by: Mark Verdecia
The Stieff Silver building, located between the Wyman Park and Hampden neighborhoods, is a remnant from a bygone era when Baltimore was a bustling hub for manufacturing. Built by the Stieff Company in the 1920’s, within two decades the building was the production center for some of America’s most high quality silver products. Nowadays the building, but more so the iconic sign hanging over its façade, is seen mostly as landmark by commuters exiting off the city’s main traffic artery on their way to Johns Hopkins University rather than as symbol of economic might. For others though, it is a reminder that cities, and their economic engines, need to adapt to remain vital. Those in the know have seen past the exterior of the main building however, which hasn’t changed much since 1929, to look onto the future of Baltimore’s economy. This is because among the buildings tenants is the FastForward accelerator program, established by The Johns Hopkins University to create home-grown biotechnology companies right here in Baltimore.
To many, including myself, it’s surprising that Baltimore is not already a major biotech hub given the presence of Johns Hopkins, the University of Maryland and several Federal agencies such as the National Institutes of Health. I’ve heard multiple arguments as to why this might be the case, but one common thread among all of these expert opinions is that there is an absence of an entrepreneurial culture in Baltimore’s life science community. I don’t know if that is an accurate assessment of Baltimore’s past or not, but I don’t believe it to be true of Baltimore today. I’ve been witnessing some interesting developments in the biotech scene here that just don’t support a “missing entrepreneur” theory. Most notably among these developments is a demographic shift in the age, experience, and goals of the founders and executives of Baltimore biotech start-up companies.
Biotech start-ups are no longer the exclusive realm of tenured professors with decades of research experience under their belt as it was when I was in graduate school. Instead, freshly minted PhDs are skipping the postdoc grind to start their own biotech companies. In many ways, Baltimore’s biotech community reminds me of the tech scene in Silicon Valley, where billion dollar companies like Facebook and Google are started by 20-something year olds just out of college. This biotech youth movement is an encouraging sign that our best scientific talent is starting to realize that entrepreneurship is a great path to an independent research career.
One of these young Baltimore biotech entrepreneurs is Dr. Elad Firnberg, co-founder of Revolve Biotechnologies. As a graduate student, he joined the lab of Professor Marc Ostermeier at the Johns Hopkins Whiting School of Engineering to study how proteins evolve to have the diversity of functions that appear in nature. This is normally done by creating thousands or millions of mutant versions of a gene, synthesizing those mutant proteins and then testing them to see how they behave relative to the original.
When Elad started his graduate work there were really only two ways to make mutants and neither of them was very efficient. One technique known as random mutagenesis accesses only a fraction of the amino acid possibilities within a protein sequence and suffers from severe bias. The other approach, site-directed mutagenesis, can only change one position at a time making it very slow. These approaches take several months and can cost over $100,000 for generating large sets of mutations.
Many scientists would have looked to answer another question, but Elad saw an opportunity. He realized that to answer his research question he was going to have to develop a different way to make all the mutations he needed. Over the next several years he developed a new method, called Pfunkel. This method allows a protein engineer to make a large library of mutations in increasingly complicated combinations. Pfunkel overcomes most of the inherent problems found in other methods while still providing greater than 97% efficiency.
Elad now had a way to efficiently address his basic research questions, but he also had another key insight that arguably was as critical as any discovery he made while developing PFunkel. He realized that his technology had major implications for the engineering of new or optimized proteins for industrial use. Protein engineers in industry optimize proteins for commercial use by mutating the amino acid sequence of a protein. Unfortunately, it is incredibly difficult to predict how any one mutation will affect the protein. This is complicated by the fact that many mutations may be required to optimize a protein or create a new or improved function.
As mentioned previously, the old ways of doing things require a lot of time, and are expensive. Most importantly, the old ways are limited in their ability to explore all combinations that could give rise to an improved protein. Imagine trying to find a needle in a haystack but you are only given 1% of the haystack to look through. Under these conditions it doesn’t matter how advanced your search technology is, however most technological advancements had been focused on developing high throughput search capabilities. Everyone forgot about recreating the search space itself. Elad realized that his technology could create a more comprehensive search space or in laymen’s terms, give the searcher the entire haystack.
Many of us probably associate protein engineering with the pharmaceutical industry. This isn’t surprising given that engineered protein therapeutics are projected to be a $168 billion industry by 2017. Proteins are attractive as therapeutics because they provide a level of specificity that produces less off-target side effects than much smaller chemical compounds and protein engineering allows companies to develop new and improved versions of these biologicals.
However, protein engineering plays a major role in products that we use every day as well. The detergents we use to clean our clothes have engineered enzymes in them. Fabrics are made with an enzyme that was created to replace a hazardous chemical. If you drink wine or beer then you’ve been enjoying the fruits of an enzymatic process that is constantly being engineered. If you drink soda, the sweetener is most likely the product of an engineered enzyme as well. Other industries using engineered enzymes include agriculture and energy. Genetically modified organisms and biofuels are also developed via protein engineering tools. Each and every one of these industries addresses markets worth billions of dollars. It’s clear that protein engineering is poised to become the “go-to” skill set for a diverse set of industries as more of them move their processes away from chemical synthesis and towards more sustainable practices based on biosynthesis.
Baltimore’s Revolve Biotechnologies is poised to become a leader in protein engineering.
I sat down with Elad at his office at FastForward to get his advice for aspiring biotechnology entrepreneurs.
What made you decide to become a protein engineer over all the other career options you had?
When I began graduate school, I knew I wanted to do something in the biomedical field, although my undergraduate training was in traditional old-school chemical engineering. My top research choices were in labs specializing in drug delivery, nanodevices, and protein engineering. Eventually I was matched to Marc’s lab, a top protein engineering group, and the rest developed from there. Protein engineering was a great fit being at the intersection of biology, physics, and engineering. There are great opportunities in this area both in academic research and in a variety of industries from industrial enzymes to pharmaceuticals.
How difficult was the decision to start your company rather than postdoc?
Technically I did do a postdoc. After defending my thesis I stayed in Prof. Ostermeier’s lab as a postdoc for another nine months further developing the PFunkel technique through a grant we got from TEDCO. Not going to another lab for a postdoc was a difficult decision. On the one hand I wanted to continue my scientific training with aspirations of a faculty position. I specifically wanted to gain experience in translational medical research. I interviewed with a few labs but soon found out that many struggled with dwindling funding and often times a postdoctoral position was contingent on coming in with a grant award. I also had a number of friends who were quite unhappy with the postdoctoral experience. Starting a company offered the possibility of earlier independence to pursue a career track, learn a new set of skills in business and entrepreneurship, while bringing a useful technology to the market that could benefit society. While starting a business always feels risky and uncertain, the FastForward program at JHU helped this process with the facilities and coaching they provide.
What do you think you missed by not doing a postdoc?
As a PhD student in academia, the environment often makes you feel that you are on a track that should culminate as a tenured professor in order to be considered successful. The postdoc is seen as a right-of-passage on this track and so not doing it feels like closing the door on the conventional career path. So that was initially unsettling for me. That part aside, the main thing that feels missed is not further expanding my scientific training, although I am learning many other things. Being successful in business or even as a researcher requires an in-depth understanding of the problems and needs people face. It is hard to solve problems when you don’t fully understand what they are. While it is possible to gain the required knowledge by other means, it can be more difficult than being immersed in the work oneself. For example, one of the customer segments for our business are companies developing biological and antibody therapeutics. To gain the required depth of understanding in this field has taken a lot of hard work and was mainly achieved by going out and interviewing a lot of folks in industry and academia and asking them questions. Having done a postdoc in this field could have provided a jump start in understanding as well as new ideas to pursue in research or business. So I think there can be a lot of value obtained from doing a postdoc that is relevant to business rather than just academia.
What do you think you’ve gained by starting a company that you couldn’t get as a postdoc?
Starting a company forces you to learn a whole new set of hard and soft skills you would never learn as a postdoc. Everything from the nitty gritty of incorporating and forming your company, managing it, to interacting with customers. Running a business also comes with negotiating a lot of agreements – with practically everyone you interact with – employees, advisors, customers, etc… Another big change for me was transitioning from the academic mindset that is very focused on your own technology and how great it is, to realizing that as a business, customers don’t care at all about the technology. All they care about at the end of the day is what value does it bring them. Once this understanding took hold, it helped me change how I approached conversations with people.
What would you have done to prepare yourself during graduate school if you had known you were going to start a company upon graduating?
I probably would have paid more attention to entrepreneurship events and taken some business classes. Also I would have started networking earlier on with people in industry, investors, advisors, etc…
What has been your biggest hurdle or obstacle thus far?
It’s hard to name just one, there are so many obstacles for a new company. A big one is finding the right people to join or help you.
Where do you see your company in 5 years? 10 years?
The company is currently offering a synthetic DNA library construction service which is our expertise. We have two parallel tracks. One is to grow our service business to the point where it may be acquired in the next 5-7 years. Secondly it is to use our technology to develop a product line in the life science tools space. There seems to be a growing effort in the state to turn Maryland into a top 3 biotech hub and so hopefully Revolve can play a part in that.
What advice do you have for any graduate students out there deciding what to do next?
If you are deciding on whether or not to start a company one piece of advice would be to go through the I-Corps program based on Steve Blank’s lean startup methodology. This is an entrepreneurial bootcamp that the NIH and NSF are instituting to supplement the SBIR program and Johns Hopkins is affiliated with the regional DC node of the program. You can also do it yourself through free resources available online but the program kicks your butt and forces you to get out of your comfort zone. This process will get you out of your building and go talk to people who you think might be your customers. Based on this experience you will determine whether people actually have a need for your technology, really want to buy it, and how big is that market. At that point you can make a much more informed go/no go decision. Also, you will get to meet a lot of people and expand your network.