Joseph DeSimone

Zierler:

Okay, this is David Zierler, Oral Historian for the American Institute of Physics. It is May 24th, 2021. I'm delighted to be here with Professor Joseph M. DeSimone. Joe, it's great to see you. Thank you for joining me today.

DeSimone:

Well, thanks for your interest, David. Appreciate it.

Zierler:

Joe, to start, would you please tell me your current title and institutional affiliation?

DeSimone:

Yes, I’m the Sanjiv Sam Gambhir Professor of Translational Medicine and of Chemical Engineering at Stanford University, and I have a joint appointment between the Department of Radiology in School of Medicine and the Department of Chemical Engineering in School of Engineering, with courtesy appointments in the Department of Chemistry and in the Graduate School of Business.

Zierler:

Joe, tell me a little bit about the chair named for Sanjiv Sam Gambhir. Who is or was this person?

DeSimone:

Well, Sam passed away in July. He was an old friend of mine. He basically put Stanford Molecular Imaging on the map. He is one of the pioneers in Molecular Imaging who came out of the Mike Phelps crew at UCLA, where Sam was a professor before coming to Stanford. He was instrumental in translating PET imaging into reimbursement in clinical trials for chemical analysis of mostly pre-cancer, but a lot of other indications as well. And in about the year 2000 when nano-medicine was emerging, there was a big call for proposals from the National Cancer Institute for Centers of Cancer Nanotechnology Excellence—CCNEs. And at the University of North Carolina, where I was a professor for 30 years, I led a team that landed one of these centers. Ours was focused on delivery of nanomedicines and vaccines. Sam also landed one of these here at Stanford. His was on early detection and molecular imaging. And so, our two centers complemented each other. There were five nationally, one at Harvard, Northwestern, down at Southern California, and I got to know Sam really well and he was on a Scientific Advisory Board at the NCI, and he actually started recruiting me after that time. Then in 2014 he approached me, but it was at the time that we had a little invention related to 3D printing, and I was distracted by that and hit the pause button on Stanford.

And then, he came—well, I was co-founder and CEO of Carbon, the company based on the 3D printing invention, for almost 7 years in Silicon Valley. When I transitioned out of the CEO role and became Chairman, I traded that position with Ellen Kullman, the former CEO of DuPont who had been Chair of our board. So, I got my life back, and Sam started recruiting me to join Stanford again. This was in November of 2019, and I didn't know at the time that he was sick. When I learned this some months later, it was heartbreaking on many levels. Sam and I talked in the past about putting together a combination of our programs and bringing our friendships together. Then in March of 2020, the Dean of the Medical School, Lloyd Minor, reached out and said, “Hey, we got some—" and I knew everybody knew Sam was sick at this point. He said, "We have some exciting news and Sam has a question for you." And so, we had a Zoom call—this was the beginning of Covid—with the Dean of the Medical School, Lloyd Minor, and Sam and I, and they started to tell me that they’d fundraised for a professorship in Sam's name and Sam then had a question and he asked me if I would be the inaugural holder of the professorship, in his name. And so, a very heavy, emotional call and as Lloyd and I were crying, Sam's video camera was off, and I busted on him for putting us through that, but yeah, so it's an important—Sam was an incredible and important person on campus who did a lot of things very translationally focused on improving people's lot in life and it's a true honor to do anything in his name. Long answer in short.

Zierler:

Yeah. No, I'm glad you told it to me. That's great for background. Joe, in terms of all of your affiliations on campus, in terms of your teaching responsibilities, where you take on graduate students, what is your home department? And what are the affiliations in terms of their importance to your overall research agenda?

DeSimone:

Well, Stanford has very low barriers between departments and divisions and so it's a pretty fluid place. But my appointment is a 50/50 appointment between the Department of Radiology in the School of Medicine, and the Department of Chemical Engineering in the School of Engineering. So those two are my home departments, and you can't have primary appointments in more than two. The courtesy appointment is a mechanism to have a presence in other departments to help advise graduate students and teach, and for me the courtesy appointments are through Chemistry and GSB, the Graduate School of Business.

But I've got students from many programs after just starting up my new lab at Stanford in late 2020. After running a research group for about 30 years at UNC—they hired me when I was 25, and I used to run very large research groups, though I don't plan to do that anymore. But I do plan to have about 15 trainees which is a good-sized group, and my current graduate students in PhD programs now come from the Department of Chemical Engineering, the Department of Bioengineering, the Department of Material Science, and the Department of Mechanical Engineering. I expect I'll have some Chemistry students join soon too, and we also have undergraduates and master’s students who are Computer Science and Material Science working in groups, so a very disciplinary-diverse team coming together.

Zierler:

Joe, given your interests in industry and applications, is there broader value given the startup culture in Palo Alto, even beyond Stanford for you?

DeSimone:

I think so. There is an esprit de corps here for translational research and entrepreneurship, and my teaching responsibilities are in that direction at the request of Stanford. I do see there's a need to also help out on the Polymer Science curriculum from a Chemistry point of view, and so I need to try to balance that. But yes, I mean, Stanford's a very special place and, look, I grew up academically in Research Triangle Park, North Carolina, and nobody is a bigger fan than I am of the potential and the capabilities of what North Carolina can bring in terms of entrepreneurship. And I always talked about how we could compete with anybody on the planet when I was in North Carolina. I ended up starting several companies there, and we moved Carbon from North Carolina to Silicon Valley because of the diversity of needs for that company.

I think for a chemically intensive company, North Carolina was at the top of the game. We were going to do hardware and software and chemistry at Carbon, and so when I was 50, and the company was getting launched, we did move it to Silicon Valley, and I will tell you, we could not have grown as fast or as well in RTP as we have in Silicon Valley. There's an infrastructure here of people, resources. We're really—our 3D printers are 100% smart hardware. Our founding VP of Engineering was the founding VP of Engineering of Tesla. We've had over 50 ex-Tesla employees in the company, and that kind of—we could have done it in North Carolina, but I don't think we could have done it at the pace that we've been able to do here in Silicon Valley. And we’re in a region that also has a really strong academic foundation between UCSF and Berkeley and Stanford and Southern California. So, it's a powerful opportunity to be here.

Zierler:

Joe, your research breadth requires, I think, some clarity on nomenclature in terms of the disciplines that are most important to you. So, I mean, it's almost everything. There is medicine and biology, there's chemical engineering, there's polymer science and soft matter physics. Is the way that you approach all of these things that you tend to de-emphasize the distinctions between these subfields, or are there some disciplines, there's some approach that you have where there is a home department or a home discipline and everything for you flows from there?

DeSimone:

That's an interesting way of framing that question. We think about having a toolbox and that toolbox is Polymer chemistry and we're good at that and we love that—using it as our foundation for impact in various fields. I think an element that has distinguished what we do versus others in the Polymer chemistry field is that I've always enjoyed unique reaction media, reaction environments that are often coupled to devices or equipment. Back in the '90s, we did polymerization reactions in compressed carbon dioxide and that required unique equipment to do things at elevated pressures and temperatures—we studied these chemical reactions in situ using nuclear magnetic resonance and neutron scattering and small-angle X-ray scattering, and even FTIR; we even did spin coating of polymers from liquid CO2. This was a wonderful interface of Hardware and Chemistry coming together, not software, but Hardware and Chemistry.

And then we got heavily into molding particles, using the tools in the microelectronics industry to fabricate particles of controlled size and shape, using roll-to-roll web-based technologies that are maybe legacy approaches from Polaroid and companies that made film, but we applied it to making particles for medicines and vaccines and so that web-based roll-to-roll approach, again, Hardware and Chemistry coming together with a little bit of design, but not a whole lot of design. And then 3D printing is new equipment, new approaches for printing, for materials, for design—and it heavily brought in the software side, a sort of third phase in my career that really brought that element to the foreground.

Zierler:

Joe, a question we're all dealing with right now, how has your science been affected one way or the other during the pandemic in the mandates of remote work?

DeSimone:

When I transitioned out of the CEO role at Carbon in November of 2019, and after six years of doing that 24/7, my wife and I disappeared to New Zealand for a good bit just to decompress and we came back to a new reality. The good thing, the cool thing at Carbon, our annual operating plan for 2020 was established in December of 2019 and we hit it, and we weren't very much affected by COVID from a business point of view, revenue point of view, that kind of thing. But what's interesting is it transformed so many things. I've been talking for a long time about the value of digital manufacturing in the context of supply chain disruption, and about distributed ways of making things, and I was always thinking earthquake or hurricane or very regionally specific or isolated events, never thinking about a global pandemic.

But the way COVID hit the world, it came in different phases in different places, and we were very resilient, and moreover, we were able to pivot our approach for making things to help people in need where they needed it. So, PPE and protecting healthcare workers was front and center. And there were massive shortages. There was also a massive shortage on testing capabilities for nasopharyngeal test swabs, which I never heard of before, and so we sort of pivoted our ecosystem and gave our customers and partners the tools to help out in their local communities. It was extremely inspiring, and it accelerated what we were talking about prior to COVID, this fact that local for local production, digital manufacturing was going to be the future, and we saw it more clearly then with a real crystal-clear example.

I think, the innovation process—well, what we were doing at the time, we managed through COVID and working remotely, also doing what we needed to do in-person because we were responding to a healthcare crisis and had some exemptions from the California Government to enable some of our teams to work in-person together since we were helping out making critical supplies—face shields, that sort of thing. But I will tell you, the innovation process is a contact sport, and as I set up my new lab at Stanford, and I'm in a couple days a week, there's nothing like dragging one person over to talk to another person in the middle of a conversation to bring clarity, and you can't do that over Zoom. I thank God, Zoom was here, but I hate it now. I mean, it's not what's needed to do what we do; the in-person contact is crucial.

So, I think we're realizing how important that is to the innovation process, but I think the hybrid model and how we learn, going to a big meeting, where there's several—thousands of people coming together to communicate science may be an efficient way to communicate information, but when it comes to innovation—it's the personal contacts, it's the dinners, it's the meeting at the poster session, that's where innovation happens, and so it's more than just communicating science. It's the ecosystem of collaboration that gets cut out when everything is remote, and it's really important for us to get through this phase and get back to doing things more in-person.

Zierler:

And just for a snapshot in time, circa May 2021, what are you up to these days? What's most important?

DeSimone:

Well, so I'm a big fan of what I refer to as a future fabricated with light. Making things with patterned light—it's driven Moore's Law for the last 50 years, and now we're trying to drive in the macroscopic world to make things without molds. And so, in that context, the things that are most exciting to me right now are new approaches to the 3D printing field in the context of both printing processes and materials, as well as software. For printing processes, I'm really eager to drive the resolution of our printing process to single-digit micron and make amazing things that range for applications from drug delivery to sampling interstitial fluid and delivering vaccines and medicines in important new ways.

I'm also interested in multi-material printing and new approaches for doing that, and I think we can take 3D printing from a mass-transport limited process to a reaction rate-limited process and get another order of magnitude more in speed. I am interested in new materials, including biodegradable and compostable and chemically recyclable materials for a circular economy. And the role of software and design and meta-materials and architecting materials is really high on the list, and so I'm pursuing things in those three big buckets.

Zierler:

Joe, because I know you're so alive to these things, what right now in terms of limits in technology are most obvious to you? In other words, ideas that you might have that are running ahead of current technological capabilities?

DeSimone:

I would say they're not technological limits, but policy and implementation limits. Look at the world of recyclable polymers, you could make the argument that you could snap the chalk-line right now and say, "Okay, no more research in recyclable polymers," and you can build a circular economy with what is known today with an intention focused on the supply chain, collection of materials. We're not being smart by throwing mixed waste in the same container and relying on municipal waste streams to get us out of this plastics problem. I think companies and business models need to be more accountable and, again, I don't think there are technological issues. I think these are societal decisions that could be made with existing technological capabilities and so that's one example.

There are other areas where technological innovations are needed, for example to get advanced material properties that are needed in other industries and still insist upon a circular economy. Take the automotive industry as an example—I think the business models for the automotive industry and the plastics suppliers center on designing new materials for advanced capabilities, but what that also means is more and more differentiation in materials, and the more differentiation in the materials themselves, the harder it is to recycle. There are too many polymers in use in the automotive industry. I think there's some 200 different plastics that go into making a car today out of 40 classes of materials. I suspect that you can make a car out of only 5 materials and I suspect that these 5 polymers could be designed to all be chemically recyclable, and that you can make up the difference in material properties by using geometry—like lattices. So, if you're only going to use 5 polymers, maybe 6, you make up the range of properties through meta-materials and architecting materials where one material with an intrinsic set of mechanical properties can actually be a family of properties, based on controlling architecture, designing lattices, that sort of thing. And so, there's a need for technological innovation here, and I think it's very doable, but again, the business models need to shift if you're actually going to make a difference in society.

Zierler:

Well, Joe, let's take it all the way back to the beginning. Let's start first with your parents. Tell me a little bit about them and where they're from?

DeSimone:

So, my father was born in Italy. Came over when he was 9, right after World War II. He was in the United States Navy and was a tailor.

Zierler:

Where in Italy was he from?

DeSimone:

From Abruzzo, on the Adriatic coast just east of Rome. And so, he came over—though my mother's not Italian. So, our household was not fully Italian, whereas my cousins, their families were completely Italian, and that was a very different experience going over to their place on Sundays and then coming to our place. But nonetheless, my mother's a good cook, just look at me.

Zierler:

Where's your mom from?

DeSimone:

My mother's sort of a mutt. She grew up in the Norristown, Philadelphia area, and my father came to that area. My mother got married when she was 18, had me when she was 20. I have a brother who's 11 months older, and I have a younger sister, and so we had a terrific upbringing. My father passed away several years ago of glioblastoma multiforme and it was interesting, being in the cancer world when he was going through that. My mother is 77 and lives in the Fredericksburg, Virginia area where my sister lives. My sister works for the Government. She's in the Senior Executive Service. She is like the number 2 person at the Ballistic Missile Defense Agency and she's keeping us safe and she’s very, very busy, very intense. She's the smart one in the family by far. My older brother's a union electrician and he works really hard physically and runs a crew and works in the Philadelphia area. So that means he's doing things like building buildings for Merck, and all those companies that are expanding up in that area.

And my wife and I met in high school, high school-sweethearts, and when I graduated college in 1986 in May, she and I got married in June of '86 and then we went down to Blacksburg, Virginia for graduate school in August of '86. And I didn't know that you could get paid to go to graduate school when I got my undergraduate degree at Ursinus College. We couldn't afford for me to live at Ursinus when I was an undergrad; it was in my neighborhood. And I worked two jobs in a pizza place in an Acme supermarket all through college, and then when we went to graduate school in Virginia Tech, Blacksburg, Virginia, and I thought that was the Deep South! We didn't go—other than jumping down to Florida—we didn't go too much further south than DC, but I enjoyed Blacksburg—Virginia Tech's an amazing University. And in 1990, my son was born in Blacksburg, and we were intending to move back home where I was going to work for DuPont or Rohm and Haas or Arco.

And then, my PhD advisor, Jim McGrath, told me about an academic position opening up at the University of North Carolina at Chapel Hill—though Virginia Tech was not a pipeline for faculty and so it was never on my radar before that. Never was on anyone's radar. But I went down and interviewed there. It was a time when I had 20 Industrial offers almost, and I interviewed for three academic positions—in Florida, Connecticut, in North Carolina, and I fell in love with UNC. And when they hired me, I was 25 and all I needed to do was teach organic chemistry and the university gave me half a million dollars to start my lab, and I thought man, I could do this. So, we moved to Chapel Hill, and felt it was a great—UNC-Chapel Hill—was an amazing university. It was a great place to grow up academically, to learn how to do good science—I had great students.

Zierler:

Joe, at what point as an undergraduate did you realize you had a knack for this, and you wanted to pursue a degree in Chemistry at the graduate level? Was it at professor? Was it a particular class? What clicked for you?

DeSimone:

So, science started for me in middle school, and I remember a class where the teacher was trying to explain pH and acidity and I'm sitting in the classroom, and I was listening to this teacher, and I realized, he didn't know what he was talking about. He couldn't explain it well. And I thought—so I went home that night, and in the encyclopedia, the little books back then we all used to have, I learned about pH myself. So, the next day in class, there was a dialogue in front of the students between me and him, and I basically educated him and the other students about pH, and I thought then I had a knack for explaining complicated things and I enjoyed that. The experience made me fall in love with teaching and science and encouraged me to think about going to college and majoring in chemistry. I also had a really great undergraduate professor at Ursinus College. Ursinus College was one of the very few places that taught polymer chemistry at an undergraduate level.

Zierler:

That's interesting. Do you know the backstory there? I mean, it's a small school. Why would it have that specialty?

DeSimone:

It's because of the professor there, Ray Schultz, who got his PhD at Lehigh University in polymer science and it was—he integrated it into undergraduate PCAP and then he taught polymer chemistry from that, and he lit me on fire regarding research. I fell in love with research at Ursinus and was supported by the close relationships with the faculty and the overall environment. It was a great place, though I'd have to drive literally 15 miles to go get dry ice and the things that you just take for granted today. And I was doing state-of-the-art polymer chemistry research there and I knew I was good at it, and then I learned that you can get paid to go to graduate school and moved in that direction where, again, I was focused on pursuing an industrial career coming out of Virginia Tech in the Polymer Science world.

Zierler:

Now, was Virginia Tech particularly strong in terms of Chemistry graduate work that was focused on industry?

DeSimone:

Especially in polymer chemistry, it was one of the top three places in the country, UMass Amherst, Virginia Tech, probably, University of Akron, these were not your places that were academic powerhouses generally. Polymers was sort of relegated to engineering as a discipline. It wasn't until a couple of Nobel prizes that it became mainstream, really interesting, de Gennes in Polymer Physics, Bob Grubbs in Chemistry, now, these people made it okay for top-notch chemistry departments to move into Polymer Science, and that's what Chapel Hill did. Chapel Hill was a top 10 Chemistry department but didn't do a lick of Polymer chemistry, and they made a cluster hire of five people, and I was one of those five to start—with an intentional focus on moving the discipline more into Polymer chemistry.

Zierler:

Joe, to go back to that academic discipline question, at that point, where is soft matter physics in all of this, given that polymers are so important in that field as well?

DeSimone:

Yeah, I think they struggled in a similar way, and they had to fight their way into that community. And at UNC, physics was Physics and Astronomy. But they started bringing in others, and part of the cluster hiring extended to multiple departments too. And so, we were building a broader capability, and what's really interesting about that, really interesting now as you help me reflect on this, UNC does not have a School of Engineering, which most people don't appreciate. Now, when you look at the federal support for research, 35% of the federal budget goes to 20 universities. So, the rich—the rich are solidly on that list and Carolina and Duke are 9 and 10 on that list every year, and there are only two schools on that list that don't have Schools of Engineering. That includes UNC-Chapel Hill, and UCSF. And there are only two schools in that list that don’t have Schools of Medicine, and there's MIT and Georgia Tech, and Caltech is like 21 or 22, so they'd be in there too, but medicine pays the lion's share of the Federal R&D budget—NIH is a big supporter of research. But it's rare to think about a school that doesn’t have engineering. So, it's interesting that Carolina, without a School of Engineering, was going into Polymer Science and Soft matter in a way—that was a big jump for them.

Zierler:

Joe, how did you develop the relationship with James McGrath?

DeSimone:

Well, when I was an undergraduate doing Polymer Research, I would read papers coming out of the McGrath Lab, and I would contact their graduate students. In fact, I just did a Zoom call with one this morning at 7:00 that I hadn't connected with in a while, a couple of grad students, and so I got familiar with his lab and then I applied to Virginia Tech for grad school. When I met Jim, he was tending bar at a social event for the Polymer Chemistry division of the American Chemical Society, and this guy was very jovial and fun to be with, and he understood structure-property relations better than anybody on the planet. He was an amazing mentor to students, and there was a good esprit de corps in his group. I was able to meet with them, and Virginia Tech had had several people prior to me from Ursinus College, and I had done well enough at Ursinus to compare well with those students, and so they rolled the red carpet out for me to come to Virginia Tech for grad school and it felt like home, it was easy.

Zierler:

How did you go about developing your dissertation topic? What was the interplay between you and James in terms of identifying the problem, figuring out what would be doable within the timeframe?

DeSimone:

It's funny you asked. So, we had to come up with an independent idea as students as part of the PhD qualifying exam, and Jim had a program to use supercritical fluids to fractionate polymers based on chemical composition and molecular weight, and it was a time when supercritical fluids were getting a lot of attention as a way of extracting caffeine from coffee beans. The process was known as naturally decaffeinated coffee “…with nature's effervescence…,” and it was high-pressure carbon dioxide, washing away the caffeine. And Jim was using that technology for fractioning polymers, and separately, he was doing polymer synthesis in different solvents that gave rise to different details of the polymerization process and actually different materials because of the role that solvent played.

Interesting, maybe this was my liberal arts background and the value of the synthesis of ideas, bridging fields—so my PhD proposal idea at Virginia Tech was to do polymer synthesis in supercritical fluids, bridging two projects in Jim's own group, and I fell in love with the idea, and I thought it was really compelling. And so, I actually-I went to Jim, and I said, "Jim, let me do this. I want to do this." And Jim was amazing. He didn't have funding for me to do that. But he didn't tell me that. What he told me was, “Joe, you're going to get a chance to do something nobody is ever able to do. You're going to be able to think about an idea for a long period of time without having to have to do an experiment. I've got this other project over here related to microelectronics that I'd like you to work on, but I want you to spend time on thinking about your idea.” I said I was a little disappointed in that. But what happened was, it became a pet peeve of mine to think about this area. It was under my skin. And so, for three years, I had an idea that I didn't work on, but I just studied the literature and kept refining it and refining it, and so when I did interview for academic positions, at the age of 25, I had a really well-thought-out idea, and I think it distinguished me from other applicants for professorships.

Zierler:

You mean in terms of articulating a Statement of Purpose for your research?

DeSimone:

And to deflect all the reasons why it might not work, because I had gone through that myself for three years. For me, no one had done it and so it was compelling. It was a novel idea. And it was funny at the University of Florida, I did not get the offer from Florida because a couple of faculty there didn't think it would work, and they had called some pioneers in Polymer Science and asked them, “What do you think of this idea?" And they said, “That's not going to work.” But in fact, when I went to UNC, I started to do this program, and we did our earliest experiments in this area where we put a monomer into a pressurized chamber with carbon dioxide, and we had a stir bar in it. The monomer would dissolve and form a clear solution, looked like water, and the stir bar would start to slow down as the polymerization took place, the viscosity was going up and then you'd vent the CO2 and you had a pile of polymer in there with precipitate.

I went to my first Gordon Conference as a professor, and I had a couple of my students with me. But it was before we published our paper, and this very senior polymer guy was sitting at my lunch table, a very arrogant guy, and I started to describe what I was doing, and in front of my students, he treated me poorly, and he said, “Don't you know that decarboxylation reactions go by a free radical pathway, and therefore, radicals will get consumed by the CO2?" And he dismissed me, in front of my students in what appeared a gleeful way. However, we had done the experiments already. And you know, I'm a polymer guy, and we had looked at the polymer made in traditional solids and looked at the polymer made in CO2, and we analyzed it using spectroscopy, and we didn't see any carbonyl bands, didn't see any incorporation of CO2, it looked like normal polymer. So, it was a little bit like, it walks like a duck, sounds like a duck, it might just well be a duck. And we ended up publishing a paper in Science on that topic shortly after I got to Carolina, and this guy saw that paper and he turned out to be one of my best letter writers—I showed him this worked, and he's been in my fan club since.

Zierler:

Joe, as a graduate student, when you were immersed so much in literature, to what extent was theory on your radar? Was that relevant at all?

DeSimone:

Not in a polymer physics world, but a lot of my classes at Virginia Tech were grounded in physical experimental science; in morphology and fundamentals and Flory-Huggins theory and why polymers phase separate; and experimental techniques for validating that, and so, it was more experimental physics than theoretical physics in understanding polymer properties and some theory that guided it. But it wasn't hardcore polymer theory—we got exposed to some of de Gennes thinking and all that, but it was a peripheral knowledge and not a hardcore part of our research.

Zierler:

Besides McGrath, who else was on your thesis committee?

DeSimone:

As you're asking your previous question, I was going through the things we got taught! So, the polymer chemistry program at Virginia Tech has an interesting story in and of itself. Tom Ward was on the faculty at Virginia Tech. Tom got his PhD at Princeton from Tobolsky and was one of the best teachers on a planet, and he recruited Jim McGrath from industry to come to Virginia Tech. And Jim worked at Goodyear and Union Carbide. He got his PhD at the University of Akron with Maurice Morton in the Morton Institute of Polymer Science at the University of Akron and was in industry and then came to Virginia Tech, and then they needed more of a chemical engineer, and they recruited Garth Wilkes, who was on Princeton’s Chemical Engineering faculty, who also got his PhD with Tobolsky. But it was Jim who recruited Garth from Princeton to Blacksburg, Virginia to go to Virginia Tech, and the three of them formed the Institute, the Polymeric Materials and Interface Laboratory, PMIL; Ward, Wilkes, McGrath.

McGrath was on the synthesis side of the house, Tom was a physical chemist, and Garth was a chemical engineer, and they created a very multidisciplinary program in close partnership with industry and they taught these short courses, these American Chemical Society short courses of Polymer Science, which were five times a year and the graduate students helped do the lab experiments with the industrial participants because a lot of chemists never had a fundamental class in Polymer Science. And we get a lot of researchers from GSK and Merck, and they were doing drug delivery and all sorts of things, but they never understood anything about polymers and the companies would send them for these courses. We students would do the short courses and would get to know these industrial scientists, and it was another 50 people, 5 times a year. And at the end of the week-long course, Jim would all take us out to a big dinner with the participants and it was a very collaborative, enjoyable environment.

And so, when I became a faculty member, I had close ties with industry mostly because of the experience at Virginia Tech teaching a lot of those people lab courses, and so they were very supportive, and it was a really strong community.

Zierler:

Now, did the opportunity at Chapel Hill come together before you seriously considered or pursued industrial jobs, or was this search happening in parallel?

DeSimone:

It came at the tail end of it. Literally, I was at a wedding for a graduate student and another graduate student in the group, my wife and I were already married at the time, and we were dancing and Jim cut in on us. I thought he was going to start dancing with my wife, but he started dancing with me and he told me about an academic position at Chapel Hill, and I cut away from him right away, like, "I'm going back to Philly." I didn't want to go further South.

And then back on campus, a post-doc in a traditional Organic Chemistry group at Virginia Tech who knew more Chemistry departments than I knew all the Polymer Science departments—he said, "UNC is a top 10 Chemistry department, amazing," and he said, "You could do this." And this post-doc, for a few weeks prior to interviewing, helped me put together how to present to faculty because no one at Virginia Tech did this. So, I was ready for chalk talk and I walked into a room, and I didn't know any of the faculty there, so I was not intimidated. If I knew who they were, I would have been because it was multiple members of National Academy of Sciences, Royce Murray, Ernest Eliel, Bob Parr, Tom Meyer. I should have been really nervous, but I didn't know who they were, and I was just myself. They asked me what I would do, and I walked them through this idea that I had been harboring for three years prior and they gave me the nod at 25 and it was interesting. They hired me and they said, "Would you like to go do a post-doc first?" I said, "No, I have ideas. I want to work on these ideas.”

And so, I started teaching Organic Chemistry and Polymer chemistry and started working on these ideas, and I got a great group of students that joined my group. And my first PhD student, Valerie Ashby, an African American woman, got her PhD in three and a half years with me, really quick. She was amazing and she was a leftover grad student, so to speak. She didn't pick up an advisor her first year and she joined my group, after her father who was a pastor had just passed away a year earlier, and she was a phenomenal student. And it's funny, she graduated, and she went and did a NATO fellowship in Germany with a really prominent physical polymer guy, and she started interviewing for faculty positions back in the States. And she had offers from MIT and Georgia Tech and NC State, and she came back and she said that she's going to go to Iowa State. I said, "Iowa State? I don't know where Iowa is! What are you talking about? I could place my first student at MIT,” and she said, in a very mature response to my immature bravado, she said, "…the faculty at Iowa State reminded her of Chapel Hill," and she was home. And for an African American woman to go to Ames, she found her church, my wife and I went out for her wedding when she got married there. She rose through the ranks at Iowa State, got tenure, and then my senior colleagues came back to me and said, “Hey, would you mind if we recruited Valerie to Chapel Hill?” And I said, "No, it'd be amazing." And we recruited her to Chapel Hill, and then her students started calling me Gramps which I did not appreciate!

Ultimately, she became Chair of Chemistry. She was in the Chemistry Department, so she became my boss. So, be kind to your graduate students! You never know when they're going to decide your salary and stuff, but it was great and then she got recruited away again. She's now the Dean at Duke University. And so, when you get great students like that—I have graduated 80 PhD students in my career, and 50% were women and those that are underrepresented in the sciences, and I started really appreciating the role that diversity plays in the whole innovation process.

Zierler:

Because by definition for science to advance you need different perspectives on looking at things.

DeSimone:

Yes, and where this really became grounded in actuality for me was—Jim McGrath was part of a big Chemical Company initiative on innovation when I was an assistant professor at Carolina, and he connected me with this effort. He told me, it'd be good to do this, and I joined their innovation committee. So, I flew to Europe and I walked into this room, and I was one of the few outside people. I think they wanted Jim, but Jim wouldn’t do it and I did it.

And I walked in this room—it was a pretty sterile board room, and not only was it all white guys around the table, but they had all graduated from the same, like, two or three research groups in Germany, and they all knew one another, and they all knew the same stuff, and I couldn't break into that conversation, into that community. I could not. They were all in resonance with one another and I was coming in from the outside, and I couldn't break into the conversation, and this was the Innovation Group! And I thought, “Boy, are they at a structural disadvantage.” The way they were organized put them at a major disadvantage to drive innovation because they weren't open-minded, the way they organized, and yeah, by that time, my group was already—Carolina being a public research university, it’s a diverse place and I had a good group of students from diverse communities, and I realized right there that diversity and how one is organized plays a really big role in the whole innovation process—not only disciplinary diversity, but human diversity.

And I've had graduate students that grew up with not much money and they think about problem-solving very differently than somebody that grew up with a lot of money. And if you're in the innovation game, you want all those ideas coming together. And so, I realized that. I'd already gotten a disciplinary diversity perspective from Virginia Tech, but I was really realizing that human diversity was at least equally important, maybe even more powerful in that sense. And so, my group has always been a very diverse—as I mentioned, over 50% of the PhD graduates from my group have been women and those from underrepresented groups in the sciences.

And then, a very important thing happened. I was asked to be a keynote speaker for an ACS Fluorine Division workshop, and I think this was in 2000 or so. So, I was a keynote speaker, and I had a very diverse group, and I then saw that the NAACP was boycotting the state of South Carolina because at the time they were flying the Confederate flag over the State Capital.

And so, my group and I were going down to this meeting in a few months, and I brought it up to my group and said, "What do you think?" And we had a great conversation about it, and we decided that we weren't going to go. So, we wrote a letter, and we wrote it as a group to the organizers who I knew, and said, "We're not coming. We're going to honor the boycott. We don't feel comfortable coming." They said, "What do you mean? You're this keynote speaker. Everyone's coming, you're the draw." But I responded that we're not coming. Period. I'm sorry, I felt bad, but we don't feel comfortable going." And they said hold on. And they called me like in a week or 10 days and said, "We really need you to come." I said, "We're not coming."

And the call came back a month later, and said, they're moving the meeting. "Everyone's paid, they're coming to see you. They're moving the meeting.” And we weren’t broadcasting our decision but what happened was that somehow Chemical & Engineering News, the official magazine of the American Chemical Society, caught wind of the story and wrote an article about our decision and included a picture of my group and my students, and what also became clear to me then was that we became a destination for excellence—a research group where people from all backgrounds would feel included.

And so, I started realizing more and more that when you’re intentional about your values and you’re clear about your values, you can become a destination for excellence, and that can really build momentum in your innovation process by having not only disciplinary diversity, but human diversity, seek you out. It really became clear to me how these things go hand in hand, and we've been doing that ever since.

Zierler:

Tell me about your affiliation at NCSU. What was attractive about having that Chemical Engineering dual position as it were?

DeSimone:

I joined Carolina's Chemistry department in 1990, and as I mentioned UNC did not have an engineering school, and I was collaborating with folks at NC State and it reinforced for me then how I needed—and I missed it from Virginia Tech, which had really great engineering—I was missing out on having engineering graduate students in my group. And so, I approached my colleagues at Carolina and said, “Guys—" I had already published a paper in Science at this point, and I felt wanted, genuinely, and I said, "Look, I hate to tell you this, but I can't stay here. My career's being held back because of not having engineering students and engineering colleagues, and nobody feels worse about this than me,” and I was very apologetic. And they didn't want to lose me. And I started telling my engineering colleagues at NC State who I was already collaborating with that I'm leaving—that I had to find a place that's got great chemistry and great engineering and included medicine.

And then the head of Chemical Engineering and the former Chair of Chemical Engineering at State approached me and said, “Why don't you just join the faculty here at NC State in addition to staying on the faculty at UNC?" And when I first heard that, I said, "That sounded illegal! How can I do this!?" And what we did is we crafted the very first joint professorship between Carolina and NC State. And I did it—Hal Hopfenberg at NC State was amazing. He's like, “Look, I'm going to simplify your life. There's going to be no salary issues with NC State. All your salary will come from Chapel Hill. You only want one boss. There'd be no teaching responsibilities at NC State. You can become a full member of our faculty. You can advise graduate students and undergraduates, and it's just research enjoyment only." And they crafted this position, and they threw a professorship on top of it to make it work and that's what happened.

And so even though it was 25 miles away, I had lab space on both campuses. Eventually, what happened was—and it's mostly because the lab space at Carolina was terrible in the beginning, but they were building new buildings, and once the new buildings opened up at Chapel Hill, my NC State students started to work at Chapel Hill. On top of that, we really tried to bring the state together through both of the two flagship institutions and tried to make that work, and we did pretty well.

Zierler:

Did you take on different graduate students with this affiliation?

DeSimone:

Yeah, very much so.

Zierler:

And that was—obviously, that was part of the attraction?

DeSimone:

That was the goal. Yeah, that was the goal.

Zierler:

And in terms of salary, in terms of responsibilities, did this become essentially a 50/50 split?

DeSimone:

No, no, there was no salary with NC State. They worked it out. They worked it behind the scenes. They didn't want me to have two bosses and feel conflicted. It was just to enable convergent research—be a full member of the faculty, advise students, but no teaching responsibilities at State. No salary issues, had one boss, and really just very collaborative, and can structure it in a very supportive way. It was really great.

Zierler:

Tell me about being named to the Kenan Chair at UNC?

DeSimone:

Well, it's pronounced “Keenan.”

Zierler:

Oh, it's “Keenan?

DeSimone:

“Keenan.” It's spelled Kenan, but it's pronounced “Keenan.” Kenan professorships are a national thing. In fact, there's some at Stanford here that I noticed, and they put this together when I got tenure as part of the bridge with NC State, and it was a real prominent thing. Again, I didn't come from what one might consider academic prestige university—I went to Virginia Tech, not a top five university—and I didn't appreciate what a professorship meant, and then it evolved, and I was doing so well, there was the chance for the Chancellor’s Eminent Professorship, sort of on top of it. This turned out to be a $3 million endowment, which basically threw off $150,000 a year. Most professorships are used to cover your salary, but that was already covered with the Kenan professorship. And then I had a professorship basically throwing off $150,000 a year of research support that I could use to seed ideas that weren't fully funded, and we can make good use of that.

And in many ways, when you think about funding, and now that I've been in academia and in industry, you start to really appreciate that the funding models are so different. This was like seed capital in the venture world, having $150,000 a year, which could support two, three graduate students—and it doesn't cost very much money to support students especially at a public research university. Very different than at Stanford. But when you think about this you can start with a premise that vision without resources is a hallucination, right, and you need dollars to make your ideas happen, and then you think about how ideas get funded in academia? It's through grants and the big funding agencies like NIH and NSF. And you have to submit grants to these agencies, and it's so competitive now where it'll go to five reviewers and you need five “excellents,” because if you get four “excellents” and one “very good,” you're likely not to get funded.

Now, put a pin in that—there's a really great book out there about ideas by Peter Thiel, who's one of the founders of PayPal, and a bit of a controversial figure, but nonetheless, great book, and the book is called Zero to One. And in that book, he talks about “zero to one” ideas and “one to n” ideas. A “zero to one” idea is an idea that is a breakthrough, seminal idea, and a “one to n” idea builds on that idea. And his thesis in the book is that at the core of most “zero to one” ideas is an idea that you alone believe in, and that nobody else does, okay?

Think about getting resources. When you are starting a company, and you go to a place like Sand Hill Road, which is a metaphor for going to visit all the venture capitalists because all the VCs are located on Sand Hill Road next to Stanford's campus—going to Sand Hill Road in an afternoon or two days, you can hit 15 VCs. And what's cool is you can go to Sand Hill Road with a “zero to one” idea, an idea that you alone believe in, and you could hit 10 VCs and you can get 9 no’s and one yes, and you're in the game. In academic circles, there's no equivalent to that. You need to get 10 “excellents” to get your idea funded because if you get one no, it will get torpedoed. And so, the point in this is that it's ironic—in academic circles, you can't propose your own ideas that you believe in unless many others believe in them too. You have to propose incremental ideas because you get chewed up so badly when your grant gets reviewed. People need to feel like it's going to work in order to give you a great score, and I find that ironic for academic circles—you think academia is supposed to be the harbor for new ideas, and it really isn't and that is because of the funding mechanisms. And so, I've got a lot of clarity now about the importance of private funding and federal funding and this entrepreneurial intersection that is really key to driving some of the biggest ideas and training people in sort of a hybrid model, and that's what I'm going to do here at Stanford.

Zierler:

Joe, how did you get involved with the NSF for environmental responsibility?

DeSimone:

NSF centers are the crown jewel of a lot of universities, and I had watched Carolina apply and not win lots of centers when I was a young PI. So, coming off of our use of supercritical fluids that I mentioned, that's an environmentally responsible way of making polymers instead of using water and organic solvents, and it just so happened that—and timing's everything—we were synthesizing fluoropolymers or cousins of Teflon in CO2, instead of the traditional way of doing it in water with added detergents, known as PFASs, the environmental pollutant that now seems to be in the weekly newspaper.

But back in 1991, when we published our paper in Science, it wasn't an issue. It wasn't known to be an issue, but we were replacing water and PFAS with simply CO2. The environmental implications of that opportunity started to emerge later in the 1990s, and so we used that perspective to establish the NSF Science and Technology Center for Environmentally Responsible Solvents and Processes. I brought a community of scholars together that covered Chemistry and Engineering and had multi-institutional support with the NC State, North Carolina A&T State University, which is an HBCU, University of Texas at Austin, and we also brought in—for the first time in Engineering Center efforts—a couple of social scientists to bring an educational framework for collaboration and effective multi-institutional, multidisciplinary research.

And NSF had never seen social scientists become embedded into a Physical Science and Engineering Center. So, we pioneered that. And our proposal got funded, and we had a 10-year run, a $37 million run from the National Science Foundation on environmentally responsible solvents and processes, and we pioneered the broad inclusion of social scientists into these centers, which became something NSF wanted to see all the time afterwards from other proposers. They started adding into RFAs, "It will be really great if you brought in social scientists into the network," because it would prove the important point that it made it a much richer experience and more successful experience.

Zierler:

What did you learn overall about science policy at the federal level in this program?

DeSimone:

That there was a lot of clear intention, but there was weak enforcement. And I realized, this PFAS thing was the slowest train wreck you could have ever seen, and it was mounting—you knew it was a problem. It was kind of like having 3M's logo, circulating in everybody. These were manmade chemicals only made by a couple of companies and you knew who they were, and they were persistent. These molecules would fit into the lipid bi-layer in cells perfectly and they were persistent. And so, what I saw was a good intention, but poor execution from the federal authorities, and then, companies could easily navigate continued use of PFAS and use reclamation and cleanup approaches instead of elimination approaches. Now, it's really destroyed lots of lives and lots of property, for example in Parkersburg, West Virginia and in North Carolina and many other places where these chemicals were made and used. And it's still proliferating—it's used as an anti-crease coating on paper and fabrics and scotch-guard and all sorts of things.

We saw this happening and I saw the industry pushing back. And in fact, at the end of the day, this is what made me become an entrepreneur because this work we did in the 1990s, we were collaborating with DuPont and I had some big fans of our work at DuPont. I won a collaboration award with them, and there was a faction at DuPont that was extremely supportive of our work. But there was a business unit and a different faction of people frankly whose bonus depended upon using an existing factory that was already paid off and running it full tilt the way it was. So, I actually learned what entrenched interests were then. And I was caught in the middle of two different factions within DuPont. And it was never fully implemented at DuPont. It was only partially implemented.

And what I saw there were these entrenched interests at the end of the day winning out, and when you believe in something, and you can't execute on it, nothing's more frustrating than that to a researcher. Nothing is more frustrating than that, and the University of North Carolina had signed an exclusive license with DuPont for our technology. So, we had nowhere else to go with it there. We're locked in and they didn't fully implement it, and then they started patenting underneath our patents and they didn't even need an exclusive license, because they had, by default, their own IP to our technology, but didn't implement it. So, it's born out of that frustration that I became an entrepreneur because I understood what entrenched interests were and again, nothing's more frustrating than believing in something and not being able to execute on it. And in entrepreneurship, there's no holds barred like that, and that's what drove us forward.

Zierler:

Joe, when did biology and specifically nanotechnology enter the same for your research? Was it a gradual— was it a gradual process? Did you meet someone and it happened suddenly? How did all of that come together?

DeSimone:

I didn't even take a Biochemistry course as an undergrad, and I get plopped into Carolina. We are influenced by our environments, like you can't believe, and Carolina is a powerhouse in medicine, but I was in the Department of Chemistry, and I was doing environmental things and Material Science things—nothing to do with Biology or Medicine, and then a colleague from the medical school, the Biochemistry department who I ran into, wanted some help from our group to deliver genes and do gene therapy and wanted to know if we could use some Polymer Science to help do that.

So, I started reading papers about what people were doing in the polymer world to help deliver genetic material, and again, as a polymer guy, I didn't even think much about DNA at that point. I thought of it as a polymer back then, but that was about the extent of it. And as I started looking into this world, I fell in love with the Central Dogma of Biology, right, DNA makes RNA makes protein, sort of back then and sort of realizing, this is like the most exquisite polymer science I've ever seen in my life, amazing control, sequence control. And at that time to deliver the genes, people were using colloids, particles, gel particles and to me, that's the essence of paint technology. And so, I was like, here we are using cousins of paint to deliver the most exquisite molecules on the planet. And I thought, man, there's got to be a better way than this because paint is pretty rudimentary!

And I had up to this point been doing a lot of work related to the microelectronics industry in developing polymers for lithography for patterning silicon wafers. That was my PhD area with Jim McGrath, and people were using cousins to paint to do gene delivery. I said, well, why couldn't we use some of the tools of the computer industry to make precision particles? And you got to, remember, again, timing is everything, but biology was getting more and more cellular focused and virus-focused for delivering things, and during the time that I was in the microelectronics world, the dimensions that one could pattern on a wafer were going from 10 microns to 1 micron to 100 nanometers to 10s of nanometers, and I realized that the vectors for delivering biological molecules were cellular size, and they were like 8 microns, and then viruses were like 10 nanometers, 20 nanometers, 30 nanometers. So, I realized that the dimensionality of the microelectronics industry was converging with the length scale that was important in biology, very fortuitous timing. And so, I said, why can't we pull in lithographic tools to make synthetic vectors, and that's when—at the same time—we started doing some imprint lithography work, molding lines and patterns for the microelectronics industry and watching what George Whitesides and John Rogers were doing at Harvard and other places, and I thought, well, why couldn't we mold particles?

So that was what became the foundation for us. And I remember, when we had some success and a couple years later, I had an opportunity to speak to Bill Gates at a meeting that I was attending in California at the time. I knew I was going to get an audience with Bill and, again, I was a seasoned entrepreneur at this point, and realized there would be a couple of minutes with Bill—so what should the elevator speech look like? What do you say to Bill Gates to get his attention? And so, I had the opportunity to introduce myself, and Bill said, what do you do? And I said, well, I'm using the tools of the computer industry to make better vaccines. And he sort of did like, a what-do-you-mean? And so that turned into a conversation and he fell in love with it. He ended up funding our company, Liquidia at the time, and so yeah, that's how we got into. It was this dissatisfaction with the emulsions used commonly in the paint industry for delivering genes that drove us to bring some of these top-down fabrication technologies from the microelectronics industry to an area that was all driven by bottom-up self-assembly approaches.

Zierler:

Joe, was part of it also just the desire to bring science to a place that was of most elemental impact to humanity?

DeSimone:

No. It was more about we had a cool approach that no one had done before. I love doing these different things. Again, I'm not—you asked me about theory earlier. Again, we're not the deepest of scientists, but what we're good at is being clever and bringing things together that hadn't been brought together before and thinking about things differently, and that's what I think distinguishes what we do.

Zierler:

Now, maybe it's a chicken or egg kind of question in terms of your interest at the time in the creation of the Institute for Advanced Materials, but is your sense more that your interest and entree into this field sort of precipitated the need for the institute or as you were getting more involved with this and you had the institute, that's where you had these opportunities to branch out?

DeSimone:

Now, the Institute for Advanced Materials was a big step in a direction for Carolina to get into engineering because we did not—unlike Virginia Tech or NC State— we did not have the shared user facilities that are common to engineering schools.

Zierler:

But this is a blind spot from NCSU in the beginning, this is not new information, Chapel Hill.

DeSimone:

Well, I know, but I kept advancing, advancing, and all of a sudden, now we have a cohort of faculty. Now, it's not just me, it's a cohort of faculty that had the same shortcomings at the institution that I had, but because we were getting so prominent, I was able to loosen up the purse strings and have them commit to faculty positions and facilities that would put us on the map—it would move us into a more substantial place to be competitive in the marketplace, so to speak.

Zierler:

What were some of the advantages to having the institute in terms of post-docs, in terms of senior people to interface with?

DeSimone:

What it did was it generated the first clean rooms on our campus, and so we got the resources—the Chancellor committed the resources to establish CHANL, the Chapel Hill Analytical Nano-fabrication Laboratory, and it would have a staff person and clean rooms and some modest equipment. CHANL brought together photoelectron spectroscopy, XPS and another TEM and other SEM, some deposition tools. These were things that Carolina never had—well, they had electron microscopy, though it was more in the bio-world. So, then everybody in the medical school became our champions too, because they saw the power of what we're doing to support medicine. And the hallmark feature of Carolina is that it's a very collaborative, supportive environment, I would say. There were people there that had the resumes to be assholes and they weren't, and that's a really neat environment. So, people were teaching me biology and my students biology, and we could be comfortable with what we didn't know and that would not be held against us.

Zierler:

You mentioned the culture of the community there. What about, as you were becoming more interested in business and entrepreneurial stuff? Was this something where you could be out in front in this? Was that something that professors were supposed to not be involved with? How did all of those things work?

DeSimone:

So, Carolina's translational entrepreneurial stuff was nascent when I was coming through and we did the partnership with DuPont, and that was arduous, and they basically traded rights for a small amount of dollars to support patent costs. But then we had a Chancellor come in—Michael Hooker. He came from the UMass system, and he said he wanted his faculty to create as many conflicts of interest as possible and have the university manage them. I thought, well, that guy's got a very different perspective on life, and I believe that too. He said, “a conflict of interest, what that really means is you have a connection with the outside world, and we've got to be for collaboration.” He said, “The problem with conflicts of interest, at the core, is when you don't know what hats people are capable of wearing, and you're not transparent.” He said, “Let's shine a bright light on everything. Let's just be really transparent. Let's manage those conflicts we can manage. Let's avoid the conflicts we can't manage and most of those are around human health, clinical trials.”

And I became part of his team, along with Holden Thorp and a few others to paint really crystal-clear guidelines on how one can manage conflicts of interest. We set up a very rigorous conflict of interest management program that had teams of faculty that would work with those who were declaring conflicts—meet with the faculty and their students together and then also independently to ultimately make sure the students were publishing and going to meetings, and I think what happened was that people realized that those who had these external collaborations were among the most prolific people in science, and their students were going to all these meetings, and that we could manage these things. And there are a lot of horror stories of faculty screwing this up, and so going into this with your eyes wide open and instituting clear policies, clear expectations, and very transparent processes, Carolina became one of the leaders.

And then we ultimately—then I got really into it, and Holden then became Chancellor at UNC. As a fellow chemist, he was frustrated with the slowness of licensing, and he asked me to chair a committee and now we're on the inside with the licensing people. And every license agreement seemed to take 9 to 18 months to get a deal done which is, like, really slow and I ended up asking, "Why is it so slow? And why is every deal so different?" There’re so many nuances. So, I said, "Well, let's gather the data.” As chair of the committee I said, "Let's look at—15 years back, let's look at all the licensing deals and terms," and what you realize is that like 90% of the deals were all identical terms, identical terms, but it still took every one of them a year and a half to get done. But if the licensing terms were identical, why does it take a year and a half, why?

To make a long story short, we established then, and we had support from the administration, something called the Carolina Express License Agreement, which basically said, if you meet these 10 or so criteria, you can get a license agreement in like 2 weeks and here are the terms. If you want something different, you can go down this other path and do something different and we'll engage in the full process. But if you can meet these standards, you can knock it out very quickly, and here are the terms. And what happened was that Carolina faculty started to become conformists, which is really rare for faculty to do (!), for expediency reasons. And the Carolina Express License Agreement started getting picked up at other universities and became a really nice way to change the whole landscape on licensing at many, mostly public universities.

Zierler:

When does cancer research come into the picture for you?

DeSimone:

It was in that Gene Therapy program. People were in that space and that's when I became a member of the Lineberger Cancer Center at UNC.

Zierler:

And more broadly, Joe, this is a time in which people are increasingly appreciating the genetic underpinnings of cancer?

DeSimone:

That's right, and gene therapy and then nanomedicine started to emerge and then a whole idea of how to develop more effective ways of delivering chemotherapeutics locally. This is also at a time when cancer detection was getting earlier and earlier when a lot of cancers were still local and not yet metastasized. But many of the chemotherapeutics, which are just general poisons, were being given systemically since cancer cells typically divide more quickly than regular cells. So, dosing up a human body with lots of chemo meant that the faster-dividing cancer cells were going to take up the chemo more quickly than regular cells that are not dividing as fast, and that was a selective way of more poisoning cancer cells than regular cells. Local delivery and targeted delivery were just beginning to emerge, and then the whole field of targeted delivery and focal delivery started to come out of that.

Zierler:

And in terms of both UNC School of Medicine and the Carolina Center of Cancer, where are you spending more of your time? Where are the more important affiliations at this point?

DeSimone:

So, I was heavily in that world, and when the North Carolina Cancer Research Fund got established, I was in that little room when it happened. I was there with a Chancellor and some really powerful state legislators, and I'll never forget the room was, maybe a 6x8 foot room. We were all crammed in this little room, and this legislator, who is really powerful, started telling us a story about how his wife was diagnosed with cancer and, of course, he was going to go to Harvard Mass General to treat her and not Carolina.

And he brought her up there, and the doc starts to describe the disease and the prognosis and her treatment, and this legislator told us that the physician at Harvard said, "Well, we could treat her here, but the world leader for this particular cancer is at UNC." And he said, "I'm going to make sure that Carolina stays at the forefront of cancer research," and he established a $50 million a year initiative, $50 million a year of taxes on cigarettes, and so all went to Lineberger. Amazing, amazing commitment—a huge endowment equivalent.

And that really put us on the map. With the extraordinary resources there, we had great tools and were able to venture into nanomedicine and the vaccine world. We were delivering genetic material and chemo with our particles. And then, one of the most challenging cancer we were getting hit over the head by the National Cancer Institute saying, "Look, you guys are all treating the same cancer. Nobody's going after glioblastoma or pancreatic cancer or ovarian cancer, and we need you to work on that because nobody is."

Very few of us in the nanomedicine field worked on these challenging cancers because we knew there was a drug delivery problem with these. With pancreatic cancer in particular there are these biological barriers, and so I was able to look at these cancers as a chemical engineer and realize that, putting chemo in the bloodstream and hoping it gets to a tumor, it's mind-boggling in some ways that people went at this in that direction. Pancreatic cancer, in particular, is really challenging to treat—I became exposed to it through some studies that my students were doing, and I don't like working on animal models myself, but they were good at it, and I'd go in the lab and watch them do their immunizations and surgeries on mice, and I'll never forget when I saw my first pancreatic cancer tumor, which was explanted from a human and put into a mouse. I thought that they grabbed the wrong tissue because it was as white as your eyeball. Most tumors have a really rich blood supply and are bloody, but this looked like cartilage. I said, "Are you guys screwing this up?" And they said, "No, no, that’s a tumor," and started to realize that pancreatic cancer tumors, when they're diagnosed, more than likely, they started about 20 years earlier.

It's a very slow-growing tumor and it's got a huge fortress of stroma around the cancer cells that start to block the lymphatic system. So, it's very slow-growing, and when it presents, it's usually too late—it's infiltrated into an area with some big blood vessels. So there's no blood supply, and we're putting medicines into the veins of mice, and not only does it have no blood supply or very little, it's got a high hydrostatic pressure, meaning the lymphatics are blocked, meaning when you give chemo, that drug is going just about everywhere else in the body except to the tumor. And I said, "This is mind-numbing." So out of that frustration, we developed a new technology that would actually put a device on the tumor and use a mild electric current, a technology called iontophoresis, and we would drive small molecule drugs directly into these tumors through this device. The work was funded using my NIH Director’s Pioneer Award, which was flexible funding at NIH and not for particular projects.

So, leveraging that funding flexibility we developed a device that could deliver drugs locally to pancreatic tumors, and lo and behold, it worked like a champ and we had the very first example of debulking of pancreatic cancer tumors—no one had seen this before. Our paper got published in Science Translational Medicine, and we'd just started nurturing that technology with seed funding and some SBIR grants and I'm happy to say, a few months ago, that our company in North Carolina was just funded with a Series A financing from Khosla Ventures based in California. And it looks like we just got another $4 million SBIR grant on top of it. So, the technology is finally coming to fruition. I have a little more time now to help lead the company. So, I'm on the board working to help the company get stable funding, and that company's taken off in North Carolina. So again, being able to do translational research and make a difference, I love doing that stuff.

Zierler:

Joe, it's a great illustration of a comment you made earlier about being not necessarily visionary, but clever. I wonder, in the worlds of cancer therapy, biology, these are not in your wheelhouse as academically in terms of your own training. Is your style such that when you're involved in these new pursuits, you're really an autodidact, you're hitting the textbooks, you're going to classes, or do you know what you bring to a collaboration and you rely on other fields, other experts to know what you don't know yourself?

DeSimone:

I would say it's a hybrid, it's both. The metaphor that people have used in the past about I-shaped people and T-shaped people, where I-shaped means you're really deep in a subject and a domain expert, whereas a T-shaped person not only is deep in a subject, but also has sufficient knowledge in other subject areas such that they are able to deftly collaborate with other disciplines—sort of the metaphor of the T. I think the metaphor today is more about being pi-shaped or comb-shaped. You’ve got to be deep in multiple subjects. Otherwise, you leave the collaboration at a level that's more like a common language, rather than being multilingual; multilingual is a higher calling, and that's where all the good stuff is today. So, if you're going to really design vaccines, for example, you've got to be—you've got to understand human immunology and the role that T-cell activation, B-cell activation plays in order to be really effective in delivering mRNA or subunit protein vaccines using the tools of Chemical Engineering—the whole realm of vaccine kinetics. And so, this goes well beyond the T-shaped metaphor. Maybe in the beginning, you get into a subject and you're being taught by others, but in order to take it over the goal line, I think you need to become more well-versed—and respect what other experts bring and not usurp those areas, and do this in a collaborative way where everybody is moving the field forward together.

Zierler:

What did the affiliation at Sloan Kettering do for you?

DeSimone:

Sloan Kettering is an iconic brand and for me, a guy like me, who knew the name, it was fun to get involved. I was on the board of scientific advisors at the NCI and, again, a lot of highfalutin people on the board, and I'm just like a guy, a jag. I was just a guy on this thing, but people loved what we were doing. And I thought, man, that's amazing.

And the head of Radiology at Sloan Kettering saw what we're doing. Now in medicine, there's a great institution that has no engineering and I look like an engineer to them. I said, "Would you come and help advise us on doing what we’re doing so we can do nanotechnology here?” And so like, man, any affiliation with him, I thought, would be fun. And I love New York City. So, my group would go up there once a year, and we’d go to Carnegie Deli and walk Central Park and then have a little mini-symposium, and they'd asked me questions about colleagues and help mentor some of their instructors. But it was just—it was fun to be in the middle of some of the best US academic medical science, and people thought what we were doing was interesting. So, it was fun to engage that way.

Zierler:

I'm trying to get to the intellectual origins of Carbon 3D. When does this first start to come together, and is it more going back to your roots in polymer chemistry?

DeSimone:

So, here, I have run the full gamut of academic research, right? I had led an NSF Science and Technology Center for 10 years. I had led a Center of Cancer Nanotechnology Excellence for 10 years, and those two centers overlap three years or so—the biggest centers that academic science has. And I had taken over the lead position at the Kenan Institute of Private Enterprise in the business school at Carolina, and I'd been looking for the next thing. I was in my late 40s, just turning 50, and I had been approached for a few academic leadership positions, and I came in second at three or four different ones. That would have taken me out of Chapel Hill.

Zierler:

And out of research?

DeSimone:

No, I actually, and this is why I probably lost those positions, I said, "No, I wasn't going to give up my research. I plan to do the administrative job you are looking to be filled while maintaining my research." And they said, "You're naive, and you're not coming here." And then I had a former post-doc of mine approach me, and I love 3D printing. I taught about it in my classes, and it was used mostly by the Dental industry, and I would teach about Invisalign, and I did some consulting with Invisalign in 2000, 2001 when they were just coming up. And my former post-doc asked me, he said, "I want to form a company in 3D Printing. I want you to join me and help make this happen." Meanwhile, I'm busy doing my thing in a business school.

I said, "Well, what's the idea, Alex?" He said, "I think we can build 3D printers cheaper than everybody else." I said, "Alex, that's an activity. That's not an idea. What's the idea?" He said, "Well, that was it." And then I asked him a question that I knew the answer to before I asked him, but I asked anyway, I said, "Did you look up any patents?" He said, "No." I knew he was going to say that. So, I said, “Well, go look up these five keywords and come back to me.” And I’m at the Kenan Institute of Private Enterprise now, so come over in the afternoon.

And three days later, he’d come back, and he was all depressed and there were like 480 patents, and I love patents. I think patents drive innovation. A lot of people think patents stifle innovation, but it's a really powerful tool to see how people think about their ideas and how did the ideas work? It's a roadmap, it's a manual of ideas. And I said, "Well, look, let's look through these patents. Let's understand how people protect their ideas. What are they doing? How's this all work?" Because I knew some things about 3D printing, but I didn't know what was important to have people protect it from the intellectual property perspective.

And what you could see is that the technology hadn't evolved very much. It was more about applying it, a lot of those patents, and almost every claim was layer-by-layer. I said, "Alex, why don't we go where no one else is playing—let's go over here and do it continuously. Let's not do it layer-by-layer." And we set up a series of conversations that were happening every two or three days. And we said, "Well, we're going to do it continuously." And so, we started setting up some simple questions and framing, "Well, how are we going to do this?" "Well, we're going to do it continuously. We're going to do Chemistry. We're just not going to do melting of polymers or sintering because that’s what others are doing. Let's do photochemistry."

And then we start thinking, "Well, do you have a big vat of liquid resin and you're going to make the part in the big vat?" And then if you're making a small part or a big part, you're still immersed in a lot of resin, and that just sounded messy and inefficient. I said, "Well, let's have the object come out of a puddle of liquid. Let's keep a reservoir. And if we needed more resin, we'll keep filling the resin up. And if it's a big part you fill it up a lot and keep adding it. If it's a little part, you don't need to fill it up. But let's have it come of the vat, out of a puddle and not have it sitting in resin." And kind of like the Terminator, T-1000, "Let's have it come out of a puddle."

So, we set that parameter up with not much more rationale than what I just told you. Then, we're going to have light coming up from underneath because we're going to pull it above and so you need to form it from underneath and we thought, "Well, if it's coming out of a puddle and you're going to pull it out from a platform, then you're always going to maintain a puddle—why don't we sort of project a focal plane through the window above the window so that we can maintain the puddle underneath and have the image be above the window?"

Well, that turned out to be a dumb idea because even though the light wasn't in focus, there was still light coming through the window and photo resin didn't care if it was in focus or not, it would still cure. So, well, how do you form a liquid layer and still have light come through it? And in Polymer Science, a fundamental realization is that oxygen is an inhibitor of photochemistry, and if you coat a table with a liquid resin, and you want to cure it with light to, for example shellac a table, you can't do it in air because if we do it in the open air, you'd have an uncured layer that the oxygen inhibited on top of the thick cured layer.

And we said, "Well, let's do that, but let's invert that idea and have a window that would allow oxygen to come through and light to come through." And by the way, the best polymer for that sounds like a material similar to a contact lens. The best polymer to do that happened to be a fluoro-polymer like what we used to make in CO2 years ago. And so, I knew exactly the fluoro- polymer—we’d made them in CO2, but I'd gotten out of that field by then. So, I called up an old DuPont-er, who was now retired, Paul Resnick, who lived in Cary, North Carolina.

And I said, "Paul, I need—so Alex started building this printer because he was good at motors and wiring, and I'm not good at doing that stuff, and Alex started building this printer and some modest software to control this little motor." I said, "Paul, I need some Teflon AF 1600, and I have no money and I just want to get it from the cheapest place. Where is the cheapest place for me to get some?" He said, "Well, Joe, I happen to have some in my closet." And he said, "But unfortunately, it's in the form of a plate, a window." He thought I wanted powder or pellets. I said, "Paul, I actually just wanted a plate, a window." He said, "Well, I have it." I said, "Well, Alex, my former post-doc can come over and get it." It's less than an hour drive. It was a Friday and we had already been building the printer and we were using other materials that weren't as permeable to oxygen, and our little apparatus wasn't working at all. It just kept sticking to the window and just wasn't working. And so, I said—I told Alex, "Go to Paul's house, come back," and it was on a Friday.

And he got there at 3 o'clock, he put the new window into the device, and at 6 o'clock, it worked like a champ. It just worked and I was there when it worked. And so, the next day, I contacted two lawyers, a business lawyer and a patent lawyer and we launched the company.

Zierler:

What was the technology that was available at the right time and the right place to make all of this happen?

DeSimone:

Well, it was a convergence of people. Alex could build a little apparatus. He wanted to move into 3D Printing. We thought about things differently and then we started talking. I got my son involved—at the time he was a business guy at Ursinus College. He had started his own e-commerce company, and he started talking to some industry experts and he came back to me and I told him, I said, "Look, we're going to be printing really fast now." He's funny, because he went and said, "I talked to some 3D industry experts, and they said they don't think speed matters.” He said, "Because we could just set it up at night and come in the next morning and it's there or set it up over the weekend." And he says, "They don't get it. They don't get it. This is perfect." So, he turned that—I would have been a little bit dissuaded by that they didn't care, because I'm often responsive to those that care about what we do. And he saw their lack of care as a huge opportunity.

So, I think it's context, it's understanding fluoropolymer characteristics, it's being entrepreneurs. It was my fourth or fifth rodeo at this point and being able to call the right attorneys is key, and then we had some seed funding that we put together very quickly, and some local investors-we got some money behind it, and then we decided to get real money behind it. And I'll never forget, we were going to go to Sand Hill Road, and we did a dry run with our friends and family in North Carolina of the technology. But we were going to go out to Sand Hill Road with a PowerPoint presentation. But when everybody showed up with our little prototype apparatus in North Carolina, we not only gave them the PowerPoint pitch, but we also showed them the technology and printed for them. They were, like, amazed.

And I went for a walk with my wife that night after that little show-and-tell and walked the dog, and we're walking and my wife says, "Joe, your pitch was really, really good." And then she stopped talking. I was like, "All right, she's about to tell me what's not great." And she says, "But the printer was way better than your talk. Why aren't you bringing the printer out to Sand Hill Road?" I said, "Well, that's not the way they do things, but you're right." Then we scrambled.

Zierler:

You made a real demo?

DeSimone:

We brought the printer with us. Yeah, a real demo. We weren't planning it and we walked into Sequoia Capital, the premier venture capital firm. We had an audience with Jim Goetz, and that happened because my son had ended up doing an internship with Brent Jones at Northgate Capital and Brent's daughter—Brent was a tight end for the 49ers and has 5 Super Bowl rings, and his daughter played on the Carolina women's soccer team, and he had taught some entrepreneurship classes of mine, and Brent knew Jim and so we got an audience with Jim.

And unbeknownst to us, Sequoia had been looking at 3D printing for the three years earlier and passed on the entire sector because there was no technological revolution that he saw, and we brought our printer—it was just him and one other guy. It was a Wednesday meeting at 9 o'clock. We flew out that morning, put the printer in a private airplane, had the chemicals in the back. We didn't realize, didn’t really think about it, but the chemicals froze and we had a tight connection. We had a tight timeline—and we landed—we were supposed to be at Sequoia. We thawed out the frozen chemistry on the way to Sequoia’s office. Weren’t sure if it was still going to work because it may have crystallized, but we set up the printer and we printed for Jim in real-time. And he said, "Holy shit." He said, "Could you do this again at 11 o'clock?"

Zierler:

What did you print?

DeSimone:

Little chess pieces. He said, "Could you do this again at 11 o'clock?" And we said, "Sure. We had some other meetings we wanted to get to, but we could do that," and he started bringing in a few others, the curmudgeons, as I say, at Sequoia Capital and he said, "Could you do this again at 3 o'clock?" And we were printing all day long and we had a roomful of Sequoia people, and they wouldn't let us leave. And we committed to a deal that day, and we got the best venture capital firm at fair terms, and we signed a deal, and we're out of the gates. And then, shortly thereafter, I'd already hired a CEO, but they came back and said, "Look, why don't you lead this?" And I told them all the reasons why it's not good to have faculty members lead companies, and they'll screw it up, and he started talking to my wife and my wife said, "Look, you've always hated the way your companies go. You've complained so much. I'm tired of hearing you complain. Why don't you go do it?" I said I’d do it for one year. Turned out to be almost seven years.

Zierler:

Joe, you mentioned Alex's skill set. What about Ed Samulski? What did he bring to the table?

DeSimone:

So, Ed hired me at Carolina, and Ed also graduated from Tobolsky's group at Princeton and I got Ed involved in everything I did. He's fun, a friend of mine—our families grew up together—and he’s smart. And he was that physical chemist who brought a lot to the table at different times. So, I always brought him in and it was fun for me to do that. He would contribute in different ways. It wasn't at the genesis of the idea, but he'd give us street cred. I always said, he always gave us great street cred.

And he became infatuated with this and there was a lot of momentum behind what we were doing. But we actually—it was curious. We started to have a different view of field, and Alex and Ed would—Ed loved Alex. I did too. Alex was hell-bent on the maker community. Maker spaces and maker communities were taking off. And remember, he wanted to build a cheaper printer, and he wanted to make a little simple printer. And I was like, "That's not of interest to me. Look, guys, we're going 25 to 100 times faster. I want to go into manufacturing. Let's not screw around with the maker community, let's go after injection molding."

Zierler:

What does the maker community mean?

DeSimone:

High schoolers and middle schoolers using printers to convert an idea into a physical object, but it was typically a brittle plastic trinket. It didn't have the properties to be a running shoe or a car part. It was brittle. And I said, "Look, making brittle things really fast is not of interest. Let's make real parts." And so, what that meant was we're going to have to go well beyond a fast printing concept—we would have to make a reliable printer, and then we needed big innovations on the materials because light alone is not useful to make the kind of polymers useful for real products. They're always going to be brittle.

And so, when I became CEO of the company, we went and raised our second round of financing from Silver Lake, the big technology private-equity firm. They were another investor that was not interested in the maker community and just getting low-price printers out, and Sequoia liked the idea of trying to revolutionize manufacturing. Sequoia, they had bet on Apple and Google and big companies. They liked to change the world, and I've wanted to change the world, and so the founders actually had a huge falling out regarding our vision between us. And I wanted to move the company to California and do manufacturing, and those guys didn’t want to do that and they didn’t. Philip and I, my son and I, moved the company to the Bay Area and those guys stayed in Chapel Hill, and we went after the whole enchilada of manufacturing. And so, it was a big departure for us.

Zierler:

Joe, to go back to those original best-laid plans of it being one year before it turns into seven as you're envisioning it, what would you want to have accomplished in that one year, at which point you were prepared to walk away or sell?

DeSimone:

I think at that point, we would have had great leadership. I would have hired—I did the things I needed to do to hire great leadership, like our VP of Engineering. I hired the founding VP of Engineering at Tesla and started getting great people, and all of a sudden, you realize that people were coming to Carbon because of me as much they were coming for the idea, and—what happens out here is people bet on people, and when you're hiring people that are going to leave Facebook and Google and Apple—and this is what Sequoia knew ahead of time—they come because they believe in the idea and the team, so there was no way I could step away at that point because they were coming to the company because of me as much as the technology and the vision.

And so, we started—and we're having a lot of—an enormous amount of fun. It was a great time! Everything was new, and we're building, and our printers worked. We were in stealth mode, and we knew we had something. And one of our investors got us connected with the curator at TED, and we got into queue at TED, and you go through lots of dry runs, and they decide who's going to speak and we got selected to be on the big stage at TED. At the same time, we had just gotten a paper accepted in Science, and TED didn't want to preempt my talk with anything published, and Science didn't want anything preempted.

And so, lo and behold, we pulled off an entrepreneurial hat trick coming out of stealth mode. In the moment I walked onto the stage on that Monday night in Vancouver, the embargo on our Science paper was lifted, and the website for the company went live and we had a big splash. And it just so happened that Larry Page and Sergey Brin were in the audience at TED, and Google Ventures ended up leading our Series C financing after Sequoia and Silver Lake, and we were off to the races.

Zierler:

Given this level of interest, what concerns did you have about being bought out, or was that actually a goal?

DeSimone:

It was always on our mind. When we launched Carbon, we had watched a 3D printing company get acquired for, I think, $200, $300 million and we thought, "My God, if that could ever happen to us, that would be an amazing win." And pretty soon, we exceeded anything close to that with our investment round. We raised $680 million and our last 260 was a $2.46 billion evaluation. So, we've exceeded, by far, all of our expectations that we had at the beginning.

Zierler:

Joe, from those chess pieces that you initially printed out, what were the internal discussions about the most impactful things to print?

DeSimone:

Yeah, that became an important driving force, "What are your superpowers?" And we always say in entrepreneurship, it’s like Entrepreneurship 101, that you need to play your superpowers, and a lot of that for us had to do with making elastomers. No one had ever 3D printed a rubber that had a wide range of properties, so that was a superpower. No one had ever printed a high impact engineering resin that was not brittle. That was a superpower. No one ever printed as fast as we were printing. That was a superpower.

Zierler:

So, you're talking more about materials than end-use applications? That's the mindset.

DeSimone:

Well, it was a realization that became the foundation for the application because people, at the time, were talking about a running shoe. There were several companies coming out with 3D printed running shoes, but they were made with the old technology, which mostly meant powder sintering, and we knew that wasn't scalable. We knew the properties were shitty. And so, we started reaching out to these running shoe companies and putting little lattices in their hands and they're like, "Wow, that's different." And we started playing the field with them, and then we realized that in that marketplace, there was no collaboration or no potential to work with multiple entities.

And then we said, "Look, this is just one industry, and they're so interested. Why don't we just lock up with one of them? Let's make this the only industry that we do exclusively, but we use them as a chaperone to cross the chasm," a sort of entrepreneurial parlance there from reading Geoffrey Moore's books Crossing the Chasm or Inside the Tornado, and so we ended up partnering with Adidas. Adidas was amazing because their engineers and designers would work hand in hand with our material scientists, and we had a good cultural vibe with them. So, they partnered with us, and here we are today with the brand new 4DFWDs that were just launched a couple weeks ago–amazing performance. It's now the best running shoe they offer and it's exciting to be at that stage.

Zierler:

Given the satisfaction that you had in the cancer world, nanotechnology, biology world, what opportunities, if at all, did you see for expanding into that with 3D Printing?

DeSimone:

Well, in many ways, this was going back to my roots, as you mentioned, in more traditional polymer science. And so, then we started getting into helmets, replacing foam with an elastomer lattice. Back to Geoffrey Moore, this time with his bowling alley analogy—for us the bowling alley was foam replacement with elastomer lattices and the first bowling pin was Adidas, but we're knocking over other bowling pins like helmet protection and bicycle saddles and other foam products, ice hockey helmets and baby seats to protective gloves and that whole area.

And an area that our engineers didn't want to go into because they became enamored with lattices and elastomers—because nobody else can make those—was the dental marketplace. Invisalign was already in this direction, and even a dental marketplace is probably 15 products, opportunities. Everyone else was doing the first one and they weren't going much further than that. All we had was a faster way of making dental models, and our engineers didn't think that was sexy enough to go after.

And so, we almost had a—this is where emotional fortitude and tenacity and conviction are key—we almost had a mutiny on our hands, because they didn't want to go after this area others were in already and I said, “Team," I said, “Look, it's okay for us just to make money and do something slightly better, faster than everybody else. But I'm also pretty convinced if we can do this beachhead here, we can go after these other 14 or 15 products that nobody else was doing,” and so it took a lot of coaxing. It was almost reminiscent of Ed and Alex wanting to build consumer printers. It was really—and I lead by—it's not an autocratic approach. It's more about bringing everybody along, and I wanted everyone to be brought along in this area, and my board was totally behind it because making money was okay for them, so we committed to this. And then all of a sudden, now we're bringing reliable printing. Those cheap printers don't work very well.

And then, as we're building a business in this space, the community loves our printers so much so that my business team that worked in this area came to me with the results of the National Dental Association survey of customers of 3D printing companies in the dental marketplace. There’s something called an NPS score, a Net Promoter Score, which indicates how much customers liked your product and your business— I didn't know what an NPS score was. Everyone was excited we got an 89. My board was excited, the business team was excited as well. And I said, “That's good, it's a B-plus,” and they said, "No, no, no, you don't understand. The score goes from -100 to +100. And most of the 3D printing companies are like -30 or -50, and we're in Apple territory." I said, "Well, that's pretty good." You know, I was being educated, and then we started moving into those other 14 or 15 products and now we have the world's first FDA-approved 3D printed denture.

And you could argue we should do nothing else but dentures. It's a $14 billion market. It's an amazing product. My wife and I are working with a group to set up a nonprofit in Durham, North Carolina in partnership with the UNC Dental School to bring affordable dentures to people in the most need. It will open up in August and it's a much better product. You go from 8 chairside visits to 2 chairside visits, and it's a better fitting product, it's more cost effective, and we're going to give people access that can't afford great health care, oral care. I think that can be a big part of upward mobility—having your teeth helps you speak properly, can help you gain better self-confidence, and can help you get a job. We're big believers in technology helping to give people broader access. So that's a great example.

We're also developing a high-resolution 3D printer. We have a paper under peer review right now at a great journal. We've been printing micro needles for transdermal delivery of vaccines, and I hope you're vaccinated. I'm vaccinated now. And I got that needle in my arm; it went deep into the muscle, but it missed a lot of the target immune cells that are in the dermis of our skin because of ineffective drug delivery. And so, we've actually developed microneedles for local delivery of vaccines to the dermis, and we’re finding that we get 50 times more antibody response by delivering vaccines to the dermis than you do to the muscle, with the same amount of vaccine—the same type of vaccine just delivered better. And so, I'm a big believer that I think microneedles could be the delivery system, the operating system for vaccines, where you can design vaccines on the means of delivery. I got a lot of people in the vaccine space, including the Modernas of the world, and others that believe that vaccines can and should be delivered via patches without a health care worker, and that they should be more cold-chain independent, and we're working with people to try to do that.

Zierler:

Joe, to go back to an earlier comment where the original plan was you would hire all the right people, and that you could step back. Obviously, that didn't happen, and you stayed on because there was something about your ongoing involvement that went beyond hiring the right people. What was that?

DeSimone:

Well, I think having people believe that they can do something really special and bringing the team and resources to fruition—I mean, I hired everybody in the building, and what's very different than academia that I felt is when I walked into the parking lot, every evening or in the morning, coming in, all I could see were car payments and mortgage payments. People left great companies to come to our company. That puts a pit in my stomach. I don't know that every CEO feels like that, especially if you're not a founder, but I bet you most founders feel this way—that it's that level of responsibility for your team and their livelihoods that goes well beyond anything I've felt as a professor. You're happy with the success of your students, but your students at the end of day have to make it on their own.

When you start a company, and people bet hundreds of millions of dollars and come to you, there's an immense amount of responsibility, and that's why I started realizing a 6-year run 24/7—it’s about all that one can humanly take, in some ways, at that level of performance and with those expectations of yourself and so, boy, it was music to my ears when Ellen Kullman was interested in getting back into the game and I was trading places like that.

Zierler:

Was the transition from academia to business gradual? Was it a long process? Was it a clean break at some point?

DeSimone:

I think it started—when I started working with DuPont in the early 1990s, right, I mean, I was getting good at the entrepreneurial thing and it's addicting. Being an entrepreneur is addicting, and it's not easy. It's weird how hard it is. I think people romance about how great it is to start companies and it's hard. It's brutal, but the specific transition was cold turkey with Ellen and I. I mean, literally—because it was at the end of the year 2019, we're putting together the 2020 plan, once we realized we're going to do it, we needed her to own the 2020 plan and the best way for that to happen was—and I'm a big believer in trust your generals—I disappeared.

My wife and I, we went to New Zealand, and we needed to get out of the picture for a time—and I was going to reemerge after the holidays, but let Ellen own it, because when you're on a board—she was on our board for four years—it's not the same as being in the trenches. You had a governance-only level and she needed to really immerse herself in stuff and that's what we did.

Zierler:

What were some of the feedback mechanisms in VC, scientifically, academically, intellectually, economically, that you were getting when you realized early on that you really had something?

DeSimone:

Feedback mechanisms, I think they're all—they're coming in a lot of different ways. One is that VCs understand when something is different. Strategy is all about being different. And if this was deep tech, and it was—they understood it, and I'm a big believer that you’ve got to teach your investors. And at the end of the day, this all comes down to teaching. To be able to teach an investor why is it that we're doing something differently and how it matters.

One of our big investments before the last year—so, Allen & Company in Sun Valley—we’d been in Sun Valley meetings, but they invited me to a very special meeting in Wyoming, and we had half a day with 12 investors from New York that would fly out to Wyoming. It was just me and 12 investors, like a trillion dollars around the table, literally. And I had a half-day to talk about the company, the concept then.

And that meeting would start back to my wife saying, "You got to bring the printer." I didn't bring the printer at this point, but they said things like, "Tell me again what you're doing?" And I'm a good teacher, back to the high school experience. I can explain complicated things to people that are not chemists and physicists and have them feel like they understand it. And without zero snake oil, I mean, just, "Look, you guys can follow this. This is what we're doing." And I walk them through it. This is why it matters. And when you bring people along, and they understand something, their level of comfort in being able to make investment goes way up. And these are really smart people. And they're bankers. They are in a different field. They're not familiar with the terminology or our field. So, if you can walk them through it, they get it. And that's what's been our ticket.

Zierler:

To go back to this idea that being in the business world can be addicting, what was difficult about letting go, even knowing that you had built something that was strong enough—had a strong enough foundation that would go on to even greater things beyond you?

DeSimone:

Well, it was an addiction, right? How do you let go of your addiction? I knew I was going to be stepping away. And then, I knew I had hired all the people in the building. And I knew they were going to be sad, but I also knew that I was done. I mean, I needed to get out of that chair. And we're—I'm in meetings that were very different at this point when we're scaling. I may be in a meeting where we're talking through the three or four different ways to enter the Brazilian marketplace and the legal aspects of different ways.

And I was like, "I could adjudicate this, but I have no experience in this, and I don't really care in some ways." For me it was more about what the technology was, and I was getting into stuff that was taking me really far away from what I enjoyed the most. And there's a coping stress with that. You can do it for a while, but Ellen is an operational guru who was on the US-China Business Council, and she loves scaling businesses internationally. I mean, this is what she lives for. And so less so than the technology, completely less so. And so, it was a nice—it's what the company needed to really get to the next stage in growth—to get to the aspirations that we all wanted for the financial success of the company. And she's been absolutely a black belt in scaling this business, and it was perfect. And so, it was really great as chair to support her in that and realize that I can help move the field along still, but I can do it through the foundational technology role that I have.

Zierler:

Joe, of course, in the tech world, seven years is a very long time. What were some of the developments beyond 3D that were relevant to Carbon, either in terms of computers, instrumentation, materials, all of the above?

DeSimone:

I think the software side, the fact that I brought in—so Sequoia hooked me up in the very beginning with a man named Craig Carlson, who was the founding VP of Engineering at Tesla. He'd just stepped out of Tesla, and I got to meet Craig and he is an interesting person. He's an icon out here in Silicon Valley, a name you don't hear much about though. He's a couple of years older than me and I kept reminding him of that. When he was an undergrad at Stanford, he started a software company that became QuickBooks at Intuit. And he was at Intuit for 17 years. And then he took a year off, like people do out here in Silicon Valley and helped raise his kids, and then he was going to go to another company without moving his house and his family because that's what happens.

There's so much diversity of opportunity. Took a year off, enjoyed life a little bit, reconnected with his family, and wanted to get back into it again. And he's a software guy, and he loved the environment. He loved cars, and he joined a little company called Tesla Motors before Elon bought his way in. And he was a founding VP of Engineering at Tesla, and he brought out the Roadster and the Model S. I asked him about Tesla. He said, "Well, it's a software play." I said, "What? It’s a battery company or maybe it's a car company at best." "No, no, no, it's software." And then started realizing that that car was designed from the ground up to be completely controllable with software. Everything—there was going to be no dumb hardware on it. Everything was going to be motorized, electrified, sensored up, and could be completely remotely controlled with software and get over-the-air software upgrades like your iPhone. He said, "Every other car company has like 7 different computer systems, they don't talk to one another, and they'll never get software upgrades, never. Culturally, they can't get there."

And up until this day, I still don't think very many companies get over-the-air software upgrades like your iPhone. I've got a couple of new cars out here and there's no software upgrades. My Tesla, I get every 6, 8 weeks, and it's got new features, new capabilities, and we designed our printers with the same DNA as a Tesla car—everything was smart hardware—and that was new. It was fun to be in the leadership role and to make sure our software engineers and our electrical engineers and mechanical engineers or optical engineers understood chemical engineering, because at the end of the day, we were doing a software-controlled chemical reaction to grow parts.

And I would teach them polymer chemistry. I would hold tutorials at Carbon to teach a software engineer what we're doing with the Chemistry side so that we could be multilingual and have a pi-shaped or comb-shaped approach to this. So, we built a convergent science company—no one in 3D printing had done that—and then ultimately, the really coolest thing was the business model that I brought to this.

I did not want to sell a piece of hardware to somebody when I knew at the end of the day, it was going to be obsolete pretty soon. And I started thinking, how do you bring somebody into a journey in the physical world and want them to join you early when something's not done? And I started talking to one of the most amazing people on this planet, Alan Mulally. I got Alan on my board. Alan was the former CEO of Ford Motor Company and before that, he was the CEO of Boeing Commercial Airplanes and he believed in digital manufacturing. We started talking about this and he pointed out and reminded me, he said, “Look, when I was lead engineer," and this was him speaking, "lead engineer on the 777, he went to his supplier, GE, and told them, he didn't want to buy a jet engine anymore," because he didn't want to be saddled with a piece of equipment that was only as good as it was on day one and it would get worse over time.

And so, he pioneered a new business model that he called Power by the Hour. He basically leased jet engines from GE and always got the most fuel-efficient jet engine. He built airplanes and they built jet engines, and they each did their own thing. So, we ended up doing that as a subscription model for our printer so that we could future-proof people from obsolescence—basically never have them buy something that would turn into a paperweight. And that had never been done in manufacturing before, and because we had a software-controlled chemical reaction to grow parts, because we had 100% smart hardware that can get over-the-air software upgrades, because we could improve the printer over time the more people use it, the better it got.

There was a network effect, we had all the tenets in place to launch a subscription business and a business that never did this before. And so, we drove that, but we told the board that we wanted to get to that, but actually from a financial point of view, it might be better just to sell printers for a while and then transition to this subscription model. And Jim Goetz, our lead investor, came back and said, “Look, every one of my companies is trying to go from a standard sale and trying to move into subscription, and it's really hard to transition the culture of a company. If you actually believe in this, I know it had been more capital-intensive, but you guys should come out of the gates with this business model." And we did. And then the really interesting thing is we said we're going to go do three-year subscriptions. And Jim was like, "Nobody does three-year subscriptions. Now, you guys have taken this too far basically. Everyone does a one-year subscription." And I said, "Well, Jim, let us try at three because we can always go to one, but if we come out at one, we can never get to three." And we launched with a three-year subscription, and it was a hard sell, but we did it. Philip did it, my son.

And we pulled it off and now what's happening is people—as you get into manufacturing, this is what Philip anticipated. As you get into manufacturing, people want to lock in their pricing, and so we're actually trending towards 4 or 5, 6, 7-year contracts. That's an amazing business model. We have tremendous visibility on revenue into future years, and that there's no businesses like that in manufacturing. So, this gives us—that's our secret weapon at the end of the day for the business, and it gives us a lot of planning latitude that you wouldn't have with a traditional business model. It's a really amazing company and it's still growing and opening up new markets, and we pinch ourselves that we figured it out.

Zierler:

Joe, to bring the conversation to 2019, did you specifically miss the professor's life? Was that something that you wanted to get back into?

DeSimone:

I missed the students. I miss teaching. I hadn't written anything in 6 years.

Zierler:

That's the professor's life.

DeSimone:

I missed it. And I'm good at it. And I missed it. I didn't do writing as CEO. And so, when this opportunity came about, it was more just, I was going to stay executive chairman and Ellen was going to be CEO. I wasn't going back to academia immediately, but as I became executive chairman, all of a sudden, I had an enormous amount of time on my hands and Stanford gave me a call. And so, I transitioned there from executive chairman to just chairman, which I'm allowed to do as an employee of Stanford, and got my life back here, right?

Zierler:

And did you even need to move physically, or you were already in place?

DeSimone:

Already in place. In fact, if I would have moved in 2014 to Stanford, I would have been moving on a normal faculty salary and we wouldn't have the place that I have now. So, it actually worked out way better.

Zierler:

Joe, last question, the theme has been from the science to the business. And so here we are in 2021, as you look forward, the most important things that you want to accomplish, if it was a pie chart, how much of it do you see purely in terms of science and how much do you see as being addicted to this? What's to say that the next great idea might not start a whole new entrepreneurial venture for you?

DeSimone:

It could. It could, but I think my career has been very episodic, and I think one is fortunate in one's career to have one Zero to One idea, let alone the three or four that we've been able to pursue. I think at the end of the day, the most satisfying part is the people though, and to be front and center on that now in a very close way with my students and faculty colleagues—that camaraderie, that teamwork is the real big part of this. And so, to do that without the intensity of being in the CEO chair and do it with some of the smartest people on the planet—I mean, I have Peter Kim, former president of Merck, as a faculty colleague. And Mark Davis, who figured out T-cell immunity, and I've got Steve Quake as a colleague—and Carolyn Bertozzi who is an amazing biochemist…just amazing colleagues, and I feel so privileged to be in that situation now.

Zierler:

Joe, it's been great spending this time with you. I'm so happy we were able to do this. I want to thank you so much.

DeSimone:

Well, thank you, David. I appreciate your questions. I appreciate all the homework you did in preparing. This has been a pleasure.

Zierler:

Absolutely.