Consider Bookhling

(((I was trying to embed the videos from the KQED site directly in the post, but apparently copy pasting embed code in HTML panel isn’t good enough for wordpress. I’ve linked to them instead. They are quite good. You should really check them out.)))

Here are two videos on synthetic biology. The first one is a short introduction to synthetic biology produced by the wonderful people at KQED QUEST program, which goes into some level of detail on what synthetic biology is and what we are doing with it at the moment. Certainly worth some of your time if you’re interested in this new exciting field of science.

The first video is the original KQED QUEST video on synthetic biology.

The second video is the extended interview with Drew Endy available off their website… While the field of synthetic biology in the form we now know and love probably began with the efforts of Tom Knight at MIT, Drew Endy is certainly one of the most active and clear thinking proponents of the scientific field of synthetic biology.

Here is the link to the second video, the extended interview with Drew Endy.

If you hadn’t guessed yet, I’m really big on synthetic biology. I think it’s one of the most exciting things happening in the sciences today, not just for biologists but for mathematicians and physicists in that synthetic biology might one day provide a comprehensive toolset for studying the most complex physical system known to humanity so far… That of complex life-like systems.

I also believe that abstraction driven synthetic biology cannot manifest without a reasonably sized community of beta-testers willing and able to use the new parts and devices within original systems of their own creation. Computer languages like python and ruby needed efforts of hundreds of developers working in conjunction with each other for a multiple years to get where they are today. Complete operating system like Linux took longer with even larger base of developers and we still have usability issues. Synthetic biology must deal with systems that are even more complex than most computerized systems, so it’s not unreasonable to think that we’ll be needing an even wider deployment of the technology to the public and active community involvement in order to make it work as engineering capable system.

So I am a little dismayed, along with legions of other people who were initially excited by the promises of synthetic biology in conjunction with diybio community, to find that access to BioBrick parts and iGEM competition is severely limited against any amateur biology group operating outside conventional academic circles.

You see, unlike computer programming, constructing synthetic biology systems require BioBrick parts from the registry of standard biological parts. Right now it is next to impossible for diy-biologist interested in synthetic biology to get his or her hands on the BioBrick components through proper channels. The DIYBio-NYC group alone had quite a few number of people lose interest because of uncertain future aspects of being allowed access to the BioBrick parts and talking to people from around the world on that issue I’m beginning to think that there are a lot more of such cases. So far the major reasoning behind the restricted access seem to be the safety issue, but considering that the regular chassis used to put together BioBrick parts is based on academic strains of E.Coli that are even more harmless than your average skin cell I can’t see much wisdom in restricting access to the parts on basis of safety.

The bottom line is, the state of synthetic biology and BioBricks foundation at the moment is forcing a lot of people, some of them quite talented, who are enthused about contributing to a new emerging field of science to back down in either confusion or disappointment. Considering that the very structure of synthetic biology itself demands some level of public deployment to stress-test and demonstrate the effectiveness and stability of its individual parts and devices (with creation of those individual parts and devices left to the highly trained professionals at up scale laboratories) this is highly unusual state of affair that is not motivated by science behind synthetic biology. I might even go as far as to say it has the distinct aftertaste of political calculations of public relations kind.

The field of synthetic biology will never achieve its true potential unless the BioBricks foundation and iGEM administrators come up with some way for people outside traditional academy settings to participate in real design and construction of synthetic biology systems.

Here’s a little bonus, the QUEST show producer’s notes on ‘Decoding Synthetic Biology.’

Just a quick note on early Sunday morning. 

I’ve been reading up a bit on the topic of quorum sensing, which turned out to be a very interesting phenomenon. I’m not qualified to get into the specifics but it’s basically a cell to cell communications method used by bacteria. The mechanism is based on signal molecules and receptors that activate or deactivate certain sets of genes depending on signal strength. The strength of the signal would be determined by the density of the signal molecules within a given area. It means that bacteria (of all kinds I think) have built-in coordination mechanism for group gene expression.  This is news to me. I always thought bacterial behavior was more or less solitary with some mathematical mechanism behind emergence of bacterial colonies, rather than any specific signal mechanism that works to coordinate their behavior as a group. I guess the deeply ingrained eukaryotes/prokaryotes and multicellular vs. unicellular organisms chart from the middle-high school days left its mark on me. The Bassler lab at Princeton University’s department of molecular biology seem to be the leader in the field of quorum sensor studies, something I should definitely check out later. Here’s a TED talk by the lab’s very own Bonnie Bassler on bacterial communication.

This reminds me of a few iGEM project outlines I read on using BioBrick parts to form some sort of macroscopic structure using bacterial components. They all more or less failed as far as I know, but maybe something like that will be possible if we can build a BioBrick based mechanism for controlling quorum sensing mechanism of the E.Coli chassis… Or maybe there’s one in the registry already? I should remember to check it out. Maybe diybio-nyc can build a cellular automata system based on quorum sensing as a demonstration project later on. The prospect of studying complexity mechanics behind the quorum sensing and coordinated bacterial behavior is intriguing to me as well.

I’m also thinking of proposing a simple artificial cell project to the group. From what I’ve been reading the first steps towards building an artificial cell isn’t that complicated as long as we keep the goals modest. For now the goal would be to have DNA replicate and produce proteins within an artificial vesicle.

Okay, here we are, the fourth meeting of the diybio nyc group. As you can see the meeting was on the April 15th, almost a week ago, so I’m a little late in writing this post. The week had been a little crazy (I’ve been saying this a lot lately), so I really didn’t have the time to get around to it… It didn’t help that I had a bunch of class works that were already overdue and I had to spend the whole of Saturday and Sunday with bunch of UN/Google/open-source people related to the openeverything conference/bar-camp, which I will have to write about soon.

The April 15th meeting was a discussion meeting wit no lab session involved. It was held in a restaurant downtown called Veselka, an Eastern European restaurant serving some good pierogi (never had one before). While the food was good, the atmosphere wasn’t the most ideal to have a complex discussion though. It’s more of a family place, with lot of people coming and going, everyone talking at rather loud volume and etc. It was a refreshing change of pace from sometimes pretentious NYC food world… But I’m not really about to write a review on the restaurant am I?

The situation worsened due to the fact that a reporter from the New York Times Magazine was planning to show up. Some people in the group had experience with journalists (one of them is a published journalist actually), so we were afraid that something we say might be used out of context. There’s a lot of scaremongering out there in regards to the possible dangers of diybio, and it’s something we really have to avoid at all costs. And then the new members showed up. Total of three. All of them came from very unusual and interesting backgrounds but the venue and the circumstances weren’t very ideal for personal introduction between the old and the new members, especially owing to the fact that the ambient noise was to such an extent that we could not hear people from across the table. I would have loved to talk to them a bit more but didn’t really get much of a chance in between trying to hear what other people were talking about and trying to get actual work done in regards to the mission statement, identity and direction of the diybio nyc as a whole. One of them came from biotech background and I’ve been keeping in touch with him for a while now, through IM and twitter. The other person came from art background, working with a type of bio-art club/collective called the Grafting Parlour, which is kind of like the SymbioticA, pursuing the techniques of biotechnology for artistic pursuits. The last person to show up was from computer sciences background with interest in film making, who seemed a little surprised that she’s the only one with computer sciences background in the whole diybio nyc group (quite frankly that surprises me as well, considering that the whole concept of biohacking came along with the advent of computer sciences and biology’s increased dependence on variety of computerized techniques). I’m afraid that some of us (including myself) might have seemed a little distant to the new members of the group. I will have to try to remedy that somehow later on. DIYbio is about the spirit of openness in science and it would contradict the implicit founding spirit of the group to make new members feel out of place. I’m especially looking forward to talking more about the activities and purposes of the bio-art movement. I believe the whole concept of bio-art itself is replete with incredible possibilities that only art can dare to explore, though the group would have to find a compromise between ethical and scientific constraints and the spirit of exploratory arts… Even finding that fine line between arts and sciences sounds intriguing to me, to be honest.

The basic agenda of the meeting was on drafting the mission statement, establishing the main short term and long term objectives of the group, and finding a way to realize those goal within realistic budget and time constraints. Whenever we talk about doing some sort of project one problem gets in our way. Any biological project of even moderate complexity requires a dedicated lab space that’s not located within residential address. We might be able to pull it off within private residential setting like those people trying to build a bio-lab within their closet, but it won’t do for any long term experiments or groups, since there are just too many legal hoops and hurdles we’d need to workaround. And the last thing diybio as a whole needs in this age of terror-related scare-mongering is questionable legality and dubious safety measures. A member of our group experienced in operation of biotech laboratories is strongly pushing for strong safety protocols comparable to those applied to commercial labs, and I agree with her point. It might sound a little bothersome right now but it will go a long way toward the group being a fully pledged biological lab space.

The problem in obtaining a real lab-worthy space in the city is that it’s just too expensive. We would need a way to raise some funds, by ourselves or with cooperation with other educational institutions in the area like one of our members suggested. We can do a lot of those things if we decide to keep things hush hush and work under the table, but again the risks are just too great. In the nightmare scenario what we do wrong might effect the diybio movement as a whole, pushing the public opinion toward opposition. It’s the group’s implicit agreement that we can’t take that kind of risk at this very crucial time. Compared to finding the space, obtaining real lab equipment is a child’s play, and we’ve already made a lot of progress in that area thanks to one of our member’s generous input.

We need to find a path that would work toward to solving the space issue, and at the moment that happens to be working toward obtaining a legal status for the diybio nyc. It’s our collective belief that having an actual legal identity will help us toward raising funds, cooperating with existing lab spaces, and establishing supply relations with bio-companies we would need to contact in order to get perishable experiment resources. The ideal legal status for a group like diybio nyc would be a registered non-profit, whose tax-exempt status would afford the group with some negotiable leverage when it comes to financial negotiation and support. Drafting mission statement and by-laws for the group would be first step in establishing legal and ideological identity of the group.

All this sounds like a lot of financial and legal talks for a group supposedly dedicated to bringing science to the open. Experiments cost money and requires space, so it can’t really be helped for the moment. At least we do have an actual wet-lab session coming up this Tuesday. It’ll be an experiment to introduce GFP plasmid vector into K12 E.Coli chassis (the E.Coli chassis in this case is completely harmless to human beings. You can actually drink it and it’ll pose no threat to you. It’s a special, non-toxic strain of the E.Coli we all know and fear, that’s been used in laboratories for about a century, as well as variety of high school biology classes). It’ll be a first experiment that would actually allow us to observe and experience the process of introducing plasmid into a bacterial chassis with visible results, so saying that I’m excited about the prospect would be an understatement.

There’s been a lot of trials and tribulations for the group, and I’m sure that there will be more to come. But we are going somewhere with this, and it’s really good to see so many people interested in learning more about the techniques and science of biology outside the traditional medium.

I got through another meeting with the diybio nyc peeps. Mostly it was management related talk with what came to be the founding members of the group, in terms of getting legal status and finding space for the group. The biggest problem for the group at the moment seem to be lack of lab-worthy space. Another big problem is finding a suitable project idea for us to go ahead with. Actually, if you ask me the lack of pervading project idea is a bigger problem then the lack of physical space, since lack of project means lack of traction and focus for the group. I would really hate to see the group evaporating due to lack of activity at this stage.

I’m wrecking my brain daily over finding an interesting enough project to proceed with, but so far I’m drawing a blank. The fact that I’m practically ignorant on the deeper nuances of the biological sciences doesn’t really help matters either.

One member of the group had been very generous in providing the group with much equipment and other resources, and the other member is doing much to get to the issue of incorporating the diybio nyc group as a nonprofit. I’m trying to look into the space issue by working with other groups outside of diybio, but I’m not too sure how it will work out… Not a lot of people want to work on unproven projects with unproven people. There is a biotech group within the city that might be able to provide us with labspace and resources but they are about incubating professional businesses which doesn’t sit well with the diybio ethos.

I’m a little embarrassed to admit that sometimes I feel like a third wheel in the group, but I guess everyone feels that way at one time or another when trying to get a meaningful movement going. I will have to remedy it by working harder… I really want to do something significant for the group but I don’t know what I should start with, and I’m getting a feeling that this is a common sentiment shared by many of the ghost members of the group (and yes, there are quite a few ghost members, it’s to be expected I guess).

At the moment all I can do is try to provide more logistical data for the group, like rent, spaces, and possible collaboration with existing hackerspaces to get those things. I guess I can give a bit more info about the S.B. 4.0, there are still whole notebooks of data on that conference. I actually gave then the booklet with abstracts of presentations and posters, I hope it will be of more use to them then it was for me, with their experience with actual wetlab and all…

I am trying to come up with a project idea, though it is more likely that we’ll be going with an idea that more experienced members of the group will come up with. Just juggling through ideas of completed projects isn’t good enough. I need to think about the realistic design and research process that will lead to that finished product, which isn’t easy for someone who still has trouble digging through some of the simpler stuff of molecular biology and pathways. I guess this is time for me to go dig up more igem stuff, and try to make sense of it all in terms of technical execution and practical resource requirements. That is, we won’t be coming up with a model of minimal cell in basement lab anytime soon (as much as I would love to see that happen).

I’m beginning to think about something on the lines of building in light sensitivity into the bacterial chassis (at least I might be able to help out with physics side of things in project like that) but what exactly? What kind of project would I be able to conceive of that incorporates light sensitivity of cells while remaining imaginative and practical within the technical limitations our group face?

E.Coli chassis that follows light? Or avoids light even. Now such idea would be a problem considering that I do not have a very clear idea of the mobility mechanism behind E.Coli (CAN they move? Or will it be a cycle of dying out when within the light rich or deficient environment?).

Considerations like that makes me feel like simply suggesting doing some exercise to make bacteria glow, document the whole process and materials used so that I and other less experienced members of the group can have clearer understanding of the techniques and limitations involved in the process- notably, introduction of foreign plasmids into a native chassis. The plus side of such an approach is that it lays nice groundwork for future experiments for those who aren’t experienced with molecular biology. The negative side would be that such experiment would dig into the resources and time the group doesn’t really have. Possibility of boring more experienced members of the group is also something I need to watch out for. Diybio nyc will not be able to sustain itself without the help of the people experienced in experimental biology.

I just don’t know what to do. Even if I were to suggest the glowing bacteria as a sort of introductory warm-up exercise, we still need to come up with a great project idea at some point.

I’m writing this in the subway on my way home. It’s beginning to sound like the diybio nyc is in some mortal peril now that I read some of the stuff I’ve written. It isn’t. Considering all the odds things are going swimmingly and possibly even better than I first expected. The whole atmosphere of excitement at being able to think about manipulating biology of living systems for academic pursuit is something that makes me feel alive. And I enjoy wrecking my brain over this stuff. It’s only that I’m under constant pressure to do more and get more things done, to make the group really work. It’s because I believe that we have something with potential for some truly wonderful stuff here. And it would be a real shame to let it die out not with a bang but a whimper.

Here’s the link to the talk between Drew Endy and Jim Thomas on various aspects of synthetic biology, sponsored by the Long Now foundation.

The talk is about two hours long, and is available for download on the website. From brief look the talk is more about basic exposition of synthetic biology and possible social and ethical implications, rather than technical execution. I’ll do a bit more detailed post on this once I get around to finish watching it.

I read an interesting article on the peculiar ability of larvae of sea floor species called sand dollars. Apparently they are able to clone themselves into two smaller copies when faced with possible danger, like the presence of fish mucus on the sea floor. Since a number of species of fish eat the larvae of sand dollars, they adapt to the situation by cloning themselves into two when fish mucus is detected in their vicinity. The term cloning, while technically correct, might come across as something of a misnomer here, since the actual mechanism relies on the original splitting into two smaller yet genetically identical versions of the original. Think of starfish and how they are able to regenerate into whole forms when cut into smaller pieces, as each of those pieces slowly grow into a whole starfish. According to the article linked above the sand dollars are biological cousins of starfish so the precise method of the ‘cloning’ itself isn’t as mysterious as it would first appear. After all, most of us have seen or are at least familiar with the variety of plant and animal species that are known for their regenerative capabilities.

What makes this species appeal to me, however, is that external trauma is unnecessary for this macroscopic and relatively complex organism to split into two identical copies of itself. Starfishes and plants need the environment to actively interfere for their regenerative mechanism to activate. However, these sand dollars seem to be able to demonstrate such behavior at will, or at least evolved in such a way that they are able to actively split and clone themselves in presence of certain chemical stimuli in the environment, with no need for physical injury. With the practice and study of synthetic biology becoming increasingly wide spread and accessible, such novel biological behavior might suggest wide variety of future utility of the specific protein/genomic mechanism behind the organism, medical, industrial, and perhaps even architectural. With the study into cloning being such a specialized discipline it is, such macroscopic and controllably ’splitting’ organism will be able to open worlds of opportunities for those who wish to study mechanics and effects of cloning. Being able to observe self-cloning at the scales of bacterium is one thing, observing and possibly controlling them at macroscopic scale is another. With the chemical stimuli in the environment as the primary factor for the organism’s decision to split, it would be a relatively simple matter to control such biological construct as we see fit, provided that we are able to engineer the organism from ground-up.

There are other, perhaps even more far-reaching subjects that might be studied using this organism. The behavioral pattern of cloned organisms in comparison to their original, for example. The precise method at which random variables of the biological evolution was able to give birth to such mechanism of selective self-cloning is very interesting to me as well. Was it really ‘random’, or was there some sort of chemical or environmental preferences that lead to such evolutionary marvel? How about the problem of identity? Can such concept be manifest at some level in rather dense organism like the sand dollars? If so, how would they cope with the moments of their ’split?’ Or are they simple biological machines feeding, expelling, and propagating without apparent ‘will?’ (whatever ‘will’ might be. On this point Lynn Margulis might have suggested that will as an expression of life form might not require complex nervous systems like that in humans) I am anxiously waiting for any follow-up study of the organism.

I’ve been looking around the synthetic biology scene for a while now. Although my academic specialty doesn’t revolve around the field of biology, I try to keep at least an amateur’s perspective upon the advances and techniques of the field. Considering that my passion lies in the study and realization of artificial life I find it important to keep broad view of things irregardless of specialty or the immediate requirements of my own job.

I’ve often noted that the field of synthetic biology had suffered quite a bit of misunderstanding since its inception (which wasn’t that long ago actually), so I thought I might as well do a little write up of what synthetic biology really is.

Synthetic biology is an approach to engineering biology instead of being an academic field of specific goals. Simply put, synthetic biology as a whole is an approach, which may be utilized toward a specific application dictated by the case/individual/group etc.

In order to become a tool in engineering biology its link with conventional genetic engineering is inevitable. The breakdown of the similarities and differences between synthetic biology and genetic engineering is as follows.

Conventional genetic engineering is composed of three primary stages.

1)Recombinant DNA

2)PCR (stands for polymerase chain reaction)

3)Automated sequencing

The step one and two are about writing the DNA of specific purpose, and the step three is about reading the recomposed/component DNA. While these three steps are integrated to the core of the field of synthetic biology, it includes three more stages which differentiates it from pure genetic engineering.

4)Automated construction of DNA

5)Standards

6)Abstraction

The fourth stage, automated construction of DNA refers to the divide between the designers and builders of the DNA. Within the structure of the synthetic biology the designing of a DNA sequence and actually working in forming such DNA sequence (which is an expensive and time-consuming process) is separate from each other, making student-amateur oriented biological machine design possible within currently existing technical/industrial infrastructure. However, simply having a separate industry deal with mechanical parts of the synthetic biology would be meaningless without stage five and six, formation of standards, and abstraction of genetic interface. The last two stages run along the lines of the advance of computer programming scene, where formation of standard (html) and abstraction (most users don’t type in zeroes and ones anymore. We click buttons) brought on an explosion of global userbase and subsequent integration of the computerization into the very fabric of modern human civilization. Synthetic biology as a field encompasses all the six stages I’ve written about so far, each of them an integral part that reinforces another. In a way, synthetic biology is intimately linked with the garage-biology or biohacking movement in that it allows individuals to focus on designing their own novel biological contraptions using freely available and globally present database of biological/genetic abstractions and standards, while leaving the complexities and drudgeries of bioengineering to the mechanism of economy/industry.

I personally consider the field of synthetic biology to be a movement. Nothing as pretentious as some political gather-up, but a real movement like a wave spreading across the surface of the human society, a tell-tale sign of something gigantic beneath the surface. People used to build computers in their garage. Look where we are now. I can’t begin to imagine to full impact of well-executed synthetic biology as movement/industry/economy in the course of the future. Many little children these days are aware of tools like python and java, and some of them even utilize them with surprising efficiency and familiarity. Imagine the same children in the future, not with imaginary numbers but with the stuff of life. A little risky, but it’s certainly the type of world I want to live in.

What I also find to be interesting is the method of thinking behind synthetic biology. I don’t know how to put it succinctly yet, but as I have noted in the previous write up ‘transhumanism and the human network’, there is an underlying method of thinking that is showing up in universal scales, regardless of locale and cultural background. Am I correct in assuming this peculiarly wide-spread method of thinking as a type of zeitgeist? If so, where and how did it originate? And what role does the human network and its emergent properties take in the shape of the world we live in?

Maybe, once the biological hacking is done, the little children will hack the human civilization itself.

For those of you interested in slightly more detailed insight into synthetic biology, I give you two links.

www.openwetware.org

The openwetware website, definitely worth a look.

http://openwetware.org/images/3/3d/SB_Primer_100707.pdf

A simple primer to synthetic biology, covers the basics so it applies to other fields of biology as well.