Dr. Patrick Fier got a bit of a non-traditional start to his chemistry education and decided early that a career in academia wasn’t for him. Once he discovered pharmaceutical process chemistry, he found his purpose and passion for applying his creative approaches to organic synthesis. Hear his story and learn about his efforts to make Molnupiavir, the so-called COVID pill.
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Process chemists are the silent heroes of modern pharmaceutical sciences. They take a drug molecule coming out of medicinal chemistry research and make sense of its chemical synthesis. With tight deadlines they often must completely reinvent chemical syntheses to meet strict efficiency and cost requirements necessary to move drugs to commercial production. It’s a challenging job that requires discipline and pragmatism, but a certain dose of chemical creativity at the same time.
Patrick Fier, from Merck, represents the perfect profile of a great process chemist. He makes the most of the incredible resources and the culture of innovation available at Merck. His chemistry is creative and intriguing, he shows that unique mix of disruptive thinking and disciplined determination that is needed to design state-of-the-art chemical syntheses. And his talent gave him the opportunity to lead the development of Molnupiravir, the so-called COVID pill, one of the most promising antivirals used in severe Coronavirus cases.
In this unique episode we have the rare opportunity to get to know a chemist who really played a key role in helping address the COVID pandemic.
Keywords: process chemistry, COVID, molnupiravir, COVID pill, pharmaceutical development, drug, antivirals, C-H functionalization, sulphonamides, phenol synthesis, medicinal chemistry, Merck Sharp & Dome
Dr. Patrick S. Fier 00:06
What really excites me is like working on developing a process that's used to supply patients with medicine around the world.
Paolo 00:14
Patrick Fier's doctoral mentor has said that Patrick invents more chemistry on a Friday afternoon than most people in a week. In 2020, he has lead Merck's research on COVID-19 antiviral drugs. So those Friday afternoons are really worth something, indeed. In this season three episode of Bringing Chemistry to Life, we speak with another member of Chemical and Engineering News' 2021 Talented 12 about their work and trends in their field. I'm your host, Paolo Braiuca, from Thermo Fisher Scientific. We began by asking Dr. Fier about his early education in Iowa and the choices that led him to his role as a global leader in process chemistry.
Dr. Patrick S. Fier 01:01
Yeah, so growing up, I mean, I grew up in a typical Iowan family, you know, surrounded by farmland. And, you know, I worked my way through high school and working kind of odd jobs at grocery stores or bussing, tables, telemarketing. I didn't want to spend a lot of money on college, I went to the community college initially, which was near my parents’ house. I had some interest in science, I didn't really know what I wanted to do I it's probably a bad reason choose career. But I started watching like medical shows like House and Scrubs was oh, that seems pretty cool. Completely, you know, oblivious to so far-fetched from reality. You know, I'll be premed or going to med school and become a doctor, I transferred to the University of Northern Iowa, I think in 2007, after two years of community college, and then I started taking, you know, premed classes biology, chemistry, you know, organic chemistry, and then the organic chemistry class. It was pretty daunting, because that's, you know, like the med, med student killer, you know, the pre-med killer, like, oh, you take organic chemistry, and you change your career. So, you know, I was very intimidated. So, I actually read the textbook ahead of time, you know, it's like a 1200-page book, I read it in advance. Something just sparked in like, oh, this is so cool. You know, the creative aspect, like the multi-step, synthetic planning, just understanding how reactions work is really cool. And then, when I was taking the chemistry class, I had no idea that there was even like, jobs for chemists. I mean, of course, I applied to a bunch of grad schools, you know, Berkeley, Harvard, MIT. I didn't get into any of those. But I did get into Illinois. So, I actually started my PhD at Illinois. So, John Hartwig was there at the time. So, yeah, so I started grad school there. And then after a year or so he announced that he was moving the group to Berkeley, so that I actually got into Berkeley kind of through the backdoor.
Paolo 02:49
What role did John Hartwig play in your development?
Dr. Patrick S. Fier 02:53
Working in the Hartwig group was, I mean, a dramatic change from what I experienced, you know, doing undergrad research, and, you know, the Hartwig group is, I think, at the time probably like, 30, to 35 people, amazing to be around these people that, you know, were doing, you know, really cool science. I was being published in, you know, good journals and getting good recognition. And then, obviously, John has developed chemistry that's used around the world, and, you know, really practical applications. And then, you know, John Hartwig specifically, I think, was a phenomenal advisor, he, you know, takes training and teaching very seriously, especially, you know, for young grad students, teaching them how to think critically, you know, teaching them all the fundamentals. And there's a lot of things he does that goes above and beyond to really train people to be scientists.
Paolo 03:35
And getting a PhD, you already were doing, you know, high level science, you have a bunch of publications, really interesting work there. Was there a moment where you understood that you could actually be a chemist full time that that could be your future in your career?
Dr. Patrick S. Fier 03:48
I guess. Yeah. I mean, the first year or so was, was pretty tough to be honest with you. Maybe in my second or third or fourth year, I don't know, when I started coming across, you know, process chemistry papers. And that was really interesting to me, it's like, oh, there's actual practical applications of organic chemistry that can have impacts in the real world. And, you know, it's not just publishing for the sake of publishing. So, you know, once I started learning more about process chemistry, that's kind of motivated me to finish my PhD on ultimately get a job.
Paolo 04:17
You went into Merck, which probably is also not particularly easy must be a sought-after type of job right? Yeah. Was it did you have Merck specifically or did you have like a few pharma was your thing, or did you want to go into process chemistry specifically for some reason, you know, maybe the practicality reason you were you were mentioning before?
Dr. Patrick S. Fier 04:39
Yeah, so I was specifically interested in process chemistry. I didn't actually apply to any like med chem, discovery chemistry jobs. Merck was really the top of my list. I met many people from Merck, kind of in my final year of grad school and super fortunate to get an interview and land a job. Merck is definitely a, you know, intense place to work. It's you know, very fast paced and competitive. And as you mentioned, there's a huge focus on, you know, innovation and new technologies. But that said, I think they also, what's really nice about it is, they take a very serious view on like, developing scientists and making sure people are successful. So, when you start, you know, it's very daunting, but there's a lot of people there to help you be successful and teach you how to become a process chemist.
Paolo 05:21
So moving from an academic research lab into process chemistry, there must be a complete change of, you know, pace and more than objectives, you know, and yet, you seem to have quite a lot of opportunities to develop, you know, new methods and produce innovation. That seems quite unbelievable, for a process chemistry person. Is that normal at Merck, is everyone doing that?
Dr. Patrick S. Fier 05:49
I always say, it's certainly supported, you know, to have these side projects, it's just. Honestly, looking back, I don't know how I did it, to be honest with you. It's, you know, it's hard to find the time to actually do these things. Because, you know, a lot of these things were completely unrelated to projects. You know, so, you know, during the day, you know, I have a full-time job as a process chemist, and then trying to squeeze in time, develop these, you know, new methodologies, and, you know, write papers and do, yes, I and all that, it takes a lot of a lot of work. Honestly, looking back, it's crazy that, you know, what, what we accomplished. But I think, what motivated us to do, it was like, you know, fun, like we would get in the lab, you know, for an hour at a time or so and just run reactions, just, you know, chat and, you know, come up with new things. And it was really fun.
Paolo 06:35
It's interesting, the way you describe it, because it seems to be motivated by passion for chemistry, you know, a bit of a friendship component there. Having, I mean, someone like-minded, you know, common interest, right? So something fun to do. Yeah. And I was kind of expecting that you had some practical motivations, I know, some problems in your process chemistry that you couldn't solve. And, you know, you were looking for some alternative methods, and, and that there might not have been the, you know, the trigger for you. But it doesn't seem to be there.
Dr. Patrick S. Fier 07:03
Yeah, so I would say there wasn't a specific project that we're trying to impact. But, you know, Kevin had been there for, you know, seven or eight years or whatever. And I'd been there for maybe about a year or so when we started doing this. And we had kind of noticed, you know, like, a few things in general that were tricky. One of them being, you know, making phenols, which on paper looks like, it's not really an issue. But in practice, it's actually not trivial. So then Kevin, and I kind of came up with this idea to make phenols more general, and, you know, under milder conditions, better functioning, tolerance, and so on. And, you know, we thought it'd be somewhat practical, but we didn't realize kind of the full potential. So, you know, when we were developing, even before we published it, and we started talking to people about it, and almost immediately, even before it's published, it was demonstrated on a couple kilos scale for a project where they needed to make a phenol and no other method was working. So that was, that was kind of cool. Like, right off the bat. We're using it in process chemistry, and then, you know, we told, you know, the med chem colleagues about it, we published it, and then over the last few years has been used, you know, hundreds and hundreds of times at Merck. So, it's really good. As well, as far as you know, yep. Yeah. So, there's a couple academic, you know, published examples of people using it to make substrates or in total synthesis. And then I have friends at other companies that say, you know, they use it quite a bit. And you know, they're colleagues.
Paolo 08:21
So let me get into some of the details here, because this is interesting. So the, you know, the way you make phenols is typically, well is a, like, an aromatic nucleophilic substitution, basically. So yeah, you start from the aryl halide, and, you know, use very strong basic conditions, and you do the nucleophilic substitution is the problem that when you start having complex multifunctional compounds, then you basically hardly have something which is tolerable or the reaction conditions you were looking for, is it was that was that the start of it?
Dr. Patrick S. Fier 08:50
Yeah, yeah, if you have, for example, an aryl halide, you can make the phenol the SNAr, if you're doing SNAr, typically, you use like something like methoxide, and then you demethylate it afterwards, because hydroxide itself is not a very good nucelophile, you can use in certain cases. And you can also do like CO coupling, you know, with hydroxide. But the issue is, you know, they're strongly basic conditions, high temperatures. And in real molecules, you're going to have function groups that are not tolerant to especially things like esters or memorizable stereocenters, where they just get destroyed. So, we were really looking for something that could react under mild conditions that would tolerate basically every single functional group you would ever have in, you know, a complex molecule. And it's where we came up with these hydroxide surrogate reagents where they're, you know, their oxygen base nucleophiles, but they're quite acidic. So, they reacted under mildly bass conditions. They're also great nucleophiles. So, then they react and then in situ, they actually fragment once you make the initial CO bond to reveal a phenol. So, it actually we had a couple of examples, one with a acetohydroxamic acid, and then another couple of papers with benzaldehyde oxime.
Paolo 09:55
I've seen your paper with the oxime. So, it's interesting because then you use oximes for something else as well, because, you know, it's just like a very interesting creative thinking or lateral thinking maybe yeah. Do you think this might actually get some proper relevant space in, in the license synthesis community?
Dr. Patrick S. Fier 10:14
I hope so I think once people use it, they realize how powerful this. So I think, you know, as more people become aware of it, and they actually use it, think it should become more mainstream?
Paolo 10:25
Have you used it yourself in any process chemistry work?
Dr. Patrick S. Fier 10:28
I have? Yeah, it's been used in a few different process chemistry projects.
Paolo 10:31
Okay, that's interesting. So let me step back a little bit, because, you know, some of our audiences might not be completely familiar about the workflow inform my so it's process chemistry is really they're part of the work, and maybe, you know, jump in and correct me, if I describe it wrong, where you take drug candidates from coming from an ISA chemistry, drug discovery, and, you know, you actually need to make a process that can be put into a plan to make them commercially viable, right, and just get them up. And, you know, I mean, something which is robust. In the old days, medicinal chemists had to just use whatever methods to produce as many compounds as quickly as possible. So process chemists usually had to start from scratch pretty much. Is this still the case these days, or has the sort of culture or the pharma workflow changed a little bit at all, in any way?
Dr. Patrick S. Fier 11:22
It definitely is a case by case basis. But a lot of times, like the the goals of discovery, chemists are very different than the goals of process chemistry. So like the syntheses, that, you know, med chemists are using could be more for, you know, SAR or multiple for SAR, where it's more, you know, divergent, and you know, complexity oriented. Whereas in process chemistry, you have a single target, just one the best way to make that one target. So, in many cases, the synthesis completely changes. And, you know, our goals are very different in discovery chemistry, if you're starting material costs, you know, $1,000, a gram doesn't really matter. But in process chemistry, you need something that costs, you know, $1 a gram, actually, typically, much less than that. So the goals are completely different in a lot of times, we start from scratch, but also, we have a lot longer time to figure out a synthesis to a molecule. So that allows us to invest in, you know, coming up with new reactions coming up, you know, a lot of times with enzymes to catalyze reactions, you know, evolving, enzymes can take a lot of time, and then you had new technologies, such as biocatalysis. And, you know, flow chemistry really come into play.
Paolo 12:25
And I'm assuming you just rely on the specialist for that. So once you have something which is amenable for biocatalytic transformations, and whatever other type of specialized catalysis, you probably have the right this, specialty teams helping out in the project.
Dr. Patrick S. Fier 12:39
Yes, we have a really strong group of in the biocatalysis group and protein engineering that you know, can identify the initial enzymes do the evolution work, and really develop this enzymatic transformation. They're, you know, awesome team, a lot of them are trained synthetic chemists are even process chemists that moved into biocatalysis later in their career. And there's also a team in flow chemistry that, you know, has expertise in flow chemistry and developing these processes where they can benefit from flow.
Paolo 13:08
Do you enjoy trying new things and getting into completely unexplored areas for you? Do you see this as learning growing opportunity? Are you? Are you ever scared of those?
Dr. Patrick S. Fier 13:19
I think initially, it's kind of daunting. Yeah. Like the, you know, the first time I was using or doing a biocatalytic step, I think from the outside, I was like Oh, by biocatalysis is so complex and scary, and is it alive. Then you start then you start working on you're like, okay, this isn't that different than, you know, normal chemistry. And you can still optimize in same way you can. Obviously, there's subtleties that make it much more complex in certain cases. But I think, yeah, it's normal to be kind of maybe scared visually. But, you know, things are not as complicated as they may seem. And again, there's people there to help you and there's experts that can help you figure out what's going on and come up with a solution.
Paolo 14:00
Do you think the average synthetic organic chemist is a bit conservative, and they look at these sorts of novel techniques with suspicion?
Dr. Patrick S. Fier 14:09
Um, I think at Merck not, but maybe in the broader community I think, yeah, I think enzymes are becoming more and more mainstream, but I think there's still a huge barrier to doing that. Even other technologies like high throughput screening, which you know, Merck's been involved with for 15 years or time, yeah, I don't know when. I think even that like in grad school, we tried to implement that technology and I think there's a huge hurdle to just doing it for the first time like setting up a 96 well plate of reactions just seems so overwhelming, but once you start doing it, you realize the power and the capabilities of that.
Paolo 14:45
So, the challenge is really setting up the work culture to be able to stimulate the sort of kind of process you need to try, you know, seeing the bio accepted.
Paolo 15:03
We hope you're enjoying this episode of Bringing Chemistry to Life. Have you heard about the rebranding of Alfa Aesar, Acros Organics and Maybridge into Thermo Scientific? Well, if you haven't, why don't you have a look at thermo fisher.com/chemicals and find out about Thermo Scientific, the new kid on the block of laboratory chemicals. That is also where you find the podcast, new home, and a lot of information about our guests. And now, back to our conversation.
Paolo 15:30
I like to jump on some of some others of your show to lateral works, because you know, your methods for synthesizing phenols are one, you know, I was reading a couple of your works on the CH functionalization period in that I noticed, you know, the commonality with the use of all these oximes. So, the reagents, and I was wondering whether that is that is the common point between, you know, your work on the phenols in this one, or if it's a complete chance. It seemed to be like a potentially very interesting case of chemical creativity and lateral thinking.
Dr. Patrick S. Fier 16:05
Yeah, kind of common theme between a lot of the work I published at Merck is like breaking, like nitrogen, hetero atom bonds, oxygen, but in other cases, like sulfonamides cleaving the NS bond. Yeah, there's definitely commonalities there. But they're kind of serving different purposes, like in the phenol case, like that nitrogen oxygen bond fragments reveal the phenol, and that also makes the oxygen more nucleophilic. And then, you know, in the pyridine in case it's acting as an oxidant, and then there's sulfonamide case, like it's a way to, you know, clean NS bond. So, yeah, there's definitely a lot of overlap there. Yeah.
Paolo 16:42
Yeah, it was, yeah, at some point I was reading so well, this guy, he really, really likes these oximes. And then, but, you know, it just makes a lot of sense, right? Because, you know, once you find the utility in a way, you know, you're tempted to kind of look at it from different angles and say, well, maybe there at some point, at any point, your logic or if it just happened by chance?
Dr. Patrick S. Fier 17:06
For a lot of these projects, that was identifying synthetic gaps or just like repeated problems that you would see like functionalization of pyridines. A lot of times people make the pyridine in oxide and then functionalized to position that way and that has its own challenges, you know, strong oxidants strong, yeah, dehydrating agents and you know, kind of limited scope. So, the motivation was you know, come up with kind of a more practical way to functionalize pyridines and also using something that's you know, inexpensive and you know, simple and kind of a fairly unique mechanism or you activate a pyridine towards nucleophilic addition and then you have this intermolecular fragmentation to rearomatize the pyridine.
Paolo 17:44
The approach is not particularly different from you know, the more traditional going by at the N oxide is the idea is, is doing an electrophilic activation of the adjacent carbon right? That's the way that works that you use, you use this sort of, this is an oxene, isn't it? Yeah, yeah. So that binds to the to the nitrogen says, you form the pyridine salts, and then you basically have your, you know, your carbo , your Carbo, which is more electrophilic. And you can use nucleophile. So what type of kind of nucleotides can use that? Okay, what kind of functionalities you cannot do anything with this?
Dr. Patrick S. Fier 18:18
Yeah, so in the original, JACS paper, it was primarily cyanide. And I think that works for a few reasons. One, it's a pretty good nucleophile. But the other thing is, I think it acidifies that CH bond adjacent to the Nitro. So, when you initially add, you have that dihydropyridine adduct, so I think the cyanide helps acidify that to then be deprotonated. And, you know, ultimately re-, rearomatize. So, there's a few other nucleophiles that worked, okay, like, proof of concept, you know, malonate or methoxide. But what I was really interested in is amine nucleophiles, because 2-amino pyridines are extremely prevalent. But the issue is, you know, I tried hundreds of reaction conditions, to install amines using that same activation concept, and it just didn't work, the amine wouldn't react at the oxeme and just, you know, kick out your pyridine and started material, or it would add to the two-position carbon. But then instead of fragmenting how we wanted to, it would just open up into this zinc aldehyde type thing where the pyridine ring would just snap open, and then it's dead end. So that's what led me and this guy, Suhong Kim, who was super superstar intern with me a couple years ago to develop what we call the Aminator. Yeah, which kind of gets around this, these issues. And it was completely redesign of the reagent to basically make 2-amino pyridines from pyridines.
Paolo 19:37
Oh, I understand. It's really interesting work. And, you know, this is immediately evident, right, you know, the utility is obvious. It's just because of the ubiquity of you know, sort of pyridine or aminopyridine, these types of groups and so it's, you know, it's an no brain to understand why you went there. What was kind of surprising to me is, you know, the work you did on the sulfonamides because the logic seems to be different. The way I've always looked at sulfonamides is are more like a sort of terminal functional group. You know, I never know maybe because I'm not good enough chemist, but I never look at them as a sort of non-terminal functionality. But with your work, it looks like it can actually be pretty handy. A pretty handy thing to functionalize, you can change the, you know, the substituent, pretty much in the sulfur or in the nitrogen in pretty flexible way there. So, can you describe their work?
Dr. Patrick S. Fier 20:26
Yep, yeah. So this came out again, like for another kind of random conversation, Kevin Maloney and I were having one day in my office. So at the time, you know, he was working on this compound that had a sulfonamide, a primary sulfonamide, and there was interest in making the same compound, but with a methyl sulfone there. So instead of NH2, it's methyl. So, you know, instead of going back to the very beginning, you know, going through this 10 Step synthesis or something to make the compound, you know, we were wondering, is there any way to convert this compound that we have, you know, 100 kilos of into this methyl sulfone? And on first glance, you're like, oh, that's impossible.
Paolo 21:02
You can't do it. Yeah.
Dr. Patrick S. Fier 21:04
So I don't know if we came up with a solution that day. But I think the next day, you know, we came back with some ideas about, you know, what if we can cleve the NS bond, how we eventually did it, and then you make a sulfonate. And then if you have a sulfonate, you can do whatever you want, you can drop with methyl iodide, or you can do you know, various other functionalizations. So then this becomes a platform for converting sulfonamides into anything.
Paolo 21:26
This is a beautiful work is still thing that you could you could make for a great medicinal chemist as well, I know, you don't want to go there. But you know. Anyway, do you find more satisfaction from these sorts of things, you know, there's a nice dose of problem solving or more from, you know, playing a role in something as big as, you know, developing the process or saying that you're not promised to end the pandemics? Or any I mean, the, and I kind of going on a tangent, but, you know, I think we need to get there, right. So, you, you, you, you work on developing the process for the molnupiravir via, you know, the COVID-19 pill, as it's called, you know, went to the press. So, yeah, you're, you're kind of famous for that, are you?
Dr. Patrick S. Fier 22:18
Yeah, yeah, I think both things are very satisfying, like, coming up with new methods that are used broadly, is definitely, you know, exciting and, you know, motivating. But, yeah, what really excites me is like working on, you know, developing a process that's used, you know, to supply patients with medicine around the world, you know, whether it's, you know, the COVID-19 molecule molnupiravir, which I can talk about, or, you know, other things I've worked on, you know, I think it's, it's super cool to, as a process chemist, like you come up with the way that the molecule is going to be made to supply millions of people around the world. It's just so cool that you go to a pharmacy, or someone goes to a pharmacy and gets a pill. And that pill was made using chemistry- I made that- you made. So yeah.
Paolo 22:58
Yeah, that must there must be something we it's particularly important, right? You obviously, because of the time we are living, did you have like a tougher timeline and targets because of how urgent and important the problem was?
Dr. Patrick S. Fier 23:14
Oh, yeah, absolutely. This was a project like no other. And it was also my first time leading a project. So, you know, in, I think, May of 2020 or so, I got promoted to principal scientist, which is, you know, leading projects and leading groups of scientists. And then, you know, a few weeks later, I got assigned to be the chemistry lead for molnupiravir. You know, and this was the fastest pace program in probably the history of, you know, pharma, awesome experience. And, you know, it was my first time leading a project. And there's, there's two efforts going on. So one of them was what became the manufacturing process. This is a five-step synthesis from uridine, on this has been used to make, I think, around 200,000 kilos of molnupiravir so far, which is, you know, many, many millions of treatment courses. And there was a second effort ongoing with a separate team again, which I was fortunate enough to lead on developing really the ultimate synthesis of molnupiravir and we came up with a three step route, starting from ribose and uracil and it uses a couple biocatalytic steps and a really interesting glycosylation step using some novel enzymes that you know never really been used before and you know, way to recycle ATP with pyruvate oxidase and air.
Paolo 24:23
The cascade reaction there in in vitro or is it you know, in a cell, is it only in fermentation conditions.
Dr. Patrick S. Fier 24:30
The enzymes are you know, fermented and an isolated isolated Okay, take those and then use them. Yeah.
Paolo 24:36
So, do you see this as being the future of the manufacturing? Oh, I know I know you made a lot a lot of drugs now and probably don't need to produce much more for in the short run but I suppose the you know, molnupiravir that's my have like a broader indications and antiviral going forward. Do you foresee Merck switching to the to the new routes to make it in the future?
Dr. Patrick S. Fier 25:01
Yes, I think it's, it's possible at this point, as you mentioned, you know, we're making it all with what we call the gen one route. So, based on, you know, how much we improve that route, and you know, all of our manufacturing sites around the world, we're able to produce enough to meet demand. That second gen process is definitely shorter. And, you know, we've demonstrated on around 100 kilo scale. So, at this point, we haven't moved that forward to commercialization, because I think we can meet demand with gen one, but you know, things may change if demand goes up, or if, you know, other indications arise.
Paolo 25:36
What, what is the reason why the, you know, the biocatalysis route is, isn't the ones the one you pick? Is it just you need more time for development? And it was just the time it was too strict?
Dr. Patrick S. Fier 25:47
Yeah, just, you know, to develop a process and demonstrate 100 kilos is, you know, one aspect of it, but then you have to, you know, implemented at commercial sites, you have to do validation. And this, this takes a lot of time. And of course, there's, you know, regulatory components to it, as well. So, I think, if that was, yeah, basically, it just takes more time. And, you know, by the time we kind of gotten into a place where we could go into validation, you know, the gen one route was already validated. And, you know, being used to make 1000s of kilos a year.
Paolo 26:18
You must be incredibly proud, though. Do you ever think about it? Did you wake up in the morning say, oh, I play the role, a real a real role in the pandemic?
Dr. Patrick S. Fier 26:27
Yeah, I think that is just, it's incredible that I was involved with that. You know, the chemistry that, you know, I worked on in the lab with my own hands is now being used, you know, to make, you know, enormous quantities of this medicine that's now being distributed around the world. So, it's super cool. And then, you know, seeing it, you know, in the news, you know, the New York Times talks about this compound, Wall Street Journal. So, it's just, it's just super cool to have been a part of it.
Paolo 26:53
How many other drugs be beyond these have you worked on that actually made it to the market? I'm just curious.
Dr. Patrick S. Fier 27:00
Yeah, so early on in my career, I worked you know, again, as just like an individual contributor on zerbaxa. So, this is ceftolozane sulfate is the active compound I worked on. So, this actually was already on the market when we started working on it. But just the route was not, didn't meet our standard. So, we kind of tweaked around, developed a new process, and then refiled that, so this, this is an antibiotic that that's been on the market for a while. And then another company work on relebactam, the MK Code is mk 7655. So, this is beta lactamase inhibitor that's used for antibiotics. So yeah, so I've been pretty fortunate to work on a couple things that I've seen on the market.
Paolo 27:43
And a lot of a lot of chemists in pharma, they work whole careers, and they never touched anything that actually goes to the market. So, you've been good. I've been lucky. But you know, there's a luck component, and working for Merck helps fairly I suppose but you know, congratulations. That's, that's, that's really, that's fantastic. You asked, do you have to be proficient? So, you know, I would go on forever, but, you know, we probably have better things to do then speaking with me, or they are, it's, you need to save the world. So, what do you think is the most important thing, you know, in your job? Because it's incredibly complicated. And, you know, there's a lot of components. So, you certainly need a healthy dose of creativity, and you are demonstrating that you need discipline at the same time. So, what do you think is the most important one?
Dr. Patrick S. Fier 28:39
Good question. Yeah, I think, you know, from a scientist point of view, you know, solving problems and, you know, actually coming up with solutions to, you know, real world problems. I think what's also important is probably, equally important is, you know, working on teams, and, you know, really, you know, working together in a team to, like actually deliver this, you know, solution to the patients.
Paolo 29:04
You're speaking about keeping in mind while you're doing right, but look, particularly when you're stuck in a problem and, you know, the solution isn't in sight, you must have a motivation. Do you ever feel like, this is a problem I'd never be able to solve?
Dr. Patrick S. Fier 29:19
I think every problem is solvable, but the solution may not be as elegant. There's always a way to like make something but it may not be as beautiful as you put on paper.
Paolo 29:32
I think it's a good time to come to my last question, which is always the same in my in my podcasts, you know, it's a good time to stop and look backwards and say, you know, after all you have done, what would you recommend? What would be your suggestion to someone who's just starting in their career?
Dr. Patrick S. Fier 29:50
You know, looking back on what's been most impactful for me not only getting through my PhD and getting a job, but you know, now, you know, at Merck. I think having a strong network and, you know, talking with people, learning from others is so incredibly important, I think, you know, for students looking for a job or looking, you know, to do a postdoc, I think, who you know, you know, and building connections with people is so extremely valuable. You know, and, you know, I owe a lot of credit to, you know, talking with people I've met at conferences to actually getting me a job, you know, interview at least at Merck, and, you know, and then talking with people at Merck, you know, just chatting with people learning from others has been instrumental in you know, coming up with these side projects, you know, I mentioned with Kevin being a good example, and then, you know, talking with a lot of other people and, you know, learning from them and becoming a successful process chemist. So, my advice is grow your network, you know, learn from others, and, you know, don't be afraid to ask for help.
Paolo 30:56
That was Dr. Patrick Fier, Principal Scientist at Merck, and one of the Chemical and Engineering News' Talented 12. Thanks for joining us for the season three episode of Bringing Chemistry to Life and keep an ear out for more. If you enjoy this conversation, you're sure to enjoy Dr. Fier'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. This episode was produced by Sarah Briganti, Matt Ferris, and Matthew Stock.