2. What is Biomedical Engineering? - Cont.

Professor Mark Saltzman: What I'm going to talk about today is to continue our discussion about what is Biomedical Engineering and go a little bit further and we'll spend about half the class doing that, and then I want to spend the last half of the class talking about some biological structures that are very important and that you might not be familiar with. I'll talk about biological membranes and lipids and how they're assembled. But first, I want to start with the assignment I gave you last time, and I asked you all to think about these two questions and write some things down. Let's start with the first, with A on this list here. What products of Biomedical Engineering have you encountered? We talked about a few of these last time but I'm sure there's others, so what things did you come up with as you were thinking, anybody? Student: [inaudible] Professor Mark Saltzman: Okay, so in the category of already available: drug delivery patches. These are now available for a variety of drugs, Scopolamine for motion sickness was one of the first that was available and nitroglycerin for treating heart disease is already available and these are really like band-aids but they're band-aids that are loaded with drugs and they're designed in such a way that if you apply this band-aid with adhesive to your skin, drug will enter your bloodstream from the band-aid through the skin, and that's been, I think, a good example. Others? Student: [inaudible] Professor Mark Saltzman: Dissolvable stitches or sutures, now what needs to be engineered in those? So they have to be engineered to be inert so that they can be safely inside a system and there's not every material you could pick would have that property. It's - a suture or a stitch has to hold the wound closed so it has to have certain mechanical strength and imagine the problem of making something that's dissolvable so it disappears but also is strong enough to hold a wound closed reliably for a length of time. Others? Student: [inaudible] Professor Mark Saltzman: Arthroscopic surgery - what are you thinking about there? Student: [inaudible] Professor Mark Saltzman: Yeah, so you're thinking about the instruments that they use in arthroscopic surgery, arthro means 'joint', scopic means 'looking', so it's looking into a joint and these are instruments that have very fine sort of needles on the end, but also cameras in them, and you can put them inside a joint and then look around and see what's happening inside. And not just a camera but there are also tools on the end of these things so you can cut and you can do manipulations through this instrument, so that's a great example also. Yeah? Student: Hearing aidsProfessor Mark Saltzman: Hearing aids - that's a good one, others? Student: [inaudible] Professor Mark Saltzman: Cochlear implants, so that's the same kind of function as a hearing aid, to improve hearing, but using a different mechanism. Not just an amplification system that you put in your ear, but actually an implant that replaces the function of an organ inside your ear. That's a good example, others? Must be a couple of others - yeah--Student: [inaudible] Professor Mark Saltzman: contact lenses. Student: Lasik surgeryProfessor Mark Saltzman: Lasik surgery - now why that one, what makes you think of that as an example? Student: [inaudible]Professor Mark Saltzman: Instruments, it involves lasers and learning how to make lasers that can do the right amount of damage to tissue, right? Because that's what the laser is doing in the surgery is cutting like a knife would do, but doing the right amount of damage and controlling it with light is an advance there. Others? Student: [inaudible]Professor Mark Saltzman: Tissue culturing - now what has to be engineered in tissue culturing? Student: [inaudible]Professor Mark Saltzman: I beg your pardon? Student: [inaudible]Professor Mark Saltzman: So what kinds of engineering do you think goes on behind that? Student: [inaudible]Professor Mark Saltzman: The technology that they use and really there's quite a lot of technology here starting from the plates that you grow them in turn out to be engineered so they have the right properties. And we're going to talk about this more when we talk about cell culturing later, and we'll talk about lots of potential applications of that as well. Student: [inaudible]Professor Mark Saltzman: Dialysis - and this is a method to replace or augment the function of your kidneys, to remove waste products really from the blood, which is something the kidney does continuously. Student: [inaudible]Professor Mark Saltzman: Cosmetic surgery - you gave two examples, one was Botox and the other was liposuction. So two different kinds of strategies, one is a surgical strategy, actually removing tissue and we talked a little bit about the engineering of surgical instruments and things like - so there's a lot of Biomedical Engineering that goes into everything that happens in the operating room. Botox is an injection of a molecule, or a complex molecule but a molecule, so in what ways would that be Biomedical Engineering? Student: [inaudible]Professor Mark Saltzman: Right and I think all of those are good, so there's lots of different ways. One is in terms of how you deliver the molecule so it goes where you want it to go and not where else you want it to go. And that's an engineering problem that we're going to talk a lot about, how to deliver drugs so that you get the action that you want, at the site that you want and not the toxicity. If you delivered Botox all over your body that wouldn't be a good thing, it might not even be a good thing if you delivered it one place in your body, but it's definitely not good if you deliver it everywhere. So controlling the dose is really important and that's going to turn out to be very important in cancer therapy because these are very potent drugs that will have bad effects in other sites and you want to localize them where they want, so we're going to talk about that. I think this is as good list so let's go and think about what might be a little bit more challenging. So in the future what things do you think Biomedical Engineering is going to produce in the future? Student: [inaudible]Professor Mark Saltzman: An AIDS vaccineStudent: [inaudible]Professor Mark Saltzman: robotic surgeryStudent: [inaudible]Professor Mark Saltzman: artificial hearts that can be used long term and that is a - there's probably several elements to that. One is long term, making them compatible with the body so that you could tolerate it for long term. And the other thing means if it's going to be long term, than probably it has to be implantable and that means all of the heart has to be implantable. This is where we don't have something that satisfies both of those categories right now. Imagine how much power it takes to drive an artificial heart, so you've got to have a battery or some way of generating power continuously to operate that and that makes it difficult to think about implantable and so that's a really good example of Biomedical Engineering. Student: [inaudible]Professor Mark Saltzman: Food supplies - food from cloned animals. We're going to talk about cloning next week, but why would cloning be an advantage in producing food? Student: [inaudible]Professor Mark Saltzman: Controlling quality because cloned animals are all genetically identical and so you wouldn't have variability that way, and so potentially you could have - pick an individual that has a really good quality meat and always reproduce that same thing. Student: [inaudible]Professor Mark Saltzman: Genetic scans for disease predictions, and we talked about one way you might do that using gene chips. Last time we talked very little about that and so we'll talk more about that next week, but certainly technology is going to be available, but there's going to need to be ways developed to put this technology together. If we looked at all 30,000 genes that were important in each individual how do you pick out which ones are important for a particular disease? Or what - and often it's not going to be just one gene, it's going to be combinations of genes, and how do you predict the fate of the individual based on all of the genes that you know to be involved in progression of a certain disease. So it's not just knowing what genes or figuring out ways to look at gene expression, it's figuring out how this expression of key genes affects the fate of the individual. That's really a complex systems problem, the kind of problems that engineers are very good at dealing with. Others? Student: [inaudible]Professor Mark Saltzman: So I'm going to call that chips implanted in the brain to control prosthetics, but I'm going to make it a little bit more general and call a brain-machine interface. So it's some way of interfacing activity in your brain with the outside world, and we'll talk about this as we go along, but there's lots of reasons to think that we're going to have this in the not too distant future. Student: [inaudible]Professor Mark Saltzman: Spinal cord regeneration - that's a good one. Student: Organs that can be cultivated …[inaudible] Professor Mark Saltzman: Organs grown from single cells. Student: [inaudible]Professor Mark Saltzman: I didn't hear the last partStudent: [inaudible]Professor Mark Saltzman: Imaging of moving parts like the - like a joint or another moving part that might be interesting to look at in motion is the heart. If you could image how the heart is moving, you would know a lot about its function. You could potentially learn a lot about its function by looking at how it moves, not just a static picture of it. There's lots of parts of our bodies that move, the lungs for example, and so yeah that's a good one. Two more--yeah--Student: [inaudible]Professor Mark Saltzman: artificial pancreas - now how are you thinking that might work? Student: [inaudible]Professor Mark Saltzman: So maybe - and here thinking about the pancreas has many functions but one of its important functions is to secrete insulin. So diabetics have lost that normal function. What if you could take just a pump that's capable of continuously administering insulin at various rates and connect it to a sensor that's able to continuously measure the sugar level in your blood? Insulin is important for regulating levels of sugar in your blood. Well if you can continuously measure and then give the amount of insulin you need to compensate for that amount of blood, those things could work together to be a totally artificial pancreas, make it totally out of synthetic parts. Now another approach would be to take pieces of the pancreas that already have all that capability within them. Individual cells of the pancreas are capable of - of a healthy pancreas are capable of both sensing glucose and secreting insulin. So what if you could take cells from a healthy individual and put them into a diabetic individual? Then maybe those new cells you put in would function as a totally natural artificial pancreas. Now why isn't that done? Why doesn't that already work, do you think? What are the engineering problems to overcome to get that to work? Student: [inaudible]Professor Mark Saltzman: The same problem is with organ transplantation is that the recipient has to be matched to the donor and so that's a problem. That's a big problem and so can you protect these cells that you give to the recipient from attack by the recipient's immune system? That's one challenge and we'll talk about ways to think about engineering approaches to solve that problem. One more--Student: control of angiogenesis within… [inaudible]Professor Mark Saltzman: control of angiogenesis, and angiogenesis - angio means 'blood' and genesis means 'new' and so angiogenesis is a development of new blood vessels. Many people believe that tumors, most tumors require blood vessels in order to grow. If a tumor starts to grow and it doesn't develop a vascular supply it doesn't develop blood vessels in it, then it can't get bigger than a certain size and there's lots of evidence from many cancers showing that this is true. So if you could stop a tumor from being able to develop blood vessels you might be able to stop its growth at a stage where it's not harmful. In fact, I don't know if in the news the pioneer in this is a man named Judah Folkman, who is a surgeon who first speculated that this was important, and sadly he died on Monday, but had a dramatic impact on our understanding of how cancers develop in people and new approaches. So there already are some approaches like this that are working, but there's more that needs to be done. So of these things that are up here, are any that seem controversial to you or that you would have said wasn't on my list and I wouldn't say that that's Biomedical Engineering? Student: [inaudible]Professor Mark Saltzman: Controversial in what sense? Student: [inaudible]Professor Mark Saltzman: Controversial in the sense that maybe it's not a good thing to do, or there might be some limits on what we want to do there in terms of integrating machines with people's brains. I think that's probably right, and there might be some others here where there might be some concerns, or others that have kind of concerns like that. Student: [inaudible]Professor Mark Saltzman: So there's some issues about how these technologies might be applied, right? If you had genetic scans that were available for disease prediction, do you want to know everything that's going to happen to you in terms of susceptibility to disease? Well, probably you want to know some of it but you might not want to know all of it right? You might not want to know all of it and that's a really complicated question for an individual to figure out and a complicated question for society to figure out, what you want to make of available in the regard. Student: [inaudible]Professor Mark Saltzman: If you can start to predict you're going to have heart disease that starts to develop when you're 45 and you're looking to buy insurance when you're 30, or you're looking for a job when you're 30 and that information is available to your insurance company or your employer, that could have dramatic effects on the choices that you get to make. So that's really - these are really difficult questions to answer. We'll talk about - we'll raise these issues as they come up. We'll try to raise them with all the technologies, we won't try to answer them, there are probably better people at Yale to answer those kinds of questions than I am. We'll talk about the technology and the questions that it brings up, but I hope some of you get interested and these will be good topics to think about for term papers as well for those you that have that kind of inclination. But any that seem like controversial or like, ‘I don't think that's Biomedical Engineering' or ‘that's not what I want to learn about in this course'. Let me put it that way; I hope we don't spend a week talking about that one because that's not what I thought Biomedical Engineering was. Any of these or do they all seem on the mark? Yeah? Student: Food from cloned animals Professor Mark Saltzman: Food from cloned animals - you didn't expect that to be Biomedical Engineering? So why? Student: [inaudible]Professor Mark Saltzman: I think - I see where you wouldn't see - I see where you would put it in that category and how you would be surprised to put it in that category. It should be in the category because it's engineering to be able to do this, right? It's a biological system that you've engineered from taking cells from one organism and cloning them and developing a whole other organism. And it's also engineering that helps humans, right? Because nutrition is going to be one of the big problems of your generation; how to have enough nutritious food for the population as it grows. Even to understand what individuals should eat, what should I be eating? That's a really complicated question that we have gotten very confused about. In large part because our government has confused us about it, but it's a confusing question to know. I think engineers have a role to play in that, but it's not sort of classical Biomedical Engineering in the way that developing an artificial heart is where you can see that. But I think it's a good example of a place where biomedical engineers of the future are going to contribute. So I want to try to put this together into a form that I've come to understand what Biomedical Engineering is and present it to you. Not only am I not an ethicist and I'm not good at those kinds of problems, I'm not much of an artist either. So this is a person - you can recognize it as a person, but let's say it was a person a long, long time ago and there was a point when one person decided to take instruments that were around them and use them to improve their life. Somebody thought about a wheel, or some group of people discovered how to use a wheel, some a knife, and some levers and these were very useful things in improving the quality of their life and that was - that's who you would call the first engineer. Then some - it couldn't have been too long after those instruments became available, but somebody, let's call them the first biomedical engineer, decided to use those instruments to look at either themselves or probably more likely, their neighbor. Take a knife and open up the skin and let's see what's inside. How do these fascinating things around me work? So people started turning these machines they developed on themselves to try to understand how they worked. This is one aspect of Biomedical Engineering, developing tools that allow you to understand how human's function and what's wrong when they have disease and so some of the things we've talked about have that category. Arthroscopic surgery in one sense is a fancy example of that, a way of looking inside a joint to see what's happening inside while the person is alive and without hurting them. Imaging of moving parts that same way is sort of advance in that. As these tools became applied more and more widely, we learned more about how human physiology worked. As we learned about how humans operate we could start to design machines that would help humans when they weren't functioning properly. I think the simplest example was that once we learned that there were bones or hard elements inside the leg, and that those bones were important in keeping the leg straight so that you could stand up, then somebody could invent an artificial bone, a splint that would be wrapped around - that would be secured to the outside of the leg to give you mechanical support even after you fell out of a tree and you broke you leg. So this is another kind of engineering, an engineering not to look more closely at how humans work but an engineering to improve their function when it's failing. As time goes on, we've developed ever more complex machines to study people and we've talked about some of these already: EKG machines, so an example of an electrical device that can be used to monitor a very elaborate function deep inside your body, the beating of your heart and the rhythm of your heart. We talked about modern imaging methods and this is an example of an fMRI, a functional MRI; a map of the brain that not only shows you the anatomy of the brain but shows you something about the chemistry of what's going on inside. You can put somebody in an MRI machine now and have them read a book and look at what parts of their brain become activated when they're reading and what parts stop activating when they stop reading, so you can learn where in their brain is reading done. You can ask them to read French and to read Spanish and you can find different locations in the brain that are involved in processing of those different languages. These are really incredible tools for understanding deep inside the body what's happening. We can even understand it on a molecular or cellular level now. This is a picture of patch clamp, it's a device that engineers built to fasten onto individual cells in order to look at how molecules in the membrane of the cell are working, and I'll talk a little bit about that as we go along. We can understand down to a very fine level now because of machines that we've built. As our understanding is improved and we've been able to build more complicated approaches to replacing function. We talked about the artificial hip which is a modern precursor of the splint I talked about before. Much more sophisticated in terms of the materials that are required and the design thinking that goes behind it. So now somebody can get an artificial hip and they can live for many decades with it and have almost full function of that hip over that period of time. This is an example of a rudimentary brain machine interface. It's a device called a deep brain stimulator, developed by a company called Medtronic, and it looks like a pacemaker that's implanted inside your body. Here is as pacemaker and this pacemaker does the same thing that a heart pacemaker does, it generates periodic electrical signals. But instead of those signals going to your heart they go into the brain. They go through these wires and into these electrodes that are deep in your brain, and they stimulate tissue inside the brain. We've found that stimulation, electrical stimulation deep in the brain can help patients that have Parkinson's Disease and can reduce the tremors and loss of muscle control that many patients with Parkinson's Disease use. Now these are electrodes that are only sending out signals. They're producing electrical signals in the brain--they're not recording from the brain, but it's not that big of a difference. It won't be long before we're using these same kind of devices to both record--to test what's going on--and to act in the right way and response. This is a beginning of real interface between machines and brains. Dialysis, this is an example of a membrane dialysis unit. Dialysis is done millions of times per day in this country and around the world, and keeps people alive when their kidneys have failed and they wouldn't survive for even a week without dialysis. You can keep people alive for many decades with periodic dialysis to remove waste products from the blood. We'll talk about these examples. What I want to leave you with is my picture, not a very elaborate picture, of what Biomedical Engineering is to me, and two parts of it. One, developing ways to understand how humans work better, how human physiology operates, and second, developing new approaches for replacing function in people when they're sick. I want to talk about - move on and talk a little bit about some general concepts from physiology that are really important and here is a table that gives characteristics of an average person. This would be an average adult male, 30 years old, the average height and weight, and surface area and temperature, and lots of characteristics of an average person. Let's think about some of these like weight. We think a lot about weight in this country, but weight is a remarkably carefully controlled parameter of a person, that is, you have to work pretty hard to gain weight or to lose weight. We take in a lot of food and water everyday, every year, and yet most of us our weight stays remarkably stable over that period of time for adults despite how much we eat and how much we drink. Your body is able to regulate your weight fairly well without you really thinking about it. Anybody - you're all too young to have tried to lose weight yet, but when you get to be older and you start to think about as your metabolism changes, trying to control your weight, you realize how hard it is to do, and you know this because people spend a lot of energy thinking about it. Weight is remarkably well controlled if you let your body do its business. Also, temperature, you could measure your temperature and you'd find variations throughout the day or maybe some throughout the year, but within a remarkably narrow range your temperature is controlled. When you go from here to going outside, to going to a much hotter room, your temperature stays the same and your body is able to control this on your own, you don't have to think about it. In fact, temperature is such a carefully controlled parameter that when it changes just a little bit by a couple of degrees, we know that something's wrong. You measure your temperature is a little up, you've got a fever, 'something's wrong, I better find out what that is' because temperature is a very highly controlled variable. You could go through a lot of these parameters and think about it in the same way that these things are really very highly controlled. Well that process of control to maintain a constant environment inside our body, whether it's an environment of constant mass or constant composition, or constant temperature, is called homeostasis. Your body has elaborate mechanisms for maintaining this state of homeostasis, that is, things staying the same; the body stays the same, homeostasis. This, in spite of the fact that we take a variety of chemicals into our bodies in different ways and we have to do that to stay alive, but we have mechanisms to control this very well. So homeostasis is enabled by sometimes complex, sometimes very simple control mechanisms. These are mechanisms that can be described not too differently from mechanisms that you're familiar with for maintaining homeostasis. For example, the thermostat in your dorm room. Maybe you don't control thermostats in your dorm room, some of you do and some of you don't probably, and maybe it doesn't work very well so it might not be a good example, but imagine a perfect thermostat that you set for a temperature and then the temperature stays the same inside the room no matter what the temperature is outside. Well how does that work? It works by a control mechanism called negative feedback, and the thermostat is measuring the temperature and then sending a signal to a heater somewhere. If the temperature drops below a certain level it sends a signal, 'turn on the heat', and that signal stays on until it gets a negative signal to turn off. When does that negative signal happen? When the temperature gets above the level you want it to be. So that's a negative feedback control system. The heater is on, it's producing heat until a negative signal is registered, 'oh we've gone too high', and then it turns off. Our bodies have mechanisms like that, that mainly use the principle of negative feedback in order to control the parameters that are important for life within a certain range. So why is temperature, for example, such an important thing to control? Why are all of us in this room within plus or minus a few tenths of a degrees at 37° Centigrade, or 98.6° Fahrenheit, why is that such an important thing? Student: [inaudible]Professor Mark Saltzman: Because that's the temperature at which many of the molecules in our bodies operate at their most efficient, and enzymes is the best example of that. Enzymes work best, enzymes are proteins that catalyze chemical reactions and our bodies operate by elaborate networks of chemical reactions, and our enzymes are optimized to work at 37°. When we're off from that temperature then they don't work properly. And there are other examples as well, but that's why it's important. So we're going to think about - in the next few weeks - we're going to think about the human organism at different levels of magnification and I've shown those levels here. The whole human organism is made up of a collection of organs, and organ systems, you know this. The cardiovascular system, which is the heart and the blood vessels which are responsible for - and the blood and so this is responsible for moving blood around the body and the blood brings oxygen and nutrients to every part of the body, you know that. Organs, organ systems like the cardiovascular system are made up of tissues and tissues are collections of cells that are working in synchrony for some function. The heart, for example, has a muscular tissue. It has a very well-developed muscular tissue and its function is to contract and relax, contract and relax. As it does that it changes the volume of the heart and gives the - creates the pressure that moves blood around your body, so it has that muscular system. It also has a blood vessel system in it. The muscles of the heart have to give blood themselves so they have blood vessels inside. Your stomach is a very complex organ that has a muscle layer, it has an epithelial layer which is the interface with food that comes in, and it also has a nervous system, so does the heart. So organs are made up of combinations of tissues where all the tissues are collections of cells that are doing some function, nervous tissue, muscular tissue, epithelial tissue, those are examples of tissues that form organs. Here I just show tissues at two levels of magnification and when we think about tissues we're going to be interested in a couple of different characteristics. One, at the first level, what are the cells that make up that tissue? Because the cells are the fundamental component of our bodies; very interesting because all of our cells in our body share many characteristics and some of those characteristics are shown on this picture. They have a nucleus, they have a cell membrane, they have organelles throughout them, they have the same DNA. All of your cells have the same DNA, so the same genetic information, and yet cells in your brain, and cells in your heart, and cells in your kidney do very different things. So how can cells, which have the same sort of master information DNA, in your brain, and your heart, and your kidney be so different? That's a question and it's one that we'll talk about in weeks to come. How do those differences between cells contribute to the properties of the tissues, which contribute to the properties of the organs, which contribute to the properties of a person and this maintenance of homeostasis? The main function of all your cells, and all your tissues, and all your organs is to maintain this homeostasis, which allows you to live in a changing environment. We're going to spend the first few weeks of the course talking about first DNA and genes. We'll talk about how they work and we'll go over that quickly because I know most of you know something about how DNA - what DNA is and how it works. Then we'll talk about engineering of DNA and why this has been such - not only a rapidly growing and advancing area but one that's so important for Biomedical Engineering. We'll talk about cells and how they work, how cells in different parts of the body are different, why, and how they contribute to tissues at a very sort of simple level so that you can understand this as we start thinking about using cells for engineering purposes. I want to just highlight what's in Chapter 2, because I told you we're not going to cover the details in Chapter 2 in the course, but I give it to you as a resource so that you - you might have other books which describe this which you like, and you've read already and so - but I'm going to assume that you understand this information to some extent. And again if you don't, and you feel like you'd like a review session on this please send me an email and I'll set one up next week. I do want to talk about one important subject which you might not have thought too much about and that's lipids, because lipids are so important to the structure of the body because they make up the membranes that form the cells that are the fundamental units. Lipids are really complex molecules on their own right, but because of their particular kind of complexity they allow certain biological structures to form. So most of the lipids, which make up cell membranes in your body are of this category of phospholipids. They're derived from a precursor called triacylglyceride, which is as glycerol molecule with three fatty acid chains dangling off of it. Fatty acid chains are fat molecules, they behave, if you have a lot of them in solution like oil. That's what triglycerides are like, they're just like oil. So if you had a jar full of triglycerides it would behave like an oil, many would be liquid at room temperature. What happens if you add them to water? You get salad dressing, right? You get glob- if you mix it you get globlets of oil, or globlets of triglycerides, they're floating around in the fluid if you mix it. If you let it sit they settle out into two phases again, that's how triglycerides behave. Now if you've gone to the doctor, often they'll measure your triaglyceride level as a measure of how healthy your liver is and how healthy your diet is. Having too much triaglyceride or fat in your blood, the wrong kind of fat in particular, is not considered a good thing. You need some of it because some of it gets converted into molecules called phospholipids, and phospholipids are different. They have two fatty acid chains and so these are the oily like parts of the molecule, the molecules that behave like oil. And then linked to the glycerol instead of a third fatty acid chain is a water soluble molecule, like a salt. Often it's a salt called phosphocholine and so you get a phospholipid that's made of choline and two lipid chains. Now this behaves very differently in water because part of it is water soluble, this part is, it's a molecule that would like to dissolve in water and part of it is like oil, it doesn't want to dissolve in water. So what happens when you put these molecules in water? Well instead of forming droplets like fat they arrange in a very particular way, they form these structures that are called self-assembled structures because they occur naturally, because of properties of the lipids. The lipids will form a bi-layer where the water soluble part of the lipid points out of this layer and the oily part points in. The fascinating part about this layer is that it solves the problem for phospholipids about how to exist in water when half of you wants to be in oil, and that the water soluble part of the top leaflet here, of the top points up into the water, and the fatty acid chains point down. The opposite leaflet does the other thing, the water soluble part points down and the fat points up, so now you have thin region of fat which is surrounded on both sides by water. This is a really interesting system because it also solves a problem for the cell. The problem it solves for the cell is how to do I make a barrier around myself to define what's in me and what's outside of me when most of what's around me and what's in me is water. So inside the cell mostly water, outside the cell mostly water, but I need to separate my water from the water outside. We'll see why they have to separate that in a minute, but they do that - these lipid bi-layers solve that problem for them and they're self-assembled structures from these molecules called phospholipids. Now that's not the only thing in cell membranes, there are also proteins in cell membranes, and these proteins are special proteins that can exist within membranes like this, and they exist because these proteins also have different segments with different properties. Some of the segments dissolve in water, the gray segments here, and the lightly colored segments don't dissolve in water, they dissolve in fat. So they like to be in the membrane and they're stable there and they won't come out because their structure allows them to exist in these unique spaces. I'm going to stop there and we'll pick up on this topic, not next week, but the week after when we start talking about cell structure. I wanted to introduce it to you so that if you don't - haven't heard about this before you might want to read a little bit about this before we get to Chapter 5. Next week we're going to talk about genes and genetic engineering, that's Chapter 3.