.130 --> 00:29:55.530 Hydrogen bonds between the galleries. 00:29:55.530 --> 00:29:57.378 Maximize, maximize, maximize. 00:30:00.310 --> 00:30:04.815 So there's what they call the base pairs, and et cetera, et 00:30:04.815 --> 00:30:05.950 cetera, et cetera. 00:30:05.950 --> 00:30:09.270 This distance is all prescribed by the fact that we 00:30:09.270 --> 00:30:11.150 have the phosphate present. 00:30:11.150 --> 00:30:11.420 OK. 00:30:11.420 --> 00:30:12.990 Now where's the information here? 00:30:12.990 --> 00:30:15.880 I said this encodes metabolic information. 00:30:15.880 --> 00:30:20.000 Well, suppose I want to direct protein synthesis. 00:30:20.000 --> 00:30:23.140 I want to put amino acids in a sequence. 00:30:23.140 --> 00:30:24.950 So I have to be able to call. 00:30:24.950 --> 00:30:27.535 You know, I'm sitting here as nature, and I'm saying, I want 00:30:27.535 --> 00:30:28.680 to make this protein. 00:30:28.680 --> 00:30:32.470 So I need this amino acid, and then I need this amino acid, 00:30:32.470 --> 00:30:34.030 and then maybe that amino acid, 00:30:34.030 --> 00:30:35.780 and put them in sequence. 00:30:35.780 --> 00:30:39.520 So I need 20 different words to call 20 00:30:39.520 --> 00:30:40.540 different amino acids. 00:30:40.540 --> 00:30:47.160 Well clearly, clearly if I have just A, C, G, and T-- 00:30:47.160 --> 00:30:54.340 so if I have one-letter words, it won't work. 00:30:54.340 --> 00:30:56.550 Because I need to call out 20. 00:30:56.550 --> 00:31:00.260 I need 20 amino acids. 00:31:00.260 --> 00:31:01.680 So how am I going to get to 20? 00:31:01.680 --> 00:31:02.840 I don't have 20 of these. 00:31:02.840 --> 00:31:05.510 I'm only using, there's only four of these. 00:31:05.510 --> 00:31:06.150 So I say, oh. 00:31:06.150 --> 00:31:07.020 I know what to do. 00:31:07.020 --> 00:31:10.380 I can use this idea. 00:31:10.380 --> 00:31:15.940 The number of words will equal the number of letters that I 00:31:15.940 --> 00:31:19.100 have in my alphabet, raised to the power, number 00:31:19.100 --> 00:31:24.800 of letters per word. 00:31:24.800 --> 00:31:25.510 OK? 00:31:25.510 --> 00:31:28.320 So if I use this idea, then I can say-- 00:31:28.320 --> 00:31:30.570 what if I have two-letter words? 00:31:30.570 --> 00:31:36.920 So in other words, to call out an amino acid, I have to take 00:31:36.920 --> 00:31:40.690 two base pairs in sequence. 00:31:40.690 --> 00:31:42.200 That means I'll have-- 00:31:42.200 --> 00:31:43.800 there's only four letters. 00:31:43.800 --> 00:31:47.080 But if I have two letters per word, that's 16, which is 00:31:47.080 --> 00:31:50.980 still less than 20, and that's no good, because I 00:31:50.980 --> 00:31:52.190 can only call 16. 00:31:52.190 --> 00:31:53.770 So what does nature do? 00:31:53.770 --> 00:31:56.500 What if I had three-letter words? 00:31:56.500 --> 00:32:01.140 Three-letter words, then, is a 64, which is greater than 20, 00:32:01.140 --> 00:32:02.710 and that works. 00:32:02.710 --> 00:32:07.550 So now I've got, in point of fact, 61 of these 00:32:07.550 --> 00:32:11.180 three-letter words. 00:32:11.180 --> 00:32:13.700 So I go down the sequence. 00:32:13.700 --> 00:32:16.290 First base pair, second base pair, third base pair. 00:32:16.290 --> 00:32:19.210 That triad represents one amino acid. 00:32:19.210 --> 00:32:24.930 I've got 61 to call out 20, And I've got three left over. 00:32:24.930 --> 00:32:25.960 For what? 00:32:25.960 --> 00:32:27.640 Well, let's think about this. 00:32:27.640 --> 00:32:29.730 See this? 00:32:29.730 --> 00:32:35.960 How do you know to read this, defined by their properties? 00:32:35.960 --> 00:32:39.120 You know to read from left to right. 00:32:39.120 --> 00:32:44.070 You know that there's a space here between words. 00:32:44.070 --> 00:32:48.900 So if I just give you this strand of 00:32:48.900 --> 00:32:53.600 DNA, where do I begin? 00:32:53.600 --> 00:32:55.730 Do I take these three, or do I start counting 00:32:55.730 --> 00:32:56.650 from here or here? 00:32:56.650 --> 00:33:00.280 So built into this, it tells you to read either from left 00:33:00.280 --> 00:33:02.100 to right, or right to left. 00:33:02.100 --> 00:33:04.090 It tells you where to start, and it tells 00:33:04.090 --> 00:33:06.340 you where to stop. 00:33:06.340 --> 00:33:08.730 These three-letter words, by the way, are called codons. 00:33:15.900 --> 00:33:18.670 So we've got sixty-one to call out 20 amino acids, which 00:33:18.670 --> 00:33:21.500 means, some amino acids have more than one name. 00:33:21.500 --> 00:33:23.820 There's one of them that has six different names. 00:33:23.820 --> 00:33:26.010 There's six different codons that can call it 00:33:26.010 --> 00:33:26.950 a given amino acid. 00:33:26.950 --> 00:33:28.530 For some of them it's only one, for some it's 00:33:28.530 --> 00:33:29.950 two, three, et cetera. 00:33:29.950 --> 00:33:30.240 OK. 00:33:30.240 --> 00:33:32.150 So that's the information. 00:33:32.150 --> 00:33:32.310 Look! 00:33:32.310 --> 00:33:32.710 Here it is! 00:33:32.710 --> 00:33:33.470 There's the information! 00:33:33.470 --> 00:33:34.470 It's all in there. 00:33:34.470 --> 00:33:38.610 Just hydrogen bonds like this, hydrogen bonds like this. 00:33:38.610 --> 00:33:41.720 It's all bonding. 00:33:41.720 --> 00:33:42.690 So here's the codon. 00:33:42.690 --> 00:33:45.060 So somewhere here, see, we take this, this, and this. 00:33:45.060 --> 00:33:48.920 This triad represents one piece of information. 00:33:48.920 --> 00:33:49.200 All right. 00:33:49.200 --> 00:33:50.770 So let's go back and look at some of the history. 00:33:50.770 --> 00:33:52.190 Who got us to this point? 00:33:52.190 --> 00:33:54.260 This is fresh! 00:33:54.260 --> 00:33:56.640 A lot of this happened in my lifetime. 00:33:56.640 --> 00:33:56.880 All right. 00:33:56.880 --> 00:33:57.810 So Oswald Avery-- 00:33:57.810 --> 00:33:59.060 this is before my lifetime. 00:34:02.370 --> 00:34:07.040 He was working at the Rochester Institute. 00:34:07.040 --> 00:34:08.380 And he was the first person-- he was 00:34:08.380 --> 00:34:10.070 born in Halifax, actually. 00:34:10.070 --> 00:34:13.360 And he worked professionally here in the United States. 00:34:13.360 --> 00:34:16.760 And he was the first person to recognize that nucleic acids 00:34:16.760 --> 00:34:19.970 store and transmit genetic information. 00:34:19.970 --> 00:34:22.960 Up until the 1940s, people thought nucleic acids-- 00:34:22.960 --> 00:34:25.580 are you ready for this?-- are too complicated. 00:34:25.580 --> 00:34:28.160 Their structure was too complex to contain 00:34:28.160 --> 00:34:29.490 information. 00:34:29.490 --> 00:34:32.550 It's precisely the complexity that gives us the abundance of 00:34:32.550 --> 00:34:33.460 information! 00:34:33.460 --> 00:34:37.820 The prevailing belief was that proteins contained the genetic 00:34:37.820 --> 00:34:38.380 information. 00:34:38.380 --> 00:34:40.390 But people couldn't figure out how to make it work. 00:34:40.390 --> 00:34:47.880 So he was the first to make the argument that the nucleic 00:34:47.880 --> 00:34:50.920 acids have the information. 00:34:50.920 --> 00:34:53.480 And then the second giant is Erwin Chargaff. 00:34:53.480 --> 00:34:57.350 Erwin Chargaff worked at Columbia in New York, and 00:34:57.350 --> 00:34:59.760 hospitals in the vicinity. 00:34:59.760 --> 00:35:03.090 And he was a painstaking analytical chemist. He did all 00:35:03.090 --> 00:35:05.490 of this work by analytical chemistry, and he gave us 00:35:05.490 --> 00:35:08.360 Chargaff's Rules, 1949. 00:35:08.360 --> 00:35:12.820 And he said that in any biological system, the 00:35:12.820 --> 00:35:14.920 concentration of a-- 00:35:14.920 --> 00:35:17.010 remember, they didn't know the structure of DNA yet. 00:35:17.010 --> 00:35:19.800 I'm going to lead up to how we get to the structure of DNA. 00:35:19.800 --> 00:35:22.410 So we're going back, this is like a flashback in a movie. 00:35:22.410 --> 00:35:24.480 Now we're going back to see how we got to the double 00:35:24.480 --> 00:35:25.820 helix, all right? 00:35:25.820 --> 00:35:29.070 People knew that the concentration of A in any 00:35:29.070 --> 00:35:32.520 nucleic acid was equal to the concentration of T. 00:35:32.520 --> 00:35:35.100 They knew that there were sugar present, they knew there 00:35:35.100 --> 00:35:36.980 were amines present, and they knew there 00:35:36.980 --> 00:35:38.860 were phosphates present. 00:35:38.860 --> 00:35:41.390 That's all they knew, based on chemical analysis. 00:35:41.390 --> 00:35:45.770 And now he tells us that, of the amines, concentration of A 00:35:45.770 --> 00:35:49.930 always equals concentration of T, concentration of G always 00:35:49.930 --> 00:35:52.150 equals concentration of C. 00:35:52.150 --> 00:35:55.510 And then the sum of concentration A plus G is the 00:35:55.510 --> 00:35:56.910 sum of C plus T. 00:35:56.910 --> 00:35:59.290 That's Chargaff's rule. 00:35:59.290 --> 00:36:02.020 And so here we are, Homo sapiens. 00:36:02.020 --> 00:36:04.940 31, 31, 19, 19, a little bit of 00:36:04.940 --> 00:36:06.600 statistical error, et cetera. 00:36:06.600 --> 00:36:07.490 But look! 00:36:07.490 --> 00:36:09.020 Corn! 00:36:09.020 --> 00:36:09.980 Yes! 00:36:09.980 --> 00:36:13.580 Corn reproduces using this same code. 00:36:13.580 --> 00:36:18.180 All living organisms on this planet use the same code. 00:36:18.180 --> 00:36:19.280 Which makes sense! 00:36:19.280 --> 00:36:22.920 If I eat corn, and I'm going to get nutrition from it, and 00:36:22.920 --> 00:36:27.410 it's going to help me build cells, and regenerate my body, 00:36:27.410 --> 00:36:32.030 and get energy from it, it has to be made of this same stuff, 00:36:32.030 --> 00:36:34.580 otherwise my body can't recognize it! 00:36:34.580 --> 00:36:37.870 Because I'm a biological machine. 00:36:37.870 --> 00:36:40.850 This is not a fireplace in here, right? 00:36:40.850 --> 00:36:42.630 If it's a fireplace, you can drink something 00:36:42.630 --> 00:36:43.790 combustible and boom! 00:36:43.790 --> 00:36:45.000 You've got energy. 00:36:45.000 --> 00:36:47.950 But we can't derive energy from something combustible. 00:36:47.950 --> 00:36:51.160 We can only derive energy from something like this. 00:36:51.160 --> 00:36:54.280 So, you know, when you think you're really hot stuff, your 00:36:54.280 --> 00:36:58.390 DNA is not that different from that of an ear of corn. 00:36:58.390 --> 00:37:01.480 So a little bit of humility might be in order. 00:37:01.480 --> 00:37:01.900 All right. 00:37:01.900 --> 00:37:03.420 And then the last person we want to talk 00:37:03.420 --> 00:37:05.730 about is Rosalind Franklin. 00:37:05.730 --> 00:37:09.100 Rosalind Franklin worked at the King's College in London, 00:37:09.100 --> 00:37:11.870 and her specialty was x-ray diffraction. 00:37:11.870 --> 00:37:15.490 And she made painstaking experiments where she could 00:37:15.490 --> 00:37:21.040 take a strand of DNA with a stainless steel needle and 00:37:21.040 --> 00:37:24.330 pull it out of an aqueous solution, and hold it in a 00:37:24.330 --> 00:37:28.140 chamber where the chamber was humidified so that the DNA 00:37:28.140 --> 00:37:29.550 didn't dry out. 00:37:29.550 --> 00:37:33.200 And while it was humidified in this chamber, take an x-ray 00:37:33.200 --> 00:37:36.800 diffraction exposure for hours, because all of the 00:37:36.800 --> 00:37:38.890 recording was done by film. 00:37:38.890 --> 00:37:41.470 By halide photography, and you had to have 00:37:41.470 --> 00:37:43.950 long exposure time. 00:37:43.950 --> 00:37:46.860 This is one of the most famous images of the 20 century. 00:37:46.860 --> 00:37:52.510 This is the image of the DNA from calf 00:37:52.510 --> 00:37:54.660 thymus, the beta structure. 00:37:54.660 --> 00:37:56.490 And this is a Laue pattern. 00:37:56.490 --> 00:38:00.240 So the symmetry of this pattern is reflective of the 00:38:00.240 --> 00:38:06.740 symmetry in the DNA structure, which people don't know yet. 00:38:06.740 --> 00:38:09.640 And what you see is five positions. 00:38:09.640 --> 00:38:12.290 One, two, three, four, five. 00:38:12.290 --> 00:38:13.540 Four is missing. 00:38:13.540 --> 00:38:16.760 There's no reflection there. 00:38:16.760 --> 00:38:20.110 But it's where you would expect a position to be. 00:38:20.110 --> 00:38:22.110 So it's sort of Bragg-like, isn't it? 00:38:22.110 --> 00:38:24.450 Not all of the lines are reflecting. 00:38:24.450 --> 00:38:28.170 On the basis of this image, this is what we learned. 00:38:28.170 --> 00:38:35.400 We learned, first of all, that the Laue pattern is indicative 00:38:35.400 --> 00:38:36.750 of a double helix. 00:38:40.300 --> 00:38:41.850 Based on X pattern. 00:38:41.850 --> 00:38:43.840 Remember, they had no computers in those days! 00:38:43.840 --> 00:38:45.700 All they had was a pencil and paper. 00:38:45.700 --> 00:38:48.590 So to do the Fourier transform, and go back out of 00:38:48.590 --> 00:38:52.040 K-space, and discern what the pattern is-- 00:38:52.040 --> 00:38:54.110 you know, today it's trivial! 00:38:54.110 --> 00:38:56.560 They did this all longhand. 00:38:56.560 --> 00:38:58.640 Number two. 00:38:58.640 --> 00:39:02.270 On the basis of that pattern, you learn that it's 3.4 00:39:02.270 --> 00:39:05.615 angstroms between nucleotides along the backbone. 00:39:15.020 --> 00:39:16.630 We don't know what the backbone is! 00:39:16.630 --> 00:39:18.150 We just know that there's sugar, there's 00:39:18.150 --> 00:39:19.230 amine, there's phosphate. 00:39:19.230 --> 00:39:20.610 There's different ways of putting this 00:39:20.610 --> 00:39:22.990 together to make a chain. 00:39:22.990 --> 00:39:26.300 And the third thing that you learn, because the strong, 00:39:26.300 --> 00:39:29.060 clear lines indicate that the heaviest 00:39:29.060 --> 00:39:36.910 elements must lie outboard. 00:39:40.670 --> 00:39:41.630 What does that mean? 00:39:41.630 --> 00:39:46.440 If you've got a double helix, based on the first finding, 00:39:46.440 --> 00:39:48.490 what's the heaviest element? 00:39:48.490 --> 00:39:50.650 Phosphorus. 00:39:50.650 --> 00:39:53.400 Because otherwise you've got carbon, oxygen, nitrogen. 00:39:53.400 --> 00:39:55.810 Nitrogen is atomic mass 14. 00:39:55.810 --> 00:39:57.940 Phosphorus is atomic mass 30. 00:39:57.940 --> 00:39:59.950 So it must be outboard. 00:39:59.950 --> 00:40:02.770 Otherwise, if it were inboard, there would be other elements 00:40:02.770 --> 00:40:05.560 farther out, and you wouldn't get the clear lines. 00:40:05.560 --> 00:40:07.500 Because the heavy elements are the ones that give the 00:40:07.500 --> 00:40:10.020 reflection, and if the heavy elements are obscured by 00:40:10.020 --> 00:40:12.270 lighter elements that are shielding them, you get a 00:40:12.270 --> 00:40:13.300 lousy reflections. 00:40:13.300 --> 00:40:15.596 Blunted reflections, blurry reflections. 00:40:15.596 --> 00:40:24.290 So all of that comes out of her findings. 00:40:24.290 --> 00:40:28.530 So what happens next? 00:40:28.530 --> 00:40:32.250 So there's the 3.4, and 10, and et cetera, et cetera. 00:40:32.250 --> 00:40:34.820 All of that happens based on the pattern that 00:40:34.820 --> 00:40:36.070 I just showed you. 00:40:36.070 --> 00:40:41.210 So I'm going to read to you what happens in those days, 00:40:41.210 --> 00:40:46.750 back in the 1950s. 00:40:46.750 --> 00:40:48.030 There was intense competition. 00:40:48.030 --> 00:40:52.470 You know, Linus Pauling had proposed a triple helix, and 00:40:52.470 --> 00:40:55.410 people in the UK were working hard on it, and so on. 00:40:55.410 --> 00:40:56.950 A lot of competition. 00:40:56.950 --> 00:41:02.210 So what happens is that Watson goes down to King's College in 00:41:02.210 --> 00:41:06.970 London, and he meets Rosalind Franklin in the hallway, and 00:41:06.970 --> 00:41:08.100 they get into a big argument. 00:41:08.100 --> 00:41:12.220 And she really chews him him out, and he goes running away. 00:41:12.220 --> 00:41:13.430 She was very tough. 00:41:13.430 --> 00:41:17.550 And so he goes to Maurice Wilkins, who was her boss. 00:41:17.550 --> 00:41:20.580 And I'm reading, now, from Freeman Judson's book. 00:41:20.580 --> 00:41:22.560 "Wilkins told Watson as they went down the hall that 00:41:22.560 --> 00:41:25.710 Franklin had found that DNA fibers, when kept wet, yielded 00:41:25.710 --> 00:41:28.540 a different x-ray pattern, suggesting a second structure. 00:41:28.540 --> 00:41:30.940 Fourteen months after the King's colloquium, despite 00:41:30.940 --> 00:41:33.590 repeated correspondence and conversations, visits, meals 00:41:33.590 --> 00:41:36.030 together between Wilkins, Watson, and Crick, the 00:41:36.030 --> 00:41:38.400 possibility of a second structure was news to Watson, 00:41:38.400 --> 00:41:39.340 he wrote." 00:41:39.340 --> 00:41:43.320 Now, this is quoting from Watson's own 00:41:43.320 --> 00:41:45.270 book, The Double Helix. 00:41:45.270 --> 00:41:48.770 'When I asked what the pattern was like, Maurice went into 00:41:48.770 --> 00:41:51.370 the adjacent room to pick up a print of the new form they 00:41:51.370 --> 00:41:53.130 called the beta structure. 00:41:53.130 --> 00:41:56.400 The instant I saw the picture, my mouth fell open, and my 00:41:56.400 --> 00:41:57.920 pulse began to raise. 00:41:57.920 --> 00:42:00.470 The pattern was unbelievably simpler than those obtained 00:42:00.470 --> 00:42:02.410 previously, the a-form. 00:42:02.410 --> 00:42:05.280 Moreover, the black cross of reflections which dominated 00:42:05.280 --> 00:42:09.670 the picture could arise only from a helical structure. 00:42:09.670 --> 00:42:12.000 With the a-form, the argument for a helix was never 00:42:12.000 --> 00:42:12.650 straightforward. 00:42:12.650 --> 00:42:15.650 With the b-form, however, mere inspection of its x-ray 00:42:15.650 --> 00:42:16.740 picture gave"-- 00:42:16.740 --> 00:42:20.810 listen to this-- "several of the vital helical parameters." 00:42:20.810 --> 00:42:21.860 I'm going to come back to that. 00:42:21.860 --> 00:42:24.540 "The picture that Wilkins showed Watson was Rosalind 00:42:24.540 --> 00:42:27.330 Franklin's, without her approval." 00:42:27.330 --> 00:42:31.590 So then Watson goes on the train back to Cambridge, and 00:42:31.590 --> 00:42:36.090 sits down with Crick, and in no time, they've put the 00:42:36.090 --> 00:42:36.860 structure together. 00:42:36.860 --> 00:42:38.000 And this is a famous picture. 00:42:38.000 --> 00:42:38.620 This is Crick. 00:42:38.620 --> 00:42:40.490 This is Watson. 00:42:40.490 --> 00:42:42.230 And I don't know if you can see really well. 00:42:42.230 --> 00:42:44.570 These are lab clamps that they're using. 00:42:44.570 --> 00:42:45.710 This is a lab stand. 00:42:45.710 --> 00:42:50.380 They're using lab clamps to put the structure together. 00:42:50.380 --> 00:42:51.556 So here's the paper. 00:42:51.556 --> 00:42:53.380 The paper as it comes out, Molecular 00:42:53.380 --> 00:42:55.120 Structure of Nucleic Acids. 00:42:55.120 --> 00:42:57.620 And this was the first image of DNA. 00:42:57.620 --> 00:43:02.360 And I submit to you that if the earth were to end in a 00:43:02.360 --> 00:43:05.860 giant explosion, and we were to only send two images in a 00:43:05.860 --> 00:43:09.890 spaceship out to let some other race discover what we're 00:43:09.890 --> 00:43:12.320 all about, it would be this image, and the 00:43:12.320 --> 00:43:13.560 image of the atom. 00:43:13.560 --> 00:43:15.162 That's all you need. 00:43:15.162 --> 00:43:18.260 Because you have the simple atom, and you've got this, and 00:43:18.260 --> 00:43:21.070 everything else is just detail in between. 00:43:21.070 --> 00:43:23.140 So there's the first image. 00:43:23.140 --> 00:43:23.620 All right. 00:43:23.620 --> 00:43:25.800 "We wish to suggest a structure for the salt of 00:43:25.800 --> 00:43:28.140 deoxyribonucleic acid. 00:43:28.140 --> 00:43:30.560 The structure has novel features which have 00:43:30.560 --> 00:43:33.020 considerable biological interest. The structure for 00:43:33.020 --> 00:43:36.660 nucleic acid has already been proposed by Pauling and Corey. 00:43:36.660 --> 00:43:39.000 They kindly made their manuscript available to us in 00:43:39.000 --> 00:43:39.810 advance." 00:43:39.810 --> 00:43:42.720 These guys never made their manuscripts available to Corey 00:43:42.720 --> 00:43:45.240 and Pauling. 00:43:45.240 --> 00:43:47.610 "Their model consists of three intertwined chains with the 00:43:47.610 --> 00:43:51.080 phosphates near the fiber axis and the bases on the outside." 00:43:51.080 --> 00:43:55.360 See, they got the positions wrong. 00:43:55.360 --> 00:43:57.450 "Without acidic--" da, da, da, da, da, and so on. 00:43:57.450 --> 00:43:59.170 Whatever. 00:43:59.170 --> 00:44:00.080 Now here's-- 00:44:00.080 --> 00:44:02.550 remember, I've quoted from Watson's book. 00:44:02.550 --> 00:44:06.240 "The previously published x-ray data on deoxyribonucleic 00:44:06.240 --> 00:44:08.280 acid are insufficient for a rigorous test of our 00:44:08.280 --> 00:44:09.830 structure." 00:44:09.830 --> 00:44:10.600 Really? 00:44:10.600 --> 00:44:13.490 "So far as we can tell, it is roughly compatible with the 00:44:13.490 --> 00:44:16.290 experimental data, but it must be regarded as unproved until 00:44:16.290 --> 00:44:18.590 it's been checked against some more exact results." 00:44:18.590 --> 00:44:21.570 Remember, he's writing this after having seen Rosalind 00:44:21.570 --> 00:44:23.980 Franklin's x-ray pattern. 00:44:23.980 --> 00:44:26.110 "Some of these are given in the following communications." 00:44:26.110 --> 00:44:28.670 Yeah, the next paper is Rosalind Franklin's paper. 00:44:28.670 --> 00:44:31.930 "We were not aware of the details of the results 00:44:31.930 --> 00:44:34.930 presented there when we devised our structure,--" 00:44:34.930 --> 00:44:36.800 That's a lie. 00:44:36.800 --> 00:44:39.690 "--which rests mainly, though not entirely, on published 00:44:39.690 --> 00:44:42.670 experimental data and stereochemical arguments." 00:44:42.670 --> 00:44:45.190 You know what? once I've given you the data, and you know 00:44:45.190 --> 00:44:48.300 what the structure is, you can give me a very, very strong 00:44:48.300 --> 00:44:49.810 stereochemical argument. 00:44:49.810 --> 00:44:51.390 But that's hindsight. 00:44:51.390 --> 00:44:54.890 If you don't know what the structure is, you have no idea 00:44:54.890 --> 00:44:56.950 what the stereochemical arguments are, because you can 00:44:56.950 --> 00:44:58.590 justify anything. 00:44:58.590 --> 00:45:02.000 So this is just absolute lies. 00:45:02.000 --> 00:45:02.900 Who are the authors? 00:45:02.900 --> 00:45:06.150 Watson and Crick, even though it's based on data that was 00:45:06.150 --> 00:45:07.880 taken from other people. 00:45:07.880 --> 00:45:08.470 So here they are. 00:45:08.470 --> 00:45:09.550 This is the acknowledgments. 00:45:09.550 --> 00:45:11.350 We're indebted to-- blah, blah, blah. 00:45:11.350 --> 00:45:14.990 The experimental results in ideas of Wilkins, Rosalind 00:45:14.990 --> 00:45:17.620 Franklin, and their coworkers at King's College. 00:45:17.620 --> 00:45:20.870 And one of us, Jim Watson, he was the American, and I think 00:45:20.870 --> 00:45:23.760 there's an irony here, was aided by a fellowship from the 00:45:23.760 --> 00:45:26.200 National Foundation for Infantile Paralysis. 00:45:26.200 --> 00:45:28.340 And I think there's a joke there, if you know anything 00:45:28.340 --> 00:45:30.540 about Jim Watson. 00:45:30.540 --> 00:45:33.230 And now contrast that with this. 00:45:33.230 --> 00:45:35.990 This is the publication of the human genome. 00:45:35.990 --> 00:45:37.790 And look at all the names here. 00:45:37.790 --> 00:45:41.110 Everybody who was involved in the enterprise was named. 00:45:41.110 --> 00:45:42.080 This is not the paper. 00:45:42.080 --> 00:45:44.190 This is just the names of the authors. 00:45:47.300 --> 00:45:50.120 Now, to be literate, there's this one phrase. 00:45:50.120 --> 00:45:52.210 Typical British understatement. 00:45:52.210 --> 00:45:55.330 Remember, this was about the structure of DNA. 00:45:55.330 --> 00:45:56.580 But there's this passage. 00:45:56.580 --> 00:45:58.100 It has not escaped our notice. 00:45:58.100 --> 00:46:00.930 This is the litotes. 00:46:00.930 --> 00:46:02.160 Understatement, right? 00:46:02.160 --> 00:46:04.810 "It has not escaped our notice that the specific pairing we 00:46:04.810 --> 00:46:08.890 have postulated immediately suggests a possible copying 00:46:08.890 --> 00:46:11.490 mechanism for the genetic material." 00:46:11.490 --> 00:46:15.780 That is the understatement all time. 00:46:15.780 --> 00:46:18.620 We've got the structure of DNA, and parenthetically, I 00:46:18.620 --> 00:46:22.500 think this is how you direct replication in all living 00:46:22.500 --> 00:46:24.910 creatures, by the way. 00:46:24.910 --> 00:46:27.380 So when this paper was published. 00:46:27.380 --> 00:46:30.150 and they rolled out the human genome 00:46:30.150 --> 00:46:33.630 as a sort of a literary-- 00:46:33.630 --> 00:46:34.880 what's the word-- 00:46:37.580 --> 00:46:38.670 allusion, thank you. 00:46:38.670 --> 00:46:41.690 The literary allusion was-- there's a passage in this 00:46:41.690 --> 00:46:44.930 paper that at one point begins "It has not escaped our 00:46:44.930 --> 00:46:46.300 noticed," da, da, da, da. 00:46:46.300 --> 00:46:50.160 So if you're ever with some Course 7 people, and you want 00:46:50.160 --> 00:46:52.420 to really get under their skin, you know, you could be 00:46:52.420 --> 00:46:54.280 at a party or something, and finally, you say you know, 00:46:54.280 --> 00:46:55.680 it's not escaped my notice. 00:46:55.680 --> 00:46:58.870 And they know what you're saying. 00:46:58.870 --> 00:47:01.345 It'll make you less popular then you are now. 00:47:04.630 --> 00:47:05.660 So let's fast forward. 00:47:05.660 --> 00:47:08.200 This is Stockholm, December 10, 1962, 00:47:08.200 --> 00:47:09.750 the Nobel Prize ceremony. 00:47:09.750 --> 00:47:12.110 Here is the King of Sweden. 00:47:12.110 --> 00:47:14.610 This is Francis Crick. 00:47:14.610 --> 00:47:15.860 This is James Watson. 00:47:15.860 --> 00:47:17.040 This is Maurice Wilkins. 00:47:17.040 --> 00:47:19.420 No Rosalind Franklin. 00:47:19.420 --> 00:47:23.540 This is Kendrew, and I'm drawing a blank. 00:47:23.540 --> 00:47:26.290 These two guys were getting the Nobel Prize in Chemistry 00:47:26.290 --> 00:47:28.730 for hemoglobin structure. 00:47:28.730 --> 00:47:31.580 This, if you look carefully, is John Steinbeck, getting the 00:47:31.580 --> 00:47:32.830 Nobel Prize in Literature. 00:47:35.600 --> 00:47:39.550 Over in Oslo is Linus Pauling, getting his second Nobel 00:47:39.550 --> 00:47:40.930 Prize, but for peace. 00:47:40.930 --> 00:47:43.450 So ironically, he's getting his Nobel Prize. 00:47:43.450 --> 00:47:46.270 They're getting the Nobel Prize not in Chemistry, not in 00:47:46.270 --> 00:47:48.340 Physics, but in Medicine. 00:47:48.340 --> 00:47:50.370 You know, what's medicine? 00:47:50.370 --> 00:47:52.520 I mean it's not really a science. 00:47:52.520 --> 00:47:53.830 But anyway. 00:47:53.830 --> 00:47:54.620 Here it is. 00:47:54.620 --> 00:47:57.100 It's worthy of a Nobel Prize. 00:47:57.100 --> 00:47:59.470 So what really happened here? 00:47:59.470 --> 00:48:00.460 What really happened? 00:48:00.460 --> 00:48:03.230 Why was there no Rosalind Franklin? 00:48:03.230 --> 00:48:05.320 She was marginalized as a woman. 00:48:05.320 --> 00:48:07.670 She was mistreated by these men. 00:48:07.670 --> 00:48:09.230 It was 1955. 00:48:09.230 --> 00:48:10.400 You realize in the 1950s-- 00:48:10.400 --> 00:48:13.500 and I'm not talking about the England of Charles Dickens. 00:48:13.500 --> 00:48:16.260 I'm talking about the England after World War II. 00:48:16.260 --> 00:48:18.840 Women were not allowed in the common room. 00:48:18.840 --> 00:48:20.940 And the common room is where everybody 00:48:20.940 --> 00:48:22.400 congregates at 4:00 p.m. 00:48:22.400 --> 00:48:24.350 to drink coffee and exchange ideas. 00:48:24.350 --> 00:48:26.650 So she couldn't go into the common room and so on. 00:48:26.650 --> 00:48:31.670 And it was just a terrible, terrible story of misuse, of 00:48:31.670 --> 00:48:34.490 information, lack of attribution, and so on. 00:48:34.490 --> 00:48:37.450 If this story were unfolded today, I guarantee you these 00:48:37.450 --> 00:48:40.260 guys would not be getting a prize, and in fact, the 00:48:40.260 --> 00:48:44.120 publication would probably be rescinded on the grounds of 00:48:44.120 --> 00:48:48.450 its fraudulent claims, that they were unaware of the 00:48:48.450 --> 00:48:50.480 previous information. 00:48:50.480 --> 00:48:53.220 So after the paper was published, she was so 00:48:53.220 --> 00:48:56.100 brokenhearted that she resigned her position at 00:48:56.100 --> 00:49:00.800 King's College, and took a job at another college in London. 00:49:00.800 --> 00:49:03.630 Her terms of severance included her signing a 00:49:03.630 --> 00:49:09.040 document in which she agreed to abandon all future work in 00:49:09.040 --> 00:49:10.290 biochemistry. 00:49:12.060 --> 00:49:14.650 I mean, imagine that you leave your job, and they tell you 00:49:14.650 --> 00:49:15.590 what you cannot do! 00:49:15.590 --> 00:49:19.440 I mean, obviously, if you were privy to intellectual property 00:49:19.440 --> 00:49:21.880 and so on, you're bound by confidentiality. 00:49:21.880 --> 00:49:25.450 But no one can tell you, you can't go to work for somebody! 00:49:25.450 --> 00:49:30.650 And so she changed fields, and made seminal discoveries in 00:49:30.650 --> 00:49:35.390 two other fields outside of the DNA work. 00:49:35.390 --> 00:49:37.080 So why isn't she here? 00:49:37.080 --> 00:49:41.070 She died of cancer in 1958, very young. 00:49:41.070 --> 00:49:44.460 And you can't get the Nobel Prize posthumously. 00:49:44.460 --> 00:49:48.530 So some people are quite outraged by this story. 00:49:48.530 --> 00:49:52.820 But there's a symbolism here to have Wilkins. 00:49:52.820 --> 00:49:54.580 It's basically saying that you two guys are not 00:49:54.580 --> 00:49:55.450 the authors of this. 00:49:55.450 --> 00:49:58.190 And so some people say that Wilkins is standing in for 00:49:58.190 --> 00:50:01.370 Rosalind Franklin, and the Nobel committee at least 00:50:01.370 --> 00:50:02.490 acknowledged that. 00:50:02.490 --> 00:50:03.630 So what's the message here? 00:50:03.630 --> 00:50:08.220 The message here is, I hope nobody in 3.091 is ever 00:50:08.220 --> 00:50:10.400 embroiled in a controversy like this. 00:50:10.400 --> 00:50:14.150 We have to acknowledge our collaborators. 00:50:14.150 --> 00:50:17.390 All of us are here because somebody helped us. 00:50:17.390 --> 00:50:18.830 Don't go away. 00:50:18.830 --> 00:50:20.060 You haven't been dismissed yet. 00:50:20.060 --> 00:50:20.970 This is important. 00:50:20.970 --> 00:50:21.950 What I'm telling you is far more 00:50:21.950 --> 00:50:24.700 important than that structure. 00:50:24.700 --> 00:50:26.150 I'm telling you how to stay out of jail. 00:50:29.250 --> 00:50:32.680 See, here, you know, 50 years ago, you cheat and steal, you 00:50:32.680 --> 00:50:33.700 get a Nobel Prize. 00:50:33.700 --> 00:50:36.020 Today you go to jail. 00:50:36.020 --> 00:50:37.470 It is a Nobel Prize in Medicine, 00:50:37.470 --> 00:50:39.840 of course, but anyway. 00:50:39.840 --> 00:50:42.750 So this is a book, if you're interested in Rosalind 00:50:42.750 --> 00:50:45.710 Franklin's story, it's fantastic reading. 00:50:45.710 --> 00:50:46.960 Real page-turner. 00:50:46.960 --> 00:50:48.360 This is James Watson's book. 00:50:48.360 --> 00:50:51.050 If you read this, you know, have your you-know-what 00:50:51.050 --> 00:50:53.620 sensors on all the time. 00:50:53.620 --> 00:50:55.240 And here's a picture of Rosalind Franklin 00:50:55.240 --> 00:50:56.870 on vacation in France. 00:50:56.870 --> 00:50:59.070 And we'll leave with The Twist by Hank Ballard, who was 00:50:59.070 --> 00:51:01.150 another person who was marginalized, 00:51:01.150 --> 00:51:02.520 because he was black! 00:51:02.520 --> 00:51:05.740 And so you couldn't listen to this music, and so there was a 00:51:05.740 --> 00:51:06.500 cover made. 00:51:06.500 --> 00:51:09.520 The version of The Twist that you have heard is probably by 00:51:09.520 --> 00:51:10.200 Chubby Checker. 00:51:10.200 --> 00:51:12.320 This is the original one by Hank Ballard. 00:51:12.320 --> 00:51:13.620 It's gritty. 00:51:13.620 --> 00:51:14.530 It's very gritty. 00:51:14.530 --> 00:51:15.900 All right. 00:51:15.900 --> 00:51:17.320 Treat each other well. 00:51:17.320 --> 00:51:18.950 Get out of here.