What is a computer? Typically, one would think of a Mac, Windows or Linux-based laptop or desktop. Going further, one could define a computer as an object made out of silicon and other metals that controls the flow of electricity to make complex calculations. However, computing isn’t just limited to these traditionally known machines. Scientists have long theorized and researched unconventional computing methods using quantum qubits, fluids, cells and molecules.
One example of molecular computing is known as DNA computing, which uses DNA to perform calculations in lieu of electronics. In some instances, computing with DNA is more effective than traditional electronics because it is a form of parallel computing, in which many calculations (chemical reactions) are simultaneously carried out. Since being first demonstrated in 1994, DNA computing, and more broadly, the biochemical computing field, has expanded rapidly.
Though the field of molecular computing is still relatively nascent, it has garnered much interest from researchers in biology, chemistry and computer science. In 2024, Hopkins hosted a global conference on DNA computing and molecular programming, which drew in hundreds of scientists from around the world.
Rebecca Schulman is a professor of Chemical and Biomolecular Engineering at Hopkins who is currently working on developing new materials that both contain and process information. Her interest in the field began during her undergraduate studies at the Massachusetts Institute of Technology (MIT), where she studied computer science. After working in Silicon Valley for a couple of years on natural language processing, she decided to move into the bioengineering field and worked on building information-processing materials in her graduate school and postdoctoral research.
“In grad school, I studied this process called algorithmic self-assembly, which sounds kind of esoteric,” Schulman said in an interview with The News-Letter. “The basic idea was that in biochemistry, often times there's a competition between multiple molecules to interact with a growing structure. If there's something about those molecules that leads you to choose one over the other, that could be viewed as a form of information processing.”
Specifically, Schulman focused on studying this process in DNA, which helped expand the applications of DNA computing technology.
“I worked on weaving DNA into little bricks that could crystallize into sheets and studied how information was transferred as these sheets formed,” Schulman recalled. “And I showed that you could grow sheets that would contain some kind of code, like a binary number, and it could copy that code as a crystal grew. We were also able to do computing, where these sheets could not just copy a number, but count.”
Though Schulman worked on limited use cases of DNA algorithmic self-assembly in graduate school, she believed that this technology was not just limited to simple operations. This idea has led to her current research, which focuses on expanding this molecular computing concept to create biologically relevant materials. Namely, Schulman’s group is working on building molecules and materials that can make decisions, sense their environments, perform actions and talk to each other to be able to solve problems.
Schulman highlighted the potential applications of the technology medical in cancer cell detection, drug delivery, and tissue and organ growth.
“Theoretically, we could harness this simple idea to make biological materials… that could look at a couple of molecules and decide whether a particular cell is a cancer cell,” Schulman stated. “This would be better than what we can do now. A little bit of logic that molecules could possess could be really useful for us as a technology.”
Last November, Schulman won a National Science Foundation (NSF) Trailblazer Engineering Impact Award for a proposal seeking to harness molecular computing to more efficiently grow organs in vitro. The organ of choice that Schulman decided on was the kidney, the organ with the highest transplant demand worldwide. In the United States, over 80% of patients on the waitlist for a lifesaving organ transplantation need a kidney. However, less than 20% of people waiting for a kidney receive one each year.
“The goal of this proposal was to pick a really big challenge that was also a national need, and try to propose an unusual way to get around roadblocks in the field,” Schulman said. “The problem of growing organs or tissues in the lab is a long-standing challenge. Our vision was that molecular programming would allow us to much more carefully create the cues that cells see as they grow in utero.”
The materials that Schulman seeks to create would be able to secrete biological materials at specific time points in the protocol, mimicking the developmental signals that organs experience during their formations.
“We’ve been working on transcribing RNA in a specific location, controlling how it spreads, and then using that precise spread to control where other molecules, like drugs, are released,” Schulman stated. “The other thing we wanted to think about was how to figure out how to release cues in a way that adapts to a growing tissue. We’ve been working on trying to build molecular processes that transcribe RNA in response to proteins made by a tissue, which would allow us to control release in this way.… We're hoping to provide the tools for complex organoid engineering to happen.”
