An opportunity to re-engineer life
Evolution is happening at this very moment, constantly. From humanity, animals and technology — everything in our world is changing at an exponential rate. With this truth comes the fact that the amount of data in our world doubles every two years.
In other words, the digital universe doubles in size every two years.
Yet, there are 100’s of unsolved mysteries that no Google search can answer. More importantly, there are countless problems we haven’t found a solution for despite our advancement; a cure to cancer, our carbon footprint and the antibiotic resistance crisis, just to name a few.
Now let’s rephrase the first two statements: there are 100’s of unsolved mysteries and countless problems that we just haven’t approached in the right way.
Often when I’m contemplating life or having a thinking session it ends a bit like the suggestions from this search.
Wishing and wondering about a different reality, one where many of the problems we face in our daily lives do not exist is pretty normal. Most of the time, when I start ranting about these thoughts to the people around me, this is the answer that I get.
What if I told you that it doesn’t have to be what it is. Imagine a world where we could reprogram yeast to make medicine and microbes to create biofuels. Well, the reality is you don’t have to imagine because we can do that. I know someone that possesses the building blocks of life and can provide us with the resources build our own organisms and reprogram life.
You might know them, they’re known as:
The world’s best engineer — Nature.
Building New Forms of life
36 years ago in 1984, professor Steven Benner synthesized a gene for the first time to create an enzymes which are proteins that act like bio-catalysts, short for biological catalysts. This was one of several breakthroughs to come. The development of this discipline known as synthetic biology has gifted us with the ability to design and create variations of biological components and systems that do not exist in the natural world and the redesign existing biological systems.
To elaborate, the field studies how we can essentially take parts of natural biological systems, characterize, simplify and convert them into components for an engineered biological system for meaningful purposes.
Synthetic biology = convergence of (engineering + biology + computing)
Programming DNA? Yes. It’s possible.
It marks a change in the way we think about engineering cells as synthetic biologists view cells as programmable machines. We can now go beyond utilizing individual genes and begin writing code that does not exist in nature.
But before we get into this, why do we specifically need synthetic biology?
Evolution didn’t exactly design cells to be understandable. Cells reproduce and mutate and this mutation can lead to uncontrolled growth of a pathogen. To avoid this, we can change their code so that they use their energy more efficiently.
Result: greener chemistries & displacing petroleum streams with biological streams
Regardless of the field, we want to create reliable, specific and predictable systems. Genetic engineering is a medical field which is often compared and confused with synthetic biology. While genetic engineering allows for reading, copying and editing DNA we can take it many steps further and improve the process to comprehensively solve issues by adding new traits to the DNA.
DNA Sequencing
Our DNA contains 6 billion paired chemical bases. What does this mean? To answer this we need to go a little bit backwards.
What is the human genome?
It is our genetic code. Our genome contains about 3 billion letters or base pairs. The twist? These letters don’t derive from the 26 letter alphabet we all sang a bit too much as kids, but instead our genetic code is a sequence of 4 nitrogenous bases — A, C, G and T. The sequences of these four letters write all of the instructions to make a human being. Your genetic code is what makes you, YOU.
One cell contains 23 pairs of chromosomes which are structures which house our DNA. The DNA is coiled into a shape called the double helix. When this structure is untwisted it resembles a ladder and is made up of paired chemical letters called bases.
This is where those 4 letters I mentioned above come in. A, C, G and T often referred to as the DNA alphabet. In essence, genomic sequencing is determining the order of these four letters (bases or DNA nucleotides) in a genome. Seems pretty straightforward, right? Well since opposite DNA binds to each other, base A only joins with base T and base G only joins with base C.
RNA: The other nucleic acid which translates the genetic code that DNA provides into proteins to carry out cellular functions.
As you can see, sequences of millions of pieces of DNA are stitched together using computer programs to create complete sequence of the genome. Our genome can be thought of as directions you give someone for a recipe, so they know how to make it but the directions in this context are the code and the recipe is our cells. In order to interpret the resulting data, the sequence must be deciphered — something scientists are still working on understanding. To learn more about how the human genome has been uncoded check this out.
Designer Bags? No. Designer Genomes
The sum of the differences in the DNA sequences in our genomes is responsible for the differences in how we look, how we act, the strength of immune systems, how easily one can fall sick, etc. This information holds extreme value when it comes to personalizing patient care and providing medical professionals with more accurate medical information when deciding treatment options for diseases and the ability to even implant new genes. Remember when I mentioned adding new traits to DNA earlier and green chemistries earlier? Might not have made much sense at that point, but this is that final puzzle piece.
The Century of Biotechnology
If we want cells to do something they haven’t done before, how do we turn this desire from a wish to reality? As the systems become more complex, it becomes more and more complicated to engineer biological systems without computation. First, we can develop intuition about the behaviour of a circuit then use computational tools to either strengthen or find gaps in the hypothesis. To make organisms which have a given function or role, we develop modules, circuits or devices using code which would be implemented in corresponding systems.
The Process
When researchers conduct studies, experiments and tests they often follow the DBT cycle; the cyclic process of
- Designing a prototype
- Building a physical instantiation (exemplar)
- Testing the functionality of the design
- Evaluating and learning from its flaws
- Creating a new design by feeding the information back in to the program
The specify and learn steps can either be viewed separately from the DBT elements or integrated into this sequence. Some key developments in this space that actually used this approach were the establishments of the standardized genetic parts registries, the availability of open-source DNA assembly methods and the ability to create genetic circuits — designed systems of DNA-encoded components.
This might get a little confusing but hear me out, these establishments have their own establishments as well.
Biobricks
Known as lego for scientists, biobricks are standardized DNA sequences that can be assembled through “standard assembly” to design synbio circuits to incorporate into living cells or organisms like e-coli and then create new biological systems. This process is user-friendly as it can be done using relatively simple molecular technology methods.
The Hierarchy of Synthetic Biology
- Parts are the building blocks that encode basic functions. They include the sequence which translates to the intended outcome and the non-coding sequences which the gene expression is dependent on. → example: such as encoding a certain protein, or providing a promoter to let RNA polymerase bind)
- Devices contain multiple parts that require a human-defined function. The assembly methods within biobricks synthesize the devices and the final product is a plasmid; extrachromosomal DNA molecule within a cell that is physically detached from chromosomal DNA → example: riboregulator producing a fluorescent protein whenever the environment contains a certain chemical
- Systems are a combination of multiple devices which perform high-level tasks (such as fluctuating between two colours at a predefined frequency)
Using Biobricks gives us a lot of opportunity since they are composable. This means that they can be ordered in any order or quantity, provided that the restriction sites between the two parts are removed. This is vital because we need to able to use the restriction enzymes without breaking apart the new and larger biobrick.
Standard assembly process: cloning techniques based on restriction enzymes, purification, ligation, and transformation
By following this process, we have boundless potential to create systems regardless of their complexity. And by we, I really do mean any of us down the road interested in eradicating issues with these parts. A registry with public-domain parts is maintained by the iGEM foundation and anyone can produce their own by following these steps.
Okay so the result of this is the design of genetic circuits. But what do they do? These parts that encode RNA or proteins can be applied to an assortment of cellular regulation processes. Using these approaches we can design circuits to enable host organisms such as e-coli to act as biosensors and bioreactors with one positive outcome being the ability to break down environmental pollutants.
- Biosensors: Analytical devices that transform biological responses into electrical signals. They can be of various types like immunosensors, or ones that are tissue-based. Their use is prevalent in the food industry, medicine, plant biology among more sectors. It’s safe to say that most if not all words with the prefix of “bio” are pretty legendary.
- Transducers: An electronic device that converts one form of energy to another. The word derives from the process of transduction.
The potential for Artificial Life
Let’s recap the DNA, RNA and proteins concepts.
Both DNA and RNA are made from nucleotides; an organic molecule made up of a nucleoside and phosphate. DNA provides RNA with the code for the cell to perform its activities which RNA then converts into proteins to actually carry out any and every particular function. Unlike in nature where we have only been able to alter amino acids slightly, in synthetic biology, we write DNA’s genetic program. Hence the proteins that RNA produces would also be designed by us and the sequence is encoded in the synthetic gene.
The new proteins can be designed in various shapes and with various functions so they can catalyze chemical functions in the body and also replace as well as replicate DNA in the human body. This is where computing comes in once again. To test different combinations of protein folds and find which structures carry out which function, we use computers.
So this brings me to the first application I want to talk about; curing cancer.
Treating Disease
When protein folds incorrectly we call it protein misfolding. It can have a negative impact on the health of the cell which can then lead to severe complications. High concentrations of misfolded protein aggregates can form amyloid‐like structures and ultimately result in degenerative diseases or cell death. But by using designer proteins we can convert our immune systems into defense systems. The prevailing problem with current cancer treatments like chemotherapy is that they kill healthy cells as well, causing brutal side-effects. Researchers at Stanford university worked on a project called RASER where they aimed to create synthetic cells that could identify cancerous cells before further damage to body occured. Proteins would rewire the grow signals of the tumours to grow into healthy cells.
This is just one of the many solutions the tools that synthetic biology provides for roadblocks we are at in healthcare and medicine.
Using Bacteria as a Drug? — Protein Vaccines
According to the Centers for Disease Control and Prevention, salmonella kills 380 individuals in the USA every year while infecting a total of about 1 million people. Shockingly, the bacterium didn’t have to be removed to stop the spread. Scientists at Prokarium created an oral vaccine that prevents the disease by using genetically altered salmonella that enters the body and is absorbed by the immune cells. The CEO Ted Fjällman describes it saying “It’s like a bioreactor in your body.” Though it is still in clinical testing, the vaccine has been successful when used against typhoid and hepatitis B, throughout the world.
Environmental Sustainability — Lab-grown Palm Oil
As our use of palm oil in our daily lives continue, rainforests in Central America to Asia are being destroyed, C02 is being released in the atmosphere and wildlife habitats are being destroyed. It’s not just in our food but our shampoo, apparel and fuel as well. To tackle this issue, c16 biosciences has been developing lab-grown palm-oil that is brewed and doesn’t require trees at all using microbial fermentation. By leveraging existing processes like fermentation and introducing the synthesis of bacteria, the firm is coming closer towards reducing our environmental footprint as a global society without needing to sacrifice the products we use. Additional impacts? The end of inhumane labor practices.
It is important to recognize that this isn’t just an opportunity to redesign biological systems for our benefit, but the implications of tinkering with the DNA of different organisms are mind-blowing.
Nature has given us both the power and tools to overcome the limitations posed by systems in our existing reality. Synthetic biology leverages these tools and uses the combination of disciplines our society is already and progressively becoming better at day by day.
Biology, design, engineering and software development aren’t new fields but being able take our knowledge and understanding and leap forward towards initiating universal betterment is what brings us closer to discovering our complete potential as humans.
It’s safe to say that it won’t be easy, it will require creative vision, determination, the passion to learn and the ability to view any and every risk as opportunity. After all if we can turn ideas into reality using synbio, we can redefine problems to discover solutions from within.
The future is all about making biology work for and with us.
It’s time to enable our imaginations to guide innovation.
Let’s start creating the future of our world.
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