So I want to talk about a subject that I think is one of the more interesting subjects around in our Since I started this morning talking about commercialization. I would insert a number now which catches the attention and that is that I was looking recently at a market survey for biomaterials However biomaterials where was defined as a field and the claim and I think it was probably roughly right is that you expect the growth in biomaterials commercially to be something in the order of ninety billion dollars globally over the next ten years and it's this is one of the larger commercial opportunities around. It's not what we do and what we're interested in particularly but it's an extremely interesting and important area for reasons that I'll come to. And I know that it's one that's a big deal here on campus. So in some to some extent I'm going to be talking to the converted. But I actually like it that way. It's less argumentative but let me just start by telling you what the first slide shows you what I want to do particularly for those of you who are our students is to give you just a little bit of a sense of material science as a sealed with I'm going to be talking from the vantage of material science and going toward biomedicine. Material Science is an extremely interesting area for the reason that it's the only respectable academic discipline that I know that was made up by the government which it was. And the argument and the origin of its of this field was the following after the belief was at the end of World War two that high technology stuff airplanes and tanks and things like that was an important part of the end result in World War two and most of this work came from laboratories like of General Electric and Dupont and integrated multi-disciplinary laboratories. And then of our Bush managed to convince the government that it was an import. And legitimate function to try to recreate in universities the kind of atmosphere that existed in these multidisciplinary Industrial Average Henri's and so. At the same time that DARPA then ARPA was established established a series of laboratories which were called the materials research laboratories and these things were purely a government construct and as the field developed it turned out it was extremely interesting and it became in a sense. Most often I know about this. There's a crude definition in material science which is that any chemical as soon as it becomes useful becomes a material so material science simply grabs all the credit from chemistry. So the evolution of the field has gone through really three phases and we are in principally on the fourth phase. The first the first part of material science was the development of technology that was really designed for military systems and so the current. Leading Edge thing there is the F. twenty two of which we will probably buy three or five or something of that sort is an amazing device with high performance nickel fan blades and and lowered our reflectivity services and all the rest of it. Fantastic. But that's pretty much over because at least for the moment we don't need it anymore. The second phase was the material science of information technology which was high performance silicon and doped insulators and zirconium oxide and all the rest of the things that go into making computer systems. And that area has also begun to fade in terms of what is the. I think probably the current focus of investment which is using computer systems for various things you know the the web and the Internet and things of that sort. Then the third phase was the development of technology to risk. Fund to globalization. And what that means is to provide function. At low cost. I mean basically what globalization does is mean that whatever we had in the past you want in the future but you want to cost half as much and less twice as long. There are phases to develop technology which had the characteristic that it was intended to be of low cost and functional and so that phase is also pretty much gone. You know which way you can make most things that you can make an inefficient and affordable way and there are some very interesting problems that remain but so the question for material science is what's the next thing you know what's the next big interesting thing. And there are a couple of opportunities put for a variety of commercial reasons probably the one that's the most relevant is the issue of going into medicine and so one already sees important. You know important examples and in due course I will show you some of these important examples perhaps at the the issues that you can think of as examples are for example stance which are after all. Metals which have a particular set of characteristics they have to have strength they have to be expandable they have to be compatible with the with rubbing against the end of the arteries contact lenses or example cochlear implants for example their wide variety of materials that have the characteristic that they have to fit in legitimately to the kinds of characteristics that one finds it biomedical systems and it raises a whole new series of problems and a whole new series of conundrum in terms of materials characteristics but the. Part that was concerned with the effort on on consumer products is really driven by this area which is the area of globalization and I point out that for those of you who are young. This is going to be an important do you know which is that it is good. To be something in which globally products will be provided wherever they can be provided at lowest cost and lowest cost means that for those of you who are here somewhere. You're going to be competing with St Petersburg and with sing La and with Beijing and with St Petersburg and I mean Moscow and all the rest of those so it really is an important thing for you to keep in mind when you're when you're thinking about your education because it's going to make a world of difference. All right so we have this kind of system now in which if you look at the way the economy runs. We have durable goods we have not durable goods we have services and we have others and one makes innovations in science and technology of a broad variety of swords and ideally what happens is that innovation which is your business needs to high end jobs iron jobs means good salary and some stability. And then there will inevitably be a process in which the high end proprietary technology becomes commodifies. Wherever it's generated and historically this is been a pathway from the U.S. to Japan to South Korea and I want Taiwan to India and China but of course these countries are getting to be very very good at what they do in addition they're not so far profoundly innovative in the sense of developing entire new fields that still goes on in the United States but boy are they good when it comes to taking an idea like flat screen display and making it really work well. Now a very interesting thing about bio medicine is that there is a bleat that the degradation in value in biomedicine may be slower than other in other fields and the reason is that mette medicine in every area is surrounded by a web of local expertise doctors and nurses and hospitals and also white regulatory structure which makes it very difficult to go to Korea and just in. Port Korean medical technology doesn't work that way there's too many other things that have to go on. So from the point of view of slowing this process going down to here medicine looks like an attractive thing to do I at least I'm getting a certain amount of feedback from this if there is a way of limiting that it would keep me from talking to myself. So the question to ask is What's the next big thing you know what is it gets going to change the world then there are probably several opportunities but let me just go through a couple of these by always going to be the one that we talk about I.T.N. for tonics will continue to be a big deal for the reason that so much of the world particularly the business world is driven by this but in the future education which is an essential part of things entertainment which is still one of the areas where there's unlimited of a fairly financial growth comes to really out of that. Intelligent Machines that is machines which don't just calculate but actually make decisions and perform functions is going to be very important globalisation the whole art of providing for a function the lowest cost. Technologies for developing economies. Most of the potential consumers in the world are actually in the third world not in the first world and the developing world as a whole series of characteristics in terms of its market needs and its cost structure which are dramatically different from the ones that we work with in the first world. The commodity infrastructure which is here and water and energy nanotechnology and others. So there are unlimited range of things to think about. So we're only thinking about one. So I think about the US is the clear global leader in this area and there are a few areas where things slip as stem cells and cloning. But it's not bad. Can you all still here in the back since they've turned down. Yeah so I guess that's what's you've turned it down to the point where. Can't be hurt. Now in the back so we need to adjust them. There is a very large but troubled industry the without going into details the medical industry. Is really in grave difficulties right now because it's not making enough new drugs and so the cost of capital and the return on invested capital of crossed the area is now a net negative cash flow and unless something is done. Not something is done with stuff and I are going to get older. Which I know my stuff is not very graceful about. A large enduring market to be all age use is wide variety of uses outside of health care consistent federal support for this which reduces the cost of capital but I point out that the groups that control federal support do not include bioengineering So those of you who are bioengineers always have to struggle to get money. It's an interesting problem. I margins not quite as high as drugs but very good and under-served areas of a variety of sorts. So it's a very attractive area from a practical point of view. So are their needs. Well in medicine there's absolutely no quality question there's a broad range of things from dealing with disease and Prevention in anticipation of cure replacement of function and monitoring are important ones and by replacement of function. What I mean is simply that if my joint wears out. You can ask what are the strategies for dealing with a worn out joint because I don't care in a sense what it is that gives the function of a bearing that's lubricate I just want to do the job and not hurt and there are a range of techniques for doing that and I'll show you some of them but it's that kind of thing asking where you have a function that you want to have replaced as opposed to a disease that you want to have cured which will be something which will provide opportunities in this area. So. If you look at this plot. It gives you a sense for some of the realities of the medical world in which this bio you know bioengineering kind of thing has to fit. There are actually pretty interesting sorts of pretty interesting sorts of curves this is death from all causes and something for those of you again to remember in the in one thousand nine hundred the average lifespan in the United States was forty two and the average lifespan now is about seventy four seventy five so many of the people who are well basically all of us who are age would be dead and you are would be halfway through your lifespan. So if you say that you're in the medical profession doesn't work the medical profession really does do over a whole a very good job. How much of that is medicine and how much is public health is an interesting question. You know what are the issues heart disease great progress cancer. Little hard to say it actually seems to be going up and then maybe drifting down but that's partially because if you don't die of heart disease you die of something stroke goes way down a chronic obstructive lung disease unintentional injuries. What you draw from this kind of thing. If you think about it for a while. Is that if you live longer. Because let's assume we make progress with this area. Things are going to get you know you're going to begin to wear out somehow and a lot of that wearing out process is where bio in your materials will come in and the basic argument for biomaterials science is that the population will continue to age and as it ages replacement of function will have to be done in various ways and some of those will be biomaterials functions is their support for the area. These are actually pretty interesting numbers from a public policy point of view to look at this is support for the. The Blue which is and I H. and related health kind of stuff. This is all the physical sciences and what this says if you're a materials scientist is a reality that I don't think is the right answer but it's the real answer and that is where the money is in medicine for research. So all of this which includes I mean this part down here is not which is in principle exploring the planets but it's really taking a very large heavy objects and heaving them into space for unknown purposes. This is all of an AI age N.S.F. and related things and it should be arguably here that you put the money because what has changed the world since World War two has really been information technology that has been the thing not health care actually biotech not as it made that much of a difference in terms of many things but the fact is that where the money is right now is very strongly in the medical area so if you want to do material science medicine is one of the areas that you are obliged to consider. So the basic background argument then is that the past has been things like airframes computers and the future is going to be things like this with the audience being not transportation not communication not military systems but rather. Human health. Right. So I'd like to classify the problems and material science into four broad groups and I'll talk about all of them. One is health care and biomedicine and preventing and treating disease and dysfunction that's going to be the major part but there is also an extremely interesting area one that I know is active here which is to look at biology look at the strategies both structural control and other things that are used in biology and extract those strategies and use them in non biological systems so that Steve's control theory kind of thing. So dynamic and out of equilibrium systems systems we don't know nearly as much as we should Iraq eco systems and related kinds of things then there's the issue of materials from biology. So so and college and you know maybe intermediates for polymers another very interesting area been around for a while. It hasn't yet taken off really but for specific applications it's clearly going to be interesting. And then since any field that's vital has to have a big future in the end it's probably this one which is hybrids between living and non-living systems and that's you know in the simplest form how do I plug my computer into my brain. How do I make a system that is both biologically sentiment and you know otherwise how do I make things that are more hybrids of biological systems and biological systems and you begin to see these already emerging. I don't know whether all of you follow it but one of the most exciting areas of this broad field to me is the area in which one causes machinery to move just by thinking about it that if you put on something the something reads patterns in the brain in a neural network like sense and those are then used to drive actuator systems that really remarkably good in allowing you to pick up an object and move it without ever touching it. And with no direct control. So that's a noninvasive hybrid system. There are many other more invasive hybrid systems to think about but very very exciting stuff for that period. And I'd like to make one other important distinction which is going to be one that will touch on here and this is the distinction between people who build tools and people who use tools and this is one of those great gaps in science and technology. If you're a tool builder your view is I built the tool I make the enemy and all the rest is technical detail. You know people image levers with it and do organic chemistry with it but it's obvious after you've done. And that if you're on the other side of the gap you say I make compounds and I image levers and I'll do it any way that I want to. And so that tool is you know that's something physicists do but I don't really have to pay a lot of attention to it. Both are essential but in this area. It is really crucially important to understand that Materials Science builds tools work tool building groups we build tools for doctors to solve problems and dysfunction. That's a tool of some kind. So we build tools the value of these tools is determined by their users and what one is really interested in here as in many things is function and that's the key word to pay attention to you don't care whether it's polyethylene or stainless steel you care whether it works in vivo to solve a problem. And that in order to determine function you have to have assayed and the essays must come from biology and medicine. So the intellectual flow in this is such that this is an area in which the physical sciences have to work for the medical sciences. That's the only way this can develop. I think in an attractive way. All right so going through this process function. Safety is a key part of this all of it depends upon and Ses and developing and finding functional last ACE to guide our Indy is one of the key barriers to entry in this area and also a big opportunity if you can find essays that allow you to build materials that I.Q. really predict the performance of the system in vivo you can make rapid progress. If you don't have that kind of assaye then you really have a much harder road to hoe because it's very difficult to tell whether you're developing developing in the right direction. So what are some examples. It would be good to have a notion of what we're talking about these are pictures of stance as you know. Most dense are made of laser machine. Titanium you put them in an artery which is clogging you put a balloon on the inside you blow up the balloon that blows up the stent and it works sort of. These are posts in teeth I stand before you as someone who had breakfast this morning. Based on these kinds of technologies and they work really well I can tell the difference between my teeth in those but the it's taken about twenty years of really rotten empiricism to get to something that works this is a technology it's been hard to deal with these many people here will get hip replacements. The interesting thing about a hip replacement at least as it used to be done is that grout out the part of the hip joint glue it in with acrylic and for about four days the patient just stinks of accolade of because there's enough of it was ing out that can't be the right way of doing it and there has to be better ways. So this technology works well but it needs to be improved a stent an expanded form has a contact lens and these are sutures with biodegradable adhesives on them by a variable string on the back. And the area is also interesting in the sense that it has a characteristic that's very different from most areas in the sense that because of the distribution of federal funds that I showed you the market for research tools for biomedicine is itself a market. I mean there's more than enough money just there and examples of material science here. These are the gels that are used for sequencing those gels are immaterial. They're Polychrome it there's no reason to think that they're the best material but they're the ones that work pretty well polystyrene dishes for ninety six. Well plates or that that happens to be in on the new six wells but neither here or there. These are quantum dots for imaging cells and those are by predators doing something I can't see from here. What it's doing but that business is in the order of you know it's getting on toward twenty billion dollars. Years something like that it's quite a big business. So if you have a good idea. It doesn't have to go into people it can go into research and that gives you an entry point which is a very attractive one. Now this is an area that bridges between science and engineering and I would like to start with a little bit of a definition since both are important. Medicine first medicine is engineering that is medicine fixes problems often without having a clue of what's going on. That's fine and you do the best you can. And if you're in engineering. If you fix it and then maybe somebody will understand it and the engineering is very stimulating as a as a area that brings up new ideas in science. What you do is you understand it and then you have this sort of one hope that somebody will eventually find a use for it and both of these work but they really have to work together. So it's. It's prototypically an area where one needs both science and engineering and if you look at the list of lenses it uses these are just some and for those of you in the back who can't read a moon drainage haemodialysis products drug delivery systems polymers typically some devices pacemakers with embedded electrodes central of Venus catheters grip lines things of that sort cochlear implant are returned to that contact lenses dental implants vascular grafts I.V. catheter is hilarious stents in orthopedic implants. That's just some of the list of things that's going on now the list of products that people are trying to put together is probably two or three times that and each one has really really interesting problems in both material science and compatibility. But you need to have a strategy. And the point I want to make here is to break up the list of problems into a graded list in terms of material science dominant and then medicine dominant. Think about various parts of replacement that one might like. So for example with the hip joint you can imagine building a replacement hip joint mechanically or mechanical heart gets to be complicated. At the other end of things there is regenerative medicine in which you have a heart attack. You have a region of the heart that becomes scar tissue but you do something which causes the tissue around the edge of the scar to differentiate invade replace the scar tissue and so you replace yourself. We are a long way from being able to do that we don't know how to do that at the moment but it clearly is all biology a growing replacement would be what's called tissue engineering Now you take a part of you you take it outside you grow a bladder you grow a kidney or you grow a heart again it's something that you can imagine but we don't know how to do it. Transplantation is sort of in between. Here you take it out of a pig or out of one of one hopes and put it into one of you if you need it but if you look at this gradient pure medicine that we have only a vague idea how to do. Only a vague idea how to do a pretty good idea how to do it. What the difficulties are and here. It's material science. So you want to try to focus your attention on problems in which a solution is not going to be obsoleted by a better biological solution in the immediate future. And. I think that for example to take Keith I don't think anybody's going to grow choose if it. If a titanium implant works perfectly well why would you bother. I suspect people will stick with hip implants. Even in the place of something more complicated on the other hand for heart or for large areas of skin or things like that. The issue may turn out to be quite different. So ultimately this technology has to be driven by biology and medicine and material science should serve not lead the fundamental biology. Understand this is not in place. If you ask about bio compatibility. We don't understand bio compatibility. We really don't know what goes on when blood flows over a piece of plastic it's still Klotz platelets still get activated. You would say after all these years we would at least understand what's going on. Biologically in the answer is we don't. So the fundamental biology here to connect living systems to man made systems is not in place. The health problems all health problems are systems problems and not materials problems. So you put in something. It's not just a question of hip replacement it's a question of bio compatibility the inflammatory response immunology all that kind of thing. But having said all of that in the land of the blind the one eyed man is king by which I mean if I hit falls out. I'll take the best replacement I can I can find and so if you know something about it as a material scientist and you're talking to a doctor I think the the applications or the opportunities are really unlimited. So here's the kind of decision that I think you need to make in terms of thinking about where an opportunity is. And these are just three examples one example is controlled release or bio and sort of an it's the second is what I'll call fracture pottery and I'll tell you what that is in a moment a third is tissue engineering. And if you look at these three and look at the level of biological content in tissue engineering biological content is very high in material science may provide a scaffold. But basically getting the growth of the cells to grow and to differentiate is essentially a biological problem. In controlled release you simply have polymers poly lactic you dissolve a drug in it and it releases its Things were so there that's a material science problem. What about this area and here and fracture party is a is a program that's just DARPA is just started a big program and it's an example. The specification of fracture party is the following and the applications are obvious for a military group you come in with a severe compound fracture pieces of bone missing and things of that kind. I would like you as a. Biomaterials person to build me a polymer that has the characteristic that I can use it as a kind of party. I take the bone fragments I have I put them in place. I connect all this stuff and then I do something I thought if a limb or eyes close the wound the patient walks out and then two years later the patient comes back and all this stuff has been replaced by normal ball. That's what a fracture put it would be. And the reason for it. There are many reasons for it. Military it's obvious but even in civilian medicine if you have a severe compound fracture the way this is all play held in places with an external metal skeleton. You can't walk for weeks months and then you have an open wound which is a source of infection you have to do an open procedure to get the stuff out. It would be much better to do this. This is we think a practical kind of problem right now this is certainly a pride to go but maybe old hat and this is probably too difficult or too much biological content for material science. So let's look at each of these in a little bit more detail what is a tissue and why is that hard. Well and obvious simple tissue is skinned you say what could be simpler than skin or is just layer on the outside. But look at what this is a cross-section to a piece of skin. Here is what skin looks like then in a kind of schematic diagram. And you have tissue you have vascular ization you have layers that are differentiated in very complicated ways you have transpiration machinery that lead stuff to go from here to here and here to here. The cells in this region are dying and and kicking out their nuclei in current currents and izing and become. Mist up there goes out here and it's really extraordinarily complicated all of this. So even skin when you think about a tissue is hard to do and people of course do make cultured skin but when you put a piece of cultured skin on a burn it never really becomes it never really replaces So even in this relatively simple occasion there is a lot of biology that these to be done. Medium difficulty is scaffolds and this is the kind of thing in which there's a lot of work going on but it's not all that well founded on out. Point out just one or two examples. The issue is if you want to build a three dimensional tissue suppose you want to build muscle which is one that people have not been able to do so far you have to grow it into a three dimensional shape which means a scaffold. But there's the shape. There's the surface chemistry. There's the compliance probably muscle has the structure that it has because it's constantly being stressed in an isotropic way. A crucial thing it's nutrients because the interesting thing about you something you may not have thought about is that every cell in you is no more than about two hundred microns from a flowing stream of blood in a capillary two hundred microns is twice the diameter of a hair I point up to mystically to my head but imagine that it had hair on it. Of So you're really if you took away all the tissue your form would still be there from this enormous network of capillaries if you get further than two hundred microns the cell begins to go in opposite. And so this this issue of building into tissue engineering that network of nutrients is crucial. Growth signals hormones environmental cues. None of this is present in tissue engineering as it's presently being done mechanical signals making nerves and making nerve connections all of that just for something that we think of as being as simple as a muscle remains to be worked out. Now let me give you an example of. What the kind of thing that material science can do even at the very simplest level because I think there's an enormous amount that doesn't have to be complex biology. This is a company I was involved in a couple of years ago and it's called jolt X.. What just takes made was simply a poly acrylamide Polychrome it's the same thing that you use for doing gene sequencing. But it had some positive charge groups negative charge groups on it that made it relatively selective for phosphate which sounds completely uninteresting. So why is it interesting and the answer is that if you eat and if your kidneys are falling out then you don't have a good way of getting rid of phosphate from the diet because phosphate is excrete it's in urine and so you begin to develop phosphate in inappropriate ways and you deposit phosphate and there are talks of cities that come from this. So the idea is that a patient on. Renal dialysis or related kinds of conditions would eat this stuff and it would sort of phosphate that was that was the notion. How did we get to this notion. Well we I won't tell you how it all started. But the original idea was to make gels that it's sort of sodium and then we did a little homework and found at a McDonald's milkshake contains forty grams of sodium in it and the reason for that is that sodium chloride is the universal flavor enhancer. So you take everything and then you dosage up with sodium chloride that tastes better. But this would have meant that to get rid of the sodium from a McDonald's milkshake you would have had to eat something like three kilos of this material and that seems the impractical. We went to when it turned out this was a bad idea. We want to foster it and it was a desperation act there were two products already on the market and the total market was twenty five billion dollars and the development product development guys said this is. Luser shut down the company but if you're going to do something. This is the only market we can find and that's fine. And we went into it and then after some various and sundry things we sold the company in two zero one which is you know this is only seven years sold it for about a billion three and. The sales at this point from this set of things is in the order of eight hundred million a year and eight hundred million a year is in the order of about ten billion dollars of market capitalization. Now my point in that is that a very simple idea in materials science which isn't a soft cross-linked an exchange resin turns out to solve a really important problem if you just know where to link and I think that everywhere you go you'll find gels degradable polymers things that have non sticky surfaces things that have sticky surfaces which are all material science problems which will have the same characteristics. And this is where this number of ninety billion dollars comes from. I mean the argument is that there is more than a lot of stuff to be done that that you can deal with that kind of volume. Let me give you some research ideas and the this section is really intended for those of you in the back who are asking whether this is even doable or not or is this something so complicated that a human being. Can't really work with it. Let me give you an example there is an area of protein pharmaceuticals called Paper lation and the notion here is that you give a patient a therapeutic protein of some sort and it has given from a coconut It's that last in vivo for a certain period of time and it has a certain distribution in tissue and so on. If you take this material and you attach to it a low molecular weight polymer polyethylene glycol the distribution changes the lifetime changes and various therapeutic indices change so you don't do any. Thing more than just attaching a polymer. And this is quite a substantial business now. Here are proteins that are sold in this form so of eight interferon for hepatitis C. of this material to last for neutropenia. This is another hepatitis C. drug and I actually don't know what this stuff does but it's another protein and there are something like ten others in development or in the clinic where you say OK this is a solved problem of course it's not a solved problem. We don't have any idea how these things work. A B. There are good zillion other very interesting polymers that could be attached. There is an enormous opportunity just to take proteins and add polymer is this something which any polymer scientist can do. Why isn't it being done. I think it's just built basically because polymer scientists don't know enough about the field to have a very good sense of what's going on or they just do their. OK. Dextre and coded iron oxide and should have had a picture of this. There's a picture at scale of nanometers Dextre and coated there now. So you actually can't see it. Let's keep doing that. And so imagine that you have a black glop which consists of iron oxide extreme coated iron oxide you inject this into the circulatory system and in this particular application. This is of more interest to some of you than to others. This is a prostate as viewed by M.R.I. and what you see here and here are regions there and they're also which light up in magnetic resonance enhanced well. Contrast meant many magnetic resonance contrast enhanced images and what's happened here is the following that you inject you give this stuff the stuff I get you injected in this particular case it is taken up by macrophages in the region of the tumour and then carried by those macrophages K. by those lymphocytes to the lymph local lymph nodes and so what you can do is to use this to trace the pathway of migration of lymphocytes from the region of a tumor to local lymph nodes which are the place where you expect metastases to occur. Now it's here are examples of the claim is that you can see a metastasis that's in the order of one hundred microns. It's interesting to me and I don't understand the arguments that this material is not used in the United States it's used in Europe but the claim is that knowing this pathway is interesting. Scientifically and interesting medically but actually doesn't help the patient because once you have the information is not clear what you do with it. I don't understand that argument but I'm not on that part of the F.D.A. but it's another example of a material science product that is biocompatible ised dextrin coated of magnetite which has a big magnetic moment and changes the relaxation times of water in the serum in the immediate vicinity. Here's the picture and then this is a picture of the cerebral vascular circulation and it's just a contrast with a soft tissue image by M.R.I. So this lights up certain features very well and that lights up other features quite well now let me begin to move toward the end by talking about some areas where there are emerging technologies and some science. Here's an example of something which I talked about at the beginning which is the idea of. Aerials from biology and there are a host of interesting opportunities here some of them are beginning to be exploited. Exploited some are not this is the structure of fiber Nekton which is a protein that's very important in cellular in fiber Nekton there is a loop that extends out in this fashion which contains an R G D asked why and why orange unit which is recognised by some of the proteins that are responsible for Cellular and he. So by working with materials that have R G D on them attached to them you can regulate where cells attach and where cells don't attach this is an example of a material or at least a hint from biology that leads to other interesting kinds of materials for applications. Another very interesting area of science right now which has the as so far not led to practical applications but it's you know it's characteristic of science that one starts with something that is driven by curiosity and moves from there. Polymer science is the science of large molecules and the characteristic of polymers is as they're made they're almost all poly disperse. So they have a range of molecular weights. Suppose you would like to have polymers that are modeled disperse How do you make them. The answer is we don't have any idea how to make them right now people have tried for a long time to do that to find ways of doing it. But in fact there is a very good procedure for doing it which is simply to use proteins the proteins have specific molecular weights determined by the gene. And the question now comes up. Can you use proteins as polymers modder dispersed polymers does the model disperse a T. give you something of value or is it possible that by working with him on a dispersed polymer and doing a modification. That you can get something of value and this field has moved sufficiently far that you can demonstrate pretty clearly that you can make mounted dispursed polymers here is a model. There is this is a job. Permeation chromatic gram of a protein that has been modified and you can see the monitors first is extremely good. Now the question is what you do with it. That remains to be seen but this is an area of science in the materials world which is at the level of science but not yet the area of application. And then of course this one has been around for a while. The question here is is toughness of materials. The abalone and many shells the abalone is an animal has a problem which is as an animal. It's a soft and relatively tasty thing in a world full of predators. So if you are that way. How are you going to build yourself a house the protection and the answer is you build some kind of armored case. But what do you build it out of and what there's not much of a range of opportunity and what the abalone uses. Is basically calcium carbonate which is quite fragile you all of you have seen calcium carbonate So how does it make something that's as tough as abalone shell is that what the abalone does is to construct a series of plates that are in the order of less than a micron thick single crystal separated by thin layers of resilient protein. So it's a single crystal calcium carbonate of protein polymer composite that has the characteristic that when a crack moves through this instead of just cleaving through the calcium carbonate it has to follow all these paths you enormously increase the length of the surface. If you have to generate and hence increase the fracture toughness. So this principle has actually been used fairly extensive now in areas like ballistic armor and the motivation. Came in fact in least in part from this. You say what else can you do well here is an example of that interesting organism that my colleague joined Eisenberg works with this is called a brittle star and the skeleton in the brittle star is also made of calcium carbonate but it turns out that in that case the calcium carbonate skeleton also acts as a series of light pipes to transmit light around in the organism. So the idea of looking at these simple organisms and then figuring out how you build a complex function from materials that you would not have guessed would have had that level of functionality in them is something which I think is an extremist emulating area nanoparticles time sure you've all seen this. So these are cadmium selenite particles and here they're stuck in mice or rats. The issue with these again it's a material science issue. This works you can do imaging but the problem is that you know that both cadmium and selenium are toxic. So how do you make nano particles that have the characteristic that they're good for a forest but perfectly bio on earth. It will pose scientific problem. We just have to figure out how to solve it. And these are examples of surfaces that have here's a cell on a surface that's on pattern here is a cell on a surface that's been patterned into a region that he see and a surrounding region that's not easy. That's a bio surface problem. And what you begin to see here is how the cell senses its environment. You say this entire region in here is that he sees what is it doing. And apparently what it does is to glue itself down with a string of glue around the outside and then the inside is free floating We have no idea why does that and more of the same kind of thing. This is just the ways of using materials in this case to measure mechanical strength in a in one. It is basically pure science. What you see here is cells that are sitting on a soft polymer. And when the cells pull what they do is to call the cause the polymer to wrinkle and by looking at that pattern of wrinkling and knowing the mechanical properties of the polymer you can then back calculate the forces that the cell exerts on the surface. So let me now finish with a couple of things that are speculative. These are areas that are attracting a lot of attention in the material science community and in which there's almost I think on limited opportunity for science but also great difficulty one of the things that people know is that biological systems are self healing. I break a leg and the leg repairs itself. So why can't I build an airplane in which it breaks away in your landing gear and the landing gear repairs itself where you put a bullet through the thing and it repairs itself and it's a very interesting thing to to think about but the way to start it. This is to think about what happens in bone healing and what happens when you break a leg. If you break the leg here is the reason the fracture that first fills with a human time on this becomes a clot then the various factors induce the migration of cells into this which forms reforms the circulatory system with that circulatory system and nutrients and oxygen cells can begin to migrate and. Work in this area damaged area to deposit a kind of low grade bone called callous and then over a period of time the callous is replaced by normal bone all of you I'm sure it had a broken bone and what you note is that when the bone first heals it's quite thick and then over the course of time that shrinks down and that reflects the formation of callous and then this. Now how does that process of. Her and it occurs by the concerted action of two classes of cells. There are osteoclasts which migrate through the bone basically pinning down their edges and creating hydrochloric acid to dissolve the bone and then walking away and that fresh surface is then of colonized by osteoblasts which sit there and deposit a layer of of the normal bone or this being done in a way that's orchestrated in some fashion that we don't understand by the stress that supplied on those very stressed responses. All that's really interesting. The question is how would you do that with a titanium landing and the idea. The answer is we don't have a clue. So it's something in which you can see an immensely interesting complicated process in biology which will suggest strategies for self healing but we don't know where and how so it's a wonderful science. Here's a second area. This is retinal prostheses vision is quite interesting in the sense that what happens in vision is that there's something out there attractive object like Bob Niro. Who the photons from Bob near him come to my lens. They are focused and there's a plane or projection of Bob in your room on my retina so there's a wonder one mapping from the two dimensional thing out there on to the retina and then that's been transformed into nerve impulses which go to the back of my head in various things happen. What's interesting about this is that there is a geographical mapping from the retina to what I see. And so the argument is that if I go into the retina. I might be able to put a pattern of electrodes into this stimulate the retina that way and be able to see in directly. So there is now a fairly active program to build a focal plane arrays. Which can be implanted inserted into the eye these have electrodes on the back the electrodes will be driven into the retina in the appropriate regions. Those will act as electrodes to stimulate nerves which are presumed still to be active to go back to this region of the brain this whole thing would be powered externally inductively and the information required to provide this focal plane or a with the information it needs would come from a camera and external whatever all of that sounds extremely complicated but in fact there actually have been experiments. Now at a very simple level in which electrode arrays of this sort enable people to see the distinction between you know the letter one in the letter or the number eight that kind of level of detail is pretty primitive but the example where this is now a work which I would have thought equally improbable is this one which is cochlear implants and for people who have functioning nerves in the coffee have but are missing the nerve cells among other things. What you do is basically take a wire with bands on it. Individually addressable electrodes wind it into this this nail shell like shape. And then this is connected by a wire to a receiver and a transmitter up here and a battery and all the rest of it and so the sound comes in here. It's separated into something in the order of twenty five different frequency bands these separate bands are used to separate to excite the twenty five separate electrodes down here and then that those excitations are transmitted picked up and transmitted as nerve impulses into the brain and it works really quite well I mean at least I've heard simulations of what patients here under these circumstances and they're very good for speech and interestingly absolutely awful for music. You can't listen to music. If you have a coffee and I'm told. Now the really big science problem here at the end is this one. How do I plug my computer into my brain. We pass by the question of whether I want to plug my computer into my brain or more properly or whether I want Bob's brain plugged into my computer and then plug into my brain I would just as soon not share this. But there's a really interesting scientific problem here which is that the basic currency of wires and our information systems are electrons and we store information in magnetic domains and we sometimes use photons but basically we move charge around with information in terms of charge and photons and we do stories in magnetic domains and in nerves information is moved around in terms of neuro transmitters and action potentials and then there are these funny things that we as as large mammals have called synapses So in a wire I simply apply a potential here and the electrons in the wire shift and I know what happens at the other end here. I have an action potential with Swan cells involved and they get to this point and they release a chemical which defuses across a gap which picks up something here which starts the process over again but we have to have it some way of moving from one of these currencies to the other and right now we don't know how to do that. So it's a very core problem in science which we have to solve. First the currency exchange problem and then how to do the addressing in three dimensions with very small things that we don't know how to do either of those so this is you know this fits into in a Cooney and sense what Mr Coon calls a problem as opposed to a puzzle that is it is something which. You don't know it can be done. You don't know how it could be done. You don't know any strategy for getting there but people really do care about the result if you could do this it would make an enormous difference in the way the world works. So it's at the opposite. One from a scaffold for tissue engineering. I mean one is doable but the the the yield is important but you know it's science that we know how to do this we don't know how to do. Now just a couple of final things. This is Science of a somewhat different kind everything that I've talked about up to this point has been materials for high technology western medicine but there are a bunch of other problems as well there's the third world which in which health care. Absolutely requires low cost. And then there are issues of a national security sort like bio defense or border security or environmental monitoring and thinking about those problems is also important. And here I think is a spectacularly interesting example in the developing world of course people are the same ocular problems that they do in our world. So how do you provide eyeglasses and the idea here is that there's a generic eyeglass in the lens instead of being glass is two pieces of I think P.D. a mouse or mylar or something like that and you simply pump into this. So then I'll And you know put it on the patient you pump in into you get the best results you can now you don't fix astigmatism you don't fix a lot of other things but you provide up to six diopters a straight correction the claim is that you can you can do these things for about ten duck bucks apiece and one size fits all. So here's a young woman who looks very happy with being able to see something and it may not be a really fashion statement that she's making with her glasses there but I don't think she cares all that much. So it's a different kind of material science with a different objective but very I think very interesting very important and I'll give you an example from our own work. What you see here is a piece of paper. We have a big program in this area now funded by our friends Gates. This is a piece of paper. This is a hydrophobic polymer and what we've done is to pattern a drop of something to detect glucose here and something that detects protein here. You put a drop of urine in here. It works its way up it distributes the self into these three ports this part turns color depending on how much glucose there is this part turns color depending on how much protein there is and then in fact what we do is to take a picture of that with a cell phone and send it to a central facility where a doctor in principle looks at it but the reason for being interested in this is that you can make an estimate that the cost of this on scale might get tens or hundreds of percent rebate to make it the same way you make comic books. And you say well that sort of low technology actually it's not understanding how to work with fibers how to think about wicking how to think about heat transport mass transport in porous media how to build these kinds of systems. Turns out to present all kinds of really interesting problems and by the way if this works in the developing world. It has the potential for changing the cost of the healthcare structure in the developed world because it then makes the step toward making information free and moving away from the current business model which is sell reagents and make money on the reagents to one in which the reagents the information becomes free and all the money comes in manipulating all the value comes in manipulating free information fundamentally different structure. So really interesting from that point of view. That's just how it's done. So I am going to take those now. Actually I did take them out in the the thing which probably is the other title but that's all right so let me do conclusions. No conclusions. There are for one thing an enormous range you can't read but it's not important. Any review will give you this. There's an enormous range of applications wound him burn. Kinds of things catheters controlled release diabetes control neurological repair rest in peace. Whatever in which one needs new kinds of biomaterials so there's no shortage of materials and or surge of problems and materials. Some of the key ideas that you need to think about are bio compatibility having function relevant bio ass A's you need to think about safety and liability from the beginning you need to incorporate into a system the doctors can and will use and I'll just give you an example they're F.D.A. clearance without a fifty a clearance you get no where you need to think about how you're going to be reimbursed and important issue thought leaders in marketing and financial and social return. Let me just give you a bit to give you a flavor of the area incorporation a system the doctors can use at one point I was involved in developing hyaluronic acid as a and he says. People go in and they open you up. They rearrange something or they cut something out and doing that they rub surfaces against one another they are braid and then what happens is the surface is good and one another. It's called in a T. shirt and that's a nuisance. So highly ironic as it is a bio polymer that comes from a variety of sources and which really makes things beautifully slippery so they don't break. And so we made thin sheets of by what he did weaving Genzyme. Of this stuff which got wrapped around a kidney or a uterus or whatever it was while people were working with things. The doctors hated it. And why the doctors hate it because they go in and all of a sudden you know. Fuck the kidney would pop out or uterus with popped out or something like this and it was too slippery and so it's really they that are the right people. Then you have to think about something that they can use because if it solves the problem as you see it it doesn't solve the problem as they see it if it's you know it's too sticky they can't get their hands on it. They can't control it. They can't see it. Those are all things. Is that really critically important and you can only get that by talking to them. So my case for this area and here I know I'm talking to the converted the case is that there are a variety of of outcomes. All of them desirable in this case in biomedicine treatment of trauma and disease new prostheses in developing sensors we haven't talked about that but a big deal new science tools for biology an understanding of all of the things than biology that are not molecular invention understanding how biological systems work in a dynamic and hierarchical an out of equilibrium system and folks nano systems of biology is full of those and maybe ultimately hybrid systems. So for example putting together living and non-living systems or having the body powder power and electrical Bapi How do you do that kind of thing. And then finally these issues that we've been talking about in national security of developing world health care biodefense change in the cost structure in the US and then some other areas that I haven't talked about. So the area is one that has to me. Norma's potential in all ways. I do think that it is one of the most attractive opportunities for material science. I do think it's one in which the medical doctors are. There to be helpful but will not come up with the solutions and in which the enormous already in place pharmaceutical industry is not competing with you which is an important area you're not in biomaterials having to deal with an billion dollars a year of investment that's already in place you can go and sort of invented on your own. So it's an extremely attractive area and one that's very important and will seem I should say even more important to you is you get older and things begin to fail. Thank you very much. Thank you.