 Hi, I'm Kate Young, and you're listening to This is Purdue, the official podcast for Purdue University. As a Purdue alum and Indiana native, I know firsthand about the family of students and professors who are in it together, persistently pursuing and relentlessly rethinking. Who are the next game changers, difference makers, ceiling breakers, innovators? Who are these boiler makers? Join me as we feature students, faculty and alumni taking small steps toward their giant leaps and inspiring others to do the same. I think Purdue's a great place for an education in science. I think it's terrific. They focus on the STEM curricula. I think the atmosphere of encouragement for translating your discoveries into something useful is very prominent and helpful here. In this episode of This is Purdue, we're featuring a boiler maker whose innovations are changing and saving lives across the world. And this isn't just any boiler maker. Dr. Phillip Lau has been a boiler maker since birth. His dad was a professor at Purdue, and he grew up in West Lafayette. Dr. Lau is Purdue University's presidential scholar for drug discovery, and the Ralph C. Corley Distinguished Professor of Chemistry, and he helped invent cytolux, a fluorescent marker which allows cancer surgeons to quickly identify malignant cells and remove them during surgery. This drug was invented at Purdue University and will be released by on-target laboratories. It was such an honor to sit down with Dr. Lau, who is as humble as he is intelligent. Dr. Lau starts at the beginning of his distinguished career and discusses why the chemistry field appealed to him. Dr. Lau, thank you so much for joining us today on This is Purdue. I know so many of our listeners connect with cancer on a personal level, and you've actually helped create a drug that can find these malignant tumors. But let's start at the beginning. How did you get into the chemistry field? Well, actually, my father was a chemist, and he was a faculty member here at Purdue University. It's actually a very famous one. As an obedient child, I took the courses in high school that I was asked to take, and he always signed me up for advanced science courses. So here at West Lafayette High School, I took advanced chemistry, advanced biology, advanced physics, and all of the math courses I could take. I wasn't stellar as a student. I mean, I struggled through those courses. They were difficult for me, but in the end, I really enjoyed chemistry the most. And so when I went to BYU to undergraduate school, I asked Dad what he thought I should major in. And he said, well, why don't you major in chemistry? I suspect there may have been some selfish motivation in that since he was a famous chemist. But also, he pointed out to me, when you finish with your degree in chemistry, you could go, if you wish, to business and go into sales. You could go into medical school or dental school, or you could continue on in science and sharpen your chemistry skills and get an advanced degree in chemistry. At the time, I really didn't know what I wanted to do. But eventually, the ducks lined up for me proceeding on and getting a PhD in chemistry. And after that, he came back to his hometown of West Lafayette, home of Purdue University. And I've heard you have very strong ties to Purdue. You talked about you went to West Lafayette High School. Your dad was a chemist here at Purdue. Why did you choose to come back here and work here? Well, it was a good job. When I first started looking for faculty positions, I only had one other job offer, and it was obvious my parents lived here. I grew up in the town. I like West Lafayette very much. So I decided to come back. And yeah, it was the obvious choice. And I'm sure other people were trying to poach you as you got more and more successful. I've been obviously given many, many offers to move to other places. And I grew up a very avid Purdue fan. When I was a kid, my dad used to usher at the basketball and football games. As a good father, he bought me tickets so that I could go along with him. So I went to all the basketball and football games starting from the earliest days I remember. And I grew up an avid Purdue fan. It's interesting. Here's a personal story that you might find interesting. I played basketball at West Lafayette High School and was fairly good. Okay. I got a basketball scholarship to BYU and I did play there. When I got my job at Purdue, shortly afterwards, BYU came out to play basketball here. I had tickets for the game. I wasn't sure who I was going to root for. And when the opening tip-off went up, immediately I was a Purdue fan. Did you wear Purdue colors? I don't think I committed myself at the time. Okay. But I do now. You stayed in each room. I have a full wardrobin. As a matter of fact, all of my kids have Purdue rooms in their homes where they have all the Purdue paraphernalia that we send them and so forth on the walls. Are you still an avid sports fan here? Yeah, I have tickets to both basketball and football games. As if that wasn't enough proof of Dr. Lau's love for Purdue, listen to this. Hi. That's a Purdue fight song on my cell phone. This moment during the interview was too good not to share. So fast forward to today, Dr. Lau is the founder of six companies and he has more than 500 patents pending under his name. He explains what attracted him to innovation. What attracted me to innovation was the opportunity to do something that matters. A lot of chemists are motivated by the discovery of basic principles in science that can have a fundamental impact on lots of different studies. I was more motivated by doing something that would save lives or help people in some way or another. And I was always very intrigued by life sciences, you know, how cells work, what caused them to be able to do so many wonderful and interesting things that cells do. And as I dug deeper, I learned, I think, a skill that a lot of people don't learn in their research careers. And that is, whenever you discover something new or read about something new, sit down and ask yourself the question, how can I use this information to do something that really matters? As I practiced that fundamental principle, I found that simply asking that question opened up opportunities that I would have never envisioned had I not stopped to think about the potential value to humanity of the work that I was doing. And gradually, that just led me from initially working on cancer to more recently branching off into autoimmune diseases. Now we're working in CNS diseases like Alzheimer's and Parkinson's, and we're also working on fibrotic diseases, bone fracture repairs and things like this. So it's actually guided me in many areas I would have never envisioned and actually was never prepared to pursue, but had to learn on the fly because the ideas that I was coming up with brought me in that direction. And ultimately, I think we have over 500 patents in all of these different areas. And of course, as you know, we've founded six different companies, all of which are successful. Sidelux was recently approved by the Food and Drug Administration in November. And this drug is the first tumor targeted fluorescent agent for ovarian cancer to be approved by the FDA. This fluorescent marker is delivered through an IV injection between one to nine hours before ovarian cancer surgery. But how does it work exactly? How do these cancer tumors glow once a patient receives Sidelux? Dr. Laut breaks it all down for us. We have taken a dive that emits light that is transparent to tissues. That is, it's light that'll pass right through your hand, for example. It's not light that's visible to the naked eye. We have to have a special camera that detects it, but it is basically light, not radiation and damaging term of radiation. At any rate, we attach that near infrared fluorescent dye to a smart molecule that homes in very selectively on cancer cells. So when the dye is piggybacked onto this homing, this smart molecule, if you inject it in, for example, into the vein of a patient that is scheduled to undergo surgery and perhaps an hour, the dye circulates through the body, but only attaches to cancer cells. And so when the surgeon opens up the patient and turns on the fluorescent light, the cancer cells glow brightly like bright stars against a black background. This allows the cancer surgeon to identify, locate and resect all of the malignant or cancer lesions in the patient and avoid removing too much healthy tissue because the healthy tissue doesn't fluoresce, but the cancer tissue does fluoresce. This is a very important problem because if you look historically and even today, 40% of recurrent cancers recur in the tumor bed that was resected or removed by the surgeon. This means that the surgeon left a lot of diseased tissue behind and that tissue grew back. And that means either another surgery or more often than not, it means because it's only caught much later that the patient is not going to do well and maybe not survive. Enabling the surgeon to very clearly see, they can just shave until all of the cancer tissue is removed, all the fluorescence is gone. When they see all the fluorescence is gone, they know they have removed all the cancer tissues. Kind of like painting by numbers, colors, you know, you see right exactly what you have to do. It's a very bright visual aid to the surgeon on how to remove the cancer. And you touched on it's important not to remove blindly some of these healthy cells. Why is that? Why is it so important to just get that cancerous cells out of there? In some cases, it's not as critical to be really highly precise and not removing healthy tissue. But in brain cancer, people are fond of their brains and want to have as much of that leftover as they can. And frankly, in other tissues, for example, in breast cancer, again, the cancer can be removed without removing extra healthy tissue. The patient would prefer that. In some cases, resection of healthy tissue actually does serious damage. And prostate cancer, for example, if a healthy nerve is accidentally severed, the patient can be incontinent and impotent after the surgery. And being able to see exactly where the cancer is and not cut anything that's non malignant will really benefit patients in all of these. Can you tell us about the difference between this targeted marker and others on the market that are specifically like tumor targeted? Well, there are some other fluorescent dyes that passively concentrate to some extent in the tumor tissue. But the contrast between the malignant tissue and the healthy tissue is blurred and the boundary between the two is always not very exact. In our case, because the cell that our dyes bind to are malignant and the cells that it doesn't bind to are non malignant, the boundary between the cancer tissue and the healthy tissue is really quite sharp. So it allows the surgeon to really make a very exact cut and preserve healthy tissue while being quantitative in removal of the cancer tissue. And as you can imagine, the creation of this pioneering drug was no easy feat. It took many different experiments and years and years of work. But as Dr. Lau explains, this whole concept of a fluorescent marker was actually discovered by accident. I could go way back and begin with the accidental discovery of a tumor homing molecule. What's we have all day? Well, okay, I was studying plant cells and asking the question, how these plant cells detected pathogens like bacteria and viruses around because a lot of plants will wilt and die because of a pathogen infection like bacterial infection. And so we found that if you ground up some pathogenic bacteria and spread the dust on the leaves of a soybean plant, that that would prevent that soybean plant from getting a bacterial infection later on somehow immunize the plant. And we wanted to find out how that information was communicated from this ground up bacterial dust to the plant to create this immunity. So I asked a graduate student to see if any of these bacterial pieces were captured by the plant cell and carried inside. I told him to radio label it and then see if any radioactivity went inside the plant cell. And he went away and then came back and said, Dr. Lau, I'm sorry, I can't do the study. And I said, well, why not? He said, because I don't want to work with radioactivity. I thought, gosh, everybody around us is doing it and we do it all the time. But anyway, so I deferred to his preferences and I asked him instead to put a biotin that's a vitamin and attach that to some of these bacterial pieces and see if that went in. He did and it went in. We celebrated. Hey, that shows how this signaling is taking place. But then I told him to conduct what we call a control study where you show that it really is recognizing the bacterial piece. So I said, now put biotin on insulin. Plants don't have insulin. And I told him to put it on bovine serum albumin. That's just a protein in the bloodstream of cows and show that it doesn't go in because we know they didn't do anything to plants. And he put the biotin on those two proteins and they went into. And so this is how science works. And he came back. He was terribly disappointed and said that, Dr. Lallow, we were wrong. The experiment didn't work. The biotin linked cow protein and the biotin linked insulin also went in. I said, Mark, you have just discovered a vitamin uptake pathway in plants. The plants are taking up the biotin because they can take up a biotin linked cow protein, a biotin linked human protein and biotin linked bacteria. To make a long story short, we decided to find out if animals had that capability too. So we looked at animal cells and then we jumped to folate, another vitamin. And by the way, animal cells did have that. And when we jumped to folate, we found out that only cancer cells had the ability to take up folate. Wow. And that was a breakthrough. By accident, I must confess, that started my first company, Endocyte. We used folate to deliver attached drugs, very selectively, to cancer cells avoiding uptake and the associated toxicity when a good drug goes into healthy cells. And that made a huge difference. The whole process got started by an accident. But the outcome was that we noticed that something useful could be developed out of that accident. And from folate, we went to lots of other homing molecules. And now we have a whole toolbox of homing molecules that we can use to target drugs to, as I said, not only cancer cells, but cells involved in all the fibrotic diseases, the autoimmune diseases, the CNS diseases, bone fractures, even inherited diseases and things of this sort. So we're covering a whole realm of human diseases based on the principle that if you can concentrate a good drug specifically in the disease cell and not have it taken up in healthy cells, you'll improve the potency of that drug and reduce its toxicity to healthy cells, making the drug far better than it was before. And all six of my companies are founded or built on that principle. Wow. So not only is Dr. Lau an on-targets drug changing the lives of people with ovarian cancer, this toolbox of homing molecules Dr. Lau talked about has the potential to impact cells involved in fibrotic, autoimmune and inherited diseases. Dr. Lau discusses the next steps his team took to get cytolux on the market. Initially, the whole discovery process has usually begun with a concept that you have, for example, a homing molecule and why not use that to color cancer cells or make them glow like light bulbs so that the surgeon can see it. And so the first step is to do the chemistry in the laboratory, which we did. And the second step was to culture cancer cells in a little dish. The initial study that we did was we cultured cancer cells in a dish in the presence of healthy cells in the same dish. They were human cancer cells and human healthy cells. We added our tuber targeted fluorescent dye, let it sit there and bathe all the cells, both the cancer and the healthy cells. And then after a few minutes, we washed off the solution on the top and looked at them under the fluorescence microscope. And only the cancer cells glowed. The healthy cells did not. So we thought by golly, we've got something important there. Then we went to some naturally occurring cancers in dogs that came into the veterinary clinic and just looked to see if we could help there in helping the surgeons there find the malignant lesions in these pet animals. It worked there. And then we had to prepare it for human clinical trials. That's a long involved process. You have to demonstrate that you can reproducibly manufacture your drug exactly the same many times over so that they know that if you run these trials that every patient's going to get the same molecules. Next, you have to show that it's stable. Then you have to show that it can be very antiseptically voluble and stored and that it's stable during storage and filling. And we had to do that. And finally, we had to submit what's called an IND, an investigational new drug application. We submitted that to the FDA with all of these data and obtain permission to begin trials in humans. But then when you start in humans, you have to start at a very, very low dose, a dose that's far too low to even have any benefit. So the first few patients received so little of this targeted fluorescent dye that you can't see anything. But we just wanted to make sure that they didn't have a fever or have accelerated heartbeat or had any adverse events. And so we gradually escalated the dose. And in the process, we reached a concentration of drug that was very effective in revealing the tumors, but not causing any associated collateral toxicity. That ended phase one. Then phase two clinical trials focused on finding really the precise dosing conditions more exactly to give you the best contrast between the tumor and the healthy tissue. Then the phase three trials were just to test in a large population of patients that exact condition that we believe works best. And then we test that in 150-200 patients. And we show that we are able to find malignant lesions in these patients that would otherwise gone undetected. And then that results in the ovarian cancer trial that has completed and was given expedited review by the FDA because it looked so impressive that the results were very impressive. They were able to find cancer that was missed without the aid of the fluorescent dye. In other words, the surgeon never knew it was there. Turned on the fluorescent lamp and while there's some extra cancer in there, they cut it out. They send it off to the pathologist. The pathologist says, yes, that's cancer. And so that confirms that the dye enabled the surgeon to find cancer that was otherwise undetectable in the patient. How did you feel when this was finally being tested on humans? And like you said, it's a matter of quite literally a matter of life and death, especially in these aggressive cancers like ovarian cancer. What were you feeling like when this all kind of was coming to fruition? Well, it was, I must confess, a eureka moment. Bringing it to this stage was certainly a difficult journey. I was not very familiar with the process and not at all actually. And so to be honest, I and my colleagues to some extent went through the school of hard knocks, making mistakes that a more experienced drug discoverer wouldn't make. But I learned about the process. I'm not making those mistakes with my subsequent companies. And I think that what I've learned will greatly benefit me in avoiding similar pitfalls in the future and moving drugs more rapidly from discovery through to clinical application. So with my more recent drugs in these other areas where the sailing has been a lot smoother, let's just say sure. After that, Dr. Loud took the data and started showing it to surgeons. And what Dr. Loud told me next shocked me. The surgeon said they didn't need this drug. They said we can find cancer very easily the way we're doing it now. These doctors knew and saw that the drug could cause tumors to glow, but they were convinced they didn't need it. And Dr. Loud heard this over and over for about eight years until he shared the data at one of his many presentations and a certain surgeon in the Netherlands took no. And then a surgeon over in the Netherlands saw the data at one of my talks and said, Oh, this is terrific. Let's do something with this. And so they introduced it into human clinical trials. And it was in ovarian cancer patients. We published the data in a very prominent scientific journal called Nature. The results showed that they were able to find five times more malignant lesions with the aid of the fluorescent diphen without it. And that 100% of these fluorescent lesions were cancer. And did you bring that back to the US and say, See, I told you. That really created a stir. I mean, it really proved unequivocally in a well run clinical trial that the surgeons really couldn't find all the cancer. And that there was a lot that was being left behind that they didn't know about. And so that changed actually the field. That paper was the first paper using a tumor targeted fluorescent dye in humans. So at that point, we were able to raise a lot of money. That was back in 2008. We created a subsequently a much better fluorescent dye. I think we patented that in about 2013 or 14 2014. And that's the fluorescent dye that just received expedited review by the FDA and should be approved within a couple of months. After the patent, Cytolux received expedited review by the FDA and was approved in late November. It's the first drug developed by one of Dr. Lau's companies to receive FDA approval. And speaking of FDA approval, the drug name needs to be approved by this administration as well. Dr. Lau explains why on target decided on the name Cytolux. Well, the prefix Cyt comes from the Latin for cell and Lux come from the Latin for light. So what you have is a lighted cell. And that's where the name stems from. One has to get these names approved through the FDA. You can't actually claim any outcome or benefit with the name. So usually go to companies that know what will be allowed and what won't be, and you select four or five and send them to the FDA with your preference in the FDA, then approve some or disapprove some. And this was approved. Chris Berries, CEO and president of on target laboratories, explained that Dr. Lau's vision didn't stop with just one molecule. Not only can this fluorescent agent light up ovarian cancer cells, but on target is also currently evaluating an imaging agent for detecting lung cancer in a phase three trial. And there's an ongoing trial for prostate cancer as well. Plus on target and Dr. Lau are making strong progress in the research lab for colon cancer. But I was curious, why did Dr. Lau start with ovarian cancer? There were a couple of reasons. First of all, ovarian cancer had the receptor we call it that was recognized by this smart fluorescent dye. And because 95% of all ovarian cancers expressed this marker, this receptor that would bind to this fluorescent dye, it was a good place to start. The second reason was that ovarian cancer is a very insidious cancer. It emerges or is first detected usually only in stage three or stage four. It's already spread. And I think the average survival is five years. That's because it's been historically almost impossible to find the metastatic lesions it spreads throughout the peritoneal cavity and little small malignant nodules. Some of them are buried underneath the viscera and the intestines, the walls of the peritoneal cavity, you know, in different surfaces. And it's just almost impossible to find. But if you turn on this fluorescent lamp, and we have videos of this, you can see the surgeon moving the viscera around and there's a fluorescent spot. So they cut that out and then they move it around. There's another fluorescent spot. These spots that are these nodules are often just, you know, a tenth of an inch or less in size. But if you let them go, they'll grow huge. They would normally go undetected because they look exactly like healthy tissue. You really can't distinguish them when they're that small. They're not a bump. They're just smooth. And they don't feel hard or anything like that. It seemed like a particularly difficult cancer to successfully resect surgically. And so it was a good place to demonstrate the benefit of having a tumor targeted fluorescent dye. As Dr. Lau admits, he's seen a lot of success throughout his career at Purdue. And not a shock here. He still has some really good ideas. Where do you think that drug discovery will be in, you know, five or even 10 years? I don't know. You know, I'm getting old. My days are long still. And everybody keeps asking me, when am I going to retire? I have a problem. I'd like to retire, but I have lots of ideas. And most of these ideas are pretty good. And so I'm not sure exactly what the future holds for me to be honest with you. I've, you know, we've been very successful, both scientifically and financially. And I don't have any problem getting companies started anymore. Not only do I have a lot of ideas, but it's a lot easier once you've been successful with one or two companies to go out and raise money for funding the drug discovery projects and the additional companies. Well, it's easier once you've been successful. The major investment banks and venture capitalists call you instead of you calling them. And how does Purdue continue to stay at the forefront of drug discovery? Dr. Lau shares more about the companies he's founded well at Purdue and his thoughts on Purdue STEM curricular. I think Purdue made a decision and maybe it was just intrinsic in the nature of the university many, many years ago to embrace the use of science for practical applications. Maybe this stems from the heavy focus on engineering, which is really an application directed science. Maybe it was the decision of earlier administrators, I don't know, but in many schools, finding a useful application for your discoveries considered prostituting yourself for filthy lucre. It's beneath the dignity of a good scientist to do something of that sort. And Purdue, it's not frowned on as a matter of fact, is encouraged. Now, in all fairness, I will tell you that that attitude has changed 180 degrees at almost all the universities. Even Purdue was skeptical about the compatibility of having a faculty member also engage in private enterprise. And I had to go up through the department head first who discouraged me from doing it, then to the dean who also discouraged me from doing it. It went to the president and the president had just returned from a trip out to Stanford where they were already beginning to do it. And he said, well, why not let him try? So I was given permission and we founded it was 1995. And it was one of the first companies to be founded based on Purdue technology. Since then, as I say, I've had over 500 patents, almost all of them through Purdue University. And Purdue is going to benefit financially a lot from these, I think, but also there's been a lot of benefit to the university in terms of the training that students have obtained in my lab. And in terms of the visibility that it brings to the university, in terms of the money it brings into the university because it's my lab is extremely well supported now. We occupy this entire top floor here. And that money has come in because of the interest from industry and supporting all of the work that we're doing. You know, I think it's a win-win situation for the faculty member and the university to promote this. Within the appropriate limitations and restrictions, I think those are important too. So what would you say to a future student who might be thinking about coming to Purdue pursue science? Well, I think Purdue is a great place for an education in science. I think it's terrific. They focus on the STEM curricula. I think the atmosphere of encouragement for translating your discoveries into something useful is very prominent and helpful here. My personal belief is it's the only way science has been going to survive in the future. I think we have to demonstrate that public support of science is going to pay the public back in their benefit to do so. For many years, it wasn't obvious. We would discover new fundamental principles, publish them in journals using language that only your colleagues would understand. And no one who worked at the local factory and came home and watched ball games on TV had any idea of how that might benefit them. And frankly, in many cases it didn't. But now with this emphasis on finding some practical use for your discoveries, I think it will become very obvious that Purdue University and other comparable universities can become an economic engine for the state and local area. Cancer has likely impacted each and every one of you listeners in one way or another. My sweet mother-in-law lost her battle to ovarian cancer in 2014 at just 55 years old before I had the chance to meet her. And my fun-loving aunt passed away from ovarian cancer at age 58 in 2016. As the story of Dr. Lau's pioneering drug came out at Purdue, I heard many colleagues who have also been impacted by ovarian cancer specifically. And I know Dr. Lau's contributions and work on Cytolux is a game changer and so meaningful, especially to those who have lost someone to cancer. Dr. Lau tells us what he personally finds most rewarding on this journey to bring Cytolux to ovarian cancer patients. It's been very gratifying to be able to help people. I just watched a video of a lady from the Philadelphia area who was so thrilled that the surgeon, Dr. Yanos Tanyi, was able to find significant extra disease tissue in her that would have gone undetected otherwise. She listed off all of the different activities she was engaged in and how important her ability to interact with these charitable organizations and these volunteer activities and so forth and her grandchildren and so forth. I was just, I guess, overwhelmingly rewarded by just seeing that what we likely did there was to give her an extra, you know, maybe 15 years or whatever to be able to carry out all of these wonderful activities that she was engaged in. I think that's the most, most rewarding aspect of it all. And it's nice to know that you can leave a footprint on the planet when you leave. I think we'll be able to say that we've done that and feel comfortable that we've made a contribution to humanity. Recently, Dr. Lau told Inside Indiana Business, quote, I think I've been blessed with ideas on how to cure or treat human diseases. So even though I probably should have retired many years ago, I don't intend to. I really think I can still do an awful lot of good. We agree, Dr. Lau. We agree. If you'd like to learn more about Dr. Lau, please check out our show notes for this episode and be sure to watch our full video interview with Dr. Lau on YouTube at youtube.com slash Purdue University. Thanks for listening to This is Purdue. For more information on this episode, visit our website at purdue.edu slash podcast. There you can head over to your favorite podcast app to subscribe and leave us a review. And as always, Boiler up.