Applications for cells

What sounds like a science fiction story is actually a real thing. The field that makes such things possible is called “synthetic biology”. Synthetic biology is in essence design-based engineering of biological systems and can include experts from various domains such as biotechnology, genetic engineering, membrane sciences or computer engineering. There is no clear point […]

What sounds like a science fiction story is actually a real thing. The field that makes such things possible is called “synthetic biology”. Synthetic biology is in essence design-based engineering of biological systems and can include experts from various domains such as biotechnology, genetic engineering, membrane sciences or computer engineering.

There is no clear point in time when synthetic biology started, but one exemplary important event to define it took place in 2000. This is when two articles appeared in Nature discussing the creation of synthetical biological circuits in E. coli [1,2].

In general, synthetic biology has two big objectives. First, they want to create biological systems with new properties useful for mankind. Secondly, they want these living organisms to be controllable [3].

By using the genetic code analogous to a software programming code, they are able to modify organisms. Synthetic biologists can program cells like computers. The circuits can sense pre-defined inputs and transfer them into wanted outputs. You can find a broad comparison below:

, Applications for cells, k-recruiting

1 Comparison of analogies between computer and cell circuits. Modified from: https://sciencebasedmedicine.org/left-brain-right-brain-myth/ (28/08/2018)

In principle there are two methods how to synthetically create organisms with new characteristics [5]. The approach of the bottom-up method can be compared to a kind of an assembly kit where you take all the pieces that you need to build something completely from scratch (in vitro). In contrast to that, the top-down technology uses existing organisms and reduces them to a minimum (in vivo).

In 2011, Craig Venters lab successfully created the first minimal cell (he nicknamed it “Synthia”) by using the bottom-up technique. It comprised all genes and biomolecular machinery necessary for basic life. Craig Venter, an American biotechnologist and once one of the Time’s 100 most influential people in the world, called it: “the first self-replicating species on the planet whose parent is a computer” [6].

Based on the possible improved stability, growth and protein production of synthetically modified organisms, they should replace most current commercial bacterial strains in the future. Not only the fast-growing artificial food market (especially meat), but also the energy, chemicals and life science sectors are among the industries that will benefit from this “era of biology by design”.

One of synthetic biology’s earliest and most praised successes was the production of a precursor to the anti-malarial drug, artemisinin (by Sanofi), in yeast. Researchers at Berkeley introduced genes encoding enzymes for the artemisinin synthesis into yeast and optimized the amount of protein produced from each gene. The combination of the single processes included in the metabolic pathway have not been present in nature before [3].

Not only special treatments like artemisinin but also everyday consumer goods like vanillin and saffron can be produced by synthetically engineered organisms. This allows a huge reduction in production costs for the different industries and suggests that this will also be the case for other goods in the near future.

Speaking about future, it needs to be pointed out that this sector is moving a lot right now, not only regarding financial funding (which is 4 times higher in Q2 2018 than it was in last year’s). Additionally, more and more innovations are being tested and pushed forward. One very interesting example is a possible cancer therapy. Current therapies like CAR-T-cell therapies have struggles due to unspecific targeting of healthy patients’ cells. This leads to unwanted adverse reactions [7]. To approach this problem, the group around Zhen Xie and Ron Weiss from the MIT programmed a logic multi-input sensing circuit to identify specific cancer cells in 2011 [8].

But how does it work?

The group included a biological circuit in herpes simplex viruses (HSV) [7]. This virus is able to spread in the whole organism (e.g. a mouse at the moment) and invade the body’s cells. When in a cell, the circuit can sense six inputs and if they match a predetermined profile of interest they have successfully identified a breast or skin cancer cell. Subsequently, a “killer protein” is released and the cell put to death.

Until now they have successfully worked to reduce the failure rate and are ready to enter the first clinical phase [7].

There are many exciting possibilities in the field of synthetic biology. The more well-characterized sets of biological circuits and easily controllable synthetic organisms we can create the more this may allow us to engineer new functionalities into organisms quickly and cost-effectively. One day, we will think about cells as useful little machines that fight cancer, provide energy for our automobiles, and produce drugs cheaply enough that those who need them can actually afford them.

Though, as common in every emerging field, growth and development are accompanied by limitations that still have to be overcome. As HSV is an existing organism utilized to transport the circuits into cells, there is a limit of “storage space” like with an USB stick. Another very important point that has be thought through in detail is the factor of uncertainty in nature [7]. Let it be supposed that a modified organism (grows fast and produces a chemical) escapes the production area / laboratory and enters the ecosystem. What happens then? Is it possible to include an “off switch”? These are exemplary questions that will be addressed by researchers in the upcoming years.

I myself want to close with a question that keeps circulating my head since I heard about synthetic biology:

What is life, and should we re-define our understanding of it?

  1. Elowitz MB, Leibler S (January 2000). “A synthetic oscillatory network of transcriptional regulators”. Nature403(6767): 335–8. doi:1038/35002125PMID 10659856.
  2. Gardner TS, Cantor CR, Collins JJ (January 2000). “Construction of a genetic toggle switch in Escherichia coli”. Nature403(6767): 339–42. doi:1038/35002131PMID 10659857.
  3. http://sitn.hms.harvard.edu/flash/2011/issue88/ (last visited on 28/08/2018)
  4. https://sciencebasedmedicine.org/left-brain-right-brain-myth/ (last visited on 28/08/2018)
  5. Jewett, M. C., & Forster, A. C. (2010). Update on designing and building minimal cells. Current Opinion in Biotechnology21(5), 697–703. http://doi.org/10.1016/j.copbio.2010.06.008
  6. https://www.boell.de/de/dossier-synthetische-biologie (last visited on 28/08/2018)
  7. Gabrielczyk T, Laqua M, Kühr M et al. (Juli 2018) “BioTechnologie Jahrbuch 2018”. Biocom. ISBN 978-3-928383-67-7
  8. Zhen Xie, Liliana Wroblewska, Laura Prochazka, Ron Weiss, Yaakov Benenson (September 2011). “Multi-Input RNAi-Based Logic Circuit for Identification of Specific Cancer Cells”. Science. 333 (6047). doi: 10.1126/science.1205527
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