Podcast
Possibly related to Andy Weir: ‘The Martian’ on Huffduffer
Hosted by Unknown author · EN
Possibly related to Andy Weir: ‘The Martian’
10episodes
Episodes
Newest firstAll episodes
Episode 5: Geoffrey West on Networks, Scaling, and the Pace of Life – Sean Carroll
Jul 16, 2019Tap to summarizeIf you scale up an animal to twice its height, keeping everything else proportionate, its volume and weight become eight times as much. Such a scaling relation was used by J.B.S. Haldane in his famous essay, “On Being the Right Size,” to help explain certain features of living organisms. But scaling relations go much deeper than that, and they are often much more subtle than the volume going as the cube of the length. Geoffrey West is a particle physicist turned complexity theorist, who studies how features from metabolism to lifespan change as we adjust the size of an organism — or of other complex systems, from cities to computer networks. His insights have important implications for innovation, sustainability, and the best ways to organize life here on Earth. Geoffrey West received his Ph.D. in physics from Stanford University. He is currently a Distinguished Professor at the Santa Fe Institute, where he served as President from 2005 to 2009. He has been listed as one of Time magazine’s 100 most influential people in the world. He is the author of Scale: The Universal Laws of Growth, Innovation, Sustainability, and the Pace of Life in Organisms, Cities, Economies, and Companies. Home page Wikipedia page Amazon page TED talk on “The Surprising Math of Cities and Corporations“ Google Scholar publications Download Episode Click to Show Episode Transcript Click above to close. 0:00:00 Sean Carroll: Hello everybody, and welcome to the Mindscape Podcast. I’m your host, Sean Carroll, and if you’re familiar with my book “The Big Picture” or any of the various talks I’ve given on that book, you’ll know that one of my favorite factoids is that the average human lifespan is three billion heartbeats. That’s not a very profound fact if you just take the fact that the average human being lives for about 75 years, and do your dimensional analysis to convert from years to heartbeats, the number works out to be about three billion for a typical human being stretching from birth to death. 0:00:34 SC: But it’s an interesting fact, because it brings home in a slightly more vivid way how short our life is. Three billion is a big number, but it’s not unimaginably big, and unlike years, heartbeats are going by all the time. You’ve squandered several of your heartbeats already listening to me talk right here. And I’ve learned this fact about the three billion heartbeats from today’s guest, Dr. Geoffrey West, who’s a distinguished professor at the Santa Fe Institute. And it’s the context of a much more profound fact about biological organisms here on earth. If you take any particular kind of organism, let’s say, mammals because human beings are mammals, they come in all shapes and sizes. There’s tiny little mice, there’s big old blue whales or elephants, but there are relationships between the size of an animal in mass, for example, the number of kilograms the thing has, and other biological facts such as how long it lives. Bigger animals, whales and elephants, live for much longer than tinier things like mice or squirrels. 0:01:38 SC: Meanwhile, there’s another relationship between your size and your heart rate. Big animals like whales and elephants have very slow heartbeats. Tiny animals have very rapid heartbeats, and you can see where this is going. These two facts exactly cancel out. The average number of heartbeats for mammals, is approximately the same for tiny little mice, or big old blue whales, or elephants. It’s not an exact relationship. In fact, the number for a typical mammal works out not to be three billion but one and a half billion which maybe you could argue is roughly what we had, we human beings, back in the state of nature before we had pasteurized milk and Obamacare and things like that. But the point is that something is going on that goes beyond mere biology, there’s some reason why there’s a relationship between how fast your heart beats, how massive you are, and how long you live. 0:02:34 SC: That’s what got today’s guest, Geoffrey West, interested in biology, networks, and complex systems. He started his academic life as a particle physicist, but he read about these scaling relations, and he realized from his physics point of view, no one understood them. No one knew why things were like that. So he and his collaborators developed a theory that explains why you get this relationship. As an animal gets bigger, it lives longer, but its heart slows down; the pace of life is slower for larger animals. These days he’s extending that analysis not just to individual animals, but to cities or cultures, or other kinds of networks that fill our daily lives today. This kind of analysis is absolutely crucial for sustainability, for thinking about how we live in the world, for choosing how to manage our life here on earth. Geoffrey West is the former president of the Santa Fe Institute, and he’s the author of a wonderful recent book called “Scale: The Universal Laws of Growth, Innovation, Sustainability and the Pace of Life in Organisms, Cites, Economies and Companies.” It’s not the most elegant title, I’ll give you that, but it’s an extremely important and hopefully influential book that helps us understand the world we live in. So, let’s go. [music] 0:04:10 SC: Geoffrey West, welcome to the podcast. 0:04:12 Geoffrey West: Hey, nice to be here, Sean. Thank you for inviting me. 0:04:14 SC: So I have to ask, when you’re on an airplane going to a conference, traveling around the world, and you find yourself sitting next to an inquisitive type and they say, “So, what do you do for a living?” [laughter] What is your answer to that kind of question? 0:04:30 GW: Oh goodness me, that’s a tough one. And it always stops me in my tracks. But because I’m slightly misanthropic and, but what do I say? I think I always lead off pretty much by saying, “I’m a physicist.” And then I quickly say, “I’m a physicist, but I work now a lot, and questions, challenges that are considered outside of usual physics and I’ve done quite a lot of work in, what I would consider fundamental questions in biology, and now about cities, companies, and I’m particularly interested in the whole question of global sustainability.” 0:05:19 SC: Right. 0:05:19 GW: So I sort of do it in that, I mean maybe not quite as linearly, as that, but effectively. 0:05:25 SC: But now, in your youth, you were more or less mainstream. Theoretically… 0:05:29 GW: Absolutely. 0:05:30 SC: So what kinds of things did you work on then, and what happened? 0:05:33 GW: So yeah, so most of my career, meaning the first 30-odd-years, I did definitely what you would call mainstream particle physics. Even entering it when I would say, the kinds of things you work on and you’ve made your name on were considered way out there… [laughter] They weren’t questions a real physicist should be answering or asking. 0:06:00 SC: Right. Cosmology’s dark era. 0:06:01 GW: Yeah yeah it was like come on, you know. And I think one of the, by the way just tangentially, one of the great things that has happened in physics is that we do ask those questions and we address them seriously and it’s now developed into its own thing, and it’s a profound influence. But back then, I was the mainstream physicist working on… Well I entered it very fortunately, at a really opportune moment because these famous experiments which got the Nobel prize at Stanford, on which eventually we interpreted as discovering quarks, were taking place, the results were just coming out, and I had been sort of… 0:06:52 SC: This is the early ’70s. 0:06:54 GW: Well they were the late ’60s actually, late ’60s. I got my PhD in ’66, and those, the accelerator at Stanford was just being completed and the first experiments were being performed and the results that changed everything, which were results on an experiment that at the time was thought of as mundane and uninteresting appeared, and they were quite surprising, and as I say eventually they were interpreted as the evidence for quarks and that was a very exciting period, as one tried to interpret those experiments, try to formulate models and then theories and, ultimately, the evolution towards something called Quantum Chromodynamics. 0:07:46 SC: QCD. 0:07:46 GW: QCD. The theory of the strong interactions and that was very exciting. 0:07:52 SC: And did you feel that this is what life was going to be like? Every few years, you would discover a new layer of structure, of matter, new fundamental laws? 0:08:00 GW: Absolutely. No, in fact I would say, during that period, from probably ’68-’70 onwards, through the ’70s into the early ’80s, we were kind of spoiled because every year there was a new fantastic discovery that either… Or confirmation of something, and it was just a marvelous period, and it culminated in the development of the so-called Standard Model where we see some part of Grand Unification, or at least we saw that you could contemplate Grand Unification of the electromagnetism with the strong forces and so on. And that was just immensely exciting and then that led to this naivety that it would only be a few more years when we could get gravity into the picture. 0:09:01 GW: As I say, it really was a period of immense excitement, but a period of being spoiled as one does. It reminds me a bit, it actually is sort of interesting when I look back on it, because it also had some of the flavor of the ’60s and ’70s in society. You know, the emergence from the ’50s and early ’60s, and kind of the image of suburban America with your 2.4 children. The image of that we all had, to suddenly the psychedelic revolution, the Vietnam War, and what the demonstrations and anti-war movement brought, the Civil Rights movement. 0:09:47 SC: But then we hit the Reagan era. 0:09:48 GW: And then we hit, exactly, and so it is that in physics, we hit not because of a Ronald Reagan or because there was a vote, but because it turns out that nature was not quite as fo...
Transcribe →The Demonization of Gluten - Freakonomics Freakonomics
Oct 19, 2017Tap to summarizeCeliac is the only autoimmune disease for which we know the trigger that turns the immune system against the body. The culprit? Gluten. (Photo: Pixabay) Our latest Freakonomics Radio episode is called “The Demonization of Gluten.” (You can subscribe to the podcast at Apple Podcasts or elsewhere, get the RSS feed, or listen via the media player above.) Celiac disease is thought to affect roughly one percent of the population. The good news: it can be treated by quitting gluten. The bad news: many celiac patients haven’t been diagnosed. The weird news: millions of people without celiac disease have quit gluten – which may be a big mistake. Below is a transcript of the episode, modified for your reading pleasure. For more information on the people and ideas in the episode, see the links at the bottom of this post. * * * In the 1930s, a Dutch pediatrician named Willem Dicke began to study a mysterious, often-fatal disease that was afflicting his patients. Children were losing weight and becoming malnourished despite consuming plenty of calories. The symptoms were intense and widespread. Alessio FASANO: The damage is the intestine. This is a systemic disease that does not spare any tissue organ in your body. That’s Alessio Fasano. FASANO: I’m professor of pediatrics at Massachusetts General Hospital for Children. Willem Dicke suspected the illness was somehow related to the children’s diet. But it wasn’t until years later that he found the proof he was looking for. It came in the form of a grotesque natural experiment produced by the Second World War. In 1940, Germany had invaded and occupied the Netherlands. In 1944, Dutch railway workers held a strike in support of the Allies. This prompted the Nazis to cut off food shipments to Dutch civilians. Alan LEVINOVITZ: This was called the Hunger Winter. That’s Alan Levinovitz, a religion scholar at James Madison University. LEVINOVITZ: It was horrific. Children everywhere were starving. Some people resorted to eating grass or tulip bulbs; thousands died of starvation. But Willem Dicke noticed something strange. His pediatric patients who’d been sick before the war … LEVINOVITZ: … were actually improving. Then in 1945, the Hunger Winter ended. Bread was dropped over Holland and everyone’s lives improved — except for those of the children , who immediately relapsed into the condition that they had been suffering before. FASANO: And this pediatrician, Dr. Dicke, would reason what we did not have during the war, now, is coming back. That can be the culprit. He made the hypothesis where grains are the culprit. That’s right, grains. Which the kids hadn’t been eating during the Hunger Winter — but now, after bread came back, they were. So Dicke ran a little experiment. FASANO: He took six of these kids, put them on a gluten-free diet, showing that the symptoms were completely gone, put them back on a regular diet, showing that the symptoms came back. That was the cornerstone, and still is of our understanding of how you trigger celiac disease. And that is how our modern understanding of celiac disease came to be. Even today, it’s still somewhat mysterious. But one thing that isn’t mysterious at all is the trigger: FASANO: And it’s gluten. Today on Freakonomics Radio, we’ll look at the recent spike in celiac disease, and why, historically, it’s been underdiagnosed: FASANO: The symptoms unfortunately are not straightforward like many autoimmune diseases. We’ll look at the intersection between health trend and media sensation: LEVINOVITZ: Jenny McCarthy was hugely influential. We look at the economic implications of the gluten-free movement — both micro … Kadee RUSS: I probably spend upwards of $1,200 a month on groceries. And macro … Jennifer BOND: The northern plains of the U.S. have seen declining plantings of wheat. “Gluten, Gluten Everywhere.” Right after this: * * * Alessio Fasano is one of the world’s leading authorities on celiac disease and gluten. FASANO: I can’t make that statement myself. But we can. And he is. By the time Fasano started his medical studies, in the 1980s, celiac disease was understood much better than in Willem Dicke’s era. So let’s start with what we know. First of all, the name, celiac. It’s from the Greek, meaning “a sickness of the belly.” And how is the disease defined? FASANO: This is truly an autoimmune disease. It’s like having diabetes, multiple sclerosis, or rheumatoid arthritis. So celiac is an autoimmune disease — with, as Fasano puts it, a recipe containing at least two ingredients. FASANO: 1) A genetic predisposition — many genes needs to come together to make you at-risk. 2) An environmental trigger that is mismanaged by your immune system. And what sometimes happens when the environmental trigger meets the genetic predisposition … FASANO: The immune system starts to attack its own body rather than get rid of the enemy. An immune system attacking its own tissues — that’s the definition of an autoimmune disease. But there’s one major way in which celiac is unlike other autoimmune diseases like rheumatoid arthritis or diabetes or multiple sclerosis. Celiac is unique among autoimmune diseases … FASANO: … because the culprit, the enemy, that turn the immune system to attack your own body, is known. And it’s gluten. This known enemy, gluten, is a protein that’s found in rye, barley, and, most prominently, in wheat. Gluten is what gives structure to foods like bread, pasta, and cake. So gluten is the trigger for celiac disease; and the treatment then is what? FASANO: The treatment is the elimination of gluten from the diet. Stephen J. DUBNER: How quickly and how completely does that treatment address the issue? FASANO: Some people will have resolution of the symptoms rather quickly. Others will take much longer. [In] the vast majority, it will be a complete resolution. DUBNER: How does it feel to know that you’re responsible for people crossing those beloved food items off their lists forever? FASANO: Being Italian, I feel awful. It is definitely a tremendous change in lifestyle. No question about that. We face this all the time. A newly diagnosed celiac will go through a serious change and feel [things] from denial to be[ing] upset — to frustrated, to depressed — because one of the most natural [things] to humankind, eating, will become a very challenging mental exercise rather than a very spontaneous activity. Fasano got his medical training in Italy. FASANO: There was a university in Naples where celiac disease was a big deal. Indeed, the University of Naples had a celiac research center; Italian schoolchildren were enrolled in large-scale screening programs. Epidemiological studies showed that roughly 1 in 300 Italians had celiac disease. That’s pretty common! And because it was fairly common, Fasano wasn’t that interested in studying it further. FASANO: One of the reason why I decide to move to the United States was because I was sick and tired [of] talk[ing] about celiac disease and work on it. In 1988, he arrived at the University of Maryland. In the U.S., celiac disease was thought to be much rarer than in Europe: 1 in 10,000 people versus 1 in 300. FASANO: Days passed by, weeks passed by, months passed by, and I didn’t see a single case of celiac disease. I went from the twenty cases a day that I [was] forced to see in Italy, to zero. Fasano’s plan to get away from celiac disease had worked. But he began to wonder why there was such a huge difference. FASANO: I was wondering, “If the genetic background is the same in Europe, and we eat the same gluten-containing grains that they consume in Europe, why is celiac disease so frequent there and does not exist here?” I reasoned, “Either the disease does not exist in United States, so it will be a very interesting proposition to understand why.” And the alternative was that it was overlooked and so was underestimated. In other words: was celiac disease really so rare in the U.S. or were American doctors just missing it? Fasano decided to find out. He headed over to his local Red Cross to get some blood samples … FASANO: … I was shocked to know that I had to pay for it. They asked me for $6 apiece. I said, “You must be out of your mind. I would never pay [that] amount of money.” We engage in this back-and-forth negotiation that is actually the heart and soul of the Neapolitan attitude. You never pay whatever they ask for. Eventually they settled on $3 apiece. Fasano bought 2,000 samples and began testing them. If someone who has celiac disease eats gluten, their body produces abnormally high rates of certain kinds of antibodies. Gluten has been recognized as an intruder and their body is trying to fight it off — but instead the antibodies end up attacking healthy cells. This activity can be detected in a blood test. So, when Fasano screened the Red Cross blood samples, what did he find? FASANO: The prevalence was one in 250. A prevalence of 1 in 250! The previous estimate in the U.S. remember, was 1 in 10,000. This new finding would make celiac disease 40 times more common in the U.S than previously thought. Under the old estimate, only 27,000 Americans likely had celiac disease; the new estimate suggested it was more like a million. FASANO: That gave us the impetus to move to this large epidemiologic study on the national scale, in which we recruited more than 40,000 people. This new, national study, published in 2003, yielded an even higher estimate. It found that 1 of every 133 Americans had celiac disease. This was pretty much in line with the most recent European numbers. So America wasn’t so different from Italy after all! According to Fasano’s research, more than 2 million Americans had celiac disease. How was it possible that a disease so well-identified in some places had been practically invisible in the U.S.? FASANO: The symptoms of celiac disease unfortunately are not straightforward li...
Transcribe →Lisa Randall — Dark Matter, Dinosaurs, and Extra Dimensions | On Being
Oct 8, 2017Tap to summarizeKrista Tippett, host: Theoretical physicist Lisa Randall started out seeking answers to questions in Standard Model physics and ventured into pondering extra-dimensional worlds. Now she’s moved into illuminating what she calls “the astounding interconnectedness” between fields which have previously operated more autonomously — astronomy, biology, paleontology. She’s pursuing a theory that dark matter might have created the cosmic event that led to the extinction of the dinosaurs and hence, humanity’s rise as a species. We explore what she’s discovering, as well as the human questions and takeaways her work throws into relief. [music: “Seven League Boots” by Zoe Keating] Lisa Randall: It’s OK to be aware of our limitations as human beings, that these are things that make it harder. It doesn’t make it impossible. And that’s the beauty of science, is that we can go beyond these prejudices, if you like, these intuitions that we have built on our ordinary, everyday experience that allows us to think about things that seem obviously wrong. They’re not obviously wrong, they’re just not obvious to us. [music: “Seven League Boots” by Zoe Keating] Ms. Tippett: I’m Krista Tippett, and this is On Being. [music: “Seven League Boots” by Zoe Keating] Ms. Tippett: Lisa Randall is the author of bestselling books for non-scientists, and she is the Frank B. Baird, Jr. Professor of Science at Harvard University. I spoke with her in 2015. Ms. Tippett: It was interesting for me to read that you grew up in Queens and that you’ve said that as a young girl, you were more entranced with books like Alice in Wonderland than the scientific books you came across. Ms. Randall: I actually don’t think I came across that many scientific books as a kid. Basically, I went to the library and read what I could. I just enjoyed reading. I liked the sense of adventure and play. But yeah, I can’t say that I’m really one of those people that said I really wanted to understand the stars. We didn’t actually see that many stars where I was. I think it was later on that I really came to appreciate nature more, really starting, probably, in graduate school, when I started hiking and exercising more. Ms. Tippett: I have to say, looking at the website at Harvard — it’s The Center for the Fundamental Laws of Nature, the High Energy Theory Group. [laughs] Ms. Randall: So I am totally not responsible for that name, which I find really arrogant and obnoxious. And I don’t think we’re responsible for the fundamental laws of nature. I think we’re responsible for the laws of nature that we can understand. Ms. Tippett: Yeah — it is very lofty. Ms. Randall: It’s not just lofty, it’s misleading. I think it’s misleading, because I think it gives this nature of science as ‘”We have this starting point, and then we derive everything.” But really, that’s not how it works. We try to find the starting point; we conjecture some theories. But we also try to work backwards, seeing what we observe and trying to see how those pieces fit together. So it’s really a push and pull. It’s not just one. Ms. Tippett: That’s such an interesting way to state it. Here’s something you wrote: “Our world is rich — so rich that two of the most important questions particle physicists ask are: Why this richness? How is all the matter that I see related?” And I just wanted to ask you to explain what you’re describing there. What does “richness” mean in the context of what you do — in that sentence? Ms. Randall: Well, I think part of what I’m referring to is simply the fact that we really don’t know how to explain why certain particles are essential to the world we live in. We know, for example, that nuclei have what we call up and down quarks inside them. But there are heavier versions. What role do they play? We know there are electrons, but there are heavier versions of the electron known as the muon and the tau. So there’s particles beyond what seem essential to nature or us or life, and we don’t really understand why they’re there. There doesn’t necessarily have to be a reason, but we’d like to see, is it somehow essential to getting us to this point in the world? So that’s part of what I’m referring to there. Ms. Tippett: So richness is just that variety of particles and qualities that’s known and unknown. Ms. Randall: I mean there is, of course, also the richness of how the pieces fit together, which is the wonderful stuff that we observe in the world. And we can see how that fits together and then how that came about and try to understand that with science, over time. So it’s kind of twofold. It’s sort of the richness at the fundamental level, but it’s also the richness of the complexity that derives from that, those simple ingredients. Ms. Tippett: And it seems that the period in which you have been a scientist, these last few decades — when did you get your Ph.D.? Ms. Randall: [laughs] I hate having to answer that, because it gives away my age. But I got my Ph.D. in ’87. But I will remind you that I took three years as my undergraduate and four years as a graduate student. Ms. Tippett: [laughs] All right, all right. But what I’m getting at is just how it’s a short — let’s just call it a very short period of time. You’re young. It’s a handful of decades. But the scientific understanding of that richness that you were just describing, even in this period, has been so revolutionary. Ms. Randall: It’s true, it’s been a very exciting time to be a physicist. I kind of joke that I’ve kind of lived in the optimal time. I mean I think some guys might say they would have liked to have been around earlier, but I think I’m at a very good time, because not only is science exciting, but it’s also a time that allows you to be a woman physicist a little more easily. So I feel like I live in the optimal time for me being a physicist. But I think, also — in terms of physics, I think the last century has just seen amazing developments. I mean cosmology wasn’t truly a science until the last century, until Einstein developed his theory of general relativity, and observations improved to the point that we could actually see what’s going on and make predictions. Particle physics really only developed — nuclear physics — all the physics I worked on is a product of, basically, the last century. Ms. Tippett: It just occurred to me — I’m kind of embarrassed to ask this question, because I feel like I should understand it. But I feel like the word — the language of cosmology and physics gets interchanged, at least in non-science circles. I mean how do you distinguish between those things? Ms. Randall: So the other thing that gets confused is astronomy, so let me try to distinguish all of them. So physics I think of as the fundamental laws of nature. So for me, physics is elementary particle physics, but there’s all sorts of physics, which are sort of the rules by which things work. Cosmology is a specific science. It has to do with how the universe itself evolved. It has to do with the Big Bang theory, the theory of cosmological inflation, all of which I talk about in my latest book. But it has to do with just how things evolved to where they are today. Astronomy is more, in a sense, looking at stars and looking at the actual objects, how they develop, putting together. So what I like to think is, physicists are looking for sort of fundamental ingredients, astronomers are putting them together in a particular way to describe what we see today, and cosmology tells you how we got to this point. And of course, they all intertwine. They’re not completely disconnected. But someone will usually identify as an astronomer or a cosmologist or a physicist. Ms. Tippett: That’s really helpful. Thank you. Ms. Randall: Good that you asked. Ms. Tippett: Well, I just suddenly realized that… Ms. Randall: I always get mislabeled, actually, so it’s pretty funny. Ms. Tippett: Yeah, so — well, let’s just leap in. Let’s just go to dark matter. And this book you’ve written this year also has this wonderful title: Dark Matter and the Dinosaurs. Ms. Randall: Thank you. Ms. Tippett: And let’s do some definition of terms, up front. I mean dark matter is, we now believe, perhaps 85 percent of the matter in the universe. Just start there. How would you talk about… Ms. Randall: So people get very disturbed about the idea of dark matter. They say, “How could there be all this matter that we don’t see?” But there’s a lot of stuff that we don’t see. If the history of physics has taught us anything, it’s — or biology or any other field of science — it’s how much we don’t see. And dark matter, I would have — if it was up to me, I probably would have called it transparent matter. It’s matter that doesn’t interact with light. Dark stuff, as you know, absorbs light, so you see it. But dark matter, it’s matter. It interacts with gravity like the matter we know. It clumps. It’s around here, in our galaxy. But it doesn’t interact with light, so we literally don’t see it. We see its gravitational effects, but we haven’t seen other effects. We know it’s there because of the many gravitational influences of large amounts of dark matter, but an individual dark matter particle has so far eluded detection. Ms. Tippett: I mean let’s clarify what ordinary matter — when we usually say “matter” — non-dark matter is… Ms. Randall: So it’s the stuff that’s all around us. It’s all matter. It’s all part of what we’re made of. It’s part of Earth. It’s people. It’s the galaxy. But there’s also dark matter surrounding us, it’s just a lot less dense in our vicinity. Nonetheless, there’s billions of dark matter particles going through us all the time. Ms. Tippett: Right now, even. Ms. Randall: Yep, right now. But we don’t see them, and they don’t interact with us. We don’t feel them. We don’t smell them. They don’t interact with our senses. People are trying to devise very clever ways to look for very subtle, small effects, but so far as...
Transcribe →#240: Mass nebulous: Our evolving understanding of dark matter | Up Close
Jul 6, 2017Tap to summarizeDownload mp3 (26.4 MB)VOICEOVERWelcome to Up Close, the research talk show from the University of Melbourne, Australia.SHANE HUNTINGTONI’m Dr Shane Huntington. Thanks for joining us. Over the last 100 years we have built increasingly large and sophisticated telescopes, even placing them in space. These scopes allow us to peer into the distant reaches of the universe, in effect, to look back in time. Our observations of the universe have led to significant changes in our understanding of how stars, galaxies and other exotic objects work. It turns out that common objects such as galaxies do not work as we predict they should and for the last 80 or so years astrophysicists have been challenged to accurately predict their rotation. Dark matter, which is said to constitute the vast majority of the matter in the universe, is a potential explanation for these discrepancies. But to date dark matter has not been observed directly and so understanding remains elusive. For a closer look at dark matter we are joined today on Up Close by cosmologist Dr Katie Mack, a Research Fellow with the Astrophysics Group in the School of Physics at the University of Melbourne. Welcome to Up Close, Katie.KATHERINE MACKThanks. It’s good to be here. SHANE HUNTINGTONYou work on dark matter. Could you give us a description in sort of broad terms of what dark matter is?KATHERINE MACKSo dark matter is the largest component of the matter in the universe and it’s made of something that we don’t yet understand. So we know what atoms are, what know what everyday objects are made of protons and neutrons and electrons. We have a standard model of particle physics, which contains all the particles that we’re aware of, all the particles we’ve understood in detectors and in laboratories. Dark matter is something else. It’s something that doesn’t interact with light so far as we can see. It doesn’t interact with other particles in any way that we’ve been able to detect except that it has gravity. So we’re able to observe that it has gravitational effects on things but we’re not able to observe it in any other way so far.SHANE HUNTINGTONNow, you mentioned it makes up most of the universe. What’s the rest?KATHERINE MACKWell, it makes up most of the matter in the universe, and that’s an important distinction. The vast majority of the energy budget of the universe is made of dark energy, which is something even weirder that I probably don’t have time to go into but it’s something that’s responsible for the way that the universe is expanding at the moment. Dark matter is the majority of the matter component so it’s most of the stuff that has gravity, most of the stuff that interacts with the gravitational force, has mass and then the rest is things that we understand, like atoms, you know, ordinary particles. We call them baryons in astronomy, generally, but that’s not the most general term but that’s the way we talk about it. So ordinary matter or what we call luminous matter, stuff that has interactions with light, that’s the rest.SHANE HUNTINGTONSo this is the stuff we can see there is.KATHERINE MACKYes.SHANE HUNTINGTONLike you and me, the stars that are visible; the visible galaxies, the parts of the universe that we can look through a telescope and observe directly.KATHERINE MACKYes but that’s only about four per cent of what’s actually in the universe.SHANE HUNTINGTONWhy do we call it dark matter? We can’t see it but is there any specific reasoning behind that term?KATHERINE MACKIt’s called dark basically just because we can’t see it. It doesn’t emit light and it doesn’t interact with light and it doesn’t produce light. It’s dark in the sense of being invisible more than it’s dark in the sense of being black. It’s not black, it’s just we just can’t see it.SHANE HUNTINGTONNow, no one’s actually detected dark matter, so how do we know that it’s actually there? It seems like an incredible construct.KATHERINE MACKRight. Well, we know that something is there, basically, so we know that there is more stuff that has gravity than the stuff that we see. We haven’t detected it directly in terms of having a particle detector or an accelerator or something like that and seeing the particle physics effects of it but we do see the gravitational effects of it. So the way we see it is by looking at the way things in the universe are moving. For instance, one of the first discoveries of the concept of dark matter was by looking at the way galaxies rotate. All galaxies have some kind of rotation, some kind of movement. Our galaxy is a spiral galaxy, it’s moving sort of as a disc. The way that the stars are moving around the centre of the galaxy can tell you about how much matter is in the galaxy. Just as looking at the orbits of planets in our solar system would tell us about how massive the sun is, similarly looking at the way that stars and galaxies are rotating around the centre of the galaxy can you tell you how much mass is in the galaxy. And n all the galaxies we’ve looked at, the stars at the outer parts of the galaxy, the stars, the gas, everything that’s moving around the outer parts of the galaxy, are moving too fast for the matter that we see to be holding it all together. So if it was just the matter we saw then the stars would be flying off into space. So there’s something there, there’s something more that’s holding all those stars together and holding the galaxy together and keeping it from flying apart. What that is, is we call that dark matter.SHANE HUNTINGTONWhy have we gone with the idea of it being another type of matter instead of just perhaps a different understanding of the physics of very large length scales and how gravity works and so forth? Why that option? It seems as though we could have gone a few different ways here.KATHERINE MACKRight. Well, there are a few reasons why we think it’s an actual new component of the universe instead of an alteration in the way that gravity works. So one is that we’ve been able to measure the number of particles of ordinary matter in the universe as a fraction of the total matter in the universe by looking at things like the cosmic microwave background, which is the leftover light from the Big Bang. We can see fluctuations in that, that tell us something about how many ordinary particles there are. And when we look at that we see that the number of ordinary particles suggested by the way that those fluctuations are distributed says that there are not enough to make up all the matter in the universe. Also the way that galaxies formed in the early universe, they couldn’t have formed that way without dark matter because ordinary matter has different properties. When ordinary matter comes together it has collisions, it heats up, it has interactions with radiation and so on that would make it harder to form galaxies. So we know that there has to be something that doesn’t interact so much with other particles, that forms the glue to hold galaxies together, because if it was just ordinary matter the galaxies wouldn’t be the shapes that we see, they wouldn’t be the sizes that we see, they couldn’t have formed in the way that we have seen them forming.But one of the most compelling reasons we think that dark matter is a separate thing and not just a misunderstanding of gravity is by looking at collisions between clusters of galaxies. So there’s a famous one called the Bullet Cluster. It got a lot of attention a few years ago when it was discovered but collisions between clusters of galaxies can separate the dark matter from the ordinary matter. The way that works is the clusters of galaxies collide. And when they collide the ordinary matter sort of gets stuck in the middle and the dark matter moves right through, because dark matter when it collides with itself and with other particles, it doesn’t heat up, it doesn’t slow down, it doesn’t stop, it just passes right through in this sort of weird ghostly way.So the dark matter was able to pass through in that cluster collision and become separated from most of the ordinary matter. As it happens, most of the ordinary matter in clusters of galaxies is hot gas that fills the cluster of galaxies. The galaxies themselves in clusters are placed far apart so those come right through the collision as well. So what you end up with is a big clump of hot, ionised gas that you can see an X-ray radiation in the centre and then two separate groups of galaxies and dark matter on the sides and you can use something called gravitational lensing to see that most of the mass is separated from most of the luminous matter. That separation tells us that it really is something different from just having luminous matter be stronger, have stronger gravity, because they really are separated by huge distances.SHANE HUNTINGTONSo you’re essentially looking at two different events then, aren’t you? You’re looking at an event where the matter that can interact in terms of the way it normally does - so you know, collisions, it could be heat and all these things - that’s one way. But then the second way with dark matter is it only interacts through gravity.KATHERINE MACKYes.SHANE HUNTINGTONSo objects can pass through each other almost. They interact gravitationally but nothing else happens. I suppose that allows you to separate those two events, almost, as completely different things. KATHERINE MACKRight. Right. Exactly. SHANE HUNTINGTONI’m Shane Huntingdon and you’re listening to Up Close. In this episode we’re talking about what we know and what we don’t know about dark matter, with cosmologist Dr Katie Mack. Katie, let’s talk a bit more about dark matter itself, this illusive substance. There must be a range of theories that explain its properties. Which of these theories are currently in the lead and which ones are being left by the wayside as we search for the true nature of dark matter?KATHERINE MACKWell, there are a number of different models for what dark matter might be made of. One of ...
Transcribe →Cancer 2
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) And he took what was left, which much be very, very small, smaller than the size of a cell because the cells were removed by filtration, and he injected it into another bird. Now, a healthy bird. And strikingly that bird developed a tumor. So he was able to transfer whatever agent it was that was associated with tumor development from this bird to this bird. He concluded that it was something smaller than a cell, and he concluded that it was a virus. And indeed he was right. Now, the tumor that these birds developed is called a sarcoma. It's a tumor of the muscle in this case. And the virus that was responsible for this tumor was named after Rous, and it goes by the name of Rous sarcoma virus or RSV. Now, there was great skepticism about the connections between viruses and cancer at that time, and actually for many decades thereafter. And so Rous' work was not fully appreciated for some time. But it was eventually appreciated. And Rous actually won the Nobel Prize 50 years after he made this discovery, when it was confirmed that indeed the stuff that he was studying was highly relevant to the situation in humans. Not analogous, necessarily, but highly relevant. Over the years, since that discovery and discoveries made by others, demonstrated that the Rous sarcoma virus viral genome carried a set of genes that were familiar. These are the same sorts of genes carried by many viruses of this class. Rous sarcoma virus happens to be a retrovirus. I'll teach you more about those in a future lecture. It's the same general class that includes HIV. And there were some familiar genes that were responsible for the replication functions of the virus. But then there was a new gene present in this strain of the virus, specific to Rous sarcoma virus, which was named Src and was later considered to be the relevant oncogene, the gene that was responsible for the tumor forming capabilities of this Rous sarcoma virus. So there was then great interest in what was this Src gene? What was this special gene that could cause normal cells to become cancer cells? And research then went on for, again, a number of years studying Src, studying its biochemical functions, but the real question that was of great interest over the years was where did Src come from? Most viruses in this class don't carry Src, and it wasn't at all clear what the origins of this cancer-causing gene were. Was it a rare viral gene or perhaps did it come from the host cells themselves? And in experiments that were done, actually by my PhD advisor, Harold Varmus and his colleague Mike Bishop, it was shown that the Src gene actually does indeed reside in the cells of the host and gets picked up by a recombination process by the virus. And I'll just illustrate that for you. It turns out that there's a related virus fairly common in chickens called avian leukosis virus. And this is the predecessor of Rous sarcoma virus. It's a virus that has in its genome just the replication genes. And I'll just draw a viral capsid around this virus. So this is the avian leukosis virus with its genome and replication genes. Now, what they showed was that the avian leukosis virus, when it infects cells, here's a normal chicken cell. Most of the time it just makes more copies of itself like viruses will do. But occasionally, through a recombination mechanism, the avian leukosis virus will actually pick up a gene which is present in the normal genome of the chicken, a gene which looks very much like the Src gene present in Rous sarcoma virus. And through this recombination mechanism, the details of which I won't go through, very rarely you'll get a recombinant virus produced which has in its genome the replication genes, but now also Src gene. And this virus, which modifies the Src gene slightly in the course of the development of the virus, now, when introduced into birds, will very efficiently cause tumors. And what this showed, what this actually Nobel Prize winning experiment showed was that the oncogene, powerful cancer-causing gene resides in the DNA of the chicken. And actually there were similar genes, very analogous genes residing in the DNA of all vertebrate species, including humans. You are sitting there with two copies of the Src gene inside of you. So a question is, if that's true, if we all have these oncogenes in our cells why don't we get cancer? Why aren't we all sitting there as one large sarcoma? Anybody? Well, there are two answers. Yeah? Somebody. Claudette is pointing to somebody. Am I blind? Oh, hi. Excellent. Yes. So what's different about the situation in the chicken cell and the situation in the viral genome is how the gene is expressed. Here it might be expressed properly under what we would call physiological control, express where it's supposed to be when it's supposed to be. And here it's been removed from that regulatory network and is expressed perhaps at two high levels at the wrong time. And under those conditions it can push cells to inappropriately divide. So the virus has hijacked this gene and changes its regulation. That's one explanation. There's potentially another explanation for why we're not all sitting around with tumors, and I'll come to that in a moment. Now, as I said, Varmus and Bishop won the Nobel Prize for this work in 1989. And the day that they won the Nobel Prize Harold Varmus' sister-in-law was standing in a cafeteria line at Berkeley and she overheard two guys talking behind her. One guy said to the other, what are you going to have for lunch? And the other guy said, I don't know but it ain't going to be the chicken because two guys just won the Nobel Prize for showing that chicken causes cancer. [LAUGHTER] Which is not exactly true. But nevertheless. Now we know since that work that there are a large number of these viruses which are called collectively acutely transforming viruses. There are a large number of acutely transforming viruses that carry in their genomes and oncogene which they have cooperated from the host cell. These viruses are not viruses of human beings. They're viruses of experimental animals and usually generated in an experimental setting. Mice, rats, chickens, turkeys, other species have been used to generate such viruses. And about 50 or so oncogenes have been discovered through this context, including one that's hopefully familiar to you already and will come again, members of the Ras gene family which I've told you about as an important signaling molecule in mitogenic signaling pathways, and another important oncogene that I'll mention briefly later called mic, and about 50 more. And it turns out that they were a very useful source to identify cancer-associated genes in humans. Many of the genes that we now know are important in human cancer were initially discovered through that process. Now, as I said, most of the time human cancer has nothing to do with viruses so don't be confused. There are a few human cancers that are virally associated. The major one is cervical cancer. About 50% of cervical cancers, particularly in the Developing World, are associated with the virus called human papillomavirus or HPV, and specifically the high-risk types. Not all papillomaviruses will cause cancer. Papillomavirus is the same virus that causes warts, for example. And there are many papillomaviruses that are not associated with true malignancies, but human papillomaviruses of the high-risk type are. And they can give rise to cervical cancer. Fortunately, companies are now developing vaccines against HPVs which are greatly affecting the risk of cervical cancer around the world. So this is a major step forward in controlling this particular cancer type. So because most human cancers are not virally associated, there was still some skepticism about the importance of this discovery for human cancer. Maybe it was true of the viruses, maybe it was true of these experimental animals, but is it true of human beings? Do these oncogenes have anything to do with human cancer? And this debate went on for a little while longer until Bob Weinberg here at MIT in about 1980 did the following experiment. He took DNA not from a bird but from a human being who carried a tumor in his bladder. So this individual had bladder cancer. This cancer was put into cell culture and turned into a cancer cell line, and it was actually this material that Weinberg's lab worked with. And they asked the question, are there genes in the cancer cell line that are cancer-causing? Are there oncogenes that I can discover within those cancer cells? So the experiment that they did was to take DNA, they isolated DNA from the cancer cells, and they introduced it into mouse cells in the laboratory that were "normal". And what I mean by that is they looked pretty normal compared to the cancer cells which had a deranged sort of architecture, as I mentioned last time. They grew flat and didn't grow on top of each other like cancer cells will do. And, importantly, if you were to inject these cells into an immunocompromised mouse they wouldn't form a tumor. They were nontumorigenic. Whereas, these cells, if injected into a mouse, would form tumors. OK? So they isolated DNA from the cancer cells and put it on the mouse cells. The mouse cells will, at some frequency, take up the DNA, incorporate the human DNA into their own genomes and begin to express the genes from the human DNA. And they found at low frequency that within this population of otherwise normal-looking mouse cells abnormal colonies of "transformed" cells could be found. And these transformed cells looked a lot like the cancer cells. Their shape was different, they grew on top of one another, and they had other properties that also made them similar to cancer cells in the sense that if they injected these cells into an immunocompromised animal, whereas t...
Transcribe →Cancer 1
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) So up until this point in the class you've learned basics about cell molecular biology, genetics and development, how things normally work, how cells normally function, how tissues are formed, how organisms are formed and function. And hopefully you've had an ample founding in understanding normal biology. We're going to take a turn today and for the next three lectures talk about abnormalities that lead to disease. And, whereas, I have tried to keep things light for you in my lectures and try to be entertaining if possible, the subject of the next three lectures is not a light one. It's a very serious one. And it is cancer. It is a disease that I know a great deal about and have worked on in my lab for the last 17 years. It's a very important and very devastating disease. And we're going to try to give you an introduction to it. And you'll see that many of the things that you've learned over the course of this class, up until this point, really prepare you to understand the details of cancer, cancer development, and hopefully also cancer treatment. And I'll say right up front that I'm actually quite optimistic that the progress that we've made over the last several years in understanding the molecular basis of cancer has put us into position to treat the disease differently than we've done in the past and more effectively. The number of drugs that have been approved by the Food and Drug Administration for the treatment of cancer today that are directed and in this more effective class is not great, but there are some. And that number will increase. So I think there's reason for optimism utilizing the information, the kinds of information, the strategies that we'll cover in the next three lectures. So cancer, I think in some respects, needs no introduction. It's a disease that probably has affected some of you already in your lives personally. Certainly everybody knows a family member or friend who has developed the disease. It is a remarkably common disease. In this country alone -- -- more than a million people are diagnosed every year with cancer. And this does not include another million who are diagnosed with the less serious forms of skin cancer, basal cell carcinoma and squamous cell carcinoma. So, in that respect, more than two million people get the diagnosis of cancer every year in this country. Moreover, each year -- -- more than half a million people die in this country from cancer. That's more than 1,500 people per day. So in two days more people die of cancer than died in the World Trade Center disaster. It's a devastating disease. Half of the men in this room and a third of the females -- -- will be diagnosed with cancer in their lifetimes. And overall more than a quarter of all deaths are attributable to cancer. A major problem. A major burden. Clearly something we need to do something about. So I'm going to show you some slides that introduce you to the disease. Cancer, as you know, is a generic term that covers a class of diseases that affect many, actually, almost all of your organs. You can get cancers in different places. They're all defined by one common property which is too many cells. Too many cells in a tissue causing a lump. Too many cells in the blood. Too many cells in lymph organs. So that's the common theme that relates to all cancers, but there are very important differences in cancers in different sites. This is a radiographic image of lung cancer. What you're looking at here is a standard chest x-ray. And this individual, you can see, has an opacity right here, a fairly large opacity that's probably about the size of your fist in this lobe of the lung. And that's fairly advanced lung cancer. This is a more precise diagnostic test called computed tomography, which is essentially a series of x-ray slices that get reconstructed. It gives better resolution. And you can see, again, a very large mass in the lung of this individual. So that's a solid tumor imaged by radiography. This is leukemia. Leukemia is also too many cells but here it's in the blood. This is a normal blood smear. These pale cells without nuclei are your red blood cells. These nucleated cells are white blood cells of different types. And you can see in this abnormal blood smear of a leukemia patient there is a vast increase in the number of white blood cells. So this is a diagnostic feature of leukemia, too many cells. And it's diagnosed by looking at blood counts. And the blood counts in leukemia patients of white cell counts can be elevated by thousands, if not hundreds of thousands of fold. You can also use other imaging techniques to detect and diagnose cancer. This is endoscopic examination, colonoscopy. It's now recommended that everyone undergoes this exam every year when they reach age 50 to detect tumors at an early stage so that they can be removed surgically which is, in fact, the most effective treatment for colon cancer. And, actually, for almost all cancers. The most effective treatment for cancer is the removal of the tumor. If you can get to the tumor at an early stage through some of these imaging techniques and eradicate it, remove it, you can greatly limit the mortality associated with the disease. So this is endoscopy. This is what a normal colon looks like, sort of a smooth structure. This is an early stage colon tumor. It's called a polyp at this stage. And I'll give you a little bit more nomenclature in a minute. This is actually not cancer. A polyp is not cancer. It's a benign tumor. This may or may not progress to a cancer, but if the doctor were to find a polyp like that they might follow it for one or two years. But if were to get bigger they would remove it. And they can actually do it endoscopically. They can remove it using a surgical endoscope. They don't actually have to do surgery to remove polyps anymore. At some frequency these polyps do progress to colon cancer. And this is a true cancer, a carcinoma which has changed its shape and importantly changed its relationship to the tissue. Whereas, the polyp is sort of sitting up on top of the tissue, having grown out of the tissue, the colon cancer has invaded into the tissue. It has become much more destructive in that sense. And also, importantly, has the capacity to move outside of the colon through that process of invasion to other parts of the body, and thereby cause problems elsewhere. Usually, when these are diagnosed by endoscopy or other methods, they are removed. This is done by surgery where a portion of the colon is actually removed and then the two resected ends joined. And you can see the colon cancer right here. If the cancer is detected at an early enough stage, surgery is curative for colon cancer. Unfortunately, it's often too late when it's diagnosed. It looks like that. Because it's already moved outside of the colon and tumor cells have found their way to other parts of the body. So surgical removal of the primary tumor, while helpful, may actually not be curative. So I want to go through in diagrammatic form some of the points that I've just made. Cancer develops in states. It doesn't happen all at once. As I showed you in the normal colon polyp to colon cancer series, things happen in stages. It's actually best worked out in the colon. But we believe the same phenomena hold true for other cancers in other places. It doesn't happen all at once. It happens in stages. And these slides illustrate the basic principles of that. This illustrates a normal tissue. It could be anywhere, but let's say that it's in the colon. And there are certain important features to pay attention to. One is that the cells have regular shape and a regular relationship to their neighbors. As you know, tissues are formed for normal function. They have particular genes expressed. They have particular structures inside them. They interact with their neighbors in order to perform their function. So the cells of the colonic epithelium line up like this touching each other, interacting with each other and interacting with the cells underneath them, as well as other material underneath them. Here is a material called the basement membrane, otherwise known as the extracellular matrix. And this helps support the cells and provides the cells with certain nutrients and growth factors. There are also cells below these cells in the colon and in other tissues which replenish these cells when they get lost. These stem or progenitor cells exist probably in all adult tissues. They get recruited when cells turnover. And we now think, and it's not illustrated on these slides, but we now think that these cells are probably very important in tumor initiation. We think that these are cells, these stem cells of the tissue are likely to be the place where the tumors initiate and then produce cells, like this brown cell here, which is already abnormal. Cells that have acquired a mutation which makes them different from their neighbors. Now, the first consequence of those early changes is that you get too many cells. And this is a process known as hyperplasia. Hyperplasia simply means hyper, too many, plasia, division, cell division. So there are too many cells. But the cells that are present there look pretty normal. They don't histologically, by looking at the tissue, appear different from their normal neighbors. There are just too many of them. This process continues until you can actually see a discernable lump, a mass, and that is a formation of a benign tumor. In the colon that tumor, that benign tumor is called an adenoma. It's called other things in other places but let's say, just for the sake of simplicity, it's a benign tumor. And, again, this is an increase in the number of cells but the cells themselves don't look very different from their normal neighbors. And these tumors are not life-threatening yet. T...
Transcribe →Stem Cells
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) Differentiation. For someone who didn't see the board. Yeah? Yeah. So what a cell will become eventually. And differentiation is the process by which it becomes that. OK. Good. So these terms are essential for you to know for today's lecture. And if they are a little murky for you then you should really make sure they become clear. OK. I'm going to talk to you today about stem cells. This is the how-to module, our second how-to module. We have two lectures, stem cells and cloning. And what I want to do today is to go beyond the media, beyond the hype and tell you about stem cells, what we really know and why there is such a fuss about them. And to put it in perspective of where you are in the course, in our game board of life we're moving right along past foundations up through formation and now into our second how-to module. So let's start with a question. And you have a handout. If you do not have a handout, Shamsah, could you be mail person? And on the other side it looks like we need another mail person. You will realize that I typically do give you a handout of the most important slides so that you don't have to grapple with things and that you don't, in fact, have to print out the PowerPoint handout before you come. So you should always just check. OK. So what is a stem cell? Well, a stem cell is something that has two important capacities. Firstly, it can self-renew. That's a very popular term. It can make more of itself. And, secondly, it can give rise to a number of different, one or more different cell fates. So it can give rise -- -- to one or more differentiated cell types. Schematically, I've represented it for you in this way. So here is something that's called an uncommitted stem cell. And you should be familiar with the term uncommitted, naive and so on. And this uncommitted stem cell can undergo cell division to make more of itself. And it can also go on to become something that's termed in the field a "progenitor cell". It's just a term. It means a cell that is going to give rise to something else. And I've depicted it here as a determine progenitor. It knows what it's going to become. And this term uncommitted stem cell, the uncommitted part is a little misleading. I'll talk about that more in a moment. This determined progenitor then goes on to give rise to a whole bunch of one or more, actually, differentiated cell types. And the number of cell types that a stem cell can go on to give rise to is a measurement of its potency. That is the definition of the term potency. So this is the notion of the stem cell concept. You have this. It's the first figure on your handout. And you'll find this in many newspaper articles and books. So what's so special about this and why are there newspaper articles and newspaper articles and newspaper articles and television programs and covers of Time Magazine about stem cells? What's the hype? Well, the deal is that it is believed by some that stem cells are going to be some kind of universal repair kit. That somehow because stem cells can give rise often to differentiated cell types and make more of themselves that they are in a position to repair parts of the body when the body needs repair. You have a heart attack, you throw in some stem cells, repair the heart, you have a brain lesion, you throw in some stem cells and you repair the damage. And if you go through the newspapers, as I did very, very briefly, it's very easy to find many, many different headlines. One of the big ones last week, I'll talk about this at the end, is that the Massachusetts House passed a law expanding the use of stem cells in research. Hopkins is beginning human trials with donor adult stem cells to repair muscle damage from heart attack. This is an enormous amount of interest in these cells because of this notion of universal repair kit-ness. There are also advertisements. The Stem Cell Bank and the Cord Blood Registry would love you to pay them to save your child's umbilical cord stem cells, or the blood cells from a newborn's umbilical cord in the possibility that you'll use these later on to save the life of this child or somebody else. And the other reason that stem cells have got so much hype is that, as we'll discuss towards the end of the lecture, they involve the use, or are likely to involve the use of human embryos. And that's a real fire point. But let's step back and let's talk about stem cells and biologically what are these things and what do you need them for? And the thing we have to consider is the question of organ maintenance. Now, I've told you several times, oh, you see, it popped up. There you go. We have to give these frogs a moment to pop up. OK. That must have been somebody's frog that popped up. I've told you several times that our bodies consist of about ten to the twelfth cells. That's a lot of cells. But it's actually much worse than that because it is not the same ten to the twelfth cells that you started with, once you got there, that you keep throughout your life. The cells in your body are constantly dying and are constantly being replenished. And, in fact, if you look at your ten to the twelfth cells, over the course of your lifetime you will make many times ten to the twelfth cells. You're not going to replace every cell in your body because some of them life forever, but for many populations of cells in your body you will replace those organs completely. OK? So we're talking about making lots and lots of cells. And the issue really is one of organ and tissue maintenance. And if one considers how organs and tissues are maintained, they fall into three categories loosely. Those that have a high turnover rate where cells do not live for very long and need to be replenished rather frequently to maintain the size and function of the organ. Those organs that have a low turnover rate and those that are said to be static. Organs with a high turnover rate include, as I'll tell you a moment, the blood, some of your hair. Organs with a low turnover rate include things like your liver and pancreases. And organs that were thought to be static, but in fact that may not be true, was the nervous system. And now we know that that's not true. So let's talk about how we get to these terms. High turnover. Low turnover. Let me just write it out. Turnover. And static natures of organ maintenance. And the way we do this, or the way this has been done is by an assay that's called a pulse-chase assay. And a pulse-chase assay, and this is the second slide on your handout, goes like this. In a cell population one can add a nucleotide analog bromodeoxyuridine. It's uridine but it's incorporated into DNA because it's got that deoxy there. And bromodeoxyuridine is a nucleotide that is incorporated and can then be detected using various stains. So you can tell which cells have incorporated BrdU by staining them appropriately. So you can tell which cells are dividing, which cells have gone through S phase by whether they are labeled or not. And if you give a cell population a short pulse, if you give BrdU for just a short time, this is called a pulse, it gets incorporated into the DNA, and then the BrdU is gone. And so you label your cell population. And then you follow the cells over a long time without any added label. And so the only cells you look at are the ones that were labeled during this pulse period. And if you do that, you see that your initially labeled cell population lives for a while, and then the cells start to disappear because they die. And you can monitor the half-life a population by counting how long cells live for. OK? So this is a pulse-chase analysis. And this will give you the cell turnover time of a particular organ. And this is very useful in trying to figure out whether cells have a high turnover rate or a low turnover rate. Now, you can do something else with this. You can look at your labeled cell population, and you can actually look not just at the numbers of cells but you can look at what those cells become. And sometimes your initially labeled cell population will be the final form, the differentiated state of the cells, but sometimes it won't. And then it's very informative to follow that labeled cell population and see what they do. This is your third handout, your third slide on your handout. And if you follow them you might see that this labeled cell population, during the chase, differentiates into something. And that's very interesting. And then later on those cells will die and you'll be able to measure a half-life as previously, but this is very interesting because it tells you that this labeled cell population was not the same as the final fate of the cells. And it implies that there is some kind of precursor cell, some kind of progenitor in your labeled cell population that's giving rise to the differentiated cells. And it implies that these initially labeled cells either are stem cells or are progenitors derived from stem cells that are responsible for repopulating a tissue as the tissue or organ needs to be maintained. So these are two assays that are very useful and are used to, have been used to define high turnover organs. So what are some of these organs that have, or tissues that have high turnover? In fact, they've been used, these assays have been used to define many tissues, those with high and those with low turnover. But it's the high turnover ones I want to talk about. The red blood cells in your body have a turnover time, half-time of about 120 days. And if you do the calculation, because you have a lot of red blood cells, you're making more than a billion cells a day. OK? As you are sitting here, you are probably, during the course of this lecture, making several million new red blood cells. Your intestine, some of the cells in your intestine that are responsible for food...
Transcribe →Morphogenesis
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) What I want to talk to you today about is the creation of 3-dimensional structures. And I want to emphasize their connection to the function of the organisms and the organ. Let's look, for example, at the kidney. This is a fantastic example of structure- function relationships. The kidney comprises thousand of tubules that are involved in filtering the blood and collecting urine for excretion. Now, not only do these tubules function to transport the urine as it is being processed, they also are connected very closely to various cell types that are involved in this filtration process. So the 3-dimensional structure of the kidney is integral, is required for its normal function. And this is true in essentially every organ. So it's very important to think about the relationship of different cells to one another in a particular organ. And if you're thinking about, for example, using tissue engineering to develop an artificial kidney and making some kind of pastiche of cells and polymers and putting that together in some functional way -- -- it's important to understand these structure-function relationships in the normal organ before you try to engineer something that is a surrogate. Individual cells also have particular shapes, and this is integral to their function. We'll talk a bunch about neurons, cells that have very long processes that transmit nervous impulses or transmit electrical impulses and communicate in that way. The shape of the neuron, the structure, the 3-dimensional structure is absolutely required for its function. Tom, I think we could have a little more light at the back there. It looks really dark if you guys are trying to take notes. Thank you. OK. We have, you've seen this movie previously. OK. This is the zebra fish. The zebra fish embryo. Isn't it dark at the back? Yeah. Tom? Oh, it takes a while. It takes a while. OK. I want to show you this movie again that you've seen a while. You have it on your website. And I want to show it to you now in a different way. We're actually going to first show that during the early development of the fish, these two cells on top initially give rise to a ball of cells sitting on top of this yoke cell that is just a ball of cells. And then suddenly these cells start to move during the gastrula and then the neurula phases of development. And it's this cell movement that builds structure. And I want to try to address with you how this cell movement occurs and how it builds structure. So let's look at this movie again. Here we go. Cell division, building up the raw materials to make the embryo. A group of cells sitting on top of the yolk. And now watch here. It starts to move. Those cells have made the decision to move, and they going to move towards this one dorsal side of the embryo. And they are going to move and move some more to build the eye, the brain and the various somites along the length of the axis. OK. So that process, the generation of 3-dimensional structure is a very large part of the process of building the embryo. And it's interdigitated with making the cell types. A muscle cell is not a muscle cell and it's not functional unless it is a fused myotube that has the appropriate 3-dimensional structure. So cell type and 3-dimensional structure are very closely related. OK. So let's talk about a toolkit that is involved in this process. And the first thing that we can discuss is what is in this toolkit. Well, actually, you don't really have much in the toolkit to build an organism. I can think of one thing. What's in your toolkit to build your 3-dimensional organism? Yes. Did I hear cells? Yeah. I hope I heard cells. Well, there are cells. And then if you want to look for something else to build the organism with there are cells and then there are cells. That's what you've got. In your toolkit you've got cells. And the challenge of the organism is to use that singular building material to build the various and the huge array of structures that there are. So what about these cells? And the first thing about these cells is that they come in two forms. They come as so-called epithelia or epithelial sheets. And they come as single cells which are called mesenchyme. And these two types of cells interconvert with one another. And it's from these two groups of cells, that can be different cell types, but they're either sheets or they're single cells, that one builds the organism. So the epithelia are sheets, the mesenchyme are single cells. And let me look at the next diagram that I drew for you. And you have it in front of you. If you don't have the handout, does anyone not have the handout? Could I have, Lesley, could you [UNINTELLIGIBLE] please? Thanks a lot. OK. If you look at the handout, you have this except for one thing I added this morning. Here is a sheet of cells. So I'm going to do minimal board work today because you have a lot of the information right in front of you. You have a sheet of cells here. And this sheet of cells called an epithelium is a sheet of cells because it is joined together very tightly. And the cells are joined together by various junctions that I've shown here in yellow or that I've shown in blue. And this sheet of cells, as Professor Jacks told you, has two part, has two sides, an apical side and a basal side. OK? Remember from cell biology? And it touches something called the basement membrane or the basement lamina, which is part of the extracellular matrix that I'll mention again later. Now, this epithelium, this sheet of cells can transform into single cells. And these single cells have the property of being non-adherent. And they don't attach very tightly to the extracellular matrix, although they are in contact with it. And in order to go from an epithelium to a mesenchymal state there are changes in gene expression that take place, we know, at the transcriptional level. And these result in changes in cell adhesion and changes in the organization of the cytoskeleton. This is a reversible process, and mesenchyme can go and turn back into epithelium. Now, the epithelial sheet is a very important part of the body, both as a building block for various structures, but also as a barrier. So your skin is a barrier because the cells in it are very tightly joined together and they form an impermeable barrier. But that's true of essentially every organ you have. Every organ you have is surrounded by an epithelium, or one or more epithelia, and these surface barriers so that stuff in the organ doesn't get out, stuff outside the organ doesn't get in. And if there is a lesion, a break in this epithelium it is a big deal. And that is wound. That's what a wound is. It's a break in the epithelium. And there is a very rapid and profound system of wound healing to repair these epithelial sheets. Now, during development there are many transitions from epithelium to mesenchyme. So the term that you really need to know is abbreviated EMT. Not to be confused with other EMTs. This refers to the epithelial mesenchymal transition, which I did not write on your handout so I will write it here. The epithelial mesenchymal transition. And it's always said that way, even if it's actually a mesenchymal epithelial transition. One of the most profound examples of epithelial mesenchymal transitions is during the formation of the nervous system. Your central nervous system, as we'll discuss in a few lectures, forms from a tube that rolls up during development. And this tube is an epithelial sheet. As the tube is rolling up, a group of cells, shown here in yellow, moves away, breaks away from the tube and undergoes an epithelial to mesenchymal transition. This group of cells is called the neural crest cell population, and these neural crest cells then migrate away from the neural tube and go and set up the entire peripheral nervous system. Not eripheral nerves, peripheral nerves. They also make all the pigment cells in the body and the adrenal medulla. This epithelial mesenchymal transition is not only crucial during development. It's also believed now to be crucial for metastasis of tumors during progression of cancer. And Professor Jacks will address that later in the course. This is a movie demonstrating the migration of the neural crest cells out from the neural tube which is in the middle here, this white tube. And these little dots migrating out are shown over a period of about 12 hours. The single cells migrating out from the neural tube as they have undergone that epithelial mesenchymal transition. All right. So I wasn't wrong in facetiously saying what's in your toolkit is cells. That's what's in your toolkit. But clearly the cells are slightly different from one another or profoundly different from one another in their disposition. And we'll talk about what mesenchyme and what epithelial can do in a moment. The other thing that's different or the other thing that's important that makes cells actually very good for building is that they are plastic. So let's go through a few things that they have going for them. I want to talk about adhesion. I'm going to mention junctions, I'm going to mention cell sorting, and I'm going to mention the extracellular matrix. And some of this stuff you've had before so I'm going to go through it quickly. This is a diagram that's on your handout, it's from your book, to indicate that there are many ways epithelial sheets are stuck together that involve very tight apposition of the cell membranes, or in the case of tight junctions or slightly less tight apposition in the case of these things called desmosomes. You can go back and remind yourselves. We mentioned these previously. The most important thing is you understand that cells are joined together. In this micrograph, to demonstrate how tightly cells are joined together, this is a sheet of cells where the nuc...
Transcribe →Internet Archive
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) So today's lecture talks about the cell cycle, the control of the cell cycle, and also cell death. So obviously, cell division is extremely important in multi-cellular organisms. We've talked a fair bit about control of the cell cycle, in terms of mitosis and meiosis, in earlier lectures. Obviously, cell division is necessary in a variety of circumstances, probably the most obvious is development. You go from one cell to ten to the thirteenth to ten to the fourteenth cells. That's accomplished by a tremendous amount of cell division that goes on over your gestational period. I've also pointed out, in fact we talked about it last time, that cell, that wound healing is, in part, a process of cell division. Fibroblasts for example, and other epithelial cells, get recruited to divide, in order to repair damage to a tissue. And even without damage, there's a lot of cell turnover, for many tissues. You may not realize this, but your blood, for example, turns over about every month, so you have to replace all your red blood cells, and all your white blood cells, and so on, periodically. Cells in other tissues, in the skin for example, your skin cells are born, they migrate up to the superficial layers of your skin, and then they get sloughed off, and of course, they have to be replaced. There's a lot of cell division that's going on naturally, in the process of what we call homeostasis, and to give you an example of that, if you consider your intestines in a human, your intestines undergo ten to the eleventh cell divisions per day. That's a remarkable number. Ten to the eleventh cells dividing in your intestines per day. If you imagine that a cell in your intestine is about ten microns in diameter, if you lined up all the cells next to each other that were born in a given period of time, in 38 days you would have enough cells lined up end-to-end to go around the earth, and in a year you'd have enough cells to make it from the earth to the moon. So you produce a tremendous number of cells just naturally, in the process of organ function and homeostasis. Of course we can have too much cell division, and this is pathological condition, which we typically associate with cancer. And indeed, many of the factors that I'm going to talk to you about today, that relate to the normal control of cell division, and also cell death, are perturbed in the development of cancer. Cancer, as you almost certainly know, is a disease of too many cells, and a major factor in that is excessive cell division. So this happens to be a human cancer cell line growing in tissue culture, and one of the hallmark features of cancer cells is that they have, in a sense, unlimited and unregulated cell division. So if you were to watch this movie, which actually comes from your book, supplementary materials from your book, you could watch these cells dividing, and they would do so in an unnatural fashion. Without response to proper growth factors that would stimulate cell division, they would divide on top of one another, which normal cells don't do, and other places and times when other cells are kept in check, cancer cells are not. So the basic process, which again is well familiar to you, is to take a single cell and turn it into two. And we discussed the very last stages of this in earlier lectures on mitosis, how the chromosomes get divided from the mother to the two daughter cells. We also have briefly alluded to the fact that there's a second, critical event, and you talked about the mechanisms of DNA replication. The DNA needs to get duplicated so that it can be properly divided, and this, as you know, occurs during a particular phase of the cell cycle, known as S-phase, for synthesis phase. And then there's chromosome segregation, and this occurs in a distinct phase of the cell cycle called M-phase, or mitosis phase. And the development of cells over the course of, say development, or in wound healing, can be thought of as a successive iteration of DNA duplication, DNA replication, and chromosome segregation. So in a sense, you go from mitosis to S-phase to mitosis to S-phase. These segments are separated by periods of time when cells are accumulating the biomaterials that they need, basically to function, and also to carry out the next phases of the cell cycle, and these are refereed to as gap phases, G1 for the one that separates mitosis from S-phase, and G2, the one that separates the S-phase from mitosis. Now, this is a cyclic process, one cell gives rise to two, that then undergoes this process again, and so we think of these things as cycles from M-to-S, connected by these gap phases, G1 and G2. Now there's another phase that we haven't told you about, which many of your cells are actually in right now, and that's a phase called G0. This is a resting phase, and this can be either permanent or temporary. Many of your cells, when they're born, will stop dividing forever. Cells in your brain, for example, or most cells in your brain, cells of your cardiac muscle, and there are many other examples. Once they get born, they undergo mitosis, they go into this resting phase, and they'll never come back out again. And that's why it's difficult, for example, to deal with brain injuries, or spinal cord injuries, because those cells cannot be recruited back into the cell cycle, they can't make more of them. But there are other cells in which the resting phase is temporary, and these cells can then reenter the cell cycle, going back from G0 to G1 and through the process again. And a lot of the progenitor cells that I referred to up there, in terms of the skin and the blood, and the intestines, are in that situation. They're resting, and then they be recruited back into the cell cycle, in order to make more derivative cells. It's also useful to consider what the chromosomes are doing in these different phases of the cell cycle. So in a G1 cell, if we think about a single chromosome, and we're representing it by a single-line, although this is of course, a double-helix. In the G1 phase there's a single, double-helical chromosome, in S-phase that gets duplicated in the process of DNA replication, initiation shown here, and it would be completed so that the single-chromosome would be ultimately duplicated into two. And then in M-phase, those two chromosomes get separated from one another, so these are now joined, separated from one another, eventually into two daughter cells, which can then go through this process again. OK? And much of what we think about, when we think about how the cell cycle is controlled is to deal with the initiation of DNA replication, and then the initiation of mitosis. OK, so this is a cyclical process, a highly ordered process, this is a representation of the cell cycle, as shown in your book, just so you know it's in there. Exactly as I described to you, mitosis and S-phase, where the action is, these gap phases, G1 and G2, and this little arrow represents G0, and I've also used this term before, interphase, that represents all the phases where the DNA is not evident under the light microscope. It's only evident in mitosis because of DNA condensation, so the rest of the cycle, G1, S, and G2, are called interphase. So this is a highly ordered process, each step preceded by a particular other step, leading to a particular outcome, events leading to a particular outcome, and in a topical sense, you can think about it as the NCAA pools, starting tomorrow there'll be individual events, games, which will lead to next events in the next round, and next events in the next round, to an ultimate conclusion, in this case, the NCAA champion, which can only occur if the proper events have happened, prior to it. And you'll see another specific example of how the order is assessed in the development of the stages of the cell cycle. OK, so we know that the cell cycle is important. The question is, how is it controlled? How do you accomplish this orderly process of cell cycle progression? What are the genes -- -- that regulate this process? What do the genes encode, what do the proteins, and what do the proteins do? What are the pathways that they regulate to ensure the stages of the cell cycle? This was a huge question for decades, and there was rather little progress in trying to understand how it happened, especially in us. Our cells are sufficiently complex, and there's relatively imprecise, or particularly was in the past, imprecise methods for dissecting complex processes in mammalian cells. And so it took experiments performed in yeast, a single-cell, eukaryotic organism, budding yeast and also fission yeast, to allow us to understand what the details of the cell cycle are. Budding yeast, as shown here in a picture from your book, is a single-cell organism. It's also haploid, or it can be at least, haploid, which means that it has a single set of chromosomes, it doesn't have two sets, single set of genes, which makes it amenable to genetic analysis. You can make mutants more easily, if you only have one copy of each gene to worry about. So that's another reason that yeast was attractive. And another reason, which is kind of seen here, not really obvious here, but when yeast cells divide, they go through a very characteristic, morphological change. They start off as spheres, like this one, and as they go through the cell cycle, they develop a small bud. That bud then gets bigger, and eventually the two, the joint between the mother cell and the bud, get severed to form two cells. And you can actually figure out where you are in the cell cycle, by examining exactly what the morphology of the yeast cell is, and I'll show you that on the next slide. This is the yeast cell cycle, with overlay of the diagram of what the cells look like in the different phases, ...
Transcribe →Genetics 4
Aug 13, 2015Tap to summarizeDownload this transcript - PDF (English - US) OK. We are wrapping up our segment on genetics today, Genetics 4. We're going to talk about human disease genetics, modes of inheritance for human diseased genes. And then we'll transition next time into molecular biology, which is the next blank square here. And then recombinant DNA cell biology and beyond. I wanted to start today by clearing up a couple of things. Firstly, the term F1, in the last lecture I gave you a list of terms, and I used this definition of the first filial generation, the F1 generation as the product of crosses between two homozygous individuals, homozygous for different alleles such that the offspring were always heterozygous, big A, little A at that particular gene. Well, it turns out that some people use the term F1 to refer to the offspring of any cross. So you have the parents and you have the F1s regardless of the genotype of the parents. So that's a looser definition of the term F1. And it's been used in Section and so on, so I didn't want to confuse you. The strict definition is the one I told you, but don't get hung up on that. We're always going to give you the relevant genotypes so you'll be able to figure out what the genotypes of the offspring are. Also, near the end of the last lecture, I talked about crosses involving linked genes. If you remember the Y and D gene controlling color and density, I think, of peas. And I told you that they were linked, and we carried out a test cross. And we then worked out what the percentages of the different phenotypes and genotypes would be. Well, in that example, I assumed that the Y allele and the D allele were together on the same chromosome. But importantly if you're just given the genotype as it's written here, you actually cannot know that. The big Y might be on the opposite chromosome from the big D. So to avoid confusion about that sort of thing, in future examples and in problems, problems, that is test questions, we'll always show you the chromosomes so you'll know that the genes are together on the same chromosome or on opposite. Yeah. And in the absence of this, if the question is to tell us what the alleles must look like and they give you the phenotype, you have to conclude the genotype. If the question is tell us what the alleles must look like then we're not going to give you the answer, but in other situations where there's ambiguity about what the alignment might be, we'll tell you what that is. OK? We also had a question from a student, actually an emailed question, those are also welcome, email question from a student. It was good question because in our discussion of dominance and recessiveness, we really haven't dealt with the molecular nature of that. And that was this individual's interest. Why is an allele dominant over another one? Why is a trait dominant over another one? And I gave an example to him, which I will give to you, which I think covers most of the examples that we've been discussing in class. And it also is an opportunity for me to reinforce the notions related to chromosomes, genes, DNA and proteins, because apparently there are some of you who are still a little fuzzy on those relationships. So let's imagine a gene which is present on a chromosome. Chromosome shown here. Gene shown here. And it's the S gene that we've talked about before that controls smooth versus wrinkled pea texture. So here's the S gene. It's made up of DNA. And based on the sequence of that DNA within the gene, therein lies the information to produce a protein. And we're going to call this protein, in our example, this is a hypothetical example, the starch synthase protein. It's an enzyme that controls a reaction, that catalyzes a reaction from some sugar substrate into some starch. And if you make enough of that starch product then you have a smooth shape. OK? This enzyme controls shape because it produces this product which is involved in the shape of a pea. OK? So this is the normal situation. The big S allele produces a functional starch synthase enzyme which produces enough product to give the pea its smooth shape. In this example, the little S allele, which is the recessive one, has a mutation within the coding sequence of the gene. We won't talk about the nature of that mutation just yet, what it is, why it causes what it does because you're going to get that in the next segment. Just suffice to say that it's a mutation, an alteration of the DNA such that the protein that's produced from this allele is nonfunctional. You might be able to see I've inserted a little X there. It's actually quite little and invisible on your handout, but you might want to just circle it if you look carefully. There's a little X there which is the result of this mutation. And that X causes the protein to be nonfunctional. The enzyme now does not catalyze the production of this starch product, so no starch product is produced. If you don't make the starch product you don't have a smooth shape, you have a wrinkled shape. OK? If the genotype of the pea is little S, little S then none of this enzyme is produced such that none of the starch product is produced such that the pea is wrinkled. OK? Now what happens if you're big S, little S, the heterozygote? Well, for many biochemical reactions, having just one copy of the gene that encodes the functional enzyme is enough. For many biochemical reactions that's true. And so in a situation where big S is dominant over little S, we assume that having one copy of big S makes enough of the starch synthase protein to make enough of that starch product to give the pea its smooth shape. OK? So that's a simple example of why big S is dominant over little S, why you only see the phenotype associated with the little S allele, the wrinkled phenotype when you have two copies of the little S allele. OK? So I hope that helps clarify the situation for you and actually is useful as we talk about human disease genes as well. So this is a slide from your book which allows us to transition from concepts of inheritance to real-life stuff. Genes that regulate how your body functions normally or in response to various environmental stresses. We're now in an era where we can relatively easily figure out whether a disease has a genetic component by looking at families that might have that disease, and based on that information and using mapping techniques like I described to you last time, we can isolate where that gene might lie on all of your chromosomes. And then using molecular techniques, which we'll talk about in future lectures, we can actually isolate that gene, determine its sequence, and based on that produce lots of various valuable things like better ways to diagnose the disease, better ways to understand how the disease process takes place such that we can then perhaps prevent the disease from occurring in the first place or treating it more effectively by replacing the gene with a new copy or producing a drug that can replace the gene in other ways. So this is what we're after. So we need to understand diseased genes and how they behave in such affected families. So there are a number of diseases which have a genetic component. And these diseases have various modes of inheritance. Some of them are autosomal dominant. The diseased gene is dominant over the wild type gene, and I'll give you examples of that. And the term autosomal means that it's not sex linked. That is the disease gene is carried on chromosomes 1 through 22, one of the those chromosomes, not on the X or the Y. It doesn't matter if your father, whether the disease gene is coming from a male or a female, passed on to a daughter or a son. There's no sex linkage for these autosomal dominant diseases. There another class of genes, disease genes which follow autosomal recessive inheritance patterns. Here the disease gene is recessive to wild type. You only see the disease phenotype when you're homozygous for the mutant allele. And, again, autosomal because it's not sex linked. There are X linked diseases which are dominant. In this case, the disease gene is on the X chromosome. There are also X linked diseases that are recessive. There are very few, but for the sake of completeness, Y linked diseases. But there are so few that we're actually not going to talk about them at all in this class. And, finally, there's a class of diseases that we're also not going to talk about but get inherited not from the genes that are in the nucleus of the cell along your chromosomes but rather get inherited from the mitochondria. And since we haven't talked about mitochondria with you really at all we're not going to expect you to know about those diseases, but just have in the back of your minds that those are relatively important. Autosomal dominant diseases are not terribly common. There are about 200 known. Autosomal recessive diseases are actually much more common, though not very frequent in the population. There are about 2,000 of these known. And together I would estimate there are about 25 sex linked diseases. So we've used the term autosomal dominant, autosomal recessive, sex linked. What does this really look like in terms of the genes and the alleles? Well, just as in the case of peas, a dominant disease allele will cause disease regardless of the nature of the other allele. It's dominant over the normal common version of the gene. So if we call this allele the disease allele of some gene -- -- and this allele the commonly found on in the population, and we refer to these often as the wild type -- -- in an individual who has this genotype for a dominant disease gene, will they develop disease? Yes, because the disease allele is dominant over the normal copy of the gene. So these individuals will develop disease. For recessive disease alleles you need to have both copies, both alleles be mutant in order ...
Transcribe →