Wisconsin Public Television University Place  Wednesday Nite at the Lab  From Diatoms To Electric Eels Michael Sussman  Sept.26,2012 UP773 CC >> Welcome, everyone, to Wednesday Nite at the Lab. I'm Tom Zinnen. I work here at the UW Madison Biotechnology Center. I also work for UW Extension Cooperative Extension, and on behalf of those institutions and our other partners, Wisconsin Public Television, the Wisconsin Alumni Association, and the Science Alliance here at UW Madison, thanks for coming to Wednesday Nite at the Lab. We do this every Wednesday night, 50 times a year. Tonight, it's my special pleasure to be able to introduce to you my boss, Mike Sussman. He's a professor of biochemistry and also director of the Biotech Center here at UW Madison. After completing his undergraduate degree at Bucknell University, he earned his PhD at Michigan State. Here at Wisconsin, his research has encompassed exploring protein kinases and signal transduction of the model plant Arabidopsis thaliana. He is also co-inventor with Franco Cerrina of the maskless array synthesizer for making DNA microarray chips and for developing new technologies of mass spectroscopy for analyzing proteins of plants. 

Tonight's a special Wednesday Nite at the Lab because it's a sneak preview for the second annual Wisconsin Science Festival. Many of you know that the Science Festival is kicking off the year of innovation here at UW Madison, and I think it's particularly great to have Mike be the speaker here because he's been such a pioneer in innovation. One of the great things about getting to work at any university, but I think especially this one, is the audacity of a university and the ingenuity that we have in innovation and invention. And if there's a better example than Mike, let me know. There might be two or three, but there's not very many. So, when you think about maskless arrays and tonight's topics of diatoms and electric eels and what that might mean for how we do things in 5, 10, or 15 years, it's a pretty great story and especially appropriate for helping to launch the year of innovation here at UW Madison. Please join me in welcoming one of the splendid innovators here at UW Madison, Mike Sussman. [APPLAUSE]  >> Thank you, Tom. As you can tell, I'm hoarse. I had some laryngitis. 

I gave a talk this morning. I just held the microphone very close, and they were able to hear. But I'm really pleased and honored to be here, and I want to thank Tom for the excellent introduction, but more important, I want to thank Tom for his many years of dedication in helping to communicate the science that goes on on this campus to the world. This is something we don't always do as well as we should, and Tom's been one of the great leaders on campus and continues. And this forum right here is a wonderful example of the many things that Tom has done that he doesn't often get recognition for. So I do want to thank Tom for that as well. [APPLAUSE]  Okay, so I gave a talk this morning. It was a bunch of graduate students and postdocs and very early, and now at the end of the day it's kind of interesting. I really love these kind of forums because I like to chat and I like to talk and I like to communicate, and I feel sometimes very isolated in the lab because a lot of the work we do is fairly isolated. You kind of live in your brain trying to think up these things and working with people. 

One of the wonderful things is working with graduate students and postdocs because the innovation really comes from them. More or less at this point, a professor like me, I'm mostly a banker. I'm writing the grants. I'm trying to get the money, and they get to have all the fun. But that's fine. That's fine. I'm going to talk about some really cool stuff tonight. I haven't talked about it in a while. And I hope you'll enjoy it. I hope it'll be informative. 

And don't hesitate to stop me at any point. I do believe it's being filmed, and tomorrow morning you will be on the internet all over the world and there will probably be riots, probably at my house, but other than that, I hope it's not too bad. But seriously, stop me at any point to make sure I'm communicating, you're understanding it. Okay, so here's the first slide. I'm going to let you read this while I catch my breath.  [LAUGHTER]  I love Pearls Before Swine. Now, obviously, I can't really do physical damage and get away with it, but this is the point. Once you have tenure, it's incredible. I have responsibility to pursue the truth no matter where it takes me, and I take that very seriously. And I try to instill that in my students to not be afraid to do the unthinkable because that's what we can do. 

I don't need to make a profit. I'm not at a company that has to have a profit. I just have to figure out what the truth is. It's not always easy, but that's what we do. Okay, that's the first slide. Here's another slide. I'm going to show you three slides. This one is a algae, a single-celled algae. It's one of the most common organisms on Earth. Thalassiosira pseudonana is the genus and species. 

It makes little glass houses. Some of you have probably seen these. This is the cell wall, and it's made of silica. And these things are, they make silica in ways that the engineers wish they could do. These are nanofabricators at one micron scale. And it's genetically controlled, and they're amazing. And then the third slide is another thing that's another subject of research in my lab is the strong voltage electric eel. I'm head of the world's electric fish genome project. I've been to the Amazon, and we are in the midst of sequencing the genome for the electric fish. We're trying to, basically, learn the secrets of how these eels generate so much voltage. 

I'm going to show a video, it's a little startling, but, basically, these eels can make 400 volts when they're big. And they can kill anything they want in the Amazon. They're the top predator simply because of their ability to generate this voltage. And they don't eat any more than you and me. So, in theory, I'm showing you an organism that can convert food directly into electrical energy at a very high rate. And that secret, I think, is important to learn.  So, here's the question: what do university professors, diatoms, and electric eels have in common? It's rhetorical. You don't have to answer. I'll give you the answer. They are all wonderful examples of nature's oddities. 

And I do believe that, and again, the universe is about 14 billion years old, the physicists tell me, the Earth is about 4 or 5 billion years of which about 3.5 billion years of life. So, from the very first cell 3.5 billion years ago to now, we've got millions of species of incredible organisms that can live in very weird places and solve some major problems. We can now sequence DNA, so we can actually look at the secrets that nature has evolved and secrets in terms of ways of doing things that the engineers would like to be able to do. And I've given you two examples. See, as a biologist, I collaborate a lot with engineers and physicists, and they always think they're god's gift to Earth. Oh, are there any here? [LAUGHTER] Oh, okay. Well, I think you know what I'm talking about. So, whenever you work with these people they say don't worry, we'll teach you what to do. You don't know how to do science. I'm trying to show engineers that there are a couple of species out there that actually can do things that even engineers can't do yet. 

But engineers are becoming biologists. They see the opportunity because biology is becoming a much different science. Being able to sequence the entire genome, predicting the structure of the 30,000 proteins that make us up, the 100,000 small molecules that make us up, these are completely getting defined at a molecular level, and it becomes an engineering problem now of how do you take 30,000 tools and change them into a way that you want them to be or at least analyzed in a way that's much better than we currently have. I'm going to start off by showing some slides today I actually haven't used in a little while. A lot of what I'm going to be talking is at a molecular level about proteins, and I want you to get the understanding that proteins are actually quite alive. They're not just egg white that just sits there immobile. If you had a microscope that could look at molecular dimensions, here's what you'd see. Before I do that... [LAUGHTER] We make elephants fly. Okay. 

Yeah, this was the Nobel Prize in 2002 where these folks discovered ways of analyzing proteins that I think have really changed everything that we do. This is a giant, I don't know if any of you have been there, it's right when you go down 90 toward Chicago and you see the big Ikea. How many people have been to Ikea? Yeah, everyone. How many people have been to Synchrotron? Oh, good, good. Recommend it. It's huge. And a lot of that is now being used to study protein structure. >> [INAUDIBLE] >> I'm sorry? >> [INAUDIBLE] >> I believe so, yes. Yes. Okay, so, here is a simulation of what we think a protein that's in your brain is doing. 

This protein is called calmodulin. And every time you have a thought, you generate an action potential, and many of your nerves generate action potentials. And they generate a calcium spike in the cytoplasm. That calcium binds to that calmodulin. The calmodulin undergoes that conformational change, this bending and unbending, and that eventually leads to memory. So we believe memory is caused by those calcium spikes being translated, by a process known as protein phosphorylation, into long-term changes in your nerves. Ultimately, it relies on that protein, starts with that protein performing that conformational change. This is myoglobin which undergoes a conformational change in your blood on your muscles when it binds O2. It can also bind CO. Just to show you the kind of wiggling around that these proteins are doing. 

This is one of my favorites. These are two different proteins. One is from a virus. One is from hepatitis A and the other one's from rhinovirus. Their amino acid sequence, or their DNA sequence, looks very dissimilar. But when you determine the structure of the protein, the three-dimensional structure of the protein, they're dead on with each other. And this is actually very interesting. What we have a situation where proteins can have completely different amino acid sequence, completely different DNA sequence, but they do the same thing. It's very hard to figure that out, but this is a good example. And there's a cysteine that they both have that binds things. 

So when you take cough lozenges, like what I'm doing, where are they? In my pocket. And they have zinc, the reason is that there's a cysteine there that thing binds to, and it affects the ability of the virus to replicate. I think this is the last one. The last one involves prions. These are fascinating proteins because it turns out that this is an infectious agent that has no DNA, has no RNA. It's completely a protein. And I and many others didn't believe this. The person who hypothesized this won the Nobel Prize for it because it was so heretical. It was like crazy. But it's true. 

And it's a protein that we all have which, when it goes bad, it calls deer, chronic wasting disease or -- and Alzheimer's may be related to this in that proteins when they go bad they obtain conformations that are not good, and they can propagate too. That's what is really scary about this is that when a good protein hits a bad protein, it converts the good protein into a bad protein, and that's how it's infectious. Here's an example. When the two proteins, then they kind of lock into this gnarl. And then you get this clumping, and that's what happens. So, we're right in the middle of a lot of studies trying to figure out this, and it's a very complicated new area that's very difficult to work with because protein conformation is technically kind of hard. I'm going to talk to you know about DNA sequencing which is a lot easier right now and also can be done very readily. And I think within 10 years, each of us in this room will have the opportunity to get our genome sequenced for probably a couple hundred dollars. Whether or not you'll want that to happen is another story, and there's a huge number of ethical issues surrounding this, including everything from not wanting an insurance company getting all that to, the question is, most of the time the sequence doesn't tell you you're going to get that disease for sure. It just says you have a 60% chance of getting the disease. 

Now, I'm one of those people who doesn't want to know that because I'm kind of neurotic and I'm a hypochondriac, and I'll get disease no matter what. I'll think I have the disease. So whether or not you want to know that information will depend on each of us making her own decisions. And there's some huge issues on this that we need to resolve, and part of the reason I really enjoy coming here and talking with you all is that these decisions need to be made collectively. You just don't want a few scientists sitting in a room making these decisions. We want to make these decisions collectively. This can help us, can guide us in the process, but you don't want them making the decisions either. This is collective. I'm a huge fan. One of the few socialists left around here, I think. 

[LAUGHTER] Although, most are capitalist. I'll show you why. Okay, so, diatoms. Remember, I was working with this engineer, and I was showing him all that can nanofabricate at a micrometer level that he can't. So, I wanted to discover how do diatoms do that, and can we change the one gene and make a different pattern, which would be very exciting because that would be kind of like modifying silica genetically instead of in a physics lab which is what it comes down to. So, I teamed up with this engineer, and we invented a new way to make DNA chips. So I want to talk about DNA chips a little bit, and I want to give it a personal flavor, though. I came here as a professor in 1982. I didn't have much money. The only reason I could buy a house was my wife's parents loaned us enough money for a down payment. 

And I was raised in a little apartment in Queens. We never had any money, and then, together with this engineering professor and my grad student, of course, we invented an instrument and formed a company. And WARF, which is one of the most incredible institutions. Does everybody here know what WARF stands for? Wisconsin Alumni Research. Okay, good. So they handled all the patenting and everything, and then when the company got sold for a lot of money, we made a lot of money. So now I have a tractor, a Porsche. My wife's got a farm, raising sheep. It's really quite amazing. Wisconsin's an incredible place, and don't let anybody tell you otherwise. 

There's huge talents in all sorts of ways. Everything from law, economics, science, many ways. The state's gone a little crazy the last couple years, but you know. [LAUGHTER] Everybody does that. So, the company that we founded commercialized the invention that was made in my lab. It was called NimbleGen. I do want to dedicate this to Franco. Unfortunately, he tragically passed away two years ago and is not here to share in the joys of this. But let me tell you what the company and what the invention was. So, why are DNA chips important? Well, okay, let's see. 

So, we have 30,000 genes in us, and how many organs do we have? About a hundred, right? Liver, intestine, pancreas, brain, all those things, right? Now, each of those organs probably uses 10% of those genes. So there's 30,000 genes, each one of them is probably using 3,000 and they share genes, they overlap. So each organ is probably using about 5,000 genes. Now, let's take a liver. A liver is normally expresses about 5,000 genes. When the liver becomes cancerous, we think only about 400-500 of those genes have changed. And it's really important to figure out which ones have changed. So one of the first things that we did with our DNA chips were to figure that out. So, DNA chips are a way to quickly and cheaply analyze what's going on with the DNA and the RNA in your body. Another big use of chips is it turns out we're not pure Homo sapiens. 

We're actually the ecosystem. And we have within us thousands of species of microbes. It's called the microbe biome. Some people are thinking that the microbe biome is actually a new organ. And it's not just if you ate dirt when you were a kid. There's something very specific about the organisms that each of us has with us. We don't share them, and nobody really understands it. A lot of that might come from the mom. But this is a very exciting area, and the DNA chips are helping us to figure that out. This was one of the first experiments that was done with DNA chips that was really cool. 

You can't read this and I'm supposed to stand here so that people can see me and point there. Is this good, Bruce? Bruce is gone. Good, so I can stand anywhere I want. [LAUGHTER] Just kidding. Okay, so, these are different types of breast cancers. These are tumors removed from 50 different patients, and they look identical. The tumors look similar under a microscope and everything, but we knew that the patients weren't responding to the drugs similarly. So we knew there were some difference. So, folks took these 50 tumors, isolated the RNA, ran them on DNA chips, and determined which of the 30,000 genes have been altered. And they found patterns that this group of people, you can see the pattern. 

These are the different genes that are being turned on or off. Red is a gene that goes up. Green is a gene that goes down. And you can see that there are patterns. This group of people seem to be behaving much differently than this group of people and this group of people here. So it looks like there's probably a half a dozen different types of tumor cells in those tumors, and you can predict which drugs these people will react to. And so did you see the news last night? Some more work in this area was done where, basically, what people are doing now is they're sequencing all of the DNA in all those tumors, which is another way of getting at the same issue. You can use the DNA chip or you can sequence. You can do both. But, basically, what's becoming obvious is that a tumor is genetically very complicated. 

Many mutations are occurring, and it's kind of like we have a new microscope that can see 30,000 things at once. That's basically what it is. A brand new way of looking at a tumor at a molecular level, and it's a very powerful approach because, again, we can predict which drugs will work. And, once we know what proteins have changed, we can start looking for drugs specifically to those proteins. Now, the instrument that we invented was a new way to make a DNA chip, and it was actually based on the same thing that's in the PowerPoint projector, or if you have one of these digital light processing TVs at home, HDTVs that's based on digital light processors, you're using the same thing we used. Basically, these are 15-micron mirrors, and if you were to come up here, don't do it now, but later on you can come up here, you'll find that there's little squares there, and this image is actually made up of about a million little squares. Each square represents a little mirror in the circuit board in that projector. And when you see a black spot, that's because that mirror is turned off. It's not letting the light here. A white spot is letting the light here. 

So we use that same, it's called a digital micromirror device, took Texas Instruments about 18 years to invent them, and we're using that same device to control the chemistry that allows us to make a piece of  glass with a million different pieces of DNA on it. And it's those million pieces of DNA that are what constitutes a DNA chip. This is an actual electron micrograph of that actual device in that PowerPoint projector. There's little mirrors. This is a schematic of what they look like, and they're doing this all the time. Flickering all the time. And, in order to make this into a DNA chip machine, we used a lot of optics that my engineering buddy was really talented at. He didn't know anything about DNA sequencing or DNA synthesis. Together we did something that neither one of us could ever do, and it's just a wonderful example. It took a couple years for us to talk the same language, but we became good friends. 

We drank a lot over beer, and then once we figured our each other's field, it became obvious what we could do, and it was really cool. So, basically, bottom line, we use this instrument to make a piece of glass containing a million different pieces of DNA, each of which represents a different gene, and that piece of DNA allows us to determine what the expression of its complement is. DNA is really cool in that it's like your zipper in that once you have one strand, there's only an exact copy that will bind to it. And if you have an inexact copy, they won't bind. So you can measure, if this thing is fluorescent and this one isn't, bind them together and if you see fluorescence together, you know they're identical. And that's basically how we did that breast cancer experiment where we have all these pieces of DNA on a glass slide, we make the breast cancer RNA fluorescent labeled, and then we throw it on the slide. Then we measure the fluorescence at each spot, and that tells us how much of each gene is being active or not. I'm not going to go into this. Basically, the original technology used contact printing. A company that had about a billion dollars basically had been using contact printing, not these little mirrors, and the mirrors are so much better for many reasons. 

Cheaper. Easier. And, basically, we made a better light bulb. And, eventually, we formed our own company. General Electric could squish it, and WARF protected that from happening, helped protect that from happening, and then our little company grew and grew and grew, and everybody wants to use our stuff so it's kind of cool. This is a joke. [LAUGHTER] I'll try it out. So, we took Van Gogh and, remember I told you about fluorescence intensity? So we took the picture and we made a DNA chip where each of six colors had a different sequence. And then we added fluorescent pieces of DNA, six-colored fluorescence, and we reconstructed this picture under a microscope using DNA. And, instead of compressions we call them expressions, gene expression. 

It's a bad joke. I gave a talk in Sweden once, and I gave a bunch of good jokes. This was not the best one, but there were some really good ones. And nobody was laughing, and I got really worried. And I asked my host, and afterward all I heard was this beep, and I asked my host afterward, and he said oh, no, you were killing them, this is northern Europe, nobody ever laughs. [LAUGHTER] You were killing them. All right, let me get back to the oddities. Diatoms. I really want to show you, so back before there was TV but there were microscopes, thousand of different diatom structures, and these were all different ways to perform silica nanofabrication genetically. You get one from Russia, one from Lake Mendota, one from Mississippi River. 

These are all over the place, and they all have different beautiful little pictures. And before TV, people used to sit around the dining room table and look at these things and go wow. I don't know if we've improved with TV, but in some ways we have. >> What's the magnification on that? >> I'd say about a thousand. >> A thousand? >> Yeah. I suspect about a thousand. They're not like bacteria. They're more like big cells. They're about 50-micron diameter cells. Okay, stop this. 

Good. Okay, I'm going to show you real data. This is not made up. This is a satellite that is imaging photosynthesis on Earth. And what it's doing is looking for chlorophyll fluorescence. It has a laser. I don't know how it does it, but it's measuring chlorophyll fluorescence on a global scale. A complete turn of the globe is a year. So every five seconds is about a month. Okay? Now, we're going to go around the globe. 

Now, when you see blue or white, very little photosynthesis. When you see red, yellow, and green, light green like that, that's photosynthesis. Red's the highest. Yellow's next. Green's next. Blue and white is nothing. Let's just go around the world. Okay, this is South America. This is an El Nino event. Do you see that? That bloom took about a month. 

Well, we're going to see it again. Australia. Asia. Watch the Sahara Desert is fertilizing the ocean here with iron, FE, from the sand. And here's the Amazon. A lot of photosynthesis there. Now watch this bloom again. There it is. So that is, about 10% of the ocean is covered with this algae. That algae is Thalassiosira pseudonana, that diatom. 

It's amazing. This diatom, by itself, fixes about 25% of the carbon dioxide on Earth each year. And there's only 12 people working on this organism. Oceanographers like to do global work. They don't do a lot of molecular work. It's changing. If any of you want to make a killing, go into molecular oceanography. It's a badly needed field. There's more and more people doing that, but it's still slow. So, when we invented this DNA chip machine, I looked around for a project and decided, hey, the diatom, and it had just been sequenced. 

So, we asked ourselves, can we device an experiment to figure out which genes in this organism is involved in silicon nanofabrication. The other nice thing about it is we'd like to learn about this organism fixing 25% of the world's CO2. So I think we should know a little more about it than we do now. The Navy has been doing these experiments, and these are published, where, let me back up. Almost all organisms on Earth are limited by FE, iron, I-R-O-N. And no organism gets enough iron, apparently, on Earth, especially in the ocean. So the Navy said let's fertilize a piece of ocean with iron to see how much increased algal growth can we do. And so they blasted a few battleships and then they imaged from space, and they actually calculated how many battleships they'd have to melt in order to reverse global warming. And it's a finite number. It's not an experiment you really want them to do because if they calculate wrong, if they use metric instead of non-metric. 

[LAUGHTER] You only have one shot at this, so hopefully they'll never do it. We'll never let them. But it's good to know that it's been studied, it's been calculated. It's an interesting thing. Okay. >> I have a question on the globe. >> Yes. >> What accounts for the red spots? I noticed one where Lake Victoria is in Africa and the other off of French Guiana. Why those two spots in particular? >> The Amazon was a very dark red one. The other really dark ones were actually right off the Sahara. 

It turns out that the main source of FE in the ocean is from the deserts blowing sand into the ocean. Or, in general, the ocean is fertilized by the land masses. And over a hundred million years, there's some very interesting things that have been going on. For example, two billion years ago there was very little silica in the ocean. There was a lot on land. And then when the land plants evolved, the grains in particular, they actually started mining silica and dumping that in a soluble form into the water. And now we have quite a lot of silica, actually, in the ocean that we didn't have a billion years ago. So there's a big interplay between the water, and anyone that tries to grow things in your garden understands. I'm quickly going to just explain this experiment. What we did was we starved these diatoms for carbon, for nitrogen, for silica, for other things, and we asked, what genes are specifically altered by silica starvation? And we hypothesized that they would be the ones that are involved in silica fabrication and silica usage. 

And that's these genes right here. So there's about 12,000 genes, 6 experiments, and these are ones we've zeroed in on. Let me just quickly show you those results. First, these are the genes that are turned with nitrogen starvation. And all you have to see is that there's only a few unknowns. Most these proteins we know what they do, and they're involved in nitrogen metabolism to varying degrees. That's because our fertile government spent $10 billion on nitrogen because it's really important for agriculture and stuff. Look at all the unknowns here, and that's because these sequences don't tell us anything. We've never studied these proteins before. Never. 

These are a whole new class of proteins that have never been studied before. I tried to get this into Science magazine. We submitted it and I figured it would be accepted within hours and a letter saying this is incredible stuff, god bless you. Instead, we got a rejection letter. I said, why? And they go, well, you don't know what they're doing. I said of course I don't know what I'm doing, but at least we know they're sequenced. It will take 10 years or more to figure that out. We got it into another journal that's pretty good too, so don't worry about it. [LAUGHTER] The postdoc that did this work is now a faculty member on his own, and he's taken these unknown proteins and he's modified them, and he's actually changed the structure of the diatom under a microscope. So he's actually got the first thing that the engineers have been trying to do which is alter nanofabrication of silica as we had predicted. 

These are - proteins so that's kind of gratifying. It takes a long time, but it's nice to know it happened. Okay, now I'm going to talk about electric fish, and this is a very exciting project. I teamed up with a bunch of ichthyologists. We went to the Amazon. South America gets flooded every year. For half a billion years, the Andes melts in the South American flood basin. And the water goes above the treeline. The water is very dark because the leaves, the tannins make very dark water. So, these fish are living in the forest like our birds do here. 

They're eating berries and things, and they can't see so they converted a muscle into an electric organ that allows them to navigate like bats using radar. So they shoot voltages that hit the surface of the river or the branches, and that's how they can see because their eyes are very poor and the water's very dark. And each of these fish also has a birdsong of different frequencies. So they spike and they, like, little songs that are very species specific. And that's their birdsong. So they're using it to find their mates. Basically, food and sex are the two most important things out there in all organisms, except for humans of course. We have TV, politics, chocolate. [LAUGHTER] We can talk about that later. Okay, the electric organ is made of a special cell known as the electrocyte. 

And it's probably got the highest concentration of the sodium channel and the sodium pump of any other cell in nature. And it generates, each cell can only generate about 300 millivolts. But it's got a positive side of the cell and a negative side of the cell. And so, you can stack them up like batteries in a flashlight, and you can generate 400 volts. I have a somewhat disturbing video of an electric eel being attacked by an alligator. Can you all see this? Do I need to make it big? No? I could though. Watch. So the alligator has, it's a caiman actually, has grabbed the electric eel. That's a big eel, by the way. That's not an eel you ever want to meet yourself. 

And it's starting to discharge. Notice the alligator isn't moving like it used to. In fact, it's thrashing around. It's getting electrocuted. And in about 10 seconds it will be dead. Unfortunately, the eel is dead too. But it's just an incredible demonstration. So even when we bring these eels into the lab, I hope that isn't too disturbing. You can go to YouTube and see that yourself just by searching for alligator and electric eel. I don't have any eels right now, but when we dissect them to isolate RNA and DNA, they'll still discharge, actually. 

You don't want to touch the organ itself. It will still be able to give you quite a shock. So it's absolutely an amazing organ. And it's evolved six times over 300 million years. It's as if there's only a few genes involved. So we're trying to figure out what these master regulatory genes are that convert a muscle cell into an electric cell. That's the goal of this research. Now let me tell you why. This is an important slide. Each cell here is about this big. 

So these are thousands of cells. Now, this is a microscopic view of a petri plate that started with human embryonic stem cells which, spontaneously over a period of months, start forming red dots. And when you zero in on those red dots, this is what you see. So these undifferentiated human  pluripotent stem cells have formed heart myocytes. These cells are connected and integrated and are actually beating. So, we can grow heart tissue. It's not easy to control it. This happens spontaneously. But we're learning how to control it, and that's part of the beauty of Jamie Thomson's work. Jamie is the world leader in this. 

He was the first one to do this work. He's right across the street. Fourth floor. Cover of Time magazine and he continues to do incredible work in this area. How do we control differentiation because the future is growing organs, growing our own organs in a lab. There will be many ways of doing it, but if you want to live older, replacement organs is one way. And people have diseases young where they need new heart cells, and this is one way to do it. Another example of differentiation and some of the research, here's an egg cell that just got fertilized, and it's going to be about five minutes sped up, two-cell stage, now it's in the four-cell stage, and it's going to get up to 6,000 cells. Now, this can be any embryo. It turns out to be a worm. 

And the reason it's a worm is that this is one of the most elegant model systems to study how a single cell becomes an organism because we can count 6,000 cells and we know each one and we know how each one is derived from another one. And so even though it's a little worm, it's got 12 nerve cells very similar to our nerve cells, doesn't have much of a brain, but it's got nerve cells just like ours. It's got the 30,000 genes much like ours. And so we can study these things very quickly and very easy, and it's real important because we can do experiments with this worm that take days here, in a human would take 20 years. Now it's a worm. So it went from one cell to 6,000 cells. It went from one egg cell and one sperm cell that didn't look like much into a beautiful worm with 6,000 gorgeous cells, heart cells and nerve cells and whatever else worms do. I'm not a worm biologist. So, basically, as we learn more and more about which genes control differentiation, can we make electric cells in organisms that don't have them? Pacemakers have batteries that are made of really nasty chemicals. And they have to be replaced, I think, after four years. 

So, wouldn't it be nice to have an electrocyte, your own electrocyte, powering your own pacemaker so it never has to be replaced? That's one immediate impact, but we're getting more and more bionic. Engineers are figuring out devices that we can use to help our muscles move, but they all require power. But wouldn't it be nice if we can generate our own power? And I believe the electrocytes are one way that we may be able to do it. And I you need more power, just eat at McDonald's, and instead of getting fat, damn thing runs your heart. [LAUGHTER] It's an ideal situation if we can figure out how electrocytes work from the electric fish because the electric fish are the only organisms on Earth that know how to do this. Whenever I tell my technician about this, she gets really upset because actually has cows, and she hates them because they're really hard to move around, and she doesn't want a cow that can also electrocute here. That would not be a happy thing. But hopefully we'll do it in a controlled, I don't really know if they'll have cows with them, but a hundred years down the road, who knows what's going to happen? But let's ask that question, down the road. So, we are entering a time in which the genetic manipulation of life will and is commonplace, but we don't know how fast. There are many ethical issues, many, many issues that need to be collectively decided. 

This is what you don't want, where we engineer a cow with a stool, but it doesn't fit our ass. [LAUGHTER] So you need to have a team. I give talks sometimes to state legislators and leaders in the state, and I try to suggest that in the past we've used our paper and our trees. We've harvested. We have crops and cows, but now is a time when we can harvest the discoveries that are being made on this campus all the time and turn them into real commercial entities. A drug company, this state does not have a drug company. No matter what you think of big companies, they have an enormous number of jobs. And we have some great scientists that can discover new drugs left and right, but what we don't have is a big company to help support that research. So we rely on the federal government, rely on the state, and we rely on WARF. And we've done damn good so far. 

But, it wouldn't be such a bad idea to have a big company too. Maybe. We'll see. So, I want to end by emphasizing that we do have a big challenge in front of us because we need to protect and preserve the natural world. There's not bigger fan of that than I. I like to go out in the woods and see chaos, nature. I don't like to see everything controlled. I hate concrete. I've always hated New York, actually. I don't go back there. 

I don't like concrete. I like the chaos of the natural world as long as it's not eating me. [LAUGHTER] But it's nice to know, I have coyotes that are near my house and my wife's freaking out because we have these rare sheep, and that's a whole other story. [LAUGHTER] Anyway, I'm hoping that we can do both. That we can preserve the natural world, we can preserve our genetic resources that have taken three billion years to evolve. We don't want them to go extinct because the secrets are there, and once they go extinct, we don't have that opportunity to work with them. At the same time, 70% of the crops we grow are genetically modified. Some people don't like it; some people love it. These decisions we need to make collectively. We need to look at it very -- and make these decisions together. 

But I do want you to know that although there are many ethical, legal, and social issues that we need to grapple with in this age of genetic engineering, overall, I'm an optimist. I believe that the future is so bright. [LAUGHTER] And I do want to emphasize this is the end. [APPLAUSE]