Admirer of Truth

This is the second blog post in my series on Synthetic Biology. My first post was about the promise of synthetic biology (i.e., what makes the field so fascinating). This second post is about the “practice” of synthetic biology (i.e., my experience in toying around with some of the critical tools in the field).

As an unapologetic hacker, I believe the only way you can truly understand a technology is by playing around with it. (MBA’s beware!). By sharing my experiences, I hope people will better understand the revolution that is taking place in synthetic biology– and the implications that has for human health and well-being. So here is my rough guide to getting your feet wet in synthetic biology:

Step 1: Set an objective

One way to think of synthetic biology is that you are programming a microscopic living factory to produce some kind of substance or behavior. So the first step is obviously setting an objective. Do you want your creation to shimmer? To produce butanol? To detect radiation?

The only constraint, aside from your imagination, is that your goal must be attainable using a cell’s biological machinery. In more technical terms, it must be feasible by translating DNA into proteins (which may in turn interact with each other and their environment in complex ways).

Step 2: Select your BioBricks

Recall from my first article that the fundamental tool you will use in synthetic biology is Tom Knight and Drew Endy’s BioBricks, which are “open source” DNA snippets that each have one specific function and can be recombined with each other. The Lego analogy is apt; you create designs by linking together these bricks.

First familiarize yourself with the directory of BioBricks. There are all kinds of bricks, just as there are all kinds legos. There are timers, sensors, switches, reporters, generators, and so forth. Think clearly about what functions you need your bio-machine to perform and read everything you can about the BioBricks necessary to code for those functions. This is very similar to what software engineers need to do when reading the documentation for a standard library or API.

Browsing Documentation of a BioBrick:

Step 3: Design a Novel BioBrick (advanced!)

Sometimes, to do something truly interesting, you’ll need to design a brand new BioBrick. This is beyond the scope of this discussion, so let’s defer discussion of this topic. But fear not. Just like you don’t need to know assembly code when writing software code, you don’t really need to know how to design a novel BioBrick to do interesting beginner’s projects in synthetic biology.

Step 4: Synthesize a DNA Fragment

Once you’ve selected your BioBricks and decided how they should be organized (i.e., what order they should be chained in your DNA fragment), it’ll be time to actually synthesize the physical DNA segment. That segment is essentially the “program” that your biological organism will execute.

Start by selecting an online provider who will manufacture the DNA strand for you. In my case, I used a service called Mr. Gene. Using the web, you literally copy and paste your desired DNA sequence into a form. In a few weeks, they send you a little DNA sample that codes your sequence. The process is so insanely simple that it deserves a couple of screen shots.

(Copy…) Reviewing the DNA Sequence of the BioBrick:

(… And Paste!) Ordering the DNA Sequence Online:

Let’s pause here for a moment and reflect on how mind-blowing this is. Do you need further proof that biology has truly become an information science? Just as it is easy to write computer code, you can now write biological code. You just read some documentation, cut/paste the relevant sequences into a form on the web, and you get the code for a biological machine delivered in the mail.

The cost is relatively low, too. Currently, it only costs 39 cents per base pair. The way the technology is progressing, it won’t be too long before it is only a penny per base pair. Eventually, you may not even need to outsource the synthesis of the DNA fragment. Someday, you’ll be able to buy a little breadbox-size device that’ll let you make DNA at home.

Step 5: Insert DNA into Organism

Okay, given that this is biology, not everything can be done on the computer. The penultimate step requires some “wet” work. You need to take the DNA fragment and insert it into an organism, such as E. coli. None of this is particularly challenging. Most high school biology labs have all the equipment necessary to complete this step– such as pipettes, petri dishes, restriction enzymes, and a few other reagents. After an afternoon of training, anybody can become fluent in the techniques necessary to get novel DNA into bacterial organism.

Step 6: Test, Iterate, and Share!

Due to my background in engineering, I can’t finish this mini-tutorial without insisting that you thoroughly test your creation. Perhaps you will think of ways to tweak your design and improve its functionality. So keep iterating and testing!

In the spirit of the Registry of Standard Parts (and the open source movement), I also insist that you document your creation and share it with the world. You were able to create your machine quickly and easily because of other people’s hard work, so it’s only fair that you contribute back to the community.

Reflections on Revolutions

I wanted to walk you through the entire process of creating a synthetic biological organism in order to illustrate one thing: it is ridiculously simple. The barriers to entry, and therefore the barriers to innovation, have been obliterated.

This is truly the beginning of a revolution. Just as the web revolution enabled a generation of software hackers innovating from their garages, the garage innovators of the next couple of decades will be biology hackers. Who knows what marvelous things are in store?

Endnote: Each time I write about synthetic biology, I can’t help but feel a need to mention the public policy implications. When we hack DNA like this, are we playing God? (My perspective: Yes, but that’s what we humans do whenever we alter the environment.) The more important message to understand is that it will soon not just be academic scientists in laboratories who are “playing God”, but also people in their garages. In the end, with pragmatic regulation, the benefits humanity will see from innovations in synthetic biology will be unquestionably worthwhile.