TRANSCRIPT: Meeting 2, Session 6

Amy Gutmann:

Welcome, everybody, to our second day of our second meeting of the Presidential Commission for the Study of Bioethical Issues. I’m Amy Gutmann, and it’s wonderful to have everybody here today.

 

Yesterday’s session, for those who couldn’t make it, we were very pleased. It was very productive for the commission members. And today we’ll focus on ways in which synthetic biology is expanding interest in biology as well as the biosecurity and biosafety concerns that are raised by synthetic biology and by emerging technologies more generally.

 

And we’ll conclude with remarks from Dr. Sydney Brenner. Many of you know Dr. Brenner as a Nobel Laureate. He has graciously been participating in the entire meeting.

 

Although the baseball metaphor I will use is not from his native land, he will be our clean up batter, as we Phillies fans like to say.

 

And now I will turn it over to our vice chair, Dr. Jim Wagner, who I’m sad to say is not a Phillies fan, but I’m very happy to say he is a great partner for me in helping us move the commission forward.

 

Jim, why don’t you take it over?

 

Jim Wagner:

I will. The comment, of course, is the neck and neck race between Atlanta and Philly, and Atlanta is leading by a game now at this point. Right?

 

Amy Gutmann:

Correct.

 

Jim Wagner:

And it’s good to help build false confidence in others. Anyway, my other reason for being here this morning is to introduce our panelists, the first panelists, Randy Rettberg and Jason Bobe. Randy is a leading educator in synthetic biology, an engineer by training. He worked for almost 30 years in the computer industry as a developer of, among other things, ARPANET and the Internet??too easy to comment on that. At MIT, Mr. Rettberg was a founder of the iGEM, the international and genetically engineered machines competition. It is an international and interdisciplinary and primarily undergraduate competition that uses synthetic bio as both a scientific goal and as an educational tool. Mr. Rettberg is also Director of MIT’s Registry of Standard Biological Parts and a principal research engineer in both the Department of Biological Engineering and the Computer Science and Artificial Intelligence Lab.

 

He is joined on our panel by Jason Bobe, who is the Director of Community for the Personal Genome Project, which I think many of us know is based out of George Church’s lab at Harvard Med. He is also co?founder of DIYbio.org, a leading organizational hub for amateur biologists worldwide uniting participants through its website, on-line forums, its blogs, and local chapters.

 

To each of you, Jason and Randy, thank you for being here. And, Randy, why don’t we start off with you?

 

Randy Rettberg:

Well, Amy and Jim, and the rest of the members of the commission, thank you very much for giving me the opportunity to describe the activities that have been happening in synthetic biology at MIT and around the world with iGEM and the Registry.

 

When I was a junior in high school I developed an interest in science, and I decided that my father was an architect of buildings and I wanted to be an architect of computers. I wanted to design computers. And at that time, it was normal for people to be interested in being astronauts, be interested in ham radio, interested in amateur rocketry, and interested in fixing your own car. These were all things you actually could do.

 

These days, I can’t fix my car. It’s entirely hopeless. My degree at MIT is not adequate to the task.

 

[AUDIENCE LAUGHTER]

 

I knew that if I was going to be designing computers I would work for IBM, CDC, or Honeywell. Those were the choices--almost certainly, IBM. And it’s such a large company, I probably wouldn’t really get to design the computer. Maybe I could design one of the panels on the front or something. It was simply too big. Those were the choices. It was a little discouraging, but it turned out that the world did not work that way.

 

Around 1965, 1970 and in through around 1980, there was a change in the way that the underlying structure of computers was put together. There was a thing called a TTL data book. TTL stands for transistor transistor logic. And before that, there was resistor transistor logic and diode transistor logic. But transistor transistor logic, TTL, came in the form of little tiny parts. They had pins that were on 1/10th-inch centers. The pins were standardized. The functions were standardized. You could have inverters, logic gates, registers. Later on you could have an entire integer piece of a computing processor.

 

This was more of a revolution than people realized at the time because with this kind of technology many groups were able to design computers. I actually designed the machine that was used as a replacement for the packet switch in the ARCANET that replaced the Honeywell machine. And that I really did with one other person, and that is kind of astonishing that something like that could be done. The manufacturing plant that put it all together was, of course, many more people. But I was able to meet my goal of designing a computer.

 

As time went on and the microprocessors came along, it was possible to make more advanced computers, and I designed a machine called the butterfly that was able to have up to 256 processors and we shipped the first of those in 1981.

 

The reason for bringing this up is that we use analogies a lot when we talk about synthetic biology, and when we use analogies it’s a very dangerous thing to do. First, your experience and mine experience are not the same. My analogy means much more to me than it means to you. Secondly, the analogies are often wrong. The thing you’re trying to compare is not accurate. And so people look at this idea of transistor transistor logic and they say, "Oh, we want to make computers inside cells. We want to do logic."

 

That’s not really right.

 

What we’re trying to do is we’re trying to say standardized parts can revolutionize an industry that is occupied by large commercial firms at the moment and provide opportunities for new and smaller firms to be developed and change the goals and the direction of a whole industry.

 

And so taking that analogy very directly of the TTL data book, we developed a thing called the Registry of Standard Biological Parts. So my friend Tom Knight at MIT--the picture on the left is his elaboration of this into the biological TTL data book. The picture on the right is one page from what I might call the Williams-Sonoma catalog of synthetic biology.

 

So in addition to the data book, we actually have a stock of parts. In our freezers at MIT, we have biological parts. These parts are things like the coding region for a protein, the DNA that codes for a protein, or a ribosome-binding site or a promoter. Tom made a method for assembling these parts into bigger systems, and we have been collecting a community collection of these parts in our freezers. iGEM, that I will be talking about in a minute, is the primary source and the primary user of this collection.

 

So as I came to biology with this background of standard parts, a question came up. And I’ve been showing this slide for many years now and I’m hoping that we’re reaching the end of its usefulness. The question is, can simple biological systems be built from standard, interchangeable parts and operated in living cells?

 

When we started, the answer was no. Biology is so complex that each case is unique. Simply true, I was told when we started iGEM that we were wasting the students’ time, that we were going to disappoint them because biology was too complicated. This was not going to work. We marched ahead anyway.

 

So if you have a question like this, how do you answer it? I tried Google, but Google didn’t know the answer. But Google might know the answer now. Somebody should check. We are not talking about something which is scientific. We’re talking about something which is kind of engineering. And so the way we approach at MIT, our primary resource is students. We have a lot of students. And in particular we have undergraduate students who have no idea what is impossible. They have not yet run into anything that was impossible for them.

 

So what we did was during the independent study period in January of 2003, my friends and I--Tom Knight, Drew Endy, Gerry Sussman, and then Pam Silver joining us the following year--ran an educational course, a design course. We divided the group of 16 students into four teams. Each team went off to design a way to make cells blink. Michael Elowitz had built the repressilator, so he had shown that it was possible. And so we figured with the MIT students they would be able to make it work much better.

 

We were very wrong. It turned out that the system that they designed was very complicated. Here is a basic diagram of it. You will see that even there, it has eight parts, eight subsections. And here is the actual design of it. Every one of these little icons is a biological part that we actually have in the freezer now. But at the time, we didn’t have it in any form.

 

The students designed this, and then we sent the design off to a DNA synthesis company and it took more than six months to get about half the parts back. Some we never got back and gave up on. Our idea that they would be able to design something and come back in the summer and test it was very optimistic, but this was 2003.

 

So since that, we were happy with the experience that the students had and we were happy that they had made so much progress and that it was very promising. So in 2004, we ran a summer competition. It was kind of a cooperation competition. We got some funding from NSF. We found five other schools, five schools that were friendly enough that if things worked out badly they wouldn’t really complain, and we paid all of the expenses. We paid for the jamboree. We paid for the ice cream at the jamboree. And those teams went off and tried to do this synthetic biology based on standard parts.

 

Since then we’ve done it every summer. You can see the curve on the left of the growth of the number of teams. The growth itself is encouraging. It shows the excitement.

 

There’s a lot of information in the growth curve. You can see the effect of the economic downturn in the last two bars. It didn’t grow as well as they had been growing before. We only grew 33 percent in 2009. Teams had to register in March. And if you remember the financial news of the time was depression, second Great Depression, or a complete meltdown. And in spite of that, we had some growth. This year, the growth was only about 15 percent because the financial crisis actually hit many of the schools.

 

There is another thing to say about this growth and scale that I would like to bring out specifically for the commission. In the early days, we sent out parts in little tubes with labels. We manufactured them pretty much by hand, and the people around us said, "Oh, that’s a bad idea" because in a while you’re going to have five hundred to a thousand teams and you won’t be able to do that anymore, and so you have to have a different solution. You should not be sending out parts. That was actually incorrect.

 

It turns out that by the time we had a hundred teams we actually had more resources and we were able to solve the problems that came up in the future. And I think that is an important theme for the commission, that we are looking forward at the problems that might come from synthetic biology without fully appreciating perhaps the increase in the tools and the resources we’ll have to solve those problems as time comes by. That has been a constant theme with iGEM, a constant looking-into-the-future-and-seeing-problems, which is a good thing to do, and then worrying a bit too much at the current time.

 

So, right now we are at 130 teams. The 130 teams will come to MIT in November for the jamboree. There is almost 2,000 people who are involved in iGEM this summer. By that, I mean they have registered with iGEM teams. Some are students--undergraduates, high school. Some of them are graduate students, and some of them are faculty advisors, faculty members from other departments. In all, about half of the people that are involved in iGEM are not students. And that’s a surprise.

 

Because, what are they doing? Clearly the field of synthetic biology has not evolved enough for them to simply be pouring their knowledge into the students. Right? What they’re doing is they are learning about synthetic biology. And so one of the biggest effects of iGEM beyond the students is the impact it’s having on the schools, on the careers of the professors and the grad students.

 

If you look at the centers for synthetic biology that have developed around the world you will find at the core people who were involved earlier on in synthetic biology. At the Imperial College, for example, there is a Center for Synthetic Biology. And Professor Kitney is the head of that, and he learned about synthetic biology through iGEM several years ago. That has been happening over and over again.

 

There is a second thing that is happening. That is that, because of the competitive aspect of iGEM, schools are teaching classes in synthetic biology to get their team ready.

 

This happened first with Valencia in Spain where, instead of going home for Easter break, all of the students stayed at the school to study synthetic biology and get ready for iGEM.

 

So now we have a large group. This is last year’s iGEM competition group at MIT. Remember, there are about 50 percent more who didn’t get to come. They are the other grad students, professors, advisors, and all of that. iGEM is pretty well spread around the world. We have had sites in Latin America including Panama this year. These are all of the sites that have participated in iGEM over the period of time. We have sites in Asia. We have a site in Africa, a lot in the US, and a lot in Europe, and a significant number in Canada.

 

So those are the sites in the United States since this is focused on the United States. You can see that once again it’s pretty well distributed. There are sites all over the country. We are happy to have the sites in many of the different schools.

 

So let’s take a look at how iGEM works. The first thing is that iGEM is about getting and giving. The teams get parts. They get information. They get knowledge from the teams before. And they contribute those parts, ideas, and experience to the teams that came after them. It’s a sharing kind of environment.

 

The community is not just iGEM teams. We now have labs that are synthetic biology labs that are part of our community. We have approximately 90 labs registered, and we send them biological parts. There is about 6,000 users altogether, and 2,500 of them have logged in this year. 1,000 have entered parts. We have 5,000 parts in our repository. Out of those, about half have been marked by the users as working in their hands.

 

So here is how iGEM works. First, you assemble your team. This is an example team from Utah State. It has five high- school students, five undergraduate students, three graduate students, and three faculty members. It’s usual that teams have that many high-school students, but it is not so unusual that the high-school students participate. In my opinion, iGEM is focused on undergraduates and not high-school students. But we do have some high schools that are teams in themselves. So Gaston Day School, for example, is a high-school team. But generally the high schools don’t have the lab resources that are critical to be able to succeed.

 

The second thing you have to do is you have to raise money, and so raising money is done by the teams. We don’t have a central source of money. We do not give grants out to teams. The teams have to pay us. They have to pay to attend. Teams generally raise in the $25,000 to $50,000 region to participate in iGEM.

 

You then attend workshops. We hold workshops in the US, Asia, and Europe. You get your biobrick parts. We sent out about a thousand parts to each team. You work at your school. The teams do not come to MIT. The teams make their own wikis and websites for presentation.

 

They come to the jamboree. They win awards. We give out medals. We give out prizes. And after that, some of them publish their work. Many of them are able to get publicity in their local press. I would say that last year we probably got about 400 articles in local press around the world. When Peking University won, we actually got complaints from the Chinese national press that in the future would be please let them know ahead of time if any Chinese teams are going to win at iGEM.

 

And so there are a number of projects??I’m pretty much out of time, but there are a number of projects that are interesting. Perhaps the one that was the most fun was bactoblood. This was bacterial blood done by UC-Berkley. They worked on the chassis. They put the hemoglobin system into bacteria. They worked on safety, kill switches for all of that. They worked a lot on the question of patents and that kind of thing as well.

 

The second project of interest is the arsenic detector done by Edinburgh. This is a bacterial detector for arsenic-contaminated wells, which is extremely low-cost, extremely easy to use, could be used by the villagers in Bangladesh, for example. The estimate is, it would save about a million lives a year.

 

Another one that’s interesting is bio-beer. And this shows how, instead of these projects coming from large pharma companies, projects come from the undergraduates. And the undergraduates don’t drink red wine. If they are old enough, they brink beer. And they wanted to live forever like the French, right, and so they put the genes from the red wine into the beer.

 

Last year’s winner was Cambridge, and they made a whole range of colors of pigmented parts. But the most important thing they were making was a general purpose detector with an interchangeable detector of things like heavy metals, lead, and all of that; a method for setting thresholds; and then pigments that could show you by color what contaminations existed in the environment.

 

Slovenia won the previous year by developing an artificial vaccine for helicobacter pylori. And they tested that in mice. Interestingly, that is a project that could not have been done by any of the teams in the United States because the safety regime for animal experiments is different in Slovenia.

 

Jim Wagner:

Randy, can we get you to ??

 

Randy Rettberg:

Yes. I’m almost at the end.

 

Jim Wagner:

We need a great example, and you can stay here more.

 

Randy Rettberg:

So there are two questions at the end. Is iGEM safe? Number one, the work is done in academic institutions that have formal programs for biological safety. They are done under the supervision of the faculty at those schools. We also require that they fill out a safety questionnaire, and we also provide medals for achievements in human factors. And many of the teams go to great lengths in that area.

 

Heidelberg in 2008 did community work--

 

Jim Wagner:

I’ll tell you what--is that your last slide?

 

Randy Rettberg:

Last slide. We have turned that over to the FBI, who was one of the sponsors of iGEM.

 

Jim Wagner:

Excellent. No, we’ll come back. This is pretty fascinating. Jason?

 

Jason Bobe:

I’m up.

 

Jim Wagner:

You’re up.

 

Jason Bobe:

Well, thank you for having me here today. I think it’s very forethinking of the commission to include in your considerations amateurs and citizen scientists. So I think part of my role here today is to describe to you a little bit almost as an arm?chair anthropologist about what is happening with amateurs and citizen scientists out there in the United States and abroad.

 

So chances are that, if you have heard of DIYbio at all up to this point, it’s probably been in the context of weapons of mass destruction. In the past year alone so far in 2010, I think there have been four articles in the press that link DIYbio with weapons of mass destruction and biosecurity. In comparison to synthetic biology, it has been linked to weapons of mass destruction ten times so far in 2010. So there is certainly a lot of anxiety by the general public about amateurs getting involved in biology. And so I think part of my role here today is to tell you what is, in fact, happening. So that’s what I’m going to do.

 

And before I start, Randy made a few references to other vibrant amateur communities in the United States and abroad. And these are a few examples from this past century from home chemistry sets to the home brew club that was really instrumental in launching Silicon Valley and the computer industry, astronomy, rocketry.

 

This is my favorite example. This is an amateur who last year built -- he actually spent, I think, around ten years building this. As a young boy, he watched the moon shot happen and got involved in high-powered rocketry as an amateur and he built a Saturn V rocket that was one?fifth the scale of the original Saturn V and launched it in Maryland last year.

 

So what is DIYbio and how big is the community? So DIYbio was founded two years ago in Boston in early 2008. Our first meeting was actually in a pub, Asgard’s Pub, with about 50 people. And we spent the first summer working on how to isolate/extract DNA from strawberries using only household chemicals. And then from there we’ve gone to more complex things and the community has grown to currently about 2,000 individuals around the world and there are local chapters in more than a dozen cities globally. And these local chapters tend to have social events, meet?ups, seminars, lectures, and sometimes hands?on workshops.

 

So the scope of activities. I think it is easiest to divide the work into two domains. On the one hand, there are exploratory biology and this tends to be focused on discovery and the application of technologies like DNA sequencing to exploring the environment and oneself.

 

And so these are two examples on the left: environmental sensing, the bio weather map, and this is using DNA sequencing to monitor the ebb and flow of microbial communities in a particular environment--in this case, on the crosswalk buttons in cities.

 

And the second example, personal biomonitoring. This is a young woman who is actually a graduate of MIT, Kay. She lives in Boston, and she has family history of hemochromatosis. And being a nerd and somebody who is technically interested, rather than going to her physician or buying a medical test on line, she started by first actually building a lab in her home and doing Allele-specific genotyping to see if she carries the same variant as her father does. Now, she, of course, said she would go and confirm the test with her medical doctor. But this is something she was interested in doing as a hobby. I think there are others out there who are interested in doing these types of experiments as well.

 

So the other area of interest is constructive biology, and this is really about engineering. And, in particular, people who may come from a background of electrical engineering or computer science are just now learning about all of the very interesting tools and toys that exist in biological laboratories and are interested in re-imagining them and refashioning them in new ways, and I will talk more about some of those developments later in my talk.

 

And then, also, people are in fact getting interested in genetic engineering. I will say that we are still in a very, very early stage and are in fact trying to catch up with AP biology classes who are now doing bacterial transformations as part of their high-school curriculum. And there was actually a pair of brothers, age 20 and 23 this year, who were using, evaluating some of these high-school AP biology bacterial transformation kits and were really discouraged by how expensive it was and how inaccessible due to expense of the equipment and protocols of reagents of these for high-school students. And so they started a company in their apartment with the R&D laboratory actually being in their apartment and launched a company to make low?cost kits for high-school students which are now being used in high schools in Northern Indiana, and they hope to expand nationally.

 

And so community labs. This is another new development just this past year. There are now three labs being set up in the United States: One in the Bay Area, Boston, and Brooklyn. The one in Boston is the Boston Open Source Science Lab, and this is a mobile bio lab which was purchased at an auction for 5 percent of the original cost. GenSpace in Brooklyn is a non-profit. It was the local DIYbio group, and they have now got space to set up a community lab. And BioCurious in San Francisco.

 

And so what is a community lab? A community lab is taking a page out of the book of clay potters and woodworkers pooling their resources to buy expensive equipment that would otherwise be beyond the scope of an individual to put something in their garage. And this is also places where people have classes. They get access to expertise, things to be new businesses. And BioCurious, by the way -- this has become common for the community to actually crowd?source funding through websites like organizations such as kickstarter. They are asking the world for $30,000 to start their lab. And, in fact, they’re at $28,000 as of today with seven days left in their campaign, and I think they will, in fact, raise the money -- an example of BioCurious.

 

So there are really two benefits or two things that people are excited about with these community labs. Amateurs and citizen scientists who don’t have the resources or the time, are happy in their professions and don’t want to go back to school, but they want to learn more about some of the advances in biology generally.

 

This is an example of the curriculum or the classes that have been held in San Francisco and the San Francisco group. And this is really, I think, informal STEM (Science, Technology, Engineering, and Mathematics) education for the general public in a way to inform help create and inform citizenry around some of these advanced biotechnologies. So the seminars and workshops range from really technical matters like DNA synthesis and PCR (Polymerase Chain Reaction) techniques and pharmatics to lectures on social affairs like what are the needs of developing communities, developing countries, around medical devices and what are some opportunities for people to contribute to those needs?

 

And I also threw in this example. This was a really great article in The New York Times earlier this year by Ashlee Vance. And DIY is currently really part of the fabric of the United States and internationally and there is a confluence of communities that are starting to happen.

 

And well, first, I should explain what TechShop is. This is a model for a membership model , and it’s really a gym for your brain. I mean, you pay $100 membership per month or something in that range, and you get access to expensive, exciting equipment like plasma cutters and 3D printers. And this is franchising around the United States right now, but there are also similar operations, enterprises, similar to TechShop, and this is really attracting adventurers, makers, tinkerers, and entrepreneurs. And these are the same people who will be attracted to the community labs. And I also fully expect that enterprises like TechShop sometime in the next five or ten years will be expanding their footprint into biotechnology. I think that would come as really no surprise.

 

Currently, to give you an example, this year there were two desk?top DNA sequencing devices that came on the market and they cost about $50,000, which is not quite the prosumer market yet but it’s getting closer. And so even though it may not be within the reach of an individual, it’s certainly is within the reach of an enterprise like TechShop or a community lab where you could go get access to that as somebody just as an average citizen.

 

And if there is time in the Q&A, I would very much like to talk about some of the devices that have come on the market this year that have been developed by members of the community.

 

I think what we are seeing already, even though we are seeing some of the fruits of innovation and really starting to get access to some of the cognitive surplus that exists out there in the United States, these are five or six examples of that. And I would like to just pick one, which is I think characteristic of the type of innovation that you will see in amateur biology which tends to be low-cost and low-waste because you don’t have any other choice.

 

This is actually the amateur’s version of a centrifuge. It was printed on a 3D printing device. I ordered it by mail. It cost about 20 bucks by a company called Shapeways where an individual actually is a pretty amazing young contributor in Ireland named Cathal Garvey sent a CAD (Computer Aided Design) file to this company, and then anybody can go order it online. And what you do is this is actually the chuck edition where I can stick this into the end of my electric screwdriver, put my tubes around the end, and I can get thousand G’s of centrifugal force for a centrifuge.

 

So one motivation for establishing DIYbio in advance of widespread amateur activity because I think we have approximately 2,000 people on our mailing list, I would estimate that somewhere between 10 and 30 percent of that are professionals in the biosecurity realm wanting to understand what is happening.

 

The number of actual contributors? It’s really hard to tell how many amateurs are out there and exactly what they are doing. But one of the goals of establishing an organization for amateurs is really to get ahead of widespread amateur activity and try to establish a framework for best practices global-wide.

 

So I’m really delighted to tell you that we have just started a collaboration with the Woodrow Wilson Center funded by the Sloan Foundation to try to develop just that, norms of practice and biosafety resources for amateurs worldwide.

 

And we are just getting underway, and we just had a survey of our community. I started a survey about two weeks ago around biosafety. And to give you a sense of the types of questions people are asking out there based on their either current or intended activities, here are a few. Here are four or five. What organic waste can we put in the drain or the compost bin? Can I share my experiments with friends? Is crystal violet a safe alternative to ethidium bromide? Are there special disposal requirements for polychloride gels? Where can I dispose of organic solvents? Do enzyme preps that contain plasma require special handling for disposal? If I want to make a GMO, do I have to tell anybody?

 

So I think there are probably good answers to all of these questions. But currently there simply are not good resources for amateurs, and we would like to change that with our project.

 

So actually I have ended, and I have a few items here that are a wish list for our community with the goal of establishing a vibrant, safe, and productive community of amateur biologists in the United States and abroad.

 

And I think that right now while amateur activity is relatively low, while we see really tremendously exciting things happening, there is no doubt that there is a lot of interest in the things that are happening in programs like iGEM and that people want to get involved and to make new things, that now is a really important time to consider how do we start now for setting the pattern for environmentally-benign practice by, not only by institutional scientists, but amateurs and citizen scientists globally. Thank you.

 

Jim Wagner:

Jason, thank you. I can tell that we may have done you both a disservice by not allowing enough time for both the information and your enthusiasm. But while we still have a yellow light, you had better explain all the rest of your --

 

Jason Bobe:

Sure, this is a brief tour. This is something that’s new this year. This is a microbial fuel cell. There are naturally existing in your backyard bacteria which breathe iron and emit electrons. So you can actually just take mud from your backyard and pack it into this device and it will begin to generate electricity like a battery, like a weak battery, and an LED light will come on on the top of this. So people are now taking this already and refashioning it in different ways and attaching our devices. You can plug it into the computer. You can monitor. People can watch the change in electricity over time, and people are starting to set up to do small competitions around saying whose compost bin has the most electrical energy in it.

 

We have two PCR devices this year. This is a portable PCR device called a Lava Amp for amplifying DNA in the field, and this is a customizable PCR device called the open PCR.

 

Then this is a gel electrophoresis box that costs about $400 with its own transilluminator. And all of these things tend to cost somewhere between 10 and 40 percent of the cost of laboratory equipment and they also tend to be open and extensible and often simpler than what you get in a laboratory but more fun.

 

Jim Wagner:

Thank you. Nelson, are you going to kick it off for us?

 

Nelson Michael:

Yes, and thanks to both of you. That was a fascinating discussion, and we definitely could stay here for another hour and just be dazzled.

 

So in the work that I do where I interact with the community in terms of medical search, it’s critical especially in parts of the world like in Africa or Asia where extensions of the US government doing research in under-resourced areas can be problematic, community engagement is essential before research activities start. And usually those activities have to start several years before research activities can begin to build the trust in those communities. And that’s something that probably consumes about 70 percent of what we do on the ground overseas.

 

It seems to me that both of you are approaching that kind of concept in terms of synthetic biology. And, Randy, in your case, your community seems more centered around academia in maybe perhaps the more traditional base of the community. And yet you describe, Jason, yourself at least one of your do?it?yourselfers, if you will forgive the term, as somebody obviously who was involved in academia as well.

 

Again, I would like for both of you to kind of expand on what space do you think that you fill? I can tell you that in my experience in medical research in the absence of community engagement you couldn’t do science. You just simply couldn’t. There would be too much community resistance.

 

What would happen if iGEM went away, and what would be the impact of having the lack of some degree of organization for do?it?yourselfers?

 

Randy Rettberg:

So as you saw on the world map, we have iGEM in many of the corners of the world. The iGEM teams, one of the things that they do specifically, is they work on human factors because with that they can win a medal. Right? And they are very excited about winning medals. And so they often do community engagement directly as iGEM teams. And so the puzzle of how you get synthetic biology kind of connected out to the community is, in fact, a problem that the iGEM teams work on themselves.

 

Also, the publicity that comes as a result of their participation in iGEM is in the local press, and there is probably in most cases three or four articles about that that happen. And we are encouraging development of iGEM teams everywhere around the world. They often solve problems that are interesting in their local environment.

 

A team from Naples, Italy made an extra virgin olive oil detector, and so they are not necessarily solving giant medical problems. But they are solving problems that the community might be interested in.

 

Jason Bobe:

I think that thinking about institutional and non-institutional science, I think it’s really instructive. For the community, there are many, many issues which are just beyond the scope of any one amateur. And so even though it’s a little odd to have an institution for non-institutional science, but I think that there is certainly a need for some organization, DIYbio or some other to fill the role because there are all sorts of issues that there is just no need for individuals each time to address as if it were the first time ever to be asked questions around basic biosafety or disposal or what are regulatory policies around these issues and can I ship this thing in the mail to my friend, etcetera. So I think there certainly is a need for institutions for non-institutional science.

 

But I also think there are going to be a lot of individuals who are interested in doing work in a home workshop that may be doing very simple things that may not require a whole lot of oversight or help using DNA sequencing technology to figure out the specific strain of heirloom tomato in their garden or what bacteria live in their dog’s mouth. I think that there are all sorts of questions that people are going to be asking as these tools become more available.

 

But thinking about synthetic biology and thinking about the types of resources that already exist inside of institutions, I think it certainly is going to be really important for there to be cross?over between institutional science and institutions that support science for amateurs and citizen scientists.

 

Jim Wagner:

Yes. And I’m happy to invite also those in the audience if you would like to come to a microphone.

 

Raju Kucherlapati:

Thank you very much. This is very exciting. I want to understand a little bit about the motivations of these different groups. Randy, I understand that in the case of iGEM that it’s essentially academic advancement. But, Jason, it would be interesting to understand a little bit about why the individuals in the community want to engage in these types of activities. And, also, I want to understand a little bit about how do they get support to undertake the kinds of projects that you have described.

 

Jason Bobe:

So we’re still learning about the people who compose the community. One of the surveys that we did about a year ago actually found that one of the major groups, subgroups, within the population are artists. And artists are typically generally always the first, the earliest, of adopters with any of these new technologies. And they have been involved in basically amateur science, amateur biology for nearly ten years now. And so there are lots of artists who are in our community.

 

But more than that, I think that what we’ve seen recently is really entrepreneurs and inventors. And if you look at the history of innovation in the United States, there has been a really strong role played by individual inventors and small business. Everything from the common zipper to the personal computer owes a serious debt of gratitude to individual inventors working usually out of their home or out of their garage. And people are now just really getting turned on to biology and many of the things they are seeing at things like iGEM and what they read in the newspapers about biofuels and new vaccines. And so I think entrepreneurial spirit is certainly something that is a major motivation.

 

And then more than that or, not more than that, but another group of people are simply people who want to tinker and people who are technically?minded and want to understand the things that they see on TV or read in the newspaper and want a chance to learn about them. And so one of the questions that we had got in the survey was from an individual who wanted to do Sanger sequencing in their garage, not because that is the most advanced technology-- that is an old, old technology for doing DNA sequencing. But they thought that it would be really educational to actually cast the gels and run the gels and to understand how DNA sequencing works where it’s more gratifying than isolating a DNA and sticking it in of the new machines and coming back in 12 hours, to actually go through all of the steps of doing DNA sequencing. And so I think there is a lot of that as well.

 

In terms of support, it’s been really amazing the way that people use the web and the community and even the general public to get support for their projects. And so this group here raised $12,000 approximately on this website called kickstarter in the course of two or three weeks, something in that range. This group, similar, got a small grant from the Improbably Institute, I think it’s called. And BioCurious, this lab, is raising money, crowd?sourcing and raising money on line. They will have raised about $30,000, I think, by the end of this week.

 

So otherwise people are just simply boot-strapping it and coming up with ways, work-arounds that when it is too expensive to buy a $2,000 centrifuge you come up with a $20 alternative.

 

And so I think another thing to consider is there is an assumption typically around that people think that amateur science is really just institutional science but you put it in a garage and they are doing everything that is happening in institutions which I think really couldn’t be further from the truth. So I expect that one of the things we’ll see happen is that you have to take existing science and look at it with a new lens. When you are forced to do things in a low?cost, low?waste environment, you actually come up with something that looks quite a bit different.

 

Jim Wagner:

And we see that in a lot of hobbyists, don’t we?

 

Jason Bobe:

Yes.

 

Jim Wagner:

I hope that in part of the time that we have remaining since don’t have much, we can talk a little about the safety issue, and we when glossed over your last slide, but I think it’s something that the commission needs to consider here. But, first, from the audience -- oh, and then Barbara.

 

Tim Trevan:

Tim Trevan, International Council for Life Sciences. I have a question for Jason. Pretty much any international meeting you go to on biological issues whether it’s the Biological Weapons Convention, International Health Regulations, or meetings on biosafety at biosecurity, at some point someone mentions bioethics. And in each of the international structures dealing with biosafety and biosecurity, states have pretty much gone as far as they can in terms of regulation, legislation, setting in places surveillance and monitoring systems. So our organization very much has got to the stage where we are looking at the issues of personal responsibility and developing awareness and pushing it down from the organizational level to the individual level to get to personal responsibility and awareness. So I was very, very pleased to hear that that’s happening with your outfit.

 

But, of course, as the officials get to mention bioethics, the kickback is almost invariably from the professionals life sciences. "What? We don’t have ethics already?" I was just very interested to know what is the reaction in your community, the do-it-yourself community, to being posed with the issue of personal responsibility and bioethics?

 

Jason Bobe:

Well, it’s a really good question. And I can say that the only requirement that there is for people to get involved in DIYbio--there is no really formal method at this time. You can just sign up with your e?mail address on a mailing list and you are a part of our community.

 

Jim Wagner:

I hope the audience won’t mind if our speakers answer your questions through the microphone.

 

Jason Bobe:

Oh, yeah, sorry about that. So by virtue of having a very, very low barrier to entry, which is something which we like, we want to reach people who are interested in doing amateur activity, but I would say every view is represented in our community. And at this time early on there is very little norms that have developed. I mean, the community itself is about two years old. And so there is no common opinion yet on issues around bioethics or biosafety. And in some circumstances there may be very little awareness about what the issues are. And so I think it’s our task now early on in the growth of this community to start to establish those.

 

But, that being said, there are professional scientists in our community. So the range of interest and knowledge about different sorts of issues, whether it be biosafety or bioethical issues, is a very wide range.

 

Jim Wagner:

Barbara?

 

Barbara Atkinson: My question is on the biosafety piece for both of you. It’s sort of the balance between innovation and invention versus the regulations about who can buy what types of sequences or those kinds of things and where should that balance be and are we not far enough on the regulation side yet or are we inhibiting the innovation side?

 

Randy Rettberg:

I think certainly in iGEM, we are not--with few exceptions, we are not very close to the edge. I would say the example exception is the work done by Slovenia where they actually were actually able to test their vaccine in a mouse as a project that started at the beginning of the summer and finished before November, and that is outside the possibility of the regulations in the United States. We actually had United States teams complaining slightly that it was unfair that they had such a regulatory advantage. I don’t know what to do about that, actually.

 

But other than that, I would say the issues and concerns about sequences that they can order??we are nowhere close to that. The work is primarily on one-level work. There is some work done in embryonic stem cells. There is some work done in yeast, but it’s not??we are not close to the problems of the regulation yet.

 

Jim Wagner:

Nita?

 

Nita Farahany:

I want to build a little bit on the biosafety concerns and first ask a question about the standard parts and then a question about ?? I know what some of the concerns are for people who are do?it?yourself biologists, so I want to understand the standard parts better.

 

What is the advantage of having the parts actually built and put into a freezer as opposed to simply publishing what the sequences are, and is it something that once you have the standard parts someone who has the sequence can simply build the parts rather than having to order it from you?

 

And that goes as well for you because one of the concerns--and it seems like there are a couple of concerns with do?it?yourselfers. One is whether they are adopting institutional norms for safety and to prevent release. But second is, if we have certain sequences that are published on the Internet and widely available and they could be easily sequenced at home is this a genuine concern that we could build these things at home, if they are pathogens, if they are the smallpox virus which no longer exists or other types of novel pathogens that don’t simply exist yet and could easily be built at home, is it feasible? Should it be something that we’re concerned about it? And is there anything we can do about it?

 

Randy Rettberg:

Okay, the standard parts. What makes them standard? The first thing is that they are all in a form where they can be assembled with other parts easily. It’s something that you can do in a day. And so having the parts actually in hand--and we send out a thousand parts at the beginning of the iGEM season--means that the teams are able to do things immediately.

 

It also eliminates the barrier of trying to think too much about, "Well, what exactly do I want to have," because if you order something it actually takes a while and it costs some amount of money. It will cost hundreds of dollars to order a gene and it may well take a couple or two to three weeks. And so actually having it on hand and in your hands is a big improvement over that.

 

It’s a little bit surprising that the feeling that people get from that is so strong. We have had e?mails coming back from professors saying, "You talked about standard parts. But when the parts arrived in our laboratory, I realized the students have something I had never had in the past," which was in-hand parts that could be used immediately. So I think that’s the big difference there.

 

The sequences are available on the website. And so people could, in fact, have them sequenced, synthesized, and some people have actually done that in the past where we had trouble with the sample in some way.

 

Nita Farahany:

And they can sequence it at home. I mean, if they have one of the thousand?dollar DNA sequencers or synthesizers at home, they could actually synthesize it themselves?

 

Randy Rettberg:

Well, synthesizing??many of the parts for protein coding regions are in the 500- to 1200-base pair, and the synthesizers are able to synthesize things in the 20- to 50- base pair region. And so actually stitching them together is something that takes some time and patience. Now it might be that some of the amateurs actually have that time and patience and might well be able to do it. But it’s not going to be something that you would do in a week probably.

 

Jason Bobe:

And just to build on that, I’m not actually sure. I think the capabilities of individuals at this time are really, really low. Of course, it’s difficult to tell. It’s difficult to know what everybody is doing. But based on the discussions that are happening online, people don’t in fact yet have these new desktop DNA sequencing devices. They are just too expensive. And I don’t know of anybody having a DNA synthesis device at home that’s functional. But there certainly is interest of people even just from an electrical engineering point of view of understanding how the machine works and doing something different with them and maybe not for actual biological use.

 

But I’m certain in the future there will be people who have DNA synthesizers and DNA sequencing machines in their home workshops or in community labs.

 

Nita Farahany:

So of the two questions I had for you, one was the concern about the release. You said a question that some people ask is, do I need to tell anybody if I have a GMO? And should we be concerned about the release into the environment or biosafety measures that are being taken at home and is there anything we can do about it?

 

And, second, I think you’ve addressed now whether or not people can build the pathogens at home. People may not have the capabilities yet.

 

Jason Bobe:

So to answer your first question then, I think it certainly is something that there needs to be an awareness of. I think in the community right now, I’m not sure that there is very much at all awareness among many individuals about even what Biosafety Level 1 versus 2 is.

 

I think there are many people who are coming in from completely different fields. I think there are certainly individuals who come from a laboratory background who may even have a Ph.D. or worked in industry and are interested in setting up a home workshop or a community lab, and they have biosafety training and experience. But there are many individuals who do not.

 

I think that it is really important to do work like refactoring NIH guidelines in ways that make sense for individuals who may not have--if you’ve read them, they take a certain knowledge to even understand Biosafety Level 1.

 

Jim Wagner:

I think I’m going to go to Anita and then --

 

Randy Rettberg:

Can I add an answer to that?

 

Jim Wagner:

Oh, sure.

 

Randy Rettberg:

When we talk about the bioethics, we are primarily talking about guidelines of what people should and should not do and what that boundary is. When we talk about the safety of releasing organisms into the environment and working with organisms in synthetic biology, we are missing another piece completely. And that is, it seems to me quite clear that the government should be explicitly supporting the development of organisms that are explicitly and intentionally designed to be safe.

 

For example, all of us share the amino acid coding table that makes proteins with all of the organisms we use in our labs. That is not necessary. We could very well develop organisms that have a different amino acid coding table so that if there was a need we could gel the genome of one of these synthetic organisms to us, our dog, our food. Nothing would happen.

 

And there is a number of things. We saw the kill switch yesterday. There are advanced versions of that we could be doing, and explicitly--when I think about bioethics as a group, I think you also have to take actions to make things be safe when you can. And that is something that I would recommend.

 

Jim Wagner:

Anita and Alex, can I ask you guys to pool your questions here?

 

Alexander Garza:

Sure.

 

Jim Wagner:

And then we’ll wrap it up.

 

Anita Allen:

Anybody who has looked at the problems of everyday ethics knows that it’s very hard for ordinary people, ordinary citizens to always follow the high ethical standards that their leaders or their community may set forth. I’m still worried about the development of appropriate norms within the citizen scientist community, Jason, because we’ve seen it in business, in sports, in politics, in education, and in science. People don’t always live up to the right standards.

 

So I’m wondering whether you think there are any self-interested incentives that might tend to make science safe, make citizen science safer that might appeal to a person even if they’re sort of top?down ethical values coming from government or other sources might impose. Are there some sort of internal incentives toward ethical conduct?

 

Jim Wagner:

So standards for a DIYers?

 

Anita Allen:

Exactly.

 

Jim Wagner:

Alex?

 

Alexander Garza:

So I get paid to be paranoid. So one thing I wanted to ask Jason--and it sort of flows, I think, from the iGEM which is a little bit more, I think, organized and the Department of Justice is very well, I think, involved in iGEM whereas the DIY side is a little bit more sort of free?flowing and things like that.

 

So what do you think would be a good approach for the biosafety, so the lab safety side, but as well as the security side to be more involved, to help out, without suppressing innovation and what people want to do but also developing a culture of the security side as well?

 

Jim Wagner:

So we’ve got a question about voluntary incentives for this and what roles institutions could play, our institutions could play also in helping to incentivize safe practices.

 

Jason Bobe:

Okay, so I will take both. I think it’s a really interesting question, Anita, and I would love to spend a day brainstorming that with social scientists and behavioral scientists. I think there are certainly things that can be done. I think the earlier that efforts like thinking about building norms--I’m so happy about the Sloan Foundation grant and working with the Woodrow Wilson Center because I fully expect this phenomenon to grow globally. And if you’re going to set the patter--whatever it is that we do today is going to be mimicked over the world in the years to come. And so I think it’s a really opportune time to start thinking about that and start setting the pattern in ways that are positive and towards that end and thinking about biosafety.

 

So one of the things I would like to do rather than building capability up from BSL 1 to 2 to 3 to 4--that doesn’t make sense--I would like to go the other direction and start thinking about building norms of practice around identifying very safe model organisms and maybe developing something called BL-compostable. So I’m thinking about what are the types of experiments that can be done in a home workshop that are truly domesticated activities that can go in the compost bin when your done.

 

And to your question around biosecurity, it is something that is already of real interest to individuals. One of the first things that community labs are doing ?? so far only three of them ?? but they are going out and reaching out to first responders and to local law enforcement and through the FBI--the local FBI chapters, the local people there. And the reason why that is important and there is already a sense of what exists is that we’ve seen circumstances in the past couple of years of individuals who are doing work at home like Victor Deeb in Marlboro, Massachusetts, who is a chemist who is trying to get a bisphenol A-free sealant for baby jars, and he had a fire in his air-conditioner and they showed up and they saw a lab, the first responders. And, of course, the first thing that they thought was this guy is making meth or this guy is a terrorist. And so they dismantle his entire home laboratory set. He had several patents and they sent him a bill for $20,000 saying "This is yours to clean up."

 

And those types of experiences are really worrying for an individual who is thinking about sequencing their heirloom tomatoes in their backyard or building some biological device, and so there is already a sense to go and reach out to first responders and FBI folks.

 

So I don’t know if that fully answers your question. But there is probably more that can be done, but there is some activity on that.

 

Jim Wagner:

Randy, any final word on these points?

 

Randy Rettberg:

I guess the thing that I would like to say is that when we think about synthetic biology and we think about iGEM, we tend to be thinking in the current mindset. And when I looked at the charge that President Obama gave to the commission, he said medicine and environment and other. And I think the greatest opportunities lie in "other."

 

And I think that major thing the world needs now is a giant synthetic biology financial bubble or something like that, some excitement, some fun. I think the DIYbio, the iGEM, the work done in the labs at the centers can all be part of a new revolution, and that is what we need.

 

Jim Wagner:

Thanks very much. And let’s offer our thanks both to Randy and Jason.

 

[AUDIENCE APPLAUSE]

 

And we are scheduled to reconvene at a quarter past the hour in ten minutes. Thank you.