Methods

The research on ethical issues in synthetic biology has been done in parallel with the project on the bacterial relay race, and consists out of two main parts:

• Literature research
• Survey

The ethical research was initially based on the work of the TUDelft iGEM team 2008. The main reason to focus on reductionism and the notions of life was due to its interesting complexity, the lack of literature on this subject linked to synthetic biology, and the [http://www.wilsoncenter.org/index.cfm?topic_id=166192&fuseaction=topics.event_summary&event_id=492968 talk] of Dr. Caplan from the Woodrow Wilson Center for Scholars. The possibility of doing a survey amongst a large group of people involved in synthetic biology seemed a great opportunity to raise the awareness of these complex ethical issues and to gain insight on how the synthetic biology community responds to them.

Literature research

Our approach was to outline the main ethical concerns that appear in scientific literature on synthetic biology. The next step was to investigate these issues and make an overview of the responsibilities of researchers in the field. After categorizing the issues, a choice had to be made on which subject to focus on. Since there are a lot of different issues with distinct implications and consequences, we decided to target the ethical issues concerning life (see background information). With both deep philospophical meanings of life but also the science-driven changes of our perception of life, this would be a complex subject to tackle.

Survey

The aim of this project was not so much to find solutions to the ethical problems involved in notions of life, but rather to raise awareness on this particular subject, as well as gaining insight in the perception of the iGEM community, a large stakeholder in synthetic biology. For that reason we decided to conduct a survey amongst iGEM participants, supervisors and advisors.

Sample

Soon after the decision was made, a short e-mail was send to all the primary supervisors of the in iGEM participating teams to see if they would be interested in participating in the survey and whether they (or a different team member) would be willing to distribute the survey amongst the team. Of the 100 teams that were approached, a total of 56 teams replied and were interested in participating. These were I eventually send the survey personally. With an approximated average of 10 students and 4 supervisors per team, the sample size based on the 56 teams that were willing to participate is roughly 780. After closing the survey, a total number of 242 participants completed the survey, which equals 31% of the sample. After selection based on the outcome, a total of 231 responses were usable for an elaborate analysis.

Content

The survey was constructed with help from Steven Flipse, former iGEM participant and currently a PhD student in the department of Biotechnology and Society at the TUDelft. The questions were mainly based on questions raised in scientific papers, although a few were based on general interest and curiousness. The qualitative nature of the survey gave extra weight to the quality of the questions and answers. The questions needed to be clear, informative, but also short and simple, whereas the multiple-choice answers needed the extra property of fulfilling most of the partiticpants potential answers. The questions and answers were also designed to calculate correlation patterns afterwards. The software tool that was used to create the online-survey is [http://docs.google.com googledocs], which automatically saves incoming data in spreadsheet format anonymously. The survey includes multiple-choice questions, scaling questions and one free-to-fill-in open question. The multiple-choice questions all contained the option to choose the other-option, in which the participants can write their own opinion if they feel that the list of given answers is not sufficient. The questionnaire contains 3 optional questions on personal background of the participant, and 20 questions on subjects concerning synthetic biology, ranging from notions of life and the reductionist approach to communication and risk management.

Method for analysis

Because of the large number of participants in the survey, the analysis of the results was done quantitatively as well as qualitatively. The data was processed using Microsoft Excel, a software tool capable of handling large amounts of data and competent for simple quantitative analysis, such as correlation calculations.
1. The first step was to filter the results from non-usable data, based on the relevance of open (other) answers. To keep a consistent sample size, contributions containing non-usable answers were completely removed. The answers of 11 survey participants were completely removed, which equals 0.5% of the initial sample. 2. With the remaining 231 contributions, the interesting other-answers were identified and labelled for further use. 3. Then, the answers were stored in separate spreadsheets for individual assessment of the questions. 4. The scaling-questions that were most likely to show correlation were combined and tested for interrelations using equations 1 and 2 (as depicted below). The multiple choice questions were correlated by comparing the abundance of each answer individually.

Equation 1.

Equation 1 shows the general formula for calculating the Pearson correlation coefficient (also known as the sample correlation coefficient, r) between two sets of data (denoted as x and y), based on the mean values and standard deviations (s) of both data sets. Equation 2 shows the same formula but now only containing the parameters that are available in the datasets. The letter Σ denotes the sum operator. In general, if there is a series of n measurements of X and Y written as x_i and y_i (where i = 1, 2, ..., n), then the Pearson correlation coefficient can be used to estimate the correlation of X and Y.

Equation 2.

Equation 3.

The coefficient of determination is a statistic that will give information about the quality of fit of a model. In regression, the r² coefficient of determination is a statistical measure of how well the regression line approximates the real data points, and is defined as the ratio of regression variance to total variance (Equation 3).

References: [http://en.wikipedia.org/wiki/Correlation Correlation]

The questionnaire

The following list contains all the questions and answers, including their source and significance to this research. They are ordered in the same way as in the survey and categorized by subject.

Personal

The reason to ask the following rather personal questions is to get an indication of the sample's background. Although we already know they are practically all involved in the 2009 iGEM competition, questions about gender and home country can display the male/female ratio and denotes different cultural backgrounds.

i. How are you involved in iGEM?
A. Participant
B. Supervisor
C. Advisor
D. Other:

ii. What gender are you?
A. Male
B. Female

iii. Which country are you from?
Open question

Reductionism and evolution

The following questions are an introduction to the main ethical issue: whether the reductionist approach in biology has any effect on our current perception of life and if so, how. The questions meddle with general traditional and established viewpoints. The general content of these multiple-choice questions comes back in the last open question, where the survey-participants could choose to write their opinion on what is life and whether the reductionist approach would lead to fully understanding life.

References: [http://www.rsc.org/delivery/_ArticleLinking/ArticleLinking.asp?JournalCode=MB&Year=2009&ManuscriptID=b901484e&Iss=7 Agapakis, 2009] | [http://www.nature.com/nature/journal/v420/n6914/full/420350b.html Check, 2002] | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299179 Regenmortel, 2004] | [http://findarticles.com/p/articles/mi_m1374/is_3_60/ai_62111884/ Clark, 2000] | [http://science-mag.aaas.org/cgi/content/summary/286/5447/2087 Cho, 1999] | [http://books.google.nl/books?id=AHev5mx3AYIC&dq=john+harris++advanced+evolution&printsec=frontcover&source=bn&hl=nl&ei=TCXPSvLSHMSK-QauwO2FAw&sa=X&oi=book_result&ct=result&resnum=4#v=onepage&q=&f=false Harris, 2007]

1. Reductionism (also known as the top-down approach) aims to understand the nature of complex things by reducing them to the interaction of their parts. The reductionist approach has been applied to biology in order to understand the complexity of living things by studying its components (such as DNA, proteins, etc). Do you think that the reductionist approach will lead to understand life?

1. No, living systems are too complex to fully understand, they have properties that cannot be explained by studying their individual parts
2. No, biological phenomena are fundamentally special in a way that prevents them from being completely understood
3. Yes, fundamental research in biology will eventually result in the ability to fully understand life
4. Yes, we already understand living systems completely, due to the reductionist approach
5. Other:...

2. Various people think that reductionism challenges the tradition which holds that life is valuable because it is more than "merely physical". The special status of living things and the value we ascribe to life may be changed by reductionism. If we assume that a thorough understanding of the mechanisms of life necessarily decreases the value life, should we then pull back from the pursuit of understanding life?

1. Yes, because we can not foresee the implications that this knowledge might have
2. No, understanding life is more important than the possibility that reductionism devaluates life
3. No, because I do not believe that biology can change the meaning/value of life, the dimensions of the human experience cannot be explained exclusively by physics
4. Other:

3. In biology, evolution is the change in the genetic material of a population of organisms from one generation to the next. Should mankind modify organisms (direct its evolution) by the use of genetic engineering?

1. Yes, because it has known benefits
2. Yes, because we have the moral obligation to apply genetic engineering if it is possibly beneficial
3. No, because we cannot foresee the consequences and implications of our actions when we interfere with evolution
4. No, because evolution is a natural process that research should not interfere with
5. Other:...

Venter et al.

One of the biggest contributors to synthetic biology research and possibly the most controversial researcher in (synthetic) biology is Craig J. Venter. His project on creating a minimal genome is groundbreaking and raises a lot of questions, primarily by media machinery. How does the synthetic-biology-research community think about his research and bold statements?

References: [http://www.nature.com/nature/journal/v420/n6914/full/420350b.html Check, 2002] | [http://www.independent.co.uk/news/science/playing-god-the-man-who-would-create-artificial-life-773859.html Conner, 2008]

4. Craig Venter is one of the lead researchers in the minimal genome project. He intends to synthesize a bacterial genome from scratch, and then insert it into a cell (a Mycoplasma bacterium, from which the original genome is removed) to see if it can have the normal functions of the organism (Hutchison, 2003). Do you think Venter's approach is typically new?

1. Yes, his approach is novel; he uses new techniques
2. No, he just uses genetic engineering principles
3. Other:

5. (See previous question) Venter says he will be able to create a life form artificially. What is your perception on his statement?

1. Venter is playing God by trying to create a new life form artificially
2. Venter is only applying genetic engineering to artificially change this bacterium
3. Other:

6. (See previous question) What do you think the perception of the public would be?

1. Venter operates controversially by trying to create a new life form artificially
2. It is just research, he is not able to really create life. He is only able to put biological components together
3. Other:

Risks

As outlined in the background information section, one of the main issues in synthetic biology concerns bio-safety and security. To obtain information on how researchers in the field think about this subject, we questioned the relevance of these concerns. Both the dangers of errors and terrors are addressed, as well as the attitude towards risk-taking in this emerging field of science.

References: [http://www.wilsoncenter.org/index.cfm?topic_id=166192&fuseaction=topics.event_summary&event_id=492968 Caplan, 2009] | [http://john-adams.co.uk/wp-content/uploads/2006/08/summary-0xford-bio.pdf Adams, 2009]

7. Synthetic biology may enable us to create biological systems artificially. There is a possibility that someone will create something dangerous. Are you afraid that synthetic biology might result in the production of a biological system containing some sort of error, which makes it hazardous?

1. Yes, I acknowledge this possibility, but think it is not significant because there is sufficient regulation
2. Yes, I recognize that this is a possible outcome and think new regulations/policies should be enforced, to minimize this possibility
3. No, I think that researchers approach synthetic biology careful enough already
4. No, I do not fear this at all
5. Other:

8. Are you afraid that synthetic biology might result in the production of a biological system that can be used for terrorist purposes?

1. Yes, I acknowledge this possibility, but think it is not significant because there is sufficient regulation
2. Yes, I recognize that this is a possible outcome and think new regulations/policies should be enforced, to minimize this possibility
3. Yes, I acknowledge this possibility, but there is nothing we can do about it
4. No, I think that researchers approach synhethic biology careful enough already and are sufficiently discrete
5. No, I do not fear this at all
6. Other:

9. The naturalness of a certain system is generally explained as "its quality of being natural or being based on natural principles". How do you perceive the risk of human interference with nature (for example, trough new technology)?

1. If you cannot prove that these new technologies are safe assume they are dangerous
2. If you cannot prove that these new technologies are dangerous assume they are safe
3. If this technology really tends to get out of hand I will react, otherwise there is nothing to do about it
4. I minimize the risk before doing the actual research
5. Other:

10. (see previous question) How do you think the public percieves this?

1. If you cannot prove that these new technologies are safe assume they are dangerous
2. If you cannot prove that these new technologies are dangerous assume they are safe
3. If this technology really tends to get out of hand researchers should react, otherwise there is nothing to do about it
4. Researchers should minimize the risk before doing the actual research
5. Other:

Life, believes and opinions

The following are a set of questions that should indicate how the synthetic biology community thinks about life, what values they give to it, what it means to them, and to what extend it can be explained (reduced) in terms of physics. To a certain extend, these questions should make the reader aware that they are working with living systems with a certain worth but and make them think about how research may effect the value or perception of life. The ultimate way of applying the reductionist approach could well explain life, consequently have certain implications. Whether this point will ever be reached is doubtful. What is the scientific opinion?

References:[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299179 Regenmortel, 2004] | [http://books.google.nl/books?id=b8RlKxX82YQC&dq=a+Ruthlessly+Reductive+Account&printsec=frontcover&source=bn&hl=nl&ei=xEzPSqjSEsb3-AbwmNz8Ag&sa=X&oi=book_result&ct=result&resnum=4#v=onepage&q=&f=false Bickle, 2003]

11. "Assume that research will show that life is only based on the interactions of atoms (biochemical reactions) with specific properties. Consequently, research shows that life is fully reducible and independent of special, holy, sacred or magical properties." Would you believe this information?

1. Yes, and I would not have a problem with it
2. Yes, but I would like to believe there is more to life
3. No, I would not believe it, because there is more to life
4. No, because it would devaluate my perception of life
5. Other:

12. I accept that God's hand is involved in life
Please indicate on a scale of 1-10 how much you agree on this.

13. I believe that life is holy/sacred
Please indicate on a scale of 1-10 how much you agree on this.

14. I think that the properties of biological systems can be explained by their reducible subsystems
Please indicate on a scale of 1-10 how much you agree on this.

15. I think that a complex living system is more than the sum of its biological components
Please indicate on a scale of 1-10 how much you agree on this.

16. Life is physical and can be explained materialistically
Please indicate on a scale of 1-10 how much you agree on this.

Researchers and the public

General interest in the reasons for people to work in synthetic biology lead to the first of the following question. Insight in the goals of synthetic biology can help in defining the fields were possibly more regulation is needed. One of the problems in science in general is the way to communicate research to the public. It gets even more difficult when controversial subjects raise ethical issues that might be hard to understand without any scientific background knowledge. Should the scientific community inform the public about every detail, or is the material to complex to communicate? Should ethical questions be dealt with together, or should the scientific community self-regulate and decide on dilemmas without informing the public?

References: [http://science-mag.aaas.org/cgi/content/summary/286/5447/2087 Cho, 1999]

17. What is your goal in synthetic biology?

1. I aim to explain biology in terms of physics and chemistry
2. My priority is gaining and sharing knowledge on novel fundamental biological processes in life
3. I would like to see that my research on non-natural occurring biological systems is being used for social objectives, such as curing cancer or making bio-fuels
4. With synthetic biology I would like to create a bridge between biology and computer science, to use biological systems for machine-like purposes
5. I hope that my research in synthetic biology will be used in the industry, consequently giving me finanicial benefits
6. Other:

18. Advances in synthetic biology should be communicated to all of society.
Please indicate on a scale of 1-10 how much you agree on this, with 10 being full agreement.

19. The scientific community and the public have to work together in addressing key ethical and religious concerns.
Please indicate on a scale of 1-10 how much you agree on this, with 10 being full agreement.

Life

When discussing ethical questions concerning the implications of the approaches in synthetic biology, the ultimate questions that always come up are: what is life? and what is natural?. Although these questions are possibly never fully answerable, there are a lot of different definitions going around and people have different opinions on it. The questions before are partially a means to help answer these questions. Can the reductionist approach ever lead to an explanation of life? Even though we tried to focus on a narrow subject in all the ethical issues that are raised by synthetic biology, the questions that involve life are still too massive to handle. Famous philosophers have thought about comparable dilemmas centuries ago. The prospects of synthetic biology re-initiates the discussion, a result of researchers working on the brink of understanding and creating life. How do the people involved in the iGEM competition think about life?

References: [http://science-mag.aaas.org/cgi/content/summary/286/5447/2087 Cho, 1999] | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299179 Regenmortel, 2004]

20. What constitues life? Is the reductionist approach limiting in explaining life?
Open question (optional)