Antibodies to Identify Proteins

TRANSCRIPT: Intro: 0:24 Inventors and their inventions. Welcome to Radio Cade, the podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida. The museum is named after James Robert Cade, who invented Gatorade in 1965. My name is Richard Miles. We'll introduce you to inventors and the things that motivate them. We'll learn about their personal stories, how their inventions work, and how their ideas get from the laboratory to the marketplace. Richard Miles: 0:41 This morning I have our guest Gerry Shaw from Encor BioTechnology. And as you'll soon discover from hearing Jerry talk, Jerry is not from here. Welcome Jerry. Gerry Shaw: 0:51 Thank you very much. Richard Miles: 0:51 So tell us a little bit about yourself. Where are you from, sort of, what were you like as a kid, all the great things that happened to you before you became an inventor? Gerry Shaw: 0:59 Well, uh, I was born in Nottingham, England, so I'm British obviously, and that explains my Downton Abbey accident and um... Richard Miles: 1:08 Which by the way, as you well learned all Americans think Brits are smarter than they are based on their accent, right? Gerry Shaw: 1:14 Yes. I never really understood that, but that's certainly people seem to think that for some reason, I don't know why. Anyway, so, uh, as a kid I was very interested in zoology and I'd go off into the woods and onto the palms and I catch little animals and put them in jam jars and look at them and study them. So when I got to be a bit older I decided that I wanted to study living things. So I had a degree in zoology in one of the London universities and then I moved to another London University. So Originally University College London and King's College London. My second degree was a PhD, so I did that in a zoology department. But as it turns out it was the same department where the DNA work was done. It was the biophysics department where Rosalind Franklin, if you know the story, actually made the picture that became the basis of Watson and Crick's elucidation of the 3D structure of DNA, which was probably the most important finding that anybody ever made in biology because the structure immediately told you basically how DNA works. Uh, that was happening about the time I was born. And I went to this lab about 20 years later and some of the people there knew this whole story, some of the original equipment was there, you know, sort of an interesting place to be a young scientist. Richard Miles: 2:29 Did this run in the family? I mean, what did your parents do? Were they scientists or any of your siblings? Did they also pursue science? Gerry Shaw: 2:37 No... A bit of entrepreneurialship in the family. I guess my brother runs a internet company. Uh, my father was a surgical appliance maker, which meant we had a good occupation during the war because a lot of people needed a new plastic legs and arms and things. And My mother was a nurse so she works in a hospital and she was a midwife for many years and she came from Ireland. I'm half Irish and she was an excellent woman but not very well educated. I think if she'd had a better education, she would have nowadays should be an MD I'm sure. But in those days the highest secret get was being a midwife and a nurse. But she was very good at that. Richard Miles: 3:15 Right. So you're exposed broadly speaking to kind of the health sciences field of medicine, I guess indirectly rather early. Gerry Shaw: 3:22 Yes, I think so. My mother, she was a fervent Catholic as well. Um, so her dream was me to be either a priest or a doctor. Richard Miles: 3:31 All right. So you have satisfied the requirements... Gerry Shaw: 3:36 Well... I'm not the right kind of doctor, though she wanted me to be an MD, so I'm a PHD, which as you know, stands for phony doctor. Richard Miles: 3:42 Um. All right, Mr. phony doctor, let's, let's talk about your invention and about Encor BioTechnology. Briefly and as simply as possible, if you could explain sort of what is the core idea behind the technology and then we'll talk about sort of how you develop the technology a little bit later. Gerry Shaw: 4:00 Right. Well basically in science, if you want to study a particular protein, you need to have some way of recognizing that the protein is there. Basically proteins are all more or less the same in terms of their composition. So you want to have something that will tag that protein so you can see where it is. And basically to do that, the standard method of doing it for quite a long time has been to use an antibody. And an antibody is a protein which just binds to another protein or some other substance binds very specifically. So if you can make an antibody to a protein that you're interested in, you can then see where that protein is in a tissue or in a cell or there's a lot of interest recently in proteins that get released into blood as a result of secondary to some particular damage or diseased state. You've probably all heard of prostate specific antigen. This is part of the test now for prostate cancer. And it's basically just a protein that leaks from the prostate when the prostate is much bigger than it is normally, which may be related to a precancerous state. And to detect this antigen, you use an antibody, the antibody will capture this protein from the blood. And then there are various methods you can use usually with a second antibody to measure how much of that protein is present. Uh, so that's in principle how this whole system works. Making antibodies and doing it really properly and getting a very high affinity reagent is quite difficult. So the basic technology is to inject an animal with the pure protein that you're interested in, uh, the animal makes a, an immune response. So basically it's vaccination of the animals so don't tell me vaccination doesn't work because my entire career is based on it. So basically the animal will make an immune response to the protein you injected because the reason you have an immune responses is to attack bacteria and viruses and cancer cells, things like that. So basically when you... if I inject a pure protein into an animal, the animal doesn't know that it's not a bacteria or a virus or something so it mounts an immune response, makes a collection of antibodies. And then there are various methods for getting these antibodies out from the blood and isolating them and purifying them in characterizing them. So basically that's what we've been doing. I started off doing this in UF as part of my and if I, even in Germany, I was making antibodies for my research purposes. And gradually the whole thing grew because I wasn't making stuff for myself and other people wanted samples and I was sending them samples and it got to be kind of a burden just sending stuff all the time off to people for free because in those days I was an idealistic person. I still am actually. You know eventually it got to the state where UF was saying "Well, you should really take this off campus and set up a small company." And I set up about at the end of 2002. I started in the SID, Martin biotechnology incubator and the company's been growing ever since. We moved out of there about four and a half years afterwards and we have a little lab just off of I-75 just outside Gainesville. And we've been there since 2006, I guess. Richard Miles: 7:03 Let's go back to sort of when you first thought about the concept, was there a particular moment? Some inventors just describe a sort of "A Ha" moment where they kind of figured out or did this develop over time as you started to realize that this was a good technique. Gerry Shaw: 7:18 It's not really an invention quite honestly, because other people do this, so I think that the strength that we have is that we actually know how to do it properly. There's a lot of people who do it and don't do a great job. I guess the "A Ha" moment, I'd just come to Florida as a young assistant professor and uh... Richard Miles: 7:37 This is in 1986. Gerry Shaw: 7:38 1986, right. Yeah. So this was just total coincidence by a peculiar set of circumstances, just knowing some people and working with some people just that I happened to randomly meet. We ended up finding out that the neurofibrillary tangles of Alzheimer's disease are coated with a protein called Ubiquitin, which I won't go into the details, but it was at the time people didn't know what neurofibrillary tangles are made of. And these are the, one of the major hallmarks of Alzheimer's disease. So, as you know, Alzheimer's is a huge problem. So knowing something about the basic science of Alzheimer's was very exciting and in fact this particular protein, and again, I won't go into the details, actually gives you a clue as to what the problem might be in Alzheimer's disease, so the thing to do is obviously have a good antibody to this protein and we developed this antibody and we were giving it out for free for quite a long time, but then I went to one of the big neuroscience meetings and just happened to randomly talk to a guy who was running a biotech company and I said, well, I've got this antibody, would you like to have some? And he said yes. So they put it in the catalog and I sent him a box of tubes with this antibody in and I didn't hear anything. I didn't have a contract. I had no idea what I was doing and that's part of my life. I never know what I'm doing. I just blunder into things and then figure out how to deal with the consequences. Anyway. Then like nine months later I got a check through the mail and I thought "Oh, thats good." At that stage, I could have not told anybody I suppose, but I was honest. I went to OTL Office of Technology Licensing in UF and they were quite pleased that I'd got a check from this company. Richard Miles: 9:16 Sure, you get a check in the mail. That's good news for everybody. Right? So let's, let's fast forward again. So you, uh, you started in the incubator, SID Marin Biotechnology in 1999 and 2006 you graduated essentially which puts a good mark of success, right? They're basically kicking you out because you're too successful for the incubator. Is that sort of the idea? Gerry Shaw: 9:37 So actually I founded the company in 1999 and I was buying equipment and I was sort of thinking about how I was going to proceed, but I didn't actually start renting lab space until 2002. And that's really when the company actually started to exist. And as you said in the biotechnology incubator, they expect you to stay five years at the most and they will kick you out. I think they have kicked out people, but I got up to about four and a half years and it's kind of a hassle driving up to Alachua every day. Um, so I was doing a 50 mile round trip every day for four and a half years and so they were just building these warehouse complex just off of I-75 and I thought "Well I'll just get one of those." And then my commute is much shorter and by that stage we had enough income that I didn't need to worry about the incubator equipment anymore because I could buy my own. So the reason why you go into an incubator, particularly for a biotech company is that you need microscopes and centrifuges and incubators and that kind of stuff and all of that stuff is expensive. But by the end of four and a half years we've had enough income that we could get our own equipment. And so there's no reason. Yeah I know it was a nice place to work but you know, we had to move out eventually anyway so we moved out. Richard Miles: 10:54 Sure. And so for our listeners who are not familiar with the geography of what we're talking about, that sort of the center of North Central Florida is Gainesville and around that there are smaller towns and so Alachua where the SID Martin Biotech incubator is probably about 20 miles out of town. So since leaving the incubator, tell us a little bit about, I guess the entrepreneurial side of running Encore. I mean you have a technology, as you said, other people have the same technology but you believe you're doing it better or more efficiently. How has that path gone? So about 12 years ago that you left the bio incubator, what has sort of been the high points and the low points of the last 12 years in terms of moving the technology into the market? Gerry Shaw: 11:37 Well, basically we've always just been trying to improve the stuff that we're making and get better characterization of the stuff we already had. And so it, it turns out that, um, a lot of people make antibodies and a lot of sell them. And there's been many articles recently in the last two or three years, particularly where people have been complaining about buying a particular antibody from a company and it doesn't work or it doesn't stain what it's supposed to or there's some quality control issue with it. So we've been... there are few companies as careful about the stuff that they sell as we are. And if somebody complains about something, we'll look into it and if it doesn't work for some reason that is our fault then we'll just refund the money. It doesn't happen very often, but it has happened sometimes. Richard Miles: 12:23 So most of your clients are who? Other researchers or medical facilities or who is actually buying the technology? Gerry Shaw: 12:29 Right now it's mostly much bigger biotech companies. I don't know if you know these companies, but the company like Ab Cam and Billy Pool and Fisher, they licensed stuff from us. So that's been most of our income up till now. We do sell directly to research labs and I think as the company grows, we'll want to do that, uh, preferentially over going through somebody else that's actually more work for us. Which means we'd have to hire more people, but the income is better for us as well. So basically that's kind of the plan to expand the company a bit and to sell them more stuff directly. So if you're working on a particular protein like, you know, Alzheimer's or Parkinson's or something, as I said, you want to tag, you want to be able to see where the protein is. Um, you can also use them therapeutically actually, that's something we haven't got into, but as you know, a lot of disease states, particularly cancer are caused by mutations in proteins. So the protein basically has changed shape from what it should be and the altered shape of the protein is causing it to do something it wasn't supposed to do. You can actually make antibodies which will inhibit that. And if you look at a lot of the recent drugs that the FDA has approved, they have MAB on the end, which indicates it's an antibody. So these are human antibodies we make. Richard Miles: 13:48 And can this be used for Alzheimer's and Parkinson's as well? Gerry Shaw: 13:52 Yes. Yes. So there's clinical trials where people are using antibodies to some of the Alzheimer proteins to try and inhibit the production of plaques and tangles. It's got to be quite a growth area. We don't make human antibodies because humans don't like being injected with things on an experimental basis, but we make mouse antibodies and you can get the mouse antibody and you have to genetically engineer it to turn it into a human antibody. But that's not such a big deal nowadays to do that. So that's something we haven't gotten into yet, but we've been thinking about it. Richard Miles: 14:24 So I asked you earlier sort of what was your biggest surprise as you developed and marketed technology and your answer was how easy it was. So none of this sounds that easy. So I'm just curious about your answer and in terms of you saw this as a relatively easy and simple thing to do. You know... explain Gerry Shaw: 14:41 What I meant there... I didn't mean that making the antibody was particularly easy, cause that could be quite challenging. And frequently you will see an antibody in our catalog and you won't know that it took us like two years to actually get that because we've tried multiple different things and finally got something that worked. But actually marketing this stuff turned out to be quite easier. As I said, I mean all I did was I put some stuff in a box and I gave it to this guy and then I go to check in the mail. And so I thought, well that's good. So obviously then I was thinking I'd get involved in a new project which would have some new proteins in that I hadn't worked on before. And I think well I could make antibodies to those and that would be good for the project. But I could also sell them, you know, as I said, about 1989 was the first time I actually started doing anything commercial. But by 2000 I was getting quite big checks in the mail and in fact the company was based on income, which is really unusual for a biotech company. So I didn't have to write grants or get venture capital or anything. So... Richard Miles: 15:41 You're generating income from almost from the very beginning, right? Gerry Shaw: 15:43 Right. Right. Even before the beginning. Yeah. Richard Miles: 15:46 So anyone who started and run their own small business or most people sort of have really good days, or good weeks and sort of bad days and bad weeds. Are there any that you can sort of recall off the top of your head where you had a milestone that was just great on a particular day or week and then on the other side were there just things that were really not catastrophic but really bad for the company that occurred and if you could share those with us. Gerry Shaw: 16:13 A lot of little good days where we'd start screening some antibody and it will come out looking fantastic and we'd know that we had something that could be a real money spinner. I suppose, looking back on it, I hadn't really thought about this for awhile, but we were very interested in a protein called NeuN. N-E-U-N. There's one company had an antibody to this protein and it was a fantastic marker of neurons. So everybody who was trying to count how many neurons there were or identify neurons in particular situations, had this antibody. But the strange thing about it was that nobody knew what the actual protein was. It was... this can happen. You turn up an antibody with these techniques. So the mouse was reacting to something but the guys that had the antibody, didn't know what it was reacting with it, but whatever it was, it was really a nice components of neurons. And I'd always been wondering, you know, what the hell is this protein? And I was actually working on it and I got scooped. I figured out pretty much what the protein was. And uh, and then somebody published that this is what this protein is. So we immediately used DNA technology to make our own version of this recombinant DNA to make this protein. We made our own antibody to it. And ours is actually, it's probably better than the original antibody and we've sold bucket loads of it since then. Um, so that was a good day. Uh, and there are many bad days where, you know, we look at something and it doesn't work or it's a big mess that we just throw that away doesn't matter. Uh, probably the worst though, recently, was when I drove my car into the side of the, to the side of the building. Richard Miles: 17:46 Alright, this sounds like theres a story behind that. That sounds to qualify as a general bad day, not just an entrepreneurial bad day. Um, no one was hurt though, I assume. Gerry Shaw: 17:57 No. Richard Miles: 17:57 Okay. Just the car and the building. Gerry Shaw: 17:58 Right. Richard Miles: 17:58 So Gerry, final question. If a young researcher came to you that was business minded, said, "Hey Gerry, you know, I want to start a biotechnology company." They're all excited about it. What words of advice would you give them as they begin their journey? Gerry Shaw: 18:14 Well, I quite often get asked this and as I said, I'm not all that useful to talk to because I didn't do the usual things that most people do. I didn't have to write grants, I didn't have to get money from people. But I can tell people that's typically what you have to do. I mean, the only other thing is the usual Protestant work ethic kind of thing. You have to be prepared to work, you want to do quality stuff, you don't want to do stuff that's not high quality and I think you have to understand the market that you're aiming for and just go for the high value targets. That's what we've always done. I mean the antibodies we make are to proteins that are going to be useful to people as you probably know there's something like 20,000 genes in the human genome and those genes make something ridiculous like, well over 100,000 different proteins basically. And um, if you chose one of those proteins at random, then there might be 50 scientists in the world who were interested in that particular protein. But there are some proteins like this molecule, NeuN I mentioned. There aren't that many people who are interested in that protein itself. But because it's such a good marker of neurons, it becomes a standard lab reagent that people want to use. If they want to count neurons in a section, they just use this antibody and we have many others like that. So there are a whole bunch of different cell types in the brain and we have markers to all of them. I don't know how useful that is. I mean just hard work, focus, determination. Don't get too depressed if your car piled into the wall. Richard Miles: 19:44 And finally don't crash your car in the side of the wall. Very good advice, Gerry. Fascinating conversation. Thank you very much for joining this morning on Radio Cade. Gerry Shaw: 19:53 Okay, thank you. Outro: 19:53 Radio Cade would like to thank the following people for their help and support. Liz Gist of the Cade Museum for coordinating and inventor interviews. Bob McPeak of Heartwood Soundstage in downtown Gainesville, Florida for recording, editing and production of the podcasts and music theme. Tracy Collins for the composition and performance of the Radio Cade theme song featuring violinist Jacob Lawson. And special thanks to the Cade Museum for Creativity and Invention located in Gainesville, Florida.