“Now we are working on the descriptive phase of molecular biology, but the real challenge will start when we enter the synthetic phase.
We will then devise new control elements. And add these new modules to the existing genome, or build up wholly new genomes.”
Wacław Szybalski, 1973
March 27th,1973. A warm spring Tuesday on the palm flanked coastal town of Zikhron Ya’aqov, Israel.
The most important geneticists from across the globe are gathering at the 18th OHOLO conference to discuss the topic of the “control of genetic expression”.
This was the decade in which molecular biology was born. The first tools to manipulate the genome, Type IIs Restriction Enzymes had not long been discovered. And only two years earlier researchers had begun synthesising DNA.
This would be the backdrop to the fervent speculation of the event.
One of the speakers is Wacław Szybalski, a famed Polish geneticist who had literally bled for his work for a Typhus vaccine and was one of the first to enzymatically synthesise DNA.
Szybalski was a prominent figure in the field, so when he uttered those words, quoted above, the collective academic mind started imagining.
Fast forward to today and Szybalski’s premonitions are coming true. Thanks to a sufficient understanding of the genome and its regulation, we are now able to program biology with deliberate and reasoned control.
The discipline that is making that possible is Synthetic Biology. More engineering than biology, more predictable than genetic engineering. It equips us with a toolkit of standards and parts that can be used to create new functions for life. Or even new forms of it. As Szybalski had predicted.
And its goals are ambitious. Ranging from the production of drugs and their targeted delivery to biofuels, novel biomaterials or cells that suck up pollution.
This is Synthetic Biology today and this is your short(ish) guide to everything you need to know.
So, what is Synthetic Biology actually?
Actually defining Synthetic Biology is a tricky one, with groups in and around the field sharing different ideas…
Generally, Synthetic Biology is seen as multidisciplinary research area that combines biology with chemistry, mathematics, computer science, and engineering. Together, researchers from these fields tackle the challenge of programming life from an engineering perspective.
This fusion of disciplines make Synthetic Biology unique. In fact, some of the pioneers of the field weren’t biologists at all. Tom Knight, who tackled modularity in Biology by turning DNA into lego bricks, was a computer engineer. His student Drew Endy, who showed how to program DNA like a circuit, started out in Civil Engineering.
Since then, researchers have outlined and argued over the exact features of the engineering approach. But the general consensus today on Synthetic Biology as engineering goes something like this:
- It follows recursive cycles of “Design-Build-Test and Learn”.
- The design phase uses models to predict function and performance.
- As much as possible, engineers use standard, well-characterised parts and modular design standards
- It possesses hierarchical design approaches using functional modules
- Manufacture uses reliable, quality-assured systems
- Testing of finished devices uses standardised measurement techniques.
Synthetic Biology is already a part of your daily life
Products from synthetic biology are already entering public markets, in fact you may have come across them while shopping.
You’ve probably already heard of Impossible Foods. You may have even tasted one of their SynBio products. With over 5000 stores in the US stocking Impossible Burgers and rollouts of their Impossible Sausages and Impossible Milk on the way. The company has brought SynBio food to the mainstream.
Beyond food, Synthetic Biology is leading to new ways to produce valuable drugs more cost-effectively. Famously, Amyris tackled cheaper production of the antimalarial Artemisinin in yeast. Although not without some challenges.
Meanwhile the same methods are allowing us to swap out the petroleum in our plastics and cosmetics. Like Dupont’s biological propanediol made with yeast and plant feedstocks. Or SynBio giant Zymergen who are bringing Hyaline to market; a high performance film for electronic devices.
Biology is Big Business
They are calling it a revolution. And despite the relative youth of the discipline, Synthetic Biology is generating some serious commercial and investment interest.
We’ve seen this movie before. We’ve seen the sequels as well. The computing revolution in the 1970s; the birth of the internet, the smart phone and the waves of new, disruptive businesses that followed.
And Synthetic Biology is being touted as the next.
In their research report on the “coming Biological Revolution”, McKinsey predict a world in 2030 where 70% of physical products are grown, generating up to $4 trillion in global economic value.
While in the present, SynBioBeta, (who watch investment in American SynBio) have documented a record breaking first quarter of 2021.
From 2004 to 2013, approximately 450 million euros were invested into the synthetic-biology field by the European Union. Over 300 million pounds have been invested in Synthetic Biology research in the United Kingdom.
In China, over 200 million dollars were invested in synthetic biology research from 2011 to 2015. Which, they then increased to one and half billion dollars for 2018–2022.
Investment is accelerating rapidly in Synthetic Biology. The question on everyone’s lips is, how far can the curve clime?
Who's doing what in SynBio?
Healthcare has been the first domain of Biotech and the story is no different for Synthetic Biology. While thanks to their “platforms” a few big players are exploring the potential of their tech across many industry verticals.
Here’s a look at some of the key players in the industry globally. We’ve broken the market down by industry vertical and then by position in the tech stack.
This view shows how companies like Novozymes and Zymergen specialise on a single layer in the stack. By building on platform technologies they are quickly turning their tech to a wide range of problems. You can also spot the dominance of healthcare markets in Synthetic Biology, followed closely by the Food industry; and the Intermediates and Fuels verticals.
Finally take note, DNA is rarely a final product (outside of gene therapy). Rather it must enter into the value chain to be “processed” culminating in whole cell technologies. This is the cutting edge of SynBio and is an exciting space where relatively few companies are operating.
A note on the horizontals.
DNA & RNA: products are applications in which the instructions for the cell are sent to the host for transcription and translation. Mainly used in gene therapies.
Proteins, Enzymes & Antibodies: direct products of translation of DNA and RNA. Requires engineering of gene expression.
Metabolites, Molecules and Polymers: post-translational products. Requires engineering of entire pathways.
Whole Cell: products in which the actual cell is the deliverable. Requires complex engineering of regulations, multiple biopathways and cell function.
Current Limits to Synthetic Biology
You could be forgiven for thinking that Synthetic Biology is already a mature discipline, with a mastery of the techniques required to engineer life. But in reality, we’ve only just scratched the surface.
True Engineering for Biology
The founding principles of engineering will allow biology as a technology to be scaled. Unless researchers can explore designs reliably using common standards, its impact as a technology will be limited. And in reality, we are long way from a universal engineering standard for the discipline.
We’ve discussed these limits in this article, and so have others. The good news is at Doulix we see reasons to be optimistic with a slow but steady increase in uptake like ideas such as modularity and prediction.
And that’s good. Because when we are able to predict on a computer how our designs will play out, we can start doing some very exciting things.
DNA is critical to Synthetic Biology. It is both the floppy disk and the code; the wetware we use to program biology.
And it’s the major limit to the type of “devices” we can build in Synthetic Biology. That’s because it is still difficult, slow and expensive to build sequences of DNA long enough to do interesting things with. And getting large amounts of long bits of DNA is hard.
Despite Synthetic Biologists working with living material, one of the major challenges to working with life is the cell itself. Unlike computer boards, cells are messy places. The chemical reactions that drive the genetic programs we write don’t happen neatly throughout the cell. This makes it difficult to model precisely what should happen.
So instead, Synthetic Biologists are getting around this challenge by skipping the cell altogether by handling reactions through enzymatic machinery outside the cell.
Public Awareness of Synthetic Biology
While Synthetic Biology may be a hot topic in academia and the world of business, this is a long way from being the case in the wider public…
You’re reading this. So chances are you already knew a bit about Synthetic Biology. Congratulations, you’re one of the rare few.
The public is somewhat behind business and academia on the topic of SynBio. A survey conducted by CISRO on more than 8000 Australians showed that eighty-five per cent of survey respondents had little or no knowledge of synthetic biology and its applications. Other surveys find similar results.
The good news is that generally, public opinion is optimistic about the potential of the discipline and the majority expressed interest in knowing more.
This is largely what is found around the world, but of course there are nuances to consider. In the US, Biotechnology is largely considered positively when applications are address social, medical and environmental problems. But of course people worry if this research is done without concern for its potential risks and long-term implications.
What appears to capture the imagination is the potential for societal and environmental good. A message we as a global society are increasingly appreciating the importance of.
Frontiers in Synthetic Biology
Nature offers an inexhaustible potential for the design of new medicines, materials, foods and more. The secret to its mastery is in the understanding and construction of DNA…
If the last century was that of the computer, this will be the century of biology. And we look out on its cusp, trying to predict where it will go.
And although commercial Synthetic Biology is still only gaining pace, the world of academia is approaching something like running speed.
Non commercial moonshot projects have grand ambitions of constructing genomes, growing living buildings and taking synthetic biology to space.
The UN has set 17 sustainable development goals aimed at addressing the world’s greatest challenges by 2030, Synthetic Biology can contribute to nearly half…
Of the 17 goals, Synthetic Biology can contribute to eight. Not bad at all. I’d say we can use a little bit of that right now.
After all, we’re coping with a pandemic, the worst forest fires in the history of four continents and a growing global wealth gap.
Surely any tool that can help should be seriously explored, right? Well, we’ve got a little under a decade to do it.
And if synthetic biology will play a part in reaching it must be more than a technological solution. It must drive, possibly ground breaking, social change.
The greatest challenges to widespread adoption are barriers to scaling up, regulation and of course, public acceptance.
Synthetic biologists now need to take the next step to making more of their world changing ideas a reality. And they need to capture public and political attention to do so with meaningful social change as well.
So, what are you waiting for? Get involved and get ambitious because we are in the new age of biology, and it could be something really quite special.