COVID-19 Inspired a Call to Arms

In early 2020, humanity faced the initial onslaught of a new, evolving, and transformative virus. Over a shockingly short period of time, SARS-CoV-2 changed the very fabric of human life, including how we worked and interacted with each other, and where and how we spent our non-work time.

Around the same time, and in response to the dire situation unfolding across the U.S. and the world, Marc Andreessen authored a blog entitled, “It’s Time to Build”.  

For a bit of background, Marc is co-founder of the venture capital firm, Andreessen Horowitz. He was previously co-creator of the early web browser, Mosaic, co-founder of the early web browser, Netscape, and co-founder of one of the earliest software-as-a-service providers, Loudcloud (Opsware).

In the thought-provoking post, Marc advocated for building something—anything, even—that could move society forward from that point.

He wrote, “Every step of the way, to everyone around us, we should be asking the question, what are you building? What are you building directly, or helping other people to build, or teaching other people to build, or taking care of people who are building? If the work you’re doing isn’t either leading to something being built or taking care of people directly, we’ve failed you, and we need to get you into a position, an occupation, a career where you can contribute to building.”

Building on the Idea

Marc’s call for building encompassed a wide scope. In context of the pandemic, he touched on personal protective equipment (PPE), medical devices, hospitals and care facilities, vaccines, and therapies. Beyond those areas, he proposed building in manufacturing, housing, education, and transportation. The tone of the essay suggested that he would welcome building in any form in any industry.

And so, to build on Marc’s idea, we would like to cast a light on something near and dear to our hearts: building with DNA.

What Does Building with DNA Look Like?

DNA is the foundational, genetic make-up of life. Anyone who has taken high school biology knows this, but that's just the tip of the iceberg when it comes to DNA’s awesome potential. Since the discovery of its double helical structure in the 1950s, scientists converged to unravel and deconstruct this humble-yet-mighty nucleic acid. Around the early 1980s, a new perspective emerged – that which sought ways to leverage DNA to conjoin and construct.  

From there, many tools have appeared in the DNA building toolbox, including notably:

• DNA origami – folding DNA strands into complex 2D and 3D shapes with or without scaffolding
• DNA encoded synthesis – using DNA tags on chemical compounds to encode and direct small bioactive molecule synthesis  
• CRISPR-Cas9 – directing precise cuts in DNA to change or edit genes

As DNA is proving to be significantly versatile beyond controlling and managing heredity, there’s no doubt that even more advanced DNA building tools are on the horizon.

Automation Paves the Way for DNA Building

The impact of using DNA to build is profound. Life-saving therapies and therapy delivery systems. Bountiful food and energy sources. Powerful photonics and electronics. Protective and durable textiles. Robust and long-lasting materials. Building with DNA could fundamentally change every aspect of our lives.

However…

No building goal can be realistically achieved at a production or commercial scale if the method relies solely on manpower. It’s simply impractical. Using manual methods, throughputs are limited. Even the most careful person can make a mistake. In context of highly sensitive DNA manipulation methods, any variation—be it from a single person or comparing one person’s performance to that of another—can profoundly skew downstream results. This isn’t a failing of the human condition, but rather a reminder that we aren’t dispassionate robots.

Automation Removes Most Sources of Variability

This is where automation comes into the picture. A robotic system performs the same tasks, with high precision and accuracy, each time it is called into service. Automation is immune from the jittery influence of too much or too little caffeine or distractions that could impact pipetting performance or incubation times. In fact, without human involvement, automation removes most sources of variability so that the workflow’s resulting data is as true and reproducible as possible.

Automation Builds Up and Out

One of the great benefits of the right automated system is the ability to adapt to changing needs. Let’s take an example of a CRISPR-Cas9 workflow. In a modular Nucleus™ automation infrastructure, this particular CRISPR-Cas9 workflow may include:

• Several nanoliter-scale dispensers or automated liquid handlers such as the Prime™

• Transfection instrument

• Washer/dispenser

• MicroSpin™ centrifuge

• NanoServe™ labware stacker carousel

• TundraStore™ automated laboratory freezer

• SteriStore™ automated laboratory incubator

• LidValet™ high-speed delidding hotel

• PlateOrient™ labware orientation device

• LidDiscard™ high-speed delid-to-waste device

• Barcode scanner

• Waste bin 

The devices are situated on stationary tables, movable carts, or floor mounts. MicroDock™ units easily facilitate integration for cart- and floor-mounted devices. They are united by a stationary rail-mounted ACell™ robotic arm affixed to a table.

Modularity allows users to add, change, or remove devices at any time. For example, if data shines light on an unexpected research avenue, the workflow can immediately adapt. Or, if and when the next viral pandemic hits, researchers can immediately pivot their focus, and that of the automated workflow, towards characterizing and battling the new pathogen.

Modularity even applies when the automated system is in operation to build efficiency. This means that while plates are continuously processed in the system, any temporarily idle devices in the workflow, like a liquid handler or the transfection device, may be decoupled and used manually without disturbing the automated workflow in process.  

As production ramps up, scalability kicks in. Additional devices may be added to shelves below the tables and carts to build functionality and increase throughput. Building the system vertically densifies the device footprint to conserve lab space.

Scalability is truly limited only by the imagination. If a single lab’s footprint becomes a limiting factor as additional modules are added to the system, rail-based or fully mobile automated sample conveyance tools are integrated. The sample conveyance tools automatically shuttle samples between “islands of automation” that are not located in close proximity. This includes systems that are located on different floors.  

Everything is managed through a single scheduling software portal that can be controlled remotely. The hands-free sample transfer and remote scheduling mean that researchers can continue to build on their science without the distraction of low-value tasks.

Now is the Time to Build with DNA and Automation

In a Forbes editorial, John Cumbers, founder and CEO of SynBioBeta, echoed the need to build with biology, saying that biology is “an awesome and formidable force” and noting that the world needs to “dramatically improve our ability to build things”. He explains, “The power of biology to get things done clearly outstrips our crude extraction economy, where goods are cobbled together rather than grown. I believe our future will be made brighter when we merge the two.”

We wholeheartedly agree, and support this building with our versatile, walkaway automated Work Cells and systems. We’re excited for the era of DNA manufacturing technology and to see the many ways that DNA can forever positively transform daily life.

Revision: BL-DIG-220311-01_RevC (Building with DNA)