A chemist is not the profession most would guess when first meeting Matt Giese, and perhaps that’s because it wasn’t his first, second, or even third profession. Join us for this phenomenal conversation with Matt, Senior Scientist at Vector Laboratories, where he takes us through his very non-traditional career journey and shares lessons learned along the way. Now working to develop technologies to make antibody drug conjugates (ADCs), we dive into the chemistry of ADCs and the tightrope balance and skill needed to design these for success. This is an episode you don’t want to miss.
Bioconjugation of antibodies to drugs via chemical linkers is how antibody drug conjugates (ADCs) are made. We’re joined by Matt Giese, Senior Scientist at Vector Laboratories, who talks us through the complex chemistry options and biodesign considerations that have to be considered and balanced when making a successful ADC.
How does one build the skillset to work in biodesign of ADCs you might ask? Well, Matt’s career path might not provide a clearcut roadmap like you might hope. That’s because Matt started his career as an auto mechanic, moved into art, went back to auto mechanics, worked as baggage handler and as a construction worker, all before ever finding chemistry. If you think that’s a convoluted path, just wait to hear about his academic and professional work journeys.
You’ll revel in following this journey, and in the lessons and diverse skills learned along the way. Join us to hear it yourself, from who might just be the most interesting man in chemistry!
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Matt Giese 00:06
Building houses, you're taking smaller pieces and ending up with a house and building molecules, you're taking smaller pieces and ending up with a molecule. And like that's when I really fell in love with like synthetic chemistry and it just blew my mind that you could do that.
Paolo 00:23
It's been a long time since Matt Giese a work on a construction site, but he's been building things for his entire life. For the past 20 plus years, he's added skill after skill to his professional toolbox, from assay development to synthetic chemistry and bioconjugation. And his journey through science is as wide ranging as it is fascinating. Thanks for joining us for this season five episode of Bringing Chemistry to Life. I'm your host, Paolo Braiuca, with Thermo Fisher Scientific. We began by asking Matt about his upbringing and the chapters in his life that eventually lead to a career in chemistry.
Matt Giese 01:01
Lucky has got a lot to do with it, hard works got a lot to do with it. Yeah. So grew up in South Milwaukee, hardworking and hard playing group of friends, group, a crowd, very blue collar. Got out of high school kind of figured I'd end up being a grease monkey. Went to Tech College to learn auto mechanics. I mean, we knew lot because that's just what we did. We'd sit around a wrenched-on cars, but figured out it probably wasn't something I wanted to do eight hours a day. And one of the instructors saw me, I was scribbling in my notebooks. So just drawing, sketching. So he's like, "You know, we have a great art program here. Why don't you try that?" So that's when I switched over to art and went to school for commercial art. Got my first associate's degree in commercial art. Got out of there and had a hard time finding a job. And that was kind of a unique experience for me, maybe a good learning point. Because there were people that were super good artists, right. That wasn't me. I was not a great artist. So all these guys that were that were super good they ended up getting jobs. And then there were people that maybe not as good as me, but man, they hustled. And they got the jobs, right. And so then I'm like, "Okay, what am I going to do now?" So went back to mechanics and worked as a diesel mechanic for a while, more like a fleet mechanic, a lot of trailer maintenance on the semis, you know, you didn't actually get to tear apart any engines. Did that for a minute and decided, yeah, mechanics wasn't for me. So that's when I went back to tech school for construction, residential construction. Man, that's a hard-earned day. Almost everybody you're working with is nursing injuries from falling off roofs or walls, or something. So that's sort of, that's when I started thinking, "Yeah. I probably don't want to do this till I'm 60. I'm not sure I'll make it." So I decided, well, maybe I'll try school. I didn't do that well in high school. So I looked at UW, this was back in Wisconsin, and started cramming for tests to get in. Switched to a part time job at a gas station to start making some money, and then I worked another part time job unloading cargo planes, at General Mitchell airport. So I work at the gas station, second shift from like, three to 11. Then I go home and sleep from like 11 to one and then at two o'clock AM I'd go to the airport and push cargo off the planes. And then you go home and sleep for a little bit. Wash, rinse and repeat. Until you get enough money and school starts. So my parents were great. They, as long as we were in school, they didn't charge room and board. Right. So that that was kind of a good deal.
Paolo 03:36
It's, but it's unbelievable, man. I mean, you know, if I think about when I was younger, you know, and I wasn't coming from a wealthy family at all, you know. Honestly, I didn't have to work for an hour, you know, in my entire life just took some jobs when I was at uni, you know, some points. And I was a football referee so you could make some pocket money, right. But you know, the way you're describing, yeah, I mean, oh, it's, I don't think it's something that many people can do. Would you consider it normal or is it that was it just the way it is?
Matt Giese 04:10
Yeah, sure. In like a blue-collar towns, people work. You know, your bricklayers and masons and carpenters and machinists. And yeah, they
Paolo 04:22
So, how many of your friends or people you knew went into science?
Matt Giese 04:28
None back then. Yeah, none. Yeah, I had no idea. I, like I said, high school was not my thing. And I was not in the science classes. I was in the trade classes. So when I decided to go back to school, you know, I got I got in. But I had to start way at the end. I know how to work. I just got to figure out how to apply that to academics. And that's kind of what I did. And I ended up actually finding out I really liked it. Right. I started out taking the math courses and I'm like, "Oh, this is pretty neat stuff." I was actually doing math when, I was doing trig when I was building houses, I just didn't know it. Right, you're doing rafter layout, you're doing skylights, I had no idea. And so it turned out, I really liked math. And then I got into the science classes and really liking chemistry. But I still, I kind of had that driven work ethic where, you know, the professor would say, “Well, do every other problem.” And I do every problem. Right. I read my calculus book and took notes on my calculus book. Like, I just kind of had that thing, because I learned pretty quick if I didn't do that, I wasn't passing the tests.
Paolo 05:37
From being a good student to kind of developing a high level of scientific career. You know, there's some, you know, there's several steps, right. So, you know.
Matt Giese 05:48
Yeah, I had a professor in undergrad, he was Dr. Judge, he was fantastic. He, he was a P-Chem Professor. And so he had a P-Chem lab, an old tube spectrometer. And so he asked if I wanted to work in his lab, do some spectroscopy. I was like, "Heck yeah, so let's do it." You know, so he's the one that started getting me into actually doing the research side of things instead of the, just the book learning and, you know, that sort of thing. And he's like, "Have you ever thought about grad school?" And I'm like, "What's grad school?" He's like, "Well, you go on for, you know, another couple of years, and you get like a master’s or PhD." I was like, "Oh, I can't afford to do that for another four years." He said, "Well, they pay you." I'm like, "What?" And actually, I had met my, my girlfriend, and now my wife, at the time, and she was planning to go into grad school, too. So yeah, we both went on to grad school after that. I got a master's was doing material science and was pretty good with math. So I thought I was going to end up in P-Chem. Somewhere about two years in I was like, "Well, I'm not sure this is going to get me into industry." I didn't think I wanted academia. And then Laura got a job offer at Eli Lilly and Indianapolis. So we're like, yeah, let's, we went to Indy. And she started at Eli Lilly, and I was looking for a job there and got hired by Roche Diagnostics, as a temp. But I really wanted to be more in the chemistry side of things. I asked if you know, they could move me to chemistry, they didn't have any openings. So then I started looking at IUPUI there, and Dr. Moser had a really cool program at IUPUI. So I applied there and got in and I left Roche and went back to grad school again. And that's when I got into organic chemistry. And that's where I found synthetic chemistry. And that was cool. Because that was right, building houses, you're taking smaller pieces and ending up with a house, and building molecules, you're taking smaller pieces and ending up with a molecule. And like that's when I really fell in love with like synthetic chemistry, and it just blew my mind that you could do that stuff. Got through that, ended up leaving there with another Master's. Because at that time, Eli Lilly is in town there. And they had opened up hiring, I think it was Pharmacia had just like, shut down. But yep, that's when I started at Lily and I loved it there.
Paolo 08:06
So what were you working on? What were you working on there?
Matt Giese 08:08
Discovery chemistry, med chem, the group I was in was nuclear hormone receptor modulators. And so you're learning all these pathways. And that was just so cool.
Paolo 08:19
And I guess doing it in a place like Eli Lilly must be super exciting, because you got all the best chemists working there, you know, the facilities, right? And all the equipment and everything you want?
Matt Giese 08:29
For sure. Yep. drug development is not easy. And it takes a lot of smart people and it takes a lot of resources. And you know, the chances of failure are pretty great. I think we had one molecule go to candidate selection, but nothing ever came of it.
Paolo 08:44
Well, even getting that, even getting there is rare. There are many people who can say hey, they you know, worked on a commercial drug. Especially from the med chem space. Right?
Matt Giese 08:54
Right. Yeah. Yeah. My wife was there in biologics, large molecules. And her group is one that worked on Trulicity. So it's not to you know, she actually did have one that eventually made it.
Paolo 09:07
That's cool.
Matt Giese 09:08
Made it out the pipe.
Paolo 09:08
That's cool. Chemistry is so fascinating. So how long have you been at Lilly?
Matt Giese 09:14
I was there about six years in the med chem. And after about six, Laura had been there just over 10. And it's just one of those things again, we decided to maybe do something different. She wanted to go back to grad school. Had actually taken a love of horticulture and actually ended up in Ohio at Quanta Biodesign. And she was at OSU for horticulture. So that's where I got introduced to bioconjugation and making these linkers at Quanta Biodesign. Their product line is based on like a dPEG Linker. So it's, hydrophilic things happen in aqueous systems in us so a lot of the linkers at the time for doing that were glutaraldehyde or SMCC, LC, just hydrophobic, kind of nasty. So that's kind of where I started getting introduced to linker. Paul gave me Bioconjugate Techniques from Greg Hermanson. These days, almost everybody's held the bioconjugate in their hand. If you've taken a COVID test, you've held a bioconjugate in your hand, right. It's either a primary or a secondary antibody loaded with labeled, conjugated to a latex dye for you see that strip show up.
Paolo 10:23
What's the fundamental building blocks of bioconjugation, in terms of chemistry? You know, you mentioned aldehydes, right. So what are the functional groups that people leverage and what is what is the mainstream and what is the frontier?
Matt Giese 10:33
So it's going to depend what you're conjugating. If one of your components is a small molecule, you can pretty much do any sort of chemistry you want, you know, at that end. But mostly what you're looking at are hetero bifunctional linkers where you have reacted groups on either side, so you can first react with this and then react with that. And then when you're looking at the biologic component, traditionally, your targets are going to be like lysines, cysteine residues, you can reduce the disulfides and have cysteine residues.
Paolo 11:05
Okay, so all you do carbon, I mean, reactions.
Matt Giese 11:09
Yep. Do active usually it's going to you're going to do an active ester reaction at the lysine and maleimide conjugation with a cysteine. There's a lot of other groups now for reacting with maleimides because the, or with cysteines, because the maleimides can have some issues with reversibility. So there's alpha halo acetamide, there's a aryl maleimides, there's maleimide acetyls. The issue with those chemistries, they've been good, but certainly with lysines, it's kind of a stochastic conjugation process. There's what 90 some lysines in an antibody. So which ones are you conjugating to? You're always dealing with this, you know, not all of them are being reacted, some you end up with dead ends, where you're not putting a payload on once it's reacted. So that's always been a challenge with lysines. With cysteines, because there's a limited amount, a lot less. And now there's techniques, there's companies now that you have, you can conjugate to the glycans on antibodies. And that gives you a really specific way to do it, because you trim these glycans down, and you just have two conjugation sites. And now at this point, you can use biorthogonal reactions. Where your crosslinker has a reactive group that's only going to react with that spot. So now you can actually start controlling your stoichiometry, you can start controlling your drug loading. So that's kind of, that's a really attractive approach, because you can still use the native antibody. Right, you can still you can trim those glycans down and it's still a native antibody.
Paolo 12:44
And as a way of controlling where you link, the orientation you will have in your final whatever, conjugates, right, and you sort of thing?
Matt Giese 12:50
Yes, another way is the hinged disulfides of the antibodies. So the disulfides, you can reduce those down and you get your eight disulfides. And a lot of times, if you're not fully saturating them, you still end up with stochastic contribution, but then you're always getting a DAR, or loading of eight. But now they have these rebridging reagents that will rebridge those disulfides. So you can get exactly a DAR of four and it also restabilizes that. So there's ways to start manipulating these native antibodies. There's also it's really cool, they've got these FC affinity peptides, and then they've got a little tagging reagent out on the FC affinity peptide, it will kind of stick that at FC reagent and just tag a specific lysine. And then you cleave the peptide away, and now you've got one reactive group down to that FC region. So there's ways that people are trying to use native antibodies and still control the amount of reactivity. Kinda on the horizon stuff is this genetic code expansion.
Paolo 13:52
That's just using the unnatural amino acid as a linking point for? Okay, I see.
Matt Giese 13:55
Yes, and this is big stuff, because these, at least on paper right now. So you get these non-natural amino acids in there. Carolyn Bertozzi started all this biorthogonal click chemistry stuff. And that's big, big. This is a case where you're going to start having this convergence of a lot of different technologies. Good protein engineering to introduce these biorthogonal sites for linking. Good chemistry to actually make efficient bioconjugation reactions, right. I mean, the copper click is okay. But now there's the copper free clicks. There's the inverse electron demand Diels Alder. Oxine ligation is kind of old, but that's still that's still pretty popular, it's another biorthogonal reaction. So those are actually becoming really cool. And then I think the, our products, these PEG linkers, they're also going to help with that because your traditional alkyl linkers because of their hydrophobicity, there's only so much you could do. Right. You can't, you can't make these large constructs and stick them on there because you're going to turn your biologic into a greaseball. But now when you have these linkers that we make that are hydrophilic, we have a lot of different architectures, you can make with them, a lot of different orthogonal functionalities on them. You can take that one conjugation site and put, you know, multiple payloads on and do it with a hydrophilic linker, so you don't end up with a greaseball on the end. So I think it's probably a convergence of a lot of those different technologies.
Paolo 15:29
We hope you're enjoying this episode of Brining Chemistry to Life. But rather than hope you are, we'd really prefer to hear from you directly about what you're enjoying and what you might like to hear more about. Send us an email at helloBCTL@thermofisher.com to tell us. We read every single email. Once again, helloBCTL@thermofisher.com. I hope to see a note from you there soon. And now back to our conversation.
Paolo 16:03
So what drives, what drives the selection? Because you know, you have several options here, right in terms of chemistry, you use, in terms of the functionalities you add, and in the chemical nature of the linkers, right? You know, what drives the rationale for what to start from and how to develop it further when you when you're at such projects?
Matt Giese 16:20
It's probably going to depend on, well one, how does it affect the functionality of your ADC? I don't make ADCs, so I don't run the assays. I don't understand that. But certainly people are first they're going to figure out how does this affect the functionality of the ADC, just
Paolo 16:35
ADC, for the sake of the non-experienced, is antibody drug conjugates, right?
Matt Giese 16:39
Yes, yeah. So how does it affect that? How does it affect its interaction? And I think one of the big things, and this was probably not appreciated for a while. So you've got a, you've got this massive antibody, right, 150 kD. You put this tiny little molecule on and you're like, "Oh, we're going to stick it on there, it's going to be fine." Turns out, it alters its properties pretty significantly. And that was kind of a big thing in the field of ADCs. Like, you could only get to like a DAR four, right, if you could load about four molecules on there before, it would just start being a nasty aggregate, start precipitating out of solution. The more hydrophobic they are, they get cleared non-specifically. And this is kind of an issue because a lot of these ADCs and drug delivery systems, they've got a linker to release the payload, but if that drug delivery system gets in a cell, that payloads come off. Even if it's not the cell that you initially decided to target. So these nonspecific interactions, I mean, that's, that's the number one killer of ADCs in the clinic right now, is this off target tox.
Paolo 17:46
It's a very delicate balance, probably right, not an easy one to find?
Matt Giese 17:50
Not an easy one to find.
Paolo 17:51
If it was easy, you know, you wouldn't need people like yourself working on it. I let my curiosity you know, jump into the technology. And as the fascinating discussion. I can have, I feel like I've interrupted your story, because it's your, your this, you know, describing your first encounter with bioconjugation when we jump into it, because it's so fascinating. But let's, yeah, let's step back for a minute, being an organic chemist, starting dealing with these macromolecules, was it was he scary, difficult or natural?
Matt Giese 18:24
It was kind of natural. So the main technology at Quanta is building that dPEG backbone. So I've actually never made our backbone. Like that, that wasn't what I was brought in for. I was brought in to try to functionalize the ends to introduce, you know, a lot of the portfolio at the time was your typical maleimide, NHS type chemistry. And you need to keep up with new technologies. So that's what I was brought in for it, I tried to make synthons to help get those other reactive groups on the end. And also to start expanding the portfolio into the functional products themselves, where we started putting fluorophores out on the end, started putting chelators out on the end. So I really was doing a lot of small molecule synthesis. The challenge came when you put it on a PEG, right? So at Lilly and dealing with small molecules, you're dealing with pretty traditional organic molecules, you're trying to make carbon-carbon bonds. When you start making some of these dyes that are sulphonated dyes, or you start making some of these chelators or you start making NHS esters, which are reactive to water. Suddenly, you start having to new learn a new set of tricks. Anybody can make the bonds on paper. Now let's see you put that thing in a bottle here. Some of these things aren't really that amenable to chromatography either. If you have this massive PEG and you do one little manipulation out on the end, it's no guarantee you're going to be able to separate those by chromatography.
Paolo 20:00
Not even, not even by prep HPLC or something like that?
Matt Giese 20:03
Look, when I first started at Quanta, we were literally in garages. Literally. Okay, that's where,
Paolo 20:09
It's not like it's for level technique to use routinely. Yeah, sure. For sure. Sure.
Matt Giese 20:14
Right. So we really tried to avoid having to use any sort of prep-scale HPLC, or anything like that. And some of them were still manual. Eventually, we moved to pretty much all automated silica gel if we could. But really, once you get to the multi kilo scale, that's not an option anymore. And that's where, you know, our guys have kind of figured out, there are some inherent processes in building these things stepwise. It's just what nature is, right. You're always going to fight with these depolymerization reactions. So you just kind of figure out tricks so you're always dealing with the devil, you know, versus, versus the devil you don't. And that way, you can force these things in ways that and, you know, the way that they figured out how to process these things and can do it at scale without chromatography is pretty impressive. So I mean, it wasn't, it wasn't a huge jump. But certainly, I had to start learning new tricks on how you kind of get these things out of water, what kind of solvents you can use. Like I said, the bonds you could deal with, but once you put an NHS ester on there, you're not going to go shaken it up in bicarb or anything, right. I mean, you got to, you got to kind of treat it carefully in order to get your product clean. So yeah, that was that was kind of, I wouldn't say it was a huge change, you just think it's like anything, even when I was at Lilly, you know, the first scaffold that I was working on was based on these dibenzyl subarones, and when you switch to another scaffold like an indole, you kind of have to learn a new set of tricks to make these different scaffolds. I think you kind of build this toolbox, you understand how to first you know, find what you're looking for, track the reaction. And I mean, those are the first things that you, and these kinds of things apply no matter what you're kind of trying to deal with.
Paolo 22:06
By at that point, you had you had the experience, the expertise, I would say or more the experience and you know, that the mindset to, you know, identify and embrace the new tools or the new chemistry, right? And, you know, at the end of the day, it's, it remains making new molecules?
Matt Giese 22:25
Yeah, that that wasn't a big jump, probably the bigger job was we were there a couple years and then we ended up going to California for a bit. There was an opportunity out there to work in it was a it was the cannabis business. They wanted to do some legit research and look at doing some different novel cultivars. So at the time, the only approved use for THC was like chemotherapy induced emesis. But the big reason people discontinued it is they don't like being stoned. Not everybody really likes being stoned. So G, GW Pharma, they had a 2:1, CBD:THC extract. So, it wasn't a native plant. So the goal was, can we kind of figure out how to make these native plants that are two to one that people would tolerate, because most people did not like, like the other ones. And we were actually able to develop these assays. So the analytical assays, there were some stuff in the literature, but it wasn't amenable to high throughput, right. If you're doing breeding, you got to move some material.
Paolo 23:27
So well, what was the nature of this technical, sort of analytical analyses? The LCMS or the GC/MS?
Matt Giese 23:34
Our big sets of analytes, where the cannabinoids and terpenoids to leverage the entourage effect. The cannabinoids, we were looking at just HPLC-UV, and the terpenoids we were looking at GC-FID. So the initial thought was yeah, let's use a mass spec. Right.
Paolo 23:54
Yeah. That's why I instinctively went there, right. You have big complex mean mixes, right.
Matt Giese 23:59
Yes, that's where we started. The issue with mass spec was when you have analytes that span such a range of concentrations, right. If you're looking at trace amounts of cannabinoids, up to 30 to 40% by weight, that's a huge linear range. And when you're looking at terpenes, that can range from you know, half a percent, up to 3%, that's a huge range. And mass spec, it became really problematic to try to get a linear range that satisfied our requirements for rapid throughput. So what we did initially is we use mass spec to at least identify the analytes, identify retention times. Terpenes you could buy standards, at that time, it was pretty difficult to get analytical standards for cannabinoids, you couldn't get you couldn't get them all. So that was certainly one thing we had to do. So we settled on GC-FID as a really broad linear range. It also has the benefit that it's somewhat universal if you have the same number of carbon atoms, so since most of your terpenes by classes are same number of carbon atoms, if we couldn't get a standard, we could kind of use the calibration curve for the one we had. And then that also held for UV. There were some standards, we couldn't get for cannabinoids, that then we could use the UV as a surrogate until we did that. So those were kind of the assays that we used. And then we had to also incorporate internal standards. Because your processing plant material, and how much material you, analyte you lose in processing can greatly affect your results. So we had to figure out how to do that. There were some published methods, but they would use controlled substances as internal standards. And that doesn't really help the situation. Now, if you're trying to get a lot of material through. There were certainly technical hurdles. When you're looking at, say cannabinoids and a terpene profile from a same sample, you can't really treat the sample the same as they would in the literature, you can't, you can't throw it in an oven and dry it because you drive off all your volatile analytes. So that was kind of interesting. This is where cross learning comes in. We just sat down and said, this is me, and Laura, and my boss Mark at the time, we had some brainstorming sessions and we settled on chemical desiccation. A lot of us had chemistry backgrounds, Dry-Rite. So we, we would take the samples, you put them in a tub of Dry-Rite. And yeah, we had great results, just drying them down establishing moisture content, and it would maintain the native profile of the analytes. Because you could not process these things wet. So it was yeah, it was a blast. It was a blast. And once we got that done, we figured out how to crank these through on throughput. And then started doing the marker assisted breeding and selection.
Paolo 26:51
Your toolbox keeps expanding and getting bigger and bigger and bigger and never, never stops, I guess. That's you, isn't it?
Matt Giese 26:57
Yeah, the downside of that is I feel like I'm probably not an expert at any one thing. I've, you know, I know a lot about, or I know a little bit about a lot of different things.
Paolo 27:10
But you have you have an unusual set of tools that allow you to tackle some problems that other people might be unable to, you know, that's another way of looking at it. And you know, so you're very good at that. So how do we get back to the labs?
Matt Giese 27:25
Okay, so this is very recent. Paul had been there a while running Quanta, and decided it was time to, for an off ramp. And Vector acquired us. And Vector has been great. So they've been around for a while, in the diagnostics area. They have an entire portfolio based on bioconjugates, right. So its secondary antibodies conjugated to enzymes and dyes for IHC. And so they've been in the bioconjugates space forever. And because we make linkers that are used in a lot of biopharmaceutical applications, that also becomes very critical, because whereas Vector had tools for helping develop biopharmaceuticals, they weren't always incorporated into the end product. Now, we have also the under the same umbrella products that are incorporated to the end product as well. So it's kind of this comprehensive portfolio of tools to both develop and produce biopharmaceuticals. Since they came on, my role as had been a little different. I've been out of the lab trying to provide subject matter support to sales and marketing efforts. Been a great bunch of people. We’re looking at, you know, how to consolidate, streamline other portfolios, things like that, and get the message out that these products can be used. And I think it's an interesting, it's an interesting point in biopharm as you start getting antibody drug conjugates becoming popular, Vijay is out at UCL on your side of the pond. And he's been doing some really cool stuff, putting antibody fragments together into these multi-specifics using click chemistry and PEG linkers to join everything. And it's, you kind of have this ultimate Lego set, whereas you start getting these more advanced chemical reactions, and these advanced linker architectures, it's really a Lego set on how you want to put things together and how you want to optimize. And maybe in the end, you want to switch to a recombinant technique that's scalable to generate your product. But these technologies do help you, hopefully, develop something faster. So yeah, that's, that's been a fun time with them.
Paolo 29:35
Really, it's really cool. And, you know, and this is possibly the most exciting chemistry, right. The boundaries with biology, you know, it's getting more and more exciting. The applications are ramping up, it's real stuff.
Matt Giese 29:48
For sure. Yeah.
Paolo 29:49
Yes. Lots of fun for you, going forward?
Matt Giese 29:52
I think that's it's kind of given second life to, I think for a while maybe synthetic chemistry and med chem was kind of a hitting a nadir and now the fact you have a lot of these bioconjugation techniques to function as drug delivery systems to help them you know, improve their therapeutic windows, we can offer products to help that out.
Paolo 30:13
It's a constant rebirth for chemistry. So right, it keeps reinventing itself. It’s been a great, a fun chat. And I need to get to my final question, which is always the same, right. You know, after all these, well, fairly complicated and fascinating, ride, what have you learned that you'd pass on to as a suggestion to somebody just starting?
Matt Giese 30:33
Based on my experience, I'll give them a quote from Quincy Jones, "When a job has just begun, never leave it till it's done. Be the labor big or small, do it well, or not at all." Find something you like to do and put in the effort to do it well. There's a lot of satisfaction from walking away from a job well done, right. One of the most satisfying jobs I've ever had was building houses. Standing back and going "That wasn't there when I started the day", right. You get that a lot in chemistry, you get that a lot in science. And if you if you find something you like to do, it's going to be a lot easier to put in the work to do it well, because like I said, you're going to have to put in the reps. There’re some gifted people out there, I was not one of them. Sometimes you got to put in the reps to get it done.
Paolo 31:18
That is, there is no real, there is no gift, there is no cheating, even if you're gifted.
Matt Giese 31:22
Yeah.
Paolo 31:22
If you don't put the work in.
Matt Giese 31:23
And I think if you do put in the reps, and you know, something funny happens is you learn some things, right. You end up learning some things and maybe more importantly, you learn how to learn things. And maybe more importantly than that, you learn how to realize what you don't know. So then you can go back. And so it's like this cycle, you know, and I think if you find something you like to do, that cycle is never ending and it can keep you occupied and happy for a really long time. And on the altruistic side, hopefully you're doing something that benefits people's health, benefits society, you're making medicines, which, if anybody, for any anybody needs medicine, you know how important that stuff is, I mean, it can truly improve the quality of lives. So yeah, that's probably what my advice would be, find something you'd like to do and get after it.
Paolo 32:11
That was Matt Giese, senior scientist at Vector Laboratories in Columbus, Ohio. If you enjoyed this conversation, you should enjoy Matt's book, video, podcasts, and other content recommendations. Look in the Episode Notes for a URL where you can access these recommendations and register for a free Bringing Chemistry to Life t-shirt. And if you haven't yet this season, please consider leaving us a positive rating or review wherever you listen to the podcast. It helps more people to find our show, so thank you in advance. This episode was produced by Sarah Briganti, Matt Ferris and Matthew Stock.