Building with Biology

By Joshua Timmons, Biology, 2016

There’s a frizzy-haired architect hunched over his keyboard at a workstation diagonal from my own in Snell. He has a colorful program open with a map of a city in two dimensions; streets, buildings, and decorations are represented by a pallet of orthogonal shapes, a gridwork of architectural complexity. To a human 100 years ago, this architectural plan would look like nonsense, but to the architect, it’s a plan. It’s a design. It’s a mental projection into the future, a careful theoretical arrangement of matter to benefit other humans. It’s engineering. It might never be, but regardless, this undergraduate has the power to come to the library one afternoon and effortlessly construct a giant theoretical arrangement of atoms so others might theoretically benefit.

The second floor was designed this way. A design firm drew up a mock for how the floor could be transformed from its original banal space — that fewer and fewer will remember — into its present creative space. Outside the library the Interdisciplinary Science & Engineering Complex has emerged and is being mounted with windows that researchers will one day look through between experiments. The atrium’s staircase was designed to “maximize serendipitous meetings.” The atrium’s floor space was made to double as a dinner space for 200. What was once a desolate black-tar parking lot was transformed with ingenuity and capital into a usable and functional space for other humans to benefit from.

From our buildings with their unnatural climates to our phones with planet-wide connectivity, everything we interact with is the byproduct of human invention and engineering. Look around and try to find something that wasn’t engineered for human existence. It won’t be easy. Surprisingly, in this world full of objects designed with intention, planning, and purpose, we’ve made ourselves the outliers. For now.

Concentric Circles

What separates 2015 from 1985, a time when many of our parents were the age we are today? Computers are the most obvious. Pocket-sized computers with screens connect us and let us call other people to come and drive us around or buy us groceries. Thirty years ago, information was distributed through a hierarchical system of newspapers, radio, and TV channels. Today, we are each wirelessly connected to one another by cell phone in an invisible nervous system. Our experiences and thoughts are more easily transmittable than ever before, and this reality is owed entirely to the research and development of electrical engineering and software engineering that made these tools possible.

It’s a generalized view that works for all emergent, widespread technologies — and therefore history. There was the Bronze Age, the Iron Age and much later the industrial revolution. The microcomputer revolution defined the last generation.

So it’s worthwhile to wonder — what might define our generation and the next?

One way to look at technology is by the increasing level of complexity required for its engineering. There’s a reason the Bronze Age came before the Iron Age. Iron is more difficult to extract from ore, and requires a more technical and nuanced approach to smelt. Bronze could be melted in a pot over fire, while iron required a special furnace. The Iron Age was first built on the metallurgy knowledge from the Bronze Age.

Chemistry was, until relatively recently, strictly a science. In the mid-nineteenth century chemistry moved beyond its original vitalism — the theory that all organic chemicals must come from a living organism — with the creation of urea from inorganic compounds. The idea and realization that organic molecules can be made, rather than isolated, spread like wildfire, leading to the creation of synthetic chemicals never before seen in nature. Not unlike the architect with his programmatic design of a city layout, chemists learned to design.

A pharmacy is a modern day shire for the religion of synthetic organic chemistry.

Synthetic organic chemistry, with its emphasis on systematically interacting molecules, led to a greater understanding of chemical principles and laid the groundwork for the rich ability to produce novel chemicals and pathways that humans have today. It’s notable that scientists were creating new reactions and molecules years before a holistic understanding of chemistry existed. It was the side by side existence of goal oriented synthetic chemistry with analytical chemistry that advanced the entire field.

An abstraction level higher… biology is chemistry. Biology is the sum product of an inconceivable number of chemical interactions through time. Membranes, enzymes, receptors, and all the other constituents of a cell — life — are defined by their chemical structures.

The newly emerging field, the theorized concentric circle of our century, is synthetic biology. Synthetic biology allows scientists to take an applied approach to biology with purpose, and design organisms to fulfill novel applications in all the areas that old approaches have thus far failed. Rather than simply providing something to observe and analyze, synthetic biology aims to engineer cells, bringing life into the circle of useful substrates.

This Century’s Circle

Physicist Freeman Dyson made the unabashed prediction is his essay, “Our Biotech Future,” that “the domestication of biotechnology will dominate our lives during the next fifty years at least as much as the domestication of computers dominated our lives during the previous fifty years.”

Imagine a future in which diabetics no longer need to inject themselves with insulin. Bacteria with recombinant DNA for insulin produce the drug they must inject. It’s only one step further to engineer a strain that lives in the microbiome of the gut and intelligently produces insulin after induction with external UV light. Similarly, it might be possible to create gut bacteria that sense high levels of interferon or other inflammatory signaling molecules, like those elevated in patients with Crohn’s disease, and then mount an adaptive response by internally induced drug production. If this seems far-fetched, consider that cells are already doing it continuously. Life for bacteria, like humans, is a series of internal responses to external stimuli.

It’s not just the insides of humans that might be augmented. Cells themselves might receive upgrades as engineers realize how to harness their metabolic activity. One emergent area of research is looking at hijacking the machinery of cells, like yeast used in breweries, to make pharmaceuticals. Long and complex (or infeasible) chemical syntheses could be exported to the genomes of yeast. The entire multi-step production processes, that today requires multimillion dollar facilities, could be written out in DNA and put into yeast, effectively making them small and self-replicating drug factories. Already, Dr. Christina Smolke and her team at Stanford have managed to recreate the entire metabolic pathway for opioid synthesis in yeast by the introduction of 23 non-native enzymes.

It’s predicted that synthetic biology will leave no industry untouched. When Dr. George Church, a Harvard professor of genetics, appeared on The Colbert Report to promote his new book Regenesis, he brought along a tiny piece of paper in his front pocket. Bringing it out he explained, to the skeptical host, that he had over 70 billion copies of his book, written in the genomic converted binary, all on a space less than the size of a period. Despite meaning it as a one-off joke, several companies immediately reached out to Church about using DNA as a storage system; his lab is now working to scale the approach.

iGEM

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Northeastern’s iGEM 2015 team[/caption]

In the middle of this emerging field is international Genetically Engineered Machine (iGEM), an undergraduate synthetic biology competition where university teams compete to build their own organism. By the novel arrangement of genomic parts, teams construct organisms that have never existed before for purposes that lack adequate existing solutions. These projects, like the synthetic biology itself, have covered a range of topics. Cells that recognize, bind to, and selectively destroy cancer cells (Penn, 2012). Peptides that attract insects to reduce their harm of food crops (NCTU Formosa, 2014). Bacteria with altered properties that would enable survival on Venus (Stanford, 2012). Because of newly affordable synthesizable DNA, many of these iGEM projects are completely novel.

In the same way that inorganic molecular precursors in synthetic chemistry can be combined to create complex natural or synthetic molecules for application, synthetic biology will be comprised of well-understood genomic components. It’s these parts that iGEM teams compete to create and then submit. Gene promoters, coding sequences, and terminators all make up the growing molecular toolbox available to synthetic biologists.

Last year was Northeastern’s first with an iGEM team. We went all out trying to demonstrate the production capabilities by making a therapeutic antibody in the nucleus on microalgae (Northeastern, 2015). Inspired by the Ebola Outbreak of 2014, and the unavailability of a life-saving antibody cocktail, ZMapp, we envisioned using microalgae as a relatively cheap and rapidly scalable production platform. While we did not produce an antibody within the summer timeframe, we submitted parts that might make antibody production possible. We also attended the competition in the Hynes Convention Center and met other undergraduates from the world over, all of whom are working towards making synthetic biology’s long-term potential future a near-term reality.

Whether Dyson’s prediction holds true is to be determined. Regardless, it only takes one look around to realize humankind’s propensity to engineer. It might be foolhardy to underestimate humankind’s ingenuity.

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