Opinion

Geoengineering and synthetic biology

This September, as part of our annual symposium, EUSynBioS will hold an Open Discussion on the topic, "Synthetic Biology and Environmental Engineering", at the National Center for Biotechnology, Madrid, Spain. We will host experts in the field to talk about the science and the more difficult aspects of public acceptance and bioethics surrounding geoengineering and synthetic biology. 

pexels-photo-90407.jpeg

Geoengineering is a word that means many things to many people. Formally defined as the "deliberate intervention in the climate system to counteract man-made global warming", for some scientists it represents a cheap and effective way to protect our planet from the ravages of climate change. To others it's symptomatic of technological hubris: a grand, doomed plan to control every aspect of our ecosystem. Dig past the rhetoric though and you find a science that's still in infancy, being developed by scientists around the globe, almost as a last resort in the (now very possible) event that on-going efforts to avert climate catastrophe by reducing global emissions fail.

Current research on geoengineering is focused on either removing carbon dioxide from the Earth's atmosphere or reducing global warming by reflecting more solar radiation away from the planet. Most proposals to achieve these goals rely on physical engineering solutions, cloud seeding for instance. A more expansive reading of "geoengineering"though, leads to several intriguing ideas on using synthetic biology to remedy the effects of intensive industrialisation/pollution on the environment.

i. pale blue dot

In 1980, the US Supreme Court issued a ruling that changed the status of living organisms forever. In Diamond v. Chakrabarty the court affirmed the right of inventors to patent living organisms that had been modified for some purpose. In this case, the patent was granted to a genetically engineered creature called the Superbug. The Superbug was a strain of Pseudonomas putida that could break down crude oil, and was posited as a tool to deal with oil spills. Since then, there's been a lot of work in developing such organisms, spawning a field of science called bioremediation that seeks to undo the damage human industry causes the environment. 

Now, a group of scientists are advocating the use of such organisms on a global scale to help mitigate the effects of climate change. Their, very SciFi-ish, ideas include: modifying particular species of bacteria that exist in harsh environments like deserts and equipping them with water harvesting capabilities; releasing entire stretches of DNA into a biosphere and allowing them to spread, equipping any host creature with water/temperature sensing capabilities, or releasing bacteria into the oceans that can cause pieces of plastic to stick to each other, solving the scourge of microplastic pollution. 

biologists are ever-aware of the conceit involved in predicting biological futures

These and other ideas find few takers though, and carry some real risks. We would have to be prepared to deal with the fact that any man-made bacteria released into a particular part of the world might escape a particular ecosystem, potentially wreaking havoc in others. Biological entities evolve, and evolution might change released modified bacteria in unpredictable ways. 

These are concerns synthetic biologists are tackling head on. In the last five years, we've made tremendous progress in engineering 'kill-switches' that could allow us to precisely control engineered bacteria in natural ecosystems. We've also developed bacteria which have been so extensively engineered that they cannot interact with other life-forms very well, or cannot reproduce, hence limiting the potential spread of synthetic DNA. Yet, biologists are ever-aware of the conceit involved in predicting biological futures and for the moment these bacteria will remain in petri dishes in labs around the world. 

ii. the red planet

The largest concern with biological geo-engineering is the fact that we might cause dangerously irreversible changes to the only habitable planet we know of. This is why, a group of scientists including NASA researchers are exploring biological options in terraforming Mars. The hopes are many, ranging from making Mars human-habitable (paving the way for eventual human colonisation), to using the red planet as a test-bed for ecosystem engineering whose lessons might then rescue the Earth from climate catastrophe. Less futuristic scenarios include the possibility of employing bacteria to harvest resources directly from Mars, or recycling consumable resources like waste-water, making manned Mars-missions a cheaper and easier endeavour. Most experts agree though that terraforming, the process of completely changing Mars' atmosphere is a process that could take centuries. A nearer-term option is something called para-terraforming. Paraterraforming envisions making smaller, enclosed spaces on Mars habitable for humans. Previous experiments in paraterraforming conducted on Earth have met with little success; however the prospect of engineering organisms specifically for terraforming makes this a more feasible proposition. 

Some however, question the ethics of using Mars as a lab-bench. One argument is that any human attempt at terraforming Mars might destroy or alter any remnant, hitherto undiscovered life on the planet. Another, that seeding Mars with terrestrial life may change a potential independent development of biological life on the planet in the distant future. These are minority opinions however. A view that, in my opinion, holds more merit suggests that the creation of Mars as a back-up planet might hinder attempts to mitigate anthropogenic climate change and pollution here on Earth.

iii. a last resort

There are two forms of climate change mitigation on the table at the moment, passive and active. Passive mitigation uses methods that are easier to swallow for most, reducing global consumption, stricter pollution controls, and switching to low-carbon sources of energy. The problem however lies in the fact that passive mitigation alone might not be enough to limit global warming to the 2°C threshold set by the Paris Agreement. Indeed, experts are highly sceptical that limiting warming to even 4°C is feasible given current trends. And the difference between a 2°C and 4°C limit is that the latter will result in massive droughts, flooding on an unprecedented scale and food shortages.

In this scenario, several climate experts have called for more drastic measures including non-biological geoengineering technologies cloud-seeding. In fact some estimates claim that cloud-seeding on a large enough scale might even bring global temperatures down to below pre-industrial levels. In this scenario then, would we even need a biological solution that might carry more risk? 

A possible benefit of biological remediation is of course that we might be able to rescue ecosystems that are on the brink of collapse, something that physical solutions like cloud seeding might never be able to achieve. Biological solutions can address biological problems in a manner that purely physical measures might struggle to. Another aspect of synthetic biology, the de-extinction of extinct species, is something that might supplement the reduction in global warming with the restoration of lost biospheres. 

On the policy front geoengineering is a topic that's often scoffed at or neglected in favour of discussions such as emissions reduction. The reasons for this are legitimate, though given the current political climate with the US backing out of climate accords, the dream of a 2°C reduction in global warming seems to be growing ever more distant. Science agencies across the world are waking up to this fact, and just a couple of months ago China announced the world's largest geoengineering research program. As of now, geoengineering remains a last resort, and biological measures even more so.

This isn't stopping scientists from experimenting with it though, and nor should it. 


Written by: Devang Mehta
Devang is currently a PhD student in Plant Biotechnology and Science & Policy at ETH Zurich. He also serves on the EUSynBioS Steering Committee as Policy Officer. Follow him on twitter at @_devangm or check out his blog at www.devang.bio

Photos: All photos used under CC0 license. 

Writing our genome

A near-outsider’s thoughts on Human Genome Project-Write.

  Journal and magazine covers celebrating the sequencing of the human genome

Journal and magazine covers celebrating the sequencing of the human genome

i. the context

Thirteen years ago, the largest ever collaborative project in biology was declared complete. Scientists from the US, the UK, Germany, France, Japan and China had deciphered a majority of the human genome — the DNA blueprint present in every human cell. To most people my age this is old news, stuff we learned about in middle school. By the time my peers and I had started on our careers in science, the genomes of most economically or scientifically important species had been deciphered and were in near complete states of annotation.

Genome Annotation: determining the functions of long stretches of DNA in the genome, such as genes.
  “Carlson Curves.” Source: Rob Carlson’s blog,   http://www.synthesis.cc/

“Carlson Curves.” Source: Rob Carlson’s blog, http://www.synthesis.cc/

You see, in the years since the completion of the Human Genome Project, the price of DNA sequencing has fallen dramatically. This includes both the cost of sequencing short fragments of DNA, which followed a Moore’s Law-equivalent reduction in costs over time, and next-generation sequencing (more high-throughput methods useful for sequencing larger DNA samples, such as genomes), which even out-paced Moore’s Law.

Moore’s Law: A prediction made by Gordon Moore at Intel that the number of transistors on an affordable CPU will double every two years.

So to us newcomers to biology, the next big thing was not, and is not ‘reading’ DNA but ‘writing’ it.

ii writing DNA

Synthesising short, single stranded fragments of DNA, calledoligonucleotides (oligos for short) has been automated and affordable for a number of years now, and almost every biology laboratory in the world uses these short fragments (usually 18–25 base-pairs — compare this to the human genome which is 3 billion base-pairs long) for applications ranging from disease diagnostics to making genetically modified plants. What really has been a game-changer in DNA synthesis is the ability to synthesise longer pieces of DNA and the ability to join these together efficiently to form synthetic gene length fragments.

This ability to synthesise DNA quickly and cheaply has excited a group of biologists who want to use it to create entire genomes from scratch. To study life by building it, gene by gene. Going further, scientists want to create a “minimal genome” to identify exactly only those genes absolutely necessary to support the most basic form of life. Genome synthesis could also enable us to create optimised strains of biological workhorses like yeast, to more efficiently produce pharmaceuticals and fuels. These ambitions have fuelled the field of synthetic genomics, beginning with the synthesis of aMycoplasma mycoides genome by Craig Venter in 2008.

Currently the most ambitious such project is Sc 2.0. Teams from the US, UK, China and Australia are synthesising a synthetic yeast genome, chromosome by chromosome. This represents a huge leap in complexity since the yeast genome is organised into 16 pairs of chromosomes (we humans have 23 pairs of chromosomes and bacteria usually have just one) and totals 12 million base pairs of DNA (the human genome is 3 billion base pairs and the synthetic Mycoplasma genome only had about half a million).

And this brings us to the title of this piece, writing a human genome.

iii Human Genome Project-Writ

  “The challenges ahead for HGP-Write.” Source: self  , see footnote 1 for details.

“The challenges ahead for HGP-Write.” Source: self, see footnote 1 for details.

This week an article authored by some of the leading researchers in synthetic biology and genetics appeared in the academic journal Science, and for the first time, publicly explored the idea of synthesising an entire human genome. Christened HGP-Write (while rechristening the original Human Genome Project as HGP-Read), the project’s main goal is to “reduce the costs of engineering and testing large (0.1 to 100 billion base pairs) genomes in cell lines by over 1000-fold within 10 years.” The next very sentence goes on to expand this goal to encompass “whole genome engineering of …other organisms of agricultural and public health significance”. The paper goes on to outline a project structure composed of loosely defined pilot projects and milestones. You can read it in full, for free, here and check out the project’s webpage at http://engineeringbiologycenter.org/. Interestingly, and unlike many scientific manuscripts, the article begins with talking about responsible innovation. The authors acknowledge the huge ELSI (ethical, legal and social implications) associated with the project and promise to enable public dialogue prior to and around the project’s implementation. More on this in a bit.

Of course, as you may have realised by now, this project is challenging, more so even that the Human Genome Project and I would argue that it’s probably the most ambitious scientific proposal ever made, spaceflight included. The authors place an launch price tag of $100 million on the project — though I reckon that the project will ultimately cost much more, given that HGP-Read cost $2.7 billion in 1991 dollars.

iv. why rewrite the human genome?

You might wonder now, why write a human genome at all? The project lists several engineering goals on it’s website ranging from growing transplantable human organs to engineering virus immunity. To me however, the more exciting, and perhaps more immediate, results will be the scientific ones. By building a complex mammalian genome from the ground up, we will start filling in holes in our understanding of genetics, from the roles of so-called junk DNA to how epigenetic factors affect cellular function. Further, the project could make available a lot of technologies and generate huge amounts of data that would benefit more distant fields of biological research.

However, in spite of the potential gains, I for one have concerns about HGP-Write.

v. questions

A. The Vision

The project explicitly states that its goal is to synthesise the human genome and to reduce the “cost of engineering and testing” genome synthesis. It envisions catalysing a steep price drop in genome-scale synthesis costs and enabling large-scale genome engineering at more affordable rates. I (like others) question the relevance of this goal to the wider biological and biotechnology industry. Most scientists and biological engineers will never synthesise a eukaryotic genome. It simply is not a technology that is universally applicable or even necessary in most biotechnological solutions.

We synthetic biologists think of ourselves as engineers — we tweak and modify self-replicating systems (aka biological chassis), and we usually make smart, targeted interventions to generate value for industry, for agriculture, for healthcare. Some of the most impressive solutions the field has come up with to date: Humulin, golden rice, artemisinin, genome editing have been done through careful, logical modifications to existing systems. And the tools developed to achieve these goals: faster cloning, metabolic models, model organisms etc. are in constant need of improvement. Perhaps the current technology most relevant to this discussion is molecular cloning.

Cloning: Unlike what Hollywood would have you believe, in molecular biology, cloning is not the making of identical twins who inevitably turn into murderous, soulless monsters. Cloning refers to the manual assembly of plasmids — circular pieces of DNA that can be propagated in bacteria. These plasmids are the basic ingredients, the ‘apps’ if you will, that allow us to customise microbes to produce insulin and make insect resistant plants etc.

Cloning used to be extremely laborious and buggy, and despite recent advances it still is, to an extent. To put it in perspective, a few decades ago, cloning a single gene would constitute an entire PhD. These days it’s routine and largely performed by miserable undergraduates, and in some labs, by even more miserable PhD students and postdocs. Cloning is also a huge market: $3 billion by one estimate. To us regular biotechnologists, the single biggest promise of cheaper DNA synthesis is to eliminate cloning. As DNA synthesis costs have fallen, we have adopted the technology more into our cloning workflows. We no longer need to laboriously isolate genes and DNA fragments from existing organisms (some of which are hard to grow in labs), we can simply order the DNA from synthesis companies. However, the technology has still not become affordable enough that we can do away with cloning entirely. In my line of research: plant synthetic biology, we work with plasmids that measure up to tens of thousands of base-pairs. No synthesis company at the moment can synthesise these plasmids for us, and if they can, it’s certainly not at a rate I could justify to my supervisors.

Would HGP-Write address this need by accelerating DNA synthesis technologies? Possibly. But how long would the price-reductions take to reach the average bioengineer making 15–20 plasmids rather than entire genomes? Would HGP-Write lead to synthesis companies focusing on low costs-per-base for high-volumes, while ignoring demand for low-volumes? I haven’t seen any answers to these questions. Would the project tie up research funding in DNA synthesis? I certainly can’t imagine grant agencies funding multiple large-scale DNA synthesis projects, although I hope they would.

B. Stakeholder engagement

HGP-Write positions itself as a successor to the original Human Genome Project, and perhaps seeks to capture the public enthusiasm that large blue-sky scientific projects sometimes enjoy. The proposal also recognises the huge ethical, social and legal implications of synthesising a human genome, and to the authors’ credit, addresses them more openly than most such research has in the past. I however think that, almost inevitably, the proposal fails to take stakeholder engagement seriously, or seriously enough. The article talks at length about enabling public dialogue, biosafety standards, regulations and intellectual property but misses a crucial point.

It does not, at least explicitly, allow for stakeholders to accept, reject or modify its primary goal — making a human genome.

This is of course, a consequence of it being named HGP-Write, and with its main raison d’être being human genome synthesis. The proposal tries to encompass alternate goals by making hints towards incorporating genome synthesis of other model organisms (thale cress, mouse, fruit fly etc.) and even “enabling research on crop plants and infectious agents and vectors in developing nations.” (This is a statement I take issue with over concerns about the consolidation of distinct research areas). Overall though, the article appears to assume that public engagement will revolve around its pilot projects and assuring biosafety, and other such concerns while implicitly allowing for the construction of a human genome.

Stakeholder engagement of this sort — where the goal is set beforehand and the means, timelines, methods, etc. are open for discussion — is of course perfectly legitimate. Most public projects, scientific and not, follow this approach. I question whether this is enough for a project where everyone of us holds a stake and where the goal is both so radical and so encompassing. Wouldn’t a more flexible proposal to build a eukaryotic genome hold more appeal in this regard? A project where public discussion could include how far we agree to proceed with genome synthesis, for what organism and at what investment? This would perhaps be a more limited project, at smaller scale and without the Human Genome Project-moniker and associated marketing pull, but I think it would ultimately get off the ground faster and with fewer ruffled feathers.

C. Promises

Synthetic biology is often defined as a subset, or extension of biotechnology and genetic engineering and the technologies used often represent a significant step-change over past approaches. The one area where synthetic biology differs most from traditional biotechnology is in it’s handling of human practices (inculcated from very early on), openness, transparency and public dialogue. Synthetic biology centres around the world engage regularly with artists, ethicists and social scientists to an extent that would have been unimaginable in the early days of recombinant DNA technology. Here in Europe, much synthetic biology research has to struggle with the memories of the GMO debates and the mistakes made in past public engagement. In this context, HGP-Write, like other large-scale research proposals makes big, bold promises that are yet a long way off and begins with less than perfect openness (I refer to how much controversy the private meeting last month has already attracted). Big promises carry large risks of under-delivery and I’m wary of the negative fallout from underwhelming expectations. There is little doubt that HGP-Write can achieve its primary goal, the issues here lie with the outcomes described in Box 1 of the article: universal(?) virus resistance, improved genome stability, and cancer (it’s always cancer.)

vi. where does this leave us

I realise upon scrolling up through this piece that it reads a little too much like strident criticism, and that too from a barely published PhD student who has never worked with genome synthesis! I originally started out writing with the intent to make the topic, and the issues surrounding it, easier to parse for non-specialists — family members, for instance. Researching further, I realised this article could perhaps become part of the public discourse invited by the authors of HGP-Write, written from the perspective of a student who still (even with the enormous help that MoClo provides) wishes he didn’t have to do any more cloning. On the other hand, as a Science & Policy student working with crop biotechnology (and genome editing) for developing nations, I couldn’t help but chip in with my take on the public engagement side of things.

If HGP-Write goes ahead to achieve even a fraction of all that it promises, I will still number among its many fans — I just think it could be done with a little less fanfare and little more openness. Overall, for all my concerns, I remain enamoured with genome-scale technologies and the promise that whole genome synthesis holds. After all, my statement of purpose letter for grad school began with that oft-cited Richard Feynman quote:

“What I cannot create, I do not understand”
 Richard Feynman's blackboard at the time of his death.

Richard Feynman's blackboard at the time of his death.

 

Footnote:

  1. This image is for illustrative purposes only, it is not an accurate representation of the genomes of any of the species shown. The estimate of 1 billion bases of gene synthesis sold in 2015 is borrowed from here. The chromosomes counts for yeast and humans is for diploid cells. There is no definition of genome complexity, however I have used the percentage of non-coding DNA as a rough guide to complexity, or mystery. The values are obtained from here and are pre-ENCODE.

Written by: Devang Mehta
Devang is currently a PhD student in Plant Biotechnology and Science & Policy at ETH Zürich. He also serves on the EUSynBioS Steering Committee as Policy Officer. Follow him on twitter at @_devangm

This article originally appeared on Devang's personal blog over at Medium. Follow him on Medium to stay updated with forthcoming articles. 


Disclaimer: Views and opinions expressed in EUSynBioS Pulse articles belong solely to the writer(s). They do not reflect the opinion of the Community, the Advisory Board or the Steering Committee.

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SynBio Breakout Sessions: what do they tell about our community?

 Participants of the first EUSynBioS Symposium in April 2016. Image by Ona Anilionyte.

Participants of the first EUSynBioS Symposium in April 2016. Image by Ona Anilionyte.

Starting from a set of activities pursued by a small number of researchers, the discipline of synthetic biology has taken a remarkable trajectory over the past decade. However, the rapid growth of synthetic biology has also provoked concerns about its prospective impact on society and the environment, which needs to be addressed by future leaders of the field.

Taking a first step towards tackling this challenge, we recently brought together students and postdoctoral researchers from ten different countries at our inaugural EUSynBioS Symposium. Various aspects relevant to building a future vision for the young synthetic biology community were discussed by attendees in scope of our SynBio Breakout Sessions facilitated by experts from ecology, design, and science policy. What have they told about the synthetic biology community of the future?

 
 SynBio Breakout Session on Diversity. Image by Christian R. Boehm.

SynBio Breakout Session on Diversity.
Image by Christian R. Boehm.

Embracing diversity is key, so agree participants of the Breakout Session led by Prof. Louise Horsfall (University of Edinburgh). However, the issue of diversity goes beyond gender and ethnic background of researchers. We should make an effort to include people from a variety of age groups, socio-economic backgrounds, and life-styles. Can a non-scientist be a true synthetic biologist? Or someone who only works part of the time because they choose to take time for family? We think yes, because otherwise we may miss out on a lot of different perspectives and potential for creativity. The synthetic biology community needs role models which appeal to various groups in society and can thus encourage both engagement and public acceptance.

 
 SynBio Breakout Session on Responsible Innovation. Image by Christian R. Boehm.

SynBio Breakout Session on Responsible Innovation. Image by Christian R. Boehm.

A Breakout Session on the issue of Responsible Innovation led by Dr. Michele Garfinkel (EMBO) surfaced several issues about researchers’ responsibilities, including in what ways the public’s views of them matters. The session participants also discussed what the emerging idea of responsible innovation means and pointed out some possible concerns about the definition of the concept in the broader scientific community. Awareness about both responsible conduct of research and responsible innovation needs to be raised generally, and there was some agreement that it should be introduced as an inherent part of good research, reinforced through the scientific community itself both at the bench and by means of discussion sessions like the ones hosted on this occasion.

 
 SynBio Breakout Session on Education&Outreach. Image by Christian R. Boehm.

SynBio Breakout Session on Education&Outreach.
Image by Christian R. Boehm.

Encouragingly, the vast majority of attendees of a Breakout Session led by Prof. Anne Osbourn (John Innes Centre, Norwich) were of the opinion that education and outreach were important, and they moreover felt a responsibility to be proactive in this area. Taking part in outreach and education was seen as a mutually beneficial activity, yet young researchers found it regrettably difficult to identify opportunities to become involved. On a related note, young researchers felt that opportunities for training in how to communicate effectively with an audience of non-scientists were rather scarce. To contribute to closing this gap, we (EUSynBioS) are actively looking for initiatives in the area of science education to work with members of our network.

 

So what is the synthetic biology community going to look like in the future? We do not know for sure yet, but the first SynBio Breakout Sessions revealed its promise: our community embraces a number of young researchers who deeply care about their impact on society and the environment. They are actively looking for opportunities to become better at engaging the public and communicating what they do to a non-specialist audience.

To realize this potential, the organizers of dedicated synthetic biology courses and graduate programs to be established over the years to come are challenged to incorporate relevant training opportunities into their curricula wherever possible. It is bound to pay off.


Written by: Christian R. Boehm

Disclaimer: Views and opinions expressed in EUSynBioS Pulse articles belong solely to the writer(s). They do not reflect the opinion of the Community, the Advisory Board or the Steering Committee.

Synthetic circuits designs for earth terraformation

A recent article presents some hypothetical  strategies to mitigate and repair some of the damage that humans have caused on earth.

 Logic diagrams showing interactions between terraformation motifs. (Sole et al, 2015)

Logic diagrams showing interactions between terraformation motifs. (Sole et al, 2015)

Do you ever wonder what would happen if our planet can no longer support life as we know it? Ricard V. Sole and his colleagues  have, sharing some plausible hypothesis to remediate the impact that human beings have had on our planet. As stated by the authors, there are already some current efforts towards the implementation of remediation mechanisms. However, these strategies are presented as a passive way to act. Because of this the authors came up with more active strategies that employ designed organisms to ‘terraform’ the biosphere.

They consider different scenarios that will assure sustainability, setting boundaries to control the introduced synthetic organism. They present such scenarios, as motifs, where one of the main constraints are ecological interactions. Without any ecological constraints, as they point out, the newly introduced organism will enjoy a positive feedback loop, leading to a fast expansion that might end up with the dominance of the new organism. Through four different motifs, they propose to overcome such positive feedback, leading to a partial control over the synthetic organism. The motifs are composed either by three or two nodes. A host or resource, a synthetic organism and a wild-type organism compose the three nodes motif. The two nodes motif is reduced to only, a resource and a synthetic organism.

In the first motif, named ‘engineered mutualism’, the synthetic organism will be a genetically modified strain from a wild-type organism already present in the environment. The synthetic organism and the host will both directly interact and act positively on each other. The authors propose to engineer the mutualistic symbiosis properties using co-evolution of plants and bacteria under strong selection. Given that the synthetic organism comes from a wild type native organism, loss of the engineered properties won’t lead to environmental catastrophe.I think such dependence is not as direct as they think it will be, in particular when the designed motif is taken from laboratory conditions to the real world. There is always a way in nature to overcome such boundaries. The same opinion is shared by one of the article’s reviewers, Prof. Eörs Szathmary. He writes, “...the proposal is too optimistic, or indeed a bit naïve…I see no guarantee for the lack of escape mutants or recombinants.”

The second motif, ‘indirect cooperation’, is based on the same principle as motif one, however here the interaction is indirect. For such an interaction to occur a particular environment is needed, they mention an aqueous environment as an example. Some organisms to be employed on the design of such motif are cyanobacteria or some plant species. Here the main task of the synthetic organism is to ameliorate the environment to promote survival of other beneficial species.From my point of view, given that both, the wild type and synthetic organism interact with the host, it might be possible that the synthetic organism would either never succeed or take over the wild type organism, and then undesirable consequences could arise.

‘Function and die-design’ is the third motif. It is also composed of three nodes that later could turn into a two. Its main characteristic is the dependence of the organism to live upon a specific substrate or resource. The edited organism will perform a specific function and use the degradation of a particular waste as source of nutrients. The presence or absence of such waste will limit the survival of the synthetic organism. The authors propose Vibrio species since it has been reported to colonize plastic waste. Again, I believe such assumption is naive, living organisms are capable of using more than one source of nutrients to survive.

The final motif, ‘sewage synthetic microbiome’, relies on the use of a synthetic environment, human created, to control the survival of the synthetic organism. Since such synthetic organism comes from a wild type that is only able to grow in a particular environmental small modification in the living conditions will affect their survival. Another advantage is that there is no need to preserve the environment. There is also the possibility to use any foreign organism to generate the synthetic organism.In my opinion this could be the more successful scenario, since the environment already sets high boundaries, but I doubt that if a completely foreign organism is introduced it will be 100% contained in such environment.

The article caught me by surprise, and from the title, I thought that the authors would talk about extra-terrestrial scenarios, for instance Mars or the Moon terraformation. Dr. Tom Ellis, the article’s second reviewer, shared a similar sentiment in his comments. I also had the feeling that the hypotheses were more oriented towards bioremediation. I would like to have read more about genetic approaches to contain a synthetic organism. Checkpoints that not only rely on interactions between species, but also interactions within the synthetic organisms. They vaguely mention the use of xenobiotics components, however they don’t elaborate more on the topic. I am quite optimistic that in some years, with the generation of semi-synthetic bacteria, like the work by Dr. Floyd Romesberg, or minimal bacteria, work lead by the Craig Venter Institute, the motifs described in this article will be more plausible, since the designed organism will be easier to contain and control. In my opinion, more than one way of control is needed, life always finds the way to prosper.


Written by:

Daniela Garcia

Daniela is a PhD student in Biochemistry and Biophysics at LMU Munich. 

Edited by: Devang Mehta

Disclaimer: Views and opinions expressed in EUSynBioS Pulse articles belong solely to the writer(s). They do not reflect the opinion of the Community, the Advisory Board or the Steering Committee

How can Synbio innovation become more responsible?

Some thoughts on an intellectual property rights (IPR) framework that can/should be applied in Synthetic Biology.

This year’s iGEM Giant Jamboree, the grand finale of the synthetic biology (Synbio) competition is almost upon us. Undergraduate students (IGEMmers) run a project, take care of the funding and the outreach, and often produce publications. Last year, the Valencia Biocampus team presented their project on IPR. An opinion article by H. König and two of the Valencia team’s members was recently published in EMBO reports, where they discuss the IPR frame of Synbio and the concept of responsible research and innovation (RRI). This is a good opportunity to reflect upon these societal aspects of Synbio, a discipline that is by definition characterized by innovation and applicability.

 Source: Patent Or  :   Photo by      BusinessSarah    on Flickr

Source: Patent Or : Photo by BusinessSarah on Flickr

According to the article, the typical criteria for patentability are novelty, inventive step, and industrial application. What the authors propose is that an index of “responsibility” should be added. RRI means that the IPR of inventions should be handled in a way that safeguards the future of the scientific and innovative field. This definition is rather generic and vague. The authors therefore go deeper into more specific cases that more suit Synbio.

Patents are a common way individuals and organizations protect their intellectual property. A patent provides the owner with exclusive rights for commercial use.  It can greatly facilitate the commercialization of an idea by reducing the competition, while strong patents are often a prerequisite for investors to commit to a project.No IPR protection acts as a discouraging factor for both stakeholders and inventors. On the other hand, generic and wide patents have been found to be damaging for the development of a specific field. They reduce the innovation that derives from free and extensive interaction and they create hindrances and uncertainties for any incremental development.

What is often forgotten is the fact that patents are not the only way to distribute and protect intellectual property. There are various forms of licensing that can be applied, covering various degrees of commercial and non-commercial use of intellectual property. I could try to elaborate more on the different legal options that exist and which data is owned by whom; however this has been expertly done in a recent perspective by M. Carroll in Plos Biology, so I will refer readers to that. Some examples of flexible IPR from the biotech industry are the anti-HIV drug stavudine and the antimalarial compound artemisinin, both of which include a licensing policy that allows non-profit production to developing countries.

 Source:   917press    on Flickr

Source: 917press on Flickr

In an ideal world, every invention would be assessed using RRI principles and would be attributed to the appropriate IPR scheme. There are no generic rules, but in some cases discoveries need to disengage from profitability in order to promote science and development. Synbio relies on the free exchange of parts, which are to be combined in novel ways. Open access software, data sharing, and open collaborations are in my opinion the driving forces behind the biotechnology boom we are experiencing at this point. They allowing researchers from different education backgrounds and from laboratories with diverse financial capabilities to retrieve information and innovate freely. Patents of course have their place in the Synbio world. In biomedical research, for example, where clinical trials are time-consuming and money-draining, the promise of an extended time frame of exclusive rights can be a strong incentive for costly research to be funded and carried out.

In all cases, RRI should be used as a shaping and not as a preventive tool, taking into account the scientific and societal benefits of a novel practice and guiding the inventors towards the most proper IPR protection option. The iGEM competition can be an ideal setting for IPR experimentation, as it combines the free part exchange with flexible options for patenting and licensing. In that context, iGEM teams can implore RRI considerations in their work and provide their usual innovative touch in the (perceived as by many) grim IPR landscape.


Written by:

Konstantinos Vavitsas

Konstantinos is a PhD student at the Copenhagen Plant Science Centre, University of Copenhagen, working on the photosynthetic production of high-value compounds (Plant Power project). Follow him on Twitter @konvavitsas.

Edited by: Devang Mehta

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