170731 Translating Fundamental Science into Products - Robert H. Grubbs

So basically, my first startup was in 1995, and so it was associated with an electronic node. A company which I'll talk more about, which is a neurological lens, which is something that goes, when you get old and have cataracts, a company called Acura, which is a spell, which would be an eye there. And it's really the thing that really started a lot of the startup. And this is truly, you know, starting out doing fundamental chemistry, trying to understand chemistry, and then getting to something where suddenly people were interested, and so then what do you do? And so that company was started in 1990. A battery company, we just started a reaction. So that would turn out to be VC-funded. It lasted five years before it got sold. Pelham Vision actually is, at least three trials, and doing really, really well. Materia is doing okay. Contemporary Energy Systems is a battery company. It was started in 2011. Closed in 2014. And then we started another company recently, which I'll talk about at the end, which is, I think, and it's angel financing. So there's one thing, one message that you should get from this. Which companies have survived? Angel funding. Which ones have not survived? Venture capital funding. And one of the problems is, venture capitalists just don't have the patience to deal with the developments. And so you see, you know, these were started a long time ago. And so it takes 15, 20 years for a technology to get developed that's really different than you. And so they're accustomed to doing, you know, Facebook, all kinds of things, where you just do computers, you've got to write a program, you know, sell it. This stuff, you've got to do real, real science, and it's really hard. So finding people who have patience is really one of the lessons. And the other thing is, which is my lesson, is do it for fun. Don't do it for money, because you're going to be disappointed almost all the time, because most companies fail. And even if they do succeed, by the time they succeed, you've raised so much money that you've lost all your ownership in the company, so you don't own anything. So do it for fun, okay? I still haven't made a cent out of any companies. I do it for fun, okay? And hopefully someday I will, at least my grandkids will be. So the first thing I'm going to talk about is this one, which is Materia, as it's spelled. And it's based on chemistry that we've done our whole career. So this is a reaction which I learned about when I was a postdoctoral fellow in 1968, which is before most of you were born. And it was an amazing reaction. I was just moving into the field, and it was a reaction where you took propylene, so three carbons, you passed it over a catalyst. And the catalyst was a mixture of a lot of stuff that nobody quite knew what it was. And what you got out of the other end very rapidly and very cleanly was ethylene and butane. So what you've done is you've shelved the carbons, and pretty early on it was demonstrated that it was a carbon-carbon double bond. So that's the metathesis reaction. Actually, when it was originally started, it was sometimes called olefin disproportionation and sometimes olefin metathesis. So I started my career at Michigan State University, and the chairman was named Mike Karabatsos. Guess where, Mike? So Mike came by one day and he said, you know, disproportionation is Latin. And the other thing is the early catalysts were, they didn't tolerate anything. They basically just did hydrocarbons. Because they were very lewis-acidic systems, and you put in any functional group, it killed the catalyst. So this didn't seem like it was very promising for doing organic, but it was an interesting mechanistic question. So we spent a lot of time worrying about mechanisms. Spent ten years working on mechanisms. And that's probably what got me from Michigan State to Caltech, and getting it all sorted out. And then we spent a long time and a long history. And then in 92, we developed our catalyst-based homework team. And this catalyst, instead of being one that was killed by functional groups, actually liked functional groups. Sort of like water, which nothing had done before. So this started opening up metathesis for lots and lots of applications. So it was a very simple complex. The key is it's non-carbonable bond, which is the key for the overall mechanism. And so with the catalyst in hand, we started publishing papers. You know, that's what it was all about. And in fact, I started doing metathesis, because I was an assistant professor, and I just wanted to get things done. It was a reaction by us at work. I didn't even think about leaving here. So, you know, I was really surprised when we finally got it to work. We published it. People started getting interested. People would call me up and say, can I get some catalysts? And I'd go down and bag my graduate student. Some of them went. He was an amazing graduate student who made our first catalyst. You know, can you give me 10 milligrams? And this was really a bad thing to do, because not only did you have to work really hard to make it, you were also going to give it to somebody who was going to compete with you. Anyway, so we installed a lot of sort of companies. Some small companies started making catalysts. And people would call me up and say, your catalyst doesn't work. And I'd say, send me some. And then the other thing is, which is really important, which really made doing academic industrial stuff really easier. And one was this act, the Pipe Goal Act, which hopefully will stay and it'll survive the present climate. And basically it gave the university rights to stuff that was discovered. So if you did things with NSF, NIH, any sort of federal funding, is that the university got the rights to it. So that really sort of changed things in the late 80s, early 90s for lots of stuff starting to happen. Then the other thing was official patents. And they came in again at about the same time. And before this, you had to write a patent, submit it, and get it covered and all kinds of stuff before you could really publish. And that makes it really hard for academics. So there is a thing called provisional patents. So you basically write things up and half the time, I'll send in a group of slides, getting ready to give a talk, or a paper, a pre-drafted paper. You send it in and it gets filed as a provisional patent. And you've got one year to collect all the data and make stuff happen. So it means you can now start to publish really fast. So that made life really easy for both. I'm not sure about this in Australia. And so then big companies started coming along. They started coming along and wanting to interact. Interact. So there was a bunch of companies. I didn't put any names here to protect the guilty. So the first one came along and we just filed a bunch of patents. You've got to work with us. We're going to bury you. That's the way to start a collaboration. Yeah, company A we started collaborating with and then we did a year promo and they said, might as well put work in this area because we're going to kill you. Company B turned out to be really good collaborators but then the champion got promoted because he was really good and so technology died for a while. Company B started manufacturing and selling catalysts, really sort of with some rights. Company C, after they were buried, left the field. They actually donated the patents to Caltech. And company B turned out to really be a good collaborator and so we've got a lot of stuff going for them. Company B sued us and sued them. And it finally got settled. And then the last one is company E and they're the evil ones. They're really patent trolls. They got control of a patent that was related to our stuff. They spent an amazing amount of money on lawyers and if you spend enough money on lawyers they get a lot of stuff done. We just finished a trial and it's still going on. Horrible thing is that the judge was an English major and the jury were people off the street and they're expected to make decisions about your life's work. It's a really brutal thing. We'll get there and soon that will be over with. So then we said okay. Working with big companies is really, really tough. The other problem is, again, what's happening in the U.S. is when I was a student and was getting out, you had a choice of going to DuPont Central Research, Dow Central Research, Union Carbide, and on and on. And there were people in those places with raper papers and jacks. They then did the translational work to get it ready to go to commercial product. So things happen. They're all gone. So there's no one there to do it. So now you almost have to do everything through small companies and through startups so you can transition the work in and then you can start interacting with big companies. So Caltech had a fund called GrubState. I don't know whether you're familiar with that term or not because it's a term that whenever a miner went in to go out and look for gold, they would get what was called the Grub, which is food, so it was there as well. So it's a fund sent to Caltech to help do translational stuff. And a postdoc really did it and he was the founding leader of the company. So then we started a company called Materia. Caltech licensed everything to them so I don't have to worry about it especially past and future, which is pretty unusual. And then the other thing is Stu, which is a thing for thinking about institutions doing this, is that Caltech has a really good policy and essentially Caltech's thing is that they want a company to succeed and if you take large upfront fees the company's not going to succeed. And if you have large licensing fees it's not going to succeed. So basically if I have a discovery I can go to our tech transfer office and say I want to start a company, I want exclusive rights, they'll give me exclusive rights to put it together and then they can negotiate a license fee and stuff. Everybody I work with wants to work. So anyway. And then the other thing is they say look, we'll make money two ways. We'll take equity in the company, not a lot but some. But if we make professors happy and we make them successful and they make money they'll give us money. So they think that's the way that they can actually do it. So there's another sort of thing that you've got to think about if you're going to develop technology. There's a kind of technology called platform technology. And this is something that goes on a lot in academics because you want things to be platform. You want it to have applications and indications. So here's the basic reaction again. Here's one of the catalysts. And it's now being used to make pharmaceuticals. So the bond right here is made by his chemistry. That turned out to be one half of the first drug that was used to cure Hepatitis C. We'll talk more about that in a minute. There's a company called Aleron which is making peptides for treating non-verbal diseases. And so this is sort of the drug business. You can make really big polymer parts. John Deere. Combines and windblades. I'll talk about some of these. Using the same catalyst. It's being used in a company in Indonesia for making products out of sea oils. It's being used to make small molecules for controlling insects. Being used in oil and gas. I'll talk about that. And it's being used in especially polymers. So it's got a lot of applications. And that seems good. But it also is one of the hardest things to do. Because when you're starting a company, the worst thing you can do is not focus. The second worst thing you can do is focus on the wrong thing. So you've got, you know, so there should be a whole business school around these courses in doing platform technology. It's really, really hard to manage. And so for example, everything is different. So pharmaceuticals, they take a long time. So here's chemistry that was done by Helen Blackwell and Scott Muller. They're both professors in 1996. 20 years ago. And you know, they did this thing where they make peptides and they start out with two double bonds and you put in a catalyst and you put those together and you lose ethylene and you make a bond. So that's how it stabilizes these structures. And here's the drug that's in the J&J thing. You see it's a peptide. That bond is put together in the same sort of fashion. So that is put together with a catalyst called Lysio. It took almost 20 years from the time we started this. And I've talked to people who did the earlier versions of this and said, yes, we've read your papers and started working on this. So it's taken a long time. And the deal is, you know, again, in developing things, this was a huge success for about two years. And then it got taken over by something else. So here it is. You can get the stuff. There was an earlier version, which was a bromide enzyme, where they made it here. This is now. If you look at this, unless you're an organic chemist, they look really close. And they are. But there's separate patents and separate everything until this one went. This one didn't. This one had some toxicity problems. It was a phenomenal drug for toxicity problems. This one, apparently, is a phenomenal drug. So that's going strong. And now there's another one. And this came out, I found out, last week. It's a ULA17, which is just approved. And again, it's a structure. It doesn't have a double bond in it, but there needs to be one. So this now is going to be part of Gilead's peptide C treatment for all the really tough pieces. So it's going to be a three drug cocktail. So that's sort of one thing. So there's another and then there's this stuff, which is stable peptides, which I talked about, which I'm going to deal around. It's going forward again, so it's another 20 years. They're just in human, but they haven't really gone very far yet. Then you can use it to make bonds and all kinds of other things, pharmaceuticals. And this is a tough business. Every one of these areas is different. For example, pharmaceutical companies are accustomed to getting everything free. So the policy in the past has been NIH funds academic researchers. They develop new reactions. They don't patent. Pharmaceutical companies take them and use them. And if you actually do patent one, they'll work with it. They put it in this one, and so it's been a real headache and a hassle. But they're changing. They're catching up. The other thing is you have absolutely no control over your business because you're totally dependent on the pharmaceutical company. Whether they go forward with it or whether it gets out of things two or three. And people are really slow to do things. I'll show you. It's 20 years. They have an interesting licensing strategy. For example, they don't license things. They buy tablets, and everything has to be in there. So all you can do in this case is sell tablets. And so you sit there, twiddling your thumbs until they call you up and say, I want to buy 100 kilos. So that's one sort of business. The other one is just another way of doing it. So Cargill, which is a large ag company, approached Materia and said, we have a lot of seed oils. And seed oils are long, fatty esters. And they have double bonds in them. So they have double bonds. You can do chemistry and find methods. And so you can make polyesters. You can make hydrocarbons. You can clean them and make all kinds of stuff. And so this looked like a really cheap source of carbon. And so they started collaboration. It looked pretty good. So they spun off the company. So now you create your own customer. So now they are going to do this. They're going to use the catalyst to make compounds. The other thing is, if you're going to do catalyst research and you wanted to do anything outside of pharmaceuticals, it has to be really, really robust. Because it turns out that this first plant, a quarter billion pound a year plant, it's in Indonesia. It's basically part of a part of a seed oil operation where they make cooking oil. Essentially it enters the scheme of biorefinement. So you start with seed oil. You do a little purification. You crack it. You distill it. You take the parts and you sell them. That's exactly like a refinery where you start with a barrel of oil. You can't do much here because it makes things too expensive. This has to be really clean so it's turned out to be a cleaning system. Put another reactor to break it. So there you go. At the time when they started, they thought this would be viable at $50 a barrel. At the time it was $120. No one ever thought it would get below $50 again. It's below $50 again right now probably. But it still turned out you make different products. So again, it's tiny. It took a long time to get there. Here's a plant in Indonesia. And what's the problem here? People advertise this as green, and green is good, but no one spends extra money on green. If it's the same as everything else, it's okay. But it's got to be there. The other problem is they're making new products. If you're making new products, they have to qualify. People have to find uses for them. So it turns out that although this looked phenomenal, it's green, etc., etc., it's taking a long time because you've got to find homes for all of them. But you can't sell them as fuel. Fuel just doesn't make it anymore. You've got to find bits and pieces for all of them. And so in 2013, they've been running off on them since then. They've made lots and lots of stuff. They've burned up a lot of cash, which is good. And so it's rolling along. So bio-renewables are good. You've got to have a good, robust system. Because in this case, you're basically taking things in Indonesia, where the humidity is 95%, and taking it right out of a tree, and brushing it, and doing stuff, so you've got to have a really robust habit. And during the crisis, it can be more expensive, or other things, and people are worrying more and more about CO2 stuff. So the cost is not quite as big a deal. It's got to be cost-effective. Just because it's green doesn't sell many things. It's got to be cost-effective. And so the other thing is, too, as I'm pointing out to people, if you're a catalyst chemist, we need catalysts. Because in the past, most of the catalysts have been involved in starting with petroleum, so carbon and hydrogen based things, and putting in functional groups, oxygen, nitrogen. Most of the time, when you start with a natural thing, they're too highly oxidized. So you have to take out functionality, and so it's a whole different sort of way of doing it. And the other part of it, too, which is really important for chemists to think about, is we're starting with acetoyl. So CO2 is taken up by the palm tree, gets turned into palm oil, so this is, you know, CO2 based. So that sounds really green, but the problem is, is that where do palm plantations come from? Forests. So the question is, and then you're taking food and turning it into chemicals and fuels. So there's all kinds of interesting questions. And so as a student, people usually make decisions in this area. You either know the science, you know the sociology, you know the economics. Not many people know all of them together. And it's going to take people like that to be able to make decisions about what's really important in this whole thing. What's really sustainable and what's not. So we'll see where this all goes. It's looking pretty reasonable now. A little bad for a while, but it's starting to move along. So another related sort of topic, and this one qualifies as sustainable and green. And this is pheromones. And I left out my good slide, which is basically how pheromones work. And so it turns out pheromones are chemicals that insects use to communicate. And what's the most important thing insects do is agree. And what do you want to do to control them? Do you want to prevent them? So it turns out that during the mating season, female insects become really good synthetic organic chemists. They make specifically one compound. And they release it out in the breeze. And the males become really good analytical chemists. In fact, they can detect this molecule almost at a single molecule level. And so what happens is the female is set up in a tree, protected from the birds and other things, and males are flying around. And they get a whiff of the pheromone and they start flying up the concentration gradient. So not only can they detect it, they can detect the concentration. So as they fly up the concentration, they fly back in. So it takes somebody from the female, she lays eggs and causes problems. So what can the farmer do? The farmer can find out what this chemical is and spread it around the field. The poor males fly around. It's everywhere. There's no concentration gradient. They don't mate. You've got the problem solved. So this actually turned out to be something that's being used more and more and more in the U.S. In certain areas now you can't use certain pesticides, and so this is the only way to control the insect. You see they're pretty simple. They look like molecules and seem like fatty acids. But they have this special bond in most of them, which is called a cis-fold bond. So the things come out the same side. They go out the other side, it's a different molecule. And so it turned out these were hard to make. And so we ended up making a new way of putting them together by metathesis. You see this is pretty complicated looking. So these we now have a point where we can now make pheromones a good deal in one or two steps rather than eight or ten steps and other kinds of things. So this now is getting licensed by a company that makes pheromones in the beginning. So hopefully pretty soon the bats will be frustrating bugs. And I put these pictures up because I talk to people and they think they're killing butterflies and beautiful insects and it's really easy to control. So pheromones, it takes a long time. It's a lot like pharma. Pheromones are not really good. So in this case when you use your license you sell pheromones. This is another area. So this is a very different area. But it's still the same catalyst. Same catalyst we use. Same flavor. So you start with the cycloproteins. So when you start with the cycloproteins and you break this bond and you piece it together, you hook a bunch of them together. So this is called a monomer and that's called a polymer. Polymers are plastics. This turns out to be a pretty complicated monomer but it's cheap. It turns out to be a byproduct of petroleum. It's a big part of the C5 stream. So when you put a barrel of oil in and you crack it, you get C2, C3, C4. Those are good for chemicals. C5 is not good for a lot of things. And then C6 and higher is gasoline. This is sometimes burned and so you make C5. You can make lots of derivatives from this. And it's really tough. Here's a piece of plastic. These are two 9 milliliter bullets. Been shot into it. You see it's not very thick. Certainly wasn't holding it. And the other question people ask is if those are 9 milliliter bullets, what's the difference? Turns out that's a US 9 milliliter and that's a Israeli 9 milliliter. It turns out they have really interesting properties. We can do a lot of things that are now commercially being used to make cell covers. So this is for putting over electrolysis cells where chlorine and phosphate is made. This is an area that's been going on for a while, oil and gas. These things are called syntholyzers. But this is really exciting. This is really the first term which was just announced last year. Essentially, what this is doing is a shell has a whole new oil field in the Gulf of Mexico. And these oil fields, they start drilling at 7,000 feet. So they start drilling at 7,000 feet. Turns out that it comes out at very high temperatures, 3 degrees C. And then as soon as it comes out it hits 1 degree water. And so you've got to keep it from cooling too fast so you can't pump it and stuff. So it's got to be a layer of insulation. So you've got these pipes that are this big around. And you've got to have about that much insulation on them to keep them from doing it. And it turns out people have been doing that for a while but all the materials they had made before decomposed about 150 degrees. So there was nothing, no way for them to recover this oil based on the technology they had. So the guys at Nigeria, since we made a polymer that's all hydrocarbon, which means water can't get in and it's really stable and doesn't hydrolyze at 100 degrees. So they made a material which is stable at 100 degrees C and has all the chemical strength and everything. So now there's 40 miles of pipe sitting in Louisiana. A pipe this big around that's coated with about that much material they didn't redeem. It will soon be put in the bottom of the Gulf. So it turned out to be the only solution. And that's sort of what you need when you're introducing new products. It's really, really hard to introduce a new product. People have got to test. If you're trying to replace an old product, they're used to the old product. So you can find a place where it's the only thing that works. You've got to hook. So this is the first time that's going to happen. So pretty soon these pipes are going to get lowered down and they get welded. It's a pretty amazing operation. So that's good, so that sort of saved the company. And then another thing is we're starting to work on making window blades. So it's based on the chemistry that's around. It's really tough stuff. Competitive pricing, etc. But why isn't it being used? One is timing. We were late. Sort of a big wave of wind turbines sort of passed. The other thing is that you have to change processing slightly. And people don't like to change processing unless you invest in new tools. So we're now trying to get in really enough in the processes so we can take advantage of the really good features of S&D. So new materials. Really long bottom line time. Requires major testing. Home materials is hard. Basic process may be easier. So the first really big application is the one gas. So this is pretty amusing because when the Noble committee made the announcement, they made a big deal about this being green. So what's the first big application? It opens up a new oil field. You never know where your technology is going to go. You do it, and it happens. Okay. So that's sort of the basic research. So this is research where we started, you know, here's a reaction. How does it work? We went to learn how it worked. Then we made a better catalyst. Then we started finding new applications. And we were sort of forced into developing a way to commercialize it. So that's one thing. The other part of it is, as I pointed out, it's a platform technology which makes it really hard to manage and really hard to do. And so people need to have questions and tools for that. What I'm going to talk about next are some of the other areas we're working in. This is sort of my hobby in my old age which I'm having real fun with. And this started in a very different kind of way. So it started in the mid-80s. So Arnold Beckman. Do people know the name Beckman? Beckman is still around. Half of Caltech is named after Arnold Beckman. He was actually a professor at Caltech. Got his PhD at Caltech, so they don't know he was a professor. And at the time, Caltech was in the middle of a bunch of oranges. And so his neighbors said, you know, we're tired of doing titrations. We want some fast way of measuring pH of our orange juice. So he built a pH meter, the first one. And it was successful. So his other neighbors wanted one. And he made a decision which really changed a lot of things at Caltech. He basically said, I can't be a professor and a businessman at the same time. So he resigned his professorship and basically started Beckman Instruments and gave a whole lot of money to Caltech. So Beckman was a really creative guy. And so in the 80s, he was, he had a lot of eye problems. He lived to 102 or 103. I was at his 100th birthday party, sitting near the cake, and he pushed him over and said, don't have to blow them all out, do I? So, but he was really interested in eye stuff, and so he was funding stuff at USC. And he wanted somebody from Caltech who knew something about polymers. And at the time, no one in academics really, in chemistry departments, it was in special sort of departments and stuff. I was just trying to do a little bit. So I got drafted to help Arnold with this polymer project. I was the only one who could say polymer twice. And so we worked on that. We actually had a patent, and so I got really involved in a lot of things. And then a real breakthrough came in the mid-90s. A character named Dan Swartz, who I still work with, showed up. He's a young guy, which we joked we both had hair then. And he he's basically a really creative man, and identifies lots of problems. And he identified a problem in the erythritis area that we came up with a solution for, and it sort of started us on a program where now we probably have 10 or 15 projects going, which are related to the eye and other medical things. And I'll give you a couple of pieces and studies of how this happened. And the first key thing is I've got to find Dan Swartz. A lot of people tell me that they're going to solve medical problems, and I ask them who you're working with, and if they don't have a really good clinician they're working with, they're not going to solve the right problem. So you've got to get people really involved really, really early on. Because they've got their own game, and you've got your own game, and you've got to be able to make it work. So here's a cataract for young people. You've got a lens. Here's a lens. There's a little lens in the eye. So they pull, and they stretch it and change the shape of the lens. When you get to be in sort of early 40s, this gets to be not as flexible. I mean, we were quite vocal in the reading classes. Then you get to be 60s, 70s, 80s, and it turns into a cataract. So now what they do is they basically go in with a sonicator and take out the lens, and then put in a little piece of plastic which is shaped like a lens, and it's the most successful surgery of your life. These are pieces of plastic, the original ones were just plastic fishing line, and they're sort of a floppy system, so you can see the problem with that. So there's about 3 million gone in the U.S. So there's a lot of these. It's usually really successful. And people have been happy with this for a very long time. And you get pretty good vision afterwards, but it turns out a lot of happy people have to work. And in the day of LASIK and everything else, a lot of people don't like it. So this turned out to be a good science problem. Maybe someday I'll have to wear glasses and get these approved in time so I can actually have my own lens. So the problem was identified by Dan. So basically the idea was, can we make a lens that looks exactly like the lens now, put it in exactly the same way, and after two weeks, after everything's healed, and you can't make good measurements ahead of time, and you can't really predict how it's going to heal, so that's the reason we have this problem. And then after it's all healed and everything in place, you do an eye exam exactly the way you do now, but instead of sending them to get glasses, you do something to change the retractor power. So that was the problem we identified in 96-97. And so Julia Marshall, another faculty member, here's Dan, where he likes to be in the recording. And then the other thing is too, which is really critical, is that Dan came, and he had a problem. We came up with a solution, but, and that happens a lot, but the thing about Dan was, I came up with a solution and he came up with cash so we could go hire a postdoc to see if it would work. And that's usually where many, many things die, is in this transition and doing the proof of concept. So we hired a guy, and he did the power stuff and got the lens made, and then we hired Chris and followed physics, and so he developed all the physics stuff. He still works at the company, and Dan and I are still sort of a spiritual gang. And the idea was pretty simple. And again, one of my rules on this thing is, if you start out simple, you might, if you start out and it's complicated, you're never going to make it. So here's a simple idea that's taken 20 years to get to a proof. So essentially what you do is you make a lens out of a cross-linked matrix of silicons, like they do now. The little red things are what we call macromers. So they're polymers, about a thousand like each other. They have photoactive end groups. And then you put in photoinitiators and all kinds of stuff. And so then the basic physics of it is that if you irradiate the middle, you cross-link the macromers so they become bigger polymers. And then over the next period of time, what happens is that you've got to go back to equilibrium. So the small ones migrate from here to here. So that shrinks this area and expands out of the area. So you change the shape. So if you do that properly, you can change the shape and we're now doing it all over the place. And then once you get it in the right position, this radiates the whole thing and it's locked into this area. So there's now about 5,000 or 6,000 people running around the world. It works pretty well. Here's some really early trials. I can't show you the US stuff, but here was a commercial thing in Germany. Here's what people saw before. And afterwards, 25% saw 2016 or better. So 2020 is considered sort of good normal provision. It's hard to tell the difference between 2020 and 2025, especially if you haven't seen very well for a long time. So everybody was pretty happy. So essentially, we're there. The trials are showing related kind of things. And we can practice stigmatism but you can put different patterns. And so how do you dial in a real shape of the pattern of light? You steal a chip out of the projector and then you can use that chip to generate the pattern of light you need. So we can now really precisely tune the shape of the light. And as I showed you, it works really, really well. We showed this work in RABiTS about 15 years ago. RABiTS don't complain about any problems. It's taken about 10 to 12 years to get through all the trials. So we're about really on the edge of getting space through Google for this. So now all these things can be solved in the last month. So it's taken, you know, 20 years. A few projects they say, we can't do FTA things. Anyway, so the system now, you know, we had to develop a lot of new science and learn how to remotely control things. And so that's an interesting thing to be able to control. You're in here, face-to-face trials are there. And something that tells you that things are about to happen is that the name's got changed. It's called InVision, which no one ever liked. And it basically turned out to be the street that Dan Swartz lives on in San Francisco. And so now it's become an Rx site, so prescription site. So you prescribe precisely where you'll be in. And anyway, so it required a lot of work between clinical science, physics, chemistry, and the whole thing. And it's been, you know, it's taken a while. And the reason is it's really hard for people to think it's really going to do this. So I've got to start thinking so this is something that I'm working on a lot. This sort of gets to be sort of where the hubby comes in. Is that Dan and I, about four or five years ago, because while we were doing this we were doing lots of other things. So we said look, you know, it's time to get other people involved. So he basically recruited 10 or 12 people from top-level clinicians from UCSF. And I recruited 10 or 12 engineers, chemists. We flew up on a Saturday morning and they spent the whole day talking to us about the problem. And out of that came four or five different projects. We just had our AT meeting at Caltech last week. Another whole bunch of projects came out of it. So it turns out that, you know, what we're trying to do now is to get clinicians and scientists and engineers together to work conditions so that they can find projects which can be solved by real engineering. These are not solving drugs. These are not cells or anything. These are mostly like common problems. It's materials, getting things and getting the right young scientists connected to the right clinicians. So we're moving far over certainly at USC. I've learned a lesson in how to do this. And so UCLA sorry, I'm sorry, USC and UCSF. Dan and I said we're going to do this. I recruited people. He recruited people. We got together and did it. And the tech transfer office did a non-disclosure agreement so we could talk about stuff. And that was it. USC wants to do it. So we go to USC. We meet the dean. The dean of medicine talks to the president of Caltech. I don't know if I should have ever... So here's another interesting project that's making progress. This is called the chemo program. This is something I never even thought about. So this is the liver cancer. The liver cancer is one of the really toughest sort of ones around and really a big problem. And so now you get chemotherapy it goes everywhere. And so now we're starting something where you put a catheter in you can put it right into the tumor and release a lot of chemotherapeutic agents. Unfortunately some of it leaks out. And so when you do it this way you get it more localized. So the basic question is could we make something where we have a filter? So you put a filter in the other end which will absorb the agent that leaks through. And some of these agents are incredibly toxic and especially carotoxic and that goes to the heart. So it's right here. And one of the ones they like is called red death. Doing bad. And so the question is can we can we do it? The basic idea was what does it bind to in the body? Binds to DNA. So what if we made something where we put a lot of DNA on it which we put right there so it came through and it would jump on the DNA. So we made it out of iron nanoparticles coated it with DNA and you know here's the chemistry of it. Iron nanoparticles you can stick on the DNA. This is mustard. This is what you put your mustard gases, nerve gases sometimes on really tight. And you can show that it's got all the goodies on it. And then you can put them in serum, put in doxyleucine which is red, and you put in your nanoparticles and pull them down and it turns out the red disappears. And here's how it works in blood. It works great in water. A lot of things work great in water but blood is a really really tough environment. So here's the control of the stuff that picks it up with the particles and I took out the gory picture. There's a pig up there which has one of these devices in it and it turns out that here's the control of the pig. Here's before and after. Here's before and after. So you know I've done all these things work and so this group of concepts and now we're trying to figure out how to move to the next level because iron nanoparticles are certainly not the things we want to... So this is again a new concept. Maybe we can start curing cancer. Another one, interesting, urinary stones. I never thought I'd be working on this. I didn't know they were important. It turns out that if you have them, it's really important. And it turns out that it's the leading cause of people coming back from arachnopathy. Young males, dehydration, hypertension. And it turns out there's been eight space missions that have been shut down because of urinary stones. Same reason. They've always been announced that they completed their experiments early, but it turns out and if man's ever going to go to Mars or any place, you're going to have to have a way to treat this outside of an operating room. So you can't have people sort of laying on the bottom screaming for two years. Anyway, so the basic idea is to develop a way of treating urinary stones outside of an operating room. We worked with Marshall Stoller who's developed most of the ways used now. The basic idea is to use nanoparticles, micro-bubbles. Micro-bubbles, when you expose them to ultrasound, expand and then collapse and form a shock wave. And so they cavitate and they break things. So the basic idea is to make these bubbles, inject them into the kidneys of the urethra, put them on the side of this that's our part, chemicals, which attach directly to the urinary stone. So you squirt them in, let them slosh around a little bit and then you sort of give a general radiation to ultrasound and create a model. So it works. So this is now actually, human trials are going on in India right now, using this technique. There's an area in India that has one here. Because we can take a treatment from a treatment that takes place in an operating room, it takes place in the doctor's office. Or it takes place in a home meeting in some place. So it's something that we hope will break the cause of this. And also, when people go in, instead of being told by the doctor, you know, come back on Wednesday, I've got time in the operating room for two days, you can go get a terminal spot. So hopefully that'll work. Anyway, so, common features of all these, can't emphasize how much. It's important to get a technician to identify real problems, rather than problems that you think are real. And also they help you define requirements. It may be troublesome, but one of the first things you've got to learn is how to make money. Anyway, so you've got to come up with a basic thing, you get post-docs to help do it, and then you've got to figure out what you're going to do with it. Are you going to license it? So we're sort of working through a lot of these things right now. So basic science engineers if you identify them properly, is getting someone to do that. And many clinicians can't do that, but so you've got to find the right ones for you. Oh yeah, a couple of things here that I should probably mention is that to do this, you've got to have time for that. Some people I've known have started companies and they try to run them, and that's two problems. One is you're an academic and you've got academic things to do. Number two, you're usually going to be a crappy CEO. And if the company survives, you'll get fired. People will put the money in. So stay out of it, find a way to get along with it. And then you've got to worry about your time commitment. And then payoffs, I pointed out. If you do it for the money, you're probably going to be disappointed, but if you do it for the fun, the excitement, being able to sort of bring technology forward, be making news about it. And if it sort of works, maybe your grandkids will make a little. Okay, so thanks.