20th Anniversary Essays From Previous Months

Matthew Gelber

 

            I’ll start by thanking my PhD advisor, Professor Bhargava, for nominating me to write a piece for the Illinois Bioengineering 20^th anniversary. This was particularly well-timed. I can only hope to have equally interesting content for the next time around.

            I left Illinois in February of 2019 to take a start-up job in my research area, additive manufacturing of biomaterials. I was the first hire. There was a loose plan in place to build and sell things, starting with bioprinters and ending with human organs. I expected I would be there a year, they would run out of money, and I would move on to a real job.

            We actually did sell digital light projection bioprinters and hydrogel bio-inks to feed them. You might still see some of our bioprinters in the wild. If you used that product, I’m sorry. It was our first try. You can contact me to discuss a better solution for your bioprinting needs. Nonetheless, the tech was novel and compelling. Soon after we’d built the product, the founders’ work made the cover of Science.  Everyone wanted in. Academic demand allowed us to raise money and hire. I postponed seeking a real job.

            That was stage 1 of the business plan. Stage 2 was to use the printer to start making something useful. We gained the attention of some larger customers in the pharmaceutical industry and tried to make money selling perfusable tissues-on-a-chip. These were supposed to be used for things like studying diseases and designing drugs.  There was a lot more competition here, and novelty was not enough for the industrial customer. The printer market was saturating, and we weren’t selling chips. We started to run out of money. This was mildly stressful.

            So stage 1 was printers. Stage 2 was supposed to be tissue chips.  Stage 3 was clinical products – printed tissues and organs. Those couldn’t be that hard. Maybe we could skip stage 2. Local investors understood the printer and the chips, but they had a hard time understanding how those things led to organs. Why now? People had been talking about 3D printed organs for years and nothing had come of it. We refined the pitch. We refined it more. Then we realized we were trying too hard. If a local investor ever tells you an idea is unrealistic, don’t change your pitch. Take it to Silicon Valley.

            We applied to prestigious tech accelerator Ycombinator and, to my surprise, got in. Ycombinator offered immediate cash to keep the lights on, lifetime cachet, and, and the end of the program, almost guaranteed funding. The program culminates in demo day – historically, an in-person event - where the world’s elite tech investors throw money at ride-sharing apps, vegan dog food, supersonic air travel, and, apparently, 3D-printed organs. Demo day would save us.

            This was spring of 2020, which you may remember as the very beginning of COVID. A week before demo day, they canceled demo day.  Recall that running out of money was already very stressful. Burning the last of the oil during a pandemic was brutal. Fortunately most of us had PhDs, so we knew how to deal with failure and scarcity. Nobody quit.

            Over the next few months, the founders stayed in San Francisco and pitched from an AirBnB. The rest of the team ground forward on the tissue chips. Slowly, the checks came in.  We would be okay. The world might be ending but tech investors still had to keep busy. Maybe they anticipated an increased future demand for lungs.

            Then, a windfall. During our journey, we had developed a close relationship with a customer that had similar ambitions towards organ printing. We had been selling them materials and, more recently, custom bioprinters. Now they wanted us to make a real organ printer. They were pitting us against their current supplier, a titan in 3D printing. They even invited both teams to their site the same week, so we could exchange dirty looks across the bar after work.

            I thought this whole situation was great fun. The competitor had a huge budget, a multibillion dollar company filled with seasoned engineers, and 40 years of experience in 3D printing. We had a ragtag team of 12, all except the CEO right out of school, a cash runway of less than 2 years, and an office above a methadone clinic. However, our platform technology had been licensed out of a national laboratory. The scientists there had been doing this longer than some of us had been alive. I thought we had a shot.

            My job was to get that printer working and shipped, even if it doubled our burn rate. To be safe, I tripled our burn rate. We bought extra parts and rushed every order. There were setbacks.  We ordered some special mirrors with a 3 month lead time. They arrived broken. Accusations and threats and were exchanged. Somehow that got fixed. We brought the entire team on to the project and hired 2 consultants. The inventor from the national lab came out and worked 12 hour days to help us get it aligned. We had gotten the custom optics right; the simulations matched the measurements. It worked. We put it on a truck and hoped the shipper wouldn’t break it.  They broke it.  We stayed on-site for two weeks fixing it. After 9 months of work, we got paid.

            Nobody really won the printer race. Organ printers are just one of those things that take a few tries to get right, and neither team had it right that try. However, I think that established us as a threat. We could make biomaterials, we could make sophisticated printers, and we could raise venture capital.

            In December of 2021, the rival printer company bought us out.  We made a lot of money on our options and got golden handcuffs as members of the newly formed liver and kidney team. People got married and bought houses. Everyone lived happily ever after. Actually we all got laid off in March of 2024, but most of the team immediately found new jobs at places with stronger balance sheets. It is a shame because a lot of stuff was working, but funding decisions in a publicly traded company cannot be made on technical merit alone.

            Synthetic organs have been 5 years away for my entire adult life. Periodically someone feels compelled to go onstage at a tech conference, glove up, take out a scaffold, and dramatically squish it, narrating a grand vision of unlimited organs for all. I think this vision will be credible after some properties unrelated to squishiness are proven. For example, a critical property for any organ is having blood vessels that don’t clot. Of course you could engineer a truly blood-compatible surface, you would be already be rich and famous from applying this to existing blood-contacting medical devices. There are a few technologies like this that should really mature independently before being integrated into a whole-organ project. Still, if somebody wants to pay you to try anyway, I’d say go for it. You’ll learn a lot and possibly invent something useful along the way. Maybe that invention will prove more valuable than what you were trying to do in the first place. So check back for the 25^th or 30^th anniversary. If we don’t have organs we’ll probably still have something good.

Catherine Applegate

 

            Bioengineering combines biology and other sciences, mathematics, and diverse areas of engineering into a synthetic whole to solve medical problems. The origins and definitions surrounding the terms “bioengineering,” or “biomedical engineering,” are nebulous. Some would go back as far as 3000 BC when Imhotep, the engineer of the first pyramid, also practiced as a physician. Or perhaps we would move further forward to 1780 AD to Luigi Galvani’s studies of animal electricity, wherein he observed that frog legs twitched when sparked with electricity, inspiring the classic tale of Frankenstein by Mary Shelley. Or just one century later to 1895 when Wilhem Conrad Röntgen discovered X-rays and subsequently donated his Nobel Prize winnings to his university and refused to patent his discovery on the grounds that all people should benefit from biomedical imaging. Scientists have clearly been merging biology and engineering for thousands of years, but it was only in the decades following WWII that bioengineering was officially established as its own discipline.

           

            Personally, I am grateful to be a cancer research scientist during such a time when bioengineering advancements are moving at such a fast pace. Chemotherapy was initiated in the 1940s, which, as we know, is just calculated poisoning with the goal being to deliver just enough poison to kill the cancer but not the patient. Forty years later, bioengineering advancements led to the development of immunotherapies that more effectively target cancers and cause less damage to healthy tissues to lead not only to better therapeutic outcomes but also to improved patient quality of life. My dad worked at Genentech as an early robotics specialist, where he worked on fixing and maintaining the instruments that produced and packaged Herceptin, which was one of the earlier immunotherapies to be FDA-approved for treatment of HER2+ breast cancers and which marked a paradigm shift in treating aggressive subtypes of breast cancer. Who could then imagine that, 20 years later, his daughter would be reaping the benefits of the work he was part of.

           

            I entered the world of bioengineering research during a chaotic phase in my life, one which continues to ebb and flow as I have recently experienced my 4^th personal cancer diagnosis with my 3^rd unique cancer. My own cancer treatment during the final year of my PhD, during which I was studying the impact of nutrition on cancer, was so inspirational and motivational, as it led me to form a deep and personal appreciation for how bioengineering was being applied to save my own life. I experienced first-hand what an improvement immunotherapy was over the more established and toxic chemotherapy. I was still sick with immunotherapy, but my body wasn’t shutting down like it started to after chemotherapy. As an outspoken cancer research advocate, I continue to see how bioengineering could be further advanced to improve outcomes and lives for fellow cancer patients.

           

            I am appreciative of the department of bioengineering here at the University of Illinois at Urbana-Champaign for harboring a diverse set of determined scientific leaders who encourage collaboration and innovation. This encouragement enables me to work on projects I feel passionate about and which can be quickly translated to a clinical setting if successful. Studying during my postdoc in the bioengineering department under extremely intelligent and supportive mentors has shaped my future path as a scientist by showing me a new way to study cancer, one which will enable me to have a quantitatively wide and meaningful impact. I am excited and honored to be granted the gift of being on both a scientific and personal journey with cancer and bioengineering, during which I get to experience and benefit from its clinical effects, provide my own biological samples for research in the hopes of helping future patients, and contribute to the development of new and improved cancer therapeutics through my own research. I hope to share the patient experience with other cancer researchers and, through bioengineering and other interdisciplinary fields, work together to design better, less toxic therapies to enable all cancer patients to experience less difficulties associated with their current treatment regimens. I am grateful for my own experience and the advanced therapy I received as a direct result of bioengineering advancements. To me, bioengineering research is a path for me to pay it forward.

           

            Bioengineering also represents a wider path for science moving forward. In an era where the convergence of diverse disciplines is imperative for addressing complex scientific challenges, bioengineering stands as a beacon of collaborative innovation, heralding a future where interdisciplinary voices unite to redefine the boundaries of human health. I consider it a great privilege to be alive during this notable time, witnessing the remarkable advancements being made in bioengineering. Being able to participate in celebrating the 20th anniversary of the Bioengineering Program, knowing its profound impact on addressing critical human health challenges, fills me with honor and gratitude. I am beyond grateful to the brilliant scientists of this program whose innovative work has brought forth clinically significant advancements, particularly impacting individuals like myself with chronic illnesses. Your dedication to improving human health through bioengineering inspires hope for countless patients worldwide.