Innovation is all about finding new approaches to solve problems but oftentimes, it is easier said than done. Unconventional thinking is an essential ingredient to innovate, yet if we looked closely at our surroundings, answers to complex problems might just be in front of our eyes. Who better to look up to than Nature, the biggest innovator there is? “For millions of years, problem-solving has occurred in nature, through the process of evolution” says Dr. Jeffrey Karp, Professor of Medicine at the Brigham and Women’s Hospital, Harvard Medical School. Dr. Karp is a leading figure in the development of bioinspired medical innovations. He is better known as a serial entrepreneur who founded seven companies and has bagged distinguished honors as a young innovator. His endeavors have attracted research funding from several prestigious organizations including biopharma and government agencies.
From Chemical Engineering to Biomedical Engineering
Dr. Jeffrey Karp’s career trajectory is an interesting one. Therefore, we got the interview started by discussing his formative years as a budding scientist. “I registered for Biology at McGill University but towards the end of my first year, I transferred to Chemical Engineering. My final exam in Biology did not go well and it got me thinking about my future. I was by then addicted to the process of working towards finding solutions to challenging problems. I remembered back to grade 12 Physics which was my favorite subject – it didn’t come easy to me. In fact I struggled a lot. I recall meeting with the teacher many times after class to better understand the concepts. I grew to love the process of failing and then trying different approaches and eventually getting it right. After some self-reflection, I decided to switch to Engineering since it was the closest discipline to Physics. I think a degree in engineering is a degree in problem solving”.
However, the coursework about how refrigerators or paper mills work, soon made him realize that his interests lie elsewhere. “Along my path, I had spent three summers working in a biotechnology lab which fueled my interest in research. By the third year, I started thinking about a career where I could design medical therapies combining both medicine and engineering. However, I got rejected by the three medical schools I applied to”.
Drawing ideas from the surroundings have always been a recurring theme in Dr. Karp’s life. By happenstance, he overheard a coffee shop conversation between students about biomedical and tissue engineering courses at McGill. After learning that these grad level courses could be taken in the final year of undergrad, he approached the professor, who then asked him to take three physiology courses as prerequisites. “I extended my undergrad by a year and took the prerequisites which included anatomy and a philosophy class which turned out to be one of my favorites of all time”. The dual expertise coupled with his research training and problem-solving skills made him pursue a doctoral degree in Chemical and Biomedical Engineering from the University of Toronto.
Love for Translational Research – The Journey to MIT
Dr. Karp then explained how he ended up at Prof. Robert Langer’s lab at the Massachusetts Institute of Technology. “In my Ph.D., I entered into the whole new world of biomedical and tissue engineering. At the time, a huge percentage of the top publications were coming out from the lab of Bob Langer, who was well renowned in the community”. He realized early that he wanted to venture beyond publishing papers and focus on translating science into applications. His Ph.D. advisors were very entrepreneurial and both started companies. “I could see huge opportunities for research being useful as a tool to positively impact the world”.
“Since Bob was also in the same mold and was at the top of the field, I decided to apply to his lab for a postdoc. I wrote an email with the subject line ‘A postdoc candidate with BIG ideas’ and described the problems I wanted to solve”. Dr. Karp shared that he eventually joined the lab after securing a two-year fellowship from the Canadian government since funding at Dr. Langer’s lab was fully committed to existing projects.
Inspiring Factors that Led to Bioinspiration
When asked what drove him to bioinspiration, Dr. Karp once again reminisced his past. While working as a postdoc, one day he noticed a journal article that had a picture of Spiderman hanging from the ceiling. It was a Nature paper where the authors, through the understanding of how Geckos attached to surfaces and hanged from a single toe, had developed a synthetic adhesive tape. The tape mimicked the nanostructures in the Gecko’s feet to macro-level structures and the researchers were able to achieve high levels of adhesion.
“The Spiderman action figure was a key proof of concept. That got me thinking about how looking at nature can be useful to develop new technologies to solve problems. At the time, we were looking at ways to develop tissue adhesives. So, we asked whether we could adopt this concept to build a biocompatible and biodegradable tape. My discussions with clinicians led to the realization that there were huge unmet needs in medicine as to finding better ways for sealing tissues or anchoring devices to tissues. That’s how I got introduced into the world of bioinspiration and our publication led to substantial funding which subsequently spiraled into bioinspiration focused projects” he said. That resulted in the launch of Gecko Biomedical (now Tissium), a company that develops novel solutions for tissue reconstruction.
Bioinspiration versus Biomimicry
When asked whether bioinspiration is a way of replicating nature precisely, Dr. Karp explained the difference between biomimicry and bioinspiration. Biomimicry is where one learns something in nature and replicates it. Bioinspiration, on the other hand, is turning to nature for inspiration while working to solve a biological problem. He says this happens with the recognition that for millions of years, problem-solving has occurred in nature through the process of evolution. “There is a good chance that the problems humans encounter must have been dealt with in some form or another by nature ages ago. If we can learn how certain creatures overcame a challenge, we can use those insights to address the problems we are working on. So, bioinspiration is not mimicking nature but learning something from it. There is also a third concept which humans have been practicing for a long time, that is using materials found in nature, like deriving compounds from plants to cure our illnesses”.
He explains that in his lab, they mostly focus on bioinspiration and use it more as a tool. “There have been projects that started based on curiosity but in general we have been translationally focused on solving problems. We turn to nature for inspiration only when we encounter barriers while advancing our projects. Bioinspiration is not an end goal and we don’t try to force it into every project”.
Juggling Different Roles and Projects
When asked how he manages to run a multidisciplinary lab while being an entrepreneur, he attributes that skill to having many interests and the desire to constantly harness it. “Exploration is always incredibly exciting and is curiosity-driven. At this point in my life I am most passionate about bringing new therapies to patients. So, I made a decision early on that I wanted to structure my lab where in addition to performing rigorous science, I wanted every single project to advance to the stage of translation”.
“Another big reason is that the engineering approach is often very team-focused and the person who is orchestrating the team needn’t necessarily have all the knowledge. They just need to have someone in the team who does and the orchestrator can focus on gaining the essential know-how to guide the project. The paradigm I have tried to establish in my lab is that of applying the problem-solving process of engineering to medical problems. We have no specific disease- or technology-focus”.
He further explained that constantly investigating new problems keeps him on his toes. Going through that process can help identify the key experiments that yield critical insights which in turn could lead to new technologies. “We are addicted to the detective work and the process of transitioning knowledge into technology. To that end, my lab is structured to be highly multidisciplinary, comprising members of varied backgrounds with minimal overlap of expertise. We have people come from over 30 countries with different education systems and exposure”. He also mentions that providing the lab with unlimited access to resources is crucial. “I have multiple affiliations and collaborations that help in reducing the activation energy to access”.
Keeping the Onus Firmly on the Process
When queried on his successful stint as an entrepreneur, Dr. Karp opines that it came out of an awareness of his goals and aligning with his passions. “Over time, through engaging in many diverse experiences and reflecting on the multiple challenges I had encountered along the way, I developed good instincts that helped me make right decisions. Interactions with people from industry and academia and identifying key questions in the community have all helped this cause. Moreover, constantly thinking about turning basic research into new translational opportunities has aided in developing newer skills”. He stressed that he picked up knowledge on intellectual property, manufacturing, clinical trial design etc. gradually. “A lot of the time, we concentrate more on the end result but I have learned the benefit of committing a large part of my brain’s real estate to focus on the process”.
Focusing on Radical Simplicity
The technologies that have come from Dr. Karp’s work have focused predominantly on the simple and basic problems. When asked if this was intentional, Dr. Karp mentioned that he would pursue any interesting problem. “We are interested in working on all kinds of problems and it doesn’t matter whether the questions come from reading, serendipity or brought to us through collaborators. There are times when we may not have the right expertise to deal with certain things. But a new challenge always keeps our thinking very dynamic. We constantly have vulnerabilities because we are not experts in a particular field”.
We requested Dr. Karp to share inside stories of some of the companies that he founded.
Skintifique is the first skincare product to protect from nickel and other metal irritant allergies. Dr. Karp narrated how the idea of working on nickel allergy came into being. “I was having dinner with Dr. Rox Anderson, a dermatologist who has translated various approaches to serve millions of patients. I was trying to figure out a way to work with him. Later that night, I was twisting my wedding ring and caught a reddening of my skin underneath. I found out that I had a nickel allergy and that was the seed of the project for which I later collaborated with Dr. Anderson”.
“In the case of Frequency Therapeutics, when Bob and I originally collaborated, we focused on the epithelium of the intestine, thinking about regenerative applications. But we made some discoveries and that led us to the inner ear and cochlea”. Frequency uses its proprietary approach called Progenitor Cell Activation (PCA) that implements combinations of small molecules to activate progenitor cells and combat sensorineural hearing loss (SNHL). The company recently IPO’d on the NASDAQ (sFREQ).
“A very talented postdoc, Praveen had developed several self-assembled novel hydrogels. I saw a lot of potential for these materials but learnt from my experience to keep things as simple as possible. We decided to examine agents that are generally recognized as safe list from the FDA”. These novel hydrogels could entrap a variety of drugs that can then be targeted and released into the inflamed tissue at the site of inflammation, depending upon internal cues.
To conclude the interview, we asked if the recent trends of personalized medicines would benefit from bioinspiration. “I tend to think more of the problems and try not to keep a grasp on recent trends. It is important to know where the investment dollars are going but I don’t think we could force bioinspiration on anything. As I mentioned, we can concentrate on defining specific problems to work on and see if bioinspiration could present solutions to overcome that”.
Interview & Edit by Rajaneesh K. Gopinath
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