Team:HZAU-China/Humanities/ethics

1.Motivation

Evolution is a process which has a direction that begins in the coded genes of life itself and looks into the nebulous fog of tomorrow. Evolution is a faithful companion of time itself, which we could not see the future, but only the present and past of. Its direction can be traced back but can hardly be predicted, and it is a direction as old and unfathomable as time itself. Nature dictates the direction of evolution with no emotion; but when this direction intersects with the welfare of humans, however, it is tinged with the human perception of good or evil, right or wrong, is or ought. Especially when it's no longer nature who inflicted this direction upon evolution.

As has been discussed in the preface, artificial evolution is synthetic biology in hindsight. Hindsight here means not intentional when doing but happened after all. What synthetic biologists are doing is not intentional interference in the evolution process, but not being intentional is not enough; as long as it happen, it's our irrevocable responsibility.

Many previous iGEM teams have done impressive work when addressing ethical issues in synthetic biology. Their discussions about many topics gave us much room for contemplation. However, after contemplating upon the ethical concerns about our project, we discovered a relatively simple approach to tackle the ethics problems in synthetic biology, and we would like to share it with everybody. Paradigm might sound a bit pretentious actually, and since we built this model from scratch, it certainly has many imperfections, so, just regard it as a bit of experience sharing! We hope future iGEMers could find it somewhat useful, and innovate more ideas on how to think about an ethic problem in synthetic biology.

And here is our ethics report, enjoy!

Balance is more than a lifestyle. It's a thinking style. We need to think about the complexities when looking at the seemingly simple things, and think in a direct and simple way when tackling the seeming complexity. [1] It's an old philosophy handed down by our Chinese ancestors from very ancient times.

Influenced deeply by this philosophy, this paradigm is very simple and easy to understand.

2. Construction from Scratch: A 3-D Model

Imagine the scope of ethical issues as we perceive in synthetic biology as a patch. A keyword is a dot, the development of this dot is a thread, any kind of relationship between two keywords is a thread, too.

     The intertwining of many threads of topics become such a patch. The X axis means "negative". The Y axis means "positive".

     Wait a moment. Talking about positive and negative in such a rush might seem childish, but sometimes children's simple dichotomy might enlighten us on an easy cut-through to an otherwise complex issue. Topics such as good, evil, right, wrong, is, or ought in relation to synthetic biology can contain a book-worth of contents if you choose to look at them the complex way, which certainly will prove very productive; for in an ethic jigsaw, we ultimately will need all the tiny pieces. Teams such as iGEM Paris 2009 have done impressive works in this, and their previous works have given us great inspiration.

     Then imagine this patch growing to be a 3-D one, with some dots and thread at the surface, some dots and threads down the surface, some threads start from the bottom and extends to the surface. This means, some issues are latent, not perceived, but have influence on the issues on the surface.

     On the surface is the plane that we deal with directly, the plane of immediate benefit and tradeoffs.

     Down this plane would be the plane of judgement and beliefs.

     Down the plane of judgement would be the plane of perceivable emotions, or attitudes.

     At the bottom would be the plane of reasons for these emotions or attitudes, which encompass much irrationality.

     A surface topic can have various root topics that give rise to it, and a root topic could give lead to various surface topics. Or just one topic lead to another.

     And the Z axis means "Awareness".

the scope of ethical issues as we perceive in synthetic biology. Word: dot; line: relationship, extension. Axis: "Positive" and "Negative"

Surface and latent topics and their relationship. Z axis: "Awareness"

Four planes from top down: the plane of immediate benefit and tradeoffs; of judgement and beliefs; of perceivable emotions, or attitudes; irrationality.

     Actually, the plane idea is inspired by the Latent Dirichlet Allocation (LDA), a topic model in natural language processing which is also widely used in bioinformatics to find the themes of a corpus.[2] However, the LDA is all about machine learning and data mining, and like any machine learning, needs a training set and is based entirely on what we already have. This model is exactly the opposite, for what we already have is nothing, and if anything, we are not intending to use it. Because, since synthetic biology is a rising field, the combination of synthetic biology and ethics might give rise to something entirely new. So instead of seeking the best of existing beaten paths, why don't we try to find some new paths even it's not as elegant or mature as the best of beaten paths? Why not try to bring something new into it when it's still early? After all, we are dealing with the unknown, not the known. Trying, succeed or not, is not a shame. So, this model is not a data-mining tool; instead, it is a thinking tool hoping to help us gain some more perspective when addressing an ethical concern.

2. Adding the 4th D, The Dimension of Stages, or Time

Inspired by our project design, the rewirable circuits, we thought deeper on the three modules that compose of our information processing system. Actually, we found that it has an underlying philosophy that has much broader applications other than in electrical and biological circuit designs.

     Any ethical concern, in synthetic biology or not, is fundamentally information, because it can be converted to words, which unfortunately lay the ground for human ideology. Facing a synthetic biology project of concern is like being exposed to some input signals. Thinking about its various implications, origins, solutions, is processing this information. When we get our answer, that's the output. It can be the end of the process if that's what we're looking for, or it can continue to act like an input signal for other processes, in cases where our answer becomes someone else's inspiration.

     Similarly, synthetic biology is about creating things. Creating things is a kind of work, and like any kind of work, it is an interaction between the entire working entity (including the one working and the one being worked on) and its environment, corporeal or spiritual. Interaction involves the processing of information, so it can be divided as different stages. And it can also be divided into the three stages, input, processing, and output. Because these stages exclude each other in one round, such division is able to include the whole process from birth to death.

     The first stage is the input stage, or planning stage, or preparatory stage; besides preparation before a certain synthetic biology project, it also has an extended meaning of the time before the advent of synthetic biology;

     The second stage is the processing stage, or the doing stage; it could be viewed as either the real lab work or the flourish of synthetic biology itself; or its present;

     The third stage is its output stage, or its "after" stage, or assessment stage; both the assessment of a certain product and the assessment of synthetic biology itself are indicated; or its future.

     Any ethical concern, whatever it is, should belong in one of the three stages.

     Questions about worthiness, ones that ask about "whether it should start", or "is it necessary at all" belong to the first stage. To answer these questions, we should look forward and try to evaluate how its performance in the third stage will fare. How it will pay off, what's its potential cost.

     And when it's a question that's about any kind of assessment concerning ending which is hard to predict, such as "what will it end up with", we could look back how this problem has come into being in the 3-D model and try to see the nature of this concern, besides the more direct analysis of the concern itself.

     Questions in the second stage mainly involves the means in which synthetic biology does its work, such as standardization, animal testing, etc.

     The "stage" dimension helps to determine the approximate location of a roughly asked question, and by realizing its place in a larger scope, we can see the surrounding issues more clearly.

     At all times, the 3-D model can apply, especially if we are trying to see the source of a problem.

3. Tracing Back to the Origin

Diversity forms the world of senses, unicity lies at the heart of intuition. "Tao produced one, one produced two, two produced three, three produced everything", says the Taoist sage Lao Tzu.

     This verse could be looked at as a simple paradigm of the development of a discipline. Synthetic biology has passed its initial stage and is somewhere on its way to a world of "everything". When complexity increases with perhaps some exponential rate with each step forward, simplicity becomes more than a style but a necessity. When going forward, perhaps sometimes we should also track backward, and the farthest we can go with rationality is the state of "one", whereas the "Tao" before that is not a thought explainable by scientific language.

     The verse could also be interpreted as a simplified paradigm on the formation of human perceptions. There is ultimately one thing, one idea, or one event that lies at the bottom of a series of issues, and this one thing was the first thing that entered the human psyche and anchored there. The rest, and the later, are but metamorphoses or projections of this one, and we cannot say we truly know ourselves if we do not delve that deep. However, the road to the depth is arduous and tricky; it's like the layers of dream in the movie Inception: the deeper you go, the more irrationality and instability you counter.

     The bottom belongs to the realms of psychology and some more arcane disciplines. "Our psyche speaks in metaphors, in analogies, in images".[3] Such as, the myths. Though, should the word "myths" even stand shoulder to shoulder with the word "science"? Perhaps not; they make an odd couple, they differ too greatly in almost everything from contents to methods. However, with the phra4se "ethics of science", then, maybe. And in some cases, definitely. Because ethics is fundamentally about humans, and since humans are composed of LARGE chunks of irrationality only plus SOME evolved rationality,[4] we think some irrationality SHOULD be employed when it comes to the exploration of human problems. Science is a great feat, but it is not all of the story.

     Then we will use an example to demonstrate how to put this theory into practice. After all, the whole framework didn't reveal itself until we have finished with our project.

4. Testing This Model With Example: When "Rewire" goes Haywire---Ethical Concerns of our Project

Our project has a lot to do with artificial evolution, and artificial evolution has a lot to do with major ethic concerns of synthetic biology. The "shoulds" and "don'ts" about synthetic biology itself mainly ask one question regarding its ending: will the organism that you create end up beneficial, or malignant?

     People trust evolution, because it has been there for millennia. It makes humans what they are today, and it's so slow we almost think we will not see the day when it finally has anything to do with us during the short span of a lifetime. People don't care about its direction, because nature has been so benign to us and we see no understandable reason for it to suddenly go mental and evolve us back to a mollusc or even better, a chimera. Artificial evolution, however, is another story. People seem to not trust it very much, because they are afraid that something will go wrong, despite the best effort of the scientist to control the potential danger. And besides, it is happening too fast for people's understanding to catch up; people can feel like the woman reported in the news who suddenly gave birth to a child on the train and she hadn't realized she had conceived. This is the issue that lies at the heart of conflict in the debate of artificiality vs. naturality: about fear and trust.

     Our project builds a rewirable circuit that can automatically rewire itself into another circuit adapting to its environment. This is an attempt at the imitation of natural evolution, and with human engineering, we were helping the circuit evolve. Like the analogy we used to describe our project: what synthetic biology has been doing is constructing cars from scratch, and what we are trying to do is evolve this car to be a bacterial amphibian vehicle, or fancier, bacteria "transformer". The concept is thrilling enough: transformer? It is a very fitting analogy, and it sounds marvellous if it succeeds.

     HHowever, there is also an unaddressed problem: what would this transformer do once come into being? Being the "Autobots", or the "Decepticons"? [5]And what if the rewire somehow goes haywire, and the whole circuit end up being a stupid mess or worse, a malignant mess?

     To answer these questions would be much more difficult than constructing the thing that raised these questions in the first place. Since our project is more a proof of concepts than its next step, real applications, we don't need to worry about the problem as long as we use the parts we are using already which do not contain nefarious or toxic materials. [6] However, just a proof of concept is just a first step towards more real-world applications. The output signals are not yet real functionalities but fluorescence intensity, so the worst that may happen will be some abnormal flashing of the fluorescence.[7] More technical details are discussed in our safety section, and it can be safe to say that, our rewirable circuit is a safe one AT THIS STAGE.

     However, we wouldn't dare to say so if we change the components, especially the output signals, to ones that may likely to have a more concrete effect on its environment; or when the output signal is changed and it is used as some vital part somewhere and suddenly it's not working due to leaky expression.

     And besides. No matter how much we address the issue of safety, we cannot claim we know it all, for claiming so would be hubristic. The right kind of claim would be that "we claim we know it all to the best of our knowledge", for in this claim we admit the limitation of knowledge and the fallibility of rationality.

     One thing all synthetic biologists are subconsciously doing is getting closer to perfection. In the definition of synthetic biology given by iGEM (see preface: Beyond Artificial Evolution), it contains the word "improve". What is the theoretical end of constant improvement? Of course, it's perfection. Good->better->best. Though it sounds a bit pitiful for those who aspire high but fall low, but perhaps it's better than not aspiring at all. After all what is the ultimate end of the endless bettering and modifying of the already existing organisms? Synthetic biologists, or the bio-engineers, take what they think is better from other organisms and engineer it into the target organism. This is molding the nature according to a certain subconscious standard: perfection, whether it is virtually reached or not.

     Because of this, there is the issue of "playing God" that has already been discussed by many.[8][9]

     When I first learned of this word, I wondered why people make it sound so sacrilegious. We all want to imitate our idols, don’t we? If the Cosmos Will that resembles God is cosplayed by a bunch of scientists, shouldn’t he feel pleased? Because this is proof that he has become the true model of the human beings so much that people want to imitate him! Though then I realized that the synthetic biologists were not imitating God by intention, they are just doing what their logic and inspirations and creative nerves tell them to do.

     But then again, it reminds me of the Old Testament, the story of God and Lucifer, and it is astounding how similar the claim sounds. God created Lucifer, the prime angel, the most perfect being, one which God loves the most. And he gives Lucifer something like freewill, that’s when Lucifer got out of control. He “ wants to be like the most high.”[10] i.e. he wants to rise above the will of God. Qur'an said he led a bunch of other angels and rebelled, and of course, Lucifer is condemned to the Hell. We can see the famous excerpt[10]:

"How you have fallen from heaven, morning star, son of the dawn! You have been cast down to the earth, you who once laid low the nations! You said in your heart, "I will ascend to the heavens; I will raise my throne above the stars of God; I will sit enthroned on the mount of assembly, on the utmost heights of Mount Zaphon. I will ascend above the tops of the clouds; I will make myself like the Most High." But you are brought down to the realm of the dead, to the depths of the pit."

     It just sounds oddly familiar. Change the protagonists in the story into scientists and their carefully engineered or synthesized organisms, wouldn't it also be the story of one of synthetic biology’s biggest nightmares?

     Joseph Campbell speaks in his book The power of Myth of the underestimated importance of myths.[11]According to him, who was influenced by Jungian Psychology[12], humans are born with a psychological construct inherited from their father’s fathers i.e. the collective subconscious[13]. Psyche can perceive the material world with its senses, but can only perceive the ideological world through words. Words, whether scientific or not, their influence has been coursing through our veins for thousands of years. As the meanings of words and stories multiply with the evolvement of human experience in time, their initial impact on human psyche has not been totally diminished. Instead, they have a very basic mode, a simple construct with perhaps not much logic, and have become metaphors in our psyche. Psyche speaks in metaphors, from which our gut-deep emotions are translated into. This has been verified by the psychoanalytic school of thought.[4]

     However, the solution to this nightmare is also present in the same story: Although God lost control of Lucifer, he designed an environment specifically to contain him, the Hell. To prevent the synthesized life from escaping control, kill switches and other kinds of repression methods are usually installed into the organism. So the organism, if its existence exceeds the intention of its master, will be disposed of quite effectively, like bringing a internalized Hell with it wherever it goes.

     However, why some people would always have an instinctual worry that something as an artificial engineered organism might end up malignant or out of control despite the initial goodwill with which scientists start their project? The safety tests are proved by independent scientists and organizations, and in some countries such as the United Kingdom, public consultation is held [iGEM Edinburgh, 2009], so why is that the skeptics always would be skeptic, despite evidence and persuasion from sources that our logic and reason would agree? Do they not listen to their reason? Are they really that scientifically illiterate as claimed by some scientific researchers? Some skeptics are also accomplished persons in other areas and their sanity and rationality are proved normal if not better than those who do not doubt.

     It’s undeniable that the most stubborn reactions of the skeptics are doubt and fear, which are usually read as a sign of weakness either of intelligence or of character and therefore despised and dismissed. Explanations of it are usually limited to the simple words of doubt or fear and just stopped there. But fear and doubt also have their origins, and since it’s deemed irrational, then perhaps its source is irrational too. If our mind is largely composed of irrationality, then is it really necessary to speak of it as a plague instead of thinking of ways to understand it?

5. How We Incorporated the Above Framework into the Analysis

     We first locate the stage in which our question belongs to. It speaks of the output stage, and is an assessment in nature. So we trace back to possible origins of such assessment in the 3-D model.

     At the surface level, we reduced the problem to be a profit-based question that have two keywords: beneficial and malignant. Then we went down to the judgment level and classified them as good and evil. We don't need to plunge into long philosophical debates about the concept of good and evil, we only need to go one level deeper to find the emotions triggered by these concepts, in this case we only care about evil, because what's good will be good, and don't need exceptional addressing; so the key words in this level are fear and anger. The next step is identifying the origin of such emotion or attitude, and possible explanations are usually found in disciplines that study human irrationalities such as some schools of thought in psychology, literature, philosophy, anthropology, sociology, archeology, mythology, religion, theology, art, etc. [15]

     A framework cannot substitute thinking, it is not universal and certainly it has imperfections. But thinking like this makes thinking a fun thing to do, rather than arduous.

6. Strength and Weaknesses

     First, on the plus side, this model doesn't need math or programming skills to understand; but on the down side, not having mathematical elements to help shape it up, the form is a bit crude. One would argue, for improvement on some exactitude, the axis can be given value to. However, how can "negativeness" or "positiveness" or "awareness" be measured? After thinking over the possibility of an inch-by-inch search to actually give some value to a word, we decided to abandon the deed, because it just seemed to be a subjective process with the facade of objectiveness. Our model could be said to be an experiment done by us to understand irrationality with irrationality, though borrowed some useful form from the world of rationality.

     Second, it's not a software where you can enter your question and it will give you the answer like a program, it just provides a direction for friendly reference if you are finding yourself at a loss. We don't believe any tool can substitute your thinking originality, but still, we wish to make this process a little bit easier, so more ethical issues could be accessed by more teams, and our understanding towards synthetic biology will expand more quickly. That's why we have produced this framework; it aims at helping future iGEMers more easily find an anchor when needing to address ethical concerns of their project, hopefully.

     Third, the model is aimed at origin digging but weaker at solution finding or future predicting; it's more aimed at deepening the understanding of a topic than actually providing a suggestion when it comes to ethical problems in synthetic biology. But it is the same with evolution and time: we can see where they come from by tracing back and recover their footsteps, but we can hardly see where they are going, so there is only one universal advice offered: better safe than sorry.

     Have fun!

Reference

[1]"Governing a country is like cooking a small fish", Confucius, http://characters.cultural-china.com/102hz203.html

[2]Blei D M, Ng A Y, Jordan M I. Latent dirichlet allocation[J]. the Journal of machine Learning research, 2003, 3: 993-1022.

[3]Duit R. On the role of analogies and metaphors in learning science[J]. Science education, 1991, 75(6): 649-672.

[4]Cohen L J. Can human irrationality be experimentally demonstrated?[J]. Behavioral and Brain Sciences, 1981, 4(03): 317-331.

[5]List of The Transformers characters. Wikipedia, the free encyclopedia. http://en.wikipedia.org/wiki/List_of_The_Transformers_characters

[6]Team iGEM HZAU-China. Labnotes. https://2014.igem.org/Team:HZAU-China/Labnotes

[7]Team iGEM HZAU-China. Safety. https://2014.igem.org/Team:HZAU-China/Safety

[8]Dabrock P. Playing God? Synthetic biology as a theological and ethical challenge[J]. Systems and synthetic biology, 2009, 3(1-4): 47-54.

[9]Dabrock P. Playing God? Synthetic biology as a theological and ethical challenge[J]. Systems and synthetic biology, 2009, 3(1-4): 47-54.

[10]Eissfeldt O. The Old Testament[M]. Blackwell, 1965.

[11]Campbell J, Moyers B. The power of myth[M]. Random House LLC, 2011.

[12]Ellwood R. The politics of myth: a study of CG Jung, Mircea Eliade, and Joseph Campbell[M]. SUNY Press, 1999.

[13]Jung C G. The archetypes and the collective unconscious[M]. Princeton University Press, 1981.

[14]iGEM Edinburgh, 2009. https://2009.igem.org/Team:Edinburgh/ethics%28legislationissues%29

[15]Dodds E R. The Greeks and the irrational[M]. Univ of California Press, 1957.