From 2007.igem.org

From Orientation to Now

Introduction

Currently, synthetic biology is a maturing discapline that combines science and engineering in order to design and build novel biological functions and systems. What makes synthetic biology distinctive from other scientific discaplines is being able to design and construct new and unique biological parts, devices, and systems. It is envisioned that synthetic biology will help researchers better understand the natural world and will hopefully provide sociably valuable advances to the world. Researchers are trying to solve real world problems through the technology of synthetic biology.

What makes UC Berkeley’s team unique is they recognize that there is a connection between the technical work that he or she does everyday in the lab to society. For the products of their hard work will eventually affect everyone outside of the lab. Than is why the team has an anthropologist on the team, as a human practices member. Human practices examines synthetic biology by looking at the reciprocal emphasis on ways that economic, political, and cultural forces may condition the development of synthetic biology. But more importantly human practice observes the ways that synthetic biology might significantly inform human security, health, and welfare through the new objects that it brings into the world.

My task, as a human practices investigator and as an anthropologist is to work in a synthetic biology lab side-by-side with the rest of my iGEM teammates under the concept that Synthetic Biology is a new and emerging field of science. If it is true that synthetic biology is an emergent field, then it can be argued that there are no experts of Synthetic Biology as such then there are problems that cannot be predicted nor solved through existing expertise. What this means is that because synthetic biology is new that there are incalculable event that may occur, which could not have been foreseen. By definition all scientific research is characterized by a measure of under-determination with regard to whether its experiments will work and what it will discover. My job is to learn of these “problems” or incalculable events as they arise in the lab. The problem will then be brought to the attention of experts whom might be able to find new models to help lower the risk that the problem might cause to Synthetic Biology and the rest of the world.

As I continued to research, observe, and interact with my teammates, I became aware of what I was going to focus my topic of inquiry on.

Bacground to inquiry

SynBERC is an organization that houses five Universities that practice Synthetic Biology: Berkeley Harvard, MIT, Prairie View, and UCSF. The National Science Foundation mainly funds this organization under the agreement to make new venues and research strategies that could be able to produce resourceful solutions for real world problems. One way of doing this collaborative research was to have an open source registry of basic biological parts. All iGEM participants also use this registry. This registry that was created by Randy Retberg, a member of SynBERC and will play an important role to my inquiry of Intellectual Property.

Registry

This registry serves a purpose as a new way for scientific researchers to pass information around to each other quickly and efficiently. It is also the goal that this registry will hold standardized and well characterized biological parts. Many scholars have seen the registry as being a new tool that could change the way in which science is conducted. One benefit of the registry is that researchers would be able to skip the administrative work that is involved with knowledge sharing between university labs. A major concern in regards to Intellectual Property is that this registry is open to the public, making patenting rather difficult. When putting the new part into the registry the idea is that he or she will put in the part’s genetic sequence and then characterize the part in a manner that can help other researchers who might wish to use that same part and will be able to understand how the part works under certain conditions. Since the registry is still rather new there are bugs that need to be worked out, but it is on its way to being a very useful tool for the scientific community.

How I went from May to Focusing on my Inquiry

I first began my fieldwork by training with my teammates. The first part of our training started with learning about what Bacto Blood is and how it would be made. Then each teammember was told how he or she would be contributing to the project.

The following day we were taught how to pipette, run gels, digest, ligate, transform, and PCR. The final product of our first day of training became our first colony. Though it only had four colonies my team and I were able to see what we were capable of doing and only with time would they be able to what they would be capable to do with time.

My second week into my fieldwork, a graduate student of Paul Rabinow began to train me in Human Practices. I read two books, one written by Latour and the second book by Nowtony these two books would teach me the basic philosophy of mode 1 and mode 2 observations. Mode 1 are known answers to known questions and mode 2 is the idea that there are questions with unknown answers. These basic concepts would help me start my observations in the lab.

During my time in the lab I got to know my teammates and watch them adjust to the lab. My favorite part about my time working with my team was watching them grow in confidence and skill. As time passed in the lab I noticed a change where many of my teammates were no longer asking technical questions like if he or she had ran a gel correclty, but now they asked questions that pertained to what they were looking at. In fact, they began to ask less questions and moved around the lab like it was second nature. They were no longer looking for pipetts or PCR tubes, they were quietly and dillegently running gels or making mini preps and complaining how time consuming and annoying mini preps had become. Where when in their first weeks, getting a mini prep to work was a great accomplishment, it was now considered busy time consuming work. I spent a lot of my time the first week in the lab watching everything that my teammates did. Once they had become acclimated to their work I spent a lot of my time in the lab reading and talking to my teammates when they PCRed or transformed.

It was during two conversations that I was able to learn about what I was going to focus my inquiry on. One conversation was with one of my teammates whom had written the Bacto-blood proposal. The other conversation was with other researchers who were not on the team, but discussed how many labs synthesize parts to get around administrative work since it takes a lot of time out of the labs research.

These two conversations would be what would cause me to focus my interest on Intellectual Property and how Bacto Blood would be able to become patentable.

Inquiry

How in a patent landscape and the need to patent is juxtaposed against an emerging field which wants to work in an open source forum? Can my team’s Bacto Blood fit into a world of intellectual property when its parts are registered in a public registry? If Bacto Blood can fit into the patent model, what then becomes patentable—the part(s) or the application of the part (s)? What starts the timeline for patenting Bacto Blood: when the part is put on the registry or when the applications of the part is made public?

Process

Since my work is conducted under the truth claim that there are no experts of Synthetic Biology because is it an emergent field of science, I am to work with my teammates to learn of new problems that would otherwise be unpredictable. Then I can direct these problems to experts that might be able to make a model in which to mitigate the problem. The experts that I first directed my Intellectual Property inquiry to were two Boalt Law Students who were studying Intellectual Property. As a human practices member I too am to collaborate with others to find unknown answers to questions.

I was first introduced to a Boalt Law Student who was to work with me on my inquiry and teach me the different Intellectual Property laws and options. Unfortunately, there was a family emergency and she was no longer able to work with me. A month later I was introduced to a new Boalt student who had recently received her PhD in Molecular Biology at MIT and is now working to get her degree in law so that she my become a patent lawyer in the Biology industry. Both law students were able to give me one answer as to how Bacto Blood would be able to fit in intellectual property.

The Technical Answer

Novelty and Non Obvious

There are existing patents relating to different types of oxygen therapeutics. These patents include PFC compunds’ as oxygen therapeutics and methods to maximize the production yields of hemoglobin using Escherichia coli expression systems. The application of Bacto Blood’s E. coli must be both novel and non-obvious over the prior art. The novelty and nonobviousness of Bacto Blood relative to other oxygen therapeutics lies in the expression of hemoglobin in an E. coli system that is genetically engineered to be safe in vivo human therapy. Bacto Blood is novel because the team created biological parts that can be used to suppress the normal replication cycle of E. coli so that it does not cause sepsis in the human body. The “aseptic” bacteria were then combined with other biological parts created by different team members. The parts and the different devices generated by the combinations of parts such as, (an oxygen carrier, a controller, a self-destruct mechanism, and a freeze drying component) were constructed and inserted

Patent application timeline

The time line for the patent application would not start when the part is listed in the registry. Instead, would begin when the application of the part has been publicly disclosed. Patentability lies in the combinations of parts that together provide a function. Parts alone may not be patentable where they are not novel or where the innovation is to small to be considered non-obvious.

Moving the Patent Forward

Patentability of Bacto Blood may depend on what aspects of the invention are claimed in a patent application. The aspects of the invention could include:

1. Methods of using Bacto Blood

2. Composition of Bacto Blood

     1.	The system as a whole

     2.	Parts of the system or devices with in the E. coli chassis

3. Methods of making Bacto Blood

Each aspect be included as a claim or a set of claims in the application. Thus each aspect may be separately patentable.

Tension between open source and patents

In general, patenting is important because it rewards the inventor of a new product for his or hers hard work and time that went into creating something new. It works the same way in the relm of research and delopment. Science is slow and it can take many years to discover something new. Patents give researchers the incentive to keep working those long hour so that he or she may one day discover an answer that could better the world. Incentive is not the only reason why patenting is important, for it also gives the researcher a sense of security that his or hers product is protected. Patents provides a strategy that protects an invention without secrecy. In other words the patent protects the inventor from competitoin. It grants the patent holder exclusive rights to the invention, preventing others from making, using, or selling it for a limited amount of time. Once an invention is discovered and pateted if others wish to make, use, or sell it he or she must ask and pay the patent holder for a licsence to use that product.

But how can patents still retaine its importance when synthetic biology wants an open sourced registry of standardized biological parts? This is where the tension of open source and patenting come to play. In the university setting, the cost of postinvention production exceeds the preinvention research outlays. If the invention is ever going to be able to become a product that everyone can use then the public sector is going to need investment from the private sector. Private industry will not fund such research unless there is guaranteed protect from competition.

There in lies the problem. The registry of standardized biological parts is open sourced, meaning anyone can look up sequencing information of a desired part, have it made, and then use it. This registry was created to benefit synthetic biologist. With an open sourced regisrt researchers in the synthetic biology can pass on knowledge to each other and help this science flourish quicker. Unfortunatly, having and maintaining an open source registry is a liability to those in the private sector who invest large sums of money into such university research projects.

Tensions are now rising in the synthetic biology relm.There are idealists who want to see synthetic biology change the way in which science is practice, one way of doing this is being transparent and passing on knowledge by having this regisrty. Others are concerned that putting his or her parts onto the registry will not only make their research vulnerable to others who could possibly “steal” their valued work but also could loose their private funding. As of now, there is a battle to keep the registry alive, for not all synthetic biologist register their parts. Even though all synthetic biologist see the strong and potential benefit to having and maintaining the registry, but because it is open sourced it makes any invention that has its parts on the regisrty unpatenable. Even UC Berkeley’s Bacto Blood has become unpatentable because of the fact that all of its parts are on the registry.

Currently, there are discussions taking place as to how the registry can be fixed in a manner where it may benefit all who are involved with these synthetic biology projects. The main problem that needs to be solved is how can open source and patents work together… if that is even possible.

Weber talk/New IP Model

In “Science as a Vocation”, Max Weber claims that to be a good scientist one must be specialized, as well as willing to understand that his or her work will eventually become obsolete due to science’s nature to always improve on itself. Weber also proclaims that all studies are a form of science… including the social science. (Why else would it be called social science?) If we consider all types of study to be a form of science I would then like to pose these two questions—Why hasn’t the social sciences been evolving to keep up with Science? When was the last time Intellectual Property was improved on to work with the ever-evolving Science?— It is in my opinion that it is time for the social sciences evolve, to “catch-up” with the rest of science. Lawyers should not be trying to work the “wording” of science to “fit” in to an archaic patent model, rather I think the time has come that a new Intellectual Property model be made that would better fit science. With this new model it would be hoped that it could better benefit sciences like Synthetic Biology, so that these researchers may still have an incentive to make new parts and put them onto the registry. A new model of Intellectual Property could help Synthetic Biology move forward rather than slow it down with administrative paper work between labs and licenses.

Having an open source registry could lead to be the most important thing that synthetic biology creates. For it could change the way in which science is practiced. Having a new intellectual property model could help the flourishing of new modes of thinking within science, which ultemately might help science move faster in finding answers to real world problems.

Further Questions

1. Can we provide distinguishable definition of a part so that we can distinguish between a device that is patentable and a part is not patentable?

     a.	Shows critical limitations of such expertise like patent lawyers. 

2. Given the challenge of integrating an open source approach with current IP practices in Biotechnology, how might synthetic biology be a driver for inventing new modes industrial practices and partnerships?

3. How does one design research protocols that draw on both biological sciences and human practices?

References

www.synberc.org

Rabinow, Paul and Gaymon Bennet. 2007. “Human Practices: Interfacing 3 Modes of Collaboration”. This paper has yet to be published. Have been given direct permission by Paul and Gaymon to use.

Weber, Max. 1946 “Science as a Vocation”. In Essays in Sociology, H. H Gerth and C. Wright Mills (eds.), pp. 128-156. Oxford University Press, NY.

Summer Orientation

The Hierarchy:

Top Professor: He/she is concerned with the more managerial issues that happen in a lab. He/she would be the person who would have the actual thought about the societal benefit to the project at stake.

Post Doc: He/she is the micromanager. They are the ones who are in the lab working and managing the researchers. They are more concerned with the techniques that the people below him/her are using to get the project finished.

Bottom Technician, Graduate Student, Undergraduate Student: The technician works above the graduate/undergraduate student. These researchers are more concerned with the fundamental practices of being a researcher. They might think about what they are doing as being a societal benefit, but it's rare.

Mission Statement:

This hierarchy chart is a great way to explain my purpose as an anthropologist in the lab. It is the professor who is the person who is thinking about “is this project going to benefit society?” the men below him rarely think about the societal implications of their work in the lab because they are too focused on the basic fundamentals in the lab, like learning a new technique to do digests, for example. For a researcher to think about the societal implications of their work on a more regular basis means that he or she would need to be a professor. This takes years to do and when he or she does become a professor they rarely are in the lab. Since the men who are in the lab on a daily basis are not constantly thinking about those issues it is my job to act as a catalyst to get he or she to think on the level of a professor.

** It must also be understood that I am apart of the team and not a separate entity. Just like my teammates I have a task to do in the lab.

** Here inlays the question: with me being apart of the lab and of the hierarchy (bottom with the rest of my teammates) is it my goal that eventually through the evolution of the lab that researchers will internally become apart of human practices rather than there always being an external “human practices” who is not doing lab procedures like the rest of the people in the lab?

• Will “human practices” always involve having an external person?

Mode 1: there are known answers to known questions. This is not to say that the answers are correct but that there are possible answers. For example, there are questions with in the lab that he or she knows the possible answer to:

** What is “good” science?

• This can be answered in the form of technology that makes science practices possible and better.

Safety/ Security: It has been brought up several times in the lab and during lunch as to where the “kill switch” should go on the E.coli.

Regulation: The researchers understand that they are to regulate themselves while in the lab. But he or she had not gone into detail as to what regulation means to them.

Q: What does regulation means today? Is it internal, external, or both? What are the institutions of regulations within the lab and outside the lab? [Read the White paper to give better explanation later on]. Institutional boards can be seen as both regulation and imposing ethical limitations. These boards are external/ bureaucratic bodies that check-up on the researchers to make sure that the researchers are following up on their own regulations as well as the regulations imposed on them by the board.

Ethics: Institutional Review Boards (IRB) can be seen as both regulation and imposing ethical limitations. These boards are external/ bureaucratic bodies that check-up on the researchers to make sure that the researchers are following up on their own regulations as well as the regulations imposed on them by the board.

• What are kinds of ethical questions are institutions like IRB or any other outside institution ask of a project like this (iGEM).

• Is the equality of access an ethical question that an IRB or any other body would ask about this project?

What about the privatization of pure whole blood verses the synthetic blood made by the lab? What type of scenarios are there if synthetic blood were to become available to the public? How would health insurance companies handle this? Would health insurance charge patients more money for the pure whole blood? Will it matter during a traumatic situation? Will people care whether he or she receives real or synthesized blood?

Optimization: Why is the team building a chassis out of E.coli especially if e.coli is seen as being dangerous bacteria to the human body?

• One of the benefits about synthetic biology is recognizing this issue and re-engineering the E.coli into a chassis that is safe for human use. The team is using E.coli as the chassis for the hemoglobin for three reasons. The first is because UC Berkeley labs have been working with E.coli and know its properties well enough to know how to make it safe for human use. The second is because E.coli is a cheap resource to hold the hemoglobin.

• If the researchers are going to make something for the society/everyone they also need to keep a business sense about the materials that they use, one being the cost of materials. E.coli is a cheap material to use for the chassis, which means that this will also make the cost of the synthetic hemoglobin at a reasonable price.

Lastly, E.coli is an effective chassis to use.

• The researchers know that E.coli is an effective chassis to use because he or she has used it for making the malaria vaccination artemesinin.

I.P.: What types of parts, devices, and chassis are to be open source? (Distinction between private and public parts.)

Mode 2: This is the idea of science where there are questions but no way to answer the question. Everyone has his or her own way of answering the question but there will never be one right answer. There is uncertainty.

** What is “good” science?

• This question in terms of ethics, security, safety, I.P., and ect. (Everyone has his or her own opinion as to what “good” science is, but there really is not a definite answer).

Safety/ Security: There is this analogy that can be used from a television show called “Modern Marvels”. In an episode they discuss engineering disasters. A disaster that they talk about on the show was about how a satellite shut down in the early 1990’s and caused pagers and networks to loose connection for a few days. The engineers found the cause of the problem to be that one of the metals used in the computer chips was reacting to another metal, making a new electrical connection that caused the satellite to face the wrong direction and not being able to receive signals. The metal causing this problem was tin, which the engineers used because they claimed it to be a readily available source and cheap. For a few years after the satellite incident tin was no longer used to make these types of chips, but then many companies decided to go back to using tin to make their chips because it was such a cheap resource. Since the reinstatement of tin, engineers have not been able to figure out how to stop this metal reaction from happening, but only that they recognize that there will be a problem in the near future and when the problem arises that they will have to “deal” with the problem.

• We can also think about this in regards to E.coli. When the engineers first built the chip all they knew was that the system worked with tin, only to find out thirty years later that the tin would react to make “wire worms” redirecting information and causing the system to “fail”. Right now we know that E.coli can be engineered in a way that is safe for the human body to consume. But what about in thirty years? Do we have any guarantee that our bodies will not later react to the E.coli in our system, causing a “failure” to the system? Are there any possible “plans” in case this was to happen? If so, how could this E.coli reaction in the body be fixed? (You can’t just physically remove the E.coli from your body once it has been put in).

** What about open source/ transparency?

• How does human practices go about answering this question?

• Is it right to “overreact” to the thought of possible bio-terrorism and close down open source access to the information? (Open source means that the information about the bio bricks is readily available to anyone).

• Rob Carlson thinks that it is best to be “dynamic” and allow the scientific information to be available to everyone. This just means that we do have to be aware of the possibility of an attack and be prepared.

-I think that we should be dynamic in the sense if we “overreact” to the possibility of bio-terrorism by shutting down open source then the terrorists have already won. It is best to no live in fear but rather to “prepare for the worse and hope for the best”. Everyone else should not be punished.

Ethics:

I.P.: Can the open source model be sustained?

Keep in mind:

• What type of implications (security/safety, ethics, and I.P.) will this have on human practices (society and science)?

• What effects does synthetic hemoglobin have on human practices?

• What is the dignity of human beings? Does the engineering of artificial biological parts take away human dignity?

- Do my colleagues think about what they are doing in this sort of manner? I would like to think that they do. From the papers that I have read the authors claim that they want "to make living things better and better living things" (Rabinow 2007: 6), but how do people feel about this on the outside of the lab? Can everyone within society eventually accept the concept of artificial biological parts?

• iGEM is making the future. What does the future look like?

- There are positive and negatives to this question. The positive is that iGEM is with the good intentions of “making living things better and better living things”. The negative could be that someone could use this new technology for contradictory intentions.

Me inside the Lab:

• It takes a while to understand that I am apart of the team. When looking over my field notes I recognize that I call my teammates “the team” or “the researchers” rather than “my teammates”, “colleagues”, or “collaborators”.

• It is also difficult to understand when to make that distinction between “my teammates”/ “colleagues” and “the team”/ “the researchers” because I do have to step back and reflect especially when I ask them questions and reflect about their answers. Is it best to just call them by their name? For they are human and apart of society just like me. I need to remember to watch my choice of language. It is interesting to see how innate our use of language is to separating science and society on its own.