Friday, 7 April 2017

Societal Challenges facing Synthetic Biology

I believe one of the biggest challenges facing Synthetic biology are excessive promises. Quotes such as “Synthetic biology has been predicted to heal us, feed us and fuel us.” (Milestones in synthetic (micro-) biology, 2014) will in time produce more harm than good. The ridiculous expectations from Synthetic biology are further fuelled by more promises from scientists and attempts to secure funding. These high expectations and slow delivery on them due to technical problems will eventually lead to some kind of backlash.
Additionally it seems that many scientists have already decided that the public is the “enemy”. In wanting to prevent the public opinion backlash which happened to previous fields such as stem cell research or GMO companies many scientists have decided to be proactive this time. However many have taken to the view that the general public is ignorant or uninformed and their opposition to some field of science stems from this (the now discredited ‘Deficit Model’). It seems many scientists have decided on the public as some obstacle for the above mentioned promise and vision for Synthetic Biology.

Public perceptions and fears of synthetic biology may obstruct research in this field, in a similar fashion to GM. This has been recognised by all stakeholders and public engagement and dialogue activities are in the process of being developed.” (EPSRC, 2009, p. 46) 

This somewhat arrogant view that scientists should know better than the public what is and isn’t to their benefit is encountered among some scientists. And indeed when it comes to communication with the general public, scientists tend to be most concerned with informing people about the potential benefits and attempting to stop people from overblowing the risks. It is a rare afterthought on whether the public should be involved in the discussion on the potential benefits concerning them. 
Instead however it seems that the general public is overall sympathetic to the goals of synthetic biology and shows understanding of balancing potential risks with potential benefits. When involved in discussion with scientists selected members of the public were both excited about the opportunities as well as concerned about risks. From these workshops (carried out in 2010) five central questions emerged: “What is the purpose? Why do you want to do it? What are you going to gain from it? What else is it going to do? How do you know you are right?” (Synthetic Biology Dialogue Report, 2010)  

I believe that these are important questions that scientists will have to face and should consider when approaching projects and deciding on their research.
Even in terms of regulations members of the public were generally sympathetic. There were acknowledgements that oftentimes risks are unforeseeable and uncontrollable and accidents do happen, however most were strongly against releasing synthetic organisms in the wild as well as generally recommending a cautious approach. One concern people showed was that regulation would not be able to keep up with scientific advancement, although I believe personally that this is less of an issue than people think. On the other hand there was also a belief that too harsh of a regulation would stifle creativity and advancement and rob society of potential benefits. Parallels with stem cell research were brought up. 

[From the Economist]

There were also concerns regarding the “creation of life”, although the general consensus seems to be that if the benefits outweigh risks this was acceptable. In general humility was appreciated, especially in the context of synthetic life. 
There are however some concerns that members of the public hold which are based on misinformation. For example one misconception is that the supposed “de-skilling” of biology together with the free availability of genomic sequences of pathogenic organisms and the relative cheapness of DNA synthesis will allow people to operate outside of professional research laboratories, allowing for some form of “bio-terrorism”. 

 A more realistic understanding of the research and the extensive knowledge required and our own lack of standardised practices in science puts any kind of risk from the misuse of de-skilled biology decades if not more into the future. 
In general I believe societal challenges are much less serious than a lot of scientists believe. In fact people will generally be supportive, and there are indeed a lot of benefits to be gained from Synthetic Biology. I believe that people are much more scared of non-governmental organisations and big Pharmaceutical companies and their involvement in Synthetic Biology than they are of basic research being done by academic institutions. 

The strawman of an uninformed and irrational public, with strong for or against views on science, and demands for 0-risk science, which has been built up in the mind of some scientists is more dangerous to public opinion than almost anything else. If anything this way of thinking will need to stop.

As with all emerging scientific fields there is a need to maintain a level of trust with the general public as well as policy regulators. Excessive hype and exaggeration over potential benefits are counterproductive for this, and instead the field as a whole will need to focus on the development of ethical models of regulation, which allow technological progress and direct it in a way that will yield the most benefit to humans and society

Sources and Further Reading

Marks NJ. Public understanding of genetics: The deficit model. In: eLS. John Wiley & Sons, Ltd; 2001. 10.1002/9780470015902.a0005862.pub2.

EPSRC. EPSRC landscape document: Materials mechanical & medical engineering programme. . 2009;1.

Bhattachary D, Pascall CJ, Hunter A. Synthetic biology dialogue report. . 2010.

Bubela T, Hagen G, Einsiedel E. Synthetic biology confronts publics and policy makers: Challenges for communication, regulation and commercialization. Trends Biotechnol. 2012;30(3):132-137.

Jefferson C, Lentzos F, Marris C. Synthetic biology and biosecurity: Challenging the ‘myths’. Frontiers in Public Health. 2014;2.

Marris C. Public views on GMOs: Deconstructing the myths. EMBO Rep. 2001;2(7):545-548.

Thursday, 6 April 2017

Technological Challenges for Synthetic Biology

Technological and scientific challenges facing synthetic biology are manifold. Natural selection has had millions of years to build complex, working systems, and although we can make intentional changes, their effect on biological output is generally unexpected and riddled with unintentional effects. Natural systems have likely considered every single feasible aspect to solve a given problem, and indeed some companies are using similar approaches, using large numbers of mutants and screening them for a “better” desired activity. This can however hardly be called engineering biology and, to return to the aerospace analogy, if airplanes were built like this we would likely be confined to the ground.

[…] relative to its ambitions, synthetic biology is where aerospace engineering was in the 1800s – pre-flight. 
(Timothy S. Gardner, 2013)

In general Biology contains few simplifying rules and principles, while exceptions to rules seem more common. We have a very limited understanding of even many relatively simple cell systems. There are several suggestions for dealing with this complexity. One is to strip down cells or create minimal cells from the ground up. The idea being that in natural cells there are many systems and genes that are not necessarily needed in controlled lab or industrial environments. The reality is that minimal cells are normally much less efficient and have slower growth than other cells. Why this is isn’t entirely clear, but it seems that it will be necessary to understand and tackle the complexity of biological systems rather than attempt to strip it down to its basic components. At the same time, building a minimal cell from scratch may reveal understanding of cells.
Biological systems have always been hard to understand as they behave with a certain stochasticity and a flexibility that does not compare with traditional engineering. Natural systems have to be able to account for varying environments and varying conditions. As a result it is hard to design systems such as a simple on/off switch, as oftentimes there is some very small level of “on” transcription. This “leakiness” of transcription is vital for cells to survive and adapt to changes in their environment but is undesirable in designed systems. Similar challenges are faced at every point when attempting to design biological systems. Cells do not behave in a standardised way, and even if a system works in one cell there is no guarantee that it will also work in another cell of even the same genus or even species or in different conditions.
Indeed the main and one of the more achievable problems to solve is the standardisation of biological characterisation. As it stands many labs have their own standards and record different background information on their own biological parts. Using these parts in different contexts may or may not work, it requires large amounts of time to track down these parts in the first place. This uncertainty and lack of full characterisation of biological parts is one of the things synthetic biology hopes to erase.

Biobricks - an attempt at standardisation of biological parts. [Image Source: MIT]

Indeed it has been said that the future of synthetic biology rests on solving the problems of measurements and design. The relative importance of design methods in synthetic biology applications can be determined by certain information based measures. Although modelling and exact mathematical design has in the past been limited by data gathering and inaccurate assay protocols. This could potentially be solved by new calibrated flow cytometry, which could provide a sufficient foundation for a further investigation into precise mathematical modelling and design.
One thing that is also needed for example are legal standards, in order to share and use genetic parts from several sources, in order to solve problems and realise applications. Current legal standards such as Material Transfer Agreements (MTAs), can take several weeks to resolve and often do not resolve rights to application of standard parts. Indeed with chemical synthesis of genes becoming cheaper, synthesis of large DNA fragments being commercially available and viable for many labs, is a reality. Therefore new legal standards which can for example protect biological parts as well as facilitate the exchange of ideas and specific parts. Another example would be setting standards for ‘barcoding’ or ‘watermarking’ DNA, in order to improve detection and authentication of designed or engineered biological systems. 

The challenges facing Synthetic biology are comparable to the challenges facing many emerging fields in academic sciences. In terms of technological challenges, revolutionising a field of science as synthetic biology is claiming to do is never easy. Biology is known to not be a discipline in which simplifying rules are common. Exceptions and strange unintuitive natural processes are prevalent, and as such standardisation of both biological parts and for characterisation of biological systems is hard and faces numerous issues.

However, I am confident that in time these challenges will be addressed and resolved. 

Sources and Further Reading

Gardner TS. Synthetic biology: From hype to impact. Trends Biotechnol. 2013;31(3):123-125.

Milestones in synthetic (micro)biology. Nat Rev Micro. 2014;12(5):309-309.

Gibson DG, Glass JI, Lartigue C, et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science. 2010;329(5987):52-56.

Annaluru N, Muller H, Mitchell LA, et al. Total synthesis of a functional designer eukaryotic chromosome. Science. 2014;344(6179):55-58.

Endy D. Foundations for engineering biology. Nature. 2005;438(7067):449-453.

Kitney R, Freemont P. Synthetic biology – the state of play. FEBS Lett. 2012;586(15):2029-2036.

Kwok R. Five hard truths for synthetic biology. Nature. 2010;463:288-290.

Carlson R. Biology is technology: The promise, peril, and new business of engineering life. Cambridge, MA: Harvard University Press; 2010. 10.1080/00033790.2010.510941.

Esvelt KM, Wang HH. Genome‐scale engineering for systems and synthetic biology. Molecular Systems Biology. 2013;9(1). doi: 10.1038/msb.2012.66.

Beal J. Bridging the gap: A roadmap to breaking the biological design barrier. Frontiers in Bioengineering and Biotechnology. 2015;2.