Engineering the Future with Synthetic Biology
In this article, we’re taking a look at some of the most groundbreaking, movie-like advancements in the field of synthetic biology to gain a better understanding of it’s impacts, shortcomings and long term objectives.
The Basics of Synthetic Biology
By it’s definition, synthetic biology is the creation and (or) alteration of a subject’s DNA for the purpose of enhancement, creation or impairment of it’s abilities, characteristics and mannerisms.
But, I’ve found that this definition along with all of the other on the internet, fail to capture the full scope of synthetic biology as we’re literally talking about making vegan beef, face creams, biofuels and cancer treaments all under the same umbrella.
So of course, there are endless ways to define the field. One can say that it intersects biology and engineering for the purpose of innovation through designing new biological components or redesigning existing systems. Scientists and engineers alike have been given the ability to manipulate biological systems to serve the purpose of robots, factories or super-powered organisms because of advancements in the field.
Now that all of this illustrates a vague and inconclusive picture of synthetic biology, let’s start with what makes it possible before getting into what is made possible!
DNA Basics: Sequencing and Synthesis
Without getting too complicated, DNA is essentially what makes an organism look, act, think, and exist the way it does.
DNA provides the set of specific instructions for each cell. When you change or alter these instructions, the organism is changed or altered whether that means it’s functions, appearance or traits. Synthetic biologists can intentionally change, add new pieces to, or completely construct DNA in the cells so that it does exactly what they want it to do.
This is made possible through gene editing, which in this case is most commonly DNA synthesis. This essentially means stitching together pieces of DNA and later inserting them into the organism’s genome, pieces that can either be found elsewhere in biological systems or could be completely new sequences.
One of the most remarkable small-scale examples of DNA synthesis:
Nearly 10 years ago, Nobel laureate Ham Smith, microbiologist Clyde Hutchison III, and genomics pioneer Craig Venter created a “synthetic living cell”.
The team constructed the entire genome of a really small bacterium called Mycoplasma mycoides in their lab and then put it into another similar microbe, replacing all of the natural genetic material in the bacterial cell with their synthetic set of genes. Gene editing had been around for a bit at this point, but this was quite the feat for many reasons.
In the past, scientists had been able to manipulate and edit existing life, but this was the first time that an entirely new organism was brought to life! It’s DNA material was made from scratch and it was brought to it’s life by humans. I’d say it was one of the most distinct instigators of the field of synthetic biology, as it showed the possibility of ‘designer’ organisms that weren't just edited, but entirely constructed.
It also helped to give scientists a better understanding of the most essential components for living organisms. In finding the bare minimum to sustain life and fully understand what each gene is responsible for, they would then be able to add other features accordingly, like power-ups in a video game. This occured nearly six years later in 2016, with the team unveiling their minimalist bacteria called Synthia 3.0, the most basic form of life on Earth. It has 473 genes in the cell (an impressive number compared to the 24,000 genes in the human genome).
Real-life Applications
Let’s look at a few recent examples of synthetic biology in practice.
Among the genetically modified crops, dairy-free milk and arsenic-detecting bacteria, there are many mind-boggling examples of synthetic biology and DNA synthesis. The best way to understand it (in my opinion) is by looking at examples, so let’s get started!
Pigeon D’or (ironically, the Golden Pigeon)
A project developed by Revital Cohen and Tuur Van Balen
What comes to mind when you think of a pigeon? A majestic beast, a wonder of the sky, nature’s finest creation? For most, it looks a little something like this:
The birds are unapologetically called ‘flying rats’ by the majority of our population. They’re not particularly smart or skilled, and are more of a nuisance than anything with their poop in the city. So a team of scientists decided to take advantage of their current ‘useless’ state and make the creatures useful in an urban setting.
They made them poop soap.
Really, the scientists rewrote a bacteria to produce a form of biological soap. The bacteria would then live in the bird’s gut and produce soap once it’s metabolized. And don’t worry, the bacteria introduced to the pigeons are supposedly as harmless to them as yogurt is to us!
These superpowered pigeons would then be used to clean our cities, simply by being alive and pooping. Although a somewhat gross and bizarre application of synthetic biology, it’s one of my personal favourites because it shows the creative possibilities of the field.
How’d they do it?
They created the special detergent-creating bacteria through the use of BioBricks.
BioBricks are essentially DNA sequences that already have their structures and functions predetermined, known as the lego pieces of genetic information. The motivation behind the technique was to introduce the engineering principles of abstraction and standardization into the field, and make a consistent medium for everyone in the field.
BioBricks follow a specific restriction-enzyme assembly standard, meaning that there are guidelines for assembling a registry of BioBricks and creating the desired product in the microorganisms. The BioBricks standard is the universal system that is used to identify DNA segments and outlines their combination with other sequences within cloning vectors.
These pieces are then compiled to create larger biological circuits that do whatever you want them to do! They can then be inserted into organisms to carry out the prescribed functions and coded information.
Something really cool about BioBricks is that engineers have the ability to combine any two BioBrick parts, making another BioBrick! This new piece can then be combined with any other BioBrick parts, as long as they are in the same standardized format. The registry helps researchers to both see which combinations work the best and allows them to input their own discoveries to ensure that the information stays up to date and relevant.
It is undoubtedly one of the most useful tools for synthetic biologists around the world, creating a more standardized way to assemble genetic sequences.
Back to the pigeons…
Taking something that isn’t useful and making it into something that serves a purpose is often a main goal of synthetic biology. And, we’re not engineering soap-dispensing pigeons here, we’re not even changing the pigeons themselves. We’re merely changing the poop of the pigeon, turning it from something that dirties our city into something that cleans it, at no harm to the pigeon!
With pretty much everyone living in cities and pigeons living mainly where the people live in order to scavenge, their poop can no longer decompose beneficially or be cycled in the environment. Instead, it sits on some unlucky person’s windshield until it’s wiped away. So, as their environment changes it’s only fitting that their impact on the environment changes so that it’s once again beneficial rather than creating another mess to clean up.
Synthetic biology enables the adaptation to our incredibly fast-paced world, allowing pigeons to make a meaningful contribution to our society!
Synthetic Jellyfish to the Rescue!
A project developed by Dr. Nina Pollak the University of the Sunshine Coast.
Let’s do the same exercise for jellyfish as we did for pigeons.
What comes to mind when you think of a jellyfish? For me, it’s a funny looking blob in the ocean that turtles eat and that stings me when I get too close.
Jellyfish are also very unique in terms of their anatomy. They are roughly 98% water, having relatively simple bodies. They move mainly by letting the current do the work for them and don’t have bones, a brain or a heart. This means that they have the ideal structures to work with and mimic, as they are not incredibly predatorial or dangerous without their ability to sting.
Now, what would happen if we could make an army of jellyfish that patrolled our coasts and fought the common enemy of oil spills?
Referenced as Dr. Pollak’s main motivation, the Deepwater Horizon spill of 2010 set records as one of the largest and most destructive marine spills in history, with 4.9 billion barrels of oil in the Gulf of Mexico, home to nearly 8,500 marine species of fish, birds, reptiles and humans too.
As you know, oil spills arent easy to clean up and the residue had a massive toll on the environment, setting records in the coming months measuring nearly 40 times more polycyclic aromatic hydrocarbons (carcinogen-filled, toxic PAHs) than it did prior to the spill.
20 percent of all sea turtles in the area died and there was a 50 percent decline in the population of bottle nosed dolphins.
One million birds died.
But as you can imagine, everyone tried their best in their remediation efforts. Cleaning up the ocean isn’t exactly an easy task, which is where a synthetic biology project comes into play.
Imagine this: an army of these little guys cleaning up the spill for us!
Dr. Pollak is developing a mini ‘army’ of pseudo jellyfish that could clean up oil spills in oceans and waterways. They would be deployed into the coastline to breakdown the toxins as they move through the contaminated area.
Jellyfish are great to mimic structurally because they are simple, spend most of their time just floating in the water and don’t produce large amounts of waste.
In application, you would have thousands of little jellyfish that are designed to be non-replicating, meaning that they would eventually all die off one they’d done their jobs.
She created her set of biodegradable, multicellular, organism-like jellyfish structures that could detect the presence of toxins like oil and chemicals. Then, they would mimic the natural processes of detoxification that occur in the human body’s liver, producing the liver enzymes to break down the toxins.
In combining the abilities of the liver and the structure of the jellyfish, they were able to create exactly what they needed. This is enabled by the powers of synthetic biology, which also allow for extreme crossbreeding which will be further discussed below. This is all still in the proof of concept stage, like many synthetic biology-based proposals. Although there are many great ideas in the field, application is relatively rare because of the effects that experiments may have.
Now, you may be wondering…
What if another animal ate the jellyfish? What if the jellyfish didn’t die? What if they carried the toxins elsewhere instead of breaking them down?
Not only is there the question of whether the jellyfish themselves malfunction, but there is also the question of whether the environment will respond accordingly. Nature is incredibly complex, with even the smallest of changes rippling into much larger effects. Which is why, with synthetic biology in particular, it’s so difficult to bring ideas into application because of the large effects they will have on the world around them.
We’re often able to create working prototypes of concepts, but the real test is how those prototypes will interact with their environments, and the magnitude of the changes they cause.
This is very similar to the GMO dispute; how does having hardier crops impact soil quality, food production and ultimately the nutritional value? Environments are already unbalanced due to climate change, pollutants and runoff, and urbanization. We have to ask ourselves and look objectively at the situation to see whether innovations, although exciting, are feasible and more beneficial than destructive. Often times, there’s not a clear answer resulting in the many promising projects that never leave the conceptual stage.
Spider-goat, Spider-goat, does Whatever a Spider can!
A project developed by Randy Lewis, a professor at Utah State University.
We all know that Spiderman isn't real, that it’s impossible to have a ‘half-human, half-spider’ combination.
Wait, that doesn’t apply to goats?
Not in the world of synthetic biology!
I would like for you to meet Freckles, a product of the work of Randy Lewis, a professor of genetics at Utah State University. She’s just one animal of a herd of goats, cattle, and sheep that are genetically engineered to produce pharmaceutical, scarce, or difficult-to-farm materials in their milk.
Often referred to as biofactories, these animals are the products of synthetic biology’s powers. She looks just like any other goat, but she is superpowered to do something no normal goat can do.
Freckles in particular was genetically engineered to produce the silk that’s made by golden orb weaving spiders, which is stronger than Kevlar but has similar properties to nylon. The silk is a very valuable substance, one which is difficult to mass produce as spiders are quite inefficient and tend to eat one another when grouped together.
Freckles’ Genetic Makeup
Freckles was implanted with spider genes as an embryo, prompting her to produce the spider silk proteins in her milk. Meaning, every single one of Freckle’s cells has some of the genetic information of a spider. This also means that her children will carry and may express the gene, passing through the generations.
Scientists started by isolating the sequence in the spiders’ genetic code that prompts the production of the dragline silk. They inserted the sequence into the embryo with everything else that codes for a normal goat, putting it alongside the goat’s milk production genes. (So no, she wasn’t bitten by a spider, but the outcome of being reprogrammed with spider abilities is still the same).
This process is made possible by the fact that goats already make different types of protein in their milk. Now, they just have to make one more!
The new embryos were then implanted into a mother goat who gave birth to the super-powered babies, aka the cutest biofactories on the market!
Let’s talk about how Freckles changed the game.
Spider-goats are just one example of the powers of extreme crossbreeding that’s made possible by current technologies and the development of synthetic biology.
I personally like this example, not because Freckles is adorable, but also because it shows the feasibility of seemingly impossible applications. Mixing a spider and a goat seems incredibly unethical on paper. Yet, with synthetic biology and intentional gene editing, Freckles is only changed a tiny bit. Spiders and goats would evidently have nothing to do with one another. Similar to our pigeon application above, in changing the product of an animal we make it more ‘useful’ without hurting the animal itself. The goats are exactly like every other goat out there, yet these ones just make an extra protein in their milk; a protein that’s also made by spiders.
Thanks to research that allows us to better understand DNA sequencing and isolation as discussed above, we’re able to pick out non-essential yet useful traits which can be reapplied elsewhere (like the embryo of a goat).We can see the use of special traits and isolating non-essential traits as seen in the Synthia bacteria explained above.
Isolating special features and understanding the essential features that sustain life are vital components of synthetic biology. We’re not fundamentally changing the goat, but in understanding the code associated with her ability to produce milk and the sequences that define the proteins that are also included, we can see how adding one more feature doesn't fundamentally change her goat characteristics and allows for her to serve another useful purpose.
Now, let’s look at the big picture
While each example discussed above does a great job at illustrating the applications of synthetic biology in our present day, they’re also effective at showing it’s short comings.
It wouldn’t be an article about gene editing without talking about the ethical issues surrounding the topic. Let’s look at a few of the most prevalent issues and concerns regarding the examples discussed above.
Misuse of Technology in Biological Terrorism or Warfare
This is generally one of the biggest concerns: how the technology will be restricted and how we can stop it from being applied dangerously. Whether that be in terms of military/government use or on an experimental scale, the seemingly unrestricted possibilities are a source of concern for many.
“Synthetic biology has the potential to enable new types of weapons,”- Michael J. Imperiale, who works as a microbiologist at the University of Michigan Medical School
In the projects discussed above, every one of them could be turned dangerous. The pigeons could poop toxic bacteria that infects waterways, the jellyfish could kill natural ecosytems and the silk from the goats could be used to make illegal equipment (these are just off of the top of my head). Everything can be turned into something dangerous, which is why restrictions and limits, although frustrating for scientists, are important.
Imperiale was also involved in a committee that released a report regarding the concerns surrounding the applications of synthetic biology. They outlined the three concerns of the utmost importance.
- The recreation of pathogenic viruses (ex. Ebola, SARS, smallpox).
- Increasing the capabilities of dangerous bacteria through inserting genes to make them resistant to antibiotics.
- The engineering of microbes to carry toxic biochemicals.
With resources becoming more readily available to the public and tools like CRISPR and DNA synthesis becoming cheaper and easier to use, there are many more opportunities for misuse. None of those tools alone is responsible for misuse, however in the wrong hands they have the potential to be incredibly dangerous.
Technical Risks
Similar to the biological warfare risks, there are many unintended issues that could arise within the field. For example, the response of genetically engineered organisms in nature on a longterm scale, the accidental contamination of artificial organisms into natural environments, or general errors with DNA sequencing that result in malfunctions.
In the projects discussed above, examples may include complications like the birds pooping the soap in rural areas, the jellyfish somehow going into a land environment or the goats escaping and reproducing outside of captivity.
“Misuse of these technologies and a failure to account for unintended consequences could cause irreversible environmental damage. The potential far-reaching impacts of synthetic biology demand governance methods and research guidelines that promote its ethical and responsible use.”- Pinya Sarasas, a UN Environment specialist coordinating the Frontiers Report.
These risks are mainly in regards to the Do-It-Yourself synthetic biologists who work outside of agencies, labs or universities and are usually untrained but equipped with complicated materials.
Ethical Concerns
Is it a living thing or a machine?
One of the most common concerns about development in the field of synthetic biology is whether the experiments will create something that lies between a living organism and a machine. Having a jellyfish that’s sole purpose is to hunt chemicals and cannot reproduce seems to be a machine. But, if that jellyfish thinks on it’s own and in all other ways resembles normal jellyfish, it would surely seem to be a normal organism.
Some people see this as reducing the value of natural life; in combining organisms with machines, we undermine the special status of living things as defined by many religions. Others are more concerned with the treatment of the products of synthetic biology. If it was a half-organism, half-robot, some are worried that it won’t be treated ethically and assigned less value because it’s reduced to a machine.
And then of course, there’s the overarching question of whether synthetic biology is Playing God.
There is said to be two ways to interpret the phrase “Playing God”.
Religious: Humans literally assuming the role of a higher power.
Secular: Humans are overstepping and not understanding limitations.
This one is honestly to be left without an answer. To many it is their personal beliefs and experiences that dictate their view, and either way it’s important to address the widespread divide on the topic.
In many cases, the ethics surrounding synthetic biology are entirely based on the example in question. Some wouldn’t be bothered by editing a bacteria, but as you move up the triangle and the organisms become more complex, the divide becomes greater. When weighing in the benefits of the advancement to our society, like cancer treatments and helping to create drought-resistant crops for overlooked communities, that divide grows once again.
It’s safe to say that there is no right answer but only the continuing discussion about how synthetic biology impacts our society and our lives.
Hopefully that discussion is one that never stops!
Thanks for taking the time to read my article and making it to the bottom! I hope you’ve learned something new and gotten a better understanding about the field. You can check out my other articles to keep exploring and feel free to reach out if you have any questions or concerns.
Have a great rest of your day!
