sybhel.org http://sybhel.org Synthetic Biology for Human Health: Ethics and Law Tue, 19 Nov 2013 19:27:09 +0000 en hourly 1 http://wordpress.org/?v=3.3.1 SYBHEL Project Final Report and Policy Recommendations http://sybhel.org/?p=893 http://sybhel.org/?p=893#comments Tue, 06 Nov 2012 08:14:21 +0000 admin http://sybhel.org/?p=893 The SYBHEL Project is now complete. Over the last three years the project partners have investigated the ethical and legal issues of synthetic biology as it pertains to human health and wellbeing. The public section of the SYBHEL Project Final Report and Policy Recommendations can be downloaded here. We would like to thank all of the academics, experts and policy makers who have attended SYBHEL Project events and provided valuable advice and feedback on our work.

SYBHEL Project Final Report and Policy Recommendations.

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SYBHEL Project Short Story Competition – Free E-Book of Short Listed Stories http://sybhel.org/?p=761 http://sybhel.org/?p=761#comments Tue, 01 May 2012 14:29:07 +0000 admin http://sybhel.org/?p=761 SYBHEL Short Story Competition – Free E-Book of Short Listed Stories

The deadline for the SYBHEL Project’s short story competition has now passed. The shortlisted entries have been collected together with an introductory essay on the ethical implications of synthetic biology and published as a kindle e-book. The e-book is available to download FREE from this site [click here] (instructions below). Or  the e-book can be purchased for the minimum price of 77p from Amazon [click here] (unfortunately Amazon insists on a minimum price).

After reading the stories, please take the time to vote for your favorite. You can vote by clicking on your favorite from the list in the column on the left of this page.

Instructions for downloading:

1. Click on the link [click here].

2. Unzip the file

3. Connect kindle to your computer

4. Copy file from your computer to the kindle -  file named “documents”

No kindle? You can download a PDF version by clicking on the cover image above.

 

Synthetic Biology & Human Health: Myths, Fables & Synthetic Futures

FLYER

ENTRY FORM

Calling all writers, film makers, animators and artists – do you have a story to tell about the impact synthetic biology may have on future people?

Throughout history people have used their imaginations to create stories. While stories often entertain, they are also used to make sense of human experience and gain insight into philosophical questions. In the 20th century, writers such as Huxley, Orwell, Burgess and Ballard have employed futuristic narratives to explore the philosophical, psychological and moral issues raised by the interaction between technology and society.

The possible health advances from the emerging science of synthetic biology may have a significant impact on both our lives and the lives of future people. It may result in medical applications which affect human experience and the sorts of people who come in to existence. It may lead to new ways of treating diseases, such as targeted cancer treatments, which could radically extend the human lifespan. Or, it could give us new psychopharmaceuticals which allow us, or other people to change our emotions and psychological states. It may also lead to people having new physical capabilities and powers which human beings have never had before

The SYBHEL Project is instigating a short story competition in order to imaginatively consider these sorts of issues through the creation of fictional narratives. We are interested in stories told using a range of different media including, writing, film, animation, graphic novels, spoken word or music. If you would like to enter and see the prizes on offer please visit www.sybhel.org for further information, you can also follow us on twitter @SYBHEL_Project.

Prize:

1st Prize £100

Two 2nd Prizes £50

In addition to the cash prize there will also be an opportunity for shortlisted stories to be published in some form on the SYBHEL website. Winners may also have the opportunity to be invited to the final SYBHEL Project event.

Format:

As the name suggests, the SYBHEL Project Short Story competition is interested primarily in the substance of the story or narrative rather than the medium through which it is expressed. As such we are interested in stories told through a variety of different media. However, we are also interested in short stories rather than epics. As such the following rules apply:

Writing: Short stories (prose or poetry) should be a maximum of 3000 words. Stories should be submitted in word (.doc or .docx) format by email to: sybhel-project@bristol.ac.uk.

Stories should be double spaced, include page numbers and a word count should be noted at the top of the first page. Poems can be single spaced.

Film & Animation: Short films should be a maximum of 10 minutes long and be provided in .av or .wmv format. Please submit them by uploading your video to vimeo.com – please classify your video as private, and then email the private link to:  sybhel-project@bristol.ac.uk.

Graphic: Graphic novel type stories should be no longer than 15 pages in .doc, .docx or PDF format and should be emailed to:

sybhel-project@bristol.ac.uk

Audio: Spoken word (with or without soundscapes) or songs should be a maximum of 8 mins and be provided in .wav or mp3 format and submitted to: sybhel-project@bristol.ac.uk

Rules:

1. The story has to be related in some way to synthetic biology as it pertains to human health and well being (broadly construed). More information on the sorts of applications which might become possible and the sorts of philosophical and moral issues that might be raised can be found at www. sybhel.org

2. The competition is open to anyone, including non-UK applicants, over the age of 16.

3. Entries must be in English, or (in the case of film) have English subtitles.

4. Entries must be original, the work of the entrant and must never have been published, self-published, published on any website or public online forum, broadcast nor winning or placed in any other competition. Any material used must not infringe copyright.

5. The closing date for the competition is 23.59, 16th April 2012.

6. Worldwide copyright of each entry remains with the author. But the SYBHEL Project will have the unrestricted right to publish the winning entries and any relevant promotional material.

7. Judging will be fair and unbiased. The judge’s decision is final and no individual correspondence can be entered into.

8. All entries must include a completed ENTRY FORM

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Call for Papers: Synthetic Biology for Human Health: Bioethics Special Issue http://sybhel.org/?p=812 http://sybhel.org/?p=812#comments Thu, 15 Mar 2012 10:51:28 +0000 admin http://sybhel.org/?p=812 Synthetic Biology for Human Health: Ethical and Policy Issues Bioethics Special Issue

Guest Editors: Nikola Biller-Andorno, Ruud ter Meulen, Ainsley J Newson
CLOSING DATE FOR SUBMISSIONS: 1st October, 2012

The Editors of Bioethics are pleased to announce a special issue in 2013 on the ethical and policy issues in synthetic biology for human health. Synthetic biology is an emerging field with important potential applications for human health, such as innovative drugs, new vaccines, tissue regeneration, or even synthetic cells. Synthetic biology aims to be able to design, engineer and build biological systems that do not occur in nature as well as re-engineer systems that already exist. This raises fundamental ethical questions about the moral status of life, the conceptualization of risks and benefits as well as possible implications for future people. Questions also arise about how we should approach these ethical issues and the moral grounding which ought to guide policy and regulatory issues in this area.
We invite submissions on all aspects of this topic. Questions include but are not limited to:

 

  • Is there anything inherently morally objectionable in creating or (re-)designing life?
  • What are appropriate methodological paradigms for ethical debates over synthetic biology for human health?
  • What questions does synthetic biology for human health pose with regards to justice
  • When should we consider the risks that may arise in the development of synthetic biology applications for human health as morally justifiable to take
  • How should we interpret contested concepts important to normative thinking about synthetic biology and human health? (e.g. life, risk, public interest, health and dignity).
  • What should be the moral grounds for any specific regulation of synthetic biology research and applications to human health?

The editors welcome early discussion of brief proposals and/or abstracts by email to:

biller-andorno@ethik.uzh.ch.

Upon submission authors should include full contact details and a few lines of biographical information in a separate electronic file. We discourage papers of more than 5000 words.
For further submission requirements, format and referencing style, refer to the Author Guidelines on the Bioethics website:

http://www.wiley.com/bw/journal.asp?ref=0269-9702

Manuscripts should be submitted to Bioethics online at http://mc.manuscriptcentral.com/biot.

Please ensure that you select manuscript type ‘Special Issue’ and state that it is for the “Synbio”, Special Issue when prompted.

 

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Discussion with Vitor Martins dos Santos Part 3 http://sybhel.org/?p=779 http://sybhel.org/?p=779#comments Wed, 11 Jan 2012 16:49:58 +0000 admin http://sybhel.org/?p=779 Discussion with Professor Vitor Martins dos Santos Part 3

This is the final part of my discussion with Prof Vitor Martins dos Santos.

Have a listen.

Discussion with Professor Vitor Martins dos Santos Part 2 – Laboratory Setup

The setup of a laboratory is not always seen as the most interesting of topics, but I found Vitor Martins do Santos’ description of the way he had different but complementary researchers working together in close proximity very revealing. Have a listen for yourself and see what you think.

Prof Vitor Martins dos Santos on how he runs his laboratory.

Discussion with Professor Vitor Martins dos Santos

Earlier this year I conducted a long and wide ranging interview with Professor Vitor Martins dos Santos of Wageningen University in the Netherlands. I am going to post extracts of that interview over the next few days. The first is relatively short and provides an insight into the relationship between Systems Biology and Synthetic Biology. You can hear it by clicking here.

Prof Vitor Martins dos Santos on Systems Biology and Synthetic Biology.

SYBHEL Conference Podcast

I have just uploaded a podcast recorded at the SYBHEL Conference in London in June 2012. It is in three parts and interviews 5 people who have been involved in producing the final recommendations from the SYBHEL Project. Have a listen!

Part One
Part Two
Part Three

Synthetic Biology and Coronary Heart Disease

Coronary heart disease, CHD, is one of the major global killers. It is a complex condition with multiple risk factors and presentations but the commonest cause of CHD related deaths is the rupture of fatty plaques in the arteries. Known as thin cap fibroatheromas, these are complex structures which have been the focus of a great deal of research. It is now known that there are eight key transcription factors involved in their development – biological molecules that control how genes are expressed. And these eight factors are known to act on around 2000 genes. This makes it fiendishly complex for researchers attempting to work out how the plaques form, and how they might be prevented from accumulating in the first place.

Now Frueh and colleagues from the Department of Bioengineering at Imperial College have published an approach combining systems and synthetic biology that they hope will help unpick exactly what is going on (Frueh, J., et al. Systems and synthetic biology of the vessel wall. FEBS Lett. (2012), http://dx.doi.org/10.1016/j.febslet.2012.04.031).
This is a complex paper featuring a multitude of different techniques. It is, though, of note for the way it goes through a number of different steps using different approaches to achieve its ends. The problem it tackles is fearsome but is also an interesting model for how to approach the many similarly complex problems that lie ahead.

The over-arching principle was to identify new pathways within the cells lining the blood vessels at the points of plaque formation. As blood is pumped through the arteries the vessels expand and contract, subjecting the cells lining the walls to significant mechanical stress. It is known that the sites of greatest stress are most prone to plaque formation so it is here that the researchers focussed their attention. They used a combination of high resolution imaging techniques and computer based analysis to identify the cells at these stress hot spots and then brought in state of the art genetic analysis. The final result was that they identified a number of signalling pathways that were not normally seen in other similar cells elsewhere in the body.

This paper is largely a demonstration of the technique which involves considerable cross discipline expertise and collaboration. The ultimate aim is to identify the genetics of plaque formation and to identify potential targets for treatments. This is the main point of intervention of synthetic biology for human health in this condition. It is still a long way off but this approach holds out the prospect of developing synthetic biology techniques to engineer blood vessels to be less susceptible or even immune to plaque formation.

Directed Evolution as a Tool for Synthetic Biology.

One of the stated aims of SynBio is to design new functionality into living systems for a whole host of reasons that include disease treatment and control, bioremediation, chemical synthesis and the production of biofuels. The basic principle has parallels in engineering, build up a complex system from known simpler elements and this has already borne fruit. However, there are two important unknowns that make this much harder than the equivalent engineering problem. The first is that simple metabolic circuits within the cell do not operate in isolation which can lead to unexpected results. The second is that not every pathway or metabolic process involved is fully understood.

This is where directed evolution comes into play. The principle is relatively straight forward and, as its name suggests, involves mimicking the process of evolution by natural selection but directing that evolution towards a specific outcome. In essence it is just a form of selective breeding, similar to the way that domestic animals have been bred to produce more milk or more meat or crops to produce greater yields. Organisms with the desired characteristics are bred with each other and the offspring with the improved properties selected and cross bred again. At each stage many offspring are rejected and only the best go on to breed further.

The directed evolution approach is to take a biological molecule, a protein or RNA for example, produce many mutated versions in the test tube and then transfer them into cells to grow. This produces a library of cells containing many variations on the original molecule which can then be screened for the desired effects. These could be a more effective drug or a gene that expresses higher levels of a desired protein. The best performers are then extracted, subjected to another round of mutation and screening and so on. The eventual outcome is a biological molecule, metabolic pathway or whole cell which exhibits enhanced desirable properties.

The crucial element here is that the production of a useful molecule can be done without needing to fully understand how it works.
This approach has already borne considerable fruit and is well reviewed in an article currently in press in the journal Methods R.E. Cobb et al., Methods (2012), http://dx.doi.org/10.1016/j.ymeth.2012.03.009. This gives examples of how directed evolution has been used to redesign or alter living systems from the protein to the cellular level. I will give a brief outline of some of these below.

Lovastatin is a common statin prescribed to millions to reduce cholesterol levels. An enzyme from Aspergillus terreus called LovD can convert an inactive precursor molecule into the active drug. However, outside it’s host cell the enzyme is relatively unstable and doesn’t work at maximum efficiency. Gao et al. (X. Gao, et. al., Chem. Biol. 16 (2009) 1064–1074.) applied directed evolution to this enzyme and after seven rounds of mutation and screening produced an version that showed an eleven fold increase in activity.

The lovastatin example is relatively straight forward and is a technique that has been used for some time. However, there are some considerably more complex procedures that have had some significant results.

These involve techniques that are aimed at metabolic pathways, networks or the whole cell. The techniques involved are complex but are based on the same principle, mutate, screen and select the offspring with the most desirable features. This approach has produced a variety of different engineered organisms. A technique called global transcription machinery engineering, or gTME, was used to produce a yeast strain that can more efficiently ferment the sugars xylose and xylose-glucose and has a greater tolerance to ethanol. The target of the mutations here were the proteins that control how genes are transcribed, the first step in producing the proteins they encode. It is a key control step in cellular metabolism and the aim is to alter the way in which genes are read to produce cells with desirable outcomes.

An alternative directed evolution approach called whole genome shuffling has been applied to a number of industrially important organisms. For example, a strain of Streptomyces was engineered to produce increased concentrations of the chemical (2S,3R) hydroxycitric acid (HCA). The significant point here is that the metabolic pathway that produces this chemical is not fully understood. This means that it cannot yet be tackled by most synthetic biology techniques which require the full details of the metabolic processes to be known. Whole genome shuffling has also been used to create a yeast strain that can grow at 55oC and tolerate 25% ethanol. As a keen amateur wine maker I know that most wine yeasts do not cope well above 30oC and struggle when the alcohol levels reach about 15%. This is a dramatic leap in operating conditions.

The flip side of these techniques is that they offer another way to understand cellular metabolism. All the mutant strains produced in this way have been analysed to work out why they behave in the way they do. This offers researchers greater insight into cellular processes and some surprises. For example, one of the yeast strains targeted by gTME had a key protein, sigma, that was full size while another had a significantly truncated one, but both had similar metabolic outcomes.

These approaches are largely still in the laboratory and have yet to make a significant impact on drug production and other processes important to human health. However, the principle of directed evolution fills in a crucial gap in the tools of synthetic biology. Many of the current approaches in synthetic biology require a complete understanding of the metabolic processes to be engineered. There are still many processes that are poorly understood and a complete description of even the simplest cell is some way off. Directed evolution allows synthetic biologists both to target these unknown processes and to understand them better.

David Sprinzak Interview Part 1

I’ve just uploaded this interview with Professor David Sprinzak. This is part one which is a brief overview of his research, part two will follow soon looking at the principles of circuits in synthetic biology.

Between Prevention and Treatment: How Synthetic Biology as a Theragnostic Technology Alters the Concept of Therapy and the Implications for Personal Responsibility

I have just uploaded the talk given by Robin Pierce on 6th Feb 2012 at the SYBHEL conference in Den Haag.

This covers the topic of theragnostics, a combination of therapy and diagnosis, and raises many different issues for the use of synthetic biology in human health. The talk is 20 minutes in total and I have uploaded it in two parts, part 1 is here and part 2 is here.

Dr Robin Pierce is Assistant Professor, Biotechnology and Society, Department of Biotechnology,
Delft University of Technology.

Abstract:
The possible use of synthetic biology in the realization of the capability to detect and intervene on the basis of biochemical markers indicative of pathology will signal a shift in the boundaries of therapy. In essence, as a theragnostic technology, synthetic biology could operate as an internal ?biophysician?, performing both diagnostic and therapeutic functions. However, this development comes with multiple complexities, not the least of which is for the conception of disease and illness. If an internal mechanism effects cure upon manifestation of emerging pathology, the ?disease? never actually materializes. The biochemical markers trigger cure, thus arresting the development to frank onset of disease.

While the development of synthetic chemical structures that are effective in preventing onset and/or recurrence may signal a major development in the promotion and maintenance of health and well-being, it fundamentally alters the concept of therapy, which traditionally has required the onset of disease before the administration of treatment. Moreover, this will also suggest implications for personal responsibility in health care. This paper will explore these potential shifts, their implications, and offer possible policy approaches for dealing with these changes.

Circuits in Synthetic Biology

One of the concepts that runs through synthetic biology is that of circuits. They are often compared to circuits in electronics but the analogy is not perfect and there are significant differences between the two.

To get a handle on the concept in biology I spoke to David Sprinzak, Assistant Professor at Tel Aviv University in the Faculty of Life Science. First, a little about his work. He studies differentiation at the cellular level, the process by which identical cells develop to perform different tasks in the adult organism.

This process happens wherever there are stem cells within an organism but it’s possibly easiest to consider an early embryo consisting of identical cells. For the embryo to develop these cells need to begin the process of differentiation, following different developmental paths to produce the many types of tissues found in the adult organism. At some crucial point adjacent, identical cells will need to head off in different directions. It is this step, the very first, that Professor Sprinzak is exploring.

Professor Sprinzak’s research is primarily investigative, working out what is going on. However, he does foresee significant potential for human health, particularly in the field of tissue engineering. The aim here is to take cells, probably from the patient, and use them to build replacement tissues and organs. A significant challenge is that organs are complex three dimensional structures composed of different types of cells. Stem cell technology provides a way of obtaining the basic cellular building blocks, but to build the organ they need to be directed to differentiate in the correct way. Having all the components of a car is only part of the problem, to build a functioning vehicle you need to put them in the right place. The work David Sprinzak and his group are doing is slowly unpicking the way cells do this naturally. This could be of great help to the tissue engineers of the future.

Audio of this conversation will be posted on this website in the near future if you want to hear more about what he is doing.

Back now to circuits. One of the functions a cell has to perform is to receive information from the outside world and respond to it in an appropriate fashion. The signal could be a signalling molecule like a hormone or a neurotransmitter which the cells receive. The response could be a decision to differentiate into a different type of tissue. In other words it has to do a bit of computation and the analogy with an electrical circuit does stand up reasonably well here.

A biological circuit, however, is made up at the level of genes and proteins and its function is produced by the way these elements interact.

An example of a simple circuit is this toggle switch, which needsjust two genes, and the two proteins produced when those genes are activated. Gene A produces a protein that turns on gene B, and gene B produces a protein that turns off gene A. If you were to monitor the levels of the proteins one would rise as the other falls and vice versa. A classic situation in which this might operate is a cell that is triggered to grow or divide in response to a certain concentration of a growth factor external to the cell. In that case, the cell needs to convert an analogue input (concentration of the growth factor) to a digital all or none switch. This is similar to an electrical switch where the switch will go from off to on only if you press it hard enough.

The circuit-bearing cell would have on its surface growth factor receptors, proteins embedded in its outer membrane to which the growth factor would bind. When they do so, the receptor will send some form of signal into the interior of the cell. This would, in turn, make its way to the nucleus. If the signal was of sufficient strength then it would activate a gene or set of genes that would trigger the cell to divide or grow or whatever. There is a classic example of a toggle switched engineered into E. coli here Timothy S. Gardner, Charles R. Cantor & James J. Collins Nature 403, 339–342. However, this is in a bacterium which, unlike a mammalian cell, has no nucleus.

This is clearly grossly simplified and I’ve glossed over the details of just what sort of signal is sent from the receptor into the nucleus.. Likewise I’ve ignored the particulars of how the cell determines the strength of the signal and the mechanism of how it activates the gene or genes it targets. These could all involve multiple steps including proteins, enzymes and further signalling molecules. The challenge for synthetic biology is to work out what the necessary components of the circuit are and re-engineer them in whatever way is desired without gumming up the system with unwanted by-products of these biological processes.

The electrical analogy, according to Professor Sprinzak, is useful but does not offer a complete explanation. This incompleteness is most noticeable in the potential for interaction between circuits. In a computer the individual circuits added together can be considered as totally separate from each other, (though there are potential unexpected interactions especially when very many circuits are crowded onto a single chip), but this is not necessarily the case for cellular circuits.

Biology has evolved to use a relatively small number of different molecules as chemical signals, but the same molecule can be part of more than one circuit. Also, the circuits are all operating inside a single cell with no physical barriers between discrete circuits. In an electrical chip, in contrast, pathways are separated by insulators. As a result in the biological cell as the concentration of a signalling molecule in one circuit rises, it can easily “leak” into another circuit. Other components may also be involved in other circuits. As a result circuits can not be considered totally in isolation and experiments often reveal unexpected levels of complexity.

This is just an introduction to the concept, if you want to read more about biological circuits in synthetic biology the following papers offer varying degrees of oversight of the subject: Zhang and Jiang Protein Cell 2010, 1(11): 974–978 and Nandagopal and Elowitz, Science p 1244-1248 Vol 333 2011. Also the audio of David Sprinzak discussing these ideas will be posted shortly on this website.

Developing health technologies from synbio: the ethics of experimental treatment

I have just uploaded an interview I conducted with Sarah Chan at the recent Sybhel meeting in Den Haag. A very interesting and thought provoking idea.

Sarah’s abstract is below and you can hear the interview here.

Sarah Chan: Developing health technologies from synbio: the ethics of experimental treatment
Abstract:
The prospect of new health technologies based on synthetic biology raises promising medical possibilities but also a range of ethical considerations. Apart from the issues involved in considering whether synbio health technologies can or should become part of mainstream medical treatment, the process of developing such therapies, from their origins in the laboratory through their progression as forms of experimental treatment to the point of clinical trials and beyond, itself entails particular ethical concerns. In this paper I consider some ways in which synbio therapies are likely to emerge and the ethical challenges these will present. I argue that developments in this new area of health technology will require us to rethink conventional attitudes towards clinical research, the roles of doctors/researchers and patients/participants with respect to research, and the relationship between science and society; and that a broader framework is required to address the plurality of stakeholder roles and interests involved in the development of synbio treatments.

What Synbio Means for our Definition of Health

I have just uploaded a short interview I conducted with Elselihn Kingma, Simon Rippon and Sune Holm at the recent Sybhel meeting in Den Haag. They all spoke on how synthetic biology is changing the concept of “health” and the potential implications of this change. It’s a short listen and a thought provoking introduction to the ideas involved.

To listen, click here.

The three contributors are:

Sune Holm
Sune is a postdoctoral research fellow in the Department of Media, Cognition and Communication at the University of Copenhagen. He did his BA and MA in philosophy at the University of Copenhagen and the University of St. Andrews. In 2006 he received his Ph.D. in philosophy from the University of St. Andrews on a dissertation entitled “The Persistence of Persons.” Since 2009 he has been working on the Ethics and Life project in association with the UNIK Synthetic Biology program launched at the University of Copenhagen. He focuses on questions concerning the moral status of synthetic life, the analogy between engineered machines and evolved organisms, and the ontology and functions of artifacts, organisms, and artifactual organisms.

Elselijn Kingma
Prof Dr Elselijn Kingma is a Research Fellow in the Centre for Humanities and Health & the Department of Philosophy at King‘s College London, and Socrates Professor in Philosophy & Technology in the Humanist Tradition at the Technical University of Eindhoven, the Netherlands. Previously she worked as a Post-Doctoral Research Fellow at the Department of Bioethics, National Institutes of Health, USA.
Elselijn‘s research interests include topics in the philosophy of medicine (concepts of health and disease; evidence based medicine), bioethics (risk, rights & consent, particularly surrounding birth), philosophy of biology (functions), and topics in philosophy of mind. Her PhD thesis entitled ?Health and Disease? was defended in 2008 at the University of Cambridge.

Simon Rippon
Dr. Simon Rippon is a Postdoctoral Research Fellow at the Oxford Uehiro Centre for Practical Ethics. His research interests lie mainly in the fields of bioethics, neuroethics and metaethics. He has recently been working on the nature and normative significance of the distinction between treatment and enhancement, the ethics of procuring organs for transplantation, and the nature of moral expertise. In his philosophy doctoral dissertation at Harvard, he argued that decisive epistemological objections to moral realism should motivate an alternative account which is constructivist, sentimentalist, and response-dependent. (Plain English translation: If we hadn’t, in some sense, made ethics up, then we couldn’t possibly have known what’s right and what isn’t. So ethics is something we have made, not something we have discovered.)

ENDS

Pathogens and Synthetic Biology

On December 20 2011 the journal Science published an extraordinary editorial. They said that they had been approached by the US Government and asked not to publish the full details of a study on the H5N1 avian‘flu virus on the grounds that it could help anyone who wished to turn the virus into a biological weapon. The denouement came on Jan 20 2012 when the researcher temporarily halted their research over concerns that it could be used by terrorists. (http://www.nature.com/nature/journal/vaop/ncurrent/full/481443a.html).

This is a very rare occurrence, but it raises an important dilemma for anyone applying synthetic biology to any potentially pathogenic organisms. It’s a problem that has been identified for some time and is articulated well by Suk et al. in “Dual-Use Research and Technical Diffusion: Reconsidering the Bioterrorism Threat Spectrum” in PLoS Pathogens, p1-3 Vol 7(1), 2011. Simply put, some research may have a dual purpose in that it can be used to harm as well as to heal. The healing potential is the ability to prepare for possible ‘flu pandemics and maintaining academic freedom. The restriction of academic freedom raises the idea of censorship, either by the state of scientific bodies, and also the value and knowledge, it’s ownership and dissemination. Furthermore, restriction could mean that the benefits of research could be available only to an elite few. These ideas are expanded upon in Calladine, A. M. and R. t. Meulen (forthcoming). Synthetic Biology. Encyclopedia of Applied Ethics, Elsevier. The potential harm is that it might provide terrorists with the knowledge to create a potent bioweapon. The ethical and legal question at the heart of this is to what extent this research can and should be made available to other researchers and the general public.

This piece will look at recent research that, while not all are synthetic biology in practice, they are of direct significance to the field. All focus on pathogens, primarily bacteria. I want to be clear. None of this research has been linked to the best of my knowledge to the dual-use question. However, it is impossible to avoid it when considering research into pathogens.

A brief aside first about the definition of synthetic biology and it’s relationship to systems biology. Calladine and R. t. Meulen (see ref above) in an up and coming publication describe the challenge of defining synthetic biology. It is not straight forward but one point well made is that it aims “toward using a variety of approaches to design, engineer and build new biological systems.” With regard to systems biology, Smolke and Silver (Cell. 2011 March 18; 144(6): 855–859) discuss the relationship between that discipline and synthetic biology. They argue that there are significant synergies between the two disciplines but that these synergies will be the driving force that produces significant advances in biotechnology. Taking these two arguments together it is clear that research that helps identify targets for synthetic biology, while not necessarily synthetic biology themselves, are crucial to the discipline. Which is my justification for talking about this first study of Thiele et. al.

The bacterium Salmonella typhimurium is a human pathogen causing gastroenteritis, and is steadily becoming resistant to the antibiotics normally used to treat it. As such it poses a significant threat, particularly to the young, elderly or immune compromised. Understanding its metabolism would provide synthetic biologists with a host of targets to develop new approaches to killing the bacterium and hence treating infections. Thiele et. al. BMC Systems Biology 2011, 5:8 (http://www.biomedcentral.com/1752-0509/5/8) describe a large scale collaborative approach to producing a knowledge-base and mathematical model of S. typhimurium strain LT2. The paper has 27 authors illustrating the scale of the effort required, and argues that community based projects will be required in order to completely describe the metabolism of similar significant organisms. The research was in the field of systems biology, and was attempt to collate and understand the multiple metabolic pathways of S. typhimurium.

The overall result of the research was to produce a metabolic reconstruction (MR) of the S. typhimurium strain. This includes detailed descriptions of 1,270 genes, 2,200 internal reactions and 1,119 metabolites. These were converted into a mathematical model that represented the metabolism of living bacteria which in turn allowed a further, significant step. The researchers were able to use this model to predict a number of potential drug targets. Again, the use of mathematical modelling is becoming increasingly important in synthetic biology, and computer languages are being developed that can aid synthetic biology design. A future blog will look at this issue in greater detail.

A particularly interesting outcome of this research was the conclusion that combination treatments, using two or more drugs, would be needed to ensure that the bacteria could not easily evolve resistance. Most current antibiotic treatments are single agents, with the notable exception of those for tuberculosis. The researchers argue that while there are many hurdles to overcome with combination therapies, their work provides good evidence that they are necessary to fight antibiotic resistance in bacterial pathogens.

One of the concerns raised about any form of genetic based medicine, including synthetic biology, is how to ensure that the introduced genes do not produce more problems than they solve. How to minimise any unintended consequences. A classic example is the inadvertent production of a lethal strain of the mousepox virus, created by adding a gene that caused the production of large amounts of Interluekin 4. The researchers did not predict this outcome and rapidly communicated their research to the scientific community, warning of the potential for harm in this study. (http://www.newscientist.com/article/dn311-killer-mousepox-virus-raises-bioterror-fears.html)

The targeted and controlled approach of synthetic biology provides an approach that may be able to prevent this type of reaction happening. A study published in 2010 by Bagh et. al. (Biotechnology and Bioengineering, Vol. 108, No. 3 ,p 645-654, 2011) illustrates one approach. The research focussed on the infection of bacterial cells by the bacteriophage ? which infects and kills E. coli by cell lysis, bursting the cells.

The researchers aim was to use synthetic biology to produce an intracellular disease spotting mechanism with the following characteristics. It should lie dormant when no disease is detected; detect the onset of a lethal disease; respond in a way that halts or mitigates the progress of the disease and have a mechanism that can be deactivated by an external mechanism when desired.

When bacteriophage ? infects an E. coli cell it’s DNA becomes integrated into the bacterial genome. From there it follows one of two paths. The first is that it lies dormant, being copied along with the rest of the bacterium’s genes as it divides and replicates, a state called lysogeny. The other route, called lysis, is where the virus replicates rapidly, produces multiple copies of itself, breaks down the cell wall killing the bacterium and releasing fresh virus into the environment. Crucially, there is a gene based switch that controls the change from lysogeny to lysis. This switch can be flicked by exposure to UV light and certain chemicals and was the focus of the synthetic biologists.

The lysogeny-lysis switch is provided by the interaction of a number of genes and proteins with a key role for a protein call CI. High levels of CI keep the bacteriophage ? dormant, low levels switch it to the active, lethal, mode. One simple approach would be to simply ensure that the bacteria always produced an excess of CI, but this would force the cell to spend energy producing excess protein that would not be needed for most of the time. A more sophisticated approach was developed that was modelled on a classical engineering principle. In essence, when there is ample CI in the cell then the synthetic biology construct detected this and turned off. However, when the levels of CI started to drop the synthetic biology circuit registered this and produced additional, lysis suppressing, CI protein. The researchers produced a number of different variants of their controller which demonstrated the key principles they laid out, that of lying dormant when not needed, detecting the onset of disease, halting it and responding to an external off switch.

This, as the authors of the study make clear, does not have any medical applications. However, it is a very interesting proof of principle, establishing some of the criteria that will be developed for future, medical benefits.

It’s also worth noting the research of Saeidi et. al. Molecular Systems Biology 7; Article number 521, which I have discussed in a previous post on this blog http://sybhel.org/?p=730. The technology is interesting, basically E. coli were modified so that they could detect and then destroy pathogenic Pseudomonas aeruginosa. If you want to know more there’s a good comment piece by Andrew Jermy in Nature Reviews Microbiology ( Nature Reviews Microbiology AOP, published online 12 September 2011). I was struck by it’s title “Licensing Bacteria to Kill” accompanied by a James Bond type graphic. While prediction is of course impossible, I would not be surprised if this area of research was the focus of some probing ethical discussions.

These, and related studies, lay the grounds for synthetic biology to tackle pathogenic organisms in a very different way. The potential for an impact on human health is very large and perhaps the most obvious immediate need is to combat the rise in antibiotic resistant bacteria. The flip side of this is that it could also allow synthetic biologists to produce more potent pathogens, perhaps giving them scope to become bio-weapons. The request by the US government to Science to withhold crucial methodology of the ‘flu research shows that they are aware of the issue. It is very likely that this will form part of the future discussions of the uses and abuses of synthetic biology.

Cancer Seek and Destroy

The many different forms of cancer still pose one of the biggest challenges to human health. The fact that cancer cells are, crudely speaking, normal cells replicating out of control poses a number of significant problems. These include detecting cancer cells in vivo; identifying potential drug targets and destroying cancer cells while leaving healthy tissue untouched. Cancer cells have effectively the same genetic makeup as normal cells, but the pattern of gene expression, and hence metabolism, is often different. One of the major potentials of synthetic biology is that it provides the tools with which to spot these metabolic differences, just what’s needed to identify cancer cells in living tissues. This approach is being applied in many different ways to cancer treatments and this entry will look at a couple of recent, diverse examples which act as interesting proofs of principle.

The first is the use of a synthetic biology approach to find out what drives metastasis of some breast cancer cells. Preventing metastasis, the movement of cancer cells from the original tumour to elsewhere in the body, is a key goal of cancer treatment. Around 90% of deaths from breast cancer are caused by metastases The approach taken by Yagi et. al. Science Signaling 4 (191), ra60, 2011, has shown how the cancer cells co-opt a set of chemicals used to control the movement of white blood cells around the body.

White blood cells are part of the immune system and move freely around the body, congregating at wound sites and other regions as and when they are needed. The signals that draw them to these sites are chemicals called chemokines, and it’s been known for some time that metastatic cancer cells respond to them. What was unclear was exactly what mechanism was used by the cancer cells to detect and follow these chemokine trails. To find out the researchers constructed a synthetic biology system that would produce a protein important in this process, called G?13, that could be turned on with an artificial signal. This meant that the researchers could control where and when the G?13 was present. The result was they found that the way the cancer cells responded to the chemokines was different to the way white blood cells did. They then went on to experiments in mice in which they inhibited this signalling pathway and found that this significantly reduced the rate at which breast cancer cells metastasised.

The significance of this research is that a synthetic biology approach allowed a very specific, detailed exploration of a complex metabolic pathway involved in cancer spread and mortality.

This study of metastatic breast cancer by Yagi et al demonstrated how synthetic biology can be used to identify potential therapeutic targets, but once identified the challenge is to exploit them. A paper by Zhen Xie, et al. in Science 333, 1307 (2011), demonstrates how synthetic biology can be used to identify the unique metabolic fingerprint of cancer cells, and a possible mechanism for killing them.

The researchers developed a synthetic biology circuit that can be inserted into a cell, detect elements of that cell’s metabolism and trigger it to self destruct if it matches a pre-determined profile. The key to this study are small RNA molecules, called endogenous microRNA’s (miRNA), that are produced as part of the cells metabolism. Different cells produce different variants and amounts of these miRNA’s and this profile can act as a form of cellular fingerprint.

The important feature of all DNA or RNA molecules is that their properties are determined by the order of the 4 different types of bases arranged along their length. That order is the sequence of the molecule. This makes each one unique and allows them to be identified in a mixture of other similar DNA or RNA molecules. The synthetic biology approach described here utilised the unique sequence of some miRNA’s produced by cultured HeLa cancer cells. They identified six that were either expressed at high or low levels by HeLa cells in a pattern of expression very different from normal, non-cancerous, cells. Then a series of genes were strung together in an artificial sequence in such a way that they would only react in the presence of the correct amounts of all six HeLa miRNA’s Basically, they had a genetic tool that could, when inserted into a cell, detect whether it was a HeLa cell or not.

Experiments determined that this DNA detective could indeed discriminate between HeLa and other types of cells. Furthermore, the researchers coupled it to the production of a protein that would prompt apoptosis, programmed cell death. So they had a tool that would, if inserted into a human cell in culture, determine whether it was a HeLa cell and if so tell it to commit suicide.

The potential for this as a cancer treatment is clear. However, this approach would have to be modified significantly before it could be used in this way. Firstly, it involves the insertion of DNA into the cells and this is both currently impossible in humans and raises major risk and ethical questions. However, as a proof of principle it demonstrates that the different metabolism of cancer cells could be targeted to kill the malignancies.

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SynBio Policy Blog – Dr. Conor Douglas http://sybhel.org/?p=467 http://sybhel.org/?p=467#comments Sun, 18 Dec 2011 14:56:35 +0000 admin http://sybhel.org/?p=467

Why critiques of SynBio

from NGOs and civil society need to be taken seriously

by: Conor Douglas, PhD

 

Earlier this month a report entitled The Principles for the Oversight of Synthetic Biology’ was released by a collection of NGOs and civil society organizations, which outlines ‘principles necessary for the effective assessment and oversight of the emerging field of synthetic biology’ (2012: 1). The emergence of yet another such a report outlining principles for oversight is not really blog-worthy in-and-of-itself as the grey literature on the governance of SynBio is well stocked with similar outputs. What is blog-worthy about this particular report is that it comes from the NGO Friends of the Earth, and their +100 signatory friends, which includes the ETC Group. Those following the public policy debates on SynBio will be aware of the ETC Group and their critical –and often referenced- position, which came first in their report The New Biomassters – Synthetic Biology and the Next Assault on Biodiversity and Livelihoods.

Unfortunately the headlines that this report is generating tend to centre on the ‘moratorium on the release and commercial use of synthetic organisms, cells, or genomes’ (2012: 3) until a series of conditions are met. Added to this regrettable treatment are the kinds of inflammatory responses science writer Elizabeth Pennisi is reporting: 

Brent Erickson from the Washington, D.C.-based Biotechnology Industry Organization (BIO) calls the report absurd. “[With] the shrillness of its tone and its lack of objectivity, I don’t ‘think it’s really helpful to policy-makers and the public.” He points out that synthetic biology is in many ways a relabeling and evolution of biotechnology that’s been going on for decades. While he agrees that existing rules and regulations may eventually need upgrading, “it’s not like we don’t have experience in dealing with those organisms,” he points out. “There are a lot of safeguards in place.”

This is a double-whammy shame because 1: Erickson’s response only works to polarize the debate and further incense the civil society signatories of the Principles document; and 2, which is perhaps more important: focusing on the call for a moratorium glosses-over the principles themselves that are the core of the report.

This blogger shall not be so careless; the principles outlined in the Principles for the Oversight of Synthetic Biology are as follows:

I. Employ the Precautionary Principle

II. Require mandatory synthetic biology-specific regulations

III. Protect public health and worker safety

IV. Protect the environment

V. Guarantee the right-to-know and democratic participation

VI. Require corporate accountability and manufacturer liability

VII. Protect economic and environmental justice

 

The importance on focusing on points of convergence

Because, the thing is, many of the scientific, policy, regulatory, and funding actors involved in SynBio want the same thing and support many –if not most- of these principles… well, this is more or less true in the European context anyways. In fact it is important to point out that this Principles documents is the product of American and Canadian lead-author NGOs where things like the precautionary principle don’t get as much play. I would hasten to remind our blog readers out there that I made this point about the differences between Europe andNorth America back in 2010 (see below for previous blogs), and this report only seems to hammer the point home.

While I am sure there may not entirely be agreement on how the NGOs articulate the principles in the remainder of the report (including our respective understandings and operationalizations of the precautionary principle), but at least there is some common ground on some basic ideas….WHICH IS CRUCIALLY IMPORTANT…particularly in a debate that runs the risk of serious polarization.

[Worker] safety, environmental protection, democratic participation, accountability and justice, these are all issues that we in the SYBHEL project are exploring when it comes to SynBio for human health, and as a result we are best-off to listen closely to these critiques and explore important areas of convergence rather than focus on high-profile points of divergence –such as the call for a moratorium- that do nothing but sell papers –or increase webpage hit counts as the case may be-  and entrench extreme positions.

 

A point of disagreement?

While one can find considerable overlap in the principles desired by the NGOs and civil society, and the heterogeneous community surrounding SynBio; questions remain on Principle II that would ‘require mandatory synthetic biology-specific regulations’.

The question of whether or not SynBio requires specific regulations is actually one of the central questions driving the SYBHEL project in general, the policy work-package specifically, and something I also addressed in my previous blog-spot. Indeed the American position is for regulatory parsimony when it comes to SynBio; however, part of the problem with this principle as outlined in the report is its positioning of SynBio as a clearly defined and well delineated singular practice. This is not the case, as SynBio represents a set of different approaches and practices that range from bioengineering, to synthetic genomics, protocell synthetic biology, unnatural molecular biology, and in silico synthetic biology. As a result, if there aren’t practices that are SynBio-specific, how would policymakers go about making ‘synthetic biology-specific regulations’?

What is more, there isn’t particularly good evidence that governmental regulations are uniquely effective in promoting safe, secure, fair and just science and technology. While the Principles report is correct in stating that ‘voluntary self-regulation by practitioners is not a substitute for synthetic biology-specific regulations enacted by governments and international treaties.’ (2012: 4); the report fails to note that the bio-security codes of conduct produced by and for gene synthesis companies set a higher regulatory standard than the code offered by the American government. This is a point that Prof. Stephen Maurer has made quite nicely in his work on self-governance (see his book Regulation Without Government: European Biotech, Private Anti-Terrorism Standards, and the Idea of Strong Self-Governance).

What is therefore required for sensible policy progress on this issue is an overview of the current regulations that could pertain to the entire diverse set of SynBio practices, and a subsequent evaluation of the ability of those regulations to deal with these diverse sets of practices. If and when there are gaps between regulations and practice, then new regulation is warranted. I think everyone would agree on that. We should also note that this review of the existing regulations was a recommendation given by the European Group on Ethics of Science and Technology in their Opinion on SynBio in 2009 (i.e. Recommendation 13 on page 52). This is a massive undertaking there is no doubt, but the European Commission is pretty massive, and doing so might go some way in addressing some commonly held concerns which could work to unify -rather than- splinter public discussion on SynBio oversight and governance.

PREVIOUS BLOG November 24th, 2012

 

Craig Venter Presentation in Rotterdam – Some Policy Questions Left Unanswered

If you have any interest  in SynBio then it is likely that you are to follow closely the moves of Craig Venter and his various institutes, companies, and centres. The biotechnology powerhouse has not only been a central player in SynBio with his flashy announcement of  the ‘creation of a bacterial cell controlled by a chemically synthesized genome’ (Gibson et al. 2010), but was centrally involved in the sequencing of the human genome.

But of course you know all that.

What you may not know is that on November 22nd The Netherlands Genomics Initiative (NGI)  held its 11th annual ‘Life Sciences Momentum’  in which -among other things- ‘the man himself’ gave a keynote presentation ‘From Reading to Writing the Genetic Code’ as a part of his address as the NVBMB (The Netherlands Society for Biochemistry and Molecular Biology) Speaker of the Year 2011.

The NGI is the financial infrastructure behind the major genomic centres that consolidate and drive research and development in this area in The Netherlands, and the ‘Life  Sciences Momentum’  is an event that offers ‘a platform on which the Netherlands’ Life Sciences sector has the chance to take stock of the current situation, look at best practices, and make plans to move forward.’ (http://www.momentum2011.nl/about.html accessed November 24th, 2012).

While this was a special opportunity to hear one of the fore-runners in the field of SynBio speak publicly, I was somewhat disappointed by the number of policy-related questions that were not only left unanswered, but due to the somewhat hokey format of an interview with a not that informed newspaper science editor (which was no fault of Venter’s), also were left unasked.

In the absence of a proper Q&A at Venter’s talk I thought I would use this format to explore some of the issues that I felt deserved some attention.

To start, it is important to get a feel for the context and content of not only Venter’s presentation, but also of his
co-keynote Feike Sijbesma CEO Royal DSM N.V.  [i.e. a life-sciences juggernaut in its own right yielding  revenues in the area of 9billion plus euros in 2010 from its work in nutrition, pharmaceuticals, performance materials and polymer intermediates  http://en.wikipedia.org/wiki/DSM_(company)].

Basically a thumb-nail sketch of all of the world’s problems were laid-out in front of us: problems related to food shortages, dangers related to climate change, deaths resulting from diseases, scarcities of sources for energy, all major issues facing the entire globe.

SynBio, and its various potentialities and products, was positioned as a (partial) answer to all of these issues.

Very dramatic, very emotive, very rhetorical.

The first thing that struck me was that social and behavioural change needed to alter the current habits that have gotten us into this mess in the first place were largely not discussed. No talk of reducing energy consumption (like riding bikes instead of driving cars); rather, use SynBio microalgae to make better biofuel. No  discussion of altering our throw-away culture that buys and replaces goods in historically unparalleled fashion; rather, develop SynBio to improve materials technology to get us off carbon-based plastics. Forget reducing individual or industrial pollution, or change your diet to eat locally produced organic fruits and veg; instead focus on micro-organisms to deal with those pollutants and engineer foods in ways that goes way beyond conventional GM or plant breeding.

So it was all a very technocratic approach to dealing with the grand challenges our world faces. We were at the NGI annual  event, these guys are in biotech, perhaps I shouldn’t have been (and really I wasn’t) surprised.

One of the other things that struck me was how both speakers were able to brush off any consideration about a future in with synthetic humans (or humans with synthetic genomes). Both speakers claimed that there was no desire to do this, and therefore it should not and will not happen; but Venter did agree that it could be technically possible by 2050. I didn’t understand how they could so easily dismiss all of the discussion around human enhancement  (which would be possible through alterations in the human genome) that is so prominent in much ethical discourse on SynBio?

Even if we ignore this issue of human enhancement (which we should not, which is why I raise it here) and accept this technocratic approach to solving the world’s problems, there were some issues about the details of a SynBio future that were noticeably absent – namely the role of patents and policies related to them.

Venter did take considerable time to explain how his team was able to transplant an entire Mycoplasma mycoides genome (from a digitize genome sequence) into an M. capricolum cell ‘to create new M. mycoides cells that are controlled only by the synthetic chromosome’(Gibson et al. 2010). What he took no time to explain was how and why his affiliated Synthetic Genomics Inc. (SGI) has chosen to apply for patent protection of the self-replicating synthetic bacteria?

According to the Craig Venter Institute (JCVI) websiste,

Over the course of the 15 years it has taken to construct the first self-replicating synthetic bacterial cell, the team at JCVI has had to develop new tools and technologies to enable this feat. SGI has funded the work at JCVI in exchange for exclusive intellectual property rights. SGI has filed 13 patent family applications on the unique inventions of the JCVI team. SGI believes that intellectual property is important in the synthetic genomics/biology space as it is one of the best means to ensure that this important area of basic science research will be translated into key commercial products and services for the benefit of society. SGI intends to provide licenses to its synthetic genomics patents.(http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/faq/#q11 accessed November 24th, 2011)

Really? ‘One of the best means’ for ensuring translation? I wonder what some of the other best means might be?

The main reason I sought explanation and discussion on this patent issue is that large parts of the diverse and diffused SynBio ‘community’ are dedicated to working with freely available and freely accessible information on biological parts necessary for the advancement of this bourgeoning field. This dedication has taken its most visible form in the BioBricks Foundation (BBF). In contrast to SGI’s position that, the BBF is

…dedicated to advancing synthetic biology to benefit all people and the planet. To achieve this, we must make engineering biology easier, safer, equitable, and more open. We do this in the following ways: by ensuring that the fundamental building blocks of synthetic biology are freely available for open innovation; by creating community, common values and shared
standards; and by promoting biotechnology for all constructive interests.
  (http://biobricks.org/ accessed November 24th, 2011)

I would have been very interested to hear how Venter thought this difference could (or would) be reconciled? I would have been interested as to what he would tell young SynBio students who use parts found in BBF for the International Genetically Engineered Machines Competition and deposit their results into the BBF?

Further, I would have liked an explanation as to why the SGI thought ‘that intellectual property is important in the synthetic genomics/biology space as it is one of the best means to ensure that this important area of basic science research will be translated into key commercial products and services for the benefit of society’ (http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/faq/#q11 accessed November 24th, 2011), particularly when large components of the SynBio community are taking an approach that is diametrically opposed to patenting?

Venter and the JCVI are very clear about their  ‘private, not for profit status’, but that status is conflated by the fact that he is the  Co-Founder, Chairman, CEO, Co-Chief Scientific Officer of SGI.

Findings from ourSYBHEL workshop hosted by the Rathenau Instituut on SynBio, European policy, and governance this past spring in Brussels suggested that the issues surrounding intellectual property are one of the main governance challenges facing SynBio in its attempt to develop applications in human health.

Unfortunately this issue does not seem to be enough of an agenda item to be discussed by one of the main movers-and-shakers in SynBio, at one of the largest genomics-based events in Europe. A failure to discuss –let alone- mention it as such does little to ‘make plans to move forwards’ on policy reconciliation between the open source and IP protection positions that stand to strangle SynBio.

 

PREVIOUS BLOGS

WHY THE NOVELTY OF SYNBIO HEALTH PRODUCTS SHOULDN’T NECESSARILY MATTER FOR POLICY

October 5th, 2011

Conor Douglas is a Post-Doctoral Researcher at the Rathenau Instituut in The Hague. He is a social scientist, and member of the SYBHEL project team.

The current regulatory discourse surrounding SynBio is trending towards a series of positions that centres on a debate about the novelty of SynBio practices and products. These positions can be crudely summarized as either:

(a) there is nothing ‘new’ or novel about SynBio, and therefore the existing regulatory measures that are in place to deal with the safety of other medicines or genetic modifications, or legal issues surrounding intellectual property, are sufficient for the task at hand;

(b) there is something new, or particular, about SynBio, but the existing regulatory measures are sufficient to address this novelty; or,

(c) there is something novel about SynBio, the existing regulatory measures are insufficient, and as a result some policy actions need to be taken.

The first two positions basically argue that while there may be future risks, this is an emerging techno-science, and as a result the current institutional arrangements, legislation, policy and regulations are sufficient to deal with the current health applications related to SynBio. After all, the European Medicines Agency exists to evaluate the safety (and efficiency) of medical products, and the Advance Therapy Medicinal Products regulation was specifically designed to deal with prospective and emerging health technologies that can be slippery to pin down in one regulatory category or another.

Whereas the third position stresses the miss-match of old policy and new scientific practices.

The problem that I have with this entire discourse is that is hinges on the issue of novelty.

For me, the novelty of SynBio practices and products is of course an important factor when assessing the adequacy of current governance mechanisms, but novelty certainly is not a necessary or sufficient characteristic upon which this assessment should be based.

The reason I don’t find the ‘novelty issue’ to be particularly helpful is that it operates on the assumption that the existing tools that can be drawn-on to govern SynBio (e.g. genetic modification regulations, medicines licensing practices, or legislation for intellectual property claims on biological materials) actually function adequately for the targets they were originally intended for.

Due to the fact that convincing arguments and empirical research have been made about the failure of the current legislation to deal with these ‘older’ scientific issues and products like genetic modification (e.g. Meyer 2011) and/or on the ability of the
existing European patent system to foster responsible innovation in the life-sciences (e.g. Calvert 2008), it doesn’t make a lick of difference whether SynBio practices and products are novel or not.

In fact this novelty discussion might just be a distraction, or misallocation of our intellectual resources, diverting us from tackling the very real issues facing SynBio for human health.

I realize that as I write this blog I too am guilty of being drawn into the novelty debate surrounding SynBio, but at the very least this is done so knowingly and in an attempt to steer the discussion away from novelty and towards the issues at hand….like how two distinctive scientific cultures of molecular biology and computer science are coming to ahead on issues of intellectual property with the Craig Ventres of the DNA world actively pursuing patent protection for biological parts that could be instrumental in SynBio product development, and the Dew Endys of the bio-engineering world constructing open access repositories for similar biological parts.

This is, one of the many, real issues facing SynBio. Let’s think about how it is going to play out, and what kind of policy interventions (if any) are necessary; rather than arguing about whether or not this is something new and specific to SynBio.

 

Bakker van Eeklo

Bakker van Eeklo by Cornelis van Dalem en Jan van Wechelen (17th century) depicts
wealthy patrons coming to have their heads removed and ‘re-baked’ for their
revitalization. Thanks to Prof. Oscar Kuipers for making the links between this
painting and parts-based approach of SynBio. Image courtesy of wikidpedia: http://nl.wikipedia.org/wiki/Bakker_van_Eeklo

REFERENCES

Meyer, H. (2011) Systemic risks of genetically modified crops: the need for new approaches to  risk assessment. Environmental Sciences Europe. 23:7.

Calvert,J. (2008). The Commodification of Emergence: Systems Biology, Synthetic Biology and Intellectual Property. BioSocieties
3: 383-398.

 

Special Regulation for SynBio? : Differences Between US and Europe.

January 20th, 2011.

The much awaited report on SynBio from the Presidential Commission for the Study of Bioethical Issues (PCSBI) was released on December 16th , 2010 (http://www.bioethics.gov/news/ ). For all of you who read the previous blog in this section, I was curious about what would come of this PCSBI report. I asked openly: “when contemplating risks and policy, and exploring social and ethical issues related to synthetic biology, are American bioethical issues the same as everyone else’s ?”

It is clearly not the scope of this blog to try and review all of the similarities and differences between the US and –for instance- Europe when it comes to their bioethical priorities. However, this science policy blogger is particularly interested in the views of the respective ethical commissions and groups with regards to the need for special and specific regulations for SynBio.

In their letter to the President at the outset of the Report the Chair of the PCSBI concluded that  “synthetic biology is capable of significant but limited achievements posing limited risks. Future developments may raise further objections, but the Commission found no reason to endorse additional federal regulations or a moratorium on work in this field at this time. Instead, the Commission urges monitoring and dialogue between the private and public sectors to achieve open communication and cooperation.” (PCBSI 2010: vii).

Later on in the Report when the PCSBI discusses the ethical principles of intellectual freedom and responsibility for assessing an emerging technology like SynBio, they state that “the Commission endorses a principle of regulatory parsimony, recommending only as much oversight as is truly necessary to ensure justice, fairness, security, and safety while pursuing the public good” (PCSBI 2010: 5).

Hmmmm.

I don’t even know how to start to translate that and break-down what parsimonious regulation means, or what they mean by ‘truly necessary’ or their definitions for vague concepts like ‘justice’ or ‘the public good’.

While leaving the latter for another blog, the former reference to  ‘regulatory parsimony’ would seem to support their earlier statement rejecting the need for ‘additional federal regulation or a moratorium on work in this field’.

So that is the American ethics position on special regulation for SynBio, is the European one any different?

Luckily we have the European Group on Ethics in Science and Technologies (EGE) Opinion on Synthetic Biology from 2009 to compare (http://ec.europa.eu/european_group_ethics/docs/opinion25_en.pdf )

On the specific point of existing regulation at the EU level the EGE also feels that much of the existing tools used for genetic modification and genetically modified organisms will also apply to SynBio.

Most of the work in synthetic biology falls within the remit of Directive 98/81 which deals with the contained use of genetically modified micro-organisms. It regulates the contained use of genetically modified microorganisms (GMM) and therefore has environmental and human health protection purposes as stated under Article 1 of the Directive (This Directive lays down common measures for the contained use of genetically modified micro-organisms with a view to protecting human health and the environment.) (EGE 2009: 27-28)’.

However, the EGE doesn’t go quite as far as to suggest ‘regulatory parsimony’. Rather, when it comes to regulations and governance more generally – to which regulation is just one element – the EGE  ‘expresses its concerns on the existing fragmented regulatory framework, which may not be sufficient to properly regulate current and emerging aspects of synthetic biology. It also stresses the need to explore a proper model of synthetic biology governance (soft law, codes of conducts etc.), also taking into consideration potential risks of delocalisation of research trials in countries where regulation may be less stringent than the one proposed in the EU (EGE 2009: 53)’.

Hmmmmmm…‘ delocalisation of research trials in countries where regulation may be less stringent than the one proposed in the EU’, could they be talking about the US? It is well known that the American’s have a much different view on GM than in Europe.

That aside, it would seem that the EGE is indeed suggesting that SynBio is somewhat different, and does indeed require special attention.

This might have something to do with 2009 Nuffield Council’s background paper on SynBio that the EGE references. The EGE notices that ‘under the current regulatory framework, risk assessments of genetically modified organisms (GMOs) compare the altered organism with the natural organism on which it is based, considering the individual traits introduced. Synthetic biology will produce organisms with multiple traits from potentially several different donor organisms. The use of an artificially expanded genetic information system or the insertion of multiple genetic traits or the synthesis of new synthetic biology products, while not excluded per se in the EU biosafety framework may not provide sufficient reliability to the risk assessment and analysis framework (EGE 2009: 29)’.

So while SynBio products will be subject to GM legislation, the very nature of SynBio –and its production of novel organisms- may mean that GM legislation is not enough.

What is perhaps even more interesting than the differences between American and European ethics commissions/groups is that the position of the EGE seems to be in-line with how European citizens feel about SynBio. According to the most recent Eurobarometer (2010) -which regularly takes the pulse of the views of Europeans on matters of science and technology- when asked under what conditions SynBio should be approved  ‘a substantial percentage across Europe (23 per cent) say they don’t know… The remaining respondents, however, are willing to voice a view despite the technology’s unfamiliarity. Some (17 per cent) say that they do not approve under any circumstances and 21 per cent do not approve except under very special circumstances. More than a third (36 per cent) approve as long as synthetic biology is regulated by strict laws and only 3 per cent fully approve and do not think that special laws are necessary. Overall, it seems safe to say that Europeans consider synthetic biology a sensitive technology that demands for precaution and special laws and regulations, but an outright ban would not find overwhelming support (Gaskell et al. 2010: 33, my emphasis)”.

The extent to which these are cultural difference between the biotech-leading American’s and a Europe that favours the precautionary principle is unclear, but the differences are there. In one of their official recommendations the ‘EGE [p]roposes that the EU takes up the question of governance of synthetic biology in relevant global fora (EGE 2009: 53)’.

I wonder if the Americans and the PCSBI would show up to such a global fora?

Stay tuned to this space for more on SynBio policy.

Conor Douglas,  January 20th, 2011.

Conor Douglas is a Post-Doctoral Researcher at the Rathenau Instituut in The Hague. He is a social scientist, and member of the SYBHEL project team.

References

The European Group on Ethics in Science and New Technologies (2009) Opinion to the European Commission on the ethics of synthetic biology. No 25 17/11/2009.

Luxembourg: Publications Office of the European Union. Also accessible at http://ec.europa.eu/european_group_ethics/docs/opinion25_en.pdf

Presidential Commission for the Study of Bioethical Issues (2010) New Directions: The Ethics of Synthetic Biology and Emerging Technologies. Washington, DC. Also accessible at: http://www.bioethics.gov/documents/synthetic-biology/PCSBI-Synthetic-Biology-Report-12.16.10.pdf

Gaskell, G.  et al. (2010) Europeans and biotechnology in 2010: Winds of change? Luxembourg: Publications Office of the European Union. Also accessible at: http://ec.europa.eu/research/science society/document_library/pdf_06/europeans-biotechnology-in-2010_en.pdf

 

International Risk Governance Council Report to Inform US Presidential Commission for the Study of Bioethical Issues’ Report on SynBio: Thanks, But Are American Bioethical Issues the Same as Everyone Else’s ?

By Dr. Conor Douglas – Postdoctoral Researcher at the Rathenau Instituut and member of the SYBHEL project team

December 8th, 2010

Two Innogen researchers (Heather Lowrie and Joyce Tait) have recently published a report ‘Risk Governance of Synthetic Biology’ that will be used as background reading for the US Presidential Commission for the Study of Bioethical Issues (PCSBI) that is preparing recommendations for the President concerning synthetic biology, to be published by the end of the year (see the press release from the Innogen website on November 30th at http://www.genomicsnetwork.ac.uk/innogen/news/latestnews/title,24203,en.html and see below post-script for more information on Innogen and the International Risk Governance Council)

There is no doubt international attention will be given to the synthetic biology report from the US PCSBI that Lowrie and Tait’s report will contribute to. After all The Commission advises the President (i.e. Mr. Obama) on ‘bioethical issues that may emerge from advances in biomedicine and related areas of science and technology’ (see http://www.bioethics.gov/ ), and will deliver the report on synthetic biology to ‘The Man’ himself in about a months time.

But the question has to be asked, when contemplating risks and policy, and exploring social and ethical issues related to synthetic biology, are American bioethical issues the same as everyone else’s ? While the ‘Risk Governance of Synthetic Biology’ report works to identify possible areas of ‘risk governance deficits’ in the hope that such deficits could be avoided if and when knowledge and products resultant from synthetic biology begin to roll out of lab and company doors, it also reflects a certain tension in thinking about risk governance for science. For instance, the Report notes that bio-security risks resultant from synthetic biology are particularly sensitive to the US (Lowrie and Tait 2010: 6). This is not to say that such bio-security concerns are irrelevant in Europe; rather, they are just not the same kind of priority issue as they are in a Post 9-11 America.  And it is these international differences that might stifle the utility of PCSBI’s recommendations for synthetic biology outside of the U.S. of A.

The authors of the report hit the nail on the head when they state that “ [t]he difficulties that arise from piecemeal and divergent national approaches to the regulation of innovative technology in life sciences were very apparent in the case of GM crops, and this experience offers lessons for synthetic biology. However, these lessons are more complex than merely ‘more and earlier stakeholder engagement’ [Tait, 2009b]. “(Lowrie and Tait 2010: 17)

Indeed, they are more complex…and that complexity goes beyond the fact that “[d]ifferent issues arise (i) for the early- stage regulation of fundamental research in synthetic biology and (ii) for the regulation of the products of synthetic biology as they come to trial and market. Ideally, both should be co-ordinated at an international level.” (Lowrie and Tait 2010: 17)

There are numerous reasons for divergent national approaches to the regulation of novel techno-science, which range from differences in how  national economies are organized (i.e. do they care about GM because they are French farmers? VS. do you care about bio-security because your economy is driven by a military-industrial-complex), to how expert advice science policy is sought and delivered (see Jasanoff 2005 Designs on Nature), to relative levels of publics engaging with science and technology ( see Hansen 2010 Biotechnology and Public Engagement in Europe).

I guess my point is that while the idea of coordinated international governance and oversight on issues like synthetic biology could facilitate the regulatory game, it is not only highly problematic to try and execute, but it is also questionable as to its desirability.

This point is particularly salient to the SYBHEL project, and the 6th work package that seeks to provide policy implications for synthetic biology at the European level. So stay tuned to this site and this blog for more about how that works out. There is no doubt that for things like the licensing of new medical devices or medicines, European-wide regulation is needed for SynBio. However, foreseeing uniform reactions of European countries to those novel medical devices or medicines -that for instance make use of human-made living organisms-  is as unlikely as the applicability of American ethical issues on European soil.

So it will indeed be interesting to see the Presidential Commission for the Study of Bioethical Issues (PCSBI) report concerning synthetic biology. Will it contain ethical issues that are universally relevant for synthetic biology? Will it contain issues pertinent to global health? Or will it reflect an understandably American-centric approach to the field?

I guess we’ll see. Stay tuned.

{end}

Post-Script

Heather Lowrie and Joyce Tait  belong to the Innogen group at the University of Edinburgh is the Centre for Social and Economic Research on Innovation in Genomics that is part of the British  Economic and Social Research Council ESRC, which was formed in October 2002, it is part of the ESRC Genomics Network.Their work on the  ‘Risk Governance of Synthetic Biology’ report  (which can be viewed at http://www.irgc.org/IMG/pdf/IRGC_Concept_Note_Synthetic_Biology_191009_FINAL.pdf ) was made possible by the International Risk Governance Council (IRGC), who ‘is an independent organisation based in Switzerland whose purpose is to help the understanding and governance of emerging, systemic global risks. It does this by identifying and drawing on scientific knowledge and the understanding of experts in the public and private sectors to develop fact-based recommendations on risk governance for policymakers’ (see http://www.irgc.org/ )

Hello all,

for those of you who that had the chance to look through the WP 6 Future Objectives, below are links to articles mentioned there in terms of when to talk to the public (in the case of nano medicine) by Jones 2008, and also included here is the link to the British Market Research Bureau report on which the Jones work refers to:

Hyperlinks for the articles are access only, so people may or may not have access:

For Jones 2008 see : http://www.nature.com/nnano/journal/v3/n10/full/nnano.2008.288.html

The nanotechnology for health care can be freely accessed at : http://files.nanobio-raise.org/Downloads/Nanotechnology%20For%20Healthcare%20-%20D_Battachary.pdf

Hope this helps.

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Panel discussion on Synthetic Biology in Zurich http://sybhel.org/?p=565 http://sybhel.org/?p=565#comments Sun, 18 Dec 2011 14:23:07 +0000 admin http://sybhel.org/?p=565

Panel discussion on Synthetic Biology in Zurich

Zurich May 11: Together with Lifescience Zurich, the Institute of Biomedical Ethics at the University of Zurich (IBME) organizes a public panel discussion on the question of how Synthetic Biology might change our understanding of life. Speakers are: Sonja Billerbeck (Synthetic Biology), Christoph Rehmann-Sutter (Philosophy), Harald Matern (Theology), Anna Deplazes-Zemp (IBME).

http://www.lifescience-zurichevents.ch/index.php?id=161

The Societal Impacts of Synthetic Biology

WASHINGTON – The Woodrow Wilson International Center for Scholars is soliciting public opinion on the most critical ethical, legal, and social implications (ELSI) for synthetic biology in a new online survey, which will provide guidance as federal agencies, foundations, industry, NGOs, and other stakeholders with limited resources seek to address key ELSI concerns.

The online survey asks respondents to rate a number of actions that could address ELSI issues, such as ensuring long-term effects of synthetic biology are benign, tracking public and private investment in the field, or labeling products that include synthetic biology in their manufacture.

By prioritizing these potential actions, resources can be better focused on areas of public concern. The results of this anonymous survey will be analyzed and compiled into a report, which will be released in mid- to late-May 2012. To take the survey, click here.

This survey builds on a workshop held Nov. 8-9, 2010, at the Wilson Center in Washington, D.C. The workshop culminated in a July 2011 report, Issues Arising from Synthetic Biology: What Lies Ahead?, which identified potential challenges and pressing research needs. A PDF of the report can be found here.

The workshop was sponsored by the Wilson Center, the Department of Energy, and the Alfred P. Sloan Foundation. Following the workshop, an online survey was conducted to gather further input about which ELSI issues should be considered in the context of synthetic biology. The list of priorities in the new survey integrates the workshop-generated ideas with the post-workshop online input.

 

The Nuffield Council on Bioethics is seeking views on the ethical issues posed by emerging biotechnologies. The Council recently set up an expert Working Party to explore this topic and views are sought to inform the Working Party’s deliberations.

The Working Party is interested in the way society and policy makers respond to new biotechnologies and how benefits from these technologies can be secured in an ethically appropriate manner. The Working Party will consider this issue in light of both current examples of emerging biotechnologies, such as synthetic biology and nanotechnology, and older cases, such as genetically modified crops and assisted reproduction technologies.

 

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Synthetic Biology: State of the Art http://sybhel.org/?p=378 http://sybhel.org/?p=378#comments Fri, 18 Nov 2011 08:25:59 +0000 admin http://sybhel.org/?p=378 Fighting Infection
Cancer
Vaccines
Friendly Bacteria
Cellular and Regenerative Medicine
Conclusion

The Clinical Applications of Syntheticology – Toby Murcott

Introduction.

One way to look at medicine is that it attempts to repair malfunctions of the human body, be they internal errors such as genetic diseases or invasions of parasites and pathogens. Synthetic biology aims to re-engineer biological processes, and to do so in such a way as to produce specific, targeted outcomes. It’s no accident, then, that a great deal of hope and effort is being invested in developing synthetic biology for many difficult to treat diseases such as cancers, antibiotic resistant infections or genetic disorders. Even though the discipline is in its infancy, there are already some promising approaches emerging from labs around the world.

In a recent review published in Science, Ruder et al. [Ruder, et al. Science 333, 1248 (2011); DOI: 10.1126/science.1206843], described a number of ways in which synthetic biology may help human health. These approaches are universally elegant and demonstrate an impressive diversity of ideas. This breadth is one of the challenges for the SYBHEL project in that each approach is likely to produce a different set of legal and ethical questions.


Fighting Infection.

The discovery and development of antibiotics has had a profound effect on human health. Many previously deadly diseases are now easily cured. But, inevitably, their impact is starting to wane as bacteria fight back and acquire resistance. Drug development has slowed and new approaches to treating antibiotic resistant infections are needed. Enter the engineered bacteriophage, variations on viruses that infect only specific bacteria.

The first approach described by Ruder et al tackles persistent bacterial infections that hide themselves inside a mucous-like protective coat called a biofilm. A bacteriophage can be engineered to force infected bacteria to do two things. The first is, on infection, to quickly produce large quantities of new virus, burst open and die. This kills the bacterium, helping to reduce the infection and spread the virus rapidly to the remaining bacteria. The virus itself poses no risk to human health. The second is to produce an enzyme that breaks down the biofilm, exposing the bacteria to both antibiotics and the body’s immune system. Lab tests showed this eventually killed 99.997% of biofilm bacteria.

A second study described by Ruder et al produced bacteriophages that, once inside an infected bacterium, turned off the mechanisms that protect it from antibiotics. Treating E. coli infected mice with both antibiotics and the engineered bacteriophage resulted in an 80% survival rate, compared to 20% with antibiotics alone.

A very different approach to infectious disease is seen in a synthetic biology approach that could be used to tackle malaria. The parasite that causes this disease has to spend part of its life cycle inside a mosquito. Genetically modified mosquitoes can be engineered to block this stage, but that will only work if the genetic alterations are spread quickly to the whole mosquito population. A piece of syntheticDNAhas been constructed that should, in principle, encourage another set of genes to spread rapidly throughout a breeding population, almost like an infectious genetic disease. And in laboratory tests it did indeed spread throughout a caged population very quickly. This was a proof of principle, and did not carry any anti-malaria payload, so to speak. The next step would be to add an anti-malaria genetic modification to this system, producing, in theory, a genetic construct that would reduce or even eradicate malaria transmission.

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Cancer.

One of the greatest challenges for cancer treatments is to eliminate cancerous cells in the human body without damaging associated tissue. Ruder et al describe two synthetic biology approaches which have produced promising results in the lab.

The first involved engineering bacteria to produce a protein that makes them stick to human cells, but to produce that protein only in the absence of oxygen. Tumours often grow in low levels of oxygen as their blood supply is poor. The hope is that when the bacteria encounter a low oxygen tumour, they will stick to and invade the cancerous cells. The engineered bacteria were shown to invade human cells in the test tube only when oxygen levels were low. A potential problem with this approach, though, is that it would rely on the blood supply to deliver the bacteria to the cancer. However, tumours often have poor blood supply, making them low in oxygen, which is why this approach works in the first place. A lack of blood makes them susceptible, but also makes delivering the treatment a challenge.

This obstacle has been circumvented in a different approach that tackles one of the genes involved in turning cells cancerous in the first place. The CTNNB1 gene is involved in many colon cancers when it behaves in an abnormal fashion. Reducing the output of this gene when this occurs could potentially stop colon tumours from growing and spreading. The researchers engineered a bacterium that could penetrate colon cancer cells and interfere with the workings of the CTNNB1 gene and demonstrated that it could indeed target colon cancer cells growing in laboratory mice.

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Vaccines.

Synthetic biology has also been turned onto the challenge of developing new vaccines. A vaccine works by offering the body’s immune system a sample of the disease causing organism, known as an antigen, so that it can remember it and attack it if it invades in the future. An established way of doing this is called attenuation, in which a virus or bacterium is crippled so it cannot cause disease, but retains enough identifying features for the immune system to recognise it. This is, however, a delicate balancing act that doesn’t always work.

One rather elegant piece of synthetic biology has been to produce an artificial cell-like body that can alert an immune system but not cause disease. It works by wrapping some genes and the mechanism to translate them in a membrane similar to our own cell membrane. The genes included can, in theory, be changed for those from any disease causing organism. This will result in little fatty bubbles, called liposomes, that resemble part of the virus or bacterium. However, because they contain nothing else they are not able to produce disease, removing at a stroke the balancing act of attenuation – that tricky process by which an infectious organism is deactivated but not totally destroyed..

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Friendly Bacteria.

We carry inside us 10-100 times more bacteria than we do human cells. These are essential for life, helping us to digest food, produce some vitamins and ward off invading pathogenic bacteria. These bacteria, collectively called the microbiome, live happily inside us and are potentially excellent targets for synthetic biologists.

One example is the development of E. coli, the common gut bacterium, that can help fight off cholera, at least in mice. The E. coli were engineered to produce a chemical signal that cholera bacteria use to coordinate infection. The signal effectively swamped and so jammed the cholera bacteria’s signals. Baby mice given these engineered bacteria followed, 8 hours later, by cholera bacteria had an increase in survival rates of 80% over mice given cholera alone.

A second approach to utilising the microbiome is to engineer bacteria to produce useful drugs inside the body. The trick here would be to make sure that they are produced in the right amounts at the right place in the body, relying on the ability of synthetic biology to build in mechanisms to respond to external stimuli. These would turn on when they detect pathological conditions (rather like the cancer targeting bacteria), and turn off again when the disease has passed.

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Cellular and Regenerative Medicine.

The final topic Ruder et al discussed was the engineering of human cells to behave in specific, useful, ways. The challenge here is that the majority of synthetic biology to date has been done in bacteria. Mammalian cells like ours are significantly more complex and therefore significantly harder to engineer. However, it has been done.

Mice have been engineered to contain a synthetic biological mechanism that is turned on by the presence of uric acid, the chemical responsible for gout, and produce enzymes that remove the uric acid. Once it is all gone then the mechanism turns off. This mimics the behaviour of many different natural cellular processes, miniature thermostats turning off and on in response to a myriad of chemical signals in the body. The system was tested in mice genetically engineered to over-produce uric acid. This new system succeeded in reducing their uric acid levels and the clinical problems such as gout and crystals in the kidneys associated with excess uric acid.

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Conclusion.

The review authors conclude by arguing for much more work to be done in mammalian cells, developing systems such as the uric acid removal mechanism. Without them it will be impossible to move synthetic biology from the laboratory into the clinic. The examples here demonstrate that it is possible to build synthetic biological systems that can effectively seek out and treat disease in the body. The potential is enormous, but real clinical treatments are still a long, long way away.

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Zsófia Clemens’ monthly report on the state of the art in synthetic biology

Synthetic Toxicology: Where engineering meets biology and toxicology.
Schmidt M, Pei L.
Toxicol Sci. 2010 Nov 10. [Epub ahead of print]

The article delineates implications of synthetic biology for toxicology. In the second part of the article ramifications of synthetic toxicology are explored with an emphasis on potential applications and their risks. Applications include: constructing toxicity testing platforms, biotransformation of toxins, designing biosensors for environmental toxicology. For example widespread arsenic contamination and its detoxification is a great challenge. A potential synthetic toxicology application might be to couple innate arsenic detoxification pathways with synthesized arsenic detection pathways. The article also discusses issues related to cell-free synthesis of toxins and toxic use reduction through synthetic biology and implications of non-natural proteins for toxicology.

Genes that move the window of viability of life: Lessons from bacteria thriving at the cold extreme: mesophiles can be turned into extremophiles by substituting essential genes.
de Lorenzo V.
Bioessays. 2011 Jan;33(1):38-42.

Recent evidence suggests that a few genes might suffice for adaptation to extreme environmental conditions. For example, genes from cold-loving bacteria expressed in E. coli allow them to grow at 5°C or even lower temperature. This feature might be exploited to develop vaccines used in warm-blooded animals, including humans. The rationale beyond is that such pathogens possess the entire antigenic repertoire but will be killed at higher temperature. So far attempts to increase heat-sensitivity have been less successful. Heat-tolerance is known to rely on heat-shock proteins but expression of these proteins in E. coli failed to augment heat tolerance. Presently heat sensitivity is one of the bottlenecks to use microorganisms in industrial processes. Other environmental extremities to be aimed by synthetic biology include humidity, surface tension, UV, radiation, pressure etc. In an application E. coli was made tolerant to the toxicity of by-products of biofuel production.

Biology by design: from top to bottom and back.
Fritz BR, Timmerman LE, Daringer NM, Leonard JN, Jewett MC.
J Biomed Biotechnol. 2010;2010:232016. Epub 2010 Nov 2.

This review article summarises basic principles of synthetic biology. Considerations regarding ”bottom-up” and “top-down” approaches are discussed and illustrated. Three topical areas of application are discussed: biochemical transformations, cellular devices and therapeutics, and approaches that expand the chemistry of life. This latter approach is aimed at designing nonnatural compounds that behave predictable and envisions components such as peptide nucleic acids or xenonucleic acids replacing DNA. These artificial molecules have the potential to expand biopolymer information storage.

Environmental biosafety in the age of synthetic biology: do we really need a radical new approach? Environmental fates of microorganisms bearing synthetic genomes could be predicted from previous data on traditionally engineered bacteria for in situ bioremediation.
de Lorenzo V.
Bioessays. 2010 Nov;32(11):926-31. doi: 10.1002/bies.201000099. Epub 2010 Oct 8.

This article suggests that fears and reservations about environmental risks of synthetic biology are exaggerated. There are examples in the article to illustrate that genetically engineered organisms (GMO) are less fit and less likely survive when competing with natural counterparts. It is highlighted that GMOs have never caused any environmental harm. Reprogramming bacteria is hindered by our limited understanding of live systems. Difficulties are also reflected in failed attempts to reprogram pathogens for fighting cancer cells. It is suggested that organisms with synthetic genomes do not represent additional risk.

A comparative analysis of synthetic genetic oscillators.
Purcell O, Savery NJ, Grierson CS, di Bernardo M.
J R Soc Interface. 2010 Nov 6;7(52):1503-24. Epub 2010 Jun 30.

This review presents state of the art in the design and construction of oscillators comparing the features of the main networks highlighting their advantages and disadvantages. Starting with the simplest Goodwin oscillator the article considers repressilators and several types of activator–repressor networks and most recent oscillators constructed in mammalian cells. Very recent oscillators include Fussenegger oscillators, Smolen oscillator, variable link oscillators and the metabolator. Features of each network, models used for their in silico design, mathematical background, validation and in vivo data are presented.

Synthetic circuits, devices and modules.
Zhang H, Jiang T.
Protein Cell. 2010 Nov;1(11):974-8. Epub 2010 Dec 10.

This mini-review summarises recent advances in designing basic building blocks for synthetic biology applications. These include artificial gene control elements such as the zinc finger protein which provides a powerful tool to modulate gene expression. Other elements include synthetic RNA for post-transcriptional regulation (such as artificial riboswitches) and synthetic proteins (such as multi-domain binding protein or scaffold proteins). The construction of higher-order genetic circuits and devices allow more sophisticated control. These artificial elements can be combined into synthetic biological modules such as in the case of an engineered cyanobacterium producing isobutyraldehyde and isobutanol directly from CO2.

Synthetic biosensing systems.
Marchisio MA, Rudolf F.
Int J Biochem Cell Biol. 2010 Nov 23. [Epub ahead of print]

This review summarises synthetic biology of sensing systems. These systems are in continuous evolution. Compared to the early synthetic gene circuits more advanced systems are constructed by coupling artificial and natural pathways. At present numerous components such as receptors, adapters, scaffolds and their interaction with ligands have been characterised. In addition, based on cell–cell communication mechanisms more complex networks such as cell phones and ecosystems have been modelled. The review describes cell-cell signalling mechanisms, post-translational biosensors, transmembrane signalling and intracellular signal transduction for biosensor applications.

Characterization of engineered actin binding proteins that control filament assembly and structure.
Brawley CM, Uysal S, Kossiakoff AA, Rock RS.
PLoS One. 2010 Nov 12;5(11):e13960.

Cytoskeleton found in eukaryotic cells is built from actin filaments. The network of actin filaments is strictly regulated in response to various stimuli. Therefore it is an ideal target for reengineering the cytosceleton. Normally there are over a hundred distinct actin binding proteins that modulate establishment of actin filaments. The actin filament is polar, with distinct ends known as the barbed and pointed ends maintaining distinct polymerization rates. Here the authors produced new artificial proteins that unlike the majority of actin binding proteins bind to the pointed end of actin filaments and regulate polymerization. These artificial proteins were generated by phage display mutagenesis. Effective strategies to select and screen for proteins with desired properties are described.

Biomaterials. 2010 Dec;31(36):9395-405. Epub 2010 Oct 8.
Recombinant self-assembling peptides as biomaterials for tissue engineering.
Kyle S, Aggeli A, Ingham E, McPherson MJ.

Synthetic self-assembling structures mimicking the natural extracellular matrix is an approach used in tissue engineering applications. The self-assembly process relies on peptides since they can be easily synthesized. P(11)-4 is a 11 amino acid peptide with well-known characteristics. The authors used simple site-directed mutagenesis to produce a series of other P(11)-family peptide expression vectors. Here they report improved recombinant expression and a new purification strategy for the self-assembling peptides. The purified peptides were analysed, characterized and tested for cytocompatibility.

J Mol Biol. 2010 Oct 28. [Epub ahead of print]
Multichromatic Control of Gene Expression in Escherichia coli.
Tabor JJ, Levskaya A, Voigt CA.

The authors recently constructed a red light-sensitive E. coli transcription system based on a cyanobacterial phytocrome and E. coli signaling pathway. Here, they expand light regulation with the development of a green light-inducible transcription system in E. coli based on a photoswitchable system from cyanobacteria. Transcriptional output in this system was shown to be proportional to the intensity of green light applied. Expression of both sensors in a single cells allows two-color optical control of transcription in engineered cells. Such a system would allow expression of different genes to be controlled with different colors of light.

Biotechnol Bioeng. 2010 Oct 21. [Epub ahead of print]
An active intracellular device to prevent lethal disease outcomes in virus-infected bacterial cells.
Bagh S, Mandal M, Ang J, McMillen DR.

One of the future goals of synthetic biology is to create genetically programmed agents that are able to fight disease. The authors here designed a system featuring several key properties that will be required for a future intracellular disease-prevention mechanism. The system detects the onset of the lytic phase of bacteriophage lambda in E. coli., responds to prevent its lethality and it can be deactivated externally by a temperature shift when desired. The authors have also formulated a mathematical model that explained the behavior of the engineered system.

Surface display of a functional minicellulosome by intracellular complementation using a synthetic yeast consortium and its application to cellulose hydrolysis and ethanol production.
Tsai SL, Goyal G, Chen W.
Appl Environ Microbiol. 2010 Nov;76(22):7514-20. Epub 2010 Oct 1.

Cellulosomes are extracellular complexes of cellulolytic enzymes of bacteria capable of degrading cellulose. In this paper a functional minicellulosome was assembled using a synthetic yeast consortium. The design consisted of four different engineered yeast strains capable of displaying different proteins of the cellulosomes such as a trifunctional scaffoldin carrying three different cohesins and corresponding dockerin-tagged cellulases. Based on the specific cohesion-dockerin interactions the secreted cellulases were docked in a highly organized manner. By expoiting the modular nature of each population it was possible to fine-tune and optimize cellulose hydrolysis and ethanol production.

Methods Mol Biol. 2011;692:235-49.
Design of synthetic mammalian quorum-sensing systems.
Weber W, Fussenegger M.

Bacterial quorum-sensing components have previously been engineered in some applications such as for controlling population density. Here the authors provide a detailed protocol of a mammalian cell-to-cell signaling device. This system comprises a sender and a receiver cell line. The sender was engineered for expression of alcohol dehydrogenase converting ethanol into acetaldehyde while the receiver for the dose-dependent translation of the acetaldehyde concentration into transgene expression. It is suggested that this design can be adapted to various cell types and transgenes for mammalian cells-based quorum-sensing systems.

Curr Opin Genet Dev. 2010 Oct 7. [Epub ahead of print]
Watch the clock-engineering biological systems to be on time.
Aubel D, Fussenegger M.

Oscillations can be found throughout in nature. Synthetic biologists have assembled a variety of synthetic clocks mimicking the dynamics of various biological processes. The review reports the repressilator, the first synthetic oscillator design, the first synthetic clock combining positive and negative feedback loops as well as the metabolator that integrates metabolism into transcriptional regulation to generate oscillation. Another synthetic clock is the mammalian intron clock referring to manipulating intron lenght and thereby manipulating oscillations. Other advanced synthetic clocs include the sense–antisense pendulum clock and low-frequency mammalian oscillators. The review also highlights major challenges such as synchronization of individual engineered cells across the population, difficulties with engineering multiple oscillator components and prevent interference between different oscillation components.

October 2010

 

Engineered polyketide biosynthesis and biocatalysis in Escherichia coli

Gao X, Wang P, Tang Y.

Appl Microbiol Biotechnol. 2010 Sep 19. [Epub ahead of print]

Polyketides constitute a diverse family of compounds synthesized by bacteria, fungi and plants. They include clinically useful drugs such as antibiotics, antifungals, cytostatics, anticholesterolemics and antiparasitics. Enzymes that synthesize polyketides are referred to as polyketide synthases (PKS). Since many of the natural hosts of PKS are difficult to culture establishing a universal heterologous host has become an important goal. The review summarizes recent advances in engineering E. coli for the biosynthesis of PKS of different types.

A nonlinear biosynthetic gene cluster dose effect on penicillin production by Penicillium chrysogenum

Nijland JG, Ebbendorf B, Woszczynska M, Boer R, Bovenberg RA, Driessen AJ.

Appl Environ Microbiol. 2010 Sep 17. [Epub ahead of print]

Production levels of penicillin by Penicillium chrysogenum have markedly increased by classical strain improvement methods. These high yielding strains contain multiple copies of the penicillin biosynthetic gene cluster. Authors of the article investigated the effect of increasing number of gene clusters on the level of penicillin production. It was found that penicillin production increased but saturated at high copy number. Remarkably, the acyltransferase enzyme located in peroxisomes saturated already at low cluster numbers. It was suggested that acyltransferaseactivity is limiting for penicillin biosynthesis at high biosyntheticgene cluster numbers.

Engineered photoreceptors as novel optogenetic tools

Möglich A, Moffat K.

Photochem Photobiol Sci. 2010 Oct 28;9(10):1286-300.

Optogenetics is a new tool in cell biology denoting the use of genetically encoded, light-gated proteins that is photoreceptors which control cellular behavior. Engineered photoreceptors resemble fluorescent reporter proteins that are designed to monitor cell processes but in addition they are able to modulate activity and therefore offer control over cells. Engineering is based on naturally occurring photoreceptors with fusing light absorbing sensor domains with an effector domain. The article summarizes basic principles and application of such engineered photoreceptors.

Using light to control signaling cascades in live neurons

Rana A, Dolmetsch RE.

Curr Opin Neurobiol. 2010 Oct;20(5):617-22.

Light as a controlling signal has several advantages including non-invasiveness, high specificity and spatio-temporal control. These two latter features are of crucial importance in the nervous system where timing of events is essential. Recently photo-activable proteins have been developed to control and manipulate cell processes. These artificial photoreceptor proteins (APP) consist of a light-sensing and an effector domain. The article summarizes potential use of APPs in the nervous system research and its challenges in practice.

A synthetic-natural hybrid oscillator in human cells

Toettcher JE, Mock C, Batchelor E, Loewer A, Lahav G.

Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):17047-52.

In this study a tunable oscillator was constructed based on the p53 signaling pathway in mammalian cells. The authors reduced this circuit to contain a single feedback loop. In contrast to natural cells, the reduced circuit exhibited damped oscillations with amplitude that depends on input strength. By constructing other variants of the circuit the authors demonstrated that important features of oscillation dynamics such as the amplitude, period, and the rate of damping can be controlled.

Using synthetic biology to understand the evolution of gene expression

Bayer TS.

Curr Biol. 2010 Sep 14;20(17):R772-9.

 

Evolution of phenotype is thought to rely on changes in gene regulation rather than changes in encoding proteins themselves. For example there are many proteins that show remarkable sequence conservation over a large evolutionary time-span. This aspect of evolution can be stated in analogy with synthetic biology which aims to manipulate gene expression basically through their regulation. This article highlights cases where synthetic biology was used to rewire regulatory networks to understand their functional advantages. Synthetic biology also allows for testing evolutionary paths not taken by currently existing organisms.

Microfluidic approaches for systems and synthetic biology

Szita N, Polizzi K, Jaccard N, Baganz F.

Curr Opin Biotechnol. 2010 Aug;21(4):517-23. Epub 2010 Sep 9.

Microfluidics deals with the behavior of fluids of small amounts. Advantages of microfluid approaches include reduction of sample volumes, shorter analysis time and increased sensitivity. The review summarizes how these advantages can be harnessed for synthetic biology. So far microfluidic chips have been developed for oligonucleotide synthesis and for facilitating electroporation, a technique used to input new DNA into cells. Microfluidic devices are currently used for circuit expression, storage and analysis. Future aims include integrating several processes in a single device allowing fully automated cell analysis and assembly of synthetic systems.

Transgenic biosynthesis of trypanothione protects Escherichia coli from radiation-induced toxicity

Fitzgerald MP, Madsen JM, Coleman MC, Teoh ML, Westphal SG, Spitz DR, Radi R, Domann FE.

Radiat Res. 2010 Sep;174(3):290-6.

Trypanothione is a unique compound found in trypanosomes which are parasitic protozoa. The major function of trypanothione is the defense against radiation and oxidative stress. Therefore trypanothione was suggested to act as a radioprotective agent when heterologously expressed in bacteria. To test this trypanothione synthetase and reductase genes from T. cruzi were introduced into E. coli. The transgenic E. coli was able to produce trypanothione and compared to control bacteria was found to be 4.3-fold more resistant to killing by gamma radiation. These results point to the possibility of using trypanothione as a novel radioprotective agent.

September 2010: Synthetic biology for translational research. Burbelo PD, Ching KH, Han BL, Klimavicz CM, Iadarola MJ. Am J Transl Res. 2010 Jul 20;2(4):381-9.

The review focuses on translational applications of synthetic biology. One application is to develop diagnostic serologic immunoassays against different pathogens. Advantage of artificial gene synthesis for antigens is that the corresponding DNA is not required. Another application is to design artificial, multi-epitope genes that can be used as vaccines. A powerful application is the synthetically attenuated virus engineering (SAVE), a procedure based on codon deoptimation in order to attenuate pathogenic viruses. Other applications include developing new drug screens, modify cells and engineer new synthetic pathways to treat cancer, neurodegeneration and infection. Another ultimate goal is to develop genetically-modified organisms to fight disease such as genetically modified bacteriophages against antibiotic resistant bacteria or engineer bacteria to invade cancer cells.

Structural synthetic biotechnology: from molecular structure to predictable design for industrial strain development Chen Z, Wilmanns M, Zeng AP. Trends Biotechnol. 2010 Aug 18. [Epub ahead of print]

Structural synthetic biotechnology is a new field with great promise for industrial biotechnology. It combines synthetic biology and structural cell biology. The latter concerns to a field designing and assembling cell components as well as revealing details about macromolecules and bioreactions at the atomic level. The review discusses developments of structural synthetic biology and its application in metabolic engineering in industrial strain development. Specific applications include: programming metabolic pathways, engineering allosteric regulation of enzymes and designing scaffold proteins that enhance the efficiency of the metabolic pathway and engineering cellular signaling pathways.

Challenges in synthetically designing mammalian circadian clocks. Susaki EA, Stelling J, Ueda HR. Curr Opin Biotechnol. 2010 Aug 12. [Epub ahead of print]

Engineering approach is typically applied to simple biological systems. This review overviews the synthetic biology approach of a complex and dynamic system, the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Complex transcriptional and post-transcriptional properties of the SCN have previously been described. The synthetic approach of the circadian clock requires implementing the signal transduction network, electrophysiological network and intercellular circuits of the SCN. Rational synthesis of circadian system properties will be important in understanding the biological clock and associated clinical problems such as sleep disorders.

Tracking, tuning, and terminating microbial physiology using synthetic riboregulators. Callura JM, Dwyer DJ, Isaacs FJ, Cantor CR, Collins JJ. Proc Natl Acad Sci U S A. 2010 Aug 16. [Epub ahead of print]

The authors previously described a synthetic, riboregulator system that controls gene expression posttranscriptionally through highly specific RNA–RNA interactions. In the present study a series of experiments are conducted to demonstrate the advantageous features of this system. These features include: component modularity, leakage minimization, rapid response time, tunable gene expression and independent regulation of multiple genes. These features make this system an ideal synthetic biology platform for interfacing with different microbial systems.

The synthetic integron: an in vivo genetic shuffling device. Bikard D, Julié-Galau S, Cambray G, Mazel D. Nucleic Acids Res. 2010 Aug 1;38(15):e153. Epub 2010 Jun 9.

The article describes generation of large number of genetic combinations of the tryptophan operon in E. coli. Recombination was carried out using the inherent gene shuffling activity of a natural bacterial site-specific recombination system, the integron. The generated operons varied in their fittess and tryptophan production capacities. Several assemblages required six recombination events and produced 11-fold more tryptophan than the natural gene. Selection of optimal arrangements from randomized libraries might be an alternative of rational design of metabolic pathways.

Oscillations by minimal bacterial suicide circuits reveal hidden facets of host-circuit physiology. Marguet P, Tanouchi Y, Spitz E, Smith C, You L. PLoS One. 2010 Jul 30;5(7):e11909.

 

A synthetic genetic circuit is presented that causes unexpected oscillations in bacterial population density over time. Contrary to expectations, oscillations did not require the quorum sensing genes. Instead, oscillations were likely due to density-dependent

plasmid amplification and parallel increase in expression of a plasmid-borne toxin that established a population-level negative feedback. A mathematical model that captured the plasmid copy number and circuit dynamics was validated by the experimental results. The results point to the importance of plasmid copy number and potential impact of interactions on the behavior of engineered gene circuits.

Synthetic gene networks in mammalian cells. Weber W, Fussenegger M. Curr Opin Biotechnol. 2010 Aug 4. [Epub ahead of print]

 

Following initial synthetic biology work that was mostly conducted in prokaryotes, there is now increasing interest towards mammalian systems given its direct link to biomedical applications. The review summarizes recent efforts in mammalian synthetic biology in the past two years. Recent advances include approaches following the classical small-molecule-based designs as well as new principles such as those using light as a trigger for controlling cells. The article also highlights synthetic gene networks exhibiting oscillating behaviour.

An engineered mammalian band-pass network. Greber D, Fussenegger M. Nucleic Acids Res. 2010 Aug 6. [Epub ahead of print

In the formation of embryonic patterns morphogens carry information depending on its concentration. In the present study the authors engineered and optimized a mammalian genetic circuit capable of sensing a specific concentration within morphogen gradient. The components involved linked mammalian transactivator and repressor control systems to detect and respond to low-treshold and high-treshold concentration levels of tetracycline. A mathematical model was also derived to simulate interactions between various modular elements. These results have implications for future tissue engineering, gene therapy and biosensing applications.

A synthetic riboswitch with chemical band-pass response Muranaka N, Yokobayashi Y. Chem Commun (Camb). 2010 Aug 19. [Epub ahead of print]

A riboswitch is an mRNA molecule that can regulate its own activity through binding small target molecules in bacteria. Rarely natural riboswitches have two binding domains, called tandem riboswitch. The authors engineered such a tandem riboswitch containing an ON and OFF riboswitch unit. The resulting complex riboswitch functions as a chemical band-pass filter circuit. It is remarkable that such a function is achieved without regulatory proteins.

Synthetic analogs tailor native AI-2 signaling across bacterial species Roy V, Smith JA, Wang J, Stewart JE, Bentley WE, Sintim HO. J Am Chem Soc. 2010 Aug 18;132(32):11141-50.

Quorum sensing (QS) is bacterial cell-cell communication brought about by the secretion and reception of small signal molecules, called autoinducers (AI) Elements of the QS system can be used to interrupt communication. Anti-QS agents that quench QS communication but are otherwise harmless to cells are thought to pose less evolutionary pressure on bacteria and therefore believed to prevent the emergence of new antibiotic-resistant strains. The authors developed agonists and antagonists of the AI-2 that mediates the QS response in multiple bacterial species and also demonstrated the biological basis of this action. The results suggest new modalities to interrupt bacterial communication and an alternative approach to treat bacterial infection.

April-July 2010

 

Recognition, neutralization, and clearance of target peptides in the bloodstream of living mice by molecularly imprinted polymer nanoparticles: a plastic antibody

Hoshino Y, Koide H, Urakami T, Kanazawa H, Kodama T, Oku N, Shea KJ.

J Am Chem Soc. 2010 May 19;132(19):6644-5.

Hoshino et al report a new technique to create plastic antibodies that are able to clear a target peptide toxin in the bloodstream. These organic antibodies are artificial versions of natural antibodies produced by lymphocytes with comparable binding affinity and selectivity. When injected into mice plastic antibodies diminished the toxic effect of the target peptide and enhanced survival. It is suggested that the reported technique could be used to generate plastic antibodies against a range of antigens and might be a cheap and simple alternative of natural antibodies that are produced slowly and in complicated ways in living mammals.

Synthetic biology of protein folding

Moroder L, Budisa N.

Chemphyschem. 2010 Apr 26;11(6):1181-7.

This article highlights the concept of using synthetic amino acids that are not found in nature for in vivo protein synthesis. This method does not alter the DNA sequence itself but produces variation at the level of protein translation. Such genetic code engineering is a useful tool to study protein folding. The article highlights two examples of alternative protein folding resulting in novel structural properties of the synthesized protein. One of the examples is the prion protein where structural conversion of the protein is thought to result in prion protein aggregation leading to a devasting neurodegenerative condition.

­

An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system

Orlinger KK, Holzer GW, Schwaiger J, Mayrhofer J, Schmid K, Kistner O, Noel Barrett P, Falkner FG.

Vaccine. 2010 Apr 26;28(19):3318-24

The article reports the first chemical synthesis of a flavivirus, the West Nile Virus. The synthesized virus contained no undesired mutations and exhibited undistinguishable properties compared to the wild-type virus. This demonstrates that chemically synthesized viruses might be also used for vaccine production or research.

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Neumann H, Neumann-Staubitz P.

Appl Microbiol Biotechnol. 2010 Jun;87(1):75-86.

This review gives an insight into biological components available to the synthetic biological approach of pharmaceutical biotechnology. Bioactive compounds, such as cyclic peptides can be maintained in the form of genetically encoded library. Combining modules of multi-enzyme complexes might result in novel properties of the enzyme such as in the case of polyketide synthases. De novo creation of metabolic pathways might be used to expand biosynthetic activity e.g. to produce terpenoids that do not naturally occur. Well-known examples of terpenoids are the anti-malarial drug artemisinin and the anti-cancer agent paclitaxel. Optimizing metabolic pathways e.g. by feeding cells with synthetic oligonucleotides, was shown to fine-tune ribosomal binding and leading to increased production of lycopene in an engineered E. coli. Recombining individual modules has been employed to design proteins that act as biosensors (such as an E. Coli strain responding to light) or to design bacteria that deliver chemotherapeutic drugs to tumour cells.

Strategies for protein synthetic biology

Grünberg R, Serrano L.

Nucleic Acids Res. 2010 May;38(8):2663-75.

This review presents state of the art of protein synthetic biology. Compared to gene engineering, design and engineering of complex protein systems lags behind due to the versatility and interactions of proteins at the modular level. The review outlines industrial and biomedical applications of protein synthetic biology and discusses potential new avenues.

Creation of a bacterial cell controlled by a chemically synthesized genome

Gibson DG et al. Science. 2010 Jul 2;329(5987):52-6.

The group of J. Craig Venter announced the creation of a synthetic cell controlled only by a synthetic genome. Creation of the synthetic cell relied on their previously established procedures including synthesis, assembly, cloning, and transplantation of a bacterial genome. Although the cytoplasm of the recipient cell is not of synthetic origin the authors refer to such a cell as “synthetic cell” since the only DNA in the cell is the synthesized DNA and phenotype of the recipient cell is diluted with protein turnover. The synthesized cell has expected phenotypic properties and capable of self-replication. As in previous studies the investigators watermarked the synthetic chromosome to distinguish it from naturally occurring cells.

Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.

Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ.

Lancet. 2010 Aug 7;376(9739):440-448.

The study reports an alternative approach of tissue regeneration. Instead of using stem cells or direct implantation the authors demonstrate that the rabbit synovial joint can regenerate with a biological cue. The articular surface of the humeral condyles was excised and replaced by an anatomically correct bioscafford infused with transforming growth factor ?3 (TGF?3). Four months after surgery, TGF?3-infused bioscaffolds were fully covered with hyaline cartilage. Compared to TGF?3-free bioscaffords, TGF?3-infused bioscaffords showed greater thickness and density. These findings suggest that the synovial joint can regenerate without cell transplantation.

The art of reporter proteins in science: past, present and future applications.

Ghim CM, Lee SK, Takayama S, Mitchell RJ.

BMB Rep. 2010 Jul;43(7):451-60.

Reporter genes are commonly used in many laboratories to study gene expression. The first reporter gene, the lacZ was published 30 years ago. The review discusses the three reporter systems: ?-galactosidase, luciferases and fluorescent proteins, their past and current applications. Novel applications include studying bacterial populations within smaller scale systems such as biofilm and microfluids. The review suggests the new generation of reporter genes might used to characterize and fine-tune biological parts to be applied in synthetic biological applications.

Synthetic biology of minimal living cells: primitive cell models and semi-synthetic cells

Stano P

Syst Synth Biol 2010

DOI: 10.1007/s11693-010-9054-3

The article discusses synthetic biology approaches to study minimal cells and synthetic cells. The articles describe attempts to define minimal life in the framework of the autopoietic (self-reproducing) theory and shows a report on autopoietic chemical systems based on fatty acid vesicles, a model which might be relevant for primitive cells. The article also contains a review of the four most advanced studies implementing some simple functions in the synthetic cell. It is concluded that semi-synthetic cell models can provide insights into the nature of cellular life and might be useful for biotechnological applications.

A comparative analysis of synthetic genetic oscillators.

Purcell O, Savery NJ, Grierson CS, di Bernardo M.

J R Soc Interface. 2010 Jun 30. [Epub ahead of print]

This review presents a comparative analysis of the main synthetic oscillators constructed in vivo or studied theoretically. A wide range of synthetic oscillators is considered starting from the simplest Goodwin oscillator, repressilators, several types of activator-repressor networks and the Fussenegger oscillators, the only oscillator that has been implemented in a eukaryotic system. This review might be used as a guideline to synthetic biologists and engineers wishing to use existing synthetic oscillator models and designs.

Ligand-dependent regulatory RNA parts for Synthetic Biology in eukaryotes.

Wieland M, Fussenegger M.

Curr Opin Biotechnol. 2010 Jul 15. [Epub ahead of print]

A variety of artificial regulatory RNA parts have been developed that are capable of controlling gene expression in eukaryotes. The genetic switch relies on a specific ligand binding to a RNA domain. Depending on the surroundings, this can affect transcription, translation or RNA interference. The article provides a summary of the main controllable RNA parts developed so far in eukaryotic systems.

 

Update on designing and building minimal cells.

Curr Opin Biotechnol. 2010 Jul 15. [Epub ahead of print]

Jewett MC, Forster AC.

This review presents the major advances occurring in the design and synthesis of minimal cells during the past few years. Minimal cell projects are proceeding in two different directions: top-down referring to in vivo reduction and bottom-up meaning in vitro construction. Major progresses include: minimization of the Escherichia coli genome, sequencing of minimal bacterial endosymbionts and identification of essential genes. The review proposes an RNA-based and a protein-based in vitro model for minimal cells and discusses their potential advantages and practical hurdles.

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The Clinical Potential of Synthetic Biology http://sybhel.org/?p=730 http://sybhel.org/?p=730#comments Thu, 17 Nov 2011 21:52:10 +0000 admin http://sybhel.org/?p=730
Fighting Infection
Cancer
Vaccines
Friendly Bacteria
Cellular and Regenerative Medicine
Conclusion

Introduction.

One way to look at medicine is that it attempts to repair malfunctions of the human body, be they internal errors such as genetic diseases or invasions of parasites and pathogens. Synthetic biology aims to re-engineer biological processes, and to do so in such a way as to produce specific, targeted outcomes. It’s no accident, then, that a great deal of hope and effort is being invested in developing synthetic biology for many difficult to treat diseases such as cancers, antibiotic resistant infections or genetic disorders. Even though the discipline is in its infancy, there are already some promising approaches emerging from labs around the world.

In a recent review published in Science, Ruder et al. [Ruder, et al. Science 333, 1248 (2011); DOI: 10.1126/science.1206843], described a number of ways in which synthetic biology may help human health. These approaches are universally elegant and demonstrate an impressive diversity of ideas. This breadth is one of the challenges for the SYBHEL project in that each approach is likely to produce a different set of legal and ethical questions.


Fighting Infection.

The discovery and development of antibiotics has had a profound effect on human health. Many previously deadly diseases are now easily cured. But, inevitably, their impact is starting to wane as bacteria fight back and acquire resistance. Drug development has slowed and new approaches to treating antibiotic resistant infections are needed. Enter the engineered bacteriophage, variations on viruses that infect only specific bacteria.

The first approach described by Ruder et al tackles persistent bacterial infections that hide themselves inside a mucous-like protective coat called a biofilm. A bacteriophage can be engineered to force infected bacteria to do two things. The first is, on infection, to quickly produce large quantities of new virus, burst open and die. This kills the bacterium, helping to reduce the infection and spread the virus rapidly to the remaining bacteria. The virus itself poses no risk to human health. The second is to produce an enzyme that breaks down the biofilm, exposing the bacteria to both antibiotics and the body’s immune system. Lab tests showed this eventually killed 99.997% of biofilm bacteria.

A second study described by Ruder et al produced bacteriophages that, once inside an infected bacterium, turned off the mechanisms that protect it from antibiotics. Treating E. coli infected mice with both antibiotics and the engineered bacteriophage resulted in an 80% survival rate, compared to 20% with antibiotics alone.

A very different approach to infectious disease is seen in a synthetic biology approach that could be used to tackle malaria. The parasite that causes this disease has to spend part of its life cycle inside a mosquito. Genetically modified mosquitoes can be engineered to block this stage, but that will only work if the genetic alterations are spread quickly to the whole mosquito population. A piece of syntheticDNAhas been constructed that should, in principle, encourage another set of genes to spread rapidly throughout a breeding population, almost like an infectious genetic disease. And in laboratory tests it did indeed spread throughout a caged population very quickly. This was a proof of principle, and did not carry any anti-malaria payload, so to speak. The next step would be to add an anti-malaria genetic modification to this system, producing, in theory, a genetic construct that would reduce or even eradicate malaria transmission.

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Cancer.

One of the greatest challenges for cancer treatments is to eliminate cancerous cells in the human body without damaging associated tissue. Ruder et al describe two synthetic biology approaches which have produced promising results in the lab.

The first involved engineering bacteria to produce a protein that makes them stick to human cells, but to produce that protein only in the absence of oxygen. Tumours often grow in low levels of oxygen as their blood supply is poor. The hope is that when the bacteria encounter a low oxygen tumour, they will stick to and invade the cancerous cells. The engineered bacteria were shown to invade human cells in the test tube only when oxygen levels were low. A potential problem with this approach, though, is that it would rely on the blood supply to deliver the bacteria to the cancer. However, tumours often have poor blood supply, making them low in oxygen, which is why this approach works in the first place. A lack of blood makes them susceptible, but also makes delivering the treatment a challenge.

This obstacle has been circumvented in a different approach that tackles one of the genes involved in turning cells cancerous in the first place. The CTNNB1 gene is involved in many colon cancers when it behaves in an abnormal fashion. Reducing the output of this gene when this occurs could potentially stop colon tumours from growing and spreading. The researchers engineered a bacterium that could penetrate colon cancer cells and interfere with the workings of the CTNNB1 gene and demonstrated that it could indeed target colon cancer cells growing in laboratory mice.

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Vaccines.

Synthetic biology has also been turned onto the challenge of developing new vaccines. A vaccine works by offering the body’s immune system a sample of the disease causing organism, known as an antigen, so that it can remember it and attack it if it invades in the future. An established way of doing this is called attenuation, in which a virus or bacterium is crippled so it cannot cause disease, but retains enough identifying features for the immune system to recognise it. This is, however, a delicate balancing act that doesn’t always work.

One rather elegant piece of synthetic biology has been to produce an artificial cell-like body that can alert an immune system but not cause disease. It works by wrapping some genes and the mechanism to translate them in a membrane similar to our own cell membrane. The genes included can, in theory, be changed for those from any disease causing organism. This will result in little fatty bubbles, called liposomes, that resemble part of the virus or bacterium. However, because they contain nothing else they are not able to produce disease, removing at a stroke the balancing act of attenuation – that tricky process by which an infectious organism is deactivated but not totally destroyed..

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Friendly Bacteria.

We carry inside us 10-100 times more bacteria than we do human cells. These are essential for life, helping us to digest food, produce some vitamins and ward off invading pathogenic bacteria. These bacteria, collectively called the microbiome, live happily inside us and are potentially excellent targets for synthetic biologists.

One example is the development of E. coli, the common gut bacterium, that can help fight off cholera, at least in mice. The E. coli were engineered to produce a chemical signal that cholera bacteria use to coordinate infection. The signal effectively swamped and so jammed the cholera bacteria’s signals. Baby mice given these engineered bacteria followed, 8 hours later, by cholera bacteria had an increase in survival rates of 80% over mice given cholera alone.

A second approach to utilising the microbiome is to engineer bacteria to produce useful drugs inside the body. The trick here would be to make sure that they are produced in the right amounts at the right place in the body, relying on the ability of synthetic biology to build in mechanisms to respond to external stimuli. These would turn on when they detect pathological conditions (rather like the cancer targeting bacteria), and turn off again when the disease has passed.

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Cellular and Regenerative Medicine.

The final topic Ruder et al discussed was the engineering of human cells to behave in specific, useful, ways. The challenge here is that the majority of synthetic biology to date has been done in bacteria. Mammalian cells like ours are significantly more complex and therefore significantly harder to engineer. However, it has been done.

Mice have been engineered to contain a synthetic biological mechanism that is turned on by the presence of uric acid, the chemical responsible for gout, and produce enzymes that remove the uric acid. Once it is all gone then the mechanism turns off. This mimics the behaviour of many different natural cellular processes, miniature thermostats turning off and on in response to a myriad of chemical signals in the body. The system was tested in mice genetically engineered to over-produce uric acid. This new system succeeded in reducing their uric acid levels and the clinical problems such as gout and crystals in the kidneys associated with excess uric acid.

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Conclusion.

The review authors conclude by arguing for much more work to be done in mammalian cells, developing systems such as the uric acid removal mechanism. Without them it will be impossible to move synthetic biology from the laboratory into the clinic. The examples here demonstrate that it is possible to build synthetic biological systems that can effectively seek out and treat disease in the body. The potential is enormous, but real clinical treatments are still a long, long way away.

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Open House at the ETH- Department of Biosystems Science and Engineering in Basel (CH) http://sybhel.org/?p=677 http://sybhel.org/?p=677#comments Fri, 23 Sep 2011 06:35:19 +0000 admin http://sybhel.org/?p=677

On October 22, 2011, the Department of Biosystems Science and Engineering (D-BSSE) of the ETH in Basel (CH) will organize a public open day for visitors who are interested in the research that is going on at this department.  http://www.bsse.ethz.ch/events/open_house

At the D-BSSE, scientists perform high profile research in synthetic biology with potential future applications for human health. Daniel Gregorowius from the SYBHEL partners from the Institute of Biomedical Ethics at the University of Zürich will give a short presentation on philosophical and ethical implications of synthetic biology with a focus on different conceptions of life. The title of his talk will be: „Was ist Leben?“ – Was die Synthetische Biologie als Lebenswissenschaft zur Beantwortung dieser Frage beitragen kann. (“What is life?” – What synthetic biology as a life science can contribute to answer this question)

 

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Website Report on the SYBHEL Final Conference and Workshops http://sybhel.org/?p=622 http://sybhel.org/?p=622#comments Wed, 18 May 2011 12:54:01 +0000 admin http://sybhel.org/?p=622

Website Report on the SYBHEL Final Conference and Workshops

Final Conference

The SYBHEL Final Conference was held in June 2012 at the British Library in London. The conference brought together a range of experts from across Europe. The objective was to discuss and help to revise a draft of the SYBHEL policy recommendations on the ethical and legal issues of synthetic biology and human health.  If you would like a copy of the SYBHEL Report and Policy Recommendations please get in touch via twitter @SYBHEL_Project. We hope that the report will be ready by November 1st 2012.

At the event film and audio interviews were also conducted with many of the participants for public engagement purposes.

A podcast is available here:

Part One
Part Two
Part Three

A number of video interviews can be found here

WP3 Panel:

Chair: Alex Calladine

Panel: Iain Brassington, David Hunter, Laurens Landeweerd and James Wilson

Synthetic Biology: James Wilson from Sybhel Project on Vimeo.

 

WP6 Panel:

Chair: Conor Douglas & Dirk Stemerding

Panel: Michele Garfinkel, Joyce Tait, Henk van den Belt, and Joy Zhang

Synthetic Biology: Joyce Tait – Public Concerns, Public Education from Sybhel Project on Vimeo.

 

WP5 Panel:

Chair Inigo de Miguel

Panel: Graham Dutfield, Muireann Quigley, David Townend, Vitor dos Santos

Synthetic Biology: Graham Dutfield – Intellectual Property and Patents from Sybhel Project on Vimeo.

 

WP4 Panel:

Chair: Heather Bradshaw

Panel: Tom Douglas, Robin Pierce, Simon Rippon and Sue Chetwynd

Synthetic Biology: Robin Pierce – The Future of Medicine from Sybhel Project on Vimeo.

 

WP2 Panel:

Chair: Anna Deplazes

Panel: Sune Holm, Sarah Chan, Joachim Boldt, Markus Schmidt

The History of Synthetic Biology: Markus Schmidt from Sybhel Project on Vimeo.

 

SYBHEL Hague Workshop

The last of the second round of SYBHEL workshops was hosted in February 2012 by the Rathenau Institute in The Hague. The workshops included experts from around the world to discuss issues ranging from global justice to property and patenting of synthetic biology with respect to human health.

Rathenau Institute

Synthetic Biology for Global Health: A Policy Discussion

The workshop considered a number of policy issues that may arise from synthetic biology with respect to global health, such as;

  • How SynBio can be used to address global health issues?
  • How policy can work to ensure fair and responsible implementation of SynBio on a global level?
  • Conditions necessary to support the use of SynBio for addressing global health

University of Bristol

Synthetic biology and human health: Choosing cure or continuity

This workshop considered various conceptions of health and the impact synthetic biology may have on them. The workshop considered the following questions;

 How might the realities of synthetic biology affect our conceptual structures?

  • What are the implications of synthetic biology for well-being, ethics and justice?
  • How should this conceptual and ethical reasoning be integrated into policy for synthetic biology and human health?

University of Deusto

Synthetic biology & human health: The principles and problems underlying patenting and regulation

This workshop, organised by the University of Deusto, considered issues of property and patenting with regards synthetic biology as it pertains to human health. The workshop considered the following questions;

  •  What should the moral limits be of patenting in synthetic biology as it pertains to human health?
  • What general principles should we adopt for regulating (or self-regulating) synthetic biology as it pertains to human health in Europe?
  • What approach to property and patenting in synthetic biology for human health should we adopt?

 SYBHEL Bristol Workshop

The first of the second round of workshops was held in the summer of 2011 at the University of Bristol and hosted by the Centre for Ethics in Medicine. The workshops were organised by The University of Bristol and the University of Zurich.

University of Bristol

Conceptual Foundations, Methodology and Ethical Frameworks

How should we interpret the essentially contested concepts that will play a foundational role in our normative thinking about synthetic biology and human health? For example, concepts such as justice, risk, public interest, health and dignity.

  • Questions concerning methodology in bioethics. For example should we draw on aspects of political philosophy and consider Rawlsian ideas such as reflective equilibrium to consider the ethical questions posed by synthetic biology and human health?
  • What methods should be employed to connect philosophical foundations to public policy in respect to synthetic biology and human health?

University of Zurich

Synthetic biology & human health: Ethical and regulatory questions raised by the aim of producing new life forms

  • What ethical concerns could the idea of producing synthetic organisms raise and how do these concerns particularly apply to medical applications of SB?
  • What forms of life should we care about?
  • Should people’s different conceptions of life be taken into account when formulating law and public policy?

SYBHEL website report on the first round of workshops.

Written by Anna Deplazes-Zemp, Conor Douglas and Inigo de Miguel.

The first round of workshops have now been completed by the SYBHEL project. These workshops were held across Europe, in Zurich, Bilbao and Brussels. The participants invited to these workshops also came from a range of different countries and disciplinary backgrounds, including bioethics, philosophy, social science and theology as well as scientists currently working in synthetic biology. The workshops reflected the work packages of the SYBHEL project. They considered questions raised by synthetic biology in terms of conceptions of life, methodology, property and the patenting, clinical applications and public policy.

Zurich SYBHEL workshops

 

IBME (Institute of Biomedical Ethics), University of Zurich

Ethics of Synthetic Life – An Intercultural Dialogue

Zurich, July 5-6, 2010

 

What happens when synthetic biologists, philosophers, ethicists and experts for different religions get together to discuss questions such as: “what is life”, “can humans synthesize life” and “does the aim of synthesizing living organisms raise moral issues”? Does such a constellation end up in dispute; will the different participants talk at cross-purposes or will there be agreement?

The first SYBHEL workshop organized by the University of Zurich started from the described situation. The aim of the workshop was to take stock of the diversity regarding the concept of life and to understand what the aim of producing new life forms means for holders of different conceptions of life. The workshop participants were asked to introduce their conception of life and to respond to the questions about life mentioned above. In order to link this discussion more closely to synthetic biology different kinds of organisms that are or might be produced by synthetic biology were discussed, for instance bacteria with a designed metabolism, bacteria with a minimal synthetic genome or living protocells. The various backgrounds of the participants resulted neither in serious dispute, nor in endless talking at cross-purposes nor in complete harmony. But each of these elements was present to some extent. There was for instance disagreement whether “life” would have been produced if scientists would manage some day to “make” a living cell from non-living material. Whereas a synthetic biologist held that in this case life would have been synthesized, other participants thought that only the preconditions for life would have been provided, but that life either would emerge by itself or come from other sources. Sometimes, the participants talked at cross-purposes because they used the same words in different ways. This was particularly the case for words such as “needs”, “interests”, “striving”…  For some participants, these terms were necessarily linked to conscious intentions whereas others associated them with all entities who live and thus depend on certain conditions to survive. Finally, we also found certain elements that appeared to be common to all positions, although interpreted in very different terms. For all positions, interaction with and response to the environment appears to be characteristic and essential for living organisms. Moreover, all participants held in one way or another that living organisms incorporate their own “organizing centre”, which means that they are organised and maintained by something, which is part of themselves. Interestingly, all participants agreed that the products of synthetic biology are alive, although they differed about whether this means that life has been produced or not.

This workshop furthered our understanding about the differences between different conceptions of life and the relevance of these differences for the discussions on synthetic biology. In our next workshop, we will focus more specifically on ethical questions and discuss in more detail, how the results of the first workshop pertain to applications of synthetic biology for human health. Moreover, we will also address the question of how one should deal with such a variety of conceptions of life at the level of policy making.

 

University of Bristol, Centre for Ethics in Medicine

How should bioethics respond to synthetic biology?

 

Our workshop was held at the picturesque location of the Institute of Biomedical Ethics in Zurich in the summer of 2010. Our workshop focused on the question; How should bioethics respond to synthetic biology?

Our workshop produced a range of high-quality papers in response to this central question and the subsidiary questions posed on the workshop flyer. Participant’s papers investigated questions such as the definition of synthetic biology; whether the process of defining synthetic biology is a neutral exercise in description or a complex political process underpinned by different values. Questions were also raised about the potential dual use of synthetic biology. This is the idea that synthetic biology may be used for bad purposes (such as the creation of biological weapons) as well as creating potentially beneficial medical applications. As such ethical questions were raised as to whether the acquisition and dissemination of scientific knowledge should be subject to greater control.

It was broadly held by many of the workshop participants that while the ethical questions raised by synthetic biology are rather similar to those raised by other forms of biotechnology, the questions raised by synthetic biology are important and require a more careful, thoughtful and deeper philosophical approach than has sometimes occurred in past responses to biotechnology.

 

To this end, in our next workshop we intend to delve deeper into the conceptual issues that underlie our normative thinking on synthetic biology. We will also consider the ways in which we might draw on other areas of philosophy, for example political philosophy in order to illuminate our thinking on the ethical questions raised by synthetic biology and human health. Finally, we hope that our next workshop we will start to consider the ways in which philosophy can connect and be of benefit to the formulation of public policy.

Bilbao SYBHEL workshops

University of Deusto

 

On the 4-5 November 2010 a workshop entitled “Synthetic biology & human health: the legal and ethical questions of property and patenting” was held in the beautiful town of Bilbao. The high interest of the topic and the high calibre of the speakers led us to use a “closed” format, as the only way of being inundated with requests for invitations. Even so, more than twenty people met to discuss these issues. In some senses, this workshop became something like an oracle. Many of the speakers’ positions have been reflected in the General Advocate of the European Court of Justice’s Opinion about the possibility of patenting human life in general and human embryonic stem cells in particular. It seems that in future altruistic research will take the place of research engaged in for commercial purposes. God save open source!

There are, however, some doubts which still remained in our minds. Will this approach be useful for the development of synthetic biology? Will the Patent Office’s really put it in practice? Will it create a world where Americans could make profit from European’s qualms about moral issues? How will we feed those poor patenting sharks if patenting will not be available in this field?  The weight of these concerns provoked in some of us the sensation that it might be necessary to keep on thinking about how to regulate synthetic biology. Please, do not get nervous! We will consider these questions in our next exciting workshop!

Knowledge Foundation

The Knowledge Foundation organised a workshop entitled “The Ethics of the Clinical Applications of Synthetic Biology”. The workshop was held at the University of Deusto on the 2nd and 3rd of November. It drew an interdisciplinary crowd of participants with backgrounds in philosophy, bioethics, theology and synthetic biology to present papers and discuss the ethical issues arising from the “state of the art” in synthetic bilogy. The workshop participants were asked to consider the following questions;

What are the most important clinical applications of Synbio?

What can we expect from Synbio in medicine in the future?

What are the ethical concerns of health-related Synbio?

The papers presented addressed these questions from different disciplinary perspectives, such as the theological aspects of synthetic biology and medicine, and as they might apply to different contexts, such as public health ethics. The participants widely agreed that continued assessment and discussion of the social and ethical implications of synthetic biology in terms of possible clinical applications is essential. It is important for policy makers and politicians to start considering these issues before any possible applications come to fruition. According to the workshop participants more cooperation between scientists and ethicists and policy makers is also desirable. Participants agreed that education of scientists on ethical challenges should be strengthened and be introduced at an early stage of university education. Ethics should not be confined to ethics evaluation and review, it should be an integral part of scientists thinking when working in laboratories even when no formal ethical or legal monitoring is required.

 

Brussels SYBHEL workshop

Rathenau Institute – Towards a European Policy for the Governance of Ethical and Legal Issues of Synthetic Biology for Human Health (A more comprehensive account of the workshop is available here SYBHEL Rathenau Webreport )

On April 14th and 15th of 2011 a group of some twenty five social and natural scientists, philosophers, European policy makers, regulators, SYBHEL project partners, policy analysts, and patient representatives met in Brussels to discuss the policy and governance implications related to health applications of synthetic biology (Synthetic biology) at the European level.

This workshop was structured around a discussion paper prepared by Conor Douglas and Dirk Stemerding of the Rathenau Instituut (The Hague), and was entitled ‘Towards a European Policy for the Governance of Ethical and Legal Issues of Synthetic Biology for Human Health’. The purpose of this discussion paper was to provide a platform for the invited experts to reflect on the ethical and legal issues raised by Synthetic biology in the context of European health policy making, and to provide some policy action-items that need to be considered in order to address any gaps between (prospective) Synthetic biology applications and tools for their governance.

The variety of workshop participants discussed a series of challenges raised by prospective synthetic biology health applications from their own disciplinary perspective and institutional setting. While the discussion paper outlined the tools for governance that are currently in place (i.e. laws and regulations; research ethics and funding; codes of conduct; and public debate) questions remained throughout the workshop about the extent to which they are sufficient to deal with ethical, legal, and social issues (ELSI) to European health.

For instance, it was unclear how synthetic biology application will be able to influence Europe health given the mixture of intellectual property arrangements including possible patent monopolies by the Venter Group, and the open-source repositories of molecular parts in the form of BioBricks Foundation.

Much discussion was also had at the workshop about the value of public engagements on synthetic biology as a form of governance, and what the outcome of such engagements should be. Are public engagements better suited for the governance of particular kinds of ELSI questions (i.e. about human enhancement or radical life extension) rather than others? If so, do such engagements need to be followed-up by concrete actions for them to operate as effective forms of governance? Questions were also asked about the whether or not it is worthwhile to have further public engagements on synthetic biology.

Going forward the Rathenau Instituut plans to pursue questions concerning policy issues related to the global development of synthetic biology, and exploring how synthetic biology can be steered towards addressing global health problems. Such questions might include the extent to which open-source options might best meet the global development of synthetic biology, or what role ‘garage’ or do-it-yourself (DIY) synthetic biology might play in addressing global health issues or the global development of this field?

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