Reinventing Biology

It all started with an anatomy class and a turtle; a turtle which just may have inspired the next big revolution in biotechnology. Sitting in that anatomy and physiology class, bored with dissections, a teenage Karen Hogan stared at a turtle swimming around in its tank. As she watched the reptile float through the water, Hogan realized that instead of cutting open a dead cat "for science," she would rather being interacting with living organisms in their natural habitats. This desire to step out of the lab and get her hands dirty is what helped transform Karen Hogan, the high school student, into Dr. Hogan, the chief scientist at Biorealize, a company reshaping the forefront of synthetic biology.

Hogan didn’t always envision herself as an academic. After deciding she wanted to pursue a nature-based career, Hogan matriculated to the University of Dayton to pursue a degree in environmental biology. Instead of just sitting in class learning out of a book, Hogan spent much of her time in the field. She studied geology in the mountains of Colorado, and instrumentation biology in the wetlands of Florda. After college, Hogan joined the Academy of Natural Sciences as a field biologist to map stream quality around Philadelphia and the surrounding regions. She soon realized, however, that to progress in science she would need a PhD, and so she came to Penn to earn her doctorate in microbial and stream ecology. Hogan, who has always embraced chaos, spent half her PhD chasing storms. This unique ability to mix field work and bench work has become invaluable to her career as an educator at Penn and entrepreneur at Biorealize.

The story of Biorealize began when Dr. Orkan Telhan, a professor in the School of Design, approached Dr. Greg Guild, then-chair of the biology department, looking for laboratory space. The unorthodox request came from Telhan’s desire to teach his design students synthetic biology. When people hear design, they tend to think of fine arts and digital media, but design is about transforming any medium to give it meaning and provide human benefit. Telhan believed that with synthetic biology as their tool, his students could use life both as a source of inspiration and as a new medium.

When Hogan heard about this ambitious request, she obliged. Little did she know, the ensuing partnership would last much longer than one semester and eventually come to redefine her teaching career. One of Telhan’s plans was to show his students how to genetically transform bacteria to make them glow, a procedure which Hogan had performed countless times with students. This time, however was different. Instead of working with students interested in careers as researchers, physicians, and engineers, Hogan was teaching designers who might never have stepped into a life sciences laboratory before. It was a moment of inspiration and beauty for her, seeing the transformation of artists into biotechnologists. This idea would become a principal goal of Biorealize’s microbial design studio. When the two instructors met afterwards in Hogan’s office, Telhan made some suggestions to improve an electrical setup Hogan was toying with for her class. Hogan had an epiphany:

"It was that exact moment that he and I really realized that there was this balance of expertise that we could bring together to pursue novel applications of biology and design."

Believing that a symbiotic relationship could exist between art and science, the two set off to create a novel class that was unheard of in undergraduate education. They envisioned natural science, engineering, and fine arts students collaborating to design new biological applications and works of art. There were massive challenges in trying to teach students with different skillsets, interests, and expertise who thought about problems differently and essentially spoke different languages.

But Telhan and Hogan remained undeterred. They sought insight from other professors during the process of creating the course, learning where there should be more science and where there should be more design. The process involved constant learning, as each instructor dived into the other partner’s field of study. As the class took shape, the two professors continually looked for ways to improve their teaching by “reinventing and recalibrating the course” over the first two years. They took in feedback from students and peers, constantly reevaluated their teaching methodology, and adapted to changing circumstances. While they may not have realized it, the process of experimentation, iterative design, and validated learning they went through to create FNAR-268 is essentially the lean startup process. By creating Integrative Design Studio: Biological Design the unlikely pair had become entrepreneurs.

In creating the successful course, both Hogan and Telhan constantly had to figure out new ways to simplify the learning curve for students and make science a less time-intensive process. Students with zero prerequisite knowledge had one semester to understand synthetic biology and manipulate it to design something brand-new, not six years to write a thesis on one topic. Biorealize is the next step in furthering Hogan and Telhan’s goal of  accelerating biological innovation by removing the tedium from research to make science more accessible and productive.

So much of our training goes into teaching people how to move small volumes of liquids around to make these discoveries, and that ends up wasting a lot of time for highly trained people who would rather spend their time thinking about experiments, designing experiments, [and] designing new applications.

Hogan has made it her mission to solve this productivity crisis by lowering the barriers of entry into biotechnology and automating time-intensive processes. With the help of Telhan, Hogan realized that anyone could be a participant in biology. She spent six years earning her PhD because it was the only way for her to advance in science, and there was currently no entry point for the regular citizen to interact with biology or have any input into scientific discovery. Biologists were academics and professional researchers who spent years in multimillion dollar laboratories conducting experiments, pursuing grants, and publishing results in academic journals. The path towards scientific discovery was agonizingly slow, where one had to spend years learning highly specialized skills in a niche area of focus in order to gain the requisite knowledge and credibility needed to run a research lab.

Through Telhan, Hogan was introduced to the world of people involved in synthetic biology. One of those people was veteran process engineer Mike Hogan (unrelated), an amateur biohacker and avid kombucha brewer. He joined the two Penn professors to create Biorealize, a microbial design studio with the goal of automating biology and enabling biotechnology to make a massive productivity leap. The studio is designed to work in tandem with researchers to allow them design and interact with experiments without constant monitoring and input. It achieves this by automatic transformation, incubation, spectrophotometry, centrifugation, and more.

Researchers go through a long, manual process to genetically manipulate bacteria. They first have to potentially dilute a solution of bacteria and incorporate synthetic DNA into their genomes. After this, they must incubate the bacteria under precise conditions with constant monitoring of the experimental variable. Since a single individual can only do one thing at a time, these manual processes waste thousands of hours and lead to many late nights in the lab.

With Biorealize's microbial design studio, users can insert up to eight different DNA solutions and eight different host organism solutions to test multiple conditions at the same time. On their computers, users design experimental procedures by determining incubation time, temperature, and other relevant conditions. The machine then electroporates the cells, creating a current that makes bacterial membranes porous enough for experimental DNA to flow into the cell. From there the DNA incorporates into the cell and the organisms are fed with media to keep them healthy. The machine can mix in any antibiotics or inducers that the user specifies before incubating the bacteria. The incubation carousel can heat, cool, and shake the samples to meet precise incubation criteria. Furthermore it can constantly monitor the bacteria through a spectrophotometer and other sensors to measure bacterial growth and the expression of different phenotypes for which the user is testing. After incubation, the organisms are mixed with reagents to inactivate them, and are transferred to vials where they can then centrifuged and further analyzed. This process relieves a massive bottleneck in biological research, but its importance goes far beyond that.

"The big moment came when we realized that it could be more than just a piece of hardware because you could connect the devices to one another [and] we could actually make it easier for scientists and product designers to collaborate..."

The microbial design studios are all networked, allowing users to an experiment across different devices. Instead of just running two setups in the same room, users from across the world could run the experiments in parallel and share their results with each other to collaborate on biological innovation. The system records the exact procedure and all the data it collects during incubation, which allows for instantly repeatable experiments. If the user chooses to share the results, they can be analyzed and verified by anyone in the world. This creates the potential for generating a massive informational library that anyone can access.

Imagine Biorealize as GitHub for biology. People around the world share their experiments and results, instead of sharing code. Others could view these protocols, download them, and run the experiments on their own. Furthermore, users could modify each others’ protocols to improve procedures or fix experiments without ever having to visit a lab in another part of the world. One could combine elements of different experimental procedures to create a novel protocol. 

Without even owning a physical device, one could test a protocol on a device anywhere around the world and have the results uploaded onto a server. This essentially creates an AWS analog where a user does not even need to own their own design studio to conduct experiments, and could instead "rent studio time" and pay another individual or organization who owns a device to conduct the experiment for them. Even better, anyone would be able to access published data from thousands of experiments to analyze the results and formulate new theories. These theories could then be tested on any microbial design studio, and be put to use by designers creating novel applications.

Biorealize doesn't just make research more productive for researchers who can run hundreds of experiments at the same time. It completely tears down the barriers to entry in biology, from both an expertise and a capital perspective. Users would not need laboratory experience to investigate new applications, and would be able to download or design new procedures and let the microbial design studio take care of the brunt of the work after that.

Biorealize is improving the efficiency and output of laboratories, as well as allowing biology to be taken out of the lab and placed into the hands of designers, innovators, and citizen scientists. The result could be the next big productivity shift in biotechnology, and the migration of research from the lab into the market faster than ever before.