Synthetic Biology — Redesigning Life

The “lively” new field of bioengineering

Amy Li
10 min readNov 23, 2020

An artificial machine created by humans will never do a plant’s job better than… a plant.

If that fact is not intuitive enough, I’ll explain through the comic below:

Goal: capture carbon from the air and transform it into oxygen

Plant: *simply exists* — goal accomplished!

Direct Air Capture machine: a machine that can filter out CO2 directly from the air… is this the solution to climate change?!

Well, there’s a catch.

Using Direct Air Capture to remove 1 million tonnes of CO2 from the atmosphere per year costs up to $35 million USD and requires 4.4 million gigajoules of energy.

  • To put that into context, that’s enough money to buy 178 Tesla Roadsters, 3390 bubble teas & 1 chihuahua 🐶.
  • And 4.4 million gigajoules of energy is enough to power 1 337 223 houses in the US for 1 year.

I think we can clearly see who’s winning the carbon capture game.

As smart as we humans think we are, there will always be someone smarter: Mother Nature — our universe’s most ingenious designer.

She created LIFE from scratch! Every tiny blood vessel, cell, atom had to have been meticulously perfect for organisms to live and stay alive.

However…

In an attempt to improve what has been given to us, we’re quite literally killing ourselves.

Basic economic logic states that if a company is clearly better than yours at doing similar things, instead of trying to compete (and repeatedly fail), a good idea would be to merge and work together to achieve a common goal.

Wouldn’t it be a good idea to work alongside nature to advance our world?

Ah but couldn’t do that… until now.

Welcome to the Synthetic Biology Revolution.

Part 1: FunDNAmentals

First things first, what is Synthetic Biology (AKA: synbio)?

Believe it or not, Synthetic Biology doesn’t have a formal definition yet!
But for now, this one will do:

Synthetic Biology: the field of science that involves engineering organisms to have useful new abilities. These organisms can be pre-existing or not yet existent.

Synthetic biologists see cells as programmable machines and DNA as the code that controls the machine.

The exciting part is that now we can code for DNA that doesn’t even exist in nature. This means that you could create a completely new species by yourself!

But wait ✋ how does one build new DNA in the first place?

To answer that question (fully understand gene synthesis), let’s zoom in on the basic structure of a strand of DNA.

Contrary to what we’re used to seeing, DNA isn’t simply a twisting ladder with multi-coloured pegs. In real life, it’s more like the image to the left.

Yes, I know, the picture looks exceptionally complicated. However, all DNA is essentially different 5 particles (P, O, N, C, H) arranged in a specific manner.

The outer “double helix” part of DNA is called the sugar-phosphate backbone. It’s simply a strand of repeating sugar and phosphate groups.

The inner “pegs” of DNA are the more important parts — the nucleotide base pairs! Humans have 4 unique nucleotides: Adenine, Thymine, Cytosine and Guanine. Adenine only bonds with Thymine through 2 hydrogen bonds and Cytosine only bonds with Guanine through 3 hydrogen bonds.

In one hand, the nucleotides hold their loyal other half (A+T, C+G), and in the other hand, they hold on to a sugar molecule on the sugar-phosphate backbone. True love is just so sweet, am I right? 🥰

Part 2: Engineering Life

Although biology is often viewed as discovering and memorizing the secrets of the universe, synthetic biology follows a different process. In fact, you might be quite familiar with it already. The backbone of all synbio research is the… engineering-design process!

Design ➡️ Build ➡️ Test ➡️ Learn & Repeat 🔁

Diagram from www.ncbi.nlm.nih.gov

Hypothetical scenario: We want to engineer a biofuel that smells like a pumpkin spice latte when burned.

Step 1: Design the desired DNA

Using computer-aided design tools, engineers design the gene that they hypothesize will smell like pumpkin spice lattes when ignited. It will essentially be a text file full of A’s, T’s, C’s and G’s.

Note: not actually what synbio computer-aided design tools look like

Step 2: Build the new gene.

🚨 New concept alert: Artificial Gene Synthesis (AGS)

In the natural world, genes are built by having a template strand of DNA to copy off of and duplicate. However, in the case of synthetic biology, there’s no template DNA! All we have are a bunch of letters on a computer.

Artificially building genes comprises of two steps: oligonucleotide synthesis (AKA: DNA printing) and connecting the oligonucleotide fragments.

The video below gives a visual explanation of the first step of AGS.

Gene sequences are millions of base pairs long. Synthesizing them all at once 100% accurately at once would be quite a phenomenal feat… and it can’t be accomplished yet. That’s why during step 1, we divide the artificially designed DNA (called construct DNA) into smaller overlapping pieces and then synthesize them individually. These pieces are typically 200–1500 base pairs long.

Once we have the smaller pieces of DNA, we can move on to the next step: combining the pieces! There are many ways of performing this step, all with unique pros and cons. However, I’ll only go into the most popular way here: the BioBricks Assembly Method.

Diagram by Lee Yun Jie via commons.wikimedia.org

Remember before when we said the DNA fragments had to be overlapping? It’s because if two overlaps match, that lets us know that the two corresponding fragments belong side by side. This overlap-matching procedure is repetitiously used to correctly organize all the fragments in the grand scheme of things.

Now once we find two adjacent fragments, how do we combine them?

The diagram above shows 2 DNA fragments inserted into 2 plasmids (circular DNA carriers). The only parts we really care about are the BioBricks (fragments A & B) and the restriction enzyme sites (E, N, X, S, N, P).

First, we remove what’s unnecessary, no big deal 🤷‍♀️. Note that sites S and X are complementary. Imagine you have two lego pieces. To connect them, the top of one lego piece (the studs) would have to be able to fit in the bottom of the other piece (the anti-studs).

^^ Official terminology from www.lego.com

The same logic applies to sites S and X. S has what X lacks and X has what S needs. They complete each other 💔→❤️, which is why they are called complementary.

All of this is is why fragment A can fit into the little space between E and X on fragment B. The E’s are the same and S fits into X. This process gets repeated over and over until the entire DNA sequence is synthesized!

^^ A more detailed explanation of the BioBricks Assembly Method

See? It’s as simple as playing with Lego. That’s why it’s the BioBricks Assembly Method.

Step 3: Test if the gene, in real life, functions as intended.

Now comes the moment of truth. The plasmid holding the newly synthesized DNA is inserted into a cell and tested to see if it actually works (assayed for function).

Does the biofuel smell like pumpkin spice lattes when burned? Is it safe to use?

The truth is, life is so very complicated. Minute details that we don’t account for in theory can make all the difference in how our creation functions in real life.

All we can do now is press play, observe and hope for the best. Fingers crossed!

Step 4: Learn — Back to the drawing board… or not?

Depending on the results of step 3, changes can be made to the initial construct design and further cycles of the engineering-design process repeated.

There is so much knowledge about the language of life that we do not yet understand. In fact, the diagram below shows all the coding DNA sequences that have been sampled by evolution compared to all the potential theoretical possibilities. 🤯

Diagram by David Baker

That means that every living thing on the earth right now — you, me, COVID-19 and everything in between, were brought into existence from DNA in that tiny grey square. And the crazy thing is that even in that tiny grey square, we barely understand how most of the sequences even work!

Although our current understanding of biological systems is vast, it is still far from complete. As of now, synthetic biology is a numbers game. The more we test, fail, learn, and form new ideas, the greater our likelihood of success.

🤔 Potential Pondering: Hmm, designing DNA… sounds a lot like gene editing doesn’t it? What’s the difference between synbio and gene editing?
Think of it this way.

Gene editing is a lot like making small edits to a really long essay. You spot the typo, move your cursor to click on it, press delete and replace it with the correct letter.

Synthetic biology is like writing that essay itself. You take words from the dictionary, perhaps make up some words yourself and write an essay from scratch.

Gene editing fixes problems whereas synthetic biology creates solutions.

^^ but both are equally important!

Part 3: Synbio in the Real World 🌎

That’s enough technical information for today. Now let’s get into the real reason I was drawn to synthetic biology — the super cool real-world implications!

James Mitchell Crow said it best:

“Imagine a future where synthetic jellyfish roam waterways looking for toxins to destroy, where eco-friendly plastics and fuels are harvested from vats of yeast, where viruses are programmed to be cancer killers, and electronic gadgets repair themselves like living organisms.”

Pretty soon, you won’t have to imagine anymore. Our future will look like all of that and more!

With the power of synthetic biology, we have been able to create an anti-malaria drug from genetically engineered yeast, new antibiotics and even flowers that glow in the dark!

🔦 Synbio Spotlight

Did you know that we can now grow brains in a lab? What does this mean for our definition of consciousness… or the future of humanity itself?

Alysson Muotri, a researcher based in Brazil, has found a way to grow brain organoids from human stem cells. The organoids are the size of sesame seeds, but still, spark with electrical activity.

These organoids are technically only one portion of the brain — the cortex. However, if we let them develop for long enough in the right environment, our stem cells just might spontaneously recreate different parts of the brain, leading to unforeseeable consequences.

Yet, there is a blind spot in the research surrounding lab-grown brains. How in the world do we define and measure consciousness?

Without a universally-agreed definition, there is a constant worry that we won’t be able to stop some experiment from crossing a line.

Here are some attempts at defining consciousness:

Physicians generally determine the level of consciousness in patients in a vegetative state by assessing the patients' response to pain or other stimuli. Blinking or flinching are examples of responses to stimuli.
Ah, but do you see a problem here?
All we have are some tiny brains on a Petri dish. Brains alone are not able to feel pain or blink/flinch either!

Okay, but there are also other ways to determine consciousness. For instance, using electroencephalogram (EEG) readings to measure how the brain responds when zapped with an electrical pulse.

Thankfully, almost all scientists and ethicists in the world agree that so far, no mad scientist has been able to create consciousness in their lab.

They reached this conclusion from an idea called integrated information theory, consciousness is determined by how densely connected neural networks in the human brain are. The more interactions between neurons, the higher the degree of consciousness — a quantity known as phi. If phi is greater than zero, the organism is considered conscious. As of now, no organoid has achieved this threshold… yet.

Learn more about this innovation here.

Working together with nature, humans are now literally able to create anything we want to — alive, not alive, and everything in between. The only limit is our imagination.

The question now is not if we can get there, but where we want to go. 🚘

💡 Food for thought: can you think of any problems certain organisms face that can be solved with synthetic biology?

Coming Soon: Part 4: Synbio it yourself!

Learn how to create a COVID-19 vaccine at home!

I’m taking a break from writing for a few days to attend to some urgent commitments but I’ll be back very soon to explain how to synbio a vaccine for the deadly virus!

⏰ Giant Synbio Event happening now!

Interested in synthetic biology? iGEM is hosting its community week for all synbio enthusiasts right now! Click here to learn more.

Thanks for making it to the end of this article! 💞

If you would like to further discuss synbio together, reach out to me on LinkedIn or email me: me.amymli@gmail.com. I’m always down for a 1-on-1 as well!

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