May 19, 2011
Jim Wikel is the Chief Chemist at Apex Therapeutics. Jim served in a variety of positions at Eli Lilly from 1971 to 2004 as a scientist and research manager including Head of Structural and Computational Sciences, Discovery Chemistry Research & Technologies as well as Senior Research Scientist. Jim was Chief Technology Officer of Coalesix Inc. a start up company in Cambridge MA from 2005 until it became a division of Icosystem Inc. in December 2006. His experiences enable him to understand and translate among the disciplines of chemistry, biology and statistics to enable medicinal chemists to optimize molecules for drug development using both predictive models and empirical approaches. He has Bachelor of Science degree in Chemistry and Master of Science degree in Organic Chemistry, both from Marshall University.
"I came from southern West Virginia, the coal fields of southern West Virginia, and it wasn’t that common for folks to go to college...when I retired, I was head of Computational Chemistry and Structural Biology with Lilly."
Interviewed by Barry Bunin, PhD, CEO, Collaborative Drug Discovery, Inc.
Listen to the Full Audio
[audio src="/wp-content/uploads/2020/12/Jim-Wikel-Spotlight.mp3"]
Edited Interview Transcript
Barry Bunin
The first question, a simple one, is just tell me about current research that you’re involved in.
Jim Wikel
The work with the medical school, Indiana University Medical School, is focused on new chemotherapies to treat cancers in children, and so we’re sharing some data with the biologists there. Historically they’ve not been interested in chemistry or chemical structures. They’ve been pursuing compounds based upon the biological drive and the need to understand the mechanism without much of a focus on how to optimize those structures or to tweak them in any way that might make them better suited for their purposes. We’re working with them to try to share that information, to educate them on the chemistry side, and at the same time I’m getting educated on the biology side in this particular area. So it’s working out nicely from that standpoint. Since we have no access to internal chemistry, we do everything through contract research organizations, and so it helps us keep track of compounds and share data internally with what compounds we’re getting made, where they’re getting made and the biological assay results.
Barry Bunin
Perhaps talk a little bit about the academic - industry side of the collaborations as well, since a number of researchers are going to be thinking about this from the industry perspective, as well as others from the academic perspective for the collaboration.
Jim Wikel
The basic science, of course, comes out of the academic environment at the medical school, and we’re taking that outside of the university setting to advance it for the drug discovery and drug optimization process. And so we’ve created a small company, spun out around that technology with the intellectual property owned by the University. The small company (Apex Therapeutics) is composed of some seasoned veterans from Big Pharma who are used to running this gauntlet and understanding what it takes to get from Step A to Step B in this whole process. We’re working very closely with our academic counterparts to develop those compounds and to make them more drug like in their appearance and in their behavior. The experience from the Pharma talent that’s represented in the small group, is being applied directly to the academic discovery that’s coming forth and has turned up the value of those assets in terms of developing a new composition of matter, making the compounds more potent, we hope, more selective, and just making them better suited to be a pharmaceutical candidate.
Barry Bunin
If the work goes as well as you can imagine, what comes out of this - and maybe also what are some more modest goals, it’s always good to think about both. If everything goes well, you had mentioned this is a project for cancer in children, just talk about the inspiration for spinning out a company from this research.
Jim Wikel
We would like to, and of course they would like to take this discovery that they have in the lab, and apply this directly to the patient population, which they see every day, and which they relate to very well, but they don’t know how to get the compound from the lab into humans to see if their idea works. What we want to do by taking it outside the university setting, is be able to apply additional resources, but also to be able to develop it fully with the intent of getting it back into the university setting or back into the clinical settings where we can get the idea and the compound tested on humans to see in fact if it works against the targeted disease. I think the advantage of taking it out, is that we get to apply a broader paintbrush to the problem, and therefore, bring additional talents and skills to address it. We would like to provide to these kids that have been non-responsive, and adults later on too, an additional form of therapy. Our ultimate goal, of course, is then to get this labeled a useful drug, and so that’s where we’re focused. I think then that in the nearer term we’re focused on the identification of a few candidates that we’d like to get additional quantities made and then tested in-vivo. We would like to get some preliminary PK data in order to set us up for a pre-IND meeting with the FDA to discuss what it’s going to take to get into this particular patient population, that is, get their advice about what kind of data will they expect to see. I think we’re on track to do that.
Barry Bunin
Before you used CDD, how did you collaborate or manage your data, and why did you choose CDD at that time?
Jim Wikel
They passed around Excel spreadsheets and/or PowerPoint slides. And I think that was working reasonably well as long as you were within the academic walls. Everyone had the Excel version and since they were all biologists, a simple identifier or common name or some kind of designation on a structure was perfectly fine with all of them. But when we got involved in the chemistry side and we also wanted to go outside the walls and share it amongst a group that was geographically different, then we had to do something else. Passing Excel spreadsheets around gave us the data, but it had certain challenges, primarily the revision log of what version you had….you had the data sheets being passed around and people adding, subtracting things, making their own comments and notes, and so it got to be a real twisted bundle of data. And the other thing that I found as a chemist, that was a real problem, is getting structures into Excel. Getting structures into a format that would allow me to see the structures but not be over burdensome on the biologist who didn’t care about what that picture was. At first we passed Excel spreadsheets around with picture files in them. There were slight problems associated with that in trying to sort the data. The pictures always didn’t get sorted. So we tried a few embedded plugins in Excel with some success, but still not ideal. And of course, even with the plugins, you didn’t have structure searching capabilities unless you could do it in on the SMART or SMILES strings. We could have done it in some of these commercial data bases; an oracle database, SQL type of database, but then that adds a layer of complexity because again, the biologist and many of the chemists don’t have the expertise and don’t really want to go there. We had to find something in the middle that gave the chemist the graphical pictures, the structure searching capabilities, but also didn’t burden the pharmacologist and biologist with that image. And CDD comes through and meets the goal in that. It’s very easy. We found it reasonably easy to use, and the fact that we’re geographically different but have access to all that, gives us the ability to see the data more or less in real time as it’s put into the database with very little training. So it’s easy and intuitive to do.
Barry Bunin
I want to move to a little more personal things on the interview here, which I think will be interesting. You could be spending your time playing with grandkids and probably don’t need to do science just to feed yourself and so forth, so just talk about what you’re doing at this stage of your career and what’s the inspiration? What makes it compelling and interesting to you given all you’ve done in science in your life?
Jim Wikel
Yes, well I’ve been retired from Big Pharma since 2004, and I can honestly say that my retirement didn’t work out, or hasn’t worked out as I thought it would because, like most of my colleagues, after I looked at what they were doing, concluded I would walk away from science. And I had my head set on that was the way it was, that was okay, in spite of the fact that I enjoyed what I was doing in research and in Big Pharma. So I left, turned my back, and headed out thinking that was it. Turned out not to be the case because in spite of all my other interests, I found that I was being pulled back into science through contacts and networks. I have other hobbies. I have grandkids, and I keep a busy day, but I always come back to a large portion of it being science, done at various hours of the day and various levels of effort as the situation dictates, because I find it enjoyable and it’s fun. And when I talk to folks about getting involved with them on projects, the bottom line is that for me it has to be fun and interesting or else I won’t do it. I’m not interested at this point in my life in taking up another job, so I do it because I want to do it, not because I have to do it. I think that makes it completely different in terms of the way you look at the task and just generally take to it. I find that I do spend a fair amount of time at this, but I don’t feel guilty if I go out and do something else, or not put in eight hours a day on a particular research topic. Basically if you don’t have to put meat on the table and you turn it into a hobby, it is very enjoyable. I don’t know when I’ll put it down.
Barry Bunin
So something some folks may not know about you is sort of the different roles that you played at Lilly over your career, and that you rose up to some points of responsibility without having a PhD, and a lot of folks think there’s a glass ceiling, and you’re living proof that there doesn’t need to be, that things can be a meritocracy. And so maybe just talk a little bit about how that came about, and the course from that beginning to where you ended up at Lilly because I think it’s an inspiring story.
Jim Wikel
I don’t know how much of this you want. I’ll give you the whole thing, and you can edit out whatever you obviously don’t want because it was an interesting road even from my standpoint of how I got there. I came from southern West Virginia, the coal fields of southern West Virginia, and it wasn’t that common for folks to go to college. Major employers in my little coal town were coal mining and railroading, so you either worked in the mine to dig the coal out of the mountain, or you worked on the railroad and hauled it away. So that was my life. When I went off to college, I was in the minority at that point, to major in of all things chemistry, which no one had ever heard of in this little town. Everybody thought you went off to college and then come back as a business man or a teacher. I got my bachelors degree in chemistry, couldn’t get a job. In 1969, the only people that were really hiring were the military. They tried to enlist me, and I failed. And so then I was stuck. No job. What do I do? I went on, enrolled in graduate school for a couple years thinking that things would be better in 1971. And they were a little bit better. I applied to, it seemed like hundreds, of pharmaceutical companies. When I was in graduate school and did my thesis research, one of the professors pointed me in the direction of this particular industry. And so when I applied, I got hundreds of rejections. Only one interview offer, at Eli Lilly & Company, and I headed here, did the interview, and got an offer. So I said that was fine, I’m going to go work. Had I not gotten a job, the backup plan was to go to graduate school some more. Where I went had a terminal masters degree, so I had also applied at other graduate schools in chemistry, as Plan B. At Lilly, I worked as a lab rat and did chemistry, learned medicinal chemistry. I had a great teacher there who allowed me some flexibility and freedom to learn and to grow, which doesn’t always happen. I look back, I was very fortunate to get associated with the person. Slowly over time, I grew up through the ranks, and eventually got my own lab with senior responsibilities. About half of my 35 years at Lilly were spent in the lab as a medicinal chemist. Somewhere in the 80s MDL came on the scene, and the power of the computers came in, and I began to get interested in computers. Of course, being of my generation, we were never exposed to computer technology. But I became interested in the power of the computer and how it might apply to chemistry. I had been developing an interesting QSAR, sort of a qualitative sense back then, since you didn’t do any heady mathematical calculations or compute any properties or anything we take for granted today. It was basically Dreiding models and a piece of paper and a pencil. So I got interested in the MDL software and began to dabble, and to actually write little programs. I hacked a little Fortran back in those days and DCL, DEC command language, and began to take things out of MACCS and reshuffle and put them back into the MACCS software and display them. I learned tricks like that, and began to take the tool and make it more useful for laboratory science. That eventually led into the opportunity when Lilly acquired a Cray supercomputer, about 1989, that created a computational chemistry group. I left the lab and joined that group of, at the time, I think probably three physical chemists, one crystallographer and myself. That group grew over a period of time and eventually got to the point where at the end of my career I was the head of the computational chemistry group. There were, approximately 20 computational chemists at that time, and another ten crystallographers that I had in my group, that I had responsibility for and responsibility to those individuals, most of whom were PhDs. And so when I left, when I retired, I was head of Computational Chemistry and Structural Biology with Lilly, and for me it was a great career. I look back, and it was a lot of fun along the way. I learned a lot, continue to learn a lot, and I don’t think I’d change a thing.
Barry Bunin
Okay. That’s wonderful.
Jim Wikel
Is that the story you heard?
Barry Bunin
That’s… Well it’s the first time I’ve heard it in such detail and so beautifully. I think it’s a great story. I had a related question for the scientific audience and, obviously, without disclosing anything confidential, but maybe you can share sort of an 'aha' moment in drug discovery or science, where something happened that just was sort of above and beyond the daily types of experiments and kind of an exciting moment. It could have been in grad school or in industry or wherever - if you have anything to share. That’s my last question.
Jim Wikel
Well I think research is full of those 'aha' moments, and I certainly, as I reflect, had my share of them. I had the opportunity to work on some early process work, as a chemist, to come up with a manufacturing process for a compound that ultimately became a marketed drug for Lilly’s agricultural division. Working out that chemistry provided a number of 'aha' moments on that side. Also I worked on a project, the size and duration is unheard of these days, but we had a research project in anti-virals and for the majority of about ten years, I was the sole chemist on that project. And over the course of ten years, a few people came and went as the intensity heated up, and the discoveries heated up, but it was all pre-molecular biology, so things went a lot slower, and the chemistry, of course, started from air, fire, and water and everything took a long time to do. But in the end, we ended up with putting two compounds into the clinic into the humans, which was very rewarding. On the human context, we had an applicant who came through Lilly one time, who was interviewing as a chemist, and as it turned out, he… Well let me back up a little bit. The clinical trials, the human trials for, in this case, the common cold, rhinovirus, was given to infected patients. You can give that disease to humans. So typically, some of these centers would, at least at that time, take students off of campus during spring break and infect some of them with rhinovirus, and some of them would get placebo, and then we’d treat both groups for a couple weeks, and just measure the runny noses and the virus titers that came out. One of the guys that came through to interview turned out was at a university and had volunteered for one of these studies. We had a good story to tell and exchanged notes about whether we thought he received the drug or placebo. I still don’t know the answer to this day. But that was a nice personal commentary on my career for me, because I related to that whole thing. And I guess from a computational sense, having worked with the Cray-2 in those early days, and having all the 'aha' moments of having spent pre-Cray, 12 to 24 hours doing a MOPAC calculation, and then all of a sudden having a Cray-2 that did the same calculation in a matter of a few minutes, was a real 'aha' moment from a technology standpoint. I just think that I’ve seen a lot in the 40 years. I’ve seen a lot of technology and a lot of changes in the business. I think one of the more recent 'aha' moments that I have witnessed , is that I reflect back over my career as a medicinal chemist in those less than 20 years, maybe making 1,000 compounds, and today, that’s just a drop in the bucket as to what someone could do in the lab. So the difference I tell folks is back then - back in those days we’d end up making a half a gram to a gram, that was just minimum quantity to get a lot of the in-vivo assays and the broad screening done, so it was a different ballgame.
Barry Bunin
I think that’s a beautiful note to end it on, and thank you for your time in the interview.
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