Team:Exeter/Human Practices/panel

Frames of Reference

The presentation to the panel went through the important discussion areas within human practices and then we discussed each topic in turn with the panel and then with the wider audience. The topics were as follows:

Data and Mis-Use

The open database and open source code were discussed as being imperative for iGEM and our funding from the Wellcome trust. This was explained as how we avoided any fraudulent issues. We discussed “dual-use” in our project and how there are many positive societal impacts, taking vaccine development as an example would save millions of lives, against the possibility of making more virulent strains, as how having an open source code would mean our research was freely available for anyone to access which led us into Bioterrorism.

Bioterrorism

The potential of bioterrorists to utilise our technology to alter pathogenicity of strains and what we are doing to prevent this from occurring was discussed. We also discussed the potential benefits of making WaaL mutants to prevent O-antigen production and that in the future we could potentially only publish conclusions and data in scientific journals to avoid bio-terrorists replicating our work.

Life and the Environment

Synthetic biologists utilise different life forms and manipulate them through rational design to design new life forms with more beneficial characteristics. But we are treating these bacteria as machines and not as a life form, raising the questions, are polysaccharide production more important than a bacterial cell’s life and although most would agree could this be acting as a springboard to the genetic manipulation of higher organisms.

We then discussed the environmental impacts if our GMO were to be released into the environment, or the polysaccharides themselves and the consequences associated. The possibility that if released strains producing different polysaccharides could dramatically affect the balance of ecosystems and this may cause unforeseen communication between bacteria and have unknown effects.

Business Impact

Considering our polysaccharide production as a product and since there is no competitor on the market we would be filling a niche and leading the way in this technology. The applications of our polysaccharides in the various sectors were discussed and how a customer would be able to order their desired polysaccharide and how we would produce it for them. Chemical synthesis was compared to our system.

Political and Social Aspects

What we are producing doesn’t exist as yet on the market so there is no guidelines surrounding our product. We talked about then, the more general aspects of genetically modified products and the public opinion surrounding them. We need to overcome the GM superstition as there is a vicious cycle between what the public think and what politicians do as they shy away from making unpopular decisions. We need to introduce our products in a friendly way and educate the public on the real risks and benefits of GM.

Questions and Answers

Q: How are you going to avoid copyright issues?

A: All our data goes on an open data base that anyone can look at. There is a great ethos surrounding iGEM that open source coding is incredibly important, allowing fruitful international collaborations based on BioBricks deposited in a publicly available database.

The fact that all our data, and previous teams data before us, is freely available means we avoid any copyright issues.

Q: How would you avoid bioterrorists getting hold of your work and replicating your experiments to produce more virulent pathogens?

A: Our project from the summer has achieved the production of polysaccharides that are not dangerous to the environment or the public. Of the polysaccahrids we have created, only one is a “dangerous” polysaccharide in it’s natural host: Hyaluronan. In Streptococcus pyogenes, Hyaluronan is a virulence determinant as it assists production of capsule which assists the bacterium in avoiding the immune system. This gene in our laboratory safe E.coli however does not create a virulent determinant due to the polysaccharide being made in the cytoplasm and not being linked to lipid A molecules and incorporated into the bacterium’s cell walls. Therefor Hyaluronan in our E.coli is completely safe.

Currently then, and our future vision of the project does incorporate the idea that you could replicate virulent factors to study them on a lab bench in a safer way than handling the pathogen directly and so assist in finding treatments for disease. We would imagine that correct licensing, training and containment protocols would be followed by those involved in this, particularly with more dangerous polysaccharides that cause disease directly.

Q: Science and other like publications only publish the data and conclusions surrounding work involved with bioweapons. You say your future developments could lead to production of dangerous polysaccharides and so would you only release the data and withhold the method? Isn’t this preventing others replicating your work and standing in the way of progression in science?

A: There is currently a huge debate about censoring science in the name of biosecurity. Dual-use highlights the positive and negative effects that a technology or product may have on society. In our iGEM project, this is the creation of bespoke polysaccharides to, for one e.g., potentially revolutionise vaccine production against a technology that allows someone to design capsular polysaccharides and increase the pathogenicity of strains. Polysaccharides themselves are not responsible for disease; it is the attachment to lipid A in forming lipopolysaccharides (LPS) that causes virulence, as it is the lipid A core which is entirely responsible for its toxicity.

The withholding of method in publications would prevent others replicating our work for proof of concept and stands in the way of the progression of science.

Q: If the bacteria are accidentally or intentionally released how are you going to prevent them from harming the environment or public?

A: Polysaccharides and the genetically modified organism themselves are different risks. The risk of the GMO has been assessed by the GM safety committee and the experiments we are doing are with laboratory safe e coli under good microbiological practice in a lab that is registered for a higher level of containment than what we are using it for.

In the unlikely event that the E coli is released into the environment, it cannot replicate out of the laboratory and the plasmids containing the genes and antibiotic resistance are non-mobilasble so cannot be passed onto any other organism.

If the polysaccharide ended up in the environment, it is a chemical hazard, so their risk needs to be viewed in different ways. We have ensured our polysacchries are not signal factors and so won’t cause communication between bacteria and they are not toxic to the environment.

Q: Why are you doing this and who is going to benefit is a better question as this needs to outweigh the risk?

A: Some people don’t like the idea of others manipulating nature and some people’s opinions you are never going to change. The public don’t like being saddled with wider risks for a project that will benefit a small group such as the case in Monsanto but here we are looking to benefit everyone in society.

Our project is to be able to design polysaccharides that can be used in every industry and sector, from food preservatives to vaccines. They would improve quality of food products, health care, engineering, our military and so the benefits of our project incorporating all of society should outweigh any small risk of release of the GMO, since every containment protocol is being followed.

Q: How do you feel you can rule out chemical synthesis as a competitor of polysaccharide synthesis?

A: Chemical synthesis as an option involves many protection reactions before the desired reaction can take place and then many deprotecion reactions after. This is time consuming and expesnive. Also some polysaccharides due to their precise steric nature, cannot be synthesised chemically at all.

Q: How much would 10mg of polysaccharide X cost vs chemical synthesis method?

A: This depends on the polysaccharide you are referring to? Vaccines are elaborate and chemical synthesis would need many chemical synthesis steps, including all the protection/deprotection methods for each step along the way. Whilst synthesis of something simple like cellulose may for the time being be cheaper to achieve in large quantities chemically.

We can’t put a price on exact costs due to there is nothing like our technology existing.

Q: Are you feeding the cultures with pure monosaccharide’s?

A: Most common are the ones the cell will use so if making lactose derived then will add and utilise lactose in the media but for more elaborate polysaccharides they would need to be added or we could also clone into these bacteria the enzymes to alter the monosaccharide’s to use the ones we want. Those using specialist monosaccharide’s would cost the user more.

Conclusions of the Panel

Environmental and public health was perhaps the topic discussed in the most depth and we gained valuable insights into public protection methods. Our laboratory containment was discussed and the lack of lipid A attachment to our polysaccharides was pointed out to us by Professor Rick Titball. This has framed the argument for accidental release of our polysaccharides ever since.

Public opinion was a matter discussed and we have taken a new approach to our ideas of tackling public opinion, in using a more benefits/risks approach. The discussion of withholding data seemed to split the room as science community members were dead against it as it did not allow the progression of research, whilst non-scientific members were more in support.