805: Creating Cell-Free Gene Editing On A Chip For Cancer Diagnosis and Treatment - Dr. Eric Kmiec
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Hi, everyone, and thanks for joining us today for Episode 805 of People Behind the Science. I'm Dr. Marie McNeely, and in this episode, we are resharing our interview with our guest, Dr. Eric Kmesh.

Listeners, Eric is well known for his pioneering work in molecular medicine and gene editing. He and his colleagues are working to develop new ways to treat cancer by destroying the genes that cause cancer cells to be resistant to typical therapies like chemotherapy, radiation, or immunotherapy. And in our interview, Eric talks more about his interests, both within and outside of science, and he shares some excellent insights and advice. So, everyone,

Everyone, I hope you enjoy this episode of People Behind the Science. Every day, discoveries are made that will change our understanding of the world around us. Dr. Marie McNeely is here to bring you the brilliant minds who are making these discoveries so they can share their incredible stories and take you on an amazing journey. Welcome to People Behind the Science. ♪

Hello, everyone, and welcome to the People Behind the Science podcast. Listeners, today I am thrilled to introduce you to our guest scientist, Dr. Eric Kamech.

So Eric, welcome to the show. How are you? Great, Maria. Thanks. It's great to be here. Well, we are delighted to have you with us today, and I'm looking forward to learning more about you and all the wonderful things you do. But before we jump into the details, I do want to take a moment to introduce you to our listeners. So listeners, Eric is director of the Gene Editing Institute of the Helen F. Graham Cancer and Research Institute at Christiana Care Health System. He also holds faculty appointments at the University of Delaware and the Wistar Institute.

Eric received his bachelor's degree in microbiology from Rutgers University, his master's in cell biology and biochemistry from Southern Illinois University, and his PhD in molecular biology and biochemistry from the University of Florida School of Medicine. He conducted postdoctoral research at the University of Rochester before joining the faculty at UC Davis in 1987. Since then, he has served on the faculty of Thomas Jefferson University,

Thank you.

was an eminent scholar and director of the Marshall University Institute for Interdisciplinary Research, and also served as co-founder, chief scientific officer, and a board member of Orphagenix. Eric has received numerous awards and honors over the course of his career, including receipt of the 2012 Proudford Foundation Unsung Hero Award in sickle cell disease, designation as an honorary commander of the 436th Air Wing at Dover Air Force Base in both 2013 and 2014, and

and also induction into the Southern Illinois University Edwardsville Alumni Hall of Fame in 2012. Further, Eric and the team at the Gene Editing Institute were recently awarded the inaugural Life Sciences and Bioinnovation Award from the Philadelphia Israeli Chamber of Commerce. Now, in our interview today, Eric is going to tell us more listeners about both his life and his science. So, Eric, let's start off with talking about life. Can you tell us what you like to do when you're not very busy doing science?

Well, I grew up in a small town in Massachusetts, and the things there that you did as a young man was play sports. So I was fully integrated into all of the major sports, and particularly took a liking to baseball and hockey. So that's kind of followed me through both my life and the life of my son. So I'm usually...

working a great deal in the sports area. I still try to play competitive baseball in the Philadelphia Men's League, although this year my shoulder is not going to cooperate. I won't say what the blank age over limit is there, but there is a competitive league and enjoy that. And then my wife and I have a house that sits on top of a creek, so there's plenty of landscaping and work to do in the woods. So that sort of keeps me occupied.

Excellent. Occupied and active, it sounds like. Yeah, active is the key. So what is your position of choice in baseball?

I actually was a catcher for a long time and I ended up at second base occasionally, but I think in my age group, I'm still one of the few guys that can actually bend down without creaking too much. So I usually get assigned to catch. That's awesome. Well, Eric, great to hear a little bit more about life outside of work, but I do want to also chat about your amazing work. So when you're talking about what you do, how do you describe it to someone who might not be familiar with your field or your research?

I think I'd describe it really as the hybrid between a professor and a scientist. Teaching has always been important and I've had academic positions throughout my career where I've had the pleasure of actually teaching undergraduate and graduate students. But from the perspective of the daily work, it's really to do science and to advance that in a research group. And in particular, what we're focused

on now is trying to develop a new way to treat cancer with a focus on trying to destroy the genes that cause resistance in standard therapy such as chemotherapy or radiation or immunotherapy. So it's really about developing new therapies for cancer and trying to build on the skills that have kind of come this way throughout my career.

Definitely. I know this is very exciting and important work that you're doing. So I look forward to learning more about it as we go through our interview today. But I do want to take a moment here towards the beginning to just talk a little bit about motivation. I think the science in and of itself can be very motivating. But do you have a favorite maybe quote or a saying or something that really keeps you going every day?

I think it really comes from my mother and I don't think she developed it or originated it, but it's really basically that you're not judged on what you do, but rather you're judged on what you do for others. And I think that that has kind of kept me motivated throughout my life, trying to help people. It sounds a bit corny and almost altruistic, but it isn't really. I think once you're around scientific research, as you know, Marie, you

You kind of engage in it and you really want things that you're doing to contribute to the better good, specifically trying to help people get healthier. Absolutely. Well, I think that is a great motivating force. And you mentioned your mother as perhaps this motivating and inspirational figure. Are there other people that really rise up in your mind who left a lasting impact on you in your career?

I think anyone who's gone through this kind of career in academia and research, there are hundreds. But I think there are two that I'd probably pull out, rise above the rest. One was a member of my PhD thesis committee, and that was Bruce Alberts, who went on to be a prominent member of the National Academy of Science, and I think eventually president of the National Academy. What I learned from Bruce is that science is what really sustains you.

And throughout your career, if you drift too far away from being involved in science or doing discovery research, you tend to lose your critical eye and lose your ability of judging what's meritorious science and more importantly, what is not. So even after all these years, I still actually get very excited about getting reviews back on a manuscript. And we are, as a laboratory, quite aggressive in publishing.

And we certainly are still quite competitive in writing grants to the federal government. I've always sort of believed that even in the age when you can get money from industry and some philanthropy as we do in a cancer center here, it's actually quite important to have peer-reviewed science if you're doing research.

The other one I'd actually say is sort of a newer one and it's my current supervisor, Nicholas Petrelli, who is the medical director of the Helen African Cancer Center here. I've known Nick for quite some time and it just was the right time to move the laboratory into the cancer center.

But Nick has a relatively important gift for vision and its ability to see what's on the horizon in new medical treatment. And I think about three years ago, we started talking about moving here as a research lab into the cancer center. And certainly there were naysayers that gene editing wouldn't flourish or anything. And we now call them members of the Flat Earth Society as well.

But against all that backdrop, he actually helped us establish this gene editing institute. And I think he's going to be richly rewarded. I do think CRISPR is going to have a big effect on cancer therapy in the future. Certainly. And I like that you mentioned that you look forward to getting reviews on manuscripts. I think this is something most people dread. Well, forward is a relative term, I think. That's right.

Well, great to hear about some of these people who've had a big impact on you and your career. But Eric, I'm really interested to hear about where this fascination and this love of science of yours came from. So if you look all the way back to your very early years, is there a particular memory where that spark was lit for you?

I actually have to be honest and say I went to Rutgers University's undergraduate basically to be a baseball player, which I've already mentioned is a favorite sport. The central problem was that I wasn't quite talented enough to play college baseball. It did turn out OK because my youngest son, Samuel,

became a starting pitcher at Wake Forest and then Wentworth University and eventually signed as a pitcher by the Cardinals. Oh, wow. Congratulations. It looks like an injury is going to sort of derail his career, but it's been a great journey to kind of fulfill that part no matter what.

Then I left and did some work at Southern Illinois University, which is a place I did my greatest accomplishment, which was to convince my wife, Jennifer, to marry me. And after 38 years this month, I still think it's my greatest accomplishment. So I went on to Florida, got my PhD in an area that was pretty remote at the time, and that's studying genetic recombination in fungus.

as you probably know, Maureen, but most listeners won't, a lot of the original work in how DNA gets exchanged inside eukaryotic cells was designed by folks studying fungal processes. So it's been kind of at the center part of my career and something that we as a laboratory continue to do, and that's to study how chromosomes exchange information. It ultimately led to

moving directly into gene editing. So for years, there was actually a group of people studying gene repair. And it was a fascinating but fairly quiet field. We were getting good NIH support. But it turned out it wasn't really occurring and taking place at a frequency that would be clinically relevant.

But obviously, when ThinkFinger Nucleases and Talons and CRISPR started to enter the scene, the whole field that was kind of working along on mechanism and regulation jumped into the main fray. And we have been able to kind of leverage our background and knowledge of the field as a whole and move into a cancer center where gene editing has to survive. In other words, gene editing as a reaction is very interesting.

But the clinical implementation will occur primarily because you are working with oncologists

And I think that's what the cancer center here has given us an opportunity to do. And that is to be down the hall or a floor above oncologists that are seeing patients and using their guidance and understanding, we've been able to, I think, make some progress in gene editing of lung cancer and moving it toward the clinic. Without their practical or clinical input, you're really just doing a lot of excellent basic science

But the problems surrounding introducing biologics into patients are enormous. And if you don't get that advice early on, then your project tends to wander a little bit and probably will take longer to get into humans. So kind of a long answer to a simple question. But starting with very basic mechanistic work, some even at the biochemical level, molecular level, we're now seeing things move forward faster.

toward the clinic. And that's been really enjoyable and certainly refreshing. Absolutely. I love that you highlight the importance of these clinical collaborations and have talked us through kind of how your own career has grown with the field. And I know you've done some very pioneering work in this field of gene editing, but I want to go back a little bit and talk about this transition where you started with a love of baseball and ended up in microbiology. For many people, that's not an obvious second choice. Dr.

Well, in high school, I actually wasn't that bad a player. I was actually a pretty good player. But I did like science in general. I've always been a little bookish and interested in science. I was most interested in bacteriology and microbiology. So Rutgers had a very, very strong microbiology department. In fact, the Waxman Institute

At the time, it was the place where a lot of antibiotics were actually developed and discovered. So I took a couple of courses and did pretty well with the other courses that were a bit of my downfall. So I was able to kind of push forward on that. And then one

Once I realized that I was not going to be a professional athlete, I got more and more interested in that. I think they were operating on parallel tracks. So it wasn't just baseball and into science, but I certainly preferred playing baseball than streaking plates. But I was doing both and I

think eventually getting into my graduate work at Southern Illinois University, where it was really more dedicated to science, I started to enjoy the path of research. So a little bit of a right turn. Honestly, I don't think there's any real explanation for it, but it was happening on parallel tracks. It didn't just sort of jump out of the blue. Gotcha. Well, I love hearing about how scientists get their start in their particular field. So thank you for sharing your own story. And I know you're working on some remarkable work today.

So is there a particular project that you want to give me and our listeners a little bit more detail on from the Gene Institute? Dr. There are actually two. So circling back to having a molecular medicine or gene editing technology in a complex situated inside a cancer center, we actually came in and began to focus on trying to develop ways in which we could use gene editing for cancer. I mean, it's the theme of the cancer center, obviously. So the

The number one cancer killer in the state of Delaware and nationally is lung cancer. And shockingly, we actually have a small amount of research dollars per lung cancer death in the country. Most people feel that a large portion of lung cancer can be prevented by not smoking or stopping smoking. And that's probably quite true.

But it turns out that a lot of people just don't do that. And some of that has to do with economic or social issues. So we decided to focus on lung cancer because it was a huge health problem.

And one of the things I did was to meet with a physician known as Greg Masters, who runs a lot of the clinical trials here, particularly and is an expert in that with regard to lung cancer. And he told me that he really felt gene editing had a role in cancer, but it was not going to be one that would be driving a cure. And I think we all kind of knew that early on. So the idea was to select a subset of patients who have non-small cell lung cancer and

and to segregate them as a target group for development. And then he said that the most important thing he would see is that if we could reduce the amount of toxicity that patients absorb from chemotherapy or immunotherapy or autoimmune responses and things that they're now beginning to see with some immunotherapy. Radiation is not really used in lung cancer very much, but it is in other forms of cancer.

So the idea is to kind of couple and do a combinatorial approach where we actually destroy genes that are causing tumor cells to be resistant to chemotherapy. And while that sounds like low hanging fruit, it isn't, it's quite challenging.

But it's actually a practical goal because we all want to make patients feel better and hopefully the tumor goes into remission. But patients that really suffer with the kind of treatments in cancer. So by focusing on that specific goal, we

we actually are helping the quality of life while trying to move forward on treating them. So that's one of the projects that's really exciting to me. And I think we're actually making good progress. And I think we're going to impact positively a fair number of patients. The other project that I'll just mention,

I'm really proud of this, too, because it goes back to my roots, which was figuring out how the mechanism of gene editing actually works. We developed something that is akin to an in vitro gene editing system or gene editing on a chip, we like to call it, where we're actually looking at how CRISPR-Cas9 works in a controlled environment, meaning outside the cell.

So with that, we used something known as the cell-free extract to process DNA molecules that have been cleaved and worked upon by CRISPR-Cas9. That actually led us to receive a BIRD grant, which is a grant that

pairs Israeli biotechnology companies with American companies or researchers, and there are very few of them given on a yearly basis. But when we talked about this in vitro system, it turned out that a biotechnology company known as Novellus

was actually doing a diagnostics and by pairing up with them, we were able to develop a strategy that would help them improve the precision and efficiency of a diagnostic assay they already are using. So it kind of combined two things. It was a practical outcome, but it was also a

basic science project that going back to what Bruce Albert was really focusing on, that stay in the science because the science itself will give you a lot of rewards for it. So that's been a lot of fun. And then the third thing I just mentioned in a tangential way was having been in this field for more years than I'd like to say, turns out that like many scientists and scientific groups around the country, you develop these model systems and test systems that you kind of stick in the back of the freezer. And it

And it occurred to me that as gene editing with CRISPR starts to emerge fairly dramatically, we might actually be able to craft one of these systems for use in an undergraduate laboratory exercise, not only in a four-year college, but also at a community college and sometimes even at the high school level. So we worked with a group at a community college here in Delaware. It's actually the one that Vice President Biden's wife, Jill, has taught out in the past.

And they were very excited about integrating a gene editing exercise. So we worked on it for a while. We put together a proposal and the National Science Foundation awarded us a grant to pursue this. So we've been able to take something that was really had gone past its use as a research system.

and transformed it into an educational kid in curriculum for high school, community college, and four-year colleges. And we're sort of partnering with various people to get this launched nationally. So while it's not really our mission to do education, Christiana Care is extremely committed to outreach. And this is something that is just a byproduct of really doing hardcore research.

keeping your eyes open for opportunities that might help the community at large. So not the central focus of our work and it won't be that's always cancer research and cancer therapy, but sometimes things peel off that have a life of their own. And I'm really happy that that one is living quite well now. Absolutely. Well, Eric, thank you so much for sharing more about what you're working on. And I think each of these projects that you mentioned is remarkable in different ways. And I really like this aspect that you highlighted throughout this discussion here that

that one of the things I think that sets this Gene Editing Institute apart are some of the collaborations they have with high schools, colleges, universities, other research institutes, as well as industry and companies. So can you talk a little bit about how these kinds of collaborations impact the work that you do there?

I think some of them drive the science. I've always liked to have an eye on the prize in that our goal in doing research is to make things work better and to contribute to therapies that will help people. And that can be all the way from developing a diagnostic or creating a

cell line for someone who's testing a drug or to directly applying gene editing toward the development of a cancer therapy. So our relationships with these companies often help us even shape our basic way of thinking about things because there are great scientists in biotechnology companies and in pharmaceutical companies. So when you engage with them, they may say something or do something that helps shape your future. So we consider them as collaborators, not so much clients.

However, gene editing tools are very interesting and aggressive to people. So fundamentally what happens is that there's a need for them to use these tools. And we're happy to provide them. We sometimes function as a core facility for other researchers at universities who may not have access to this.

So I think they kind of shape the way we do business and having more people around the table and critiquing your work and talking about it is very important for advancing the field. We don't want to just contribute to the literature. We want to really advance the field. And I think the more collaborations that are manageable, and that's important, I think you achieve that goal a lot better and faster.

Certainly. And I think we've talked about a lot of wonderful aspects of your career, Eric, but we haven't yet touched on the trials, the tribulations, the troubles and the struggles. I am sure there are many of them. So do you have a favorite story of maybe a challenge you've faced or a failure that you've had that you can share with me and our listeners today? There are too many of them, Marie, but I can give you one that is kind of an overview and

And this is kind of how science sometimes work and it's not always pleasant. We started thinking about gene editing actually in the mid-90s to late 90s. And the reason for it was that was the boom days and the extremely booming part of gene therapy where a corrective gene was added to your favorite virus and injected into people and it was sent in to augment or replace the function of a disabled gene in a chromosome.

And there were very good people working on that. Obviously, it was a huge field and billions of dollars were invested in it. But it always seemed to me that it was treating the symptom, not the problem. And so we began by saying, look, why don't we try to do gene repair? And in the old days, we call it gene repair. Now it's gene editing, which is, I think, a better term.

And pretty much people dismissed us as being heretics and us means about 10 or 12 labs that we're thinking about this together. And you always know how much respect you get in the field as to where you get asked to speak in a national meeting. And we were always on Sunday morning, the last day of the meeting. And basically the audience in that session was the other speakers.

So that was hard to keep going and a number of people got quite discouraged by the sort of pushing this aside because the money was flowing from NIH very specifically for adenoviral gene therapy, AAV and others. So the bulk of the field was kind of thinking we'll just do this downstream.

We had to hang in there for a long time. Unfortunately, the NIH believed in us and in some of the other groups enough to continue to fund us with RO1s for 13, 14 years so that we were able to kind of withstand being pushed aside a little bit until basically Zink, Fingers, Talents, and Crusader hit the airways and now we're kind of mainstreamed.

And it wasn't just me. There were a number of other folks who had to sort of withstand being second-class citizens in the field because the bulk of the field was really convinced that augmentative gene therapy was going forward. And I personally always felt that a rising tide raises all boats. So in

In their successes, we would have success, but that's not always the way people feel in science. As you know, grand competition is pretty tough, and humans are humans. I'm not blaming people, but it just was difficult. So the tough times were really just believing that gene editing would eventually come through, and more importantly, by other people.

Rich scientific advancements occur when other people kind of piggyback on each other's work. And sometimes the early work was not robust. We were kind of flailing around in a dark room. So it wasn't one thing, but it was a number of years that we were kind of out there almost on our own. And I know this now because I get requested to give the historical content of gene editing. So it makes you feel like an elder statesman a bit.

But I'm glad that the field has now come mainstream because I do think there's a lot of excellent work. And ironically, a lot of the early purveyors of viral gene therapy are now doing gene editing. So as I keep reminding them, they finally saw the light. That's right. So I'm curious, what kept you going or maybe kept you from changing your research area when there were all these people maybe doubting and dismissing you? I think a lot of it has to do with believing in the science. It

It sounds kind of hokey, but it's actually true. I really felt that unless you corrected the mistake at the level of the chromosome, this was all going to be problematic. And while there are, by the way, some successes in viral gene therapy, I think almost everybody would consider that not to have been a success as we all had hoped.

I hope we don't make the same mistake twice when it comes to gene editing. But I think I felt really strongly about the science. And as I said, we're doing really good basic science, understanding the mechanism. So we were being rewarded by doing fundamental mechanistic studies. We're publishing nucleic acid research and DNA repair and JBC and sort of the guts journals of the field that produce really good science, but was not the public relations statements that you often see

quoted in the New York Times and things like that. It really was a love for the science and the belief that this will eventually work. We just need a few more tools. Absolutely. And I think that persistence and that patience are key in science. And in this case, they absolutely paid off for you. So congratulations on the amazing work you've done in the field. But I also would like to talk maybe about some specific successes you've experienced. So do you have a favorite story of success you'd like to share with us today, Eric?

So there's an old one and a new one. When the field was young, I was thinking about how RNA would actually participate in gene editing. It's actually a true story. We believed RNA, which is actually a major part, as you know, of the CRISPR complex, must be playing some role because there's so much of it. And it actually is one of the few pieces of single-stranded DNA that binds to DNA and can invade a helix because that's what transcription essentially does.

But I couldn't figure out how to put the whole thing together. So, strangely enough, I was mowing the lawn with my oldest son. He was probably five or six at the time on my knee. And I was talking to him. I used to talk to him about the projects all the time. And he would give me great advice like, "I'm tired of listening to that," or, "That's stupid," or something. But then he kind of said something that said, "Well, why don't you just put DNA and RNA together and protein and buy protein to RNA?"

And we started to kind of work on that and believe it or not, that's turned out to be what CRISPR is. Now, CRISPR was obviously in bacterial cells. So that little comment by Tyler actually pushed us in a direction. So that was an unexpected one. And then the second one, which is current, is the great pledge. And Marie, I'm sure you've experienced this, that every once in a while, a student comes along who comes into your lab, who just is the right student with the right hands on the right project. And

The most recent development of this gene editing on a chip, this in vitro system, is being handled by a terrific young graduate student, Brett Sandsbury. She is a graduate student at the University of Delaware and is about as good an experimentalist as I've ever seen. She's careful, methodical, she thinks clearly before she does anything, and she's a second-year student. So, that's fun to watch someone of that skill level develop. I think we've

in our careers have seen these. And I've been fairly fortunate to have kind of one of those star students in the lab for 20 years. They move and they spend four years and get their PhD and then go on. And Brett is the latest one in that. So that's a great feeling and it gives you a great deal of reward. Plus they can move on.

They go and do great things. I've had a couple of Howard Hughes postdocs with scholars. We've had people go to Harvard for postdocs. And usually people call us, and it's more a reflection of them than me, because as you know, there's no replacement for skill and talent. Hard work is great. We all believe in it.

But frankly, it doesn't always cut the mustard. You really have to be skilled. So watching a student develop now and Brett Sandsbury is the current one, really gives me a great deal of pleasure because she's very talented. And I'm also, I have a tendency to graduate a lot of women with PhDs. So that makes me even happier because we certainly need to improve the number of women that are in major leading roles in science. So I'm doing my part.

Absolutely. Well, congratulations, Eric, on these successes. I love both of these stories that you shared. And I think this piece of advice you got from your five-year-old son while mowing the lawn is just a remarkable story. It's unbelievable. He reminds me of that still, by the way. He's getting married next month and he continued to remind me that he sort of started the field. So that may be a bit of a stretch, but I'll take it. So how did you reward him for this brilliant insight?

I think he was more interested in going to McDonald's. So a happy meal then, yeah? Yeah, happy meal. I think that was probably his focus at the time. That is phenomenal. Thank you so much for sharing some of these amazing success stories. And we've talked about some different aspects of your life, both within and outside of science. And one of the things that I love to talk to all of our guests about is what they are reading or what their favorite books have been. So do you have a book recommendation, whether it's a science book or a non-science book, that you can give me and our listeners today?

I've always tried to have sort of a diverse interest in reading, and my wife is a very, very big reader, and I wish I read half as many books as she does. But I've always been kind of fascinated by biographies written by true historians, not sort of fictional writers that then pose as historians, but people who really dig in and are good writers. Ultimate historical papers that are published in journals are too deep for me and can really sort of knock you out.

But I recently read a book by Walter Isaacson. It's the new biography of Leonardo da Vinci. Obviously, nothing needs to be said about da Vinci in terms of his impact and his genius. But it was interesting to read because Isaacson did not just relay the facts about where he was, what he did, although that's in the book. It was more about what inspired him. And the thing that struck me about da Vinci

within this book was that it actually kind of followed the scientific method. So here's da Vinci as a young man painting curtains. And it sounds ridiculous that he was a part of a team of Italian and Spanish painters who were under this master painter,

and they were doing all these team paintings. And you thought that was fairly ridiculous, but as the book progresses, you suddenly realize that that's where he learned to get such incredible detail and realistic depictions of hair and of muscles and of body. And I thought, there's somebody who's dealing in some obscure fungal genetic stuff

who then watches the field go forward into that. And it showed that the creative process is pretty common among artists and scientists in that you kind of learn something. And if you do it really well and you're persistent and you learn your craft well, that what initially seems to be quite boring work can actually turn into the foundation of great things and masterpieces that we all enjoy. So the book is extremely good. It's not the traditional masterpieces.

we've done and have to slog through the teenage years, he gets right to the problem and he treats each chapter as a great work and where did this come from? So I really enjoyed that. Well, excellent recommendation. We will put that out on our website for our listeners to find. And I really love that you brought up this idea of creativity being important in science. And I think there are so many creative and funny and amazing scientists that I've worked with over the years and gotten to meet.

And I think this is contrary to a lot of the stereotypes that people have in their minds about what scientists are like. So I love sharing stories on our program about some of these creative moments or quirky traditions or just fun or funny things that scientists do together. So Eric, do you have a story of your own that kind of fits this mold that you can share with me and our listeners?

Well, when I was a graduate student, actually, I used to go to Cold Spring Harbor and attend the meetings. They were long. They were six, seven days of very heavy science. But one of the great things about Cold Spring Harbor was you kind of walk around the corner and there would be James Watson standing or Frank Stahl or Charles Ratting, the pillars of genetic recombination and the Great East Group that was there forever.

for many, many years with Amar Klar and Jester Thurn. So I had a number of opportunities to kind of sit and walk and listen to Watson talk about the creative process. And he really influenced me because at the time that I see him and discuss things with him, and it'd be unfair to say I really knew him well, but I think well enough that he'd know me, that he was telling me how wrong Alex Rich was about left-handed DNA.

And how he sort of broke that down. Now, I never knew if this was true or not because the science was way beyond my skill set to understand it.

But listening to people like that at Cold Spring Harbor in three or four years, I went as a graduate student because as you get older, you have your own mission. Your research is focused and you're not as absorbent as a sponge then because you can't be. You have to be writing grants and papers and being focused. And even postdocs are kind of crafting their own career. But as a graduate student, the opportunity to walk among those giants and listen to them

And even then, critique your own work, because I would often be asked to give a presentation at Cold Spring Harbor. It was a great thing. Not that I was particularly happy when James Watson raised his hand in the audience. Well, in fact, he never raised his hand. He walked down the middle of the aisle and said his question.

Oh, wow. Fortunately, it turned out well for me. So I was pleased with that. But I think that was an inspirational moment and certainly one that I think teaches you the creativity of how these men think and how these women think. Unfortunately, at the time, it was mostly men. But I think you want to learn how people think about problems and how they approach creativity. That, I think, influenced me a great deal.

I think even as a young scientist, maybe in graduate school, finding that these people that you've looked up to as the giants in the field are actually quite approachable, this being able to have a conversation. Exactly. And they want the truth. That's the thing that struck me most is they really do want the answer. That doesn't mean there weren't a ton of egos in that room. In fact, probably more than I knew, but they were persuaded by data. And that's not always the case nowadays in science. You're sort of persuaded by argument more than data at times.

Certainly. Well, thank you for sharing this memory of yours about some of the people that you've been able to interact with as a scientist. And I think you've also touched on some of the places you've been able to travel. And I think this is also an amazing aspect of careers in science. So Eric, do you have a favorite place, maybe other than Cold Spring Harbor, that your science has taken you?

Well, there's been a number of them. Certainly, the Keystone meetings in Colorado, where the focus on molecular biology have always been memorable for me. The Gordon conferences used to go to New Hampshire. Now they're, I think, spread everywhere throughout the world, but they were particularly in New Hampshire for a long time and Tilden College. And there you're kind of sequestered away in the hills of New Hampshire or Vermont, and you're at a boarding school. So there is no TV. There's usually a common bathroom. So we're

when people say, well, I really got to know these scientists, in those conditions, you really do get to know these scientists. Right. You're having shower conversations and yeah. Right. And I think that you're put there primarily to communicate with each other. And those were the days, although I hesitate to say this because it'll date me, where there were no cell phones and there were no computers. So you actually were forced to communicate verbally. And I think that's the thing that's lost in science a little bit because you get

You get the intonation and you get the intent of the conversation when you're sitting across from someone. So I think the Gordon conferences, not just one, but a number of them in DNA repair and recombination in my early career were really inspirational. And they weren't always the beauteous places in the world to go, but they worked because you had a chance to really talk to people on a regular basis. And people did communicate with each other at the time.

Absolutely. So is there a particular meeting that you've been to recently, maybe either one of these Gordon meetings or a Keystone meeting that really left a lasting impact on you?

I think the one that actually left a lasting impact on me was in Montreal. It was neither of those. It was called Genome Canada. And that was a meeting that brought together a lot of the high-powered technologies, but people were asked to describe not the technology, but its impact on the field. It was a unique situation, and they have it every year. I was asked to give one of the keynotes on gene editing a couple of years ago. So I

I like that approach a lot. It wasn't just here's the latest gives money. Everybody does DNA sequencing, next gen sequencing. And so you oftentimes you'd hear talks like that and I couldn't understand it after the first couple of minutes, but these were different.

People spent time talking about why this was important and where did they see the field going. So I thought the Genome Canada meetings were terrific. Yeah, and I absolutely understand. I know you go to these conferences and everyone is very detail-oriented and working in the same field, more or less, but very different aspects of it. And you're absolutely right. Oftentimes you find yourself two or three minutes into the presentation and you have no idea what's going on. So the focus on the impacts and the big picture, I think, is really important.

Right. I agree. So you're tackling some amazing questions with the work that you're doing there at the Gene Editing Institute. But I imagine that there's a thing or two standing in the way of you and sort of your dream questions. So, Eric, if we gave you all of the funding, the technology, the feasibility, whatever you could possibly ask for today, what is the question you would most want to tackle?

Well, I'd ask my friend who's an orthopedic surgeon to repair my shoulder so I could play in the men's league in Pennsylvania. But beyond that, I think gene editing is at a really interesting point. And thinking about this question now, I think it's such a unique topic that it will engage a lot of people, ethicists, lawyers, and even insurance executives.

I tend to step back from this technology a little bit and ask, let's assume that things go great. Let's assume that there's enough money to develop this and with your proffer there. If that is, that's great. But if we actually build something in research, will anyone come and use it? And the answer to that is not as easy as you might think.

The general public needs to be educated that gene editing is not going to create four-headed salamanders or... Frankensteins, yeah, right. I say something like that and Hollywood drops this Wolf Eagle something on their movie Rampage out of the sky. So you're battling commercial entertainment. And I think that movie actually does mention CRISPR. So that's always great to hear. So there's a public perception about gene editing that's extremely important to control.

And I'm not just talking about the obvious thing, which is it ethical? Does it touch religious beliefs by editing a human embryo? I'm personally opposed to that. And we would not do that here at Christiana. But I think it's more than that. Let's say we develop this treatment for lung cancer and it all goes great and there's enough funding to move it through.

Is an insurance company gonna pay for the patient that receives that at a community cancer center? That's what is kind of unique about the situation we're in. 85% of cancer patients get treated at community cancer centers around the country. And a lot of these patients are important for clinical trials because they're naive. They haven't been treated with another drug.

But having said that, they're not always as adept at having the information at their fingertips of why this will work or not. So I think there's a huge amount of education that needs to take place as we develop CAR T cells, as we develop gene editing for anything. So I think if that money were available, I'd spend some time developing something that we've kind of termed here gene editing 360.

We have launched this a little bit by having a symposium last week here at Christiana Care, where we did have ethicists, lawyers, and insurance executives talking about the issues that are going to face the public going forward. So I'd love to have more research funding. I think any scientist would at any time because we try to be creative people and do legitimate peer-reviewed science.

But at the same time, for this specific topic, I put a lot more money into kind of engaging the public now. It's very similar to what we went through in the 70s when recombinant DNA became online.

the same worries. In fact, talking to a couple of ethicists, they're saying, "Geez, I went back and read those reports and guess what? They're the same worries came forward in 1970 that are almost 50 years later here and we're worried about the same thing." So I sort of developed a gene editing 360 module where ethicists, lawyers, the public,

Even religious would come in and talk about what are they concerned with. So we're not at the verge where we actually have an excellent, well-debted, terrific therapy and people run away from it because they have their own impression. So again, another long answer to a pretty simple question, but I sort of think that in particular is something that needs to be worked on early on. There are other folks doing this, but what I certainly don't think enough, we're starting here and hope to continue that.

Absolutely. And Eric, I think you brought up so many important points on how critical it is to open these communication channels with the public and the community and have that support going forward or you're kind of at a dead end once you find a solution. Right. And then who's going to pay for it? Exactly.

Well, thank you for giving me and our listeners a lot to ponder today. And you shared some great insights about your life and your career throughout our interview. But there's one last thing I'd like you to give our listeners, and that is a piece of advice. What is the best piece of advice, Eric, that you received at some point in your career that you can share with them today? Well,

I grew up in a sports environment and I think the almost tough love advice, which may or may not be appropriate today, but I think if you spin it in this way, it actually makes some sense. And that you have to accept failure as part of the learning process. And it's how you respond to failure that will enable you to succeed in the future. So

Failure is difficult. It's painful. As scientists, we fail every day in multiple ways, but I think it's what you learn from your failed attempts that lead you to success. I heard someone once say that I'm giving you my resume and my resume is a list of my accomplishments. What

What I'd like to really do is give you my resume of failure and that documents a lot longer. And that's the way that I approach science, that my resume of failure is a lot longer than my resume of success. But I kept going and I fought through and we sit here today. Definitely. And I think you learn so much from those failures if you weren't failing. Oh, absolutely. And you have to. Absolutely. Well, great advice for our listeners. Eric, is there any last message you'd like to leave them with today?

I think that there are a lot of good stories around of scientists who were pushed aside, but there's no sympathy for that, by the way. You have to make things work yourself. So I think hang in there. If you've got a good idea, keep fighting for it. And eventually, if it's real, the success and the truth will always come out. Well, excellent message to leave our listeners with. Eric, can you tell them if they want to learn more about you and more about the Gene Editing Institute, where should they go?

You can certainly email me directly at eric.b.com.

at ChristianaCare, one word, .org. We have Facebook at GeneEditingDE, GeneEditing is one word, and then our Twitter account is GeneEditingDE as well. We have a website, so if you look at the Gene Editing Institute Delaware, I'm sure that website will pop up, but we're happy to interact with all kinds of folks, so looking forward to hearing from your audience at any time.

Wonderful. Well, thank you, Eric. And listeners, definitely get in touch, get connected on social media and check out those websites. And Eric, thank you so much for sharing a piece of your story on our show today. Marie, thank you. It's been an honor and a pleasure to talk to you. Well, it's been so much fun to chat with you as well. And listeners, glad to have you here with us. We'll see you next time on another episode of People Behind the Science.