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Dartmouth Engineer - The Magazine of Thayer School of EngineeringDartmouth Engineer - The Magazine of Thayer School of Engineering

A Conversation with Dartmouth Engineering Alum Drew Endy Th’98

By Anna Fiorentino
November 2013 • CoolStuff

Now a professor of bioengineering at Stanford University, Drew Endy Th'98 directed his team five years ago to pursue the core elements of a computer that would work where silicon-based computers don’t—inside a living cell. In a series of three papers published over the past year, Endy’s team demonstrated data storage, logic, and communication in a cell. The potential applications are far-reaching. For example, by programing a genetic counter to track cell division and kill uncontrollably dividing cells, scientists might one day preempt cancer. Endy talked with us about his team’s work:

Drew Endy
Drew Endy Th'98

How exactly do you go about building a computer inside of a living cell?

We realized three inventions. First, we made a data storage system that works by flipping specific DNA sequences back and forth between two possible orientations, representing perfect binary digit (bit) registers that can be used to store arbitrary information. Next, we used our ability to flip DNA to create a new type of amplifying digital genetic switch, which we called the “transcriptor.” We used transcriptors to implement all of mathematician and philosopher George Boole’s logical operations. Finally, we repurposed a virus to transmit arbitrary DNA messages among populations of cells (in place of the virus’ own DNA), including our DNA data registers and genetic logic gates, so that we can reprogram populations of cells.

What are your research goals?

Our long-term goal is to make biology much easier to engineer, an area of research we call “synthetic biology.” Our work on biological computers sits at the intersection of fundamental engineering research puzzles and important applications. We’re asking, for example, can you make a reliable computer out of noisy self-mixing molecular systems or living cells? We’re also looking at whether we can we get better at combining biological molecules to make systems that behave as expected. With cellular computers we are not trying to compete with silicon-based or other existing types of computers. We’re not going to replace your laptop or cellphone. We are trying to implement computers in places where silicon-based systems will never work—in every cell in our bodies.

Where do you hope to be five years from now with your research?

I’d like to see us get up to 1 byte (8 bits) of data storage by the end of the decade. This would let us and others study and reprogram aging and development in most animals. For example, we could program cells to count or divide in particular ways, tracking or controlling up to 256 cell division events. Right now we only have a two-bit computer, limited by the specific enzymes we use to flip DNA—each bit requires one or two different enzymes. Before we published our work, there were only two labs in the world studying the enzymes we need, and the global market for genetic data storage and computing was approximately zero dollars per year. We are starting to see much more activity now.

How did Dartmouth impact your research and your educational approach?

While earning my doctorate at Thayer School, I worked with excellent people without huge egos, and this enabled everyone to work across disciplinary boundaries. It’s a really big deal to have an engineering school without internal department boundaries. This enabled me to pursue research by learning whatever is needed as an idea develops. Since leaving Thayer I’ve worked in microbiology, chemical engineering, cell biology, molecular biology, and now bioengineering. Thayer really provides an outstanding environment for PhD students to wrestle with the hard underlying questions of what to work on, and to kill a project that isn’t working. Many of the big PhD programs preemptively direct their students to work on a project drawn from a pre-established list of topics. I’ve worked hard to recreate the Thayer experience for all my PhD students at Stanford, and the amazing thing is they come up with projects and advances that are much better than I could imagine.

In a nutshell, what other significant biological engineering advancements have you been involved with?

I’ve been part of the BIOFAB and BioBricks projects that are slowly developing a free-to-use language for programming DNA. It will take us a few decades still to get there. I also helped start the International Genetically Engineered Machine competition, or iGEM, a worldwide synthetic biology competition for undergraduates, high school students and entrepreneurs, as well as Gen9, Inc. a company that is working to get better at building DNA.

Tags: alumni, engineering in medicine, research

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